OBJECTIVE To explore the therapeutic effect and safety of Maiwei Yangfei Decoction(MWYF)in the treatment of idiopathic pulmonary fibrosis of qi-yin deficiency type.METHODS A total of 58 patients with idiopathic pulmonary fibrosis of qi-yin deficiency type were randomly divided into an experimental group and a control group with 29 cases in each group according to a 1:1 ratio.Two cases dropped out of the experimental group and three cases dropped out of the control group.The control group received standardized treatment of Western medicine,and the experimental group received MWYF on the basis of the treatment of the control group.The treatment course of both groups was 3 months.The TCM syndrome score,lung function,6-minute walking distance(6MWD),transcutaneous blood oxygen saturation(SpO2),high-resolution computed tomography(HRCT)score,St.George's respir-atory questionnaire(SGRQ)score and serum sialoglycoprotein antigen(KL-6)level of the two groups were compared before and after treatment.Blood routine and liver and kidney function of the two groups were detected before and after treatment,and the occurrence of adverse reactions during treatment was recorded.RESULTS After treatment,the total score of TCM syndrome of the two groups was significantly improved(P<0.01),and the experimental group was better than the control group(P<0.01);the DLCO%of the experi-mental group increased(P<0.05),and the experimental group was higher than the control group(P<0.05).The experimental group showed significant improvement in 6MWD,HRCT grid shadow,SGRQ symptom score and total score,and serum KL-6 level(P<0.05,P<0.01),which was better than the control group(P<0.05,P<0.01).No serious adverse events occurred in either group dur-ing the treatment.CONCLUSION MWYF combined with standardized Western medicine treatment can effectively improve the clini-cal symptoms of patients with idiopathic pulmonary fibrosis of qi-yin deficiency type,reduce the expression level of serum KL-6,and has a definite effect and good safety.

Objective: To examine the effect of SiO2 exposure on the airway surface microenvironment and NIMA-related kinase 7 (NEK7)/nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome in rats. Methods: Twenty-four specific pathogen-free male rats of the SD strain were randomly divided into the control group and the model group, of 12 rats in each group. Rats in the model group were given SiO2 suspensions through disposable tracheal intubation perfusion to model silicosis in rats, while rats in the control group was perfused with the same amount of physiological saline. The pH value and glucose level were measured in the rat bronchoalveolar lavage fluid (BALF) 14 and 28 days after modeling. Lung tissues were stained with HE and Masson and the distribution of inflammatory cells and the deposition of pulmonary interstitial collagens were observed in lung tissues under a light microscope. The expression of transforming growth factor β1 (TGF-β1), collagen type Ⅰ(ColⅠ), collagen type Ⅲ (Col Ⅲ), interleukin-1β (IL-1β), NLRP3, N-terminal domain of Gasdermin D (GSDMD-NT), caspase-1, and NEK7 was quantified in lung specimens using immunohistochemistry. Results: Lower pH values were measured in rat BALF in the model group than in the control group 14 [(6.38±0.05) vs. (6.68±0.08), P<0.05] and 28 days after modeling [(6.63±0.14) vs. (6.86±0.05), P<0.05], while higher glucose levels were seen in the model group than in the control group 14 [(0.39±0.06) vs. (0.31±0.04) mg/dL, P<0.05] and 28 days after modeling [(0.39±0.08) vs. (0.31±0.06) mg/dL, P<0.05]. HE and Masson staining showed mild to moderate alveolitis and pulmonary fibrosis in rats 14 days post-exposure to SiO2, and showed moderate to severe alveolitis and pulmonary fibrosis 28 days post-exposure. Immunohistochemistry detected higher TGF-β1, ColⅠ, Col Ⅲ, IL-1β, NLRP3, GSDMD-NT, caspase-1 and NEK7 expression in rat lung tissues in the model group than in the control group (all P<0.05). Conclusions SiO2 exposure may cause changes in rat airway surface microenvironment, including BALF acidification and elevated glucose. Pyroptosis induced by activation of NEK7-associated NLRP3 inflammasome may be an important mechanism of pulmonary fibrosis caused by silicosis.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1β release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.

