ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

Object To study the efficacy and potential mechanism of Tongbianling capsule in constipation. Methods The effects of Tongbianling capsule on intestinal motility in normal mice and carbon powder propulsion rate in small intestine of constipation model mice after were observed administration. The potential targets and key pathways of Tongbianling capsule in treating constipation were identified through network pharmacology. To verify the mechanism, the expression of p-PI3K/PI3K, p-AKT/AKT and CASP3 proteins in mouse colon tissue was detected by the western blot. Results The time for mice to excrete the first black stool was shortened and the number of fecal particles was increased in Tongbianling capsule administration group, and the carbon powder propulsion rate of mice in each Tongbianling capsule administration group was increased. The results of network pharmacology showed that treatment of constipation by Tongbianling capsule may be related to signaling pathways such as PI3K-Akt signaling pathway and 5-HT. The protein expression of p-PI3K/PI3K, p-AKT/AKT, and CASP3 in mouse colon tissue could be significantly downregulated in administration group. Conclusion Tongbianling capsule could effectively promote intestinal peristalsis in mice, increase the frequency of defecation, and effectively treat constipation. The mechanism of its action may be related to the direct or indirect regulation of intestinal motility by the PI3K-Akt signaling pathway.

Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

BACKGROUND:Microcirculation,as the only place for the energy metabolism of body substances,is closely related to the human movement ability.Resistance exercise is an effective way to improve the function of microcirculation,but some studies have also pointed out that blood flow restriction exercise can also improve the function of microcirculation and has the advantages of small load and high safety. OBJECTIVE:To compare the effects of 6-week low-load blood flow restriction exercise and high-intensity resistance exercise on the thigh microcirculation function of athletic young men,and to explore the possible mechanism by which exercises improve microcirculation function from the perspective of vascular endothelial function. METHODS:Sixty sports students from Hubei Minzu University were divided into control group,high-intensity resistance exercise group and low-load blood flow restriction exercise group according to the random number table method,with 20 students in each group.The low-load blood flow restriction exercise group performed a low-load blood flow restriction exercise for 6 weeks(three times a week,90 minutes each,at an exercise intensity of 30%1RM).The high-intensity resistance exercise group received a high-intensity resistance exercise for 6 weeks(three times a week,90 minutes each,at an exercise intensity of 70%1RM).The control group did not perform any form of exercise training during this period.Microcirculatory blood perfusion,transcutaneous partial pressure,muscle oxygen saturation,nitric oxide,endothelial nitric oxide synthase,endothelin 1,vascular endothelial cell growth factor,thigh circumference,and muscle strength were tested in each group on the day before the intervention and the morning after the end of the 6-week intervention. RESULTS AND CONCLUSION:After the exercise intervention,heating values of microcirculatory blood flow perfusion and blood cell movement speed in the low-load blood flow restriction exercise group and the high-intensity resistance exercise group were significantly different from those in the control group and before the exercise intervention(P<0.05).The heating values of microcirculatory blood flow perfusion and blood cell movement speed showed significant differences between the low-load blood flow restriction exercise group and the high-intensity resistance exercise group(P<0.05).After the exercise intervention,the levels of nitric oxide,endothelial nitric oxide synthase,endothelin 1,and vascular endothelial cell growth factor were significantly different in the low-load blood flow-limiting exercise group and the high-intensity resistance exercise group compared with the control group and the pre-exercise intervention(P<0.05).After the exercise intervention,thigh circumference and thigh muscle strength were significantly different in low-load blood flow restriction group and high-intensity resistance exercise groups compared with the pre-exercise intervention(P<0.05).All these findings indicate that 6-week low-load blood flow restriction exercise and high intensity resistance exercise may regulate the secretion of vascular factors such as endogenous nitric oxide synthase,endothelin-1 and vascular endothelial growth factor to improve the function of thigh microcirculation and increase the contractile strength of the thigh muscle.In addition,And low-load blood flow restriction exercise has better intervention effects on microcirculatory blood perfusion volume and blood cell movement speed,so low-load blood flow restriction exercise is more advantageous than high-intensity resistance exercise in improving microcirculation function.

IgG4-related disease （IgG4-RD） is an idiopathic fibroinflammatory condition characterized by a predilection for tumor-forming lesions， an increase in the serum level of IgG4， excessive infiltration of IgG4-positive plasma cells， storiform fibrosis， and/or obliterative phlebitis. This article reports a rare case of IgG4-RD in which the patient developed recurrent transient ischemic attacks （TIA） after the diagnosis of IgG4-RD. This report explores the potential pathological mechanisms， clinical features， treatment， and prognosis of IgG4-RD with TIA， in order to enhance the awareness of the possible neurological complications associated with IgG4-R among clinicians.
Glucocorticoids

