NS Group Research Articles

Protective effects of fructose-1,6-bisphosphate postconditioning on myocardial ischemia-reperfusion injury in patients undergoing valve replacement：a randomized, double-blind, placebo-controlled clinical trial.

Pharmacological postconditioning can protect against myocardial ischaemia-reperfusion injury during cardiac surgery with extracorporeal circulation. The aim of this study was to observe the protective effects of fructose-1, 6-bisphosphate (FDP) postconditioning on myocardial ischaemia-reperfusion injury in patients undergoing cardiac valve replacement with extracorporeal circulation. Patients undergoing elective mitral valve replacement and/or aortic valve replacement were divided into normal saline postconditioning group (NS group) and FDP postconditioning group (FDP group). The primary outcome was the plasma concentration of creatine kinase-MB (CK-MB). The secondary outcomes were the plasma concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity C-reactive protein (hs-CRP), alpha-hydroxybutyrate dehydrogenase (α-HBDH) and cardiac troponin I (cTnI), the spontaneous cardiac rhythm recovery profile, the extracorporeal circulation time and duration of surgery, ICU and postoperative hospitalization. Forty patients were randomly assigned to receive intervention and included in the analysis. The serum concentrations of CK-MB, LDH, CK, cTnI, α-HBDH and hs-CRP at T1∼4 were lower in the FDP group than in the NS group (P < 0.001). Compared with the NS group, the dosage of dopamine administered 1∼90min after cardiac resuscitation, the spontaneous cardiac rhythm recovery time and the incidence of ventricular fibrillation were lower in the FDP group (P < 0.001, P < 0.001 and P = 0.040, respectively). The values of ST- changes were increased more significantly in the NS group than in the FDP group （median [standard deviation] 1.3 [0.3] mm vs 0.7 [0.2] mm）(P < 0.001). Compared with the NS group, the time of recovery of ST-segment deviations was shorter in the FDP group（50.3 [12.3] min vs 34.6 [6.9] min） (P < 0.001). The fructose-1, 6-bisphosphate postconditioning could improve both myocardial ischaemia-reperfusion injury and the spontaneous cardiac rhythm recovery during cardiac valve surgery with extracorporeal circulation.

A clinical study to compare the effectiveness of dexmedetomidine in attenuating sympathoadrenal response induced by laryngoscopy and endotracheal intubation in smokers versus non-smokers

Background: The process of laryngoscopy and tracheal intubation is potent stressful stimuli that cause sympathetic activation, which is transient. Some of the modalities for attenuation of laryngoscopic and intubation response have been found to be less effective in smokers than in non-smokers. In view of this, the present study was performed to compare the effectiveness of dexmedetomidine in male smoker and non-smoker patients. Aims and Objectives: The aim of this study was to compare the effectiveness of dexmedetomidine in suppressing sympathoadrenal pressor response due to laryngoscopy and endotracheal intubation between smokers and non-smokers. Materials and Methods: This was a hospital-based non-randomized controlled study. Sixty patients were divided into two groups: 30 patients with no history of smoking (Group NS) and 30 patients with a smoking history (Group S). Both groups were received dexmedetomidine 0.75 mcg/kg over 10 min intravenous infusion. Hemodynamic parameters and Ramsay sedation score were measured at perioperative period. Results: Group S patients showed a significant rise in heart rate (HR), systolic blood pressure (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and rate pressure product (RRP) during the immediate post-intubation period, but Group NS showed a decrease in HR, SBP, DBP, MAP and RRP throughout the post-intubation period. Conclusion: Single dose of 0.75 mcg/kg IV dexmedetomidine given over a period of 10 min before the induction of anesthesia is completely effective in attenuating the hemodynamic responses associated with laryngoscopy and intubation in non-smokers, but it is not efficient in smokers.

Surgery Plays a Leading Role in Breast Cancer Treatment for Patients Aged ≥90 Years: A Large Retrospective Cohort Study

BackgroundThe population aged ≥90 years is increasing worldwide, yet nearly 50% of elderly breast cancer (BC) patients receive suboptimal treatments, resulting in high rates of BC-related mortality. We analyzed clinical and survival outcomes of nonagenarian BC patients to identify effective treatment strategies.MethodsThis single-institution retrospective cohort study analyzed patients aged ≥90 years diagnosed with stage I–III BC between 2007 and 2018. Patients were categorized into three treatment groups: traditional surgery (TS), performed according to local guidelines; current-standard surgery (CS), defined as breast surgery without axillary surgery (in concordance with 2016 Choosing Wisely guidelines) and/or cavity shaving; and non-surgical treatment (NS). Clinicopathological features were recorded and recurrence rates and survival outcomes were analyzed.ResultsWe collected data from 113 nonagenarians with a median age of 93 years (range 90–99). Among these patients, 43/113 (38.1%) underwent TS, 34/113 (30.1%) underwent CS, and 36/113 (31.9%) underwent NS. The overall recurrence rate among surgical patients was 10.4%, while the disease progression rate in the NS group was 22.2%. Overall survival was significantly longer in surgical patients compared with NS patients (p = 0.04). BC-related mortality was significantly higher in the NS group than in the TS and CS groups (25.0% vs. 0% vs. 7.1%, respectively; p = 0.01). There were no significant differences in overall survival and disease-free survival between the TS and CS groups (p = 0.6 and p = 0.8, respectively), although the TS group experienced a significantly higher overall postoperative complication rate (p < 0.001).ConclusionsIndividualized treatment planning is essential for nonagenarian BC patients. Surgery, whenever feasible, remains the treatment of choice, with CS emerging as the best option for the majority of patients.

