Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

AIM:To predict the active compo-nents and targets of Piperlongum L.and the associ-ated signaling pathways involved in pulmonary fi-brosis using network pharmacology and molecular docking technique and evaluate the mechanism of Piperlongum L against pulmonary fibrosis by in vi-tro experiments.METHODS:The active ingredients and targets were retrieved from TCMSP,Swiss Tar-get Prediction and PubChem databases.The dis-ease-related targets were retrieved from Gene-Cards and OMIM databases.The intersection tar-gets of the drugs and disease-related targets were identified using jvenn online tool.String database was used to construct the"drug-component-tar-get"and PPI network and the networks were visual-ized using Cytoscape 3.9.1 software.GO and KEGG enrichment analysis were performed on the inter-section targets using the DAVID tool.The top 20 KEGG pathways,core targets and drug components were used to construct a"component-target-path-way"network and the network visualization was performed using Cytoscape 3.9.1 software.The in-teractions between drug compounds and the tar-gets were evaluated by molecular docking,and the docking results were visualized using Discovery stu-dio.HFL-1 cells were cultured and the effect of the drug compounds on cell viability was determined by MTT assay.The inhibition rate was then calculat-ed to determine the optimal drug concentration.HFL-1 cells were cultured in vitro and were as-signed into 4 groups:control group,TGF-β1 group,TGF-β1+LD group(LD group),TGF-β1+HD group(HD group).CCK-8 kit was used to evaluate the anti-proliferative activity of the drug compounds against HFL-1 cells at 24,48 and 72 h.Plate clone formation assay was performed to evaluate the ef-fect of drugs on the colony formation ability of HFL-1 cells.RT-qPCR and western blot were conducted to determine the effect of the compounds on the mRNA and protein expression levels of α-smooth muscle actin(α-SMA),collagen type Ⅰ(COI-Ⅰ),and collagen type Ⅲ(COI-Ⅲ)in each group.RESULTS:A total of 197 intersection targets of Piperlongum L and anti-pulmonary fibrosis were identified.The core PPI network comprised 29 nodes(targets)and 199 edges(interactions).GO functional analysis showed that the significantly enriched biological processes associated with the compounds in Piper-longum L included negative regulation of apopto-sis,signal transduction,and protein phosphoryla-tion.Significantly enriched cellular components in-cluded cytoplasm,nuclear cytoplasm,plasma mem-brane.Enriched molecular functions associated with the compounds included the same protein binding,serine/threonine/tyrosine kinase activity,and protein binding.A total of 155 significantly en-riched KEGG signaling pathways were identified,with PI3K-Akt signaling pathway was highly associ-ated with PF and was the fourth most enriched pathway.PIK3CA,MAPK3,MAPK1,MTOR,SRC,CCND1,EGFR,PRKCA,BCL2,and GSK3B had the highest connectivity in the components-target-pathway network.Piperlongine,N-(2,5-dimethoxy-phenyl)-4-methoxybenzamide,tetrahydrotanshi-none,pisigenin and piperine were the key com-pounds in Piperlongum L.The molecular docking results showed that all the compounds except N-(2,5-dimethoxyphenyl)-4-methoxybenzamide had good binding activities with interactions observed with 10 proteins.The proliferation ability of the cells in the LD group was significantly lower than that of the TGF-β1 group at 48 h and 72 h(P＜0.05).The proliferation ability of cells HD group was sig-nificantly lower than the LD group at 24,48 and 72 h.The number of clones in each drug group was significantly reduced after treatment with the drugs(P＜0.05).The mRNA and protein expression levels of α-SMA,COI-Ⅰ,COI-Ⅲ in LD and HD groups were significantly lower than the expression levels in the TGF-β1 group.The protein expression levels of p-PI3K/PI3K and p-Akt/AKT were significantly lower in the two dose groups compared with the TGF-β1 group(P＜0.01).CONCLUSION:The results showed that the effect of Piperlongum L against PF is probably through modulation of the PI3K-Akt sig-naling pathway.

Objective To evaluate the clinical efficacy and hemorheological effects of traditional Chinese medicine injection combined with conventional Western medicine in the treatment of stable angina pectoris in coronarrt heartdisease using a mesh meta-analysis system.Methods Computer searches were conducted on China National Knowledge Infrastructure(CNKI),WanFang Data Knowledge Service Platform(WanFang Data),VIP,SinoMed,PubMed,Cochrane Library,Web of Science,and other clinical randomized controlled trials(RCTs)related to the combination of traditional Chinese medicine injection and conventional Western medicine for the treatment of stable angina pectoris in coronary heart disease.The search was conducted until April 2023.The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies,and Stata13.0 software was used for meta-analysis.Results 57 RCTs were ultimately included,involving 5 types of traditional Chinese medicine injections.The results of the network meta-analysis showed that:① in terms of clinical total effective rate,the efficacy of traditional Chinese medicine injection was ranked in the following order:conventional Western medicine treatment combined with Shenmai injection>Shenxiong glucose injection>Shenfu injection>Ciwujia injection>Huangqi injection>conventional Western medicine treatment;② In terms of the effective rate of angina symptoms,the order of efficacy of traditional Chinese medicine injection is conventional Western medicine treatment combined with Shenxiong glucose injection>Ciwujia injection+conventional therapy>Huangqi injection>Shenfu injection>Shenmai injection>conventional Western medicine treatment;③ In terms of the effective rate of electrocardiogram,the order of efficacy of traditional Chinese medicine injection is conventional Western medicine treatment combined with Shenmai injection>Shenxiong glucose injection>Huangqi injection>Ciwujia injection>Shenfu injection>conventional Western medicine treatment;④ In terms of improving the high shear viscosity of whole blood,the efficacy of traditional Chinese medicine injection is ranked in the following order:conventional Western medicine treatment combined with Shenmai injection>Shenxiong glucose injection>Shenfu injection>Huangqi injection>Ciwujia injection>conventional Western medicine treatment;⑤ In terms of improving whole blood low shear viscosity,the efficacy of traditional Chinese medicine injections is ranked in the following order:conventional Western medicine treatment combined with Shenfu injection>Shenmai injection>Shenxiong glucose injection>Ciwujia injection>Huangqi injection>conventional Western medicine treatment;⑥ In terms of improving plasma viscosity,the order of efficacy of traditional Chinese medicine injection is conventional Western medicine treatment combined with Huangqi injection>Shenfu injection>Shenmai injection>Shenxiong glucose injection>Ciwujia injection>conventional Western medicine treatment;⑦ In terms of improving fibrinogen,the efficacy ranking of traditional Chinese medicine injection is conventional Western medicine treatment combined with Shenfu injection>Shenxiong glucose injection>Shenmai injection>Ciwujia injection>conventional Western medicine treatment.Conclusion The combination of traditional Chinese medicine injection and conventional Western medicine treatment has a significant effect on stable angina pectoris in coronary heart disease.Among them,Shenmai Injection has the best therapeutic effect in terms of clinical total effective rate,electrocardiogram,and improvement of whole blood high shear viscosity;In terms of improving angina symptoms,Shenxiong Glucose Injection has the best effect;In terms of improving whole blood low shear viscosity and fibrinogen,Shenfu Injection has the best effect;In terms of improving plasma viscosity,Shenfu Injection has the best effect,but currently it is limited by the number and quality of studies included,and the above conclusions still need to be verified by more high-quality studies.

Objective To investigate the expression of serum CC chemokine ligand 2(CCL2),CX3C chemokine ligand 1(CX3CL1)and CXC chemokine ligand 10(CXCL10)in postmenopausal osteoporosis(PMOP)patients and the value of combination with fracture risk assessment tool(FRAX)in predicting fracture occurrence.Methods A total of 120 patients with PMOP admitted to Hainan West Central Hospital from January 2022 to June 2023 were selected,and they were divided into fracture group(n=52)and non-fracture group(n=68).According to the FRAX score examination,they were divided into a high-risk fracture group(n=73)and a low-risk fracture group(n=47).The levels of serum CCL2,CX3CL1 and CXCL10 in each group were compared.Multivariate Logistic regression was used to analyze the fracture risk factors in PMOP patients.ROC curve was drawn to analyze the value of CCL2,CX3CL1 and CXCL10 combined with FRAX score in predicting fracture of PMOP.Results The levels of serum CCL2(134.98±32.24 pg/ml),CX3CL1(186.25±41.60 pg/ml)and CXCL10(223.47±56.43 pg/ml)in the fracture group were higher than those in the non-fracture group(82.26±17.30 pg/ml,105.23±23.78 pg/ml,151.47±43.14 pg/ml),and the differences were statistically significant(t=11.503,13.452,7.923,all P＜0.001).The levels of serum CCL2(119.70±37.56 pg/ml),CX3CL1(161.43±53.79 pg/ml)and CXCL10(204.06±61.41pg/ml)in the high-risk group for fractures were higher than those in the low-risk group(82.43±17.23 pg/ml,107.55±24.75 pg/ml,149.45±42.50pg/ml),and the differences were statistically significant(t=6.377,6.436,5.327,all P＜0.001).Multivariate Logistic regression analysis showed that elevated levels of serum CCL2,CX3CL1 and CXCL10 were risk factors for fractures in PMOP patients.The ROC curve showed that the combination of CCL2,CX3CL1 and CXCL10 combined with FRAX scores predicted the highest AUC(95％CI)for PMOP fractures[0.951(0.892～0.993)],with sensitivity and specificity of 98.2％and 85.6％,respectively.Conclusion The increased levels of serum CCL2,CX3CL1 and CXCL10 are risk factors for fracture in PMOP patients,and the combination with FRAX score has a good predictive value for fracture.

