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.

Background and objective Low-dose spiral computed tomography(LDCT)has been recommended for lung cancer screening in high-risk populations.However,evidence from Chinese populations was limited due to the dif-ferent criteria for high-risk populations and the short-term follow-up period.This study aimed to evaluate the effectiveness in Chinese adults based on the Lung Cancer Screening Program in Minhang District of Shanghai initiated in 2013.Methods A total of 26,124 subjects aged 40 years or above were enrolled in the Lung Cancer Screening Program during the period of 2013 and 2017.Results of LDCT examination,and screen-detected cancer cases in all participants were obtained from the Report-ing System of the Lung Cancer Screening Program.The newly-diagnosed cases and their vital status up to December 31,2020 were identified through a record linkage with the Shanghai Cancer Registry and the Shanghai Vital Statistics.Standardized incidence ratio(SIR)and 95％CI were calculated using the local population at ages of 40 or above as the reference.Proportions of early-stage cancer(stage 0-Ⅰ),pathological types,and 5-year observed survival rates of lung cancer cases were estimated and compared between the cases derived from the screened and non-screened populations.Cox regression models were applied to evaluate the hazard ratio(HR)and 95％CI of LDCT screening with all-cause death of the lung cancer cases.Results The crude and age-standardized incidence of lung cancer in screened population were 373.3(95％CI:343.1-406.1)and 70.3 per 100,000 person-years,respectively,with an SIR of 1.8(95％CI:1.6-1.9),which was observed to decrease with following-up time.The early-stage cancer accounted for 49.4％of all lung cancer cases derived from the screened population,significantly higher than 38.4％in cases from the non-screened population during the same period(P＜0.05).The proportion of lung adenocarcinoma(40.7％vs 35.9％)and 5-year survival rate(53.7％vs 41.5％)were also significantly higher in the cases from the screened popu-lation(all P＜0.05).LDCT screening was associated with 30％(HR=0.7,95％CI:0.6-0.8)reduced all-cause deaths of the cases.Conclusion The participants of the screening program are at high-risk of lung cancer.LDCT favors the early-detection of lung cancer and improves 5-year survival of the screened cases,indicating a great potential of LDCT in reducing the disease burden of lung cancer in Chinese populations.

Objective:This study aimed to explore the clinical value of myostatin(MST) and follistatin(FST) as biological biomarkers in evaluating sarcopenia in elderly women.Methods:This was a retrospective cross-sectional study that enrolled 350 females aged 20-89 years who underwent physical examinations in Shanghai Huadong Hospital in 2021. Demographic characteristics, muscle mass, fat mass, bone mineral density, hand grip strength, gait speed, and serum indices of MST and FST were collected.Results:The serum levels of MST did not change significantly with age. However, the serum levels of FST increased with age. In women aged≥60 years, MST was positively correlated with total lean mass and appendicular skeletal muscle index(ASMI; r=0.236, P=0.041; r=0.289, P=0.014), while FST was negatively correlated with ASMI( r=-0.265, P=0.030). In multivariate stepwise regression analysis, after adjusting for age, body mass index, hip bone mineral density, and total fat mass, only FST was independently correlated with ASMI( β=-0.238, P=0.006), while MST was not correlated with ASMI. The receiver operating characteristic curve was plotted using muscle mass reduction as the state variable and serum FST level as the test variable. The area under the curve was 0.753. And when the FST cutoff value was 17.49 ng/mL, the maximum Jordan index was 0.46, with a sensitivity of 77.3% and a specificity of 68.7%. Women aged ≥60 years were divided into three groups based on serum FST levels. Compared to the upper third of the serum FST level group, the low third of the FST level group had a significantly reduced risk of suffering from sarcopenia( OR=0.098, P =0.036). Conclusions:Serum FST lever has a better correlation with muscle mass among elderly women, making it a promising biomarker for evaluating muscle mass.

ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of different concentration of rutin （3.125， 6.25， 12.5， 25， 50， 100， 200 μmol·L^-1） on 3T3-L1 cell activity， and Western blot to examine the effect of rutin （12.5， 25， 50 μmol·L^-1） on the expression of thermogenesis-associated proteins uncoupling protein 1 （UCP1）， PR domain containing 16 （PRDM16） and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in adipocytes. After the optimal concentration of rutin was determined， the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining， and the expression of nuclear respiratory factor 1 （NRF1）， nuclear respiratory factor 2 （NRF2） and mitochondrial transcription factor A （TFAM）， which were the landmark proteins of mitochondrial biosynthesis， was detected by Western blot. ResultCompared with the blank group， 200 μmol·L^-1 rutin inhibited 3T3-L1 cell activity （P<0.01）. Compared with the blank group， at the concentration of 12.5， 25， 50 μmol·L^-1 rutin significantly promoted the expression of thermogenesis-associated proteins （UCP1， PRDM16， and PGC-1α） （P<0.01）， which was determined as the optimal concentration. Compared with the blank group， 50 μmol·L^-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells （P<0.01） and the expression of the markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM） （P<0.01）. In addition， 50 μmol·L^-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes （P<0.01）. ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins （UCP1， PRDM16， and PGC-1α） and markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM）， thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice ; Animals ; Adipose Tissue, Brown ; Sirtuin 1/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Morus/metabolism* ; Flavonoids/metabolism* ; Prospective Studies ; Signal Transduction ; Adipose Tissue, White ; Plant Leaves ; Uncoupling Protein 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*

ObjectiveTo investigate the medicinal effect of total flavonoids of mulberry leaves on regulating liver lipid metabolism disorder in diabetes mellitus type 2 （T2DM） rats， and the mechanism based on liver peroxidase proliferators activate receptors-α （PPAR-α） and carnitine palmityl transferase-1 （CPT-1） proteins. MethodTotal flavonoids of mulberry leaves were extracted and purified by ethanol extraction + macroporous resin purification and then identified. T2DM rat model was induced by high fat diet （HFD） + streptozocin（STZ）method. Rats with blood glucose ≥ 11.1 mmol·L^-1 were divided into three administration groups with the high dose （300 mg·kg^-1）， medium dose （150 mg·kg^-1）， and low dose （75 mg·kg^-1） of total flavonoids of mulberry leaves for 8 weeks， respectively， to observe the weight and blood glucose of the rats. The pathological changes of rat livers were observed by hematoxylin-eosin （HE） staining. Biochemical method was used to detect the levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein-cholesterol （LDL-C）， and high density lipoprotein-cholesterol （HDL-C） of blood lipid metabolism in rats. The messenger ribonucleic acid （mRNA） and protein expressions of PPAR-α and CPT-1 were determined by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultAfter 8 weeks of intervention of total flavonoids of mulberry leaves， compared with the control group， the food intake， liver index， and fasting blood glucose of rats in the model group increased significantly （P<0.01）. Compared with the model group， the food intake， fasting blood glucose， and liver index of rats in the administration groups decreased significantly （P<0.01）. The results of HE staining showed that the liver tissue structure of rats in the control group was complete and there was no obvious abnormality. The model group showed vacuolar degeneration and inflammatory infiltration of hepatocytes of rats. There was no obvious abnormality in the liver structure of rats in the administration groups. The results of blood lipid showed that compared with the control group， the levels of TC， TG， and LDL-C increased significantly （P<0.01）， but the level of HDL-C decreased significantly （P<0.01） in the model group. Compared with the model group， the levels of TC， TG， and LDL-C decreased significantly （P<0.05， P<0.01）， whereas the level of HDL-C increased significantly （P<0.01） in the administration groups. The results of Real-time PCR showed that compared with the control group， the mRNA expression of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the mRNA expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.01）. The results of Western blot showed that compared with the control group， the protein expressions of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the protein expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.05， P<0.01）. ConclusionTotal flavonoids of mulberry leaves can effectively reduce blood glucose and improve liver lipid metabolism disorder in T2DM rats. The total flavonoids of mulberry leaves could regulate lipid metabolism and play a hypoglycemic role by activating and regulating PPAR-α and CPT-1 proteins and promoting oxidative decomposition of fatty acids.

