Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

Objective:To evaluate the therapeutic efficacy of combined therapy with a speaking valve and transcranial direct current stimulation (tDCS) for dysphagia in stroke patients post-tracheostomy.Methods:This retrospective case-control study enrolled 120 stroke patients with post-stroke tracheostomy-associated dysphagia, admitted to the Department of Rehabilitation Medicine at Huai′an Second People′s Hospital. Participants were randomly allocated to either a control group [45 males and 15 females, aged from 46 to 78 (65.78±8.68) years]receiving tDCS and conventional rehabilitation or an intervention group [41 males and 19 females, aged from 46 to 79 (66.32±9.18) years]receiving tDCS plus speaking valve therapy, with 60 patients per group. Swallowing function was assessed before and after a 3-week intervention using the Standardized Swallowing Assessment (SSA), Water Swallowing Test (WST) grading, Functional Oral Intake Scale (FOIS), and Swallowing-quality of life score (SWAL-QOL).The SPSS 22.0 was used for statistical analysis.Results:The intervention group demonstrated a significantly higher overall treatment response rate than the control group [95.0%(57/60) vs 78.3%(44/56), χ2=-6.056, P<0.001]. Post-treatment, the intervention group showed significantly greater improvements, as evidenced by a lower SSA score (21.50±1.82 vs 24.92±1.42, t=-11.480, P<0.001) and superior WST grades (observation group: 45 cases at grade 1, 12 cases at grade 2, 5 cases at grade 3; control group: 33 cases at grade 1, 11 cases at grade 2, 16 cases at grade 3, Z=5.484, P<0.001). Furthermore, the intervention group achieved significantly higher FOIS scores (observation group: 1 case at grade 1, 1 case at grade 2, 1 case at grade 4, 8 cases at grade 5, 7 cases at grade 6, 45 cases at grade 7; control group: 2 cases at grade 1, 7 cases at grade 2, 3 cases at grade 3, 4 cases at grade 4, 5 cases at grade 5, 6 cases at grade 6, 33 cases at grade 7, Z=-3.559, P<0.001) and greater improvements in SWAL-QOL scores ( P<0.001), indicating enhanced oral intake and quality of life. Conclusion:The combination of a speaking valve and tDCS effectively promotes the swallowing recovery and improves quality of life in stroke patients with post-tracheostomy dysphagia. This combined modality represents a promising and effective therapeutic strategy for this patient population.

Objective To observe the clinical and transthoracic echocardiographic manifestations of mitral annular disjunction(MAD).Methods Transthoracic echocardiographic data of 990 individuals were retrospectively analyzed.Based on the distance between the attachment point of posterior mitral valve and posterior wall of left ventricle measured on echocardiography,whether there was MAD was judged,and the subjects were divided into MAD group and non-MAD(NMAD)group,and clinical data and echocardiographic parameters were compared between groups.Taken parameters being significantly different between groups as independent variables and the presence or absence of MAD as dependent variable,multivariate binary logistic regression analysis was used to explore correlations of patients' clinical characteristics and transthoracic echocardiographic parameters of MAD.Results MAD was detected in 186 cases(186/990,18.79％).Patients' age,left atrial diameter(LAD),left ventricle diameter(LVD),late diastolic velocity of mitral valve(A)and early diastolic velocity of mitral valve orifices(E)/A in MAD group were all lower than those in NMAD group,while the proportion of moderate and above mitral regurgitation in MAD group was higher than that in NMAD group(all P＜0.05).Patients' age,A and E/A measured with transthoracic echocardiography were all correlated with MAD(all P＜0.05).Conclusion Clinical and transthoracic echocardiographic manifestations of MAD had certain characteristics.

