Pulmonary hypertension (PH), marked by sustained elevation of pulmonary artery pressure, imposes a heavy burden on the right ventricle and may culminate in right heart failure. Its pathogenesis is multifaceted, encompassing endothelial dysfunction, vascular smooth muscle proliferation, inflammation, thrombosis, and genetic factors. Animal models serve as core tools for exploring PH mechanisms and therapies, each with unique strengths and limitations. The single-dose monocrotaline (MCT) model is one of the most commonly used experimental animal models of PH and is widely applied in mechanistic studies, drug screening, and efficacy evaluation; it offers simplicity and cost-effectiveness, can induce PH within a short period, yet its pathophysiology differs to some extent from human idiopathic PH. In contrast, the Sugen5416 combined with chronic hypoxia model better mimics PH progression by placing animals under hypoxic conditions to induce pulmonary vasoconstriction and vascular remodeling, but it requires a longer modelling time, and the degree of hypoxia has a substantial impact on experimental outcomes. Beyond these two commonly used modeling approaches, a variety of emerging techniques have been applied in PH research; gene-editing technologies enable precise investigation of specific gene functions in PH. Additionally, induced pluripotent stem cell-based 3D organoid technology allows for individualized modelling while preserving patients' genetic information for precise clinical translation. Each model or technology can simulate different aspects of the pathological processes of human PH, and their findings provide key insights into the nature of the disease and serve as an important platform for the development of novel therapeutic targets. This paper comprehensively describes various animal models and emerging technologies used in PH research, analyzing their characteristics, applications, and limitations, with the aim of providing experimental and technical support for the development of new therapeutic strategies and drugs.

ObjectiveTo investigate the correlation between neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， systemic immune-inflammation index （SII） and the severity of intrauterine adhesions （IUA）. MethodsThe retrospective study included 380 patients who underwent transcervical resection of adhesions （TCRA） from December 2019 to March 2025. Based on the American Fertility Society （AFS） classification， patients were divided into mild （n=61）， moderate （n=225）， and severe （n=94） groups. NLR， PLR， and SII were calculated from preoperative blood tests. Statistical analyses included Kruskal-Wallis test and ordinal Logistic regression. ResultsNLR， PLR， and SII were significantly higher in the severe IUA group compared to the mild group （P<0.05）， with SII showing the strongest predictive ability （OR=1.004， P=0.001）. The number of intrauterine procedures was an independent risk factor （OR=1.27/level， P=0.016）. The predictive model ［Logit（P）=-0.676+0.241×operation times+0.004×SII］ effectively identified severe IUA cases. ConclusionInflammatory markers （particularly SII） are correlated with IUA severity and may serve as non-invasive tools for clinical assessment.

