G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9％NaCl),model group(intraperitoneal injection of 40％CC14 peanut oil solution induced HF model,intragastric administration of 0.9％NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.

Objective To observe the clinical efficacy and safety of traditional Chinese medicine(TCM)constitution correction based on the theory of preventive treatment of disease on the patients with early asymptomatic diabetic peripheral neuropathy(DPN).Methods A total of 87 patients with early asymptomatic DPN were randomly divided into the control group with 43 cases and the trial group with 44 cases.The control group was required to have standard diet,do exercises and take medicines for diabetes.On the basis of treatment for the control group,the trial group was given the corresponding TCM constitution correction regimen according to the predominated constitution types of the patients.The course of treatment for the two groups lasted for 48 weeks.Before and after intervention,the two groups were observed in the alteration of TCM constitution types,and the changes of body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and nerve conduction velocity(NCV).Moreover,the safety of the two groups was evaluated.Results(1)After the intervention,the constitution of 17 patients in the trial group was transformed into the balanced constitution,while only the constitution of 5 patients in the control group was transformed into balanced constitution.There was a statistically significant difference in the distribution of TCM constitution between the two groups(P＜0.05).(2)Before intervention,there were no significant differences in the levels of BMI,SBP,DBP,FPG,HbA1c,TC,TG,HDL-C and LDL-C between the two groups(P＞0.05).After intervention,the levels of BMI,SBP and DBP in the two groups and the levels of HbA1c,TC,TG and LDL-C in the trial group were lower than those before intervention(P＜0.05 or P＜0.01),while the levels of FPG and HDL-C in the control group were higher than those before intervention(P＜0.05 or P＜0.01).The intergroup comparison showed that the levels of FPG,HbA1c,TG and LDL-C in the trial group were significantly lower than those in the control group(P＜0.05 or P＜0.01).(3)After the intervention,10 cases in the control group had typical clinical symptoms of DPN,while only 6 cases in the trial group had the clinical symptoms of DPN.Before intervention,there was no significant difference in the motor nerve conduction velocity(MNCV)of bilateral tibial nerve and common peroneal nerve and in the sensory nerve conduction velocity(SNCV)of bilateral sural nerve and superficial peroneal nerve between the two groups(P＞0.05).After intervention,the MNCV of bilateral tibial nerve and common peroneal nerve and the SNCV of bilateral sural nerve and superficial peroneal nerve in the control group were slower than those before intervention(P＜0.05),while the above indicators of nerve conduction velocity in the trial group were mildly increased compared with those before intervention,but the differences were not significant(P＞0.05).The intergroup comparison showed that the MNCV of bilateral tibial nerve and SNCV of bilateral sural nerve and superficial peroneal nerve in the trial group were higher than those in the control group,and the differences were statistically significant(P＜0.05).(4)During the intervention,no obvious adverse reactions occurred in the two groups,with high safety.Conclusion The TCM constitution correction can adjust the biased constitution of patients with early asymptomatic DPN,and has certain protective effect on the glucose and lipid metabolism,MNCV of tibial nerve,and SNCV of bilateral sural nerve and superficial peroneal nerve.

Objective:To analyze the clinical features and genetic characteristics of a patient with Shwachman-Diamond syndrome (SDS) due to compound heterozygous variants of SBDS gene.Methods:A female child with SDS who was admitted to the Children's Hospital Affiliated to Zhengzhou University in February 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her elder sister and parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The child, a 1-year-and-1-month-old girl, had mainly manifested with diarrhea, hematochezia, growth retardation and malnutrition, along with increased transaminases and decreased neutrophils and hemoglobin. The anteroposterior X-ray of her left wrist indicated significantly delayed bone age. Colonoscopy revealed that her colorectal mucosa was erosive with oily food residues attached to the intestinal lumen. Genetic testing revealed that she has harbored c. 258+ 2T>C and c. 100A>G compound heterozygous variants of the SBDS gene. The c. 258+ 2T>C variant has derived from her father and known to be pathogenic, whilst the other has derived from her mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 100A>G variant was classified as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PM5+ PP3). Conclusion:The compound heterozygous variants of c. 258+ 2T>C and c. 100A>G probably underlay the SDS in this child. For children with refractory diarrhea, liver damage and growth retardation, SDS should be suspected, and genetic testing can facilitate the diagnosis and treatment.