Effects of Different Agents of the Lubrication of i-gel Airway on the Incidence of Postoperative Sore Throat: A Prospective Randomised Controlled Trial.

The aim of this study is to compare the effect of different lubricating agents used with the i-gel® laryngeal mask airwayon the incidence of postoperative sore throat. After obtaining institutional ethics approval, this prospective trial was conducted on 150 patients who were scheduled for minor surgical procedures. The study population was placed in three groups of 50 each, after randomization with computer-generated random numbers, based on the lubricant used (Group LJ: with lignocaine jelly as the lubricant, Group WJ: with water-based jelly as a lubricant, Group NS: with 0.9% normal saline as a lubricant). The time taken to secure the airway (from insertion to the first end-tidal carbon dioxide (ETCO2) tracing and five-point auscultation) and the number of attempts were noted. During extubation, blood staining was noted. In the postoperative period, sore throat was monitored with the numerical rating scale for the first 24 hours. Postoperative hoarseness of voice, cough and difficulty in swallowing were the other parameters noted. The results were entered in a standard spread sheet. Statistical analysis was done using JASP version 0.18.3.0 using the independent samples t-test and the Chi-square test for quantitative variables. All three groups were comparable in terms of demography (p > 0.05). The time taken to insertion, number of attempts and securing of the airway were also comparable amongst the three groups (p > 0.05). Blood staining during LMA removal was comparable between the three groups (p > 0.05). In the postoperative period, sore throat was comparable between the three groups (p > 0.05). The incidence of hoarseness of voice in the postoperative period however was more significant in Group LJ when compared to the other two (p < 0.05). Postoperative swallowing discomfort was also significantly higher in Group LJ than in the other two groups (p < 0.05). We conclude that lignocaine jelly, water-based jelly and normal saline used as lubricating agents on the i-gel airway did not show a difference in the incidence of postoperative sore throat. Lignocaine jelly was associated with a higher incidence of hoarseness of voice and swallowing discomfort when compared to the other lubricants.

Association of PLCE1 (rs7922612) and COL4A3 (rs375290088) Genetic Variants with the Risk of Nephrotic Syndrome in Egyptian Pediatric Patients.

Nephrotic syndrome is one of the most prevalent pediatric kidney illnesses seen in pediatric nephrology clinics. Steroid resistance in children with nephrotic syndrome is a primary cause of renal failure and is characterized by nephrotic range proteinuria that does not respond to conventional steroid therapy. The current work was intended to investigate the possible role of the Phospholipase C epsilon 1 (rs7922612) and collagen4 alpha 3 (rs375290088) single nucleotide polymorphisms as risk factors for developing nephrotic syndrome among Egyptian children. The study was conducted on 100 children with nephrotic syndrome and 100 age- and sex-matched healthy individuals. Geno typing was performed by two methods of polymerase chain reaction for the analysis of PLCE1 (rs7922612) and COL4A3 (rs375290088) variants. We observed a higher percentage of the heterozygous and homozygous variant genotypes of PLCE1 (rs7922612) SNP in NS patients in comparison with the controls (P < 0.001 for both). The frequencies of the PLCE1 (rs7922612) variant showed a statistically significant elevated risk of NS using several genetic models, including the dominant (OR = 9.12), recessive (OR = 2.31), and allelic (OR = 1.62) models (P < 0.001 for each). In addition, the PLCE1 (rs7922612) genotypes and alleles frequencies did not differ significantly between SRNS compared to SSNS cases. Furthermore, there was no significant difference regarding COL4A3 (rs375290088) polymorphism, neither between the NS and control groups nor between SDNS and SRNS. PLCE1 (rs7922612) is considered an independent risk factor for nephrotic syndrome in Egyptian pediatrics.COL4A3 (rs375290088) polymorphism is not correlated to Egyptian NS patients.

Chronic Electro-Acoustic Stimulation May Interfere With Electric Threshold Recovery After Cochlear Implantation in the Aged Guinea Pig.

