Objective:To investigate the relationship between adiponectin (ADIPOQ) gene polymorphism and postpartum type 2 diabetes mellitus (T2DM) in pregnant women with gestational diabetes mellitus (GDM).Methods:A retrospective study was conducted on 236 GDM postpartum women admitted to the Affiliated Hospital of Jining Medical College from June 2020 to June 2021 as observation subjects. They were divided into a T2DM group and a non T2DM group based on the occurrence of T2DM after delivery. The clinical data of the two groups were compared. The double deoxygenation end termination method was used to detect the single nucleotide polymorphism (SNP) of the ADIPOQ gene, and the four loci rs17366568, rs822395, rs1501299, and rs2241766 were classified. The relationship between ADIPOQ genotype polymorphism and postpartum T2DM was analyzed using a logistic regression model.Results:The G allele carrying the rs2241766 locus in ADIPOQ gene was negatively correlated with the occurrence of T2DM ( OR=0.71, 0.68, P<0.05). Compared with T2DM patients with TT genotype, the GT+ GG genotype at the rs2241766 locus had a lower risk of occurrence for gestational age ≥2 and HbA 1c>85%. Similarly, T2DM patients with pre pregnancy body mass index (BMI)>25 kg/m 2 were more likely to be carriers of the rs2241766 TT genotype ( P=0.026). The (GT+ TT) genotype carrying the T allele at the rs1501299 locus was a protective factor for gestational age and HbA 1c in T2DM patients. Conclusions:The rs2241766 and rs1501299 polymorphisms of the ADIPOQ gene are associated with susceptibility to postpartum T2DM in GDM women. Individuals with rs2241766 and rs1501299 mutant genotypes belong to the high-risk population for T2DM.

Objective:To observe the recurrence condition of hepatitis B in different risk groups after liver transplantation in an attempt to provide useful information on whether to discontinue hepatitis B immunoglobulin (HBIG) in the future at an early stage.Methods:The patient population was divided into high, low-risk, and special groups [especially primary hepatocellular carcinoma (HCC)] according to the guidelines for the prevention and treatment of hepatitis B recurrence after liver transplantation. The recurrence condition and risk factors in this population were observed for hepatitis B. Measurement data were analyzed using a t-test and a rank-sum test. Count data were compared using a χ2 test between groups. Results:This study finally included 532 hepatitis B-related liver transplant cases. A total of 35 cases had HBV recurrence after liver transplantation, including 34 cases that were HBsAg positive, one case that was HBsAg negative, and 10 cases that were hepatitis B virus (HBV) DNA positive. The overall HBV recurrence rate was 6.6%. The recurrence rate of HBV was 9.2% and 4.8% in the high- and low-risk HBV DNA positive and negative groups before surgery ( P = 0.057). Among the 293 cases diagnosed with HCC before liver transplantation, 30 had hepatitis B recurrence after surgery, with a recurrence rate of 10.2%. The independent related factors for the recurrence of hepatitis B in patients with HCC after liver transplantation were HCC recurrence ( HR =181.92, 95% CI 15.99~2 069.96, P < 0.001), a high postoperative dose of mycophenolate mofetil dispersible tablets (MMF) ( HR =5.190, 95% CI 1.289~20.889, P = 0.020), and a high dosage of HBIG ( HR = 1.012, 95% CI 1.001~1.023, P = 0.035). Among the 239 cases who were non-HCC before liver transplantation, five cases (recurrence rate of 2.1%) arouse postoperative hepatitis B recurrence. Lamivudine was used in all cases, combined with on-demand HBIG prophylaxis after surgery. There was no hepatitis B recurrence in non-HCC patients who treated with entecavir combined with HBIG after surgery. Conclusion:High-barrier-to-resistance nucleotide analogues combined with long-term HBIG have a good effect on preventing the recurrence of hepatitis B after liver transplantation. The discontinuation of HBIG may be considered at an early stage after administration of a high-barrier-to-resistance nucleotide analogue in low-risk patients. Domestically, the HBV infection rate is high, so further research is still required to explore the timing of HBIG discontinuation for high-risk patients, especially those with HCC.