OBJECTIVE:Some studies have shown that physical exercise can effectively improve knee extensor strength and cardiorespiratory function in burn patients;some studies have also shown that physical exercise is not effective in improving respiratory function in burn patients.Improvement effects of physical exercise on physical functions(muscle function,walking function,cardiopulmonary function,and lean body mass)of burn patients were evaluated by a systematic evaluation and meta-analysis.METHODS:Based on databases including Web of Science,PubMed,Embase,Cochrane Library,CNKI,WanFang,and the Chinese Biomedical Database,literature on the improvement of physical function in burn patients through physical exercise was searched using subject headings and free terms.With muscle function,walking ability,cardiopulmonary function,and lean body mass as the primary outcome measures,a meta-analysis was conducted to compare the efficacy of physical exercise with traditional physical therapy or conventional care methods.RESULTS:A total of 38 papers were included,of which 26 papers were included in the meta-analysis,involving 1 658 patients.Meta-analysis results showed that:(1)Physical exercise significantly enhances the knee extensor strength of the dominant leg in burn patients(mean difference[MD]=8.34,95％confidence interval[CI]:6.95-9.72,P＜0.000 01),increases quadriceps strength,peak oxygen uptake,forced vital capacity and maximum ventilation volume in 1 second,and resting heart rate(standardized mean difference[SMD]=4.41,95％CI:2.52-6.30,P＜0.000 01;MD=4.91,95％CI:3.52-6.29,P＜0.000 01;MD=5.86,95％CI:0.09-11.63,P=0.05;MD=6.90,95％CI:2.93-10.87,P=0.000 7;MD=5.03,95％CI:1.45-8.61,P=0.006),and improves the 6-minute walking distance,gait parameters,and total lean body mass(MD=45.29,95％CI:24.7-65.89,P＜0.0001;SMD=7.84,95％CI:6.05-9.63,P＜0.000 01;MD=2.47,95％CI:2.01-2.93,P＜0.000 01).(2)The subgroup analysis results indicated that the improvement in knee extensor strength of the dominant leg may be better in children than in adults and better in the extra-heavy group than in the heavy group.Improvement in the 6-minute walking distance is better in children than in adults,and higher degree of burn indicates better improvement effects,with no difference from the control group for＜12 weeks.Peak oxygen uptake may be better in adults and severe burn groups than in children and moderate burn groups,resistance combined with aerobic exercise modalities may be better than aerobic exercise alone,and exercise duration＞60 minutes may be better than＜60 minutes.CONCLUSION:Physical activity is effective in improving physical function in burn patients,as evidenced by improvements in muscle strength,walking ability,cardiorespiratory fitness,and lean body mass.The quality of evidence recommended for all indicator results is moderate or below,with imprecision and inconsistency being the main factors for downgrading.Therefore,more high-quality randomized controlled trials are needed in the future to verify the reliability of the results.

OBJECTIVE:Some studies have shown that physical exercise can effectively improve knee extensor strength and cardiorespiratory function in burn patients;some studies have also shown that physical exercise is not effective in improving respiratory function in burn patients.Improvement effects of physical exercise on physical functions(muscle function,walking function,cardiopulmonary function,and lean body mass)of burn patients were evaluated by a systematic evaluation and meta-analysis.METHODS:Based on databases including Web of Science,PubMed,Embase,Cochrane Library,CNKI,WanFang,and the Chinese Biomedical Database,literature on the improvement of physical function in burn patients through physical exercise was searched using subject headings and free terms.With muscle function,walking ability,cardiopulmonary function,and lean body mass as the primary outcome measures,a meta-analysis was conducted to compare the efficacy of physical exercise with traditional physical therapy or conventional care methods.RESULTS:A total of 38 papers were included,of which 26 papers were included in the meta-analysis,involving 1 658 patients.Meta-analysis results showed that:(1)Physical exercise significantly enhances the knee extensor strength of the dominant leg in burn patients(mean difference[MD]=8.34,95％confidence interval[CI]:6.95-9.72,P＜0.000 01),increases quadriceps strength,peak oxygen uptake,forced vital capacity and maximum ventilation volume in 1 second,and resting heart rate(standardized mean difference[SMD]=4.41,95％CI:2.52-6.30,P＜0.000 01;MD=4.91,95％CI:3.52-6.29,P＜0.000 01;MD=5.86,95％CI:0.09-11.63,P=0.05;MD=6.90,95％CI:2.93-10.87,P=0.000 7;MD=5.03,95％CI:1.45-8.61,P=0.006),and improves the 6-minute walking distance,gait parameters,and total lean body mass(MD=45.29,95％CI:24.7-65.89,P＜0.0001;SMD=7.84,95％CI:6.05-9.63,P＜0.000 01;MD=2.47,95％CI:2.01-2.93,P＜0.000 01).(2)The subgroup analysis results indicated that the improvement in knee extensor strength of the dominant leg may be better in children than in adults and better in the extra-heavy group than in the heavy group.Improvement in the 6-minute walking distance is better in children than in adults,and higher degree of burn indicates better improvement effects,with no difference from the control group for＜12 weeks.Peak oxygen uptake may be better in adults and severe burn groups than in children and moderate burn groups,resistance combined with aerobic exercise modalities may be better than aerobic exercise alone,and exercise duration＞60 minutes may be better than＜60 minutes.CONCLUSION:Physical activity is effective in improving physical function in burn patients,as evidenced by improvements in muscle strength,walking ability,cardiorespiratory fitness,and lean body mass.The quality of evidence recommended for all indicator results is moderate or below,with imprecision and inconsistency being the main factors for downgrading.Therefore,more high-quality randomized controlled trials are needed in the future to verify the reliability of the results.

