Objective:To explore the relationship between gene mutation in the pre-C region of hepatitis B virus (HBV) and acute-on-chronic liver failure (ACLF) associated with hepatitis B.Methods:Fifty-eight patients with chronic hepatitis B (CHB) admitted to the General Hospital of Northern Theater Command of the Chinese People′s Liberation Army from May 2020 to May 2023 were selected as the CHB group, 51 patients with chronic hepatitis B liver cirrhosis (CHB-LC) were selected as the CHB-LC group, and 52 patients with hepatitis B-related acute-on-chronic liver failure were selected as the ACLF group. The clinicopathological data of the three groups were collected for retrospective analysis. Peripheral serum HBV DNA of the three groups was collected. The pre-C region genes of HBV in the three groups were amplified by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR), and then gene sequencing was performed. The variation at position 1896 of the pre-C region gene of HBV in the three groups was recorded. The general data, hepatitis B e antigen (HBeAg), HBV DNA quantification, triglycerides (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and gene mutation in the pre-C region of the three groups were observed and compared. Logistic regression analysis was performed on the related influencing factors of the onset of hepatitis B-related ACLF.Results:There were no statistically significant differences in gender, age, disease course, body mass index (BMI), TG, TC, and BUN among the three groups (all P>0.05), and there were statistically significant differences in HBeAg, HBV DNA quantification, ALT, and AST among the three groups (all P<0.05). The HBV DNA quantification, ALT, and AST in the ACLF group were higher than those in the CHB group and the CHB-LC group (all P<0.05). The mutation rate at position 1896 of the pre-C region gene of HBV in the ACLF group was higher than that in the CHB group and the CHB-LC group (all P<0.05); The results of logistic multivariate regression analysis showed that HBV DNA quantification, ALT, and gene mutation in the pre-C region were independent influencing factors for the onset of hepatitis B-related ACLF ( OR=1.042, 1.570, 1.413, P<0.05). Conclusions:The variation at position 1896 of the pre-C region gene of HBV is common in patients with HBV infection at different disease courses. The incidence of its variation shows a gradually increasing trend in CHB, CHB-LC, and ACLF. Elevated HBV DNA and ALT and gene mutation in the pre-C region of HBV are independent risk factors for the occurrence of hepatitis B-related ACLF. The progress of the disease in such patients requires clinical attention.

Objective:To investigate the clinical characteristics of psoriasis and status quo of medical care for patients in county areas of China.Methods:This study was a cross-sectional investigation. Based on the “Qianxian Wuyin” Project (a national project for upgrating ability for psoriasis care at county level), an online questionnaire survey was conducted in the dermatology departments of 459 county hospitals in 404 pilot administrative counties across China from February to June 2023. The questionnaire included demographic information of patients (gender, ethnicity, age, place of residence, education, marital status), and clinical characteristics of psoriasis (disease course, type, comorbidities, body surface area (BSA) and previous treatment. The Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were applied for assessing the quality of life and disease severity, and completed by patients or guardian and doctors, respectively.Results:A total of 16 935 patients completed the questionnaire. The age of patients was 1-102(44.17±11.58)years, and 71.0% (12 036/16 935) were 30-59 years old. The ratio of male to female was 2.21∶1; 24.3%(4 117/16 935) of patients had high school education; there were 9 940 patients(58.7%) with previous or current smoking and/or alcohol use; 42.8%(7 218/16 855) of patients had a disease course of 1-5 years. There were 15 630 patients(92.3%) with DLQI≥10, 8 346 patients(49.7%) with PASI≥10, 15 017 patients(89.2%) with BSA≥10%. The plaque type was the most common disease type ( n=14 965, 88.7%), and spotting type ranked the second ( n=1 141, 6.8%). The most common initial site was the trunk ( n=12 309, 72.9%). Among the comorbidities, hypertension was the most common one ( n=1 681, 10.0%). There were 7 650 reports of treatment response to conventional topical drug therapy and 3 112 reports of treatment response to systemic drug therapy, with 6 269 (81.9%) and 2 493 (80.1%) reporting poor or no response, respectively. Conclusions:The survey shows that in the county areas of China, the majority of psoriasis patients are severe patients with short course of disease, plaque type is the most common type, and hypertension is the most common comorbidity; and the conventional treatment is less effective for most patients.

