Pathological Indicators Research Articles

Efficacy of high-dose-rate brachytherapy with different radiation source activities among cervical cancer patients and risk factors for long-term outcomes: A 6-year retrospective study

PURPOSEThis study aimed to assess the impact of dose rates due to natural decay of Iridium-192 sources and the risk factors of clinical outcomes for cervical cancer patients treated with high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALSFour ninety-four patients were divided into relatively-high-radioactive (rHR), relatively-medium-radioactive (rMR), and relatively-low-radioactive (rLR) groups for retrospective treatment response comparison. The short-term outcomes were evaluated using the 1-month /3-month follow-up results based on RECIST 1.1. Local recurrence-free survival (LRFS) and metastatic recurrence-free survival (MRFS) were selected as long-term outcomes. A class of transformation models with adaptive lasso was applied to assess the risk factors of long-term outcomes. RESULTSNo significant difference was identified in short- or long-term outcomes of different radioactive groups. Subgroup analyses demonstrated similar findings. In multivariate factor analysis, advanced stage was significantly associated with higher risk of local recurrence and metastatic recurrence (HR = 1.66, 95%confidence interval [CI] = 1.14–2.43, p = 0.008; HR = 1.57, 95%CI = 1.23–2.00, p < 0.001). Significant associations were observed between local recurrence and pathology, and between metastatic recurrence and pre-treatment serum indices, respectively (HR = 8.62, 95%CI = 2.28–32.60, p = 0.002; HR = 1.98, 95%CI=1.20–2.26, p = 0.008). CONCLUSIONSOverall, there was no significant difference in long- or short-term efficacy of the HDR brachytherapy among the groups with different levels of activity of radiation sources. Stage, pathology, and pretreatment serum indices were crucial factors that affected the long-term outcomes.

Rosmarinic acid treatment protects against lethal H1N1 virus-mediated inflammation and lung injury by promoting activation of the h-PGDS-PGD2-HO-1 signal axis

BackgroundRosmarinic acid (RosA) is a natural phenolic compound that possesses a wide-range of pharmacological properties. However, the effects of RosA on influenza A virus-mediated acute lung injury remain unknown. In this study, we aimed to explore whether RosA could protect against H1N1 virus-mediated lung injury and elucidate the underlying mechanisms.MethodsMice were intragastrically administered with RosA for 2 days before intranasal inoculation of the H1N1 virus (5LD50) for the establishment of an acute lung injury model. At day 7 post-infection (p.i.), gross anatomic lung pathology, lung histopathologic, and lung index (lung weight/body weight) were examined. Luminex assay, multiple immunofluorescence and flow cytometry were performed to detect the levels of pro-inflammatory cytokines and apoptosis, respectively. Western blotting and plasmid transfection with hematopoietic-type PGD2 synthase (h-PGDS) overexpression were conducted to elucidate the mechanisms.ResultsRosA effectively attenuated H1N1 virus-triggered deterioration of gross anatomical morphology, worsened lung histopathology, and elevated lung index. Excessive pro-inflammatory reactions, aberrant alveolar epithelial cell apoptosis, and cytotoxic CD8+ T lung recruitment in the lung tissues induced by H1N1 virus infection were observed to be reduced by RosA treatment. In vitro experiments demonstrated that RosA treatment dose-dependently suppressed the increased levels of pro-inflammatory mediators and apoptosis through inhibition of nuclear factor kappa B (NF-κB) and P38 MAPK signaling pathways in H1N1 virus-infected A549 cells, which was accompanied by promoting activation of the h-PGDS-PGD2-HO-1 signal axis. Furthermore, we strikingly found that h-PGDS inhibition significantly abrogated the inhibitory effects of RosA on H1N1 virus-mediated activation of NF-κB and P38 MAPK signaling pathways, resulting in diminishing the suppressive effects on the increased levels of pro-inflammatory cytokines and chemokines as well as apoptosis. Finally, suppressing h-PGDS prominently abolished the protective effects of RosA on H1N1 virus-mediated severe pneumonia and lung injury.ConclusionsTaken together, our study demonstrates that RosA is a promising compound to alleviate H1N1 virus-induced severe lung injury through prompting the h-PGDS-PGD2-HO-1 signal axis.

The effects of Phycocyanobilin on experimental arthritis involve the reduction in nociception and synovial neutrophil infiltration, inhibition of cytokine production, and modulation of the neuronal proteome.

