1.Development of a nomogram-based risk prediction model for chronic obstructive pulmonary disease incidence in community-dwelling population aged 40 years and above in Shanghai
Yixuan ZHANG ; Yiling WU ; Jinxin ZANG ; Xuyan SU ; Xin YIN ; Jing LI ; Wei LUO ; Minjun YU ; Wei WANG ; Qi ZHAO ; Qin WANG ; Genming ZHAO ; Yonggen JIANG ; Na WANG
Shanghai Journal of Preventive Medicine 2025;37(8):669-675
		                        		
		                        			
		                        			ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies. 
		                        		
		                        		
		                        		
		                        	
2.Classification of bladder cancer based on immune cell infiltration and construction of a risk prediction model for prognosis.
Guicao YIN ; Shengqi ZHENG ; Wei ZHANG ; Xin DONG ; Lezhong QI ; Yifan LI
Journal of Zhejiang University. Medical sciences 2024;():1-11
		                        		
		                        			OBJECTIVES:
		                        			To classify bladder cancer based on immune cell infiltration score and to construct a risk assessment model for prognosis of patients.
		                        		
		                        			METHODS:
		                        			The transcriptome data and data of breast cancer patients were obtained from the TCGA database. The single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells. The classification of breast cancer patients was realized by unsupervised clustering, and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed. The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis (WGCNA), and the key genes in the modules were extracted. A risk scoring model and a nomogram for risk assessment of prognosis for bladder cancer patients were constructed and verified.
		                        		
		                        			RESULTS:
		                        			The immune cell infiltration scores of normal tissues and tumor tissues were calculated, and B cells, mast cells, neutrophils, T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer. Breast cancer patients were clustered into two groups (Cluster 1 and Custer 2) based on immune cell infiltration scores. Compared with patients with Cluster 1, patients with Cluster 2 were more likely to benefit from immunotherapy (P<0.05), and patients with Cluster 2 were more sensitive to Enbeaten, Docetaxel, Cyclopamine, and Akadixin (P<0.05). WGCNA screened out 35 genes related to key immune cells, and 4 genes (GPR171, HOXB3, HOXB5 and HOXB6) related to the prognosis of bladder cancer were further screened by LASSO Cox regression. The areas under the ROC curve (AUC) of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-, 3- and 5-year survival of patients were 0.735, 0.765 and 0.799, respectively. The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-, 3-, and 5-year overall survival of bladder cancer patients.
		                        		
		                        			CONCLUSIONS
		                        			According to the immune cell infiltration score, bladder cancer patients can be classified. And the bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.
		                        		
		                        		
		                        		
		                        	
3.Research progress on the mechanism of traditional Chinese medicine intervening in esophageal cancer by microRNA regulation
Zhiwen SHEN ; Liqun LI ; Mingyao XU ; Xin LIU ; Jing HUANG ; Xiaoning ZHANG ; Jiaqi YIN ; Sheng XIE
China Pharmacy 2024;35(8):1016-1022
		                        		
		                        			
		                        			Esophageal cancer (EC) is a common malignant tumor of the digestive system with an extremely poor prognosis. MicroRNA (miRNA) is an important regulator in tumor occurrence and development, and can participate in malignant biological behaviors such as tumor cell proliferation, invasion, metastasis and apoptosis. Traditional Chinese medicine has the characteristics of accurate curative effects, wide range of effects, and few side effects. The review uses miRNA as the entry point to systematically elaborate on the mechanism of traditional Chinese medicine-mediated miRNA intervening in EC. The results showed that active ingredients of traditional Chinese medicine (including curcumin, Tussilago farfara polysaccharides, Atractylodes macrocephala polysaccharides and ophiopogonin B) and Dougen guanshitong oral liquid could up-regulate the expressions of miRNAs such as miRNA-532-3p (miR-532-3p), miR-551b-3p, miR-99a, miR-34a, miR-199a-3p and miR-377; and the active ingredients/parts of traditional Chinese medicine (including chrysin and Actinidia arguta extract), and Chinese herbal formulas (including Chaihu shugan san combined with Xuanfu daizhe decoction and Modified jupi zhuru decoction) could down-regulate the expressions of miRNAs such as miR-199a-3p, miR-451 and miR-21, which could regulate the expressions of signaling pathways (phosphoinositide 3-kinase/protein kinase B, etc.) or their downstream protein(zinc-finger and homeobox protein 1, etc.) or enzymes(thymidine kinase-1, etc.), inhibit the proliferation, invasion and metastasis of EC cells and induce apoptosis, thereby ultimately achieving the purpose of preventing the disease from aggravating.
		                        		
