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 summarize the medication law of TCM in the treatment of chronic bronchitis;To provide reference for clinical medication.Methods Medical records of patients with chronic bronchitis who were hospitalized in the Respiratory Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 1,2016 to December 31,2021 were extracted based on HIS electronic medical record data.After screening,the TCM prescriptions used by patients with chronic bronchitis were input into Excel 2019 to establish a database.Based on the software Lantern 5.0,the latent structure model was learned,hidden variables and explicit variables were obtained,and the model was interpreted.SPSS Modeler 18.0 was used to establish model points with Apriori algorithm for Chinese materia medica with a frequency greater than 6%,to obtain the association rules between drugs,and to analyze the medication law of TCM in treating chronic bronchitis.Results A total of 3 410 cases were included,involving 423 kinds of Chinese materia medica,with a cumulative frequency of 82 766 times.Among them,109 kinds of Chinese materia medica with a frequency of>6 % had a cumulative frequency of 69 845 times.The top five commonly used medicines were Fritillariae Cirrhosae Bulbus,Poria,Atractyodis Macrocephalae Rhizoma,Asteris Radix et Rhizoma,Citri Reticulatae Pericarpium,mainly with medicines of reducing cough and phlegm,antiasthmatic medicine,tonifying deficiency,clearing heat,relieving superficies,promoting blood circulation and removing blood stasis.The medicinal properties were warming,cold and mild,and the main tastes were bitter,sweet and pungent,and the meridians were mainly lung,spleen,liver and stomach meridians.Through analysis of latent structure,49 hidden variables and 149 hidden classes were obtained.Combined with professional knowledge,10 comprehensive clustering models and 21 core formulas were deduced,such as Sangbaipi Decoction,Xuefu Zhuyu Decoction,Xiaoqinglong Decoction,Erchen Decoction,Shashen Maidong Decoction,Liuwei Dihuang Pills,Yinqiao Powder,Zhisou Powder,Yupingfeng Powder,Xuefu Zhuyu Decoction combined with Daotan Decoction,etc.It was concluded that the chronic bronchitis syndrome included phlegm-heat stagnation lung syndrome,qi stagnation blood stasis syndrome,cold fluid attacking lung syndrome,phlegm-dampness accumulation lung syndrome,lung qi and yin deficiency syndrome,kidney yin deficiency syndrome,wind heat attacking lung syndrome,wind cold attacking lung syndrome,lung qi and spleen deficiency syndrome,phlegm stasis interjunction syndrome.A total of 41 strong association rules were screened in the analysis of association rules,including 5 strong association rules for two and 36 strong association rules for three.The high confidence rules were Saposheikovize Radix + Angelicae Sinensis Radix →Atractyodis Macrocephalae Rhizoma,Saposheikovize Radix + Codonopsis Radix → Atractyodis Macrocephalae Rhizoma,Codonopsis Radix + Citri Reticulatae Pericarpium → Atractyodis Macrocephalae Rhizoma;the higher degree of improvement were Bupleuri Radix + Mori Cortex → Scutellariae Radix,Perillae Fructus + Belamcandae Rhizoma → Fritillariae Cirrhosae Bulbus,Armeniacae Semen Amarum + Pinelliae Rhizoma → Citri Reticulatae Pericarpium,etc.Conclusion In the treatment of chronic bronchitis,TCM is mainly used to reduce phlegm,relieve cough and asthma,and the method of promoting blood circulation and removing blood stasis is commonly used to help eliminate phlegm.In addition,TCM pays attention to the application of methods such as tonifying lung and securing the exterior,invigorating spleen and benefiting qi.

【Objective】 To evaluate the efficacy and safety of intravaginal fractional superpulse CO2 laser in the treatment of mild to moderate female stress urinary incontinence (SUI), so as to provide reference for the treatment options for female SUI. 【Methods】 A total of 41 female mild-to-moderate SUI patients confirmed at the Department of Urology, The First Affiliated Hospital, Air Force Medical University, during Aug.2019 and Nov.2020 were involved.All patients received 3 intravaginal fractional superpulse CO2 laser treatments (1/month).The improvement of urinary incontinence symptoms after treatment was evaluated with International Consultation on Incontinent Questionnaire Short Form (ICI-Q-SF).The motion of bladder neck and rotation angle of bladder and urethra were measured with pelvic ultrasound before and after treatment.The therapeutic effects, pain and patients’ satisfaction were evaluated, and adverse reactions such as bleeding, infection and scar were observed. 【Results】 Three months after treatment, urinary incontinence symptoms improved to varying degrees, the ICI-Q-SF score decreased, the motion of bladder neck [ (28.70±3.11) mm vs.(19.10±4.54) mm] and the vesicourethral rotation angle [(52.78°±15.79°) vs.(41.56°±13.24°)] significantly decreased (P<0.05).The total effective rate was 100.0%.No patients complained severe pain during treatment.All patients were satisfied with the treatment.No adverse reactions such as bleeding, infection or scar occurred. 【Conclusion】 Intravaginal fractional superpulse CO2 laser is effective and safe in the treatment of mild to moderate female SUI, but the long-term efficacy still needs further observation.

Objective:To observe the changes of pelvic floor structure and function in female vaginal laxity after CO 2 fractional laser transvaginal treatment. Methods:This study reviewed the improvement of pelvic floor structure and function after CO 2 fractional laser transvaginal treatment in 28 female patients [aged 26-59 (37.5±8.3) years] with vaginal laxity syndrome seen at the Department of Dermatology, the First Affiliated Hospital of Air Force Medical University from March 2020 to November 2021. A total of 28 female patients with vaginal laxity syndrome underwent intravaginal treatment by CO 2 fractional laser instrument once/month for 3 times. The clinical efficacy and safety were evaluated according to the pre- and post-treatment transverse vaginal diameter, FSFI score of female sexual function, VHIS score of vaginal environment, vaginal tactile imaging system (VTI), pelvic ultrasound and MRI, tissue biopsy, patient satisfaction, pain score, and postoperative adverse effects. Results:Twenty-one of the twenty-eight female patients with vaginal laxity syndrome showed significant improvement in symptoms related to vaginal laxity syndrome after intravaginal treatment with CO 2 fractional laser therapy. All patients showed improvement in all indexes before and 1 month after treatments the mean vaginal transverse diameter decreased from (3.00±0.39) fingers to (2.71±0.40) fingers ( P<0.05), VHIS increased from (17.12±3.97) to (21.69±3.61) ( P<0.05), FSFI score improved from (23.11±3.70) to (27.43±5.33) ( P<0.05), and VTI examination showed that vaginal muscle strength and elasticity were improved to different degrees, and there was a statistical difference compared with that before treatment (total contractility of the anterior vaginal wall: t=26.23, P<0.001; total contractility of posterior vaginal wall: t=39.02, P<0.001; the mean contractility of the anterior vaginal wall: t=17.92, P<0.001; the mean contractility of the posterior vaginal wall: t=22.57, P<0.001). At the same time, questionnaire score of international consultation on incontinent questionnaire short form (ICI-Q-SF scale) of 13 patients with combined mild to moderate stress urinary incontinence showed a statistically significant decrease compared with those before treatment (8.97±2.99 before treatment and (7.18±1.79) one month after treatment; t=2.792, P<0.01). Pelvic ultrasound and magnetic resonance examination indicated a tightening of the vaginal wall structure, and pelvic ultrasound observed a significant decrease in bladder neck mobility and a significant decrease in vesicourethral rotation angle. Vaginal tissue biopsy indicated an increase in the thickness of the vaginal mucosa and an increase in the number and more regular arrangement of collagen fibers after treatment. All patients had high treatment satisfaction and there were no adverse effects such as infection and bleeding during the treatment. Conclusions:Transvaginal CO 2 fractional laser treatment can improve the pelvic floor structure and function around the vagina, treat female vaginal laxity syndrome, stress urinary incontinence and female sexual dysfunction, with significant clinical efficacy and good safety.

