1.Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models: A Cross-sectional Study in Rural Guangxi
Jian Yu LIANG ; Hui Jia RONG ; Xiu Xue WANG ; Sheng Jian CAI ; Dong Li QIN ; Mei Qiu LIU ; Xu TANG ; Ting Xiao MO ; Fei Yan WEI ; Xia Yin LIN ; Xiang Shen HUANG ; Yu Ting LUO ; Yu Ruo GOU ; Jing Jie CAO ; Wu Chu HUANG ; Fu Yu LU ; Jian QIN ; Yong Zhi ZHANG
Biomedical and Environmental Sciences 2024;37(1):3-18
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 (Pinteractions 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.
2.Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population.
Meng Fan LIU ; Rui Xia MA ; Xian Bao CAO ; Hua ZHANG ; Shui Hong ZHOU ; Wei Hong JIANG ; Yan JIANG ; Jing Wu SUN ; Qin Tai YANG ; Xue Zhong LI ; Ya Nan SUN ; Li SHI ; Min WANG ; Xi Cheng SONG ; Fu Quan CHEN ; Xiao Shu ZHANG ; Hong Quan WEI ; Shao Qing YU ; Dong Dong ZHU ; Luo BA ; Zhi Wei CAO ; Xu Ping XIAO ; Xin WEI ; Zhi Hong LIN ; Feng Hong CHEN ; Chun Guang SHAN ; Guang Ke WANG ; Jing YE ; Shen Hong QU ; Chang Qing ZHAO ; Zhen Lin WANG ; Hua Bin LI ; Feng LIU ; Xiao Bo CUI ; Sheng Nan YE ; Zheng LIU ; Yu XU ; Xiao CAI ; Wei HANG ; Ru Xin ZHANG ; Yu Lin ZHAO ; Guo Dong YU ; Guang Gang SHI ; Mei Ping LU ; Yang SHEN ; Yu Tong ZHAO ; Jia Hong PEI ; Shao Bing XIE ; Long Gang YU ; Ye Hai LIU ; Shao wei GU ; Yu Cheng YANG ; Lei CHENG ; Jian Feng LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(6):579-588
Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female
;
Humans
;
Adolescent
;
SARS-CoV-2
;
Smell
;
COVID-19/complications*
;
Cross-Sectional Studies
;
COVID-19 Vaccines
;
Incidence
;
Olfaction Disorders/etiology*
;
Taste Disorders/etiology*
;
Prognosis
3.Study of incubation period of infection with 2019-nCoV Omicron variant BA.5.1.3.
Wei Xia LI ; Li CAO ; De Hao ZHANG ; Chang CAI ; Li Ju HUANG ; Jian Nong ZHAO ; Yi NING
Chinese Journal of Epidemiology 2023;44(3):367-372
Objective: To study the incubation period of the infection with 2019-nCoV Omicron variant BA.5.1.3. Methods: Based on the epidemiological survey data of 315 COVID-19 cases and the characteristics of interval censored data structure, log-normal distribution and Gamma distribution were used to estimate the incubation. Bayes estimation was performed for the parameters of each distribution function using discrete time Markov chain Monte Carlo algorithm. Results: The mean age of the 315 COVID-19 cases was (42.01±16.54) years, and men accounted for 30.16%. A total of 156 cases with mean age of (41.65±16.32) years reported the times when symptoms occurred. The log-normal distribution and Gamma distribution indicated that the M (Q1, Q3) of the incubation period from exposure to symptom onset was 2.53 (1.86, 3.44) days and 2.64 (1.91, 3.52) days, respectively, and the M (Q1, Q3) of the incubation period from exposure to the first positive nucleic acid detection was 2.45 (1.76, 3.40) days and 2.57 (1.81, 3.52) days, respectively. Conclusions: The incubation period by Bayes estimation based on log-normal distribution and Gamma distribution, respectively, was similar to each other, and the best distribution of incubation period was Gamma distribution, the difference between the incubation period from exposure to the first positive nucleic acid detection and the incubation period from exposure to symptom onset was small. The median of incubation period of infection caused by Omicron variant BA.5.1.3 was shorter than those of previous Omicron variants.
