After 50 years of clinical development， endoscopic retrograde cholangiopancreatography （ERCP） has become the preferred method for the clinical diagnosis and treatment of cholangio-pancreatic duct diseases； however， the major postoperative complications of ERCP， such as pancreatitis， hemorrhage， and perforation， are still a difficult issue faced by clinicians， and postoperative perforation is associated with an extremely high risk of death. Therefore， it is very important to explore the risk factors for perforation after ERCP， make a definite diagnosis of perforation in a timely manner， and formulate precise prevention and treatment measures. By reviewing a large number of articles， this article summarizes the influencing factors for perforation after ERCP and related diagnosis and treatment measures.

There is a certain correlation and interaction between circulating tumor cells and recurrence-metastasis of colorectal cancer. The circulating tumor cells hidden in the human body can lead to the recurrence and metastasis of colorectal cancer， and the recurrence and metastasis of colorectal cancer can in turn cause a sharp increase in the number of circulating tumor cells， which is consistent with the characteristics of latent pathogens in traditional Chinese medicine leading to diseases. Starting from the theory of latent pathogens， this article summarized the etiology and disease mechanism of recurrence-metastasis of colorectal cancer as harmed healthy qi， latent pathogenic qi， prolonged latent pathogens， and triggering healthy qi deficiency. This article also proposes four major treatment methods as reinforcing healthy qi， assisting yang， opening the exterior， and expelling pathogen， in order to provide ideas and methods for the prevention and treatment of recurrence and metastasis of colorectal cancer.

Objective To explore the application status and development trend of machine learning in the field of pharmacovigilance worldwide,and to provide reference for the research on the application of machine learning in the field of pharmacovigilance.Methods Relevant literature was searched in the Web of Science with the key words of"machine learning"and"pharmacovigilance"from the inception to March 1,2023.R language and other software were used to quantitatively analyze the literature data in this field.The clustering,co-occurrence and emergence visual analysis were carried out on the characteristics of annual published papers,institutions,countries,keywords and other aspects.Results A total of 904 literature were included.The number of literature published showed a fluctuating upward trend since 1994.There was cross-regional,cross-regional and cross-agency cooperation among the cooperative network institutions.The top 5 countries in the number of publications were the United States,China,Japan,South Korea and India,China and the United States had relatively close cooperation in this field.Signal detection,social media and electronic health records were high-frequency keywords in this field.Clustering and association rule analysis showed that this field focused on three aspects signal recognition,unstructured text mining and analysis,and processing and analysis of electronic medical information.At present,machine learning has made significant progress in signal recognition,social media information mining,and unstructured text processing of electronic medical information,which broaden the data sources of pharmacovigilance,improve the real-time monitoring ability of adverse drug reactions,bringing innovation impetus to the field of pharmacovigilance.Conclusion The rapid development of big data and artificial intelligence technologies has led to an increasing integration of machine learning into the field of pharmacovigilance,which promotes technical exchanges and cooperation and cross-disciplinary integration.It is necessary to optimize each machine learning algorithm to improve its accuracy and stability in pharmacovigilance,strengthen the protection measures of data privacy and security to ensure the safety of patient information.Integrating expertise in the fields of science,medicine,and data statistics with a view to promoting technological progress in the field of pharmacovigilance.