Objective To construct a set of graduation internship curriculum system suitable for undergraduate students majoring in biomedical engineering to facilitate standardizing the curriculum system of biomedical engineering major.Methods An initial version of the curriculum system was established with the way of letter and the methods of questionnaire survey,Delphi,expert interview and expert brainstorming;then the initial version was adjusted and refined using 2 rounds of expert consultation to form a set of curriculum system for graduation internship for undergraduate students majoring in biomedical engineering,and the curriculum system was validated.Results The curriculum system included 5 first-level catalogs,11 second-level catalogs and 39 third-level catalogs;the 36 third-level catalogs had a curriculum compliance rate of 0.85 to 0.97.Conclusion The curriculum system constructed can be used for graduation internship of biomedical engineering undergraduates,and references are provided for developing standardized and generally applicable graduation internship curriculum system for biomedical engineering undergraduates.[Chinese Medical Equipment Journal,2024,45(9):89-94]

Objective:To evaluate the effect of virtual reality arthroscopic simulation system combined with case-based learning (CBL) in orthopedic clinical teaching.Methods:From January 2021 to June 2022, a total of 36 residents who took the standardized residency training at Department of Articular Orthopedics in The Third Affiliated Hospital of Soochow University were enrolled in this study. They were randomized into an experimental group and a control group, with 18 trainees in each group. The experimental group adopted the virtual reality arthroscopic simulation system combined with CBL teaching mode, while the control group adopted simple endoscopic simulation training box with traditional teaching mode. Theoretical and practical tests and questionnaire survey were carried out to evaluate the teaching effects in two groups. SPSS 22.0 was performed to conduct t-test on the measurement data between the two groups. Results:The theoretical and practical test scores of the experimental group [(89.39±3.09) and (82.72±4.28)] were better than those of the control group [(86.22±4.43) and (76.61±5.65)], with statistically significant differences ( t= 2.49, P=0.018; t=3.66, P=0.001). The questionnaire survey showed that the experimental group was better than the control group in creating novel forms of courses [(4.94±0.24) vs. (4.11±0.58), t=5.62, P<0.001], simulating more real scenes [(4.83±0.38) vs. (3.78±0.43), t=7.80, P<0.001], inspiring learning interests [(4.78±0.43) vs. (4.00±0.59), t=4.51, P<0.001], improving practical skills [(4.83±0.38) vs. (3.83±0.51), t=6.61, P<0.001], and building career confidence [(4.50±0.62) vs. (3.06±0.54), t=7.47, P<0.001], with statistically significant differences (all P<0.001). Conclusions:The virtual reality arthroscopic simulation system combined with CBL teaching mode can better simulate the real clinical scenes, help inspire the interest of learning and quickly improve practical skills, thereby improving the effect of orthopedic clinical teaching.

Three novel sesquiterpenoid heterodimers,designated as auckcostusolides A-C(1-3),were isolated from Aucklandia costus leaves.The structures of compounds 1-3 were elucidated through comprehensive spectroscopic analysis,with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism(ECD)calculations.Notably,compounds 1 and 2,despite sharing identical planar structures derived from two identical sesquiterpenoids,exhibited oppos-ite configurations at C-11 and C-8'.This configurational difference can be attributed to distinct Diels-Alder cycloaddition processes between the sesquiterpenoid monomers.Additionally,the cytotoxic effects of compounds 1-3 were evaluated against colorectal can-cer HCT116 cells,fibrosarcoma HT1080 cells,and hepatocellular carcinoma HepG2 cells.Compounds 1-3 induced cell death was characterized by endoplasmic reticulum(ER)swelling and cytoplasmic vacuolization,typical morphological changes associated with paraptosis.Mechanistic studies revealed that compounds 1 and 3 triggered paraptosis-like cell death through the accumulation of react-ive oxygen species(ROS),activation of ER stress,and stimulation of the MAPK signaling pathway.