The incidence of diabetes has been on the rise as the result of lifestyle changes， especially the high-fat diet and reduced exercise. Thus， it has become a global public health problem and it is an urgent task to explore effective therapy. There has been an explosion of research on the relationship of transforming growth factor-β （TGF-β） signaling pathways with diabetes complications and tumors， but the role of the pathways in the occurrence and progression of diabetes remains unclear. TGF-β signaling pathways can be activated by many factors， directly or indirectly leading to the apoptosis of islet β cells and insulin resistance （IR）， and thus they are expected to become new targets for the treatment of diabetes. TGF-β-related signaling pathways involve AMP-activated proteinkinase （AMPK）， protooncogene （c-Myc）， Ski-relatednovel protein N （SnoN）， Smad ubiquitination regulatory factor 1 （Smurf1）， miR-335-5p， and other signaling molecules. They participate in the occurrence and development of IR， apoptosis of islet β cells， insulin secretion disorder， fibrosis of adipocytes， and metabolic disorder of adipocytes， and inhibit the browning of white adipose tissue， playing an important part in the pathological process of human diabetes. According to traditional Chinese medicine （TCM）， the pathogenesis of diabetes is the deficiency of Qi and Yin， and the late stage is characterized by the syndrome of Qi deficiency， and Yang deficiency and blood stasis， which should be treated according to the principle of replenishing Qi and nourishing Yin， warming Yang and activating blood. It has been found that the efficacy of some Chinese medicinals and compound prescriptions on diabetes is closely related to the TGF-β signaling pathways. This paper reviews TGF-β-associated signaling pathways， elucidating the roles of them in pathogenesis of diabetes， and analyzes the relationship of TGF-β-associated signaling pathways with the effect of compound Chinese medicine prescriptions against diabetes. This study is expected to lay a theoretical basis for the research on the treatment diabetes.

Objective:To investigate the risk factors of bone cement leakage and recompression of injured vertebrae after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF).Methods:A case-control study was performed to analyze the clinical data of 297 patients with single-segment OVCF who underwent PKP in First Affiliated Hospital of Soochow University from January 2017 to January 2021, including 67 males and 230 females; aged 60-92 years [(69.5±8.2)years]. According to the occurrence of bone cement leakage, the patients were divided into leakage group ( n=36) and no leakage group ( n=261). According to the occurrence of recompression of injured vertebrae, the patients were divided into recollapse group ( n=40) and no recollapse group ( n=257). The gender, age, fracture segment, type of fracture, fracture severity, cortical disruption, intravertebral cleft, preoperative and postoperative local kyphosis angle, correction value of local kyphosis angle, bone cement injection volume, bone cement distribution, and postoperative anti-osteoporosis treatment were recorded. Univariate analysis was used to analyze the correlation of those factors with bone cement leakage and recompression of injured vertebrae after PKP, followed by multivariate Logistic regression analysis to identify the independent risk factors. Results:Univariate analysis showed that fracture severity, cortical disruption and bone cement injection volume were related to bone cement leakage ( P<0.05 or 0.01). Gender, age, fracture segment, type of fracture, intravertebral cleft, preoperative and postoperative local kyphosis angle, correction value of local kyphosis angle, bone cement distribution, and postoperative anti-osteoporosis treatment were not related to bone cement leakage (all P>0.05). Univariate analysis showed that intravertebral cleft, bone cement distribution, and postoperative anti-osteoporosis treatment were associated with recompression of injured vertebrae (all P<0.01). Gender, age, fracture segment, type of fracture, fracture severity, cortical disruption, preoperative and postoperative local kyphosis angle, correction value of local kyphosis angle, and bone cement injection volume were not related to recompression of injured vertebrae (all P>0.05). Multivariate Logistic regression analysis showed that severe fracture ( OR=4.23, 95% CI 1.52-11.81, P<0.01), cortical disruption ( OR=3.29,95% CI 1.52-7.13, P<0.01), and bone cement injection volume >8 ml ( OR=2.31,95% CI 1.09-4.92, P<0.05) were significantly related to bone cement leakage. Multivariate Logistic regression analysis showed that intravertebral cleft ( OR=2.10, 95% CI 1.03-4.30, P<0.05), solid type of bone cement distribution ( OR=2.56, 95% CI 1.25-5.27, P<0.05) and no anti-osteoporosis treatment after operation ( OR=3.06, 95% CI 1.46-6.40, P<0.01) were significantly related to recompression of injured vertebrae. Conclusions:For OVCF patients, severe fracture, cortical disruption, and bone cement injection volume>8 ml are independent risk factors for bone cement leakage after PKP. Intravertebral cleft, solid type of bone cement distribution, and no anti-osteoporosis treatment after operation are independent risk factors for recompression of injured vertebrae after PKP.

