OBJECTIVE: Exploring the formation and aggregation of human islet amyloid polypeptide (hIAPP) (amylin) fibers is significant for promoting the prevention and treatment of type II diabetes mellitus (T2DM). Flavones in pomelo peel have visible biological activity in the anti-diabetes aspect. The present study aimed to investigate the effects of five flavones [naringin (NRG), narirutin (NRR), nobiletin (NOB), sinensetin (SIN), and neohesperidin (NHP)] in pomelo peel on peptide aggregation and explore its possible mechanisms. The cell viability of flavones against peptide aggregation was also evaluated. METHODS: The thioflavin T (ThT) assay and transmission electron microscopy (TEM) were used for evaluating the inhibition and disaggregation of flavones on peptide aggregation. The interaction mechanism was analyzed by endogenous fluorescence, molecular dynamics (MD) simulations, ultraviolet spectroscopy (UV) and isothermal titration calorimetry (ITC) experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and immune assays were performed to characterize the cell viability of flavones against peptide aggregation. RESULTS: The five flavones showed a decrease in fluorescence intensity, fiber number and size under incubation with different molar ratios of hIAPP. The compounds can bind to the aromatic tyrosine (Tyr) residueTyr 37, resulting in the intrinsic fluorescence quenching of the peptides. Five flavones can form hydrogen bonds with hIAPP, which is likely to be based on their phenolic hydroxyl structure. They showed strong binding affinity with peptides. The reaction system of NRG and NRR observed an exothermic reaction, and the others were endothermic reactions. The absorption peaks of the compounds with hIAPP changed and showed hypochromic effects, indicating that there may be π-π stacking interaction. Flavones noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide oligomers. CONCLUSION A total of five flavones in pomelo peel have inhibitory and depolymerization effects on amyloid fibrils, and can significantly protect cells from the toxic effect of hIAPP and reduce the production of toxic oligomers.

Objective To analyze the possible mechanism and drug treatment plan of diffuse alveolar hemorrhage induced by human granulocyte colony-stimulating factor injection, point out medication risks and provide reference for medical treatment and pharmaceutical care of such patients. Methods The abnormal lung conditions of a patient treated with human granulocyte colony-stimulating factor injection was found by clinical pharmacists, who participated in clinical diagnosis and treatment by analyzing of adverse drug reactions, optimization of medical treatment and pharmaceutical care. Results Diffuse alveolar hemorrhage was likely an adverse drug reaction caused by human granulocyte colony-stimulating factor injection. The physician discontinued the medication immediately and provided treatment such as oxygen inhalation, high-dose hormone shock, plasma exchange, etc. The patient’s oxygen saturation was improved, alveolar bleeding was decreased, and the condition was improved. Conclusion Clinical pharmacists participate in patients’ medication treatment, carry out pharmaceutical guardianship, and assist physicians in adjusting treatment plans, which could contribute to the effectiveness and safety of patient treatment.

β-Thalassemia is a single-gene disease caused by mutations in β-globin and has a distinct geographical characteristics. Current treatment for patients with moderate to severe thalassemia has mainly relied on long-term blood transfusion and/or hematopoietic stem cell transplantation. B cell lymphoma/leukemia 11A (BCL11A) as a transcriptional repressor plays a vital role in monitoring γ/β hemoglobin switching, maintaining the normal function of hematopoietic stem cells, and regulating erythrocyte differentiation and lymphocyte development. With the rapid progress in gene editing technology, the BCL11A as a therapeutic target for β-thalassemia has shown promising results. This article has systematically summarized the regulatory mechanism and therapeutic potential of the BCL11A, with an aim to provide new ideas for the treatment of β-thalassemia.

