Relationship between new surrogate marks of insulin resistance and bone mineral content in adolescents / 中国学校卫生

Objective@#To analyze the relationship between new surrogate marks of insulin resistance (IR) and bone mineral content (BMC) in adolescents, and predictive value of the new surrogate marks on low bone mass, so as to provide scientific basis for early identification and prevention of skeletal related diseases in adolescents.@*Methods@#A total of 1 594 adolescents aged 12-18 years in Yinchuan City were selected by convenience sampling and stratified cluster random sampling from September 2017 to September 2020, and triglyceride and glucose index (TyG), triglyceride glucose-body mass index (TyG-BMI) and triglyceride/high density lipoprotein cholesterol (TG/HDL-C) were calculated as new simplified IR index. The correlation between different simplified IR indexes and BMC level was analyzed by partial correlation. Binary Logistic regression was used to analyze the relationship between IR index and low bone mass, and receiver operating characteristic (ROC) curve was constructed to analyze its evaluation effect on low bone mass.@*Results@#After adjusting for confounding factors such as gender, age, smoking, drinking, family history of hypertension, systolic blood pressure (SBP) and diastolic blood pressure (DBP), the new surrogate marks of IR were positively correlated with BMC level (TyG: r =0.11, TyG-BMI: r =0.58, TG/HDL-C: r =0.21, P <0.01). After further adjustment of body mass index (BMI), fat mass (FM) and lean mass (LM), the relationship between IR indexes and BMC turned into negative correlation (TyG: r =-0.20, TyG-BMI: r =-0.18, TG/HDL-C: r=-0.14, P <0.01). After adjusting for confounding factors such as gender, age, smoking, drinking, family history of hypertension, SBP and DBP, Logistic regression results showed that the increase of TyG, TyG-BMI and TG/HDL-C levels reduced the possibility of low bone mass in adolescents (TyG: OR=0.63, 95%CI = 0.40-0.98, TyG-BMI: OR=0.94, 95%CI =0.93-0.96, TG/HDL-C: OR=0.31, 95%CI=0.17-0.58, P <0.01). After adjusting BMI, FM and LM, the above results were completely reversed. Girls with high TyG and TG/HDL-C levels were 4.95 and 4.38 times more likely to have low bone mass than those with low TyG and TG/HDL-C levels (TyG: OR=4.95, 95%CI =1.29- 18.95 , TG/HDL-C: OR=4.38, 95%CI=1.04-18.50, P <0.05). ROC curve showed that TyG-BMI had the best predictive value on low bone mass (AUC=0.80, 95% CI=0.77-0.83, P <0.01).@*Conclusion@#The new surrogate marks of IR in adolescents are negatively correlated with adolescent BMC, of which TyG-BMI is the best for assessing of low bone mass and can serving as a reliable indicator for early identification of low bone mass.

Study on the Role and Mechanism of METTL3 Mediating the Up-regulation of m6A Modified Long Non-coding RNA THAP7-AS1 in Promoting the Occurrence of Lung Cancer / 中国肺癌杂志

