Saline Group Research Articles

The Preventive Effect of Preoperative and Postoperative Selenium on the Medication-Related Osteonecrosis of the Jaw: An Animal Study in Rats

BackgroundMedication-related osteonecrosis of the jaw (MRONJ) is a condition that can occur primarily in patients undergoing or have previously undergone therapy with bisphosphonates, particularly in the presence of risk factors, such as tooth extraction (TE). PurposeThis study aimed to evaluate the effect of selenium (SEL) administration on the prevention of osteonecrosis of the jaw in an MRONJ animal model. Study design, setting, and sampleThis study was a longitudinal, in vivo animal study using a TE model in a sample of 48 Wistar rats. Predictor variableThe predictor variables were SEL exposure, timing of SEL exposure, and zoledronic acid (ZOL) exposure. The animals were randomly assigned to four treatment groups (n = 12 per group): 1) saline (negative control), 2) ZOL (positive control), 3) SELpreop+ZOL, and 4) ZOL+SELpostop. The animals were administered saline (negative control) or ZOL (0.06 mg/kg, intraperitoneally) once a week for 5 weeks. All rats underwent TE at the end of the 5th week. Selenium (0.3 mg/kg, intraperitoneally) was administered once daily for 15 days to the SELpreop+ZOL group before TE and to the ZOL+SELpostop group after TE. All animals were sacrificed at the end of the 9th week. Main outcome variablesThe primary outcome variables were new bone area, necrotic bone area, fibrosis, new connective tissue formation, and inflammatory cell infiltration in the histopathological analysis, as well as angiogenesis and percentage of osteoblasts in the immunohistochemical analysis. CovariatesThere was none. AnalysesStatistical analysis was conducted using the Kruskal–Wallis test, followed by post-hoc Bonferroni-corrected Mann–Whitney U tests, with a significance level of p ≤ 0.05. ResultsThe new bone area was higher in the ZOL+SELpostop group (3.00 score) than in the saline group (0.58 ± 1.08 score, p < 0.001) and the ZOL group (0.82 ± 1.40 score, p = 0.001), while the necrotic bone area was lower in the ZOL+SELpostop group (0.08 ± 0.29 score) than in the ZOL group (2.82 ± 0.40 score, p < 0.001) and the SELpreop+ZOL group (1.67 ± 0.89 score, p = 0.007). The percentage of osteoblasts was higher in the ZOL+SELpostop group (18.73%) than in the saline group (8.63%, p < 0.001) and the ZOL group (0.07%, p < 0.001), and it was also higher in the SELpreop+ZOL group (18.49%) than in the ZOL group (0.07%, p < 0.001). ConclusionIn conclusion SEL prevents MRONJ, with postoperative SEL demonstrating greater prevention effects. Given these findings, we hypothesize that SEL exposure may decrease the risk of MRONJ.

Minimum effective dose of intrathecal hyperbaric bupivacaine for cesarean section with and without prophylactic norepinephrine infusion: Randomized triple-blinded trial.

Vasopressor usage can affect the rostral spread of intrathecal drug and, hence, its requirement during cesarean delivery. Although a decreased spread is evidenced with phenylephrine, there is no data for norepinephrine usage. The present study aimed to evaluate the minimum effective dose of intrathecal hyperbaric bupivacaine for cesarean section with and without prophylactic norepinephrine infusion. Patients scheduled for elective cesarean section under combined spinal-epidural block were randomized to receive intravenous infusion of norepinephrine (0.05 μg/kg/min) or normal saline (placebo), initiated immediately after intrathecal injection. Postspinal hypotension in either group (systolic arterial pressure ≤0.8 baseline) was treated with norepinephrine 4 μg rescue. Dose of intrathecal hyperbaric bupivacaine (0.5%) was decided for individual patients using up-and-down sequential allocation method. Primary outcome measure was the minimum effective dose of intrathecal hyperbaric bupivacaine (0.5%) defined as ED50, while secondary observations included spinal block characteristics and neonatal outcomes. Demographic parameters were statistically similar between both groups (P > 0.05). ED50 of intrathecal hyperbaric bupivacaine was 7.8 mg (95% confidence interval [CI]: 6.7-8.8) and 7.4 mg (95% CI: 6.1-8.7) for normal saline and norepinephrine group respectively (P = 0.810). Block characteristics were similar between both groups as was neonatal APGAR score, but umbilical artery base excess was greater for norepinephrine versus normal saline group (-4.4 ± 3.6 vs. -6.5 ± 2.4, P = 0.038). Use of prophylactic norepinephrine (0.05 μg/kg/min) during cesarean delivery does not require adjustment of intrathecal hyperbaric bupivacaine.

