Genetic variation and distribution characteristics of thalassemia in people of childbearing age in Hubei Province / 中华地方病学杂志

Objective:To study the genetic variation and distribution characteristics of thalassemia in people of childbearing age in Hubei Province, and to provide clinical basis for the local government decision-making departments to formulate and promote appropriate policies for prevention and control of thalassemia.Methods:Venous blood samples were collected from 44 849 people of childbearing age in hospitals in Hubei Province from May 13, 2019 to August 17, 2021. PCR-flow fluorescence hybridization and PCR+diversion hybridization were used to screen thalassemia genes. Spouses of those who tested positive were also tested for thalassemia genes. When both spouses carried the same type of thalassemia gene, the amniotic fluid of pregnant women was extracted for prenatal diagnosis and followed up.Results:Among the 44 849 people of childbearing age, 2 286 cases were diagnosed as thalassemia gene carriers through genetic testing, and the total detection rate was 5.10% (2 286/44 849). Among them, 1 488 cases were diagnosed as α-thalassemia, and the detection rate was 3.32% (1 488/44 849); 767 cases were diagnosed as β-thalassemia, and the detection rate was 1.71% (767/44 849); 31 cases were diagnosed as α-thalassemia combined with β-thalassemia, and the detection rate was 0.07% (31/44 849). The top three genotypes of α-thalassemia were -α 3.7/αα, -- SEA/αα, and -α 4.2/αα, accounting for 58.06% (864/1 488), 26.14% (389/1 488), and8.74% (130/1 488), respectively. The top three genotypes of β-thalassemia were β IVS-Ⅱ-654/β N, β CD41-42/β N, and β CD17/β N, accounting for 41.72% (320/767), 21.25% (163/767), and 16.04% (123/767), respectively. The main genotypes of α-thalassemia combined with β-thalassemia were -α 3.7/αα complex β IVS-Ⅱ-654/β N and -α 3.7/αα complex β CD41-42/β N, accounting for 29.03% (9/31) and 16.13% (5/31), respectively. A total of 59 people of childbearing age were conducted prenatal diagnosis, among fetus, there were 4 cases of severe thalassemia (2 cases of severe α-thalassemia, 2 cases of severe β-thalassemia), 5 cases of intermediate α-thalassemia, 5 cases of intermediate or severe β-thalassemia, 19 cases of mild thalassemia (8 cases of mild α-thalassemia, 11 cases of mild β-thalassemia), 13 cases of stationary α-thalassemia, and 1 case of stationary α-thalassemia combined with mild β-thalassemia, there were 12 cases without α-thalassemia or β-thalassemia genes. After follow-up, 4 cases of severe thalassemia, 2 cases of intermediate α-thalassemia, and 5 cases of intermediate or severe β-thalassemia were terminated pregnancy by the joint decision of both parents. Conclusions:In Hubei Province, the detection rate of thalassemia is high, and α-thalassemia is the main mutation type. The combination of thalassemia gene screening and prenatal diagnosis is of great significance in reducing the birth rate of children with thalassemia.

Research on the mining, sorting and transforming of traditional exercise prescription from the perspective of sports and health integration / 中华行为医学与脑科学杂志

Based on promoting the " sports and health integration" and with the aim of the positive role of traditional sports in promoting public health in an all-round and whole-cycle way, this paper uses the literature research method to explore the connotation of traditional sports in ancient Chinese books and literatures, such as " treating no diseases" , " treating mild diseases" , " treating desired diseases" and " treating existing diseases" . The traditional exercise prescription is interpreted from the modern language such as the amount of exercise and intensity, application time, role, standardization and matters needing attention, so as to provide the theoretical basis for the integration of traditional exercise prescription into grassroots health management by providing exercise promotion services for healthy, sub-healthy, sick and rehabilitated people.

Design of a Precise Prevention and Control Plan for the Cardio-cerebrovascular Diseases Based on Electronic Medical Records / 医学信息学杂志

Purpose/Significance Based on big data,a cardiovascular and cerebrovascular electronic medical record(EMR)analy-sis platform is developed.By utilizing imaging data analysis techniques and clinical document analysis techniques,the platform provides patients with precise diagnosis,treatment plans,scientific administration,prognosis prediction,smart health education prescriptions and other precise services.Method/Process The medical ontology,knowledge rules and knowledge graph for cardiovascular and cerebrovas-cular diseases are developed and constructed by using Protégé.On the basis of constructing a knowledge graph,a knowledge base for clinical diagnosis,treatment,pathological analysis and prognosis judgment of cardiovascular and cerebrovascular diseases is formed.A EMR analysis platform for cardiovascular and cerebrovascular diseases is designed based on the knowledge base.Result/Conclusion The designed cardiovascular and cerebrovascular EMR analysis platform is conducive to providing personalized diagnosis and treatment plans for different populations,and providing patients with various precise diagnosis and treatment services.

A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.

Evaluation of ICUs and weight of quality control indicators: an exploratory study based on Chinese ICU quality data from 2015 to 2020 / 医学前沿

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.

Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.

Single-cell transcriptomic atlas of mouse cochlear aging

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.

