OBJECTIVES: To investigate the synergistic mechanism of the traditional Chinese medicine Rosa laevigata Michx. (RLM) for treatment of pulmonary arterial hypertension (PAH). METHODS: Network pharmacological analysis was carried out to screen the active ingredients of RLM and PAH disease targets and construct the "component-target-disease" interaction network, followed by gene enrichment analysis and molecular docking studies. In the cell experiments, primary cultures of rat pulmonary arterial smooth muscle cells were exposed to hypoxia for 24 h and treated with solvent or 100, 200 and 300 mg/mL RLM, and the changes in cell proliferation were detected using Western blotting for PCNA and immunofluorescence staining. In the animal experiment, male SD rats were randomized into 5 control group, monocrotaline (MCT) solvent group, and MCT with RLM (100, 200 and 300 mg/mL) treatment groups. HE staining and immunofluorescence staining were used to observe histopathological changes in the pulmonary blood vessels of the rats. RESULTS: Seven core active ingredients (including β-sitosterol and kaempferol) in RLM and 39 key disease targets were identified, and molecular docking showed that SRC was a high-affinity target. KEGG enrichment analysis showed that the differential genes were significantly enriched in calcium signaling and PI3K-AKT pathways. In rat pulmonary arterial smooth muscle cells, hypoxic exposure significantly up-regulated cellular expression of PCNA and phosphorylation levels of Src and AKT1, which were obviously lowered by RLM treatment. In RLM-treated rat models, the mean pulmonary artery pressure and right ventricular hypertrophy index (Fulton index) were significantly reduced, the tricuspid annular plane systolic excursion (TAPSE) was improved, and pulmonary vascular wall thickening and fibrosis were obviously ameliorated. CONCLUSIONS RLM inhibits pulmonary arterial smooth muscle cell proliferation in rat models of hypertension possibly by regulating the Src-AKT1 axis, suggesting the potential of RLM as a new natural drug for treatment of pulmonary hypertension.
Animals ; Cell Proliferation/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Pulmonary Artery/cytology* ; Male ; Rats ; Myocytes, Smooth Muscle/cytology* ; Hypertension, Pulmonary/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Muscle, Smooth, Vascular/cytology* ; src-Family Kinases/metabolism* ; Cells, Cultured

Objective:To analyze the incidence and progression of overactive bladder(OAB)symp-toms following radical prostatectomy for prostate cancer patients and to identify related risk factors.Methods:A retrospective study was conducted on 263 local stage prostate cancer patients who underwent radical prostatectomy at Peking University Third Hospital from January 2013 to May 2017.Clinical base-line information,comprehensive imaging features,perioperative parameters,preoperative urinary control status,pathological diagnosis,and the incidence of OAB within one year postoperatively were collected and analyzed.In the imaging features,two parameters were defined:Bladder wall thickness(BWT)and bladder mucosal smoothness(BMS),which were used to predict the occurrence of OAB.Patients were evaluated based on their clinical baseline characteristics,including age,body mass index(BMI),co-morbidities,and prostate-specific antigen(PSA)levels.The imaging characteristics were assessed using preoperative MRI,focusing on BWT and BMS.Perioperative parameters included operative time,blood loss,and length of hospital stay.The OAB symptoms were assessed using the overactive bladder symptom score(OABSS)and the international prostate symptom score(IPSS).These scores were correlated with the postoperative incidence of OAB.Results:Among the 263 patients who underwent radical prostatecto-my,52(19.8％)exhibited OAB within one year postoperatively.Of the 40 patients with preoperative OAB symptoms,17(42.5％)showed remission postoperatively,while 23(57.5％)had persistent symptoms.Additionally,29 patients developed new-onset OAB,accounting for 55.77％of all postopera-tive OAB cases.Univariate analysis indicated that BWT,BMS,OABSS,and IPSS score were all associ-ated with the occurrence of postoperative OAB.Further multivariate analysis identified BMS as an inde-pendent risk factor for long-term OAB(P＜0.001).Conclusion:Long-term postoperative overactive bladder is a common complication following radical prostatectomy.The findings suggest that preoperative MRI measurements of bladder wall thickness and bladder mucosal smoothness during bladder filling phase can predict the risk of OAB occurrence postoperatively.Identifying these risk factors preoperatively can help in counseling patients about potential complications and in developing strategies to mitigate the risk of developing OAB after surgery.Early detection and management of these parameters might improve the quality of life for patients undergoing radical prostatectomy.