Comparing Treatment with Nebulized 3% Hypertonic Saline Versus Nebulized 0.9% Saline In Patients With Acute Bronchiolitis: A Double-Blind Randomized Controlled Trial

Objective: To establish the therapeutic role of nebulized hypertonic saline solution in the management of acute bronchiolitis in terms of primary and secondary outcomes. Methods: This randomized control trial was conducted in the Pediatric department of Holy Family Hospital, Rawalpindi for 8 months from September 2021 to April 2022 after ethical approval. A total of 65 cases of acute bronchiolitis were enrolled who were divided into two groups. The intervention group was nebulized with 3 ml of 3% hypertonic saline 6 hourly while the control group was nebulized with 0.9% saline 6 hourly during hospital stay in addition to the standard treatment. Children in both groups were monitored in terms of clinical severity score, feeding, hydration status, length of hospital stay, duration of oxygen supplementation, development of any adverse effect, and outcome (length of hospital stay and clinical severity score) was observed. Data was collected on a predesigned proforma, and SPSS version 21 was used to analyze the data. Results: Two groups were comparable for age, gender, and baseline characteristics including clinical severity score. Length of hospital stay was significantly less in the hypertonic saline group 75.53 ±43 .87 versus 45.92 ± 12.19 (p-value 0.000). Similarly, in patients requiring oxygen, treatment with hypertonic saline significantly reduced the duration of nebulization, 27.21 ±26.20 versus 10.67± 7.91 (p-value 0.03). However clinical severity score between the two groups was not different, 5.42 ± 2.88 in the saline group and 4.50 ± 2.88 p value 0.921. Conclusion: Nebulization with hypertonic saline reduces oxygen requirement and benefits in reducing the length of hospital stay. Keywords: Bronchiolitis, Hypertonic saline (HS), Normal saline (NS)

Effect of a single small volume fluid bolus with balanced or un-balanced fluids on chloride and acid-base status: a prospective randomized pilot study (the FLURES-trial).

To compare the short-term effects on acid base, electrolyte status and urine output of a single fluid bolus of saline to that of the balanced solution Plasmalyte® in critically ill patients. Prospective, randomized, controlled trial. Adult patients (≥ 18years) admitted to the ICU receiving a fluid bolus were randomized to receive 1 L of saline (NaCl 0.9%, Baxter) or a balanced fluid [Plasmalyte® (Baxter)]. Blood samples and urine output were collected just before (T0), just after (T1), 2 h after (T2) (only for urinary output) and three hours after termination of the fluid bolus (T4). The effect of fluid boluses on serum chloride, apparent strong ion difference, base excess, urinary output and blood pressure or vasopressor need were analyzed. Patients who received a 1 L saline fluid bolus had a significant increase in serum chloride (1.60; 95% CI 1.10 to 2.10; P < 0.001) and short-term decrease in apparent strong ion difference (-1.85; 95% CI -2.71 to -0.99; P < 0.001) and base excess (-0.90; 95% CI -1.31 to -0.50; P < 0.001). We observed a 17% increase in patients developing hyperchloremia in the saline group (0.17; 95% CI 0.05 to 0.29; P = 0.005). No significant difference in urinary output, blood pressure or vasopressor need was observed in either group. Even a single, small bolus of saline, administered to critically ill patients, causes a significant increase in chloride concentration and a decrease in apparent strong ion difference and base excess, and an increase in the number of patients developing hyperchloremia. No difference in effect on urinary output, blood pressure or vasopressor need was observed between the two groups. 2014-001005-41; date of registration: 28/10/2014. EC project number 2014/038.

Differentially expressed genes involved in immune pathways following Vibro parahaemolyticus challenge: A study on red swamp crayfish Procambarus clarkii

This study conducted a comprehensive analysis of the damage mechanism of Vibrio parahaemolyticus (V. parahaemolyticus) on crayfish, utilizing pathological section observations, biochemical indicator detection, and transcriptomics analysis. Histopathological examination showed fragmentation of the gill lamellae, spotted pigment deposition on the branchial membrane, degeneration of epithelial cells, and disruption of the normal structure of gill tissues. Biochemical tests indicated a significant decrease in the activity of antioxidant-related enzymes in crayfish injected with V. parahaemolyticus compared with the phosphate-buffered saline group. Transcriptomics analysis identified 2307 upregulated and 1721 downregulated differentially expressed genes (DEGs). Gene ontology enrichment analysis highlighted that DEGs were primarily involved in the regulation of lipid metabolic processes, cellular nitrogen compound biosynthesis and metabolic processes, and the negative regulation of neuron death. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed significant enrichment in N-glycan biosynthesis, fatty acid metabolism, and the mTOR signaling pathway. Gene set enrichment analysis indicated pathways related to immunity and oxidative stress, including oxidative phosphorylation and tyrosine metabolism. Quantitative reverse transcription–polymerase chain reaction results for selected genes involved in the oxidative phosphorylation pathway and immune-related genes corroborated the RNA-Seq trends, confirming the transcriptomics data's reliability. The findings suggest that infection with V. parahaemolyticus leads to excessive oxidative stress due to bacterial proliferation, overwhelming the crayfish's antioxidative defense. This causes a continuous increase in reactive oxygen species levels, leading to irreversible damage to the oxidative phosphorylation and innate immune systems. This study elucidated the mechanism of oxidative stress damage in crayfish following V. parahaemolyticus infection, providing valuable insights for reducing bacterial and viral diseases in aquaculture. A deeper understanding of pathogen affects the physiology and immune systems of aquatic organisms can help develop more effective prevention and control strategies, thereby improving the efficiency and sustainability of aquaculture.