Electro-acoustic stimulation (EAS) combines electric stimulation via a cochlear implant (CI) with residual low-frequency acoustic hearing, with benefits for music appreciation and speech perception in noise. However, many EAS CI users lose residual acoustic hearing, reducing this benefit. The main objectives of this study were to determine whether chronic EAS leads to more hearing loss compared with CI surgery alone in an aged guinea pig model, and to assess the relationship of any hearing loss to histology measures. Conversely, it is also important to understand factors impacting efficacy of electric stimulation. If one contributor to CI-induced hearing loss is damage to the auditory nerve, both acoustic and electric thresholds will be affected. Excitotoxicity from EAS may also affect electric thresholds, while electric stimulation is osteogenic and may increase electrode impedances. Hence, secondary objectives were to assess how electric thresholds are related to the amount of residual hearing loss after CI surgery, and how EAS affects electric thresholds and impedances over time. Two groups of guinea pigs, aged 9 to 21 months, were implanted with a CI in the left ear. Preoperatively, the animals had a range of hearing losses, as expected for an aged cohort. At 4 weeks after surgery, the EAS group (n = 5) received chronic EAS for 8 hours a day, 5 days a week, for 20 weeks via a tether system that allowed for free movement during stimulation. The nonstimulated group (NS; n = 6) received no EAS over the same timeframe. Auditory brainstem responses (ABRs) and electrically evoked ABRs (EABRs) were recorded at 3 to 4 week intervals to assess changes in acoustic and electric thresholds over time. At 24 weeks after surgery, cochlear tissue was harvested for histological evaluation, only analyzing animals without electrode extrusions (n = 4 per ear). Cochlear implantation led to an immediate worsening of ABR thresholds peaking between 3 and 5 weeks after surgery and then recovering and stabilizing by 5 and 8 weeks. Significantly greater ABR threshold shifts were seen in the implanted ears compared with contralateral, non-implanted control ears after surgery. After EAS and termination, no significant additional ABR threshold shifts were seen in the EAS group compared with the NS group. A surprising finding was that NS animals had significantly greater recovery in EABR thresholds over time, with decreases (improvements) of -51.8 ± 33.0 and -39.0 ± 37.3 c.u. at 12 and 24 weeks, respectively, compared with EAS animals with EABR threshold increases (worsening) of +1.0 ± 25.6 and 12.8 ± 44.3 c.u. at 12 and 24 weeks. Impedance changes over time did not differ significantly between groups. After exclusion of cases with electrode extrusion or significant trauma, no significant correlations were seen between ABR and EABR thresholds, or between ABR thresholds with histology measures of inner/outer hair cell counts, synaptic ribbon counts, stria vascularis capillary diameters, or spiral ganglion cell density. The findings do not indicate that EAS significantly disrupts acoustic hearing, although the small sample size limits this interpretation. No evidence of associations between hair cell, synaptic ribbon, spiral ganglion cell, or stria vascularis with hearing loss after cochlear implantation was seen when surgical trauma is minimized. In cases of major trauma, both acoustic thresholds and electric thresholds were elevated, which may explain why CI-only outcomes are often better when trauma and hearing loss are minimized. Surprisingly, chronic EAS (or electric stimulation alone) may negatively impact electric thresholds, possibly by prevention of recovery of the auditory nerve after CI surgery. More research is needed to confirm the potentially negative impact of chronic EAS on electric threshold recovery.

Effects of normal saline versus isotonic balanced crystalloid on acid–base balance and renal functions in patients undergoing intracranial tumor resection surgeries

BackgroundNormal saline (NS) infusion in large volumes may result in hyperchloremic metabolic acidosis and renal compromise. Balanced crystalloid (BC) with physiochemical composition akin to that of plasma may avoid these problems associated with NS. The present study aimed to evaluate effects of NS versus BC on acid–base balance and renal functions in patients undergoing intracranial tumor resection surgeries.MethodsFifty adult patients scheduled to undergo elective neurosurgery for intracranial tumor resection were randomized to receive either NS or BC as intraoperative or maintenance fluid. Metabolic and renal parameters were estimated prior to induction (baseline), at 1 h and 2 h after induction, at the end of surgery and 4 h after extubation. Serum neutrophil gelatinase-associated lipocalin (NGAL) was measured postoperatively. Brain relaxation score was assessed by the operating surgeon.ResultsBaseline values of variables were similar between the groups. At rest of the observed time-points, pH was significantly lower, while blood urea, serum creatinine, sodium, chloride, NGAL and plasma osmolality were significantly higher in the NS group as compared to the BC group. Brain relaxation score, serum bicarbonate and base excess were comparable between the two groups.ConclusionUse of balanced crystalloid (plasmalyte) resulted in better metabolic and renal profile as compared to normal saline in neurosurgical patients.

P-167 The sperm parameters in doubling oocytes by the 1st polar body transfer technique: does it matter?

Abstract Study question Does sperm parameters affect the effectiveness of the 1st polar body (PB) transfer in oocytes and embryo doubling? Summary answer Certain sperm conditions affect the transfer technique efficiency. What is known already Previous studies have shown the effectiveness of the 1st polar body (PB) transfer. The technique allows for the modification of donor oocytes to increase the number of cells suitable for fertilization and at the same time preserve the genetic relatedness to the patient. We established that the effectiveness depends on the morphology of the 1stPB. We also showed that the yield of high-quality blastocysts does not depend on whether fresh or thawed donor oocytes are used. But it is also important to understand whether sperm parameters have a significant effect on the performance of the technique. Study design, size, duration The study was performed in the Medical Center IGR from December 2017 to December 2023 and involved 93 patients (mean age 39.7±5.4 years) who underwent the 1st PB transfer and had indicated sperm parameters used for fertilization, including: normozoospermia (NS, n = 43), asthenozoospermia (AS, n = 24), asthenoteratozoospermia (ATS, n = 20), oligozoospermia (OS, n = 5), cryptozoospermia (CS, n = 1). We evaluated the pronuclear scoring, number of embryos on the 3rd and the 5th post-fertilization day, euploidy according to sperm conditions. Participants/materials, setting, methods We used donor oocytes, patients’ oocytes and their 1stPBs obtained from 93 women and their partners sperm with defined parameters in accordance with WHO norms for 2021. The procedure of donor oocyte enucleation and the 1stPBs transfers was carried out using Nikon Ti Eclipse(Japan) inverted microscope, Saturn 3 laser console(UK). Preimplantation genetic testing for aneuploidy was performed using trophectoderm biopsy. Samples were diagnosed using Ion S5(USA). Statistical analysis was carried out using Chi-square test. Main results and the role of chance The total number of donor oocytes modified by the 1stPB of patient’ oocytes was 364, which were distributed as follows by sperm status: NS - 159 oocytes, AS - 103 oocytes, ATS - 77 oocytes, OS - 19 oocytes, and CS - 6 oocytes. The mean age of the female patients according to the groups was similar (39.6±4.9, 39.8±6.2, 40.0±3.8, 37.8±6.1,40, respectively). The number of 2PN pattern during pronuclear scoring was distributed among groups (NS:AS:ATS:OS:CS) with the following percentages 69.2:65.1:62.3:73.7:66.7, respectively. Among the developing embryos on the 3rdday the distribution was 46.6:46.5:36.4:57.9, respectively. No viable embryos were formed in the CS group, so the group was not included in further calculations. Statistically significant difference (SSD) was not found between the groups on the above-mentioned stages of development (p0.05). On the 5thday the number of developing embryos (percents) was distributed as follows: 23.3:28.2:11.7:31.6 for NS:AS:ATS:OS, respectively. It is worth noting that SSD was found between NS and ATS, OS and ATS groups (p &amp;lt; 0.05) and AS and ATS groups (p &amp;lt; 0.001). Percentage of euploid embryos relative to the number of examined blastocysts from groups NS:AS:ATS was 30.8:23.1:22.2, respectively, SSD wasn’t found between the groups(p &amp;gt; 0.05). Limitations, reasons for caution To increase performance of the 1st PB transfer technique it is also worth considering such parameters as sperm DNA fragmentation and level of sperm oxidative stress, which reflect the chromatin state of the male gamete. Wider implications of the findings The study showed that among patients with asthenoteratozoospermia, the yield of viable embryos was significantly lower compared to the other sperm conditions studied. This fact must be taken into account when predicting the result of using the 1st PB transfer technique. Trial registration number N/A