		                        		
		                        		
		                        	
4.Role of NF-κB Signaling Pathway in "Reflux Esophagitis-esophageal Cancer" and Traditional Chinese Medicine Intervention:A Review
Mingyao XU ; Liqun LI ; Xin LIU ; Zhiwen SHEN ; Xiaoning ZHANG ; Jing HUANG ; Jiaqi YIN ; Zhu LIU ; Sheng XIE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):221-233
		                        		
		                        			
		                        			Reflux esophagitis is an inflammatory disease of esophageal mucosa damage caused by the reflux of gastric contents into the esophagus. Its incidence is on the rise, and it has become an important precancerous disease of esophageal cancer. Studies have shown that the continuous inflammatory response stimulates the esophageal mucosa, causing abnormal proliferation of esophageal epithelial cells and damage to esophageal mucosal tissue, which eventually leads to the occurrence of heterogeneous hyperplasia and even carcinogenesis. The nuclear transcription factor-kappa B (NF-κB) signaling pathway is one of the most classical inflammatory and cancer signaling pathways. It has been found that abnormal activation of the NF-κB signaling pathway is crucial to the development and prognosis of reflux esophagitis and esophageal cancer. It is widely involved in the proliferation, autophagy, apoptosis, and inflammatory response of esophageal epithelial cells and tumor cells, accelerating the transformation of reflux esophagitis to esophageal cancer and making it a potential target for the treatment of reflux esophagitis and esophageal cancer. Currently, there is no specific treatment for reflux esophagitis and esophageal cancer, and large side effects often appear. Therefore, finding a promising and safe drug remains a top priority. In recent years, traditional Chinese medicine scholars have conducted a lot of research on NF-κB signaling pathway, and the results indicate that NF-κB signaling pathway is an important potential target for traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer, but there is a lack of comprehensive and systematic elaboration. Therefore, this paper summarized the relevant studies in recent years, analyzed the relationship among NF-κB signaling pathway, reflux esophagitis, esophageal cancer, and transformation from inflammation to cancer, and reviewed the research literature on the regulation of the NF-κB signaling pathway in traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer, so as to provide new ideas for the prevention and treatment of reflux esophagitis and esophageal cancer. 
		                        		
		                        		
		                        		
		                        	
5.Quality Analysis of Schefflera kwangsiensis Merr.Based on HPLC Fingerprinting Combined with Chemometrics
Xin YANG ; Nianzhi XU ; Wenfeng FU ; Wentao ZHANG ; Hanzhi YIN ; Bing LI
Herald of Medicine 2024;43(2):267-273
		                        		
		                        			
		                        			Objective Based on HPLC fingerprinting and chemometrics,to evaluate the quality of Schefflera kwangsiensis Merr.from Guangxi.Methods HPLC was used to establish fingerprints of Schefflera kwangsiensis Merr.from ten different origins,and gradient elution was carried out with methanol-0.1%phosphoric acid aqueous solution as mobile phase.Cluster analysis(CA),principal component analysis(PCA)and orthogonal partial least squares-discriminant analysis(OPLS-DA)were applied to evaluate quality.Results The fingerprints of Schefflera kwangsiensis Merr.from ten different origins were established by HPLC,a total of 22 common peaks were calibrated,with a similarity range of 0.922-0.999.Four chromatographic peaks were identified as rhodopsin,4,5-bis-O-caffeoylquinic acid,caffeic acid,and naringin.The samples were classified into four types according to the CA and OPLS-DA.PCA identified four principal components with a cumulative contribution rare of 95.39%.Conclusion The quality of Schefflera kwangsiensis Merr.can be comprehensively evaluated by fingerprinting combined with CA,PCA and OPLS-DA analysis.The Study can provide a reference for improving the quality control and assessment of Schefflera kwangsiensis Merr.
		                        		
