Objective To investigate the effect and mechanism of verteporfin (Vp) in airway remodeling of experimental asthma. Methods (1) Animal experiment: Twelve female BALB/c mice were divided into 3 groups (4 each): control group experimental asthma group and Vp intervention asthma group. Mice in experimental asthma group were treated by intranasal delivery of house dust mite (HDM) extract, in Vp intervention group were treated with intraperitoneal injection of Vp before HDM stimulation, and in control group was treated with the same amount of normal saline. Lung tissues and bronchoalveolar lavage fluid (BALF) of mice were collected, HE staining, Masson staining and Periodic Acid-Schiff (PAS) staining were used to observe the pathological changes of lung tissue, Wright-Giemsa staining was used to count the inflammatory cells in BALF, and the expressions of Yes-associated protein (YAP) and phosphorylated Yes-associated protein (p-YAP) in lung tissues were detected with immunohistochemistry, RT-PCR and Western blotting were performed to detect the expressions of YAP, p-YAP, osteopontin (OPN)and smooth muscle myosin heavy chain (SMMHC). (2) Cell experiment: Human airway smooth muscle cells (HASMC) were divided into control group (treated with the same amount of normal saline), HDM group (treated with 50 μg/ml HDM for 24 hours)and HDM+Vp group (treated with 0.05 mg/L Vp for 2 hours, and then with 50 μg/ml HDM for 24 hours). The cell proliferation of HASMC was detected by CCK-8. The apoptosis rate of HASMC were detected by flow cytometry. The protein levels of YAP, OPN and SMMHC in cells were detected by Western blotting. Results (1) Animal experiment: Compared with control group, the lung inflammation was aggravated, the bronchial basement membrane, airway smooth muscle (ASM) and airway wall were thickened in experimental asthma group [(1.13±0.38) μm vs. (0.79±0.36) μm, (6.49±2.36) μm vs. (4.56±1.52) μm, (33.85±5.95) μm vs. (22.08±3.30) μm, P<0.05]. The deposition proportion of collagen fiber around airway and PAS staining area increased(5.85%±2.35% vs. 0.36%±0.12%, 28.81%±5.89% vs. 13.57%±2.08%, P<0.01). The mRNA and protein expression levels of YAP and OPN increased (P<0.05 or P<0.01), and the ratio of p-YAP/YAP and the mRNA and protein expression levels of SMMHC decreased (P<0.05 or P<0.01). Compared with experimental asthma group, the lung inflammation was reduced, and the thickness of bronchial basement membrane, ASM and airway wall were thinned in Vp intervention group [(0.93±0.27) μm, (4.99±1.75) μm,(26.59±2.76) μm, P<0.05]. The deposition proportion of collagen fiber around airway and PAS staining area decreased obviously(2.14%±0.89%, 17.92%±1.89%, P<0.05). The mRNA and protein expression levels of YAP and OPN decreased markedly (P<0.05 or P<0.01), and the ratio of p-YAP/YAP and the mRNA and protein expression levels of SMMHC increased (P<0.05). (2) Cell experiment: Compared with control group, the cell proliferation ability was higher (0.2874±0.0055 vs. 0.2626±0.0051, P<0.01)and apoptosis rate was lower in HDM group (5.14%±0.82% vs. 6.75%±0.21%, P<0.05). The protein expressions of YAP and OPN increased (3.14±0.48 vs. 1.51±0.61, 5.87±2.42 vs. 0.94±0.23, P<0.01), while of SMMHC decreased (0.80±0.19 vs. 2.96±0.96,P<0.01). Compared with HDM group, the cell proliferation ability reduced (0.2748±0.0043, P<0.05) and apoptosis rate increased(6.29%±0.49%, P<0.05), the protein expressions of YAP and OPN decreased (2.02±0.53, 2.93±1.09, P<0.05), while of SMMHC increased (2.11±0.85, P<0.05) in HDM+Vp group. Conclusions The abnormal expression of YAP may be involved in the airway remodeling in experimental asthma, and Vp may restrain the airway remodeling in experimental asthma by decreasing the YAP activity and nuclear shift, and reversing the HASMC phenotypic transformation.