Objective:To explore whether cytoplasmic linker protein 170(CLIP170)affects papillary thyroid cancer(PTC)cell metastasis and invasion and clarify the underlying mechanisms.Methods:We analyzed CLIP170 expression levels in PTC using GEO and TCGA data and con-structed CLIP170 knockdown(CLIP170KD)cells using lentiviral transfection.Then,we evaluated their functions through Transwell transfer and invasion assays.We assessed how CLIP170 affected the cellular actin structure via immunofluorescence analysis.We detected transforming growth factor-β 1(TGF-β1)release in the cell culture medium using enzyme-linked immunosorbent assay(ELISA).We also assessed epithelial-mesenchymal transition(EMT)and TGF-β signaling pathway molecule expression using immunoblotting and reverse-transcription quantitat-ive fluorescence PCR and validated the results in a nude mouse lung metastasis model.Results:CLIP170 expression level in PTC was lower than that in normal thyroid tissue.Regarding the function,CLIP170KD significantly enhanced PTC cell metastasis both in vitro and in vivo.Re-garding the underlying mechanism,CLIP170KD triggered TGF-β pathway activation,subsequently promoted tumor cell migration and invasion.The inhibitor of TGF-β effectively inhibited TGF-β activation,and this inhibition significantly reversed the CLIP170KD-induced tumor metastasis.Conclusions:CLIP170 could be a promising therapeutic target to mitigate metastatic tendencies in PTC.

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 prepare a new antibacterial agent triggered by near infrared light to combat bacterial infection and promote wound healing. METHODS The synthesis of antibacterial agengt was supported by the results from transmission electron microscopy, Ultraviolet-visible absorption spectroscopy and Fourier-transform infrared spectroscopy. The antibacterial agent was irradiated under near infrared(NIR) laser with different concentrations to study the photothermal properties. Release of ciprofloxacin from the antibacterial agent was determined under different conditions. Observed antibacterial activity of the agent by spread plate method and bacterial growth curve. The infected wound was made on the back skin of mice, and the mice were treated with different methods to observe the healing process of the wound and study its influence on the wound healing. RESULTS The synthesized antimicrobial agent could be heated repeatedly without attenuation under near-infrared light, and could still reach a high temperature of 45 ℃ at a low concentration of 125 µg·mL-1. At the same time, it could promote the release of loaded antibiotics, and the release rate reached 86%. Compared with 200 µg·mL-1 solution obtained by physical mixing of polydopamine and ciprofloxacin, the synthesized antimicrobial agent combined with near-infrared light showed more excellent antibacterial ability, and the bacteriostatic rate against Escherichia coli and Staphylococcus aureus was 99.9%. Antimicrobial agents with concentrations of only 0.312 5 µg·mL-1 and 1.25 µg·mL-1 combined with near infrared light significantly inhibited the growth of Escherichia coli and Staphylococcus aureus. Through the mouse skin defect model infected by Staphylococcus aureus, it was proved that the synthetic antibacterial agent still had excellent antibacterial effect in practical application, and could accelerate the healing of infected wound. CONCLUSION The synthesized antimicrobial agents have excellent antibacterial effect in vitro, and still have good antibacterial effect and promote wound healing under the conservative power irradiation without causing skin damage in vivo.

