1.Mechanism of Yantiao Fang regulating the Rho/ROCK signaling pathway in apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis
Qian CHEN ; Di WANG ; Dingyi ZHANG ; Sailei JIA ; Lihui WANG ; Yujing CAO ; Xian LI ; Yanhong LI
Chinese Journal of Comparative Medicine 2024;34(2):16-24
Objective To investigate the effect of Yantiao Fang on apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis by regulating the Rho/ROCK signaling pathway.Methods Seventy BALB/c mice were randomly divided into normal,sham,and model groups.Except for normal and sham groups,mice were subjected to cecal ligation and perforation to establish a mouse model of acute gastrointestinal injury caused by sepsis.The mouse models were randomly divided into model,Low,Medium,and High dose of Yantiao Fang,and ROCK inhibitor groups.Histopathological changes of the ileum were observed by HE staining.Serum levels of IL-1β,IL-6,TNF-α,and IL-10 were measured by ELISA.PCNA and Ki-67 expression was detected by immunohistochemistry.Cleaved caspase3 and Bax expression was detected by Western blot.ROCK and MLC mRNA expression in the ileum was measured by RT-qPCR.Results Compared with normal and sham groups,Chiu's pathological score,proinflammatory factor(IL-1β,IL-6,and TNF-α)levels,cleaved caspase3 and Bax protein expression,and ROCK and MLC mRNA levels were increased in the model group(P<0.05).Moreover,anti-inflammatory mediator IL-10 and expression of PCNA and Ki-67 in the ileum were decreased in the model group(P<0.05).Compared with the model group,histopathological changes of the ileum in all Yantiao Fang groups were improved by various degrees with the increase in dose.Chiu's pathological score,IL-1β,IL-6,and TNF-α serum levels,cleaved caspase3 and Bax protein expression,and ROCK and MLC mRNA levels were decreased in Yantian Fang groups(P<0.05).The IL-10 level and expression of PCNA and Ki-67 in the ileum were increased in Yantian Fang groups(P<0.05).Conclusions Yantiao Fang may inhibit apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury due to sepsis by regulating the Rho/ROCK signaling pathway,thereby alleviating intestinal tissue inflammation and ultimately preventing intestinal mucosal tissue injury.
2.Stepwise treatment strategy for spontaneous osteonecrosis of the medial femoral condyle of the knee joint
Jianke PAN ; Meiping YANG ; Yanhong HAN ; Di ZHAO ; Hetao HUANG ; Houran CAO ; Jun LIU ; Minghui LUO ; Xiang LI ; Hongyun CHEN ; Weiyi YANG
Chinese Journal of Tissue Engineering Research 2024;28(12):1907-1913
BACKGROUND:Currently,there have been a variety of conservative and surgical treatment plans for spontaneous osteonecrosis of the knee,achieving excellent results.However,a broad consensus on indication and guide of surgical treatment has not been announced.In clinical practice,there is still a misunderstanding that unicondylar replacement or total knee arthroplasty should be performed upon the discovery of spontaneous osteonecrosis of the knee,while an urgent need for universal access to the concept of stepwise therapy. OBJECTIVE:To summarize and find the factors leading to the poor effect of conservative treatment in spontaneous osteonecrosis of the knee,which occurred on the medial femoral condyle,from the literature and clinical cases,at the same time,combined with the Koshino stage,to propose the strategy of stepwise spontaneous osteonecrosis of the knee treatment on the medial femoral condyle. METHODS:A systematic search of the literature database was conducted to summarize the factors leading to poor outcomes of conservative treatment in spontaneous osteonecrosis of the medial femoral condyle.Meanwhile,according to the Clinical&Health Records for analytics&Sharing system,the cases receiving conservative and surgical treatment in spontaneous osteonecrosis of the medial femoral condyle in the Department of Orthopedics of Guangdong Provincial Hospital of Chinese Medicine from January 2017 to January 2023 were analyzed retrospectively,then the causes of success and failure in typical cases were summarized and analyzed. RESULTS AND CONCLUSION:(1)Early diagnosis and treatment of spontaneous osteonecrosis of the knee were very important for prognosis.For sudden knee pain in some patients,if no obvious abnormality was found in the X-ray examination,and the symptoms persisted and could not be relieved for more than 1 week,an MRI examination was recommended to detect early spontaneous osteonecrosis of the knee.