ObjectiveTo investigate the effects of artemisinin （ART） on histopathological damage and salivary secretion in the submandibular gland （SMG） of mice with Sjögren's syndrome （SS） model，and on the expression of aquaporin 5 （AQP5） in SMG cells. MethodsThe NOD/Ltj mice were used as a model of SS and randomly divided into the SS model group，the ART group，and the hydroxychloroquine sulfate （HCQ） group，with six mice per group. Another 6 female BALB/c mice at the same week were selected as the control group. Mice in the ART group was fed with the ART solution daily in the dosage of 50 mg·kg^-1，and mice in the HCQ group was given with the HCQ solution （1 300 mg·kg^-1）. Mice in the SS model and control groups were given saline daily. The treatment lasted for 8 weeks. The 24-hour average water intake，salivary flow rate，SMG pathology scores of mice in each group were measured，as well as the expression levels of AQP5 protein and gene in the SMG tissues. ResultsCompared with the control group，the 24-hour average water intake of mice in the model group was significantly increased （P<0.01），and the saliva flow rate was significantly decreased （P<0.01）. Compared to the SS model group，the 24-hour average water intake of mice in the ART and HCQ groups was significantly reduced （P<0.01），and the salivary flow rate was significantly increased in the ART group（P<0.01），comparisons between groups showed that the ART was superior to the HCQ in reducing water intake and improving saliva flow rate in SS model mice （P<0.05）. The HE staining results showed that，compared with the normal group，the number of lymphocyte infiltration foci in SMG tissue in the model group increased，and the pathological score increased （P<0.01）. Compared to the SS model group，after the intervention of the ART and HCQ，the number of lymphocytic infiltration foci in the SMG tissue decreased，the area of the lymphocytic infiltration foci was reduced，and the pathology score of the SMG tissues was lowered in the ART group（P<0.01）. However，there was no difference in pathological scores between the ART and HCQ groups . The results of IHC，Western blot，and Real-time PCR showed that，compared with the normal group，the expression levels of AQP5 protein and gene in SMG tissue in the model group significantly decreased （P<0.05）. Comparing with the SS model group，the ART and HCQ groups could significantly up-regulated the expression levels of AQP5 protein and mRNA in the SMG tissue，and the treatment effect was better than that of HCQ. ConclusionART was able to ameliorate SMG structural damage and salivary secretion function in SS model mice，and its mechanism of action may be related to the up-regulation of AQP5 protein and gene expression levels in SMG cells.

Degenerative cervical myelopathy(DCM)is a group of diseases caused by cervical spine degeneration that compresses the spinal cord.It is a major cause of spinal cord dysfunction in adults,and its incidence is increasing globally.In the late stage,DCM could lead to paralysis due to spinal cord injury,which makes rapid,effective,and accurate medical diagnosis clinically significant.Deep learning(DL)technology can assist physicians in the rapid and accurate diagnosis of DCM by analyzing and processing a large amount of imaging data to extract features of the affected regions.In recent years,DL algorithm models have been leveraged for DCM-related research,which has become a focal point of intelligent medical development.In this review,domestic and international literature is surveyed,and the research progress and application of DL technology in the auxiliary diagnosis and prognosis evaluation of DCM are systematically summarized,aiming to provide a reference for intelligent diagnosis in clinical practice.

Advancements in artificial intelligence(AI)and emerging technologies are rapidly expanding the exploration of chemical space,facilitating innovative drug discovery.However,the transformation of novel compounds into safe and effective drugs remains a lengthy,high-risk,and costly process.Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development.Despite this need,no comprehensive tool currently supports systematic evaluation and efficient screening.Here,we present druglikeFilter,a deep learning-based framework designed to assess drug-likeness across four critical dimensions:1)physicochemical rule evaluated by systematic determination,2)toxicity alert investigated from multiple perspectives,3)binding affinity measured by dual-path analysis,and 4)compound synthesizability assessed by retro-route prediction.By enabling automated,multidimensional filtering of compound libraries,druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates,which can be freely accessed at https://idrblab.org/drugfilter/.