Male
;
Humans
;
Adult
;
Middle Aged
;
SARS-CoV-2
;
COVID-19
;
Bayes Theorem
;
Infectious Disease Incubation Period
;
Nucleic Acids
4.Clinical value of nucleic acid detection for hepatitis B virus screening in hospitalized patients
Chunhong DU ; Junhua HU ; Yuan ZHANG ; Jiwu GONG ; Jun ZHOU ; Qin MENG ; Juan LIU ; Jiangcun YANG ; Rong GUI ; Xianping LYU ; Rong XIA ; Fenghua LIU ; Li QIN ; Shu SU ; Jinqi MA ; Juan CAI ; Huifang JIN ; Qi ZHANG ; Jun ZHANG ; Rongyi CAO ; Xiying LI ; Peng WANG
Chinese Journal of Laboratory Medicine 2023;46(1):27-31
Objective:To explore clinical value of nucleic acid detection for hepatitis B virus (HBV) screening in hospitalized patients.Methods:This cross-sectional study collected and analyzed plasma samples from patients admitted to 10 domestic medical institutions from July 2021 to December 2021. Serological immunoassay and nucleic acid screening were used to simultaneously detect hepatitis B markers such as hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e Antigen (HBeAg), hepatitis B e antibody (HBeAb), hepatitis B core antibody (HBcAb),and HBV DNA. Statistical analysis was performed on the serology, nucleic acid test results and clinical information of the patients.Results:Of the 8 655 collected samples, HBsAg was positive in 216 (2.50%) samples,HBV DNA was positive in 238 (2.75%) samples ( P>0.05); 210 (2.43%) samples were positive for both HBsAg and HBV DNA, 28 (0.32%) were HBsAg negative and HBV DNA positive, 6 cases (0.07%) were HBsAg positive and HBV DNA negative. Conclusion:These results indicate that the HBV DNA testing is equally effective as hepatitis B virus serological detection for hepatitis B virus screening in hospitalized patients.
5.A multicenter study assessing the efficacy of various preoperative/pre-transfusion screening methods for blood transmitted disease
Junhua HU ; Li QIN ; Juan LIU ; Xinghuan MA ; Qin MENG ; Peng WANG ; Jiangcun YANG ; Rong GUI ; Chunhong DU ; Xiying LI ; Xianping LYU ; Rong XIA ; Fenghua LIU ; Shu SU ; Jinqi MA ; Yuan ZHANG ; Juan CAI ; Huifang JIN ; Qi ZHANG ; Jun ZHANG ; Rongyi CAO ; Bing HAN ; Jiwu GONG ; Jun ZHOU
Chinese Journal of Laboratory Medicine 2023;46(1):32-37
Objective:This multi-centre study was conducted to assess the efficacy of various preoperative/pre-transfusion screening methods for blood transmitted disease.Methods:From July 2021 to December 2021, plasma samples of patients admitted to 10 hospitals were collected for screening preoperative/pre-transfusion blood transmitted disease. Nucleic acid detection technology was used to detect hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA and human immunodeficiency virus (HIV)(1+2) RNA, and the results were compared with the immuno-serological methods. χ 2 test and Kappa test were used to analyze the efficacy of these two methods. Results:A total of 8 655 valid specimens were collected from 10 hospitals. There was a statistically significant difference in the positive detection rate of HCV between the two methods ( P<0.001). There was no significant difference in the positive detection rate of HBV and HIV assessed by the two methods ( P>0.05), but the number of positive cases detected by HBV DNA and HIV RNA (218 and 4 cases) was significantly higher than the corresponding serological results (216 and 2 cases). At the same time, there were HBV, HCV and HIV immuno-serological omissions by the immuno-serological methods, among which 28 cases were HBsAg negative and HBV DNA positive, 2 cases were HCV antibody negative and HCV RNA positive, and 2 cases were HIV antigen/antibody negative and HIV RNA positive. In addition, in the 66 samples with inconsistent results from the two detection methods, 83.3% (55/66), 68.2% (45/66), 63.6% (42/66) and 62.1% (41/66) of patients aged was>45 years, tumor, surgery and male, respectively. Conclusions:Compared with immuno-serological tests, nucleic acid tests have the advantage in terms of sensitivity on detecting HBV, HCV and HIV infection and could reduce missed detection. The risk of transmission can be reduced by adding HBV, HCV, and HIV nucleic acid tests to preoperative/pre-transfusion immuno-serological tests screening for patients over 45 years of age and tumor patients.
