Objective: To analyze the disease burden of chronic obstructive pulmonary disease (COPD) and changes in its risk factors among residents in Zhejiang Province from 1990 to 2021, so as to identify key priorities for COPD prevention and control. Methods: Data on COPD mortality and disability-adjusted life years (DALY) for residents in Zhejiang Province from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Standardized mortality and standardized DALY rate were calculated using the GBD 2021 world population standard structure. Premature mortality was computed via the life table method. The average annual percent change (AAPC) was applied to analyze trends in COPD mortality, DALY rate, and premature mortality. Changes in deaths of COPD risk factors were evaluated using population attributable fraction (PAF). Results: From 1990 to 2021, the standardized COPD mortality in Zhejiang Province decreased from 272.40/100 000 to 70.56/100 000 (AAPC=-4.395%), and the standardized DALY rate declined from 4 167.37/100 000 to 1 071.89/100 000 (AAPC=-4.396%). Similar downward trends were observed in both males (AAPC=-3.933%, -4.173%) and females (AAPC=-4.785%, -4.480%), all P<0.05. Crude mortality and DALY rates increased with age, and the crude mortality and DALY rates of various age groups in Zhejiang Province showed decreasing trends from 1990 to 2021 (all P<0.05). The premature mortality declined from 4.37% to 0.60% from 1990 to 2021 (AAPC=- 6.206%), with consistent trends across males and females (AAPC=- 6.144%, - 6.379%, all P<0.05). From 1990 to 2021, particulate matter pollution showed the largest reduction in PAF (- 56.76%), while ambient ozone pollution had the largest increase (103.07%) in Zhejiang Province. By 2021, smoking became the leading risk factor for deaths of COPD (PAF=43.32%). Conclusions The standardized mortality, standardized DALY rate, and premature mortality for COPD show consistent declining trends in Zhejiang Province from 1990 to 2021. However, risk factors such as smoking and ambient ozone pollution require intensified focus to further reduce disease burden of COPD.

Loss-of-function variants of low-density lipoprotein receptor-related protein 5 (LRP5) can lead to reduced bone formation, culminating in diminished bone mass. Our previous study reported transcription factor osterix (SP7)‍-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration. However, the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown. In this study, we used mice with a conditional knockout (cKO) of LRP5 in mature osteoblasts, which presented decreased osteogenesis. The in vitro experimental results showed that SP7 could promote LRP5 expression, thereby upregulating the osteogenic markers such as alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2), and β‍-catenin (P<0.05). For the in vivo experiment, the SP7 overexpression virus was injected into a bone defect model of LRP5 cKO mice, resulting in increased bone mineral density (BMD) (P<0.001) and volumetric density (bone volume (BV)/total volume (TV)) (P<0.001), and decreased trabecular separation (Tb.‍Sp) (P<0.05). These data suggested that SP7 could ameliorate bone defect healing in LRP5 cKO mice. Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.
Animals ; Low Density Lipoprotein Receptor-Related Protein-5/metabolism* ; Osteoporosis/genetics* ; Mice ; Mice, Knockout ; Sp7 Transcription Factor/physiology* ; Osteogenesis ; Bone Density ; Osteoblasts/metabolism* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Mice, Inbred C57BL ; beta Catenin/metabolism*

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Objective To investigate the effects of open reading frame 1 protein(ORF1p),encoded by long interspersed nuclear element-1(LINE-1),on the proliferation,migration,and invasion of esophageal squamous cell carcinoma(ESCC)cells,and explore the underlying molecular mechanism.Methods① Western blotting was performed to compare the expression of ORF1p between normal esophageal squamous epithelial cells and ESCC cells.② Immunohistochemistry(IHC)assay was used to examine ORF1p expression in ESCC tissues and paired normal tissues adjacent to tumor.③ The effects of ORF1p knockdown and overexpression on malignant behaviors in ESCC cells were determined through functional assays.④ Xenograft tumor model in nude mice was established to evaluate the impact of ORF1p on tumor growth in vivo.⑤ Transcriptome sequencing combined with cell functional rescue experiments were conducted to identify downstream targets regulated by ORF1p.Results ① Western blot analysis demonstrated the expression of ORF1p was significantly higher in the ESCC cell lines than the normal esophageal squamous epithelial cells(P<0.05).② IHC confirmed remarkable up-regulation of ORF1p in ESCC tissues than paired adjacent normal tissues(P<0.000 1).③ Functional assays and experiments on xenograft tumor models revealed that ORF1p substantially enhanced the proliferation,migration,and invasion of ESCC cells,as well as tumorigenic potential in vivo(P<0.05).④ Functional rescue experiments showed that ORF1p facilitated the proliferation,migration,and invasion of ESCC cells by modulating AJUBA expression(P<0.05).Conclusion ORF1p is significantly up-regulated in ESCC and promotes the proliferation,migration,and invasion of ESCC cells by regulating AJUBA expression.