(2)The X-ray images of Koshino stage 1 and stage 2 of spontaneous osteonecrosis of the medial femoral condyle were difficult to be distinguished,which needed to be probed by MRI.MRI images of Koshino stage 1 were mainly characterized by bone marrow edema,and an osteonecrosis area with a clear boundary was not formed,while MR images of Koshino stage 2 showed a necrotic area with a clear boundary.(3)Five factors leading to the poor effect of conservative treatment on spontaneous osteonecrosis of the medial femoral condyle were summarized:a.The necrotic area was>5 cm2;b.The necrotic area accounted for more than 40%of the condyle;c.relative compression percentage of medial meniscus≥33%(with or without medial meniscus injury and subchondral bone marrow edema);d.MRI depth of necrotic area(anterior-posterior diameter of sagittal necrotic area)>20 mm;e.varus deformity of lower limb>6°.(4)Conservative treatment of spontaneous osteonecrosis of the knee in Koshino stage 1 was good.For spontaneous osteonecrosis of the knee in Koshino stage 2,conservative treatment was preferred or combined with drilling decompression.If there was no relief or improvement of symptoms or in MRI after 3 months,while the patient had any of the previous five factors,then knee preservation surgery should be considered.For spontaneous osteonecrosis of the knee in Koshino stage 3 and stage 4,knee preservation surgery should be selected based on the previous five factors,including age,gender and activity level of the patient.Total knee arthroplasty was used for spontaneous osteonecrosis in Koshino stage 4,which was associated with symptomatic patellofemoral arthritis,valgus alignment,or necrotic area,which greatly affected the stability of unicondyle prosthesis.
3.National bloodstream infection bacterial resistance surveillance report (2022) : Gram-negative bacteria
Zhiying LIU ; Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(1):42-57
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.
4.Summary Analysis of National Surveillance on Kashin-Beck Disease from 1990 to 2023
Cui SILU ; Liu HUI ; Pei JUNRUI ; Li JIAXIN ; Jiao ZHE ; Deng QING ; Liu NING ; Cao YANHONG ; Yu JUN
Biomedical and Environmental Sciences 2024;37(9):1056-1066
Objective To analyze the epidemiological characteristics and epidemic situation of children with Kashin-Beck disease (KBD) in China,and provide the basis for formulating prevention and control measures. Methods Fixed-point monitoring,moving-point monitoring,and full coverage of monitoring were promoted successively from 1990 to 2023. Some children (7-12 years old) underwent clinical and right-hand X-ray examinations every year. According to the KBD diagnosis criteria,clinical and X-ray assessments were used to confirm the diagnosis. Results In 1990,the national KBD detectable rate was 21.01%. X-ray detection decreased to below 10% in 2003 and below 5% in 2007. Between 2010 and 2018,the prevalence of KBD in children was less than 0.4%,which fluctuated at a low level,and has decreased to 0% since 2019. Spatial epidemiological analysis indicated a spatial clustering of adult patients prevalence rate in the KBD areas. Conclusion The evaluation results of the elimination of KBD in China over the last 5 years showed that all villages in the monitored areas have reached the elimination standard. While the adult KBD patients still need for policy consideration and care.