Objective:To investigate the effect of levodopa and benserazide combined with pramipexole in the treatment of Parkinson's disease (PD) and its influence on cognitive function and oxidative stress indicators.Methods:From January 2021 to December 2023, the clinical datas of 110 PD patients in the Neurocritical Rehabilitation Center of Xi'an International Medical Center Hospital were selected for a prospective study. Based on the principle of balanced and comparable baseline features between groups, they were divided into single drug group (odd number, 55 cases, oral levodopa and benserazide, effective dose: 500-1 000 mg/d) and combined group (even number, 55 cases, pramipexole based on single drug group, effective dose: 0.375-4.500 mg/d) according to the simplified randomization method (odd-even number method). The therapeutic effect (Unified Parkinson's Disease Rating Scale (UPDRS)), improvement status of symptoms, cognitive ability (Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA)), oxidative stress indicators (superoxide dismutase (SOD), malondialdehyde) and brain injury indicators (central nervous system specific protein β (S100β), human Parkinson protein 7 (PARK7)) before and after treatment and adverse drug reactions were compared between groups of patients.Results:After treatment, the scores of UPDRS Ⅰ, Ⅱ and Ⅲ dimensions in the two groups were significantly decreased, and the above scores with ((5.53±1.16, 20.43±3.98, 14.37±3.07) points) in combined group were significantly lower than ((7.06±1.64, 24.56±4.37, 17.32±3.83) points) in single drug group ( t values were 5.65, 5.18 and 4.46, respectively; all P<0.001). After treatment, the autonomic disorder and sensory disturbance were significantly improved in both groups, but the proportion of sensory disturbance after treatment in combined group (20.00%, 11/55) was significantly lower than that in single drug group (38.18%, 21/55), and the difference was statistically significant ( χ2=4.41, P=0.036). The MMSE score in the two groups after treatment was decreased significantly while the MoCA score was increased significantly, but the MMSE score in combined group with ((10.38±1.95) points) was significantly lower than ((12.27±2.26) points) in single drug group. The difference was statistically significant ( t=4.70, P<0.001) while the MoCA score with ((18.46±3.21) points) was significantly higher compared with ((16.84±3.07) points) in single drug group.The difference was statistically significant ( t=2.71, P=0.008). After treatment, SOD in the two groups was risen significantly while malondialdehyde was declined significantly, and SOD in combined group with ((82.53±10.63) U/L) was significantly higher than ((76.54±8.85) U/L) in single drug group, while malondialdehyde with ((4.64±0.85) μmol/L) was significantly lower than ((6.46±1.26) μmol/L) in single drug group. The difference is statistically significant ( t values were 3.21 and 8.88, respectively; P values were 0.002 and <0.001). The levels of S100β and PARK7 in both groups were reduced significantly after treatment, and the combined group ((73.64±5.72) ng/L, (78.04±6.93) μmol/L) had significantly lower levels than the single drug group ((15.73±3.25) ng/L, (22.23±3.84) μmol/L). The differences were statistically significant ( t-values were 3.63 and 9.58, respectively; both P<0.001). There was no statistical difference in incidence of adverse drug reactions between groups ( P>0.05). Conclusion:Levodopa and benserazide combined with pramipexole can enhance the cognitive function of PD patients and improve the oxidative stress indicators, with few adverse reactions, safe and effective, and is worthy of application.

OBJECTIVE To mine the risk sig nals o f iodine contrast media from spontaneous reporting system. METHODS Reporting odds ratio ，proportional reporting ratio ，Medicines and Healthcare Products Regulatory Agency and Bayesian confidence propagation neural network were used to mine risk signals of 5 iodine contrast media （iopamidol，iohexol，iopromide，ioversol， iodixanol）. RESULTS 1 164（2 446 case times ）adverse drug reaction of iodine contrast media were included ，a total of 14 risk signals involving systems/organs such as respiratory system （3，2，4，3，2 for the above 5 iodine contrast media ）and immune system and 32 specific adverse drug reaction signals including anaphylactic shock ，rash and flushing （11，7，7，3，4 for the above 5 iodine contrast media ）were found in 5 iodine contrast media. CONCLUSIONS The risk signals of 5 iodine contrast media verify that there is a certain correlation between these drugs and above adverse drug reactions. It is suggested that before using iodine contrast media in clinic ，it is necessary to pay attention to whether the patient has a history of tumor and combined medication ，evaluate the patient’s renal function ，and give preventive measures such as hydration in advance. When using iodine contrast media ，it is necessary to pay attention to the temperature ，dose and injection rate. And medical staff need to follow up the patient ’s situation in time after using iodine contrast media to avoiding the impact of delayed adverse reactions.

Combinatorial therapies have been recently proposed to improve the efficacy of anti-cancer treatment.The SynergyFinder R package is a software used to analyze pre-clinical drug combination datasets.Here,we report the major updates to the SynergyFinder R package for improved interpretation and annotation of drug combination screening results.Unlike the exist-ing implementations,the updated SynergyFinder R package includes five main innovations.1)We extend the mathematical models to higher-order drug combination data analysis and implement dimension reduction techniques for visualizing the synergy landscape.2)We provide a statistical analysis of drug combination synergy and sensitivity with confidence intervals and P values.3)We incorporate a synergy barometer to harmonize multiple synergy scoring methods to provide a consensus metric for synergy.4)We evaluate drug combination synergy and sensitivity to pro-vide an unbiased interpretation of the clinical potential.5)We enable fast annotation of drugs and cell lines,including their chemical and target information.These annotations will improve the interpretation of the mechanisms of action of drug combinations.To facilitate the use of the R package within the drug discovery community,we also provide a web server at www.s ynergyfinderplus.org as a user-friendly interface to enable a more flexible and versatile analysis of drug combination data.

