Thymocyte selection-associated high mobility group box (TOX), a member of the high mobility group protein super-family, plays an important role in T cell development, functional maintenance, and exhaustion. It has been recently found that TOX exerts critical immunoregulatory functions during pathogen infections, and TOX expression is strongly associated with the intensity and tolerance of host immune responses. This review systematically summarizes the structural and functional features of TOX and focuses on its expression dynamics, mechanisms of action, and immunomodulatory effects during viral, bacterial, and parasitic infections, which provides a theoretical support to better understanding of the role of TOX in infectious diseases and provides new insights into development of potential immunotherapeutic strategies targeting TOX.

Aim To establish limited sampling strategy to esti-mate area under the drug concentration versus time curve(AUC0-t)of lymphoma patients treated with autologous stem cell transplantation(ASCT)who had busulfan intravenous infu-sion.Methods Twelve lymphoma patients treated with ASCT received a conditioning regimen containing busulfan 105 mg·m-2,Ⅳ infusion for 3 h.Blood samples were obtained 1 h after the start of the first dose of the busulfan infusion,at 5 min,1 h,2 h,4 h,6 h and 18 h after the end of the drug administration.LC-MS/MS was used to determine the busulfan serum concentra-tion.After obtaining the clinical pharmacokinetic parameters of busulfan by traditional pharmacokinetic method,multiple linear stepwise regression analysis was used to establish the AUC0-t es-timation model of busulfan based on limited sampling method.The model was further verified by Jackknife and Bootstrap meth-od.Bland-Altman plots were used to evaluate the consistency between the limited sampling method and the classical pharma-cokinetic method.Results The multiple linear regression equa-tion analysis of C60min,C180min and C300min was obtained by the limited sampling method.The regression equation was AUC0-t=295.003C60min+233.050C180min+273.163C300min-1202.713,r2=0.995,MPE=-0.87％,RMSE=2.40％.Conclusion The limited sampling model with three-point estimation can be used to estimate the AUC0-t of busulfan exposure in lymphoma patients with ASCT to provide reference for clinical application of busulfan.

Gastric ulcer is a common digestive system disease,and the long-term use of non-steroidal anti-inflammatory drugs(NSAIDs)is the second most important cause.NSAID-induced gastric ulcer animal models are key experimental tools for studying the pathogenesis,corresponding treatment method,and effective mechanisms of NSAID-induced gastrointestinal injury.However,there are currently a lack of reviews on NSAID-induced gastric ulcer animal models.This review summarizes and compares the relevant literature on animal research into indomethacin-and aspirin-induced gastric ulcers in the past 10 years,including the selection of experimental animals,drug solvents,and specific modeling method.The limitations of current models,such as the cumbersome modeling method,incomplete modeling details,inadequate models for clinical use,and lack of comparative drug research,are discussed.Feasible solutions are proposed with the aim of providing an effective reference for research in this field.

Objective:To analyze the construction of human resources in specialized public health institutions in China,with a view to providing reference for strengthening the construction of human resources in public health in China.Methods:Based on the data of China Health and Wellness Statistical Yearbook,descriptive statistical analysis,Gini coefficient and health resource agglomeration were used to analyze the quantity and quality of human resources in specialized public health institutions and the equity of human resource allocation in different regions of China from 2012 to 2021.Results:From 2012 to 2021,the average annual growth rate of the number of specialized public health institution personnel nationwide was 4.10%,and the average annual growth rate of the number of specialized public health institution personnel per 1 000 population was 3.71%.In 2021,the Gini coefficient of human resources in China's specialized public health institutions allocated by population was 0.1002,and the Gini coefficient of the allocation of human resources according to the geographic area was 0.6706,and 21 provinces'health resource agglomeration value were greater than 1.Conclusion:the total amount of human resources in China's specialized public health institutions has steadily increased during the decade,and the quality has been greatly improved,but there is still a gap with the expected development goal;the development of human resources in different specialized public health institutions is not balanced;demographic fairness is better than geographic fairness in the allocation of human resources in public health,and there are significant inter-provincial differences.