Objective To explore the clinical application value of semiconductor laser combined with flat-panel CT guidance in foramen ovale puncture for trigeminal neuralgia(TN).Methods A total of 86 patients with primary TN were selected and randomly divided into control group(n=43)and observation group(n=43).The control group used empirical manual puncture,and the observation group used semiconductor laser combined with flat-panel CT-guided radiofrequency ablation.The first puncture success rate,puncture success time,total operation time,and intraoperative flat-panel CT scan times were carefully evaluated.Results The puncture success time,total operation time,and intraoperative flat-panel CT scan times in the observation group were significantly lower than those in the control group(P＜0.05).In addition,the first puncture success rate and surgical efficiency 12 months after surgery were significantly improved(P＜0.05).The incidence of facial congestion in the observation group was significantly lower than that in the control group(P＜0.05),but there was no statistically significant difference in the incidence of chewing weakness,cerebrospinal fluid leakage,and intracranial infection between the two groups(P＞0.05).Conclusion Minimally invasive foramen ovale puncture under the guidance of semiconductor laser combined with flat-panel CT for the treatment of TN has the advantages of simple operation,accurate positioning,low risk,and few complications,with important clinical application value.

Objective:The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach.Methods:Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis.Results:A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score ( r = 0.47, P = 0.002), albumin-bilirubin score ( r = 0.37, P = 0.001), Lok index ( r = 0.36, P = 0.02), liver stiffness ( r = 0.58, P = 0.01), and spleen stiffness ( r = 0.77, P = 0.01), while negatively correlated with albumin ( r = -0.42, P = 0.006). Conclusion:The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

Objective:To compare and analyze the correlation between two kinds of point-of-care testing (POCT) instruments and Roche electrochemiluminescence instrument in detecting myocardial biomarkers,so as to provide reference for the selection of POCT instruments in clinical testing. Methods:A total of twenty patient's samples were selected,which concentration range covered the reportable range of detection results. Two kinds of POCT instruments (named respectively A and B) were used to detect the concentrations of plasma myoglobin (Myo),creatine kinase isoenzyme mass (CK-MB mass),cardiac troponin I(cTnI),and N-terminal fragment of B-type natriuretic peptide (NT-proBNP)/Brain natriuretic peptide (BNP). The results of the electrochemiluminescence instrument were used as reference,and Pearson correlation analysis and Kappa test evaluation were used to evaluate respectively the correlation and consistency of the detected results between the two kinds of POCT instruments and Roche electrochemiluminescence instrument. Results:Our study demonstrated that there were good correlations in the detected results of Myo,CK-MB mass,cTnI,NT-proBNP/BNP between the instrument A and Roche electrochemiluminescence instrument,and between the instrument B and Roche electrochemiluminescence instrument (rinstrumentA=0.994,0.989,0.917,0.996,rinstrumentB=0.928,0.934,0.883,0.977,P<0.05),respectively. In the comparisons about consistencies,the concordance rates between instrument A and electrochemiluminescence instrument were respectively 90％,100％,70％ and 100％ in detecting Myo,CK-MB,cTnI and NT-proBNP,and the concordance rates between instrument B and electrochemiluminescence instrument were respectively 90％,100％,70％ and 100％ in detecting them. Both two kinds of POCT instruments had favorable consistencies with Roche electrochemiluminescence instrument (Kappainstrument A=0.798,1.00,0.429,1.00,Kappainstrument B=0.794,0.886,0.429,1.00),respectively. The precisions of both instruments were less than 10％. Conclusion:Both two kinds of POCT instruments can meet the requirements of clinical test,which have favorable correlations with electrochemiluminescence instrument in detecting myocardial biomarkers.