The pathogenesis of neurodegenerative diseases (NDDs) is fundamentally linked to complex and profound alterations in metabolic networks within the brain, which exhibit marked spatial heterogeneity. While conventional bulk metabolomics is powerful for detecting global metabolic shifts, it inherently lacks spatial resolution. This methodological limitation hampers the ability to interrogate critical metabolic dysregulation within discrete anatomical brain regions and specific cellular microenvironments, thereby constraining a deeper understanding of the core pathological mechanisms that initiate and drive NDDs. To address this critical gap, spatial metabolomics, with mass spectrometry imaging (MSI) at its core, has emerged as a transformative approach. It uniquely overcomes the limitations of bulk methods by enabling high-resolution, simultaneous detection and precise localization of hundreds to thousands of endogenous molecules—including primary metabolites, complex lipids, neurotransmitters, neuropeptides, and essential metal ions—directly in situ from tissue sections. This powerful capability offers an unprecedented spatial perspective for investigating the intricate and heterogeneous chemical landscape of NDD pathology, opening new avenues for discovery. Accordingly, this review provides a comprehensive overview of the field, beginning with a discussion of the technical features, optimal application scenarios, and current limitations of major MSI platforms. These include the widely adopted matrix-assisted laser desorption/ionization (MALDI)-MSI, the ultra-high-resolution technique of secondary ion mass spectrometry (SIMS)-MSI, and the ambient ionization method of desorption electrospray ionization (DESI)-MSI, along with other emerging technologies. We then highlight the pivotal applications of spatial metabolomics in NDD research, particularly its role in elucidating the profound chemical heterogeneity within distinct pathological microenvironments. These applications include mapping unique molecular signatures around amyloid β‑protein (Aβ) plaques, uncovering the metabolic consequences of neurofibrillary tangles composed of hyperphosphorylated tau protein, and characterizing the lipid and metabolite composition of Lewy bodies. Moreover, we examine how spatial metabolomics contributes to constructing detailed metabolic vulnerability maps across the brain, shedding light on the biochemical factors that render certain neuronal populations and anatomical regions selectively susceptible to degeneration while others remain resilient. Looking beyond current applications, we explore the immense potential of integrating spatial metabolomics with other advanced research methodologies. This includes its combination with three-dimensional brain organoid models to recapitulate disease-relevant metabolic processes, its linkage with multi-organ axis studies to investigate how systemic metabolic health influences neurodegeneration, and its convergence with single-cell and subcellular analyses to achieve unprecedented molecular resolution. In conclusion, this review not only summarizes the current state and critical role of spatial metabolomics in NDD research but also offers a forward-looking perspective on its transformative potential. We envision its continued impact in advancing our fundamental understanding of NDDs and accelerating translation into clinical practice—from the discovery of novel biomarkers for early diagnosis to the development of high-throughput drug screening platforms and the realization of precision medicine for individuals affected by these devastating disorders.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of toripalimab （Tor） combined with chemotherapy （CT） in the treatment of locally advanced or metastatic non-small cell lung cancer （NSCLC）. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CBM， CNKI， Wanfang Data， and Health Technology Assessment （HTA） related websites were searched to collect the HTA reports， systematic reviews/meta-analyses and pharmacoeconomic studies of Tor+CT in the treatment of locally advanced or metastatic NSCLC from database/website inception to March 31， 2025. After data extraction and quality evaluation， the results of the included studies were analyzed descriptively. RESULTS A total of eleven studies were included， involving five systematic reviews/meta-analyses， and six pharmacoeconomic studies. Among the five systematic reviews/ meta-analyses， two were of high quality， while there was one each of moderate， low， and very low quality. All six pharmacoeconomic studies were of good quality. In terms of efficacy， compared with CT， Tor+CT significantly improved patients’ progression-free survival （PFS） and overall survival （P＜0.05）. In addition， compared with ipilimumab+CT， durvalumab， durvalumab+tremelimumab and sugemalimab+CT， Tor+CT could also improve the PFS （P＜0.05）. In terms of safety， there was no significant difference in the incidence of grade≥3 adverse events between patients receiving Tor+CT and CT （P＞0.05）； while Tor+CT had a lower incidence of grade≥3 adverse E-mail： events， compared with camrelizumab+CT， pembrolizumab+ 3233255290@qq.com ipilimumab， nivolumab+CT and atezolizumab+CT （P＜0.05）.In terms of cost-effectiveness， Tor+CT treatment had certain cost-effectiveness advantages， compared with CT. CONCLUSIONS Compared with CT， other programmed death-1/programmed death-ligand 1 inhibitors alone， or their combination with CT， Tor+CT for the treatment of locally advanced or metastatic NSCLC has good efficacy， safety and cost-effectiveness.

