ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

Objective: To investigate the current status of latent tuberculosis infection (LTBI) among freshmen in junior and senior high schools in Lanzhou, so as to provide scientific basis for improving the tuberculosis prevention and control strategy in schools. Methods: The screening results of 74 516 freshmen in senior and boarding junior high schools in Lanzhou during 2023 and 2024 were collected. The Chi square test and multivariate Logistic regression model were applied to analyze LTBI level, strongly positive risk for tuberculin skin test (TST) and related factors of the freshmen. Results: During 2023 and 2024, the screening rate of tuberculosis among freshmen in senior and boarding junior high schools in Lanzhou was 93.45%, of which the positive rate for TST was 5.71%, the infection rate for LTBI was 3.80%, and the strongly positive rate for TST was 1.24%. There were statistically significant differences in the screening rate of tuberculosis among freshmen in different years, grades, regions, school types and districts ( χ 2=5.34, 2 463.88, 3 516.13, 132.34, 4 436.56, all P <0.05). Multivariate Logistic regression analysis showed that senior high schools ( OR =1.62, 2.18) and urban areas ( OR =2.08, 3.07 ) were all related factors for LTBI and strong positivity for TST among freshmen; schools located in Xigu District, Honggu District, Yongdeng County, Yuzhong County, and Lanzhou New Area ( OR =3.57, 5.67, 9.12, 3.70, 3.64) were related factors of strong positivity for TST among freshmen (all P <0.05). Conclusions The LTBI level among freshmen in senior and boarding junior high schools in Lanzhou is relatively low. Grades and regions are related factors for LTBI and strong positivity for TST.

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.

Gastric ulcer （GU） is a high-incidence digestive system disease characterized pathologically by disruption of gastric mucosal integrity， with clinical features including a prolonged course and periodic recurrence. Modern medicine attributes its pathogenesis to the dynamic imbalance between aggressive and defensive factors，while traditional Chinese medicine （TCM） posits its development as closely linked to spleen deficiency. Current therapies combining acid suppressants and antibiotics face challenges such as high recurrence rates，poor mucosal healing，and adverse drug reactions. Long-term use may induce metabolic disturbances like hypergastrinemia and reduced intestinal microbiota diversity. Therefore，exploring safer and longer-lasting therapeutic strategies has become a critical focus. TCM has extensive clinical experience and unique advantages in GU prevention and treatment. Studies demonstrate that the classic formula Shenling Baizhu San exhibits therapeutic properties of "invigorating spleen and tonifying Qi to restore physiological balance and eliminating dampness and regulating middle energizer to unblock Qi movement"， enabling a holistic approach targeting both symptoms and root causes in GU with spleen deficiency as the core pathology by suppressing aggressive factors and strengthening defensive factors. Experimental research reveals its mechanisms involve enhancing the physicochemical barrier of the mucus layer，repairing epithelial barriers and microcirculation，modulating gastric acid secretion and gastrointestinal motility，and regulating microecological barriers and mucosal immunity. Clinical evidence confirms its synergistic effects in promoting ulcer healing，improving Helicobacter pylori eradication rates，and reducing recurrence risks. This review examined the etiology and pathogenesis of GU and systematically evaluated Shenling Baizhu San from three perspectives-clinical application，pharmacological effects， and experimental research-to provide insights for optimizing integrated traditional Chinese and Western medicine protocols and expanding its clinical applications.

This study identified six novel azaphilones, isochromophilones G-L (1-6), and three novel biosynthetically related congeners (7-9) from Diaporthe sp. SCSIO 41011. The structures and absolute configurations were elucidated through comprehensive spectroscopic analyses combined with experimental and calculated electronic circular dichroism (ECD) spectra. Significantly, three highly oxygenated azaphilones contain an acetyl group at the terminal chain (4) or linear conjugated polyenoid moieties (5 and 6), which occur infrequently in the azaphilone family. Additionally, several compounds demonstrated inhibition of lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) activation in RAW 264.7 macrophages at 20 μmol·L^-1. The novel compound (1) effectively inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation without exhibiting cytotoxicity in bone marrow and RAW 264.7 macrophages, indicating its potential as a promising lead compound for osteolytic disease treatment. This research presents the first documented evidence of azaphilone derivatives as inhibitors of RANKL-induced osteoclastogenesis.
Animals ; Mice ; RANK Ligand/genetics* ; RAW 264.7 Cells ; Osteoclasts/metabolism* ; Benzopyrans/isolation & purification* ; Osteogenesis/drug effects* ; Macrophages/metabolism* ; Molecular Structure ; Pigments, Biological/isolation & purification* ; Ascomycota/chemistry* ; NF-kappa B/genetics* ; Cell Differentiation/drug effects*