Objective:To explore the efficacy of adjuvant chemotherapy and adjuvant immunotherapy combined chemotherapy after radical cystectomy for muscle-invasive bladder cancer (MIBC) with high recurrence risk (pT 2 with positive lymph nodes, and pT 3-4a with or without positive lymph nodes). Methods:A retrospective analysis was conducted on clinical data of 217 patients with bladder cancer admitted to Tianjin Medical University Second Hospital from August 2016 to January 2022. Among them, 183 were male (84.3%) and 34 were female (15.7%), with an average age of (67.3±8.6) years old. All 217 patients underwent radical cystectomy with pelvic lymph node dissection. Based on postoperative adjuvant treatment, the patients were divided into an observation group (147 cases, 67.7%) and a treatment group (70 cases, 32.3%). The observation group and treatment group had similar demographic and pathological characteristics. The age of the observation group and treatment group was (67.4±9.0) years and (66.3±7.6) years, respectively ( P=0.14). The postoperative pathological stages T 2 with lymph node positivity were observed in 8 cases (5.4%) in the observation group and 6 cases (8.6%) in the treatment group. For stages T 3-4awith lymph node positivity, there were 34 cases (23.1%) in the observation group and 18 cases (25.7%) in the treatment group. And there were 105 cases (71.5%) in the observation group and 46 cases (65.7%) in the treatment group of stages T 3-4a without lymph node positivity, respectively( P>0.05). Tumor diameter ≥3 cm was found in 118 cases (80.3%) in the observation group and 54 cases (77.1%) in the treatment group ( P>0.05), while tumor diameter <3 cm was observed in 29 cases (19.7%) in the observation group and 16 cases (22.9%) in the treatment group ( P>0.05).In the treatment group, 36 patients (16.6%) received postoperative chemotherapy with gemcitabine (1 000 mg/m 2, days 1 and 8) and cisplatin (75 mg/m 2, days 2 to 4) (chemotherapy group), while 34 patients (15.7%) received postoperative immunotherapy with checkpoint inhibitors (intravenous infusion of sintilimab 200 mg, terlizumab 200 mg, or toripalimab 240 mg on day 1) in combination with albumin-bound paclitaxel (200 mg on day 2)(immunotherapy combined chemotherapy group). The age of the chemotherapy group and immunotherapy combined chemotherapy group was (66.8±8.4) years and (65.8±6.8) years, respectively ( P>0.05). Postoperative pathological stages T 2 with lymph node positivity were observed in 3 cases (8.3%) in the chemotherapy group and 3 cases (8.8%) in the immunotherapy combined chemotherapy group ( P>0.05). For stages T 3-4awith lymph node positivity, there were 6 cases (16.7%) in the chemotherapy group and 12 cases (35.3%) in the immunotherapy combined chemotherapy group. And there were 27 cases (75.0%) in the observation group and 19 cases (55.9%) in the treatment group of stages T 3-4a without lymph node positivity, respectively( P>0.05). Lymph node involvement was seen in 9 cases (25.0%) in the chemotherapy group and 15 cases (44.1%) in the immunotherapy combined chemotherapy group ( P>0.05). Tumor diameter ≥3 cm was found in 30 cases (83.3%) in the chemotherapy group and 10 cases (29.4%) in the immunotherapy combined chemotherapy group ( P>0.05), while tumor diameter <3 cm was observed in 6 cases (16.7%) in the chemotherapy group and 24 cases (70.6%) in the immunotherapy combined chemotherapy group ( P>0.05). Kaplan-Meier method and multivariate Cox regression test were used to analyze the overall survival (OS) at 1 and 3 years in the observation group and treatment group, as well as the disease-free survival (DFS) at 1 and 3 years in the chemotherapy group and immunotherapy combined chemotherapy group. Additionally, common adverse events were evaluated and compared between the chemotherapy group and immunotherapy combined chemotherapy group based on the criteria published by the U. S. Department of Health and Human Services. Results:The median follow-up time in this study was 18.4 (8.2, 34.7) months. The median follow-up time in the observation group and treatment group was 19.0 (8.3, 35.2) months and 17.5 (7.9, 33.2) months, respectively. The 1-year survival rate was significantly higher in the treatment group compared to the observation group (90.0% vs. 76.2%, χ2=6.92, P=0.009). Similarly, the 3-year survival rate was significantly higher in the treatment group compared to the observation group (82.9% vs. 57.8%, χ2=13.22, P<0.01). The median OS was 35.9 months in the observation group and was not reached in the treatment group, with a statistically significant difference ( HR=2.51, 95% CI 1.36-4.65, P=0.003).In the chemotherapy group and immunotherapy combined chemotherapy group, the median follow-up time was 10.7 (7.4, 22.1) months and 14.4 (6.3, 40.7) months, respectively. The 1-year disease-free survival rate was significantly higher in the immunotherapy combined chemotherapy group compared to the chemotherapy group (91.2% vs. 67.6%, χ2=4.60, P=0.032). The 3-year disease-free survival rate was significantly higher in the chemotherapy group compared to the immunotherapy combined chemotherapy group (88.2% vs. 55.6%, χ2=8.37, P=0.004). The median DFS was 27.7 months in the chemotherapy group and was not reached in the immunotherapy combined chemotherapy group, with a statistically significant difference ( HR=3.39, 95% CI 1.46-7.89, P=0.016).The treatment group had complications classified as follows: 140 cases of grade 1, 39 cases of grade 2, 8 cases of grade 3, 2 cases of grade 4, and 0 case of grade 5 adverse reactions. In the chemotherapy group and the immunotherapy combined chemotherapy group, there were both 5 cases with adverse reactions of grade 3 or higher. Specifically, in the chemotherapy group, there were 2 cases of anemia, 2 cases of decreased platelet count, and 1 case of decreased neutrophil count. In the immunotherapy combined chemotherapy group, there was 1 case of anemia, 1 case of decreased platelet count, and 2 cases of decreased neutrophil count. Additionally, there was 1 case with elevated gamma-glutamyltransferase (γ-GT) in the immunotherapy combined chemotherapy group. The incidence of adverse events of grade 3 or higher in the chemotherapy group and immunotherapy combined chemotherapy group was 13.9% and 14.7%, respectively, with no statistically significant difference( χ2=0.01, P=0.922). Conclusions:Adjuvant therapy significantly prolongs the overall survival in high risk of recurrence for MIBC patients after radical cystectomy. For patients intolerant to platinum-based chemotherapy or refusing platinum-based adjuvant chemotherapy, immunotherapy with checkpoint inhibitors combined with albumin-bound paclitaxel can be considered as an effective and well-tolerated adjuvant treatment after radical cystectomy.

