Objective:To screen the interacting protein of ubiquitin-conjugating enzyme E2S(UBE2S)and construct the hepatocellular carcinoma(HCC)based on UBE2S interacting protein prognosis model(UIPM),and to discuss the value of UIPM in assessing the prognosis of the HCC patients.Methods:Co-immunoprecipitation(Co-IP)was used to screen the protein complexes binding to Flag-UBE2S.After validation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting methods;liquid chromatography-mass spectrometer(LC-MS)was used to identify the UBE2S interacting proteins;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted on these proteins;the prognosis-related proteins from The Cancer Genome Atlas(TCGA)were cross-referenced with UBE2S interacting proteins by survival package of R software;the key proteins were extracted through LASSO regression analysis to build the UIPM;the prognostic model risk scoring formula was established.The HCC patients in TCGA were divided into high risk group and low risk group based on median value of the risk scores.The predictive accuracy of UIPM was evaluated by receiver operating characteristic curve(ROC),and the predictive accuracy was further validated by International Cancer Genome Consortium(ICGC)Database;univariate regression analysis and multivariate Cox regression analysis were used to detect whether the UIPM risk score was an independent prognostic factor for HCC.Furthermore,the nomogram model was built.Results:A total of 97 UBE2S interacting proteins were identified through Co-IP combined with LC-MS analysis.The GO functional enrichment analysis and KEGG signaling pathway enrichment analysis results showed that the interacting proteins were closely associated with cysteine-type endopeptidase activity,oxidative stress,and cell death.The TCGA revealed 5 163 HCC prognosis-related proteins;after intersecting with UBE2S interacting proteins,40 prognosis-related interacting proteins were found.Seven key proteins were determined through LASSO regression analysis,including UBE2S,heat shock protein family A member 8(HSPA8),heterogeneous nuclear ribonucleoprotein H1(HNRNPH1),chaperonin containing TCP1 subunit 3(CCT3),eukaryotic translation initiation factor 2 subunit 1(EIF2S1),receptor for activated C kinase 1(RACK1),and actin related protein 2/3 complex subunit 4(ARPC4),and the UIPM was constructed.There was significant difference in survival rate of the patients between high risk group and low risk group(P<0.05).The ROC curve analysis results showed the area under ROC curve(AUC)values of UIPM for predicting 1-year,2-year,and 3-year survival risk scores of the HCC patients were all greater than 0.7,indicating the model had high predictive accuracy.This was also confirmed by ICGC Database data.The univariate and multivariate Cox regression analysis results showed that the UIPM risk score was an independent prognostic risk factor for the HCC patients(P<0.05).The nomogram results showed good consistency between predicted survival rate and actual survival rate of the patient.Conclusion:A total of 97 interacting proteins that interact with UBE2S may promote the occurence and devolopment of HCC through oxidative stress and dysregulation of ferroptosis pathways.The UIPM risk score is an independent risk factor for the prognosis of HCC and can be used to predict the outcomes of the patients.UBE2S,HSPA8,HNRNPH1,CCT3,EIF2S1,RACK1,and ARPC4 could be regarded as the new biomarkers and therapeutic targets for HCC.

Abstract On 18 May 2021, the Center for Disease Control and Prevention (CDC) of X District in P City, Z Province received a co-investigation of a suspected case of intentional HIV transmission from the public security branch, and conducted epidemiological investigations on Zhao and Wang (both males). Wang was confirmed HIV-positive in 2019. Zhao had unprotected sexual encounters several times with Wang in March 2021 without being informed of Wang's HIV infection. Zhao developed fever, sore throat and other symptoms of acute infection phase on 28 March, and were confirmed HIV positive by the CDC of P City on 11 May. Zhao did not have sex with anyone else before or after having sex with Wang. In addition, Zhao had no history of surgery, blood transfusions, drug use or any other history of HIV exposure. Laboratory tests conducted by the CDC of Z Province showed that the HIV nucleic acid sequences between the samples of Zhao and Wang had a high degree of homology. Combined with the epidemiological investigation, laboratory testing and the evidence from the public security branch, it was concluded that Wang intentionally transmitted HIV to Zhao through unprotected anal sex without disclosing his HIV infection status.

