Objective To explore the impact of sinomenine on bleomycin A5-induced pulmonary fibrosis (PF) in rats and the underlying mechanism. Methods MRC-5 cells were cultured and treated with sinomenine to determine its optimal concentration and time through the MTT assay. Subsequently, MRC-5 cells were incubated with 80 μmol/L sinomenine for 48 hours or transfected with miR-21 mimic/a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1) siRNA prior to sinomenine treatment. The expression of miR-21, ADAMTS-1, collagen type 1 (Col1) and collagen type 3 (Col3) was detected by quantitative real-time PCR (qRT-PCR) and/or Western blot analysis. Thirty SD rats were randomly divided into control group, sinomenine group and sinomenine combined with miR-21 agomir group, with 10 animals in each group. Bleomycin A5 were intratracheally administered to establish the PF model. Then, rats in control group, sinomenine group and sinomenine +miR-21 agomir group were treated with 9 g/L sodium chloride solution, sinomenine and sinomenine+miR-21 agomir, respectively. On day 28, all rats were sacrificed. HE and Masson staining was performed in pulmonary tissue. The expression of ADAMTS-1, Col1 and Col3 in pulmonary tissue were detected by qRT-PCR and/or Western blot analysis. ELISA was used to measure serum procollagen type 1 carboxyterminal propeptide (P1CP) and procollagen type 3 aminoterminal propeptide (P3NP) levels. Results Administration of sinomenine decreased miR-21 levels, up-regulated ADAMTS-1 expression, and promoted Col1 and Col3 degradation in MRC-5 cells. Importantly, interfering with the miR-21/ADAMTS-1 signaling pathway partially reversed the promotive effect of sinomenine on Col1 and Col3 degradation. Treatment of SD rats with sinomenine reduced alveolitis and PF scores, decreased serum P1CP and P3NP levels, up-regulated pulmonary ADAMTS-1 expression, and down-regulated Col1 and Col3 expression. However, these effects were reversed by miR-21 agomir. Conclusion Sinomenine promotes Col1 and Col3 degradation and inhibits PF in rats by miR-21/ADAMTS-1 pathway.
Rats ; Animals ; Pulmonary Fibrosis/genetics* ; Procollagen/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Bleomycin/adverse effects* ; Collagen Type III/metabolism* ; MicroRNAs/metabolism*

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

AIM: To explore the protective effects of sinomenine (SIN) on oxidative stress and pulmonary fibrosis and its relationship with the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. METHODS: MRC-5 cells were treated with hydrogen peroxide (H2O2) to establish the oxidative stress injury model, followed by administration with SIN. Cell viability was detected using the CCK-8 method. The biochemical kits were employed to measure malondialdehyde (MDA) content and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities. The protein expression of Keap1 and Nrf2 was examined by western blot. Thirty SD rats were randomly divided into control group, bleomycin A5 (BLM) group and BLM + SIN group, with 10 animals in each group. Bleomycin A5 were intratracheally administered to the rats in BLM group and BLM+SIN group to establish the pulmonary fibrosis model. The rats in control group received the same volume of 9 g/L sodium chloride solution. The second day after model construction, the rats in BLM+SIN group were gavaged with SIN, while the rats in the other two groups were treated with 9 g/L sodium chloride solution. On day 28, all rats were sacrificed. Pulmonary tissue was isolated, and HE and Masson staining was performed to observe the pathological changes. The MDA content and SOD, GSH-Px and CAT activities in pulmonary tissue were evaluated. Western blot was used to assay pulmonary tissues Keap1 and Nrf2 protein expression. RESULTS: When compared with H2O2 group, SIN treatment increased cell viability, decreased MDA content, elevated SOD, GSH-Px and CAT activities, down-regulated Keap1 expression, and promoted nuclear translocation of Nrf2 in MRC-5 cells. In comparison with BLM group, administration of SIN decreased alveolitis and pulmonary fibrosis pathological changes and scores as well as pulmonary tissue MDA content, enhanced pulmonary tissues SOD, GSH-Px and CAT activities, down-regulated pulmonary tissues Keap1 expression, and raised Nrf2 levels in the nucleus. CONCLUSION: SIN alleviates oxidative stress and pulmonary fibrosis possibly by activating the Keap1/Nrf2 signaling pathway.

