OBJECTIVE: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments. METHODS: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments. RESULTS: A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01). CONCLUSION LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Humans ; Male ; Network Pharmacology ; Apoptosis/drug effects* ; Mice

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Objective To development and validate a predictive model for distinguishing between malignant pleural effusion(MPE)and benign pleural effusion(BPE).Methods A total of 428 patients diagnosed with pleural effusion(PE)and hospitalized at the First Hospital of Huai'an Affiliated to Nanjing Medical University from July 2020 to May 2022 were selected.The patients were divided into BPE group(211 cases)and MPE group(217 cases)according to diagnostic criteria.The basic information and clinical data of these patients were collected.Boruta method was used for univariate screening,followed by multivariate Logistic regression to construct a basic nomogram model.Bootstrap method was used for internal validation to evaluate the performance of the nomogram,including dis-crimination,accuracy,and clinical applicability.Results The model included 8 key variables:dyspnea,chest pain,general symp-toms,X-ray/CT with malignant tumor features,serum carcinoembryonic antigen,serum neuron-specific enolase,pleural lactate dehy-drogenase,and pleural carcinoembryonic antigen.Internal validation showed that the area under the receiver operating characteristic curve(AUCROC)of the model was 0.933(95%confidence interval:0.912-0.954),with good accuracy(P＞0.05).Decision curve a-nalysis(DCA)indicated that this predictive model for predicting MPE risk had a significant net benefit when the probability threshold exceeded 1%.Conclusion The constructed prediction model could effectively distinguish between MPE and BPE.

Recent developments indicated that Bowman capsule rupture (BCR) is observed in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN). We aimed to explore the relationship between BCR and clinical manifestations, pathological changes, and prognosis in children with myeloperoxidase (MPO)-AAGN. Methods: A total of 56 children with MPO-AAGN were divided into BCR (+) and BCR (–) groups according to the status of Bowman’s capsule. Results: After retrospective analysis of the data, 24 children (42.9%) were found to have BCR. The results showed that BCR positively correlated with intrarenal immune cell infiltrates, obsolescence and crescents in glomeruli, tubulointerstitial inflammation, tubulitis, and tubular atrophy negatively correlated with normal glomeruli and immunoglobulin G deposition in the kidney. The clinical features and kidney pathological changes were more severe in the BCR (+) group than BCR (–) group, and the renal survival rate was significantly poorer in the BCR (+) group than BCR (–) group (χ2 = 5.45, p = 0.02). Moreover, estimated glomerular filtration rate (≤15 mL/ min/1.73 m2), BCR and ANCA renal risk score (ARRS) were independent risk factors for the development of end-stage kidney disease (ESKD) in children with MPO-AAGN. After combining BCR with the Berden classification and ARRS, our data suggested that the Berden classification + BCR and ARRS + BCR showed better predictive values for ESKD than those of the Berden classification and ARRS, respectively. Conclusion: BCR is an important pathological lesion that correlates with severe clinical manifestations, pathological changes, and poor prognosis in children with MPO-AAGN.

Objective To development and validate a predictive model for distinguishing between malignant pleural effusion(MPE)and benign pleural effusion(BPE).Methods A total of 428 patients diagnosed with pleural effusion(PE)and hospitalized at the First Hospital of Huai'an Affiliated to Nanjing Medical University from July 2020 to May 2022 were selected.The patients were divided into BPE group(211 cases)and MPE group(217 cases)according to diagnostic criteria.The basic information and clinical data of these patients were collected.Boruta method was used for univariate screening,followed by multivariate Logistic regression to construct a basic nomogram model.Bootstrap method was used for internal validation to evaluate the performance of the nomogram,including dis-crimination,accuracy,and clinical applicability.Results The model included 8 key variables:dyspnea,chest pain,general symp-toms,X-ray/CT with malignant tumor features,serum carcinoembryonic antigen,serum neuron-specific enolase,pleural lactate dehy-drogenase,and pleural carcinoembryonic antigen.Internal validation showed that the area under the receiver operating characteristic curve(AUCROC)of the model was 0.933(95%confidence interval:0.912-0.954),with good accuracy(P＞0.05).Decision curve a-nalysis(DCA)indicated that this predictive model for predicting MPE risk had a significant net benefit when the probability threshold exceeded 1%.Conclusion The constructed prediction model could effectively distinguish between MPE and BPE.

