Effects of butylphthalide combined with ozagrel sodium on National Institutes of Health Stroke Scale score, activities of daily living score, and coagulation function in patients with acute cerebral infarction / 中国基层医药

Objective:To investigate the effects of butylphthalide combined with ozagrel sodium on the National Institutes of Health Stroke Scale (NIHSS) score, activities of daily living (ADL) score, and coagulation function in patients with acute cerebral infarction.Methods:Ninety-four patients with acute cerebral infarction who were admitted to Gujiao Medical Group Central Hospital from January 2019 to November 2021 were included in this study. They were randomly assigned to undergo treatment with either ozagrel sodium (control group, n = 47) or butylphthalide combined with ozagrel sodium (observation group, n = 47) for 14 consecutive days. Before and after treatment, NIHSS score, ADL score, coagulation function (thrombin time, prothrombin time, D-dimer, activated partial thrombin time), bilateral middle cerebral artery blood flow status (mean blood flow velocity (Vm), resistance index, pulsatility index), brain tissue damage factor (brain natriuretic peptide, neuron-specific enolase, S100 β protein) and the incidence of adverse drug reactions were compared between the two groups. Results:Before treatment, there were no significant differences in NIHSS and ADL scores between the two groups (both P > 0.05). After treatment, the NIHSS score was significantly lower in the observation group than that in the control group [(8.70 ± 1.62) points vs. (9.45 ± 1.2) points, t = 2.51, P < 0.05]; the ADL score was significantly higher in the observation group than that in the control group [(65.15 ± 7.41) points vs. (61.20 ± 6.32) points, t = 2.78, P < 0.05]. Before treatment, there were no significant differences in thrombin time, prothrombin time, D-dimer, and activated partial thrombin time between the two groups (all P > 0.05). After treatment, thrombin time, prothrombin time, and activated partial thrombin time were significantly higher in the observation group than those in the control group ( t = 4.34, 3.00, 2.63, all P < 0.05). After treatment, D-dimer level in the observation group was significantly lower than that in the control group ( t = 3.39, P < 0.05). Before treatment, mean blood flow velocity, resistance index, and pulsatility index were similar between the two groups (all P > 0.05). After treatment, the mean blood flow velocity in the observation group was significantly higher than that in the control group ( t = 3.23, P < 0.05). The pulsatility index and resistance index were significantly lower in the observation group than those in the control group ( t = 2.14, 3.16, both P < 0.05). Before treatment, there were no significant differences in brain natriuretic peptide, neuron-specific enolase, and S100 β protein levels between the two groups (all P > 0.05). After treatment, brain natriuretic peptide, neuron-specific enolase, and S100 β protein levels in the observation group were significantly lower than those in the control group ( t = 3.09, 2.18, 3.33, all P < 0.05). There was no significant difference in incidence of adverse reactions between the observation and control groups [6.38% (3/47) vs. 2.13% (1/47), P > 0.05]. Conclusion:Butylphthalide combined with ozagrel sodium for the treatment of acute cerebral infarction can reduce neurological dysfunction and brain tissue injury, and improve coagulation function, hemodynamic state of the middle cerebral artery, and activities of daily life, without increasing adverse reactions.

Cholesterol paradox in the community-living old adults: is higher better? / 老年心脏病学杂志（英文版）

OBJECTIVE@#To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.@*METHODS@#A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators.@*RESULTS@#A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death.@*CONCLUSIONS@#In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Construction of TRAF6 ubiquitin site 331 mutant colorectal cancer cell stable line and its effect on biological behavior of colorectal cancer cells / 中华肿瘤杂志