OBJECTIVE: To analyze a Chinese pedigree affected with Non-syndromic autosomal recessive deafness type 12 (NFNB12), validate the function of candidate variants, and explore the underlying mechanisms. METHODS: A NFNB12 pedigree presented at Henan Provincial People's Hospital in February 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing of the pedigree members. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the level of mRNA transcription in the peripheral blood samples from the pedigree members, and protein expression was evaluated with Western blotting assay. This study was approved by Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2019-134). RESULTS: WES analysis revealed that the proband has harbored homozygous c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene, for which both parents were identified as heterozygous carriers. RT-PCR analysis demonstrated the sole presence of the variant mRNA in the proband, and both the variant and wild-type mRNAs in both parents. Furthermore, Western blotting analysis indicated that the proband had exclusively expressed the truncated CDH23 protein, while both the normal and truncated forms of the protein were noted in her parents. CONCLUSION The c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene probably underlay the pathogenesis of NFNB12 in this pedigree. The loss of function of the CDH23 gene resulting from this variant is not related with nonsense-mediated mRNA decay, but rather production of a truncated protein. Above finding has not only enriched the mutational spectrum of the CDH23 gene and offered a method for investigating the function of its variants using peripheral blood samples, but also delineated the molecular basis for the loss of function, which has provided crucial evidence for genetic counseling and prenatal diagnosis for this family.
Humans ; Pedigree ; Male ; Female ; Asian People/genetics* ; Cadherins/genetics* ; Exome Sequencing ; Deafness/genetics* ; Mutation ; China ; Adult ; Cadherin Related Proteins ; Hearing Loss, Sensorineural/genetics* ; East Asian People

Objective To observe the effects of Shenfu Injection on ferroptosis-related factors and oxidative stress-related indexes in rat cardiomyocytes treated with isoproterenol;To explore its mechanism in treating chronic heart failure.Methods Isoproterenol was used to induce rat H9c2 cardiomyocyte injury.The cells were divided into normal group,model group,Shenfu Injection group and Ferrostatin-1 group,and treated with corresponding intervention.Transmission electron microscopy was used to observe the ultrastructure of cellular mitochondria,ferrous ion fluorescent probe was used to detect Fe2+content in cells,flow cytometry was used to detect intracellular contents of ROS and Lipid-ROS;colorimetry was used to detect the contents of MDA,GSH,SOD and GSH-Px in cells;Western blot and RT-qPCR were used to detect the protein and mRNA expressions of GPX4,FTH1,SLC7A11,p53,COX2 and Nrf2 in cells.Results Compared with the normal group,the survival rate of H9c2 cells in the model group was significantly reduced(P<0.01),with cell swelling and rupture,mitochondrial shrinkage,decreased quantity and disordered arrangement,more damaged mitochondria,the contents of Fe2+,ROS,Lipid-ROS and MDA in cells significantly increased(P<0.01),while the contents of GSH,SOD and GSH-Px significantly decreased(P<0.01),the expressions of p53,COX2 protein and mRNA significantly increased(P<0.01),the expressions of GPX4,FTH1,SLC7A11 and Nrf2 protein and mRNA significantly decreased(P<0.01).Compared with the model group,the survival rates of H9c2 cells in Shenfu Injection group and Ferrostatin-1 group significantly increased(P<0.01),there was a larger number of normal mitochondria and a more complete structure,the contents of Fe2+,ROS,Lipid-ROS and MDA in cells were significantly decreased(P<0.01),while the contents of GSH,SOD and GSH-Px were significantly increased(P<0.05,P<0.01),the expressions of p53,COX2 protein and mRNA were significantly decreased(P<0.05,P<0.01),while the expressions of GPX4,FTH1,SLC7A11 and Nrf2 protein and mRNA significantly increased(P<0.01).Conclusion Shenfu Injection can reduce p53 expression,weaken its inhibitory effect on SLC7A11,thereby promoting GPX4 expression,inhibiting ferroptosis,reducing lipid peroxide accumulation,increasing cellular antioxidant capacity,and alleviating myocardial cell oxidative damage.