Objective To investigate the mechanism of artificial ulcer fibrosis of stenosis after full circumcision of esophageal mucosal dissection in porcine model based on TGF-β₁/Smads/ACTA2 signaling pathway. Methods A total of eight pigs were randomized into two groups (4 in each group): sham operation group and model group. Animals in the model group received full circumcision of ESD to establish the esophageal artificial ulcer fibrosis model. Three weeks after the surgery, we collected esophageal tissues from animals. We further analyzed the tissues with Hematoxylin-eosin (HE) staining to observe the pathological characteristics of esophageal tissues. The real-time quantitative polymerase chain reaction (qRT-PCR) was employed to detect the mRNA relative expression levels of TGF-β₁, Smad2, Smad3, and ACTA2. We then examined the positive expression of CTGF and ACTA2 using immunohistochemistry. Lastly, we detected the protein relative expression levels of TGF-β₁, Smad2/3,p-Smad2/3, Smad4, Smad7, CTGF, and ACTA2 using Western blotting. Results Compared with the sham operation group, the fibroblasts in the artificial ulcer site proliferated rapidly with a more transformed myofibroblast phenotype in the model group. In the model group, the qRT-PCR results showed up-regulated mRNA levels of TGF-β₁ (P<0.001), Smad3 (P=0.004), and ACTA2(P=0.001). The results of immunohistochemistry showed that the positive expression of CTGF (P<0.001) and ACTA2 (P<0.001)in the model group were higher than those in the sham operation group. We also observed up-regulated levels of TGF-β₁ (P=0.002),Smad2/3 (P=0.003), p-Smad2/3 (P=0.002), Smad4 (P<0.001), Smad7 (P=0.016), CTGF (P<0.001), and ACTA2 in the model group, compared with the sham operation group. Conclusion A porcine model of stenosis after full circumcision of esophageal mucosal dissection was successfully established, and the mechanism may be related to the artificial ulcer fibrosis by TGF-β₁/Smads/ACTA2 signaling pathway.

Objective To observe the effect of iron overload on the cardiac function of mice and cardiac myocytes ferroptosis of rats, and explore the mechanism of action of iron transporter receptor (TFRC) in cardiac myocytes ferroptosis of rats. Methods Fourteen C57BL/6J mice were randomly divided into normal-iron diet (NID) group and high-iron diet (HID)group (7 each), fed with normal diet or high-iron diet for 8 weeks, respectively. The mice cardiac function was then detected by echocardiography; The content of malondialdehyde (MDA) in the heart was detected with ELISA; Masson staining was performed to detect the cardiac fibrosis; Propidium iodide (PI) staining and lipophilic fluorescent dye (C11) were used to detect the cell mortality and the content of lipid peroxide. The effect was observed of ferric ammonium citrate (AIC) and ferroptosis inhibitor ferrostatin-1 (Fer-1) on the cardiac myocytes of H9C2 rat. H9C2 cells were treated with AIC and ferroptosis inducer Erastin,Western blotting was performed to detect the expression level of TFRC and glutathione peroxidase 4 (GPX4) protein, qRT-PCR was used to detect the mRNA level; at the same condition, small interfering RNA was applied to knock-down the expression of TFRC,detect the mortality of H9C2 cells and the content of lipid peroxide. Results Compared with mice in NID group, the mice in HID group showed obviously increased interventricular septal thickness (IVSd), left ventricular posterior wall thickness (LVPWd), MDA relative content and area of collagen deposition (0.96±0.12 vs. 0.73±0.09, 1.18±0.28 vs. 0.84±0.07, 2.08±0.8 vs. 1.00±0.50,4.04±0.60 vs. 1.00±0.21, P<0.05); But no significant difference between the two groups on left ventricular ejection fraction and shortening fraction. Treated with 500 μmol/L AIC, the death rate and lipid peroxide content of H9C2 increased obviously(33.73%±1.20% vs. 2.30%±1.73%, 5.36±0.06 vs. 1.00±0.19, P<0.05), while after treatment with Fer-1, the death rate and lipid peroxide content of H9C2 decreased markedly (19.63%±0.81% vs. 33.73%±1.20%, 2.03±0.12 vs. 5.36±0.06, P<0.05). Treated with 500 μmol/L AIC, the expression level increased obviously of TFRC in H9C2 cell (P<0.05), while knocked-down of TFRC, the cell death rate and the content of lipid peroxide induced by high-iron decreased markedly (P<0.05). Under inducement of Erastin,the expression levels of TFRC and GPX4 protein in H9C2 cells obviously up- and down-regulated, respectively; and after knocked-down of TFRC, the cell death rate induced by Erastin decreased markedly (P<0.05). Conclusions HID may induce the damage of myocardial ferroptosis, and TFRC participated in the pathologic process induced by iron overload, which may be as a new target point for the treatment of heart diseases.