OBJECTIVE: To investigate the clinicopathological features and prognosis of urinary bladder urothelial carcinoma (UBUC) with incidental prostate cancer (IPCa). METHODS: We retrospectively analyzed the clinicopathological features of 65 cases of UBUC and 38 cases of UBUC + IPCa after radical cystoprostatectomy (RCP) from January 2017 to February 2020. We compared their expressions of the immunohistochemical markers androgen receptor (AR) and (human epidermal growth factor receptor 2,HER2) between the two groups of patients, and analyzed their clinicopathological characteristics by chi-square test and their survival rates using the Kaplan-Meier method and log-rank test. RESULTS: The detection rate of UBUC + IPCa was 16.5%, and that of clinically significant IPCa was 39.5%, with preoperative PSA≥4 μg/L in 23.7% of the patients. Compared with the patients with UBUC, most of the UBUC + IPCa cases had no smoking history (73.8% vs 92.1%, P = 0.024), and fewer had histological variants (43.1% vs 10.5%, P = 0.003). The incidence rate of vascular invasion was significantly higher in the UBUC than in the UBUC + IPCa group (49.2% vs 21.1%, P = 0.005), and so was the rate of advanced cases (67.7% vs 31.6%, P<0.001). In comparison with the patients of the UBUC group, those of the UBUC + IPCa group showed remarkably higher expressions of AR (9.2% vs 31.6%, P = 0.004) and HER2 (43.1% vs 71.1%, P = 0.006). The mean overall survival time was longer in the UBUC + IPCa than in the UBUC group (48.8 mo ［95% CI: 2.5－42.6 mo］ vs 39.9 mo ［95% CI: 2.8－34.5 mo］), but with no statistically significant difference between the two groups (P = 0.608). CONCLUSION Standardized sampling of prostate samples after RCP helps to improve the detection rate of IPCa. Preoperative level of PSA is not a good predictor of IPCa. Few patients with UBUC + IPCa have a history of cigarette smoking, and the predominant histological type of the malignancy is high-grade invasive urothelial carcinoma, which is not significantly different from UBUC in prognosis. The expressions of HER2 and AR are significantly higher in UBUC + IPCa than in UBUC, suggesting that UBUC + IPCa may benefit from HER2- and AR-targeted therapy.
Humans ; Male ; Urinary Bladder Neoplasms/metabolism* ; Receptors, Androgen/metabolism* ; Prostatic Neoplasms/metabolism* ; Retrospective Studies ; Receptor, ErbB-2/metabolism* ; Prognosis ; Middle Aged ; Aged ; Survival Rate ; Prostatectomy

Establishing a comprehensive mechanism for the initiation and review of investigator-initiated trial(IIT) plays an important role in ensuring the scientific validity of clinical research and improving research quality.Since 2021, Zhongshan Hospital affiliated to Fudan University had actively explored improvements in the project management of IIT. The hospital had established a standardized grading review management process, developed an integrated clinical research management system, established a three-level clinical research training system, built a methodological support platform, and formulated research plan templates, gradually formed a standardized grading project approval review management mode. As of February 2024, the hospital had completed 400 quick reviews and more than 400 expert letter reviews based on the integrated clinical research management system. The efficiency and quality of IIT project approval had been improved. At the same time, over 40 academic salons and forums had been held, cultivating a group of young clinical research talents, providing data management training for more than 30 clinical departments, and promoting the improvement of the quality of research protocol. In the future, hospitals should further optimize their information systems, expand the influence of their training systems, enhance the capabilities of their methodological support platforms, and improve the efficiency of the application of clinical research protocol templates, so as to escort the establishment and implementation of high-quality clinical research projects and provide references for other hospitals′ IIT project management.

In the context of delayed marriage and parenthood, decreased willingness in having children, and population aging in China, maternal and child health has become an important and urgent issue. Being essential platforms for research in maternal and child health, the importance of birth cohorts has been widely recognized. In the past 20 years, tens of birth cohorts have been established in major cities and regions of China, with cohorts ranging from thousands to hundreds of thousands. These cohorts, particularly those large ones launched in recent years, have collected a wide spectrum of data and biological samples from mothers and children. Although they have made considerable preliminary achievements, there remain difficulties and challenges. The significant challenges include small and medium-sized cohorts' lacking of clear research themes; insufficient recognition of and emphasis on behavioral and social determinants of health while emphasizing biological determinants of health; variations in types of variables and quality of data collected, which make it difficult for cohorts to be merged and shared; lack of and difficulties in long-term follow-up; significant uncertainties in resources for long-term sustention of the cohorts, and so on. So, we argue that birth cohorts should focus on essential and urgent issues in maternal and child health in the country and seek recognition and support from the government and the entire society. Last but not least, the overall success of birth cohorts in the country requires scientists to be not only academically capable, but also realistic, persistent, altruistic, and collaborative.

Objective To explore the imaging features, clinical outcome, and prognosis of indeterminate pulmonary nodules (IPN) in patients with high-grade soft tissue sarcoma. Methods A retrospective study of 82 patients with high-grade soft tissue sarcoma who have IPNs. The clinical characteristics, imaging features of IPN, and survival of patients were analyzed with statistical software. Results The IPN size of 82 patients was 6.453±0.864 mm. IPN diameter, shape, density, and nodule discovery interval may be CT imaging features related to malignancy tendency. Age (HR=1.047, 95%CI: 1.007-1.088) and interval between each nodule discovery (HR=3.194, 95%CI: 1.052-9.694) are independent factors that affect the survival of patients with malignant IPN. Conclusion The imaging features of chest CT may provide important guidance for determining the nature and survival prognosis of benign and malignant nodules.