6.Cost-effectiveness analysis of nucleic acid screening for hepatitis B and C in hospitalized patients in China
Shu SU ; Qi ZHANG ; Peng WANG ; Rong GUI ; Chunhong DU ; Xiying LI ; Xianping LYU ; Rong XIA ; Fenghua LIU ; Li QIN ; Jiameng NIU ; Lili XING ; Leilei ZHANG ; Jinqi MA ; Junhua HU ; Yuan ZHANG ; Juan CAI ; Huifang JIN ; Jun ZHANG ; Rongyi CAO ; Jiwu GONG ; Jiangcun YANG
Chinese Journal of Laboratory Medicine 2023;46(1):38-44
Objective:To compare the cost-effectiveness of hospitalized Chinese patients undergoing nucleic acid screening strategies for hepatitis B and hepatitis C, immunological screening strategy, and no screening strategy under different willingness to pay (WTP). The results might aid to decision-making for the optimal strategy.Methods:In this study, nucleic acid screening, immunological screening and no screening were used as screening strategies, and China′s GDP in 2021 (80 976 yuan) was used as the threshold of WTP to construct a Markov model. After introducing parameters related to the diagnosis and treatment of hepatitis B and C in inpatients, a cohort population of 100 000 inpatients was simulated by TreeAge Pro 2021 software, the total cost, total health effects, incremental cost-effectiveness ratio and average cost-effectiveness ratio of different screening strategies were calculated, and cost-effectiveness analysis was conducted. Univariate and probabilistic sensitivity analysis were used to assess the impact of parameter uncertainty on the final results.Results:Compared with the non-screening strategy, the incremental total cost of the hepatitis B immunological screening strategy for cohort patients was 11 049 536 yuan, and the incremental cost-effectiveness ratio was 24 762 yuan/quality-adjusted life years (QALY), while the total incremental cost of nucleic acid screening was 19 208 059 yuan, and the incremental cost-effectiveness ratio was 29 873 yuan/QALY; the incremental cost-effectiveness ratio of nucleic acid screening and immunological screening was 45 834 yuan/QALY. Compared with the non-screening strategy, the incremental cost-effectiveness ratio of hepatitis C immunological screening strategy was 5 731 yuan/QALY, the incremental cost-effectiveness ratio of nucleic acid screening strategy was 8 722 yuan/QALY, the incremental cost-effectiveness ratio of nucleic acid screening and immunological screening was 45 591 yuan/QALY. The results of probabilistic sensitivity analysis showed that when the cost of nucleic acid testing exceeded 214.53 yuan, it was not cost-effective to perform hepatitis B nucleic acid screening under the WTP as 1 fold GDP. When the cost of nucleic acid testing exceeded 132.18 yuan, it was not cost-effective to conduct hepatitis C screening under the WTP as 1 fold GDP.Conclusions:Nucleic acid screening strategy can achieve more cost-effectiveness and is worthy of vigorous promotion. Compared with no screening, both the nucleic acid and immunological screening strategies are cost-effective, and hepatitis nucleic acid screening is the optimal strategy for hospitalized patients.