Objective To systematically evaluate the relationship between the dietary inflammatory in-dex(DII)and the onset risk of gestational diabetes mellitus(GDM).Methods The databases such as PubMed,Web of Science,Embase,Cochrane Library,CNKI and Wanfang Data were retrieved.The retrieval time was from the database establishment to September 10,2023.Two researchers separately screened the lit-eratures,extracted the data and conducted the bias risk assessment.The meta analysis was conducted by the RevMan 5.4 software.Results A total of 8 observational studies were included,involving 96 904 pregnant women.The results of meta-analysis showed that in the classified DII,compared with the DII anti-inflammato-ry tendency group,the risk of GDM onset in the DII pro-inflammatory tendency group was increased(OR=1.27,95％CI:1.07-1.50,P=0.006).In the continuous DII,for every unit increase in DII,the risk of GDM was increased by 29％(OR=1.29,95％CI:1.13-1.48,P＜0.001).In the subgroup analysis,the most of the stratified analysis results were consistent with the main analysis results.Conclusion The current evidence suggests that the high DII scores will increase the risk of GDM onset,but the aforementioned conclusion re-quires the validation through more high quality,large samples and multicenter studies.

Background and aims:Kehuang(KH)capsule is an herbal medical product approved for the treatment of liver diseases,including liver injury,in China.However,the mechanism is still unclear.This study aimed to elucidate the protective effects of KH capsule against carbon tetrachloride(CCl4)-induced acute liver injury(ALI)in a murine model.Methods:Mice were randomly divided into control,model(CCl4),CCl4+KH_Low and CCl4+KH_High group.Liver enzyme levels and histological changes were assessed to evaluate liver injury.Oxidative stress markers and inflammatory cell infiltration in liver tissues were measured.Additionally,network pharmacology was employed to explore the potential mechanisms of KH capsule.Results:KH capsule significantly reduced serum alanine aminotransferase(ALT)and aspartate amino-transferase(AST)levels,as well as the necrotic area in liver tissue.KH capsule also decreased the infil-tration of macrophages and neutrophils,thereby inhibiting the expression of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β).Furthermore,KH capsule decreased liver malondialdehyde(MDA)levels and increased superoxide dismutase(SOD)activity.The number of ter-minal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive cells in liver tissue was also reduced.The expression of nuclear factor erythroid 2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins was significantly elevated,while the protein expression of cyto-chrome P450 2E1(CYP2E1)was significantly reduced.Mass spectrometry identified genistein,galangin,wogonin,skullcapflavone Ⅱ,and hispidulin as potential active ingredients of KH capsule.Network pharmacology analysis revealed enrichment in the mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)signaling pathways.Western blot analysis confirmed that KH capsule suppressed AKT,extracellular signal-regulated kinase(ERK),and p38 signaling.Conclusions:These findings suggest that KH capsule could exert protective effects against CCl4-induced ALI,with the inhibition of MAPK and PI3K-AKT signaling pathways playing a crucial role in its mecha-nism of action.

Chronic hepatitis B is a public health issue worldwide. Nucleotide analogues and interferon therapy can effectively inhibit HBV replication, but they still have the shortcomings such as inability to achieve the clearance of HBV cccDNA and low HBsAg clearance rate. The academic viewpoint of "kidney-tonifying therapy for chronic hepatitis B" provides new ideas and methods for the treatment of hepatitis B. During long-term clinical practice, Department of Hepatology in Shuguang Hospital has identified that "deficiency of spleen and kidney with damp heat remaining" is the key pathogenesis of the continuous progression of chronic hepatitis B and has established the treatment regimen for chronic hepatitis B with the basic treatment method of tonifying the kidney, strengthening the spleen, and promoting diuresis. The clinical research of National Science and Technology Major Project from The 11th Five Year Plan to The 13th Five Year Plan has validated the clinical efficacy of this regimen and clarified that regulating the immune function of the body is the main mechanism of the kidney-tonifying, spleen-strengthening, and diuresis-promoting therapy in the treatment of chronic hepatitis B.

