1.Study on the neuroprotective effect and mechanism of Tianma Gouteng Decoction on combining rat model of Hyperactivity of Liver Yang and MCAO based on autophagic flux and CXCL12/CXCR4 axis
Xiaoli WANG ; Jing SHAO ; Wei ZHANG ; Ping TIAN ; Xuexia ZHANG ; Changhe LIU ; Kaiyan LI ; Dan YANG ; Xiaoyan GUO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(8):1037-1048
AIM:To investigate autophagic status in ischemic stroke with Liver Yang Hyperactivity and the mechanism of Tianma Gouteng Decoction(TMGTD).METHODS:SD rats were divided into sham,model,TMGTD high/medium/low-dose(20.52/10.26/5.13 g·kg-1·d-1),and Nimodipine(30 mg·kg-1·d-1)groups.A Liver Yang Hyperactivity and cerebral ischemia-reperfusion model was es-tablished using Fuzi Decoction(2 g·kg-1·d-1)and thread-occlusion.After 21 days of Fuzi decoction pretreatment,rats received daily drug administra-tion for 12 days.Syndrome indicators(irritability,24-hour water intake,24-hour urine volume,facial temperature)were recorded,plasma NE,E,cAMP,and cGMP were measured by ELISA,neurological function was assessed using Zea Longa and mNSS methods,brain histopathology was evaluated by HE staining,protein expression of soluble/insoluble p62 and LC3B was detected by Western blot,au-tophagy-related genes were analyzed by PCR array,additionally,mRNA and protein levels of CXCR4 and CXCL12 were measured by qRT-PCR and Western blot.RESULTS:Compared to the sham group,the model group showed increased irritability,24-hours water intake,24-hours urine volume,facial temper-ature,and level of NE,E,cGMP(P<0.01),neurologi-cal scores(P<0.01),LC3B-Ⅱ,insoluble p62,CXCR4,CXCL12 expression(P<0.01),but decreased soluble p62(P<0.01).TMGTD groups exhibited reduced irri-tability,water intake,urine volume,facial tempera-ture,NE,E,cGMP(P<0.05,P<0.01),neurological scores(P<0.05,P<0.01),p62 expression(P<0.01),alongside increased LC3B-Ⅱ(P<0.01)and improved cortical pathology.TMGD also reversed dysregulat-ed autophagy-apoptosis genes(CXCR4,Lamp1,Tgfb1,APP,Rab24)and reduced CXCR4,CXCL12 ex-pression(P<0.01).CONCLUSION:In the Liver Yang Hyperactivity and cerebral ischemia-reperfusion model,autophagy genes were activated but flux was impaired,and Tianma Gouteng Decoction may protect by restoring autophagic flux and inhibiting the CXCL12/CXCR4 axis.
2.Constructing an integrative Chinese and western medical clinical pathway for knee osteoarthritis based on guideline recommendations
Luping LIU ; Xiyou WANG ; Lingyun ZHANG ; Yuan LEI ; Yi AN ; Yixuan GAO ; Zhendong XING ; Jiaqi LIU ; Changhe YU
International Journal of Traditional Chinese Medicine 2025;47(1):9-17
Knee osteoarthritis (KOA) is a common chronic degenerative disease that not only causes pain and reduces the quality of life for patients but also imposes a significant societal burden. Clinical pathways can be developed by referencing recommendations from clinical practice guidelines to localize guidelines within the context of integrated traditional Chinese and western medical systems. However, existing clinical pathways suffer from shortcomings such as deficiencies in integrated traditional Chinese and western medical diagnosis and treatment, inadequate shared decision-making between healthcare providers and patients, and suboptimal visualization of clinical pathways. This study aimed to address and optimize the clinical pathway of KOA by comprehensively organizing and localizing the recommended guidelines. The concept of integrated traditional Chinese and western medicine was reflected through the construction of a path of joint decision-making between doctors and patients, emphasizing the coexistence of diagnosis and screening, the combination of clinical and imaging staging, joint decision-making between doctors and patients, and treatment stages. This pathway emphasizes patient-centered approach, with pain relief and functional rehabilitation running parallel, achieving the implementation of evidence-based concepts in practical medical practice. It provides a concrete basis for joint decision-making between doctors and patients in the integrated treatment of KOA with traditional Chinese and western medicine, which helps to improve diagnosis and treatment efficiency and patient quality of life.
