OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

OBJECTIVE: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. METHODS: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC_0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored. RESULTS: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC_0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000). CONCLUSION SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).
Alkaloids ; Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy* ; Double-Blind Method ; Glycated Hemoglobin A ; Humans ; Hypoglycemic Agents/therapeutic use* ; Morus ; Tablets/therapeutic use* ; Treatment Outcome

Amyloidosis/diagnostic imaging* ; Biopsy ; Heart ; Humans

Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E₂ and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E₂ levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.
AMP-Activated Protein Kinases ; Animals ; Cyclin D2 ; Female ; Follicle Stimulating Hormone/therapeutic use* ; Humans ; Luteinizing Hormone/therapeutic use* ; Metformin/pharmacology* ; Mice ; Mice, Inbred C57BL ; Oogonial Stem Cells/metabolism* ; Ovarian Cysts/drug therapy* ; Ovarian Neoplasms ; Polycystic Ovary Syndrome/drug therapy* ; Proliferating Cell Nuclear Antigen/therapeutic use* ; TOR Serine-Threonine Kinases

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Objective: To compare the efficacy between laparoscopic and open proximal gastrectomy with double-tract reconstruction for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) 18 to 80 years old; (2) Siewert II and III AEG was confirmed by preoperative gastroscopy and biopsy, which could not be resected by endoscopy; patients undergoing radical proximal gastrectomy with double-tract reconstruction; (3) contrast-enhanced abdominal CT staging was cT1-2N0M0; (4) Eastern Cooperative Oncology Group (ECOG) physical status score <2 points, American Association of Anesthesiologists (ASA) grade 1 to 2; (5) patients agreed to perform proximal gastrectomy and signed an informed consent. Those who had undergone neoadjuvant radiochemotherapy, suffered from serious mental diseases and had incomplete data were excluded. According to the above criteria, clinical data of 84 consecutive patients with Siewert II and III AEG undergoing surgery at General Surgery Department of The Affiliated Tumor Hospital of Zhengzhou University from October 2010 to December 2018 were collected and analyzed. Of 84 patients, 61 underwent open proximal gastrectomy with double-tract reconstruction (OPG group), while 23 underwent laparoscopic proximal gastrectomy with double-tract reconstruction (LPG group). The perioperative complications and postoperative reflux esophagitis of two groups were compared. A P-value of <0.05 was considered to be statistically significant. Results: Among 84 cases, 74 were male and 10 were female. There were 43 cases of Siewert type II and 41 cases of Siewert type III. There were no significant differences in age, gender, body mass index, comorbidities, Siewert type, and tumor staging between the two groups (all P>0.05). As compared to the OPG group, the LPG group had longer operation duration [(223±21) minutes vs. (161±14) minutes, t=15.352, P<0.001], less intraoperative blood loss [195 (150, 215) ml vs. 208 (192, 230) ml, Z=2.143, P=0.032], and shorter time to flatus [(2.8±0.7) days vs. (3.3±0.9) days, t=2.477, P=0.015]. There were no significant differences in the number of harvested lymph nodes, time to the first meal and postoperative hospital stay between the two groups (all P>0.05). Postoperative complications developed in 2 cases (8.7%, 1 case each for anastomotic leakage and intestinal obstruction) in the LPG group and 5 cases (8.2%, 1 case each for anastomotic leakage, anastomotic bleeding, and anastomotic stenosis, 2 cases of incision infection) in the OPG group (χ(2)=5.603, P=0.231). The median follow-up was 41.2 (12.8-110.5) months. One patient (1.6%,1/61) had obvious reflux symptoms in the OPG group, compared with none in the LPG group (χ(2)=0.644, P=0.422). Esophagitis occurred in 1 case (4.8%, 1/21) in LPG group, compared with 4 patients (7.1%, 4/56) in the OPG group, without significant difference between the two groups (χ(2)=0.505, P=0.477). Conclusion: Laparoscopic proximal gastrectomy with double-tract reconstruction is safe and feasible without increasing the risk of postoperative complication and reflux esophagitis.
Adenocarcinoma/surgery* ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Esophagogastric Junction/surgery* ; Female ; Gastrectomy ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Treatment Outcome ; Young Adult

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

BACKGROUND: Metabolic syndrome (MetS) is relatively common worldwide and an important risk factor for cardiovascular diseases. It is closely linked to arterial stiffness of the carotid artery. However, the association of MetS with the safety of carotid revascularization has been rarely studied. The aim of this study was to observe the current status of MetS and its components in Chinese carotid revascularized patients, and investigate the impact on major adverse clinical events (MACEs) after carotid endarterectomy (CEA) or carotid artery stenting (CAS). METHODS: From January 2013 to December 2017, patients undergoing CEA or CAS in the Neurosurgery Department of Xuanwu Hospital were retrospectively recruited. The changes in prevalence of MetS and each component with time were investigated. The primary outcome was 30-day post-operative MACEs. Univariable and multivariable analyses were performed to identify the impact of MetS on CEA or CAS. RESULTS: A total of 2068 patients who underwent CEA (766 cases) or CAS (1302 cases) were included. The rate of MetS was 17.9%; the prevalence rate of MetS increased with time. The occurrence rate of MACEs in CEA was 3.4% (26 cases) and in CAS, 3.1% (40 cases). There was no statistical difference between the two groups (3.4% vs. 3.1%, P = 0.600). For CEA patients, univariate analysis showed that the MACE (+) group had increased diabetes history (53.8% vs. 30.9%, P = 0.014) and MetS (34.6% vs. 15.8%, P = 0.023). For CAS patients, univariate analysis showed that the MACE (+) group had increased coronary artery disease history (40.0% vs. 21.6%, P = 0.006) and internal carotid artery tortuosity (67.5%% vs. 37.6%, P < 0.001). Furthermore, the MACE (+) group had higher systolic blood pressure (143.38 ± 22.74 vs. 135.42 ± 17.17 mmHg, P = 0.004). Multivariable analysis showed that the influencing factors for MACEs in CEA included history of diabetes (odds ratio [OR] = 2.345; 95% confidence interval [CI] = 1.057-5.205; P = 0.036) and MetS (OR = 2.476; 95% CI = 1.065-5.757; P = 0.035). The influencing factors for MACEs in CAS included systolic blood pressure (OR = 1.023; 95% CI = 1.005-1.040; P = 0.010), coronary artery disease (OR = 2.382; 95% CI = 1.237-4.587; P = 0.009) and internal carotid artery tortuosity (OR = 3.221; 95% CI = 1.637-6.337; P = 0.001). CONCLUSIONS The prevalence rate of MetS increased with time in carotid revascularized patients. MetS is a risk for short-term MACEs after CEA, but not CAS.
Carotid Arteries/surgery* ; Carotid Stenosis/surgery* ; China/epidemiology* ; Endarterectomy, Carotid/adverse effects* ; Humans ; Metabolic Syndrome/epidemiology* ; Retrospective Studies ; Risk Factors ; Sample Size ; Stents/adverse effects* ; Stroke ; Time Factors ; Treatment Outcome

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome