ObjectiveTo study the effect of Zuoguiwan on the development of skin barrier in the neonatal rat model of congenital kidney deficiency and unveil the underlying mechanism. MethodsSixty rats were paired in a female-to-male ratio of 2∶1， and the pregnant rats were assigned into control， congenital kidney deficiency， and low- and high-dose （2 and 8 g·kg^-1， respectively） Zuoguiwan groups. The pregnant rats in other groups except the control group were exposed to chronic unpredictable mild stress for the modeling of congenital kidney deficiency. The rats in the control group and congenital kidney deficiency group were administrated with normal saline by gavage， and those in Zuoguiwan groups with Zuoguiwan suspension by gavage from day 1 of pregnancy. The serum level of interleukin-6 （IL-6） in the neonatal rats on the day of birth was determined by enzyme-linked immunosorbent assay. The full-thickness skin of neonatal rats on the day of birth was removed from the same position on the back and stained with hematoxylin-eosin for observation of histopathological changes， measurement of skin thickness， and counting of hair follicles. Terminal deoxynucleotidyl transferase-mediated nick end labeling was used to detect the apoptosis of skin tissue cells. The expression of interleukin-6 receptor （IL-6R） and interleukin-17A （IL-17A） in the skin tissue was assessed by immunohistochemistry and Western blot， and the expression of occludin， connexin 43 （Cx43）， and zonula occludens-1 （ZO-1） in the skin tissue was assessed by immunofluorescence and Western blot. ResultsCompared with those in the control group， the neonatal rats in the congenital kidney deficiency group showed a rise in the serum IL-6 level （P<0.01）， decreases in stratum corneum thickness， skin thickness， and number of hair follicles （P<0.01）， increases in the expression of IL-6R and IL-17A in the skin tissue （P<0.01） and the number of apoptotic cells （P<0.01）， and decreases in the expression of occludin， Cx43， ZO-1 （P<0.05）. Compared with the congenital kidney deficiency group， the low- and high-dose Zuoguiwan groups showed declines in serum IL-6 level （P<0.05）. The low-dose group showed increased number of hair follicles （P<0.05）， and the high-dose group presented thickened stratum corneum （P<0.01）， increased number of hair follicles （P<0.01）， and down-regulated expression of IL-6R and IL-17A in the skin tissue （P<0.05， P<0.01）. Both Zuoguiwan groups showcased decreased number of apoptotic cells （P<0.05， P<0.01）， and the high-dose group showed up-regulated expression of occludin， Cx43， and ZO-1 in the skin tissue （P<0.05， P<0.01）. ConclusionZuoguiwan can reduce the levels of IL-6 in the serum and IL-6R and IL-17A in the skin tissue and improve the expression of intercellular junction proteins， thereby ameliorating the abnormal development of the skin barrier in the neonatal rat model of congenital kidney deficiency.

ObjectiveTo study the effect of Zuoguiwan on the development of skin barrier in the neonatal rat model of congenital kidney deficiency and unveil the underlying mechanism. MethodsSixty rats were paired in a female-to-male ratio of 2∶1， and the pregnant rats were assigned into control， congenital kidney deficiency， and low- and high-dose （2 and 8 g·kg^-1， respectively） Zuoguiwan groups. The pregnant rats in other groups except the control group were exposed to chronic unpredictable mild stress for the modeling of congenital kidney deficiency. The rats in the control group and congenital kidney deficiency group were administrated with normal saline by gavage， and those in Zuoguiwan groups with Zuoguiwan suspension by gavage from day 1 of pregnancy. The serum level of interleukin-6 （IL-6） in the neonatal rats on the day of birth was determined by enzyme-linked immunosorbent assay. The full-thickness skin of neonatal rats on the day of birth was removed from the same position on the back and stained with hematoxylin-eosin for observation of histopathological changes， measurement of skin thickness， and counting of hair follicles. Terminal deoxynucleotidyl transferase-mediated nick end labeling was used to detect the apoptosis of skin tissue cells. The expression of interleukin-6 receptor （IL-6R） and interleukin-17A （IL-17A） in the skin tissue was assessed by immunohistochemistry and Western blot， and the expression of occludin， connexin 43 （Cx43）， and zonula occludens-1 （ZO-1） in the skin tissue was assessed by immunofluorescence and Western blot. ResultsCompared with those in the control group， the neonatal rats in the congenital kidney deficiency group showed a rise in the serum IL-6 level （P<0.01）， decreases in stratum corneum thickness， skin thickness， and number of hair follicles （P<0.01）， increases in the expression of IL-6R and IL-17A in the skin tissue （P<0.01） and the number of apoptotic cells （P<0.01）， and decreases in the expression of occludin， Cx43， ZO-1 （P<0.05）. Compared with the congenital kidney deficiency group， the low- and high-dose Zuoguiwan groups showed declines in serum IL-6 level （P<0.05）. The low-dose group showed increased number of hair follicles （P<0.05）， and the high-dose group presented thickened stratum corneum （P<0.01）， increased number of hair follicles （P<0.01）， and down-regulated expression of IL-6R and IL-17A in the skin tissue （P<0.05， P<0.01）. Both Zuoguiwan groups showcased decreased number of apoptotic cells （P<0.05， P<0.01）， and the high-dose group showed up-regulated expression of occludin， Cx43， and ZO-1 in the skin tissue （P<0.05， P<0.01）. ConclusionZuoguiwan can reduce the levels of IL-6 in the serum and IL-6R and IL-17A in the skin tissue and improve the expression of intercellular junction proteins， thereby ameliorating the abnormal development of the skin barrier in the neonatal rat model of congenital kidney deficiency.

ObjectiveSodium hyaluronate (HA) was used as the research object to modify it with phenolic acid in order to obtain the molecular structure with better antioxidant activity or even new activity. MethodsIn this study, 5 kinds of phenolic acid-sodium hyaluronate was prepared by free radical-mediated grafting method, and the grafts with the highest grafting degree were selected to optimize the synthesis conditions. Then, grafts structure and physicochemical properties were analyzed. The grafts were characterized by IR, UV, ¹H NMR, FESEM and TGA spectra. The in vitro antioxidant capacity of grafts was determined by the scavenging ability of DPPH·, ABTS⁺· and O^2-·. ResultsAmong 5 kinds of phenolic acid-sodium hyaluronate, the grafting rate of ferulic acid-sodium hyaluronate copolymer (FA-HA) was highest , which was chosen as experimental sample in the following tests. Firstly, the reaction conditions were investigated and the highest grafting rate was (16.59±0.31) mg/g at the optimal preparation conditions. Then, FA-HA structure and physicochemical properties were analyzed. Data from UV, IR, ¹H NMR analyses, TGA showed that FA were successfully grafted to HA. Compared with HA, the results of gel permeation chrematography (GPC) showed that the molecular mass distribution ofFA-HA copolymer decreased from 34.4 to 31.5 ku, but the uniformity of molecular distribution was improved. FESEM results showed that the structure of copolymer exhibited a closely connected lamellar structure with a relatively smooth surface. TGA results showed that thermal stability of FA-HA had a little decline. The antioxidant performance in vitro results showed that, during 0.25-10 g/L, FA-HA can eliminate (83.76±4.86)% DPPH·, (76.95±5.06)% ABTS⁺· and (83.08±2.51)% O^2-· respectively at 10 g/L. which were higher than that of native HA and FA. ConclusionFA and HA were successfully grafted together by free radical grafting, and the grafted FA-HA had better antioxidant activity in vitro, which provided a theoretical basis for further research and development of phenolic acid-HA grafts.

As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.