Objective To screen and validate the traditional Chinese medicine (TCM) monomer that may regulate adipocyte function and improve obesity. Methods Data sets GSE70353 and GSE72158 were downloaded from Gene Expression Omnibus(GEO) database. The former contains 770 men (45-73 years old) with different BMI corresponding gene expression in subcutaneous white adipose tissue (SAT), and the latter contains 42 women (before and 1 year after bariatric surgery) corresponding SAT. The differentially expressed genes (DEGs) of data sets GSE70353 and GSE72158 in GEO were analyzed with R language, and the co-expressed DEGs of the two data sets were screened. Functional annotation Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of co-expressed DEGs were conducted by R language,protein-protein interaction (PPI) network construction and the hub genes screening were completed by STRING database and Cytoscape software. Connectivity map (cMAP) was used to screen the TCMs that can regulate the hub gene. The bergenin (0, 0.4, 2,10 μmol/L) and ginkgolide A (0, 0.01, 0.1, 1 μmol/L) were selected to treat mature white adipocytes (WAT) induced by 3T3-L1 cells for 24 h. The mRNA levels of interleukin-6 (IL-6) and peroxisome proliferator-activated receptor γ (PPARγ) were detected by qRT-PCR. Results There were 64 co-expressed DEGs in the two data sets, GO and KEGG analysis showed that DEGs were enriched in immune cell chemotaxis, complement-related cascade activation, and various inflammatory signaling pathway, responding to nutrient and lipid protein. The 18 hub genes [APOB (up-regulated), ACP5, C1QB, C1QC, CCL2, CCND1, CD163, CD68, FCER1G, ITGB2,MMP9, MS4A6A, MS4A7, PLEK, SPP1, TNFRSF11B, TYROBP, VSIG4 (down-regulated)] were identified by Cytoscape. Twenty-eight TCMs that could regulate hub genes were screened by cMAP, and 22 of them showed the ability of improving obesity. Compared with the control group, the mRNA level of PPARγ decreased in 0.4 μmol/L bergenin group and 0.1 μmol/L ginkgolide A group(P<0.05), and IL-6 mRNA levels decreased in 0.4 μmol/L bergenin group, 10 μmol/L bergenin group and 0.1 μmol/L ginkgolide A group (P<0.05). Conclusion A total of 28 TCMs were screened, of which 22 TCMs have been proved to be able to improve obesity.It has been initially confirmed in present study that bergenin and ginkgolide A could regulate the function of adipocyte.

Objective To screen the risk factors of preeclampsia and construct the predictive model of preeclampsia based on machine learning algorithm. Methods A retrospective study was conducted to collect the clinical data of 1609 hospitalized pregnant women from January 2016 to December 2018 on the big data platform of Academy of Medical Data Science of Chongqing Medical University. The 1609 cases were divided into preeclampsia group (n=291) and non-preeclampsia group (n=1318) according to the occurrence of preeclampsia during hospitalization. The clinical data of 70% patients were randomly selected as the training set (n=1126) to construct the prediction model, and the remaining 30% were used as the test set (n=483) for verification, and a consistency check between training set and test set was performed. The independent risk factors were screened by univariate analysis and logistic regression analysis, and the optimal parameters of LightGBM algorithm were searched by 5-fold cross-validation algorithm, and the prediction model was constructed based on LightGBM machine learning algorithm. Results A total of 58 indicators were collected, 13 indicators with missing rate ≥30% were excluded, and 45 indicators were finally included. Significant differences of 35 indicators existed between preeclampsia group and non-preeclampsia group (P<0.05) such as gamma-glutamyl transferase (GGT), alanine aminotrans ferase (ALT), thrombin time, aspartase transaminase (AST) and specific gravity of urine.Logistic regression analysis showed that specific gravity of urine, uric acid, hemoglobin concentration of erythrocyte, globulin, platelet distribution width, potassium ion, visiting age, family history of hypertension, systolic blood pressure, diastolic blood pressure,pulse and gestational age ≥34 weeks were independent risk factors for preeclampsia. The results of 5-fold cross-validation showed that, when num_leaves=5, max_depth=3, min_data_in_leaf=91, feature_fraction=0.8, bagging_fraction=0.6, and bagging_freq=5,the LightGBM model achieved the best effect the area under the curve (AUC), sensitivity and specificity of LightGBM model were 0.964, 84.9% and 92.7%. Conclusion The prediction model of preeclampsia based on LightGBM machine learning algorithm has a higher prediction effect, which can effectively predict the occurrence of preeclampsia in pregnant women in Chongqing, and provide decisions for clinicians.

