1.Effect and mechanism of HSPA1A on apoptosis of H9c2 cardiomyocytes in hypoxic environment
Acta Universitatis Medicinalis Anhui 2025;60(4):634-641
Objective :
To investigate the effects of heat shock protein 70 ku protein 1A(HSPA1A) on H9c2 inflammation and apoptotic injury in rat cardiomyocytes under hypoxia, and to analyze its mechanism.
Methods:
H9c2 cells were treated with normal oxygen(Nor) and hypoxia(Hyp), and the expression of HSPA1A was detected by RT-qPCR and Western blot. Normal H9c2 cells were divided into Nor group(normoxia culture), sh-HSPA1A+Nor group(cells transfected with HSPA1A shRNA, normoxia culture), Hyp group(hypoxia culture), sh-HSPA1A+Hyp group(cells transfected with HSPA1A SHRNA, hypoxia culture), the expression level of HSPA1A in H9c2 cells in each group was detected by RT-qPCR and Western blot, the morphology of H9c2 cells in each group was observed by inverted microscope, and the activity of H9c2 cells in each group was detected by CCK-8, the contents of inflammatory factors tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1β and the activities of myocardial injury markers lactate dehydrogenase(LDH), creatine kinase(CK) in the supernatant of H9c2 cells were detected by ELISA, apoptosis rate of H9c2 cells in each group was detected by Annexin V-FITC/PI double staining, the expression levels of TNF receptor-associated factor 2(TRAF2)/nuclear factor κB(NF-κB) pathway-related proteins in H9c2 cells of each group were detected by Western blot.
Results:
Compared with Nor group, the relative expression of HSPA1A mRNA and protein in H9c2 cells in Hyp group after hypoxia induction was significantly up-regulated(P<0.05). Compared with Nor group, the number of H9c2 cells in Hyp group significantly decreased, some cells were wrinkled and disordered, the cell activity significantly decreased(P<0.05), the contents of TNF-α, IL-6, IL-1β and the activities of LDH and CK in supernatant significantly increased(P<0.05), the cell apoptosis rate significantly increased(P<0.05), the relative expressions of TRAF2 protein and the phosphorylation level of p65 and inhibitor of nuclear factor κB alpha(IκBα) were significantly up-regulated(P<0.05); compared with Hyp group, the morphology of H9c2 cells in sh-HSPA1A+Hyp group was improved, the cell arrangement was more dense, the cell activity significantly increased(P<0.05), the contents of TNF-α, IL-6 and IL-1β in supernatant decreased, the activities of LDH and CK significantly decreased(P<0.05), the apoptosis rate significantly decreased(P<0.05), the relative expressions of TRAF2 protein and the phosphorylation level of p65 and IκBα were also significantly down-regulated(P<0.05).
Conclusion
The expression of HSPA1A in rat cardiomyocytes H9c2 is increased by hypoxia, and inhibition of HSPA1A expression can improve the hypoxia-induced inflammatory response of H9c2 cells and reduce apoptosis damage, which may be related to the regulation of TRAF2/NF-κB pathway.