Objective To explore the CT manifestations and clinical features of checkpoint inhibitor-related pneumonitis(CIP).Methods Chest CT images and clinical data of 34 patients with CIP in Ningbo No.2 Hospitael were collected to retrospectively analysis.According to the site of tumor occurrence,22 patients were divided into lung cancer group and 12 patients in other malignant tumor group,and the differences in CT manifestations between two groups were compared.Results Cough(70.59％)and dyspnea(52.94％)were the common clinical symptoms.CIP occurred earlier and over a greater time span in lung cancer group 114.5(41.50,281.50)d than in other maligment tumor group 144(55.75,226.25)d.Eosinophil count was significantly higher only in other maligment tumor group(P=0.009).After hormonal therapy 18 patients improved,8 were stable and 8 progressed or even died.CT signs were prevalent in ground glass shadow(70.59％)and solid shadow(76.47％),and the imaging pattern was dominated by organic pneumonia pattern(47.6％),which was not related to type of primary tumor,and some of them could show nodular granulomatous reaction.Compared to lung cancer group,the other maligment tumor group was more likely to exhibit symmetrical infiltration(58.33％)distribution.Conclusion The clinical features of CIP are nonspecific,compared with other patients with primary malignancies,lung cancer patients are more likely to develop CIP,which is difficult to relieve after treatment,and are easy to develop severe disease.

Objective:To investigate the safety and efficacy of one-stage transurethral prostatectomy for prostatic hyperplasia accompanied by non-neurogenic detrusor acontractility.Methods:The clinical data of 35 patients with benign prostatic hyperplasia accompanied by non-neurogenic detrusor acontractility admitted to The Second Affiliated Hospital of Zhengzhou University from January 2015 to Octorber 2021 were analyzed.The average age was (74.0±7.9) years old. The average volume of prostate was (77.8±44.5)cm 3. The average total prostate specific antigen(tPSA)was(8.9±8.7)ng/ml. The preoperative international prostate symptom score(IPSS) was (19.1±4.3) and the preoperative quality of life score(QOL)was 5(5, 5). All the patients were treated with one-stage transurethral prostatectomy and suprapubic cystostomy. After removing the cystostomy tube, the post-void resident volume(PVR), the maximum urine flow rate(Q max), IPSS, QOL were recorded, and complications were followed up. Successful treatment is defined as the removal of the cystostomy tube without worsening of upper urinary tract hydronephrosis. Results:All the operations were successfully completed. The success rate of treatment was 85.7%(30/35), and the median time to resume spontaneous urination was 4.0(3.3, 4.5) weeks. The average postoperative Q max was (12.6±2.3)ml/s, and the average PVR was(27.7±9.5)ml. The postoperative IPSS was (5.5±2.4), which was significantly improved compared to preoperative( P<0.001). The postoperative QOL score was 1(1, 2) points, which was significantly lower than preoperative( P<0.001). The patients voiding spontaneously were followed up for 3-69 months, and no complications such as urinary retention, recurrent urinary tract infection and hydronephrosis occurred. Conclusions:One-stage transurethral prostatectomy for patients with benign prostatic hyperplasia accompanied by non-neurogenic detrusor acontractility has a high success rate and few complications, which greatly improves the quality of life of patients.

