Effects of probiotics combined with dietary intervention on glucose and lipid metabolism and pregnancy outcome in gestational diabetes mellitus / 重庆医学

Objective To investigate the effects of probiotics combined with dietary intervention on pe-ripheral blood glucose and lipid metabolism indicators,placental tissue insulin signaling pathway proteins ex-pression and pregnant outcome in the patients with gestational diabetes mellitus(GDM).Methods A total of 83 patients with GDM in this hospital from December 2021 to December 2022 were selected as the study sub-jects and divided into the probiotics group(probiotics combined with diet intervention,43 cases)and control group(simple diet intervention,40 cases)by the random number table method.The levels of peripheral blood glucose,lipid and insulin resistance related indicators before the intervention and in 8 weeks after the interven-tion were compared between the two groups.The histological changes of placenta were observed by HE stai-ning.The pathological indicators were compared between the two groups.The expression levels of insulin re-ceptor substrate-1(IRS-1),glucose transporter 4(GLUT4)and synaptosome-associated protein of 23 kDa(SNAP23)in placental tissue were detected by immunohistochemistry.The pregnant adverse outcomes were compared between the two groups,and the clinical efficacy of probiotics was evaluated.Results Compared with the control group,the levels of fasting blood glucose(FBG),fasting insulin(FINS),serum triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)in 8 weeks after intervention in the probiotics group were significantly decreased(P＜0.05),and the level of serum high density lipoprotein cholesterol(HDL-C)was significantly increased(P＜0.05).There were no significant differences in the incidence rates of poor villi maturation,thickening of dry villi arterioles and capillary filling in villi interstitial between the two groups(P＞0.05).Compared with the control group,the expression levels of IRS-1,GLUT4 and SNAP23 in placen-tal tissue of the probiotics group were significantly increased(P＜0.05).The incidence rates of neonatal hy-poglycemia and neonatal hyperbilirubinemia in the probiotics group were significantly lower than those in the control group(P＜0.05).Conclusion Compared with simple dietary intervention,probiotics combined with dietary intervention has more advantages in improving glucose and lipid metabolism of GDM patients,moreo-ver reduces the adverse events occurrence in newborns.

Effects of different concentrations of lidocaine infiltration and analgesia in pleural cavity after lung cancer surgery on rehabilitation of patients / 局解手术学杂志

Objective To explore the effects of different concentrations of lidocaine infiltration and analgesia in pleural cavity after lung cancer surgery on rehabilitation of patients.Methods A total of 86 patients with lung cancer were selected and divided into the high concentration group(43 cases)and low concentration group(43 cases)by random number table method.Patients in the high concentration group received injection of 2.0%lidocaine hydrochloride in pleural cavity through the epidural catheter 1st day after surgery,and patients in the low concentration group received injection of 1.5%lidocaine hydrochloride in pleural cavity.In addition,patients in the two groups were treated with patient-controlled intravenous analgesia after surgery.The first time of getting out of bed,first time of exhaustion,first time of defecation and hospital stay after surgery of the two groups were compared.The visual analogue scale(VAS)scores 6 hours,12 hours,24 hours and 48 hours after surgery,the occurrence of agitation during the postoperative awakening period,and the number of analgesic pump compressions and the dosage of analgesic drugs within 24 hours after surgery were compared.The incidence of adverse drug reactions 24 hours after surgery were recorded and the quality of recovery of patients 24 hours after surgery was evaluated by 40-item quality of recovery score(QoR-40).Results The first time of getting out of bed,first time of exhaustion,first time of defecation and hospital stay after operation of patients in the high concentration group were shorter than those in the low concentration group(P<0.05).The VAS scores of the two groups 12 hours and 24 hours after surgery were higher than those 6 hours after surgery(P<0.05),the VAS scores 24 hours and 48 hours after surgery were lower than those 12 hours after surgery(P<0.05),and the VAS scores 48 hours after surgery were lower than those 24 hours after surgery(P<0.05).The VAS scores 6 hours,12 hours,24 hours,and 48 hours after surgery of patients in the high concentration group were lower than those in the low concentration group(P<0.05).The occurrence of agitation during the postoperative awakening period,and the number of analgesic pump compressions and the dosage of analgesic drugs within 24 hours after surgery for patients in the high concentration group were lower/less than those in the low concentration group(P<0.05).There was no significant difference in the total incidence of adverse drug reactions between the two groups(P>0.05).The total QoR-40 score of patients in the high concentration group were higher than those in the low concentration group(P<0.05).Conclusion The use of 2.0%lidocaine infiltration and analgesia in pleural cavity for patients after lung cancer surgery can reduce the agitation during the awakening period,alleviate the postoperative pain,improve the quality of postoperative recovery,and promote the postoperative recovery of the patients,with certain safety.