		                        		
		                        		
		                        	
6.Expressions of cytokines and procalcitonin in infective endocarditis
Ruo-Xin WANG ; Liang FU ; Jin-Long ZHAO ; Zong-Hui CHEN ; Yin-Kai NI ; Feng LI
Journal of Regional Anatomy and Operative Surgery 2024;33(1):55-58
		                        		
		                        			
		                        			Objective To investigate the expressions of 12 cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-α,IFN-γ,TNF-α)and procalcitonin in patients with infective endocarditis(IE).Methods Ten IE patients admitted to our hospital from December 2021 to December 2022 were included into the IE group,10 patients with non-infectious and non-rheumatic valvular diseases who were admitted to our hospital at the same period were randomly selected as the control group,and blood sampling of all patients were conducted at admission.The expressions of 12 cytokines and blood routine indexes were detected by flow cytometry,and the level of procalcitonin was detected by ELISA.The correlations among the expression levels of cytokines in IE patients were analyzed by Pearson method and the correlations of IL-8 level and white blood cell count with procalcitonin in IE patients were analyzed by Spearman method.Results Compared with the control group,the levels of cytokines of IL-1β,IL-2,IL-6,IL-10,TNF-α,IFN-α,IFN-γ and IL-12p70 in the IE group were significantly increased(P<0.05),the white blood cell count,neutrophil percentage and procalcitonin were significantly increased(P<0.05).There was no significant difference in the percentage of monocytes between the two groups(P>0.05).IFN-α of IE patients was positively correlated with IL-2,TNF-α,IL-1β and IL-12p70,IL-2 was positively correlated with TNF-α and IL-1β,IL-12p70 was positively correlated with IFN-γ,and procalcitonin was significantly positively correlated with IL-8 and white blood cell count,with statistically significant differences(P<0.05).Conclusion The levels of IL-1β,IL-2,IL-6,IL-10,TNF-α,IFN-α,IFN-γ,IL-12p70 and procalcitonin in IE patients are significantly higher than those in the normal population,and the detections of these indicators are of guiding significance for the early diagnosis of IE and the evaluation of the severity of the disease.
		                        		
		                        		
		                        		
		                        	
7.Spinal cord electrical stimulation with neurophysiological monitoring for treatment of high-risk diabetic foot
Zhitao LI ; Wenhan LI ; Shaoya YIN ; Baolong LIU ; Nan QIN ; Xin LIU
Chinese Critical Care Medicine 2024;36(3):298-302
		                        		
		                        			
		                        			Objective:To evaluate the clinical efficacy of a single-session implantation of spinal cord electrical stimulation with neurophysiological monitoring a spinal cord electrical stimulator under general anesthesia with neurophysiological monitoring for the treatment of high-risk diabetic foot.Methods:The clinical data of seven patients with high-risk diabetic foot who underwent spinal cord electrical stimulation in neurosurgery ward nine of Tianjin Huanhu Hospital from May 2022 to May 2023 were collected. The operation was performed under general anesthesia with the "C" arm X ray machine guidance and neurophysiological monitoring. The arterial diameter and peak flow rate of lower extremity, lower extremity skin temperature (calf skin temperature, foot skin temperature), visual analog scale (VAS), continuous distance of movement, blood glucose level and toe wound were compared between patients before and after surgery.Results:A total of seven patients with high-risk diabetic foot were included. The diameters and peak flow rates of femoral artery, popliteal artery, anterior tibial artery, posterior tibial artery and dorsal foot artery in both lower limbs were significantly improved after surgery. All patients had different degrees of lower limb pain before operation. After operation, VAS score decreased significantly (1.1±0.9 vs. 6.8±3.4), the pain was significantly relieved, and the calf skin temperature and foot skin temperature were significantly higher than those before surgery [calf skin temperature (℃): 33.3±0.9 vs. 30.9±0.7, foot skin temperature (℃): 31.4±0.8 vs. 29.1±0.6], fasting blood glucose and postprandial blood glucose were significantly lower than those before surgery [fasting blood glucose (mmol/L): 7.6±1.4 vs. 10.5±1.2, postprandial blood glucose (mmol/L): 9.3±2.3 vs. 13.5±1.1], the differences were statistically significant (all P < 0.01). The lower limb movement of all seven patients was significantly improved after surgery, including one patient who needed wheelchair travel before surgery, and one patient who had intermittent claudication before surgery. Among them, one patient needed wheelchair travel and one patient had intermittent claudication before surgery. All patients could walk normally at 2 weeks after operation. Among the seven patients, two patients had the diabetic foot wound ulceration before surgery, which could not heal for a long time. One month after surgery, blood flow around the foot wound recovered and the healing was accelerated. The wound was dry and crusted around the wound, and the wound healed well. Conclusion:For diabetic high-risk foot patients who are intolerant to diabetic peripheral neuralgia and local anesthesia spinal cord electrical stimulation test, one-time implantation of spinal cord electrical stimulator under general anesthesia under neurophysiological monitoring can effectively alleviate peripheral neuralgia and other diabetic foot related symptoms, improve lower limb blood supply, and reduce the risk of toe amputation. Clinical practice has proved the effectiveness of this technique, especially for the early treatment of diabetic high-risk foot patients.
		                        		