Objective To explore the application value of modified prophylactic ileostomy in natural orifice specimen extraction surgery(NOSES)for patients with mid-low rectal cancer.Methods We retrospectively analyzed 63 patients who received prophylactic ileostomy in NOSES for mid-low rectal cancer in our hospital from September 2017 to May 2023.The patients were divided into the observation group(those who received modified ileostomy,n=31)and the control group(those who received conventional loop ileostomy,n=32)according to different ostomy methods.The operation time of ostomy,operation time of ostomy reversal surgery,early-stage complications(stoma leakage,peristomal dermatitis,stoma pain,peristomal trocar hole infection,stoma bleeding,stoma ischaemic necrosis,stoma oedema,peristoma skin-mucosal separation and stoma proximal bowel obstruction)and long-stage complications(stoma stenosis,stoma retraction,stoma prolapse,parastomal hernia),tumor recurrence and death of the two groups were compared and analyzed.Results Both prophylactic ileostomy and ostomy reversal surgery were successfully completed in all the 63 cases.The operation time of ostomy in the observation group was 7(6-8)min,which was significantly shorter than that of 23(21-24)min in the control group(Z=-6.853,P=0.000),and the operation time of ostomy reversal surgery in the observation group was(63.2±5.7)min,which was significantly shorter than(93.5±4.7)min in the control group(t=-23.109,P=0.000).Neither stoma bleeding nor stoma ischaemic necrosis were observed in both groups.The incidence of stoma pain in the observation group was lower than that in the control group[6.4％(2/31)vs.65.6％(21/32),x2=21.766,P=0.000].The incidence of peristomal incision infection in the observation group was lower than that in the control group[0％(0/31)vs.53.1％(17/32),P=0.000].There was no stoma stenosis in both groups.There were 3 cases of parastomal hernia,1 case in the observation group and 2 cases in the control group,the difference of the incidence being not statistically significant(P=1.000).There was 1 case of stoma retraction and 1 case of stoma prolapse in the control group.All the 5 cases with complications received prompt treatment in the second ostomy reversal surgery.Follow-up visits for 6-60 months in the 63 cases showed no tumor recurrence or death.Conclusion Modified prophylactic ileostomy in NOSES for patients with mid-low rectal cancer is safe,feasible,and easy to operate,having certain practicality and promotion value.

