This review is based on the research progress and challenges of immune checkpoint inhibitors (ICIs) in the treatment of hepatocellular carcinoma (HCC). ICIs block the PD-1/PD-L1 and CTLA-4 pathways; thereby reactivate the body’s anti-tumor immune response, providing a new therapeutic option for patients with advanced HCC. However, the effect of ICIs is still compromised by factors such as primary and acquired resistance, immune-related adverse events and tumor microenvironment inhibition. This reveiw deeply analyzes these key mechanisms that affect the efficacy of ICIs, and proposes strategies to optimize the treatment, including combination with targeted therapy, chemotherapy and radiotherapy, modulation of tumor microenvironment, and the development of novel biomarkers. Future research should focus on personalized treatment that integrates the molecular and immunological characteristics of patients to enhance the precision and efficacy of ICIs therapy for patients with HCC.

This review is based on the research progress and challenges of immune checkpoint inhibitors (ICIs) in the treatment of hepatocellular carcinoma (HCC). ICIs block the PD-1/PD-L1 and CTLA-4 pathways; thereby reactivate the body’s anti-tumor immune response, providing a new therapeutic option for patients with advanced HCC. However, the effect of ICIs is still compromised by factors such as primary and acquired resistance, immune-related adverse events and tumor microenvironment inhibition. This reveiw deeply analyzes these key mechanisms that affect the efficacy of ICIs, and proposes strategies to optimize the treatment, including combination with targeted therapy, chemotherapy and radiotherapy, modulation of tumor microenvironment, and the development of novel biomarkers. Future research should focus on personalized treatment that integrates the molecular and immunological characteristics of patients to enhance the precision and efficacy of ICIs therapy for patients with HCC.

OBJECTIVE To explore the color and odor changes of Salvia miltiorrhiza Bge.slices from different origins,and com-bine modern machine learning technology to achieve rapid differentiation of origins.METHODS Intelligent sensory technology was used to quantify the color and represent the odor of Salvia miltiorrhiza Bge.slices from different geographical origins.Various data a-nalysis methods including principal component analysis(PCA),discriminant analysis,discriminant factor analysis(DFA),component heat maps,correlation analysis,machine learning and so on,were employed to establish a discrimination function for distinguishing the origin of Salvia miltiorrhiza Bge.slices based on color data.RESULTS Classification and screening of odor information led to the i-dentification of 10 differential markers:ethanol,carbon disulfide,cyclopentane,3-methylfuran,propylene glycol,nonane,phenol,1,5-octadienone,1,8-cineole,and sotolon.It was also found that there was a significant correlation between the color and odor of the slices.Furthermore,based on the concept of data fusion,the study established classification models such as subspace clustering,and compared to single-color discriminant analysis,the classification accuracy was improved to 94.4%.CONCLUSION The feasibility and superiority of intelligent sensory technology in classifying the geographical origin of TCM is confirmed,providing new methods and insights for quality control of Salvia miltiorrhiza Bge.slices.

OBJECTIVE To explore the color and odor changes of Salvia miltiorrhiza Bge.slices from different origins,and com-bine modern machine learning technology to achieve rapid differentiation of origins.METHODS Intelligent sensory technology was used to quantify the color and represent the odor of Salvia miltiorrhiza Bge.slices from different geographical origins.Various data a-nalysis methods including principal component analysis(PCA),discriminant analysis,discriminant factor analysis(DFA),component heat maps,correlation analysis,machine learning and so on,were employed to establish a discrimination function for distinguishing the origin of Salvia miltiorrhiza Bge.slices based on color data.RESULTS Classification and screening of odor information led to the i-dentification of 10 differential markers:ethanol,carbon disulfide,cyclopentane,3-methylfuran,propylene glycol,nonane,phenol,1,5-octadienone,1,8-cineole,and sotolon.It was also found that there was a significant correlation between the color and odor of the slices.Furthermore,based on the concept of data fusion,the study established classification models such as subspace clustering,and compared to single-color discriminant analysis,the classification accuracy was improved to 94.4%.CONCLUSION The feasibility and superiority of intelligent sensory technology in classifying the geographical origin of TCM is confirmed,providing new methods and insights for quality control of Salvia miltiorrhiza Bge.slices.

