Effects of soybean isoflavones on the reproductive development of young mice / 中国药房

OBJECTIVE To investigate the effects of soybean isoflavones （SI） on the reproductive development of young mice. METHODS C57BL/6 young mice were randomly divided into control group， SI low-dose and high-dose groups （10， 100 mg/kg）， with 10 mice in each group （half male and half female）. The young mice in each group were given corresponding liquid intragastrically， once a day， for 2 consecutive weeks. After the last administration， the percentage of body weight increase was calculated； serum estradiol and testosterone levels， malondialdehyde （MDA） content， total antioxidant capacity （T-AOC）， superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activities in the reproductive organs of the young mice were determined. The histopathological changes in the reproductive organs were observed. The cell apoptosis of reproductive organs was detected. RESULTS Compared with the control group， the percentage of body weight increase in female mice was increased significantly in the SI high-dose group， while that of male mice was decreased significantly （P＜0.05 or P＜0.01）. Cystic follicles could be seen in the ovarian tissue in SI groups， a loose arrangement of spermatocytes could be seen in the testicular tissue， and partial epithelial cell shedding could be seen in epididymal tissue. The serum level of testosterone in female young mice and the serum levels of testosterone and estradiol in male young mice in SI groups， GSH-Px activity in the ovarian tissue of female young mice in the SI low-dose group， T-AOC activities in the ovarian tissue of female young mice in SI groups as well as the apoptotic rates of cells in testicular and epididymal tissue of male young mice in SI groups were increased significantly （P＜0.05 or P＜ 0.01）； the serum level of estradiol in female young mice in SI groups， SOD activity in the ovarian tissue of female young mice in the SI high-dose group， and MDA contents in the ovarian tissue of female young mice in SI groups as well as the apoptotic rates of cells in ovarian tissue of female mice in SI groups were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS SI can enhance the antioxidant stress capacity of ovarian tissue in female young mice and reduce their oxidative stress damage， but it has certain toxicity to reproductive organs in male mice.

Prevalence of hearing loss among community-dwelling older people in China in 2020 / 中华老年医学杂志

Objective:To investigate the prevalence of hearing loss among community-dwelling older people aged 60 and over, and also to compare the discrepancies between self-reported hearing loss and hearing loss diagnosed via audiometry.Methods:Subjects were from the Prevention and Intervention on Neurodegenerative Disease for the Elderly in China(PINDEC)project.By using the stratified multi-stage cluster random sampling method, a total of 10 347 residents aged 60 years and over were selected from 12 counties and districts in Liaoning, Henan and Guangdong Provinces and hearing function assessment was performed in 2020 through otoscopy, pure-tone audiometry and questionnaires.Hearing loss(HL)was defined by the World Health Organization criteria.Self-reported hearing loss was assessed by asking participants whether they had difficulty in hearing.The χ2 and Cochran-Armitage trend tests were used to analyze the differences in HL between different groups.The multivariate Logistic regression model was applied to assess factors influencing HL. Results:In 2020, the prevalence of HL among the elderly aged 60 and older in Liaoning, Henan and Guangdong Provinces was 69.8%(95% CI: 68.9%-70.7%). The prevalence of HL in men was higher than that in women, and increased gradually with age.The prevalence of mild HL was 47.2%, and the prevalence of moderate, severe and profound HL were 18.0%, 3.6% and 0.9%, respectively.Multivariate Logistic regression analysis showed that factors positively correlated with HL were aging, male sex, living in rural areas and working in manual labor.Education level was negatively correlated with HL.Of the 7223 participants who were found to have HL, 5106(70.7%)self-reported having good hearing.Those of a younger age, with a higher educational achievement, having a spouse, or with mild HL were more likely to report having good hearing(all P<0.05). Conclusions:Hearing loss is quite prevalent among community-dwelling older people, and there is a large discrepancy in prevalence between self-reported HL and HL diagnosed via audiometry.Screening and comprehensive intervention for hearing loss for the elderly should be strengthened.

Awareness of diabetes knowledge and its influencing factors among health examination population / 中华健康管理学杂志

Objective:To investigate the awareness of diabetes knowledge among the health examination population and its influencing factors.Methods:A cross-sectional study. From september to november 2022, the subjects of six health examination centers located in six different cities (Beijing, Shanghai, Tianjin, Chongqing, Xiamen, Hangzhou) in China were investigated in the form of questionnaires to investigate the awareness of diabetes core information and the level of trust to different information sources of diabetes knowledge. According to the questionnaire results, the subjects were divided into a high awareness group of diabetes core information and a low awareness group. Logistic regression was used to analyze the influencing factors of diabetes core information awareness; the t-test was used to compare the trust degree of the two groups to different information sources. Results:A total of 9 315 people were included in the six centers, including 4 932 men (52.90%) with an average age of (39.36±12.64) years and 4 383 women (47.10%) with a mean age of (37.47±11.85) years. Only 36% of the people had high awareness of diabetes core information; variables such as gender, age, education level, physical examination frequency in the past three years, package price of this physical examination, self-evaluation of diabetes knowledge, diabetes status, and city of residence were variables that affect the level of awareness of core information related to diabetes (all P<0.05). Compared with the low awareness group of diabetes core information, the high awareness group trusted professional medical staff ( t=-9.597, P<0.05) and community health promotion more ( t=-5.014, P<0.05), but did not trust the emerging popular science propaganda means, such as WeChat official accounts/WeChat groups/QQ groups, Internet web page, Tiktok/Kwai and other short video APPs. Conclusion:The awareness rate of diabetes knowledge among the health examination population is low, and it is affected by many factors; Health education on diabetes knowledge should be carried out for people undergoing physical examination.

