Objective: To investigate whether Tuina alleviates fibrotic symptoms in myofascial trigger points (MTrPs) by regulating transforming growth factor (TGF)-β1/Smad3 signaling pathway, thereby deactivating these points. Methods: This study comprised two experimental phases. In phase 1, 27 specific pathogen-free (SPF) grade female Sprague-Dawley (SD) rats were randomized into three groups: control 1, model 1, and Tuina 1 groups. Model 1 and Tuina 1 groups underwent an 8-week MTrPs modeling protocol involving blunt impact and eccentric exercise. After successful modeling, rats in Tuina 1 group received manual pressing on nodules or cord-like taut bands on the medial aspect of the left hindlimb. Pain sensitivity and tissue stiffness were evaluated via pressure pain threshold (PPT) and soft tissue tension (STT). Muscle histopathology and fibrosis were observed using hematoxylin and eosin (HE) and Masson staining. Inflammatory factors in muscle were measured by enzyme-linked immunosorbent assay (ELISA), while immunofluorescence (IF) and Western blot (WB) were used to detect the expression levels of α-smooth muscle actin (α-SMA), collagen Ⅲ, and TGF-β1. In phase 2, 45 SPF female SD rats were randomized into five groups: control 2, model 2, Tuina 2, TGF-β1 inhibitor (TI), and Tuina + TGF-β1 agonist (Tuina + TA) groups. All groups except control 2 underwent standardized MTrPs modeling. Rats in Tuina 2 group received consistent pressing manipulation. TI group received intraperitoneal injections of oxymatrine, while Tuina + TA group received intraperitoneal injections of SRI-011381 hydrochloride followed by the same pressing protocol as Tuina 2 group. WB was used to detect the expression of collagen I, collagen III, TGF-β1, and phosphorylated-Smad3 (p-Smad3)/Smad3. Results: In phase 1, Tuina significantly improved PPT and STT in MTrPs of rats (P < 0.01), reversed pathological damages including disorganized muscle fiber arrangement, abnormal myocyte morphology, and exacerbated fibrosis. In addition, in MTrPs of rats in model 1 group, expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and fibrosis markers (α-SMA, collagen I, and collagen III) were upregulated, and all exhibited a significant downward trend after Tuina intervention (P < 0.05 or P < 0.01). This indicates that the therapeutic effects of Tuina are directly associated with reduced local inflammation and fibrosis in MTrPs. In phase 2, compared with model 2 group, rats in TI and Tuina 2 groups had decreased expression levels of TGF-β1 and p-Smad3/Smad3 in MTrPs, alongside reduced levels of inflammatory factors (IL-1β, IL-6, NF-κB, and TNF-α) and fibrosis markers (α-SMA, collagen I, and collagen III) (P < 0.05 or P < 0.01). When co-administered with TGF-β1 agonist, the therapeutic effects of Tuina were significantly attenuated, with rebounded TGF-β1 expression and p-Smad3/Smad3 in local MTrPs, and fibrosis and inflammatory responses were re-exacerbated (P < 0.05 or P < 0.01). Conclusion Tuina can effectively reduce inflammatory responses and fibrosis in MTrPs tissue, and its mechanism is closely related to the inhibition of the TGF-β1/Smad3 signaling pathway, which plays a critical role in Tuina-mediated regulation of MTrPs fibrosis.

