ObjectiveTo investigate the mechanisms of Tongmai Yangxin pills （TMYX） and Tongxinluo capsules （TXL） in treating no-reflow （NR） after myocardial ischemia and reperfusion following the concept of treating the same disease with different methods， based on integrative pharmacology and experimental validation. MethodsEighty 8-week-old SPF-grade SD rats were randomly assigned into four groups （n=20）： sham operation， NR， TMYX （4 g·kg^-1）， and TXL （2 mg·kg^-1）. A rat model of myocardial ischemia-reperfusion no-reflow was established by in-situ ligation of the left anterior descending coronary artery. Gastric gavage was first performed 4 h after the operation， and samples were collected on day 7. Thioflavin S staining was used to observe the NR area in rat myocardium. Echocardiography was performed to examine the cardiac function. Hematoxylin-eosin （HE） staining was conducted to observe the pathological changes of the myocardial tissue. An automatic biochemical analyzer was adopted to measure myocardial enzyme activity. Then， integrated pharmacology was applied for Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Finally， Western blot was employed to quantify the protein levels of key targets in the myocardial tissue， including soluble guanylyl cyclase （sGC）， cyclic guanosine monophosphate （cGMP）/dependent protein kinase （PKG）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， and hypoxia-inducible factor-1α （HIF-1α）. ResultsCompared with the sham operation group， the NR group showed increased NR area of myocardium， decreased left ventricular ejection fraction （EF）， left ventricular fractional shortening （FS）， left ventricular outflow tract peak velocity （LVOT Peak）， and left ventricular stroke volume （LVSV） （P<0.01）， fractured and disordered myocardial fibers as well as inflammatory cell infiltration in the myocardial tissue， enhanced activities of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in the myocardial tissue （P<0.01）， and downregulated protein levels of sGC， PKG， phosphorylated （p）-PI3K （Tyr458）， and p-Akt （Tyr315） in the myocardial tissue （P<0.05， P<0.01）. The expression level of HIF-1α protein showed a downward trend. Compared with the NR group， the TMYX group and TXL group exhibited a decreasing trend in myocardial NR area， EF， FS， and LVOT Peak significantly increased （P<0.05， P<0.01）， LVSV showed an upward trend， ameliorated myocardial pathological morphology and inflammatory infiltration， reductions in CK， CK-MB， and LDH activities （P<0.05， P<0.01）， and upregulated protein levels of sGC， PKG， p-PI3K （Tyr458） in myocardial tissue （P<0.05， P<0.01）， the protein expressions of p-Akt （Tyr315） and HIF-1α showed an upward trend. A comparison of the therapeutic effects between the two compound prescriptions showed that TMYX tended to exert a better effect in restoring cardiac function and protecting cardiac structure in NR rats， whereas TXL was more effective in reducing myocardial NR area and lowering myocardial enzyme activities in NR rats. Integrative pharmacology analysis combined with experimental verification demonstrated that both TMYX and TXL could alleviate NR through the following mechanisms： activating the cyclic cGMP/PKG signaling pathway to regulate vascular tone， activating the PI3K/Akt signaling pathway to dilate blood vessels， and activating the HIF-1 signaling pathway to inhibit oxidative stress. However， TMYX had an advantage in activating the cGMP/PKG pathway， while TXL was superior in activating the PI3K/Akt pathway. The two compound prescriptions exerted comparable effects on the HIF-1 signaling pathway， which might serve as their common therapeutic pathway. ConclusionBoth TMYX and TXL could alleviate NR damage. TMYX exerts its protective effect against NR mainly by activating the cGMP/PKG signaling pathway， while TXL exerts its effect mainly through the PI3K/Akt pathway. The HIF-1α signaling pathway may be a common pathway for the two compound prescriptions to exert their protective effects against NR. This study reveals the similarities and differences between TMYX and TXL in the treatment effect and mechanism for NR， providing an experimental basis and a theoretical basis for better clinical application of the two compound prescriptions.