Objective: To investigate the effect of ubiquitin mutation at position 331 of tumor necrosis factor receptor related factor 6 (TRAF6) on the biological characteristics of colorectal cancer cells and its mechanism. Methods: lentivirus wild type (pCDH-3×FLAG-TRAF6) and mutation (pCDH-3×FLAG-TRAF6-331mut) of TRAF6 gene expression plasmid with green fluorescent protein tag were used to infect colorectal cancer cells SW480 and HCT116, respectively. The infection was observed by fluorescence microscope, and the expressions of TRAF6 and TRAF6-331mut in cells was detected by western blot. Cell counting kit-8 (CCK-8) and plate cloning test were used to detect the proliferation ability of colorectal cancer cells in TRAF6 group and TRAF6-331mut group, cell scratch test to detect cell migration, Transwell chamber test to detect cell migration and invasion, immunoprecipitation to detect the ubiquitination of TRAF6 and TRAF6-331mut with ubiquitinof lysine binding sites K48 and K63. Western blot was used to detect the effects of TRAF6 and TRAF6-331mut over expression on the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinase mitogen-activated protein kinase (MAPK)/activating protein-1(AP-1) signal pathway. Results: The successful infection of colorectal cancer cells was observed under fluorescence microscope. Western blot detection showed that TRAF6 and TRAF6-331mut were successfully expressed in colorectal cancer cells. The results of CCK-8 assay showed that on the fourth day, the absorbance values of HCT116 and SW480 cells in TRAF6-331mut group were 1.89±0.39 and 1.88±0.24 respectively, which were lower than those in TRAF6 group (2.09±0.12 and 2.17±0.45, P=0.036 and P=0.011, respectively). The results of plate colony formation assay showed that the number of clones of HCT116 and SW480 cells in TRAF6-331mut group was 120±14 and 85±14 respectively, which was lower than those in TRAF6 group (190±21 and 125±13, P=0.001 and P=0.002, respectively). The results of cell scratch test showed that after 48 hours, the percentage of wound healing distance of HCT116 and SW480 cells in TRAF6-331mut group was (31±12)% and (33±14)%, respectively, which was lower than those in TRAF6 group [(43±13)% and (43±7)%, P=0.005 and 0.009, respectively]. The results of Transwell migration assay showed that the migration numbers of HCT116 and SW480 cells in TRAF6-331mut group were significantly lower than those in TRAF6 group (P<0.001 and P<0.002, respectively). The results of Transwell invasion assay showed that the number of membrane penetration of HCT116 and SW480 cells in TRAF6-331mut group was significantly lower than those in TRAF6 group (P=0.008 and P=0.009, respectively). The results of immunoprecipitation detection showed that the ubiquitin protein of K48 chain pulled by TRAF6-331mut was lower than that of wild type TRAF6 in 293T cells co-transfected with K48 (0.57±0.19), and the ubiquitin protein of K63 chain pulled down by TRAF6-331mut in 293T cells co-transfected with K63 was lower than that of wild type TRAF6 (0.89±0.08, P<0.001). Western blot assay showed that the protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-HCT116 cells were 0.63±0.08, 0.42±0.08 and 0.60±0.07 respectively, which were lower than those in TRAF6-HCT116 cells (P=0.002, P<0.001 and P<0.001, respectively). The expression level of AP-1 protein in TRAF6-HCT116 cells was 0.89±0.06, compared with that in TRAF6-HCT116 cells. The difference was not statistically significant (P>0.05). The protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-SW480 cells were 0.50±0.06, 0.51±0.04, 0.48±0.02, respectively, which were lower than those in TRAF6-SW480 cells (all P<0.001). There was no significant difference in AP-1 protein expression between TRAF6-331mut-SW480 cells and TRAF6-SW480 cells. Conclusion: The ubiquitin site mutation of TRAF6 gene at 331 may prevent the binding of TRAF6 and ubiquitin lysine sites K48 and K63, and then affect the expressions of proteins related to downstream NF-κB and MAPK/AP-1 signal pathways, and inhibit the proliferation, migration and invasion of colorectal cancer cells.

Effects of berberine on colon dermal cell apoptosis in mice with ulcerative colitis based on JAK/STAT signaling pathway / 中国药理学通报