Objective To investigate the association of triglyceride-glucose index(TyG)with non-alcoholic fatty liver disease(NAFLD)and its diagnostic value for NAFLD in non-obese individuals.Methods We retrospectively collected the data of non-obese individuals(BMI<25 kg/m2)undergoing routine health examination at Second Affiliated Hospital of Xi'an Jiaotong University between May,2020 and December,2023,who all received abdominal ultrasound examination for NAFLD screening.The nonlinear relationship between TyG and non-obese NAFLD was explored using restricted cubic splines(RCS),and LASSO regression was used for variable screening;the correlation between TyG and NAFLD risk was analyzed using multivariate logistic regression.The diagnostic value of TyG for non-obese NAFLD was assessed using receiver-operating characteristic(ROC)curves and sensitivity analysis.Results A total of 3723 non-obese subjects were enrolled in this study,including 432(11.6%)patients with NAFLD.Compared with the healthy individuals,the patients with NAFLD had significant elevations of systolic and diastolic blood pressures,total cholesterol,triglycerides,LDL-C,blood uric acid,fasting blood glucose,and TyG index and a decreased HDL-C level(P<0.05).Multivariate logistic regression revealed that for each one-unit increase of TyG,the risk of non-obese NAFLD increased by 2.2 folds(OR=3.22,95%CI:2.53-4.12,P<0.001).Compared with a TyG index in the lowest quartile Q1,a TyG index in the Q2,Q3 and Q4 quartiles was associated with an increased risk of NAFLD by 1.52 folds(OR=2.52,95%CI:1.20-5.95),3.56 folds(OR=4.56,95%CI:2.28-10.46),and 8.66-folds(OR=9.66,95%CI:4.83-22.18),respectively.The RCS curve demonstrated a significant linear correlation between TyG index and non-obese NALFD risk(P for nonlinear=0.019).For diagnosing non-obese NALFD,TyG index had an area under ROC curve of 0.819 with a sensitivity of 78.0%and a specificity of 71.2%.Conclusion An increase of TyG index is correlated with increased risks of NAFLD in non-obese individuals and can serve as an indicator for screening early NAFLD in healthy individuals.

Objective:Hepatic fibrosis is a common pathological basis for many chronic liver diseases and can progress to cirrhosis,a leading cause of mortality in liver diseases.Early identification and reversal of hepatic fibrosis are key in the treatment of chronic liver disease.This study aims to compare the expression levels of serum core fucosylated low molecular weight kininogen(LMWK-Fc)and alpha-galactosylated(α-Gal)antibodies in patients with hepatic fibrosis at different stages,and to evaluate their diagnostic efficacy for hepatic fibrosis. Methods:A retrospective analysis was conducted on 275 patients with chronic liver disease who visited the Department of Infectious Diseases at the Second Xiangya Hospital of Central South University between June 2022 and March 2023.Among these,115 patients underwent liver biopsy.Based on the extent of collagen deposition and its impact on liver structure and microcirculation,patients were staged from 0 to 4:S0(no significant collagen deposition in liver tissues;liver structure and microcirculation are normal),S1(mild collagen deposition in liver tissues,with partial disruption of lobule structure,but microcirculation remains largely normal),S2(moderate collagen deposition in liver tissues,with partial disruption of lobule structure and microcirculation),S3(extensive collagen deposition in liver tissues,with substantial disruption of lobule structure and microcirculation),and S4(development of cirrhosis,with heavy collagen deposition,complete disruption of lobule structure,and severe impairment of microcirculation).Patients were grouped as no fibrosis(S0),fibrosis(S1-S2),and significant fibrosis(S3-S4).For the 160 patients without liver biopsy,they were categorized based on liver stiffness measurement(LSM)value:no fibrosis(F0:LSM＜7.3 kPa),fibrosis(F1-F2:LSM 7.3-12.4 kPa),and significant fibrosis(F3-F4:LSM＞12.4 kPa).Demographic data(age,gender)and laboratory indicators(alanine transaminase,aspartate transaminase,gamma-glutamyl transferase,alkaline phosphatase,alpha-fetoprotein,platelet count)were collected to calculate the fibrosis-4 index(FIB-4)and aspartate aminotransferase-to-platelet ratio index(APRI).Serum LMWK-Fc and α-Gal