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 explore the effect of traditional Chinese medicine enema combined with acupoint massage on postoperative intestinal function recovery.Methods A total of 80 patients with abdominal surgery admitted to First Affiliated Hospital of Huzhou University from January 2022 to June 2023 were selected and divided into study group and control group according to random number table method,with 40 cases in each group.The control group was treated with conventional Western medicine,while the study group was treated with traditional Chinese medicine enema combined with acupoint massage on the basis of conventional Western medicine treatment.The therapeutic effect,postoperative recovery time,gastrointestinal hormone level,abdominal distension pain and gastrointestinal reaction score were compared between two groups.Results Postoperative bowel sound recovery time,first anal defecation time and full-flow diet recovery time in study group were significantly shorter than those in control group(P<0.05).At 5 days after surgery,the levels of motilin(MTL),gastrin(GAS)and gastric inhibitory peptide(GIP)in two groups were significantly higher than those in this group at 1 day after surgery(P<0.05).The levels of MTL,GAS and GIP in study group were significantly higher than those in control group(P<0.05).At 5 days after surgery,abdominal distension score and gastrointestinal reaction score in two groups were significantly lower than those in this group 1 day after surgery(P<0.05),and abdominal distension score and gastrointestinal reaction score in study group were significantly lower than those in control group(P<0.05).The total effective rate of study group was significantly higher than that of control group(χ2=3.914,P=0.048).Conclusion Traditional Chinese medicine enema combined with acupoint massage can effectively shorten the recovery time of intestinal function,improve the level of gastrointestinal hormone,relieve abdominal distension pain and gastrointestinal reaction after abdominal operation,and the effect is significant,worthy of clinical application.

AIM:This study aims to investigate the effects and mechanisms of silent information regulator 6(SIRT6)on carbon tetrachloride(CCl4)-induced liver fibrosis in mice,as well as the expression changes in the down-stream pathways of hepatic stellate cells after SIRT6 silencing.METHODS:Thirty male C57BL/6J mice were randomly divided into a normal control group(n=6)and a model group(modeling at 2,4,8,12 weeks,n=24).A liver fibrosis model in mice was prepared by intraperitoneal injection of CCl4 twice a week for 12 weeks.Serum alanine aminotransfer-ase(ALT)and aspartate aminotransferase(AST)levels were measured to assess liver injury.Hematoxylin-eosin(HE)and Masson staining were used to observe the pathological changes in mouse liver tissues.Immunohistochemical staining was conducted to detect the expression of α-smooth muscle actin(α-SMA)in the liver,Western blot analysis was used to measure the expression of liver α-SMA,SIRT6,acetyl histone H3 at Lys9(H3K9ac),acetyl histone H3 at Lys56(H3K56ac),interleukin-1β(IL-1β),and IL-18 proteins.Hepatic stellate cells-T6(HSC-T6)underwent SIRT6 gene si-lencing,divided into NC siRNA group and SIRT6 siRNA group,with Western blot performed to detect the expression of SIRT6,H3K9ac,and H3K56ac proteins.RESULTS:Compared with the normal control group,the serum ALT and AST levels in the model group were significantly increased(P<0.05);HE and Masson staining results showed that the patho-logical changes in the liver of the model group worsened over time,with an increase in collagen fiber deposition.Both im-munohistochemistry and Western blot showed that the expression of liver α-SMA significantly increased at 8 and 12 weeks in the model group(P<0.05).Western blot results showed that the expression of SIRT6 protein in the liver of all model group mice was lower than that in the normal control group(P<0.05),and decreased gradually with the progression of liv-er fibrosis;also,the expression levels of H3K9ac,H3K56ac,IL-1β,and IL-18 in the liver of the model group mice were significantly elevated at 8 and 12 weeks(P<0.05);after SIRT6 silencing,compared with the NC siRNA group,the levels of H3K9ac and H3K56ac in the SIRT6 siRNA group significantly increased(P<0.05).CONCLUSION:The deficiency of SIRT6,by abnormally increasing H3K9ac and H3K56ac,raises the expression of IL-1β and IL-18,intensifying the in-flammatory response and promoting the progression of liver fibrosis,indicating that the aberrant expression of SIRT6 is in-volved in the development of liver fibrosis.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