Aim To analyze the effects of berberine on the apoptosis of colon epithelial cells and polymorpho-nuclear neutrophils ( PMNs) in mice with ulcerative colitis ( UC ) by regulating JAK/STAT signaling pathway. Methods The UC mouse models were established by dextran sulfate sodium ( DSS) method and were randomly divided into control group, UC group, low-dose, middle-dose and high-dose berberine groups and positive drug group ( mesalazine enteric-coated tablet group) . In addition, the mice were randomly di¬vided into UC group, high-dose berberine group, AG490 group, and high-dose berberine + AG490 group. Levels of serum tumor necrosis factor a (TNF-α) and interleukin 6 (IL-6) and colon epithelial cell apoptosis and PMN apoptosis were compared among the groups. Western blot was used to detect the expres¬sions of colon tissue apoptosis-related and JAK/STAT signaling pathway-related proteins. Results The lev¬els of serum TNF-α and IL-6, apoptosis rate of colon epithelial cell and protein expressions of Fas, FasL, Bax, caspase-3, p-JAK2/JAK2 and p-STAT3/STAT3 in each dose berberine group and positive drug group were significantly lower than those in UC group (P < 0.05), and the above indicators in berberine groups were reduced gradually (P <0.05) . The PMN apoptosis rate and Bcl-2 protein expression were significantly higher in each dose berberine group and positive drug group than those in UC group (P <0. 05) , and the two indicators increased gradually in berberine groups ( P < 0.05). AG490 could reverse the above effects of berberine ( P < 0. 05 ). Conclusions Berberine can inhibit the apoptosis of colon epithelial cell and promote the apoptosis of PMN in UC mice by regulating the JAK/STAT signaling pathway, and then play a role in the treatment of UC.

Impact of asthma action plan-based remote joint management model on asthma control in children / 中华儿科杂志

Objective: To compare the effects of the China Children's Asthma Action Plan (CCAAP)-based remote joint management model with traditional management model on the control of childhood asthma. Methods: A retrospective cohort study was conducted to analyze the general data and asthma control assessment data of 219 children with asthma who attended the respiratory department of Guangzhou Women's and Children's Medical Center from April 2021 to October 2021 and were followed up for 1 year or more. According to the follow-up management model, the CCAAP-based remote joint management model was used in the observation group and the traditional management model was used in the control group, and the propensity score matching method was applied to match the data of children in the two management models for comparison. Paired-samples t-test, Wilcoxon signed-rank test, McNemar χ2-test or χ2-test or nonparametric tests were used to compare the general data and asthma control assessment data between the two matched groups of children. Results: Among 219 children with asthma, 145 were male and 74 were female, aged at consultation (7.2±2.4) years. There were 147 cases in the observation group and 72 cases in the control group, and 27 cases in each of the observation and control groups were successfully matched. The number of asthma exacerbation aura, acute exacerbations, and emergency room visits or hospitalizations for asthma exacerbations were lower in the observation group than in the control group after pairing (1 (0, 2) vs. 3 (1, 5) times, 0 (0,0) vs. 0 (0, 1) times, 0 (0,0) vs. 1 (0, 1) times, Z=-3.42, -2.58, -3.17, all P<0.05). The use of peak flowmeters was higher in children aged 5 years and older in the observation group than in the control group after pairing (100% (22/22) vs. 13% (3/23), χ2=54.00,P<0.001). The ratio of actual to predicted 1st second expiratory volume of force after follow-up in the observation group after pairing was higher than that before follow-up in the observation group and after follow-up in the control group ((95±11)% vs. (85±10)%, (95±11)% vs. (88±11)%, t=-3.40, 2.25, all P<0.05). The rate of complete asthma control after follow-up was higher in both the observation and control groups after pairing than before follow-up for 12 months in both groups (93% (25/27) vs. 41% (11/27), 52% (14/27) vs. 41% (11/27), H=56.19, 45.37, both P<0.001), and the rate of complete control of asthma in children in the observation group was higher than that in the control group at 3 and 12 months of follow-up management (56% (15/27) vs. 25% (5/20), 93% (25/27) vs. 52% (14/27), χ2=47.00, 54.00, both P<0.001). The number of offline follow-up visits, inhaled hormone medication adherence scores, and caregiver's asthma perception questionnaire scores were higher in the observation group than in the control group after pairing (6 (4, 8) vs. 4 (2,5), (4.8±0.3) vs. (4.0±0.6) score, (19.3±2.6) vs. (15.2±2.7) score, Z=6.58, t=6.57, 5.61, all P<0.05), and the children in the observation group had lower school absences, caregiver absences, asthma attack visit costs, and caregiver PTSD scores than the control group (0 (0,0) vs.3 (0, 15) d, 0 (0,0) vs. 3 (0, 10) d, 1 100 (0, 3 700) vs. 5 000 (1 000, 10 000) yuan, 1.3 (1.1, 1.9) vs. 2.0 (1.2, 2.7) score, Z=-2.89, -2.30, 2.74, 2.73, all P<0.05). Conclusion: The CCAAP-based joint management model of asthma control is superior to the traditional management model in the following aspects: it can effectively improve asthma control, self-monitoring, and lung function in children; it can improve treatment adherence and caregivers' asthma awareness; and it can reduce the duration of absenteeism from school, the cost of asthma exacerbation visits, and caregiver's negative psychology.

