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 evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

Objective To explore the treatment effects and mechanism of Fangji Huangqi Xiaozhong Prescription in metabolic syndrome phenotype osteoarthritis(MS-OA)based on PPARγ/NF-κB signaling pathway.Methods SD rats were randomly divided into sham-operation group,OA group,MS-OA group,Western medicine group,and TCM high-and low-dasage groups.The modified Hulth method was used to make the OA model,and OA model was added with high-carbohydrate high-fat diet to make the MS-OA model.TCM high-and low-dosage groups were given 15.12,7.56 g/kg Fangji Huangqi Xiaozhong Prescription for gavage.The Western medicine group was given 16.2 mg/kg of losoprofen sodium by gavage,while the other groups were given physiological saline by gavage once a day for 6 consecutive weeks.Rat body mass was measured,biochemical detection of blood lipids and blood glucose was conducted,ELISA was used to detect the contents of serum TNF-α,IL-1β,IL-10 and leptin,morphological changes in cartilage tissue were observed using safranin O-fixed green and HE staining,immunohistochemical staining was used to detect expressions of Acan,ColⅩ,MMP13,TNF-α,IL-1β and PPARγ in cartilage tissue,Western blot was used to detected the expression of PPARγ,NF-κBp65 and p-NF-κBp65 protein in cartilage tissue.Results Compared with the sham-operation group,body mass and serum TC,TG,LDL-C,TNF-α,IL-1β and leptin of MS-OA group increased significantly(P<0.01),the contents of HDL-C and IL-10 decreased(P<0.01),cartilage tissue degeneration was significant,and the Mankin score increased(P<0.01),the expression of ColⅩ,MMP13,TNF-α,IL-1β,p-NF-κBp65 protein increased(P<0.05,P<0.01),and the expression of Acan and PPARγ protein decreased(P<0.01).Compared with the MS-OA group,the contents of serum TC,TG,LDL-C,TNF-α and leptin decreased in TCM high-dosage group(P<0.05,P<0.01),the content of IL-10 increased(P<0.05),the pathological damage of cartilage tissue improved,the Mankin score decreased(P<0.01),the expressions of ColⅩ,MMP13,TNF-α,IL-1β and p-NF-κBp65 protein in cartilage tissue decreased(P<0.05,P<0.01),and the protein expressions of Acan and PPARγ protein increased(P<0.01,P<0.05).Conclusion Fangji Huangqi Xiaozhong Prescription can improve lipid metabolism disorder,improve intra-articular inflammatory environment,balance cartilage metabolism,and delay cartilage degeneration in MS-OA rats.Its mechanism may be related to the regulation of PPARγ/NF-κB signaling pathway.

Objective To validate the mechanism of Mori Cortex-Lycii Cortex(MCLC)in intervening acute lung injury(ALI)based on network pharmacology,molecular docking combined with animal experiments.Methods The TCMSP database was used to obtain the active components of MCLC;the SwissTargetPrediction database was used to predict the targets of active components;the GeneCards database and DisGeNET database were used to collect the disease targets of ALI;the key targets were screened by constructing a PPI network,and the key targets were subjected to GO and KEGG pathway enrichment;a drug-component-target-pathway network was constructed using Cytoscape software;AutoDock and PyMOL software were used to validate the molecular docking of some of the compounds and targets;LPS was used to establish a mouse model of ALI for experimental validation,and experimental validation was performed to main targets and pathways.Results Totally 44 active components of MCLC and 138 action targets were obtained;26 potential targets of MCLC intervention in ALI were obtained,mainly TNF,EGFR,NFKB1,MPO,TNFRSF1A,NOX4,etc.,and the key pathways were MAPK signaling pathway,IL-17 signaling pathway,NF-κB signaling pathway,etc.;molecular docking results showed that the core active components of MCLC and the main targets had strong binding activities;animal experiments showed that MCLC at medium and high dosages could effectively improve the lung histopathological damage in ALI mice,decrease the contents of IL-6 and TNF-α in serum(P<0.01),and increase IL-10 content(P<0.01);MCLC inhibited protein expressions of EGFR,PI3K,AKT,NF-κB p65 in lung tissue(P<0.01).Conclusion MCLC may intervene ALI by components such as quercetin and buddleoside,acting on targets including EGFR and TNF,through ulti-pathways of EGFR/PI3K/NF-κB signaling pathway,etc.