Objective:To explore the effect of SBAR (situation, background, assessment, recommendation) communication model combined with scenario simulation in clinical teaching of blood purification center.Methods:Sixty interns in the blood purification center from March 2019 to March 2020 were collected in the study, and randomly divided into experimental group ( n=30) and control group ( n=30). The two groups of students studied in two different treatment groups in the blood purification center. The control group used the method of traditional teaching, while the experimental group used SBAR communication combined with situational simulation for teaching on the basis of traditional teaching, with a total clinical practice time of two months. All trainees underwent theoretical examination, clinical operation examination, self-efficacy evaluation and teaching satisfaction survey after training. SPSS 22.0 was performed for t test. Results:Through SBAR communication model combined with situational simulation teaching, the scores of theoretical examination [(88.13±3.22) vs. (85.51±3.17)], clinical operation assessment [(91.31±3.48) vs. (84.17±4.94)], self-efficacy evaluation [(11.13±1.08) vs. (9.21±1.89)], teaching satisfaction [(95.71±2.87) vs. (91.18±3.08)], and communication ability [(12.27±1.13) vs. (8.63±1.45)] in the experimental group were higher than those in the control group; while there was no significant difference in the scores of theoretical assessment between the two groups ( P<0.05). Conclusion:SBAR communication model combined with situational simulation teaching can improve the learning ability, operation ability and comprehensive application ability of special training trainees, especially in communication ability, which is worthy of popularization and application in clinical teaching.

The main treatment options for cervical cancer include surgery and/or radiotherapy combined with chemotherapy. Radiotherapy consists of external beam radiotherapy and brachytherapy (BT). BT contains high-dose-rate (HDR-BT) and low-dose-rate brachytherapy (LDR-BT). The prognosis of cervical cancer is relatively good. However, some patients experience substantial treatment failures, such as intra-pelvic and/or extra-pelvic recurrences. Recurrent cervical cancer (RCC) has poor prognosis due to lack of effective and safe approach. In 2002, Professor Wang Junjie introduced CT-guidance into the field of LDR-BT, and fully applied 3D printing technology in BT in 2015, which met the requirement of preoperative LDR-BT planning, and significantly improving the precision, quality and efficiency of BT. In 2018, Professor Wang Junjie proposed the concept of stereotactic ablation brachytherapy (SABT). Chinese experts have attempted to treat RCC with BT for nearly two decades and accumulated certain clinical experience. Based on the 3D-printing template (3D-PT) assisted CT-guidance, the standard and consensus of BT for RCC were established, including the indications, dosimetric requirements, technological procedures and radiation protection, etc. At present, there is still a lack of phage Ⅲ clinical and evidence-based medicine for the treatment of RCC with 3D-PT guidance, which requires prospective multi-center, randomized studies to improve the evidence-based level of BT.

Objective:To evaluate the role of autophagy in ischemia postconditioning (IPO)-induced attenuation of intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 9-12 weeks, weighing 25-29 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (group S), intestinal I/R group (group IIR), group IPO and IPO plus 3-methyladenine (3-MA) group (group IPO+ 3-MA). The model of intestinal I/R was established by occlusion of superior mesenteric artery for 45 min followed by 2-h reperfusion in anesthetized animals.The mice underwent 3 cycles of 30-s reperfusion followed by 30-s ischemia before restoration of reperfusion in group IPO.Blood samples from the femoral artery were collected at 2 h of reperfusion for determination of concentrations of serum diamine oxidase (DAO), D-lactate (D-LA) and intestinal fatty acid binding protein (I-FABP). The animals were then sacrificed and intestinal tissues were removed for microscopic examination of the pathologic changes which were scored according to Chiu and for determination of the expression of autophagy-related proteins Beclin-1 and p62 (by Western blot). The water content of intestinal tissues was calculated. Results:Compared with group S, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, water content of intestinal tissues, and LC3Ⅱ/LC3Ⅰ ratio were significantly increased, Beclin-1 expression was up-regulated, and p62 expression was down-regulated in IIR, IPO and IPO+ 3-MA groups ( P<0.05). Compared with group IIR, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, water content of intestinal tissues, and LC3Ⅱ/LC3Ⅰ ratio were significantly decreased, Beclin-1 expression was up-regulated, and p62 expression was down-regulated in group IPO ( P<0.05). Compared with group IPO, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, and water content of intestinal tissues were significantly increased, LC3Ⅱ/LC3Ⅰratio was decreased, Beclin-1 expression was down-regulated, and p62 expression was up-regulated in group IPO+ 3-MA ( P<0.05). Conclusion:Autophagy is involved in ischemia postconditioning-induced attenuation of intestinal I/R injury in mice.