Objective:To analyze the use of medicare antiviral drugs (ART) and related factors among HIV-infected people in Ningbo City.Methods:The retrospective data was collected related to infection and treatment of HIV-infected people in ART in Ningbo up to February 2023 through the National Infectious Disease Surveillance System. Binary logistic regression was used to analyze the factors related to medicare antiviral drug use in HIV-infected people. R 4.2.2 software was used for statistical analysis.Results:A total of 6 433 HIV-infected people with ART records were collected, among which 5 783 were in ART. The prevalence of medicare drugs use among people in ART was 24.8% (1 435/5 783, 95% CI: 23.7%-25.9%). Beilun District (8.7%, 43/497) and Fenghua District (5.7%, 14/247) had the lowest level in medicare drugs use. Among people in ART using medicare or out‐of‐pocket drugs, the prevalence of those who had at least one viral load test in the last year (84.9%, 1 352/1 593) was significantly lower than that of those using free drugs (91.4%, 3 829/4 190) ( χ2=52.50, P<0.001). The results of multivariate logistic analysis showed that the factors influencing medicare drug use included low educational level (junior high school and below: a OR=0.24, 95% CI:0.17-0.34), farmer or worker (farmer: a OR=0.60, 95% CI: 0.39-0.91; worker: a OR=0.42, 95% CI: 0.27-0.64), low monthly income (<3 000 Yuan: a OR=0.29, 95% CI: 0.18-0.45), the longer interval time between diagnosis and treatment (≥21 days: a OR=0.47, 95% CI: 0.30-0.74). Conclusions:Significant regional differences on the prevalence of medicare antiviral drugs use in HIV-infected people exist in Ningbo City. Follow-up management program of patients should be improved to strengthen patient compliance to mobilize medicare drug promotion. Meanwhile, publicity of medicare drugs should be strengthened for farmers or workers with low education level and patients with delayed treatment.

Fragile X-associated tremor/ataxia syndrome(FXTAS)is a neurodegenerative disorder caused by a pre-mutationof the fragile X mental retardation protein 1(FMR1)gene on the X chromosome,and its low incidence rate and complex clinical manifestations often lead to misdiagnosis and missed diagnosis,which requires improving the awareness of this disease among clinicians.This article reviews the recent research advances in the pathogenesis,clinical manifesta-tions,pathological features,and diagnostic criteria of FXTAS.

Prefoldin (PFDN) acts as a co-companion protein to stabilize newly synthesized peptides and prevent protein misfolding and aggregation. PFDN plays an important role in cytoskeleton formation. PFDN is upregulated in glioma, breast cancer, lung cancer, gastric cancer, liver cancer, colorectal cancer and other tumor tissues and is closely linked with the proliferation and migration of tumor cells. A deeper understanding of the role of PFDN in tumorigenesis and development may provide new ideas and insights for PFDN in preventing or reversing tumor progression.

Purpose: Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes. Materials and Methods: CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group. Results: A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003). Conclusion Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

Objective To investigate the prevalence and influencing factors of soil-transmitted nematode infections in Ningbo City from 2016 to 2021, so as to provide insights into the development of targeted control measures against soil-transmitted nematodiasis. Methods Permanent residents at ages of 3 years and older were sampled in Ningbo City using a multi-stage sampling method each year during the period from 2016 to 2021. Soil-transmitted nematode eggs were detected in stool samples using a modified Kato-Katz thick smear method (two slides for each stool sample), and Enterobius vermicularis eggs were additionally identified among children at ages of 3 to 12 years using the adhesive cellophane-tape perianal swab method. The time- and regions-specific prevalence of soil-transmitted nematode infections was calculated, and the factors affecting hookworm infections were identified using a multivariate logistic regression model. Results A total of 11 573 person-times were detected for soil-transmitted nematode infections in Ningbo City from 2016 to 2021, and 296 egg-positives were detected, with a mean prevalence rate of 2.56% [95% confidential interval (CI): (2.28%, 2.87%)]. Hookworm was the predominant species of soil-transmitted nematode among egg-positives in Ningbo City (98.31%, 291/296), and there was a significant difference in the prevalence of hook-worm infections among years (χ² = 190.27, P < 0.01). The highest prevalence of hook-worm infections was observed in Ninghai County (4.06%), and there was a region-specific prevalence rate of hookworm infection in Ningbo City (χ² = 148.43, P < 0.01). Multivariate logistic regression analysis showed that elderly residents at ages of over 60 years [odds ratio (OR)= 1.94, 95% CI: (1.07, 3.54), P < 0.05], males [OR = 2.19, 95% CI: (1.72, 2.80), P < 0.01], farmers [OR = 6.94, 95% CI: (3.37, 14.29), P < 0.01] and residents with a low education level [illiteracy or semi-illiterate: OR = 3.82, 95% CI: (1.56, 9.35), P < 0.05; primary school: OR = 2.70, 95% CI: (1.11, 6.59), P < 0.05] were at a higher risk for hookworm infections. Conclusions The overall prevalence of soil-transmitted nematode infections was low among residents in Ningbo City from 2016 to 2021. The surveillance and health education for human hookworm disease remain to be reinforced among male farmers with a low education level at ages of over 60 years in Ninghai County.

In recent years, artificial intelligence (AI) has been widely applied in the field of drug discovery and development.In particular, natural language processing technology has been significantly improved after the emergence of the pre-training model.On this basis, the introduction of graph neural network has also made drug development more accurate and efficient.In order to help drug developers more systematically and comprehensively understand the application of artificial intelligence in drug discovery, this article introduces cutting-edge algorithms in AI, and elaborates on the various applications of AI in drug development, including drug small molecule design, virtual screening, drug repurposing, and drug property prediction, finally discusses the opportunities and challenges of AI in future drug development.