The antinociceptive and pharmacological activities of C-Phycocyanin (C-PC) and Phycocyanobilin (PCB) in the context of inflammatory arthritis remain unexplored so far. In the present study, we aimed to assess the protective actions of these compounds in an experimental mice model that replicates key aspects of human rheumatoid arthritis. Antigen-induced arthritis (AIA) was established by intradermal injection of methylated bovine serum albumin in C57BL/6 mice, and one hour before the antigen challenge, either C-PC (2, 4, or 8 mg/kg) or PCB (0.1 or 1 mg/kg) were administered intraperitoneally. Proteome profiling was also conducted on glutamate-exposed SH-SY5Y neuronal cells to evaluate the PCB impact on this key signaling pathway associated with nociceptive neuronal sensitization. C-PC and PCB notably ameliorated hypernociception, synovial neutrophil infiltration, myeloperoxidase activity, and the periarticular cytokine concentration of IFN-γ, TNF-α, IL-17A, and IL-4 dose-dependently in AIA mice. In addition, 1 mg/kg PCB downregulated the gene expression for T-bet, RORγ, and IFN-γ in the popliteal lymph nodes, accompanied by a significant reduction in the pathological arthritic index of AIA mice. Noteworthy, neuronal proteome analysis revealed that PCB modulated biological processes such as pain, inflammation, and glutamatergic transmission, all of which are involved in arthritic pathology. These findings demonstrate the remarkable efficacy of PCB in alleviating the nociception and inflammation in the AIA mice model and shed new light on mechanisms underlying the PCB modulation of the neuronal proteome. This research work opens a new avenue to explore the translational potential of PCB in developing a therapeutic strategy for inflammation and pain in rheumatoid arthritis.

Predicting Risk of 30-day Postoperative Morbidity Using the Pathologic Fracture Mortality Index.

The purpose of this study was to evaluate the ability of the Pathologic Fracture Mortality Index (PFMI) to predict the risk of 30-day morbidity after pathologic fracture fixation and compare its efficacy with those of the American Society of Anesthesiologists (ASA) physical status, modified Charlson Comorbidity Index (mCCI), and modified frailty index (mFI-5). Cohorts of 1,723 patients in the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2020 and 159 patients from a tertiary cancer referral center who underwent fixation for impending or completed pathologic fractures of long bones were retrospectively analyzed. National Surgical Quality Improvement Program morbidity variables were categorized into medical, surgical, utilization, and all-cause. PFMI, ASA, mCCI, and mFI-5 scores were calculated for each patient. Area under the curve (AUC) was used to compare efficacies. AUCs predicting all-cause morbidity were 0.62, 0.54, and 0.56 for the PFMI, ASA, and mFI-5, respectively. The PFMI outperformed the ASA and mFI-5 in predicting all-cause ( P < 0.01), medical ( P = 0.01), and utilization ( P < 0.01) morbidities. In the 2005 to 2012 subset, the PFMI outperformed the ASA, mFI-5, and mCCI in predicting all-cause ( P = 0.01), medical ( P = 0.03), and surgical ( P = 0.05) morbidities but performed similarly to utilization morbidity ( P = 0.19). In our institutional cohort, the AUC for the PFMI in morbidity stratification was 0.68. The PFMI was associated with all-cause (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.12 to 1.51; P < 0.001), medical (OR, 1.19; 95% CI, 1.03 to 1.40; P = 0.046), and utilization (OR, 1.32; 95% CI, 1.14 to 1.52; P < 0.001) morbidities but not significantly associated with surgical morbidity (OR, 1.21; 95% CI, 0.98 to 1.49; P = 0.08) in this cohort. The PFMI is an advancement in postoperative morbidity risk stratification of patients with pathologic fracture from metastatic disease. III.

System biology analysis to develop diagnostic biomarkers, monitoring pathological indexes, and novel therapeutic approaches for immune targeting based on maggot bioactive compounds and polyphenolic cocktails in mice with gastric cancer

Early diagnosis and prognosis are prerequisites for mitigating mortality in gastric cancer (GaCa). Identifying some causative or sensitive elements (coding RNA (cRNA)-non-cRNAs (ncRNAs)) can be very helpful in the early diagnosis of GaCa. Notably, despite significant development in the GaCa treatment, the outcome of patients does not remain satisfactory due to limitations such as multi-drug resistance and tumor relapse. Therefore, more attention has been drawn to complementary therapies and the use of supplements. In this regard, Polyphenol natural compounds (PNC) and maggot larvae (MaLa) alone or in combination were administered along with chemotherapy (paclitaxel) to N-methyl-N-nitrosourea (MNU)- induced murine tumor model. In addition, in order to identify potential diagnostic or prognostic biomarkers, transcriptomics analysis was performed through a bioinformatics approach. Then transcription profile of ncRNAs with their target hub genes was assessed through qPCR Real-Time, Western blot, and ELISA. According to the bioinformatics results, 17 hub genes (e.g., IL-6, CXCL8, MKI67, IL-2, IL-4, IL-10, IL-1β, SPP1, LOX, COL1A1, and IFN-γ) were explored that contribute towards inflammation and oxidative stress and ultimately GaCa development. Upstream of the mentioned hub genes, regulatory factors (lncRNA XIST and NEAT1) were also identified and introduced as prognosis and diagnosis biomarkers for GaCa. Our results showed that PNC alone and in combination with MaLa was able to reduce the size and number of tumors, which is related to the reduction of genes expression levels (including IL-6, CXCL8, MKI67, IL-2, IL-4, IL-10, IL-1β, SPP1, LOX, COL1A1, IFN-γ, NEAT1, and XIST). In conclusion, PNC and MaLa have the potential to be considered as complementary and improving chemotherapy due to their effective compounds. Also, the introduced hub gene and lncRNA in addition to diagnostic and prognostic biomarkers can be used as druggable proteins for novel therapeutic targeting of GaCa.