2.Construction of Clinical Questions and Outcome Indicators of Clinical Practice Guidelines of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome Based on the Modified Delphi Method
Lixin MA ; Xueping ZHANG ; Xinxin HU ; Qianying WANG ; Zhuotai ZHONG ; Suowei WU ; Lei CHEN ; Weiqi SUN ; Wei CHEN ; Chen YANG ; Wei WEI ; Xiaolan SU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(9):128-134
Objective To explore and construct the clinical questions and outcome indicators of the Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome;To provide a basis for the subsequent preparation of this guide to form recommendations.Methods First,by searching the databases of seven major Chinese and English journals,including CNKI,the preliminary list of clinical problems and outcome indicators in the Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome were sorted out,and then the clinical questions and outcome indicators that formed the recommendations of the guide were finally determined based on the modified Delphi method in the form of three rounds of online.The first two rounds were conducted in the form of online questionnaires filled out by experts,and the importance ratings of clinical issues and outcome indicators were imported into the SPSS 27.0 software for statistical analysis.The first and second rounds of clinical questions and outcome indicators were rated as the average score≥4,full score frequency≥30%,and the coefficient of variation≤25%,respectively;the inclusion criteria for entering the second round of evaluation were an average score of≥7 and an average score of≤25%.The third round would be further discussed and voted on by experts in an online consensus meeting,with a voting rate of≥80%as the standard to determine the final items to be included in the guidelines.Results A total of 109 questionnaires were distributed nationwide in the first round of inquiry,and 107 were collected;a total of 20 questionnaires were distributed for the second round of expert research,and 20 were collected.The positive coefficients of the first and second rounds of experts were 98.17%and 100%;the Cronbach coefficients of clinical questions were 0.937 and 0.943,respectively;the Cronbach coefficients of the outcome indicators were 0.970 and 0.940,respectively.In the third round,a total of 22 experts participated in the meeting and all voted,resulting in a positive coefficient of 100%and an authority coefficient of 0.88.13 clinical questions and 17 outcome indicators were finally included in Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome.Conclusion According to the results of the above three rounds of modified Delphi method,it indicates that the questionnaire survey in the process of formulating the guidelines is highly reliable,which can provide a reliable basis for the writing of this guide,and to provide a reference for the development of acupuncture guidelines in related fields.
3.Sub-committee of Anesthesiology of Guangzhou Integrated Traditional Chinese and Western Medicine Society.
Yi LU ; Cunzhi LIU ; Wujun GENG ; Xiaozhen ZHENG ; Jingdun XIE ; Guangfang ZHANG ; Chao LIU ; Yun LI ; Yan QU ; Lei CHEN ; Xizhao HUANG ; Hang TIAN ; Yuhui LI ; Hongxin LI ; Heying ZHONG ; Ronggui TAO ; Jie ZHONG ; Yue ZHUANG ; Junyang MA ; Yan HU ; Jian FANG ; Gaofeng ZHAO ; Jianbin XIAO ; Weifeng TU ; Jiaze SUN ; Yuting DUAN ; Bao WANG
Journal of Southern Medical University 2025;45(8):1800-1808
OBJECTIVES:
To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and.
RESULTS:
Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.
CONCLUSIONS
The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans
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Medicine, Chinese Traditional
;
Cancer Pain/therapy*
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Drugs, Chinese Herbal/therapeutic use*
;
Drug Delivery Systems
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Pain Management/methods*
;
China
4.How Fear Memory is Updated: From Reconsolidation to Extinction?
Jiahui CHEN ; Zhuowen FANG ; Xiaolan ZHANG ; Yanrong ZHENG ; Zhong CHEN
Neuroscience Bulletin 2025;41(6):1054-1084
Post-traumatic stress disorder (PTSD) is a psychiatric disorder caused by traumatic past experiences, rooted in the neurocircuits of fear memory formation. Memory processes include encoding, storing, and recalling to forgetting, suggesting the potential to erase fear memories through timely interventions. Conventional strategies such as medications or electroconvulsive therapy often fail to provide permanent relief and come with significant side-effects. This review explores how fear memory may be erased, particularly focusing on the mnemonic phases of reconsolidation and extinction. Reconsolidation strengthens memory, while extinction weakens it. Interfering with memory reconsolidation could diminish the fear response. Alternatively, the extinction of acquired memory could reduce the fear memory response. This review summarizes experimental animal models of PTSD, examines the nature and epidemiology of reconsolidation to extinction, and discusses current behavioral therapy aimed at transforming fear memories to treat PTSD. In sum, understanding how fear memory updates holds significant promise for PTSD treatment.
