Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity/epidemiology* ; Overweight/epidemiology* ; Puberty ; Puberty, Precocious ; Sexual Development

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

BACKGROUND: Hemorrhoids are one of the most common conditions that lead to surgery, and until now surgical hemorrhoidectomy has been the major effective treatment. Post-operative pain from hemorrhoidectomy has been experienced by thousands of patients and remains a major inconvenience of the operation. OBJECTIVE: This study evaluates the clinical efficacy of the pestle needle therapy, an acupoint stimulation method, for relief of post-hemorrhoidectomy pain. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This was a single-center, patient-assessor-blinded and randomized controlled trial with 154 patients receiving Milligan hemorrhoidectomy surgery. Eligible patients were randomly assigned to either a treatment group or a control group at a ratio of 1:1. The treatment group received the pestle needle therapy, with manual stimulation at Yaoshu (DU2), Mingmen (DU4), Changqiang (DU1), Chengshan (BL57), Erbai (EX-UE2) and the perianal points (1, 3, 5, 7, 9, and 11o'clock around the lesion); while the control group received a sham treatment with very light pressure. Three sessions of treatment were performed at 30 min, 4 h and 12 h after the surgery, and each lasted for 15 min. MAIN OUTCOME MEASURES: The primary outcome was post-operative pain measured with the visual analogue scale (VAS) at 12 h after surgery. The secondary outcomes included the VAS scores measured at 0.5, 2, 4, 6, 8, 24 and 48 h after surgery, the analgesic dose, the time and the VAS score of the patients' first defecation after surgery, as well as the Hamilton Rating Scale for Anxiety (HAMA) evaluated before discharge. RESULTS: The mean pain score of the treatment group was significantly lower than that of the control group (3.10 ± 1.27 vs 4.82 ± 1.29; P < 0.001) at 12 h after surgery. Compared with the control group, patients in the treatment group needed a smaller dose of analgesic within the first 24 hours after surgery (P = 0.002); and their HAMA scores before discharge were lower (4.07 ± 2.40 vs 5.10 ± 2.45, P = 0.009). Compared to the treatment group, patients in the control group had a greater time to the first defecation after surgery ([52.34 ± 15.72] h vs [27.08 ± 13.68] h; P < 0.001), but there was no difference in their VAS scores at the first defecation (P = 0.092). CONCLUSION The pestle needle therapy was effective for relieving pain, reducing anxiety and improving bowel function after hemorrhoidectomy, and it is worthy of clinical application.

This study was designed to investigate the effect of dihydromyricetin (DHM) on inducing apoptosis of ovarian cancer cells A2780 through endoplasmic reticulum stress (ERS) pathway and the mechanisms involved in vitro and in vivo. A2780 cells were treated with different concentrations of DHM, and the protein expression levels of glucose-regulated protein 78 (GRP78) which is related to ERS increased, apoptotic proteins C/EBP-homologous protein (CHOP), and cysteinyl aspartate specific proteinase-12 (caspase-12) elevated. After pretreatment with ERS inhibitor, 4-phenyl butyric acid (4-PBA), following the intervention with DHM, the A2780 cell viability decreased and apoptotic rate increased. All animal welfare and experimental procedures were approved by the Animal Ethics Committee of Chongqing Medical University. Intraperitoneal injection of DHM suspension into nude mice with ovarian cancer could significantly inhibit the growth of transplanted tumor in vivo, increase the protein expression levels of GRP78, CHOP, and caspase-3. Moreover, swollen and broken endoplasmic reticulum could be observed in tumor tissues, suggesting that DHM intervention induces apoptosis mediated by ERS. The results indicated that DHM could induce apoptosis of ovarian cancer cells and inhibit the growth of transplanted tumors in nude mice, which might be related to the activation of ERS pathway.

Objective To assess the schistosomiasis transmission risk in Nanjing County, so as to provide the scientific evidence for the development of the schistosomiasis control strategy and consolidation of the control achievements. Methods On May 2019, the Deqiu Village in Deqiu Town and Baiyun Village in Nanjing Town of Yunnan Province, where schistosomiasis were historically relatively highly endemic, were selected to assess the risk of transmission of schistosomiasis by means of a retrospective review of the data pertaining to the historical endemic situation and schistosomiasis control, combined with a cross-sectional survey of snail and wild feces distribution. Results During the period between 2017 and 2018, the mean sero-prevalence rates of Schistosoma japonicum infections were 6.76% (202/2 990) and 2.86% (142/4 971) in humans and 0 (0/1 160) and 10.65% (31/291) in bovines in Deqiu and Baiyun villages of Nanjian County, respectively; however, no egg-positives were identified; in addition, there were 21.06 hm² snail habitats found, but no S. japonicum infections were detected in snails. In 2019, there was 6.17 hm² snail habitats detected, with 2.17% (245/11 298) occurrence of frames with snails and a 0.06 snails/0.1 m² density of living snails; however, no positives for nucleic acid detection were seen in snails; among the 136 wild fecal samples captures from 23 settings, no S. japonicum infections were identified. Conclusions The risk of schistosomiasis transmission remains at a low level in Nanjian County; however, the factors affecting the transmission of schistosomiasis have not been completed eliminated. The integrated schistosomiasis control strategy with an emphasis on the control of the source of S. japonicum infections requires to be reinforced to consolidate the control achievements.