Influenza B virus (IBV) is more likely to cause complications than influenza A virus (IAV) and even causes higher disease burden than IAV in a certain season, but IBV has received less attention. In order to analyze the genetic evolution characteristics of the clinical strain IBV (B/Guangxi-Jiangzhou/1352/2018), we constructed genetic evolution trees and analyzed the homology and different amino acids of hemagglutinin and neuraminidase referring to the vaccine strains recommended by World Health Organization (WHO). We found that strain B/Guangxi-Jiangzhou/1352/2018 was free of interlineage reassortment and poorly matched with the vaccine strain B/Colorado/06/2017 of the same year. We also determined the median lethal dose (LD₅₀) and the pathogenicity of strain B/Guangxi-Jiangzhou/1352/2018 in mice. The results showed that the LD₅₀ was 10^5.9 TCID₅₀ (median tissue culture infective dose), the IBV titer in the lungs reached peak 1 d post infection and the mRNA level of the most of inflammatory cytokines in the lungs reached peak 12 h post infection. The alveoli in the lungs were severely damaged and a large number of inflammatory cells were infiltrated post infection. The study demonstrated that the clinical strain IBV (B/Guangxi-Jiangzhou/1352/2018) could infect mice and induce typical lung inflammation. This will facilitate the research on the pathogenesis and transmission mechanism of IBV, and provide an ideal animal model for evaluation of new vaccines, antiviral and anti-inflammatory drug.
Amino Acids/genetics* ; Animals ; Antiviral Agents/pharmacology* ; China ; Cytokines/metabolism* ; Hemagglutinins/metabolism* ; Humans ; Influenza B virus/pathogenicity* ; Influenza, Human/virology* ; Mice ; Neuraminidase/genetics* ; Orthomyxoviridae Infections/virology* ; Phylogeny ; RNA, Messenger/metabolism* ; Virulence/genetics*

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Objective:To explore the potential of dosiomics in predicting the incidence of radiation pneumonitis by extracting dosiomic features of definitive radiotherapy for lung cancer, and building a machine learning model.Methods:The clinical data, dose files of radiotherapy, planning CT and follow-up CT of 314 patients with lung cancer undergoing definitive radiotherapy were collected retrospectively. According to the clinical data and follow-up CT, the radiation pneumonia was graded, and the dosiomic features of the whole lung were extracted to establish a machine learning model. Dosiomic features associated with radiation pneumonia by LASSO-LR with 1000 bootstrap and AIC backward method with 1000 bootstraps were selected. Training cohort and validation cohort were randomly divided on the basis of 7:3.Logistic regression was used to establish the prediction model, and ROC curve and calibration curve were adopted to evaluate the performance of the model.Results:A total of 120 dosiomic features were extracted. After LASSO-LR dimensionality reduction, 12 features were selected into the "feature pool".After AIC, 6 dosiomic features were finally selected for model construction. The AUC of training cohort was 0.77(95% CI: 0.65 to 0.87), and the AUC of validation cohort was 0.72 (95% CI: 0.64 to 0.81). Conclusion:The dosiomics prediction model has the potential to predict the incidence of radiation pneumonia, but it still needs to include multicenter data and prospective data.

Objective:To investigate the clinicopathological and molecular characteristics of pulmonary enteric adenocarcinoma (PEAC).Methods:The clinical and pathological data of 19 cases of PEAC in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively collected from 2015 to 2019. Immunohistochemistry (IHC) was used to detect the relevant immunophenotypes, amplification refractory mutation system (ARMS) and fluorescence in situ hybridization (FISH) were used to detect the expression of EGFR, KRAS and ALK genes. The patients were followed up, and the relevant literature was reviewed and analyzed.Results:There were 19 cases, including 10 males and 9 females, with a mean age of 58 years (range 33-71 years). Microscopically, the tumors showed moderately to highly differentiated adenoid and/or papillary growth patterns. The tumor cells were highly columnar and sometimes showed pseudostratification. Inflammatory necrosis and scattered nuclear fragmentation were seen in some glandular lumens. IHC showed variable expression of CK7 (19/19), TTF1 (8/19), Napsin A (6/19), villin (17/19), CK20 (16/19) and CDX2 (10/19). Molecular testing showed KRAS mutation in nine cases (9/19), EGFR mutation in one case (1/19), and positive ALK split signal in one case (1/19). In the literature, the reported mutation rate of KRAS in PEAC was much higher than that of EGFR and ALK. All 19 cases underwent surgical resection and 11 cases were subjected to chemotherapy or radiotherapy.Conclusions:PEAC is a rare variant of invasive pulmonary adenocarcinoma, and has similar histological and cytological features to that of colorectal adenocarcinoma. However, detailed medical history, histologic heterogeneity, an IHC combination of CK7 +/villin + and high KRAS mutation rate are the key points of diagnosis. The prognosis needs long-term follow-up and big data statistics.

