Development and validation of the Salt Intake-Related Knowledge, Attitude, and Practice Questionnaire for Malaysian adults

@#Introduction: Malaysian adults consume excessive amounts of salt daily, which could lead to hypertension. Understanding knowledge, attitudes, and practices (KAP) surrounding salt intake is crucial for designing effective interventions to reduce excessive consumption and its associated health risks. Therefore, this study aimed to adapt an existing salt intake-related KAP questionnaire that was previously employed in a local population-based survey and to validate and test its reliability. Methods: This cross-sectional study comprised two phases: (1) adaptation, content validation (CV), and face validation (FV); (2) pilot testing and reliability testing. CV and FV involved a total of seven experts and ten Malaysian adults from the Klang Valley, respectively. Pilot testing involved 139 Malaysian adults to determine the questionnaire’s reliability. Content validity index (CVI) and Face validity index (FVI) values were calculated to analyse CV and FV. Reliability of each domain was analysed by obtaining Cronbach’s alpha (α) values. Results: A self-administered questionnaire comprising six items each for knowledge, attitude, and practice was developed. The questionnaire demonstrated acceptable item-level CVI (I-CVI) and item-level FVI (I-FVI) values of at least 0.83, indicating that the items were relevant, clear, non-ambiguous, and simple. Reliability test showed acceptable α values of at least 0.70 for each domain, suggesting that the questionnaire was reliable. Conclusion: This tool could be considered valid and reliable for assessing the level of KAP towards salt intake among adults in Malaysia.

Antibiofilm activity of polyethylene glycol-quercetin nanoparticlesloaded gelatin-N,O-carboxymethyl chitosan composite nanogels against Staphylococcus epidermidis

Background@#Biofilms, such as those from Staphylococcus epidermidis, are generally insensitive to traditional antimicrobial agents, making it difficult to inhibit their formation. Although quercetin has excellent antibiofilm effects, its clinical applications are limited by the lack of sustained and targeted release at the site of S. epidermidis infection. @*Objectives@#Polyethylene glycol-quercetin nanoparticles (PQ-NPs)-loaded gelatin-N,Ocarboxymethyl chitosan (N,O-CMCS) composite nanogels were prepared and assessed for the on-demand release potential for reducing S. epidermidis biofilm formation. @*Methods@#The formation mechanism, physicochemical characterization, and antibiofilm activity of PQ-nanogels against S. epidermidis were studied. @*Results@#Physicochemical characterization confirmed that PQ-nanogels had been prepared by the electrostatic interactions between gelatin and N,O-CMCS with sodium tripolyphosphate. The PQ-nanogels exhibited obvious pH and gelatinase-responsive to achieve on-demand release in the micro-environment (pH 5.5 and gelatinase) of S. epidermidis.In addition, PQ-nanogels had excellent antibiofilm activity, and the potential antibiofilm mechanism may enhance its antibiofilm activity by reducing its relative biofilm formation, surface hydrophobicity, exopolysaccharides production, and eDNA production. @*Conclusions@#This study will guide the development of the dual responsiveness (pH and gelatinase) of nanogels to achieve on-demand release for reducing S. epidermidis biofilm formation.

Sleep-improving mechanisms of Jiu Wei Bu Xue Oral Liquid on regulating Glu/GABA balance in insomnia rats based on network pharmacology and experimental verification / 药学学报

