Primary biliary cholangitis （PBC） is an autoimmune disease characterized by cholestasis of the intrahepatic bile ducts. Anti-mitochondrial antibody （AMA） is currently the key serum marker for the diagnosis of PBC， and however， there are still 5%—10% of patients with PBC who have undetectable AMA in their serum and need liver biopsy to make a confirmed diagnosis. Noninvasive diagnosis remains a challenge in AMA-negative PBC patients. This article reviews the research advances in specific serum markers other than AMA， summarizes the advantages and disadvantages of these serum markers in the diagnosis of AMA-negative PBC， and analyzes the types of new biomarkers that may be used in the noninvasive diagnosis of patients with AMA-negative PBC， in order to provide new ideas for identifying serum markers with higher sensitivities.

Objective: To explore incidence trend of hepatitis C in Chifeng City, Inner Mongolia Autonomous Region from 2008 to 2022, so as to provide the basis for formulating prevention and control measures for hepatitis C. Methods: Data of reported hepatitis C cases in Chifeng City from 2008 to 2022 was collected through the Infectious Disease Information Reporting Management System. Trends in incidence of hepatitis C were analyzed using annual percent change (APC) and average annual percent change (AAPC). Impact of age, period and birth cohort on the risk of developing hepatitis C were analyzed by an age-period-cohort model. Results: The annual average reported incidence rate of hepatitis C in Chifeng City was 59.13/105 from 2008 to 2022. The incidence showed an upward trend from 2008 to 2018 (APC=9.405%, P<0.05) and a downward trend from 2018 to 2022 (APC=-17.475%, P<0.05), but the overall trend was not statistically significant (AAPC=0.937%, P>0.05). The age-period-cohort model analysis showed that the incidence risks of hepatitis C in the residents aged 0 to 4 years and 45 to 84 years were higher than those in the residents aged 40 to 44 years (the control group). The incidence risk of hepatitis C increased with age from 40 to 79 years. Compared with 2008-2012, the incidence risk of hepatitis C showed an increasing trend followed by a decline in 2008-2022. The incidence risk was higher in 2013-2017 and lower in 2018-2022 than in 2008-2012. The incidence risk of hepatitis C showed an increasing trend followed by a decreasing trend by using the birth cohort from 1968 to 1972 as the control. The birth cohort from 1953 to 1977 had a higher incidence risk of hepatitis C than other birth cohorts. Conclusions The overall incidence of hepatitis C in Chifeng City from 2008 to 2022 appeared a tendency towards a decline, and the incidence risk increased with age. Screening and health education for the elderly and high-risk birth cohorts should be strengthened.

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

BACKGROUND:Sepsis is one of the main causes of mortality in intensive care units(ICUs).Early prediction is critical for reducing injury.As approximately 36%of sepsis occur within 24 h after emergency department(ED)admission in Medical Information Mart for Intensive Care(MIMIC-IV),a prediction system for the ED triage stage would be helpful.Previous methods such as the quick Sequential Organ Failure Assessment(qSOFA)are more suitable for screening than for prediction in the ED,and we aimed to find a light-weight,convenient prediction method through machine learning. METHODS:We accessed the MIMIC-IV for sepsis patient data in the EDs.Our dataset comprised demographic information,vital signs,and synthetic features.Extreme Gradient Boosting(XGBoost)was used to predict the risk of developing sepsis within 24 h after ED admission.Additionally,SHapley Additive exPlanations(SHAP)was employed to provide a comprehensive interpretation of the model's results.Ten percent of the patients were randomly selected as the testing set,while the remaining patients were used for training with 10-fold cross-validation. RESULTS:For 10-fold cross-validation on 14,957 samples,we reached an accuracy of 84.1%±0.3%and an area under the receiver operating characteristic(ROC)curve of 0.92±0.02.The model achieved similar performance on the testing set of 1,662 patients.SHAP values showed that the five most important features were acuity,arrival transportation,age,shock index,and respiratory rate. CONCLUSION:Machine learning models such as XGBoost may be used for sepsis prediction using only a small amount of data conveniently collected in the ED triage stage.This may help reduce workload in the ED and warn medical workers against the risk of sepsis in advance.