BACKGROUND:Macrophages play a key role in the occurrence and progression of lung diseases,and autophagy plays an important role in maintaining environmental homeostasis and functional stability in macrophages.It has been suggested that macrophage autophagic activity has two sides in lung inflammatory diseases.OBJECTIVE:To summarize the relationship between macrophage autophagy and lung diseases,thereby providing reference for exploring the prevention and treatment strategies of lung inflammatory diseases by targeting macrophage autophagy.METHODS:Literature retrieval was performed in CNKI and PubMed for relevant literature published from database inception to September 2024.The search terms were"macrophage autophagy,efferocytosis,macrophage polarization,acute lung injury,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis,asthma"in Chinese and English,respectively.The search results were included or excluded based on the selection criteria,and 100 papers that met the criteria were finally included in the review.RESULTS AND CONCLUSION:(1)The obstruction of autophagy flow will induce the polarization imbalance of macrophages and impair their efferocytosis,resulting in the increase of M1 macrophages and aggravating inflammation.(2)The judgment of autophagic activity should be based on whether the autophagy flow is smooth or not,and it is essential to evaluate the degradation ability of autophagy.Some studies failed to comprehensively detect the degradation ability of autophagy lysosomes to assess whether the autophagy flow is unobtrusive.As a result,the so-called two-sided view of pulmonary macrophage autophagy in pulmonary inflammatory diseases in such studies is actually related to the one-sided judgment of autophagy activity.(3)The pathological manifestations vary across different pulmonary diseases and even at different stages of the same disease.Activation of macrophage autophagy plays a positive role in regulating pulmonary inflammatory homeostasis in conditions such as acute lung injury,infectious pneumonia,mild chronic obstructive pulmonary disease,early-stage pulmonary fibrosis,and secondary asthma.However,in the severe fibrotic stage of chronic obstructive pulmonary disease and the progressive stage of pulmonary fibrosis,the activation of pulmonary macrophage autophagy aggravates pulmonary fibrosis,reflecting the dual nature of macrophage autophagy.In allergic asthma,autophagy is activated in lung-resident macrophages but suppressed in infiltrating monocyte-derived macrophages from circulation.The former is closely related to airway stenosis,and the latter aggravates pneumonia disorders.Therefore,identifying the types and progression stages of lung diseases,along with accurately assessing autophagic activity,is crucial for future investigations into the relationship between macrophage autophagy and disease pathogenesis,thereby facilitating the development of therapeutic strategies in the future.

BACKGROUND:Macrophages play a key role in the occurrence and progression of lung diseases,and autophagy plays an important role in maintaining environmental homeostasis and functional stability in macrophages.It has been suggested that macrophage autophagic activity has two sides in lung inflammatory diseases.OBJECTIVE:To summarize the relationship between macrophage autophagy and lung diseases,thereby providing reference for exploring the prevention and treatment strategies of lung inflammatory diseases by targeting macrophage autophagy.METHODS:Literature retrieval was performed in CNKI and PubMed for relevant literature published from database inception to September 2024.The search terms were"macrophage autophagy,efferocytosis,macrophage polarization,acute lung injury,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis,asthma"in Chinese and English,respectively.The search results were included or excluded based on the selection criteria,and 100 papers that met the criteria were finally included in the review.RESULTS AND CONCLUSION:(1)The obstruction of autophagy flow will induce the polarization imbalance of macrophages and impair their efferocytosis,resulting in the increase of M1 macrophages and aggravating inflammation.(2)The judgment of autophagic activity should be based on whether the autophagy flow is smooth or not,and it is essential to evaluate the degradation ability of autophagy.Some studies failed to comprehensively detect the degradation ability of autophagy lysosomes to assess whether the autophagy flow is unobtrusive.As a result,the so-called two-sided view of pulmonary macrophage autophagy in pulmonary inflammatory diseases in such studies is actually related to the one-sided judgment of autophagy activity.(3)The pathological manifestations vary across different pulmonary diseases and even at different stages of the same disease.Activation of macrophage autophagy plays a positive role in regulating pulmonary inflammatory homeostasis in conditions such as acute lung injury,infectious pneumonia,mild chronic obstructive pulmonary disease,early-stage pulmonary fibrosis,and secondary asthma.However,in the severe fibrotic stage of chronic obstructive pulmonary disease and the progressive stage of pulmonary fibrosis,the activation of pulmonary macrophage autophagy aggravates pulmonary fibrosis,reflecting the dual nature of macrophage autophagy.In allergic asthma,autophagy is activated in lung-resident macrophages but suppressed in infiltrating monocyte-derived macrophages from circulation.The former is closely related to airway stenosis,and the latter aggravates pneumonia disorders.Therefore,identifying the types and progression stages of lung diseases,along with accurately assessing autophagic activity,is crucial for future investigations into the relationship between macrophage autophagy and disease pathogenesis,thereby facilitating the development of therapeutic strategies in the future.

