As a novel long-acting glucagon-like peptide-1 （GLP-1） receptor agonist， semaglutide plays a pivotal role in the treatment of obesity and related metabolic diseases. This article systematically reviews the research progress of semaglutide in the treatment of obesity and related metabolic diseases from three aspects： mechanism of action， clinical applications， and existing challenges. It is found that its mechanism of action involves multi-organ synergistic regulation and metabolic intervention. Its clinical applications encompass the treatment of obesity， diabetes， polycystic ovary syndrome， and liver-related metabolic syndromes， and it demonstrates groundbreaking value in cardiovascular and renal protection. However， it still faces multiple challenges in terms of adverse reactions， individualized treatment， economic accessibility， ethical controversies， and risks. In the future， it is essential to further accumulate long-term safety data on semaglutide， optimize combination treatment regimens， and address key issues such as individualized medication for special populations， in order to fully realize its clinical application value.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Objective:To explore the value of pre-treatment contrast-enhanced computed tomography (CT)-based texture analysis in predicting response to non-small cell lung cancer (NSCLC) immunotherapy.Methods:From January to July 2018, a total of 51 lesions from 42 patients with advanced non-small cell lung cancer receiving immunotherapy at Shanghai Chest Hospital were selected in this retrospective study. Pre-treatment contrast-enhanced CT-based texture features were extracted by MaZda software. Ten optimal texture features were chosen based on three different methods: Fisher coefficient, mutual information measure (MI) and minimization of classification error probability combined average correlation coefficients(POE+ ACC), respectively. According to the efficacy of the first immunotherapy, 51 lesions were divided into non-progressive disease (non-PD, n=26) and progressive disease (PD, n=25). The differences were tested in each texture feature set between the two groups. The immunotherapy effects of target lesions were analyzed by principal component analysis(PCA), linear discriminant analysis (LDA) and nonlinear discriminant analysis (NDA). The sensitivity, specificity, accuracy, positive-predictive value (PPV) and negative-predictive value (NPV) were calculated. The area under the curve (AUC) was used to quantify the predictive accuracy of the three analysis models for each texture feature set and compare them with the actual classification results. Results:In all of three texture feature sets, the texture parameter differences of Perc.50%, Perc.90%, "S(5, 5)SumEntrp" and "S(4, 4)SumEntrp" were higher in PD group than those in non-PD group (all P<0.05). The classification result of texture feature set chosen by POE+ ACC and analyzed by NDA was identified as the best model (AUC=0.802, 95% CI: 0.674-0.930), and its sensitivity, specificity, accuracy, PPV and NPV were 72%, 88.5%, 80.4%, 85.7%, 76.7%, respectively. Conclusion:Pre-treatment contrast-enhanced CT-based texture characteristics of NSCLC may function as non-invasive biomarkers for the evaluation of response to immunotherapy.

Objective:To explore the value of pre-treatment contrast-enhanced computed tomography (CT)-based texture analysis in predicting response to non-small cell lung cancer (NSCLC) immunotherapy.Methods:From January to July 2018, a total of 51 lesions from 42 patients with advanced non-small cell lung cancer receiving immunotherapy at Shanghai Chest Hospital were selected in this retrospective study. Pre-treatment contrast-enhanced CT-based texture features were extracted by MaZda software. Ten optimal texture features were chosen based on three different methods: Fisher coefficient, mutual information measure (MI) and minimization of classification error probability combined average correlation coefficients(POE+ ACC), respectively. According to the efficacy of the first immunotherapy, 51 lesions were divided into non-progressive disease (non-PD, n=26) and progressive disease (PD, n=25). The differences were tested in each texture feature set between the two groups. The immunotherapy effects of target lesions were analyzed by principal component analysis(PCA), linear discriminant analysis (LDA) and nonlinear discriminant analysis (NDA). The sensitivity, specificity, accuracy, positive-predictive value (PPV) and negative-predictive value (NPV) were calculated. The area under the curve (AUC) was used to quantify the predictive accuracy of the three analysis models for each texture feature set and compare them with the actual classification results. Results:In all of three texture feature sets, the texture parameter differences of Perc.50%, Perc.90%, "S(5, 5)SumEntrp" and "S(4, 4)SumEntrp" were higher in PD group than those in non-PD group (all P<0.05). The classification result of texture feature set chosen by POE+ ACC and analyzed by NDA was identified as the best model (AUC=0.802, 95% CI: 0.674-0.930), and its sensitivity, specificity, accuracy, PPV and NPV were 72%, 88.5%, 80.4%, 85.7%, 76.7%, respectively. Conclusion:Pre-treatment contrast-enhanced CT-based texture characteristics of NSCLC may function as non-invasive biomarkers for the evaluation of response to immunotherapy.