BACKGROUND@#Lung cancer is a major threat to human health. The molecular mechanisms related to the occurrence and development of lung cancer are complex and poorly known. Exploring molecular markers related to the development of lung cancer is helpful to improve the effect of early diagnosis and treatment. Long non-coding RNA (lncRNA) THAP7-AS1 is known to be highly expressed in gastric cancer, but has been less studied in other cancers. The aim of the study is to explore the role and mechanism of methyltransferase-like 3 (METTL3) mediated up-regulation of N6-methyladenosine (m6A) modified lncRNA THAP7-AS1 expression in promoting the development of lung cancer.@*METHODS@#Samples of 120 lung cancer and corresponding paracancerous tissues were collected. LncRNA microarrays were used to analyze differentially expressed lncRNAs. THAP7-AS1 levels were detected in lung cancer, adjacent normal tissues and lung cancer cell lines by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The diagnostic value of THAP7-AS1 in lung cancer and the relationship between THAP7-AS1 expression and survival rate and clinicopathological parameters were analyzed. Bioinformatics analysis, methylated RNA immunoprecipitation (meRIP), RNA pull-down and RNA-immunoprecipitation (RIP) assay were used to investigate the molecular regulation mechanism of THAP7-AS1. Cell proliferation, migration, invasion and tumorigenesis of SPC-A-1 and NCI-H1299 cells were determined by MTS, colony-formation, scratch, Transwell and xenotransplantation in vivo, respectively. Expression levels of phosphoinositide 3-kinase/protein kenase B (PI3K/AKT) signal pathway related protein were detected by Western blot.@*RESULTS@#Expression levels of THAP7-AS1 were higher in lung cancer tissues and cell lines (P<0.05). THAP7-AS1 has certain diagnostic value in lung cancer [area under the curve (AUC)=0.737], and its expression associated with overall survival rate, tumor size, tumor-node-metastasis (TNM) stage and lymph node metastasis (P<0.05). METTL3-mediated m6A modification enhanced THAP7-AS1 expression. The cell proliferation, migration, invasion and the volume and mass of transplanted tumor were all higher in the THAP7-AS1 group compared with the NC group and sh-NC group of SPC-A-1 and NCI-H1299 cells, while the cell proliferation, migration and invasion were lower in the sh-THAP7-AS1 group (P<0.05). THAP7-AS1 binds specifically to Cullin 4B (CUL4B). The cell proliferation, migration, invasion, and expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphoinositide-3 kinase, catalytic subunit delta (PIK3CD), phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-protein kinase B (p-AKT) and phospho-mammalian target of rapamycin (p-mTOR) were higher in the THAP7-AS1 group compared with the Vector group of SPC-A-1 and NCI-H1299 cells (P<0.05).@*CONCLUSIONS@#LncRNA THAP7-AS1 is stably expressed through m6A modification mediated by METTL3, and combines with CUL4B to activate PI3K/AKT signal pathway, which promotes the occurrence and development of lung cancer.

Research progress of traditional Chinese medicine monomer and compound intervention on the Wnt signaling pathway in regulating bone metabolism / 中国药房

Bone metabolism refers to the decomposition and anabolism occurring during bone remodeling， and its balance is regulated by bone resorption and bone formation. A slight deviation of this balance causes various skeletal diseases， such as osteoporosis and renal osteodystrophy. Traditional Chinese medicine （TCM） monomers and compounds have certain advantages in treating bone metabolism diseases. The Wnt signaling pathway includes the canonical Wnt signaling pathway， dependent on β-catenin， and the non-canonical Wnt signaling pathway， independent of β-catenin. Both types of pathways can maintain bone metabolism balance by regulating bone formation and bone resorption and are essential for bone development， bone mass maintenance， and bone remodeling. A variety of TCM monomers （albiflorin， catalpol and icariin） and formulas （Zuogui pill， Yishen gugu prescription， Duzhong jiangu prescription， etc.） have been confirmed to promote differentiation of bone marrow mesenchymal stem cells， proliferation and differentiation of osteoblasts， bone injury repair， and osteoporosis improvement by activating the Wnt signaling pathway in recent years. Here， this article summarizes the research progress in the Wnt signaling pathway regulation of bone metabolism by TCM monomers and compounds to provide ideas for the clinical application of TCM and the research and development of new drugs for the prevention and treatment of bone metabolism diseases.

Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models: A Cross-sectional Study in Rural Guangxi / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength.@*METHODS@#We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.@*RESULTS@#In the multimetal linear regression, Cu (β = -2.119), As (β = -1.318), Sr (β = -2.480), Ba (β = 0.781), Fe (β = 1.130) and Mn (β = -0.404) were significantly correlated with grip strength ( P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95% confidence interval: -1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn ( P interactions of 0.003 and 0.018, respectively).@*CONCLUSION@#In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Comprehensive Analysis of Proteins and Their Phosphorylation in Milk-derived Exosomes From Different Species / 生物化学与生物物理进展