3.Exploration of the effect and design of placebo manipulation in clinical trials of manipulation
Changhe YU ; Hualong LU ; Zhifeng LIU ; Hui SHAO ; Baolin JIA ; Hao WANG ; Xiyou WANG ; Yanan SUN
International Journal of Traditional Chinese Medicine 2025;47(10):1353-1358
This article summarized the current status and challenges of manipulation therapy for musculoskeletal pain and its placebo effect in clinical trials, analyzing the impact of the placebo effect on the evaluation of therapeutic efficacy. The efficacy of different manual manipulation techniques remains uncertain, and the degree of blinding and patient expectations play a crucial role in efficacy assessment. The article suggested improving trial design through standardized placebo intervention design, comprehensive investigation of patient expectations and psychological states, rigorous training of practitioners, and optimized diagnostic and treatment scenarios and doctor-patient relationship, to ensure consistency between intervention and placebo groups. Specific measures include the application of the DITTO (Deconstruct, Identify, Take out, Think, Optimize) framework, the use of standardized questionnaire tools, and multi-center, large-sample randomized controlled trials to enhance the external validity and statistical power of research results, thereby providing more scientifically reliable evidence for clinical practice.
4.Cross-sectional study of drug resistance in newly diagnosed HIV-1 infected patients in Shanghai
Qianru LIN ; Xuqin WANG ; Wenqi TANG ; Yuan DONG ; Qing YUE ; Chunyan HE ; Xiaolei YU ; Changhe LIU ; Yiqing HAN ; Wanqing FENG ; Zhen NING ; Xin SHEN ; Xin CHEN ; Yi LIN
Chinese Journal of Experimental and Clinical Virology 2025;39(1):69-74
Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.
5.Study on the neuroprotective effect and mechanism of Tianma Gouteng Decoction on combining rat model of Hyperactivity of Liver Yang and MCAO based on autophagic flux and CXCL12/CXCR4 axis
Xiaoli WANG ; Jing SHAO ; Wei ZHANG ; Ping TIAN ; Xuexia ZHANG ; Changhe LIU ; Kaiyan LI ; Dan YANG ; Xiaoyan GUO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(8):1037-1048
AIM:To investigate autophagic status in ischemic stroke with Liver Yang Hyperactivity and the mechanism of Tianma Gouteng Decoction(TMGTD).METHODS:SD rats were divided into sham,model,TMGTD high/medium/low-dose(20.52/10.26/5.13 g·kg-1·d-1),and Nimodipine(30 mg·kg-1·d-1)groups.A Liver Yang Hyperactivity and cerebral ischemia-reperfusion model was es-tablished using Fuzi Decoction(2 g·kg-1·d-1)and thread-occlusion.After 21 days of Fuzi decoction pretreatment,rats received daily drug administra-tion for 12 days.Syndrome indicators(irritability,24-hour water intake,24-hour urine volume,facial temperature)were recorded,plasma NE,E,cAMP,and cGMP were measured by ELISA,neurological function was assessed using Zea Longa and mNSS methods,brain histopathology was evaluated by HE staining,protein expression of soluble/insoluble p62 and LC3B was detected by Western blot,au-tophagy-related genes were analyzed by PCR array,additionally,mRNA and protein levels of CXCR4 and CXCL12 were measured by qRT-PCR and Western blot.RESULTS:Compared to the sham group,the model group showed increased irritability,24-hours water intake,24-hours urine volume,facial temper-ature,and level of NE,E,cGMP(P<0.01),neurologi-cal scores(P<0.01),LC3B-Ⅱ,insoluble p62,CXCR4,CXCL12 expression(P<0.01),but decreased soluble p62(P<0.01).TMGTD groups exhibited reduced irri-tability,water intake,urine volume,facial tempera-ture,NE,E,cGMP(P<0.05,P<0.01),neurological scores(P<0.05,P<0.01),p62 expression(P<0.01),alongside increased LC3B-Ⅱ(P<0.01)and improved cortical pathology.TMGD also reversed dysregulat-ed autophagy-apoptosis genes(CXCR4,Lamp1,Tgfb1,APP,Rab24)and reduced CXCR4,CXCL12 ex-pression(P<0.01).CONCLUSION:In the Liver Yang Hyperactivity and cerebral ischemia-reperfusion model,autophagy genes were activated but flux was impaired,and Tianma Gouteng Decoction may protect by restoring autophagic flux and inhibiting the CXCL12/CXCR4 axis.