Screening and genotyping of groundnut (Arachis hypogea L.) inbred lines and landraces in the North Central Nigeria

The study evaluated 33 accessions of groundnut in the field, consisting of 23 landraces from Nasarawa communities in Nigeria and 10 inbred lines. Assessment entailed the determination of plant survivorship, yield related parameters and pathological indices while genetic diversity study was undertaken using SSR and RAPD molecular markers. Data analysis was done on the Minitab 17.0 software. Significant variability was noted in all traits except in pod sizes, seed sizes and % infected seeds. About 33.3% of the accessions had a survival rate of ≥ 70.0% where 9/10 Inbred lines were found with overall yield (kg/ha) ranging from 4.0 ± 1.6 in Akwashiki-Doma to 516.8 ± 46.9 kg/ha in Samnut 24 × ICGV–91328. Five accessions (15.5%) had pathological indices of zero indicating no traces of any disease of any type and they included one landrace called Agric-Dazhogwa and four Inbred lines: Samnut 25 × ICGV–91317, Samnut 26 × ICGV–19324, Samnut 26 × ICGV–91328 and Samnut 26 × ICGV–91319. Coefficients of yield determination R2 by survivorship and pathological index were 50.6% and 15%, respectively. A fit model was established (Yield in kg/ha = –146 − 7.94 × Pi + 5.88 × S). Susceptibility to diseases depends on the type of variety (χ2(32) = 127.67, P = 0.00). Yield was significantly affected by BNR@30 (F = 5.47, P = 0.025, P &lt; 0.05) and DSV@60*RUST@60 interaction effect (F = 4.39, P = 0.044, P &lt; 0.05). The similarity coefficient ranged from 28.57 to 100 in plant morphology. Four varieties had no amplified bands with SSR primers whereas amplified bands were present only in four landraces accessions using the RAPD primer. The dendrogram generated by molecular data gave three groups where genetic similarity ranged from 41.4 to 100.0. The Inbred lines were noted for their high survivorship, good yield and disease resistance. Samnut 24 × ICGV–91328, an inbred line, had the highest yield but was susceptible to diseases. Among the landraces, Agric-Musha, Bomboyi-Dugu and Agric-Dazhogwa were selected for high survivorship and disease resistance. The selected inbred lines and landraces are valuable genetic resources that may harbour useful traits for breeding and they should be presented to the growers based on their unique agronomic values. The highest yielding inbred lines should be improved for resistance to late leaf spot diseases while the outstanding landraces should be improved for yield.

Metabolic profile changes of kidney aging and protective effects of Polygonatum sibiricum polysaccharides on D-galactose-induced aging mice

ObjectiveTo investigate the metabolic trajectory of kidney aging and the effects of Polygonatum sibiricum polysaccharides (PSP) against kidney aging in D-galactose (D-gal)-induced aging mice, based on ultra-performance liquid chromatography/Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive MS/MS). MethodsA total of 36 C57 BL/6J mice were randomly allocated to six groups: control (CON), model (MOD), PSP low-dose (PSP-L), PSP medium-dose (PSP-M), PSP high-dose (PSP-H), and positive drug ascorbic acid (VC) groups. To create models of aging mice, D-gal was intraperitoneally administered to all other groups of mice except the CON group. After modeling, the appropriate Chinese medicine [PSP-L: 150 mg/(kg·d), PSP-M: 300 mg/(kg·d), PSP-H: 600 mg/(kg·d)] or positive drug [ascorbic acid, 300 mg/(kg·d)] was administered for intervention. Key markers of renal function in urine and serum of mice in each group, such as creatinine (Crea), urea nitrogen (BUN), and uric acid (UA) levels, as well as key indicators of oxidative stress in serum and kidney, including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were determined to validate the successful establishment of kidney aging models and to estimate the effects of PSP. Hematoxylin and eosin (HE), periodic acid Schiff (PAS), and β-galactosidase staining were used to assess the renal pathological changes. The metabolic profiles of serum, kidney, and urine samples from CON, MOD, and PSP-H groups were analyzed by UPLC-Q-Exactive MS/MS, and pattern recognition methods were used to outline the metabolic trajectory of kidney aging and to identify the characteristic metabolites. ResultsAge-related alterations in renal histopathology and impaired renal function in mice were also associated with oxidative stress indicators. Following the injection of PSP [PSP-H: 600 mg/(kg·d)], the pathological indices associated with aging were adjusted to normal levels, renal function and oxidative stress were improved in aging mice, and renal pathological damage was markedly improved. Meanwhile, the potential biomarkers were identified by UPLC-Q-Exactive MS/MS analysis and were further analyzed to form related metabolic pathways, with P < 0.05 as a threshold. The results showed that purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms were the main metabolic pathways associated with aging. After administration of PSP, these pathological indices returned to normal levels, and biomarkers related to the aging process, such as adenosine monophosphate (AMP), tryptophan, and 5-hydroxytryptophan, also demonstrated, to some degree, reverse regulation (promoting synthesis). ConclusionMetabolomics methods based on UPLC-Q-Exactive MS/MS and multivariate statistical analysis can be adopted to establish metabolic profiles in aging mice. PSP has been shown to protect against kidney aging by interfering with the purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms in the kidney.

