Objective:To detect the prevalence of mosaic loss of chromosome Y in adult men in ten study areas in China, describe the epidemiological distribution of mosaic loss of chromosome Y (mLOY) carriers and assess its prospective association with lung cancer.Methods:Based on the data from baseline survey, genetic analysis and follow-up (as of December 31, 2018) from China Kadoorie Biobank, we used Mosaic Chromosomal Alterations pipeline to detect mLOY carriers in 10 areas in China and described the epidemiological characteristics of mLOY carriers in adult men, including age, area distribution, lifestyle and disease history. We used multivariate logistic regression model to identify the potential relevant factor of mLOY. Cox proportional hazard regression model was fitted to assess the prospective association of mLOY with lung cancer. Stratification analysis were conducted to evaluate the potential modification effects of smoking and age. We also conducted mediation analysis to assess the mediating effect of mLOY in the association between smoking and lung cancer.Results:A total of 42 859 adult men were included in our analysis, in whom 2 458 mLOY carriers were detected (5.7%). The detection rate increased with age ( P<0.05). The detection rate was higher in urban area (7.3%±0.2%) than that in rural area (4.7%±0.1%). The results of logistic regression analysis indicated that smoking might be a risk factor for the detection of mLOY ( OR=1.49, 95% CI:1.36-1.64). After follow-up for average 11.1 years, 1 041 lung cancer cases were observed. The prospective analysis showed that mLOY carriers had an increased risk for lung cancer by 24% compared with non-mLOY carriers ( HR=1.24, 95% CI:1.01-1.52) and expanded mLOY carriers (mLOY cell proportion ≥10%) had an increased risk for lung cancer by 50% ( HR=1.50, 95% CI:1.13-2.00). Stratification analysis showed no modification effects of smoking and age in the association between mLOY and lung cancer (interaction P>0.05). Mediation analysis showed that mLOY could be a mediating factor in the association between smoking and lung cancer, the estimated effect was 0.09 (0.01-0.17). Conclusions:There were significant differences in the detection rate of mLOY in adult men with different social-economic characteristics and lifestyles in ten areas in China. Besides, mLOY carriers, especially expanded mLOY carriers, had increased risk for lung cancer and mLOY might be a mediating factor in the association between smoking and lung cancer.

[Objective]To explore the application of alcohol in unearthed medical literature,so as to provide reference for the clinical application of alcohol in modern Chinese medicine.[Methods]Based on the unearthed literatures such as Wushier Bingfang,Wuwei Medical Bamboo Slips of Han Dynasty,ZHOU Jiatai Medical Bamboo Slips of Qin Dynasty,Tianhui Medical Bamboo Slips and so on,combined with the relevant records in the handed down literature,the application of alcohol in the unearthed literatures was compared and summarized.[Results]Although there is no specific reason for the use of alcohol in the unearthed medical literature,a comprehensive analysis can be made from the related records in the contemporaneous literature.The analysis showed that in the pre-Qin,Qin and Han Dynasties,most of the alcohol was yellow wine,which was used in the way of alcohol mixing,alcohol decoction and impregnation,and was widely used in the treatment of various diseases.It is concluded that the alcohol has the effect of"changing the medicinal properties,direct to the disease""warming the channels and clearing the collaterals,removing blood stasis and relieving pain""correcting the odor,enhancing the drug effect"and so on.The application of alcohol in the later literature showed different characteristics in each period,but all developed on the basis of the application of alcohol in the Qin and Han Dynasties.[Conclusion]Alcohol has great potential in the clinical treatment of modern Chinese medicine,but the soaking and decocting time of alcohol for medicine,the effect of different temperatures is worth further study.

Urothelial carcinoma (UC) is one of the most common malignant tumors. The development of omics technologies has provided new perspectives for the diagnosis and treatment of UC. Genomics, transcriptomics, and proteomics have unveiled the molecular mechanisms and biological characteristics of UC, which are conducive to the discovery of new therapeutic targets and biomarkers. Single-cell omics and spatial transcriptomics have further deepened the understanding of cellular heterogeneity and the tumor microenvironment. These technologies show great potential in molecular typing, non-invasive diagnosis, early screening, and personalized treatment of UC. This article, in response to the national key strategy, will delve into how omics technologies can drive new developments in the diagnosis and treatment of UC, as well as the application and translation prospects of these technologies in UC.

Urothelial carcinoma (UC) is one of the most common malignant tumors. The development of omics technologies has provided new perspectives for the diagnosis and treatment of UC. Genomics, transcriptomics, and proteomics have unveiled the molecular mechanisms and biological characteristics of UC, which are conducive to the discovery of new therapeutic targets and biomarkers. Single-cell omics and spatial transcriptomics have further deepened the understanding of cellular heterogeneity and the tumor microenvironment. These technologies show great potential in molecular typing, non-invasive diagnosis, early screening, and personalized treatment of UC. This article, in response to the national key strategy, will delve into how omics technologies can drive new developments in the diagnosis and treatment of UC, as well as the application and translation prospects of these technologies in UC.

