1.Effect of Xinfeng Capsules Combined with Chronic Disease Management of Traditional Chinese Medicine on Rapid Disease Control and Short-term Prognosis of Patients with Rheumatoid Arthritis
Dandan TIAN ; Hong ZHAO ; Man LUO ; Shanping WANG ; Li YANG ; Tingting ZHANG ; Xi CHEN ; Chuanbing HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):137-144
ObjectiveTo investigate the effects of Xinfeng capsules combined with chronic disease management of traditional Chinese medicine (TCM) on rapid disease control and short-term prognosis of patients with rheumatoid arthritis (RA). MethodsA total of 80 RA patients hospitalized in the Department of Rheumatology of The First Affiliated Hospital of Anhui University of Chinese Medicine from January 2022 to March 2024 were enrolled and randomly divided into an observation group (40 cases) and a control group (40 cases). The control group was treated with conventional methotrexate combined with standard chronic disease management, while the observation group was additionally treated with Xinfeng Capsules combined with TCM chronic disease management. The treatment course lasted 24 weeks. The outcomes were compared between two groups, including disease activity [28-joint disease activity score (DAS28), clinical disease activity index (CDAI), simplified disease activity index (SDAI)], visual analogue scale (VAS) for pain, TCM syndrome score, tender joint count (TJC), swollen joint count (SJC), morning stiffness duration, Health Assessment Questionnaire (HAQ), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), American College of Rheumatology (ACR) 20%, 50% and 70% response rates (ACR20/50/70), erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (CCP-Ab), interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), and serum immunoglobulin G (IgG). The Chronic Disease Self-Management Scale (CDSMS) was used to evaluate patients’ self-management ability, self-care ability, and nursing satisfaction. Patients were followed up for 12 weeks to assess prognosis, and COX regression analysis was performed to determine the impact on short-term prognosis. ResultsAfter treatment, TJC, SJC, morning stiffness duration, DAS28, CDAI, SDAI, VAS, TCM syndrome score, ESR, hs-CRP, RF, CCP-Ab, IL-6, IL-1β, TNF-α, IgG, HAQ, SAS, SDS, chronic disease self-management behavior, self-efficacy, and self-care ability all improved significantly in both groups compared with baseline (P<0.05,P<0.01). Compared with the control group, the observation group showed more significant improvements in TJC, SJC, morning stiffness duration, DAS28, CDAI, SDAI, VAS, TCM syndrome score, ESR, IL-1β, IgG, HAQ, SAS, SDS, self-care ability, chronic disease self-management behavior, and self-efficacy (P<0.05 or P<0.01). The ACR70 response rate and nursing satisfaction were significantly higher in the observation group than in the control group (P<0.01). COX regression analysis showed that Xinfeng capsules combined with TCM chronic disease management reduced the risk of poor short-term prognosis in RA patients. ConclusionXinfeng capsules combined with TCM chronic disease management facilitates rapid disease control in RA patients, effectively improves short-term prognosis, and plays an important role in the treatment of the disease.
2.Saikosaponin regulates HIF-1α/BNIP3 signaling pathway to inhibit mitochondrial autophagy for the treatment of functional dyspepsia in rats with liver-gastric disharmony
Zheng-Liang QI ; Xiao LIU ; Man TIAN
Chinese Pharmacological Bulletin 2024;40(12):2256-2261
Aim To investigate the effect of saikosapo-nin on mitochondrial autophagy in rats with functional dyspepsia(FD)of liver stomach disharmony type by regulating the hypoxia inducible factor-1α(HIF-1α)/BCL2/adenovirus E1B interacting protein 3(BNIP3)signaling pathway.Methods A compound factor method was used to construct a liver stomach disharmo-ny type FD rat model.The rats were randomly separa-ted into a blank group,a model group,a dompendone group,and low,medium,and high dose saikosaponin groups,with 10 rats in each group.The gastrointesti-nal function of rats in each group was observed,inclu-ding gastric emptying rate and small intestine propul-sion rate,ELISA method was applied to detect serum levels of motilin(MTL)and gastrin(GAS),his-topathologic changes of the gastric sinus were observed by HE staining,transmission electron microscopy was applied to observe the mitochondrial structure of gastric antrum tissue,reagent kit was applied to detect levels of ROS,MDA,and SOD,Western blot was applied to detect the expression of mitochondrial LC3,Beclin1,p62,HIF-1α,and BNIP3 proteins in gastric antrum tissue.Results Compared with the blank group,the gastric antrum tissue of rats in the model group showed a small amount of inflammatory cell infiltration,mito-chondrial swelling and deformation,and a large num-ber of autophagosomes,the gastric emptying rate,small intestine propulsion rate,MTL,GAS,SOD,and p62 were greatly reduced,the levels of ROS,MDA,the protein expression of LC3 Ⅱ/LC3 I,Beclin1,HIF-1α,and BNIP3 were greatly increased(P<0.05);compared with the model group,the symptoms of gastric antrum tissue were greatly improved in the dompendone group,low,medium,and high-dose sai-kosaponin groups,with clear mitochondrial cristae and reduced autophagosomes,the gastric emptying rate,small intestine propulsion rate,MTL,GAS,SOD,and p62 were greatly increased,the levels of ROS,MDA,the protein expression of LC3 Ⅱ/LC3 Ⅰ,Beclin1,HIF-1α,and BNIP3 were greatly reduced(P<0.05).Conclusion Saikosaponin can improve gas-trointestinal function and inhibit mitochondrial autoph-agy in liver stomach disharmony type FD rats,and its mechanism of action may be related to the inhibition of the HIF-1α/BNIP3 signaling pathway.