Objective To investigate the effect of plasma microRNA(miR)-93-5p on ovarian granulosa cell proliferation in patients with polycystic ovary syndrome(PCOS)and its possible mechanism.Methods A total of 120 PCOS patients of childbearing period who were treated at Jiaozuo People's Hospital from January 2022 to January 2023 were selected as the PCOS group,and 18 healthy women of childbearing period who were physically examined at the same hospital during the same period were selected as the control group.The age,body weight and height of the subjects in the two groups were recorded,and the body mass index(BMI)was calculated.Fasting venous blood was collected from the subjects during the follicular phase of the natural menstrual cycle or the progesterone-induced withdrawal bleeding phase,and serum levels of luteinizing hormone(LH),follicle-stimulating hormone(FSH),total testosterone(TT),anti-Mullerian hormone(AMH),aspartate aminotransferase(AST),alanine aminotransferase(ALT),fasting insulin(FINS),and fasting blood glucose(FBG)were measured by using the electrochemical method;and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression level of miR-93-5p in plasma of patients in the two groups.Human ovarian granulosa cells(KGN cells)in logarithmic growth phase were cultured in 6-well plates with 3 × 105 cells per well,and they were randomly divided into the miR-93-5p mimics group,LY294002+miR-93-5p group,AZD5363+miR-93-5p group,negative control(NC)group,and blank control group.The KGN cells in the miR-93-5p group were transfected with miR-93-5p mimics;the KGN cells in the LY294002+miR-93-5p group were transfected with miR-93-5p mimics and treated with 50 mmol·L-1 LY294002 one hour before transfection;the KGN cells in the AZD5363+miR-93-5p group were transfected with miR-93-5p mimics and treated with 50 μmol·L-1 AZD5363 one hour before transfection;the KGN cells in the NC group were transfected with the negative control plasmids;and the KGN cells in the blank control group were not treated at all.The expression of miR-93-5p in the KGN cells in each group was detected by qRT-PCR,and the proliferation of the KGN cells in each group was detected by cell counting kit-8.Results There was no significant differences in age,FSH,ALT,and AST levels of patients between the PCOS group and the blank control group(P＞0.05).The BMI,TT,AMH,LH,FINS,FBG,and HOMA-IR of patients in the PCOS group were significantly higher than those in the blank control group(P＜0.05).The relative expression of miR-93-5p in plasma of patients in the PCOS group was significantly higher than that in the blank control group(t=-5.549,P＜0.001).miR-93-5p was moderately positively correlated with TT,FINS and HOMA-IR(r=0.434,0.622,0.586;P＜0.001)and was mildly positively correlated with FBG and LH(r=0.398,0.398;P＜0.001).The receiver operating characteristic curve showed that the optimal cut-off value for plasma miR-93-5p in diagnosing PCOS was 1.380,the area under the curve was 0.906(95％confidence interval:0.839-0.973,P＜0.001),the sensitivity was 0.858,the specificity was 0.833,and the Youden index was 0.691.The relative expression of miR-93-5p in the KGN cells in the miR-93-5p mimics group,LY294002+miR-93-5p group and AZD5363+miR-93-5p group was significantly higher than that in the blank control group and NC group(P＜0.05).After 24,48 and 72 hours of culture,the proliferation of the KGN cells in the miR-93-5p mimics group,LY294002+miR-93-5p group and AZD5363+miR-93-5p group was significantly higher than that in the blank control group and the NC group(P＜0.05);the proliferation of the KGN cells in the LY294002+miR-93-5p group and AZD5363+miR-93-5p group was significantly lower than that in the miR-93-5p mimics group(P＜0.05).Conclusion miR-93-5p in plasma is overexpressed in PCOS patients,and it may be involved in the occurrence and development of PCOS by mediating the proliferation of ovarian granulosa cells through the phosphoinositide 3 kinase/protein kinase B signaling pathway.The miR-93-5p level in plasma has a certain diagnostic value for PCOS.