		                        		
		                        		
		                        	
8.Effect of RDN on long-term blood pressure in refractory hypertensive patients with different cardiovascular risk stratification
Li WANG ; Chao LI ; Dasheng XIA ; Qiang HE ; Xiangdong ZHAO ; Xin CHEN ; Suzhen GUO ; Xuemei YIN ; Chengzhi LU
Chinese Journal of Cardiology 2024;52(8):899-905
		                        		
		                        			
		                        			Objective:To investigate the long-term therapeutic effects and safety of renal denervation (RDN) on hypertensive patients with different cardiovascular risks, as well as its impact on adverse events, cardiovascular death and all-cause mortality.Methods:This was a single-center, single-arm, real-world retrospective study. Patients with refractory hypertension who underwent RDN at Tianjin First Central Hospital from July 6, 2011 to December 23, 2015 were enrolled and divided into either a high or intermediate-low risk group based on baseline cardiovascular risk. The treatment responsiveness of hypertensive patients with different cardiovascular stratification to RDN was assessed by comparing the results of office blood pressure, home blood pressure, and 24-h ambulatory blood pressure monitoring at 1, 5, and 11 years after RDN. Long-term safety of RDN was assessed by creatinine, and estimated glomerular filtration rate (eGFR) at 1 and 11 years after RDN. In addition, the total defined daily dose (DDD) of antihypertensive medications and the incidence of long-term adverse events, cardiovascular deaths, and all-cause deaths after RDN were followed up 11 years after RDN in person or by telephone.Results:A total of 62 patients with refractory hypertension, aged (50.2±15.0) years, of whom 35 (56.5%) were male, were included. There were 35 cases in high-risk group and 27 cases in low and medium risk group. The decrease in clinic systolic blood pressure (high risk vs. low-medium risk: (-38.0±15.1) mmHg vs. (-25.0±16.6) mmHg(1 mmHg=0.133kPa), P=0.002), home self-measured systolic blood pressure ((-28.4±12.7) mmHg vs. (-19.7±13.1) mmHg, P=0.011) and clinic systolic blood pressure 11 years after RDN ((-43.0±18.4) mmHg vs. (-27.8±17.9) mmHg, P=0.003) in the high-risk group was significantly higher than that in the low-medium risk group. The differences in heart rate and the decrease in total DDD number of antihypertensive drugs between the two groups were not statistically significant (all P>0.05). Creatinine and eGFR levels in the two groups at 1 and 11 years after RDN were not statistically significant when compared with the baseline values (all P>0.05). The cumulative cardiovascular mortality rate was 1.6% (1/62) and 8.1% (5/62), and the cumulative all-cause mortality rate was 3.2% (2/62) and 11.3% (7/62) at 5 and 11 years after RDN, respectively. The differences in the incidence rate of adverse events, cardiovascular mortality, and all-cause mortality rate between the two groups were not statistically significant (all P>0.05). Conclusions:RDN has long-term antihypertensive effect and good safety. Hypertensive patients who belong to the high-risk stratification of cardiovascular risk may respond better to RDN treatment.
		                        		