Exploring risk factors for combined coronary microvascular dysfunction in patients with ischemia and non-obstructive coronary artery disease / 中华核医学与分子影像杂志

Objective:To investigate the risk factors for combined coronary microvascular dysfunction (CMD) in patients with ischemia and non-obstructive coronary artery disease (INOCA).Methods:From October 2020 to May 2022, 100 INOCA patients with myocardial ischemic symptoms who underwent coronary angiography (CAG) suggestive of <50% stenosis in all three coronary arteries at the Tenth People′s Hospital of Tongji University were prospectively recruited. Myocardial perfusion imaging (MPI), transthoracic echocardiography and cadmium-zinc-telluride (CZT) SPECT coronary flow quantification were performed in the same month, and 93 INOCA patients (36 males and 57 females, age (63.0±10.9) years) were finally included. CMD was defined as coronary flow reserve (CFR)<2.5. Independent-sample t test, Mann-Whitney U test and χ2 test were used to compare MPI results and left ventricular volume parameters between CMD and non-CMD groups. ROC curve analysis was used to analyze the efficacy of each index in predicting CMD, and independent risk factors for CMD were screened by multivariate logistic regression analysis. Results:Among 93 INOCA patients, 29 were in the CMD group and 64 were in the non-CMD group. The age, proportion of hypertension, left ventricular mass index (LVMI), summed stress score (SSS), summed difference score (SDS), left ventricular internal diameter systolic (LVIDS), interventricular septum thickness (IVST), and left ventricular posterior wall thickness (LVPWT) in the CMD group were higher than those in the non-CMD group ( t values: 2.42-3.76, χ2=8.94, z values: -3.31, -3.41, all P<0.05). ROC curve analysis showed that LVMI, SSS, SDS, LVPWT, IVST and age were significant in predicting CMD (AUCs: 0.67-0.72). Multivariate logistic regression analysis showed that LVMI (odds ratio ( OR)=1.08, 95% CI: 1.01-1.17), SDS ( OR=5.37, 95% CI: 1.95-14.78), hypertension ( OR=5.68, 95% CI: 1.34-24.18) and age ( OR=1.10, 95% CI: 1.03-1.18) were risk factors for CMD. Conclusion:LVMI, SDS, hypertension and age are strongly associated with combined CMD in INOCA patients, which can be used for early risk stratification of INOCA patients.

The value of radiomics based on contrast-enhanced spectral mammography of internal and peripheral regions combined with clinical factors in predicting benign and malignant breast lesions of breast imaging reporting and data system category 4 / 中华放射学杂志

Objective:To evaluate the value of radiomics based on contrast-enhanced spectral mammography (CESM) of internal and peripheral regions combined with clinical factors in predicting benign and malignant breast lesions of breast imaging reporting and data system category 4 (BI-RADS 4).Methods:A retrospective analysis was performed on the clinical and imaging data of patients with breast lesions who were treated in Yantai Yuhuangding Hospital (Center 1) Affiliated to Qingdao University from July 2017 to July 2020 and in Fudan University Cancer Hospital (Center 2) from June 2019 to July 2020. Center 1 included 835 patients, all female, aged 17-80 (49±12) years, divided into training set (667 cases) and test set (168 cases) according to the "train-test-split" function in Python software at a ratio of 8∶2; and 49 patients were included from Center 2 as external validation set, all female, aged 34-70 (51±8) years. The radiomics features were extracted from the intralesional region (ITR), the perilesional regions of 5, 10 mm (PTR 5 mm, PTR10 mm) and the intra-and perilesional regions of 5, 10 mm (IPTR 5 mm, IPTR 10 mm) and were selected by variance filtering, SelectKBest algorithm, and least absolute shrinkage and selection operator. Then five radiomics signatures were constructed including ITR signature, PTR 5 mm signature, PTR 10 mm signature, IPTR 5 mm signature, IPTR 10 mm signature. In the training set, univariable and multivariable logistic regressions were used to construct nomograms by selecting radiomics signatures and clinical factors with significant difference between benign and malignant BI-RADS type 4 breast lesions. The efficacy of nomogram in predicting benign and malignant BI-RADS 4 breast lesions was evaluated by the receiver operating characteristic curve and area under the curve (AUC). Decision curve and calibration curve were used to evaluate the net benefit and calibration capability of the nomogram.Results:The nomogram included ITR signature, PTR 5 mm signature, PTR 10 mm signature, IPTR 5 mm signature, age, and BI-RADS category 4 subclassification for differentiating malignant and benign BI-RADS category 4 breast lesions and obtained AUCs of 0.94, 0.92, and 0.95 in the training set, test set, and external validation set, respectively. The calibration curve showed good agreement between the predicted probabilities and actual results and the decision curve indicated a good net benefit of the nomogram for predicting malignant BI-RADS 4 lesions in the training set, test set, and external validation set.Conclusion:The nomogram constructed from the radiomics features of the internal and surrounding regions of CESM breast lesions combined with clinical factors is attributed to differentiate benign from malignant BI-RADS category 4 breast lesions.