Objective To investigate the influencing factors for prognosis in non-severe (mild to moderate) pulmonary acute respiratory distress syndrome (ARDS) patients, and evaluate the efficacy of the risk factors to predict the prognosis. Methods The data of 123 patients with non-severe pulmonary ARDS, hospitalized in the Department of Respiratory and Critical Care Medicine of Beijing Chaoyang Hospital (West Campus) from January 2017 to June 2021, were retrospectively enrolled, and divided into two groups according to 30-day survival condition, i.e., non-survivor group (n=45) and survivor group (n=78). Baseline characteristics, complications, arterial blood gas, blood routine, and levels of fibrinogen, C-reactive protein (CRP), procalcitonin,albumin and brain natriuretic peptide (BNP) were compared between the two groups. Kaplan-Meier and Cox survival analysis were adopted to analyze the risk factors which could affect the survival situation of patients with non-severe pulmonary ARDS.ROC curves were used to assess the efficacy of the risk factors to predict prognosis. Results Compared with survivor group, the proportion of patients with renal insufficiency, deep venous thrombosis and shock, APACHE Ⅱ score, body temperature, respiratory rate, neutrophil to lymphocyte ratio (NLR), fibrinogen and CRP levels in non-survivor group increased, and arterial partial pressure of carbon dioxide (PaCO₂), platelet count and albumin levels decreased (P<0.05). Kaplan-Meier survival analysis showed that kidney failure, deep venous thrombosis and shock were the risk factors of 30-day death in patients with non-severe pulmonary ARDS (P<0.05). Univariate Cox analysis demonstrated that heart rate, temperature, respiratory rate, PaCO₂, NLR, WBC, platelet count, fibrinogen, CRP, albumin and APACHE Ⅱ score were the risk factors of 30-day death in patients with non-severe pulmonary ARDS (P<0.05). Multivariate Cox analysis showed that higher APACHE Ⅱ score (HR=1.094, 95%CI 1.009-1.120, P=0.031), higher NLR (HR=1.087, 95%CI 1.012-1.167, P=0.021) and the presence of shock presented during course (HR=3.135, 95%CI 1.315-6.964, P=0.010) were independent risk factors for 30-day death of patients with non-severe pulmonary ARDS. The cut-off value of APACHE Ⅱ score and NLR in predicting mortality were 16.5 and 8.13, and the area under the curve (AUC) were 0.803 (95%CI 0.727-0.879) and 0.772 (95%CI 0.688-0.856), respectively. Conclusions APACHE Ⅱ score >16.5, NLR >8.13 and presence of shock were the independent risk factors of mortality for patients with non-severe pulmonary ARDS, and these factors could effectively predict prognosis.

Status epilepticus is one of the critical illnesses involving multiple clinical disciplines. Although treatment is comprehensive, rapid termination of status epilepticus episodes is critical. The purpose of this article is to provide an actionable approach to rapidly terminating status epilepticus episodes by organizing multidisciplinary experts to improve patient outcomes.In the consensus, the experts put forward the purpose of the consensus, the scope of adaptation, the method and clinical practice of rapid termination of status epilepticus, and discuss several issues that need to be paid attention to in the treatment of status epilepticus, hoping to provide clinicians with an alternative when faced with status epilepticus.

Radical hepatectomy is the well-established and highly effective therapeutic tool for early- and middle-stage hepatocellular carcinoma (HCC) to improve the survival. However, the majority of HCC patients in China are not amenable to surgical excision due to the advanced tumor stage at the initial diagnosis. Therefore, it is the bottom line to convert and downstage unresectable tumor into resectable tumor in clinical practice, which is an important means for improving patient survival rate and is currently a clinical research focus as well. In recent years, the rate of conversion surgery for unresectable advanced HCC has achieved dramatic improvement thanking to the accumulating effective therapeutic arsenals, and an increasing number of patients benefit from conversion therapy. Herein, several clinically relevant issues on conversion therapy for HCC were discussed in this review, including the definition of conversion therapy, the optimal selection of patients as well as conversion strategy, and the timing of sequential surgery together with strategy and safety of surgery.