Objective To investigate the liver disease phenotypes and clinical features of patients with different genotypes of Wilson's disease(WD).Methods A retrospective analysis was performed for 163 patients with WD who were diagnosed and underwent genetic testing in The Fifth Medical Center of Chinese PLA General Hospital from August 2008 to June 2023,and clinical manifestations,laboratory examination,pathological examination,imaging examination,and ATP7B genetic testing results were collected.According to ATP7B gene mutation,the patients were divided into groups as follows:R778L mutation group and non-R778L mutation group;P992L mutation group and non-P992L mutation group;truncation mutation group and non-truncation mutation group.Liver disease phenotypes and clinical features were analyzed for the patients with c.2333G>T/p.R778L mutation(R778L mutation),c.2975C>T/p.P992L mutation(P992L mutation),and truncation mutation of the ATP7B gene.The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of continuous data between groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results The 163 patients with WD had varying severities of liver disease phenotypes,among whom 121(74.23%)were diagnosed with chronic liver disease,36(22.09%)were diagnosed with decompensated cirrhosis,and 6(3.68%)were diagnosed with fulminant WD,and in addition,there were 5 patients(2 with chronic liver disease and 3 with decompensated cirrhosis)with neurological abnormalities.For the 163 patients with WD,R778L mutation(with an allele frequency of 28.2%)was the most common mutation in the ATP7B gene,followed by P992L mutation(with an allele frequency of 12.6%),and truncation mutation showed an allele frequency of 11.0%.There was no significant difference in the distribution of the three mutations across different liver disease phenotypes(P>0.05).The R778L mutation group had a significantly lower level of ceruloplasmin(CP)than the non-R778L mutation group[0.04(0.02-0.08)g/L vs 0.08(0.03-0.13)g/L,Z=-2.889,P=0.004].Compared with the non-P992L mutation group,the P992L mutation group had significantly higher levels of alanine aminotransferase[135.0(80.5-237.0)U/L vs 80.5(36.0-173.3)U/L,Z=2.684,P=0.007]and aspartate aminotransferase[121.4(77.0-195.0)U/L vs 84.0(39.0-123.3)U/L,Z=3.388,P<0.001].Compared with the non-truncation mutation group,the truncation mutation group had significantly lower levels of CP[0.03(0.02-0.08)g/L vs 0.06(0.03-0.11)g/L,Z=-3.136,P=0.002]and serum copper[3.20(2.15-5.00)mg/L vs 4.20(2.60-7.50)mg/L,Z=-2.296,P=0.025].Conclusion R778L mutation,P992L mutation and truncation mutation are not associated with liver disease phenotype in WD patients;however,R778L mutation is associated with a lower level of CP,P992L mutation is associated with higher levels of ALT and AST,and truncation mutation is associated with lower levels of CP and serum copper.

Objective To explore the value of blood inflammatory load in predicting overall survival of elderly patients with epithelial ovarian cancer(EOC).Methods Elderly patients with EOC were selected,and their clinical data and peripheral blood parameters were collected.We constructed an inflammation-related blood scoring system using univariate and multivariate Cox regression analysis.The Kaplan-Meier method was used for survival analysis.We used Cox proportional hazards analysis to identify the independent prognostic factors.A nomogram model was constructed based on independent prognostic factors,and the receiver operating characteristic curve,C-index,and calibration curve were used to evaluate the model.Results Patients with high blood inflammatory load had worse prognosis(P=0.002).Compared with the low inflammatory load group,patients with high inflammatory load had later clinical stages and larger ascites volume(P<0.05).Cox regression analysis showed that ACCI,CA125,residual lesions,and blood score were independent factors affecting overall survival(P<0.05).Conclusion The blood inflammatory load is the biomarker for the prognosis of elderly patients with EOC.Scoring the inflammatory load in the blood can assist in efficacy monitoring and treatment intervention of ovarian cancer patients.

Objective:To analyze the clinical manifestations, pathology, and gene variant characteristics in children with progressive familial intrahepatic cholestasis type 3 (PFIC3).Methods:This retrospective study assessed the clinical manifestations, pathological features, gene variants, and prognosis data of 11 children with PFIC3 hospitalized in the Department of Hepatology, Fifth Medical Center, PLA General Hospital, from January 2015 to December 2022. Panel or whole exome sequencing was performed on the probands, followed by Sanger sequencing for verification within the family. Detected pathogenic variants were compared with known disease databases. Additionally, the new variants were predicted the deleteriousness and protein structure using relevant software to evaluate their pathogenicity.Results:Among the 11 PFIC3 children, 8 were boys and 3 were girls. The age of onset was 3.1 (0.2, 15.6) years. The main complaint of onset was different in the 11 patients;5 of them were abnormal liver function, 3 of them were liver and spleen enlargement, 2 of them were abdominal distension, and 1 of them was jaundice. Alanine aminotransferase, asparate aminotransferase and γ-glutamyltransferase increased in all the patients, which were(113±40), (150±44) and (270±156) U/L respectively. Moreover, direct bilirubin increased in 9 patients, and cholestasis was showed in 8 patients. All patients showed liver fibrosis on imaging, and 8 patients had cirrhosis. The pathological features of 8 cases by liver biopsy were as follows: 8 cases of fibrosis in the portal area, 7 cases of small bile duct hyperplasia, 4 cases of positive copper staining, and 5 cases of cirrhosis. A total of 17 ABCB4 gene variants were detected, including 9 new variants: c.589C>T(p.Q197X), c.1230+1G>A(Splicing), c.2914G>A(P.D972N), c.1058G>A(p.C353Y), c.956G>T(p.G319V), c.473T>A(p.L158Q), c.164T>C(p.L55S), c.2493G>C(p.R831S), and c.1150G>C(p.G384R). All 11 patients were treated with ursodeoxycholic acid and followed up for 5.1(0.6, 7.4) years. Among them, 4 cases of cirrhosis progressed continuously, 3 cases had liver transplantations, and the remaining 4 cases were stable after medical treatment.Conclusions:Children with PFIC3 have early onset, diverse clinical manifestations, rapid progression of fibrotic and cholestasis, as well as poor prognosis. Genetic testing helps to confirm the diagnosis.