5.Effects of Unicompartmental and Total Knee Arthroplasty on the Biomechanical Characteristics of Patients with Knee Osteoarthritis During Stair Ascent and Descent
Chuanbao CAO ; Donglin SHI ; Guangwei CHAI ; Xin WANG ; Yanhong ZHANG ; Gang MA ; Shifang YAN
Journal of Medical Biomechanics 2024;39(4):670-676
Objective To explore the clinical efficacy of single unicompartmental knee arthroplasty(UKA)and total knee arthroplasty(TKA)for the treatment of knee osteoarthritis.Methods A total of 21 patients who underwent TKA and 15 who underwent UKA were randomly recruited.Biomechanical tests were performed before surgery and at 6th and 12th month after surgery.A Vicon infrared motion capture system and Kistler three-dimensional force plate were used to simultaneously acquire the kinematic and kinetic data of the patients during stair walking.Results During stair ascent,the peak knee flexion moment in the TKA group was significantly lower than that in the UKA group;the time to peak knee flexion/adduction moment,knee flexion moment impulse,and load rate of the peak knee adduction moment in the UKA group were significantly lower than those in the UKA group.During stair descent,the peak knee extension power in the UKA group was significantly lower before surgery and at 6th month after surgery;the load rate of the peak vertical ground reaction force was significantly higher before surgery and the peak knee extension moment was significantly greater at 6th month after surgery;at 12th month after surgery,there was no significant difference in the biomechanical characteristics during stair ascent and descent.Conclusions The TKA and UKA groups showed similar knee joint function after surgery;however,compared with the UKA group,the TKA group may adopt a different lower extremity biomechanical pattern.The UKA group showed better quadriceps control after surgery and improved postural control during stair descent,whereas the TKA group adopted a conservative stair gait strategy to reduce the knee load.Compared with the peak moment,the time to peak moment and load rate of the peak moment were more sensitive indicators for determining the difference in the knee load.
6.Investigation of different sterilization methods of Astragali Radix decoction pieces and research on the best sterilization process
Yanhong GAO ; Ling CAO ; Linlin CUI ; Zongyuan JIN ; Bing ZHOU ; Chenpeng LI ; Lizhi ZHAO
China Pharmacist 2024;27(7):1134-1141
Objective To investigate the effects of different sterilization methods on the quality of Astragali Radix decoction pieces by comparing the properties,odor,fingerprint,sterilization effect,extract and active component contents of Astragali Radix decoction pieces,and to further optimize the best sterilization process parameters of Astragali Radix decoction pieces.Methods The effects of moist heat sterilization,irradiation sterilization and dry heat sterilization on the quality of Astragali Radix decoction pieces were compared,and the best sterilization method was selected.Based on this,taking the content of astragaloside IV,the content of isoflavone glucoside,the total content of the two and the sterilization rate as the assessment indicators,taking the sterilization temperature,sterilization time and material thickness as the assessment factors,on the basis of the single-factor test,the response surface method was used to optimize the optimal dry heat sterilization process of Astragali Radix decoction pieces.Results The dry heat sterilization method was selected to sterilize Astragali Radix decoction pieces.The best process for dry heat sterilization was as follows:the sterilization temperature of 113℃,sterilization time of 5.1 h,and the material thickness of 19 mm.Conclusion Considering the sterilization effect,the influence on the content of active ingredients,operability and cost,selecting dry heat sterilization is the best sterilization method for Astragali Radix decoction pieces,and the optimal sterilization process is stable and feasible,with good repeatability,which can provide scientific basis for its industrial production application.
7.National bloodstream infection bacterial resistance surveillance report(2022): Gram-positive bacteria
Chaoqun YING ; Yunbo CHEN ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(2):99-112
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive 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:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units,and the top five bacteria were Staphylococcus aureus( n=1 147,36.3%),coagulase-negative Staphylococci( n=928,29.3%), Enterococcus faecalis( n=369,11.7%), Enterococcus faecium( n=296,9.4%)and alpha-hemolyticus Streptococci( n=192,6.1%). The detection rates of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)were 26.4%(303/1 147)and 66.7%(619/928),respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome,rifampin,compound sulfamethoxazole,linezolid,minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%(2/369),and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions( χ2=14.578, P=0.002),while the detection rate of MRCNS in northern China was significantly higher than that in other regions( χ2=15.195, P=0.002). The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals( χ2=13.519 and 12.136, P<0.001). The detection rates of MRSA and MRCNS in economically more advanced regions(per capita GDP≥92 059 Yuan in 2022)were higher than those in economically less advanced regions(per capita GDP<92 059 Yuan)( χ2=9.969 and 7.606, P=0.002和0.006). Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China, Staphylococci is the most common while the MRSA incidence decreases continuously with time;the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China,with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.