Effect of remnant cholesterol levels on carotid intima thickness in patients with type 2 diabetes mellitus evaluated by ultra-high frequency ultrasound / 中华超声影像学杂志

Objective:To discuss the effect of remnant cholesterol (RC) levels on carotid intima thickness (CIT) in patients with type 2 diabetes mellitus (T2DM) by ultra-high frequency ultrasound.Methods:A total of 60 patients with T2DM who received treatment in Henan Provincial People′s Hospital from May 2021 to July 2022 were prospectively recruited, and they were divided into a higher RC group (31 cases) and a lower RC group (29 cases) according to the RC levels. Thirty-one age, sex and body mass index(BMI)-matched healthy volunteers were selected as control group. Carotid CIT, carotid media thickness(CMT) and intima-media thickness(CIMT) were measured by 24 MHz ultra-high frequency ultrasound probe. The difference of general clinical data, laboratory indicators and CIMT, CIT, CMT among the three groups were compared, and the influencing factors of CIT in T2DM patients were explored by multivariate regression analysis.Results:①There were no statistical significances in gender, age, BMI, high-density lipoprotein cholesterol (HDL-C) and CMT among the three groups (all P>0.05). There were no statistical significances in duration of diabetes, fasting blood-glucose and glycated haemoglobin between the two subgroups of T2DM (all P>0.05). ②Compared with the control group, CIMT and CIT were thicker in the T2DM group (both P<0.05). ③CIT was thicker in the higher RC group than in the lower RC group ( P<0.05), while the difference of CIMT was not statistically significant the two groups ( P>0.05). ④Multivariate regression analysis showed that RC was the influence factor of CIT in patients with T2DM(β=0.610, P=0.005). Conclusions:CIT is significantly thicker in T2DM patients with higher RC than in those with lower RC, and RC is the influence factor of CIT, which suggests that more attention should be paid to the detection of RC in T2DM patients.

Iodine nutrition status and influencing factors of thyroid volume of children aged 8 - 10 years in Shiyan City, Hubei Province / 中华地方病学杂志

Objective:To study the iodine nutrition status and influencing factors of thyroid volume of children aged 8 - 10 years in Shiyan City, Hubei Province.Methods:From June 2019 to October 2020, in 8 counties (cities, districts) under the jurisdiction of Shiyan City, Hubei Province, each county (city, district) was divided into 5 districts according to the east, west, south, north, and center. One township (street) was selected in each district, and 40 children aged 8 to 10 years from one primary school (age balanced, half male and half female), were selected in each township (street), and their home salt samples and once random urine sample were taken to detect salt iodine and urinary iodine levels. At the same time, thyroid volume measurements and physical examination were performed.Results:A total of 3 172 salt samples were collected from children's homes, with a salt iodine content of 23.68 mg/kg. The iodine salt coverage rate was 99.81% (3 166/3 172), and the qualified iodine salt consumption rate was 96.72% (3 068/3 172). A total of 3 172 urine samples were collected from children, with a median urinary iodine level of 241.87 μg/L, indicating that iodine nutrition was at a super optimal level. There were statistically significant differences in the median urinary iodine among children of different genders and regions ( Z = - 3.63, H = 160.83, P < 0.001). The thyroid of 1 191 children was examined, and the goiter rate was 0.67% (8/1 191), and there were statistically significant differences in the goiter rate of children of different ages and regions (χ 2 = 6.41, 11.91, P = 0.040, 0.002). The correlation analysis results showed that there was a negative correlation between urinary iodine and thyroid volume in children ( r = - 0.08, P = 0.025); according to age stratification, there were positive correlation between height, weight, body surface area, and thyroid volume in children aged 8, 9 and 10 years ( P < 0.05). Conclusions:The iodine nutrition of 8 - 10 years old children in Shiyan City is in an over appropriate level, and the goiter rate is low. Urinary iodine, height, weight, and body surface area of children are all factors influencing thyroid volume.

A comparative study of iodine content in serum, plasma and whole blood / 中华地方病学杂志