Objective:To investigate the clinical manifestations, pathological, and gene mutation characteristics of ABCB4 gene variant-associated cholestatic liver disease in adults. Methods:Eight adult cases of ABCB4 gene variant-associated cholestatic liver disease who were hospitalized in the Department of Hepatology, Fifth Medical Center of the People's Liberation Army General Hospital from May 2010 to December 2022 were enrolled in this study. The clinical manifestations, pathological features, gene variant features, and prognostic conditions were analyzed. Patient gene testing and biological information analysis were performed using whole-exome next-generation sequencing. SPSS 19.0 software was used to conduct descriptive analysis. Results:Among the eight adult cases of the ABCB4 gene variant, there were three males and five females, with a median age of onset of 24 (20, 37) years. There were three cases with a compound heterozygous variant in ABCB4, and the clinical phenotypes included two cases of progressive familial intrahepatic cholestasis type 3 and one case of intrahepatic cholestasis of pregnancy overlapping with low-phospholipid-associated cholelithiasis syndrome. There were five cases with a single heterozygous variant in ABCB4, and the clinical phenotypes included two cases of intrahepatic cholestasis of pregnancy overlapping with drug-induced liver injury and three cases of low-phospholipid-associated cholelithiasis syndrome. Imaging of all eight cases showed liver fibrosis, and six cases already had cirrhosis. All patients underwent liver histopathological examination, which mainly showed cholestasis and portal fibrosis in eight cases, small bile duct hyperplasia in seven cases, copper deposition in three cases, and cirrhosis in five cases. ABCB4 screening revealed 11 different mutations, including eight new mutations. The pathogenicity assessment showed that c.2394+82C>T (intron) was a benign mutation, and the rest were deleterious mutations. Ursodeoxycholic acid was the treatment for all patients, with a follow-up time of 7.5 (0.5, 12.7) years. One case died of end-stage liver disease, two cases developed cholestatic cirrhosis, and five cases were in stable condition. Conclusion:The adult ABCB4 gene variant-associated cholestatic liver disease are mostly single heterozygous mutations, the clinical phenotypes are diverse and overlapping, the disease is more severe in those who carried non-functional mutations.

From the perspective of medical institutions, this paper sorted out the background of the promulgation and important changes of Measures for Ethical Review of Life Science and Medical Research Involving Humans, and summarized the changes that may significantly affect the ethical review of medical institutions. It involved terminology changes and expansion of the scope of ethic review, clarification of the responsibilities and independence of the ethics committee, the refinement of the ethical review process, the emphasis on the protection of personal information and the rights and interests of subjects, and first proposal to exempt from ethical review. In addition, based on the concept of strengthening the ethical governance of science and technology in the new version of regulations, this paper shared the consideration on the governance of ethical review within medical institutions, including safeguarding the dignity and rights of subject, clarifying the role and position of ethical review, exempting the implementation of ethical review, and managing entrusted ethical review. With a view to providing a certain reference for the ethics practitioners and researchers in various medical institutions.