Risk of Hepatitis B Virus (HBV) Reactivation in HBsAg-Negative, Anti-HBc-Negative Patients Receiving Rituximab for Autoimmune Diseases in HBV Endemic Areas

Background/Aims@# Rituximab is known to be associated with high hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation (HBVr) in rheumatic patients receiving rituximab is limited. To assess the HBVr rate in hepatitis B surface antigen (HBsAg)-negative patients receiving rituximab for autoimmune diseases in a large real-world cohort. @*Methods@# From March 2006 to December 2019, 900 patients with negative HBsAg receiving at least one cycle of rituximab for autoimmune diseases in a tertiary medical center in Taiwan were retrospectively reviewed. Clinical outcome and factors associated with HBVr were analyzed. @*Results@#After a median follow-up period of 3.3 years, 21 patients developed HBVr, among whom 17 patients were positive for hepatitis B core antibody (anti-HBc) and four were negative. Thirteen patients had clinical hepatitis flare, while eight patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, undetectable serum hepatitis B surface antibody level at rituximab initiation and a higher average rituximab dose were associated with a higher HBVr rate. There was no significant difference in the HBVr risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBVr (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). @*Conclusions@#In HBV endemic areas where occult HBV is prevalent, anti-HBc-negative patients, may still be at risk for HBVr after rituximab exposure. HBVr may still be considered in HBsAgnegative patients developing abnormal liver function after rituximab exposure, even in patients with negative anti-HBc.

18F-FDG PET/CT Prognostic Role in Diffuse Large B-cell Lymphoma Following Chemotherapy / 中山大学学报(医学科学版)

ObjectiveTo assess the prognostic value of 18F-FDG PET/CT parameters for predicting therapeutic response in diffuse large B-cell lymphoma （DLBCL）. MethodsWe retrospectively analyzed the clinical data and 18F-FDG PET/CT radiomics features of 81 DLBCL patients enrolled between June 2015 and October 2020. Multivariate logistic regression analysis was used to identify the predictive factors for therapeutic response of DLBCL， based on which a predictive model was developed accordingly. The performance of the model was evaluated by receiver operating characteristic （ROC） curves and calibration plots. ResultsDuring the two years after first chemotherapy， 23 patients （28.3%） developed relapse and 58 patients （71.7%） had progression-free survival （PFS）. The analysis for the predictive capability of the binary logistic regression model incorporating the PET/CT features revealed that the imaging features of 18F-FDG PET/CT after chemotherapy were independent prognostic factors for PFS. Among them， SUVTHR-mean2 was the most important factor for predicting therapeutic response in DLBCL patients after chemotherapy， with a cutoff value of 2.00 （AUC=0.81）. Conclusions18F-FDG PET/CT showed a valuable prognostic performance for PFS in DLBCL patients after chemotherapy， with the imaging feature after chemotherapy SUVTLR-mean2 being the optimal independent predictor. Our predictive model of imaging features might have an important prognostic value in assessing the risk of disease progression， guiding the treatment and follow-up protocol， improving therapeutic efficiency and cutting down the medical cost.

Two pairs of phloroglucinol enantiomers from Hypericum wightianum and their stereochemical structures / 中国中药杂志

The chemical constituents in the ethanol extract of Hypericum wightianum(Hypericaceae) were purified by column chromatography and identified via magnetic resonance imaging(NMR), high-resolution mass spectrum, and circular dichroism. A total of 22 compounds were identified, including eight polyprenylated phloroglucinols(1-8), three chromones(9-11), and three terpenoids(14-16) and so on. Among them, compounds 16 and 17 were first reported in the genus Hypericum, and compounds 1-11, 14, 15, and 19 were first isolated from H. wightianum. Compounds 1-4 were previously reported as two pairs of enantiomers. This study reported the chiral resolutions and absolute configurations of compounds 1-4 for the first time.

