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 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.

The prevalence of periodontal disease in Chinese population is more than 90％.The present treatment techniques can only control the development of the disease,inducement of bone tissue regeneration is a promising strategy and a challenge for the treatment.Exosomes are multivesicle structures derived from endosomes.More and more studies have been conducted on their application in perio-dontal regeneration.This paper reviews the application of exosome in periodontal regeneration in recent years,which is expected to pro-vide new idea for periodontal regeneration therapy.

Objective:To study the iodine nutritional status of pregnant women in the third trimester in the Southwest of Shandong Province, analyze its impact on their cardiac electrical activity, and provide a basis for scientific supplementation of iodine during pregnancy.Methods:From January 2021 to June 2022, a cross-sectional survey was conducted using cluster random sampling method. According to the inclusion and exclusion criteria, 200 pregnant women in the third trimester were selected from 3 tertiary hospitals in three cities in the Southwest of Shandong Province, and were divided into the third trimester group ( n = 600), and 100 non-pregnant women were selected as the control group ( n = 300). The urinary iodine content was detected by arsenic-cerium catalytic spectrophotometry, and the pregnant women in the third trimester group were subdivided into iodine deficiency subgroup [G1 subgroup, median urinary iodine (MUIC) < 150 μg/L] based on the MUIC, iodine excess subgroup (G2 subgroup, MUIC≥500 μg/L) and moderate iodine subgroup (G3 subgroup, 150 μg/L≤MUIC < 500 μg/L). Chemiluminescence immunoassay was used to measure the serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT 4) and free triiodothyronine (FT 3). The cardiac electrical indexes were detected by a 12-lead surface electrocardiogram (ECG) machine. Results:There was no statistically significant difference in urinary iodine levels between pregnant women in the third trimester group and non-pregnant women in the control group among the 3 tertiary hospitals in the Southwest of Shandong Province ( H = 3.63, 3.27, P > 0.05). In the third trimester group, the proportion of pregnant women in the G1, G2 and G3 subgroups was 27.67% (166/600), 6.83% (41/600) and 65.50% (393/600), respectively. There was a statistically significant difference in urinary iodine levels between the subgroups and the control group ( H = 11.56, P < 0.001). The serum FT 3 and FT 4 levels in the G2 subgroup were lower than those in the G1 and G3 subgroups ( P < 0.001), but there was no statistically significant difference in serum TSH levels among the three subgroups ( P > 0.05). The normal rates of ECG in the G1, G2, G3 subgroups, and the control group were 38.55% (64/166), 41.46% (17/41), 92.37% (363/393), and 95.33% (286/300), respectively. The difference between the groups were statistically significant (χ 2 = 461.25, P < 0.001), the normal rate of ECG in the G1 and G2 subgroups was lower than that in the control group ( P < 0.001). Short P-R intervals and ST-T changes were the most common abnormal ECG in the third trimester group. Conclusions:The incidence of iodine deficiency, iodine excess, and other abnormal iodine nutritional status in pregnant women in the third trimester of the Southwest of Shandong Province is relatively high. Short P-R intervals, ST-T changes, and other arrhythmia caused by this are more common. It is necessary to strengthen monitoring of iodine nutritional status and ECG during pregnancy, and adjust intervention strategies such as iodine supplementation in a timely manner.