7.Mediating effect of patient motivation between health literacy and self-management behaviour in patients with knee osteoarthritis
Yuna CAI ; Xixi HUANG ; Jie YAO ; Jingjing CAO ; Yuanyuan FANG ; Xia SHAO ; Xiaowei LI ; Yan GUO
Modern Clinical Nursing 2023;22(10):16-23
Objective To investigate the status quo of health literacy,motivation and self-management behaviours of patients with knee osteoarthritis(KOA),to explore the influence of health literacy and motivation on self-management behaviours to the patients with KOA,and to clarify the relationships among the three factors.Methods Convenience sampling method was used to select 169 KOA patients who were treated in 3 tertiary hospitals in Xianyang between September and December 2021.General status table,chronic disease health literacy scale,patient motivation scale and chronic disease self-management behaviour scale were employed in the on-the-spot survey.Pearson correlation was used to analyze the correlation of health literacy,motivation and self-management behaviour of patients with KOA.Results Total scores of health literacy,motivation and self-management behaviour of the patients with KOA were 79.66±11.91,54.97±9.95 and 23.75±8.89,respectively.It was found that health literacy and motivation of the patients were positively correlated with their self-management behaviour(r=0.872,r=0.822,both P<0.01).Health literacy of the patients was positively correlated with motivation of patients(r=0.877,P<0.01).Health literacy of the patients could be used to directly predict self-management behaviour of patients(β=0.708,95%CI:0.539-0.876),as well as to predict self-management behaviour of the patients through the mediating effect of patient motivation(β=0.228,95%CI:0.676-0.787).The mediating effect accounted for 24.36%of the total effect.Conclusions The health literacy,motivation and self-management behaviours of patients with KOA are all poor and they should be further improved.Patient motivation is the mediating variable in health literacy and self-management behaviour of the patients.It is suggested that nursing staff could encourage the motivation of patients hence to improve the self-management behaviour in the patients with KOA based on an improvement of health literacy.
8.A multicenter epidemiological study of acute bacterial meningitis in children.
Cai Yun WANG ; Hong Mei XU ; Jiao TIAN ; Si Qi HONG ; Gang LIU ; Si Xuan WANG ; Feng GAO ; Jing LIU ; Fu Rong LIU ; Hui YU ; Xia WU ; Bi Quan CHEN ; Fang Fang SHEN ; Guo ZHENG ; Jie YU ; Min SHU ; Lu LIU ; Li Jun DU ; Pei LI ; Zhi Wei XU ; Meng Quan ZHU ; Li Su HUANG ; He Yu HUANG ; Hai Bo LI ; Yuan Yuan HUANG ; Dong WANG ; Fang WU ; Song Ting BAI ; Jing Jing TANG ; Qing Wen SHAN ; Lian Cheng LAN ; Chun Hui ZHU ; Yan XIONG ; Jian Mei TIAN ; Jia Hui WU ; Jian Hua HAO ; Hui Ya ZHAO ; Ai Wei LIN ; Shuang Shuang SONG ; Dao Jiong LIN ; Qiong Hua ZHOU ; Yu Ping GUO ; Jin Zhun WU ; Xiao Qing YANG ; Xin Hua ZHANG ; Ying GUO ; Qing CAO ; Li Juan LUO ; Zhong Bin TAO ; Wen Kai YANG ; Yong Kang ZHOU ; Yuan CHEN ; Li Jie FENG ; Guo Long ZHU ; Yan Hong ZHANG ; Ping XUE ; Xiao Qin LI ; Zheng Zhen TANG ; De Hui ZHANG ; Xue Wen SU ; Zheng Hai QU ; Ying ZHANG ; Shi Yong ZHAO ; Zheng Hong QI ; Lin PANG ; Cai Ying WANG ; Hui Ling DENG ; Xing Lou LIU ; Ying Hu CHEN ; Sainan SHU
Chinese Journal of Pediatrics 2022;60(10):1045-1053
Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent
;
Brain Abscess
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Child
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Child, Preschool
;
Escherichia coli
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Female
;
Humans
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Hydrocephalus
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Infant
;
Infant, Newborn
;
Male
;
Meningitis, Bacterial/epidemiology*
;
Retrospective Studies
;
Streptococcus agalactiae
;
Streptococcus pneumoniae
;
Subdural Effusion
;
beta-Lactamases
9.Effects of exosomes from hepatocyte growth factor-modified human adipose mesenchymal stem cells on full-thickness skin defect in diabetic mice.