Objective To summarize and analyze the composition features of large adrenal mass for guiding the clinical treatment. Methods The clinical data of 493 cases of large adrenal mass (≥4 cm), admitted in the Chinese PLA General Hospital from January 2016 to December 2020, were collected and retrospectively analyzed, including gender, age, reason for first visit,operation or not, postoperative pathological diagnosis and imaging data. According to the endocrine function evaluation results,all the cases were divided into functional adrenal masses (n=264) and non-functional masses (n=229), and then, according to the tumor nature, they were divided into benign masses (n=348) and malignant masses (n=145), the spectrum of large adrenal masses were analyzed. Results (1) The mean age was (47.7±14.3) years old. Adrenal incidentalomas is the mainly reasons for first visit (n=289, 58.6%). (2) Of the 493 patients reviewed, the proportion of functional adrenal masses (n=264) was higher than non-functional masses (n=229) [53.6% vs. 46.4%]. Pheochromocytomas occupied the highest proportion among functional masses(65.5%), Myelolipoma occupied the highest proportion among non-functional masses (22.3%). There was no significant difference in age, gender, lesion location and tumor diameter between functional masses group and non-functional masses group. (3) Of the 493 patients, the proportion of benign adrenal masses was higher than malignant masses [70.6% (348/493) vs. 29.4% (145/493)].Compared with benign masses, the tumor diameter in malignant masses group was significantly larger [(73.85±29.84) mm vs.(67.12±26.69) mm, P<0.05]. Pheochromocytoma occupied the first proportion in both benign (32.2%) and malignant masses(42.1%). There was no significant difference in age, gender, and lesion location between the two groups. Conclusions Among the patients with large adrenal mass (≥4 cm), pheochromocytomas occupied the highest proportion and adrenal incidentalomas was the mainly reasons for visiting doctors. Functional adrenal masses were more than non-functional adrenal masses, and benign masses were more than malignant adrenal masses. Malignant masses showed the larger tumor diameter.

Objective To investigate the current situation of patients with adrenocortical carcinoma (ACC) in China,for providing references to clinical diagnosis and treatment of ACC. Methods The information was collected of patients (from adrenocortical tumor patient group) definitely diagnosed as ACC from 2010 to 2019 by questionnaire, including gender, age, clinical manifestations, course of disease, surgical and adjuvant treatment methods and curative effects, and retrospective analysis was conducted. Results A total of 156 ACC patients were included with a male to female ratio of 1:1.33. Patients aged 40-60 years accounted for the highest proportion. Except one patient with bilateral adrenal tumors, the others were unilateral involved, and the proportion of left adrenal tumor was slightly higher than that of the right side. Eighty-one (51.9%) patients had adrenocortical hormone hypersecretion, 33 patients (21.2%) of them had manifestations of hypercortisolism such as full moon face, buffalo back,centripetal obesity, and muscle weakness, and 12 patients (7.7%) had spontaneous hypersecretion of two or more adrenal hormones, including cortisol. One hundred and forty-seven patients underwent surgery, of which open surgery accounted for the highest proportion (n=86, 55.1%), followed by laparoscopic surgery (n=51, 32.7%). The most common distant metastasis sites were liver(n=50, 32.1%), lung (n=46, 29.5%) and retroperitoneal lymph nodes (n=34, 21.8%). 79.5% of the studied population (n=124)used mitotane for adjuvant treatment, and 66.9% (n=83) of the patients started medication due to postoperative recurrence and metastasis. The median stable dosage of mitotane was 2.0 g. 64.4% (n=58) of the patients could achieve partial or complete response,26.7% (n=24) of the patients were in stable condition, and the remaining 8.9% (n=8) had disease progression. After the combined application of other adjuvant treatments was included in the analysis, no significant difference was observed in the response among the three groups of mitotane alone, mitotane combined with chemotherapy, and mitotane combined with other treatments (P>0.05). Conclusions Functional occupancy accounted for more than 50% in ACC patients, and the proportion of cortisol hypersecretion is the highest. Some patients are prone to retroperitoneal lymph node metastasis, therefore, lymph node dissection should be performed routinely in radical operations. As an essential adjuvant therapy, mitotane possesses high response rate when used alone or in conjunction with chemotherapy or other adjuvant medicines.