Management and prognosis of extremely preterm infants with gestational age ≤25+6 weeks / 中华儿科杂志

Objective: To investigate the outcomes including major complications and prognosis of extremely preterm infants with gestational age ≤25+6 weeks. Methods: The cross-sectional study enrolled 233 extremely preterm infants with gestational age ≤25+6 weeks who were admitted to the Department of Neonatology of Shenzhen Maternity and Child Healthcare Hospital from January 2015 to December 2021. The clinical data including perinatal factors, treatments, complications, and prognosis were extracted and analyzed. These extremely preterm infants were also grouped according to gestational age and year of admission to further analyze their survival rate, major complications, causes of death, and long-term outcomes. The comparisons between the groups were performed with Chi-square test and Kruskal-Wallis. Results: Among these 233 extremely preterm infants, 134 (57.5%) were males and 99 (42.5%) females. The gestational age was (24.6±0.9) weeks, the birth weight was 710.0 (605.0,784.5) g, and the overall survival rate was 61.8% (144/233). Among the surviving extremely preterm infants, the earliest gestational age was 22+2 weeks and the lowest birth weight was 390 g. There were 17.6% (41/233) of extremely preterm infants had treatment withdrawn and were discharged in line with the will of guardians. Among the rest 192 extremely preterm infants managed with aggressive treatments, 14 (7.3%) died in hospital and 34 (17.7%) had treatment withdrawn later due to severe complications. Of the 192 extremely preterm infants, 144 (75.0%) survived, and the survival rate increased year by year (χ2=26.28, P<0.001) while the mortality decreased year by year (χ2=14.09, P=0.027). Among the survivors, 20.8%(30/144) had no major complications, and the incidence of complications was also negatively related with the gestational age (χ2=7.24, P=0.044), and the length of invasive ventilation was negatively related to the gestational age (χ2=29.14, P<0.001). In the group of less than 23+6 weeks, all extremely preterm infants had one or more major complications. The follow-up were completed in 122 infants and revealed that delayed motor development, language retardation, and hearing and vision impairment accounted for 17.2% (21/122), 8.2% (10/122) and 17.2% (21/122), respectively. Conclusions: Extremely preterm infants with gestational age ≤25+6 weeks are difficult to treat, but the survival rate of infants undergoing aggressive treatments increases year by year. Although the prevalence of major complications is still high, most extremely preterm infants have acceptable prognosis during follow-up.

A medium-and long-term comparative observation on volumetric changes of cervical disc herniation after symmetrically or asymmetrically decompression and conservative treatment for cervical spondylotic myelopathy / 中华外科杂志

