The therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with intestinal probiotics on the wound healing of diabetic mice and its potential mechanism were explored. A diabetic wound mouse model was established, and 25 male C57BL/6J mice were randomly divided into five groups: blank control group, model group, hUCMSCs treatment group, probiotics treatment group, and hUCMSCs combined with probiotics treatment group. The wound healing conditions were photographed and recorded on days 0, 3, 6, 9, and 12 after modeling, and the differences in wound healing rates among the groups were analyzed. HE and Masson staining were used to observe the histopathological changes and collagen deposition. CD31 immunofluorescence was used to detect angiogenesis. Collagen I immunohistochemistry was used to evaluate the formation of type I collagen. ELISA was used to detect the expression levels of anti-inflammatory factors (Arg1) and pro-inflammatory factors (IL-6, IL-1β, TNF-α) in wounded skin tissue and serum. The results showed that on day 12 after modeling, compared with the other groups, the combined treatment group had the most significant wound contraction and the fastest healing rate. HE and Masson staining showed that the combined treatment group had the fastest epithelialization and the most collagen deposition. Immunofluorescence and immunohistochemistry showed that the combined treatment group had the highest expression levels of CD31 and Collagen I. ELISA results indicated that the combined treatment group had higher expression levels of Arg1 in wound skin tissue and serum than the other groups, while the expression levels of IL-6, IL-1β, and TNF-α were significantly lower. These results suggest that the combined treatment of hUCMSCs and intestinal probiotics can accelerate wound healing in diabetic mice through mechanisms such as promoting angiogenesis, enhancing collagen deposition, and regulating the inflammatory microenvironment. The therapeutic effect was significantly better than that of single treatment, providing a new potential strategy for the clinical treatment of diabetic foot.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Objective:To investigate the clinicopathological features, pathological classification, and molecular characteristics of pulmonary hamartomas.Methods:A retrospective analysis was conducted on 316 cases of pulmonary hamartomas diagnosed at Nanjing Chest Hospital, Nanjing, China from January 2015 to June 2024. Next generation sequencing (NGS) was performed on 15 cases of this study. The clinical data, histopathological features, immunophenotypes, and molecular alterations were analyzed. Relevant literature was reviewed.Results:Among the 316 patients, there were 154 males and 162 females, with an average age of 56±10 years. Among the 316 cases, 310 were intrapulmonary hamartomas and 6 were intraluminal bronchial hamartomas. Microscopically, there were complex proliferative mesenchymal components and epithelial components, presenting various combinations and hamartomatous morphologies. These hamartomas were morphologically classified into mesenchymal-type hamartomas (cartilaginous, fibrous, smooth muscle, adipose tissue, and mixed types) and epithelial-mesenchymal mixed-type hamartomas (respiratory epithelial-mesenchymal mixed and mucosal gland-mesenchymal mixed types). The cartilaginous hamartomas accounted for 72.8% (230/316) of them, and the non-cartilaginous hamartoma accounted for 27.2% (86/316). Secondary changes such as calcification, ossification, collagenization, mucin degeneration, and cystic changes were commonly present. The immunophenotype was CK7 +/TTF1 + for respiratory epithelial cells, or TTF1 -/CK7 +/p40 + for interstitial cells. Interstitial cells might express desmin, SMA, S-100, caldesmon, etc, while CD34 +/CD10 +/ER + spindle-shaped interstitial cells were also commonly noted. Genetic variations were detected in 11 of the 15 cases that were subject to NGS, including HMGA2-related fusion genes, EP300 mutations, FLT1 mutations, JAK1 mutations, SETD2 and TAP2 mutations, and high-copy amplification of CDK4/PHF1/TSPAN31. The patients were followed up for 6 to 110 months without any known recurrence or metastasis. Conclusions:Pulmonary hamartomas mainly occur in the peripheral lung parenchyma, with the cartilaginous type being the most common. Their clinical pathological and molecular features of pulmonary hamartomas are characterized and the histological types are roughly ascertained in this study, with emphasis of the key points of diagnosis and differential diagnosis. Classification of pulmonary hamartomas is valuable for guiding future research. Pulmonary hamartomas overall have a good prognosis. However, those with cystic changes or intraluminal hamartomas in the bronchus may cause serious airway lesions and therefore require special attention.