3.Effects of alone and co-administration of berberine and 5'-N-ethylformamidoadenosine on cardiomyocyte hypoxia/reoxygen injury
Mei-Na GONG ; Ya-Yun GAO ; Shu-Ying ZHANG ; Xiao-Qian PANG ; Wei TIAN ; Jing-Man XU
Chinese Pharmacological Bulletin 2024;40(12):2311-2318
Aim To investigate the effects of berberine(BBR)combined with 5'-n-ethylformamidoadenosine(NECA)on myocardial H9c2 and HL-1 cell damage induced by hypoxia/reoxygenation(H/R).Methods H9c2 and HL-1 cells were divided into the Control group,BBR group,NECA group,combined administra-tion group,H/R group,BBR+H/R group,NECA+H/R group,and combined administration+H/R group.CCK-8 was used to detect cell viability in each group.The TMRE kit was used to detect MMP.DCFH-DA was used to detect ROS content.The Mito SOX Red fluorescent probe was used to detect mitochondrial su-peroxide.The expressions of COX Ⅳ,Tom20,and Tim23 were detected by Western blot.The expression of COX Ⅳ and Tom20 genes was detected by qRT-PCR.Results In H9c2 cells,the cell viability and TMRE fluorescence intensity in the H/R group were significantly decreased compared with the Control group.The protein expressions of COX Ⅳ,Tom20,and Tim23,gene expressions of COX Ⅳ and Tom20,ROS,and mitochondrial superoxide contents were significant-ly increased.Compared with the H/R group,the cell viability of BBR and NECA were enhanced after ad-ministration alone.The contents of ROS and mitochon-drial superoxide were significantly decreased.In HL-1 cells,cell viability in the H/R group was significantly decreased compared with the Control group.The con-tents of ROS and mitochondrial superoxide were signifi-cantly increased.Compared with the H/R group,BBR and NECA alone and combined administration en-hanced cell viability.The contents of ROS and mito-chondrial superoxide were significantly decreased.Conclusion The administration of BBR and NECA a-lone or in combination can reduce the production of mi-tochondrial superoxide and cell ROS,thereby allevia-ting mitochondrial damage,alleviating oxidative stress damage,and ultimately reducing H/R-induced myocar-dial cell damage.