Objective:To explore the relevant factors affecting the efficacy of microscopic spermatic cord surgery and build a predictive model for postoperative pain relief.Methods:A retrospective analysis was conducted on the clinical data of 324 patients with spermatic cord pain who visited the Department of Urology at Peking University People's Hospital between October 2015 and April 2023.This cohort included 212 patients with varicocele-related spermatic cord pain and 112 patients with idiopathic sper-matic cord pain.All the patients underwent microsurgical procedures:varicocele-related pain was treated with microsurgical varicocelectomy,and idiopathic pain was treated with microsurgical denervation of the spermatic cord.The patients were categorized into effective and ineffective groups based on whether their pain had decreased by more than 50％six months post-surgery compared with pre-surgery levels.Base-line data were preliminarily screened for clinical indicators using t tests and univariate analysis.Clinical predictor variables[age,duration of pain,diameter of varicocele,patient health questionnaire-9(PHQ-9)score,generalized anxiety disorder-7(GAD-7)score]were selected using Lasso regression.Aclini-cal prediction model for effective pain relief following microscopic spermatic cord surgery was constructed using Logistic regression and presented as a nomogram.The model's internal validation was performed using the bootstrap method.Its predictive power and clinical utility were evaluated through the concor-dance index,the area under the receiver operating characteristic curve,and calibration plots.Results:Post-microscopic varicocele ligation,156 patients(73.58％)experienced significant pain relief,as did 94 patients(83.93％)following microscopic denervation.Independent predictors for postoperative out-comes included age,PHQ-9 score,GAD-7 score,chronic pain duration,and varicocele diameter,diffe-ring slightly between varicocele-related and idiopathic pain groups.The models demonstrated excellent predictive ability,with areas under the curve of 0.909 and 0.913 for varicocele and idiopathic groups,respectively,and high concordance indices.Conclusion:The postoperative efficacy prediction model based on age,pain duration,PHQ-9 score,GAD-7 score,and varicocele diameter has good predictive ability and clinical applicability,and can be used in clinical practice.

Aim To investigate the effects of naringenin on atherosclerotic plaque extracellular matrix remodeling and plaque stability.Methods Murine vascular smooth muscle cells were isolated and treated with various doges of naringenin.ApoE-/-mice were fed with high-fat diet and received naringenin by lavage for 16 weeks.Intraplaque nec-rotic core,contents of collagen and fibrous cap thickness were measured by Sirius red-Haematoxylin staining.Elastin was detected by Van Gieson staining.Matrix metalloproteinase(MMP)activity was determined by gelatin zymography and fluorescence-gelatin staining.Results Naringenin(50 μmol/L)increased signal tansducer and activator of transciption 6(STAT6)phosphorylation and promoted tissue inhibitor of metalloproteinase-3(TIMP-3)expression by 3.1-fold(P＜0.001).After naringenin(80 mg/kg)treatment,compared with the control group,the area of plaque necrotic core in aor-tic root decreased by 53％(P＜0.01),the thickness of fibrous caps increased by nearly 50％(P＜0.05),and the degree of elastic fiber degradation decreased.At the same time,naringenin promoted the expression of TIMP-3 in plaques,and corre-spondingly reduced the activity of MMP in plaques.Lentivirus mediated inhibition of TIMP-3 expression in vivo could reduce the protective effect of naringenin on plaque stability.Conclusion Naringin can increase the expression of TIMP-3 in smooth muscle cells,improve the composition of extracellular matrix,and promote the stability of atherosclerotic plaque.