Puerariae Lobatae Radix and Puerariae Thomsonii Radix are the dried roots of Pueraria lobata and Pueraria thomsonii of the Leguminosae family， respectively. Since their separate inclusion in the 2005 edition of Pharmacopoeia of the People's Republic of China， the two herbs have been individually recorded. Although they share the same functions and indications， the required content of puerarin differs by a factor of up to eightfold between them. The current quality standard relies solely on a single indicator， puerarin， which fails to reflect the correlation between chemical constituents and core therapeutic effects. This has resulted in prominent issues of mixed use in clinical practice and production， thereby constraining the high-quality development of the industry. Modern research has demonstrated that Puerariae Lobatae Radix contains a comprehensive range and higher content of isoflavonoid constituents， while Puerariae Thomsonii Radix is rich in starch and polysaccharides. Puerariae Lobatae Radix exhibits stronger effects in antipyresis， cardiovascular and cerebrovascular protection， and central analgesia， while Puerariae Thomsonii Radix demonstrates greater advantages in anti-inflammation， hypoglycemia， and peripheral analgesia. Based on this， the chemical material bases of Puerariae Lobatae Radix and Puerariae Thomsonii Radix at both the macromolecule and micromolecule levels were systematically reviewed and compared. The pharmacodynamic material bases and mechanisms of action underlying their three core therapeutic effects， namely "relieving exterior syndrome and clearing heat"， "promoting fluid production to quench thirst"， and "dredging channels and activating collaterals"， were summarized. The most highly correlated common metabolic pathway shared by both herbs for these three therapeutic effects is the arachidonic acid metabolic pathway， and their common core target is prostaglandin-endoperoxide synthase 2 （PTGS2）. This review provided clinical application recommendations based on the therapeutic differences between the two herbs， elucidated the scientific connotation of their "same origin but different effects"， and， grounded in the quality marker （Q-Marker）， proposed the concept of efficacy-related Q-Marker based on "substance-efficacy-syndrome" association， as well as a novel strategy for efficacy-oriented quality evaluation. Preliminary screening of quality markers associated with different therapeutic effects was also conducted. This study aims to provide critical scientific evidence for the precise clinical application of Puerariae Lobatae Radix and Puerariae Thomsonii Radix， the improvement of quality standards， and the high-quality development of the industry.

Objective: To analyze the epidemiological characteristics of hand, foot and mouth disease (HFMD) among children aged 0-9 years in Guangzhou, so as to provide reference basis for further exploring scientifically effective prevention and control measures. Methods: Reported cases of HFMD in children aged 0-9 years in Guangzhou City from 2013-2025 were selected from China disease prevention and control information system, and the incidence in different years was analyzed descriptively; the trends of the composition ratio and incidence in various age groups were analyzed by using the Joinpoint regression model, spatial autocorrelation analyses were performed at the district level, and the seasonal autoregressive integrated moving average model (SARIMA) was applied to predict annual incidence rate for 2026. Results: From 2013 to 2025, the average annual reported incidence rate of HFMD among children aged 0-9 years in Guangzhou was 2 513.98/100 000, showing a fluctuating trend. Peaks of incidence occurred from May to July and from September to October. The male to female ratio was 1.49∶1. The average annual incidence rate was 4 743.99/100 000 in the 0-1 years age group, 3 298.19/100 000 in the 2-5 years age group, and 544.22/ 100 000 in the 6-9 years age group. Joinpoint regression analysis showed a decreasing trend in the proportion of the 0-1 years age group (APC= -6.02 %, t =-3.77) and an increasing trend in the proportion of the 6-9 years age group (APC=16.39%, t =5.67) (both P < 0.05 ). No significant global spatial clustering was observed at the district level; however, local scattered clusters were identified in certain areas. Using the SARIMA(2,0,0)(2,0,0) 12 model, the predicted annual incidence rate of HFMD among children aged 0-9 years in Guangzhou in 2026 was 2 680.56/100 000. Conclusions From 2013 to 2025, the annual incidence rate of HFMD among children aged 0-9 years in Guangzhou exhibited a fluctuating trend; the highest incidence rate is observed in the 0-1 years age group, while the proportion of cases in the 6-9 years age group increase year by year;and local spatial clusters of abnormal distribution are identified. It is essential to enhance risk monitoring and health education in key populations and areas to mitigate the risk of infection in children.