Clinical efficacy and anti-inflammation/anti-fibrosis effect of tripterygium glycosides in the treatment of diabetic nephropathy / 中国临床药理学与治疗学

AIM: To observe the clinical efficacy of multi -glycoside of tripterygium wilfordii (GTW) on diabetic nephropathy. METHODS: Fifty-one patients with diabetic kidney disease (DKD) with a history of GTW dosing admitted to the outpatient clinic of Yijishan Hospital affiliated to Wannan Medical College from June 2019 to October 2022 were selected as study subjects, and were followed up regularly to observe the changes in laboratory indexes before and after GTW dosing and adverse drug reactions after 6 months of treatment. The t-test, Mann-Whitney U-test or χ

Geographic Variations in the Prevalence, Awareness, Treatment, and Control of Dyslipidemia among Chinese Adults in 2018-2019: A Cross-sectional Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the spatial patterns of the prevalence, awareness, treatment, and control rates of dyslipidemia at the provincial level in China.@*METHODS@#A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in mainland China in 2018-2019, using a multi-stage, stratified, cluster-randomized sampling design. Subjects, as households, were selected, followed by a home visit to collect information. Both descriptive and linear regression procedures were applied in the analyses.@*RESULTS@#The overall prevalence of dyslipidemia was 35.6%, and wide geographic variations of prevalence, treatment, and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1 ± 13.8 years. The highest-lowest difference regarding the provincial level prevalence rates were 19.7% vs. 2.1% for high low-density lipoprotein cholesterol, 16.7% vs. 2.5% for high total cholesterol, 35.9% vs. 5.4% for high triglycerides, and 31.4% vs. 10.5% for low high-density lipoprotein cholesterol. The treatment rate of dyslipidemia was correlated with the socio-demographic index ( P < 0.001), urbanization rate ( P = 0.01), and affordable basic technologies and essential medicines ( P < 0.001).@*CONCLUSION@#Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence, treatment, and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management.

A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors / 中华肿瘤杂志

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors / 中华肿瘤杂志

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

Doublecortin-like kinase 1 activates Hippo pathway to promote migration, invasion and proliferation of pancreatic cancer cells / 中华肿瘤杂志

Objective: To explore the mechanism of Doublecortin-like kinase 1 (DCLK1) in promoting cell migration, invasion and proliferation in pancreatic cancer. Methods: The correlation between DCLK1 and Hippo pathway was analyzed using TCGA and GTEx databases and confirmed by fluorescence staining of pancreatic cancer tissue microarrays. At the cellular level, immunofluorescence staining of cell crawls and western blot assays were performed to clarify whether DCLK1 regulates yes associated protein1 (YAP1), a downstream effector of the Hippo pathway. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to analyze the expressions of YAP1 binding transcription factor TEA-DNA binding proteins (TEAD) and downstream malignant behavior-promoting molecules CYR61, EDN1, AREG, and CTGF. Transwell test of the DCLK1-overexpressing cells treated with the Hippo pathway inhibitor Verteporfin was used to examine whether the malignant behavior-promoting ability was blocked. Analysis of changes in the proliferation index of experimental cells used real-time label-free cells. Results: TCGA combined with GTEx data analysis showed that the expressions of DCLK1 and YAP1 molecules in pancreatic cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Moreover, DCLK1was positively correlated with the expressions of many effectors in the Hippo pathway, including LATS1 (r=0.53, P<0.001), LATS2 (r=0.34, P<0.001), MOB1B (r=0.40, P<0.001). In addition, the tissue microarray of pancreatic cancer patients was stained with multicolor fluorescence, indicated that the high expression of DCLK1 in pancreatic cancer patients was accompanied by the up-regulated expression of YAP1. The expression of DCLK1 in pancreatic cancer cell lines was analyzed by the CCLE database. The results showed that the expression of DCLK1 in AsPC-1 and PANC-1 cells was low. Thus, we overexpressed DCLK1 in AsPC-1 and PANC-1 cell lines and found that DCLK1 overexpression in pancreatic cancer cell lines promoted YAP1 expression and accessible to the nucleus. In addition, DCLK1 up-regulated the expression of YAP1 binding transcription factor TEAD and increased the mRNA expression levels of downstream malignant behavior-promoting molecules. Finally, Verteporfin, an inhibitor of the Hippo pathway, could antagonize the cell's malignant behavior-promoting ability mediated by high expression of DCLK1. We found that the number of migrated cells with DCLK1 overexpressing AsPC-1 group was 68.33±7.09, which was significantly higher than 22.00±4.58 of DCLK1 overexpressing cells treated with Verteporfin (P<0.05). Similarly, the migration number of PANC-1 cells overexpressing DCLK1 was 65.66±8.73, which was significantly higher than 37.00±6.00 of the control group and 32.33±9.61 of Hippo pathway inhibitor-treated group (P<0.05). Meanwhile, the number of invasive cells in the DCLK1-overexpressed group was significantly higher than that in the DCLK1 wild-type group cells, while the Verteporfin-treated DCLK1-overexpressed cells showed a significant decrease. In addition, we monitored the cell proliferation index using the real-time cellular analysis (RTCA) assay, and the proliferation index of DCLK1-overexpressed AsPC-1 cells was 0.66±0.04, which was significantly higher than 0.38±0.01 of DCLK1 wild-type AsPC-1 cells (P<0.05) as well as 0.05±0.03 of DCLK1-overexpressed AsPC1 cells treated with Verteporfin (P<0.05). PANC-1 cells showed the same pattern, with a proliferation index of 0.77±0.04 for DCLK1-overexpressed PANC-1 cells, significantly higher than DCLK1-overexpressed PANC1 cells after Verteporfin treatment (0.14±0.05, P<0.05). Conclusion: The expression of DCLK1 is remarkably associated with the Hippo pathway, it promotes the migration, invasion, and proliferation of pancreatic cancer cells by activating the Hippo pathway.