antibodies were measured and compared across the groups,and their correlation with fibrosis severity was analyzed.The receiver operating characteristic(ROC)curve was used to assess the predictive value of serum LMWK-Fc and α-Gal antibody levels for hepatic fibrosis. Results:Among the 160 patients without complete liver biopsy,serum α-Gal antibody and LMWK-Fc levels increased progressively from the no fibrosis group to the significant fibrosis group,with statistically significant differences(P＜0.05).Among the 115 patients with liver biopsy,serum LMWK-Fc levels were significantly higher in the fibrosis group and the significant fibrosis groups compared with the no fibrosis group,and α-Gal antibody levels were significantly higher in the significant fibrosis group compared with the no fibrosis group and the fibrosis group(P＜0.001,P=0.032,respectively).Univariate and multivariate linear regression analyses showed that hepatic fibrosis was correlated with gender and LMWK-Fc levels(both P＜0.05),but not with age,α-Gal antibody levels,FIB-4,or APRI(all P＞0.05). Conclusion:The expression levels of serum LMWK-Fc and α-Gal antibodies vary across different stages of hepatic fibrosis,suggesting a potential association with fibrosis progression.LMWK-Fc levels have a certain predictive value for the diagnosis of hepatic fibrosis.

Objective To investigate the prognosis of patients with hepatitis B virus(HBV)-related intrahepatic cholangiocarcinoma(ICC)whose HBV DNA was negative before surgical.Methods A retrospective analysis was conducted on the clinical data of 97 ICC patients who underwent surgery resection at the Fifth Medical Center of Chinese PLA General Hospital between October 2010 and January 2017.All patients were divided into HBV-related ICC(HBV-ICC)group(n=62)and non-HBV-related ICC(Con-ICC)group(n=35).HBV-ICC group included 34 patients with HBV core antigen positive(HBcAb+)and HBV surface antigen positive(HBsAg+),and 28 patients with HBcAb positive and HBsAg negative.Kaplan-Meier analysis was used to plot survival curves and compare the overall survival(OS)and postoperative recurrence-free survival(RFS)among patients in Con-ICC,ICC patients with HBsAg+/HBcAb+,and ICC patients with HBsAg-/HBcAb+.Univariate and multivariate Cox proportional hazard models were used to analyze independent influencing factor for OS,RFS and early postoperative recurrence among gender,age,pathogenic factor,liver cirrhosis,Child-Pugh grade,carbohydrate antigen 19-9(CA199),alpha-fetoprotein(AFP),glutamine transferase(GGT),alkaline phosphatase(ALP),total bilirubin(TBil),direct bilirubin(DBil),American Joint Committee on Cancer(AJCC)stage,tumor size,tumor number,tumor differentiation,microvascular invasion,lymph node metastasis,hepatectomy procedure,cholecystectomy,and follow-up treatment.Results Of the 97 patients,the median age was 56 years,and 79(81.4%)of them were male.The median follow-up time was 92.2 months.Eighty-eight(90.7%)patients presented with tumor recurrence and 73(75.3%)died.In multivariate analyses,HBV-ICC and CA199>37 kU/L were independent predictors of OS(HR=0.45,95%CI 0.26-0.77,P=0.003;HR=2.10,95%CI 1.24-3.57,P=0.006),RFS(HR=0.43,95%CI 0.27-0.68,P<0.001;HR=1.78,95%CI 1.12-2.81,P=0.014),and postoperative early recurrence(HR=0.42,95%CI 0.26-0.70,P=0.001;HR=2.02,95%CI 1.20-3.39,P=0.008).AJCC stage Ⅲ was an independent risk factor for postoperative RFS(HR=1.81,95%CI 1.04-3.14,P=0.037).Multiple tumor lesions was an independent risk factor for postoperative RFS and early recurrence(HR=1.73,95%CI 1.07-2.77,P=0.024;HR=1.90,95%CI 1.12-3.24,P=0.017).There was no statistically significant difference in OS,RFS,and early recurrence between HBV-ICC patients with HBsAg-/HBcAb+and Con-ICC patients(P<0.05),whereas HBsAg+/HBcAb+was a significant factor affecting postoperative OS(HR=0.32,95%CI 0.16-0.62,P=0.001),RFS(HR=0.32,95%CI 0.18-0.55,P<0.001),and early recurrence(HR=0.29,95%CI 0.15-0.54,P<0.001)in ICC patients.Conclusions The prognosis of HBV-ICC patients with preoperative HBV-DNA-is better than that of Con-ICC patients.The prognosis of HBV-ICC patients with HBcAb+/HBsAg-is worse than that of HBV-ICC patients with HBcAb+/HBsAg+,but similar to Con-ICC patients.Therefore,the postoperative stratified management of HBV-ICC patients should be emphasized.

