ObjectiveTo investigate the effect of 1，25（OH）₂D₃ on the level of peroxisome proliferator-activated receptor-γ （PPAR-γ） in the liver， the phenotype of hepatic macrophages， and liver inflammation in a rat model of nonalcoholic steatohepatitis （NASH）， as well as the mechanism of 1，25（OH）₂D₃ improving liver inflammation. MethodsAfter 1 week of adaptive feeding， 24 specific pathogen-free Wistar rats were randomly divided into normal group ［choline-supplemented L-amino acid-defined （CSAA） diet］， normal+1，25（OH）₂D₃ group ［CSAA diet+1，25（OH）₂D₃］， model group ［choline-deficient L-amino acid-defined diet （CDAA） diet］， and model+1，25（OH）₂D₃ group ［CDAA diet+1，25（OH）₂D₃］， with 6 rats in each group. The dose of 1，25（OH）₂D₃ was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） were measured， liver histopathology was observed， and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages， and ELISA was used to measure the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in liver tissue， and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups， and the least significant difference t-test was used for further comparison； the Pearson method was used for correlation analysis. ResultsCompared with the normal group， the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT （P=0.019 and P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P<0.001）， as well as a significant increase in the level of TNF-α （P<0.001） and a significant reduction in the level of IL-4 in liver tissue （P=0.025）. The 1，25（OH）₂D₃ group had significant reductions in the serum levels of ALT （P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P=0.001）， the level of IL-1β （P<0.001） and a significant increase in the level of M2 hepatic macrophages （P=0.017）， the level of IL-10 （P=0.039）， the level of IL-4 （P<0.001）， the level of PPAR-γ （P=0.016）. There were significant interactions between CDAA diet-induced NASH model and 1，25（OH）₂D₃ in serum the levels of AST and ALT （P=0.007 and P=0.008）， the SAF scores of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， the level of M2 hepatic macrophages （P=0.008）， the ratio of M1 and M2 of hepatic macrophages （P=0.005）， the level of TNF-α （P<0.001）， the level of IL-10 （P=0.038）， the level of IL-4 （P<0.001） and the level of PPAR-γ （P=0.009）. The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages （r=-0.415， P=0.044） and was positively correlated with M2 hepatic macrophages （r=0.435， P=0.033）， IL-10 （r=0.433， P=0.035）， and IL-4 （r=0.532， P=0.007）. ConclusionThis study shows that 1，25（OH）₂D₃ improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.

As an important strategy in antiviral drug development, nucleoside analogs (NAs) have attracted considerable attention due to their unique mechanisms of action and favorable safety profile. This review systematically summarizes recent advances in the mechanisms of action of NAs, focusing on the following four aspects: (1) Targeting viral polymerases, inhibiting viral replication through mechanisms such as non-absolute termination, delayed chain termination and induction of viral RNA mutations in addition to classical chain termination, which has been newly discovered; (2) Regulating RNA methylation modifications—for instance, competitively inhibiting methyltransferases, which significantly reduces viral replication efficiency; (3) Depleting nucleotide pools—by affecting host cell purine nucleotide synthesis pathways, thereby indirectly inhibiting viral replication; and (4) Immunomodulatory functions—including activation of the STING pathway to promote interferon production. Furthermore, this review systematically discusses the breakthrough progress in prodrug technologies for addressing key clinical challenges such as drug resistance and off-target toxicity of NAs. These advances provide crucial technical support for the clinical translation of NAs. These advances provide key technical support for the clinical translation of NAs. This review clarifies the multi-target action rules of NAs and provides a theoretical framework for the design of next-generation broad-spectrum antiviral agents.

Objective:To investigate the current situation of satisfaction with graduate education among recent medical graduates in China, and analyze the differences between different populations, and to propose countermeasures and suggestions.Methods:From June to July 2023, a self-made questionnaire was used to survey 16 903 medical graduates who had recently earned a post-graduate degree from 78 institutions about their satisfaction with curriculum sessions, practical sessions, research training, tutoring, and institutional management. The degrees of satisfaction with education among different populations were compared through the t test and analysis of variance with the use of SPSS 26.0. Results:The scores of satisfaction of the graduates with tutoring, curriculum sessions, practical sessions, institutional management, and research training were 4.44, 4.03, 4.02, 3.90, and 3.82, respectively. Satisfaction scores for individual dimensions were significantly higher for males, doctors, non-transfers, comprehensive universities, non-agricultural household registration, moderate-to-high annual household income per capita, parents with high educational levels, and parents with mid- or senior-level occupations ( P<0.05). Conclusions:There is room for improvement in students' satisfaction with medical graduate education. To improve the quality of medical graduate education, attention should be paid to key populations, education policies, school management, and tutoring to provide appropriate education for different students.