4.A multicenter clinical study on the treatment of lateral epicondylitis of humerus by manipulation
Xiao-Zhou HOU ; Jing YIN ; Hai-Yang WANG ; Jin-Yu GU ; Tian-Hao WAN ; Man-Hong YANG ; Di XIA ; Qing ZHANG
China Journal of Orthopaedics and Traumatology 2024;37(3):251-257
Objective To investigate clinical effect of tendons pulling,poking and kneading for the treatment of external humeral epicondylitis.Metods From January 2018 to December 2021,a multicenter randomized controlled study was per-formed to collect 192 patients with external humeral epicondylitis in Wangjing Hospital,Beijing Dianli Hospital,and Beijing Fengsheng Osteotraumatology Hospital,respectively,and they were divided into treatment group and control group by random number table method.There were 96 patients in treatment group,including 36 males and 60 females,aged from 28 to 60 years old with an average of(41.20±5.50)years old;the course of disease ranged from 1 to 14 days with an average of(5.24±1.35)days;they were treated once every other day for 2 weeks.There were 96 patients in control group,including 33 males and 63 females,aged from 26 to 60 years old with an average of(43.35±7.75)years old;the course of disease ranged from 1 to 14 days with an average of(5.86±1.48)days;they were treated with topical voltaalin combined with elbow joint fixation for 2 weeks.Visual analogue scale(VAS)and Hospital for Surgery Scoring System(HSS)elbow pronation and supination angles,wrist metacarpal flexion and dorsal extension angles,elbow tenderness between two groups were compared before treatment and at 1,3,5,7,11 and 13 days after treatment;Hospital for Surgery Scoring System 2(HSS2)was compared before treatment and the final treatment.Results All patients were followed up for 10 to 14 days with an average of(12±1.6)days.VAS between treatment group and control group before treatment were 6.83±1.36 and 6.79±1.58,respectively,and decreased to 1.49±1.09 and 2.11±1.81 after the final treatment.VAS of treatment group were significantly lower than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P<0.05).HSS between two groups were 61.73±11.00 and 36.47±12.45 before treatment,respectively,and increased to 94.42±5.9 and 91.44±9.11 at the final treatment.HSS of treatment group were signifi-cantly higher than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P<0.05).On the 5th day after treat-ment,the external and internal rotation angles of elbow in treatment group were(66.41±12.69)° and(66.35±13.54)°,while those in control group were(62.08±16.03)° and(61.77±16.35)°.On the 7th day after treatment,the external and internal ro-tation angles of elbow were(69.79±12.64)° and(70.02±13.55)° in treatment group,and(65.28±15.86)° and(65.09± 16.67)° in control group.Elbow joint motion in treatment group was higher than that in control group(P<0.05).On the 5th day after treatment,angles of wrist dorsiflexion and palm flexion were(39.43±15.94)°and(46.68±11.10)° in treatment group,and(38.51±18.49)° and(44.27±13.58)° in control group.On the 7th day after treatment,angles of wrist dorsiflexion and palm flexion were(42.52±16.50)° and(49.23±10.96)° in treatment group,and(41.18±20.09)° and(46.64±14.63)° in control group.The motion of wrist joint in treatment group was higher than that in control group(P<0.05).On the 13th day after treatment,HSS2 in treatment group 93.61±6.32 were higher than those in control group 92.06±7.94(P<0.05).There was no significant difference in elbow tenderness between two groups at each time point(P>0.05).Conclusion Voltaren external treatment combined with elbow fixation and tendons pulling,poking and kneading could effectively improve symptoms of exter-nal humeral epicondylitis.Compared with voltaren external treatment,tendons pulling,poking and kneading has advantages of longer analgesic time and better elbow function recovery.
5.Epidemic characteristics and spatial heterogeneity of hemorrhagic fever with renal syndrome in Hubei Province from 2005 to 2021,China
Yang WU ; Tian LIU ; Jing ZHAO ; Man LIU ; Ye-Qing TONG ; Xu-Hua GUAN ; Hong-Bing PEI
Chinese Journal of Zoonoses 2024;40(7):678-688