Objective To explore the expression level of microRNA(miR)-320a-3p in peripheral blood in patients with polycystic ovary syndrome(PCOS)and its possible mechanism for regulating PCOS.Methods A total of 149 PCOS patients admitted to the Jiaozuo People's Hospital from July 2021 to July 2022 were selected as the research subjects(PCOS group),and 18 healthy volunteers with a regular menstrual cycle(28-35 d),no clinical or biochemical manifestations of hyperandrogenism,and no polycystic ovary changes detected by ultrasonography were selected as the control group.Clinical data of the subjects in the two groups were collected and compared.The expression level of miR-320a-3p in plasma of subjects in the two groups was detected by using the real-time quantitative polymerase chain reaction.The correlation between plasma miR-320a-3p expression and clinical indexes was evaluated by using the Pearson partial correlation analysis.The predictive value of miR-320a-3p for PCOS was analyzed by using the receiver operating characteristic curve.The relationship between miR-320a-3p and androgen receptor was evaluated by using the dual luciferase reporter gene assay.Results There was no significant difference in age,hip circumference,follicle stimulating hormone(FSH),prolactin(PRL),and high-density lipoprotein cholesterol(HDL-C)between the two groups(P＞0.05).The body mass index,waist circumference,total testosterone(TT),anti-Miillerian hormone(AMH),luteinizing hormone(LH),fasting insulin(FINS),fasting blood glucose(FBG),2-hour postprandial blood glucose(2 h BG),homeostasis model assessment of insulin resistance(HOMA-IR),total cholesterol,triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)of patients in the PCOS group were significantly higher than those in the control group,while the level of estradiol(E2)was significantly lower than that in the control group(P＜0.05).The relative expression level of miR-320a-3p in plasma of patients in the PCOS group was significantly lower than that in the control group(P＜0.05).The expression level of miR-320a-3p was moderately negatively correlated with TT(r=-0.594,P＜0.05)and slightly negatively correlated with waist circumference,FINS,2 h BG,HOMA-IR,and LDL-C(r=-0.293,-0.208,-0.227,-0.208,-0.208;P＜0.05),and showed no significant correlation with hip circumference,AMH,FSH,E2,PRL,FBG,TG,and HDL-C(r=-0.079,0.020,-0.042,0.089,0.005,-0.141,-0.116,0.059;P＞0.05).The area under the curve of miR-320a-3p for predicting PCOS was 0.968(95％confidence interval:0.922-1.000,P＜0.05),with a cut-off value of 0.515,a sensitivity of 0.917,a specificity of 0.789,and a Jordon index of 0.706.miR-320a-3p negatively regulated androgen receptors.Conclusion miR-320a-3p is abnormally low expressed in peripheral blood of PCOS patients and may participate in the occurrence and development of PCOS by negatively regulating androgen receptors to increase TT levels.It has high predictive value for diagnosing PCOS.

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.

Objective To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus(SLE)and lupus nephritis(LN)in children,as well as their diagnostic value for active SLE and LN.Methods A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital,Central South University from January 2016 to March 2019 as the SLE group,all of whom were tested for anti-C1q antibodies.A control group was formed by collecting 70 hospitalized children with other autoimmune diseases(OAD)during the same period.The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed,and the diagnostic value of anti-C1q in SLE and LN was evaluated.Results The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group(P<0.05).The SLE disease activity index score was positively correlated with anti-C1q antibodies(rs=0.371,P<0.001)and positively correlated with anti-double-stranded DNA antibodies(rs=0.370,P<0.001).The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90%and 53.90%,respectively,with an area under the curve of 0.720(P<0.05)and a critical value of 5.45 U/mL.The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50%and 85.00%,respectively,with an area under the curve of 0.675(P<0.05)and a critical value of 22.05 U/mL.Conclusions Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.

ObjectiveTo investigate the influencing factors for the clinical outcome of patients with drug-induced liver injury （DILI）， and to establish a nomogram prediction model for validation. MethodsA retrospective analysis was performed for the general information and laboratory data of 188 patients with DILI who were admitted to Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology from January 2017 to December 2022， and according to their clinical outcome， they were divided into good outcome group with 146 patients and poor outcome group with 42 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the independent influencing factors for the clinical outcome of DILI patients. R Studio 4.1.2 software was used to establish a nomogram model， and calibration curve， receiver operating characteristic （ROC） curve， and decision curve analysis （DCA） were used to perform internal validation. ResultsThe univariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI， platelet count， cholinesterase， albumin， prothrombin time activity， IgM， and IgG were associated with adverse outcomes in patients with DILI. The multivariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI （odds ratio ［OR］=0.072， 95% confidence interval ［CI］： 0.022‍ ‍—‍ ‍0.213， P<0.001）， clinical classification （OR=0.463， 95%CI： 0.213‍ ‍—‍ ‍0.926， P=0.039）， alanine aminotransferase （OR=0.999， 95%CI： 0.998‍ ‍—‍ ‍1.000， P=0.025）， prothrombin time activity （OR=0.973， 95%CI： 0.952‍ ‍—‍ ‍0.993， P=0.011）， and IgM （OR=1.456， 95%CI： 1.082‍ ‍—‍ ‍2.021， P=0.015） were independent influencing factors for clinical outcome in patients with DILI. The nomogram prediction model was established， and after validation， the calibration curve was close to the reference curve. The area under the ROC curve was 0.829， and the DCA curve showed that the model had good net clinical benefit. ConclusionThe nomogram prediction model established in this study has good clinical calibration， discriminative ability， and application value in evaluating the clinical outcome of patients with DILI.

Aim To study the effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension and explore the underlying mechanism in mice. Methods 10 to 12 weeks old wild type (WT) mice and TRPM8 gene knockout (TRPM8