This study aimed to investigate the mechanism of Jiu Wei Bu Xue Oral Liquid on insomnia rats combining the methods of network pharmacology, molecular docking and experimental verification. UPLC-Q-TOF-MS/MS method and TCMIP, TCMSP databases were used to collect the ingredients and targets of Jiu Wei Bu Xue Oral Liquid. Protein-protein interactions and network analysis were performed to screen the key network targets and putative active ingredients of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia, and then following by biological function and KEGG pathway analysis. Then binding ability for key network targets and putative active ingredients were predicted with molecular docking. The prediction targets were validated in para-chlorophenylalanine (PCPA) induced insomnia rats with administration of Jiu Wei Bu Xue Oral Liquid (2, 4, 8 mL·kg-1) for 7 days. Pentobarbital sodium induced sleeping test were performed to evaluate the synergistic sleep-aiding effect of Jiu Wei Bu Xue Oral Liquid. Then glutamic acid (Glu), γ-aminobutyrate (GABA) content and glutamate decarboxylase 1 (GAD67) activity in hypothalamus or hippocampus were evaluated, and the expressions of GAD67, γ-aminobutyric acid receptor subunit α1 (GABRA1) and γ-aminobutyric acid receptor subunit β2 (GABRB2) in hippocampus were detected by qRT-PCR and Western blot methods. Animal experiments were approved by the Institutional Committee on Animal Care of Guangxi Institute of Chinese Medicine & Pharmaceutical Science (the number of permission: 2022060802). Results showed that 16 key network targets and 16 putative active ingredients were obtained by analyzing the herbs-ingredients-targets network of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia. Network pharmacology and molecular docking all indicated these active ingredients, for example atractylenolide Ⅲ, showed better binding ability with GABRA1 and GABRB2. Animal study indicated that, compared to PCPA-induced insomnia model, Jiu Wei Bu Xue Oral Liquid remarkably shortened the sleeping latency and increased the sleeping duration, increased GAD67 activity and the production of GABA in hippocampus of insomnia rats, as well as the expressions of GAD67, GABRA1 and GABRB2, while decreased Glu content in hypothalamus, leading to decreasing of Glu/GABA ratio and recovery of Glu-GABA balance. These results indicated that Jiu Wei Bu Xue Oral Liquid improved insomnia symptoms and helped maintain the Glu-GABA balance within hypothalamus and hippocampus, and reduced the excitatory neurotoxicity within brain. The mechanism may due to the elevation of GAD67 expression and enzyme activity, and the enhancement of type-A GABA receptor (GABAAR)-mediated neurons inhibition.

Analysis of 4 children with DYNC1H1 gene related spinal muscular atrophy with lower extremity predominant 1 / 中华儿科杂志

Objective: To investigate the clinical features and gene variation characteristics of children with dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene associated spinal muscular atrophy with lower extremity predominant (SMALED) 1. Methods: The clinical data of 4 SMALED1 children admitted to Peking University First Hospital from December 2018 to May 2021, who were found to have pathogenic variation of DYNC1H1 gene through genetic testing, except for other genes known to be related to motor retardation, were retrospectively summarized to analyze the phenotype and genotype characteristics. Results: There were 3 males and 1 female. The age of onset was 1 year, 1 day, 1 day and 4 months, respectively. The age of diagnosis was 4 years and 10 months, 9 months, 5 years and 9 months, and 3 years and 1 month, respectively. The clinical manifestations were muscle weakness and muscular atrophy of lower limbs, 2 cases with foot deformity, 1 case with early non progressive joint contracture, 1 case with hip dislocation and 1 case with mental retardation. De novo heterozygous missense variations in DYNC1H1 gene were found in all 4 children. According to the rating of American College of medical genetics and genomics, they were all possible pathogenic and pathogenic variations, with p.R598C, p.P776L, p.Y1109D variations had been reported, and p.I1086R variation had not been reported. Conclusions: For those with unexplained lower limb muscle weakness, muscle atrophy, joint contracture and foot deformity, upper limb motor ability related retention, with or without mental retardation, as well as the motor ability progresses slowly, it is necessary to consider the possibility of SMALED1 and the detection of DYNC1H1 gene when necessary.

CiteSpace knowledge map of research hotspots and frontiers of Polygalae Radix / 中国中药杂志

In this study, the Web of Science and China National Knowledge Infrastructure(CNKI) were searched comprehensively for the literature about the research on Polygalae Radix. After manual screening, 1 207 Chinese articles and 263 English articles were included in this study. Excel was used to draw the line chart of the annual number of relevant publications. CiteSpace 6.1.R3 was used for the visual analysis of author cooperation, publishing institutions, keyword co-occurrence, keyword clustering, and bursts in the research on Polygalae Radix. The results showed that the number of articles published in Chinese and English increased linearly, which indicated the rising research popularity of Polygalae Radix. WANG J and LIU X were the authors publishing the most articles in Chinese and English, respectively. Shanxi University of Chinese Medicine and Chinese Academy of Medical Sciences were the research institutions with the largest number of Chinese and English publications in this field, respectively. The institutions publishing the relevant articles in English formed a system with the Chinese Academy of Medical Sciences as the core. According to the keywords, the research hotspots of Polygalae Radix included variety selection and breeding, quality standard, extraction and identification of active chemical components, prescription compatibility, processing, clinical medication rules, and pharmacological mechanism. The research frontiers were the molecular mechanisms of Polygalae Radix and its active components in exerting the protective effect on brain nerve, regulating receptor pathways, alleviating anxiety and Alzheimer's disease, as well as data mining and clinical medication summary. This study has reference significance for the topic selection and frontier identification of the future research on Polygalae Radix.

Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses / 中华儿科杂志

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

Dihydroergotamine ameliorates synaptic atrophy in Alzheimer’s disease states and its effect on cognitive function / 中国药科大学学报

@#Studies suggest that synaptic damage is closely associated with cognitive dysfunction, and lemur tyrosine kinase 1 (LMTK1) is a key kinase that affects synaptic growth. Dihydroergotamine (DHE) is an ergot alkaloid derivative with high biological activity, which could regulate cognition, memory processing and motor control.This study aims to investigate the effect of DHE on synapse atrophy and plasticity as well as cognition in Alzheimer’s disease (AD) model animals.SAMR1 mice were selected as control group (n = 12).SAMP8 mice were randomly divided into 3 groups (n = 12 for each group):AD group, DHE low-dose group and high-dose group.The DHE groups were injected DHE intraperitoneally daily for 8 weeks.Immunofluorescence experiments, Golgi staining experiment, electrophysiological experiment, Morris water maze experiment (MWM) and Western blot experiment were conducted to investigate the effect of DHE on synaptic morphology, synaptic plasticity, cognitive function as well as the phosphorylation level of LMTK1 downstream TBC1D9B in AD model mice.Subsequently, the LMTK1 silencing and overexpression cells were constructed.Immunofluorescence experiments were used to study the effect of DHE on synaptic length of nerve cell after LMTK1 silencing and overexpression.In the hippocampus of AD mice, the postsynaptic marker PSD95 was significantly increased after DHE administration, which suggested that DHE could increase the synaptic density. In Golgi staining experiment, synaptic atrophy was observed in the hippocampal of AD mice, which could be improved by high-dose DHE.Compared with normal mice, the long-term potentiation (LTP) level of AD model mice was significantly reduced (P < 0.000 1), DHE could increase LTP significantly.The MWM experiment further showed that DHE could improve cognitive function in AD mice.WB experiments showed that the level of P-LMTK1 in the hippocampus of AD mice increased significantly, and the level of downstream P-TBC1D9B decreased significantly after DHE administration.Cell immunofluorescence experiments in vitro had shown that DHE significantly improved synaptic atrophy in overexpressed C17.2 cells, while its improvement disappeared when LMTK1 was silenced. This research suggests DHE may improve synaptic atrophy and cognitive dysfunction in AD by targeting on LMTK1.

A retrospective analysis of 2 601 cases of in-hospital cardiac arrest / 中华急诊医学杂志

Objective:To study the epidemiological data of 2601 in-hospital cardiac arrest (IHCA) patients in Renmin Hospital of Wuhan University from October 2019 to December 2021, describe the characteristics of IHCA, and discuss the early warning and prevention of IHCA.Methods:The patients were divided into cardiopulmonary resuscitation (CPR) group and DNAR group according to resuscitation implementation, and ROSC group and non- ROSC group according to resuscitation results. The characteristics of IHCA were retrospectively analyzed.Results:The male to female ratio of IHCA was 1.9, and the age was (67.05±16.23) years old. Acid-base imbalance/electrolyte disturbance, pulmonary infection, respiratory failure, and hypertension were the top four pre-cardiac arrest conditions, which occured in more than half of patients. The ROSC rate of all IHCA patients undergoing CPR was 24.3%, and the success rate of resuscitation in ICU patients was significantly higher than that in the general ward. The ROSC rate decreased significantly when IHCA occurred between 0 and 7 o 'clock.Conclusions:IHCA occurs mostly in elderly men. Early identification of risk factors before cardiac arrest is beneficial to early warning of cardiac arrest and improve the treatment rate of IHCA.

Fabrication of self-healing injectable hyaluronic acid hydrogel for promoting angiogenesis / 上海交通大学学报（医学版）