With the application of immune checkpoint inhibitors (ICIs), the acute kidney injury (AKI) caused by ICIs has attracted increasingly extensive attention. The incidence of ICIs-induced AKI is 0.8%-29%, which can occur weeks or months after the first drug use or even after drug withdrawal. The typical renal histopathological features of AKI are acute tubulointerstitial nephritis, and glomerulopathy can also be seen. The risk factors include combined application of ICIs, the use of proton pump inhibitors, and having chronic kidney diseases, etc. After the diagnosis of AKI, it is necessary to decide whether to reduce the dose or stop using ICIs and start glucocorticoid treatment or add other immunosuppressive drugs according to the degree of disease and the specific situation of the patient. In case of level 3-4 AKI, ICIs shall be permanently discontinued.

Objective:To explore the characteristics and factors affecting the occurrence of renal injury in patients with abnormal biochemical indexes of renal function after the use of immune checkpoint inhibitors (ICIs), and to provide reference for selection of clinical treatment regimen.Methods:Patients who were treated with immune checkpoint inhibitors researched and developed independently in China including camrelizumab, sintilimab, tislelizumab, and toripalimab from March 1, 2021 to February 28, 2022 and showed estimated glomerular filtration rate (eGFR) <90 ml/(min·1.73 m 2) and/or serum creatinine (Scr)>105 μmol/L were retrieved from the China Hospital Pharmacovigilance System. The clinical data including general information, anti-tumor treatment regimen, laboratory test results, and concomitant medications were collected. Patients were divided into kidney injury group and non-kidney injury group, and all the clinical characteristics were compared between the 2 groups, the influencing factors of kidney injury were analyzed using a binary logistic regression model, the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated. Results:A total of 222 patients were entered in the analysis, including 170 males and 52 females, with a median age of 67 (36, 85) years. Of them, 144 patients were treated with carrilizumab, 38 with sindilizumab, 31 with tirelizumab, and 9 with treprolizumab; 29 patients (13.1%) developed kidney injury, including 26 cases of grade 1 and 3 cases of grade 2 renal injuries; the time of renal injury occurrence was 19-355 days after the first application of ICIs, and the median time was 108 days. After diagnosed of kidney injury, 13 out of 29 patients stopped ICIs, of which 6 had recovered kidney function and 7 had no improvement; 16 patients continued the ICIs treatment, of which 10 patients had recovered or improved kidney function and 6 had no improvement. The clinical characteristics of patients in the 2 groups were compared, and 10 variables including age, gender, baseline renal function, previous use of carboplatin, previous radiotherapy, combined chemotherapy containing cisplatin, combined paclitaxel chemotherapy, combined tyrosine kinase inhibitor (TKI) anti-vascular therapy, combined proton pump inhibitors, and combined radiotherapy were screened for the binary logistic regression analysis. The results showed that female ( OR=3.046, 95% CI: 1.149-8.077), ≤65 years ( OR=3.649, 95% CI: 1.435-9.274), combined TKI anti-vascular therapy ( OR=4.773, 95% CI: 1.496-15.227), and combined radiotherapy ( OR=8.655, 95% CI: 1.268-59.076) were independent risk factors for the development of kidney injury. Conclusions:The incidence of kidney injury in patients with eGFR <90 ml/(min·1.73 m 2) and/or Scr >105 μmol/L after using ICIs is 13.1%. In these patients, female, ≤65 years, combined TKI anti-vascular therapy, and combined radiotherapy may be risk factors for the development of ICI-associated kidney injury.

With the application of immune checkpoint inhibitors (ICIs), the acute kidney injury (AKI) caused by ICIs has attracted increasingly extensive attention. The incidence of ICIs-induced AKI is 0.8%-29%, which can occur weeks or months after the first drug use or even after drug withdrawal. The typical renal histopathological features of AKI are acute tubulointerstitial nephritis, and glomerulopathy can also be seen. The risk factors include combined application of ICIs, the use of proton pump inhibitors, and having chronic kidney diseases, etc. After the diagnosis of AKI, it is necessary to decide whether to reduce the dose or stop using ICIs and start glucocorticoid treatment or add other immunosuppressive drugs according to the degree of disease and the specific situation of the patient. In case of level 3-4 AKI, ICIs shall be permanently discontinued.