Efficacy of bilateral catheter superficial parasternal intercostal plane blocks using programmed intermittent bolus for opioid-sparing postoperative analgesia in cardiac surgery with sternotomy: A randomized, double-blind, placebo-controlled trial

Study objectiveThis study investigated whether catheter superficial parasternal intercostal plane (SPIP) blocks, using a programmed intermittent bolus (PIB) with ropivacaine, could reduce opioid consumption while delivering enhanced analgesia for a period exceeding 48 h following cardiac surgery involving sternotomy. DesignA double-blind, prospective, randomized, placebo-controlled trial. SettingUniversity-affiliated tertiary care hospital. Patients60 patients aged 18 or older, scheduled for cardiac surgery via sternotomy. InterventionsThe patients were randomly assigned in a 1:1 ratio to either the ropivacaine or saline group. After surgery, patients received bilateral SPIP blocks for 48 h with 0.4% ropivacaine (20 mL per side) for induction, followed by bilateral SPIP catheters using PIB with 0.2% ropivacaine (8 mL/side, interspersed with a 2-h interval) or 0.9% normal saline following the same administration schedule. All patients were administered patient-controlled analgesia with hydromorphone. MeasurementsThe primary outcome was the cumulative morphine equivalent consumption during the initial 48 h after the surgery. Secondary outcomes included postoperative pain assessment using the Numeric Rating Scale (NRS) at rest and during coughing at designated intervals for three days post-extubation. Furthermore, recovery indicators and ropivacaine plasma levels were diligently documented. Main resultsCumulative morphine consumption within 48 h in ropivacaine group decreased significantly compared to saline group (25.34 ± 31.1 mg vs 76.28 ± 77.2 mg, respectively; 95% CI, −81.9 to −20.0, P = 0.002). The ropivacaine group also reported lower NRS scores at all recorded time points (P < 0.05) and a lower incidence of nausea and vomiting than the saline group (3/29 vs 12/29, respectively; P = 0.007). Additionally, the ropivacaine group showed significant improvements in ambulation (P = 0.018), respiratory exercises (P = 0.006), and self-reported analgesia satisfaction compared to the saline group (P = 0.016). ConclusionsBilateral catheter SPIP blocks using PIB with ropivacaine reduced opioid consumption over 48 h, concurrently delivering superior postoperative analgesia in adult cardiac surgery with sternotomy.

Abstract 6021: Lutetium-177 (177Lu) radiolabeled engineered antibody fragment against human prostate stem cell antigen (hPSCA) demonstrates targeting and antitumor effects in a syngeneic mouse model of pancreatic ductal adenocarcinoma (PDAC)

Abstract Introduction: hPSCA is a cell surface protein overexpressed in PDAC but minimally expressed in normal tissues, making it a promising therapeutic marker for targeted radiopharmaceutical therapy (TRT). Anti-hPSCA A2 scFv-Fc2DM antibody (A2DM) was engineered with a double mutation in the FcRn binding site for rapid blood clearance to the liver, reducing bone marrow and kidney radiotoxicity. The potential of using 177Lu radiolabeled A2DM antibody for targeted anti-hPSCA imaging and TRT was investigated in a syngeneic mouse model of PDAC. Methods: hPSCA knock-in mice were engrafted subcutaneously with KPC cells overexpressing hPSCA (KPC-hPSCA). ImmunoPET with zirconium-89 (89Zr) radiolabeled with A2DM was conducted to confirm in vivo targeting. For imaging, A2DM and an isotype control (anti-CD20) antibody were radiolabeled with 89Zr. Mice (n = 5; tumor sizes: 150 mm3 - 180 mm3) were i.v. injected with 89Zr-A2DM or 89Zr-isotype control (administered activity: 1.5 MBq/10 µg) or co-injected with excess cold antibody. ImmunoPET was acquired at 21 h post-injection. Ex vivo biodistribution was conducted and %ID/g was calculated based on decay-corrected standards. For therapy, KPC-hPSCA tumor bearing mice (n = 8 - 9, average tumor sizes: 20.1 ± 5.1 mm3) was i.v. injected with 177Lu-A2DM (administered activity: 17.8 MBq/10 µg or 9.25 MBq/10 µg) or saline. Tumor sizes and body weights measured every 2-3 days. Results: 89Zr immunoPET and biodistribution of A2DM demonstrated significantly higher tumor uptake (15.6 ± 0.6 %ID/g) than theisotype control (10.7 ± 1.0 %ID/g, p= 0.0001) or blocked control with 70-fold excess cold antibody (8.6 ± 1.3 %ID/g, p&amp;lt; 0.0001), suggesting A2DM binds to hPSCA-positive tumors in an antigen-specific manner. Therapy studies show tumor growth inhibition in a dose-dependent manner when treated with 17.8 MBq of 177Lu-A2DM (tumor size at day 25: 178 ± 119 mm3) or 9.25 MBq of 177Lu-A2DM (tumor size at day 25: 309 ± 182 mm3) (tumor size at day 25: 740 ± 317 mm3, p= 0.006, 0.04 respectively, compared to saline). Median survival was significantly improved in mice treated with high dose of 17.8 MBq 177Lu-A2DM compared to saline-treated group (48 vs. 25 days, p= 0.002). Median survival of mice treated with low dose 9.25 MBq of 177Lu-A2DM showed a trend towards improved survival but results were not significant (48 vs. 34 days, p= 0.25). Minimal weight loss observed in the 177Lu-A2DM and saline groups, suggesting the 177Lu therapy was well tolerated. Conclusions: 89Zr immunoPET studies confirmed specific targeting of A2DM to KPC-hPSCA tumors in vivo. 177Lu-A2DM therapeutic studies demonstrated significant tumor growth delay in a dose-dependent manner. Future studies will explore dose fractionation strategies, with the aim to enhance tumor growth control for PDAC. Citation Format: Bao Ying Chen, Masoud Farshbaf, Felix B. Salazar, Saad N. Ahmed, Sunidhi Jaiswal, Jennifer Chean, Anakim Sherman, Teresa Hong, Paul J. Yazaki, Tove Olafsen, Kirstin A. Zettlitz, Anna M. Wu. Lutetium-177 (177Lu) radiolabeled engineered antibody fragment against human prostate stem cell antigen (hPSCA) demonstrates targeting and antitumor effects in a syngeneic mouse model of pancreatic ductal adenocarcinoma (PDAC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6021.

