1.Environmental contamination related to the first patient with carbapenem-resistant Acinetobacter baumannii infection and the infection status of pa-tients in the intensive care unit in Tibetan areas
Cuo-Ta QIE ; Ding-Ying HE ; Fu-Yan LONG ; Xiao-Hua ZHANG ; Chun-Hua PENG ; Xiang-Xiang JIANG ; Ming-Lei DENG ; Cong FU ; Guo-Ping ZUO
Chinese Journal of Infection Control 2024;23(2):220-224
Objective To investigate the environmental contamination related to first patient with carbapenem-re-sistant Acinetobacter baumannii(CRAB)infection and the infection status of relevant patients in a newly established intensive care unit(ICU)of a hospital in Tibetan area,and analyze the transmission risk.Methods From the ad-mission in ICU of a patients who was first detected CRAB on November 15,2021 to the 60th day of hospitalization,all patients who stayed in ICU for>48 hours were performed active screening on CRAB.On the 30th day and 60th day of the admission to the ICU of the first CRAB-infected patient,environment specimens were taken respectively 2 hours after high-frequency diagnostic and therapeutic activities but before disinfection,and after disinfection but before medical activities.CRAB was cultured with chromogenic culture medium.Results Among the 13 patients who were actively screened,1 case was CRAB positive,he was transferred from the ICU of a tertiary hospital to the ICU of this hospital on November 19th.On the 40th day of admission to the ICU,he had fever,increased frequency for sputum suction,and CRAB was detected.The drug sensitivity spectrum was similar to that of the first case,and he also stayed in the adjacent bed of the first case.64 environmental specimens were taken,and 9 were positive for CRAB,with a positive rate of 14.06%,8 sampling points such as the washbasin,door handle and bed rail were positive for CRAB after high-frequency diagnostic and therapeutic activities.After routine disinfection,CRAB was detected from the sink of the washbasin.Conclusion For the prevention and control of CRAB in the basic-level ICU in ethnic areas,it is feasible to conduct risk assessment on admitted patients and adopt bundled prevention and con-trol measures for high-risk patients upon admission.Attention should be paid to the contaminated areas(such as washbasin,door handle,and bed rail)as well as the effectiveness of disinfection of sink of washbasin.
2.Research progress on the impact of lipid metabolism on endometrial receptivity and embryo implantation
Li-Na MA ; Ying QIN ; Ke-Hua WANG ; Cong-Hui PANG ; Li-Ge LU ; Wen-Xian YUAN ; Duo-Jia ZHANG ; Xiao-Ke WU
Medical Journal of Chinese People's Liberation Army 2024;49(9):1088-1093
Lipids,including fats(triglycerides)and lipoids(phospholipids and sterols),not only serve as an energy source for the body but also play a pivotal role throughout the reproductive process,particularly in the establishment and maintenance of early pregnancy.This encompasses the regulate of early embryonic development and uterine tolerance,and the facilitation of embryo implantation.Given the diversity of lipids,this review focuses on extensively studied lipid mediators such as polyunsaturated fatty acids,endocannabinoids,prostaglandins,lysophosphatidic acid,sphingolipids and steroid hormones.It systematically elaborates on the regulatory effects of fatty acid,phospholipid,and cholesterol metabolism on the formation of endometrial receptivity and embryo implantation,as well as the potential underlying mechanisms.The review aims to provide new insights and feasible intervention approaches for predicting and improving the outcomes of natural pregnancy and/or assisted reproductive technology.
3.Longitudinal intussusception versus end-to-side vasoepididymostomy:Comparison of their recanalization rates
Lu-Gang ZHAO ; Hong CHEN ; Gui-Hua LIU ; Cong FANG ; Xiao-Yan LIANG ; Jing ZHANG
National Journal of Andrology 2024;30(11):1002-1008
Objective:To compare the recanalization rate of 2-suture longitudinal intussusception vasoepididymostomy(LIVE)with that of4-suture end-to-side vasoepididymostomy(ESVE).Methods:This retrospective case-control study included 127 cases of obstructive azoospermia(OA)treated by LIVE(n=87)or ESVE(n=40)in our Center of Reproductive Medicine from October 2013 to July 2024.We analyzed the clinical data and compared the age,testis volume,level of serum follicle-stimulating hormone(FSH),operation time and postoperative recanalization rate between the two groups.Results:Spermatozoa were observed in 90(70.9%)of the 127 cases after surgery.There were no statistical differences in age,testis volume and FSH between the two groups of patients(all P>0.05),and nor were there any serious surgical complications.The operation time was significantly longer in the ESVE than in the LIVE group(22.0[20.0-25.8]vs 17.0[15.0-23.0]min,P<0.05),while the postoperative recanalization rate remarkably higher in the former than in the latter group(85.0%vs 64.4%,P<0.05).Vasoepididymostomy was performed at the caput epididymis in 11 cases,with a higher recanalization rate in the ESVE than in the LIVE group(50.0%[1/2]vs 33.3%[3/9]).Conclusion:ESVE achieved a higher postoperative recanalization rate than LIVE in the treatment of OA,but its advanta-ges need further investigation.