Objective: To compare the volumetric changes of cervical disc herniation (CDH) after cervical microendoscopic laminoplasty(CMEL),expansive open-door laminoplasty (EOLP) and conservative treatment. Methods: A retrospective study was conducted involving 101 patients with cervical spondylotic myelopathy(CSM),at the Department of Orthopaedics,the First Affiliated Hospital of Zhengzhou University from April 2012 to April 2021. The patients included 52 males and 49 females with an age of (54.7±11.8) years(range:25 to 86 years). Among them, 35 patients accepted CMEL treatment,33 patients accepted EOLP treatment,while 33 patients accepted conservative treatment. Volume data of CDH were measured by three-dimensional analysis of the initial and follow-up MRI images. The absorption rate and reprotrusion rate of CDH were calculated. The happening of resorption or reprotrusion was defined when the ratio was greater than 5%. The clinical outcomes and quality of life were evaluated by the Japanese Orthopaedic Association (JOA) score and the neck disability index (NDI).Quantitative data was analyzed by one-way ANOVA with post LSD-t test (multiple comparison) or Kruskal-Wallis test. Categorical data was analyzed by χ2test. Results: The follow-up time of the CMEL group,EOLP group and the conservative treatment group were (27.6±18.8)months,(21.6±6.9)months and(24.9±16.3)months respectively with no significant difference(P>0.05). Changes of CDH volume in patients:(1) There were 96 CDH of 35 patients in the CMEL group,among which 78 showed absorption. The absorption frequency was 81.3%(78/96) and the absorption rate was ranged 5.9% to 90.9%;9 CDH showed reprotrusion,the reprotrusion frequency was 9.4% (9/96) and the reprotrusion rate was 5.9% to 13.3%;(2) There were 94 CDH of 33 patients in the EOLP group,of which 45 showed absorption. The absorption prevalence was 47.9% (45/94) and the absorption rate was 5.0% to 26.7%;20 CDH showed reprotruded,with the reprotrusion frequency of 21.3% (20/94) and the reprotrusion rate was 5.8% to 28.3%;(3) There were 102 CDH in 33 patients of the conservative group. Among them, 5 showed absorption. The absorption frequency was 4.9% (5/102),and the absorption rate was 7.2% to 14.3%;58 CDH showed reprotruded with the re-protrusion ratio of 56.9% (58/102) and the re-protrusion rate was 5.4% to 174.1%. The absorption ratio and reprotrusion ratio of the CMEL group were statistically different from EOLP group or the conservative group (P<0.01).The absorption ratio and reprotrusion ratio of the EOLP group was different from conservative group (P<0.01). In terms of clinical outcomes, the excellent/good rate of the JOA score and NDI scores in the CMEL group were different from that of conservative group (P<0.01) but not from that of the EOLP group(P>0.05). Conclusions: CMEL is an effective method for the treatment of CSM,making CDH easier to resorption compared to the EOLP or conservative treatment,thus making a better decompression effect on the nerves. This study enlightened on a new strategy for the clinical treatment of CSM.

Relationship between body mass index and sexual development in Chinese children / 中华儿科杂志

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.

Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study / 中华血液学杂志

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study / 中华血液学杂志

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

Total Saponins of Panax notoginseng Activate Akt/mTOR Pathway and Exhibit Neuroprotection in vitro and in vivo against Ischemic Damage / 中国结合医学杂志

OBJECTIVE@#To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons.@*METHODS@#The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence. Middle cerebral artery occlusion (MCAO) was developed in rats as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological scoring, tail suspension test, 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl stainings. Western blot analysis, immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin (mTOR) signaling pathway.@*RESULTS@#MTT showed that TSPN (50, 25 and 12.5 µ g/mL) protected cortical neurons after OGD/R treatment (P<0.01 or P<0.05). Flow cytometry and live/dead cell assays indicated that 25 µ g/mL TSPN decreased neuronal apoptosis (P<0.05), and immunofluorescence showed that 25 µ g/mL TSPN restored the dendritic morphology of damaged neurons (P<0.05). Moreover, 12.5 µ g/mL TSPN downregulated the expression of Beclin-1, Cleaved-caspase 3 and LC3B-II/LC3B-I, and upregulated the levels of phosphorylated (p)-Akt and p-mTOR (P<0.01 or P<0.05). In the MCAO model, 50 µ g/mL TSPN improved defective neurological behavior and reduced infarct volume (P<0.05). Moreover, the expression of Beclin-1 and LC3B in cerebral ischemic penumbra was downregulated after 50 µ g/mL TSPN treatment, whereas the p-mTOR level was upregulated (P<0.05 or P<0.01).@*CONCLUSION@#TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss. TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage, which may be the mechanism that underlies the neuroprotective activity of TSPN.

Comparison of Application of MD-VF-Auto SEM Method and Plankton Gene Multiplex PCR System in the Diagnosis of Drowning / 法医学杂志