Abstract 4113: AST-301,a pDNA-based cancer vaccine encoding HER2-ICD, enhances anti-tumor effect of HER2-ADC in a HER2-expressed gastric cancer xenograft model

Abstract Background: In gastric cancer, the HER2 overexpression (6% to 29.5% of gastric cancers) is considered to increase proliferation activity and suppress apoptosis of the cancer cells. However, HER2-targeting therapy in gastric cancer has not been fully evaluated. Currently, new approaches with HER2-tageted antibody-drug conjugates (ADCs) have led to promising results in HER2-related solid tumors. ADCs may have immune-modulating properties and that the payloads delivered by ADCs may induce immunogenic cell death. Based on this rationale, ADC and cancer vaccine combination would be potentially synergistic to improve clinical outcomes. This study was conducted to evaluate an synergistic effect and immune response of the combination of AST-301 and HER2-ADC in HER2-expressed gastric cancer xenograft model. AST-301 phase 1 study (PN109) was completed and phase 2 randomized-control trials (CornerStone-001, CornerStone-003) have been conducted in breast cancer and gastric cancer. Methods: NCI-N87 cells were mixed with the same amount of matrigel at 1x107 cells to formation tumors in the flanks of athymic BALB/c nude mice. After the tumor size of mice reached 100-200 mm3, all of them were randomly classified into four groups (n=7/group) and drug administration was initiated. AST-301 (100 μg/animal, intradermal injection, mixed with rhuGM-CSF as an immune adjuvant) was administered once a week to a total of fourth. LCB01 (1 mg/kg, intravenous injection) was administered to once. Enhertu (1 or 3 mg/kg, intravenous injection) was administered to twice for four weeks. The relative tumor size and TGI rate at day 25 were key endpoints of efficacy. To evaluate the mechanism underlying the enhanced anti-tumor effect due to the combined administration of AST-301 and HER2-ADCs, immune-cell profiling was also conducted using FACS analysis. Results: Our previous study has shown that AST-301 has anti-tumor effects in human gastric cancer xenograft athymic BALB/c nude mouse model. It was showed that adding AST-301 to LCB01 or Enhertu inhibited tumor growth based on a TGI rate at days 25; AST-301 combining with LCB01 vs LCB01 mono (52 % vs 43 %), AST-301 combining with Enhertu vs Enhertu mono (42 % vs 24 %).As an explorative endpoint, it was observed that myeloid-derived suppressor cells (MDSCs) elevation was modestly inhibited in tumor site in AST-301 mono or certain combination regimen adding AST-301. It was remarkable (or observed or captured) that MDSCs elevation was inhibited in tumor site in the combination groups of all ADCs with AST-301 compared to normal saline groups. Conclusion: With combining AST-301 and HER2 ADCs, it was demonstrated that anti-tumor effect was likely synergistic in the athymic mouse model. Phase 2 study of AST-301 in HER2-expressed gastric cancer has been on going (CornerStone-003, NCT 05771584). Citation Format: Jinho Kang, Hyo-Hyun Park, Jee Hyun Choi, Jinback Lim, Seong-Yong Jang, Min-Ah Kim, Myeong-Kyu Park, Yun-Hee Park, Soyeon Lim, Chul-Woong Chung, Jin Kyeong Choi, Eunkyo Joung, Ashley Yongmin Kim, Hun Jung. AST-301,a pDNA-based cancer vaccine encoding HER2-ICD, enhances anti-tumor effect of HER2-ADC in a HER2-expressed gastric cancer xenograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4113.

Effects of paternal arachidonic acid supplementation on offspring behavior and hypothalamus inflammation markers in the mouse.

Arachidonic acid (AA) is involved in inflammation and plays a role in growth and brain development in infants. We previously showed that exposure of mouse sires to AA for three consecutive generations induces a cumulative change in fatty acid (FA) involved in inflammation and an increase in body and liver weight in the offspring. Here, we tested the hypothesis that paternal AA exposure changes the progeny's behavioral response to a proinflammatory insult, and asked whether tissue-specific FA are associated with that response. Male BALB/c mice were supplemented daily with three doses of AA for 10 days and crossed to non-supplemented females (n = 3/dose). Two-month-old unsupplemented male and female offspring (n = 6/paternal AA dose) were exposed to Gram-negative bacteria-derived lipopolysaccharides (LPS) or saline control two hours prior to open field test (OFT) behavioral analysis and subsequent sacrifice. We probed for significant effects of paternal AA exposure on: OFT behaviors; individual FA content of blood, hypothalamus and hypothalamus-free brain; hypothalamic expression profile of genes related to inflammation (Tnfa, Il1b, Cox1, Cox2) and FA synthesis (Scd1, Elovl6). All parameters were affected by paternal AA supplementation in a sex-specific manner. Paternal AA primed the progeny for behavior associated with increased anxiety, with a marked sex dimorphism: high AA doses acted as surrogate of LPS in males, realigning a number of OFT behaviors that in females were differential between saline and LPS groups. Progeny hypothalamic Scd1, a FA metabolism enzyme with documented pro-inflammatory activity, showed a similar pattern of differential expression between saline and LPS groups at high paternal AA dose in females, that was blunted in males. Progeny FA generally were not affected by LPS, but displayed non-linear associations with paternal AA doses. In conclusion, we document that paternal exposure to AA exerts long-term behavioral and biochemical effects in the progeny in a sex-specific manner.