Objective:To evaluate the consistency of individual iodine nutrition levels by serum iodine, plasma iodine and whole blood iodine, and to provide reference for iodine-related epidemiological investigation.Methods:Healthy adults aged 18 - 59 years were recruited from the Research Center of Environment and Health in Water Source Area of South-to-North Water Diversion of Hubei University of Medicine. Whole blood sample was collected and serum and plasma were separated. The content of iodine in serum, plasma and whole blood was determined by inductively coupled plasma mass spectrometry (ICP-MS), and the linear relationship, precision and accuracy of the standard curve of the detection method were evaluated. The difference of three kinds of blood iodine levels was analyzed by variance analysis of compatibility group design, and Passing-Bablok regression and Bland-Altman plot were used to evaluate the consistency between serum iodine and plasma iodine.Results:The linear range of iodine in serum, plasma and whole blood was 0.0 - 25.0 μg/L, and the correlation coefficients ( R2) were all > 0.999. The relative standard deviation of 8 mixed blood samples ranged from 1.9% to 4.3% ( n = 6), and the determination results of blood iodine certified standard substances were all within the reference range. The recovery rate of the added standard ranged from 99% to 106%. The iodine levels in serum, plasma and whole blood of 50 volunteers were (57.31 ± 8.06), (57.49 ± 8.50) and (33.89 ± 5.40) μg/L, respectively, and there was no statistically significant difference between serum iodine and plasma iodine ( P = 0.904). The results of Passing-Bablok regression showed that there was no statistically significant difference in bias between serum iodine and plasma iodine ( P = 0.538). The Bland-Altman plot indicated that the difference between serum iodine and plasma iodine was within the consistency limit. Conclusion:The results of plasma iodine and serum iodine are in good agreement, and plasma iodine can be used as an evaluation index of individual iodine nutrition level. But there is no consistency between whole blood iodine and serum iodine.

Predictive analysis of the number of hospitalized patients with acute pancreatitis based on time series model / 中华胰腺病杂志

Objective:To predict and analyze the number of acute pancreatitis (AP) inpatients based on time series model, and to explore the predictive efficiency of the model.Methods:Clinical data of AP inpatients in the Affiliated Hospital of Southwest Medical University from January 2014 to December 2019 were collected. R software was used to collect the time series of AP inpatients, and the trend and seasonal characteristics of AP inpatients from 2014 to 2018 were analyzed. Furthermore, the autoregressive moving average (ARIMA) model was established through stationarity test, model ordering and model testing steps, and the best selected model was used to predict the monthly number of inpatients in 2019 to verify its prediction efficiency.Results:A total of 3 939 AP patients were included in the study. The most common etiology for AP was cholestrogenic (48.2%), followed by hyperacylglyceremia (36.3%). The peak age of hospitalization was from 40 to 60 years old. Time series analysis showed that the number of AP inpatients increased year by year. The highest peak of the disease was from February to March, followed by September to November; and there was seasonal variation and the incidence was relatively small in summer. The established original training set sequence did not pass the stationarity test ( P=0.061), so the ARIMA model was established after it was transformed into a stationarity sequence by first-order difference. According to the criterion of minimum AIC value, ARIMA(2, 1, 1)(1, 1, 1) 12 was selected as the best model. The model was used to predict the number of AP inpatients in 2019, showing that it could better fit the trend of onset time and had good short-term prediction effect. The mean root error and absolute error were 6.8790 and 4.7783, respectively. Conclusions:The number of AP inpatients increases year by year with seasonal changes. ARIMA model is effective in predicting the number of AP inpatients and can be used for short-term prediction.

SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity / 药物分析学报

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa+Nppb+Ankrd1+cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after Ml.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

Safety and efficacy of levosimendan in patients with acute heart failure: a prospective, multicenter, and observational study / 中华急诊医学杂志

Objective:To investigate the indication, effectiveness, tolerance, and safety of levosimendan in patients with acute heart failure (AHF) in 20 hospitals in Beijing, China.Methods:This prospective, observational, and multicenter study consecutively enrolled AHF patients who were treated with levosimendan at 20 hospitals in Beijing from April 2020 to March 2022. Baseline demographics, laboratory parameters, clinical presentation, concomitant diseases and medications were collected. After initiation of levosimendan, levosimendan administration, laboratory parameter pre- and post-administration, symptoms improvement, and adverse events were also collected.Results:Totally 800 AHF patients were included, 67% of whom were male, aged (65 ±17) years, 50% of whom had ischemic heart disease, and the left ventricular ejection fraction (LVEF) was (36±11)%. The dose of levosimendan was (11.84 ±2.11) mg and the mean infusion time was (1 450±307) min. Dyspnea was improved in 83.4% of AHF patients at 24 h after treatment. The level of B-type natriuretic peptide (BNP) significantly decreased from 689 (406-1509) pg/mL to 410 (156-697) pg/mL in all patients at 24-72 h after treatment ( P<0.001), and the level of N-terminal pro-brain natriuretic peptide (NT-pro BNP) decreased from 6910 (3 715-13 914) pg/mL to 2 851 (1 288-6 191) pg/mL ( P<0.001). Meanwhile, LVEF level also improved significantly [(40±11)% vs. (36±11)%, P<0.001]. During levosimendan administration, adverse events occurred in 74 (9.3%) patients, including hypotension (5.9%), arrhythmia (1.9%), and other symptoms (1.1%). Among them, 7 patients ( 2 patients with hypotension and 5 patients with ventricular tachycardia) interrupted levosimendan administration. Conclusions:The use of levosimendan is safe, and can improve symptoms reduce BNP or NT-pro BNP levels and increase LVEF level in AHF patients.