6.Cross-sectional study of drug resistance in newly diagnosed HIV-1 infected patients in Shanghai
Qianru LIN ; Xuqin WANG ; Wenqi TANG ; Yuan DONG ; Qing YUE ; Chunyan HE ; Xiaolei YU ; Changhe LIU ; Yiqing HAN ; Wanqing FENG ; Zhen NING ; Xin SHEN ; Xin CHEN ; Yi LIN
Chinese Journal of Experimental and Clinical Virology 2025;39(1):69-74
Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.
7.Mechanism of Xinnao shutong capsule alleviating cerebral ischemia-reperfusion injury in rats by regulating ferroptosis
Huani LI ; Changhe LIU ; Xiaoyan GUO ; Xin ZHONG ; Wei ZHANG ; Wenjing GE
China Pharmacy 2025;36(3):306-311
OBJECTIVE To study the mechanism of Xinnao shutong capsule alleviating cerebral ischemia reperfusion injury(CIRI)in rats by regulating the ferroptosis pathway.METHODS SD rats were randomly divided into sham operation group,model group,Xinnao shutong low-dose,high-dose group(220,440 mg/kg),Ginkgo biloba leaves extract group(positive control,150 mg/kg).Each group of rats was orally administered with the corresponding medication/normal saline for 7 consecutive days.Transient occlusion of the middle cerebral artery was adopted to induce the CIRI model;the samples were taken 24 h after the operation;the cerebral infarction area of rats was detected,and the cerebral infarction rate was calculated.The pathological changes of brain tissues were observed,and the levels of lipid peroxide(LPO),malondialdehyde(MDA)and glutathione(GSH)in cerebral tissue were detected;mRNA and protein expressions of nuclear factor-erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1)and glutathione peroxidase 4(GPX4)were all detected in cerebral tissue of rats.RESULTS Compared with model group,the cerebral infarction rate,the content of total iron in cerebral tissue and serum level of LPO(except for Ginkgo biloba leaves extract group and Xinnao shutong low-dose group)were all decreased significantly in G.biloba leaves extract group and Xinnao shutong groups(P<0.05 or P<0.01);the serum level of GSH,the protein and mRNA expressions of Nrf2,HO-1 and GPX4 were all increased significantly(P<0.05 or P<0.01).The pathological damage to brain tissue was reduced,the number of nerve cells increased,the edema was alleviated,and the nuclear membrane was flattened.CONCLUSIONS Xinnao shutong capsule can inhibit ferroptosis and reduce CIRI,the mechanism of which may be associated with the activation of the Nrf2/HO-1/GPX4 signaling pathway.