BACKGROUND: The KangDuo-Surgical Robot-01 (KD-SR-01) system is a new surgical robot recently developed in China. The aim of this study was to present our single-center experience and mid-term outcomes of urological procedures using the KD-SR-01 system. METHODS: From August 2020 to April 2023, consecutive urologic procedures were performed at Peking University First Hospital using the KD-SR-01 system. The clinical features, perioperative data, and follow-up outcomes were prospectively collected and analyzed. RESULTS: A total of 110 consecutive patients were recruited. Among these patients, 28 underwent partial nephrectomy (PN), 41 underwent urinary tract reconstruction (26 underwent pyeloplasty, 3 underwent ureteral reconstruction and 12 underwent ureterovesical reimplantation [UR]), and 41 underwent radical prostatectomy (RP). The median operative time for PN was 112.5 min, 157.0 min for pyeloplasty, 151.0 min for ureteral reconstruction, 142.5 min for UR, and 138.0 min for RP. The median intraoperative blood loss was 10 mL for PN, 10 mL for pyeloplasty, 30 mL for ureteral reconstruction, 20 mL for UR, and 50 mL for RP. All procedures were successfully completed without conversion, and there were no major complications in any patient. The median warm ischemia time of PN was 17.3 min, and positive surgical margin was not noted in any patient. The overall positive surgical margin rate of RP was 39% (16/41), and no biochemical recurrence was observed in any RP patient during the median follow-up of 11.0 months. The surgical success rates of pyeloplasty and UR were 96% (25/26) and 92% (11/12) during the median follow-up of 29.5 months and 11.5 months, respectively. CONCLUSION The KD-SR-01 system appears feasible, safe, and effective for most urological procedures, based on our single-center experience.
Male ; Humans ; Robotic Surgical Procedures/methods* ; Robotics ; Treatment Outcome ; Retrospective Studies ; Ureter/surgery* ; Urologic Surgical Procedures/methods* ; Laparoscopy/methods*

Objective:To explore the mechanism of Shuerjing Capsule in treating primary dysmenorrhea based on molecular docking of network pharmacology and in vivo experiment.Methods:By using TCMSP to screen the active components and targets of Shuerjing Capsule; by using GeneCards and DrungBank databases to retrieve targeted proteins of primary dysmenorrhea, and the intersection targets of drugs and diseases were obtained through Weishengxin online platform; by using Cytoscape 3.9.1 software to produce component-target network of Shuerjing Capsule for the treatment of primary dysmenorrhea; by STRING databases to construct drug-disease target PPI network; by DAVID database to perform GO and KEGG pathway enrichment analysis.The key active components of the drug and the core targets of the disease were obtained with molecular docking. The rats were randomly divided into control group, model group, the low-dose group, medium-dose group and high-dose group of Shujing Capsule (0.15, 0.21, 0.42 g/kg), and ibuprofen group (20 mg/kg), with 10 rats in each group. The animal model of primary dysmenorrhea was established by subcutaneous injection of estradiol benzoate and intervented by drugs. The number of writhing reaction, uterine contractile inhibition rate and uterine index of rats were observed. The expressions of TNF-α, IL-6 and IL-1 in serum and the levels of PTGS2 and VEGFA in uterine tissue were detected by ELISA.Results:A total of 188 active ingredients of Shuerjing Capsule were screened, and 51 targets of Shuerjing Capsule and primary dysmenorrhea were identified. TNF, IL-6, AKT1 and TP53 may be the key targets of Shuerjing Capsule in the treatment of primary dysmenorrhea. A total of 519 GO biological processes and 119 related signaling pathways were obtained, among which estrogen, IL-17, HIF-1 and other signaling pathways were closely related to the treatment of primary dysmenorrhea. The results of molecular docking were good, among which stigmasterol had the strongest binding ability to TP53. The experimental results showed that compared with the model group, the uterine index and the number of torsion were decreased in the low -, medium - and high-dose Shuojing Capsule groups ( P<0.05), the uterine contraction inhibition rate increased ( P<0.05); Serum levels of TNF-α, IL-6 and IL-1 of medium and high dose group decreased ( P<0.05), the levels of PTGS2 and VEGFA in uterine tissues decreased ( P<0.05). Conclusion:Shuerjing Capsule has the effect of anti-inflammatation and improveing hypoxia, which may be related to the inhibition of TNF-α, IL-6 and IL-1 inflammatory factors in serum and the expression of PTGS2 and VEGFA proteins in uterine tissues.