Objective:To analyze the risk factors for postoperative pathological upgrade of prostate cancer patients with single core positive biopsy,and to attempt to build a mathematical model for predic-ting postoperative pathological upgrade in these cancer patients with single core positive biopsy.Methods:A retrospective analysis was conducted on 1 349 patients diagnosed with prostate cancer and undergoing radical prostatectomy at Peking University First Hospital from January 2015 to August 2020.The pa-tients'age,body mass index,clinical stage,prostate imaging reporting and data system(PI-RADS)scores,prostate volume in magnetic resonance imaging(MRI),Gleason score of biopsy,serum prostate specific antigen(PSA)before biopsy and operation,surgical method and pathological stage were inclu-ded in the analysis.The variables with P＜0.1 in univariate analysis were included to construct multi-variate Logistic regression and the nomogram was drawn.The model was evaluated using the receiver operating curve.Results:A total of 71 patients were included in this research,with 34 patients in the upgraded group and 37 patients in the non-upgraded group.There were no significant differences in the pa-tients'age(P=0.585),body mass index(P=0.165),operation method(P=0.08),prostate volume in MRI(P=0.067),clinical stage(P=0.678),PI-RADS score(P=0.203),difference of PSA density(P=0.063),Gleason score in biopsy(P=0.068),PSA before puncture(P=0.359)and operation(P=0.739)between the two groups.However,there were significant differences in the proportion of tumor tissue(P=0.007),postoperative pathological stage(P＜0.001)and postoperative Gleason score(P＜0.001)between the two groups.The preoperative variables with a P value of less than 0.1(prostate volume in MRI,difference of PSA density,proportion of tumor tissue and Gleason score in biopsy)in univariate analysis were included in the Logistic regression,and the nomogram was drawn.Only the prostate volume in MRI had a P value of less than 0.05.The area under the curve of the model was 0.773.Conclusion:In patients with sin-gle core positive biopsy,if the prostate volume is small or the proportion of tumor in positive core is small,clinicians should be alert to the possibility of postoperative pathology upgrading,preoperative risk stratifica-tion should be carefully considered for patients with possible pathological upgrading.This model can be used to predict the pathological upgrade of patients with single core positive biopsy.

Objective:To investigate the interventional effect of bone marrow mesenchymal stem cell (BMMSC) transplantation with different doses of X-ray irradiation induced hepatic injury in mice.Methods:Eighteen female C57BL/6J mice were randomly divided into 0, 2, and 3 Gy irradiation groups and 0, 2, and 3 Gy transplantation groups. The irradiation group was used as the control and injected with an equal volume of culture medium. The mice in the transplantation group were irradiated with different doses of X-ray irradiation, and BMMSCs were intravenously infused into the bone marrow. The mice were sacrificed for sampling at the end of the 21st day. Mice body weight changes were recorded daily. The changes in the content of peripheral blood lymphocytes, red blood cells, platelets, and hemoglobin were detected by an automatic blood tester. The morphological changes in mice liver tissues were observed by hematoxylin-eosin staining. The serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by a biochemical analyzer. The reduced glutathione contents in liver tissue were detected by the microplate method. The malondialdehyde content in liver tissue was detected by thiobarbituric acid. The content of total superoxide dismutase (T-SOD) in liver tissue was detected by the hydroxylamine method. The expression of the F4/80 protein in liver tissue was detected by the immunohistochemistry method. The protein expression of nuclear transcription factor erythroid 2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in liver tissue was determined by the western blotting method. The mRNA expression of NLRP3, IL-6, and Nrf2 in liver tissue was detected by a real-time quantitative polymerase chain reaction. The multiple-group comparisons were analyzed by factorial analysis of variance. The inter-group comparisons were analyzed by the LSD method for statistical analysis.Results:The contents of peripheral blood lymphocytes, erythrocytes, platelets, and hemoglobin were significantly decreased in the 3 Gy irradiation group than the 0 Gy irradiation group ( P<0.05), while the activities of serum ALT and AST were significantly increased ( P<0.05). The malondialdehyde content, F4/80 protein expression level, nucleotide-binding domain and leucine-rich repeats, nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3), and interleukin 6 mRNA expression levels were significantly increased in liver tissue, while the contents of T-SOD and glutathione, Nrf2 and HO-1 protein expression levels, and Nrf2 mRNA expression level in liver tissue were significantly decreased ( P<0.05). The contents of peripheral blood lymphocytes, red blood cells, platelets, and hemoglobin were significantly increased in the 3 Gy transplantation group than the 3 Gy irradiation group ( P<0.05), while the activities of serum ALT and AST were significantly decreased ( P<0.05). The malondialdehyde content, F4/80 protein expression level, NLRP3 and interleukin-6 mRNA expression levels in liver tissue were significantly decreased ( P<0.05), while the content of T-SOD and glutathione, Nrf2 and HO-1 protein expression levels, and Nrf2 mRNA expression level in liver tissue were significantly increased ( P<0.05). Conclusion:X-ray irradiation at a dose of 3 Gy can induce liver oxidative damage in mice. BMMSC transplantation can improve X-ray irradiation-induced liver oxidative damage in mice, and its mechanism of action may be related to the regulation of the Nrf2/HO-1 pathway.