Objective:To investigate the current status of the implementation of active health management in tumor care in community health service institutions in Shanghai.Methods:This cross-sectional study was conducted in July 2022. A questionnaire was designed based on tumor management practices according to active health principles was designed and distributed to all 247 community health service institutions in 16 administrative districts of Shanghai. Data were collected on tumor screening, establishment of health records for tumor patients, and follow-up practices.Results:Of the 247 questionnaires distributed, 239 were returned, with 228 valid responses (effective response rate: 92.3%). Of the 228 institutions, 72 (31.6%) were located in urban areas, 101 (44.3%) in suburban areas, and 55 (24.1%) in rural areas. Tumor screening was performed by 89.0% (203/228) of the institutions, mainly for colorectal, lung, liver, breast, and gastric cancers. Health records for tumor patients were established by 92.5% (211/228) of institutions. Follow-up of tumor patients was conducted by 99.1% (226/228) of institutions, with 29.6% (67/226) performing 1-2 annual follow-ups. Telephone follow-up was used by 99.1% (224/226) of institutions, while 42.5% (96/226) adjusted the frequency of follow-up based on patients′ Karnofsky Performance Status scores. Targeted health education for patients and families was provided by 84.6% (193/228) of institutions, including exercise guidance (78.8%, 152/193) and psychological support (76.2%, 147/193). No statistically significant differences were observed among urban, suburban, and rural institutions in tumor screening, health record establishment, follow-up frequency, assessment content, follow-up methods, and tumor health education and content (all P>0.05). Conclusions:The coverage of tumor screening in Shanghai′s community health service institutions remains incomplete, the quality of follow-up needs to be improved, and health education programs are not comprehensive. There were no regional differences in tumor screening, health record establishment, follow-up practices, or tumor health education among urban, suburban, and rural populations.

ObjectiveThe utilization of assisted reproductive technology to rescue genetically modified mouse strains with reproductive disorders provides a reference for improving techniques to preserve valuable experimental mouse strains. MethodsIn vitro fertilization-embryo transfer (IVF-ET) technology was performed on 28 strains of infertile male mice aged 9-18 months. Several indicators such as sperm density and sperm motility in infertile male mice were assessed to select the most viable sperm for IVF-ET experiments. Fertility rate, abnormal egg rate, and birth rate were recorded after the birth of the pups. An optimized ovarian transplantation procedure was applied to 12 strains of infertile female mice aged 8-18 months. 6-week-old female mice with the same genetic background were selected as recipients. One intact ovary was removed from each recipient mouse, and the contralateral oviduct was ligated. An ovary from a donor mouse was isolated and transplanted orthotopically into the side where the ovary had been removed in the recipient mouse. Twenty-one days post-surgery, recipient mice were co-housed with 8-week-old wild type male mice of the same genetic background for breeding. Data such as the pregnancy rate and live birth rate of the recipients were recorded after the birth of the pups. ResultsIVF-ET successfully rescued 28 mouse strains, with the oldest male mice being 18 months old. The success rate of the first round of IVF-ET experiments was 89.29% (25/28). The average fertility rate of IVF in infertile male mice was (51.01±14.97)%, the abnormal egg rate was (9.03±5.28)%, and the birth rate of offspring mice was (18.60±7.03)%. 39 out of 40 ovarian transplant recipient mice survived, with a pregnancy rate of 33.33% (13/39) for ovarian transplant recipients, and a live birth rate of 17.95% (7/39). Four mouse strains were successfully rescued using optimized ovarian transplantation technology, with the oldest female mice being 18 months old. 8 strains were not rescued as they failed to produce offspring that survived to sexual maturity. ConclusionIVF-ET is an effective approach for rescuing mice with reproductive disorders caused by different reasons, especially for those beyond the optimal breeding age. Ovarian transplantation technology can also be used as an alternative for aged female mice. But its success rate is relatively lower than that of IVF-ET, and carries a higher experimental risk.