ObjectiveExosomes are microvesicles which could be secreted by all cell types with diameters between 30 and 150 nm. It was widely distributed in body fluids including blood, urine, and breast milk. Exosomes are considered as potential biomarkers and drug carriers by reason of containing nucleic acids, lipids, proteins and other bioactive molecules. Milk-derived exosomes have been widely used as drug delivery carriers to treat targeted diseases with a lower cost, higher biocompatibility and lower immunogenicity. Until now, there is no research about the milk-derived exosomes phosphorylation to reveal the difference of protein phosphorylation in different species of milk. To investigate the pathways and proteins with specific functions, phosphorylated proteomic analysis of milk-derived exosomes from different species is performed, and provide new ideas for exploring diversified treatments of disease. MethodsWhey and exosomes derived from bovine, porcine and caprine milk were performed for proteomics and phosphoproteomics analysis. The relationship between milk exosome proteins from different species and signaling pathways were analyzed using bioinformatics tools. ResultsA total of 4 191 global proteins, 1 640 phosphoproteins and 4 064 phosphosites were identified from 3 species of milk-derived exosomes, and the exosome proteins and phosphoproteins from different species were significantly higher than those of whey. Meanwhile, some special pathways were enriched like Fcγ-mediated phagocytosis from bovine exosomes, pathways related with neural and immune system from caprine exosomes, positive and negative regulation of multiple activities from porcine exosomes. ConclusionIn this study, the proteomic and phosphoproteomic analyses of exosomes and whey from bovine, porcine and caprine milk were carried out to reveal the difference of composition and related signaling pathways of milk exosome from different species. These results provided powerful support for the application of exosomes from different milk sources in the field of disease treatment.

Ku70 Functions as an RNA Helicase to Regulate miR-124 Maturation and Neuronal Cell Differentiation / 生物化学与生物物理进展

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

Pharmaceutical care in a case of myocardial infarction complicated with antithrombotic therapy after tricuspid valve repair / 药学实践与服务

Objective To investigate the antithrombotic therapy for acute myocardial infarction patients after PCI stenting combined with tricuspid valve repair. Methods The risk of bleeding and embolization was evaluated, relevant data were reviewed, professional knowledges of pharmacy were utilized through the whole treatment process, individualized medication plan for patients was designed and used. Results A better therapeutic effect was achieved through the implementation of pharmaceutical care and medication education to the patients. Conclusion Clinical pharmacists carry out pharmaceutical care in antithrombotic drugs utilities，which could improve the safety level of drug use and provide basis for clinical rational drug use.

Qualitative and Quantitative Analysis of Five Indoles or Indazole Amide Synthetic Cannabinoids in Suspected E-Cigarette Oil by GC-MS / 法医学杂志

OBJECTIVES@#To establish the GC-MS qualitative and quantitative analysis methods for the synthetic cannabinoids, its main matrix and additives in suspicious electronic cigarette (e-cigarette) oil samples.@*METHODS@#The e-cigarette oil samples were analyzed by GC-MS after diluted with methanol. Synthetic cannabinoids, its main matrix and additives in e-cigarette oil samples were qualitatively analyzed by the characteristic fragment ions and retention time. The synthetic cannabinoids were quantitatively analyzed by using the selective ion monitoring mode.@*RESULTS@#The linear range of each compound in GC-MS quantitative method was 0.025-1 mg/mL, the matrix recovery rate was 94%-103%, the intra-day precision relative standard deviations (RSD) was less than 2.5%, and inter-day precision RSD was less than 4.0%. Five indoles or indazole amide synthetic cannabinoids were detected in 25 e-cigarette samples. The main matrixes of e-cigarette samples were propylene glycol and glycerol. Additives such as N,2,3-trimethyl-2-isopropyl butanamide (WS-23), glycerol triacetate and nicotine were detected in some samples. The content range of synthetic cannabinoids in 25 e-cigarette samples was 0.05%-2.74%.@*CONCLUSIONS@#The GC-MS method for synthesizing cannabinoid, matrix and additive in e-cigarette oil samples has good selectivity, high resolution, low detection limit, and can be used for simultaneous qualitative and quantitative analysis of multiple components; The explored fragment ion fragmentation mechanism of the electron bombardment ion source of indole or indoxamide compounds helps to identify such substances or other compounds with similar structures in cases.