Burned-out testicular germ cell tumors: a clinicopathological analysis of three cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and possible mechanisms of burned-out testicular germ cell tumors. Methods: The clinical and imaging data, histology and immunophenotypic characteristics of three cases of burned-out testicular germ cell tumors diagnosed at the Ruijin Hospital, Medical College of the Shanghai Jiaotong University, from 2016 to 2020 were retrospectively analyzed. The relevant literature was reviewed. Results: The mean age of the three patients was 32 years. Case 1 had an elevated preoperative alpha-fetoprotein level (810.18 μg/L) and underwent "radical pancreaticoduodenectomy and retroperitoneal lesion resection" for a retroperitoneal mass. Postoperative pathology showed embryonal carcinoma, which needed to exclude gonadal metastasis. Color Doppler ultrasound showed a solid mass of the right testis, with hypoechoic lesion and scattered calcification in some areas. Case 2 was a "right supraclavicular lymph node biopsy specimen." Chest X-ray showed multiple metastases in both lungs. The biopsy showed metastatic embryonic carcinoma and bilateral testicular color Doppler ultrasound revealed abnormal calcifications in the right testicle. Case 3 showed a cystic mass of the right testis with calcification and solid areas. All 3 patients underwent radical right orchiectomy. Grossly, borders of the testicular scar areas were well defined. Cross sectioning of the tumors showed a gray-brown cut surface and single focus or multiple foci of the tumor. The tumor maximum diameter was 0.6-1.5 cm. Microscopically, lymphocytes, plasma cells infiltration, tubular hyalinization, clustered vascular hyperplasia and hemosiderin laden macrophages were found in the scar. Atrophic and sclerotic seminiferous tubules, proliferation of clustered Leydig cells and small or coarse granular calcifications in seminiferous tubules were present around the scar. Seminoma and germ cell neoplasia in situ were seen in case 1, germ cell neoplasia in situ was seen in case 2 and germ cells with atypical hyperplasia were seen in case 3. Immunohistochemistry showed that embryonic carcinoma expressed SALL4, CKpan(AE1/AE3) and CD30, seminoma and germ cell tumor in situ expressed OCT3/4, SALL4 and CD117, and spermatogenic cells with atypical hyperplasia expressed CD99 and SALL4. The Ki-67 positive index was about 20%, while OCT3/4 and CD117 were both negative. Conclusions: Burned-out testicular germ cell tumors are rare. The possibility of gonad testicular metastasis should be considered first for extragonadal germ cell tumor. If fibrous scar is found in testis, it must be determined whether it is a burned-out testicular germ cell tumor. The burned-out mechanisms may be related to the microenvironment of tumor immune-mediated and local ischemic injury.

Level of serum FABP1 and its relationship with Helicobacter pylori infection in patients with gastric cancer / 国际肿瘤学杂志