Denervation aggravates renal ischemia reperfusion injury via BMAL1-mediated Nrf2/ARE pathway

AimTo explore the change of clock gene rhythm under renal denervation (RDN) and its effect on renal function and oxidative stress during renal ischemia-reperfusion (IR) injury. MethodC57/BL6 mice were randomly divided into 4 groups at daytime 7 A M (zeitgeber time [ZT] 0) or at nighttime 7 P M (ZT12) in respectively: Sham (S) group, RDN group, IR group and RDN + IR (DIR) group. Renal pathological and functional changes were assessed by H&E staining, and serum creatinine, urea nitrogen and neutrophil gelatinase-associated lipocalin levels. Renal oxidative stress was detected by SOD and MDA levels, and renal inflammation was measured by IL-6, IL-17 A F and TNF-ɑ levels. BMAL1, CLOCK, Nrf2 and HO-1 mRNA and protein expressions were tested by qPCR and Western Blot. ResultCompared with S groups, the rhythm of BMAL1, CLOCK and Nrf2 genes in the kidney were disordered in RDN groups, while renal pathological and functional indexes did not change significantly. Compared with IR groups, renal pathological and functional indexes were significantly higher in the DIR groups, as well as oxidative stress and inflammation in renal tissues. The nocturnal IR injury in the RDN kidney was the worst while the BMAL1, Nrf2 and HO-1 expressions were the highest. In DIR groups, renal injury was aggravated after the Brusatol treatment, but there was no significant improvement after the t-BHQ treatment at night, which might be consistent with the changes of Nrf2 and HO-1 protein expressions. ConclusionRDN lead to the disruption of BMAL1-mediated Nrf2 rhythm accumulation in the kidney, which reduced the renal ability to resist oxidative stress and inflammation, due to the impaired effect of activating Nrf2/ARE pathway in renal IR injury at nighttime.

Effects of moxibustion at "Tianshu"（ST25） and "Shangjuxu" （ST37） on colonic metabolites and inflammatory factors in rats with Crohn's disease

To observe the effects of moxibustion at "Tianshu"（ST25） and "Shangjuxu"（ST37） on the colonic metabolites and inflammatory factors in rats with Crohn's disease（CD）, so as to explore the mechanisms of moxibustion in protecting colon of CD rats based on metabolomics. Twelve rats were first randomly selected from 36 male SD rats as a normal group（NG）. The CD model was induced by 2, 4, 6 trinitrobenzene sulfonic acid（TNBS） enema on the rest 24 rats. After successful modeling, rats were randomly divided into model（TNBS） and moxibustion（TNBS+MOX） groups（n=10 rats/group）. Moxibustion was applied at bilateral ST25 and ST37 for 30 min, once daily for 7 consecutive days in the TNBS+MOX group, while rats in the NG and TNBS groups did not receive any interventions. Body weight of rats was recorded and disease activity index（DAI） was assessed during the experiment. After interventions, HE staining was performed to observe pathological damage of colon. Serum levels of inflammatory factors were measured by ELISA. NMR hydrogen spectroscopy was used to detect colonic metabolites of each group, and orthogonal partial least squares discriminant analysis（OPLS-DA） was used to screen differential colonic metabolites between groups, followed by pathway analysis using MetaboAnalyst 5.0 platform. After modeling, compared with the NG group, the body weight of the rats in the TNBS group was significantly decreased（P<0.05）, the DAI score was increased （P<0.05）, the colon had obvious inflammatory damage and the pathological injury index was increased（P<0.05）, and levels of serum tumor necrosis factor-α（TNF-α）, interleukin（IL）-1β and interferon-γ（IFN-γ） were significantly increased（P<0.05）. After moxibustion intervention, compared with the TNBS group, the body weight was significantly increased（P<0.05）, while the levels of serum TNF-α, IL-1β, IFN-γ, and DAI score of the rats in the TNBS+MOX group were significantly decreased（P<0.05）, with alleviated colonic inflammatory injury detected by HE staining. Compared with the NG group, the relative expressions of colonic hypoxanthine, betaine, creatine, inositol, taurine, uracil, and methanol of the TNBS group were decreased（P<0.05）, while the relative expressions of histidine, leucine, proline, lysine, isoleucine, phenylalanine, tyrosine, propionic acid, and valine were increased（P<0.05） in the TNBS group, among which, relative expressions of hypoxanthine, leucine, lysine, isoleucine, betaine, tyrosine, and taurine were reversed in the TNBS+MOX group relevant to the TNBS group, mainly involving phenylalanine, tyrosine and tryptophan biosynthesis, and taurine and subtaurine metabolism pathway. The mechanism of moxibustion at ST25 and ST37 for CD may be related to improving colon metabolic disorder state by regulating multiple metabolic metabolites and metabolic pathways, and reducing the level of inflammatory factors, so as to maintain intestinal immune homeostasis.