Objective To investigate the effect and mechanism of dabrafenib （DAB） combined with tremelimumab （TREM） on melanoma. Methods The effects of DAB combined with TREM on cell viability, cytotoxicity and cell migration of A375 cells were evaluated by Cell Counting Kit-8 （CCK-8） method, lactate dehydrogenase （LDH） method and scratch assay. The levels of reactive oxygen species （ROS）, adenosine triphosphate （ATP）, malondialdehyde （MDA）, and superoxide dismutase （SOD） were detected to evaluate the effects of combined drugs on oxidative stress and energy metabolism. In addition, A375 tumor-bearing nude mice model was used to evaluate the inhibitory effect of the combined treatment on tumor growth in vivo, and the degree of cell apoptosis and cell proliferation in tumor tissues were analyzed by terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling （TUNEL） and proliferating cell nuclear antigen （PCNA） immunohistochemical staining. Results The combined treatment significantly inhibited the survival rate and migration ability of A375 cells and enhanced the cytotoxicity. The combined intervention also significantly increased ROS level, decreased ATP, SOD and MDA levels. It effectively inhibited tumor growth in tumor-bearing nude mice, increased the apoptosis rate of tumor cells and inhibited cell proliferation. Conclusion DAB combined with TREM may improve the therapeutic effect of melanoma by enhancing oxidative stress, inhibiting energy metabolism, and promoting cell apoptosis. This combination therapy may provide a new therapeutic strategy to overcome the limitations of singledrug therapy.

This review briefs the anti-hyperuricemia(HUA)mechanism of nutrition targeting the gut,such as the gut microbiota promoting the catabolism of purine and uric acid(UA),and increased its metabolites like uric acid.The review also summarizes the probiotics and prebiotics that have the effect of lowering uric acid targeting at the gut,providing reference and guidance for further research.In addition,this paper reviews the effects of various di-ets,such as the dietary approaches to stop hypertension(DASH)diet,the Mediterranean diet,and the low-purine diet,as well as the effects of individual foods including alcohol,coffee and tea,cherries,dairy products,fructose,and vitamin C on hyperuricemia and gout outcomes.

Objective: To investigate the association between screen time (ST) during leisure time and anxiety-depression symptoms among middle school students, so as to provide a basis for formulating relevant intervention measures. Methods: From November to December 2023, a stratified cluster random sampling method was used to select 2 542 students from junior and senior high school in Taiyuan City. A self designed questionnaire, the Generalized Anxiety Disorder Scale (GAD-7), and the Patient Health Questionnaire (PHQ-9) were used to investigate ST and anxiety/depression symptoms among middle school students. The Logistic regression model was used to explore the association of ST with symptoms of anxiety and depression, as well as with anxiety and depression comorbiditles (CAD). Results: The detection rates of anxiety symptoms, depression symptoms, and CAD were 13.69%, 15.77%, and 10.11%, respectively. The median ST was 2.00 h/d [interquartile range ( IQR =2.38) for weekly averages], with 0.33 h/d ( IQR =1.67) on work days and 5.00 h/d ( IQR=5.50) on rest days. Logistic regression analysis indicated that the total ST of mobile phones during rest days ( OR =1.07, 1.10, 1.11) and the averages ST of mobile phones over a week ( OR = 1.20 , 1.22, 1.29), as well as the total ST of all screen types during rest days ( OR =1.04, 1.04, 1.05) and the averages ST of all screen types over a week ( OR =1.08, 1.09, 1.21) were positively correlated with anxiety symptoms, depression symptoms, and CAD (all P <0.01). Conclusions Among middle school students in Taiyuan City, screen time is positively correlated with symptoms of anxiety or depression and the comorbidity of anxiety and depression, especially smartphone screen time and weekend screen use. Therefore, measures should be implemented to reduce unnecessary screen time among middle school students, especially the use of mobile phones, in order to mitigate the occurrence of anxiety and depression.