Objective·To construct a self-healing injectable hyaluronic acid(HA)-based hydrogel(HAPD-Cu)and investigate the effects of different copper ions on the properties of the hydrogel and its vasogenic effiicacy to evaluate its feasibility for clinical wound healing.Methods·Bisphosphonated hyaluronic acid(HAPD)was prepared via a blue-light mediated thiol-ene click reaction between thiolated hyaluronic acid(HASH)and acrylated bisphosphonate(Ac-PD)in the presence of photoinitiator 2959.Then,HAPD was further interacted with Cu2+through metal coordination to prepare HAPD-Cu hydrogels with different Cu2+concentrations,i.e.HAPD-Cu1,HAPD-Cu2,HAPD-Cu3 and HAPD-Cu4.The molecular structures of HASH,Ac-PD,HAPD and HAPD-Cu were verified with 1HNMR and FTIR.Microscopic morphology of HAPD-Cu was observed under SEM.The shear-thinning and self-healing properties of HAPD-Cu were verified by rheometer.The Cu2+release from HAPD-Cu was determined with ICP.Live-dead staining and CCK-8 assay were applied to evaluate the biocompatibility of HAPD-Cu.The in vitro vasculogenic activity of HAPD-Cu was determined by a tubule-forming assay with human umbilical vein vascular endothelial cells and the in vivo vasculogenic activity of HAPD-Cu was assessed by CD31 tissue staining.A rat wound defect model was established in vitro to evaluate its actual repair effect.Results·The preparation of the materials was demonstrated through chemical qualitative and quantitative analytical means.In vitro studies showed that all HAPD-Cu with a loose porous internal structure exhibited outstanding self-healing,injectability and degradability,with a one-week degradation cycle and abrupt release behavior,which can meet the needs of wound healing cycle.All HAPD-Cu showed good biocompatibility except HAPD-Cu4,due to its high Cu2+concentrations.Moreover,its angiogenic effect in vitro or in vivo was enhanced with increasing Cu2+concentrations within the permissible Cu2+concentration range.In vitro wound model experiments also showed that the HAPD-Cu hydrogel significantly promoted wound healing compared with the control group.Conclusion·HAPD-Cu hydrogel constructed via the metal coordination shows excellent shape plasticity,allowing the filling of defective sites in a minimally invasive form,and the release of Cu2+greatly facilitates the establishment of early vascular networks,with giant potential for use in the repair of clinically irregular wounds.

Diagnostic value of ultrasound-based hemodynamic examination of superior mesenteric artery for acute suppurative appendicitis / 医疗卫生装备

Objective To investigate the characteristics of hemodynamic changes in superior mesenteric artery(SMA)of patients with acute suppurative appendicitis(ASA)to facilitate the diagnosis of ASA.Methods Ninety-three ASA patients diagnosed by ultrasound and confirmed by pathology in some hospital from January 2015 to December 2022 were enrolled into an ASA group,and 88 soldiers without abnormalities in the annual physical examination at the hospital in 2021 were divided into a control group,and the two groups were compared in terms of SMA hemodynamic indexes including peak systolic velocity(PSV),end diastolic velocity(EDV),resistance index(RI)and systolic/diastolic ratio(S/D).The statistically significant data of the above indexes were selected to draw the ROC curve and obtain the cut-off values.SPSS 22.0 software was used for statistical analysis.Results The PSV was(212±69)cm/s in the ASA group and(118±26)cm/s in the control group,with statistically significant differences(P＜0.05),and the two groups had the differences in EDV,RI,and S/D not statistically significant(P＞0.05).The ROC curve was plotted based on the PSV data,and a cutoff value of 238 cm/s was obtained with an AUC of 0.714.Conclusion Ultrasound examination of SMA hemodynamic changes in suspected ASA patients facilitates a definitive diagnosis and is of guidance for clinical treatment.[Chinese Medical Equipment Journal,2023,44(10):64-67]

Clinical and imaging features of acute encephalopathy with biphasic seizures and late reduced diffusion in children / 中华儿科杂志

Objective: To explore the clinical and imaging features of acute encephalopathy with biphasic seizures and late reduced diffusion(AESD) in children. Methods: For the case series study, 21 children with AESD from Peking University First Hospital, Provincial Children's Hospital Affiliated to Anhui Medical University, Children's Hospital of Fudan University, and Shanxi Children's Hospital who were diagnosed and treated from October 2021 to July 2023 were selected. Clinical data were collected to summarize their clinical information, imaging, and laboratory tests, as well as treatment and prognostic characteristics. Descriptive statistical analysis was applicated. Results: Of the 21 cases with AESD, 11 were males and 10 were females, with the age of onset of 2 years and 6 months (1 year and 7 months, 3 years and 6 months). Of the 21 cases, 18 were typical cases with biphasic seizures. All typical cases had early seizures within 24 hours before or after fever onset. Among them, 16 cases had generalized seizures, 2 cases had focal seizures, and 7 cases reached the status epilepticus. Of the 21 cases, 3 atypical cases had late seizures in biphasic only. The late seizures in the 21 cases occurred on days 3 to 9. The types of late seizures included focal seizures in 12 cases, generalized seizures in 6 cases, and both focal and generalized seizures in 3 cases. Diffusion-weighted imaging (DWI) test on days 3 to 11 showed reduced diffusion of subcortical white matter which was named "bright tree sign" in all cases. The diffuse cerebral atrophy predominantly presented in the front-parietal-temporal lobes was found in 19 cases between day 12 and 3 months after the onset of the disease. Among 21 cases, 20 had been misdiagnosed as autoimmune encephalitis, central nervous system infection, febrile convulsions, posterior reversible encephalopathy syndrome, acute disseminated encephalomyelitis, and hemiconvulsion-hemiplegia-epilepsy syndrome. All the cases received high-dose gammaglobulin and methylprednisolone pulse therapy with poor therapeutic effect. By July 2023, 18 cases were under follow-up. Among them, 17 cases were left with varying degrees of neurologic sequelae, including 11 cases with post-encephalopathic epilepsy; 1 recovered completely. Conclusions: AESD is characterized by biphasic seizures clinically and "bright tree sign" on DWI images. Symptomatic and supportive treatments are recommended. The immunotherapy is ineffective. The prognosis of AESD is poor, with a high incidence of neurological sequelae and a low mortality.