AIM:To compare the formation and release of neutrophil extracellular traps(NETs)af-ter exposure to the high-altitude hypoxic environ-ment for different periods,and their relationship with the dynamic changes of microcirculatory disor-ders associated with pulmonary edema.METH-ODS:SD rats were raised under normoxic condi-tions at an altitude of 400 m and under hypoxic conditions at an altitude of 4 200 m.The rats raised under hypoxic conditions at an altitude of 4 200 m for 7 days were returned to normoxic con-ditions at 400 m to observe the changes in physio-logical and pathological indicators of the rats.The dynamic changes of neutrophil extracellular traps(NETs)release and microcirculatory disorders relat-ed to pulmonary edema after high-altitude hypoxia exposure and after returning to the plain were ex-plored by blood routine determination,rat arterial blood gas analysis,ELISA experiment,lung water content determination,H&E staining,and immuno-histochemical staining.RESULTS:In the hypoxic en-vironment at 4 200 m,rats exhibited significant re-ductions in arterial oxygen saturation(SaO2)and partial pressure of oxygen(PO2)(P＜0.01),accompa-nied by a marked increase in lung-tissue water con-tent(P＜0.01).The complete blood count revealed elevated levels of red blood cells,white blood cells,lymphocytes,and neutrophils(P＜0.01).In addition,the formation and release of NETs in neutrophils in-creased,accompanied by an aggravation of the in-flammatory response.After returning to the low-al-titude normoxic area at 400 m,the above indica-tors gradually returned to normal levels on the 7th day.Pathological changes such as alveolar epitheli-al cell shedding and inflammatory cell infiltration were observed in the lung tissues of rats in the high-altitude area,and the pathological changes were restored after returning to the low-altitude normoxic environment.CONCLUSION:The release of NETs from neutrophils is closely related to the re-covery of pulmonary edema and pulmonary ede-ma-related microcirculatory disorders after high-al-titude hypoxia exposure.

Game-based psychological assessment utilizes game mechanisms and elements to enhance partic-ipants'motivation and improve measurement accuracy,but similar to traditional methods,it mainly focuses on static results.By integrating game-based psychological assessment with artificial intelligence technology,this paper propo-ses the paradigm of intelligent psychological assessment based on interactive environment.With analyzing dynamic process data within the game,this paradigm can accurately depict the participants'actions and results in the interac-tive context,more effectively representing individual psychological states and behavioral characteristics.This new paradigm demonstrates advancements and significant potential for development in terms of demand,data collection,and analysis techniques.

OBJECTIVE To explore the clinical characteristics and risk factors for refractory drug-resistant Pseudo-monas aeruginosa infection and evaluate the prognosis so as to provide theoretical bases for effective prevention and control of the refractory drug-resistant P.aeruginosa infection.METHODS A total of 95 patients who were di-agnosed with refractory drug-resistant P.aeruginosa infection and were treated in People's Hospital of Guangdong Province from Jan.2019 to Dec.2023 were assigned as the infection group.Meanwhile,95 patients who did not have drug-resistant P.aeruginosa infection,matched by the age and hospitalization period,were chosen as the non-infection group in a case-control(1∶1 ratio).The basic information and clinical data were collected from the two groups of patients.The characteristics and risk factors for the drug-resistant P.aeruginosa infection were ana-lyzed,and the prognosis of the patients was evaluated.RESULTS Among the clinical isolates of drug-resistant P.aeruginosa,78 were isolated from respiratory secretions;there were 59 patients from intensive care unit(ICU),13 patients from respiratory medicine department and 8 patients from geriatrics department.Fever,dyspnea,moist rales and cough were the major clinical manifestations.The proportions of patients with history of respirato-ry tract disease(P＜0.001),renal disease(P=0.008),nervous system disease(P=0.005),diabetes mellitus(P=0.017),hepatic disease(P=0.007),previous utilization rate of aminoglycosides(P=0.002)and previous u-tilization rate of no less than 3 types of antibiotics were higher in the infection group than in the non-infection group.Multivariate analysis showed that the history of respiratory tract disease(OR=2.813,95％CI:1.366 to 5.792,P=0.005),history of diabetes mellitus(OR=2.465,95％CI:1.129 to 5.382,P=0.024)and history of nervous system disease(OR=2.386,95％CI:1.151 to 4.944,P=0.019)were the risk factors for the drug-resist-ant P.aeruginosa infection.The mortality rate of the infection group was 30.53％,higher than 6.32％of the non-infection group(x2=18.527,P＜0.001).CONCLUSIONS The mortality rate of the patients with drug-resistant P.aeruginosa infection is high.The history of respiratory tract disease,history of diabetes mellitus and history of nervous system disease are the major risk factors for the infection.It is necessary for the hospital to strengthen the awareness of prevention of the drug-resistant P.aeruginosa infection so as to curb the hospital-associated infection.

ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective:To explore the effect of non-invasive intervention on preventing maternal breast tenderness, and to provide references for clinicians to select the optimal non-invasive intervention for the prevention of maternal breast tenderness.Methods:Literature focused on the effect of different non-invasive interventions to prevent maternal breast tenderness by randomized controlled trials design was searched in the databases, including China National Knowledge Infrastructure, VIP, Wanfang, SinoMed, PubMed, Web of Science, Embase and Cochrane Library, from inception to April 8, 2024. Two researchers independently screened the literature, extracted the data and evaluated the quality of the literature. Stata 16.0 was used to conduct a network Meta-analysis.Results:A total of 21 studies involving 2 298 women, covering 5 non-invasive interventions (low-frequency pulse electrotherapy, breast massage combined with low-frequency pulse electrotherapy, breast massage and acupoint massage, breast massage and acupoint massage combined with ear point pressure bean, breast massage and acupoint massage combined with external application of Chinese medicine). The network meta-analysis results showed that, compared with routine care, five non-invasive interventions had statistically significant differences in reducing the incidence of maternal breast tenderness ( OR values ranging from 0.20 to 0.39, all P<0.05). Breast massage combined with low-frequency pulse electrotherapy ranked first in terms of effectiveness on preventing of breast tenderness. Conclusions:All five non-invasive interventions are effective on preventing maternal breast tenderness, with breast massage combined with low-frequency pulse electrotherapy being the most effective.

AIM:To compare the formation and release of neutrophil extracellular traps(NETs)af-ter exposure to the high-altitude hypoxic environ-ment for different periods,and their relationship with the dynamic changes of microcirculatory disor-ders associated with pulmonary edema.METH-ODS:SD rats were raised under normoxic condi-tions at an altitude of 400 m and under hypoxic conditions at an altitude of 4 200 m.The rats raised under hypoxic conditions at an altitude of 4 200 m for 7 days were returned to normoxic con-ditions at 400 m to observe the changes in physio-logical and pathological indicators of the rats.The dynamic changes of neutrophil extracellular traps(NETs)release and microcirculatory disorders relat-ed to pulmonary edema after high-altitude hypoxia exposure and after returning to the plain were ex-plored by blood routine determination,rat arterial blood gas analysis,ELISA experiment,lung water content determination,H&E staining,and immuno-histochemical staining.RESULTS:In the hypoxic en-vironment at 4 200 m,rats exhibited significant re-ductions in arterial oxygen saturation(SaO2)and partial pressure of oxygen(PO2)(P＜0.01),accompa-nied by a marked increase in lung-tissue water con-tent(P＜0.01).The complete blood count revealed elevated levels of red blood cells,white blood cells,lymphocytes,and neutrophils(P＜0.01).In addition,the formation and release of NETs in neutrophils in-creased,accompanied by an aggravation of the in-flammatory response.After returning to the low-al-titude normoxic area at 400 m,the above indica-tors gradually returned to normal levels on the 7th day.Pathological changes such as alveolar epitheli-al cell shedding and inflammatory cell infiltration were observed in the lung tissues of rats in the high-altitude area,and the pathological changes were restored after returning to the low-altitude normoxic environment.CONCLUSION:The release of NETs from neutrophils is closely related to the re-covery of pulmonary edema and pulmonary ede-ma-related microcirculatory disorders after high-al-titude hypoxia exposure.

Objective:To explore the effect of non-invasive intervention on preventing maternal breast tenderness, and to provide references for clinicians to select the optimal non-invasive intervention for the prevention of maternal breast tenderness.Methods:Literature focused on the effect of different non-invasive interventions to prevent maternal breast tenderness by randomized controlled trials design was searched in the databases, including China National Knowledge Infrastructure, VIP, Wanfang, SinoMed, PubMed, Web of Science, Embase and Cochrane Library, from inception to April 8, 2024. Two researchers independently screened the literature, extracted the data and evaluated the quality of the literature. Stata 16.0 was used to conduct a network Meta-analysis.Results:A total of 21 studies involving 2 298 women, covering 5 non-invasive interventions (low-frequency pulse electrotherapy, breast massage combined with low-frequency pulse electrotherapy, breast massage and acupoint massage, breast massage and acupoint massage combined with ear point pressure bean, breast massage and acupoint massage combined with external application of Chinese medicine). The network meta-analysis results showed that, compared with routine care, five non-invasive interventions had statistically significant differences in reducing the incidence of maternal breast tenderness ( OR values ranging from 0.20 to 0.39, all P<0.05). Breast massage combined with low-frequency pulse electrotherapy ranked first in terms of effectiveness on preventing of breast tenderness. Conclusions:All five non-invasive interventions are effective on preventing maternal breast tenderness, with breast massage combined with low-frequency pulse electrotherapy being the most effective.