Tao CAO ; Dan XIAO ; Peng JI ; Zhi ZHANG ; Wei Xia CAI ; Chao HAN ; Wen LI ; Ke TAO
Chinese Journal of Burns 2022;38(11):1004-1013
Objective: To investigate the effects and mechanism of exosomes from hepatocyte growth factor (HGF)-modified human adipose mesenchymal stem cells (ADSCs) on full-thickness skin defect wounds in diabetic mice. Methods: The experimental study method was adopted. Discarded adipose tissue of 3 healthy females (10-25 years old) who underwent abdominal surgery in the Department of Plastic Surgery of First Affiliated Hospital of Air Force Medical University from February to May 2021 was collected, and primary ADSCs were obtained by collagenase digestion method and cultured for 7 days. Cell morphology was observed by inverted phase contrast microscope. The ADSCs of third passage were transfected with HGF lentivirus and cultured for 5 days, and then the fluorescence of cells was observed by imaging system and the transfection rate was calculated. The exosomes of ADSCs of the third to sixth passages and the HGF transfected ADSCs of the third to sixth passages were extracted by density gradient centrifugation, respectively, and named, ADSC exosomes and HGF-ADSC exosomes. The microscopic morphology of exosomes was observed by transmission electron microscopy, and the positive expressions of CD9, CD63, and CD81 of exosomes were detected by flow cytometry, respectively. Twenty-four 6-week-old male Kunming mice were selected to make the diabetic models, and full-thickness skin defect wounds were made on the backs of mice. According to the random number table method, the mice were divided into phosphate buffer solution (PBS) group, HGF alone group, ADSC exosome alone group, and HGF-ADSC exosome group, with 6 mice in each group, and treated accordingly. On post injury day (PID) 3, 7, 10, and 14, the wounds were observed and the wound healing rate was calculated; the blood flow intensity of wound base was detected by Doppler flowmeter and the ratio of relative blood flow intensity on PID 10 was calculated. On PID 10, the number of Ki67 positive cells in wounds was detected by immunofluorescence method, and the number of new-vascularity of CD31 positive staining and tubular neovascularization in the wounds was detected by immunohistochemistry method; the protein expressions of protein endothelial nitric oxide synthase (eNOS), phosphatidylinositol 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (Akt) and phosphorylated Akt (p-Akt) in wounds were detected by Western blotting, and the ratios of p-PI3K to PI3K and p-Akt to Akt were calculated. On PID 14, the defect length and collagen regeneration of wound skin tissue were detected by hematoxylin and eosin staining and Masson staining, respectively, and the collagen volume fraction (CVF) was calculated. The number of samples is 3 in all cases. Data were statistically analyzed with repeated measurement analysis of variance, one-way analysis of variance, and Tukey test. Results: After 7 days of culture, the primary ADSCs were spindle shaped and arranged in vortex shape after dense growth. After 5 days of culture, HGF transfected ADSCs of the third passage carried green fluorescence, and the transfection rate was 85%. The ADSC exosomes and HGF-ADSC exosomes were similar in microscopic morphology, showing vesicular structures with an average particle size of 103 nm and 98 nm respectively, and both were CD9, CD63, and CD81 positive. On PID 3, the wounds of mice in the 4 groups were all red and swollen, with a small amount of exudate. On PID 7, the wounds of HGF-ADSC exosome group were gradually reduced, while the wounds of the other three groups were not significantly reduced. On PID 10, the wounds in the 4 groups were all reduced and scabbed. On PID 14, the wounds in HGF-ADSC exosome group were basically healed, while the residual wounds were found in the other three groups. On PID 3, the healing rates of wounds in the four groups were similar (P>0.05); On PID 7 and 10, the wound healing rates in HGF-ADSC exosome group were significantly higher than those in PBS group, HGF alone group, and ADSC exosome alone