The inhibitory effect of Averrhoa carambola DMDD on high glucose-induced endoplasmic reticulum stress IRE1α pathway and inflammation in renal tubular epithelial cell HK-2 / 中国药理学通报

Aim To investigate the inhibition effect of 2-dodecyl-6-methoxycyclohexa-2, 5-diene-l, 4-dione ( DMDD) on renal tubular epithelial cell HK-2 endo¬plasmic reticulum stress and inflammatory responses induced by high glucose. Methods HK-2 cells were cultured in vitro and divided into normal group, high glucose group, endoplasmic reticulum stress inhibitor 4-PBA group (5 mmoL • L ) , DMDD high, medium and low dose groups (8,4,2 μmol • L

Mechanism of effect of Zhuang medicine Semiliquidambar cathayen. Sis Chang on depression inflammation based on network pharmacology, molecular docking and animal experiments / 中国药理学通报

Aim To predict the key targets and signaling pathways of Semiliquidambar cathayen. sis Chang (JLBFH) by network pharmacology and molecular docking,etc, then to explore the mechanism of JLBFH' s effect on inflammatory response to depression through reserpine-induced depression rat model. Methods The target of drug and disease was predicted by network pharmacological database, protein interaction network diagram was constructed, biofunctional enrichment and pathways were analyzed, and molecular docking prediction was performed by AGFR software. Based on reserpine-induced depression, the role of JLBFH in depression inflammation was verified by behavior, molecular biology and pathological examination, and so on. Results A total of 13 active ingredients were screened, 11 key targets of JLBFH modulation of depression were selected, and the bioenrichment results were mainly related to cognition, prominent plasticity regulation, etc. The pathways were mainly related to Rapl signaling pathway, Toll-like receptor signaling pathways. The results of validation experiments showed that high and low doses of JLBFH extract significantly shortened the forced swimming immobility time in mice, markedly reduced the retention time in the circle of rats, increased serum levels of 5-HT and DA, decreased serum levels of IL-6, improved inflammatory infiltration in the prefrontal cortex, decreased brain tissue levels of IL-6,IL-1β ,TNF-α mRNA expression,and increased AKT1 mRNA expression in brain tissue. Conclusions The present study reveals that JLBFH can exert antidepressant effects through multi-component, multi-target and multi-pathway, and the experimental validation results show that JLBFH can improve the d¬pression-like symptoms by improving the inflammatory response of depression through TOLL-like signaling pathway.

Up-regulated miR-452-5p suppressed the expression of RORα and promoted the proliferation and migration of HCC cells / 中国药科大学学报

@#To study the prognosis-related regulation mechanism of miR-452-5p and its influence on the proliferation and migration of hepatocellular carcinoma (HCC) cells, liver hepatocellular carcinoma (LIHC) dataset in The Cancer Genome Atlas (TCGA) was used to validate the differential expression of miR-452-5p and perform the Kaplan-Meier analysis of overall survival (OS).Target genes of miR-452-5p from TargetscanHuman and miRDB databases were predictived; and differentially expressed genes(DEGs) and weighted gene co-expression network analysis (WCGNA) were completed with GSE14520.Lipofectmine-2000 was used to transfect miR-452-5p mimics, mimics negative control, miR-452-5p inhibitor and inhibitor negative control into Huh7 cells,respectively.The mRNA and protein expression level of RORα in 4 groups were determined by RT-qPCR and Western blot.CCK-8 assay and Transwell assay were conducted to testify the capabilities of proliferation and migration.The regulation between miR-452-5p and RORα was confirmed by the dual luciferase reporter assay.After analysis in the TCGA-LIHC dataset, miR-452-5p had higher expression in HCC tissue than that in normal tissue, which was also associated with a shorter OS.RORα and LAMC1 were discriminated by intersecting of DEGs, WGCNA module genes, and predictive target genes.Survival analysis exhibited that dysregulation of RORα was significantly related to the OS.Overexpression of miR-452-5p in HCC cells suppressed the expression of RORα both in mRNA and protein, and also enhanced the viability and migration of HCC cells.The results of the dual luciferase reporter assay showed that miR-452-5p targeted 3′UTR of RORα.Up-regulated miR-452-5p inhibited the expression of RORα, facilitated the proliferation and migration of HCC cells, and promoted the progression and poor prognosis of HCC.