Objective:To understand the epidemiological characteristics of metabolic syndrome(MetS) among adult residents in Zhejiang Province and compare three diagnostic criteria in adult residents.Methods:In this cross-sectisnal study participants were randomly chosen using multi-stage stratified cluster sampling method from 10 national chronic disease risk factor monitoring sites in Zhejiang Province of the 2018 China Chronic Disease and Risk Factors Surveillance Project. Demographics and information on chronic disease prevalence were obtained through questionnaire, physical measurements, and laboratory. After complex weighting of the data, an analysis and comparison of the prevalence of MetS under different diagnostic criteria among adult residents in Zhejiang Province was conducted.Results:A total of 5 369 adult residents were included, 2 411 males and 2 958 females. The prevalence of MetS using JIS, CDS and IDF diagnostic criteria was 33.62%, 25.32%, and 24.25%, respectively. The consistency rate between IDF and JIS was the highest(89.11%) and the Kappa value was 0.768( P<0.001). The consistency rate between IDF and CDS diagnostic criteria was 84.53%, and the Kappa value was 0.631( P<0.001). The consistency rate between JIS and CDS was the lowest(83.17%), and the Kappa value was 0.621( P<0.001). Under CDS diagnostic criteria, the prevalence of MetS was associated to gender, marital status, smoking and drinking. Conclusion:The prevalence of MetS is at a relatively high level among adult residents in Zhejiang province. The consistency between IDF and JIS diagnostic criteria is the highest. Screening for MetS should be strengthened to detect high-risk individuals early, reduce the risk of cardiovascular and cerebrovascular diseases and diabetes, and improve the quality of life of residents.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objectives:To investigate the clinical value of endoscopy and mucosal histology for digestive tract diseases in infants.Methods:Clinical data of 357 infants who underwent 422 gastrointestinal endoscopies from January 2010 to December 2021 were collected. The indications, endoscopic manifestations, histological features of mucosa and diagnosis were analyzed.Results:A total of 159 gastroscopies and 263 colonoscopies were performed. Diarrhea (185 cases), bloody stool (178 cases) and vomiting (46 cases) were common symptoms. Endoscopy showed manifestations including non-specific inflammatory changes (265 cases), ulcer-like changes (72 cases), and normal mucusa (48 cases). A total of 373 biopsies were performed, including 260 cases of abnormal mucosal histology, 109 cases of normal mucosal histology, and 4 cases of too small biopsy specimens for analysis. Diagnoses were 208 cases of anaphylactic disease, 45 cases of inflammatory bowel disease, 15 cases of variation of structure, 10 cases of intestinal lymphangiectasis, 2 cases of autoimmune enteropathy, and 1 case of celiac disease. There was only 1 colonic perforation complicating endoscopy in terms of endoscopic complication.Conclusions:It is safe and effective to perform endoscopy standardly for digestive tract diseases in infants. Endoscopy with biopsies is a greatly informative test for diagnosis in infants.

Objective To extract the total protein of K326 tobacco leaves with high expression of Nicotiana alata defensin 1(NaD1) gene and analyze its bioactivity.Methods Total proteins were extracted from Nicotiana alata flowers,wild type(WT) and K326 tobacco leaves(transgenic) with high expression of NaD1 gene,and determined for the concentrations by Bardford method,while for the antibacterial activity against fungi by filter paper method,and for the inhibition activity on cancer cells(HeLa cells) by CCK-8.Results The total protein concentrations of Nicotiana alata flowers,WT and transgenic K326 tobacco leaves were 11.25,10.33 and 10.14 mg/mL,respectively.The antibacterial activity of total protein from transgenic K326 tobacco leaves against Candida albicans was(85.68±3.08)%,which was 1.33 and 1.14 times that of total protein from WT K326 tobacco leaves and Nicotiana alata flowers,respectively(F=15 339,P <0.05);The antibacterial activity against Fusarium oxysporum was(148.48±2.47)%,which was 1.09 and 1.08 times that of total protein from WT K326tobacco leaves and Nicotiana alata flowers,respectively(F=4.927,P <0.05).The IC_(50) value of transgenic K326 tobacco leaf protein on HeLa cells was the smallest(6.11 mg/mL),and the inhibitory activity was 1.56 and 1.21 times that of total protein of WT K326 tobacco leaves and Nicotiana alata flowers,respectively(F=89.748,P <0.05).Conclusion The total protein of K326 tobacco with high expression of NaD1 gene has good antibacterial and anticancer bioactivities,which provides an experimental basis for producing antibacterial and anticancer biological agents with tobacco as bioreactor.

OBJECTIVE: To investigate the changes in gray matter volume in depressive-like mice and explore the possible mechanism. METHODS: Twenty-four 6-week-old C57 mice were randomized equally into control group and model group, and the mice in the model group were subjected to chronic unpredictable mild stimulation (CUMS) for 35 days. Magnetic resonance imaging was performed to examine structural changes of the grey matter volume in depressive-like mice. The expression of brain-derived neurotrophic factor (BDNF) in the grey matter of the mice was detected using Western blotting and immunofluorescence staining. RESULTS: Compared with the control mice, the mice with CUMS showed significantly decreased central walking distance in the open field test (P < 0.05) and increased immobile time in forced swimming test (P < 0.05). Magnetic resonance imaging showed that the volume of the frontal cortex was significantly decreased in CUMS mice (P < 0.001, when the mass level was greater than or equal to 10 756, the FDRc was corrected with P=0.05). Western blotting showed that the expression of mature BDNF in the frontal cortex was significantly decreased in CUMS mice (P < 0.05), and its expression began to decrease after the exposure to CUMS as shown by immunofluorescence staining. The volume of different clusters obtained by voxel-based morphometry (VBM) analysis was correlated with the expression level of mature BDNF detected by Western blotting (P < 0.05). CONCLUSION The decrease of frontal cortex volume after CUMS is related with the reduction of mature BDNF expression in the frontal cortex.
Animals ; Mice ; Blotting, Western ; Brain-Derived Neurotrophic Factor ; Cerebral Cortex ; Depression/physiopathology* ; Frontal Lobe/pathology*