ObjectiveTo explore the influencing factors of willingness to quit smoking in smokers， and to provide reference for further smoking cessation intervention. MethodsThrough purposive sampling， smokers were recruited from 4 residential communities and 3 companies in Shanghai for an online questionnaire survey. The survey included general demographic characteristics， willingness to quit smoking， smoking condition， tobacco addiction， awareness of influence of smoking， smoking abstinence self-efficacy， and smoking rationalization belief. T-test， χ² test and multiple logistic regression were used to analyze the data. ResultsA total of 336 valid questionnaires were collected. The average age of the smokers was （37.1±10.2） years， and most of their education level was college or above （58.3%）. The daily number of cigarette use was （11.46±7.22） and most of smokers were classified as low nicotine dependence （58.3%）. Today 248 smokers planned to quit smoking in the next six months. Compared with smokers with low smoking abstinence self-efficacy， smokers with high self-efficacy were more likely to quit smoking （OR=2.406，95%CI： 1.357‒4.267）； Smokers with low smoking rationalization belief were more likely to quit smoking than those with high rationalization belief （OR=2.112， 95%CI： 1.167‒3.821）. ConclusionSmoking abstinence self-efficacy has a positive impact on willingness to quit smoking， while smoking rationalization belief has a negative impact on the willingness to quit smoking. Efforts to improve smoking abstinence self-efficacy and dispel smoking rationalization beliefs of smokers should be made to promote the intention to quit among smokers.

The aim of this study was to produce recombinant porcine interferon gamma (rPoIFN-γ) by Chinese hamster ovarian (CHO) cells expression system and to analyze its antiviral activity. Firstly, we constructed the recombinant eukaryotic expression plasmid pcDNA3.1-PoIFN-γ and transfected into suspension cultured CHO cells for secretory expression of rPoIFN-γ. The rPoIFN-γ was purified by affinity chromatography and identified with SDS-PAGE and Western blotting. Subsequently, the cytotoxicity of rPoIFN-γ was analyzed by CCK-8 test, and the antiviral activity of rPoIFN-γ was evaluated using standard procedures in VSV/PK-15 (virus/cell) test system. Finally the anti-Seneca virus A (SVA) of rPoIFN-γ activity and the induction of interferon-stimulated genes (ISGs) and cytokines were also analyzed. The results showed that rPoIFN-γ could successfully expressed in the supernatant of CHO cells. CCK-8 assays indicated that rPoIFN-γ did not show cytotoxicity on IBRS-2 cells. The biological activity of rPoIFN-γ was 5.59×10⁷ U/mg in VSV/PK-15 system. Moreover, rPoIFN-γ could induced the expression of ISGs and cytokines, and significantly inhibited the replication of SVA. In conclusion, the high activity of rPoIFN-γ was successfully prepared by CHO cells expression system, which showed strong antiviral activity on SVA. This study may facilitate the investigation of rPoIFN-γ function and the development of novel genetically engineered antiviral drugs.
Swine ; Animals ; Cricetinae ; Interferon-gamma/pharmacology* ; Cricetulus ; CHO Cells ; Sincalide ; Recombinant Proteins/pharmacology* ; Antiviral Agents/pharmacology*

Objective:To systematically evaluate the intervention effect of exposure and response prevention (ERP) on obsessive compulsive disorder (OCD).Methods:PubMed, Web of Science Core Collection, EBSCO, Cochrane Library, Embase, Science Direct, Wanfang Data, China National Knowledge Infrastructure and VIP-CSTJ were used to collect randomized controlled studies related to ERP for OCD.Randomized controlled studies that met the criteria were included, with the score of Yale-Brown obsessive-compulsive scale as the primary outcome indicator and the scores of anxiety and depression scale as secondary outcome indicators, while the included literatures were evaluated for literature quality and data extraction.Review Manager 5.3 and Stata 16.0 softwares were used to conduct Meta-analysis on the extracted data.Results:Twenty-seven studies with a total of 1 239 patients were included, and 599 cases in the ERP group and 640 cases in the control group.Meta-analysis results showed that the efficacy of ERP group was significantly better than that of blank control group(MD=-6.55, 95% CI: -8.75--4.35, P<0.001) and significantly better than chlorpromazine control group treatment (MD=-5.88, 95% CI: -8.20--3.56, P<0.001) for improving patients' obsessive-compulsive symptoms, but not significantly different from CBT intervention (MD=0.21, 95% CI: -1.62-2.04, P=0.82), and the efficacy of ERP and CBT had no significant during the post-intervention follow-up period (MD=0.41, 95% CI: -2.45-3.27, P=0.78). For improving patients' depressed mood, ERP was effective in improving patients' depressed mood (SMD=-0.45, 95% CI: -0.74--0.17, P=0.002), but not significantly different from CBT (SMD=-0.05, 95% CI: -0.27-0.16, P=0.62). For improving anxiety, the efficacy of ERP group was not different from that of control group (SMD=-0.17, 95% CI: -0.56-0.23, P=0.41). Conclusion:ERP has good feasibility in improving obsessive-compulsive symptoms and depression in patients with OCD.However, long-term efficacy was not verified for improving anxiety and maintaining long-term efficacy during the follow-up period.