Objective:To explore the safety of inactivating coronavirus disease 2019(covid-19)vaccine in liver transplantation(LT)recipients.Methods:Retrospective analysis was performed for clinical data of 151 LT recipients from March 2003 to October 2019.They had stable conditions and completed the course of covid-19 vaccine.Frequencies of pain at injection site, fatigue, headache and pruritus after vaccination were recorded.The safety profiles were compared between recipients with and without local and general adverse reactions after vaccination.At the same time, recipients completing two doses of covid-19 vaccines were grouped.According to vaccine companies, they were classified into Sinovac Biotech Ltd and Beijing Biological.Based upon more than or less than 60 years, they were grouped into <60 years and ≥60 years.The safety profiles of inactivating COVID-19 vaccine were compared in subgroups.Results:Among 151 eligible LT recipients, 98 of them were in group of age <60 years and 53 in group of age >60 years.The median period between vaccination and LT was 8.44(4.37, 12.39)years and the median concentration of tacrolimus 2.5(1.8, 3.9)ng/L.Eighty-three cases completed two doses of Sinovac Biotech Ltd(Sinovac Biotech Ltd group)and 40 cases Beijing Biological(Beijing Biological group); 14 cases had combined course of Sinovac Biotech Ltd and Beijing Biological, four recipients were vaccinated with inactivated vaccine from other companies and ten recipients did not know their inactivated vaccine' companies.After immunization, 24/151(15.9%)recipients had a local and general adverse reaction.The prevalence of pain at injection site, fatigue, headache and pruritus was 9.9%( n=15), 5.2%( n=8), 1.3%( n=2)and 0.7%( n=1)respectively.No significant differences existed in age( P=0.602), gender( P=0.752), period after LT( P=0.890), trough concentration of tacrolimus( P=0.377)or versions of covid-19 vaccine( P=0.582)between 24 cases with general adverse reaction and 127 without.Local and general reactions occurred in 16/83(19.3%)in Sinovac group and 5/40(12.5%)in Beijing Biological.There was no significant inter-group difference( P=0.769). There were 98 cases(64.9%)in <60 years group, 17 cases(17.3%)had local and general reaction, 53 cases(35.1%)in ≥60 years group and 7 cases(13.2%)had a local and systemic reaction.There was no significant inter-group difference( P=0.507). Conclusions:Covid-19 vaccine is safe for long-term survival LT recipients with normal liver function.Few participants present with mild fatigue and pain at injection site.

Objective:To explore the clinical value of one-step CT angiography from deep vein of lower limbs to pulmonary artery in the direction of head and foot.Methods:Twenty-eight patients who presented Haikou Affiliated Hospital of Central South University Xiangya School of Medicine from January 2017 to June 2019 were collected. All patients who underwent one-step CT angiography of the deep veins of the lower extremities to the pulmonary artery were randomly divided into two groups, A or B, and scanned from the entrance of the thorax to 10 cm below the knee joint. Group A was foot-head direction group with delayed time scanning according to empirical method. Group B was the head-foot direction group with a single point triggered automatic tracing scan at the level of the main pulmonary artery trunk. The independent sample t-test was used to compare the scan time, dose length product (DLP), and mean CT value of enhancement of the pulmonary artery opening between the two groups. Results:The average scanning time of the foot-head scanning group was (36.4±1.2)s, the average DLP was (684.4±37.8) mGy·cm, and the average enhanced CT value of pulmonary artery image was (181.3±15.5) HU. The average scanning time of the head foot scanning group was (16.4±0.3) s, the average DLP was (441.8±34.4) mGy·cm, and the average enhanced CT value of the pulmonary artery image was (257.9±24.5) HU. Scanning time, mean DLP, and pulmonary artery level enhancement values were significantly different between the two groups ( t=17.92, 4.71, 2.44, P<0.05). Conclusions:The clinical value of one-step CT angiography from deep vein of lower limbs to pulmonary artery in the head-foot direction is significantly better than that in the head-foot direction. It can significantly shorten the scanning time, reduce the radiation dose, and increase the enhancement value of pulmonary artery to improve the detection of pulmonary embolism.

Objective: Due to the complicated compounds and the synergistic effect of multi-compounds, the quality control and assessment of Chinese materia medica (CMM) encounters a great challenge about how to identify the key compounds, which are directly correlated with its efficacy and safety. On the guidance of study on quality marker (Q-Marker), identification of Q-Markers was performed from Hedan Tablet (HDT) by the aid of the “spider-web” mode and hepatotoxicity evaluation derived from our previous researches and literatures. Methods: By the established ultra performance liquid chromatography with photodiode array detector (UPLC-PDA) method, online UPLC-DPPH· and offline antioxidant assay, 21 candidate compounds of HDT were systematically investigated and comprehensively evaluated by the “spider-web” mode for them properties of Q-Marker based on “content-stability-activity”. In addition, the Q-Markers related with hepatotoxicity based on our previous researches and literatures were identified. Results: Salvianolic acid B (SaB), quercetin-3-O-glucuronide (Qug), isoquercitrin (IQ) and hyperoside (Hyp) were adopted as the preferable Q-Markers of HDT according to the shaded area (A) of tested compounds in “spider-web” mode. Psoralen (Ps), isopsoralen (IP), psoralenoside (PO) and isopsoralenoside (IPO) were also strongly recommended as Q-Markers closely related with safety by considering hepatotoxicity of the accumulated Ps and IP and conversion between glycoside (PO and IPO) and aglycone (Ps and IP). Conclusion: This study provided scientific evidence for quality control and assessment of HDT, and also provided a meaningful reference for application of Q-Markers in CMM.