Skoochies and its component substances induced testicular damage and impaired sperm function via increased generation of reactive oxygen species and impairment of the glutathione system in rats

ObjectiveTo study examined the effect of skoochies, an illicit cocktail drink, on testicular and sperm function in male rats. DesignTwenty-five adult male Wistar rats were assigned randomly into five groups (n = 5), as follows: Normal saline (NS group), skoochies (SK group), cannabis sativa (CS group), codeine (CO group), and tramadol (TM group). The cocktail (skoochies) used for this study was formulated using the following composition: codeine (5mg/kg), tramadol (20mg/kg) and cannabis extract (2mg/kg). These doses are as previously reported. Administration was done once daily for twenty-eight (28) days. ResultsSkoochies increased reactive oxygen species generation and impaired the antioxidant system resulting in inflammation that eventually damage the testicular tissue. Skoochies causes oxido-inflammatory injury to the testicular tissues resulting in impaired testicular functions. This was evident by the distorted cytoarchitecture, reduced sperm count, motility and impaired testicular DNA integrity. ConclusionThus, our results infer that Skoochies induced the impairment of testicular and sperm function through the increased generation of reactive oxygen species and impairment of the glutathione system.

Rat nasal mucosa-derived ectodermal mesenchymal stem cells: A new therapeutic option for chronic rhinosinusitis.

To investigate the effect of nasal mucosa-derived ectodermal mesenchymal stem cells (NM-EMSCs) on the inflammatory state of rats with chronic rhinosinusitis (CRS) and the underlying therapeutic mechanism. NM-EMSCs were isolated and extracted to construct a rat model of CRS. Fifteen Sprague‒Dawley (SD) rats were randomly divided into threegroups: CK + NS group rats were injected locally with saline in the nasal mucosa; CRS + NS group rats were injected locally with saline in the nasal mucosa; and CRS + EMSCs group rats were injected locally with NM-EMSCs in the nasal mucosa. One rat from the CRS + EMSCs group was randomly euthanized at 2, 4, and 6 days after injection, and the nasal mucosa tissues were collected for HE staining, Masson's trichrome staining, and periodic acid-Schiffstaining. NM-EMSCs specifically expressing CD73, CD105, and CD90 were successfully isolated from the nasal mucosa of rats and were able to differentiate into adipocytes, osteoblasts, and chondrocytes. After saline and NM-EMSC injection, compared with those in the blank control CK + NS group, the nasal mucosa in the CRS + NSand CRS + EMSC groups exhibited obvious thickening, a large amount of inflammatory cell infiltration, and increased collagen and mucin distribution. Four days post-NM-EMSC injection, the thickening of the nasal mucosa in the CRS group was gradually alleviated, the inflammatory cell infiltration gradually decreased, and the distribution of collagen and mucin and the collagen-positive area gradually decreased. Moreover, only a small number of inflammatory cells were visible, and the distribution of mucins was limited to 6 days post-NM-EMSC injection. NM-EMSCs effectively attenuated inflammation in the nasal mucosa of CRS model rats.

HDAC6 modulates the cognitive behavioral function and hippocampal tissue pathological changes of APP/PS1 transgenic mice through HSP90-HSF1 pathway.