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.
Siderophores/metabolism* ; Iron/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Cryoelectron Microscopy ; Adenosine Triphosphate/metabolism* ; ATP-Binding Cassette Transporters

Objective This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials(RCTs)assessing the clinical efficacy of acupuncture for chronic stable angina(CSA).Methods PubMed,The Cochrane Library,Embase,CNKI,VIP,WanFang Data,CBM databases,ClinicalTrial.gov and Chinese Clinical Trial Registry were electronically searched to collect randomized controlled trials(RCTs)of acupuncture for CSA and only RCTs that included acupuncture as the sole or combination of acupuncture in the treatment of CSA.The retrieval period was from the establishment of the database to May 19,2022.The primary outcome measure was the frequency of angina attacks,and the secondary outcome measures were angina efficacy,total effective rate of ECG improvement,nitroglycerin use after treatment,patient-perceived overall effectiveness,performance on the Six-Minute Walk Test(6-MWT),depression as measured by the anxiety as measured by the Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS),adverse effects.Results Twelve studies with a total of 1605 case subjects were included and grade quality of evidence reviews had 1 outcomes as medium quality evidence,5 outcomes as low quality evidence and 4 outcomes as very low quality evidence.Acupuncture treatment resulted in significantly greater reductions in angina attacks,visual analog scale(VAS),6-minute walk test,angina efficacy,electrocardiogram improvement rate,angina efficacy,total clinical response rate.Conclusion The efficacy of acupuncture combined with western medicine in treating CSA is better than that of Western medicine alone,thanks to restricted by the number and quality of included researchs,higher quality studies are required to prove above conclusions.

