1.Exploring Multi-target Effect of Erzhiwan on Improving Myocardial Injury in Ovariectomized Mice Based on Non-targeted Metabolomics
Ying YANG ; Jing HU ; Pei LI ; Ruyuan ZHU ; Zhiguo ZHANG ; Haixia LIU ; Yanjing CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):74-84
ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected, 40 female C57BL/6 mice were randomly divided into sham operation group, model group, estrogen group(estradiol valerate, 1.3×10-4 g·kg-1), Erzhiwan low and high dose groups(3.12, 9.36 g·kg-1), with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage, and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function, hematoxylin-eosin(HE) staining was used to observe myocardial morphological changes, and enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of estrogen, N-terminal pro-brain natriuretic peptide(NT-proBNP), hypersensitive troponin T(hs-TnT), total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C), interleukin(IL)-1β, IL-18 and tumor necrosis factor-α(TNF-α). The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS), and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase(PI3K) and protein kinase B(Akt) in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the protein expression levels of PI3K, Akt, phosphorylated(p)-Akt were detected by Western blot. ResultsCompared with the sham operation group, the model group showed abnormal cardiac function, increased myocardial fiber space, cardiomyocyte atrophy, sarcoplasmic aggregation, and occasional dissolution or rupture of muscle fiber, the level of estrogen in the serum was decreased, the levels of NT-proBNP, hs-TnT, IL-1β, IL-18, TNF-α, TG, TC and LDL-C were increased, and the level of HDL-C was decreased(P<0.01). Compared with the model group, Erzhiwan could increase the level of estrogen, improve the abnormal cardiac function, reduce the pathological injury of myocardial tissue, decrease the levels of myocardial injury markers(NT-proBNP, hs-TnT) and inflammatory factors(IL-1β, IL-18, TNF-α), decrease the levels of TG, TC, LDL-C, and increased the level of HDL-C(P<0.01). The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan, which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway, PI3K-Akt pathway, cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG) pathway and other metabolic pathways. Compared with the sham operation group, the levels of phosphatidylcholine(PC, 11 types) and phosphatidylethanolamine(PE, 5 types) in mouse myocardial tissue of the model group were increased(P<0.05, P<0.01), and the mRNA and protein expressions of PI3K and p-Akt were decreased(P<0.05, P<0.01). Compared with the model group, the levels of PC(11 types) and PE(5 types) were decreased(P<0.05, P<0.01) in myocardial tissue of Erzhiwan group, the mRNA and protein expressions of PI3K and p-Akt were elevated(P<0.01). ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice, improve the abnormal cardiac function, improve lipid metabolism disorder, and reduce the levels of myocardial injury markers and inflammatory factors, which involves a number of signaling and metabolic pathways in the heart, among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.
2.Monitoring of bacterial contamination of water specimens at different pre-discharge time of flexible endoscopic final rinse water before daily use:a multicenter study
Jing ZHEN ; Liuji CHEN ; Yangyang ZHANG ; Ziyi HUANG ; Haixia LIU ; Xianhuang LI ; Xi HUANG ; Jiuhong MA
Chinese Journal of Infection Control 2025;24(2):236-241
Objective To investigate the bacterial contamination of water specimens at different pre-discharge time of flexible endoscopic final rinse water before daily use,and provide reference basis for choosing the optimal pre-dis-charge time in clinical work.Methods From August to December 2023,the water produced by the purified water equipment of the digestive endoscopy centers of 4 tertiary first-class medical institutions in Jiangxi Province,as well as the final rinsing water at the terminal-point at different pre-discharge times(before pre-discharge,discharge of 1,3,5,and 10 minutes)were subjected to on-site sampling,the collected water specimens were performed microbio-logical cultures by pouring and filter membrane methods,unqualified water specimens were performed bacterial i-dentification.Results 48 specimens of water produced by purified water equipment were collected,with qualified rate of 100%.480 final water specimens were collected,with a qualified rate of 0 before pre-discharge.The quali-fied rates of pre-discharge at 1,3,5,and 10 minutes were 0,21.88%,55.21%,and 73.96%,respectively.Bac-terial colony counts in the final rinse water with different pre-discharge times in 4 medical institutions showed statis-tically significant differences(all P<0.001).As the pre-discharge time increased,bacterial colony counts in the fi-nal rinse water of all four medical institutions showed a decreasing trend.The pairwise comparison of the overall bacterial colony count of the final rinse water at different pre-discharge time showed that there was no statistically significant difference in the bacterial colony count of the final rinse water at 5 and 10 minutes of pre-discharge(P>0.05),while the pairwise comparison between other time points showed statistically significant differences(all P<0.001).Environmental contaminated bacteria such as Micrococcus luteus,Cupriavidus paucula,and Sphin-gononas paucimobilis were detected from the unqualified water specimens.Conclusion With the extension of pre-discharge time,the degree of bacterial contamination in the final rinse water significantly decreases.All levels of medical institutions need to pre-discharge the final rinse water daily,and the pre-discharge time should last for at least 5 minutes.