Primary liver cancer is a major global public health issue and currently the second leading cause of cancer death worldwide. The continuous changes in early cancer detection and treatment strategies have improved the overall survival rate of patients. Emerging organoid technologies have had a dramatic impact on cancer research in recent years, and tumor organoids are widely used in basic and translational cancer research. Tumor organoid culture technology will bridge the gap among molecular genetics, biology and clinical treatment. In this review, we discussed the recent different applications of liver organoids in liver cancer biology and clinical translation, involving liver cancer molecular studies, microenvironment and metastasis studies and drug screening trials, in order to provide a reference for clinical practice.

Objective:To investigate the influence of effects of transarterial chemoembo-lization (TACE) before liver transplantation on the prognosis of hepatocellular carcinoma.Methods:The retrospective cohort study was conducted. The clinicopathological data of 311 hepatocellular carcinoma patients undergoing TACE before liver transplantation who were admitted to the Third Medical Center of Chinese PLA General Hospital from January 2005 to December 2012 were collec-ted. There were 276 males and 35 females, aged from 47 to 59 years, with a median age of 52 years. All the 311 patients underwent TACE before liver transplantation. Observation indicators: (1) effects of hepatocellular carcinoma patients undergoing TACE and its relationship with clinicopathological factors; (2) follow-up; (3) influencing factors for prognosis of hepatocellular carcinoma patients after liver transplantation. Follow-up was conducted using outpatient examination or telephone interview to detect recurrence and metastasis of tumor and survival and graft loss of patients up to December 2017. The patients were followed up every 2 to 4 weeks within 3 months after liver transplantation, and once every 1 to 3 months thereafter. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the nonparametric rank sum test. The COX regression model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to draw survival curves and calculate survival rates, and the Log-rank test was used for survival analysis. Results:(1) Effects of hepatocellular carcinoma patients undergoing TACE and its relationship with clinicopathological factors. Of the 311 patients undergoing TACE, 57 cases had pathologic complete response (pCR) and 254 cases had pathologic partial response (pPR), respectively. Cases with alpha fetoprotein (AFP) <20 μg/L,20?400 μg/L, >400 μg/L, cases with microvascular invasion, cases with tumor number as single nodule, cases with tumor distribution at right lobe of liver, cases with tumor caliber of feeding artery (CFA) >1 mm were 26, 26, 5, 51, 6, 43, 46 in patients with pCR, versus 87, 64, 103, 158, 59, 125, 159 in patients with pPR, showing significant differences in the above indicators ( Z=3.35, χ2=4.54, 15.71, 12.89, 6.79, P<0.05). (2) Follow-up. All the 311 patients were followed up for 47.0 to 59.0 months, with a median follow-up time of 44.6 months. There were 11 cases undergoing tumor recurrence and 11 cases undergoing tumor metastasis in the 57 patients with pCR, and there were 96 cases undergoing tumor recurrence and 66 cases under-going tumor metastasis in the 254 patients with pPR. The 1-, 3-, 5-year tumor recurrence free rates were 98.2%, 91.1%, 80.3% in the 311 patients, respectively. The 1-, 3-, 5-year tumor recurrence free rates were 100.0%, 91.1%, 80.3% in the 57 patients with pCR, versus 82.0%, 68.4%, 59.4% in the 254 patients with pPR, showing significant differences in the above indicators ( χ2=13.47, P<0.05). Cases with graft loss were 11 and 96 in the 57 patients with pCR and the 254 patients with pPR, respectively, showing a significant difference ( χ2=7.06, P<0.05). (3) Influen-cing factors for prognosis of hepatocellular carci-noma patients after liver transplantation. Results of univariate analysis showed that gender, basic diseases as viral hepatitis C, AFP (20?400 μg/L, >400 μg/L), Milan criteria, microvascular invasion, tumor number, tumor distribution, tumor CFA, times of TACE, effects of TACE were related factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=0.49, 3.97, 1.78, 1.84, 2.41, 1.96, 3.00, 1.76, 0.19, 2.01, 3.07, 95% confidence interval as 0.30?0.81, 2.23?7.05, 1.03?3.06, 1.18?2.85, 1.63?3.56, 1.28?3.01, 2.04?4.40, 1.20?2.59, 0.13?0.28, 1.28?3.14, 1.63?5.76, P<0.05). Results of multi-variate analysis showed that AFP >400 μg/L, exceeding Milan criteria, tumor number as multiple nodule,effects of TACE as pPR were independent risk factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=1.59, 2.06, 1.99, 2.05, 95% confidence interval as 1.22?2.07, 1.35?3.13, 1.29?3.07, 1.02?4.10, P<0.05) and tumor CFA >1 mm was an independent protective factor influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=0.10, 95% confidence interval as 0.05?0.19, P<0.05). Conclusions:The effects of TACE are related to AFP, microvascular invasion, tumor number, tumor distribution and tumor CFA. AFP >400 μg/L, exceeding Milan criteria, tumor number as multiple nodule,effects of TACE as pPR are independent risk factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation and tumor CFA >1 mm is an independent protective factor influencing prognosis of hepatocellular carcinoma patients after liver transplantation.