[Objective]To elucidate the meridian manipulations described in the Han bamboo slips of Zhangjiashan from a meridian perspective,providing a theoretical foundation for the application of ancient meridian manipulations in modern clinical practice.[Methods]Based on the records in the unearthed literature and cultural relics of the pre-Qin,Qin and Han Dynasties,this paper summarizes the Daoyin technique in the pre-Qin,Qin and Han Dynasties,explores the in-depth relationship between Daoyin technique and meridian muscles,and selects the common orthopedic diseases in modern clinic,such as neck pain,ankle pain,knee pain and shoulder pain,which are closely related to meridian muscles.The original text and Daoyin movements are analyzed,and the Daoyin movements are discussed from the perspective of meridian muscles.[Results]It is found that the Daoyin described in the pre-Qin,Qin and Han Dynasties is mainly simple body movements.The meridians described in the Book of Pulse are mostly meridiansand tendons,so the theory of meridians and tendons may be more suitable for the thinking of the physicians at that time.Using the theory of meridians and tendons to analyze the Daoyin in Yinshu,it is found that the Daoyin therapy for neck pain in the book should be mainly treated for the neck pain of the sun meridian muscles;the treatment of lateral ankle pain is mainly adjusted by the Shaoyang meridian muscles of the foot,and the treatment of medial ankle pain is mainly adjusted by the Taiyin meridian muscles of the foot;the Daoyin therapy for knee pain is used to adjust the meridian muscles of the six meridians of the foot;the treatment of shoulder pain,the use of"Yuanxing three hundred"to treat the shoulder pain caused by the Shaoyang and Yangming meridian muscles of the hand,the use of"Qianyuan"to treat the shoulder pain caused by the sun meridian muscle disease,the use of"Zhiluo"to treat the shoulder pain caused by the sun meridian muscle disease,and the use of"Houfu"to treat the shoulder pain caused by the Taiyin meridian muscle disease.It is more reasonable to explain the treatment principles of Daoyin using the theory of meridian sinew,which can further elucidate the treatment principles of Daoyin and clarify the corresponding disease indications for different Daoyin.[Conclusion]Looking at the Daoyin manipulations in Yinshu from the perspective of meridians and tendons can further clarify the diseases treated by Daoyin manipulation,make the treatment more accurate and effective,and provide more ideas for the clinical application of Daoyin manipulation in modern traditional Chinese medicine.

Objective:To investigate the clinical and pathological characteristics and prognosis of upper tract urothelial carcinoma (UTUC) with concurrent other histological variants.Methods:The clinical data of 566 UTUC patients admitted to Peking University People's Hospital from January 2007 to April 2021 were retrospectively analyzed. Among them, 289 were males and 277 were females, with an average age of (67.3±10.0)years old. Among the patients, 97 had a history of smoking, 29 had undergone kidney transplantation, 120 had diabetes, 76 had coronary heart disease, 146 had hyperlipidemia, 271 had hypertension, and 50 had a history of chronic kidney disease. Among the UTUC cases, 366 had concurrent hydronephrosis, 55 had concurrent bladder cancer, and 43 had a history of previous bladder cancer. The distribution included 210 cases of renal pelvis carcinoma, 5 cases of carcinoma at the renal pelvis-ureter junction, 226 cases of ureteral carcinoma, and 125 cases of multifocal tumors. Patients were classified into the pure UTUC group and the UTUC with concurrent other histological variants group based on postoperative pathology, and their clinical and pathological features were compared. Logistic regression analysis was used to explore risk factors for the occurrence of histological variations in UTUC. The log-rank test was employed to compare the overall survival (OS) and cancer-specific survival (CSS) between the two groups, while Cox regression analysis was performed to investigate prognostic factors.Results:Among the 566 cases, 511 were pure UTUC and 55 were UTUC with concurrent other histological variants. Among the latter, 30 cases had squamous differentiation, 6 had glandular differentiation, 5 had mucinous differentiation, 5 had sarcomatoid carcinoma, 2 had micropapillary carcinoma, 2 had neuroendocrine carcinoma, 1 had giant cell carcinoma, and 4 had other mixed histological variations. The proportion of patients with a history of kidney transplantation was higher in the UTUC with concurrent histological variants group than that in the pure UTUC group [14.5% (8/55) vs. 4.1% (21/511)], with statistically significant difference ( P=0.003). In the UTUC with concurrent histological variants group, the proportion of postoperative high-grade tumors [98.2% (54/55) vs. 80.2% (410/511)], muscle-invasive tumors [89.1% (49/55) vs. 68.1% (348/511)], lymph node metastasis tumors [10.9% (6/55) vs. 2.3% (12/511)], and maximum tumor diameter [(3.60±2.64) cm vs. (2.96±1.98) cm] were higher than those in the pure UTUC group ( P<0.05). Multivariate logistic regression analysis showed that a history of kidney transplantation ( OR=4.991, 95% CI 1.749-13.615, P=0.002) was an independent predictive factor for the occurrence of histological variants. Follow-up was conducted for 1 to 174 months, with a median follow-up time of 32.8 months. UTUC with concurrent histological variants was significantly associated with worse OS and CSS ( P<0.05). Multivariate Cox regression analysis indicated that histological variants were an independent risk factor for OS ( HR=1.860, 95% CI 1.228-2.816, P=0.003) and CSS ( HR=2.146, 95% CI 1.349-3.412, P=0.001). Conclusions:UTUC with concurrent other histological variants exhibited higher postoperative tumor grade and stage compared to pure UTUC, and UTUC with concurrent other histological variants was an independent risk factor for worse prognosis.