3.Clinical analysis of anti-GT1a antibody-positive Guillain-Barré syndrome in 25 children
Dan CHEN ; Chi HOU ; Haixia ZHU ; Jie YU ; Yani ZHANG ; Kelu ZHENG ; Yuanyuan GAO ; Xiaojing LI
Chinese Journal of Pediatrics 2025;63(10):1092-1096
Objective:To summarize the clinical characteristics, treatment, and prognosis of children with anti-GT1a antibody-positive Guillain-Barré syndrome (GBS).Methods:A case series study was conducted, including 25 children diagnosed with serum anti-GT1a antibody-positive GBS at Guangzhou Women and Children′s Medical Center from March 2019 to December 2024. Clinical data, treatment protocols, and follow-up outcomes were analyzed. Mann Whitney U test was used to compare the changes in Hughes functional grading scale (HFGS). Results:A total of 25 children included 12 boys and 13 girls, and the age at first onset was (71±8) months. There were 16 children (64%) had preceding infections, and of which 13 children had predominantly respiratory tract infections. At disease peak, neurological manifestations included limb weakness (21 cases (84%)), bulbar palsy (13 cases (52%)), drowsiness (7 cases (28%)), limb pain (9 cases (36%)), ataxia (6 cases (24%)), respiratory muscle paralysis (5 cases (20%)), ophthalmoplegia (5 cases (20%)), and unilateral facial nerve palsy (4 cases (16%)). Cerebrospinal fluid analysis in 23 children revealed albuminocytological dissociation in 18 children. All 25 children underwent whole-spine magnetic resonance imaging (MRI), demonstrated spinal nerve root enhancement in 18 children, with leptomeningeal enhancement combined with spinal nerve root enhancement in 1 child. Electromyography in 16 children showed 15 children abnormality, of which demyelinating lesions in 8 children, mixed demyelinating-axonal changes in 4 children, and pure axonal involvement in 3 children. Intravenous immunoglobulin (IVIG) was administered to 21 cases (84%), of which 3 children required mechanical ventilation and blood purification (plasma exchange in 2 children and immunoadsorption in 1 child) due to disease progression. Four children (16%) received intravenous methylprednisolone (IVMP) instead of IVIG, with 1 child requiring ventilatory support due to respiratory muscle paralysis, and the tracheal tube was removed after continued sequential IVMP treatment. The hospitalization duration of 25 children was (23±3) d. At discharge, HFGS was 1.6 (0.6, 2.7) score. At a follow-up of 12 (4, 18) months, HFGS was 0.1 (0.0, 0.5) score, and higher than that at discharge ( Z=4.38, P<0.05). Two children relapsed but achieved remission after IVIG retreatment with no recurrence during 1-year follow-up. Conclusions:Anti-GT1a antibody-positive GBS in children predominantly presents with limb weakness and bulbar palsy, occasionally complicated by respiratory failure in the acute phase. Demyelinating neuropathy and spinal nerve root enhancement on MRI are characteristic. IVIG therapy yields favorable outcomes, with low residual disability. Relapses are rare but manageable with re-treatment.