Redox-responsive nanomedicine of doxorubicin-conjugated poly-L-glutathione oxidized for cancer therapy

BackgroundDoxorubicin (Dox) is a potent anticancer drug with severe side effects to normal tissues. To fabricate a nanomedicine with Dox is a better method to address the side effects of Dox in normal tissues. However, nanomedicines with unapproved materials could not be easily applied in clinic, hence, a nanomedicine fabricated by endogenous materials is a potential method to increase the possibility of clinical application. MethodsIn this study, a redox-responsive nanomedicine with clinical-applied anticancer of Dox and endogenous molecule of l-glutathione oxidized (GSSG) was prepared for cancer therapy.: The carboxyl and amino groups in l-glutathione oxidized can be reacted itself to form the poly-l-glutathione oxidized peptide-like polymer. Meanwhile, the Dox were conjugated in poly-l-glutathione oxidized polymer by amnio group in Dox and the structure of Dox-conjugated poly-l-glutathione oxidized polymer (Dox-Poly GSSG) was confirmed by FT-IR, NMR and MALDIT-TOF. Afterward, the drug loading of Dox (22 %) in poly-GSSG was measured by UV–vis and the accumulative Dox release rate of Dox-Poly GSSG is 46 % in 5 mg/mL reduced glutathione (GSH) environment at 72 h The size stability of Dox-Poly GSSG in PBS and PBS with GSH was evaluated by dynamic laser scatter (DLS) and transmit emission microscopy (TEM). Furthermore, cell viabilities of Dox-Poly GSSG were similar with free Dox evaluated by CCK-8 assay and flow cytometry experiment, respectively. The distribution of Dox-Poly GSSG in nuclei and tumor tissues was evaluated by Confocal laser scanning microscope and in vivo imaging system, respectively. Significant FindingsThe drug release results showed that the Dox could be controllable released in high concentration of GSH in tumor tissues. The tumor inhibition, H&E and TUNEL experiments showed that the Dox-Poly GSSG group can significantly inhibit the tumor growth compared to saline group and avoid major side effects to normal tissues compared to free Dox. This redox-responsive nanomedicine with clinical-applied anticancer of Dox and endogenous molecule of GSSG is a potential candidate for clinical application.

Water–Rock Interaction Processes in Tíscar and Larva Active Faults (Betic Cordillera, SE Spain)

A hydrochemical and mineral study of groundwaters and damaged rocks from the Tíscar and Larva fault zones (Betic Cordillera, Iberian Peninsula) was carried out in order to (a) describe the physical and chemical properties of the groundwaters; (b) recognize significant locations with deep-origin fluids related to active tectonics; (c) and to describe the water–rock interaction and the neoformation of clay mineral processes and their importance in the seismicity of the faults. A sampling campaign was completed between November 2012 and November 2013, during which data were obtained from 23 different groundwater sites in the fault areas. Two main groups of waters were distinguished: (a) Ca2+-Mg2+-HCO3− facies characterized by poor conductivity and salinity; and (b) saline waters (up to 30 meq/L) rich in Ca2+-Mg2+-SO4-Cl− and with an elevated conductivity (frequently &gt; 1000 μS/cm). In addition, a minor group of saline and warm waters (T &gt; 16.5 °C) was found to be Na+-rich and show moderately high B values (&gt;0.33 ppm), and which mig ht be hosted in aquifers deeper than the two main groups. This group of deep-origin waters is oversaturated in clay minerals and is in equilibrium for Ca-Mg carbonate minerals. X-ray diffraction and scanning and transmission electron microscopy data corroborate the crystallization forecast of authigenic smectite, which appears as thin films coating carbonate fragments. The origin of smectite is related to the fragile strain and thermal–fluid–mineral interactions in fault rocks. Smectite could lubricate carbonate rocks, which favor creep deformation versus seismic slip. This work provides locations where groundwater physico-chemical properties and composition suggest tectonic fault activity.

Effect of Zusanli Acupoint Injection with Anisodamine on Postoperative Recovery Quality of Patients Undergoing Bariatric Surgery