The Expression Level and Diagnostic Value of Serum Free Light Chain in B-Cell Non-Hodgkin Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression level and the diagnostic value of serum free light chain in B-cell non-Hodgkin's lymphoma (B-NHL).@*METHODS@#We retrospectively analyzed the results of serum free light chain (sFLC) of 394 newly treated B-NHL patients in our hospital from January 2014 to December 2021 and compared the secretion levels of sFLC among different subtypes of B-NHL. The value of sFLC secretion levels in the diagnosis of WM was evaluated using ROC.@*RESULTS@#Increased proportion of sFLC, abnormal ratio of sFLC (κ / λ) and the secretion levels of sFLC (κ+λ) were different in different B-NHL subtypes, Waldenstrom's macroglobulinemia (WM) had the highest proportion of elevated sFLC(82.68%) and abnormal sFLC(κ/ λ)(87.0%), the proportion of FL(18.0%) and DLBCL patients(12.8%) with elevated sFLC was lower (P<0.05). The expression levels of sFLC can helpful in the diagnosis of WM (AUC=0.874，P<0.001， 95% CI: 0.779-0.970). At the same time, higher sFLC levels and sFLC cloning patterns predicted the possibility of bone marrow infiltration of lymphoma.@*CONCLUSION@#The serum free light chains is common in patients with B-NHL. The elevated level and type of free light chain are associated with the type of lymphoma, and the patients with bone marrow infiltration have higher sFLC（κ+ λ） expression level.

Neuropsychological development of large for gestational age infants at the age of 12 months / 中国当代儿科杂志

OBJECTIVES@#To investigate the level of neuropsychological development in large for gestational age (LGA) infants at the age of 12 months.@*METHODS@#The infants, aged 12 to <13 months, who attended the Outpatient Service of Child Care in the First Affiliated Hospital of Shandong First Medical University from December 2021 to June 2023, were enrolled as subjects. According to the gestational age and birth weight, they were divided into preterm appropriate for gestational age (AGA) group, preterm LGA group, early term AGA group, early term LGA group, full-term AGA group, and full-term LGA group. A modified Poisson regression analysis was used to investigate the association between LGA and neuropsychological development outcome at 12 months of age.@*RESULTS@#After adjustment for confounding factors, compared with the full-term AGA group at the age of 12 months, the full-term LGA group had a significant increase in the risk of language deficit (RR=1.364, 95%CI: 1.063-1.750), the early term LGA group had significant increases in the risk of abnormal gross motor, fine motor, language, and the preterm LGA group had significant increases in the risk of abnormal language, social behavior, and total developmental quotient (P<0.05); also, the early term AGA group had higher risks of developmental delay across all five attributes and in total developmental quotient at the age of 12 months (P<0.05); except for the language attribute, the preterm AGA group had higher risks of developmental delay in the other 4 attributes (P<0.05).@*CONCLUSIONS@#The neuropsychological development of LGA infants with different gestational ages lags behind that of full-term AGA infants at 12 months of age, and follow-up and early intervention of such infants should be taken seriously in clinical practice.

Genomic, transcriptomic, and epigenomic analysis of a medicinal snake, Bungarus multicinctus, to provides insights into the origin of Elapidae neurotoxins

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Establishment and applicability comparison of four models of acute liver ischemia/reperfusion injury in rat / 中华危重病急救医学