Silicotic nodules and pulmonary fibrosis are histopathological appearance in silicosis patients after long-term inhalation of crystalline silica particles, and are difficult to reverse and recover. Research on the pathogenesis and treatment strategies of silicosis has significantly lagged behind medical progress and clinical needs, resulting in the disease remaining a thorny clinical problem. Traditional Chinese medicine extracts or compound preparations have become a hot issue in exploring silicosis treatment strategies in recent years. This paper described the main pathological processes of pulmonary fibrosis caused by silicosis, followed by introducing its main pathogenesis mechanisms, including transforming growth factor-β1 (TGF-β1)/Smad signaling pathway, oxidative stress reaction, apoptosis, and autophagy. In addition, it briefly described the research progress, targets, and intervention effects of selected traditional Chinese medicine extracts, which provides a scientific basis for the theoretical and clinical research of traditional Chinese medicine extracts in inhibiting pulmonary fibrosis. To change the clinical status quo of silicosis fibrosis which is difficult to control and reverse, the paper proposed that we can further explore the pathogenesis and progression mechanisms of silicosis and drug treatment strategy, and focus on the transformation of basic research into clinical practice.

Endometrial cancer has been identified by The Cancer Genome Atlas program with four molecular subtypes by genome sequence analysis. Clinical trials to select suitable immunotherapeutic agents based on the different immune characteristics of each subtype have been conducted in several countries and have made important progress. The main clinical applications of immune checkpoint inhibitors include anti-programmed cell death protein-1/programmed death-ligand 1 antibodies and poly ADP-ribose polymerase inhibitors. Optimizing drug selection and drug combination based on the target characteristics of different immune checkpoint inhibitors may provide new opportunities for immunotherapy of endometrial cancer and bring new light to improve survival rates.

Objective: To investigate the correlation between the proliferation inhibition effect of glucocorticoid (GC) on peripheral blood mononuclear cell (PBMC) and the pure tone average (PTA) improvement in SSNHL patients. Methods: Sixty inpatients with SSNHL were included from July 2013 to October 2015 in Nanjing Drum Tower Hospital, Medical School of Nanjing University. Peripheral venous blood was collected before receiving treatment, then the PBMC was isolated for GC proliferation inhibition. PBMCs of each patient were cultivated into 4 groups: Group A: PBMCs+ Medium; Group B: PBMCs+ Medium+ lipopolysaccharide (LPS, 1 μmol/L); Group C: PBMCs+ Medium+ LPS+ Dexamethasone; Group D: Medium. PBMCs were maintained in a humidified 5% CO₂ atmosphere at 37°C and were observed after 24 hours. 5-diphenyltetrazolium bromide (MTT) was used to measure PBMC proliferation inhibition rate. The PBMC proliferation inhibition rates were calculated according to the absorbance at 490 nm wavelength under a microtiter plate reader. Independent sample t tests of PBMC proliferation inhibition rate were performed between different groups. χ² tests were performed between gender, affected ear side, accompanied by vertigo or not, audiometric curve, time period from onset to treatment, PBMC proliferation inhibition rate and the improvement of pure tone average (PTA). Linear correlation analyses were performed between PBMC proliferation inhibition rate, the time period from onset to treatment and the hearing improvement. Results: The proliferation inhibition effect of GC on PBMC varied significantly among patients. The PBMC proliferation inhibition rate in GC insensitive group was lower than that in GC sensitive group (26.72%±21.82% vs 64.44%±25.48%, t=6.113, P<0.05). The PBMC proliferation inhibition rate in refractory group was lower than that in initial group (40.93%±28.57% vs 57.04%±31.19%, t=2.035, P=0.046). There was no statistical significance between gender, affected ear side, accompanied by vertigo or not, audiometric curve and the hearing improvement (χ² value was 2.320, 0.031, 2.143, 0.106, respectively, all P>0.05). Both in initial group and refractory group, the linear correlation analyses showed a significant positive correlation between PBMC proliferation inhibition rate and the PTA improvement (r value was 0.615, 0.657, respectively, all P<0.05), as well as a significant negative correlation between time period from onset to treatment and the PTA improvement(r value was -0.542, 0.370, respectively, all P<0.05). Conclusions The proliferation inhibition rate of PBMC in vitro by GC is correlated with patients′ hearing improvement. The proliferation inhibition test might be used to predict the sensitivity to GC treatment and be helpful for individualized treatment of SSNHLin clinical practice.