In-hospital mortality and related risk factors after knee replacement in China: based on national hospital quality monitoring system data / 中华骨科杂志

Objective:To estimate in-hospital mortality after knee replacement (KR) and to assess its trend and risk factors in China.Methods:We included patients undergoing KR in the Hospital Quality Monitoring System in China (2013-2019) to estimate in-hospital mortality after KR and assessed relation of patient's and hospital's characteristics (year of surgery, age, gender, marital status, primary indication, Charlson comorbidity index, geographic location, hospital type, hospital volume of KR, and surgery type) to in-hospital mortality using multivariable Poisson regression.Results:The annual amount of KR has increased from 20 307 in 2013 to 35 757 in 2019, and has maintained an upward trend for 7 years. The mean age of patients having KR increased from 64.9 years in 2013 to 66.6 years in 2019. Of the total 218 923 KRs, 63 deaths (0.29‰) occurred within 30 days before discharging. Older age was associated with higher in-hospital mortality ( P for trend <0.001). Male gender had higher incidence of in-hospital mortality compared with female [relative risk (RR), 2.5; 95% CI: 1.5, 4.1]. Single marital status was associated with higher, albeit non-statistically significant, in-hospital mortality than married patients (RR, 2.1; 95% CI: 0.9, 4.6). Higher Charlson comorbidity index was associated with increased risk of in-hospital mortality ( P for trend <0.001). Risk of in-hospital mortality decreased with more hospital-year knee replacement surgeries ( P for trend <0.001). In-hospital mortality varied by geographic regions, with the lowest mortality in East region (0.16‰), followed by South-West (0.31‰), South-Central (0.31‰), North region (0.33‰), North-West (0.54‰) and North-East (0.59‰). Conclusion:In-hospital mortality after KR in China was relatively low. Older age, male gender, higher Charlson comorbidity index and lower hospital-year knee replacement surgeries were risk factors for in-hospital mortality. The mortality varied greatly according to the geographic location of hospital.

A family of hereditary protein S deficiency with the onset of pulmonary embolism and literature review / 中华儿科杂志

Objective: To explore the clinical characteristics and genotype of PROS1 gene related hereditary protein S deficiency (PSD) with the onset of pulmonary embolism in children. Methods: A family with pulmonary embolism was diagnosed as hereditary PSD in the Department of Pediatrics of Peking University First Hospital in November 2020, and the clinical data, including clinical manifestations, laboratory tests, imaging and genetic results, were collected for a retrospective research. The family members were also screened for protein S activity and PROS1 gene mutations. A literature search with "PROS1" "protein S deficiency" "homozygous" and "complex heterozygous" as key words was conducted at PubMed, China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform (up to October 2021). Case reports of patients with PROS1 gene homozygous or complex heterozygous variants and related clinical features, protein S activity, and genotype were reviewed and analyzed. Results: The proband, a 14-year-old girl, was admitted to the hospital for a 9-day history of coughing and a 4-day history of chest pain in November 2020. After admission, laboratory tests showed that D-dimer was 8.38 mg/L (reference:<0.24 mg/L). An urgent CT pulmonary angiography confirmed bilateral pulmonary embolism and right lower pulmonary infarction, while an ultrasonography showed deep vein thrombosis in her left leg. Further examination revealed that protein S activity was less than 10%. The proband's second sister, a 12-year-old girl, was admitted to the hospital in December 2020. Her protein S activity was 8% and an ultrasonography showed deep vein thrombosis in her right leg. The protein S activity of the proband's father and mother were 36% and 26%, respectively. Trio-whole-exome sequencing detected compound heterozygous PROS1 gene variants (c.-168C>T and c.200A>C (p.E67A)) for the proband and her second sister, that were inherited from her father and mother, respectively. The proband's third sister's protein S activity was 28%; she and the proband's grandfather both carried c.200A>C (p.E67A) variants. The proband and her younger sister were treated with rivaroxaban and responded well during the 3-month follow-up. A total of 1 Chinese report in literature and 18 English literature were retrieved and 14 patients with protein S deficiency caused by homozygous or complex heterozygous variants of PROS1 gene were enrolled, including 8 male and 6 female patients. The ages ranged from 4 days to 35 years. Three patients experienced fulminant purpura or severe intracranial hemorrhage in early neonatal-period, while the remaining 11 patients developed venous thromboembolism in adolescence. Protein S activity was examined in 11 patients, and all showed less than 10% of activity. Missense variants was the most common type of gene variants. Conclusions: For children with pulmonary embolism, if there are no clear risk factors for thrombosis, hereditary protein S deficiency should be considered, and protein S activity should be examined before oral anticoagulant drugs. If protein S activity is less than 10%, protein S deficiency caused by homozygous or complex heterozygous variants should be considered.