OBJECTIVE@#To clarify the preparation methods of four rat models of liver ischemia/reperfusion injury (IRI) and to determine a liver IRI animal model that is consistent with clinical conditions, has stable pathological and physiological injury, and is easy to operate.@*METHODS@#A total of 160 male Sprague-Dawley (SD) rats were randomly divided into four groups using an interval grouping method: 70% IRI (group A), 100% IRI (group B), 70% IRI with 30% hepatectomy (group C), and 100% IRI with 30% hepatectomy (group D), with 40 rats in each group. Each model was further divided into sham operation group (S group) and ischemia groups of 30, 60, and 90 minutes, with 10 rats in each group. After surgery, the survival status and awakening time of the rats were observed, and the liver lobectomy weight, bleeding volume, and hemostasis time of groups C and D were recorded. Blood samples were collected by cardiac puncture after 6 hours of reperfusion for determination the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), serum creatinine (SCr), and γ-glutamyl transpeptidase (γ-GT) in the serum to assess liver and kidney function. Hematoxylin-eosin (HE) staining and immunohistochemical staining of macrophages were performed to analyze the liver tissue structure damage from a pathological perspective.@*RESULTS@#Rats in group A exhibited earlier awakening and acceptable mental status, while rats in the other groups showed delayed awakening and poor mental status. The hemostasis time in group D was approximately 1 second longer than that in group C. The mortality of rats subjected to 60 minutes of 70% hepatic ischemia was 0. Compared to the sham operation group, rats in each experimental group showed significant increases in serum levels of AST, ALT, ALP, BUN, SCr, and γ-GT, indicating impaired liver and kidney function in the rat models of liver IRI. In groups A, B, and C, the 90-minute ischemia subgroup exhibited more pronounced elevation in AST, ALT, ALP, BUN, SCr, and γ-GT levels compared to the 30-minute ischemia subgroup [AST (U/L): group A, 834.94±56.73 vs. 258.74±18.33; group B, 547.63±217.40 vs. 277.67±57.92; group C, 930.38±75.48 vs. 640.51±194.20; ALT (U/L): group A, 346.78±25.47 vs. 156.58±13.25; group B, 408.40±138.25 vs. 196.80±58.60; group C, 596.41±193.32 vs. 173.76±72.43; ALP (U/L): group A, 431.21±34.30 vs. 315.95±15.64; group B, 525.88±62.13 vs. 215.63±17.31; group C, 487.53±112.37 vs. 272.46±92.33; BUN (U/L): group A, 18.35±5.63 vs. 14.32±2.30; group B, 30.21±4.55 vs. 17.41±8.14; group C, 20.50±3.64 vs. 15.93±3.22; SCr (U/L): group A, 27.47±8.91 vs. 22.37±5.66; group B, 43.60±15.57 vs. 36.80±7.95; group C, 63.81±20.24 vs. 42.47±7.03; γ-GT (U/L): group A, 15.64±3.57 vs. 6.82±1.48; group B, 9.28±1.91 vs. 5.62±1.21; group C, 10.98±3.18 vs. 5.67±1.10; all P < 0.05]. The 100% IRI 90-minute group and 100% IRI 90-minute group with 30% hepatectomy exhibited more pronounced increases in the above-mentioned indicators compared to the corresponding 70% IRI control group, indicating increased liver and kidney damage in rats subjected to combined blood flow occlusion and hepatectomy. HE staining showed clear liver tissue structure with intact and orderly arranged cells in the sham operation group, while the experimental groups exhibited cell structure damage, including cell rupture or collapse, cell swelling, nuclear pyknosis, deep cytoplasm staining, cell shedding, and necrosis. The interstitium showed infiltration of inflammatory cells. Immunohistochemical staining revealed a higher number of macrophages in the experimental groups compared to the sham operation group.@*CONCLUSIONS@#Four models of liver IRI in rat were successfully established. As the duration and severity of hepatic ischemia increased, liver cell ischemia worsened, leading to increased hepatocellular necrosis and exhibiting characteristic features of liver IRI. These models can effectively simulate liver IRI following liver trauma, with the group subjected to 100% ischemia and 30% hepatectomy showing the most severe liver injury. The designed models are reasonable, easy to perform, and exhibit good reproducibility. They can be used for investigating the mechanisms, therapeutic efficacy, and diagnostic methods related to clinical liver IRI.