Effects of moxibustion at "Tianshu"（ST25） and "Shangjuxu" （ST37） on colonic metabolites and inflammatory factors in rats with Crohn's disease

To observe the effects of moxibustion at "Tianshu"（ST25） and "Shangjuxu"（ST37） on the colonic metabolites and inflammatory factors in rats with Crohn's disease（CD）, so as to explore the mechanisms of moxibustion in protecting colon of CD rats based on metabolomics. Twelve rats were first randomly selected from 36 male SD rats as a normal group（NG）. The CD model was induced by 2, 4, 6 trinitrobenzene sulfonic acid（TNBS） enema on the rest 24 rats. After successful modeling, rats were randomly divided into model（TNBS） and moxibustion（TNBS+MOX） groups（n=10 rats/group）. Moxibustion was applied at bilateral ST25 and ST37 for 30 min, once daily for 7 consecutive days in the TNBS+MOX group, while rats in the NG and TNBS groups did not receive any interventions. Body weight of rats was recorded and disease activity index（DAI） was assessed during the experiment. After interventions, HE staining was performed to observe pathological damage of colon. Serum levels of inflammatory factors were measured by ELISA. NMR hydrogen spectroscopy was used to detect colonic metabolites of each group, and orthogonal partial least squares discriminant analysis（OPLS-DA） was used to screen differential colonic metabolites between groups, followed by pathway analysis using MetaboAnalyst 5.0 platform. After modeling, compared with the NG group, the body weight of the rats in the TNBS group was significantly decreased（P<0.05）, the DAI score was increased （P<0.05）, the colon had obvious inflammatory damage and the pathological injury index was increased（P<0.05）, and levels of serum tumor necrosis factor-α（TNF-α）, interleukin（IL）-1β and interferon-γ（IFN-γ） were significantly increased（P<0.05）. After moxibustion intervention, compared with the TNBS group, the body weight was significantly increased（P<0.05）, while the levels of serum TNF-α, IL-1β, IFN-γ, and DAI score of the rats in the TNBS+MOX group were significantly decreased（P<0.05）, with alleviated colonic inflammatory injury detected by HE staining. Compared with the NG group, the relative expressions of colonic hypoxanthine, betaine, creatine, inositol, taurine, uracil, and methanol of the TNBS group were decreased（P<0.05）, while the relative expressions of histidine, leucine, proline, lysine, isoleucine, phenylalanine, tyrosine, propionic acid, and valine were increased（P<0.05） in the TNBS group, among which, relative expressions of hypoxanthine, leucine, lysine, isoleucine, betaine, tyrosine, and taurine were reversed in the TNBS+MOX group relevant to the TNBS group, mainly involving phenylalanine, tyrosine and tryptophan biosynthesis, and taurine and subtaurine metabolism pathway. The mechanism of moxibustion at ST25 and ST37 for CD may be related to improving colon metabolic disorder state by regulating multiple metabolic metabolites and metabolic pathways, and reducing the level of inflammatory factors, so as to maintain intestinal immune homeostasis.

Modeling the importance of fish condition, overall health, and disease on the fecundity of White Perch in the Choptank River.

Modeling of fecundity with allometric, nutritional, and environmental covariates has increased sensitivity of reproductive metrics in many fish species. In estuaries with heavy anthropogenic influence, resident species often experience sublethal health impacts because of increased stress, which can include increases in gonadal pathology, intersex, or potential reproductive failure. This study models the fecundity of the estuarine species White Perch Morone americana in response to health parameters identified as signals of habitat stress, including gross pathology presentation, nutritional condition, and disease presence. Subpopulation fecundity in the Choptank River (Maryland) of the Chesapeake Bay was estimated using stereological fecundity sampling methods and modeled using information-theoretic approaches of model selection. Nutritional and health parameters identified through health assessment techniques, specific somatic indices, and disease presence were selected as covariates. Nutrition demonstrated limited influence on model fit as compared to models with only conventional allometric variables such as weight and length. Of the health variables, gross pathology and somatic indices showed minimal influence on selection, but mycobacterial infection, a chronic condition in the Chesapeake Bay among temperate basses, showed measurable influence. Models with mycobacteriosis included were 40 times more likely the best fit when compared to models with only allometric parameters. Whether this has a region-wide influence on all subpopulations will require further research and sampling of the magnitude of mycobacteriosis infection.

Absence of ST-Segment Elevation in Inferior and Lateral Leads in Patients With Complete Right Bundle Branch Block Is an Index of Underlying Cardiac Pathology

A recent report called attention to the nature of the ST-segment elevation (STSE) in some or all inferior and/or lateral electrocardiogram (ECG) leads (i.e., I, II, III, aVL, aVF, V5, and V6), which are frequently encountered in patients with stable or transient complete right bundle branch block (RBBB). These STSEs represent secondary repolarization changes due to late depolarization RBBB alterations; are stable over the course of many years in patients with RBBB; and do not reflect cardiac pathology, as the automated ECG interpretation algorithms erroneously indicate. Indeed, the absence of such STSEs in patients with RBBB suggests the presence of underlying acute or old myocardial infarction, acute myocardial ischemia, or left ventricular hypertrophy and thus constitute an as yet undescribed ECG index of cardiovascular pathology.

