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.

Stresses induced by the deficiency or excess of trace mineral elements, such as manganese (Mn), represent a common limiting factor for the production of crops like Brassica napus. To identify key genes involved in Mn allocation in B. napus and elucidate the underlying mechanisms, a member of the metal tolerance protein (MTP) family obtained in the previous screening of cDNA library of B. napus under Mn stress was selected as the research subject. Based on the sequence information and phylogenetic analysis, it was named as BnMTP10. It belongs to the Mn-cation diffusion facilitator (CDF) subfamily. Expression of BnMTP10 in yeast significantly improved the tolerance of transformants to excessive Mn and iron (Fe) and reduced the accumulation of Mn and Fe. However, the yeast transformants exhibited no significant changes in tolerance to excess cadmium, boron, aluminum, zinc, or copper. The qRT-PCR results demonstrated that the flowers of B. napus had the highest expression of BnMTP10, followed by roots and leaves. Subcellular localization studies revealed that BnMTP10 was localized in the endoplasmic reticulum (ER). Compared with wild-type plants, transgenic Arabidopsis overexpressing BnMTP10 exhibited enhanced tolerance to excessive Mn stress but showed no significant difference under Fe stress. Correspondingly, under excessive Mn stress, the Mn content in the roots of transgenic Arabidopsis increased significantly. However, under excessive Fe stress, the Fe content in transgenic Arabidopsis did not alter significantly. According to the results, we hypothesize that BnMTP10 may alleviate excessive Mn stress in plants by mediating Mn transport to the ER. This study facilitated our understanding of efficient mineral nutrients, and provided theoretical foundations and gene resources for breeding B. napus.
Brassica napus/genetics* ; Manganese/metabolism* ; Plants, Genetically Modified/genetics* ; Plant Proteins/physiology* ; Arabidopsis/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Cation Transport Proteins/metabolism* ; Stress, Physiological

Objective:To explore the curative effect of surgical treatment for Crohn′s disease (CD), to investigate the timing of surgical intervention and the choice of surgical methods.Methods:From January 1, 2016 to August 31, 2020, at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, the clinical data of 123 patients with CD and receiving surgical treatment were retrospectively analyzed, which included the type of lesion, the location of lesion, clinical manifestation, surgical method, preoperative inflammatory and nutritional indicators, postoperative recovery of digestive tract function, and the development and treatment of postoperative complications. CD was diagnosed according to Consensus opinion on diagnosis and treatment of inflammatory bowel disease ( Beijing 2018). Patient was classitied according to the Montreal Classification. Postoperative complications were graded according to the Clavien-Dindo Criteria. Mann-Whitney U test was used for statistical analysis. Results:Among 123 patients, according to the Montreal classification, two cases (1.6%) were diagnosed at ≤16 years old (type A1), 66 cases (53.7%) were diagnosed at 17 to 40 years old (type A2), and 55 cases (44.7%) were diagnosed at >40 years old (type A3). The lesions were 52 cases (42.3%) of terminal ileum (L1) type, 20 cases (16.3%) of colon (L2) type, and 51 cases (41.5%) of ileocolon (L3) type. Four cases (3.2%) were non-stenosis and non-penetrating (B1) type, 87 cases (70.7%) were stenosis (B2) type, and 32 cases (26.0%) were penetrating (B3) type. Eighteen patients (14.6%) underwent emergency surgery due to complete intestinal obstruction (10 cases), gastrointestinal perforation (five cases), gastrointestinal bleeding (two cases), and rectovesical fistula complicated with septic shock (one case). One hundred and five patients (85.4%) received selective surgery due to poor conservative treatment effects. 51 cases (41.5%) underwent traditional open surgery and 72 cases (58.5%) underwent laparoscopic surgery. Nineteen patients (15.4%) received temporary or permanent ostomy. The preoperative C reactive protein level of patients with emergency surgery was higher than that of patients undergoing selective surgery ((39.23±24.13) mg/L vs. (11.48±2.68) mg/L), while the levels of plasma albumin (ALB) and pre-ALB were lower than those of patients receiving selective surgery ((29.90±10.60) g/L vs. (38.38±8.30) g/L, (146.00±125.49) mg/L vs. (209.06±61.19) mg/L), and the differences were statistically significant ( Z=9.603, 8.754 and 7.111, all P<0.01). During the follow-up, a total of 23 cases (18.7%) developed postoperative complications, including one case of postoperative intra-abdominal hemorrhage and underwent re-operation (Clavien-Dindo grade Ⅲ complication); four cases of anastomotic leakage after operation; six cases of postoperative paralytic ileus; 11 cases of surgical site infection, all of which were Clavien-Dindo grade Ⅱ complications, and one case of deep venous thrombosis of lower extremity. No patient with severe intraoperative complication was observed, and no patients died during the operation or hospitalization. The postoperative exhaust time of patients was (3.2±1.4) d, the time of open fluid diet was (5.8±0.8) d, the length of hospital stay was (18.0±14.1) d, and the length of postoperative hospital stay was (11.2±8.8) d. Conclusions:The concept of multidisciplinary collaboration should be emphasized in the treatment of CD. Surgical treatment can effectively control the complications and improve the quality of life of patients, but the timing of operation and the choice of surgical methods should be decided prudently after perioperative treatment, multi-disciplinary participated and regulation of the internal environment. The standardized and targeted treatments for the surgical difficulties of inflammatory bowel disease should be conducted.