8.Relationship between prognostic nutritional index and myocardial injury after non-cardiac surgery
Zhao LI ; Hao LI ; Chang LIU ; Siyi YAO ; Jingsheng LOU ; Yanhong LIU ; Jiangbei CAO ; Weidong MI
Chinese Journal of Anesthesiology 2024;44(11):1317-1322
Objective:To evaluate the relationship between prognostic nutritional index (PNI) and myocardial injury after non-cardiac surgery (MINS).Methods:This was a retrospective cohort study. The clinical data of adult patients ( n=2 203) who underwent liver resection surgery with general anesthesia at our center from January 2016 to August 2019 were retrospectively collected. The predictive value of preoperative PNI for MINS and the optimal cut-off value of PNI were evaluated and determined according to the receiver operating characteristic curve, and the patients were divided into 2 groups based on the cut-off value: high PNI group and low PNI group. Logistic regression analyses were applied to investigate the relationship between preoperative PNI and MINS. According to the same inclusion and exclusion criteria, the clinical data of patients at our center from January 2022 to December 2023 were collected as the validation set ( n=2 525), and they were grouped using the same PNI cutoff value. Logistic regression analyses were used to verify the relationship between PNI and MINS. Results:The receiver operating characteristic curve analysis showed that the area under the curve of preoperative PNI for predicting MINS was 0.651 (95% confidence interval [ CI] 0.602-0.699), with an optimal cut-off value of 46.193, and the specificity and sensitivity were 0.729 and 0.519 respectively. The integer 46 was considered as the optimal cutoff value for PNI, and the patients were divided into low PNI group (PNI<46, n=606) and high PNI group (PNI≥46, n=1 597). Both univariate and multivariate logistic regression analyses showed that preoperative low PNI was an independent risk factor for the occurrence of MINS (univariate: OR=2.873, 95% CI 2.063-4.003, P<0.001; multivariate: OR=1.844, 95% CI 1.241-2.600, P=0.003). The results in the validation set were still robust (univariate: OR=2.694, 95% CI 1.890-3.833, P<0.001; multivariate: OR=1.602, 95% CI 1.071-2.385, P=0.021). Conclusions:Preoperative low-level PNI is an independent risk factor for MINS, with a certain predictive value.
9.The influence of interleukin-35 on the balance between regulatory T cells and T helper 22 cells in patients with Hashimoto′s thyroiditis
Lichao ZHAO ; Jianlin ZHAO ; Huifang CAO ; Jiangyan LI ; Yanhong ZHOU
Chinese Journal of Endocrinology and Metabolism 2024;40(8):669-675
Objective:To observe the expression of interleukin-35(IL-35) in Hashimoto's thyroiditis(HT) patients, and evaluate its regulatory effect on the balance between regulatory T cells(Treg) and T helper 22(Th22) cells.Methods:Forty-two HT patients and eighteen controls were consecutively enrolled. Plasma and peripheral blood mononuclear cells(PBMC) were isolated. Treg were purified. Plasma IL-35 and IL-22 were detected with enzyme-linked immunosorbent assay. Treg and Th22 percentages were measured using flow cytometry. Real-time quantitative PCR was used to assess mRNA levels of forhead box protein 3(FoxP3) and aryl hydrocarbon receptor(AhR). Treg were stimulated with exogenous IL-35, and were co-cultured with autologous PBMC to induce Treg-to-Th22 phenotypic differentiation, evaluating the effect of IL-35 on Treg function and differentiation.Results:There was imbalance between Treg and Th22 cells in HT group. HT group had reduced Treg percentage, plasma IL-35 and FoxP3 mRNA( P<0.001), while had elevated Th22 percentage and AhR mRNA( P<0.001). There was no significant difference in plasma IL-22 level between two groups( P=0.775). The suppressive capacity of Tregs in the HT group was diminished( P=0.013), and secretion levels of IL-35 and IL-10 were lower than those in the control group( P<0.001). The ability of Tregs in the HT group to differentiate into Th22 cells was increased, with higher levels of CCR4, CCR6, CCR10, AhR mRNA, and IL-22 secretion compared to the control group( P<0.01). IL-35 stimulation induced elevation of Treg percentage, FoxP3 mRNA, and IL-35/IL-10 secretion( P<0.05), but did not affect Th22 percentage, AhR mRNA, or IL-22 secretion( P>0.05). IL-35 stimulation enhanced Treg function in HT group, increasing proliferation inhibition and secretion of IL-35 and IL-10( P<0.05). IL-35 stimulation reduced the differentiation of Treg to Th22 phenotype in HT group, with decreased levels of CCR4, CCR6 CCR10, AhR mRNA, and IL-22 secretion( P<0.05). Conclusion:IL-35 enhances the immunosuppression of Tregs in HT patients and inhibits its differentiation into Th22 cells, thus regulating the balance between Tregs and Th22 cells.
