Objective To mine and analyze adverse drug events(ADEs)of novel agents for multi-drug-resistant tuberculosis(MDR-TB)based on the FDA Adverse Event Reporting System(FAERS)database,to explore the signals of ADEs,and to provide reference for clinical use.Methods The FAERS database was searched and extracted from Q1 of 2015 to Q4 of 2023,and the ADE reports about bedaquiline,delamanid,and pretomanid were collected.Data mining and analysis were carried out on relevant reports of the drug using the reporting odds ratio(ROR),proportional reporting ratio(PRR),medicines and healthcare products regulatory agency(MHRA),and the Bayesian confidence progressive neural network(BCPNN).Results The number of ADE reports for the target drugs bedaquiline,delamanid,and pretomanid were 2 477,1 630,and 173,respectively.ADE of the target drugs involved multiple organ systems.Positive signals detected by the ROR,PRR,MHRA,and BCPNN methods were 246,246,215,204 for bedaquiline;251,251,224,200 for delamanid;and 25,25,24,22 for pretomanid.Clinically significant high-risk signals include prolonged QT interval on ECG,anemia,liver toxicity,peripheral neuropathy,etc.Conclusions The signal mining of ADEs based on the FAERS database indicates that close attention should be paid to risks such as prolonged QT interval on ECG,anemia,liver toxicity,and peripheral neuropathy during the clinical use of bedaquiline,delamanid,and pretomanid.In addition,monitoring of new potential ADE signals(such as acute heart failure,respiratory failure,acute kidney injury,etc.)should be strengthened,and timely intervention measures should be taken to ensure medication safety.

Objective To mine and analyze adverse drug events(ADEs)of novel agents for multi-drug-resistant tuberculosis(MDR-TB)based on the FDA Adverse Event Reporting System(FAERS)database,to explore the signals of ADEs,and to provide reference for clinical use.Methods The FAERS database was searched and extracted from Q1 of 2015 to Q4 of 2023,and the ADE reports about bedaquiline,delamanid,and pretomanid were collected.Data mining and analysis were carried out on relevant reports of the drug using the reporting odds ratio(ROR),proportional reporting ratio(PRR),medicines and healthcare products regulatory agency(MHRA),and the Bayesian confidence progressive neural network(BCPNN).Results The number of ADE reports for the target drugs bedaquiline,delamanid,and pretomanid were 2 477,1 630,and 173,respectively.ADE of the target drugs involved multiple organ systems.Positive signals detected by the ROR,PRR,MHRA,and BCPNN methods were 246,246,215,204 for bedaquiline;251,251,224,200 for delamanid;and 25,25,24,22 for pretomanid.Clinically significant high-risk signals include prolonged QT interval on ECG,anemia,liver toxicity,peripheral neuropathy,etc.Conclusions The signal mining of ADEs based on the FAERS database indicates that close attention should be paid to risks such as prolonged QT interval on ECG,anemia,liver toxicity,and peripheral neuropathy during the clinical use of bedaquiline,delamanid,and pretomanid.In addition,monitoring of new potential ADE signals(such as acute heart failure,respiratory failure,acute kidney injury,etc.)should be strengthened,and timely intervention measures should be taken to ensure medication safety.

To report a case of clonorchiasis (Clonorchis sinensis infection) combined with intrahepatic cholangiocarcinoma and review relevant literature to improve the awareness of the clinical physicians regarding Clonorchis Sinensis and provide references for clinical diagnosis and treatment. A retrospective analysis was conducted on a case of clonorchiasis combined with intrahepatic cholangiocarcinoma, admitted to Guangzhou Red Cross Hospital of Jinan University on March 15, 2021, along with a review of related literature. The patient, a 55-year-old male, presented with abdominal distension and poor appetite for over two months and had a history of diabetes and hypertension for many years. He had been consuming raw fish for more than ten years. Upon admission, physical examination revealed a solid mass measuring 8 cm×8 cm was palpable below the xiphoid process in the upper abdomen, with an uneven surface, slightly hard texture, poor mobility, and positive tenderness. Laboratory tests revealed the presence of Clonorchis Sinensis eggs in the stool, and the patient tested positive for Clonorchis Sinensis IgG antibodies. After a comprehensive evaluation that included abdominal ultrasound, abdominal plain CT scan, and contrast-enhanced CT, the patient was diagnosed with "intrahepatic cholangiocarcinoma with multiple intrahepatic metastases." Due to the patient's poor liver function, praziquantel was not administered, and albendazole was instead used at a dose of 10 mg/(kg·d) once daily for seven days. Upon re-admission one month after discharge, no Clonorchis Sinensis eggs were found in the stool. A follow-up after 12 months revealed that the patient had passed away due to liver failure. The serious infection of Clonorchis Sinensis is relatively rare, but it can lead to severe consequences in high-risk individuals, especially when it progresses to intrahepatic cholangiocarcinoma. Clinicians should enhance their awareness of clonorchiasis and promptly identify and provide symptomatic treatment for infections, as early as possible and provide appropriate treatment. Early diagnosis and treatment are crucial for improving the prognosis of patients.