		                        		
		                        		
		                        	
9.miR-4645-5p regulates malignant biological behavior of esophageal cancer cells by targeting MUC16
Zhen ZHOU ; Linna JIANG ; Peng HE ; Feng YIN ; Ping WEI ; Xin AN ; Xianghong LI
International Journal of Laboratory Medicine 2024;45(1):54-59
		                        		
		                        			
		                        			Objective To investigate the effect of microRNA(miR)-4645-5p on the proliferation,invasion and epithelial-mesenchymal transition of esophageal cancer cells by targeting mucin 16(MUC16)and its mo-lecular mechanism.Methods The expression of miR-4645-5p in esophageal cancer tissues was analyzed online by TCGA database.The expression level of miR-4645-5p in esophageal cancer cell lines was analyzed by fluo-rescent real-time fluorescence quantitative polymerase chain reaction(qPCR).KYSE-30 cells were transfected with miR-4645-5p mimic and negative control mimic by lipofection technology,and were divided into miR-4645-5p group and control mimic group.The proliferation ability,migration ability and invasion ability of transfected KYSE-30 cells were analyzed by CCK-8 method,scratch test and Transwell test respectively.The target gene of miR-4645-5p was predicted by the bioinformatics website,and the binding of miR-4645-5p to the target gene was detected by the dual-luciferase reporter gene assay.The expression level of MUC16 mR-NA was detected by qPCR,and the protein expression levels of MUC16,transcription factor-1(ZEB-1),zonal atresia protein(ZO-1),tight junction protein-1(Claudin-1)and α-smooth muscle actin(α-SMA)were detected by Western blotting.Results The expression level of miR-4645-5p in esophageal cancer tissues was signifi-cantly lower than that in adjacent tissues(P<0.01).Compared with HET-1 A,the expression of miR-4645-5p was lower in esophageal cancer cell lines(P<0.05).After overexpression of miR-4645-5p,the proliferation a-bility of KYSE-30 cells was significantly reduced(P<0.05),the migration ability was significantly reduced(P<0.01)and the invasion ability was significantly reduced(P<0.01).miR-4645-5p targeted and negatively regulated the expression of MUC16 mRNA(P<0.01).After overexpression of miR-4645-5p,the protein ex-pression levels of MUC16,ZEB-1 and α-SMA were all down-regulated,and the protein expression levels of ZO-1 and Claudin-1 were up-regulated.Conclusion miR-4645-5p regulates the malignant biological behavior of esophageal cancer KYSE-30 cells by targeting MUC16.
		                        		
		                        		
		                        		
		                        	
10.Classification of bladder cancer based on immune cell infiltration and construction of a risk prediction model for prognosis
Guicao YIN ; Shengqi ZHENG ; Wei ZHANG ; Xin DONG ; Lezhong QI ; Yifan LI
Journal of Zhejiang University. Medical sciences 2024;53(1):47-57
		                        		
		                        			
		                        			Objective:To classify bladder cancer based on immune cell infiltration score and to construct a prognosis assessment model of patients with bladder cancer.Methods:The transcriptome data and clinical data of breast cancer patients were obtained from the The Cancer Genome Atlas(TCGA)database.Single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells.The classification of breast cancer patients was achieved by unsupervised clustering,and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed.The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis(WGCNA),and the key genes in the modules were identified.A risk scoring model and a nomogram for prognosis assessment of bladder cancer patients were constructed and verified.Results:B cells,mast cells,neutrophils,T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer.The patients were clustered into two groups(Cluster 1′ and Custer 2)based on immune cell infiltration scores.Compared with patients with Cluster 1′,patients with Cluster 2 were more likely to benefit from immunotherapy(P<0.05),and patients with Cluster 2 were more sensitive to Enbeaten,Docetaxel,Cyclopamine,and Akadixin(P<0.05).35 genes related to key immune cells were screened out by WGCNA and 4 genes(GPR171,HOXB3,HOXB5 and HOXB6)related to the prognosis of bladder cancer were further screened by LASSO Cox regression.The areas under the ROC curve(AUC)of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-,3-and 5-year survival of patients were 0.735,0.765 and 0.799,respectively.The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-,3-,and 5-year overall survival of bladder cancer patients.Conclusions:According to the immune cell infiltration score,bladder cancer patients can be classified.Furthermore,bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.
		                        		
		                        		
		                        		
		                        	
            
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