4.TubA suppresses ferroptosis and ameliorates ulcerative colitis
Haixia CHEN ; Minjia CHEN ; Jingqi SONG ; Ruixia HE ; Jing LIU ; Xiuqin CAO ; Zhiwei YANG
Immunological Journal 2025;41(3):129-137
Objective To explore the mechanism of TubA in the treatment of ulcerative colitis in mice,and to lay a foundation for the treatment strategy of ulcerative colitis.Methods Twenty C57BL/6 mice aged 6-8 weeks were randomly divided into 4 groups(n=5):the control group drank pure water every day,the model group and the treatment groups drank 3%dextran sulfate sodium(DSS)every day,and the treatment groups were injected with 10 mg/kg TubA and 20 mg/kg TubA every day from the third day,respectively.The weight changes of mice in all groups were recorded.Nine days later,the serum of mice was collected,and the expression levels of inflammatory factors IL-1β,IL-6 and IL-10 in serum were detected by ELISA.HE staining was used to observe the pathological changes of the mouse colon.The expression of myeloperoxidase(MPO)was detected by immunohistochemistry,the mRNA levels of inflammatory factors IL-1β,IL-6 and IL-10 were detected by RT-qPCR,and the expressions of GPX4 and FTH were detected by immunohistochemistry.The mRNA and protein expression levels of GPX4,GCLM,FTH,Nrf2,Keap1 and HO-1 in colon tissues were detected by RT-qPCR and Western blotting.Results Compared with the control group,the body weight and colon length of the model group decreased significantly.HE staining showed that inflammatory cells infiltrated the mucosa and submucosa of colon tissue,goblet cells were lost and crypt structure disordered and disappeared.Immunohistochemistry showed that the expression of MPO and FTH proteins were significantly increased,while the expression of GPX4 protein was significantly decreased(P<0.05).The mRNA and protein expression levels of IL-1β and IL-6 were significantly increased,while the mRNA and protein expression levels of IL-10 were significantly decreased(P<0.05).The mRNA and protein expression levels of FTH,Nrf2 and HO-1 were significantly increased,while the mRNA and protein expression levels of GPX4,GCLM and Keap1 were significantly decreased(P<0.05).After TubA treatment,compared with the model group,all these changes mentioned above suppressed(P<0.05).Conclusion TubA may reduce ulcerative colitis symptoms by inhibiting ferroptosis,providing new ideas for the treatment of ulcerative colitis.
5.Causal relationship between 25-hydroxyvitamin D and ankylosing spondylitis:A two-way Mendelian randomization study
Lang XIONG ; Zong JIANG ; Weiya LAN ; Fang TANG ; Wukai MA ; Xueyong CHEN ; Shanshan CAI ; Haixia TU ; Yuqing DAI ; Shanyan CAI
China Modern Doctor 2025;63(19):1-5
Objective To explore causal relationship between 25-hydroxyvitamin D[25(OH)D]and ankylosing spondylitis(AS).Methods Genetic data of 25(OH)D and AS were extracted from the genome-wide association study.The causal effect of 25(OH)D on AS was estimated by MR-Egger regression method,weighted median,inverse variance weighted(IVW),simple mode and weighted mode,and sensitivity analysis was conducted for verification.Results The IVW results indicated that there was a causal relationship between 25(OH)D concentration and AS(OR=0.805,95%CI:0.686-0.944,P=0.008),and the maximum likelihood ratio(OR=0.799,95%CI:0.678-0.940,P=0.007)showed consistent results.The IVW results of the reverse Mendelian randomization study showed that there was no causal relationship between the two(OR=1.019,95%CI:0.995-1.043,P=0.110).In addition,MR-Egger intercept,Cochran Q test,"leave-one-out"and MR-PRESSO analysis showed no horizontal pleipotency or heterogeneity.Conclusion There may be a genetic causal relationship between the concentration of 25(OH)D and the onset of AS.AS cannot cause changes in the concentration of 25(OH)D in the body.
6.Allogeneic hematopoietic stem cell transplantation for the treatment of BCR::ABL-negative neutrophilic myeloid neoplasms: a clinical analysis of 12 cases
Tingting HAN ; Yun HE ; Jing LIU ; Yao CHEN ; Fengrong WANG ; Jingzhi WANG ; Yuhong CHEN ; Haixia FU ; Lanping XU ; Xiaohui ZHANG ; Xiaojun HUANG ; Yu WANG
Chinese Journal of Hematology 2025;46(9):827-832
Objective:To investigate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of BCR::ABL-negative chronic neutrophilic leukemia (CNL) and MDS/MPN with neutrophilia.Methods:This study retrospectively analyzed 12 cases of CNL and MDS/MPN with neutrophilia that underwent allo-HSCT from March 2017 to June 2024, comprising 7 males and 5 females with a median age of 48 ( IQR: 28, 59) years. The 2-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplantation-related mortality (TRM) rates were analyzed. Complications were also assessed. Results:Of the 12 patients, 6 received matched sibling HSCT and 6 received haploidentical HSCT. All patients had successful engraftment, and the median times of neutrophil and platelet engraftment were 17 ( IQR: 11, 24) days and 15 ( IQR: 9, 28) days, respectively. Grade Ⅱ–Ⅳ acute graft versus host disease (GVHD) and chronic GVHD occurred in 2 and 4 cases, respectively. The 2-year OS, DFS, CIR, and TRM rates were (65.6 ± 16.4) %, (41.7 ± 16.6) %, (47.2 ±18.2) %, and (11.1 ± 11.4) %, respectively, after a median follow-up time of 637 ( IQR: 330, 943) days. One patient died from treatment-related complications due to respiratory failure caused by coronavirus disease 2019. Two patients died due to relapse. Conclusion:Allo-HSCT can be applied as a safe and effective approach to treat CNL and MDS/MPN with neutrophilia.
7.Respiratory syncytial virus and influenza virus regulate the host cell CCR1-HSP90 axis to facilitate their intracellular proliferation
Jiao LI ; Ling XUE ; Jiajun QIAO ; Yijia CHEN ; Haixia ZHANG ; Yushan LIN ; Xue GAO ; Miao LI ; Cuiqing MA
Chinese Journal of Microbiology and Immunology 2025;45(1):17-25
Objective:To investigate the underlying mechanism behind the significant reduction in intracellular virus loads after respiratory syncytial virus (RSV) and influenza viruses infect respiratory epithelial cells overexpressing the chemokine (C-C motif) receptor 1 (CCR1).Methods:A549 cells were infected with respiratory syncytial virus (RSV), influenza A viruses (H1N1, H3N2), or influenza B virus (FluB), and the expression of chemokine (C-C motif) ligand 5 (CCL5) and CCR1 were detected by qRT-PCR, ELISA, and Western blot. After overexpressing or knocking down CCR1 in A549 cells, these cells were infected with RSV, H1N1, H3N2, or FluB, and the expression of CCR1, heat shock protein 90 (HSP90), cyclin-dependent kinase 1 (CDK1), and viral proteins were detected by qRT-PCR and Western blot. After stimulating CCR1-overexpressed A549 cells with CCL5, Western blot was used to detect the expression of HSP90 and CDK1, and co-immunoprecipitation was used to detect the interaction between HSP90 and CCR1. CCR1 -/- mice were infected with RSV, H1N1, or H3N2 to observe the changes in the expression of HSP90, CDK1, and viral proteins with Western blot, and the inflammation in lung tissues with HE staining. One-way analysis of variance and t test were used for statistical analysis. Results:RSV, H1N1, H3N2, and FluB infections induced high expression of CCL5 in A549 cells ( P<0.05), but the expression of CCR1 showed an overall downward trend. After activating its receptor CCR1, CCL5 inhibited the replication of RSV and influenza viruses by suppressing the activity of HSP90 ( P<0.05). The experiments conducted on CCR1 -/- mice confirmed that the enhanced activity of HSP90 facilitated the replication of RSV and influenza viruses. Conclusion:RSV and influenza viruses may reduce the binding of CCL5 to CCR1 by downregulating the expression of CCR1 in respiratory epithelial cells, thereby weakening the inhibitory effect of CCR1 on HSP90 activity, which enables them to evade host immune defense.
8.Establishment and application of standard operational procedure for cleaning and disinfection of biopsy valves of flexible endoscope:a multi-center study
Haixia LIU ; Xianhuang LI ; Jing ZHEN ; Liuji CHEN ; Jiuhong MA
Chinese Journal of Infection Control 2025;24(7):988-992
Objective To investigate the current status of cleaning and disinfection of endoscopic biopsy valves in three digestive endoscopy centers in Jiangxi Province,and evaluate the effectiveness of establishing a standard opera-tional procedure(SOP)of cleaning and disinfection for flexible endoscopic biopsy valves.Methods The cleaning and disinfection procedures of biopsy valves in three digestive endoscopy centers were recorded using on-site investi-gation method(the control group).Based on relevant literature and manufacturer manuals at home and abroad,SOP was established and cleaning and disinfection training for cleaning professional was provided(the trial group).Biop-sy valve specimens from two groups were taken.The disinfection qualified rate,microbial positivity rate before dis-infection,and microbial load after disinfection before and after procedure improvement were compared between two groups.Results A total of 180 biopsy valve specimens were taken from two groups(60 specimens from endoscopy centers A,B,and C each).On-site investigation showed that the cleaning and disinfection procedure for biopsy valves was inconsistent among the three endoscopy centers.The total qualified rate of disinfection in the trial group was higher than that in the control group(95.5%vs 83.3%),with statistically significant difference(P<0.05).The total microbe positive rate of biopsy valves from the trial group was lower than that from the control group(25.0% vs 57.2%),with statistically significant difference(P<0.05).The difference in microbial load after disin-fection between two groups of biopsy valves was statistically significant(Z=-6.47,P<0.05).Conclusion Al-though being a tiny accessory,the flexible endoscopic biopsy valve can be a potential source of infection if not tho-roughly cleaned and disinfected.Developing SOP can help improve the cleaning effectiveness of biopsy valves.At present,there is no unified standards for the cleaning and disinfection procedure of endoscopic biopsy valves.In the future,standardization of the SOP for biopsy valves should be continuously explored,so as to reduce the risk of cross infection.