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

Objectives:To investigate the outcomes of cochlear implantation in Mandarin-speaking cochlear implant (CI) users with single-sided deafness (SSD).Methods:This study was a single-center prospective cohort study. Eleven Mandarin-speaking adult SSD patients who underwent CI implantation at Capital Medical University Beijing Tongren Hospital from August 2020 to October 2021 were recruited, including 6 males and 5 females, with the age ranging from 24 to 50 years old. In a sound field with 7 loudspeakers distributed at 180°, we measured root-mean-square error(RMSE)in SSD patients at the preoperative, 1-month, 3-month, 6-month, and 12-month after switch-on to assess the improvement of sound source localization. The Mandarin Speech Perception (MSP) was used in the sound field to test the speech reception threshold (SRT) of SSD patients under different signal-to-noise locations in a steady-state noise under conditions of CI off and CI on, to reflect the head shadow effect(S SSDN NH), binaural summation effect(S 0N 0) and squelch effect(S 0N SSD). The Tinnitus Handicap Inventory (THI) and the Visual Analogue Scale (VAS) were used to assess changes in tinnitus severity and tinnitus loudness in SSD patients at each time point. The Speech, Spatial and Qualities of Hearing Scale(SSQ) and the Nijmegen Cochlear Implantation Scale (NCIQ) were used to assess the subjective benefits of spatial speech perception and quality of life in SSD patients after cochlear implantation. SPSS 19.0 software was used for statistical analysis. Results:SSD patients showed a significant improvement in the poorer ear in hearing thresholds with CI-on compared with CI-off; The ability to localize the sound source was significantly improved, with statistically significant differences in RMSE at each follow-up time compared with the preoperative period ( P<0.05). In the S SSDN NH condition, which reflects the head shadow effect, the SRT in binaural hearing was significantly improved by 6.5 dB compared with unaided condition, and the difference was statistically significant ( t=6.25, P=0.001). However, there was no significant improvement in SRT between the binaural hearing condition and unaided conditions in the S 0N 0 and S 0N SSD conditions ( P>0.05). The total score of THI and three dimensions were significant decreased ( P<0.05). Tinnitus VAS scores were significantly lower in binaural hearing compared to the unaided condition ( P<0.001). The total score of SSQ, and the scores of speech and spatial dimensions were significant improved in binaural hearing compared to the unaided condition ( P<0.001). There was no statistical difference in NCIQ questionnaire scores between preoperative and postoperative ( P>0.05), and only the self-efficacy subscore showed a significant increase( Z=-2.497, P=0.013). Conclusion:CI could help Mandarin-speaking SSD patients restore binaural hearing to some extent, improve sound localization and speech recognition in noise. In addition, CI in SSD patients could suppress tinnitus, reduce the loudness of tinnitus, and improve subjective perceptions of spatial hearing and quality of life.

ObjectiveTo explore the distribution characteristics of traditional Chinese medicine （TCM） syndromes in postoperative gastric cancer patients， and to analyse the factors associated with yang deficiency syndrome and its severity. MethodsTotally， 173 patients who underwent postoperative gastric cancer surgery and were treated in four centers nationwide from February 22， 2022 to March 21， 2023， were enrolled. General information and TCM syndromes were collected， and Diagnostic Scale for Yang Deficiency Syndrome in Gastric Malignancies was filled in. The frequency of TCM syndromes after gastric cancer surgery was analyzed， and univariate analysis and multivariate logistic regression analysis were performed on the related factors of yang deficiency syndrome versus non-yang deficiency syndrome and between different severity of yang deficiency syndrome. ResultsThe most common syndrome after gastric cancer surgery was qi deficiency （95 cases， 54.91%）， followed by yang deficiency （87 cases， 50.29%）. Patients with yang deficiency syndrome were often suffered from qi deficiency， qi stagnation， and phlegm dampness syndrome. Comparing yang deficiency syndrome with non-yang deficiency syndrome， univariate analysis showed that history of alcohol consumption， pathological stage， degree of differentiation， Lauren grade， signet ring cell carcinoma， vascular cancer thrombus， and nerve invasion were statistically significant （P＜0.05）； and multivariate logistic regression analysis showed that history of alcohol consumption， signet ring cell carcinoma， pathological stage Ⅲ， Ⅳ， and vascular cancer thrombus may be correlated with yang deficiency syndrome in postoperative gastric cancer patients （P＜0.05）. The univariate analysis showed that age， pathological stage， precancerous lesions， and body mass index grade were significantly different when compared between mild and severe yang deficiency syndrome （P＜0.05）； multivariate logistic regression analysis showed that age， low body weight， and pathological stage Ⅲ and Ⅳ might be correlated with severe yang deficiency syndrome after gastric cancer surgery （P＜0.05）. ConclusionQi deficiency and yang deficiency are common TCM syndromes in postoperative patients with gastric cancer. Alcohol consumption history， pathological staging （stage Ⅲ and Ⅳ）， signet ring cell carcinoma， and the presence of vascular cancer thrombus may be correlated with the occurrence of yang deficiency syndrome， and higher age， low body weight， and pathological staging （stage Ⅲ and Ⅳ） may be the correlates of severe yang deficiency syndrome.