Objective To investigate the change of plasma visfatin in patients with coronary heart disease and its clinical significance.Methods A total of 310 patients with coronary heart disease (ACS group:n =217; SAP group:n =93) and of 90 healthy subjects with a matched age and gender were included in this study.The plasma concentration of visfatin of each subject was measured using ELISA assay,and each patient underwent selective coronary angiography examination.A total of 85 cases of patients in CHD group underwent 64-slice CT coronary imaging to evaluate the main plaque within the coronary.Results The visfatin,LDL,BMI,blood glucose levels was significantly higher in CHD group[ ( 128.18 ± 13.86)ng/ml,(3.63 ± 1.48) mmol/L,( 26.18 ± 1.82) kg/m2,(7.25 ± 2.03 ) mmol/L] than in control group [ (75.96 ± 10.27 )ng/ml,(2.64 ± 0.53 ) mmol/L,( 23.51 ± 0.89 ) kg/m2,(5.11 ± 1.53 ) mmol/L,P ＜ 0.05 ],respectively.The visfatin level in the ACS group [ ( 145.57 ± 19.95 ) ng/ml ] was significantly higher than the SAP group [ (110.79 ±7.78)ng/ml,P ＜0.05].The visfatin concentration gradually increased with the aggravation of the complexity of coronary lesion types and severity of coronary lesions( P ＜ 0.05).The plasma visfatin concentrations in Soft plaque group and the fibrous plaque group were significantly higher than calcified plaque (P ＜ 0.05).HDL-C and Gensini score of coronary lesions were negatively correlated ( r =- 0.055,P ＜0.05) ; LDL-C,Glu,and visfatin was positively correlated with coronary lesions Gensini score ( r =0.464,0.279,0.531,P ＜ 0.05 ),respectively.Conclusions The plasma visfatin level in patients with Coronary heart disease increased and affected its lipid metabolism.It may be an important inflammatory factors promoting arterial atherosclerosis occurs and development,which has a certain value to the judgment of coronary lesions and plaque stability combined with 64-slice spiral CT examination.

Objective To explore the association between plasma resistin levels and acute coronary syndrome. Methods Four hundred patients were divided into coronary heart disease (CHD) group（310）and control group（90）according to the coronary Angiography (CAG). And CHD group was divided into ACS subgroup（n＝217）and SAP subgroup（n＝93）according to the clinical information. 85 cases in CHD group were underwent 64-slice spiral computed tomography coronary artery imaging. The severity and extent of coronary lesions were analyzed by CAG and graded by means of Gensini coronary score system. Resistin level in plasma of all patients was determined by enzyme linked immunosorbent assay. Results Resistin levels in CHD group［(889.1±248.2)pg/ml］ were significant higher compared with the control group［(261.6±111.9)pg/ml］ (P＜0.05), and resistin levels in ACS subgroup［(1260.0±368.0)pg/ml］ were much higher than that in SAP subgroup［(518.3±128.4)pg/ml］ (P＜0.05). Conclusions The resistin levels of patients with acute coronary syndrome increased significantly and might be associated with the vulnerable plaque. Resistin levels and 64 slice spiral computed tomography coronary artery imaging can be used to detect the vulnerable plaque in CHD patients.