Objective:To predict potential target genes in dexamethasone-induced open-angle glaucoma via bioinformatics technology.Methods:The GEO datasets GSE16643, GSE37474, and GSE124114 were used to analyze the differentially expressed genes by GEO2R.Gene Set Enrichment Analysis (GSEA) was performed on the differentially expressed genes between GSE37474 and GSE124114.Intersection of the three datasets were displayed by Venn diagram.The annotation and enrichment analysis of the intersection genes were performed through Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and then were compared with normal tissue in GTEx Portal database.The corresponding protein interaction network was obtained by STRING.Finally, the candidate genes were searched for their transcription factors in UCSC and JASPAR.Primary human trabecular cells were divided into dexamethasone group and control group, treated with 2 ml 500 nmol/L dexamethasone and the same amount of ethanol, respectively.The expression of BDKRB1 and TAGLN in trabecular cells was detected by Western blot.Results:Differential genes between GSE37474 and GSE124114 datasets enriched in complement and coagulation cascade by GSEA.There were 89 intersecting genes of the three datasets.These genes mainly regulated the formation of extracellular matrix by GO analysis.The gene with the highest enrichment score and collagen-containing extracellular matrix was found to be associated with fibroblasts in GTEx Portal database.ACTA2, MYL9, TAGLN, and LMOD1 were closely related in STRING protein-protein interaction network.Transcription factor SP1 in UCSC and JASPAR according to related genes, BDKRB1, NID1, MFGE8 and TAGLN.The relative expression levels of BDKRB1 and TAGLN proteins were 1.32±0.14 and 0.44±0.09 in dexamethasone group, respectively, which were significantly higher than 1.00±0.00 and 0.20±0.10 in the control group, respectively ( t=-3.61, 2.89; both at P<0.05). Conclusions:Bioinformatics analysis showed that transcription factor SP1 may play a role in human trabecular meshwork cells to myofibroblasts transition after dexamethasone treatment.

Objective:To investigate the safety and efficacy of FOLFOX (5-fluorouracil + calcium folinate + oxaliplatin) hepatic arterial infusion chemotherapy (FOLFOX-HAIC) combined with immune and targeted therapy as triple combination therapy for patients with single China Liver Cancer Staging (CNLC) Ⅰb hepatocellular carcinoma.Methods:A total of 20 patients with single CNLC Ⅰb hepatocellular carcinoma who received FOLFOX-HAIC combined with immune and targeted therapy as triple combination therapy in the First Affiliated Hospital of Guangxi Medical University from October 2021 to August 2022 were included. The clinical data of all patients was retrospectively analyzed. There were 18 males and 2 females, with the age of (55.1±9.9) years. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were used to evaluate the efficacy of FOLFOX-HAIC combined with immune and targeted therapy, and the clinical safety of triple combination therapy was evaluated by common terminology criteria for adverse events 4.0.Results:According to RECIST 1.1, objective response rate of 20 patients was 70.0% (14/20) and disease control rate was 100.0% (20/20) after 2 cycles of treatment (one cycle of FOLFOX-HAIC plus programmed death-1 antibody). According to mRECIST, objective response rate was 90.0% (18/20) and the disease control rate was 100.0% (20/20) after 2 cycles of treatment. Following the treatment, 12 patients (60.0%) received liver tumor resection, and all of them achieved R 0 resection, 2 patients (10.0%) received radiotherapy, 3 patients (15.0%) stopped drug treatment for surgery, 2 patients (10.0%) refused surgery, and 1 patient (5.0%) died of multiple organ failure caused by immune hepatitis. According to pathological results, 3 patients (25.0%, 3/12) achieved pathological complete response, and 4 patients (33.3%, 4/12) achieved major pathological response. In the safety evaluation, the overall incidence of adverse events was 100.0% (20/20). Seven patients (35.0%) had grade 3 adverse events and 1 patient (5.0%) died of multiple organ failure due to immune hepatitis (grade 5). Grade 1-3 adverse events could be relieved after symptomatic treatment. Conclusion:The triple combination therapy of FOLFOX-HAIC combined with immune and targeted therapy is safe and has high objective response rate and disease control rate, which could be a new strategy for the neoadjuvant treatment of hepatocellular carcinoma.