PurposeTo evaluate the influence of anisodamine injection at the Zusanli (ST36) on early postoperative recovery quality in patients who have undergone laparoscopic sleeve gastrectomy.Materials and Methods141 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into the control group (group C), the normal saline group (group S) and the anisodamine group (group A). Acupuncture point injections were administered after induction of general anesthesia. The quality of recovery-40 questionnaire (QoR-40) scores were documented preoperatively (D0) and on the 1st (D1), 3rd (D3) and 7th (D7) days postoperatively. Additional metrics included: the numerical rating scale (NRS) for pain, postoperative nausea and vomiting (PONV), assessment and analgesic consumption 24-h post-extubation and the initial postoperative times for ambulation and anal exhaust. Substance P (SP), β-endorphin (β-EP), motilin (MTL) and gastrin (GAS) were quantified at 24-h post-surgery.ResultsCompared with group C, group A demonstrated an elevation in QoR-40 scores and physical comfort dimensions during D1-3, and an increased pain scores during D1-7; group S exhibited an augmentation in QoR-40 scores and pain scores on D1 (p < 0.05). Compared with group S, group A improved QoR-40 scores on D1 and pain scores during D1-3 (p < 0.05). SP, β-EP, MTL and GAS presented significant variances among the groups 24-h post-surgery (p < 0.05). There were significant differences between the groups in NRS pain scores and PONV scores at 24-h postoperatively, dosage of dizocin on the first postoperative day, and time to first anal defecation (p < 0.05).ConclusionThe administration of anisodamine via ST36 acupoint injections has been demonstrated to facilitate the recuperation of gastrointestinal functionality, to alleviate postoperative pain and nausea, and substantially to enhance the quality of early postoperative recovery.Graphical

Intradermal and Subcutaneous Lignocaine for Arterial Blood Gas Sampling: A Randomized Controlled Trial

Introduction: The use of local anesthesia (LA) prior to arterial blood gas sampling is recommended but is not widely used. We tested the hypothesis that intradermal administration of local anesthesia would be as effective as subcutaneous administration in reducing pain from arterial blood gas sampling. Aims: The primary aim of this study was to evaluate the effect of intradermal and subcutaneous lignocaine on patient-perceived pain during arterial blood gas sampling. The secondary aims were to evaluate if different routes of LA administration had an impact on the difficulty and complications of ABG sampling. Methods: We undertook a randomized, single-blind, placebo-controlled trial in New Zealand. We enrolled patients attending a nurse-led outpatient oxygen clinic who were 18 to 90 years of age and who had an oxygen saturation of 93% or less at rest. Patients were randomly assigned to receive intradermal 1% lignocaine, subcutaneous 1% lignocaine, or subcutaneous normal saline. Patients and nurse assessors were blinded to the treatment allocation. The primary endpoint was a patient-assessed pain score using a graphic rating scale (0-10). Results: 135 patients were randomized (54 patients in the intradermal lignocaine group, 54 patients in the subcutaneous lignocaine group, and 27 in the subcutaneous saline group). The mean patient-assessed pain score for the intradermal lignocaine group was 1.8 (+/- 1.1), which was a relative reduction of 47% (95% C.I. 31%-59%, p &lt; 0.0001) from the mean patient-assessed pain score of 3.4 (+/- 1.1) for the subcutaneous saline group. The mean patient-assessed pain score for the subcutaneous lignocaine group was 2.1 (+/- 1.1), which was also a significant relative reduction of 36% (95% C.I. 17%-51%, p = 0.0001) compared to the subcutaneous saline group. Intradermal lignocaine reduced pain more than subcutaneous lignocaine, with a relative pain reduction difference of 20% (95% CI -4%-49%, p = 0.05). Bruising was more frequent in the subcutaneous lignocaine group (9.3%) than in the intradermal (0%) and saline groups (0%). Conclusion: Intradermal lignocaine is at least as effective as subcutaneous lignocaine for reducing patient-perceived pain from arterial blood gas sampling and results in less bruising.

Effect of plasminogen activator urokinase receptor gene on the activation and apoptosis of neutrophil

Objective: To investigate the effect of plasminogen activator urokinase receptor (PLAUR) gene on neutrophil activation and apoptosis in neutrophil-like cell model. Methods: Human acute myeloid leukemia cell line HL60 was cultured in vitro and induced to differentiate into neutrophil-like cells by all-trans retinoic acid (ATRA). Lentiviral vectors interfering with human PLAUR gene was constructed and transfected into neutrophil-like cells (siRNA group). The phosphate buffer saline (PBS) group (untransfected neutrophil-like cells) and normal blank control group (NC group) (neutrophil-like cells transfected with blank plasmid) were used as controls (n=3). After starvation culture and addition of interleukin-17 afterwards in these 3 groups, the expression of CD11b on the cell membrane was detected by flow cytometry, and the levels of myeloperoxide (MPO) and extracellular neutrophil traps (NETs) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA) to investigate the activation of neutrophil-like cells. The apoptosis was detected by flow cytometry with annexin V/propidium iodide (PI) double staining and the expressions of apoptosis-related proteins caspase-3, bax and bcl-2 were detected by Western blotting. Results: The expression of CD11b in siRNA group (32.37±8.17) was lower than that in PBS group (46.27±1.54) and NC group (53.07±8.14) (P<0.05) by flow cytometry. The levels of MPO and NETs (33.37±1.11, 57.69±3.03) in the supernatant of siRNA group were significantly lower than those in PBS group (41.64±2.20, 77.60±4.33) and NC group (40.84±5.11, 76.15±2.10) (P<0.05). Flow cytometry with annexin V/PI showed that the expression of apoptosis in siRNA group (20.42%±2.45%) was significantly higher than that in PBS group (11.91%±2.23%) and NC group (11.13%±2.56%) (P<0.05). The relative expression of caspase-3 protein and bax protein (0.84±0.05, 0.83±0.04) in siRNA group was significantly higher than that in PBS group (0.68±0.02, 0.63±0.08) and NC group (0.71±0.01, 0.66±0.10) (P<0.05), and the relative expression of anti-apoptosis protein bcl-2 decreased in siRNA group (0.38±0.02) than in PBS group (0.73±0.05) and NC group (0.69±0.06) (P<0.05). Conclusion: PLAUR promotes the activation of neutrophil-like cells and inhibits the apoptosis.