OBJECTIVES@#To compare the application effect of microwave digestion - vacuum filtration - automated scanning electron microscopy (MD-VF-Auto SEM) method and plankton gene multiplex PCR system in the diagnosis of drowning.@*METHODS@#Lung, liver and kidney tissue of 10 non-drowning cases and 50 drowning cases were prepared for further MD-VF-Auto SEM method analysis and plankton gene multiplex PCR system analysis. The positive detection rate of the two methods in each tissue was calculated.@*RESULTS@#The positive rate of the MD-VF-Auto SEM method detecting diatoms in drowning cases was 100%, and few diatoms were detected in the liver and kidney tissues of 6 non-drowning cases. By using the plankton gene multiplex PCR system, the diatom positive rate of drowning cases was 84%, and all the non-drowning cases were negative. There were significant differences in the positive rate of the liver, kidney tissues between MD-VF-Auto SEM method and plankton gene multiplex PCR system (P<0.05), as well as the total positive rate of cases. However, no significant differences were found in the positive rates of lung tissues (P>0.05).@*CONCLUSIONS@#MD-VF-Auto SEM method is more sensitive than plankton gene multiplex PCR system in diatom test. But the plankton gene multiplex PCR system can also detect plankton other than diatoms. Combination of the two methods can provide a more reliable basis for the diagnosis of drowning.

Identification of factors affecting Oncomelania hupensis density in Eastern Dongting Lake regions / 中国血吸虫病防治杂志

Objective To evaluate the impact of water pollutants, water levels and meteorological factors on the Oncomelania hupensis density in Eastern Dongting Lake regions, so as to provide insights into schistosomiasis control. Methods O. hupensis snails were surveyed using a systematic sampling method in snail-infested marshlands in Eastern Dongting Lake regions from 2007 to 2014, and data pertaining to water pollutants, water levels and meteorological factors were collected. The duration of submergence and the date of the start of submergence were calculated. The snail density and its influencing factors were descriptively analyzed, and a linear mixed model was generated to examine the impacts of variables on the snail density. In addition, smooth curves were fitted to investigate the relationship between snail density and variables. Results The snail density appeared a fluctuation in Eastern Dongting Lake regions during the period from 2007 to 2014, with the highest density on October, 2010 (52.79 snails/0.1 m2) and the lowest density on January 2009 (2.15 snails/0.1 m2). Linear mixed-model analysis showed that permanganate index, total phosphorus and the date of the start of submergence affected the snail density (t = 6.386, −2.920 and −3.892, all P values < 0.01). Smooth curve analysis revealed that the associations of the snail density with the permanganate index and total phosphorus appeared an approximately quadratic curve. After the end of April, the earlier date of the start of submergence resulted in a higher snail density. Conclusion Permenganate index, total phosphorus and the date of the start of submergence affect the O. hupensis snail density in Eastern Dongting Lake regions.

Triterpenoids from leaves of Ilex guayusa / 中国中药杂志

The chemical constituents from the leaves of Ilex guayusa were investigated. Sixteen triterpenoids were isolated from the 95% ethanol extract of dried leaves of I. guayusa by silica gel, Sephadex LH-20, and ODS column chromatographies and semi-prepa-rative HPLC. Those triterpenoids were identified by NMR, HR-MS, and literature analysis: 3β-hydroxy-11α,12α-epoxy-24-nor-urs-4(23)-ene-28,13β-olide(1), 3β-hydroxy-24-nor-4(23),12-oleanadien-28-methyl ester(2), oleanolic acid(3), 3β,28-dihydroxy-12-oleanene(4), 2α,3β-dihydroxy-11α,12α-epoxy-24-'nor-olean-4(23)-ene-28,13β-olide(5), ursolic acid(6), 3β,23-dihydroxy ursolic acid(7), 3β,28-dihydroxy-12-ursene(8), 3β-28-nor-urs-12-ene-3,17-diol(9), 3β-hydroxyurs-11-ene-28,13β-olide(10), 13β,28-epoxy-3β-hydroxy-11-ursene(11), 3β-hydroxy-28,28-dimethoxy-12-ursene(12), 3β-hydroxy-24-nor-urs-4(23),12-dien-28-oic acid(13), 3β-hydroxy-24-nor-urs-4(23),12-dien-28-methyl ester(14), 2α,3β-dihydroxy-11α,12α-epoxy-24-nor-urs-4(23)-ene-28,13β-olide(15) and 2α,3β-dihydroxy-11α,12α-epoxy-24-nor-urs-4(23),20(30)-dien-28,13β-olide(16). Compounds 1-2 were new compounds, and compounds 4-5, 7 and 9-16 were isolated from I. guayusa for the first time.