Objective To investigate whether long non-coding RNA(lncRNA)myocardial infarct-associat-ed transcription factor(MIAT)promotes sepsis-induced acute kidney injury(AKI)by regulating microRNA-338-3p(miR-338-3p)/platelet thromboplastin-1(THBS1)axis.Methods Septic AKI model was established by cecal ligation and puncture.The rats were divided into control group and sepsis AKI group,with 10 rats in each group.The expression levels of lncRNA MIAT,miR-338-3p and THBS1gene in renal tissue were detec-ted by quantitative real-time PCR(qPCR).The levels of serum urea nitrogen(BUN)and creatinine(Cre)were detected by automatic biochemical analyzer.Renal tubular epithelial NRK-52E cells were induced by li-popolysaccharide(LPS)to establish a cell model of sepsis induced AKI.NRK-52E cells were divided into CK group,LPS group,LPS+si-NC group,LPS+si-lncRNA MIAT group,LPS+si-lncRNA MIAT+inhibitor NC group,LPS+si-lncRNA MIAT+miR-338-3p inhibitor group,LPS+si-lncRNA MIAT+oe-NC group,LPS+si-lncRNA MIAT+oe-THBS1 group.qPCR was used to detect the expression levels of lncRNA MIAT,miR-338-3p and THBS1 gene in each group.Cell counting kit 8 was used to detect cell proliferation in each group.Flow cytometry was used to detect the apoptosis rate of each group.Enzyme-linked immunosorbent assay was used to detect the levels of lactate dehydrogenase(LDH),tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-10,malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)and catalase(CAT)in each group.The expression of NOD-like receptor pyrin domain-containing protein 3(NLRP3),Caspase-1,cleaved caspase-3 and THBS1 protein were detected by Western blot.The targeting relationship between miR-338-3p and lncRNA MIAT and THBS1 was verified.Results The expression levels of BUN,Cre,lncRNA MI-AT and THBS1 gene were increased(P<0.05),and the expression level of miR-338-3p was decreased in sep-sis AKI group(P<0.05).Compared with CK group,the expression of lncRNA MIAT,THBS1 gene,apopto-sis rate and the levels of IL-6,LDH,TNF-αand MDA were significantly increased(P<0.05),the protein ex-pression levels of NLRP3,Caspase-1,cleaved caspase-3 and THBS1 were significantly increased(P<0.05),while the expression of miR-338-3p,A450(24,48 h)value and IL-10 level were significantly decreased(P<0.05),and the activities of CAT and SOD were significantly decreased in LPS group and LPS+si-NC group(P<0.05).Compared with LPS+si-NC group,the expression of lncRNA MIAT,THBS1 gene,apoptosis rate and the levels of IL-6,LDH,TNF-α and MDA were significantly decreased(P<0.05),the protein expression levels of NLRP3,Caspase-1,cleaved caspase-3 and THBS1 were significantly decreased(P<0.05),while the expression of miR-338-3p,A450(24,48 h)value and IL-10 level were significantly increased(P<0.05),and the CAT and SOD activities were significantly increased in LPS+si-lncRNA MIAT group(P<0.05).Silen-cing miR-338-3p expression or up-regulation of THBS1 gene expression could attenuate the improvement effect of lncRNA MIAT on sepsis AKI(P<0.05).Conclusion lncRNA MIAT promotes sepsis-induced AKI through regulating miR-338-3p/THBS1 axis.