Molecular epidemiological characterization of hypervirulent carbapenem-resistant Klebsiella pneumoniae in a hospital in Henan Province from 2020 to 2022 / 中华预防医学杂志

Objective: The study investigated the clinical distribution, antimicrobial resistance and epidemiologic characteristics of hypervirulent Carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) in a hospital in Henan Province to provide a scientific basis for antibiotic use and nosocomial infection prevention and control. Methods: A retrospective analysis of the clinical data from the cases was carried out in this study. Clinical data of patients infected with the CRKP strain isolated from the clinical microbiology laboratory of Henan Provincial Hospital of Traditional Chinese Medicine from January 2020 to December 2022 were retrospectively analyzed. A string test, virulence gene screening, serum killing, and a G. mellonella infection model were used to screen hv-CRKP isolates. The clinical characteristics of hv-CRKP and the drug resistance rate of hv-CRKP to twenty-five antibiotics were analyzed using WHONET 5.6. Carbapenemase phenotypic characterization of the hv-CRKP was performed by colloidal gold immunochromatographic assay, and Carbapenemase genotyping, multi-locus sequence typing (MLST) and capsular serotyping of hv-CRKP isolates were performed by PCR and Sanger sequencing. Results: A total of non-duplicate 264 CRKP clinical isolates were detected in the hospital from 2020 to 2022, and 23 hv-CRKP isolates were detected, so the corresponding detection rate of hv-CRKP was 8.71% (23/264). The hv-CRKP isolates in this study were mainly from the intensive care unit (10/23) and neurosurgery department (8/23), and the main sources of hv-CRKP isolates were sputum (10/23) and bronchoalveolar lavage fluid (6/23). The hv-CRKP isolates in this study were highly resistant to β-lactam antibiotics, fluoroquinolones and aminoglycosides, and were only susceptible to colistin, tigecycline and ceftazidime/avibactam. The detection rate of the blaKPC-2 among 23 hv-CRKP isolates was 91.30% (21/23) and none of the class B and class D carbapenemases were detected. Results of MLST and capsular serotypes showed that ST11 type hv-CRKP was the dominant strain in the hospital, accounting for 56.52% (13/23), and K64 (9/13) and KL47 (4/13) were the major capsular serotypes. Conclusion: The hv-CRKP isolates from the hospital are mainly from lower respiratory tract specimens from patients admitted to the intensive care department and the drug resistance is relatively severe. The predominant strains with certain polymorphisms are mainly composed of the KPC-2-producing ST11-K64 and ST11-KL47 hv-CRKP isolates in the hospital.

Molecular epidemiological characterization of hypervirulent carbapenem-resistant Klebsiella pneumoniae in a hospital in Henan Province from 2020 to 2022 / 中华预防医学杂志

Objective: The study investigated the clinical distribution, antimicrobial resistance and epidemiologic characteristics of hypervirulent Carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) in a hospital in Henan Province to provide a scientific basis for antibiotic use and nosocomial infection prevention and control. Methods: A retrospective analysis of the clinical data from the cases was carried out in this study. Clinical data of patients infected with the CRKP strain isolated from the clinical microbiology laboratory of Henan Provincial Hospital of Traditional Chinese Medicine from January 2020 to December 2022 were retrospectively analyzed. A string test, virulence gene screening, serum killing, and a G. mellonella infection model were used to screen hv-CRKP isolates. The clinical characteristics of hv-CRKP and the drug resistance rate of hv-CRKP to twenty-five antibiotics were analyzed using WHONET 5.6. Carbapenemase phenotypic characterization of the hv-CRKP was performed by colloidal gold immunochromatographic assay, and Carbapenemase genotyping, multi-locus sequence typing (MLST) and capsular serotyping of hv-CRKP isolates were performed by PCR and Sanger sequencing. Results: A total of non-duplicate 264 CRKP clinical isolates were detected in the hospital from 2020 to 2022, and 23 hv-CRKP isolates were detected, so the corresponding detection rate of hv-CRKP was 8.71% (23/264). The hv-CRKP isolates in this study were mainly from the intensive care unit (10/23) and neurosurgery department (8/23), and the main sources of hv-CRKP isolates were sputum (10/23) and bronchoalveolar lavage fluid (6/23). The hv-CRKP isolates in this study were highly resistant to β-lactam antibiotics, fluoroquinolones and aminoglycosides, and were only susceptible to colistin, tigecycline and ceftazidime/avibactam. The detection rate of the blaKPC-2 among 23 hv-CRKP isolates was 91.30% (21/23) and none of the class B and class D carbapenemases were detected. Results of MLST and capsular serotypes showed that ST11 type hv-CRKP was the dominant strain in the hospital, accounting for 56.52% (13/23), and K64 (9/13) and KL47 (4/13) were the major capsular serotypes. Conclusion: The hv-CRKP isolates from the hospital are mainly from lower respiratory tract specimens from patients admitted to the intensive care department and the drug resistance is relatively severe. The predominant strains with certain polymorphisms are mainly composed of the KPC-2-producing ST11-K64 and ST11-KL47 hv-CRKP isolates in the hospital.