Jump training for basketball shooting / Treinamento de salto para arremesso no basquetebol / Entrenamiento de salto para lanzamiento en el baloncesto

ABSTRACT Introduction: Basketball has become popular, and important basketball groups have been created for fun and training. However, many athletes do not acquire a professional education, creating a gap between athletes and sports enthusiasts. Objective: Study the technical characteristics of the jump shot in basketball and explore its training methods. Methods: Intra-group control was selected to train the volunteer enthusiasts. The experiment was conducted twice a week for 6 weeks. Data regarding physical performance were acquired before and after the experiment, subjected to analysis, and discussed confronting the literature. Results: After six weeks of training, the total time of the three phases on the sports enthusiasts was 1.14378s, and the average time of the ball preparation phase was 0.72262s, representing 63.178% of the total time. The average time spent in the take-off phase was 0.2011s, representing 17.582% of the total time; the average time spent in the vacancy phase was 0.22006s, representing 19.240% of the total time. Conclusion: The jump-throw training protocol showed benefits over 6 weeks of training. The technical characteristics of the participants in the sports enthusiast group were improved statistically. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O basquetebol tem se tornado popular, e importantes grupos de basquetebol foram criados para diversão e treinamento. No entanto, muitos esportistas não adquirem um ensino profissionalizante, gerando uma lacuna entre os atletas e os entusiastas do esporte. Objetivo: Estudar as características técnicas do salto para arremesso no basquetebol e explorar seus métodos de treinamento. Métodos: O controle intra-grupo foi selecionado para treinar os entusiastas voluntários. O experimento foi realizado duas vezes por semana durante 6 semanas. Os dados referentes ao desempenho físico foram adquiridos antes e após o experimento, submetidos a análise e discutidos confrontando a literatura. Resultados: Após seis semanas de treinamento, o tempo total das três fases sobre os entusiastas do esporte foi de 1.14378s, e o tempo médio da fase de preparação da bola foi de 0,72262s, representando 63,178% do tempo total. O tempo médio gasto na fase de decolagem foi de 0,2011s, representando 17,582% do tempo total; o tempo médio gasto na fase de vacância foi de 0,22006s, representando 19,240% do tempo total. Conclusão: O protocolo de treinamento de salto para arremesso apresentou benefícios ao longo de 6 semanas de treinamento. As características técnicas dos participantes no grupo de entusiastas do esporte foram aprimoradas estatisticamente. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El baloncesto se ha popularizado y se han creado importantes grupos de baloncesto para divertirse y entrenar. Sin embargo, muchos deportistas no adquieren una formación profesionalizante, lo que genera una brecha entre los atletas y los aficionados al deporte. Objetivo: Estudiar las características técnicas del salto para lanzar en baloncesto y explorar sus métodos de entrenamiento. Métodos: Se seleccionó un control intragrupo para entrenar a los voluntarios entusiastas. El experimento se realizó dos veces por semana durante 6 semanas. Los datos relativos al rendimiento físico se adquirieron antes y después del experimento, se sometieron a análisis y se discutieron confrontándolos con la bibliografía. Resultados: Tras seis semanas de entrenamiento, el tiempo total de las tres fases en los entusiastas del deporte fue de 1,14378s, y el tiempo medio de la fase de preparación del balón fue de 0,72262s, lo que representa el 63,178% del tiempo total. El tiempo medio empleado en la fase de despegue fue de 0,2011s, lo que representa el 17,582% del tiempo total; el tiempo medio empleado en la fase de vacante fue de 0,22006s, lo que representa el 19,240% del tiempo total. Conclusión: El protocolo de entrenamiento de salto para lanzamiento presentó beneficios a lo largo de 6 semanas de entrenamiento. Las características técnicas de los participantes del grupo de entusiastas del deporte mejoraron estadísticamente. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Guiqi Baizhu Prescription Combined with Oxaliplatin Protects Intestinal Barrier of Tumor-bearing Mice with Gastric Cancer by Regulation of VIP/cAMP/PKA/AQP Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of Guiqi Baizhu prescription combined with oxaliplatin on the intestinal barrier of tumor-bearing mice with gastric cancer by regulating downstream aquaporin 3 （AQP3） and aquaporin 4 （AQP4） through the vasoactive intestinal peptide （VIP）/cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA） signaling pathway. MethodThe gastric cancer cell lines MFC with a density of 1×107/mL were prepared into cell suspension. The tumor-bearing mouse model of gastric cancer was established by inoculating 0.2 mL cell suspension under the right axilla of mice. After successful modeling， mice were randomly divided into 5 groups， namely， model group， oxaliplatin group （10 mg·kg-1）， and high， medium， and low-dose oxaliplatin + Guiqi Baizhu prescription groups （17.68， 8.84， 4.42 g·kg-1）， with 10 mice in each group， and the remaining 10 mice were set as a blank group. Mice in each group were treated with Chinese medicine， oxaliplatin， or normal saline by gavage or intraperitoneal injection for 14 d. The next day after the last dose， blood was taken from the eyeball to separate serum and take colonic samples. Hematoxylin-eosin （HE） staining was used to observe the changes in tissue morphology. The content of D-lactate acid （D-LA） and diamine oxidase （DAO） in the serum was determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expressions of VIP， cAMP， PKA， AQP3， and AQP4 were detected by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the blank group， the model group showed edema in the colonic submucosa， disordered arrangement of intestinal glands in the mucosal layer， loss of goblet cells， infiltration of inflammatory cells， and villus shedding. However， there were different degrees of improvement in each administration group. As compared with the blank group， the serum levels of DAO and D-LA in the model group were significantly increased （P<0.01）. As compared with the model group， the levels of DAO and D-LA in the high-dose oxaliplatin + Guiqi Baizhu prescription group and the level of D-LA in the medium-dose oxaliplatin + Guiqi Baizhu prescription group were decreased （P<0.05， P<0.01）. As compared with the oxaliplatin group， the levels of D-LA in the high and medium-dose oxaliplatin + Guiqi Baizhu prescription groups were decreased （P<0.05）， and the levels of DAO and D-LA in other administration groups were decreased as well， but the difference had no statistical significance. As compared with the blank group， the mRNA and protein expression levels of VIP， cAMP， PKA， AQP3， and AQP4 in the model group were significantly decreased （P<0.05， P<0.01）. As compared with the model group， the mRNA and protein expression levels of VIP， cAMP， PKA， AQP3， and AQP4 in each administration group were increased， and those in the high-dose oxaliplatin + Guiqi Baizhu prescription group were significantly increased （P<0.05， P<0.01）， while the protein expression level of cAMP in the medium-dose oxaliplatin + Guiqi Baizhu prescription group were increased （P<0.05）. As compared with the oxaliplatin group， the protein expression levels of cAMP in the high-dose oxaliplatin + Guiqi Baizhu prescription group were increased （P<0.05）， and the mRNA and protein expressions of these indexes in the other groups were also increased but the differences were not statistically significant. ConclusionGuiqi Baizhu prescription combined with oxaliplatin can regulate AQP3 and AQP4 through the VIP/cAMP/PKA signaling pathway to protect the intestinal barrier of tumor-bearing mice with gastric cancer.

Platycladi Semen oil ameliorates Aβ_(25-35)-induced brain injury in mice based on network pharmacology and gut microbiota / 中国中药杂志