Effectiveness of Butorphanol in alleviating intra- and post-operative visceral pain following microwave ablation for hepatic tumor: a dual-central, randomized, controlled trial

Many patients who underwent hepatic percutaneous microwave ablation (MWA) reported experiencing pain during the procedure. This study utilized a well-designed multicentral, randomized, and placebo-controlled format to investigate the effects of Butorphanol. Patients who underwent MWA were randomly assigned to either Butorphanol or normal saline group. The primary outcomes of the study were assessed by measuring the patients' intraoperative pain levels using a 10-point visual analog scale (VAS). Secondary outcomes included measuring postoperative pain levels at the 6-h mark (VAS) and evaluating comprehensive pain assessment outcomes. A total of 300 patients were divided between the control group (n = 100) and the experimental group (n = 200). Butorphanol showed statistically significant reductions in intraoperative pain levels compared to the placebo during surgery (5.00 ± 1.46 vs. 3.54 ± 1.67, P < 0.001). Significant differences were observed in postoperative pain levels at the 6-h mark and in the overall assessment of pain (1.39 + 1.21 vs. 0.65 + 0.81, P < 0.001). Butorphanol had a significant impact on reducing the heart rate of patients. The empirical evidence supports the effectiveness of Butorphanol in reducing the occurrence of visceral postoperative pain in patients undergoing microwave ablation for hepatic tumor. Furthermore, the study found no noticeable impact on circulatory and respiratory dynamics.

Balanced Crystalloid Solution or Normal Saline in Fluid Resuscitation in Critically Ill Patients: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

Background: Both balanced crystalloid solution and normal saline are commonly used for fluid therapy in critically ill patients. However, the association between the types of crystalloid solution and patient outcomes remains inconclusive. Materials and Methods: The authors performed a search using Pubmed, Embase, and Cochrane Central Register through January 2022. Randomized controlled trials (RCTs) comparing balanced crystalloids and normal saline in non-perioperative fluid resuscitation for critically ill adult patients were included. The primary outcome was 30-day mortality. A trial sequential analysis (TSA) was performed to assess the effect of each type of fluid on the outcomes. Secondary outcomes included the incidence of acute kidney injury (AKI), renal replacement therapy (RRT), and other pre-specified outcomes. Results: Ten RCTs were identified and included 36,233 participants. Between the balanced crystalloids and the normal saline group, there were no significant differences in mortality at 30 days (relative risk [RR] 0.95, 95% confidence interval [CI] 0.89 to 1.02, I²=0), the incidence of AKI (RR 0.95, 95% CI 0.90 to 1.01, I²=0), and RRT (RR 0.93, 95% CI 0.86 to 1.01, I²=13). However, patients receiving balanced crystalloids demonstrated a significantly lower serum chloride level than the patients receiving normal saline (MD –1.95, 95% CI –3.45 to –0.45, I²=99). There was also no mortality difference in the sepsis and traumatic brain injury subgroups. The TSA confirmed the absence of an effect on mortality at 30 days and the incidence of AKI. Conclusion: In critically ill patients, the use of balanced crystalloids does not decrease 30-day mortality or the incidence of AKI and RRT. However, data in specific subgroups of patients were underpowered and further studies are required. There were signals of benefit and risk of the balanced salt solution in the subgroups of sepsis and traumatic brain injury. Trial registration: The present study was registered in the PROSPERO database, CRD42021275796. Keywords: Balanced crystalloid; Normal saline; Critically ill patients; Mortality; Acute kidney injury

A Novel Model of Staphylococcus aureus-Induced Lymphoplasmacytic Rhinosinusitis in Rats.

Chronic rhinosinusitis (CRS) is characterized by sinonasal mucosal inflammation. Staphylococcus aureus (S. aureus) is associated with severe CRS phenotypes. Different animal models have been proposed to study the association of CRS and S. aureus. However, current animal models are expensive due to the use of large animals, have high barriers to ethics approval, or require invasive surgical intervention, necessitating a need for a model that can overcome these limitations. This study aimed at establishing a reliable and efficient rat lymphoplasmacytic inflammatory model for rhinosinusitis. Sprague Dawley rats received a daily intranasal application of 20 μL of saline, S. aureus CI-182 exoprotein (250 μg/mL), or exoprotein CI-182 in combination with S. aureus clinical isolate (CI-908 or CI-913) 108 colony-forming unit (CFU)/mL. The rats' sinuses were harvested at 1 and 2 weeks post-intervention. The CFU and histopathologic examination of inflammation were evaluated. S. aureus clinical isolates CI-908 or CI-913 in combination with the exoprotein (CI-182) had higher CFUs and caused persistently higher inflammation at both the 1 and 2-week post-intervention compared to the exoprotein and saline group. The observed inflammatory cell type was lymphoplasmacytic. This study provided evidence that the combination of a S. aureus exoprotein with S. aureus induces inflammation that persists for a minimum of two weeks post-intervention. This model is the first known animal model to create the lymphoplasmacytic inflammation subtype seen in CRS patients. This offers a cost-effective, accessible, non-invasive, and easy-to-replicate model to study the causes and treatment of such inflammation.

Inhibition of SIRT1 in the nucleus accumbens attenuates heroin addiction-related behavior by decreasing D1 neuronal autophagy.