Objective:To study the clustered regularly interspaced short palindromic repeats (CRISPR) genotype of Yersinia pestis and its regional distribution characteristics in natural plague focus of Tibet Autonomous Region. Methods:A total of 125 representative Yersinia pestis strains isolated from natural plague focus in Tibet Autonomous Region at different times, regions, hosts and vectors were selected as experimental strains, and the phenol chloroform mixed extraction method was used to extract Yersinia pestis DNA. Three pairs of CRISPR primers (for YPa, YPb, YPc locus) were used to amplify the DNA of the experimental strains, and the CRISPR genotype of Yersinia pestis was determined by sequencing. Results:All 125 strains of Yersinia pestis had three CRISPR locus: YPa, YPb, and YPc. A total of 18 spacer were found, including 8 in YPa loci, 6 in YPb loci, and 4 in YPc loci. Two new types of spacers had been discovered, namely b52 and c14. CRISPR typing revealed 10 genotypes, including G1, G7, G7-b4''', G7-b52, G7-c2 -, G8, G22, G22-a4 -, G22-b4''', and G22-c14, of which 6 were newly discovered genotypes. Among the 125 experimental strains, G7 was the main genotype, accounting for 65.6% (82/125), which was distributed in 6 prefecture level citys and 1 region of Tibet Autonomous Region. Next were G22 and G7-c2 - genetypes, accounting for 14.4% (18/125) and 11.2% (14/125), respectively. G22 gene type was distributed in Nagqu, Changdu, Lhasa citys, and Ngari Prefecture, while G7-c2 - genetype was distributed in Shigatse and Shannan cities. Conclusion:The CRISPR locus of Yersinia pestis in natural plague focus of Tibet Autonomous Region is highly polymorphic, and the Yersinia pestis strains with different genotypes have obvious regional distribution characteristics.

【Objective】 To investigate the current situation of social anxiety in children with attention deficit hyperactivity disorder (ADHD), and to analyze the factors influencing social anxiety in ADHD children, in order to provide reference for improving the clinical management of ADHD children. 【Methods】 A total of 206 school-age children with ADHD were selected from the Children′s Psychology Clinic of Mianyang Central Hospital from January 2020 to January 2023. The relevant clinical data of the children were collected through the general data questionnaire. Children′s Social Anxiety Scale (SASC) was used to assess social anxiety, and the Social Response Scale (SRS) was used to assess social ability. The Chinese version of Swanson,Nolan and Pelham Rating Scale Ⅳ (SNAP-Ⅳ) was used to assess core symptoms. Multivariate Logistic regression analysis was used to determine influencing factors of social anxiety in children with ADHD. 【Results】 There were 128(62.14%) cases detected with social anxiety among 206 children with ADHD. The score of SASC was 14.02±4.06. The proportions of girls (χ²=6.057), comorbid autism spectrum disorder(ASD) (χ²=4.929), and main caregivers with junior high school education or below (χ²=13.345), the total score of SRS(t=5.842) and SNAP-Ⅳ(t=7.848) and the scores of all dimensions were significantly higher than those in the non-anxious group (P<0.05). Multivariate Logistic regression analysis showed that higher SRS total score(OR=5.217, 95%CI: 2.309 - 11.791), higher SNAP-Ⅳ total score(OR=4.150, 95%CI: 1.974 - 8.722), girls(OR=2.268, 95%CI: 1.423 - 3.616), primary caregivers with junior high school education or below (OR=1.527, 95%CI: 1.162 - 2.005), and comorbid ASD (OR=1.551, 95%CI: 1.209 - 1.990) were risk factors for social anxiety in ADHD children (P<0.05). 【Conclusions】 Children with ADHD have a higher prevalence rate of social anxiety. Cognitive behavioral therapy and psychological intervention should be strengthened for high-risk children to improve social ability and reduce the risk of social anxiety.