The present study aimed to investigate the protective effect and underlying mechanism of Platycladi Semen oil(SP) on Aβ_(25-35)-induced brain injury in mice to provide a theoretical basis for the clinical treatment of Alzheimer's disease(AD). Male Kunming(KM) mice were randomly divided into a control group, a model group(brain injection of Aβ_(25-35), 200 μmol·L~(-1), 0.15 μL·g~(-1)), a positive drug group(donepezil, 10 mg·kg~(-1)), and low-and high-dose SP groups(0.5 and 1 mL·kg~(-1)). Learning and memory ability, neuronal damage, levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, related indicators of apoptosis and oxidative stress, and immune cells, and protein and mRNA expression related to the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)/sphingosine-1-phosphate receptor 5(S1PR5) signaling pathway of mice in each group were determined. In addition, compounds in SP were analyzed by gas chromatography-mass spectrometry(GC-MS). The mechanism of SP against AD was investigated by network pharmacology, 16S rDNA gene sequencing for gut microbiota(GM), and molecular docking techniques. The results showed that SP could improve the learning and memory function of Aβ_(25-35)-induced mice, reduce hippocampal neuronal damage, decrease the levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, and indicators related to apoptosis and oxidative stress in the brain, and maintain the homeostasis of immune cells and GM. Network pharmacology and sequencing analysis for GM showed that the therapeutic effect of SP on AD was associated with the sphingolipid signaling pathway. Meanwhile,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid, the components with the highest content in SP, showed good binding activity to SPHK1 and S1PR5. Therefore, it is inferred that SP exerts anti-apoptosis and antioxidant effects by regulating GM and inhibiting SPHK1/S1P/S1PR5 pathway, thereby improving brain injury induced by Aβ_(25-35) in mice. Moreover,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid may be the material basis for the anti-AD effect of SP.

The hippocampal proteomics mechanism of thalidomide in Alzheimer's disease model mice induced by Aβ / 中国药理学通报

Aim To observe the effect of thalidomide on the learning and memory ability and hippocampal tissue proteome of Alzheimer's disease(AD)mice,to screen the differential proteins of thalidomide in preventing and treating AD,the pathways involved in regulation,and to explore its possible mechanism. Methods The experimental mice were randomly divided into blank control group,model group,and thalidomide high and low dose groups. The drugs were administered by gavage every day for 21 days. After the administration,Morris water maze test was used to evaluate the learning and memory abilities of the mice,HE staining and Nissl staining were used to observe the pathological tissue morphology of the mouse hippocampus,ELISA was employed to detect the mitochondrial respiratory chain enzyme complex in mouse brain,and the Label-free proteomics method was used to screen different groups of hippocampal proteome proteins. Results The results of the Morris water maze showed that compared with the model group,the escape latency time of the drug group was significantly reduced,and the number of crossing the platform significantly increased(P<0.05). Thalidomide administration could improve the morphological structure of neurons in hippocampus,and could increase the activity of the mitochondrial respiratory chain complex ,Ⅱ, and of the brain tissues of AD mice(P<0.05). A total of 4 378 differential proteins were identified,which had a significant regulatory effect on the expression of 580 proteins in hippocampus of AD mice(P<0.05). Energy metabolism may jointly participate in the regulation of neurodegeneration pathways-changes in pathways such as various diseases and Alzheimer's disease. Conclusions Thalidomide can significantly improve the learning and memory function of AD model mice induced by Aβ

Assessment of risk factors for bronchopulmonary dysplasia with pulmonary hypertension and construction of a prediction nomogram model / 中华儿科杂志

Objective: To explore the risk factors of pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD), and to establish a prediction model for early PH. Methods: This was a retrospective cohort study. Data of 777 BPD preterm infants with the gestational age of <32 weeks were collected from 7 collaborative units of the Su Xinyun Neonatal Perinatal Collaboration Network platform in Jiangsu Province from January 2019 to December 2022. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 8∶2 by computer, and non-parametric test or χ2 test was used to examine the differences between the two retrospective cohorts. Univariate Logistic regression and multivariate logistic regression analyses were used in the training cohort to screen the risk factors affecting the PH associated with BPD. A nomogram model was constructed based on the severity of BPD and its risk factors,which was internally validated by the Bootstrap method. Finally, the differential, calibration and clinical applicability of the prediction model were evaluated using the training and verification queues. Results: A total of 130 among the 777 preterm infants with BPD had PH, with an incidence of 16.7%, and the gestational age was 28.7 (27.7, 30.0) weeks, including 454 males (58.4%) and 323 females (41.6%). There were 622 preterm infants in the training cohort, including 105 preterm infants in the PH group. A total of 155 patients were enrolled in the verification cohort, including 25 patients in the PH group. Multivariate Logistic regression analysis revealed that low 5 min Apgar score (OR=0.87, 95%CI 0.76-0.99), cesarean section (OR=1.97, 95%CI 1.13-3.43), small for gestational age (OR=9.30, 95%CI 4.30-20.13), hemodynamically significant patent ductus arteriosus (hsPDA) (OR=4.49, 95%CI 2.58-7.80), late-onset sepsis (LOS) (OR=3.52, 95%CI 1.94-6.38), and ventilator-associated pneumonia (VAP) (OR=8.67, 95%CI 3.98-18.91) were all independent risk factors for PH (all P<0.05). The independent risk factors and the severity of BPD were combined to construct a nomogram map model. The area under the receiver operating characteristic (ROC) curve of the nomogram model in the training cohort and the validation cohort were 0.83 (95%CI 0.79-0.88) and 0.87 (95%CI 0.79-0.95), respectively, and the calibration curve was close to the ideal diagonal. Conclusions: Risk of PH with BPD increases in preterm infants with low 5 minute Apgar score, cesarean section, small for gestational age, hamodynamically significant patent ductus arteriosus, late-onset sepsis, and ventilator-associated pneumonia. This nomogram model serves as a useful tool for predicting the risk of PH with BPD in premature infants, which may facilitate individualized early intervention.