Objective:To study the changes in serum small molecule metabolites after brucella infection in humans using untargeted metabolomics methods, and screening representative biomarkers. Methods:A total of 109 serum samples collected from January 2019 to December 2021 at the Brucellosis Clinic of the Baotou Center for Disease Control and Prevention were divided into acute phase group ( n = 40), chronic phase group ( n = 35) of brucellosis, and healthy group ( n = 34) based on clinical diagnosis. Ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry technology was used to test serum samples and screen for differential metabolites. Receiver operating characteristic curve was used to evaluate the predictive ability of differential metabolites for brucellosis. Enriched pathways were screened using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to identify metabolic pathways significantly affected. Results:A total of 17 differential metabolites were screened between the acute phase group and the healthy group, and 12 differential metabolites were screened between the chronic phase group and the healthy group. There were a total of 5 differential metabolites (oleamide, linoleamide, stearamide, palmitoleic acid, α-linolenic acid) statistically significant among the three groups ( F = 16.84, 17.52, 14.31, 13.01, 20.76, P < 0.05). KEGG pathway analysis showed that the differential metabolites in the acute phase group were enriched in metabolic pathways such as ether lipid metabolism, glycerophosphate metabolism, sphingolipid signal and sphingolipid metabolism. The differential metabolites in the chronic phase group were enriched in metabolic pathways such as glycerophosphate metabolism, ether lipid metabolism, protein digestion and absorption metabolism. Conclusion:Untargeted metabolomics methods can screen out serum small molecule metabolites that undergo changes after brucella infection in the human body, including oleamide, linoleamide, stearamide, palmitoleic acid, α-linolenic acid can serve as potential biomarkers to distinguish brucellosis patients from healthy people.

Objective Explore changes in polysaccharides in Jiangxiangru before and after ginger juice preparation,and evaluate polysaccharide anti-inflammatory and antioxidant activities before and after processing.Methods The contents of Jiangxiangru polysaccharide(JXRPs)and Ginger juice processed of Jiangxiangru polysaccharide(JZJXRPs)before and after processing were determined by phenol-sulfuric acid method.We used the swelling model in rats and endotoxin(LPS)to establish the RAW264.7 mouse macrophage inflammation model.The optimal administration concentration was determined using a cell proliferation(MTT)assay.Enzyme-linked immunosorbent assay(ELISA)were used to measure Interleukin-6(IL-6),Interleukin-12(IL-12),Nitric oxide(NO),Interleukin-4(IL-4),and Interleukin-10(IL-10).Bleeding time of mice by tail cutting was observed to evaluate the hemostatic effect.The ability to remove 1,1-diphenyl-2-picryl-hydrazyl radical(DPPH)and 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate)(ABTS)was used to evaluate in vitro antioxidant activity.Results The contents of JXRPs and JZJXRPs were 13％and 22％,respectively.In swollen rats at 4 h after injection,compared with the model group,200 mg/kg JXRPs and 100 mg/kg JZJXRPs significantly reduced rat swelling(P＜0.05).In vitro anti-inflammation assessment showed that the polysaccharides before and after processing significantly inhibited secretion of IL-6,IL-12,and NO(P＜0.01)and promoted secretion of IL-4 and IL-10(P＜0.01),and also that processing post-effects were stronger.The hemostatic experiment show that,compared with the control group,JXRPs increased hemostasis,but without a significant difference,and no significant difference was found using JZJXRPs,although high doses showed a trend to increase hemostasis.In vitro antioxidant activity showed that JXRPs and JZJXRPs had different scavenging abilities for DPPH and ABTS with IC50 values of JXRPs of 0.2215 and 0.2110 mg/ml,respectively,and IC50 values of JZJXRPs of 0.1651 and 0.1884 mg/mL,respectively.Conclusions After Jiangxiangru is produced in ginger juice,it promotes dissolution of polysaccharides and increases polysaccharide content.Anti-inflammatory,hemostasis,and antioxidant capacities are stronger in JZJXRPS than JXRPS,which lays the foundation for follow-up research and clinical applications of JXRPS.

ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules （百蕊颗粒） in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter， double-blind， double-simulation， randomised controlled trial was conducted， in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited， and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group， 108 cases were orally administered with Bairui Granules plus Reyanning Granules （热炎宁颗粒） simulant， and in the control group， 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days， with a follow-up visit on the 6th day. Full analysis set （FAS） analysis and per protocol set （PPS） were used for analysis， respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment； the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment， as well as the visual analogue score （VAS） of sore throat before treatment， every day during the treatment， and follow-up on day 6， and the traditional Chinese medicine （TCM） syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6， and the changes of vital signs， blood routine， urine routine， liver functions， kidney function， the adverse events before and after the treatment were recorded， and safety analysis set （SS） was analysed. Results162 patients entered the FAS and SS analyses， and 158 cases （105 cases in the trial group and 53 cases in the control group） entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% （87/108） in the trial group and 64.81% （35/54） in the control group， and the difference between groups was statistically significant （χ² = 5.10， P = 0.0239）. PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% （84/105） in the trial group and 64.15% （34/53） in the control group， and the difference between groups was statistically significant （χ² =4.85， P = 0.0277）. FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant （P＞0.05）. Compared with those before treatment， the VAS scores of sore throat were lower in both groups during treatment on day 2， 3， 4， 5， and follow-up on day 6 （P＜0.01）， but the difference between groups at each time point was not statistically significant （P＞0.05）. TCM syndrome scores of both groups at the follow-up were lower than that before treatment， and those of the trial group were lower than those of the control group （P＜0.01）. The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group （P＜0.01）. There was no significant difference in blood routine， urine routine， liver function， kidney function between groups before and after treatment （P＞0.05）， and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome， and it could significantly improve the clinical symptoms， accelerate the disappearance time of sore throat with good safety.