group, respectively (with q values of 13.11, 13.11, 11.89, 12.85, 11.28, and 7.74, respectively, all P<0.01); on PID 14, the wound healing rate in HGF-ADSC exosome group was significantly higher than that in PBS group, HGF alone group, and ADSC exosome alone group (with q values of 15.50, 11.64, and 6.36, respectively, all P<0.01). On PID 3, there was no obvious blood supply in wound base of mice in the 4 groups. On PID 7, microvessels began to form in the wound base of HGF-ADSC exosome group, while the wound base of the other three groups was only congested at the wound edge. On PID 10, microvessel formation in wound base was observed in the other 3 groups except in PBS group, which had no obvious blood supply. On PID 14, the blood flow intensity of wound base in HGF-ADSC exosome group was stronger than that in the other 3 groups, and the distribution was uniform. On PID 10, the ratio of wound base relative blood flow intensity in HGF-ADSC exosome group was significantly higher than that in PBS group, HGF alone group, and ADSC exosome alone group (with q values of 23.73, 19.32, and 9.48, respectively, all P<0.01); The numbers of Ki67-positive cells and new-vascularity of wounds in HGF-ADSC exosome group were significantly higher than those in PBS group, HGF alone group, and ADSC exosome alone group, respectively (with q values of 19.58, 18.20, 11.04, 20.68, 13.79, and 8.12, respectively, P<0.01). On PID 10, the protein expression level of eNOS of wounds in HGF-ADSC exosome group was higher than that in PBS group, HGF alone group, and ADSC exosome alone group (with q values of 53.23, 42.54, and 26.54, respectively, all P<0.01); the ratio of p-PI3K to PI3K and the ratio of p-Akt to Akt of wounds in HGF-ADSC exosome group were significantly higher than those in PBS group, HGF alone group, and ADSC exosome alone group, respectively (with q values of 16.11, 11.78, 6.08, 65.54, 31.63, and 37.86, respectively, P<0.01). On PID 14, the length of skin tissue defect in the wounds of HGF-ADSC exosome group was shorter than that in PBS group, HGF alone group, and ADSC exosome alone group (with q values of 20.51, 18.50, and 11.99, respectively, all P<0.01); the CVF of wounds in HGF-ADSC exosome group was significantly higher than that in PBS group, HGF alone group and ADSC exosome alone group (with q values of 31.31, 28.52, and 12.35, respectively, all P<0.01). Conclusions: Human HGF-ADSC exosomes can significantly promote wound healing in diabetic mice by increasing neovascularization in wound tissue, and the mechanism may be related to the increased expression of eNOS in wounds by activating PI3K/Akt signaling pathway.
Female
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Humans
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Male
;
Mice
;
Animals
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Child
;
Adolescent
;
Young Adult
;
Adult
;
Exosomes
;
Proto-Oncogene Proteins c-akt
;
Hepatocyte Growth Factor
;
Diabetes Mellitus, Experimental
;
Phosphatidylinositol 3-Kinases
;
Ki-67 Antigen
;
Adipose Tissue
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Skin Abnormalities
;
Soft Tissue Injuries
;
Collagen
;
Mesenchymal Stem Cells
10.Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021.
Hui Yao HUANG ; Da Wei WU ; Qi ZHU ; Yue YU ; Hai Xue WANG ; Jun WANG ; Man GA ; Xin Yu MENG ; Jing Ting DU ; Shuang Man MIAO ; Zhi Xia ZHAO ; Xin WANG ; Pu SHANG ; Min Jiang GUO ; Li Hong LIU ; Yu TANG ; Ning LI ; Cai CAO ; Bing He XU ; Yan SUN ; Jie HE
Chinese Journal of Oncology 2022;44(3):276-281
Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China
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Gastrointestinal Agents/therapeutic use*
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Gastrointestinal Neoplasms
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Humans
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Pharmaceutical Preparations
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United States
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United States Food and Drug Administration

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