Objective:To observe the effects of recombinant human growth hormone(rh-GH)on depressive-like behavior in mice with chronic restraint stress(CRS),and to discuss its possible mechanism.Methods:The CRS method was used to establish an animal model of depression;a total of 45 mice were didided into control group(non-modeled,n=15),and CRS model group(modeled,n=30)the sucrose preference test(SPT)was used to detect the sucrose preference rate of the mice;the tail suspension test(TST)was used to detect the immobility time of the mice;the open field test(OFT)was used to detect the total moving distance of the mice within 5 min and the time spent in the central area.The CRS mice were randomly divided into CRS model+saline group and CRS model+rh-GH group(n=10);the mice in CRS model+saline group were injected with normal saline;the mice in CRS model+rh-GH group were subcutaneously injected with rh-GH daily for 1 month;the peripheral blood of the mice was collected before and after intervention to detect the expression levels of growth hormone(GH)and insulin-like growth factorⅠ(IGF-Ⅰ)proteins in serum;after all behavioral experiments,the hippocampus tissue was taken to detect the expression level of synapsin-1(SYN-1)protein in the tissue of the mice.Results:Compared with control group,the body weight of the mice in CRS model group was significantly decreased(P<0.01),the sucrose preference rate in SPT was significantly decreased(P<0.01),the immobility time in TST was significantly prolonged(P<0.01);in OFT,the total moving distance of mice showed no significant change(P>0.05),while the time spent in the central area was significantly shortened(P<0.05).Compared with control group,the expression levels of GH and IGF-Ⅰ proteins in serum of the mice in CRS model group were significantly decreased(P<0.01).Compared with CRS model+saline group,the sucrose preference rate in SPT of the mice in CRS model+rh-GH group was significantly increased(P<0.01),the immobility time in TST was significantly shortened(P<0.05),the total moving distance in OFT showed no significant difference(P>0.05),and the time spent in the central area was significantly increased(P<0.01).Compared with model+saline group,the expression levels of GH and IGF-Ⅰ proteins in serum of the mice in CRS model+rh-GH group were significantly increased(P<0.01).Compared with model group,the expression level of SYN-1 protein in hippocampus tissue of mice in drug-treated model group was significantly increased(P<0.05).Conclusion:rh-GH has ameliorative effects on depressive-like behavior induced by chronic restraint stress in mice,and its mechanism may be associated with regulation of the GH/IGF-Ⅰ axis and increased expression of SYN-1 in hippocampus tissue.

Objectives:This study aims to investigate the expression changes of transient receptor potential vanilloid type 1 (TRPV1) channel and inflammatory factors in the peripheral blood of patients with schizophrenia, and to evaluate their potential value for diagnostic prediction.Methods:This cross-sectional study was conducted at Renmin Hospital of Wuhan University from September 2023 to June 2024. A total of 35 patients with schizophrenia (patient group) from the outpatient/inpatient departments and 35 age-and sex-matched healthy individuals (control group) were recruited. Psychiatric symptoms and cognitive function were evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Brief Assessment of Cognition in Schizophrenia (BACS), respectively. The between-group comparisons of the total scores of these two instruments were calculated using independent samples t-tests. Fasting peripheral blood samples were collected from all participants. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated for subsequent analysis. TRPV1 protein expression was quantified by Western blotting, while inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10), were measured using enzyme-linked immunosorbent assay (ELISA). The between-group differences in TRPV1 and inflammatory cytokines were analyzed using the analysis of covariance (ANCOVA), controlling for age and sex. Pearson correlation analysis was employed to examine relationships between continuous variables, controlling for years of education, age, and sex. The diagnostic performance of TRPV1 and inflammatory cytokines for schizophrenia was assessed using receiver operating characteristic (ROC) curve analysis. Results:Significant between-group differences were observed in BACS total and subscale scores ( t=2.57-9.72, all P<0.01). Compared with the control group, the patient group exhibits significantly decreased expression of TRPV1, IL-4, and IL-10 ( t=6.78, 2.75, 2.53, all P<0.01), increased expression of TNF-α, IL-2, and IL-6 ( t=4.08, 2.64, 2.63, all P<0.01), and an increased IL-6/IL-10 ratio ( t=3.18, P<0.01). Correlation analyses revealed that in the patient group, the TRPV1 expression level was negatively correlated with levels of TNF-α and IL-6, and positively correlated with levels of IL-4 and IL-10 ( r=-0.589, -0.234, 0.341, 0.293, all P<0.05). In the patient group, the TRPV1 expression level was negatively correlated with the negative symptom score of PANSS ( r=-0.299, P<0.05), and the IL-6 level was positively correlated with the negative symptom score, the general pathology score, and the total score of PANSS ( r=0.387, 0.356, 0.321, all P<0.05). The TRPV1 level was positively correlated with the total score of BACS in both the control group and the patient group ( r=0.144, 0.828, all P<0.01). The IL-6/IL-10 ratio was positively correlated with the total score of PANSS and negatively correlated with the total score of BACS in the patient group ( r=0.623, -0.333, all P<0.05). The area under the ROC curve for the combination of TRPV1 level and IL-6/IL-10 ratio was 0.98 (95% confidence interval=0.96 to 1.00). Conclusions:Patients with schizophrenia exhibit reduced expression levels of TRPV1 along with an imbalanced inflammatory response. The combined assessment of TRPV1 level and IL-6/IL-10 ratio has demonstrated a high predictive and diagnostic value for schizophrenia.