This study was aimed at summarizing the epidemiological characteristics and spatial-temporal changes of hemorrhagic fever with renal syndrome(HFRS)in Hubei Province,China from 2005 to 2021,to provide scientific evi-dence for HFRS prevention and control.Data on individual HFRS cases and population information in Hubei Province from 2005 to 2021 were collected from the China Disease Pre-vention and Control Information System.The temporal,spa-tial,and demographic distribution characteristics of HFRS cases are described,and statistical methods such as medians,rates,and composition ratios were used for analysis.Joinpoint re-gression and Spearman's rank correlation were used to analyze the temporal trends in incidence rates or composition ratios.Global autocorrelation and hotspot analysis were conducted for spatial clustering analysis.Binary logistic regression was per-formed to analyze risk factors for HFRS mortality.A total of 5 790 HFRS cases were reported from 2005 to 2021,including 117 deaths.The average annual incidence rate was 0.57 per 100 000 population,and the case fatality rate was 2.02%.The overall incidence rate of HFRS in Hubei Province showed an increasing trend(AAPC=4.05%,95%CI:1.32%-6.78%),whereas the case fatality rate showed a decreasing trend over the years(r,=-0.72,P=0.002).HFRS exhibited a bimodal pattern,with peaks in the spring/summer months(May to July)and in the autumn/winter months(November to January of the following year).The incidence rate during the autumn/winter peak was slightly higher than that in the spring/summer peak.The incidence rate in males was higher than in females(RR=2.96,95%CI:2.79-3.14).The three age groups with the highest incidence rates were 60-64 years(747 cases,1.55 per 100 000),65-69 years(515 cases,1.39 per 100 000),and 55-59 years(762 cases,1.23 per 100 000).The incidence rate(2005:0.05 per 100 000;2021:0.08 per 100 000)and proportion(2005:2.69%;2021:1.94%)of HFRS cases in individuals 14 years or younger showed no significant trend over the years(AAPC=0.14%,95%CI:-0.03%-0.31%;AAPC=-3.64%,95%CI:-8.79%-1.50%).The incidence rate(2005:0.58 per 100 000;2021:1.59 per 100 000)and proportion(2005:14.80%;2021:44.31%)in the age group of 60 years or a-bove showed an increasing trend over the years(AAPC=10.52%,95%CI:4.38%-16.66%;AAPC=175.98%,95%CI:143.20%-208.75%).HFRS cases exhibited significant spatial clustering(P<0.05).The hotspots of HFRS in Hubei Province shifted from the northern region(Xiangyang,Suizhou,Jingmen)in 2005-2007 to the southern region(Qianjiang,Xiantao,Tianmen,Jingzhou)in 2020-2021.Older age(OR=1.02,95%CI:1.01-1.04)and the period of 2005-2008 versus 2017-2021(OR=0.98,95%CI:0.97-0.99)were associated with relatively higher risk of HFRS mortality.In recent years,the HFRS epidemic in Hubei Province has continued to escalate,and areas such as Qianjiang City and other ares in the middle and lower reaches of the Yangtze River have experienced high incidence rates.The population 60 years of age or above is gradually becoming more susceptible to the disease.Targeted measures should be implemented to curb the rising trend of HFRS.
6.Research on a model of risk perception of venous thromboembolism in pregnant women
Haoxin LIU ; Lili HUANG ; Xiaohua CUI ; Fuying TAO ; Man ZHOU ; Panpan ZHANG ; Yingying TIAN
Chinese Journal of Nursing 2024;59(18):2229-2237
Objective To construct a theoretical model of venous thromboembolism(VTE)risk perception in pregnant women,so as to provide a scientific basis for promoting pregnant women to form a correct risk perception of VTE and actively take preventive behaviors.Methods A qualitative research approach guided by the procedural grounded theoiy was adopted.Data were collected by a semi-structured deep interview on 18 pregnant women who received prenatal examination in the outpatient department of a tertiary A obstetrics and gynecology hospital in Nanjing from June to July 2023,and the data were analyzed by three-level coding and continuous comparison method.Results The VTE risk perception of pregnant women was affected by 6 factors including social coupling system,self health status,life behavior habits,knowledge on disease,compliance behavior and emotional stimulation.Pregnant women perceived VTE risk from 3 aspects:threats to maternal and child safety,increased family economic burden and increased time cost,impact on social roles.Thus,3 health behavior decisions were formed,including taking preventive behaviors,overcoming implementation barriers,and seeking knowledge behaviors,in order to reduce their own risk of VTE,and prevent the occurrence of VTE.Conclusion The theoretical model of VTE risk perception of pregnant women can guide medical staff to comprehensively consider the influencing factors of VTE risk perception of pregnant women,optimize the form and content of VTE health education,give pregnant women individualized and sustainable VTE prevention guidance,and strengthen pregnant women's perception of VTE risk and the benefits of preventive behavior,so as to actively take the correct health behavior decisions.