Objective To investigate the application value of serum auto-antibody detection combined with low-dose spiral computed tomography (LDCT) in early lung cancer screening. Methods From 12568 medical examination crowd (7453 males and 5115 females), 1324 people with high-risk cases of lung cancer in our medical examination center were divided randomly into three groups (LDCT, serum auto-antibody, and serum auto-antibody combined with LDCT groups). All people in this research were screened by chest X-ray. Follow-up was conducted for one year, and the positive screening and diagnosis rates of early lung cancer screening were compared between these groups of high-risk people with lung cancer. Results The positive screening and diagnostic rates of high-risk lung cancer in the serum auto-antibody combined with LDCT group was significantly higher those that in other two groups (P < 0.001). The specificity and sensitivity of serum auto-antibody combined with LDCT group were 89.1% and 88.4%, respectively; the area under the ROC curve was 0.863. Conclusion Serum auto-antibody detection combined with low-dose spiral CT can significantly improve the positive screening rate of lung cancer in high-risk populations, providing a strong theoretical support for lung cancer screening pathway.

Objective:To investigate the diagnostic value of integrated 18F-fluorodeoxyglucose (FDG) PET/MRI multimodal imaging in the grading of adult diffuse gliomas. Methods:A retrospective analysis was performed; 29 patients accepted cranial 18F-FDG PET/MRI multimodal imaging and diagnosed as having adult diffuse gliomas in our center from January 2020 to December 2021 were chosen; their clinical and image data were collected. These patients were divided into low-grade group (WHO grading II, n=13) and high-grade group (WHO grading III and IV, n=16) according to the pathological results confirmed by surgery or biopsy. T1WI, T2WI, DWI, arterial spin labeling (ASL), magnetic resonance spectroscopy (MRS) and PET were performed in these patients. Differences in T1WI and T2WI signs between the two groups were compared. Differences in maximum standard uptake value (SUV max), apparent diffusion coefficient (ADC), choline/ N-acetylaspartate (Cho/NAA), NAA/creatine (Cr), Cho/Cr, relative cerebral blood flow (rCBF) between the two groups were compared. The diagnostic efficacies of above parameters in differentiating high-grade from low-grade adult diffuse gliomas were determined by receiver-operating characteristic (ROC) curves. The predictive probabilities for differentiating high-grade from low-grade adult diffuse gliomas using combined parameters were obtained by binary Logistic regression analysis. Results:There were no statistical differences in T1WI and T2WI signs, proportion of adjacent parenchyma edema, proportion of crossing the midline into the contralateral side, proportion of mass effect, proportion of cystic degeneration/necrosis, or site of growth between low-grade and high-grade groups ( P>0.05). The values of SUV max, ADC, Cho/NAA, Cho/Cr and rCBF were statistically different between the two groups, and the order of diagnostic efficiency was SUV max>ADC>Cho/NAA>rCBF>Cho/Cr>NAA/Cr. SUV max had the highest diagnostic efficacy in differentiating high-grade from low-grade adult diffuse gliomas with an area under the curve (AUC) of 0.894, a sensitivity of 75% and a specificity of 100%; the diagnostic efficacy of combined parameters (mean AUC>0.9) was higher than that of single parameter, and the combined parameters of SUV max and Cho/NAA showed the highest diagnostic efficacy with an AUC of 0.933, a sensitivity of 81.3% and a specificity of 92.3%. Conclusion:The 18F-FDG PET/MRI multimodal imaging is helpful in the grading diagnosis of adult diffuse gliomas, and combination of PET and MRS may play a greater role.