Objective To discuss the prediction value of the early efficacy of hepatic arterial infusion chemotherapy(HAIC)in treating stage Ⅱ-Ⅲ hepatocellular carcinoma(HCC).Methods The clinical data of 81 patients with stage Ⅱ-Ⅲ HCC,who received at least 3 times of HAIC at the Nanchang Municipal Central Hospital of China from November 2021 to March 2024,were retrospectively analyzed.CT or MRI was used to compare patient's local tumor response after each treatment cycle.Based on modified Response Evaluation Criteria in Solid Tumors(mRECIST),the curative effects of patients after receiving the first,the second,and the last HAIC treatment were compared between each other.The prediction value of the early efficacy of HAIC in treating patients with stage Ⅱ-Ⅲ HCC was analyzed.Results In the 67 patients,the efficacy of the last time HAIC was equal or similar to that of the first time HAIC,and in the remaining 14 patients the efficacy of the last time HAIC was different from that of the first time HAIC,with an efficacy prediction rate of 82.72％.The efficacy of the last time HAIC was equal or similar to that of the second time HAIC in 71 patients,and in the remaining 10 patients the efficacy of the last time HAIC was different from that of the second time HAIC,with an efficacy prediction rate of 87.65％.Conclusion In treating stage Ⅱ-Ⅲ HCC with HAIC,the early efficacy can be used to predict the final efficacy after completion of the total treatment course.

Objective:To observe changes in intestinal flora in children with anorexia and the effects of pediatric Tuina(Chinese therapeutic massage)on their intestinal flora,and to explore the relationship between alterations in intestinal flora and anorexia,as well as the therapeutic mechanisms of pediatric Tuina in treating children with anorexia.Methods:A total of 60 healthy children who underwent physical examinations were recruited as the blank group.One hundred and twenty children with anorexia were randomly divided into a Tuina group and a medication group,with 60 children in each group,according to the random number table method.The blank group received no intervention;the Tuina group was treated with pediatric Tuina therapy;the medication group was treated with Jian Wei Xiao Shi(stomach-invigorating and digestion-promoting)tablets.Both groups underwent continuous treatment for 7 d as one course,with a 1-day rest period between courses,for a total of 4 courses.Fecal samples were collected from the three groups.The intestinal flora was detected using the 16S rDNA method.Results:Before treatment,compared to the blank group,the abundance of Firmicutes in the Tuina and medication groups was significantly lower(P<0.05).After treatment,the abundance of Firmicutes in the Tuina group was significantly increased compared to before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05);in the medication group,there was a trend of increased abundance of Firmicutes,but there was no significant difference compared to that before treatment in the same group(P>0.05),and the difference compared to the blank group remained significant(P<0.05).Before treatment,compared to the blank group,the abundance of Faecalibacterium prausnitzii(F.prausnitzii)in the Tuina and medication groups was significantly lower(P<0.05).After treatment,the abundance of F.prausnitzii in the Tuina group was significantly increased compared to before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05);in the medication group,there was a trend of increased abundance of F.prausnitzii,but no significant difference was showed compared to before treatment in the same group(P>0.05),and the differences compared to the blank and Tuina groups were significant(P<0.05).Before treatment,compared to the blank group,the abundance of Eubacterium in the Tuina and medication groups was significantly lower(P<0.05);after treatment,the abundance of Eubacterium in both Tuina and medication groups was significantly increased compared to that before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05).Before treatment,compared to the blank group,the abundance of Roseburia in the Tuina and medication groups was significantly lower(P<0.05);after treatment,the abundance of Roseburia in both Tuina and medication groups was significantly increased compared to that before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05).Conclusion:The reduction of beneficial intestinal flora may be involved in the pathogenesis of pediatric anorexia.Pediatric Tuina can promote the recovery of intestinal flora balance by increasing the abundance of beneficial flora.