Clinical significance of matrix metalloproteinase-9 expression in papillary thyroid carcinoma: a meta-analysis

ObjectiveThe purpose of this study was to investigate the relationship between the expression of matrix metalloproteinase-9 (MMP-9) and pathological indexes in papillary thyroid carcinoma (PTC).Evidence obtainedThe database was searched in PubMed, Embase, CNKI, and Web of Science databases for relevant clinical trials. The odds ratio (OR) and 95% confidence interval (CI) show the effect of MMP-9 expression and age, tumour size, gender, lymph node metastasis (LNM), and TNM (tumour, lymph node, metastasis) stage. Statistical analysis of the data was performed using Stata 17.0.Evidence synthesisA total of 1433 patients with PTC were included in this meta-analysis. MMP-9 expression was significantly correlated with LNM (OR = 3.92, 95% CI = 2.71–5.65, P = 0.000), tumour size (OR = 1.69, 95% CI = 1.13–2.52, P = 0.011), and TNM stage (OR = 2.95, 95% CI = 2.10–4.13, P = 0.000), but not with gender (OR = 0.90, 95% CI = 0.66–1.22, P = 0.487) and age (OR = 1.36, 95% CI = 0.93–1.98, P = 0.115).ConclusionsOur meta-analysis showed that MMP-9 was significantly associated with LNM, tumour size, and TNM stage; therefore, MMP-9 may be a reliable prognostic biomarker for patients with PTC. However, more high-quality studies are needed to support these findings further.

STRUCTURAL AND FUNCTIONAL PARAMETERS OF THE ENDOMETRIUM AND OVARIAN TISSUE IN PATIENTS WITH IMPAIRED REPRODUCTIVE POTENTIAL AND OBESITY

According to the WHO, every second woman has a problem with excess weight, while about 23% of women indicate a pathological body mass index, and excess weight (the so-called “pre-obesity”) is noted in 25% of women.&#x0D; The aim of the research was to evaluate the structural and functional parameters of the endometrium and ovarian tissue and to optimize the diagnostic algorithm and monitoring of the endometrium in women with obesity and impaired reproductive function.&#x0D; Materials and methods. 110 patients of reproductive age with impaired reproductive health underwent a comprehensive clinical and laboratory examination within the framework of this research. The main group included 64 patients with overweight and class 1 obesity, and the comparison group consisted of 46 women with a normal body mass index. The proposed diagnostic algorithm included a sonographic study of the structural parameters of the endometrium and ovaries, as well as an assessment of the features of the blood supply to the pelvic organs and statistical processing of the results.&#x0D; Research results and their discussion. The presented results allow us to note a significant percentage of comorbidity of somatic and gynecological pathology in overweight and obese patients. Pregnancy is accompanied by a higher percentage of early reproductive losses (14.0%), preterm birth (10.9%), preeclampsia (42.2%), placental dysfunction (46.4%) and low birth weight (17.2%). The main clinical forms of endometrial pathology in the main group were polyposis (32.8%), endometrial hyperplasia (23.4%) and dyschronosis of morphological changes of the endometrium (28.1%). The combination of endometrial hyperplasia with/or uterine leiomyoma, adenomyosis, benign ovarian tumors and retention formations was noted in 53.6% of observations in both groups; in 46.4% of women the isolated form was noted. The morphological characteristics of endometrial polyposis allowed us to note the dominance of glandular-fibrous polyps (45.2%) and in the case of a combination with myoma or ovarian retention cysts - glandular forms (32.3%). The most frequent sonographic marker of dysfunction of the endometrial potential (inconsistency of the ultrasound image of the endometrium with the phase of the menstrual cycle) was revealed in more than half of the cases (62.5%). Sonographic evaluation of the structural parameters of the endometrium and ovarian tissue showed an increase in the anterior-posterior size of the uterus and the thickness of the endometrium by 2.8 times, the volume of the ovary – by 2.0 times. It should be noted that the patients of the main group had a greater proportion of cysts and endometriomas. According to dopplerometry data, significantly lower parameters of the vascular resistance index were confirmed in the ovarian arteries and in the arteries of the stroma; in almost half of the observations, varicose veins of the parametrium were noted.&#x0D; Conclusions. Changes in steroidogenesis against the background of lipid metabolism disorders are accompanied by an increase in the volume of the endometrium and ovarian tissue, growing proportion of cystic formations in the appendages, an increase in the hemodynamic imbalance of blood flow in pelvic organs, which requires optimization of the monitoring program at the stage of preconception preparation and elimination of risk factors for placental dysfunction.