Objective:To investigate the serum level of fatty acid binding protein 1 (FABP1) and its relationship with Helicobacter pylori (Hp) infection in patients with gastric cancer. Methods:Forty gastric cancer patients (gastric cancer group) who were hospitalized in Affiliated Hospital of Qinghai University from August 2021 to August 2022 were selected as the research subjects, and 40 physical examination subjects during the same period were selected as the normal control group and 40 chronic atrophic gastritis patients were selected as the CAG group. The Hp infection were detected by 13C breath test, and the levels of serum FABP1 were detected by enzyme-linked immunosorbent assay. The Hp infection status, serum FABP1 levels, and the relationship between the two in the three groups of study subjects were analyzed. And the relationships between the level of serum FABP1 and the clinicopathological features of gastric cancer patients were analyzed. The diagnostic value of serum FABP1, CA19-9, CA72-4 and combined test of 3 indexes were evaluated by receiver operating characteristic (ROC) curve. Results:The Hp infection rates in the control group, CAG group, and gastric cancer group were 32.50% (13/40), 55.00% (22/40), and 60.00% (24/40), respectively, with a statistically significant difference ( χ2=6.87, P=0.032). Among them, the Hp infection rate in the control group was compared with that in the gastric cancer group, with a statistically significant difference ( P<0.05), and there were no statistically significant differences between the CAG group and the control group, the gastric cancer group (both P>0.05). The levels of serum FABP1 in the control group, CAG group, and gastric cancer group were [63.47 (37.53, 71.59) ] ng/ml, [65.26 (51.15, 79.67) ] ng/ml, and [72.84 (53.44, 82.25) ] ng/ml, respectively, with a statistically significant difference ( H=6.62, P=0.037). Among them, there was a statistically significant difference between the control group and the gastric cancer group ( H=19.93, P=0.031), while there were no statistically significant differences between the CAG group and the control group, the gastric cancer group ( H=1.50, P=0.133; H=1.09, P=0.277). Among all study subjects, the levels of serum FABP1 in the Hp positive group ( n=59) and Hp negative group ( n=61) were [77.05 (68.90, 83.54) ] ng/ml and [47.80 (37.76, 63.32) ] ng/ml, respectively, with a statistically significant difference ( Z=7.45, P<0.001). In the control group, the levels of FABP1 in the serum of Hp positive and Hp negative persons were [77.34 (68.84, 86.31) ] ng/ml and [39.79 (36.83, 63.75) ] ng/ml, respectively, with a statistically significant difference ( Z=4.46, P<0.001). In the CAG group, the levels of FABP1 in the serum of Hp positive and Hp negative patients were [76.51 (65.30, 80.97) ] ng/ml and [49.34 (39.92, 59.41) ] ng/ml, respectively, with a statistically significant difference ( Z=4.32, P<0.001). In the gastric cancer group, the levels of FABP1 in the serum of Hp positive and Hp negative patients were [77.15 (72.62, 84.13) ] ng/ml and [50.57 (44.54, 68.97) ] ng/ml, respectively, with a statistically significant difference ( Z=4.32, P<0.001). There were significant correlations between the serum level of FABP1 and smoking ( t=2.54, P=0.015), tumor diameter ( t=2.23, P=0.035), and lymph node metastasis ( t=3.22, P=0.003) in gastric cancer patients. And there were no significant correlations between FABP1 and gender ( t=0.98, P=0.333), age ( t=1.60, P=0.117), alcohol consumption ( Z=0.10, P=0.925), tumor site ( F=1.06, P=0.356), degree of differentiation ( t=0.61, P=0.545), the depth of infiltration ( t=1.41, P=0.166), distant metastasis ( Z=1.96, P=0.050) and TNM staging ( Z=0.66, P=0.508). ROC curve analysis showed that the area under the curve (AUC) of serum FABP1 for gastric cancer diagnosis was 0.62, 95% CI: 0.51-0.72, the sensitivity and specificity were 57.50% and 68.70%, respectively; the AUC of CA19-9 for gastric cancer diagnosis was 0.89, 95% CI: 0.83-0.95, the sensitivity and specificity were 77.50%, 86.30%, respectively; the AUC of CA72-4 for gastric cancer diagnosis was 0.88, 95% CI: 0.81-0.94, the sensitivity and specificity were 70.00%, 93.70%, respectively; the AUC of combined test of 3 indexes for gastric cancer diagnosis was 0.91, 95% CI: 0.82-0.97, the sensitivity and specificity were 67.50% and 95.00%, respectively. Conclusion:The Hp infection rate of gastric cancer patients is higher than that of the health examiners, the serum FABP1 level of gastric cancer patients is higher than that of the healthy health examiners, the serum FABP1 level of Hp positive persons is higher than that of Hp negative persons, and Hp infection and FABP1 level may have a common carcinogenic mechanism in the occurrence and development of gastric cancer.