Objective:To investigate the association between photodynamic diagnosis(PDD)and treatment efficacy of 5-aminolevu-linic acid(ALA)photodynamic therapy(PDT)in patients with cutaneous squamous cell carcinoma in situ(cSCCis).Methods:A pro-spective cohort study was conducted among the patients with cSCCis who underwent ALA-PDT in Department of Dermatology,Huashan Hospital,Fudan University,from January 2020 to November 2024.All patients were diagnosed with cSCCis based on biopsy,and invasive squamous cell carcinoma was excluded.Clinical information was collected and PDD was performed before treatment,and the patients were divided into moderate fluorescence group and strong fluorescence groups based on fluorescence intensity.All patients received six sessions of PDT treatment at an interval of 1-2 weeks.The primary endpoint was the initial complete clearance rate at 3 months after the last treatment session,and secondary endpoints were the sustained complete clearance rate at 12 months after the last treatment session and treatment failure rate.The multivariate regression analysis,the survival curves,and the Cox regression analysis were used to investigate the association between PDD fluorescence intensity and treatment efficacy,as well as other influencing factors for treatment efficacy.Results:Compared with the strong fluorescence group,the moderate fluorescence group had significantly lower initial complete clearance rate[57.14%(8/14)vs.93.33%(28/30),odds ratio OR=0.100,P=0.010]and sustained complete clearance rate[42.86%(6/14)vs.76.67%(23/30),OR=0.230,P=0.030)].The multivariate regression analysis showed that moderate fluores-cence was an independent risk factor for initial complete clearance(OR=0.030,P=0.030).The moderate fluorescence group had a significantly higher treatment failure rate than the strong fluorescence group[57.14%(8/14)vs.23.33%(7/30),P=0.030].The survival analysis and the Cox regression analysis showed that moderate fluo-rescence was an independent risk factor for PDT treatment failure(hazard ratio=3.040,P=0.048).There were no significant differences in adverse reactions between the two groups.Conclusion:PDD fluorescence intensity can predict the efficacy of ALA-PDT in patients with cSCCis.Moderate fluorescence indicates a higher risk of treatment failure,which can help to guide clinicians in develop-ing individualized treatment strategies.

Myocardial infarction (MI) is the leading cause of cardiovascular disease-related death worldwide. Nonetheless, existing therapeutic approaches for MI are hampered by issues such as reliance on pharmacological agents and suboptimal patient adherence. Caffeic acid (CA) is a bioactive polyphenolic compound with important anti-inflammatory, anti-bacterial and anti-oxidant functions. Still, its specific role and mechanism in treating cardiovascular disease remain to be further studied. In recent years, a large number of studies have shown that the kelch-like ECH-associated protein 1/nuclear factor erythroid 2 related factor 2 (Keap1/Nrf2) pathway is a key factor in the occurrence and development of cardiovascular diseases. In this study, H₂O₂-induced oxidative stress model of H9c2 cells and left anterior descending branch (LAD) conjunctival induced acute myocardial infarction reperfusion (AMI/R) model were used to evaluate the protective effect of CA on the heart. The interaction between CA and Keap1 was analyzed by CA-labeled fluorescence probe, target fishing, isothermal titration calorimetry (ITC), protein crystallography and surface plasmon resonance (SPR). Our results suggested that CA binds Keap1 and degrades Keap1 in a p62-dependent manner, further promoting nuclear transcription of Nrf2 and thus effectively reducing oxidative stress. In addition, based on the three-dimensional eutectic structure, it was confirmed that CA directly targets Keap1 protein by interacting with residues M550 and N532, inducing conformation changes in Keap1 protein. We also found that the CA analog chlorogenic acid (GCA) can bind Keap1. In conclusion, this study elucidates a novel molecular mechanism and structural basis for the protective effects of CA against oxidative damage via the Keap1-Nrf2 pathway.

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*