Objective:To evaluate the efficacy of lamb′s tripe extract and vitamin B 12 capsule (LTEVB 12C) on chronic atrophic gastritis (CAG) at different locations (antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and corpus greater curvature). Methods:From August 2011 to January 2013, 715 patients with CAG in a multicenter, randomized, double-blind, placebo-controlled trial were enrolled from 16 tertiary first-class hospitals across the country, including the First Affiliated Hospital of Air Force Medical University, Nanfang Hospital of Southern Medical University, the First Hospital of Jilin University, West China Hospital of Sichuan University, etc., there were 476 cases in the LTEVB 12C group and 239 cases in the placebo group. The patients of the LTEVB 12C group received LTEVB 12C, and the patients of placebo group received LTEVB 12C mimetic, all the medications were taken 3 capsules each time and 3 times a day after meals, and the treatment course of 2 groups were both 6 months. The efficacy evaluation criteria included the effective rate (a decrease of ≥1 in histopathological score compared with baseline after 6 months of treatment) and the reversal rate (a decrease of ≥ 2 in histopathological score compared with baseline after 6 months of treatment in the patients with moderate to severe CAG). The impact of lesion sites on the therapeutic effects of LTEVB 12C was analyzed by logistic regression analysis. The two-way unordered Cochran-Mantel-Haenszel chi-square test considering the center effect and Pearson chi-square test were used for statistical analysis. Results:The effective rates of chronic inflammation at the antrum greater curvature and corpus greater curvature (23.3%, 110/473 vs. 13.0%, 31/239; 20.3%, 96/472 vs. 12.6%, 30/239), the effective rates of atrophy at the antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and the corpus greater curvature (27.0%, 118/437 vs. 15.7%, 34/216; 29.2%, 126/432 vs. 18.5%, 38/205; 27.8%, 121/435 vs. 16.7%, 36/216; 32.5%, 127/391 vs. 19.8%, 37/187; 33.0%, 119/361 vs. 21.8%, 39/179), and the effective rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (45.0%, 112/249 vs. 29.8%, 31/104; 53.8%, 86/160 vs. 33.9%, 21/62; 45.8%, 103/225 vs. 24.0%, 25/104; 51.9%, 83/160 vs. 28.3%, 17/60) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=10.76, 6.39, 9.69, 7.91, 11.05, 9.62, 8.57, 5.20, 7.11, 12.45, and 6.73; all P<0.05). The reversal rates of chronic inflammation at the corpus lesser curvature and corpus greater curvature (5.2%, 12/231 vs. 0, 0/123; 4.7%, 8/170 vs. 0, 0/88), the reversal rates of atrophy at the antrum lesser curvature, antrum greater curvature, corpus lesser curvature, and the corpus greater curvature (6.8%, 22/323 vs. 1.3%, 2/151; 9.2%, 29/315 vs. 1.4%, 2/144; 14.2%, 38/267 vs. 2.5%, 3/121; 20.8%, 35/168 vs. 5.8%, 4/69), and the reversal rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (29.8%, 39/131 vs. 9.1%, 4/44; 41.0%, 32/78 vs. 12.5%, 3/24; 33.3%, 44/132 vs. 4.8%, 3/63; 50.0%, 37/74 vs. 8.7%, 2/23) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=6.58, 5.12, 5.60, 8.61, 11.43, 6.59, 7.30, 4.95, 15.92, 7.62; all P<0.05). There were no statistically significant differences in the effective rates and reversal rates of active inflammation at different locations between the LTEVB 12C group and the placebo group (all P>0.05). The results of logistic regression analysis (taking the antrum lesser curvature as the reference) further confirmed that the reversal rates of chronic inflammation ( OR=0.22, 95% confidence interval (95% CI): 0.07 to 0.67; OR=0.24, 95% CI: 0.07 to 0.80), atrophy ( OR=0.28, 95% CI: 0.16 to 0.49; OR=0.28, 95% CI: 0.16 to 0.49), and intestinal metaplasia ( OR=0.42, 95% CI: 0.24 to 0.77; OR=0.20, 95% CI: 0.08 to 0.52) at the corpus lesser curvature and corpus greater curvature were all higher than those at the antrum lesser curvature, and the differences were statistically significant (all P<0.05). There were no statistically siginificant differences in the reversal rates of the aforementioned pathological features between the antrum greater curvature, gastric angle, and the antrum lesser curvature (all P>0.05). Conclusion:LTEVB 12C can achieve good efficacy in the treatment of CAG, and the chronic inflammation, atrophy, and intestinal metaplasia at multiple locations are improved, especially at the corpus lesser curvature and the corpus greater curvature.