The aim of this study was to investigate histone deacetylase 6 (HDAC6) modifies the heat shock protein 90 (HSP90) and heat shock transcription factor 1 (HSF1) affect the levels of pathological markers such as Aβ oligomers (Aβo) and Tau phosphorylation (p-Tau) in APP/PS1 double transgenic mice hippocampal tissues or HT22 neurons as well as the changes in cognitive behavioral functions of mice. (1) APP/PS1 transgenic mice (6 months old, 25 ~ 30g) were randomly assigned to 5 experimental groups, C57BL/6J mice (6 months old, 25 ~ 30g) were used as 4 control groups, with 8 mice in each group. All mice underwent intracerebroventricular (i.c.v.) cannulation, and the experimental groups were administered with normal saline (APP + NS group), HDAC6 agonist tubastatin A hydrochloride (TSA) (APP + TSA group) or HDAC6 agonist theophylline (Theo) (APP + Theo group), HSP90 inhibitor Ganetespib (Gane) (APP + Gane group), or a combination of pre-injected Gane by TSA (APP + Gane + TSA group); the control group received i.c.v. injections of Gane (Gane group), TSA (TSA group), Theo (Theo group) or NS (NS group), respectively. (2) Mouse hippocampal neurons HT22 were randomly divided into a control group (Control) and an Aβ1-42 intervention group (Aβ). Within the Aβ group, further divisions were made for knockdown HSP90 (Aβ + siHSP90 group), overexpression HSP90 (Aβ + OE-HSP90 group), knockdown HSF1(Aβ + siHSF1 group) and knockdown HSF1 followed by overexpression HSP90 (Aβ + siHSF1 + OE-HSP90 group), resulting in a total of 6 groups. Morris water maze test was used to evaluate the cognitive behavior of the mice. Western blot and immunohistochemistry or immunofluorescence were performed to detect the levels of HDAC6, HSP90, HSF1, Aβ1-42, Tau protein, and p-Tau in the hippocampal tissue or HT22 cells. qRT-PCR was used to measure the levels of hdac6, hsp90, and hsf1 mRNA in the hippocampus or nerve cells. (1) The levels of HDAC6, Aβ1-42 and p-Tau were elevated, while HSP90 and HSF1 were decreased in the hippocampal tissue of APP/PS1 transgenic mice (all P < 0.01). Inhibiting HDAC6 upregulated the expressions of HSP90 and HSF1 in the hippocampal tissue of APP/PS1 mice, while decreasing the levels of Aβ1-42 and p-Tau as well as improving the spatial cognitive behavior in mice (P < 0.05 or P < 0.01). The opposite effects were observed upon HDAC6 activation. However, inhibiting HSP90 reduced the expression of HSF1 (P < 0.01) and increased the levels of Aβ1-42 and p-Tau (P < 0.05 or P < 0.01) but did not significantly affect the expression of HDAC6 (P > 0.05). No significant changes were observed in the aforementioned indicators in the 4 control groups (P > 0.05). (2) In the Aβ1-42 intervention group, HDAC6 and Aβ1-42, p-Tau expression levels were elevated, while HSP90 and HSF1 expressions were all decreased, and cell viability was reduced (P < 0.05 or P < 0.01). Overexpression of HSP90 upregulated HSF1 expression, decreased the levels of Aβ1-42 and p-Tau, and increased cell viability (P < 0.05 or P < 0.01). Knocking down HSP90 had the opposite effect; and knocking down HSF1 increased the levels of Aβ1-42 and p-Tau and decreased cells viability (all P < 0.01), but did not result in significant changes in the expression levels of HSP90 (P > 0.05). Inhibiting HDAC6 can upregulate the expressions of HSP90 and HSF1 but reduce the levels of Aβ1-42 and p-Tau in the hippocampus of APP/PS1 mice and improvement of cognitive behavioral function in mice; Overexpression of HSP90 can increase HSF1 but decrease Aβ1-42 and p-Tau levels in the hippocampal neurons and increase cell activity. It is suggested that HDAC6 may affect the formation of Aβ oligomers and the changes in Tau protein phosphorylation levels in the hippocampus of AD transgenic mouse as well as the alterations in cognitive behavioral functions by regulating the HSP90-HSF1 pathway.

Comparison of long-term survival of neoadjuvant therapy plus surgery versus upfront surgery and the role of adjuvant therapy for T1b-2N0-1 esophageal cancer: a population study of the SEER database and Chinese cohort.

For stage T1b-2N0-1 esophageal cancer, the impact of neoadjuvant therapy plus surgery (NS), surgery alone (SA), and surgery plus adjuvant therapy (ST) on cancer-specific survival (CSS) and overall survival (OS) is uncertain. Stage T1b-2N0-1 esophageal cancer patients from the SEER database and two Chinese cancer centers were included in this study. The Kaplan-Meier method was used to plot survival curves, which were compared using the log-rank test. Propensity score matching was used to equalize differences between the groups. Cox proportional hazards regression models were used to analyze prognostic factors. A nomogram for OS was developed after screening the variables using the Cox proportional hazards regression model and the least absolute shrinkage and selection operator. The performance of the nomogram was assessed by the Harrell concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic curve, calibration plots, and decision curve analysis. After propensity score matching analysis, the 3-year CSS and OS rates in the NS group compared to the SA group were 80.3% versus 62.1% (P=0.016) and 75.8% versus 55.5% (P=0.006), the 3-year CSS and OS rates in the NS group compared to the ST group were 71.3% versus 68.3% (P=0.560) and 69.8% versus 62.9% (P=0.330), the 3-year CSS and OS rates in the SA group compared to the ST group were 54.6% versus 66.7% (P=0.220) and 50.2% versus 57.9% (P=0.290), respectively. The predictive nomogram for OS in T1b-2N0-1 patients ultimately incorporated five clinicopathological variables: T stage, N stage, age, examined lymph nodes , and therapy modality. The nomogram C-index for predicting OS was 0.648, 0.663, and 0.666 in the training group, external validation group-1, and external validation group-2, respectively. The 1-, 3-, and 5-year predicted AUC values of the OS prediction model were 0.659, 0.639, and 0.612 for the training group, and 0.786, 0.758, and 0.692 for validation group-1, and 0.805, 0.760, and 0.693 for validation group-2, respectively. For patients with stage T1b-2N0-1 esophageal cancer, neoadjuvant therapy significantly improves prognosis compared to surgery alone, those presenting with positive lymph nodes after upfront surgery can achieve survival benefits from adjuvant therapy.

Comparative analysis of intestinal microbiota composition between free-ranged captive yak populations in Nimu County.