Objective To explore the value of support vector machine(SVM)model based on gray matter volume(GMV)for identifying amyotrophic lateral sclerosis(ALS),also to analyze the relevant brain regions.Methods MR 3D T1WI data of 60 ALS patients(ALS group)and 60 healthy volunteers(control group)were retrospectively analyzed.Taken GMV of each brain region obtained by voxel-based morphometry as the input features.F-score analysis was used to select feature with the highest classification accuracy to construct SVM model.Receiver operating characteristic curve was drawn to evaluate the efficacy of SVM model for identifying ALS,and top 10％was used as the weight threshold to obtain gray matter brain regions contributed the most to this model.Results SVM model constructed based on the top 40％GMV features had the highest classification accuracy(82.50％),with sensitivity,specificity and area under the curve(AUG)of 85.05％,80.40％and 0.890,respectively.The left precentral gyrus,left anterior cingulate gyrus and paracingulate gyrus,right middle temporal gyrus,opercular part of left inferior frontal gyrus,right dorsolateral superior frontal gyrus,left temporal pole:middle temporal gyrus,right superior occipital gyrus,orbital part of right middle frontal gyrus,right calcarine fissure and surrounding cortex,right fusiform gyrus were the top 1-10 gray matter brain regions contributed to this model.Conclusion ALS had specific GMV change pattern.SVM model based on GMV could be used to effectively identify ALS,while the left precentral gyrus was the most contributive brain region to this model.

Objective:To observe the curative effect of a personalized surgical scheme based on scanning source optical coherence tomography (SS-OCT) image features in the treatment of congenital optic disc pit (ODP) with maculopathy (ODP-M).Methods:A prospective interventional cohort study. From September 2019 to May 2024, 15 patients with 15 eyes who were diagnosed with ODP-M by ophthalmology examination in Department of Ophthalmonogy of The First Affiliated Hospital of Zhengzhou University were included in the study. Best corrected visual acuity (BCVA) and SS-OCT were performed in all affected eyes. Standard E word visual acuity chart was used for BCVA examination, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The center retinal thickness (CRT) was measured by SS-OCT examination of macular area using VG200D of Henan SVision Imaging Technology Co., LTD. According to the morphological characteristics of ODP and the splitting, edema and detachment of macular region, combined with the degree of pulling of the boundary membrane between the posterior vitreous cortex and macular region, a personalized surgical method was designed. Class I: pars plana vitrectomy combined with macular boundary film stripping, ODP boundary film packing and vitreous cavity gas filling. Class Ⅱ: pars plana vitrectomy combined with non-retained macular boundary film stripping or ODP inner boundary film packing, vitreous cavity gas filling. Class Ⅰ and Class Ⅱ operations were performed in 10 and 5 eyes of 15 eyes, respectively. The postoperative follow-up time was >6 months. Follow-up time was performed with the same equipment before surgery. BCVA changes, CRT reduction rate and complications were observed. BCVA and CRT were compared before and after operation by paired sample t test. Results:There were 15 eyes in 15 cases, 4 eyes in 4 males and 11 eyes in 11 females. The age was (28.87±16.5) years. logMAR BCVA of the affected eye was 0.94±0.51. CRT was (697.80±301.80) μm. At the last follow-up, the logMAR BCVA was 0.53±0.49. CRT was (392.53±167.55) μm. Compared with before operation, BCVA and CRT were significantly improved, and the difference was statistically significant ( t=3.23, 3.25; P=0.006, 0.006). After surgery, transient intraocular hypertension occurred in 2 eyes, and the intraocular pressure returned to normal level after 3 to 7 days without special treatment. Two eyes underwent an unexpected second operation. Among them, one eye underwent Class Ⅰ surgery, the tunnel at ODP was closed after surgery, and there was a small amount of subretinal fluid in the macular area. Class Ⅱ surgery was performed in 1 eye with retinal reattachment. Conclusion:Personalized surgical treatment of ODP-M based on SS-OCT image features can reduce CRT and improve visual acuity.