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

OBJECTIVE: To evaluate the performance of recombinase-aided amplification (RAA) assay in detection of Clonorchis sinensis metacercariae in freshwater fish samples, so as to provide insights into standardization and field application of this assay. METHODS: Wild freshwater fish samples were collected in the rivers of administrative villages where C. sinensis-infected residents lived in Jiangyan District, Xinghua County and Taixing County of Taizhou City, Jiangsu Province from June to September 2022. Genomic DNA was extracted from six freshwater fish specimens (5 g each) containing 0, 1, 2, 4, 8 and 16 C. sinensis metacercariae for fluorescent RAA assay, and the diagnostic sensitivity was evaluated. Fluorescent RAA assay was performed with genomic DNA from C. sinensis, Metorchis orientalis, Haplorchis pumilio and Centrocestus formosanus metacercariae as templates to evaluate its cross-reactions. In addition, the detection of fluorescent RAA assay and direct compression method for C. sinensis metacercariae was compared in field-collected freshwater fish samples. RESULTS: Positive amplification was found in fresh-water fish specimens containing different numbers of C. sinensis metacercariae, and fluorescent RAA assay was effective to detect one C. sinensis metacercaria in 5 g freshwater fish specimens within 20 min. Fluorescent RAA assay tested negative for DNA from M. orientalis, H. pumilio and C. formosanus metacercariae. Fluorescent RAA assay and direct compression method showed 5.36% (93/1 735) and 2.88% (50/1 735) detection rates for C. sinensis metacercariae in 1 735 field-collected freshwater fish samples, with a statistically significant difference seen (χ² = 478.150, P < 0.001). There was a significant difference in the detection of C. sinensis metacercariae in different species of freshwater fish by both the direct compression method (χ² = 11.20, P < 0.05) and fluorescent RAA assay (χ² = 20.26, P < 0.001), and the detection of C. sinensis metacercariae was higher in Pseudorasbora parva than in other fish species by both the direct compression method and fluorescent RAA assay (both P values < 0.05). CONCLUSIONS Fluorescent RAA assay has a high sensitivity for detection of C. sinensis metacercariae in freshwater fish samples, and has no cross-reactions with M. orientalis, H. pumilio or C. formosanus metacercariae. Fluorescent RAA assay shows a higher accuracy for detection of C. sinensis infections in field-collected freshwater fish than the direct compression method.
Animals ; Clonorchis sinensis/genetics* ; Metacercariae/genetics* ; Recombinases ; Fresh Water ; Fishes ; DNA ; Fish Diseases/diagnosis*

Abstract OBJECTIVE To study the effect of berberine(BBR) on autophagy of human breast cancer HCC1937 cells under hypoxia condition. METHODS Cultured human breast cancer HCC1937 cells, CCK-8 method was used to determine the effects of different concentrations of BBR(0, 5, 10, 20, 40, 80, 160 μmol·L-1) on cell viability under normoxia and hypoxia conditions, and select the drug concentration for further experiments. Cultured HCC1937 cells were randomly divided into 4 groups: control group, 20 μmol·L-1 BBR group, hypoxia group, hypoxia+20 μmol·L-1 BBR group. LIVE/DEAD cell viability/cytotoxicity kits were used to measure the cell death rate. The expressions of autophagy related proteins Beclin1, LC3 and P62 in each group were determined by Western blotting. The cells were infected with mCherry-GFP-LC3 adenovirus, and the number of autophagosomes and autophagolysosomes in each group were counted by laser confocal microscopy to determine the effect of BBR on the autophagy flow of HCC1937 cells. RESULTS BBR decreased the cell viability of human breast cancer HCC1937 cells in a concentration-dependent manner. After hypoxia treatment, the cell death rate of HCC1937 cells was not significantly changed, and the intracellular Beclin1, LC3-II and LC3-II/LC3-I ratio were significantly increased, while P62 without significant changes, and the autophagy flow was increased. BBR significantly increased cell death rate, decreased Beclin1 and LC3II/LC3-I ratio, increased intracellular P62, significantly reduced the number of autophagosomes and autophagolysosomes, and inhibited the formation and clearance of autophagosomes under both normal and hypoxia conditions. CONCLUSION BBR increases the death rate of human breast cancer HCC1937 cells under hypoxia condition, and its effect is related to the inhibitory effect of berberine on autophagy under hypoxia condition.