Evaluation of ICUs and weight of quality control indicators: an exploratory study based on Chinese ICU quality data from 2015 to 2020 / 医学前沿

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.

Meloxicam Inhibits Hepatocellular Carcinoma Progression and Enhances the Sensitivity of Immunotherapy via the MicroRNA-200/PD-L1 Pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) has become the sixth most common cancer and the third leading cause of cancer death in the world. Although the research achievements of tumor immunotherapy have made great progress, especially the combination of immune targeted therapy has achieved good curative effect in HCC, but only a few patients are suitable for it and benefit from it. Therefore, there is an urgent need to find new effective drugs to treat HCC or to enhance the sensitivity of immunotherapy. METHODS: Meloxicam, a COX2 inhibitor with strong anti-HCC potential, was screened from 800 small molecules approved by FDA. The effect of meloxicam on the proliferation, invasion, and migration of HCC cell lines was evaluated by cell phenotype analysis. The Human Protein Atlas database and the TISCH database were used to analyze COX2 data in single cells, and the TISIDB database was used to analyze the correlation of COX2 with immune function. The real-time quantitative polymerase chain reaction (qRT-PCR) and western blot were used to evaluate the level of PD-L1 and CD155 in HCC cell lines treated with meloxicam and further explore its possible mechanism. In vivo experiments were applied to verify the effect of meloxicam combined with anti-PD1 therapy on HCC tumor growth in mice. RESULTS: Meloxicam can significantly inhibit the proliferation, invasion, and migration of HCC cells. The TISIDB database indicated that the COX2 was strongly associated with immunoinhibitors and immunostimulators. Meloxicam upregulated the level of PD-L1 in HCC cell lines and animal models. In terms of mechanism, meloxicam inhibited microRNA-200, thereby upregulating PD-L1. In vitro experiments showed that both meloxicam and anti-PD1 had inhibitory effects on the growth of HCC tumors. Compared with meloxicam and anti-PD1 alone, the combination therapy showed stronger antitumor properties. Immunohistochemical analysis confirmed that meloxicam enhanced the antitumor immune activity in the tumor microenvironment. CONCLUSION: Our study showed meloxicam inhibited HCC progression and enhanced the sensitivity of immunotherapy via the microRNA-200/PD-L1 pathway.

Influencing factors for positive results in early postpartum depression screening / 中华围产医学杂志

Objective:To investigate the risk factors associated with the positive results of early postpartum depression screening.Methods:This study involved 2 889 women who were negative in prenatal depression screening and delivered in the Maternal and Child Health Hospital of Hubei Province from 1 March to 30 April 2021. The Edinburgh Postnatal Depression Scale (EPDS) score, Adaptation Partnership Growth Affection Resolve (APGAR) score, and related living habits of the enrolled subjects were investigated on the 5th to 7th day after delivery. All patients were divided into two groups with 2 354 in the negative group (EPDS score<13) and 535 in the positive group (EPDS score≥13), based on the EPDS scores at 5 to 7 days postpartum. Chi-square test, trend Chi-square test, and rank-sum test were used for univariate analysis. Risk factors associated with positive depression screening were analyzed using binary logistic regression. Results:Univariate analysis suggested that there were statistically significant differences between the two groups in maternal personality, marital relationship, family functioning, sleep quality during pregnancy, smoking and drinking habits during pregnancy, prenatal EPDS score, mode of delivery, whether or not to have intrapartum cesarean section and forceps delivery, duration of labor in vaginal delivery, the proportions of puerperae and neonates who were transferred to intensive care unit (ICU), twin pregnancy, placenta previa, abnormal fetal position, premature birth, postpartum hemorrhage, and having three or more complication (all P<0.05). Binary logistic regression analysis suggested that extravertion ( OR=0.483, 95% CI:0.369-0.632), good marital relations ( OR=0.540, 95% CI:0.422-0.691) and good sleep during pregnancy ( OR=0.340, 95% CI:0.245-0.471) were protective factors for early postpartum depression, while introversion ( OR=1.632, 95% CI:1.275-2.088), poor marital relations ( OR=3.495, 95% CI: 1.946-6.276), moderate family dysfuntion ( OR=4.038, 95% CI:2.667-6.114) and severe family dysfunction ( OR=20.234, 95% CI: 2.446-167.364), smoking ( OR=2.071, 95% CI:1.315-3.263) and drinking during pregnancy ( OR=1.924, 95% CI:1.142-3.243), twin pregnancy ( OR=2.680, 95% CI:1.435-5.005), placenta previa ( OR=2.567, 95% CI:1.316-5.009), having three or more complications ( OR=1.876, 95% CI: 1.316-2.674), forceps delivery ( OR=3.043, 95% CI:1.185-7.816), intrapartum cesarean section ( OR=1.917, 95% CI:1.232-2.982), postpartum hemorrhage ( OR=1.668, 95% CI:1.069-2.604), and postpartum ICU admission ( OR=2.601, 95% CI: 1.112-6.086) were risk factors for early postpartum depression. Conclusions:Healthy living habits, and good mood contribute to decreasing postpartum depression in pregnant women. Education for parturients with serious illness or complications should be strengthened to help develop a proper understanding of the disease.