7.Value of 18F-FAPI PET/CT in evaluating early-stage of liver graft fibrosis in adult liver transplantation recipients
Youwei ZHAO ; Xiaohan FANG ; Qiuju TIAN ; Qun ZHANG ; Man XIE ; Guangjie YANG ; Jinzhen CAI ; Zhenguang WANG ; Wei RAO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(7):385-389
Objective:To explore the value of 18F-fibroblast activation protein inhibitor (FAPI) PET/CT in the assessment of early-stage graft fibrosis (S1-S2) after liver transplantation (LT). Methods:From November 2021 to April 2022, 17 adult liver transplant recipients (12 males and 5 females; age (52.6±7.9) years) in the Affiliated Hospital of Qingdao University were enrolled retrospectively in this study. All 17 patients received laboratory examinations, FibroScan, 18F-FAPI PET/CT and liver biopsy. According to the Scheuer scoring system, hepatic tissue was divided into no fibrosis (S0) and early fibrosis (S1-S2). Independent-sample t test was used to compare SUV max between two groups, and Mann-Whitney U test was used to compare liver stiffness measurement (LSM). ROC curve analysis was used to evaluate the diagnostic efficacy of LSM and SUV max in the early fibrosis of liver grafts. Delong test was used to compare the difference of AUCs. Results:Among 17 adult LT recipients, 11 were in stage S0, 5 were in stage S1, and 1 was in stage S2. There were significant differences in LSM and SUV max between no fibrosis group and early fibrosis group (LSM: 5.4(4.7, 6.6) vs 12.9(5.6, 19.9) kPa, z=-2.01, P=0.044; SUV max: 1.7±0.8 vs 3.9±1.6, t=-3.14, P=0.019). The threshold value of LSM in predicting early-stage graft fibrosis was 8.2 kPa and the AUC was 0.80 (95% CI: 0.54-0.95), which was 2.0 and 0.92 (95% CI: 0.78-1.00) for SUV max respectively. There was no significant difference in AUC between the two tools ( z=0.80, P=0.421). Conclusion:18F-FAPI PET/CT can precisely evaluate the early fibrosis of allografts, with the similar diagnostic efficacy with FibroScan (LSM), which is expected to be a new non-invasive diagnostic tool for predicting the early-stage of graft liver fibrosis.
8.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.
9.Effects of sodium hydrosulfide on HK2-NLRP3-GSDMD pathway and pyroptosis induced by lung ischemia/reperfusion in rats
Lu SHI ; Xiaoting WANG ; Zhenzhen LUO ; Jun CHENG ; Sian CHEN ; Jun-Peng XU ; Qihao ZHANG ; Wenjie CAO ; Man HUANG ; Yunna TIAN ; Xuguang JIA ; Wantie WANG
Chinese Journal of Pathophysiology 2024;40(6):1105-1113
AIM:To investigate the effects of sodium hydrosulfide(NaHS)on hexokinase 2(HK2)-nucleo-tide-binding oligomerization domain-like receptor protein 3(NLRP3)-gasdermin D(GSDMD)pathway and pyroptosis in-duced by lung ischemia/reperfusion(I/R)in rats.METHODS:Male Sprague-Dawley rats were divided into 6 groups:control group,control+NaHS group,I/R group,low-dose NaHS+I/R(L+I/R)group,medium-dose NaHS+I/R(M+I/R)group,and high-dose NaHS+I/R(H+I/R)group,with 6 rats in each group.The NaHS was administered via intraperi-toneal injection at 1.5 mL,30 min before modeling.The left lung tissues were collected 30 min after ischemia and 1 h af-ter reperfusion,and the wet/dry weight ratio and total lung water content were recorded.Hematoxylin-eosin(HE)staining was used to examine lung tissue morphological changes.The levels of malondialdehyde(MDA),myeloperoxidase(MPO)and lactate in lung tissues were measured with test kits.ELISA was employed to determine the levels of interleukin-1β(IL-1β)and IL-18.The expression of glycolysis-and pyroptosis-related indicators was analyzed by Western blot,qRT-PCR and immunofluorescence staining.RESULTS:Compared with control group,the rats in NaHS group showed no signifi-cant differences in all laboratory tests(P>0.05).The rats in I/R group exhibited significant lung injury,oxidative stress,increased lactate level,and up-regulated glycolysis and pyroptosis(P<0.05 or P<0.01).Compared with I/R group,the indicators in L+I/R group showed a downward trend(P<0.01)or no difference(P>0.05),while those in M+I/R group dis-played a significant reduction(P<0.05 or P<0.01).However,the indexes in H+I/R group exhibited no significant dif-ferences in these tests(all P>0.05).CONCLUSION:A moderate dose(56 μmol·L-1·kg-1)of NaHS mitigated the oc-currence of pyroptosis by inhibiting the HK2-NLRP3-GSDMD pathway,thus contributing to the attenuation of lung I/R in-jury in rats.
10.miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1-containing AMPA receptors in a mouse model of Alzheimer's disease.
Man LUO ; Yayan PANG ; Junjie LI ; Lilin YI ; Bin WU ; Qiuyun TIAN ; Yan HE ; Maoju WANG ; Lei XIA ; Guiqiong HE ; Weihong SONG ; Yehong DU ; Zhifang DONG
Acta Pharmaceutica Sinica B 2024;14(2):635-652
Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

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