Objective:To evaluate the clinical value of percutaneous transhepatic one-step biliary fistulation(PTOBF)lithotomy plus laparoscopic cholecystectomy(LC) in the treatment of choledocholithiasis combined with cholecystolithiasis.Methods:From Jul 2012 to Jun 2018, 44 patients with cholecystolithiasis and choledocholithiasis were treated by PTOBF + LC ( n=20) vs laparoscopic common bile duct exploration(LCBDE)+ LC( n=24). Results:The success rate of one-step operation in both groups was 100%.The average intra-operative hemorrhage and the average hospital stay after operation were higher in LCBDE+ LC group (all P<0.05). The post-operative complication rate of PTOBF lithotomy + LC group was 10.0% (2/20), recurrence rate of observation period was 10.0% (2/20), while that of LCBDE+ LC group was 8.3% (2/24), and 12.5% (3/24), the difference was not statistically significant (all P>0.05). Conclusion:PTOBF lithotomy combined with LC is a safe, effective and feasible minimally invasive method for the treatment of choledocholithiasis combined with gall stones.

Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3

Objective:To study the use of percutaneous transhepatic one-step biliary fistulation based on three-dimensional visualization technology (3D-PTOBF) in the treatment of complex hepatolithiasis.Methods:A retrospective analysis was conducted on 116 patients with complex hepatolithiasis treated in the First Affiliated Hospital of Guangzhou Medical University from January 2016 to December 2019. There were 56 patients in the 3D-PTOBF group (treated by 3D-PTOBF), and 60 patients in the traditional PTOBF group (received traditional PTOBF approach). The stone clearance rate, postoperative complication rate, intraoperative blood loss, hospitalization time, number of cholangioscopic treatment procedures and stone recurrence rate were compared between the two groups.Results:When compared with the traditional PTOBF group, the 3D-PTOBF group had significantly less procedures (1.43±0.71 vs. 2.07±1.22, P<0.05), and shorter hospital stay (4.6±2.3 d vs. 6.1±2.9 d, P<0.05). There were no significant differences in the immediate stone clearance, final stone clearance, postoperative complications and stone recurrence rates between the two groups (all P>0.05). Conclusion:3D-PTOBF was safe and feasible to treat complex hepatolithiasis. When compared with PTOBF, it had the advantages of shorter operation time and decreased hospital stay.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Fulminant myocarditis (FM) in children is an acute inflammatory myocardial disease, prominently manifesting as hemodynamic disorder.Because of acute onset and rapid progression, FM can cause myocardial cell edema, necrosis, cardiac shock and sudden death.Early symptoms of FM are usually atypical and laboratory tests are nonspecific, thus leading to misdiagnosis.If in time identification and diagnosis of FM is failed, its premature mortality rate can be significantly risen.Electrocardiogram, echocardiogram and cardiac magnetic resonance examinations are of great importance for early detection of FM and prognosis evaluation.Currently, mechanical circulation support is the effective therapeutic strategy for FM.A growing number of studies have focused on the clinical diagnosis and treatment of FM in children, especially the early diagnosis and active interventions, which is of great significance to improve the survival and quality of life in the future.In this paper, the advance on current diagnosis and treatment of FM in children were reviewed.