The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore's development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in commemoration of the International Day of Radiology in 2020, as well as the 200th anniversary of the Singapore General Hospital in 2021. This pictorial essay comprises gastroenterology, musculoskeletal and obstetrics and gynaecology cases from the archives.

The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore's development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in 2020 in commemoration of the 20th anniversary of the formation of SingHealth, the 55th National Day of Singapore, and the 125th anniversary of the International Day of Radiology. This pictorial essay comprises cardiovascular, respiratory and neurological cases from the archives.

Tripartite motif 5 (TRIM5) plays a significant function in autophagy and involves in immune and tumor processes. While the function of TRIM5 remains poorly understood in glioma. We purpose to evaluate the possible prognostic role of TRIM5 in glioma via bioinformatics analyses. The database clinical samples of glioma in this study included low grade glioma (LGG) and glioblastoma multiforme (GBM). TRIM5 expression in glioma tissues were explored in Oncomine, GEPIA and The Cancer Genome Atlas (TCGA) databases. Survival analysis and the multivariate Cox regression analysis of TRIM5 based on TCGA were used to evaluate the prognostic role of TRIM5. The protein networks of TRIM5 was detected by STRING database. KEGG enrichment analyses were performed to predict the potential molecular pathways of TRIM5 in glioma. In addition, immune infiltration analysis was conducted by CIBERSORT and TIMER databases. We found that TRIM5 was strongly increased in glioma samples compared with normal samples in Oncomine, GEPIA and TCGA databases. Higher TRIM5 was significantly contributed to worse overall survival (OS) in LGG+GBM patients and LGG patients, while was no correlated with OS of GBM patients. Interaction networks analysis identified that IRF3, IRF7, OAS1, OAS2, OAS3, OASL, GBP1, PML, BTBD1 and BTBD2 proteins were contacted with TRIM5. Moreover, KEGG revealed that apoptosis and cancer- and immune-related pathways were enriched with elevated TRIM5. Specifically, TRIM5 could influence the immune infiltration levels, such as activated NK cells, monocytes, activated mast cells and macrophages in glioma. In conclusion, our data indicated that TRIM5 was upregulated in glioma tissues and associated with poor prognosis and immune infiltration. TRIM5 may be acted as a biomarker in prognosis and immunotherapy guidance of glioma.

The corona virus disease 2019 (COVID-19), which started in Wuhan in December 2019, is a new infectious disease. The disease is highly contagious, and the correct selection of effective disinfectants is essential. This article analyzed the environmental resistance of coronavirus and its sensitivity to commonly used disinfectants by reviewing domestic and foreign literatures, and concluded that coronavirus has strong survivability in the environment, but it can be efficiently inactivated by most disinfectants. However, it should be noted that the commonly used concentration of chlorine-containing disinfectants (effective chlorine concentration of 500 mg/L) cannot quickly kill coronavirus, and a concentration of 1 000 mg/L or higher is required. Other biocidal agents, such as benzalkonium chloride and chlorhexidine digluconate, are less effective. This article aimed to provide references for selecting the appropriate disinfectants and disinfection methods to cut off the spread of the virus.