Objective:To investigate the expression and clinical significance of angiomotin-like protein 1 (AMOTL1) and downstream related molecules of Hippo signaling pathway yes-associated protein (YAP) and TAZ in different cervical tissues.Methods:From January 2017 and July 2018 ,102 cervical cancer tissues, 50 cervical squamous epithelial high-grade lesions (HSIL) tissues, 45 low-grade lesions (LSIL) tissues and 50 chronic cervicitis tissues, all of which underwent surgical treatment and pathological diagnosis at Xuzhou Medical University Affiliated Hospital from January 2017 to July 2018, were selected. The expression of AMOTL1 and Hippo pathway downstream related proteins YAP and TAZ were evaluated by immunohistochemistry and their relationship with the clinicopathological parameters of cervical cancer were examined in the cervical tissues of each group. The comparison of inter group rates in count data was conducted using the chi square test. Adopting Spearman correlation analysis method to analyze the relationship between AMOTL1, YAP, and TAZ. Single factor survival analysis was performed using Kaplan Meier curves. Kaplan Meier method and multivariate Cox regression analysis were used to investigate the factors affecting the prognosis of cervical cancer patients.Results:The immunohistochemical results showed that the positive rates of AMOTL1 in chronic cervicitis, LSIL, HSIL, and cervical cancer were 12.00% (6/50), 17.78% (8/45), 28.00% (14/50), and 76.47% (78/102), respectively. The positive expression status of AMOTL1 in chronic cervicitis, LSIL, HSIL and cervical cancer were 12.00%(6/50), 17.78%(8/45), 28.00%(14/50), 76.47%(78/102). The positive rates of YAP in chronic cervicitis, LSIL, HSIL, and cervical cancer were 10.00% (5/50), 15.56% (7/45), 30.00% (15/50), and 63.73% (65/102), respectively. The positive expression of YAP in cervical cancer tissues was higher than that in other groups ( χ2=56.66, P<0.001). The positive rates of TAZ in chronic cervicitis, LSIL, HSIL, and cervical cancer were 8.00% (4/50), 17.78% (8/45), 30.00% (15/50), and 71.57% (73/102), respectively. The positive expression of TAZ in cervical cancer tissues was higher than that in other groups ( χ2=74.71, P<0.001), AMOTL1 positive expression is associated with the International Federation of Gynecology and Obstetrics (FIGO) staging ( χ2=16.28, P=0.001), tissue differentiation degree ( χ2=30.16, P<0.001), and lymph node metastasis ( χ2=5.81, P=0.016), YAP positive expression is associated with FIGO staging ( χ2=15.99, P<0.001), differentiation degree ( χ2=25.06, P<0.001), tumor diameter ( χ2=13.63, P=0.003), and lymph node metastasis ( χ2=5.78, P=0.016), and TAZ positive expression is associated with FIGO staging ( χ2=14.49, P<0.001). tissue differentiation degree ( χ2=25.32, P<0.001), and the presence or absence of lymph node metastasis ( χ2=4.95, P=0.026) are related. Spearman correlation analysis showed a positive correlation between AMOTL1 and YAP expression ( r=0.65, P<0.001), and a positive correlation between AMOTL1 and TAZ expression ( r=0.72, P<0.001), There was a positive correlation between YAP and TAZ expression ( r=0.68, P<0.001). Kaplan Meier survival analysis showed that individuals with positive expression of AMOTL1, YAP, and TAZ proteins had shorter survival times than those with negative expression ( χ2 values were 9.84, 8.64, and 18.57, respectively; P values were 0.002, 0.003, and <0.001, respectively). Multivariate Cox regression analysis showed that FIGO staging ( HR=3.18, 95% CI 1.09-9.29, P=0.034), lymph node metastasis ( HR=16.74, 95% CI 3.20-87.45, P=0.010), AMOTL1 positive expression ( HR=13.06, 95% CI 1.41-121.08, P=0.024), and YAP positive expression ( HR=9.75, 95% CI 1.59-59.52, P=0.014) were risk factors for poor prognosis in cervical cancer patients. Conclusion:AMOTL1, YAP, and TAZ may jointly participate in the malignant transformation process of cervical cancer. AMOTL1 and YAP are closely related to prognosis and may become potential prognostic indicators for cervical cancer.

Case report form(CRF)is an important tool to obtain clinical research data.Scientifically designed and properly recorded CRF is of great significance to improve the quality of clinical research.The author summarized the common problems existing in the design and recording of CRF in traditional Chinese medicine(TCM)clinical studies,including:①Delayed design time point.②Unstandardized CRF design,recording and modification.③Imperfect records of combined medication/therapy.④Insufficient quantification of syndrome efficacy indicators and objectification of tongue and pulse.⑤ Insufficient protection of subjects' privacy.⑥ Unstandardized records of adverse events.Accordingly,this paper discusses some solutions to provide reference for other TCM researchers,including:①Advance CRF design time.②Standardize CRF design,recording and modification.③Design drug combinations/therapies according to Clinical Data Acquisition Standards Harmonization(CDASH).④Standardization of syndrome and tongue and pulse.⑤Use of subject identification codes to protect privacy.⑥AE records should vary from study to study.