Objective:To explore the prognostic differences between liver resection and transarterial chemoembolization (TACE) in patients with Budd-Chiari syndrome (BCS) complicated by hepatocellular carcinoma (HCC) and to identify independent risk factors affecting patient survival.Methods:The clinical and follow-up data of 103 patients with stage Ⅰa-Ⅲa BCS complicated by HCC treated at the First Affiliated Hospital of Zhengzhou University from Aug 2015 to Sep 2023 were retrospectively analyzed.Results:Patients were divided into two groups based on their initial treatment choices: the liver resection group ( n=20) and the TACE group ( n=83). Before propensity score matching(PSM), the median overall survival in the liver resection group was 42 months longer than in the TACE group (74 months vs. 32 months, P=0.002). After PSM, the median overall survival remained significantly longer in the liver resection group by 39 months (74 months vs. 35 months, P=0.032). In terms of disease-free survival, before PSM, the liver resection group was 30-month longer than the TACE group (42 months vs. 12 months, P=0.001). After PSM, the difference in median disease-free survival between the two groups was 23 months (35 months vs. 12 months, P=0.018). Multivariate Cox regression analysis identified treatment modality and maximum tumor diameter as independent risk factors for overall survival, while treatment modality was the only independent factor for disease-free survival. Conclusions:Liver resection significantly prolongs both overall survival and disease-free survival in resectable HCC in BCS patients compared to TACE. Treatment modality and tumor size are key prognostic factors influencing overall survival.

This study evaluates the safety and early clinical outcomes of a novel 3D-printed titanium alloy "sleeve" component for revising fractured femoral stem prostheses in distal femoral megaprostheses without removing the fractured stem. The six patients included 2 males and 4 females, with an age range of 8-57 years. They were treated at Peking University People's Hospital between August 2020 and December 2023 and underwent revision surgery using the customized sleeve. A self-designed 3D-printed titanium alloy "sleeve" component was used for revision without removing the fractured stem, in the form of an external sleeve around the stem. Postoperative imaging was performed every three months to assess implant stability and bone integration. Functional outcomes were evaluated using the Musculoskeletal Tumor Society (MSTS)-93 score. All six patients successfully completed the surgery and follow-up, with surgical durations ranging from 120 to 230 minutes and intraoperative blood loss ranging from 150 to 800 ml. The follow-up period ranged from 6 to 46 months. At three months postoperatively, X-ray and CT imaging showed cortical bridging between the host bone and the "sleeve" component. By six months, full integration of the host cortical bone with the metal trabecular interface of the "sleeve" was observed. At the final follow-up, MSTS-93 scores ranged from 26 to 29 points, with no complications such as wound healing issues, implant loosening, fracture, infection, or degenerative arthritis. These findings suggest that 3D-printed titanium "sleeve" provide an effective, bone-preserving solution for femoral stem revision in oncologic megaprostheses, leading to favorable early stability and functional recovery.