8.Effects and mechanism of persimmon leaf extract on IEC-6 cell ferroptosis induced by H2O2
Xuexia ZHANG ; Min ZHOU ; Hongyan ZHOU ; Lifei WANG ; Huani LI ; Changhe LIU ; Hongde XU ; Mingli ZHANG
China Pharmacy 2025;36(1):64-70
OBJECTIVE To investigate the effects and potential mechanism of persimmon leaf (PL) extract against ferroptosis induced by H2O2 in IEC-6 cells.METHODS Using IEC-6 cells as object,the effects of ferroptosis inhibitor ferrostatin-1 on IEC-6 cell viability induced by H2O2 were investigated;IEC-6 cells were divided into control group,H2O2 group,H2O2+PL 25 μg/mL group and H2O2+PL 50 μg/mL group.The levels of oxidant stress indexes[content of malondialdehyde (MDA),activity of superoxide dismutase (SOD),and levels of reactive oxygen species (ROS)],mitochondrial membrane potential (MMP) as well as mRNA and protein expressions of nuclear factor-erythroid-2 related factor 2 (Nrf2),heme oxygenase-1 (HO-1),NADPH/quinone oxidoreductase-1 (NQO-1),cystine/glutamate anti-porter (xCT),glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH) were detected.RESULTS Ferroptosis inhibitor ferrostatin-1 could significantly increase the survival rate of H2O2-induced cells (P<0.01).Compared with the control group,MDA content,ROS level,mRNA expressions of Nrf2 and NQO-1 as well as protein expressions of Nrf2 and HO-1 were increased or up-regulated significantly,while SOD activity,MMP,mRNA expressions of xCT,GPX4 and FTH as well as protein expressions of GPX4 and FTH were decreased or down-regulated significantly (P<0.01 or P<0.05).Compared with the H2O2 group,oxidative stress indexes of H2O2+PL 25,50 μg/mL groups were reversed to different extents,MMP level was increased significantly,as well as mRNA and protein expressions of Nrf2,HO-1,NQO-1,xCT,GPX4 and FTH were up-regulated to different extents;there were statistical significances in some indexes between groups (P<0.01 or P<0.05).CONCLUSIONS PL extract can alleviate mitochondrial membrane damage and abnormal accumulation of ROS caused by H2O2,which may be related to the inhibition of ferroptosis by activating the Nrf2/HO-1 signaling pathway.
9.Protocol for the Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome
Lingyun ZHANG ; Xiyou WANG ; Daxin LIU ; Qiang HE ; Xuefeng WANG ; Xun LI ; Yutong FEI ; Yi XIAO ; Xiaoxue LAN ; Yuanwen LIANG ; Xiaoxuan LIN ; Rong ZHOU ; Sirui GU ; Ying ZHANG ; Yue WANG ; Xingzhu YE ; Wenke LIU ; Hong CHEN ; Changhe YU
International Journal of Traditional Chinese Medicine 2024;46(8):961-966
In order to standardize the clinical diagnosis and treatment of upper airway cough syndrome (UACS) for children in China, Dongzhimen Hospital of Beijing University of Chinese Medicine and Affiliated Hospital of Liaoning University of Traditional Chinese Medicine initiated the development of this Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome based on evidence-based medical evidence. This guideline will process registration, write a plan, and develop relevant processes and writing norms, develop and publish official documents. This plan mainly introduces the scope of the guidelines, the purpose and significance, the composition of the guidelines working group, the management of conflicts of interest, the collection, selection and determination of clinical problems, the retrieval, screening and rating of evidence, and the consensus of recommendations. Registration information: This study has been registered in the international practice guidelines registry platform with the registration code of PREPARE-2023CN087.
10.Preparation instructions of the Technical operation specification for TCM health care services (non-medical) foot bath (2024 edition)
Lingyun ZHANG ; Changhe YU ; Changxin LIU ; Luping LIU ; Yixuan GAO ; Jiayu LIU ; Yuhan WANG ; Mengmeng ZHANG ; Yang ZHANG ; Xiyou WANG
International Journal of Traditional Chinese Medicine 2024;46(10):1258-1263
Foot bath technique is booming in daily health care services. In order to develop a more standardized and complete technical operation process, the working group recorded the whole process of document formulation while writing the Technical Operation Specification for TCM Health Care Services (Non-Medical) Foot Bath (2024 edition). Work profile (including task background, task source, drafting unit, participant grouping and responsibilities), main technical content (including the basis and principles of preparation, key technical content of technical specifications), main preparation process (formation of working groups, registration and plan writing, selection and determination of clinical issues, literature research, drafting of the first draft, consensus on the main content of technical specifications, soliciting opinions, testing applications and external review), the relationship of current mandatory national standards or policies and regulations, the treatment process and basis of major differences, publicity and implementation and post-effect evaluation, the proposal to abolish the current relevant guidelines and the corresponding annexes were under detailed and in-depth description, which can assist the relevant practitioners of non-medical institutions to better understand and apply this technical specification.

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