Retrospectively analysis of the effect of low-dose aspirin on primary prevention of non-fatal myocardial infarction and cerebral infarction in patients with type 2 diabetes mellitus / 中国临床药理学与治疗学

AIM: To investigate the effect of low-dose aspirin on primary prevention of non-fatal myocardial and cerebral infarction in patients with type 2 diabetes mellitus. METHODS: From January 2015 to December 2016,40-90 years old patients with type 2 diabetes were treated in the Department of Endocrinology of Yijishan Hospital of Wannan Medical College for more than 2 times (the interval of hospitalization was more than 3 months) , we use the hospital's his system to search out-patient and in-patient files, patients were divided into aspirin group and non-aspirin group according to the use of low-dose aspirin within 1 year after the first visit, the basic data of the first visit were collected: name, sex, age, course of diabetes, systolic and diastolic blood pressure, patients were recorded for laboratory markers including fasting blood glucose, glycated hemoglobin, triglyceride, total cholesterol, Low-density lipoprotein, high-density lipoprotein, creatinine, and platelets, complications such as hypertension, coronary heart disease, atrial fibrillation, hyperlipidemia, diabetic nephropathy and arteriosclerosis were recorded. A Chi square test and a Cox proportional hazard model were used to compare baseline data and cerebrovascular disease after the first use of aspirin. RESULTS: Of the 4 176 patients, 2 137 were type 2 diabetes, 417 were eligible for admission, including 198 males, 219 females, 224 aspirin users and 193 non-users. There was no significant difference in the incidence of cerebral infarction between the aspirin group and the non-aspirin group (χ2=0.820, P=0.365). The incidence of non-fatal myocardial infarction was lower than that of the aspirin non-aspirin group (χ2=10.099, P=0.01) , the incidence of massive hemorrhage was significantly higher than that of aspirin-free group χ2=5.425, P=0.020) . In a subgroup analysis of aspirin use, patients younger than 60 years of age had a lower incidence of ischemic stroke (cerebral infarction) and a risk ratio of 0.428 (95%CI: 0.255-0.719, P=0.001) compared with patients older than 60 years of age, the incidence of cerebral infarction was higher in female patients with a risk ratio of 1.574 (95%CI: 1.018-2.434, P=0.041). CONCLUSION: In this study of patients with type 2 diabetes, low-dose aspirin reduced the incidence of nonfatal myocardial infarction but had no significant effect on the incidence of nonfatal ischemic stroke, and significantly increase the incidence of major bleeding events, we should reconsider the use of low-dose aspirin as a potential benefit of nonfatal cerebral infarction in patients with type 2 diabetes.

Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Evaluation of Qi-deficiency Model Based on Urine Non-targeted Metabonomics / 中国实验方剂学杂志

ObjectiveTo evaluate the success of Qi-deficiency model of Balb/C-nu mice established by swimming exhaustion test from the view of biomarkers and metabolic pathways by metabonomics. MethodBalb/C-nu mice were randomly divided into the normal group and Qi-deficiency group， Qi-deficiency model was established by swimming with 5% body weight metal fixed at the tail for 15 consecutive days until exhaustion （nose tip immersion time>5 s）. The urine metabonomics was analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS）， and the mobile phase was acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-1 min， 5%-8%A； 1-4 min， 8%-8.5%A； 4-5 min， 8.5%-12%A； 5-10 min， 12%-40%A； 10-12 min， 40%-100%A； 12-15 min， 100%A）， the flow rate was 0.3 mL·min-1， the injection volume was 10 μL， electrospray ionization （ESI） in positive and negative ion modes was used in MS analysis， the MS data were acquired in full-scan mode from m/z 50-1 000. Principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， human metabolome database （HMDB）， high collision energy ion fragments collected by MSE and tandem MS （MS/MS） ion information were used to identify potential biomarkers. Kyoto Encyclopedia of Genes and Genomes （KEGG） database and MetaboAnalyst 5.0 were used to analyze the corresponding metabolic pathways and pathway enrichment of biomarkers. ResultEndogenous substances in urine of mice in normal group and Qi-deficiency group were obviously separated， and there were 24 biomarkers with significant difference. The metabolic pathways involved in these biomarkers were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism， steroid hormone biosynthesis and tryptophan metabolism. Among them， the metabolic pathways related to energy were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism and steroid hormone biosynthesis. ConclusionThrough the investigation of urine metabonomics， combined with the physical signs， the Qi-deficiency model established by swimming exhaustion test in Balb/C-nu mice is successfully evaluated， and it is also verified that there is a close correlation between Qi-deficiency and energy metabolism.

Evaluation of Qi-deficiency Model Based on Urine Non-targeted Metabonomics / 中国实验方剂学杂志