4.A comparative study for the efficacies of transaxillary non-inflatable endoscopic surgery versus traditional surgery for papillary thyroid carcinoma.
Xiao Lei CHEN ; Chao LI ; Yu Qiu ZHOU ; Yong Cong CAI ; Yu Dong NING ; Chun Yan SHUI ; Xu WANG ; Zi Xun ZENG ; Gang QIN ; Ming Hua GE ; Chuan Ming ZHENG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(4):351-357
Objective: To compare the efficacies between open surgery and axillary non-inflatable endoscopic surgery in papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 343 patients with unilateral PTC treated by traditional open surgery (201 cases) and transaxillary non-inflating endoscopic surgery (142 cases) from May 2019 to December 2021 in the Head and Neck Surgery of Sichuan Cancer Hospital. Among them, 97 were males and 246 were females, aged 20-69 years. 1∶1 propensity score matching (PSM) was performed on the enrolled patients, and the basic characteristics, perioperative clinical outcomes, postoperative complications, postoperative quality of life (Thyroid Cancer-Specific Quality of Life), aesthetic satisfaction and other aspects of the two groups were compared after successful matching. SPSS 26.0 software was used for statistical analysis. Results: A total of 190 patients were enrolled after PSM, with 95 cases in open group and 95 cases in endoscopic group. Intraoperative blood losses for endoscopic and open groups were [20 (20) ml vs. 20 (10) ml, M (IQR), Z=-2.22], postoperative drainage volumes [170 (70)ml vs. 101 (55)ml, Z=-7.91], operative time [135 (35)min vs. 95 (35)min, Z=-7.34], hospitalization cost [(28 188.7±2 765.1)yuan vs. (25 643.5±2 610.7)yuan, x¯±s, t=0.73], postoperative hospitalization time [(3.1±0.9)days vs. (2.6±0.9)days, t=-3.24], and drainage tube placement time [(2.5±0.8) days vs. (2.0±1.0)days, t=-4.16], with statistically significant differrences (all P<0.05). There was no significant difference in surgical complications (P>0.05). There were significant diffferences between two groups in the postoperative quality of life scores in neuromuscular, psychological, scar and cold sensation (all P<0.05), while there were no statistically significant differences in other quality of life scores (all P>0.05). In terms of aesthetic satisfaction 6 months after surgery, the endoscopic group was better than the open group, with statistically significant difference (χ2=41.47, P<0.05). Conclusion: Endoscopic thyroidectomy by a gasless unilateral axillary approach is a safe and reliable surgical method, which has remarkable cosmetic effect and can improve the postoperative quality of life of patients compared with the traditional thyroidectomy.
Male
;
Female
;
Humans
;
Thyroid Cancer, Papillary/surgery*
;
Retrospective Studies
;
Quality of Life
;
Thyroid Neoplasms/pathology*
;
Endoscopy
;
Thyroidectomy/methods*
5.Genotyping Characteristics of Human Fecal Escherichia coli and Their Association with Multidrug Resistance in Miyun District, Beijing.
Wei Wei ZHANG ; Xiao Lin ZHU ; Le Le DENG ; Ya Jun HAN ; Zhuo Wei LI ; Jin Long WANG ; Yong Liang CHEN ; Ao Lin WANG ; Er Li TIAN ; Bin CHENG ; Lin Hua XU ; Yi Cong CHEN ; Li Li TIAN ; Guang Xue HE
Biomedical and Environmental Sciences 2023;36(5):406-417
OBJECTIVE:
To explore the genotyping characteristics of human fecal Escherichia coli( E. coli) and the relationships between antibiotic resistance genes (ARGs) and multidrug resistance (MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data.
METHODS:
Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs, multilocus sequence typing (MLST), and polymorphism trees were analyzed using whole-genome sequencing data (WGS).
RESULTS:
This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal (49/70) and healthy groups (15/24).
CONCLUSION
We developed a random forest (RF) prediction model of TEM.1 + baeR + mphA + mphB + QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers.