Objective:To investigate the diagnostic value of serum CircRNA_0048211 expression level in postmenopausal osteoporosis (PMOP) and its correlation with bone-specific alkaline phosphatase (BALP), osteopontin (OPN), procollagen type I N-terminal propeptide (PINP) and β-crosslaps (β-CTX). Methods:Data of postmenopausal women who underwent physical examination in our hospital from January 2019 to December 2021 were collected. All subjects were measured bone mineral density (BMD) by dual-energy X-ray absorptiometry and divided into PMOP group, decreased bone mass group and normal bone mass group according to BMD level. The serum CircRNA_0048211, BALP, OPN, PINP and β-CTX levels were compared in each group. Binary logistic regression was used to analyze the risk factors of PMOP, the receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic value of CircRNA_0048211, BALP, OPN, PINP and β-CTX on PMOP. The correlation between CircRNA_0048211 expression level and BALP, OPN, PINP and β-CTX was analyzed by Pearson correlation analysis. Results:A total of 218 patients were included in this study. Age is 60.52±6.83 years (range, 47-76 years), body mass index is 24.27±2.28 kg/m 2 (range, 22.18-25.73 kg/m 2) and menopausal time is 10.16±4.25 years (range, 2.30-21.80 years). There were 40 cases in PMOP group, 97 cases in osteopenia group and 81 cases in normal bone mass group. The serum CircRNA_ 0048211, BALP, OPN, PINP and β-CTX was significantly different between PMOP group, osteopenia group and normal group ( F=21.15, P<0.001; F=12.52, P<0.001; F=17.86, P<0.001; F=14.32, P<0.001; F=15.52, P<0.001). The serum CircRNA_0048211 level in PMOP group (0.37±0.08) were significantly lower than that of osteopenia group (1.05±0.46) and normal bone mass group (1.73±0.81), the difference was statistically significant ( P<0.05). The levels of BALP (28.42±7.35 μg/L), OPN (17.28±7.30 ng/ml), PINP (58.40±14.37 ng/ml) and β-CTX (1.52±0.28 μg/L) in PMOP group were significantly higher than those in osteopenia group (22.61±5.93 μg/L, 11.95±5.64 ng/ml, 49.16±11.24 ng/ml, 0.81±0.17 μg/L) and normal bone mass group (16.30±4.18 μg/L, 7.62±3.25 ng/ml, 35.48±7.12 ng/ml, 0.37±0.10 μg/L), the difference was statistically significant ( P<0.05). Binary logistic regression analysis showed that decreased CircRNA_0048211 expression level [ OR=3.53, 95% CI (2.73, 10.32)] was a risk factor for the occurrence of PMOP ( P<0.001). ROC curve showed that CircRNA_0048211≤0.76 has a diagnostic significance on PMOP, and its combination of BALP, OPN, PINP and β-CTX has the highest AUC [0.95, 95% CI (0.89, 1.00)] in diagnosing PMOP. Correlation analysis showed that CircRNA_0048211 expression level were negatively correlated with BALP, OPN, PINP and β-CTX ( r=-0.46, P<0.001; r=-0.80, P<0.001; r=-0.81, P<0.001; r=-0.69, P<0.001). Conclusion:The CircRNA_0048211 showed low expression in PMOP, which was negatively correlated with BALP, OPN, PINP and β-CTX. The combination of these five factors has certain clinical value in the diagnosis of PMOP.

Objective:To study the diagnostic value of the artificial intelligence (AI) diagnostic system, ACR TI-RADS classification and AI+ ACR TI-RADS combined diagnostic performance in benign and malignant thyroid nodules and its guiding significance for surgical treatment.Methods:From Nov. 1, 2021, to Feb. 26, 2022, 349 patients with 605 thyroid nodules who received surgical treatment in Department of Thyroid (Hernia) Surgery, Department of General Surgery, the First Medical Center of the PLA General Hospital, were selected. There were 95 males and 254 females, male: female=1:2.67, aged 16-78 years, and the nodule diameter was 0.2-5.6 cm. SPSS 26.0 and R studio software were used for data processing. AI diagnostic system, ACR TI-RADS grading and AI+ ACR TI-RADS combined diagnostic efficacy were statistically analyzed, respectively. ROC curve analysis was performed in parallel.Results:The AUC value of AI+ ACR TI-RADS combined diagnosis was 0.900, greater than 0.857 of AI diagnostic system and 0.788 of ACR TI-RADS, and the difference was statistically significant ( Z= 7.631, both P<0.001) . The sensitivity of the combined diagnosis was 95.32%, the specificity was 84.61%, the accuracy was 92.56%, the positive predictive value was 94.69%, the negative predictive value was 86.27%, the missed diagnosis rate was 4.68%, and the misdiagnosis rate was 15.38%, which were better than the other two diagnostic methods. With an excellent coincidence rate with postoperative pathological results ( Kappa=0.804, P<0.001) . The accuracy of combined diagnosis in identifying the maximum diameter of different tumors was 89.58% for d≤0.5 cm, 96.09% for 0.54.0 cm, better than the other two diagnostic methods. Conclusions:The combined application of AI+ACR TI-RADS has a certain primary screening value in evaluating thyroid nodule properties. The combined diagnosis of the two can more effectively determine the benign and malignant thyroid nodules.