Distinguishing between Artemisia stolonifera and A. argyi by specific PCR of leaves and non-glandular trichomes / 中国中药杂志

Artemisia stolonifera is a relative of A. argyi. The two species are difficult to be distinguished due to the similarity in leaf shape and have even less distinctive features after processing. This study aims to establish a method to quickly distinguish between them. At the same time, we examined the reasonability and applicability of the specific polymerase chain reaction(PCR) method. The C/T single nucleotide polymorphism was detected at the position 202 of the sequence, based on which specific primers were designed to identify these two species. The PCR with the specific primer JNC-F and the universal primer ITS3R produced a specific band at 218 bp for A. argyi and no band for A. stolonifera, which can be used to detect at least 3% of A. argyi samples mixed in A. stolonifera samples. The PCR with the specific primer KY-F and the universal primer ITS3R produced a specific band at 218 bp for A. stolonifera and no band for A. argyi, which can be used to detect at least 5% of A. stolonifera samples mixed with A. argyi. The limit of detection of the established method was 5 ng DNA. The established PCR method can accurately distinguish between A. stolonifera and A. argyi, which provides an experimental basis for the quality control of A. stolonifera and determines whether the herbs are adulterated.

Constructions and advances of animal models of Pseudomonas aeruginosa infection / 中华预防医学杂志

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogenic bacterium with complex pathogenesis and drug resistance mechanisms. It has high morbidity and mortality and can cause acute and chronic infections in immunocompromised individuals, with lung infections, wound infections, and bloodstream infections being the most common. The animal infection model of P. aeruginosa is of great value for in-depth research on the pathogenicity, drug resistance, and therapeutic measures of P. aeruginosa by simulating the pathways of human bacterial infections. This article firstly summarizes the selection, anesthesia, and disposal of experimental animals in the construction of animal models of P. aeruginosa infection, and then reviews the methods of construction, model evaluation, and applications of animal models of P. aeruginosa pulmonary infection, wound infection, and bloodstream infection, in order to provide a reference for scientific research related to P. aeruginosa infectious diseases.

Forecasting the burden of disease from diabetes under the scenarios of specific risk factors control in China in 2030 / 中华流行病学杂志