10.Nuanxinkang Inhibits Endothelial-to-Mesenchymal Transition to Reduce Plaque Formation in Mice with Obstructive Sleep Apnea-Hypopnea Syndrome Comorbid with Atherosclerosis
Mingyang WANG ; Lingjun WANG ; Birong LIANG ; Zixin CHEN ; Yanhong CAO ; Yubing ZHANG ; Shuxian LI ; Jing LIU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):789-797
Objective To investigate the effect and mechanism of Nuanxinkang on plaque formation in obstructive sleep apnea-hypopnea syndrome(OSAHS)comorbid with atherosclerosis(AS)mice by inhibiting endothelial-to-mesenchymal transition(EndMT).Methods Male ApoE-/-mice were randomly divided into six groups:control group,model group,atorvastatin group(2.6 mg·kg-1)and Nuanxinkang low-,medium-and high-dose groups(crude drug 3.5,7.0,14.0 g·kg-1),with eight mice in each group.The mice were exposed to chronic intermittent hypoxia(CIH)environment during sleep for a long time,and fed with high-fat diet to replicate OSAHS comorbid with AS mouse model.Oil red O staining was used to observe the formation of plaque on aortic intima in mice.Masson trichrome staining was used to evaluate the collagen content of atherosclerotic plaques in the aortic root of mice.The expressions of endothelial cell marker CD31 and EndMT marker Vimentin in aortic plaque were detected by immunofluorescence.Blood lipid levels were determined by ELISA;the mRNA expression levels of EndMT markers α-SMA and Cdh2 in aortic tissue were detected by qPCR.Results Compared with the control group,the area of aortic atherosclerotic plaque in the model group was significantly increased(P<0.01),and the area of collagen deposition in the aortic root plaque was significantly increased(P<0.01).The number of CD31 positive cells in the plaque were significantly decreased(P<0.01),and the number of Vimentin positive cells were significantly increased(P<0.01).Serum TG,T-CHO and LDL-C levels were significantly increased(P<0.01),and HDL-C level was significantly decreased(P<0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue were significantly increased(P<0.01).Compared with the model group,the area of aortic atherosclerotic plaque in Nuanxinkang groups were significantly reduced(P<0.05,P<0.01),and the collagen deposition area of aortic root atherosclerotic plaque were significantly reduced(P<0.05,P<0.01).The number of CD31 positive expression cells in the plaque of Nuanxinkang high-dose group were significantly increased(P<0.05),and the number of Vimentin positive expression cells in the plaque of Nuanxinkang medium-and high-dose groups were significantly decreased(P<0.05,P<0.01).The serum TG level of mice in the high-dose group of Nuanxinkang was significantly decreased(P<0.01).The serum T-CHO and LDL-C levels of mice in each Nuanxinkang administration group were significantly decreased(P<0.05,P<0.01).The serum HDL-C levels of mice in the medium-and high-dose groups of Nuanxinkang were significantly increased(P<0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue of mice in each treatment group were significantly decreased(P<0.01).Conclusion Nuanxinkang can effectively reduce the plaque formation in OSAHS comorbid with atherosclerosis mice,which may be related to its inhibition of EndMT and reduction of collagen fiber formation.

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