Heartbeat-aware convolutional neural network for R-peak detection of wearable device ECG data / 南方医科大学学报

OBJECTIVE@#To develop a method for R-peak detection of ECG data from wearable devices to allow accurate estimation of the physiological parameters including heart rate and heart rate variability.@*METHODS@#A fully convolutional neural network was applied to predict the R-peak heatmap of ECG data and locate the R-peak positions. The heartbeat-aware (HA) module was introduced to enable the model to learn to predict the heartbeat number and R-peak heatmap simultaneously, thereby improving the capability of the model for extraction of the global context. The R-R interval estimated by the predicted heartbeat number was adopted to calculate the minimum horizontal distance for peak positioning. To achieve real-time R-peak detection on mobile devices, the deep separable convolution was adopted to reduce the number of parameters and the computational complexity of the model.@*RESULTS@#The proposed model was trained only with ECG data from wearable devices. At a tolerance window interval of 150 ms, the proposed method achieved R peak detection sensitivities of 100% for both wearable device ECG dataset and a public dataset (i.e. LUDB), and the true positivity rates exceeded 99.9%. As for the ECG signal of a 10 s duration, the CPU time of the proposed method for R-peak detection was about 23.2 ms.@*CONCLUSION@#The proposed method has good performance for R-peak detection of both wearable device ECG data and routine ECG data and also allows real-time R-peak detection of the ECG data.

Analgesic Effects of Two Types of Spinal Manipulation in Acute Lumbar Radiculopathy Model Rats / 中国结合医学杂志

OBJECTIVE@#To compare the analgesic effects of two types of spinal manipulation (SM) in acute lumbar radiculopathy (ALR) model rats induced by self-transplantation of autologous nucleus pulposus (ANP), and clarify the therapeutic mechanism.@*METHODS@#Totally 108 male Sprague-Dawley rats were randomly divided into 6 groups by a random number table (18 rats in each group), including a blank group with no interference, a sham operation group with a surgery by making a local soft tissue incision on the left side of L5-6 vertebral segment, a model group with ALR of L5 extraforaminal nerve by ANP self-transplantation without other interference, a sham manipulation (SMA) group with simulating physical rotation, as well as a mobilization (MOB) group with simulating low-velocity and variable-amplitude rotation and a manipulation (MAN) group with simulating high-velocity and low-amplitude rotation. The interventions in SMA, MOB, and MAN groups started 1 day after modeling followed by another 5 treatments at days 3, 5, 8, 10 and 12. Rats in the other 3 groups did not receive any special intervention. Behavioral pain tests of 50% mechanical pain withdrawal threshold (50% PWT) and paw withdrawal latency (PWL) were conducted 1 day before operation followed by another 10 tests on days 1-7, 10, 12 and 14. Immunohistochemical expression of nitric oxide synthase (NOS) was investigated on days 5 and 12 after operation.@*RESULTS@#After 3 experimental SM interventions, 50% PWT and PWL were higher in the MAN group than the SMA group on days 6 and 7, and higher on days 10, 12 and 14 postoperatively (P<0.05 or P<0.01), while the same indices were significantly higher in the MOB group than MAN group on days 1-4 (P<0.05 or P<0.01). The expression of NOS was lower in the MAN and MOB groups than SMA group on day 12 postoperatively (P<0.01).@*CONCLUSIONS@#Both manipulation and mobilization produced better results than sham interference in relieving pain by reducing neuroinflammation possibly. At the early period, compared with manipulation, mobilization presented less sensitive response to pain until later visit. SM may inhibit the overexpression of NOS, thereby alleviating severe radiculopathy.