Early diagnosis of pulmonary diseases is of great significance for their prevention and treatment. Serum Krebs von den Lungen-6 (KL-6) assay can reflect the damage degree of alveolar epithelium and stromal tissue, and is simple, non-invasive and low-cost. Pervious study showed that the serum KL-6 level was higher in patients with various interstitial lung diseases (e.g. idiopathic pulmonary fibrosis and connective tissue disease, primary Sjögren's syndrome, rheumatoid arthritis, idiopathic inflammatory myopathy and systemic sclerosis combined with interstitial lung disease), non-small cell lung cancer, various pneumonias and chronic obstructive pulmonary disease compared to healthy controls. Therefore, serum KL-6 has good sensitivity and specificity for the early diagnosis of these diseases. Occupational pneumoconiosis is an interstitial lung disease with a well-established etiology. Pervious study has shown that serum KL-6 level was higher in patients with occupational silicosis, occupational asbestosis, and dust-exposed workers compared to healthy controls. However, due to the limited sample size and the inconsistent findings on different studies, further research is needed to study the role of serum KL-6 in the early diagnosis of pneumoconiosis. Future studies should increase the sample size, improve the detection methods for serum KL-6, explore its feasibility as an early diagnostic biomarker for occupational pulmonary diseases, and investigate the efficacy andvalue of its combined application with other biomarkers in the early diagnosis of various pulmonary diseases, including occupational lung diseases, to fully exploit its predictive role in pulmonary diseases.

Prostate cancer (PCa) is a pernicious tumor with high heterogeneity, which creates a conundrum for making a precise diagnosis and choosing an optimal treatment approach. Multiparametric magnetic resonance imaging (mp-MRI) with anatomical and functional sequences has evolved as a routine and significant paradigm for the detection and characterization of PCa. Moreover, using radiomics to extract quantitative data has emerged as a promising field due to the rapid growth of artificial intelligence (AI) and image data processing. Radiomics acquires novel imaging biomarkers by extracting imaging signatures and establishes models for precise evaluation. Radiomics models provide a reliable and noninvasive alternative to aid in precision medicine, demonstrating advantages over traditional models based on clinicopathological parameters. The purpose of this review is to provide an overview of related studies of radiomics in PCa, specifically around the development and validation of radiomics models using MRI-derived image features. The current landscape of the literature, focusing mainly on PCa detection, aggressiveness, and prognosis evaluation, is reviewed and summarized. Rather than studies that exclusively focus on image biomarker identification and method optimization, models with high potential for universal clinical implementation are identified. Furthermore, we delve deeper into the critical concerns that can be addressed by different models and the obstacles that may arise in a clinical scenario. This review will encourage researchers to design models based on actual clinical needs, as well as assist urologists in gaining a better understanding of the promising results yielded by radiomics.
Male ; Humans ; Artificial Intelligence ; Magnetic Resonance Imaging/methods* ; Prostatic Neoplasms/diagnostic imaging* ; Image Processing, Computer-Assisted/methods* ; Precision Medicine ; Retrospective Studies

Objective:To investigate the predictive value of serum proenkephalin A 119-159 (penKid) on incidence and the 28-day mortality in patients with sepsis-associated acute kidney injury (SA-AKI).Methods:This study was a single center, observational cohort study. Sepsis/septic shock patients admitted to Department of Critical Care Medicine of Taizhou People's Hospital Affiliated to Nanjing Medical University from September 2021 to September 2022 were selected and divided into the SA-AKI group and the non-SA-AKI group according to whether acute kidney injury (AKI) occurred within 28 days. Patients in the SA-AKI group were subdivided into the death group and the survival group according to whether death occurred within 28 days. Baseline data and laboratory indicators such as penKid concentration were compared among different groups. COX regression analysis was used to explore the risk factors of death within 28 days in the SA-AKI patients, And Kaplan-Meier curve was used to analyze patient prognosis.Result:A total of 161 patients were included in this study, of whom 66 (41.0%) developed AKI. The baseline penKid concentration in the SA-AKI group was significantly higher than that in the non-SA-AKI group [(2.99 ± 0.68) μg/L vs. (1.86±0.75) μg/L, P<0.05]. Multivariate COX regression analysis showed that the baseline penKid ( HR=5.608, 95% CI: 3.507-8.967, P<0.001) and lactate (LA) ( HR=1.089, 95% CI: 1.003-1.183, P=0.043) were independent risk factors for AKI in sepsis/septic shock patients. Of the 66 SA-AKI patients, 27 (40.9%) died within 28 days, and the baseline penKid concentration in the death group was significantly higher than that in the survival group [ (3.55 ± 0.54) μg/L vs. (2.60±0.47) μg/L, P<0.05]. COX regression analysis showed that penKid ( HR=5.892, 95% CI: 2.457-14.132, P<0.001) was an independent risk factor for mortality in SA-AKI patients. Kaplan-Meier curve showed that the 28-day mortality of patients with baseline penKid ≥ 3.24 μg/L was significantly higher than that of patients with baseline penKid <3.24 μg/L ( P<0.001). Conclusions:In sepsis/septic shock patients, the penKid concentration measured on the first day in the SA-AKI group is significantly higher than that in the non-SA-AKI group. In SA-AKI patients, the penKid concentration measured in patients who survived within 28 days is significantly lower than that in the death group. PenKid is an independent risk factor for the occurrence and death of SA-AKI.