9.Clinical Characteristics and Prognostic Analysis of Maintenance Hemodialysis Patients with Initial Treatment Tuberculosis
Haixia GU ; Jiangli PENG ; Anxin CHEN ; Rui YIN ; Qiqi XIAO ; Jie CHEN
Journal of Kunming Medical University 2025;46(4):129-135
Objective To analyze the clinical characteristics,treatment and prognosis of patients undergoing the maintenance hemodialysis and treatment-naive tuberculosis and to explore the prognostic factors,so as to provide a reference for the clinical treatment of patients undergoing hemodialysis due to tuberculosis.Methods The clinical data of 70 patients undergoing hemodialysis with treatment-naive tuberculosis admitted to the Third People's Hospital of Kunming from October 31,2020~October 31,2023 were retrospectively collected,the clinical characteristics of the patients were analyzed,and the occurrence of adverse reactions,treatment outcomes and prognostic factors were observed.Results Among the 70 patients,pulmonary tuberculosis was the primary type(64 cases,accounting for 91.43%),and extrapulmonary tuberculosis was also quite common(56 cases,accounting for 80.00%).The most widely used anti-tuberculosis regimen was isoniazid,rifampicin,ethambutol,and moxifloxacin in a four-drug combination;During the anti-tuberculosis treatment,55 patients(78.57%)improved.A total of 13 adverse reactions occurred in 11 patients(15.71%),and the most common ones were itching,rash and blurred vision.The hemoglobin,lymphocyte count and CD8+T lymphocyte count in the treatment improvement group were higher than those in the ineffective group(P<0.05).Conclusion Dialysis patients have a high risk of tuberculosis infection,mainly pulmonary tuberculosis,and extrapulmonary tuberculosis is more common.78.57%of the patients hare improved after the tuberculosis treatment,but the overall prognosis is poor,and the low hemoglobin level is associated with ineffective treatment.
10.Efficacy of Nucleotide Analog Monotherapy and Combination Therapy with Interferon in Treating Chronic Hepatitis B
Rui YIN ; Guowei MA ; Wenxi YUE ; Haixia GU ; Ying ZHOU ; Jie CHEN
Journal of Kunming Medical University 2025;46(6):79-88
Objective To analyze the efficacy of different nucleoside(acid)analogs(NAs)used as monotherapy and in combination with pegylated interferon α-2b(Peg-IFN-α-2b)in the treatment of chronic hepatitis B(CHB).Methods A retrospective analysis was conducted on 229 CHB patients who visited the Hepatology Department of the Third People's Hospital of Kunming from September 2022 to August 2023.Patients were divided into six groups based on their antiviral regimen:entecavir(ETV)group(A,n=47),ETV combined with Peg-IFN-α-2b group(B,n=19),Tenofovir Alafenamide(TMF)group(C,n=64),TMF combined with Peg-IFN-α-2b group(D,n=35),Tenofovir Disoproxil Fumarate(TDF)group(E,n=29),and TDF combined with Peg-IFN-α-2b group(F,n=35).The blood routine,liver function,kidney function,HBV serological markers,and HBV-DNA levels were compared before and after 24 weeks of treatment.Results After 24 weeks of treatment,there were no statistically significant differences in efficacy rates and HBV-DNA positivity rates between the monotherapy with NAs and the combination with Peg-IFN-α-2b(P>0.05).Comparing before and after treatment,the ETV group had the highest effective rate,while TDF combined with Peg-IFN-α-2b group had the lowest effective rate.TDF group had the highest efficiency,while ETV combined with Peg-IFN-α-2b group had the lowest efficiency.Except for ETV+Peg-IFN-α-2b and TDF+Peg-IFN-α-2b groups,the HBV-DNA positivity rates in the other four groups were significantly lower after treatment compared to before(P<0.05).There was a significant difference in HBsAg levels among the different treatment regimens of monotherapy with NAs and combination with Peg-IFN-α-2b(P=0.0483).Additionally,except for the ETV and TDF groups,the serum HBsAg levels in the other four groups were significantly lower after treatment compared to before(P<0.05).There were no significant difference in LSM and GFR before and after treatment(P>0.05).In the monotherapy groups,ALT and GGT levels were significantly lower after treatment compared to before(P<0.05),while in the combination Peg-IFN-α-2b group,WBC,NEUT,and PLT levels were significantly lower after treatment compared to before(P<0.05).Conclusion Combination therapy with Peg-IFN-α-2b can reduce HBsAg levels and may be more effective in controlling the virus;however,it may cause adverse reactions such as bone marrow suppression,increasing risks.Physicians and patients need to weigh the benefits against the risks and develop personalized treatment plans based on individual circumstances.

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