Objective To investigate the advantage of neuronavigation assisted microsurgical resection of gliomas in eloquent areas of brain. Methods The clinical data of 99 patients with gliomas in eloquent areas of brain and underwent microsurgery in the First Affiliated Hospital of Sun Yat-sen University from January 2012 to December 2017 were analyzed retrospectively. All patients were divided into two groups: neuronavigator-guided microsurgery group (neuronavigation group,46 cases) and non-neuronavigator-guided microsurgery group (non-neuronavigation group,53 cases). The neuronavigation group received neuronavigation assisted microsurgery, while the non-neuronavigation group received general microsurgery. MRI examination, Karnofsky performance scale (KPS) score and symptomatic improvement rate were used to analyze the extent of resection and postoperative function. Results The total resection rate of neuronavigation group was 91.3% (42/46). Comparing with 73.6% (39/53) total resection rate in non-neuronavigation group,the difference of total resection rate was statistically significant (Z=-2.343,P＜0.05). The postoperative symptoms improved both in neuronavigation group and non-neuronavigation group,and the KPS score at discharge were higher than that before operation (P＜0.05). No aggravation of symptoms and signs or new complications occurred in all patients except one case of postoperative muscle strength decline in non-neuronavigation group after the surgery. According to tumor size,the total resection rate of neuronavigation group and non-neuronavigation group among patients whose maximum size of tumor≥3cm were 89.5%(34/38) and 72.5%(37/51) respectively. The difference of total resection rate was statistically significant between these two groups (Z=-2.040,P＜0.05). Conclusion Neuronavigation assisted microsurgical resection of gliomas in brain eloquent areas can improve the rate of total resection and postoperative quality of life without increase in postoperative complications.

Objective The aim of the study is to evaluate the early and long-term outcomes of mitral valve repair for degenerative mitral regurgitation.Methods From January 2003 to December 2015,clinical profiles of 1 903 patients with degenerative mitral regurgitation who underwent mitral valve repair at our institution were analyzed retrospectively.There were 1 312 males (68.9 ％) and 591 females (31.1％) the mean age was (54.2 ± 13.1) years.Early and long-term outcomes were summarized and risk factors for adverse events were assessed.Results There were 35 in-hospital deaths(1.8％) and in-hospital mortality for isolated mitral valve repair was 0.9％ (10/1 163).Perioperative complications included central nerve system complications(0.7％),respiratory failure requiring tracheotomy(1.8％),acute renal injury requiring hemodialysis(1.2％) and reoperation for bleeding(0.7 ％).NYHA function class Ⅲ-Ⅳ (OR =3.65),atrial fibrillation (OR =2.85) and ejection fraction ＜0.6(OR =2.34) were identified as independent risk factors for in-hospital mortality.12 years over follow-up,overall survival,freedom from reoperation for mitral valve and freedom from recurrent moderate/severe regurgitation were 85％ 、91％ and 75％,respectively.Age ＞ 60 years(HR =7.43),preoperative stroke(HR =6.51),ejection fraction ＜ 0.6 (HR =3.87),left ventricular end-systolic dimension ＞ 40 mm (HR =3.98) and pulmonary systolic pressure ＞ 50 mmHg (1 mmHg =0.133 kPa) (HR =2.85) were independent predictive factors for late death.Ejection fraction ＜ 0.6 (HR =4.01),left ventricular end-diastolic dimension ＞ 60 mm(HR =1.88),leaflet lesion involving anterior leaflet (HR =2.40) and residue mild regurgitation(HR =4.17) were independent predictors for late recurrent regurgitation.Leaflet lesion involving anterior leaflet(HR =2.40) and residue mild regurgitation (HR =3.35) were independent predictor for late reoperation for mitral valve.Conclusion Mitral valve repair is safe and effective in degenerative mitral regurgitation.Early surgical intervention for asymptomatic patients with preserved left ventricular function before onset of atrial fibrillation and pulmonary artery hypertension is associated with decreased incidence of adverse events and improved long-term outcomes.Early surgical intervention should be restricted in experienced high-volume centers.

AIM: To evaluate the effect of inhibiting ubiquitin-specific protease 14 (USPl4) activity on oxidative stress induced by H2O2 of H9c2 cells.METHODS: The H9c2 cells were incubated with H2O2 at 25 μmol/L for 2 h to establish the oxidative stress injury model.The cells were divided into control group, H2O2 group, IU1 group (25 μmol/L or 50 μmol/L) and IU1+ H2O2 group.The H9c2 cells activity was measured by MTS assay.The level of intracellular reactive oxygen species (ROS) and cell survival rate were analyzed by flow cytometry assay.The changes of the mitogen-activated protein kinase (MAPK) family related proteins were detected by Western blot.RESULTS: Compared with control group, the cell activity and the viability rate in H2O2 group were decreased (P<0.05), while the intracellular ROS, the protein levels of Bax/Bcl-2, P53, p-ERK1/2, p-JNK and p-P38 were increased (P<0.05).Compared with H2O2 group, the cell activity and the viability rate of the H9c2 cells in IU1+H2O2 group were increased (P<0.05), while the intracellular ROS, the protein levels of Bax/Bcl-2, P53, p-ERK1/2, p-JNK and p-P38 were decreased (P<0.05).CONCLUSION: Inhibition of USPl4 activity reduces the oxidative stress injury of the H9c2 cells.The mechanism may be related to inhibition of the MAPK signaling and down-regulation of apoptosis related proteins.