Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Hepatic fibrosis(HF)is a pathophysiological outcome of chronic liver injury and is characterized by excessive accumulation of extracellular matrix protein.A number of studies have confirmed that the signaling pathways formed by transforming growth factor-β1(TGF-β1)and its downstream Smad family play an important role in the occurrence and development of HF,and the traditional Chinese medicine(TCM)research targeting this pathway is currently a hot spot in the reversal of HF.Therefore,taking TGF-β1/Smads signaling pathway as the entry point,this paper reviewed the mechanism of action of TCM compound formula and single drug extract in intervening TGF-β1/Smad pathway and related factors upstream and downstream of the pathway to reverse HF in recent years,revealed the targeted therapeutic effect of TCM,and provided new strategies for clarifying the mechanism of TCM.

Aprocitentan is a dual endothelin receptor antagonist.Based on the effective evidence of Ⅲ phases of clinical trials,the drug was approved for marketing by the U.S.Food and Drug Administration on March 19,2024 for the treatment of refractory hypertension.At present,multiple clinical studies have confirmed that Aprocitentan has excellent antihypertensive effects and good tolerability.This article reviews the pharmacological effects,preclinical.

Objective:To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR.Methods:A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m 2 day 1, cisplatin 25 mg/m 2 days 1-3, and capecitabine 800 mg/m 2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results:A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm 3. The T stage ( OR=12.71, 95% CI: 1.4-112.5, P=0.022) and the volume ( OR=7.1, 95% CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion:The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Transcatheter aortic valve replacement(TAVR)has become one of the effective methods for treating patients with aortic valve disease.With the continuous maturity of technology,innovation of instruments and increasing experience,the indications for TAVR has been expanded.Following international trends,the number of TAVR in China has steadily increased with each passing year.In 2023,the long-term follow-up results of TAVR in low-risk AS patients further confirm the long-term benefits of TAVR.The relevant research on TAVR for patients with aortic regurgitation and patients with bicuspid aortic stenosis provide evidence support for the expansion of TAVR indications.At the same time,the development of valve devices and new technological innovations are emerging in an endless stream,and the new concept of full life cycle management is increasingly being valued.Especially in China,the development of local devices is progressing rapidly,and multiple devices have entered the clinical research stage.The clinical manifestations and research results are worth pursuing.

Jinqi Jiangtang Capsule (JQJTC) is clinically used for the prevention and treatment of type 2 diabetes, but the contents of its main chemical components are not yet clear. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established for the determination of 15 components in JQJTC, including new chlorogenic acid, chlorogenic acid, cryptochlorogenic acid, formononetin, ononin, calycosin, calycosin-7-glucoside, astragaloside IV, berberine, epiberberine, berberrubine, coptisine, jatrorrhizine, palmatine and magnoflorine. The method was used to determine the contents of 15 components in the capsule and then to investigate the influence of excipients on the contents of the components in JQJTC. The separation was performed on a ACQUITY UPLC BEH C₁₈ column (100 mm × 2.1 mm, 1.7 μm) with a mobile phase consisting of 0.1% acetic acid and 5 mmol·L^-1 ammonium acetate (A) and acetonitrile (B) with gradient elution at a flow rate of 0.3 mL·min^-1 and a column temperature at 40 ℃. Electron spray ionization was used for mass spectrometry in positive ion mode. The established method meets the requirements of methodology of content determination in Chinese pharmacopoeia. The contents of 15 components in JQJTC varied from high to low. The top 5 contents were berberine, chlorogenic acid, magnoflorine, coptisine, and cryptochlorogenic acid, accounting for 87.31% of the total content. The contents of 10 components, including the alkaloids of coptidis rhizoma (berberine, epiberberine, berberrubine, coptisine, jatrorrhizine, palmatine and magnoflorine) and the organic acids of honeysuckle (new chlorogenic acid, chlorogenic acid, and cryptochlorogenic acid) in the whole formula extract without excipients was significantly lower than that in the capsule. These components accounted for 99.20% of the determined component contents. In this experiment, an accurate, sensitive and efficient UHPLC-MS/MS method for the determination of multi-components in JQJTC was established, which stably and reliably detected the contents of 15 components in the capsule and could provide the basis for more comprehensive quality analysis. It was also found that excipients had an increasing effect on the contents of detected alkaloid and organic acid components, which may be beneficial to the effectiveness of the capsules.

Deep vein thrombosis(DVT)is a common peripheral vascular disease in clinical practice.The lack of precise and efficient early diagnostic techniques renders it susceptible to being overlooked or misdiagnosed,and therefore,identifying trustworthy biomarkers is a major issue that has to be resolved.In this study,the endogenous metabolites in the urine of DVT rats were screened by metabolomics technology based on gas chromatograph-mass spectrometry(GC-MS)and the characteristic metabolites were identified by multiple feature selection algorithms and multivariate statistical analysis,for the development of a machine learning-based diagnostic model for DVT.The urine samples in metabolic cage in the thrombus development phase(between 48 and 72 h)of rats were collected,which was used as the models for inferior vena cava ligation.The metabolic profiles of the control group and DVT were obtained using the GC-MS method.A total of 176 kinds of endogenous metabolites were identified in rat urine through comparison with the FiehnLib database,26 kinds of differential metabolites associated with DVT were screened through a combination of the Mann-Whitney U test and orthogonal partial least squares discriminant analysis(OPLS-DA),and 13 kinds of significant metabolites strongly correlated with DVT were further evaluated in conjunction with various machine learning feature selection techniques.For DVT diagnosis,machine learning models such as Gaussian Naive Bayes(GNB),support vector machine(SVM),logistic regression(LR),and linear discriminant analysis(LDA)were developed.The diagnostic model constructed using 13 kinds of key metabolites demonstrated excellent accuracy and stability,and surpassed the predictive performance of the models utilizing 176 kinds of metabolites and 26 kinds of differential metabolites,as evidenced by examination and comparison of each model's efficacy.The study showed that the integration of multiple feature selection algorithms for analyzing metabolite information in DVT rat urine was capable of effectively identifying reliable potential markers of DVT.Furthermore,the developed machine learning model offered a novel technical approach for the automated diagnosis of DVT.