Objective To analyze risk factors and pathogenic characteristics of intestinal colonization of carbape-nem-resistant Enterobacterales(CRE)in patients from intensive care unit(ICU).Methods A total of 392 ICU pa-tients who underwent intestinal CRE screening in a tertiary hospital in Changzhou from March to December,2023 were divided into the colonization group(n=42)and the non-colonization group(n=350)according to the screening results.Clinical data of patients,including age,gender,underlying diseases,malignant tumors,radiotherapy,chemotherapy,infection before the last screening,antimicrobial use,and invasive procedures were collected for the analysis on risk factors and pathogenicity.Results Among 42 patients with positive CRE screening results,44 CRE strains were detected,mainly Klebsiella pneumoniae(65.91％),followed by Escherichia coli(15.91％)and En-terobacter cloacae(13.64％).The average time from admission in ICU to positive screening results of intestinal CRE in the colonization group was 14 days.Long term use of carbapenem antibiotics(OR=1.47,95％CI:1.31-1.65),mechanical ventilation(OR=1.14,95％CI:1.06-1.22),and Enterobacterales infection(OR=10.10,95％CI:3.28-32.09)were independent risk factors for intestinal CRE colonization.Patients who received carbap-enem antibiotics for ≥15 days(x2=167.52,P＜0.001)and those who received mechanical ventilation for ≥15 days(x2=101.03,P＜0.001)had higher risks for intestinal CRE colonization.Conclusion In clinical practice,it is necessary to improve pathogen detection,treat Enterobacterales infection timely,choose carbapenem antibiotics carefully,shorten treatment course,actively evaluate indications for mechanical ventilation,and wean off ventilator timely.