Host cell residue DNA is one of the most common impurity which can affect the safety of biological products,therefore,domestic and international regulatory agencies have required the limit for host cell residue DNA in different biological products,either at the final product qualification or the appropriate intermediate control stage.The removal effect is verified by monitoring the residue DNA of products in different production stages,which is beneficial for assuring the scientificity and stability of the production process.In order to strengthen the understanding of control strategy about host cell residual DNA,the paper reviews progress in host cell residual DNA in biological products by authors'work experience and other's research,which provides reference for future work.

BACKGROUND: Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC). METHODS: We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: The abundance of fecal Veillonella parvula ( V . parvula ) decreased significantly after BBR administration ( P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect. CONCLUSION: BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula , thereby blocking the development of colorectal tumors. TRIAL REGISTRAION ClinicalTrials.gov, No. NCT02226185.
Animals ; Humans ; Berberine/therapeutic use* ; Carcinogenesis ; Veillonella ; Colorectal Neoplasms/genetics* ; Tumor Microenvironment

Objective:To investigate the efficacy of camrelizumab combined with second-line therapy in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC) in the real-world settings.Methods:Clinical data of 48 patients with esophageal cancer who met the inclusion criteria were retrospectively analyzed. The types of failure after first-line treatment, clinical efficacy, side effects and prognostic factors of second-line treatment were analyzed. SPSS 25.0 software was used for statistical analysis. Count data were expressed by composition ratio and analyzed by Chi-square test or Fisher's exact test. Survival analysis was conducted by Kaplan-Meier curve and log-rank test. Non-normally distributed data were recorded with the median, range and quartile. Results:There were 26, 14, and 4 cases of combined chemoradiotherapy, chemotherapy and radiotherapy in the treatment of second-line camrelizumab, and 4 cases received immunotherapy alone. The median duration of immunotherapy was 6 cycles (range, 2-39 cycles). After second-line treatment, the short-term efficacy of 17, 27 and 4 cases was partial remission (PR), stable disease (SD) and progressive disease (PD), respectively. The overall response rate (ORR) was 35.4% and disease control rate (DCR) was 91.7%. The 1- and 2-year OS rates were 42.9% and 22.5%, and 1- and 2-year PFS rates were 29.0% and 5.8%. The median OS and PFS were 9.0 months (95% CI=6.4-11.7) and 8.5 months (95% CI=1.5-5.6), respectively. Multivariate analysis showed that combined immunotherapy mode, number of cycles of immunotherapy and short-term efficacy were the independent prognostic indicators affecting OS in this group of patients ( HR=2.598, 0.222, 8.330, P=0.044, <0.001, <0.001). Lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), combined immunotherapy mode and short-term efficacy were the independent prognostic indicators affecting PFS in this group ( HR=3.704, 3.598, 6.855, 2.159, 2.747, P=0.009, 0.008, <0.001, 0.049, 0.012). Conclusions:Camrelizumab combined with second-line therapy can bring survival benefit to patients with recurrent or metastatic ESCC after first-line therapy, especially immunotherapy combined with chemoradiotherapy can significantly provide survival benefit. Peripheral blood inflammatory biomarkers are independent indicators affecting clinical prognosis of patients. Patients with better short-term efficacy also achieve better prognosis. The final conclusion remains to be validated by a large number of randomized controlled studies.