Objective: To explore the effects of high-altitude hypoxia on thyroid hormone(TH) synthesis by quasi-targeted metabolomics technology. Methods: Twenty SPF male SD rats were randomly divided into Control group and Hypoxia group. An acute hypoxia injury model was established in SD rats by simulating hypoxia stress in a hypobaric oxygen chamber at an altitude of 6 km for 48 hours. The body weight, arterial oxygen partial pressure(PaO2) and blood oxygen saturation(SaO2) were detected. KEGG enrichment analysis was performed after the metabolites in the blood of two groups were detected by quasi-targeted metabolomics technology. The expression levels of sodium iodide symporter(NIS), thyroid peroxidase(TPO) and thyroglobulin(TG) were detected by RT-PCR and Western blot in TH synthesis pathway. The content of serum thyroxine(T4) and the expression levels of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) were detected by ELISA. The expression levels of toll-like receptors-4(TLR-4), interleukin-6(IL-6), nuclear factor-κB/p65(NF-κB/p65) and tumor necrosis factor-α(TNF-α) were detected by RT-PCR, Western blot and ELISA. The expression levels of Pro apoptotic protein Bcl-2 associated X protein(Bax) and inhibitor of apoptosis protein B-cell lymphoma/leukemia-2(Bcl-2) were detected by RT-PCR and Western blot in rats thyroid tissue. Results: Compared with the Control group, the body weight, PaO2and SaO2of rats in the Hypoxia group significantly decreased(P<0.01). The differential metabolites in arterial serum of hypoxia group rats were significantly enriched in the TH synthesis pathway, and the content of the pathway end product T4decreased significantly(P<0.01). In addition, the mRNA and protein expression levels of NIS, TPO, TG in rats thyroid tissue significantly decreased(P<0.05). The ELISA validation results showed that the changes of T4content were completely consistent with the above results. Compared with the Control group, the enzyme activities of SOD and GSH-Px in the serum of rats in the hypoxia group decreased, while the content of MDA increased(P<0.01); the mRNA, protein expression levels and contents of TLR-4, IL-6, NF-κ B/p65, TNF-α significantly increased(P<0.05), while the mRNA and protein expression levels of Bax in thyroid tissue significantly increased, Bcl-2 significantly decreased(P<0.05). Conclusion Hypoxia stress at high altitude leads to apoptosis of thyroid follicular epithelial cells by promoting oxidative stress and inflammatory response, which effects thyroid function and ultimately reduces thyroid hormone synthesis.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective: To analyze the disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019, so as to provide the basis for prevention and control of colorectal cancer. Methods: Based on data of 2019 Global Burden of Disease (GDB 2019), disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019 was assessed using years of life lost (YLL), years lived with disability (YLD), disability-adjusted life years (DALY). Results: In 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province were 496.15/105, 31.81/105 and 527.96/105, respectively. From 1990 to 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province increased by 114.90%, 482.60% and 123.38%, respectively, showing increasing trends (average annual percent change values were =2.663, 6.283 and 2.800, respectively,all P<0.05). From 1990 to 2019, the YLL rate, YLD rate and DALY rate in the age groups of 15 to 49 years, 50 to 69 years and 70 years and older showed increasing trends (all P<0.05). In 1990, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in calcium, diet low in milk, diet low in whole grains, smoking, alcohol use, low physical activity, high fasting plasma glucose, diet high in red meat, diet low in fiber and high body mass index. In 2019, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in milk, diet low in whole grains, diet low in calcium, alcohol use, diet high in red meat, high body mass index, high fasting plasma glucose, low physical activity, diet low in fiber and diet high in processed meat. Conclusions The disease burden of colorectal cancer in Zhejiang Province showed an upward trend from 1990 to 2019. The top ten risk factors for colorectal cancer remained between 1990 and 2019, while there was a slight change in ranking.