Objective To investigate the association between dietary patterns and adolescent development in girls in Pudong New Area，Shanghai. Methods Using a stratified cluster sampling method, a total of 998 girls were selected from the cohort of growth, development, and health of children and adolescents in Pudong New Area of Shanghai. Physical development examinations and dietary surveys were conducted on these girls. Principal component analysis was used to determine girls' dietary patterns, and their relationship with adolescent development was analyzed using logistic regression. Results Among the 998 participants, 770 (77.15%) were pubertal girls. The factor analysis identified three dietary patterns, fungi and algae~nuts~legumes pattern, meat-vegetables and fruits-cereals pattern, and milk-eggs pattern. Logistic regression analysis revealed that after adjusting for age, waist circumference, residential district, mother's education level, and father's education level, the Q2 level (OR=0.54, 95% CI: 0.30-0.99), Q3 level (OR=0.50, 95% CI: 0.27-0.91), and Q4 level (OR=0.49, 95% CI: 0.26-0.90) of the fungi and algae-nuts-legumes pattern were negatively correlated with adolescent development. The Q2 level (OR=0.48, 95% CI: 0.27-0.87) and Q3 level (OR=0.49, 95% CI: 0.27-0.88) of the milk-eggs pattern were also negatively correlated with adolescent development. Conclusion The fungi and algae~nuts~legumes pattern and milk-eggs patterns are inversely related to pubertal development.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Objective To evaluate the modeling characteristics and predictive performance of models for predicting post-stroke neurological deterioration(ND)published in existing literatures.Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidance for scoping reviews,a comprehensive search was conducted in PubMed,CINAHL,Cochrane Library,Embase,Web of Science,Scopus,CNKI,Wanfang Data,and VIP databases from inception to December 15,2024.The search strategy combined Medical Subject Headings(MeSH)and free-text terms,with key words including"Stroke""Ischemic Stroke""Neurological Deterioration""Nomograms""Risk Prediction""Predictive Models""卒中""脑梗死""脑出血""神经功能恶化"and"预测模型".Base on the data extraction checklist and critical appraisal,data extraction covered three domains:(1)basic characteristics,including author,publication year,country,study design(retrospective,prospective,registry-based),sample source(single-center,multicenter),stroke subtypes(acute ischemic stroke[AIS]-conservative therapy,AIS-intravenous thrombolysis[IVT],AIS-endovascular therapy[EVT],intracerebral hemorrhage[ICH]),ND time windows(acute[≤72 h],subacute[≤ 7 d],long-term[≤90 d]),and outcome types(single/composite endpoints);(2)model evaluation metrics,including missing data handling(complete-case analysis,multiple imputation),model development methodologies(multivariate Logistic regression,least absolute shrinkage and selection operator regression,machine learning),presentation formats(nomograms,web calculators,risk prediction tool),discrimination(area under the curve,C-index),calibration(Hosmer-Lemeshow test,calibration curve and slope),clinical utility(decision curve analysis[DCA],global metrics Brier score,R2,AIC),sample size(training set,internal validation set,external validation set),sample size requirements(events per variable[EPV]≥10 to mitigate overfitting),and validation(internal/external);(3)predictor features,including selection strategies(prior knowledge-driven,univariate analysis),quantity,and attributes(demographics,medical history,physical examination,treatment intervention information,imaging/laboratory indicators).Predictive models that meet exclusion criteria from prior literature were analyzed by their discrimination,calibration,clinical utility and global metrics.Forest plots were utilized to visualize discrimination(evaluated via difference in area under the curve)of the extracted models.The prediction model risk of bias assessment tool(PROBAST)was applied to assess bias risk and clinical applicability.Occurrence frequencies of the post-stroke neurological deterioration predictors were ranked and the top 6 high-frequency predictors were extracted.Results(1)Among 3 728 screened studies,25 were included based on the inclusion and exclusion criteria.