ObjectiveTo observe the effect of Zuoguiwan on ovarian reserve in the female offspring rat model of prenatal stress （PS） and explore the mechanism based on Toll-like receptor 4/nuclear factor-κB p65 （TLR4/NF-κB p65） signaling pathway. MethodThirty-two pregnant rats were prepared and randomized into four groups （n=8）： control， model， Zuoguiwan （18.9 mg·kg^-1）， and vitamin E （1.44 mg·kg^-1）. Except the control group， the other three groups were subjected to chronic unpredictable mild stress （CUMS） from day 11 of pregnancy， and the modeling was accompanied by gavage with corresponding drugs until delivery. The PS model was evaluated by the sucrose preference test， open field test， and serum corticosterone （CORT） level. The estrous cycle was monitored and the morphological changes in the ovarian tissue were observed. The serum levels of estradiol （E₂）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， and anti-Mullerian hormone （AMH） in the 75-day-old offspring rats were measured by enzyme-linked immunosorbent assay （ELISA） to evaluate the ovarian reserve. The ovary and uterus indices were calculated. The serum levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. The morphology of the ovarian tissue in the offspring on the day of birth and day 75 after birth was observed by hematoxylin-eosin staining. The transport of NF-κB p65 to the nucleus in the ovaries of the 75-day-old offspring was detected by the immunofluorescence （IF） assay. The expression of TLR4， NF-κB p65 and other related proteins in the ovarian tissue was determined by Western blot. ResultCompared with the control group， the model group showed reduced primordial follicles in the offspring on the day of birth （P<0.01） as well as disturbed estrous cycle， decreased ovary index and uterus index （P<0.01）， reduced corpus luteum， increased atretic follicles （P<0.01）， lowered serum levels of AMH and E₂ （P<0.01）， elevated serum levels of LH， FSH， IL-1β， and TNF-α （P<0.05， P<0.01）， and up-regulated protein levels of TLR4， NF-κB p65， recombinant myeloid differentiation factor 88 （MyD88）， and phosphorylated NF-κB inhibitor （p-IκBα） （P<0.01） in the 75-day-old offspring rats. Compared with the model group， Zuoguiwan and vitamin E increased the primordial follicles in the offspring on the day of birth （P<0.01）. Moreover， they resumed the estrous cycle， increased the ovary and uterine indices （P<0.05， P<0.01） and corpus luteum （P<0.01）， reduced atretic follicles （P<0.01）， elevated the serum levels of AMH and E₂ （P<0.05， P<0.01）， lowered the serum levels of LH， FSH， IL-1β， and TNF-α （P<0.05， P<0.01）， and down-regulated the expression of TLR4， NF-κB p65， MyD88， and p-IκB-α （P<0.05， P<0.01） in the 75-day-old offspring. ConclusionZuoguiwan can improve the ovarian reserve in the offspring rat model of congenital kidney deficiency by regulating the TLR4/NF-κB p65 signaling pathway.

Objective To investigate the association of triglyceride-glucose index(TyG)with non-alcoholic fatty liver disease(NAFLD)and its diagnostic value for NAFLD in non-obese individuals.Methods We retrospectively collected the data of non-obese individuals(BMI<25 kg/m2)undergoing routine health examination at Second Affiliated Hospital of Xi'an Jiaotong University between May,2020 and December,2023,who all received abdominal ultrasound examination for NAFLD screening.The nonlinear relationship between TyG and non-obese NAFLD was explored using restricted cubic splines(RCS),and LASSO regression was used for variable screening;the correlation between TyG and NAFLD risk was analyzed using multivariate logistic regression.The diagnostic value of TyG for non-obese NAFLD was assessed using receiver-operating characteristic(ROC)curves and sensitivity analysis.Results A total of 3723 non-obese subjects were enrolled in this study,including 432(11.6%)patients with NAFLD.Compared with the healthy individuals,the patients with NAFLD had significant elevations of systolic and diastolic blood pressures,total cholesterol,triglycerides,LDL-C,blood uric acid,fasting blood glucose,and TyG index and a decreased HDL-C level(P<0.05).Multivariate logistic regression revealed that for each one-unit increase of TyG,the risk of non-obese NAFLD increased by 2.2 folds(OR=3.22,95%CI:2.53-4.12,P<0.001).Compared with a TyG index in the lowest quartile Q1,a TyG index in the Q2,Q3 and Q4 quartiles was associated with an increased risk of NAFLD by 1.52 folds(OR=2.52,95%CI:1.20-5.95),3.56 folds(OR=4.56,95%CI:2.28-10.46),and 8.66-folds(OR=9.66,95%CI:4.83-22.18),respectively.The RCS curve demonstrated a significant linear correlation between TyG index and non-obese NALFD risk(P for nonlinear=0.019).For diagnosing non-obese NALFD,TyG index had an area under ROC curve of 0.819 with a sensitivity of 78.0%and a specificity of 71.2%.Conclusion An increase of TyG index is correlated with increased risks of NAFLD in non-obese individuals and can serve as an indicator for screening early NAFLD in healthy individuals.