Renal interferon-inducible protein 16 expression is associated with disease activity and prognosis in lupus nephritis

BackgroundLupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). However, the current management of LN remains unsatisfactory due to sneaky symptoms during early stages and lack of reliable predictors of disease progression.MethodsBioinformatics and machine learning algorithms were initially used to explore the potential biomarkers for LN development. Identified biomarker expression was evaluated by immunohistochemistry (IHC) and multiplex immunofluorescence (IF) in 104 LN patients, 12 diabetic kidney disease (DKD) patients, 12 minimal change disease (MCD) patients, 12 IgA nephropathy (IgAN) patients and 14 normal controls (NC). The association of biomarker expression with clinicopathologic indices and prognosis was analyzed. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were utilized to explore potential mechanisms.ResultsInterferon-inducible protein 16 (IFI16) was identified as a potential biomarker for LN. IFI16 was highly expressed in the kidneys of LN patients compared to those with MCD, DKD, IgAN or NC. IFI16 co-localized with certain renal and inflammatory cells. Glomerular IFI16 expression was correlated with pathological activity indices of LN, while tubulointerstitial IFI16 expression was correlated with pathological chronicity indices. Renal IFI16 expression was positively associated with systemic lupus erythematosus disease activity index (SLEDAI) and serum creatinine while negatively related to baseline eGFR and serum complement C3. Additionally, higher IFI16 expression was closely related to poorer prognosis of LN patients. GSEA and GSVA suggested that IFI16 expression was involved in adaptive immune-related processes of LN.ConclusionRenal IFI16 expression is a potential biomarker for disease activity and clinical prognosis in LN patients. Renal IFI16 levels may be used to shed light on predicting the renal response and develop precise therapy for LN.

Low and High Ankle-Brachial Index Are Both Associated with Mortality in German Nursing Home Residents-The Five-Year Follow-Up of the "Allo-Study" Cohort.

Peripheral arterial disease (PAD) is associated with high cardiovascular morbidity and mortality. We aimed to examine this relation in a population that tends to be under-represented in research on the topic. In a prospective observational cohort study, residents of 45 nursing homes in Germany were screened for pathological ankle-brachial index (ABI) and observed for five years. Of 1333 participants (median age 84 years), 55.5% had a pathological ABI (≤0.9 or >1.4) on one or both legs. 84.7% of the probands with a low ABI (indicating PAD) had no previously known PAD diagnosis. The five-year mortality was 73.0%. Mortality was higher in individuals with a pathological ABI (76.5%) than in those with a normal ABI (68.7%, p = 0.003). An ABI > 1.4 was associated with a higher mortality (79.4%) than a reduced (74.7%) or normal ABI (68.7%, p = 0.011). Pathological ABI values were associated with an increase in mortality after correction for age, sex and all recorded comorbidities, including cardiac disease. Although PAD is highly prevalent in nursing home residents, it is underdiagnosed and undertreated. In the study cohort, both high and low ABI were important predictors of mortality. PAD deserves more attention in this high-risk population.

Grading of steatosis, fibrosis, lobular inflammation, and ballooning from liver pathology images using pre‐trained convolutional neural networks

AbstractThis study aims to automatically detect the degree of pathological indices as a reference method for detecting the severity and extent of various liver diseases from pathological images of liver tissue with the help of deep learning algorithms. Grading is done using a collection of pre‐trained convolutional neural networks, including DenseNet121, ResNet50, inceptionv3, MobileNet, EfficientNet‐b1, EfficientNet‐b4, Xception, NASNetMobile, and Vgg16. These algorithms are performed by fine‐tuning the trainable layers of the networks. The results showed that compared to other methods, the EfficientNet‐b1 network provides a better response to grade the stage of liver disease among all indicators from pathological images, due to its structural features. This classification accuracy was 97.26% for fibrosis, 94.1% for steatosis, 90.2% for lobular inflammation, and 98.0% for ballooning. Consequently, this fully automated framework can be very useful in clinical methods and be considered as an assistant or an alternative to the diagnosis of experienced pathologists.