Objective: To forecast mortality, age-standardized mortality, and probability of premature mortality from diabetes, and to simulate the impact of controlling risk factors by 2030 in China. Methods: We simulated the burden of disease from diabetes in six scenarios according to the development goals of risk factors control by the WHO and Chinese government. Based on the theory of comparative risk assessment and the estimates of the burden of disease for China from the Global Burden of Disease Study 2015, we used the proportional change model to project the number of deaths, age-standardized mortality, and probability of premature mortality from diabetes under different scenarios of risk factors control in 2030. Results: If the trends in exposures to risk factors from 1990 to 2015 continued. Mortality, age-standardized mortality, and probability of premature mortality from diabetes would increase to 32.57/100 000, 17.32/100 000, and 0.84% by 2030, respectively. During that time, mortality, age-standardized mortality and probability of premature mortality for males would all be higher than for females. If the goals of controlling risk factors were all achieved, the number of deaths from diabetes in 2030 would decrease by 62.10% compared to the predicted numbers based on the historical trends in exposure to risk factors, and the probability of premature mortality would drop to 0.29%. If only the exposure to a single risk factor were achieved by 2030, high fasting plasma glucose control would have the greatest impact on diabetes, resulting in a 56.00% reduction in deaths compared to the predicted numbers based on the historical trends, followed by high BMI (4.92%), smoking (0.65%), and low physical activity (0.53%). Conclusions: Risk factors control plays an important role in reducing the number of deaths, age-standardized mortality rate, and probability of premature mortality from diabetes. We suggest taking comprehensive measures to control relevant risk factors for certain populations and regions, to achieve the goal of reducing the burden of disease from diabetes as expected.

Analysis of respiratory syncytial virus nonstructural protein 1 amino acid variation and clinical characteristics / 中华儿科杂志

Objective: To investigate the relationship between amino acid variations of respiratory syncytial virus (RSV) nonstructural protein (NS) 1 and the clinical characteristics. Method: A retrospective case review was conducted. From December 2018 to January 2020, a total of 81 cases of hospitalized children who were tested only positive for RSV by RT-PCR or PCR at the Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University were included in the study. The NS1 genes of RSV subtype A and subtype B were amplified by PCR and sequenced. The amino acid sequences were analyzed. The Chi-square test and Mann-Whitney rank sum test were used to compare the clinical characteristics and type Ⅰ interferon levels of children with or without NS1 variation in the variation and non-variation groups. Results: Among 81 cases, there were 58 males and 23 females. There were 11 cases in the variation group, the age of onset was 2.0 (1.0, 11.0) months, included 4 cases of subtype A (variant sites were: 2 cases for Lys33Gln, one case for Gly2Asp, Pro67Ser, Leu137Phe, respectively) and 7 cases of subtype B (variant sites were: two cases for Val121Ile, one case for Tyr30Cys, Val65Met, Asn85Ser, Ser118Asn, Asp124Asn, respectively). These variant sites all appeared at a very low frequency 0.08 (0.04, 0.29) % in the NCBI PROTEIN database. There were 70 cases in non-variation group, the onset age was 3.5 (1.0, 7.0) months. The proportion of dyspnea in the variation group was higher than that in the non-variation group (10/11 vs. 47% (33/70), χ2=7.31, P<0.01). Conclusions: There are some variant sites in nonstructural protein NS1 of RSV. Children may be prone to have dyspnea with NS1 variations.

Clinical characteristics and risk factors for bronchoscopic airway mucus hypersecretion in childhood pneumonia infected by different pathogens / 中华儿科杂志

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×106 vs. 490 (210, 1 510)×106/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.

Mitochondrial pyruvate carrier deficiency: 3 cases report and literature review / 中华儿科杂志