Objective:To analyze the dose-response relationship of 99Tc m-dimercaptosuccinic acid (DMSA) in pediatric renal static imaging. Methods:A retrospective analysis of children (model group: n=199, 81 males, 118 females; validation group: n=30, 13 males, 17 females; all age: 1 month-14 years) who underwent 99Tc m-DMSA renal static imaging from January 2022 to November 2023 in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology were conducted. Post-administration radiation counts and related clinical data were collected. Imaging quality was evaluated using visual analogue scoring (VAS). ROC curve analysis was used to assess the relationship between radiation count intensity (RCI) and imaging quality. A nonlinear mixed-effects modeling method was employed to establish the dose-response relationship for 99Tc m-DMSA in pediatric renal static imaging. Internal and external validations of the model were performed. Final model was utilized to evaluate patient dosing protocols. Results:Body weight was considered as a significant determinant of the dose-response relationship in 99Tc m-DMSA renal static imaging( χ2 values: 120.79, 116.36, both P<0.05). ROC curve analysis showed that the quality of diagnostic images was acceptable when the anterior renal RCI was ≥32.61 (cut-point) and the posterior renal RCI was ≥35.46 (cut-point). Both internal and external validation results demonstrated that the dose-response model established exhibited good prediction performance. Based on the final model graph, the image quality could meet the requirements for clinical diagnosis. Conclusions:The 99Tc m-DMSA dose-response model for pediatric renal static imaging is successfully established. Individualized dosage based on the model can provide a reference for clinical individualized dosing decision-making.

Objective To investigate the relationship of benign prostatic hyperplasia(BPH) with abnormal glucose and lipid metabolism in the elderly. Methods A total of 152 elderly patients with BPH were selected as study subjects. The levels of fasting plasma glucose (FPG), 2-hour postprandial glucose (2 hPG), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood uric acid (UA), and prostate-specific antigen (PSA) were measured. Their systolic blood pressure (SBP) and diastolic blood pressure (DBP) were also measured. Prostate volume (PV) and annual prostate growth rate were calculated, and the International Prostate Symptom Score (IPSS) was assessed. Based on blood glucose, blood lipids, and IPSS, the patients were divided into normal blood glucose group(99 cases) and hyperglycemia group(53 cases), normal blood lipid group(112 cases) and dyslipidemia group(40 cases), and moderate symptom group(91 cases) and severe symptom group(61 cases). The clinical characteristics of patients in each group were compared, and the relationships of abnormal glucose and lipid metabolism with the severity of lower urinary tract symptoms in patients with BPH were analyzed. Results Compared with the normal blood glucose group, patients in the hyperglycemia group had higher age, SBP, annual prostate growth rate, IPSS, and levels of FPG, 2 hPG, FINS, and PSA, larger PV, and lower HDL-C level (P < 0.05). Compared with the normal blood lipid group, patients with BPH in the dyslipidemia group had higher age, SBP, annual prostate growth rate, IPSS, and levels of FPG, FINS, TC, TG, LDL-C, and UA, larger waist circumference and PV, and lower HDL-C level (P < 0.05). Compared with the moderate symptom group, patients in the severe symptom group had higher age, BMI, SBP, annual prostate growth rate, and FPG levels, higher incidence rates of hyperglycemia and dyslipidemia, larger PV, and lower HDL-C levels (P < 0.05). Multivariate Logistic regression analysis indicated that age ≥70 years, SBP ≥140 mmHg, hyperglycemia, dyslipidemia, increased PV, and elevated annual prostate growth rate were all independent risk factors for the occurrence of severe lower urinary tract symptoms in patients with BPH (P < 0.05). Conclusion Elderly BPH is closely related to abnormal glucose and lipid metabolism, and abnormal glucose and lipid metabolism are risk factors for the exacerbation of lower urinary tract symptoms.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*