ObjectiveTo investigate the pharmacological effects of modified Xiexintang ointment on anti-infection and promotion of wound healing in mice with deep second-degree scalds， as well as its underlying mechanisms. MethodsA mouse model of deep second-degree scald was established and mice were randomly divided into six groups： blank group， model group， positive control group （Jingwanhong ointment， 0.1 g·cm^-2）， low-， medium-， and high-dose modified Xiexintang ointment group （0.05， 0.1， and 0.2 g·cm^-2）， with 10 mice in each group. Treatment was administered for 16 days. Wound recovery was recorded by photography， and the wound healing rate was calculated. Hematoxylin-eosin （HE） staining was used to observe histopathological changes in the scalded skin tissues. The levels of inflammatory cytokines， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）， were measured by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry was used to evaluate the expression levels of vascular endothelial growth factor （VEGF） and cluster of differentiation 31 （CD31） in wound tissues. Western blot analysis was performed to determine the protein expression levels of nerve growth factor （NGF）， its high-affinity receptor tropomyosin receptor kinase A （TrkA）， and its low-affinity receptor nerve growth factor receptor （NGFR）. ResultsCompared with the blank group， the burn site in the model group showed swelling and whitening on the day of modeling， followed by hardening and scab formation on the next day. HE staining on day 2 revealed dermal tissue damage， swelling and degeneration of collagen fibers with homogeneous eosinophilic staining， partial destruction of hair follicles and sebaceous glands， and inflammatory cell infiltration in the dermis， indicating successful model establishment. Compared with the model group， from day 8 of treatment， the low-， medium-， and high-dose groups of modified Xiexintang ointment significantly increased the wound healing rate （P<0.01）. Compared with the model group， all dose groups significantly promoted thickening of the newly formed epidermis， reduced hemorrhage， decreased inflammatory cell infiltration， and increased neovascularization. Compared with the model group， all dose groups significantly reduced the levels of pro-inflammatory cytokines IL-1β， IL-6， and TNF-α in wound tissues （P<0.01）. Meanwhile， the expression levels of angiogenesis-related proteins VEGF and CD31 in wound tissues were significantly increased in all dose groups （P<0.01）. Compared with the model group， the protein expression levels of NGF， NGFR， and TrkA were increased in the medium-dose group （P<0.05， P<0.01）. With increasing dosage， the high-dose group showed a more pronounced increase in NGF， NGFR， and TrkA expression compared with the model group （P<0.01）. ConclusionModified Xiexintang ointment exerts anti-infective and wound-healing effects on skin wounds in mice with deep second-degree scalds. The underlying mechanisms may be related to the regulation of VEGF， CD31， NGF， TrkA， and NGFR protein expression， thereby reducing inflammation and promoting angiogenesis and nerve regeneration at the wound site.

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.

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.

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.

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.

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.

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.

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.

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.

ObjectiveTo construct the core outcome set （COS） for premature ovarian insufficiency （POI） treated with traditional chinese medicine （TCM）， thereby standardizing the effect evaluation system of POI clinical researches. MethodsDatabases including PubMed， EMbase， Cochrane Library， Web of Science， CNKI， Wanfang， VIP， SinoMed from January 2017 to December 31， 2021， and Chinese Clinical Trials Registry （ChiCTR）， ClinicalTrials.gov were searched to collect the outcomes used in clinical studies of POI. Supplemented with the patients preferred outcomes through semi-structured interviews， the outcome pool was then constructed. Finally through the Delphi survey and consensus conference， the COS for POI was obtained. ResultsA total of 554 clinical researches and 14 registered clinical research protocols were included. A semi-structured interview was conducted within 20 patients. A total of 77 outcomes were included in the pool after consolidation. After two rounds of Delphi surveys， 20 outcomes were initially included. The COS， which was finalized through expert consensus conference， consists of 8 outcomes in 3 domains， which were ovarian reserve function （follicle stimulating hormone， estradiol， anti-Mullerian hormone， sinus follicle count）， menstruation-related indicators （menstrual symptoms condition） and fertility indicators （pregnancy rate， live birth rate and the numbers of retrieved oocytes）. Through expert discussion， the corresponding measurement methods as well as the measurement time points of the COS were determined. ConclusionThis study formed COS for clinical studies of TCM in the treatment of POI， by practicing the general method of developing COS， and exploring the key points of developing COS with TCM features.