Objective: To analyze the clinical and genetic features of patients with mitochondrial pyruvate carrier deficiency (MPYCD). Methods: This was a case series research. The clinical data, genetic characteristics, and glutamine treatment efficacy of 3 patients diagnosed with MPYCD at the Department of Neurology, Beijing Children's Hospital, Capital Medical University and Department of Pediatrics, Guizhou Provincial People's Hospital, from August 2019 to June 2023 were retrospectively collected. A literature search with "MPC1 gene" "MPC2 gene and" "mitochondrial pyruvate carrier deficiency" as keywords was conducted at the Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure (CNKI) and PubMed (up to June 2023). Clinical and genetic characteristics of patients with MPYCD were summarized. Results: Case 1 was a 3 years and 11 months old boy, while case 2 was a 4 years and 10 months old boy and case 3 was an 8 years and 9 months old girl. Case 2 and case 3 were siblings from one consanguineous family. All 3 patients presented with general developmental delay, growth failure and elevated serum lactate. Cranial magnetic resonance imaging (MRI) showed subtle bilateral symmetrical T2 signal hyperintensity in basal ganglia and thalamus in case 1, but normal in case 2 and 3. Trio-WES revealed case 1 harboring compound heterozygous missense variants c.208G>A (p.Ala70Thr) and c.290G>A (p.Arg97Gln) in MPC1 gene, while case 2 and 3 revealed a homozygous variant c.290G>A (p.Arg97Gln) in the same gene. All 3 cases were diagnosecl as MPYCD. Clinical symptoms including motor ability, cognition and activity endurance were improved in these 3 patients after taking glutamine for 2 years. A total of 5 articles published in English were reviewed, and no Chinese literature was found. Including these 3 cases, 15 cases were enrolled for analysis. Eleven patients carried MPC1 gene variants and 4 cases carried MPC2 gene variants. Except for 3 cases died during prenatal period, 9 of 12 enrolled born cases were onset before 6 months old. The most common clinical symptoms were mental and motor general developmental delay, microcephaly, growth failure and hypotonia. All patients had elevated blood lactate and pyruvate, but the ratio of lactate/pyruvate was normal. Seven patients performed cranial MRI, 3 exhibited non-specific changes, 2 showed bilateral symmetrical T2 signal hyperintensity in basal ganglia and thalamus, and 3 were normal. A total of 5 MPC1 gene missense variants and 2 MPC2 gene variants were identified in 15 cases. Conclusions: Onset age of patients with MPYCD is usually within 6 months. The main clinical characteristics are developmental delay, microcephaly and growth failure, accompanied by increased serum lactate and pyruvate. Glutamine supplement could lead to clinical improvements.

Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis, Synaptic Plasticity, and Cognitive Behavior in Mice / 神经科学通报·英文版

The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)-mediated trimethylation of histone H3 lysine 27 (H3K27me3) regulates neural stem cell proliferation and fate specificity through silencing different gene sets in the central nervous system. Here, we explored the function of EZH2 in early post-mitotic neurons by generating a neuron-specific Ezh2 conditional knockout mouse line. The results showed that a lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and increased dendritic spine density. Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal morphogenesis. In particular, the gene encoding p21-activated kinase 3 (Pak3) was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of the dominant negative Pak3 reversed Ezh2 knockout-induced higher dendritic spine density. Finally, the lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 acts to control multiple steps of neuronal morphogenesis during development, and has long-lasting effects on cognitive function in adult mice.

Saikosaponin D regulates apoptosis and autophagy of pancreatic cancer Panc-1 cells via Akt/mTOR pathway / 中国中药杂志

This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 μmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 μmol·L~(-1)), low-concentration(10 μmol·L~(-1)) saikosaponin D, and high-concentration(16 μmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.

Research progress in signaling pathways related to treatment of functional dyspepsia with traditional Chinese medicine / 中国中药杂志

Functional dyspepsia(FD) is a prevalent functional gastrointestinal disease characterized by recurrent and long-lasting symptoms that significantly impact the quality of life of patients. Currently, western medicine treatment has not made breakthrough progress and mainly relies on symptomatic therapies such as gastrointestinal motility agents, acid suppressants, antidepressants/anxiolytics, and psychotherapy. However, these treatments have limitations in terms of insufficient effectiveness and safety. Traditional Chinese medicine(TCM) possesses unique advantages in the treatment of FD. Through literature search in China and abroad, it has been found that the mechanisms of TCM in treating FD is associated with various signaling pathways, and research on these signaling pathways and molecular mechanisms has gradually become a focus. The main signaling pathways include the SCF/c-Kit signaling pathway, 5-HT signaling pathway, CRF signaling pathway, AMPK signaling pathway, TRPV1 signaling pathway, NF-κB signaling pathway, and RhoA/ROCK2/MYPT1 signaling pathway. This series of signaling pathways can promote gastrointestinal motility, alleviate anxiety, accelerate gastric emptying, reduce visceral hypersensitivity, and improve duodenal micro-inflammation in the treatment of FD. This article reviewed the research on TCM's regulation of relevant signaling pathways in the treatment of FD, offering references and support for further targeted TCM research in the treatment of FD.