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.

OBJECTIVE To evaluate the antioxidant activity compounds extracted from the pine needle of Cedrus deodara. METHODS Using vitamin C （VC） and gallic acid as positive control， HPLC method was employed to determine the changes of the DPPH peak area after antioxidant compounds from pine needle of C. deodara were treated with 1， 1-diphenyl-2-picrylhydrazyl radical （DPPH）. Then， the antioxidant activities of 3 active parts and 8 monomer compositions from pine needle of C. deodara were evaluated by calculating the inhibition rate of DPPH free radicals and the half inhibitory concentration （IC50）. HPLC conditions were using Agilent Eclipse Plus-C18 column （250 mm × 4.6 mm， 5 μm） with acetonitrile-water （62∶38， V/V） as the mobile phase. The detection wavelength was 517 nm； the flow rate was 1.0 mL/min； the column temperature was 25 ℃ ； the injection volume was 20 μL. RESULTS The order of DPPH free radical inhibition activity of active parts from pine needle of C. deodara was total flavonoids＞total polyphenols＞total lignans， with IC50 of 76.10， 100.50 and 115.40 μg/mL， respectively. Compared with positive control， except for kaempferol-3-O-β-D-glucoside， the sequence of seven monomer compounds for DPPH free radical inhibition activity was dihydromyricetin＞hypericin＞protocatechuic acid＞gallic acid＞ferulic acid＞myricetin＞ kaempferol-3-O-（6″-O-E-feruloyl）-β-D-glucopyranoside＞VC＞isohamnin， with IC50 of 16.50， 19.40， 23.73， 27.24， 32.10， 32.20， 47.60， 93.20 and 297.20 μg/mL， respectively. CONCLUSIONS HPLC-DPPH method is established to evaluate the antioxidant activity of pine needle of C. deodara. The pine needle of C. deodara has strong antioxidant activity， among which the effective compounds of total flavonoids， total polyphenols， monomer dihydromyricetin and hypericin are natural antioxidants with development prospects.

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 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 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.

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 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  The International Medical Services Department of Peking Union Medical College Hospital (PUMCH) has gradually promoted the concept and practice of palliative care since 2016. This study aims to analyze the death status of end-of-life patients before and after the promotion endeavor, in order to evaluate the impact of palliative care on the death quality.  Methods  All clinical data from end-of-life patients who died at the International Medical Services Department of PUMCH in 2013 and 2019 were retrospectively collected, and their diagnosis and treatment details before death were compared.  Results  A total of 36 end-of-life patients who died in 2013 and 37 end-of-life patients who died in 2019 met the inclusion and exclusion criteria. In 2013, there were 19 males and 17 females, with an average age of (72.1±14.0) years, and 19 cases had advanced cancer. In 2019, there were 19 males and 18 females, with an average age of (70.8±15.3) years, and 27 cases had advanced cancer. Compared to patients who died in 2013, a lower proportion of the patients in 2019 who were transferred to the ICU before death(0 vs. 22.2%, P=0.008), received cardiopulmonary resuscitation (0 vs. 16.7%, P=0.011), had tracheal intubation(5.4% vs. 36.1%, P=0.001), invasive mechanical ventilation(2.7% vs. 33.3%, P=0.001), and total parenteral nutrition(32.4% vs. 61.1%, P=0.014), while a higher proportion received palliative care consultations(29.7% vs. 0, P<0.001), and humanistic care(40.5% vs. 16.7%, P=0.024). In 2019, compared to the patients who did not receive palliative care consultations, those who received palliative care consultations had a higher proportion of humanistic care(90.9% vs. 19.2%, P<0.001).  Conclusions  After concept promotion and practice of palliative care, the proportion of end-of-life patients receiving invasive treatments before death in the International Medical Services Department of PUMCH has significantly decreased, the proportion receiving humanistic care has significantly increased, and the quality of death has been improved to a certain extent.

Objective:To investigate the incidence and influencing factors of allergic reactions to cephalosporins.Methods:A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021.The incidence of allergic reactions to cephalosporins was investigated,and the influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression.Results:A total of 56 155 patients were included in this study.The total incidence of allergic reactions to cephalosporin was 1.67‰,the highest incidence of anaphylaxis occurred for ceftizoxime(4.27‰),followed by ceftriaxone(3.49‰)and cefotaxime(2.40‰).There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests(1.75％o vs.1.63‰,RR=1.07,95％CI:0.70-1.63,P＞0.05).Poisson regression showed that body mass index(BMI)＜18.5 kg/m2(RR=2.43,95％CI:1.23-4.82,P＜0.05)and history of β-lactam antibiotics allergy(RR=33.88,95％CI:1.47-781.12,P＜0.05)increased cephalosporin-induced anaphylaxis.Compared with cefuroxime,the risk of allergic reactions was increased for ceftriaxone(RR=3.08,95％CI:1.70-5.59,P＜0.01),ceftazidime(RR=1.89,95％CI:1.03-3.47,P＜0.05),and ceftizoxime(RR=3.74,95％CI:1.64-8.50,P＜0.01).Conclusions:Lower BMI and history of β-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions.The routine skin test may not reduce the occurrence of allergic reactions to cephalosporins. This study has been registered at Chinese Clinical Trial Registry(ChiCTR2200064314).

The endothelial glycocalyx(EG)is a polyglycoprotein complex present on the internal vascular surface,and its impairment is associated with the progression of multiple diseases,including atherosclerosis,stroke,sepsis,diabetes,kidney disease,hypertension,and lung edema.Therefore,glycocalyx health can be used as a biomarker to evaluate vascular health.Aging leads to dysfunctional changes in the glycocalyx;for example,its thickness decreases,and the genes of enzymes involved in its synthesis and digestion are dysregulated.As a natural barrier to the vascular system,age-related glycocalyx disruption is associated with vascular dysfunction,including impairment of vascular contraction and dilation,enhancement of permeability,dysregulation of inflammatory and immune reactions,and imbalance of anticoagulation and thrombin.From the perspective of'structure determines function'studies on the changing regularity of the thickness,components,microstructure,and mechanical properties of EG with aging and its relationship with vascular dysfunction are of great significance for the prevention,diagnosis,and treatment of atherosclerosis and other age-related cardiovascular diseases.