Osteosarcoma (OS) stood as the most prevalent primary malignant bone tumor among children and adolescents, characterized by its aggressive nature and high propensity for metastasis, thus earning its classification as a highly malignant disease. The primary routes of metastasis in osteosarcoma encompassed hematogenous dissemination (the most common metastasis was lung metastasis) and lymph node involvement, with lymph node metastasis carrying a notably poorer prognosis when contrasted with lung metastasis. However, it was noteworthy that, at that time, clinical practice often overlooked the crucial aspect of conducting regional lymph node screening for newly diagnosed osteosarcoma patients, and there remained a dearth of standardized treatment protocols for osteosarcoma lymph node metastasis. The intricate mechanisms at the heart of osteosarcoma lymph node metastasis primarily revolved around the infiltration of lymphatic vessels by osteosarcoma cells possessing metastatic capabilities and the induction of lymphatic vessel formation by these cells. Nevertheless, it was imperative to underscore that our understanding of the comprehensive mechanisms underpinning the initiation and progression of these processes still remained incomplete. Moreover, following the adaptive proliferation of osteosarcoma cells within regional lymph nodes, there existed a complex biological process that involved a myriad of cytokines and signaling pathways. This process facilitated the metastasis of osteosarcoma cells to distant target organs, most notably the lungs, by virtue of the intimate anatomical relationships between the lymphatic and circulatory systems. Consequently, that comprehensive review sought to provide an all-encompassing exposition on various facets of osteosarcoma lymph node metastasis. These facets included the direct invasion of surrounding lymphatic vessels by osteosarcoma cells, the osteosarcoma cell-induced development of lymphatic vessels through the VEGFC/VEGFR-3 signaling axis, the remodeling of the lymph node microenvironment by osteosarcoma cells via Hsp5B and the Wnt/β-Catenin signaling pathway to ensure their adaptation and survival, the epithelial-mesenchymal transition of osteosarcoma cells promoting metastasis from lymph nodes to the lung, and the utilization of small-molecule compounds in the battle against osteosarcoma lymph node metastasis. The aim was to provide a comprehensive and systematic elucidation of the intricate mechanisms governing osteosarcoma lymph node metastasis and to furnish invaluable insights for the development of therapeutic strategies.

Objective:To investigate the feasibility and safety of suprapubic bladder puncture and gland fixation in transurethral enucleation of the prostate.Methods:The clinical data of 15 patients with benign prostatic hyperplasia admitted to the First Affiliated Hospital of Guangxi Medical University from January 2020 to June 2020 were retrospectively analyzed. The age was (70.27±5.35) years old, preoperative serum prostate-specific antigen (PSA) level was (3.03±1.37) ng/ml, preoperative total prostate weight was 80.3(70.49, 96.78)g, preoperative postvoid residual urine volume(PVR)was 80 (55, 108)ml, and the maximum urine flow rate (Q max) was (6.13±2.25) ml/s. The international prostate symptom score(IPSS) was 25(22, 27), quality of life (QOL)score was 5(5, 6), international erectile function index-5 (IIEF-5) score was (15.38±5.10). All 15 patients underwent conventional transurethral plasma enucleation of prostate by using the three-lobe method, and the enucleated gland was pushed into the bladder completely. Then a laparoscopic pneumoperitoneum needle was used to perform suprappubic cystipuncture, and ureteral grasping forceps were inserted through the outer sheath. The forceps were used to fix the enencied gland. A rapid harvesting electric resection was performed in the broad space of the bladder, and the Ellick was rinsed to remove the tissue fragments. Surgical indicators and complications were recorded. The improvement of subjective score (IPSS, QOL, IIEF-5) and objective index (Q max, PVR) was compared between preoperative and postoperative. Results:All the 15 operations were completed successfully and there were no complications such as blood transfusion, capsule perforation, transurethral resection syndrome, bladder injury, bladder puncture site laceration and bleeding. The weight of resected prostate tissue was 44(40, 60)g, with blood loss (79.20±18.93)ml.The time of enucleation operation was (54.13±10.88)min, with harvest cutting time (14.67±2.50)min, evisceration efficiency (0.89±0.08)g/min, harvesting efficiency (3.26±0.36)g/min, bladder irrigation time (2.47±0.52) d. The time of indwelling catheter was (3.73±0.80)d.The postoperative hospital stay was (4.40±0.91) d. Temporary urinary incontinence occurred in 1 case after operation. All patients were followed up for 6 months after operation. The IPSS score was 3(2, 3), QOL score was 0(0, 1), IIEF-5 score was (20.12±2.30), Q maxwas (21.80±2.14) ml/s and PVR was 10(5, 15)ml, which were all significantly different compared with those before surgery ( P<0.05). The symptoms of the patients were significantly improved. Conclusions:Transurethral plasma enucleation of prostate combined with suprapubic bladder puncture and fixed gland is effective in the treatment of benign prostatic hyperplasia. The subjective symptoms and objective examination of patients have been significantly improved, and no adverse operation-related complications have occurred. It is a suitable method for enucleation of prostate in units which are not equipped with transurethral tissue planer.