Background: Androgenetic alopecia (AGA) leads to thinning of scalp hair and affects 60%~70% of the adult population worldwide. Developing more effective treatments and studying its mechanism are of great significance. Previous clinical studies have revealed that hair growth is stimulated by 650-nm red light. Objective: This study aimed to explore the effect and mechanism of 650-nm red light on the treatment of AGA by using ex vivo hair follicle culture. Methods: Human hair follicles were obtained from hair transplant patients with AGA. Hair follicles were cultured in Williams E medium and treated with or without 650-nm red light.Real-time RT-PCR and immunofluorescence staining were used to detect the expression level of genes and proteins in hair follicles, respectively. RNA-sequencing analysis was carried out to reveal the distinct gene signatures upon 650 nm treatment. Results: Low-level 650 nm red light promoted the proliferation of human hair follicles in the experimental cultured-tissue model. Consistently, 650 nm red light significantly delayed the transition of hair cycle from anagen to catagen in vitro. RNA-seq analysis and gene clustering for the differentially expressed genes suggests that leukocyte transendothelial migration, metabolism, adherens junction and other biological process maybe involved in stimulation of hair follicles by 650-nm red light treatment. Conclusion The effect of 650-nm red light on ex vivo hair follicles and the transcriptome set which implicates the role of red light in promoting hair growth and reversing of miniaturization process of AGA were identified.

Objective:To explore whether CD5 + CD19 + B cells has the function of secreteing interleukin-10 (IL-10) in vitro, and to further investigate its possible effects and mechanisms on CD8 + cells in the process of hepatitis B virus (HBV) infection. Methods:From July 2017 to June 2018, at Wuxi Second People′s Hospital Affiliated to Nanjing Medical University, 23 patients with chronic hepatitis B (chronic hepatitis B group), 18 patients with liver cirrhosis (liver cirrhosis group) and 19 healthy individuals in the same period as healthy controls (healthy control group) were enrolled. Peripheral blood mononuclear cell (PBMC) were isolated and cultured. CD5 + CD19 + B cells were isolated. The cells were analyzed by flow cytometry. The ratio of high CD5 + CD19 + B cells content (>6 % of lymphocytes), the secretion of IL-10 by CD5 + CD19 + B and the ratio of high IL-10 + cells content (>4 % of lymphocytes) of three groups were compared. The effects and possible mechanisms of CD5 + CD19 + B cells on the secreting of interferon-γ (IFN-γ) by CD8 + cells were analyzed. Liver biopsy and immunohistochemistry examination were conducted in 18 patients (13 patients with chronic hepatitis B and 5 patients with liver cirrhosis) and the expression of CD5 + CD19 + B cells in human liver tissues was analyzed. Chi square test and Fisher exact probability test were used for statistical analysis. Results:The ratio of high CD5 + CD19 + B cells content of liver cirrhosis group was higher than that of healthy control group (8/18 vs. 2/19) and the difference was statistically significant (Fisher exact probability test, P=0.029). The precentage of CD5 + CD19 + B cells in healthy control group ( n=10), chronic hepatitis B group ( n=23) and liver cirrhosis group ( n=18) accounted for 81.6%, 82.3% and 70.1%of IL-10 + cells, respectively, and the number of patients with high IL-10 + cells precentage was 2, 7 and 2, respectively. There were no statistically significant differences among three groups (all P>0.05). After stimulated with lipopolysaccharide and cultured for 48 hours, the precentage of CD8 + IFN-γ + cells in lymphocytes of healthy control group ( n=10), chronic hepatitis B group ( n=10) and liver cirrhosis group ( n=10) were compared, and the differences were not statistically significant (all P>0.05). After CD5 + CD19 + B cells were eliminated, the precentage of CD8 + IFN-γ + cells in lymphocytes increased in 5, 4 and 4 patients of healthy control group ( n=10), chronic hepatitis B group ( n=10) and liver cirrhosis group ( n=10). After adding IL-10 receptor blocker, the precentage of CD8 + IFN-γ + cells in lymphocytes in PBMC increased compared with that before the addition of IL-10 receptor blocker (7.23% vs. 6.87%). The results of immunohistochemistry examination of liver biopsy indicated that CD4 + and CD8 + cells were strong expressed in portal area of liver tissue of patients, while CD5 + and CD19 + were less expressed. Conclusions:CD5 + CD19 + B cells do not show obvious quantitative and functional differences in the process of chronic HBV infection, however the ability of CD8 + cells to secrete IFN-γ, which may be achieved by secreting IL-10 rather than by direct contact between cells.