Objectives: . Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods: . We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results: . A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion . We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

OBJECTIVE: To assess the application value of mapping allele with resolved carrier status (MaReCs) technique for preimplantation genetic testing (PGT). METHODS: The characteristics of MaReCs for PGT and outcome of patients were retrospectively analyzed. RESULTS: Compared with those who could not use the technique, carriers who have used the MaReCs technique were younger, had significantly higher level of anti-Mullerian hormone, more antral follicles, occytes, mature occytes, biopsied embryos and euploid embryos, and lower risks for de novo chromosomal abnormality (P<0.05). It was necessary for couples with fewer oocytes, mature oocytes and balstocyst to preserve discarded embryos to facilitate the test. Carriers who have used the MaReCs technique had higher clinical pregnancy rate and abortion rate compared with those undergoing routine PGT, albeit no significant difference was found between the two groups (P> 0.05). Carriers undergoing MaReCs test could preferentially select embryos with normal chromosome structures for the transfer. CONCLUSION Application of MaReCs has a prerequisite for having a minimum number of occytes and biopsied embryos and using discarded embryos sometimes. MaReCs is efficient for the detection of carrier status of embryos and attaining higher rate of pregnancy and live birth, which can significantly improve the outcome for couples carrying chromosomal translocations.
Alleles ; Aneuploidy ; Blastocyst ; Female ; Fertilization in Vitro ; Genetic Testing ; Humans ; Pregnancy ; Preimplantation Diagnosis ; Retrospective Studies ; Translocation, Genetic

Objective:To explore the effects of estrogen pretreatment on the outcomes of in vitrofertilization and embryo transfer (IVF-ET) treatment of gonadotrophin-releasing hormone antagonist (GnRH-A) protocol with controlled ovarian hyperstimulation. Methods:Retrospective analysis was performed on the clinical data of 1042 patients who have underwent IVF-ET treatment of GnRH-A protocol in the Center of Reproductive Medicine Teaching Hospital of Fujian University of Traditional Chinese Medicine from January 2015 to December 2016. According to whether the estrogen pretreatment were conducted, patients were divided into pretreatment group and non-pretreatment group. Clinical data and treatment outcomes of IVF-ET between two groups were compared according to different ovarian reactions (high response, normal response, and low response).Results:Compared with non-pretreatment group, the level of serum follicle stimulation hormone (FSH) and luteinizing hormone (LH), antral follicle diameter and coefficent of varience (CV) significantly decreased in pretreatment group (all P<0.001). Total dosage and duration of gonadotropin (Gn) used [(1 693.4±569.8) IU， (2 242.5±635.8) IU， (2 686.4±833.8) IU； (9.7±1.1) d， (9.6±1.1) d， (9.5±1.6) d] in non-pretreatment group were less than those in pretreatment group [(1 897.9±508.0) IU， (2 458.9±759.1) IU， (2 942.1±756.0) IU； (10.8±1.1) d， (10.5±1.4) d， (10.5±1.6) d] ( P<0.001， P=0.019， P=0.029； P<0.001， P<0.001， P<0.001). In patients with normal ovarian response and poor ovarian response, the follicular unsynchronization rate in Gn used day 5/6, day 7/8 and the day of human chorionic gonadotropin (hCG) injection significantly reduced with estrogen pretreatment (all P<0.05), and the number of follicles with a diameter≥14 mm on the day of hCG injection, the number of oocytes retrieved and mature oocytes, two pronuclear fertilization rate and the number of high-quality embryos of pretreatment group were larger than those of non-pretreatment group (all P<0.05). In patients with high ovarian response, the follicular unsynchronization rate (17.7%) in Gn used day 5/6 of pretreatment group was lower than that of non-pretreatment group (26.7%, P=0.012), while other clinical outcomes and indexes relevant to the laboratory of two groups were not statistically significant (all P>0.05). In patients with normal and poor ovarian response, the differences in the number of oocytes retrieved, mature oocytes, and high-quality embryos between pretreatment group and non-pretreatment group were statistically significant ( P<0.001, P<0.001; P<0.001, P<0.001; P<0.001, P=0.018).In patients with normal ovarian response, the cumulative clinical pregnancy rate (81.3%) of pretreatment group was higher than that of non-pretreatment group (70.5%， P=0.044). In people with different ovarian responses, the clinical pregnancy rate, the miscarriage rate in fresh cycle and the clinical pregnancy rate in the first thaw cycle after freeze-all were not statistically significant between the two groups (all P>0.05). Conclusion:In patients with normal and poor ovarian response, estrogen pretreatment before GnRH-A protocol can improve the homogeneity of follicular development, increase the number of mature oocytes and high-quality embryos, and thus improve clinical pregnancy outcomes. While in patients with high ovarian response, estrogen pretreatment show no superiority and clinical application value for its larger total Gn dosage and stimulation duration.