Overactive bladder is a syndrome characterized by urgent urination, often accompanied by frequent urination and nocturia. The incidence of the disease is high all over the world, and it has a great impact on the lives of patients, which has been paid more and more attention by scholars at home and abroad. It is currently estimated that 50 million to 100 million people worldwide suffer from the disease. Mirabegron is an agonist of human β-3 adrenergic receptor used to treat symptoms of overactive bladder. In this study, the synthesis process of mirabegron was improved based on literatures. Using p-nitrophenethylamine hydrochloride, R-(-)-mandelicacid and 2-aminothiazole-4-acetic acid as starting materials, the target product with high purity was obtained through four steps of amide condensation, carbonyl reduction, nitro reduction and amide condensation, and one-step purification, with a total yield of 39%. In this study, the hydrogen source of nitro reduction in step 3 was changed from hydrogen to ammonium formate, which increased the feasibility of industrialization, and mirabegron was refined to improve the purity of the product. The improved process has the advantages of simplified operation and mild reaction conditions, which provides a new method for the preparation and purification of mirabegron.

Objective To investigate the effect of different extraction methods on anti-inflammatory and analgesic activity of Anemone hupehensis.Methods The different abstracts were prepared from the whole herb of Anemone hupehensis.The analgesic effect was observed by adopting the mouse torsion and electric heating plate method,and the anti-inflammatory activity was comprehensively evaluated by using the mouse ear tumefaction,toe tumefaction and tampon granulation tumefaction exprements.Results Compared with the blank model group,the anti-inflammatory action difference of low dose in the water layer parts of mouse ear tumefaction,toe tumefaction and tampon granulation tumefaction had no statistical significance(P＞0.05),and the extracting parts of rest doses all had significant anti-inflammatory and analgesic effect (P＜0.05).Ethyl acetate part had strongest activity in the electric heating plate experiment.N-butanol part had strongest activity in the ear tumefaction,toe tumefaction,tampon granulation tumefaction experiments and torsion method.Conclusion The whole herb of Anemone hupehensis has prominent anti-inflammatory and analgesic effect,and the ethyl acetate part E and N-butanol part are main effective parts.

Objective To create multi-parameter analysis model by conventional two-dimensional echorcardiography( 2DE) and three-dimensional speckle tracking imaging( 3D-STI) in order to improve the early diagnosis in MYH7G + P- mutation carriers of familiar hypertrophic cardiomyopathy( HCM ) . Methods Twenty-eight MYH7 mutation carriers without left ventricular hypertrophy ( MYH7G + P- ) were enrolled as the research group , while 27 MYBPC3 mutation carriers without left ventricular hypertrophy ( MYBPC3G + P- ) were selected as the control group . The clinical data ,conventional 2DE and tissue Doppler imaging ( TDI) parameters of the two groups were acquired ,including the maximum of the thickness of interventricular septum( IVS) and left ventricular posterior ventricular wall thickness( LVPWT ) in end of diastole ,mitral flow E and A velocities ,E peak deceleration time( EDT ) ,atrioventricular filling time ,mitral annulus velocity of interventricular septum IVS-e' and lateral wall L-e' ,interventricular septum IVS-a' and lateral wall L-a' peak in diastole ,calculate mean value e' and a' ,and calculate E/ e' ,E/A ,left atrial volume index( LAVI) ,left ventricular mass index( LVMI) ,left ventricular ejection fraction( LVEF) and isovolumic relaxation time( IVRT ) ,isovolumic contraction time( IVCT ) . The global longitudinal peak strain( GLS) , global radial peak strain( GRS) ,global circumferential peak strain( GCS) and global area peak strain( GAS) were acquired by 3D-STI . All parameters were compared between research group and control group . Results Compared with the control group ,research group significantly increased in LAVI , maximum IVS and LVPWT ,LVMI and GAS( P < 0 .01) . There were no significant difference in TDI parameters( P > 0 .05) . For single parameter ,the area under ROC curve( AUC) were successively LVPWT > LAVI > IVS > LVMI >GAS( 0 .772 ,0 .738 ,0 .733 ,0 .719 ,0 .714 ,respectively) . AUC of multi-parameters was 0 .912 ,the sensitivity and specificity were 85 .2％ and 96 .3％ ,respectively . Conclusions Multi-parameter analysis model by conventional 2DE and 3D-STI can significantly improve the recognition efficiency of early diagnosis MYH7G + P- of familiar HCM . With further ,maximum LVPWT is an independent predictor of distinction MYH7G + P- and MYBPC3G + P- .