Fear/psychology*
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Extinction, Psychological/physiology*
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Animals
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Stress Disorders, Post-Traumatic/psychology*
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Humans
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Memory Consolidation/physiology*
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Memory/physiology*
5.14-day Dual Therapy With Vonoprazan and Amoxicillin Versus 10-day Bismuth-containing Quadruple Therapy for Eradication of Helicobacter pylori Infection:A Comparative Study
Haihui HUANG ; Yi CHEN ; Biqing WEN ; Xiaolan ZHONG
Chinese Journal of Gastroenterology 2025;30(2):111-115
Background:With the widespread use of vonoprazan-based dual therapy for Helicobacter pylori(Hp)eradication,a comparative analysis of its efficacy and safety against bismuth-containing quadruple therapy is warranted.Aims:To compare the efficacy and safety of vonoprazan and amoxicillin-based 14-day dual therapy and 10-day bismuth-containing quadruple therapy for eradication of Hp infection.Methods:This study is a single-center,prospective,randomized,controlled,open-label,non-inferiority trial.Patients with chronic gastritis,diagnosed with Hp infection and scheduled for eradication therapy at Yuancheng District People's Hospital between December 2023 and December 2025 are planned to enroll in this study and randomly assigned into two groups.Patients in the control group received bismuth-containing quadruple therapy(vonoprazan 20 mg+bismuth potassium citrate 220 mg+amoxicillin 1.0 g+furazolidone 0.1 g,all twice daily)for 10 days,and those in the treatment group received dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1.0 g three times daily)for 14 days.Both groups were supplemented with compound lactobacillus capsule.Adverse events were recorded during the treatment period.Hp eradication was assessed by 13C-or 14C-urea breath test at least four weeks after the completion of therapy.Results:As of the interim analysis,a total of 160 patients have been enrolled in the study,with 80 in each group.The per-protocol(PP)Hp eradication rates were 93.6%(95%CI:85.6%-97.9%)for the treatment group and 94.7%(95%CI:86.8%-98.5%)for the control group,with an intergroup difference of-1.147%(95%CI:-8.5%-6.1%).While in intention-to-treat(ITT)analysis,the Hp eradication rates were 91.2%(95%CI:82.9%-96.4%)for the treatment group and 90.0%(95%CI:81.2%-95.6%)for the control group,with an intergroup difference of 1.25%(95%CI:-7.8%-10.4%).Non-inferiority was confirmed for both PP and ITT analyses(P=0.012,P=0.021).No significant difference in symptoms relieve was observed between the two groups(92.1%vs.91.0%,P=0.81).The incidence of adverse events was significantly lower in the treatment group(7.7%vs.18.4%,P=0.043).The symptoms were mild and required no intervention.Conclusions:The 14-day vonoprazan-amoxicillin dual therapy is non-inferior to 10-day bismuth-containing quadruple therapy in Hp eradication rate with fewer adverse events,making it a preferred option for family-based management and primary care settings for Hp eradication.
6.14-day Dual Therapy With Vonoprazan and Amoxicillin Versus 10-day Bismuth-containing Quadruple Therapy for Eradication of Helicobacter pylori Infection:A Comparative Study
Haihui HUANG ; Yi CHEN ; Biqing WEN ; Xiaolan ZHONG
Chinese Journal of Gastroenterology 2025;30(2):111-115
Background:With the widespread use of vonoprazan-based dual therapy for Helicobacter pylori(Hp)eradication,a comparative analysis of its efficacy and safety against bismuth-containing quadruple therapy is warranted.Aims:To compare the efficacy and safety of vonoprazan and amoxicillin-based 14-day dual therapy and 10-day bismuth-containing quadruple therapy for eradication of Hp infection.Methods:This study is a single-center,prospective,randomized,controlled,open-label,non-inferiority trial.Patients with chronic gastritis,diagnosed with Hp infection and scheduled for eradication therapy at Yuancheng District People's Hospital between December 2023 and December 2025 are planned to enroll in this study and randomly assigned into two groups.Patients in the control group received bismuth-containing quadruple therapy(vonoprazan 20 mg+bismuth potassium citrate 220 mg+amoxicillin 1.0 g+furazolidone 0.1 g,all twice daily)for 10 days,and those in the treatment group received dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1.0 g three times daily)for 14 days.Both groups were supplemented with compound lactobacillus capsule.Adverse events were recorded during the treatment period.Hp eradication was assessed by 13C-or 14C-urea breath test at least four weeks after the completion of therapy.Results:As of the interim analysis,a total of 160 patients have been enrolled in the study,with 80 in each group.The per-protocol(PP)Hp eradication rates were 93.6%(95%CI:85.6%-97.9%)for the treatment group and 94.7%(95%CI:86.8%-98.5%)for the control group,with an intergroup difference of-1.147%(95%CI:-8.5%-6.1%).While in intention-to-treat(ITT)analysis,the Hp eradication rates were 91.2%(95%CI:82.9%-96.4%)for the treatment group and 90.0%(95%CI:81.2%-95.6%)for the control group,with an intergroup difference of 1.25%(95%CI:-7.8%-10.4%).Non-inferiority was confirmed for both PP and ITT analyses(P=0.012,P=0.021).No significant difference in symptoms relieve was observed between the two groups(92.1%vs.91.0%,P=0.81).The incidence of adverse events was significantly lower in the treatment group(7.7%vs.18.4%,P=0.043).The symptoms were mild and required no intervention.Conclusions:The 14-day vonoprazan-amoxicillin dual therapy is non-inferior to 10-day bismuth-containing quadruple therapy in Hp eradication rate with fewer adverse events,making it a preferred option for family-based management and primary care settings for Hp eradication.