ObjectiveTo evaluate the success of Qi-deficiency model of Balb/C-nu mice established by swimming exhaustion test from the view of biomarkers and metabolic pathways by metabonomics. MethodBalb/C-nu mice were randomly divided into the normal group and Qi-deficiency group， Qi-deficiency model was established by swimming with 5% body weight metal fixed at the tail for 15 consecutive days until exhaustion （nose tip immersion time>5 s）. The urine metabonomics was analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS）， and the mobile phase was acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-1 min， 5%-8%A； 1-4 min， 8%-8.5%A； 4-5 min， 8.5%-12%A； 5-10 min， 12%-40%A； 10-12 min， 40%-100%A； 12-15 min， 100%A）， the flow rate was 0.3 mL·min-1， the injection volume was 10 μL， electrospray ionization （ESI） in positive and negative ion modes was used in MS analysis， the MS data were acquired in full-scan mode from m/z 50-1 000. Principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， human metabolome database （HMDB）， high collision energy ion fragments collected by MSE and tandem MS （MS/MS） ion information were used to identify potential biomarkers. Kyoto Encyclopedia of Genes and Genomes （KEGG） database and MetaboAnalyst 5.0 were used to analyze the corresponding metabolic pathways and pathway enrichment of biomarkers. ResultEndogenous substances in urine of mice in normal group and Qi-deficiency group were obviously separated， and there were 24 biomarkers with significant difference. The metabolic pathways involved in these biomarkers were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism， steroid hormone biosynthesis and tryptophan metabolism. Among them， the metabolic pathways related to energy were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism and steroid hormone biosynthesis. ConclusionThrough the investigation of urine metabonomics， combined with the physical signs， the Qi-deficiency model established by swimming exhaustion test in Balb/C-nu mice is successfully evaluated， and it is also verified that there is a close correlation between Qi-deficiency and energy metabolism.

Immunomodulatory Mechanism of Kangxian Yixin Prescriptions on Autoimmune Injury Mice Based on Th17/Treg Cell Balance / 中国实验方剂学杂志

ObjectiveTo investigate the immunomodulatory mechanism of Kangxian Yixin prescription （KYP） on autoimmune injury mice and its relationship with the T helper 17 （Th17）/regulatory T cell （Treg） balance. MethodSixty healthy 8-week-old male BALBc mice were randomly divided into a normal group and an experimental group at a ratio of 1∶5. On the 0th， 7th， and 28th days， 0.2 mL of porcine cardiac myosin emulsion （containing 0.1 mg of porcine cardiac myosin） was subcutaneously injected into the groin， armpit， and back of the mice in the experimental group to induce an animal model of myocardial immune injury. Mice with myocardial immune injury were randomly divided into a model group （Model）， a KYP group （20.4 g·kg-1·d-1， ig）， and a valsartan group （12 mg·kg-1·d-1， ig）. Mice in the control group and the model group received the same amount of normal saline by gavage. After four weeks of intervention， the heart tissues were collected. Hematoxylin-eosin （HE） staining and Masson staining were used to detect pathological damage in heart tissues. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of type B-type natriuretic peptide （BNP）， anti-cardiac antibody， interleukin-17 （IL-17）， and interleukin-10 （IL-10） in the serum of mice， and the expression levels of Th17 cells and Tregs in the spleen were detected by flow cytometry. The protein expression of B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X （Bax） in heart tissues was detected by Western blot， and the mRNA expression of retinoid-related orphan receptor gamma t （RORγt） and forkhead box P3 （FoxP3） in the spleen was detected by quantitative real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the control group， the model group showed worsened pathological damage in heart tissues， elevated serum levels of BNP， anti-myocardial antibody， and IL-17， decreased serum expression of IL-10 （P<0.05）， increased expression of Th17 cells and reduced expression of Tregs in spleen tissues （P<0.05）， increased protein expression of Bax， diminished Bcl-2 protein expression， elevated Bax/Bcl-2 ratio， up-regulated mRNA expression of RORγt， dwindled mRNA expression of FoxP3， and elevated ratio of RORγt/FoxP3 （P<0.05）. Compared with the model group， the KYP group and the valsartan group displayed relieved pathological damage in heart tissues， decreased serum expression of BNP， anti-myocardial antibody， and IL-17， increased serum expression of IL-10 （P<0.05）， reduced expression of Th17 cells and increased Tregs in spleen tissues （P<0.05）， dwindled protein expression of Bax and elevated protein expression of Bcl-2 in heart tissues （P<0.05）， diminished Bax/Bcl-2 ratio， reduced mRNA expression of RORγt， up-regulated FoxP3， and down-regulated ratio of RORγt/FoxP3 （P<0.05）. ConclusionKYP may improve myocardial immune damage by regulating the Th17/Treg cell balance.