Objective: To explore the clinical manifestations, diagnosis, treatment and prognosis of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) . Methods: A retrospective study identified 91 patients diagnosed with ALCAPA at Shanghai Children′s Medical Center from March 2010 to August 2017. According to the left ventricular ejection fraction (LVEF) at the time of consultation, patients were divided into the cardiac insufficiency group (n=54) and the normal cardiac function group (n=37). Clinical features (age of onset, clinical performance, etc) and auxiliary examinations (electrocardiogram, echocardiography, etc) between the two groups were compared using a t-test and a Chi-square test. Prognostic factors were analyzed by an ordered logistic regression and a Pearson correlation coefficient. Results: (1) The age of diagnosis of patients in the cardiac insufficiency group who were usually misdiagnosed as cardiomyopathy was (10.0±2.6) months (20/54) , whereas the age of diagnosis of patients in the normal cardiac function group who were usually misdiagnosed as valvular diseases was (40.0±7.8) months (4/37). According to the pathophysiological mechanism, forty of the 54 (74%) patients in the cardiac insufficiency group were infantile type, and 78% patients (29/37) in the normal cardiac function group were adult type. (2) Preoperative electrocardiogram showed the deep Q wave in lead I occurred more frequently in the cardiac insufficiency group than in the normal cardiac function group (28/54 vs. 11/37, χ²=4.388, P=0.036). (3) Twenty patients died in the cardiac insufficiency group including 12 patients who died from postoperative cardiac pump failure and 8 children who did not undergo surgery due to poor prognosis and died from other reasons. There was no death in the normal cardiac function group. (4) Preoperative LVEF was the unique risk factor affecting prognosis (F=16.872, P=0.005). The preoperative LVEF was significantly lower than the postoperative LVEF ((37±11)% vs. (45±14)%, t=3.614, P=0.001) in the cardiac insufficiency group. During the follow-up period, 6 patients in the cardiac insufficiency group still presented with postoperative cardiac dysfunction, and the patients in the normal cardiac function group still had normal cardiac function. Conclusions Preoperative LVEF was the unique risk factor affecting prognosis of ALCAPA. Patients with infantile type ALCAPA and preoperative cardiac insufficiency should receive long-term follow-up treatment.

Objective To explore the clinical manifestations, diagnosis, treatment and prognosis of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). Methods A retrospective study identified 91 patients diagnosed with ALCAPA at Shanghai Children′s Medical Center from March 2010 to August 2017. According to the left ventricular ejection fraction (LVEF) at the time of consultation, patients were divided into the cardiac insufficiency group (n=54) and the normal cardiac function group (n=37). Clinical features (age of onset, clinical performance, etc) and auxiliary examinations (electrocardiogram, echocardiography, etc) between the two groups were compared using a t‐test and a Chi‐square test. Prognostic factors were analyzed by an ordered logistic regression and a Pearson correlation coefficient. Results (1) The age of diagnosis of patients in the cardiac insufficiency group who were usually misdiagnosed as cardiomyopathy was (10.0±2.6) months (20/54), whereas the age of diagnosis of patients in the normal cardiac function group who were usually misdiagnosed as valvular diseases was (40.0 ± 7.8) months (4/37). According to the pathophysiological mechanism, forty of the 54 (74%) patients in the cardiac insufficiency group were infantile type, and 78% patients (29/37) in the normal cardiac function group were adult type. (2) Preoperative electrocardiogram showed the deep Q wave in lead I occurred more frequently in the cardiac insufficiency group than in the normal cardiac function group (28/54 vs. 11/37, χ2=4.388, P=0.036). (3) Twenty patients died in the cardiac insufficiency group including 12 patients who died from postoperative cardiac pump failure and 8 children who did not undergo surgery due to poor prognosis and died from other reasons. There was no death in the normal cardiac function group. (4) Preoperative LVEF was the unique risk factor affecting prognosis (F=16.872, P=0.005). The preoperative LVEF was significantly lower than the postoperative LVEF ((37±11)% vs. (45±14)%, t=3.614, P=0.001) in the cardiac insufficiency group. During the follow‐up period, 6 patients in the cardiac insufficiency group still presented with postoperative cardiac dysfunction, and the patients in the normal cardiac function group still had normal cardiac function. Conclusions Preoperative LVEF was the unique risk factor affecting prognosis of ALCAPA. Patients with infantile type ALCAPA and preoperative cardiac insufficiency should receive long‐term follow‐up treatment.