7.Construction of Clinical Questions and Outcome Indicators of Clinical Practice Guidelines of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome Based on the Modified Delphi Method
Lixin MA ; Xueping ZHANG ; Xinxin HU ; Qianying WANG ; Zhuotai ZHONG ; Suowei WU ; Lei CHEN ; Weiqi SUN ; Wei CHEN ; Chen YANG ; Wei WEI ; Xiaolan SU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(9):128-134
Objective To explore and construct the clinical questions and outcome indicators of the Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome;To provide a basis for the subsequent preparation of this guide to form recommendations.Methods First,by searching the databases of seven major Chinese and English journals,including CNKI,the preliminary list of clinical problems and outcome indicators in the Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome were sorted out,and then the clinical questions and outcome indicators that formed the recommendations of the guide were finally determined based on the modified Delphi method in the form of three rounds of online.The first two rounds were conducted in the form of online questionnaires filled out by experts,and the importance ratings of clinical issues and outcome indicators were imported into the SPSS 27.0 software for statistical analysis.The first and second rounds of clinical questions and outcome indicators were rated as the average score≥4,full score frequency≥30%,and the coefficient of variation≤25%,respectively;the inclusion criteria for entering the second round of evaluation were an average score of≥7 and an average score of≤25%.The third round would be further discussed and voted on by experts in an online consensus meeting,with a voting rate of≥80%as the standard to determine the final items to be included in the guidelines.Results A total of 109 questionnaires were distributed nationwide in the first round of inquiry,and 107 were collected;a total of 20 questionnaires were distributed for the second round of expert research,and 20 were collected.The positive coefficients of the first and second rounds of experts were 98.17%and 100%;the Cronbach coefficients of clinical questions were 0.937 and 0.943,respectively;the Cronbach coefficients of the outcome indicators were 0.970 and 0.940,respectively.In the third round,a total of 22 experts participated in the meeting and all voted,resulting in a positive coefficient of 100%and an authority coefficient of 0.88.13 clinical questions and 17 outcome indicators were finally included in Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome.Conclusion According to the results of the above three rounds of modified Delphi method,it indicates that the questionnaire survey in the process of formulating the guidelines is highly reliable,which can provide a reliable basis for the writing of this guide,and to provide a reference for the development of acupuncture guidelines in related fields.
8.Machine-learning-based models assist the prediction of pulmonary embolism in autoimmune diseases: A retrospective, multicenter study
Ziwei HU ; Yangyang HU ; Shuoqi ZHANG ; Li DONG ; Xiaoqi CHEN ; Huiqin YANG ; Linchong SU ; Xiaoqiang HOU ; Xia HUANG ; Xiaolan SHEN ; Cong YE ; Wei TU ; Yu CHEN ; Yuxue CHEN ; Shaozhe CAI ; Jixin ZHONG ; Lingli DONG
Chinese Medical Journal 2024;137(15):1811-1822
Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.