Two new pyranonaphthoquinones from Mansoa alliacea / 中国中药杂志

Mansoa alliacea,commonly known as garlic vine,is native to the tropical rain forests of South America and widely cultivated in South China. As a popular folk medicine with various biological activities,however,this plant remains to be fully elucidated in terms of its phytochemical constituents. In this study,two new pyranonaphthoquinones were isolated from the 95% ethanol extract of the leaves and twigs of M. alliacea by various chromatographic approaches including silica gel,octadecyl silica( ODS),Sephadex LH-20,and preparative high-performance liquid chromatography( PHPLC). Their structures were determined to be 8,9-dimethoxy-α-lapachone( 1) and 7-hydroxy-8,9-dimethoxy-α-lapachone( 2) by comprehensive spectroscopic analyses and therefore respectively named as mansonin A( 1) and mansonin B( 2).

Direct-to-implant breast reconstruction following nipple-sparing mastectomy: predictive factors of adverse surgical outcomes in Asian patients

Background@#Direct-to-implant (DTI) breast reconstruction after nipple-sparing mastectomy (NSM) with the use of acellular dermal matrix (ADM) provides reliable outcomes; however, the use of ADM is associated with a higher risk of complications. We analyzed our experiences of post-NSM DTI without ADM and identified the predictive factors of adverse surgical outcomes. @*Methods@#Patients who underwent NSM and immediate DTI or two-stage tissue expander (TE) breast reconstruction from 2009 to 2020 were enrolled. Predictors of adverse endpoints were analyzed. @*Results@#There were 100 DTI and 29 TE reconstructions. The TE group had a higher rate of postmastectomy radiotherapy (31% vs. 11%; P=0.009), larger specimens (317.37±176.42 g vs. 272.08±126.33 g; P=0.047), larger implants (360.84±85.19 g vs. 298.83±81.13 g; P=0.004) and a higher implant/TE exposure ratio (10.3% vs. 1%; P=0.035). In DTI reconstruction, age over 50 years (odds ratio [OR], 5.43; 95% confidence interval [CI], 1.50–19.74; P=0.010) and a larger mastectomy weight (OR, 1.65; 95% CI, 1.08–2.51; P=0.021) were associated with a higher risk of acute complications. Intraoperative radiotherapy for the nipple-areolar complex increased the risk of acute complications (OR, 4.05; 95% CI, 1.07–15.27; P=0.039) and the likelihood of revision surgery (OR, 5.57; 95% CI, 1.25–24.93; P=0.025). @*Conclusions@#Immediate DTI breast reconstruction following NSM is feasible in Asian patients with smaller breasts.

Direct-to-implant breast reconstruction following nipple-sparing mastectomy: predictive factors of adverse surgical outcomes in Asian patients

Background@#Direct-to-implant (DTI) breast reconstruction after nipple-sparing mastectomy (NSM) with the use of acellular dermal matrix (ADM) provides reliable outcomes; however, the use of ADM is associated with a higher risk of complications. We analyzed our experiences of post-NSM DTI without ADM and identified the predictive factors of adverse surgical outcomes. @*Methods@#Patients who underwent NSM and immediate DTI or two-stage tissue expander (TE) breast reconstruction from 2009 to 2020 were enrolled. Predictors of adverse endpoints were analyzed. @*Results@#There were 100 DTI and 29 TE reconstructions. The TE group had a higher rate of postmastectomy radiotherapy (31% vs. 11%; P=0.009), larger specimens (317.37±176.42 g vs. 272.08±126.33 g; P=0.047), larger implants (360.84±85.19 g vs. 298.83±81.13 g; P=0.004) and a higher implant/TE exposure ratio (10.3% vs. 1%; P=0.035). In DTI reconstruction, age over 50 years (odds ratio [OR], 5.43; 95% confidence interval [CI], 1.50–19.74; P=0.010) and a larger mastectomy weight (OR, 1.65; 95% CI, 1.08–2.51; P=0.021) were associated with a higher risk of acute complications. Intraoperative radiotherapy for the nipple-areolar complex increased the risk of acute complications (OR, 4.05; 95% CI, 1.07–15.27; P=0.039) and the likelihood of revision surgery (OR, 5.57; 95% CI, 1.25–24.93; P=0.025). @*Conclusions@#Immediate DTI breast reconstruction following NSM is feasible in Asian patients with smaller breasts.