OBJECTIVE: To observe the effects of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on myocardial transferrin receptor 1 (TfR1), ferroptosis suppressor protein 1 (FSP1), atrial natriuretic peptide (ANP), and typeⅠcollagen myocardial collagen fibers (CollagenⅠ) in rats with chronic heart failure (CHF), and to explore the mechanism of moxibustion for ameliorating myocardial fibrosis and improving cardiac function in CHF. METHODS: Fifty SD rats were randomly divided into a normal group (n=10) and a modeling group (n=40). The CHF model was established in the modeling group by ligating the left anterior descending coronary artery. After successful modeling, the rats were randomly divided into a model group (n=9), a moxibustion group (n=8), a rapamycin (RAPA) group (n=9), and a moxibustion+RAPA group (n=9). In the moxibustion group, moxibustion was delivered at bilateral "Feishu"(BL13) and "Xinshu" (BL15), 15 min at each point in each intervention, once daily, for 4 consecutive weeks. In the RAPA group, RAPA solution was administered intraperitoneally at a dose of 1 mg/kg, once daily for 4 consecutive weeks. In the moxibustion+RAPA group, RAPA solution was administered intraperitoneally after moxibustion. Ejection fraction (EF) and left ventricular fractional shortening (FS) were measured after modeling and intervention. After intervention, morphology of cardiac muscle was observed using HE staining and Masson's trichrome staining. Total iron content in myocardial tissue was detected using a colorimetric method. Western blot and qPCR were adopted to detect the protein and mRNA expression of TfR1, FSP1, ANP, and CollagenⅠ in myocardial tissue. RESULTS: Compared with the normal group, the EF and FS values decreased (P<0.01); necrosis, edema, degeneration, and arrangement disorder were presented in cardiomyocytes; inflammatory cells were obviously infiltrated, the structure of myocardial fibers was disarranged, the collagen fibers were obviously deposited and fibrosis increased (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue were elevated (P<0.01), while the protein and mRNA expression of FSP1 were reduced (P<0.01) in the model group. Compared with the model group, the moxibustion group showed that EF and FS increased (P<0.01); myocardial cell morphology was improved, and myocardial fibrosis was alleviated (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while the protein and mRNA expression of FSP1 increased (P<0.01, P<0.05). Compared with the model group, the myocardial fibrosis was increased (P<0.05); the total iron content and the protein and mRNA expression of TfR1, ANP, CollagenⅠ in myocardial tissue were increased (P<0.01), while protein and mRNA expression of FSP1 decreased (P<0.01) in the RAPA group. When compared with the RAPA group and the moxibustion + RAPA group, EF and FS were elevated (P<0.01, P<0.05); myocardial cells were improved in morphology, the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while protein and mRNA expression of FSP1 increased (P<0.01) in the moxibustion group. In comparison with the moxibustion + RAPA group, the RAPA group showed the decrease in EF and FS (P<0.01), the worsened myocardial fibrosis (P<0.01), the increase in the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue (P<0.01), and the decrease in the protein and mRNA expression of FSP1 (P<0.01). CONCLUSION Moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) can slow down the process of myocardial fibrosis and improve cardiac function in CHF rats. The mechanism of moxibustion may be related to inhibiting ferroptosis through regulating autophagy.
Animals ; Rats ; Heart Failure/physiopathology* ; Moxibustion ; Rats, Sprague-Dawley ; Male ; Receptors, Transferrin/genetics* ; Myocardium/metabolism* ; Acupuncture Points ; Humans ; Chronic Disease/therapy* ; Antigens, CD/metabolism*

Volatile organic compounds (VOCs) and semi-volatile organic compounds (SVOCs) are common organic compounds in indoor and outdoor air, and enter the human body primarily through the respiratory tract and directly damage the respiratory system. Previous studies have suggested that exposure to VOCs/SVOCs may associate with the prevalence, incidence, and progression of asthma, but the extent of the associations is still vague. Furthermore, biomarkers for efficient and simple asthma diagnosis, typing, and attack prediction remain unclear at this stage. From the perspective of the collection and detection methods of VOCs/SVOCs, this paper summarized the epidemiological associations and underlying biological mechanisms between VOCs/SVOCs exposure and the prevalence, incidence, and progression of asthma in children/adults. It also demonstrated the application of VOCs/SVOCs in recent years in assisting asthma diagnosis, such as distinguishing asthma patients from the healthy population, differentiating different asthma phenotypes, and predicting asthma acute exacerbations, aiming to provide a scientific basis for improving current asthma management.

To summarize the clinical practice of continuous medical service for patients at Shanghai Children′s Medical Center, affiliated with Shanghai Jiao Tong University School of Medicine, from September 2023 to December 2024, following the approval of its extended care qualification. This study utilized a mixed-methods research design that integrates quantitative and qualitative approaches. The quantitative study included a total of 117 subjects, with an age range of 18 to 35 years, an average age of 21.56 years, and a median age of 19 years; there were 59 males and 58 females. The disease types covered four major categories: childhood leukemia and solid tumors (68 cases), congenital structural malformations (25 cases), congenital hereditary metabolic diseases (4 cases), and rare diseases (20 cases). Among the subjects, 57.26% (67 cases) were first-time visitors to SCMC. The patients came from 20 provinces, autonomous regions, and municipalities across the country, with 88.03% (103 cases) from outside Shanghai. The treatment outcomes showed improvement or cure in 80.34% (94 cases) of the subjects, and there were no medical complaints. In addition, a qualitative study was conducted to deeply explore the experiences, confusions, and challenges of receiving or implementing continuous medical services from the perspectives of patients and their families, as well as medical staff. According to the inclusion and exclusion criteria, a total of 44 subjects were included in the study, among them, there were 12 patients, 12 family members who were taking care of the patients in SCMC, and 20 corresponding medical staff members. The results of the qualitative study showed that trust in the attending physicians of the children′s specialty hospital, a good doctor-patient relationship, satisfactory treatment outcomes, and support from medical insurance policies are the main driving forces for patients over 18 years old to receive continuous treatment at children′s specialty hospitals. The medical staff of the hospital also believed that this model can promote patient benefits. In conclusion, under the policy support of the Shanghai Municipal Health Commission, the "Six Fixed" Model for continuous treatment established by SCMC has achieved certain positive results in practice. This provides practical references for the development of continuous treatment in China and offers new strategies for the application of preventive medicine in the field of children′s health.