Objective To analyze the clinical characteristics,drug resistance and risk factors for poor prognosis in children patients with carbapenem resistant Klebsiella pneumoniae(CRKP)infection.Methods The samples of CRKP isolated from the children inpatients in this hospital from August 5,2016 to December 31,2020 were collected.The clinical data and drug resistance of CRKP in the patients with CRKP positive were analyzed.The risk factors in the poor prognosis group and good prognosis group of children pa-tients with CRKP infection conducted the correlation analysis.Results A total of 106 strains of non-repeti-tive CRKP were collected,which were mainly isolated from the patients ≤ 1 year old.The department distri-bution was dominated by the neonatal ICU and comprehensive ICU.CRKP showed the high resistance to mul-tiple antibacterial drugs,and its resistance rates to amikacin,levofloxacin,gentamicin,ciprofloxacin,minocy-cline and chloramphenicol were less than 30％.The poor prognosis rate in the children patients with CRKP in-fection reached 27.4％.The logistic multivariate regression analysis results showed that the multiple organ dysfunction and anemia were the independent risk factors for poor prognosis in the children patients with CRKP infection(P＜0.05).Conclusion The children CRKP infection is mainly the infants ≤1 years old,and CRKP shows the high resistance to multiple antibacterial drugs,the independent risk factors of poor prognosis include the multiple organ dysfunction and anemia

Objective:To explore the evaluation value of serum levels of positive pentameric protein 3 (PTX3) and creatine kinase isoenzyme MB (CK-MB) on volume load in patients with chronic decompensated heart failure (CDHF).Methods:A total of 300 CDHF patients who visited the Xingtai Central Hospital from July 2019 to July 2022 were selected and divided into a capacity overload group ( n=182) and a non capacity overload group ( n=118) based on their capacity balance level. Two clinical data sets were compared and analyzed. The receiver operating characteristic (ROC) curve was used to analyze the evaluation value of serum PTX3 and CK-MB levels on the volume load of CDHF patients. The clinical disease characteristics of the two groups of patients were analyzed using univariate analysis, and the influencing factors of volume load of CDHF patients were analyzed using logistic regression. A column chart model was constructed and validated. Results:The body mass index (BMI), waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose (FBG), glycosylated hemoglobin (HbA 1c), C-reactive protein (CRP), uric acid (UA), homeostasis model assessment of insulin resistance (HOMA-IR) of patients in the capacity overload group were higher than those in the non-capacity overload group, and the differences were statistically significant (all P<0.05). The PTX3, CK-MB, pulmonary capillary wedge pressure (PCWP), and CVP levels of patients in the capacity overload group were higher than those in the non-capacity overload group, while albumin, hemoglobin, and hematocrit were lower than those in the non-capacity overload group, and the differences were statistically significant (all P<0.05). The ROC curve showed that the area under the curve (AUC) of PTX3 and CK-MB for predicting capacity overload in CDHF patients are 0.795 and 0.718, with sensitivity of 86.2% and 83.7%, specificity of 65.4% and 68.6%, respectively, indicating high predictive accuracy; The AUC of the two joint predictions is 0.817, the sensitivity was 92.5%, and the specificity was 70.6%. The prediction accuracy was higher than PTX3 ( Z=3.812, P<0.05) and CK-MB ( Z=3.365, P<0.05). PTX3, CK-MB, albumin, hemoglobin, hematocrit, PCWP, and central venous pressure (CVP) were all influencing factors of volume load status in CDHF patients (all P<0.05). The column chart risk prediction model established based on these factors had high accuracy and strong applicability in clinical treatment. Conclusions:Serum PTX3 and CK-MB levels are influencing factors for volume overload in CDHF patients. A column chart model constructed in combination with indicators such as albumin, hemoglobin, hematocrit, PCWP, and CVP has high predictive value for the volume overload status of CDHF.

Objective:To retrospectively analyze the molecular epidemiological features and genetic recombination of coxsackievirus A4 (CVA4) strains isolated in Jiangsu from 2015 to 2022.Methods:Throat or anal swab samples were collected from patients with herpangina or hand, foot and mouth disease (HFMD). Real-time PCR was used to detect CVA4. A comprehensive and systematic phylogenetic analysis was conducted based on 72 whole genomes and 99 VP1 sequences of CVA4 strains. Several bioinformatics software including DNAStar, MEGA7.0 and Similarity plots3.5.1 was used for analysis of homology, genetic recombination and amino acid variation sites.Results:Four genotypes (A, B, C and D) and five sub-genotypes (C1-C5) of CVA4 were identified based on the VP1 nucleotide sequences. C2 was the predominant sub-genotype causing HFMD. The Jiangsu strains showed high homology with the CVA4 prototype in the P1 region, and higher identity with other strains of enterovirus group A (EV-A) in the P2 and P3 regions. Genetic recombination analysis revealed that the Jiangsu strains had three genetic recombination patterns with other EV-A epidemic strains in the P2, P3 and 3′-UTR regions. These recombination patterns took place during the sustained and widespread circulation of CVA4 in people and increased the transmissibility of CVA4.Conclusions:This study analyzes the phylogenetic and molecular features of 28 whole genomes of Jiangsu CVA4 strains, which helps to better understand the genomic diversity of CVA4. By analyzing the genetic recombination and amino acid mutations in the VP1 region, this study elucidates the evolution and transmission of CVA4, which is conducive to the control and prevention of CVA4 infection.