Humans
;
Escherichia coli/genetics*
;
Escherichia coli Infections/epidemiology*
;
Multilocus Sequence Typing
;
Genotype
;
Beijing
;
Drug Resistance, Multiple, Bacterial/genetics*
;
Anti-Bacterial Agents/pharmacology*
;
Diarrhea
;
Microbial Sensitivity Tests
6.Identification of Q-markers for Schisandrae Sphenantherae Fructus in treating drug-induced liver injury based on network pharmacology, fingerprint and quantitative analysis.
Lu-Jie LIN ; Ming-Xiao ZHANG ; Hua LI ; Xue-Mei LAN ; Xiao-Lu WEI ; Cong GUO ; Bin YANG
China Journal of Chinese Materia Medica 2023;48(20):5460-5473
This study aims to establish the ultra-performance liquid chromatography(UPLC) fingerprint and multi-indicator quantitative analysis method for Schisandrae Sphenantherae Fructus(SSF) and to screen out the potential quality markers(Q-markers) of hepatoprotection based on network pharmacology. The similarity analysis was performed using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System, which showed that the similarity of the fingerprints of 15 samples from different regions ranged from 0.981 to 0.998. Eighteen common components were identified, from which 3 differential components were selected by cluster analysis and principal component analysis. The "component-target-pathway" network was built to predict the core components related to the hepatoprotective effects. Fourteen core components were screened by network pharmacology. They acted on the targets such as AKT1, CCND1, CYP1A1, CYP3A4, MAPK1, MAPK3, NOS2, NQO1, and PTGS2 to regulate the signaling pathways of lipid metabolism and atherosclerosis, hepatitis B, interleukin-17, and tumor necrosis factor. Considering the chemical measurability, characteristics, and validity, schisantherin A, anwulignan, and schisandrin A were identified as the Q-markers. The content of schisantherin A, anwulignan, and schisandrin A in the test samples were 0.20%-0.57%, 0.13%-0.33%, and 0.42%-0.70%, respectively. Combining the fingerprint, network pharmacology, and content determination, this study predicted that schisantherin A, anwulignan, and schisandrin A were the Q-markers for the hepatoprotective effect of SSF. The results can provide reference for improving the quality evaluation standard and exploring the hepatoprotective mechanism of SSF.
Schisandra/chemistry*
;
Network Pharmacology
;
Drugs, Chinese Herbal/chemistry*
;
Chemical and Drug Induced Liver Injury/drug therapy*
7.Influence of posttraumatic blood pressure variability on post-traumatic stress disorder
Cong HUANG ; Xiao LIU ; Lin LIU ; Aiming YAO ; Xianliang YAN ; Tie XU ; Rong HUA
Chinese Critical Care Medicine 2022;34(9):952-957
Objective:To investigate the relationship between blood pressure variability (BPV) and incidence of post-traumatic stress disorder (PTSD) in trauma patients.Methods:Patients admitted to the department of emergency medicine of the Affiliated Hospital of Xuzhou Medical University for acute trauma from January 2018 to December 2021 were enrolled. The clinical data and blood pressure at admission (T1), 10 minutes before anesthesia (T2), 60 minutes after surgery (T3), and 24 hours after surgery (T4) were collected. Coefficient of variation of blood pressure variation [CV-BP, including coefficient of variation of systolic blood pressure (CV-SBP), coefficient of variation of diastolic blood pressure (CV-DBP), coefficient of variation of mean arterial pressure (CV-MAP)] and its quartile were calculated. Patients were divided into Q1 group (CV-MAP ≤ 7.27), Q2 group (7.27 < CV-MAP ≤ 9.50), Q3 group (9.50 < CV-MAP ≤ 14.05) and Q4 group (CV-MAP > 14.05) according to CV-MAP quartile. The PTSD symptoms of the patients were evaluated using the PTSD scale (PCL-5) one month later, and the patients were divided into the PTSD group and the non-PTSD group according to whether PCL-5 score higher than 38. Then the differences of the above indicators were compared and analyzed. Spearman correlation analysis was used to analyze the relationship between each index and PCL-5 score; the risk factors of PTSD were analyzed by univariate binary Logistic regression. Variables with P < 0.05 were included in the multivariate binary Logistic regression model. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of CV-MAP on the incidence of PTSD. Results:A total of 112 patients were enrolled, including 24 in PTSD group and 88 in non-PTSD group. Compared with non-PTSD group, the proportion of women, T1 shock index, proportion of intraoperative and postoperative blood transfusion in PTSD group was higher. Besides, PTSD group also had longer PT, more intraoperative and postoperative blood transfusion, and lower postoperative hemoglobin (Hb) level (all P < 0.05). The T1 SBP, DBP, MAP and T4 MAP of patients in PTSD group were significantly lower than those in non-PTSD group [T1 SBP (mmHg, 1 mmHg≈0.133 kPa): 105.0 (86.3, 121.3) vs. 122.0 (112.0, 132.8), T1 DBP (mmHg): 62.5 (50.0, 77.3) vs. 76.0 (68.5, 82.8), T1 MAP (mmHg): 77.8 (60.4, 91.3) vs. 93.3 (82.5, 99.0), T4 MAP (mmHg): 83.8±9.1 vs. 88.7±10.4, all P < 0.05], CV-SBP, CV-DBP and CV-MAP were higher than those in the non-PTSD group [CV-SBP: 12.80 (10.12, 19.16) vs. 9.30 (6.07, 12.95), CV-DBP: 16.62±6.47 vs. 12.40±5.61, CV-MAP: 14.10 (9.25, 18.85) vs. 8.90 (6.93, 13.29), all P < 0.05]. Spearman correlation analysis showed that there was a positive correlation between CV-MAP and PCL-5 scores in patients with acute trauma ( r = 0.429, P < 0.001); multivariate binary Logistic regression analysis showed that only CV-MAP [odds ratio ( OR) = 1.128, 95% confidence interval (95% CI) was 1.015-1.254, P = 0.025] and CV-DBP ( OR = 1.114, 95% confidence interval (95% CI) was 1.016-1.221, P = 0.022) was the risk factor for PTSD in acute trauma patients. Compared with Q1 group, Q4 group was significantly more likely to develop PTSD ( OR = 18.6, 95% CI was 1.9-179.1, P = 0.012). CV-SBP, CV-DBP and CV-MAP had certain predictive value on PTSD diagnosis in patients with acute trauma according to ROC curve analysis results [area under the ROC curve (AUC) was 0.713, 0.682 and 0.726, respectively], among which CV-MAP has the highest predictive value. When the cut-off value of CV-MAP was 12.158, the sensitivity was 75.0% and the specificity was 69.3%. Conclusion:Higher BPV after trauma is a risk factor for PTSD. Maintaining stable blood pressure in trauma patients is of great significance for prevention and treatment of PTSD.
8.Effect of Shenmai Injection on Long-Term Prognosis of Patients with Chronic Heart Failure: A Multicenter, Large Sample Capacity, Long-Term Follow-Up Retrospective Cohort Study.
Hui GUAN ; Guo-Hua DAI ; Wu-Lin GAO ; Tong ZHANG ; Cong SUN ; Li-Li REN ; Xiao-Ming HOU ; Zhang LIU
Chinese journal of integrative medicine 2022;28(4):312-318
OBJECTIVE:
To explore the effect of Shenmai Injection (SMI) on the long-term prognosis of patients with chronic heart failure (CHF).
METHODS:
The Hospital Information System was used to extract data of CHF patients, and the retrospective cohort study was conducted for analysis. In non-exposed group, standardized Western medicine treatment and Chinese patent medicine or decoction were applied without combination of SMI while in the exposed group, SMI were applied for more than 7 days. Evaluation indicators are followed with New York Heart Association functional classification (NYHA classification), left ventricular ejection fraction (LVEF), N-terminal brain natriuretic peptide precursor (NT-ProBNP), cardiogenic death and heart failure (HF) readmission. Statistical analysis includes Kaplan-Meier analysis and Cox regression which are used to explore the relationship between SMI and outcome events.
RESULTS:
A total of 1,211 eligible CHF patients were involved and finally 1,047 patients were followed up successfully. After treatment, the cases of NYHA classification decline in the exposed and non-exposed groups accounted for 64.30% and 43.45%, respectively; the improvement values of LVEF were 8.89% and 7.91%, respectively; the improvement values of NT-ProBNP were 909 pg/mL and 735 pg/mL, respectively. After exposure on SMI, the rates of cardiogenic death and HF readmission reduced from 15.43% to 10.18% and 38.93% to 32.37%. According to Kaplan-Meier analysis, the log-rank P value of SMI and cardiogenic death was 0.014, while the counterpart of SMI and HF readmission was 0.025. Cox regression analysis indicated that for cardiogenic death, age, cardiomyopathy, diabetes, and NYHA classification were risk factors while β-blockers, aldosterone receptor antagonists, Chinese patent medicine/decoction and SMI were protective factors. Likewise, for HF readmission, age, cardiomyopathy, and NYHA classification were risk factors while SMI was a protective factor.
CONCLUSION
Combination with SMI on the standardized Western medicine treatment can effectively reduce cardiogenic mortality and readmission rate in CHF patients, and thereby improve the long-term prognosis.