Objective:To Analysis of the current status of occupational hazard factors of 1, 2-dichloroethane (1, 2-DCE) in workplaces of enterprises in a certain district of Chongqing City, to provide a basis for its prevention and control.Methods:In January 2024, the monitoring data from the 2023 key occupational disease survey in the district were collected and organized. Qualitative analysis was conducted on the organic solvents used by enterprises in their production processes, and the detection results of 1, 2-DCE were statistically analyzed.Results:A total of 88 organic solvent samples were collected, with a qualitative detection rate of 21.6% (19/88) for 1, 2-DCE. A total of 30 enterprises using organic solvents were surveyed and tested, with an enterprise detection rate of 36.7% (11/30) for 1, 2-DCE. The workplace exceedance rate for 1, 2-DCE was 37.0% (34/92), and the post exceedance rate was 15.4% (4/26) .Conclusion:The degree of occupational exposure hazard related to 1, 2-DCE remains severe. It is necessary to strengthen the management of organic solvents used by enterprises and implement effective measures to prevent acute and chronic poisoning caused by 1, 2-DCE.

Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*

Objective:To investigate whether intermittent fasting alleviates insulin resistance in a polycystic ovary syndrome(PCOS) mouse model through the regulation of autophagy.Methods:Fifty 3-week-old female C57BL/6J mice were randomly assigned into the following groups using a random number table: normal control(NC) group( n=10), maintained on a standard chow diet; high-fat diet(HFD) group( n=10) fed a diet with 60% of calories derived from fat; and PCOS model group( n=30), established by combining a HFD with dehydroepiandrosterone(DHEA) administration. Successful modeling was confirmed by disrupted estrous cycles, hyperandrogenism, and polycystic ovarian morphology. The PCOS model mice were further divided into three groups: PCOS group( n=9), PCOS with intermittent fasting group(PCOS+ IF, n=9), and PCOS with intermittent fasting plus the autophagy inhibitor 3-methyladenine(3-MA) group(PCOS+ IF+ 3-MA, n=9). Autophagy levels were assessed by detecting markers LC3 and p62 and observing autophagosomes via transmission electron microscopy. Glucose tolerance test(GTT) and insulin tolerance test(ITT) were performed, and the area under the curve(AUC) was calculated to evaluate insulin resistance. Western blotting was used to detect phosphorylation levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(Akt), mammalian target of rapamycin(mTOR), and p70S6 kiase(p70S6K). Results:Compared with the NC group, the PCOS model group showed absent estrous cycles, significantly elevated serum testosterone, sex hormone binding globulin, and luteinizing hormone(LH) levels( P<0.001), and polycystic ovarian changes on hematoxylin-eosin staining, confirming successful model establishment. Immunohistochemistry, transmission electron microscopy, and Western blotting demonstrated that autophagy levels were increased in the PCOS+ IF group compared with the PCOS group, while 3-MA administration reduced the intermittent fasting - induced autophagy. The AUC values for both GTT and ITT were significantly lower in the PCOS+ IF group than those in the PCOS group( P<0.001, P=0.003), but increased in the PCOS+ IF+ 3-MA group compared to the PCOS+ IF group( P<0.001, P=0.020). Western blotting analysis showed that phosphorylation levels of PI3K, Akt, mTOR, and p70S6K were significantly decreased in the PCOS+ IF group compared with the PCOS group( P=0.002, P=0.001, P=0.001, and P<0.001, respectively), and increased in the PCOS+ IF+ 3-MA group compared with the PCOS+ IF group( P=0.021, P=0.041, P=0.047, and P=0.024, respectively). Conclusions:Intermittent fasting alleviates insulin resistance in a PCOS mouse model through inhibitiing PI3K/Akt/mTOR signaling pathway and promoting autophagy.