Objective:To explore the expression of YARS1, the subform of protein-based tRNA synthase ( YARS1), and its prognostic effect on the analysis of gene set enrichment in hepatocellular carcinoma Methods:The expressional condition of the YARS1 gene in tumor tissue samples (374 cases) and adjacent tissue samples (50 cases) of hepatocellular carcinoma patients was compared and recorded by mining the Cancer Genome Atlas database. Hepatocellular carcinoma patients were divided into high expression and low expression groups according to this data. Logistic regression was used to analyze the relationship between YARS1 and the clinical pathological characteristics of hepatocellular carcinoma patients. The effect of YARS1 expression on the prognosis of hepatocellular carcinoma patients was analyzed by the Kaplan-Meier method and log-rank test. The prognostic value of the YARS1 gene for hepatocellular carcinoma was analyzed by univariate and multivariate Cox regression. Gene set enrichment analysis was used to evaluate the gene pathways related to YARS1 in the occurrence and development of hepatocellular carcinoma. Results:The expression of the YARS1 gene was higher in hepatocellular carcinoma tissue than in normal tissue ( P<0.001). The expression level of YARS1 was correlated with the grade of patients ( P<0.05), but not with age, gender, TNM stage, and others ( P>0.05). The results of Kaplan-Meier method and log-rank test showed that the survival rate was lower in patients with high YARS1 gene expression than that of patients with low YARS1 gene expression ( P<0.001). The results of multivariate Cox regression analysis showed that YARS1 was used as an independent prognostic factor for hepatocellular carcinoma [hazard ratio=1.10, 95% confidence interval (1.050-1.156), P<0.001]. The results of gene set enrichment analysis showed that YARS1 was involved in pyrimidine metabolism, purine metabolism, aminoacyl tRNA biosynthesis, fatty acid metabolism, ppar signal transduction pathway, oocyte meiosis, amino acid and nucleotide sugar metabolism, RNA degradation, complement pathway, valine and isoleucine degradation, spliceosome, and other pathways. Conclusion:The high expression of YARS1 is associated with the progression and prognosis of hepatocellular carcinoma. Therefore, this gene is expected to become a novel biomarker and a sort of target for biological therapy in hepatocellular carcinoma.

Objective This study aimed to develop an automated method for syndrome element differenti-ation in Traditional Chinese Medicine(TCM).Methods We first constructed and trained an Instruction-tuned Multi-Task TCM text embedding model(Instr-MT-TCM)using four distinct TCM task datasets,including domain knowledge,synonymous terminology,syndrome differentiation and treatment,and TCM case labels.Subsequently,five TCM diagnostics experts holding master's degrees or higher were organized to screen a real-world TCM case dataset and annotate symptoms and signs.The purpose was to evaluate the F1-score of the proposed method—the combination of Instr-MT-TCM and a Large Language Model(LLM)—by comparing its performance against the manual annotation result on the syndrome element differentiation task.Finally,to validate its feasibility in real-world clinical settings,the method was applied to 48 prostate cancer cases to calculate the syndrome element scores.Results The Instr-MT-TCM model showed rapid performance improvement in its early training phase,achieving a Recall@1(R@1)of 0.848.Experts curated a dataset of 1,793 real-world clinical cases,covering 34 common diseases and 66 syndrome patterns.In the syndrome element differentiation task,the collaborative framework of LLM and Instr-MT-TCM achieved a mean F1-score of 0.927,outperforming the 0.512 from manual annota-tion.The syndrome element analysis revealed that the predominant elements of disease nature were fire(heat)and yin deficiency,while the main elements of disease location were bladder and kidney.Conclusion This study proposes and validates a novel method for automated TCM syndrome element dif-ferentiation based on the synergy between LLM and our custom Instr-MT-TCM model.Achieving a high F1-score(0.927)on real-world data,the method demonstrates excellent accuracy and generalization ability.Its application in prostate cancer analysis highlights its significant clinical potential,offering effective technical support,and a new research direction for intelligent TCM syndrome element differentiation.