ObjectiveTo determine the syndrome of a rat model of follicular dysplasia induced by Tripterygium glycosides based on prescriptions and investigate the mechanism of traditional Chinese medicine intervention via the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/hypoxia-inducible factor-1 （HIF-1）/vascular endothelial growth factor （VEGF） pathway. MethodForty-eight rats with regular estrous cycles were randomly assigned into a normal group （n=8） and a modeling group （n=40）. The rats in the modeling group were administrated with Tripterygium glycoside suspension （75 mL·kg^-1） by gavage for 30 days. The modeled rats were assigned into model， Siwutang （3.69 g·kg^-1）， Youguiyin （3.11 g·kg^-1）， Zuoguiyin （7.29 g·kg^-1）， and Guishenwan （10.35 g·kg^-1） groups， with 8 rats in each group. The drug intervention lasted for 14 days. The changes of estrous cycle were detected by Pap staining， and a stereoscope was used to observe the morphology of the ovarian tissue. Hematoxylin-eosin staining was employed to observe the pathological changes and follicle count in the ovarian tissue. Enzyme-related immunosorbent assay （ELISA） was used to measure the levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E₂） in the serum. Real-time fluorescence quantitative polymerase chain reaction and Western blot were employed to determine the mRNA and protein levels， respectively， of AMPK， mTOR， HIF-1， and VEGF in the ovarian tissue. ResultCompared with the normal group， the model group had a disordered estrous cycle， reduced secondary and mature follicles， increased atretic follicles， elevated FSH and LH levels， lowered E₂ level， up-regulated mRNA and protein levels of AMPK， and down-regulated mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with the model group， Guishenwan increased secondary and mature follicles， decreased atretic follicles， lowered the FSH and LH levels， elevated the E₂ level， down-regulated the mRNA and protein levels of AMPK， and up-regulated the mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with Guishenwan group， Siwutang， Youguiyin， and Zuoguiyin decreased mature follicles， increased atretic follicles （P<0.01）， elevated the LH （P<0.01） and FSH （P<0.05） levels， and lowered the E₂ level （P<0.05）. In addition， Youguiyin up-regulated the protein level of AMPK （P<0.05） and down-regulated the mRNA levels of mTOR and HIF-1 （P<0.01） as well as the mRNA and protein levels of VEGF （P<0.01）. Siwutang down-regulated the mRNA levels of mTOR and HIF-1 as well as the mRNA and protein levels of VEGF （P<0.05）. Zuoguiyin down-regulated the mRNA level of mTOR and the protein and mRNA levels of VEGF （P<0.05）. ConclusionGuishenwan may improve the ovarian function and promote follicle maturation in a rat model of follicular dysplasia by inhibiting the AMPK/mTOR/HIF-1/VEGF pathway， with the therapeutic effect superior to Zuoguiyin， Youguiyin， and Siwutang. It was hypothesized that this model presented the syndrome of kidney-essence deficiency.

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

Objective:To investigate the enrollment scale and distribution of Master's Degree in Pediatrics programs in China, and to provide a reference for promoting pediatric education and disciplinary development.Methods:Data on colleges and universities authorized to award Master's Degree in Pediatrics in 2023 were collected, sorted, and analyzed for the number, structure, distribution, and enrollment scale and direction of these institutions using descriptive statistics.Results:Among the 117 clinical medicine academic master's degree programs in China, 72 enroll pediatric academic master's degree candidates, with an enrollment of 260 students. Among the 120 master's degree programs in clinical medicine, 104 enroll professional master's degree candidates, enrolling 1 195 students. Enrollment is mainly concentrated in East China, "non-double first-class" colleges and universities, medical colleges and universities with subject level B, and enrollment is carried out in the direction of secondary disciplines.Conclusions:The number of colleges and universities authorized to award Master's Degree in Pediatrics was small, and the distribution of these colleges and universities was unbalanced. The enrollment scale was small and the orientation of Professional Master's Degree was not reasonable. Some colleges and universities were authorized to award Master's Degree in Pediatrics, but did not enroll any students. It is suggested to increase the number of colleges and universities authorized to award Master's Degree in Pediatrics and strengthen the staffing of pediatric departments. The aim is to expand the enrollment scale of candidates for Master's Degree in Pediatrics, improving the differential training of candidates for Academic Master's Degree and Professional Master's Degree, and attach importance to the construction of pediatrics.