Objective:To explore whether autophagy is involved in dysfunction of vascular endothelial induced by sodium arsenite (NaAsO 2). Methods:Human primary umbilical vein endothelial cells were isolated and cultured. The cells were treated with different levels of NaAsO 2 [0 (control)), 2, 5, 10, 20, 30, 50 μmol/L] for 24 h, and cell viability was determined using CCK8. According to the results of CCK8, the levels of arsenite used in subsequent experiments were determined, intracellular nitric oxide (NO) content (incubated by NaAsO 2 for 4 h) was detected by flow cytometry, LC3 levels (incubated by NaAsO 2 for 0, 6, 12 and 24 h) was detected using Western blotting, and autophagosome (incubated by NaAsO 2 for 12 h) was observed by electron microscope. At the same time, human primary umbilical vein endothelial cells were pretreated with 0.1 mmol/L 3-MA (autophagy inhibitor) for 2 h, and induced by 30 μmol/L NaAsO 2, and the above detection indicators were compared with those of the 30 μmol/L NaAsO 2 group. Results:Human primary umbilical vein endothelial cells were successfully isolated and cultured. Compared with the control group [cell viability: (99.97 ± 5.33)%, NO content: 42 048.34 ± 789.61], the cell viability [(73.00 ± 0.86)%] and NO content (23 353.97 ± 971.85) of 30 μmol/L NaAsO 2 group were remarkably lower, and the differences were statistically significant ( P < 0.01). Incubated with 30 μmol/L NaAsO 2 at different time points 6, 12, 24 h, LC3Ⅱ levels (5.782 ± 2.789, 9.692 ± 2.222, 5.573 ± 2.941) were significantly elevated than those of control group (1.000 ± 0.383, P < 0.05), and the LC3 Ⅱ level was the highest at 12 h. After treatment with 30 μmol/L NaAsO 2 for 12 h, the number of autophagosome in cells observed under electron microscope was significantly higher than that of the control group. Compared with 30 μmol/L NaAsO 2 group [cell viability: (68.78 ± 1.55)%, LC3 Ⅱ level: 5.680 ± 0.545, NO content: 13 025.78 ± 962.61], cell viability [ (79.54 ± 4.99) %] in 3-MA+ NaAsO 2 group was increased, the LC3Ⅱ level (3.956 ± 0.398) was decreased, and the differences were statistically significant ( P < 0.05); intracellular NO content (13 988.51 ± 1 671.07) increased, whereas the difference was not statistically significant ( P > 0.05). Conclusion:Autophagy is involved in the vascular endothelial dysfunction induced by arsenic.

Objective To investigate the clinical significances of additional chromosome abnormalities and t(15;17) in acute promyelocytic leukemia (APL). Methods A total of 90 newly diagnosed APL patients in the Affiliated Hospital of Qingdao University from January 2007 to June 2014 were analyzed retrospectively. Patients with different chromosome karyotypes were divided into four groups: additional chromosome number abnormalities group (16 cases), additional chromosome structural abnormalities group (14 cases), additional chromosome number and structural abnormalities group (4 cases) and typical chromosome group (56 cases). According to whether the patient contained t(15;17), the patients were divided into group with t (15;17) and group without t (15;17). The short-term efficacy and survival of each group were analyzed and compared. Results The rate of complete remission in additional chromosome number abnormalities group, additional chromosome structural abnormalities group, additional chromosome number and structural abnormalities group and typical t(15;17) chromosome changes group were 56.3％(9/16), 100.0％(14/14), 25.0％(1/4) and 82.1％(46/56), the early mortality rates were 25.0％(4/16), 0 (0/14), 75.0％(3/4) and 8.9％ (5/56) respectively. Among them, the additional number and structural abnormalities group had lower complete remission rate and higher early mortality rate, and compared with other groups, the differences were statistically significant (all P< 0.05). The complete remission rates of the group with t (15;17) and the group without t (15;17) were 80.5％ (66/82) and 50.0％ (4/8), respectively, and the difference was not statistically significant (P= 0.070). Conclusions APL patients with karyotypes with additional number and structural changes have low complete remission rate, high early mortality rate and poor prognosis. Patients with t(15;17)have a high rate of complete remission.

Objective To study and analyze the current situation of patient medication guide in foreign countries, aiming to provide references for the preparation of patient medication guide in China. Methods The current situation of patient medication guide by consulting literatures was mastered. In addition,the design concept of patient medication guide in foreign countries was summarized, the existing problems were analyzed, and the need for improvement was discussed. Results America,Australia,European countries and some Asian countries have developed a mature patient medication guide system under the supervision of the government departments. Patient medication information overseas takes patients ' health literacy into consideration.It employs the concept of information design,focuses on risks and adverse reactions of drugs,and tells patients how to communicate with doctors and pharmacists.At the same time,it has some problems such as improper content and presentation, excessive emphasis on medication risk, not satisfying drug information demand of patients, as well as a lack of medication information for special groups such as the elderly. Conclusion The design,management and practice of patient medication guide in foreign countries set a good example for us.

OBJECTIVE:To provide suggestions for standardizing and protecting the off-label drug use. METHODS:Accord-ing to the field interviews with pharmacists and lawyers,the present situation of off-label drug use in judicial practice at home and abroad,and relevant countermeasures were put forward. RESULTS & CONCLUSIONS:At present,there was no mechanism for off-label drug use in the laws and regulations in China;there was only"special circumstances"statement in sporadic terms,while lacking explanation. In judicial practice of medical disputes,judges had different identifications in various references,such as the le-gality of routine and guidelines,teaching medical materials,clinical pathways,and internal regulations of medical institutions pre-pared by authoritative departments. Meanwhile,the judicial environment of hearing cases by identification made the off-label drug use had impartial adjudication. Legislation in 6 countries,including America,allows reasonable off-label drug use;FDA required off-label drug use must be for the benefit of patients rather than clinical trials,and it also should protect the patient's right to know. China should establish the authority specification of off-label drug use,providing scientific identification procedures,protect the patient 's informed consent by law. Medical institutions should develop relevant management system and processes to regulate medical prac-tices and ensure off-label drug use in line with the interests of doctors and patients.