Objective:To explore the effect of small dose of low molecular weight heparin on the prognosis of elderly patients with severe pneumonia using systematic evaluation method.Methods:Databases including Wanfang data, VIP, CNKI, SinoMed, PubMed, Embase and Cochrane Library were searched for randomized controlled trial (RCT) studies about the comparison of conventional therapy and low molecular weight heparin on prognosis of elderly patients with severe pneumonia from the time of database establishment to August 2019. The patients in conventional treatment group were treated by improving ventilation, anti-infection, eliminating phlegm, relieving asthma and maintaining homeostasis while those in low molecular weight heparin group were subcutaneously injected with low molecular weight heparin of 4 000 U, once a day for 7 days. The patients' main outcomes included the oxygenation index (PaO 2/FiO 2) after 7 days of treatment, duration of mechanical ventilation, mortality in hospital, and secondary outcomes included acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score and coagulation function after 7 days of treatment, the length of intensive care unit (ICU) stay, and incidence of bleeding. Data extraction and quality evaluation were conducted. The Meta-analysis of included studies that met the quality standards was performed using RevMan 5.3 software. Funnel diagram analysis was used to analyze the parameters with no less than 10 studies enrolled. Results:A total of 14 RCT studies were enrolled involving 1 173 elderly patients with severe pneumonia, among whom 590 received low molecular weight heparin while the other 583 received conventional therapy. All the included studies were well designed and of high quality. The results of Meta-analysis showed that compared with conventional therapy, small dose of low molecular weight heparin significantly elevated PaO 2/FiO 2 after 7 days of treatment [mean difference ( MD) = 19.25, 95% confidence interval (95% CI) was 16.88 to 21.61, P < 0.000 01], shortened the duration of mechanical ventilation ( MD = -48.88, 95% CI was -67.42 to -30.33, P < 0.000 01), and decreased mortality in hospital [odds ratio ( OR) = 0.40, 95% CI was 0.22 to 0.73, P = 0.003] and APACHEⅡ score after 7 days of treatment ( MD = -3.38, 95% CI was -3.94 to -2.83, P < 0.000 01), and shortened the length of ICU stay ( MD = -4.51, 95% CI was -5.75 to -3.27, P < 0.000 01). There was no significant difference in the changes of coagulation parameters after 7 days of treatment or the incidence of bleeding between low molecular weight heparin group and conventional therapy group [7-day thrombin time (TT): MD = 0.57, 95% CI was -0.15 to 1.28, P = 0.12; 7-day prothrombin time (PT): MD = 0.32, 95% CI was -0.35 to 0.98, P = 0.35; 7-day fibrinogen (FIB): MD = -0.17, 95% CI was -0.45 to 0.10, P = 0.22; incidence of bleeding: OR = 0.86, 95% CI was 0.36 to 2.07, P = 0.74]. The funnel diagram showed that there was publication bias of included 10 studies about APACHEⅡ score after 7 days of treatment. Conclusion:Small dose of low molecular weight heparin can improve the prognosis of elderly patients with severe pneumonia and it has no obvious side-effect on coagulation function.

According to the pathological characteristics of symptomatic chronic thoracic and lumbar osteoporotic vertebral fracture (SCOVF), the different clinical treatment methods are selected, including vertebral augmentation, anterior-posterior fixation and fusion, posterior decompression fixation and fusion, and posterior correction osteotomy. However, there is still a lack of a unified understanding on how to choose appropriate treatment method for SCOVF. In order to reflect the new treatment concept and the evidence-based medicine progress of SCOVF in a timely manner and standardize its treatment, the clinical guideline for surgical treatment of SCOVF is formulated in compliance with the principle of scientificity, practicability and advancement and based on the level of evidence-based medicine.