Clinical investigation and ret proto / 西安交通大学学报(医学版)

【Objective】 To investigate the clinical features and gene analysis of one pedigree with multiple endocrine neoplasia type 2A （MEN2A） so as to clarify the diagnosis and classification of the disease， guide treatment and prevention， and improve prognosis. 【Methods】 The clinical data of a 36-member MEN2A family， including 6 probands， with medullary thyroid carcinoma， were investigated， and the peripheral blood genomic DNA of 28 family members （blood sample of one proband was not collected） was extracted. PCR amplification was performed on exons 8， 10， 11， 13， 14， 15 and 16 of the RET gene， and the products were directly sequenced. 【Results】 Review of the medical history showed that two probands with medullary thyroid carcinoma were accompanied with hyperparathyroidism， and one family member had pheochromocytoma. The RET gene mutation test confirmed that 13 family members， consisting of 5 probands and 8 family members， had the RET proto-oncogene exon 10 missense mutation. The heterozygous missense had mutation c.1852T>A， leading to the conversion of cysteine （TGC） at position 618 to serine （AGC） （Cys618Ser）. All subjects carrying RET gene Cys618Ser mutation had abnormal thyroid ultrasound change， accompanied with elevated calcitonin levels. Subjects carrying wild type of RET gene had normal calcitonin levels. The family was finally diagnosed with MEN2A by RET gene detection. 【Conclusion】 RET gene detection plays key role in the diagnosis and treatment of patients with MEN2A family and has guiding value in the follow-up and prognosis of asymptomatic carriers. There is a positive correlation between calcitonin level and the RET protooncogene mutation Cys618Ser. Patients suspected of MEN2A should be screened in time.

Adherence to Cancer Prevention Guidelines and Endometrial Cancer Risk: Evidence from a Systematic Review and Dose-Response Meta-analysis of Prospective Studies / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The evidence of adherence to cancer prevention guidelines and endometrial cancer (EC) risk has been limited and controversial. This study summarizes and quantifies the relationship between adherence to cancer prevention guidelines and EC risk. @*Materials and Methods@#The online databases PubMed, Web of Science, and EMBASE were searched for relevant publications up to June 2, 2020. This study had been registered at PROSPERO. The registration number is CRD42020149966. Study quality evaluation was performed based on the Newcastle-Ottawa Scale. The I2 statistic was used to estimate heterogeneity among studies. Egger’s and Begg’s tests assessed potential publication bias. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between adherence to cancer prevention guidelines score was assigned to participants by summarizing individual scores for each lifestyle-related factor. The scores ranged from least healthy (0) to most healthy (20) and the EC risk was calculated using a randomeffects model. @*Results@#Five prospective studies (four cohort studies and one case‑cohort study) consisted of 4,470 EC cases, where 597,047 participants were included. Four studies had a low bias risk and one study had a high bias risk. Summary EC HR for the highest vs. lowest score of adherence to cancer prevention guidelines was 0.54 (95% CI, 0.40 to 0.73) and had a high heterogeneity (I2=86.1%). For the dose-response analysis, an increment of 1 significantly reduced the risk of EC by 6%. No significant publication bias was detected. @*Conclusion@#This study suggested that adherence to cancer prevention guidelines was negatively related to EC risk.

Expression of SOX4 gene and its biological effects in endometrial carcinoma / 解剖学报

Objective To investigate the expression of sex determining region Y box protein 4(SOX4) gene and its biological effects in endometrial carcinoma. Methods 156 cases of endometrial carcinoma tissues, adjacent tissues of endometrial carcinoma and 156 cases of endometrial atypical hyperplasia were collected; Immunohistochemistry was used to detect the expression of SOX4 in endometrial cancer, endometrial dysplasia and normal endometrial tissue, and to analyze the relationship between SOX4 and the clinical characteristics of patients with endometrial cancer. After establishing the SOX4 overexpression/silencing Ishikawa cell strain using the lentivirus transfection technique, MTT, flow cytometry and Transwell chamber method were used to detect the cell proliferation, apoptosis, migration and invasion ability, and Western blotting method was used to detect SOX4, β-catenin and E-cadherin protein expression changes. Results The expression of SOX4 in endometrial cancer tissue was higher than that in normal endometrial tissue and endometrial atypical hyperplasia (P<0.05). SOX4 expression was correlated with invasion depth, International Federation of Obstetrics and Gynecoogy (FIGO) stage and lymph node metastasis (P<0.05). Compared with control group, SOX4 overexpressed Ishikawa cells have significantly increased proliferative ability, migration and invasion ability, significantly reduced apoptosis rate, significantly increased SOX4 and β-catenin protein expression, and significantly reduced E-cadherin protein expression (all P< 0.05). while the proliferation ability, migration and invasion ability of Ishikawa cells interfered by SOX4 were significantly reduced, the apoptosis rate was significantly increased, the expression of SOX4 and β-catenin protein was significantly reduced, and the expression of E-cadherin protein was significantly increased (all P<0.05). Conclusion S0X4 gene is highly expressed in endometrial cancer tissues, which may promote the development of endometrial cancer by activating Wnt/β-catenin signaling pathway.