(2)Basic characteristics:retrospective(72％[18/25])and single-center(64％[16/25])designs dominated.With most models targeted on AIS(92％[23/25]),and the rest(8％[2/25])on ICH.ND was primarily defined by neurological scale changes(60％[15/25];e.g.,National Institutes of Health stroke scale[NIHSS]score increase or Glasgow coma scale[GCS]score decrease),with time windows categorized as acute(36％[9/25]),subacute(48％[12/25]),or long-term(16％[4/25]).(3)Model evaluation:multivariate Logistic regression(96％[24/25])and nomograms(88％[22/25])were predominant.Only 24％(6/25)explicitly addressed missing data handling methods,and 52％(13/25)with EPV≥10.The median area under the curve was 0.865(range:0.650-0.981).44％(11/25)of the studies reported calibration curves,and 4％(1/25)reported calibration slopes.All studies utilized DCA to validate their clinical applicability,84％(21/25)of the studies conducted internal validation,while only 32％(8/25)conducted external validation.PROBAST evaluation revealed low overall bias risk in 8％(2/25;no error across participant,predictor,outcome,or analysis domains)and low clinical applicability risk in 44％(11/25;alignment with target populations,accessible predictors,and clinically relevant outcomes)of the studies.(4)Predictors:64％(16/25)of the predictor were screened predominantly through the prior knowledge-driven based strategy.The top 6 high-frequency predictors are NIHSS score(64％[16/25]),age(36％[9/25]),blood glucose/diabetes(36％[9/25]),blood pressure/hypertension(32％[8/25]),the Alberta stroke program early CT score(20％[5/25]),and neutrophil-to-lymphocyte ratio(20％[5/25]).AIS-ND predictors emphasized readily available metrics,such as NIHSS(65％[15/23]),age(35％[8/23]),while ICH-ND primarily relied on imaging markers(e.g.,baseline hematoma volume[2/2],location[1/2]).Conclusion Current post-stroke ND predictive models demonstrate satisfactory performance on discrimination and multimodal integration,but their practical application are hindered by insufficient calibration quantification,high bias risk,and limited clinical translatability.

This article reports the diagnosis and treatment process of a case with secondary infective femoral artery pseudoaneurysm after intervention surgery for cerebral infarction,who improved after anti-infection and surgical treatment and was discharged.The patient was a 52-year-old female who underwent percutaneous balloon dilatation of basilar artery due to basilar artery stenosis.After surgery,she developed secondary methicillin-resistant Staphy-lococcus aureus(MRSA)bloodstream infection and infective femoral artery pseudoaneurysm.After treatment with vancomycin and linezolid,femoral artery pseudoaneurysm resection,and autovascular replacement,the patient re-covered well after the surgery and discharged from hospital.CT angiography(CTA)re-examination showed artifi-cial blood vessel patency.This study is expected to provide experience for the diagnosis and treatment of such pa-tients in clinical work.

This article reported two cases of congenital myotonic dystrophy. Case 1 was a premature infant born at 35 weeks of gestation, with severe asphyxia as the initial manifestation. After admission, the infant had limited spontaneous activity, low muscle tone, weak spontaneous respiration, inability to swallow independently, and bilateral talipes equinovarus. The initial diagnosis was neonatal hypoxic-ischemic encephalopathy. However, clinical observation suggested the possibility of other diseases and genetic testing indicated that the number of CTG trinucleotide repeats in the DMPK gene was>150 times, suggesting a high possibility that the child's mother was also affected, but remained undiagnosed due to lack of testing. Case 2 was a full-term infant born at 37 weeks and 1 day of gestation, who presented with asphyxia and dyspnea initially. It also presented with limited spontaneous activity, low muscle tone, weak respiration, and bilateral talipes equinovarus, which was highly similar to the clinical situation of Case 1. The genes of the child and his mother were tested, and the results showed that the number of CTG trinucleotide repeats in the DMPK gene was >150 times for both. Both children died within a few hours after being discharged from the hospital due to the family's decision to abandon treatment.