Objective To study the colonization rate and antibiotic resistance of group B Streptococcus (GBS) in gravidas during late pregnancy,and to evaluate the effectiveness of GBS screening in late pregnancy and intrapartum antibiotic prophylaxis (IAP) for the prevention of neonatal early-onset GBS disease (EOGBS).Methods A retrospective study was conducted to analyze the colonization rate and antibiotic resistance pattern of GBS in 14 204 gravidas who were screened for GBS at 35-37 gestational weeks during March 2016 to March 2018 in the University of Hongkong-Shenzhen Hospital (HKU-SZH).Differences in the incidence of EOGBS before and after GBS screening and IAP were analyzed using Chi-square or Fisher's exact test.Results Among the 14 204 gravidas,2 027 cases were GBS positive with a colonization rate of 14.27％.Incidence rates of EOGBS before and after GBS screening were 0.6‰ (4/6 356) and 0.07‰ (1/14 403),respectively (Fisher's exact test,P=0.033).GBS isolates were 100％ (2 027/2 027) sensitive to penicillin and vancomycin.Resistance rates to clindamycin and erythromycin were 67.2％(1 363/2 027) and 65.7％ (1 332/2 027),respectively.Conclusions Routine GBS screening in late pregnancy and IAP can significantly decrease the incidence of EOGBS.Penicillin is the optimal choice for prevention and treatment of GBS infection.

Objective To explore the effect of apolipoprotein E (ApoE) on secretions of matrix metalloproteinase-9 (MMP-9),matrix metalloproteinase tissue inhibitor-1 (TIMP-1) and inflammatory factors in spleen macrophages at early stage of experimental autoimmune encephalomyelitis (EAE).Methods In accordance with random number table,20 ApoE knockout (ApoE-/-) C57BL/6J mice were divided into ApoE-/-EAE group and ApoE-/-control group (n=10);and 20 wild type (WT) C57BL/6J mice were divided into WT EAE group and WT control group (n=10).Myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) was used as antigen to induce EAE models in the ApoE-/-EAE group and WT EAE group,and MOG35-55 was replaced by normal saline in ApoE-/-control group and WT control group.The spleen macrophages were isolated from mice after 7th d of modeling and cultured in vitro;the rnacrophages of the ApoE-/-EAE group and WT EAE group were stimulated by MOG35-55,while the macrophages of the ApoE-/-control group and WT control group were treated with equivalent normal saline.Forty-eight hafter that,the contents of MMP-9,TIMP-1,interferon gamma-γ(IFN-γ),tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the culture medium were determined by ELISA.Results The contents of MMP-9,TFN-γ TNF-α and IL-6 in the WT EAE group were significantly higher than those in the WT control group (P＜0.05);the contents of MMP-9,IFN-γ 、TNF-α and IL-6 in the ApoE-/-EAE group were significantly higher than those in the ApoE-/-control group (P＜0.05);the content ofMMP-9,IFN-γ,TNF-cα and IL-6 in ApoE-/-EAE group were significantly higher than those in the WT EAE group (P＜0.05).The TIMP-1 secretion ofmacrophages in WT EAE group was significantly higher than that in WT control group (P＜0.05).Conclusions At early stage of EAE,macrophages secrete high levels of MMP-9 and inflammatory factors,and the deficiency of ApoE further contributes to the secretions of MMP-9 and inflammatory factors by macrophages.ApoE may play a role in protecting the integrity of blood-brain barrier and alleviating the inflammatory response of the central nervous system through the effects on macrophages.