Total Flavones of Spatholobi Caulis Regulate Hippocampal Neuroplasticity in Depressed Rats Through CREB/BDNF Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of total flavones of Spatholobi Caulis （TFSC） against depression in rats. MethodThe fifty KM mice were randomly divided into the normal group and high-， medium-， and low-dose （1， 0.5， 0.25 g·kg-1） TFSC groups and gavaged with the corresponding drugs for 12 successive days. One hour after the last administration， the immobility time in forced swimming test and tail suspension test was recorded. The SD rats were randomly divided into the normal group， model group， fluoxetine （5 mg·kg-1） group， and high- and low-dose （1， 0.25 g·kg-1） TFSC groups. Following the exposure of rats to two different kinds of stimuli daily for inducing chronic unpredictable stress， they were administered with the corresponding drugs for 21 d. After the experiment， the levels of serum neurotransmitters and inflammatory factors in rats were detected by enzyme-linked immunosorbent assay （ELISA）. The changes in hippocampal neurons of rats were observed by hematoxylin-eosin （HE） and Nissl staining. The mRNA expression levels of nuclear factor-κB （NF-κB） and tumor necrosis factor-α （TNF-α） in the hippocampus of rats were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expression levels of cAMP-response element binding protein （CREB）， phosphorylated CREB （p-CREB）， and brain-derived neurotrophic factor （BDNF） in hippocampal tissues by Western blot. ResultCompared with the normal group， TFSC significantly shortened the immobility time of mice in tail suspension and swimming tests （P<0.05）. Compared with the normal group， the model group exhibited reduced sucrose intake and wilderness activity （P<0.01）， decreased 5-HT， DA， NE （P<0.05， P<0.01）， MAO， IL-6， TNF-α （P<0.05， P<0.01）， damaged neurons， increased mRNA levels of TNF-α and NF-κB （P<0.01）， and down-regulated BDNF and CREB protein expression （P<0.05）. Compared with the model group， TFSC significantly enhanced sucrose intake and wilderness activity of rats （P<0.05）， increased the serum 5-HT， DA and NE （P<0.05， P<0.01）， and decreased the serum MAO， IL-6， and TNF-α （P<0.05， P<0.01） as well as NF-κB and TNF-α mRNA expression （P<0.01）， up-regulated the protein expression levels of BDNF and CREB （P<0.01）， and improved the pathological symptoms of hippocampus. ConclusionTFSC improved the hippocampal neurons of rats via CREB/BDNF signaling pathway and reduced depressive pathological damage， thus relieving depression.

Effect of Mahonia bealei Leaf Extract on Inflammation in Depression of Rats via NF-κB/NLRP3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Mahonia bealei leaf extract on depression of rats and the underlying mechanism. MethodThe chemical constituents of the extract were analyzed by HPLC-MS/MS. Forced swimming test and tail suspension test were carried out to estimate the antidepressant effect. The mice were randomly assigned into the following groups： blank group， positive control group （fluoxetine， 10 mg·kg-1）， and Mahonia bealei leaf extract groups （10， 2.5 g·kg-1）. The gavage lasted for 12 days and the immobility time of the mice in the tests was recorded 1 h after the last administration. Furthermore， to explore the underlying mechanism of the antidepressant effect， we established the rat depression model by intraperitoneal injection with reserpine （0.5 mg·kg-1）. Rats were grouped as follows： blank group， model group， positive control group （fluoxetine， 1.8 mg·kg-1）， and Mahonia bealei leaf extract groups （10， 2.5 g·kg-1）. The gavage， once a day， lasted for 10 consecutive days. The depression of rats was detected by behavioral tests 1 h after the last administration. The levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in serum of rats were detected by enzyme-linked immunosorbent assay （ELISA）. The protein expression of IL-6 and interleukin-1β （IL-1β） in brain tissue was detected by immunohistochemical staining. The protein levels of nuclear transcription factor-κB （NF-κB） and NOD-like receptor protein 3 （NLRP3） in hippocampus of rats were detected by Western blot. ResultSeven chemical constituents， mainly alkaloids， were identified from the extract. Compared with the blank group， Mahonia bealei leaf extract shortened the immobility time of mice in tail suspension and forced swimming tests. Compared with the blank group， the modeling of rat depression increased the blepharoptosis incidence and retention time in circles （P<0.05， P<0.01）， elevated the levels of IL-6 and TNF-α in serum （P<0.05）， and up-regulated the protein levels of IL-6， IL-1β， NF-κB， and NLRP3 in brain tissues （P<0.01）. Compared with the model group， high dose of Mahonia bealei leaf extract shortened the retention time in circles （P<0.05）， lowered the levels of IL-6 and TNF-α in serum （P<0.05， P<0.01）， and down-regulated the protein levels of IL-6， IL-1β， NF-κB， and NLRP3 （P<0.01） in brain tissues. ConclusionMahonia bealei leaf extract had significant antidepressant effect and alleviated the inflammatory response in reserpine-induced rat model of depression， the mechanism of which may be related to the inhibition of NF-κB/NLRP3 signaling pathway.