The intestinal microbiota assumes a pivotal role in modulating host metabolism, immune responses, overall health, and additional physiological dimensions. The structural and functional characteristics of the intestinal microbiota may cause alterations within the host's body to a certain extent. The composition of the gut microbiota is associated with environmental factors, dietary habits, and other pertinent conditions. The investigation into the gut microbiota of yaks remained relatively underexplored. An examination of yak gut microbiota holds promise in elucidating the complex relationship between microbial communities and the adaptive responses of the host to its environment. In this study, yak were selected from two distinct environmental conditions: those raised in sheds (NS, n=6) and grazed in Nimu County (NF, n=6). Fecal samples were collected from the yaks and subsequently processed for analysis through 16S rDNA and ITS sequencing methodologies. The results revealed that different feeding styles result in significant differences in the Alpha diversity of fungi in the gut of yaks, while the gut microbiota of captive yaks was relatively conserved. In addition, significant differences appeared in the abundance of microorganisms in different taxa, phylum Verrucomicrobiota was significantly enriched in group NF while Firmicutes was higher in group NS. At the genus level, Akkermansia, Paenibacillus, Roseburia, Dorea, UCG_012, Anaerovorax and Marvinbryantia were enriched in group NF while Desemzia, Olsenella, Kocuria, Ornithinimicrobium and Parvibacter were higher in group NS (P<0.05 or P<0.01). There was a significant difference in the function of gut microbiota between the two groups. The observed variations are likely influenced by differences in feeding methods and environmental conditions both inside and outside the pen. The findings of this investigation offer prospective insights into enhancing the yak breeding and expansion of the yak industry.

A nomogram prediction of gingival recession in mandibular incisors of orthodontic-orthognathic treated skeletal class III malocclusion with or without PAOO: A retrospective cohort study

BackgroundTo assess the alterations in gingival thickness and the occurrence gingival recession subsequent to orthodontic-orthognathic treatment of mandibular incisors in skeletal Class III and identify risk factors associated with gingival recession. MethodsIn this retrospective cohort study, we enrolled 33 patients exhibiting skeletal Class III malocclusion, totaling 131 mandibular incisors, who were undergoing orthodontic- orthognathic treatment that did not involve extraction of mandibular teeth. The subjects were categorized into surgery group (S; n = 17; ANB = −5.55 ± 3.26; IOFTN = 4.60 ± 0.51, scores ranging: 4.3–5.3) and non-surgery group (NS; n = 16; ANB = −3.00 ± 4.08; IOFTN = 4.63 ± 0.50, scores ranging: 4.3–5.4), based on if they had history of Periodontally Accelerated Osteogenic Orthodontics surgery (S) or not (NS). Patients in S group received orthognathic surgery about 1–1.5 years after Periodontally Accelerated Osteogenic Orthodontics surgery. Alterations in gingival thickness, gingival recession, and keratinized gingival width were compared before and after orthodontic-orthognathic treatment. Logistic regression analysis was used to construct a gingival recession prediction model and draw nomograms. ResultsAfter orthodontic-orthognathic treatment, the gingival thickness and keratinized gingival width in NS group decreased by 0.15 ± 0.21 mm and 0.74 ± 0.91 mm, whereas those in the S group increased by 0.32 ± 0.28 mm and 2.09 ± 1.51 mm (P < 0.05). After orthodontic-orthognathic, the percentage of gingival recession increased by 47.62 % in NS group, which was 14.77 times that of S group (P < 0.05). Multivariate regression analysis indicated that skeletal Class III patients with a gingival thickness below 0.72 mm, an alveolar bone height exceeding 2.36 mm, and an alveolar bone thickness under 0.45 mm might be at elevated risk for developing gingival recession following orthodontic - orthognathic therapy. ConclusionsDrawing on the findings of our investigation, we concluded the risk of gingival recession of mandibular anterior teeth increased after orthodontic-orthognathic treatment in skeletal Class III, whereas Periodontally Accelerated Osteogenic Orthodontics surgery could significantly improve the periodontal phenotype and prevent gingival recession.

Analgesic Effect of SKI306X on Chronic Postischemic Pain and Spinal Nerve Ligation-Induced Neuropathic Pain in Mice.

Neuropathic pain (NP) results from lesions or diseases affecting the peripheral or central somatosensory system. However, there are currently no drugs that are particularly effective in treating this condition. SKI306X is a blend of purified extracts of three oriental herbs (Clematis mandshurica, Trichosanthes kirilowii, and Prunella vulgaris) commonly used to treat osteoarthritis for their chondroprotective effects. Chronic postischemic pain (CPIP) and spinal nerve ligation (SNL) models were created by binding the upper left ankle of mice with an O-ring for 3 h and ligating the L5 spinal nerve, respectively. Mice with allodynia were injected intraperitoneally with 0.9% normal saline (NS group) or different doses (25, 50, or 100 mg/kg) of SKI306X (SKI groups). We assessed allodynia using von Frey filaments before injection and 30, 60, 90, 120, 180, and 240 min and 24 h after injection to confirm the antiallodynic effect of SKI306X. We also measured glial fibrillary acidic protein (GFAP) levels in the spinal cord and dorsal root ganglia to confirm the change of SKI306X administration. Both models exhibited significant mechanical allodynia. The intraperitoneal injection of SKI306X significantly increased the paw withdrawal threshold in a dose-dependent manner, as the paw withdrawal threshold was significantly increased after SKI306X administration compared with at baseline or after NS administration. GFAP levels in the SKI group decreased significantly (p < 0.05). Intraperitoneal administration of SKI306X dose-dependently attenuated mechanical allodynia and decreased GFAP levels, suggesting that GFAP is involved in the antiallodynic effect of SKI306X in mice with CPIP and SNL-induced NP.