Objective:To explore the effect of pectin on improving intestinal barrier injury in elderly stroke patients.Methods:A total of 60 elderly stroke patients who received enteral nutrition in Department of Critical Care Medicine of Taizhou People's Hospital from November 2020 to October 2021 were included. The control group included 30 cases, using conventional enteral nutrition solution. The other 30 cases were in the study group, and pectin was added on the basis of routine enteral nutrition solution. The levels of serum diamine oxidase (DAO) and D-lactic acid (D-LA) were measured on the first and 7th days of enteral nutrition to evaluate the intestinal barrier function of elderly stroke patients. The levels of interleukin-6 (IL-6), procalcitonin (PCT) and high-sensitivity C-reactive protein (CRP) were measured to evaluate the inflammatory response level of elderly stroke patients. The clinical prognosis of the two groups was compared.Results:Compared with the control group, the values of DAO [(4.05±1.56)ng/mL] and D-LA [(6.11±2.20) μmol/L] in the study group were significantly lower than those in the control group on the 7th day (all P < 0.05). Also the levels of IL-6 [(15.43±12.53) ng/mL], PCT [(0.82±0.98) ng/mL] and CRP [(6.94±6.60) mg/L] in the study group were lower than those in the control group, and the difference between the two groups was statistically significant (all P < 0.05). Compared with the control group, the length of ICU stay and total length of hospital stay in the study group were shorter than those in the control group ( P<0.05), but there was no significant difference in the incidence of stroke-related pneumonia (16.7% vs. 30.0%) and 30-day mortality (16.7% vs. 20.0%) between the two groups ( P>0.05). Conclusions:The enteral nutrition with pectin supplementation can improve intestinal barrier function and reduce inflammatory response in elderly stroke patients.

ObjectiveTo investigate the effect of sustained virologic response on disease progression and the development of hepatocellular carcinoma (HCC) in patients with compensated hepatitis B cirrhosis receiving antiviral therapy with nucleos(t)ide analogues (NAs). MethodsA total of 542 patients with compensated hepatitis B cirrhosis who attended Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 1 to December 31, 2013, received antiviral therapy, and were followed up for more than 5 years were enrolled, and according to the status of virologic response during follow-up, they were divided into a sustained virologic response cohort with 496 cases and a non-sustained virologic response cohort with 46 cases. With disease progression as the outcome event, general information and examination data were collected during the 5-year follow-up period. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A multivariate logistic regression analysis was performed; relative risk and 95% confidence interval (CI) were used to investigate the degree of correlation of factors measured with the progression of liver cirrhosis. The life-table method was used to calculate the 1-, 3-, and 5-year progression-free survival rates, and the Kaplan-Meier method was used to plot survival curves; the log-rank test was used for univariate analysis, and the Cox regression model was used for multivariate regression analysis. ResultsFor the 542 patients, the mean progression-free survival time was 62.50 months (95% CI: 61.01-63.92), and the 1-, 3-, and 5-year progression-free survival rates were 94%, 82%, and 71%, respectively. The sustained virologic response cohort had a significantly longer mean progression-free survival time than the non-sustained virologic response cohort ［63.10 months (95% CI: 61.65-64.55) vs 55.95 months (95% CI: 50.19-61.71), χ2=12.058, P=0.001］. Compared with the non-sustained virologic response cohort, the sustained virologic response cohort had significantly lower 5-year cumulative incidence rate of HCC than (20.6% vs 34.8%, χ2=5.759, P=0.016) and 5-year cumulative incidence rate of decompensated cirrhosis (5.0% vs 15.2%, χ2=8.239, P=0.004). Virologic response was an independent risk factor for disease progression (hazard ratio=232, 95% CI: 1.45-3.72). ConclusionSustained virologic response can reduce the incidence rates of complications and HCC, improve long-term prognosis, and prolong survival time in patients with compensated hepatitis B cirrhosis.