This study was designed to investigate the inhibitory effects of Jiawei Foshou San (JWFSS) capsule in vitro on five major human liver microsomes CYP1A2, CYP2C9, CYP2D6, CYP2E1, CYP3A4, as well as on rat liver microsomes CYP1A2, CYP2C9, CYP2D2, CYP2E1, CYP3A1/2. The test groups included a negative control group, an inhibitor positive control group, an ferulic acid (FA) group, a ligustrazine (LZ) group, a tetrahydropalmatine (THP) group, and an JWFSS capsule group. After incubating the liver microsomes with a cocktail of probe drugs, the metabolites were quantitated with LC-MS/MS, and IC 50 values were calculated to assess the inhibitory effect of JWFSS capsule and its components on five rat/human CYP450 enzymes. All of the IC₅₀ values for the FA and the LZ for the five CYPs could not be determined. The IC₅₀ of the THP for rat CYP3A1/2 and for human CYP2D6 was 7.46 and 9.24 μmol·L^-1, respectively. The IC₅₀ of the JWFSS capsule for rat CYP2D2, CYP2E1 and CYP3A1/2 was 241.3, 369.8 and 293.0 mg ·L^-1, for human CYP2D6, CYP2E1 and CYP3A4 was 123.9, 189.9 and 171.3 mg·L^-1 respectively. The results indicated there were little probability that FA and LZ inhibited the activity of rat and human liver five CYPs; THP was identified as moderate-intensity inhibitor of rat liver CYP3A1/2 and human liver CYP2D6; JWFSS capsule might have a inhibitory effect on the activity of rat and human liver CYP2D, CYP2E1 and CYP3A in vitro, showing that there was a strengthened efficacy and a prolonged effective time for drugs metabolized by CYP2D, CYP2E1, CYP3A and combined with JWFSS capsule.

To investigate the effect of Jiawei Foshou San and its various combined administration on hepatic P450 enzyme activity and hepatocyte morphology in rats. Rats were orally administered with drugs for four weeks and then sacrificed to prepare liver microsomes. The liver microsomes were incubated with the cocktail method; The metabolites were determined with the rapid liquid chromatography with tandem mass spectrometry (LC-MS/MS) to investigate the hepatocyte P450 enzyme activity. In addition, the hepatic pathological changes were observed by using the hematoxylin and eosin (HE) staining. Compared with the control group, the enzyme activity of CYP1A2 and CYP3A4 in the Jiawei Foshou san group showed a significant rise (P < 0.05); the enzyme activity of CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 in the ferulic acid + ligustrazine group and the ligustrazine + tetrahydropalmatine group showed a significant rise (P < 0.05) ; the enzyme activity of CYP1A2, CYP2D6 and CYP2E1 in the ligustrazine group showed a significant rise (P < 0.05); the enzyme activity of CYP3A4 in the ferulic acid group showed a significant reduction (P < 0.05). After the administration with various drugs, the hepatocyte morphologies in the ferulic acid group and the ligustrazine group were normal. The pathological changes were observed in the tetrahydropalmatine group, such as unclear boundary of hepatic lobules, disordered hepatic cell arrangement, blurred edge, anisokaryosis and infiltration of inflammatory cells. The ferulic acid + tetrahydropalmatine group, the ligustrazine + tetrahydropalmatine group and the Jiawei Foshou San group also showed inflammatory infiltration, but with less pathological changes, particularly the Jiawei Foshou San group. The study result shows that Jiawei Foshou San can induce the enzyme activity of CYP1A2 and CYP3A4, and ligustrazine may be the effective substance for inducing CYP1A2. Its combination with ferulic acid and ligustrazine can significantly reduce the liver toxicity of tetrahydropalmatine.
Animals ; Cytochrome P-450 Enzyme System ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Hepatocytes ; drug effects ; enzymology ; Microsomes, Liver ; drug effects ; enzymology ; Rats ; Rats, Sprague-Dawley

The release behavior of single pellet was investigated by LC/MS/MS method with tamsulosin hydrochloride (TSH) as the model drug of the research and then the pellets were divided into four groups according to the drug loading. Comparison of dissolution profiles of each group and capsule were performed using f1 and f2 factor methods to study the difference and similarity. The release profiles of single pellet, each group and capsule were analyzed using principle component analysis (PCA). The particle system was built through Matlab to get the target release profile. The result of this research demonstrated the release behavior of single pellet correlated well with the drug loading. While the dissolution profile of capsule as a reference, the similarity factor of dissolution profiles of the lower drug loading groups were 62.2, 67.1, 53.9, respectively and, 43.3 for highest drug loading group. The particle systems with different pellet distribution and same release profiles were built through release behavior of single pellet. It is of significance to investigate the release behavior of single pellets for studying the release regularity of multiple-unit drug delivery system.
Capsules ; Chemistry, Pharmaceutical ; Chromatography, Liquid ; Delayed-Action Preparations ; Drug Delivery Systems ; Drug Liberation ; Principal Component Analysis ; Sulfonamides ; administration & dosage ; chemistry ; Tandem Mass Spectrometry ; Technology, Pharmaceutical