Use of 3D-CT-derived psoas major muscle volume in defining sarcopenia in colorectal cancer

BackgroundSarcopenia is characterized by reduced skeletal muscle volume and is a condition that is prevalent among elderly patients and associated with poor prognosis as a comorbidity in malignancies. Given the aging population over 80 years old in Japan, an understanding of malignancies, including colorectal cancer (CRC), complicated by sarcopenia is increasingly important. Therefore, the focus of this study is on a novel and practical diagnostic approach of assessment of psoas major muscle volume (PV) using 3-dimensional computed tomography (3D-CT) in diagnosis of sarcopenia in patients with CRC.MethodsThe subjects were 150 patients aged ≥ 80 years with CRC who underwent primary tumor resection at Juntendo University Hospital between 2004 and 2017. 3D-CT measurement of PV and conventional CT measurement of the psoas major muscle cross-sectional area (PA) were used to identify sarcopenia (group S) and non-sarcopenia (group nS) cases. Clinicopathological characteristics, operative results, postoperative complications, and prognosis were compared between these groups.ResultsThe S:nS ratios were 15:135 for the PV method and 52:98 for the PA method. There was a strong positive correlation (r = 0.66, p < 0.01) between PVI (psoas major muscle volume index) and PAI (psoas major muscle cross-sectional area index), which were calculated by dividing PV or PA by the square of height. Surgical results and postoperative complications did not differ significantly in the S and nS groups defined using each method. Overall survival was worse in group S compared to group nS identified by PV (p < 0.01), but not significantly different in groups S and nS identified by PA (p = 0.77). A Cox proportional hazards model for OS identified group S by PV as an independent predictor of a poor prognosis (p < 0.05), whereas group S by PA was not a predictor of prognosis (p = 0.60).ConclusionsThe PV method for identifying sarcopenia in elderly patients with CRC is more practical and sensitive for prediction of a poor prognosis compared to the conventional method.

The EC50 of propofol with different doses of dexmedetomidine during gastrointestinal endoscopy: A double-blind, placebo-controlled trial.

The goal of this study was to evaluate the dose-response relationship between dexmedetomidine and propofol in sedating patients and to determine the optimal dosage of dexmedetomidine during gastrointestinal endoscopy. One hundred fifty patients were divided into 5 groups, each receiving a loading dose of dexmedetomidine (0.4, 0.6, 0.8, 1.0 µg/kg) or saline, with propofol for sedation. The median effective concentration (EC50) of propofol was calculated using the modified Dixon up-and-down approach. Adverse effects, vital signs, procedure, and recovery times were recorded. The EC50 of propofol in groups NS, D0.4, D0.6, D0.8, and D1.0 were 3.02, 2.44, 1.97, 1.85, and 1.83 µg/mL, respectively. Heart rate in the dexmedetomidine groups decreased more than the NS group (P < .001). The mean arterial pressure (MAP) in the NS group experienced a decline compared to groups D0.8 and D1.0 when the plasma concentration and effect-site concentration reached equilibrium. Additionally, the respiratory rate was found to be lower in groups NS, D0.4, D0.6, and D0.8 (P < .05). Recovery time in groups D0.8 and D1.0 was longer than the NS group (P < .05). Bruggemann comfort scales score was higher in group D1.0 (P < .05). No significant difference was found in the incidences of hypotension and bradycardia, and the dose of ephedrine and atropine. Respiratory depression was significantly reduced in groups D0.8 and D1.0 compared to the NS group. A single dose of 0.6 to 0.8 µg/kg of dexmedetomidine should be recommended in combination with propofol for gastrointestinal endoscopy. And the EC50 of propofol is 1.97 to 1.85 µg/mL.

Association between circulatory microRNA-218 expression, serum PCSK9 levels, inflammatory markers, and monocyte subsets in coronary artery disease patients: impact of statin therapy

BackgroundProprotein convertase subtilisin/kexin type-9 (PCSK9), an enzyme produced mainly by hepatocytes and breaks low-density lipoprotein receptor (LDL-R), inflammatory markers [toll like receptor 4 (TLR4), high mobility group box 1 (HMGB1), tumor necrosis factor alpha (TNFα), c-reactive protein (CRP)], and monocyte subtypes are associated with coronary artery disease (CAD) pathogenesis. The circulating microRNA-218 (miR-218) can relieve CAD through the suppression of HMGB1 in monocyte-derived inflammatory cytokines. Herein, we explored the association between circulatory miR-218 expression and serum levels of PCSK9, inflammatory markers, and monocyte subtypes in statin and non-statin CAD patients. This study involved 91 healthy (control) and 91 stable CAD participants which were subdivided into no-statin (NS, n = 25), low-statin (LS, n = 25), and high-statin (HS, n = 41) groups. low-density lipoprotein cholesterol (LDL-C) and CRP serum levels were calorimetrically determined. Serum levels of PCSK9, TLR4, HMGB1, and TNFα were detected by ELISA, while monocyte subsets [classical (CM), intermediate (IM), non-classical (NC)] were calculated by flow cytometry. Circulatory miR-218 expression was detected by real-time PCR.ResultsThe CAD group had significantly lower miR-218 expression and significantly higher levels of PCSK9, inflammatory markers (HMGB1, CRP, TLR4, and TNFα), and IM% than the control group. Among CAD patients, LS and HS groups had significantly lower miR-218 expression, LDL-C levels, and inflammatory markers and significantly higher levels of PCSK9 than the NS group. The HS group exhibited the lowest miR-218 expression and inflammatory markers and the highest PCSK9 levels. However, there were no significant changes in IM% among statin and non-statin groups. In the three CAD groups, miR-218 showed a significantly negative correlation with PCSK9 and inflammatory markers (HMGB1, CRP, TLR4, and TNFα), while this expression exhibited a significantly negative correlation with CM%, IM%, and NCM% only in the NS group. Results of multivariable linear regression indicated a correlation between miR-218 and five independent variables (PCSK9, HMGB1, CRP, TLR4, and TNFα) in the total statin (LS + HS) group, and eight independent variables (PCSK9, HMGB1, CRP, TLR4, and TNFα, CM%, IM%, NCM%) in the NS group. Provided that all other independent variables are constant, miR-218 expression was significantly correlated to CRP (Beta = 0.234) and PCSK9 (Beta = − 0.875) in the total statin group; TLR4 (Beta = − 0.554) in the LS group; HMGB1 (Beta = − 0.507) in the HS group; and CRP (Beta = − 0.745) in the NS group.ConclusionsStatin-treated CAD patients have a unique negative correlation between miR-218 and PCSK9, HMGB1, and TLR4, and subsequently with CAD progress. Therefore, it could be recommended to combine activators of miR-218 and inhibitors of PCSK9, HMGB1, and TLR4 with statin to efficiently treat CAD.

Novel Active Proteins for Sepsis Prognosis Revealed through ScRNA-seq and Quantitative Proteomics.

To uncover critical active proteins influencing sepsis outcomes through multi-omics analysis. This study collected peripheral blood from sepsis patients (NS = 26, SV = 27) and controls (Con = 16). Cellular heterogeneity was assessed using scRNA-seq. Cellular populations were identified through clustering and annotation. GSVA was employed to detect pathway alterations in sepsis, while the Viper algorithm estimated protein activity at the single-cell level. Signaling networks were investigated via cell-cell communication analysis. Differentially expressed proteins were identified by DIA proteomics and confirmed through integrated analysis. Prognostic value was evaluated via meta and survival analyses. scRNA-seq of 22,673 features within 34,228 cells identified five cellular clusters and 253 active proteins via Viper, validated by DIA (FC > 2, P < 0.05). Four proteins (SPI1, MEF2A, CBX3, UBTF) with prognostic significance were discovered and mapped onto the cellular landscape. GSVA enrichment analysis revealed that the NS group exhibited significant alterations in pathways related to cellular apoptosis and inflammatory responses, while the SV group displayed increased activity in DNA repair and cellular survival pathways. The study's findings advance the understanding of sepsis pathophysiology by linking differentially active proteins to patient prognosis, paving the way for targeted therapeutic strategies.

#1749 Influence of high saline diet on myocardial remodeling, microRNA-21i and NFkB expression in myocardium

Abstract Background and Aims There is now increased interest in the study of morpho-functional myocardial changes in excess NaCl consumption, which develop independently of AD dynamics. Myocardial remodeling may involve microRNAs that modulate gene expression at the post-transcription level. However, their role in this process has not been fully explored. The purpose of the study is to assess the levels of expression of the nucleic transcription factor kV (NFkB), microRNA-21 and structural changes in the myocardium at long-term consumption of Wistar diet with high (8%) table salt content. Method Male Wistar rats (body mass 280.5 42.7 g) were divided into two groups of 10 animals. For 4 months, the control rats (NaCl) received a standard diet (0.34% NaCl), and the animals of the other group received a high salt diet (8% NaCl) (HS). Laboratory food varied only in NaCl content. 4 months later in rats systolic AD was measured, myocardial mass index (IMM) was evaluated, myocardial histology was performed (paraffin coloration - hematoxylin-eosin, Masson), relative expression levels of my RNA-determined 21 and NFkB in the myocardium, sodium content in the urine and blood serum. Statistical analysis used the t-Student criterion and the Mann-Whitney test. The differences were considered significant at p &amp;lt; 0.05. Results Excess NaCl (8%) in the diet had no effect on animal body weight (370.5 32.0 g in HS group, 393.0 21.4 g in NS group, p &amp;gt; 0.05) and systolic AD. In the HS-Group, the average AD was 134.5 8.9 mm old, and in the NS-Group - 134.8 5.2 mm old. (p &amp;gt; 0.05). However, HS-group IMM rats were 25% higher than NS-group rats (p &amp;lt; 0.05). The daily water consumption in the HS group was on average 33% higher than in the control, the daily diuresis also increased (10.5 5.7 ml against 5.7 2.9 ml in the NS-group, p &amp;lt; 0.001) and the sodium content in the urine (81.25.72 mmol/l against 161.18.57 mmol in the NS-01). There was no difference in the sodium content of the blood serum. Hypertrophy of cardiomyocytes, protein dystrophy, and increased wall thickness of arterial vessels (NS-20,42 3,53, HS-27,61 4,93, µm were identified in the HS-group; p &amp;lt; 0.01). The area of perivascular fibrosis in rats of the HS group (14876 ± 3803.7 µm2) was almost 1.8 times higher than that in the NS group (8426.0 ± 3012.2 µm2, p &amp;lt; 0.03). The thickness of cardiomyocytes (NS-12.97 1.53, HS-20.28 1.90 µm, p &amp;lt; 0.001) also increased in rats on the HS diet. In animals of the HS group, the relative expression levels of NFkB (more than 2 times) and microRNA-21 (almost 6 times) in the myocardium increased compared to the NS group. It can be assumed that the adverse effect on the cardiovascular system of high-salt diets is partially realized through NFκB-associated signaling pathways and the activation of microRNA-21. Conclusion Long-term use of a high-salt diet in Wistar rats results in myocardial remodeling unrelated to changes in AD levels. In this case, the high salt intake effects on the myocardium may be mediated by an increase in NFkBy and microRNA-21 expression levels.