Potential targets of Euodiae Fructus in treatment of insomnia based on network pharmacology / 中国中药杂志

The acupoint application of Euodiae Fructus at Yongquan(KI1) can significantly improve the sleep quality of patients with insomnia with berberine as the main effective component for the efficacy. Nineteen active compounds and 203 drug targets were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). After comparison with GeneCards and Online Mendelian Inheritance in Man(OMIM), 24 common genes of diseases and drugs were obtained. STRING 11.0 was used to construct a protein-protein interaction(PPI) network of the overlapping genes, and Matthews correlation coefficient(MCC) was employed to screen the core genes, which were then subjected to enrichment analysis with gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG). The results revealed that the main compounds of Euodiae Fructus, such as berberine and rutaecarpine, participated in the biological processes(such as neurotransmitter receptor activity) by regulating C-reactive protein(CRP), estrogen receptor 1(ESR1), 5-hydroxytryptamine(5-HT) receptor, and interleukin-6(IL-6) to exert sedative, anxiolytic, and antidepressant effects. Sixty 4-week-old SPF mice were randomly divided into a control group, a model group, a positive drug(diazepam tablets) group, and low-, medium-, and high-dose berberine groups. Medication with corresponding drugs was performed for one week. The results demonstrated that berberine was potent in reducing the activities and standing times of mice, down-regulating the levels of CRP and IL-6 mRNA in the hypothalamus, and up-regulating the expression of 5-HT(P<0.01); however, no significant effect on ESR1 was observed. The network of Euodiae Fructus in treating insomnia was constructed by network pharmacology and verified by tests. The findings indicated that the therapeutic efficacy of Euodiae Fructus in treating insomnia was achieved by participating in multiple biological processes, such as neurotransmitter receptor activity, which provided a scientific basis for its clinical application.

Clinicopathological features and survival analysis of gastric cancer patients with neuroendocrine differentiation after radical resection / 中华胃肠外科杂志

Objective: To compare the clinicopathological characteristics and the prognosis of gastric adenocarcinoma patients with and without neuroendocrine differentiation (NED) after radical gastrectomy plus D2 lymph node dissection. Methods: A retrospective cohort study was performed. The inclusion criteria were as follows: (1) patients who underwent radical resection of gastric cancer plus D2 lymph node dissection and were confirmed as gastric adenocarcinoma by postoperative pathology and received immunohistochemical examination of neuroendocrine markers Syn and/or CgA; (2) patients aged 20 to 75 years with normal organ function; (3) patients who did not receive neoadjuvant chemotherapy or radiotherapy before operation; (4) patients with postoperative pathological stage I to III according to the 8th edition of tumor staging system of American Joint Committee on Cancer (AJCC); and (5) patients who completed adjuvant chemotherapy according to the postoperative pathological stage. Those who had other malignant tumors in the past 5 years and who could not be followed up according to the required rules were excluded. According to the above criteria, the clinicopathological characteristics of gastric cancer patients who underwent radical resection plus D2 lymph node dissection in Zhongshan Hospital of Fudan University from January 2010 to June 2017 were collected and compared. All patients were followed up till June 2020. The disease-free survival (DFS) and overall survival (OS) between the patients with and without NED were compared, and the effect of NED on the prognosis was corrected by Cox proportional hazards model. The propensity score matching method was used for sensitivity analysis. Results: A total of 539 patients were enrolled in this study, including 35 with NED and 504 without NED. Compared with the patients without NED, the patients with NED were older [(65.0±7.5) years vs. (54.5±11.3) years, t=-7.681, P<0.001], had higher proportion of undergoing proximal gastrectomy [22.9% (8/35) vs. 7.6% (36/504), χ(2)=10.335, P=0.006], higher proportion of intestinal-type based on Lauren classification [77.1% (27/35) vs. 42.5% (214/504), χ(2)=14.553, P<0.001], and higher proportion of pathologic stage III [65.7% (23/35) vs. 27.6% (139/504), χ(2)=25.653, P<0.001]. The 3-year DFS of patients with NED and those without NED was 48.9% (95% CI: 33.8%-70.8%) and 37.4% (95% CI: 32.9%-42.5%) respectively, and no significant difference was found (P=0.44). The 3-year OS was 56.1% (95% CI: 39.9%-79.1%) and 64.3% (95% CI: 59.3%-69.7%) respectively, and no significant difference was found as well (P=0.32). Univariate and multivariate analyses showed that NED was not an independent risk factor for DFS and OS (all P>0.05). Sensitivity analysis showed that there was no significant difference in DFS and OS between the two groups after propensity score matching. Conclusion: Compared with patients without NED, patients with NED were older at onset, had a higher proportion of proximal gastrectomy, intestinal-type, and later diagnostic stage, but the survival prognosis had no significant difference with that of patients without NED.

A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse / 中华医学杂志(英文版)

BACKGROUND@#It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011.@*METHODS@#A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided).@*RESULTS@#The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107).@*CONCLUSIONS@#The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly.@*TRIAL REGISTRATION NUMBER@#NCT03620565, https://register.clinicaltrials.gov.