#3428 DEPLETED HDAC3 ATTENUATES HYPERURICEMIA-INDUCED RENAL INTERSTITIAL FIBROSIS VIA MIR-19B-3P/SF3B3 AXIS

Abstract Background and Aims Hyperuricemia (HN) is a threat for the occurrence of renal interstitial fibrosis (RIF). Dysfunctional histone deacetylase 3 (HDAC3) elicit renal fibrosis and damage. This study aimed to explore the role of HDAC3 in HN-induced RIF from microRNA-19b-3p/splicing factor 3b subunit 3 (miR-19b-3p/SF3B3) axis. Method 1. The HN model was established on rats to induce RIF by oral administration of adenine and potassium oxalate; 2. HN rats were injected with related vectors (sh-HDAC3, mimic-miR-19b-3p, sh-HDAC3+miR-19b-3p inhibitor) to suppress and/or promote HDAC3 and/or miR-19b-3p; The detection indicators are listed as follows: (1) Blood samples and urine samples were collected for UA, BUN, Scr and 24 h urine protein measurement; (2) Renal pathological damages, RIF index and renal cell apoptosis were measured by HE, Masson and TUNEL staining; (3) α-SMA, TGF-β1 and FN contents in renal tissues were detected by IHC staining; (4) mRNA and protein levels of HDAC3, miR-19b-3p and SF3B3 in renal tissues were detected by RT-qPCR and/or WB. (5) Interaction of HDAC3 and miR-19b-3p was detected by ChIP and dual luciferase reporter gene assay; (6) Interaction of miR-19b-3p and SF3B3 was predicted/detected by bioinformatics website/dual luciferase reporter gene assay. Results 1. HN induced renal dysfunction, renal pathological damages, RIF and renal cell apoptosis of rats; HN rats showed elevated HDAC3, SF3B3 and reduced miR-19b-3p in renal tissues. 2. Suppressed HDAC3 or promoted miR-19b-3p relieved HN-induced renal dysfunction, renal pathological damages, RIF and renal cell apoptosis; HDAC3 bound to the promoter of miR-19b-3p; miR-19b-3p negatively regulated SF3B3; miR-19b-3p depletion abrogated down-regulated HDAC3-induced effects on HN-induced RIF. Conclusion HDAC3 bound to the promoter of miR-19b-3p to regulate SF3B3. Depressed HDAC3 relived HN-induced RIF by restoring miR-19b-3p and knocking down SF3B3. Targeting HDAC3 and miR-19b-3p/SF3B3 axis may be a promising therapeutic strategy for preventing HN-induced RIF.

Roghan Mālish ‘A Topical Formulation’ Attenuates Joint Pain, Down-Regulates C-Reactive Protein Level and Improves Quality of Life in Patients with Waja‘ al-Mafāṣil (NUMC: L-4) (Arthralgia) – A Pilot Clinical Study

Roghan Mālish is a cost effective topical application recommended for joint pain management. This prospective pilot study evaluated the safety, analgesic, and anti-inflammatory effect of Roghan Mālish in patients with arthralgia to validate the therapeutic claim and generate evidence for further studies. The study was conducted in patients with joint pain as chief complaint, with or without swelling and morning stiffness. The study was approved by Institutional ethic committee prior to initiation. Patients were advised to apply Roghan Mālish (2.5 mL/joint) followed by gentle massage in circular motion for 5 mins twice daily for 14 days. The efficacy was calculated from the reduction in Visual Analogue Scale (VAS), C-Reactive Protein (CRP) level and improvement in Quality of Life Scale (QOLS). Relevant pathological and biochemical indices and the observation of adverse events were used to evaluate the safety. A total number of 58 patients completed the trial with the mean age of 46.2 years and the majority (70.7%) being female. The overall therapeutic response was 93%. A significant (P&lt;0.05) decrease in VAS score and CRP level, and significant improvement in QOLS was observed after treatment with Roghan Mālish. No significant difference in pathological and biochemical indices was observed before and after treatment. Roghan Mālish was well tolerated upon topical application with no any undesirable side effects. The study results indicate that the topical application of Roghan Mālish is safe and may be used successfully to treat arthralgia.

Renal C4d is a potential biomarker of disease activity and severity in pediatric lupus nephritis patients.

Systemic lupus erythematosus (SLE), a multisystemic autoimmune disease, is very aggressive in pediatric-onset patients as they are prone to develop lupus nephritis (LN). Although renal C4d positivity is correlated with the activity of renal disease and SLE in adult-onset LN patients, available information for pediatric-onset patients is limited. To evaluate the potential diagnostic significance of renal C4d staining in pediatric LN patients, we retrospectively detected C4d staining by immunohistochemistry on renal biopsy specimens from 58 pediatric LN patients. The clinical and laboratory data at the time of the kidney biopsy and the renal disease activity of histological injury were analyzed according to the C4d staining status. Glomerular C4d (G-C4d)-positive staining was detected in all 58 cases of LN. Patients with a G-C4d score of 2 displayed more severe proteinuria than those with a G-C4d score of 1 (24-h urinary protein: 3.40 ± 3.55 g vs. 1.36 ± 1.24 g, P < 0.05). Peritubular capillary C4d (PTC-C4d) positivity was found in 34 of 58 LN patients (58.62%). The PTC-C4d-positive patient groups (patients with a PTC-C4d score of 1 or 2) had higher serum creatinine and blood urea nitrogen levels as well as renal pathological activity index (AI) and SLE disease activity index (SLEDAI) scores; however, they had lower serum complement C3 and C4 levels compared to PTC-C4d-negative patients (P < 0.05). In addition, there was positive tubular basement membrane C4d (TBM-C4d) staining in 11 of 58 LN patients (18.96%), and a higher proportion of TBM-C4d-positive patients than TBM-C4d-negative patients (63.63% vs. 21.27%) had hypertension. Our study revealed that G-C4d, PTC-C4d, and TMB-C4d were positively correlated with proteinuria, disease activity and severity, and hypertension, respectively, in pediatric LN patients. These data suggest that renal C4d is a potential biomarker for disease activity and severity in pediatric LN patients, providing insights into the development of novel identification and therapeutic approaches for pediatric-onset SLE with LN.