Biomarkers
;
Drug Combinations
;
Drugs, Chinese Herbal
;
Follow-Up Studies
;
Heart Failure/drug therapy*
;
Humans
;
Natriuretic Peptide, Brain
;
Peptide Fragments
;
Prognosis
;
Retrospective Studies
;
Stroke Volume
;
Ventricular Function, Left
9.Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study.
Wei SHEN ; Zhi ZHENG ; Xin-Zhu LIN ; Fan WU ; Qian-Xin TIAN ; Qi-Liang CUI ; Yuan YUAN ; Ling REN ; Jian MAO ; Bi-Zhen SHI ; Yu-Mei WANG ; Ling LIU ; Jing-Hui ZHANG ; Yan-Mei CHANG ; Xiao-Mei TONG ; Yan ZHU ; Rong ZHANG ; Xiu-Zhen YE ; Jing-Jing ZOU ; Huai-Yu LI ; Bao-Yin ZHAO ; Yin-Ping QIU ; Shu-Hua LIU ; Li MA ; Ying XU ; Rui CHENG ; Wen-Li ZHOU ; Hui WU ; Zhi-Yong LIU ; Dong-Mei CHEN ; Jin-Zhi GAO ; Jing LIU ; Ling CHEN ; Cong LI ; Chun-Yan YANG ; Ping XU ; Ya-Yu ZHANG ; Si-Le HU ; Hua MEI ; Zu-Ming YANG ; Zong-Tai FENG ; San-Nan WANG ; Er-Yan MENG ; Li-Hong SHANG ; Fa-Lin XU ; Shao-Ping OU ; Rong JU
Chinese Journal of Contemporary Pediatrics 2022;24(2):132-140
OBJECTIVES:
To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China.
METHODS:
A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined.
RESULTS:
The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05).
CONCLUSIONS
It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female
;
Fetal Growth Retardation
;
Gestational Age
;
Hospitalization
;
Humans
;
Incidence
;
Infant
;
Infant, Newborn
;
Infant, Premature
;
Infant, Very Low Birth Weight
;
Prospective Studies
;
Risk Factors
10.The mechanism of ShengMaiSan reducing calcium leak and protecting myocardial contractile function in diabetic rats based on network pharmacology
Cong HUANG ; Ming-jie SUN ; Hai-feng CUI ; Li-hua SUN ; QIAN WU ; Qu ZHAI ; Xiao-lu SHI
Acta Pharmaceutica Sinica 2022;57(10):3115-3123
In this study, network pharmacology research and animal experiments were used to predict and validate the potential targets of ShengMaiSan (SMS) in the treatment of diabetic cardiomyopathy. The active components of SMS were obtained through TCMSP and BATMAN databases. The potential targets of the active components and diabetic cardiomyopathy were predicted by Swiss Target Prediction and GeneCards databases, respectively. The protein-protein interaction (PPI) network was constructed by String database. Cytoscape software was adopted to perform topological analysis to select the core action target. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed using Metascape platform. To validate the potential targets, a type I diabetic rat model which induced by intraperitoneal injection of streptozotocin (STZ) was prepared. Rats were divided into sham group, model group, SMS group and trimetazidine (TMZ) group. Left ventricular hemodynamics was detected after 4 weeks administrated of SMS or TMZ. Myocardial contraction and calcium transients were detected synchronously in cardiomyocytes, as well as sarcoplasmic reticulum calcium content, calcium leak level and ryanodine receptor 2 (RyR2) expression were detected. Based on network pharmacology, 1 288 targets of SMS, 1 066 targets of diabetic cardiomyopathy, and 180 overlapped targets were obtained. The 39 core targets were screened, and 159 pathways including calcium signaling pathway were screened by KEGG pathway analysis. According to the previous studies and focusing on the contractility of diabetic cardiomyopathy, this study was involved calcium signaling regulation pathway in the SMS protection mechanism. The results showed that, compared with sham group, the systolic function of left ventricular and myocardial cells were decreased, and the calcium transport was in disorder in model group; compared with model group, both SMS group and TMZ group increased the maximum systolic pressure of left ventricle and the maximum systolic rate of left ventricular contraction. In addition, SMS group and TMZ group increased the contraction amplitude of cardiomyocytes, decreased the diastolic calcium concentration, the sarcoplasmic reticulum calcium leak and decreased the phosphorylation level of RyR2. There was no significant difference between SMS and TMZ groups. In summary, SMS could reduce the calcium leak of the sarcoplasmic reticulum and enhance the myofilament sensitivity of calcium to increasing contractile function of diabetic rats. The animal welfare and experiment procedures of this study were in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences.

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