9.Pathogenesis of Spleen and Stomach Diseases and Therapeutic Effect of Banxia Xiexintang Based on Theory of "Mutual Interference of Clear and Turbid Qi" in Huangdi Neijing
Xueping ZHANG ; Qianying WANG ; Zhuotai ZHONG ; Mengxi YAO ; Lei CHEN ; Tao ZHANG ; Wei WEI ; Xiaolan SU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):225-231
Based on the theory of "mutual interference of clear and turbid Qi" in Huangdi Neijing(《黄帝内经》), this study explored the pathogenesis of spleen and stomach diseases and the therapeutic effects of Banxia Xiexintang on them. It suggested that "mutual interference of clear and turbid Qi" represents a pathological state of Yin and Yang disturbance and imbalance in Qi circulation due to the mixture of clear and turbid Qi, which can elucidate the pathogenesis of spleen and stomach diseases. According to this theory, the pathogenesis of spleen and stomach diseases was summarized as Qi disorder in spleen and stomach, disharmony between Ying Qi and Wei Qi, and conflict between cold and heat. Banxia Xiexintang, as a crucial prescription for treating spleen and stomach diseases, achieves its therapeutic effects by dispersing stagnation with pungent flavor, descending adverse Qi with bitterness, regulating Ying Qi and Wei Qi, and harmonizing cold and heat. By regulating Qi circulation, balancing internal and external factors, and addressing deficiency and excess, it can rectify the pathological state of "mutual interference of clear and turbid Qi" of spleen and stomach diseases. Modern research reveals that Banxia Xiexintang can modulate gastrointestinal motility, restore mucosal immune barrier function of the digestive system, and exhibit optimal therapeutic effects when combined with both cold-cool and warm-hot medicines, aligning with its therapeutic role under the theory of "mutual interference of clear and turbid Qi". By delving into the essence of the "mutual interference of clear and turbid Qi" theory and exploring the pathogenesis of spleen and stomach diseases and the therapeutic effects of Banxia Xiexintang based on this theory, this study further elucidated the inherent connection between spleen and stomach diseases and the "mutual interference of clear and turbid Qi" theory, offering insights and theoretical references for the clinical diagnosis and treatment of spleen and stomach diseases.
10.Application of p16INK4a combined with human papillomavirus and liquid-based cytology in clinical diagnosis of cervical intraepithelial neoplasia
Xue XIAO ; Yuqi WANG ; Wei JING ; Shaotao ZHONG ; Cuiliu ZHAO ; Dan LIU ; Rongshao TAN ; Xiaolan LAI
Modern Hospital 2024;24(1):140-143
Objective To analyze the detection efficiency of p16INK4a protein combined with human papillomavirus and liquid-based cytology(LCT)in the screening of cervical precancerous lesions,and to provide a basis for cervical cancer preven-tion and treatment.Methods The results of p16INK4a staining of cervical epithelial cells,human papillomavirus testing and cer-vical cytology were analyzed in 139 inpatients at Guangzhou Women's and Children's Medical Center between January 2019 and December 2020.Of them,there were 111 patients with cervical intraepithelial neoplasia(CIN)and 28 cases of cervical inflam-matory disease.The efficacy of the three methods alone and in combination to screen for CIN lesions was compared.Results In the detection of CIN patients,the sensitivity of p16INK4a,microfluidic microarray and cervical cytology for detecting CIN and a-bove lesions was 91.89% ,94.59% and82.88% ,with specificity of 57.14% ,17.86% and46.43% ,and AUC of 0.75,0.56 and 0.65,respectively;while the sensitivity of"p16INK4a+LCT","p16INK4a+hrHPV","LCT+hrHPV"and their sen-sitivity were 96.40% ,97.30% ,94.59% and 99.10% ,their specificity was 85.71% ,92.86% ,89.29% and 92.86% ,and the AUC was 0.91,0.95,0.92 and 0.96,respectively.Conclusion The combined p16INK4a and hrHPV test helps to improve diagnostic accuracy and early detection,thus allowing for earlier intervention or treatment.This combined application allows for more accurate identification of low-grade and high-grade cervical intraepithelial neoplasia,providing more information for indi-vidualized patient management.


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