Objective Acute pancreatitis exhibits different clinical and ultrasonic features in patients complicated with acute acalculous cholecystitis ( AAC) at different stages .The aim of this study was to analyze the ultrasonic characteristics of acute pancreati-tis complicated with AAC at different stages . Methods We retrospectively analyzed the clinical data about 41 cases of acute pancrea-titis with moderate to severe AAC .According to whether AAC developed within or after 2 weeks of the onset of acute pancreatitis , we divided the patients into an early-stage group (n=18) and a late-stage group (n=23).We recorded the gallbladder size, gallbladder wall thickness , fluid around the gallbladder , biliary sludge deposition and the Murphy′s sign by ultrasonography , obtained AAC-related clinical and laboratory data concerning body temperature , Murphy′s sign, WBC count and C-reactive protein level , and analyzed the ultrasonic features of AAC at different stages in the acute pancreatitis patients. Results All the patients experienced a fever of >38.5℃, 38.89%with chills in the early onset group and 47.83%in the late onset group .Increases were observed in patients of the early-and late-stage groups in the WBC count ( 94.44%vs 82.61%) , the C-reactive protein level ( 100%vs 91.30%) , and the fluid volume around the gallbladder (94.44%vs 60.86%, P<0.05), but incidence rate of gallbladder wall thickening was significantly lower in the former than in the latter group (11.11%vs 78.26%, P<0.01). Conclusion AAC developing at different stages of acute pancreatitis has different ultrasonic features , with higher incidence rates of fluid around the gallbladder in the early stage and gallbladder wall thickening in the late stage.

Objective To investigate the effect of systematic health education on the ultrasound guided interventional therapy for pa -tients with cysts.Methods Totally 181 patients with cysts who received the ultrasound guided interventional therapy in our hospital ,were randomly divided into observation group and control group .The patients in the observation group received systematic health education ,while patients in control group received convention health education .Results The differences of pain score between two groups were statistical significance(P<0.05).By health education,the patients in the observation group had a deeper knowledge of the operation and became more cooperative(P<0.05).Conclusion Systematic health education could alleviate the pain and improve the psychological indisposition reac -tions of patients,and enhance therapeutic compliance of patients with ultrasound guided interventional therapy .In the meantime,systematic health education could improve the quality of work and enhance the diathesis of paramedic .

Objective To analyze the misdiagnosis reasons in renal tumors with contrast-enhanced ultrasound (CEUS) and to improve cognition on CEUS. Methods Two-hundred and eighty-five cases were compared with pathology, the images in 22 cases misdiagnosed on CEUS were reviewed retrospectively and the reasons were analyzed. Results The diagnosis accuracy and misdiagnosis rate of CEUS were 92. 28 % (263/285) and 7. 72%(22/285), respectively. In these 22 cases, 9 cases misdiagnosed as renal cell carcinoma (RCC) were conformed by pathology as renal angiomyolipoma(RAMD), showed 5 cases "fast wash-in and fast wash-out", 4 cases "fast wash-in and slowly wash-out". Seven cases were conformed as RCC, in which 5 were misdiagnosed as RAML, showed 4 cases "fast wash-in and slowly wash-out", 1 cases "simultaneously wash-in and simultaneously wash-out", and 2 were misdiagnosed as renal cyst with no enhancement founded. Four cases misdiagnosed as hematoma were conformed as pyelo-carcinoma, with no enhancement founded in renal pelvis. The remaining 2 cases misdiagnosed as inflammatory pseudotumor were conformed as RCC, showed "fast wash-in and slowly wash-out". Conclusions With the high diagnosis accuracy,CEUS is an important method in diagnosis of renal tumors. Analyzing the misdiagnosed reasons may improve the cognition on CEUS and decrease the misdiagnosis.