Objective:To investigate the distribution and clinical significance of subtypes of antimitochondrial antibodies (AMA)-M2, M4, M9 in primary biliary cholangitis (PBC).Methods:A total of 1 367 patients were detected with AMA-M2, M4, M9 in Peking Union Medical College Hospital (PUMCH) from Jan 2014 to Dec 2019 and the clinical parameters were collected. The distribution patterns of AMA subtypes in different groups were analyzed and the diagnostic sensitivity and specificity of AMA subtypes in PBC were calculated. Chi-square test was used for statistical analysis.Results:In 1 367 patients, 236 of whom were positive for AMA subtypes. The positivity of AMA subtypes in female was significantly higher than in male (20.34% vs 9.41%, χ2=23.792, P<0.01). In addition, the positivity of AMA subtypes was significantly higher in 30-65 years old patients than in patients younger than 30 years old or older than 65 years old [(20.00%(193/965) vs 10.97%(17/155) vs 10.53%(26/247), χ2=17.209, P<0.01]. 110 patients with positive AMA subtypes were diagnosed with PBC. The diagnostic sensitivity and specificity of AMA-M2 were both desirable [94.64%(106/112) and 92.35%(1 159/1 255)]. Although the specificity of AMA-M4 was as high as 99.12%(1 244/1 255), its sensitivity was very low [15.18%(17/122)]. Combined detection of different AMA subtypes could not improve the diagnostic sensitivity and specificity significantly. Diseases other than PBC can be positive for AMA subtypes, predominantly for AMA-M2. Conclusion:Female and 30-65 years old patients were more frequently positive for AMA subtypes. AMA-M2 was the most valuable AMA subtype for diagnosing PBC.

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

Objective:To evaluate the immunogenicity and immune persistence of purified Vero cells rabies vaccine (PVRV) with Zagreb and Essen regimen.Methods:Prospective study: Patients with first Class II exposure to rabies were recruited from the Dog Injury Cinic of Guangxi Center for Disease Control and Prevention (Guangxi CDC) and randomly divided into the Zagreb (2-1-1) and Essen (1-1-1-1-1) regimen group. All patients were inoculated with the vaccines from the same manufacturer and batch, and 3 ml serum was collected at the 45th day and in 1-year, 2-year and 3-year after immunization. Rapid fluorescent inhibition test (RFFIT) was used to detect rabies virus neutralizing antibody (RVNA). The attenuation of RVNA positive rate and geometric mean titer (GMT) with time was analyzed. Retrospective study: The informed consents for rabies vaccine in the Dog Injury Clinic of Guangxi CDC were checked out. The patients who were injected with PVRV (same manufacturer but unlimited batch) but without passive immune agents for the first time within 3 years were selected and divided into 1-year, 2-year and 3-year group. Each group was further divided into Zagreb and Essen regimen group. The serum (3 ml) was collected at 1 year, 2 years and 3 years after immunization and detected the RVNA by RFFIT.Results:Prospective study: The RVNA positive rates on the 45th day and in 1-year, 2-year and 3-year after immunizationin in the Zagreb and Essen regimen group were 100%, 95%, 85%, 80% and 98.25%, 89.47%, 89.47%, 85.96%, respectively. There was no statistically significant difference in the RVNA positive rates at the same time point between the two regimen groups ( P>0.05). The RVNA GMT on the 45th day and in 1-year, 2-year, and 3-year in the Zagreb and Essen regimen group were 11.32 IU/ml, 1.69 IU/ml, 1.30 IU/ml, 1.30 IU/m and 13.18 IU/ml, 2.13 IU/ml, 1.87 IU/ml, 1.84 IU/m, respectively. There was no significant difference in the RVNA GMT levels at the same time point between the two regimen groups ( F=1.971, P=0.164). The RVNA GMT levels in the two regimen groups had the same trend of attenuation over time (time*group F=0.702, P=0.435). Retrospective study: The RVNA positive rates in 1-year, 2-year and 3-year after immunization in the Zagreb and Essen regimen group were 100%, 95%, 91.43%和94.73%, 86.21%, 87.5%, respectively. There was no statistically significant difference in the RVNA positive rates at the same time point between the two regimen groups ( P>0.05). The RVNA GMT in 1-year, 2-year, and 3-year groups after immunization in the Zagreb and Essen regimen group were 2.65 IU/ml, 2.03 IU/ml, 1.57 IU/ml和3.2 IU/ml, 2.58 IU/ml, 2.45 IU/ml, respectively. There was no significant difference in the RVNA GMT levels at the same time point between the two regimen groups ( P>0.05). Conclusions:The PVRV showed the same excellent immunogenicity and immune persistence after the vaccination with the Zagreb and Essen regimens.