This study aimed to investigate the effects of SIRT1 modulation on heroin addiction-like behavior and its possible biological mechanisms. Wild-type C57BL/6J and Sirt1loxp/loxp D1-Cre mice were used in this experiment, and Sirt1 loxp/loxp D1-Cre(-) mice were used as a control for conditional knockout mice. Mice were divided into saline control and heroin-dependent groups. Behavioral methods were used to record the withdrawal response, conditioned place preference (CPP) changes, and open field test results. Transmission electron microscopy (TEM) was used to observe the structure of autophagosomes in nucleus accumbens (NAc) neurons. The expression of SIRT1 and autophagy-related proteins and genes, such as LC3Ⅱ, ATG5 , and ATG7 , was detected in the NAc of each mouse group via western blot, real-time quantitative PCR (qPCR) analyzes, and immunofluorescence. The results of this experiment showed that compared with the saline group, mice in the wild-type heroin-dependent group showed marked withdrawal symptoms, with more autophagosomes observed in NAc via TEM. Compared with wild-type and Sirt1loxp/loxp D1-Cre(-) heroin-dependent groups, CPP formation was found to be reduced in the conditional knockout mouse group, with a significant decrease in spontaneous activity. Western blot, qPCR, and immunofluorescence results indicated that the expression of LC3Ⅱ, ATG-5, and ATG-7 was significantly reduced in the NAc of the Sirt1loxp/loxp D1-Cre(+) group. It was still, however, higher than that in the saline control group. These results suggest that inhibition of Sirt1 expression may prevent heroin-induced addiction-related behaviors via reducing D1 neuronal autophagy.

Effects of Aspirin Eugenol Ester on Liver Oxidative Damage and Energy Metabolism in Immune-Stressed Broilers.

The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on liver oxidative damage and energy metabolism in immune-stressed broilers. In total, 312 broilers were divided into 4 groups (saline, LPS, SAEE, and LAEE). Broilers in the saline and LPS groups were fed a basal diet; the SAEE and LAEE groups had an added 0.01% AEE in their diet. Broilers in the LPS and LAEE groups were injected with lipopolysaccharides, while the saline and SAEE groups were injected with saline. Results showed that AEE increased the body weight, average daily gain, and average daily feed intake, as well as decreasing the feed conversion ratio of immune-stressed broilers. AEE protects against oxidative damage in immune-stressed broiler livers by elevating the total antioxidant capacity, superoxide dismutase activity, and glutathione S-transferase alpha 3 (GSTA3) and glutaredoxin 2 (GLRX2) expression, while decreasing malondialdehyde content. AEE lessened inflammation by reducing prostaglandin-F2α production and prostaglandin-endoperoxide synthase 2 (PTGS2) and interleukin-1beta (IL-1β) expression. AEE decreased oxidative phosphorylation rates by increasing succinic acid levels and lowering both adenosine diphosphate (ADP) levels and ceroid lipofuscinosis neuronal 5 (CLN5) expression. AEE modulated the metabolism of phenylalanine, tyrosine, lipids, and cholesterol by reducing the phenyllactate and L-arogenate levels, lowering dopachrome tautomerase (DCT) and apolipoprotein A4 (APOA4) expression, and increasing phenylpyruvic acid and dopa decarboxylase (DDC) expression. In summary, AEE can effectively alleviate liver oxidative damage and energy metabolism disorders in immune-stressed broilers.

Local application of zoledronate inhibits early bone resorption and promotes bone formation.

Nonunion resulting from early bone resorption is common after bone transplantation surgery. In these patients, instability or osteoporosis causes hyperactive catabolism relative to anabolism, leading to graft resorption instead of fusion. Systemic zoledronate administration inhibits osteoclastogenesis and is widely used to prevent osteoporosis; however, evidence on local zoledronate application is controversial due to osteoblast cytotoxicity, uncontrolled dosing regimens, and local release methods. We investigated the effects of zolendronate on osteoclastogenesis and osteogenesis and explored the corresponding signaling pathways. In vitro cytotoxicity and differentiation of MC3T3E1 cells, rat bone marrow stromal cells (BMSCs) and preosteoclasts (RAW264.7 cells) were evaluated with different zolendronate concentrations. In vivo bone regeneration ability was tested by transplanting different concentrations of zolendronate with β-tricalcium phosphate (TCP) bone substitute into rat femoral critical-sized bone defects. In vitro, zolendronate concentrations below 2.5 × 10-7M did not compromise viability in the three cell lines and did not promote osteogenic differentiation in MC3T3E1 cells and BMSCs. In RAW264.7 cells, zoledronate inhibited extracellular regulated protein kinases and c-Jun n-terminal kinase signaling, downregulating c-Fos and NFATc1 expression, with reduced expression of fusion-related dendritic cell‑specific transmembrane protein and osteoclast-specific Ctsk and tartrate-resistant acid phosphatase (. In vivo, histological staining revealed increased osteoid formation and neovascularization and reduced fibrotic tissue with 500μM and 2000μM zolendronate. More osteoclasts were found in the normal saline group after 6weeks, and sequential osteoclast formation occurred after zoledronate treatment, indicating inhibition of bone resorption during early callus formation without inhibition of late-stage bone remodeling. In vivo, soaking β-TCP artificial bone with 500μM or 2000μM zoledronate is a promising approach for bone regeneration, with potential applications in bone transplantation.