Objective:To compare the clinical efficacy and safety of intra-articular platelet rich plasma combined with hyaluronic acid and platelet rich plasma alone in the treatment of knee osteoarthritis.Methods:The relevant literatures published between January 2010 and December 2021 on the randomized control study of intra-articular injection of platelet rich plasma and hyaluronic acid and injection of platelet rich plasma only in the treatment of knee osteoarthritis were searched. The bias risk of all the literatures included in the study was evaluated by Revman 5.3 software, and the data were processed and analyzed by Stata 16.0 software. The standardized mean difference ( SMD) was calculated for the difference of efficacy indexes, and the difference was compared by t- test. The odds ratio ( OR) was calculated for the difference of safety in-dex, and the difference was compared by t- test. Results:①A total of 7 relevant research literatures were in-cluded, all of which were in English. ②A total of 675 patients were included in the study, of which 330 patients were treated with intra-articular injection of platelet rich plasma and hyaluronic acid, and 345 patients were treated with intra-articular injection of platelet rich plasma only. ③The VAS scores of patients with platelet rich plasma and hyaluronic acid injection combined with injection and platelet rich plasma injection alone were compared. After 1 and 3 months of injection, the VAS scores of patients with platelet rich plasma combined with hyaluronic acid injection were compared with those of patients with platelet rich plasma injection only. There was no significant difference[ SMD(95% CI)=-0.02(-0.30, 0.27), t=-0.12, P=0.902; SMD(95% CI)=-0.40(-0.80, 0.00), t=-1.97, P=0.051]. After 6 months of injection, the VAS scores of patients with combined injection of platelet rich plasma and hyaluronic acid were significantly lower than those of patients with injection of platelet rich plasma only, and the difference was statistically significant [ SMD(95% CI)=-0.33 (-0.55, -0.11), t=-2.98, P=0.012]. ④The WOMAC scores of patients with combined injection of platelet rich plasma, hyaluronic acid and platelet rich plasma only were compared. After 12 months of treatment, the WOMAC scores of patients with combined injection of platelet rich plasma and hyaluronic acid were significantly higher than those of patients with PRP only, and the difference was statistically significant [ SMD(95% CI)=-0.30(-0.58, -0.03), t=-2.14, P=0.033]. ⑤The incidence of adverse events of platelet rich plasma combined with hyaluronic acid was lower than that of platelet rich plasma only [ OR(95% CI)=0.55(0.33, 0.93), P=0.021]. Conclusion:Compared with intra-articular injection of platelet rich plasma only, the short-term clinical efficacy of combined injection of platelet rich plasma and hyaluronic acid is equivalent to that of injection of platelet rich plasma only, but the long-term clinical efficacy is significantly better, and the safety of combined injection of platelet rich plasma and hyaluronic acid is significantly better.

Objective:To assess the association between warm ischemia time (WIT) and renal function in patients undergoing laparoscopic partial nephrectomy.Methods:A total of 344 patients treated with laparoscopic partial nephrectomy in Peking University People’s Hospital were included. There were 240 males (69.8%) and 104 females (30.2%) with a median age of 57 (23-89) years.The median BMI was 25.6 (16.7-36.0) kg/m 2.213 cases (61.9%) were associated with hypertension.There were 66 (19.2%) patients with diabetes mellitus. There were 92 cases (26.7%) with smoking history. The median preoperative creatinine was 73 (32-170) μmol/L. The median preoperative estimated glomerular filtration rate (eGFR) was 95 (33-142) ml/(min·1.73m 2). The maximum diameter of the tumor was 2.5 (7-9) cm.314 (91.3%) patients with renal cancer stage T 1. All patients underwent warm ischemia during the operation. The patients were divided into three groups for analysis. Restricted cubic spline regression analysis was used to assess the association between WIT as a continuous variable and percentage change of eGFR. Analysis of covariance was used to compare postoperative eGFR among the three groups, and to adjust for preoperative eGFR and tumor diameter. Results:There were statistically significant differences in the percentage change of postoperative eGFR ( P=0.009) and tumor diameter ( P<0.001) among the three groups. Restricted cubic spline regression analysis showed that with the prolongation of WIT, the percentage change of postoperative eGFR gradually decreased, and the curve began to stabilize after 30 minutes (R 2=0.044, P=0.015). The results of covariance analysis showed that after adjusting for baseline preoperative eGFR and tumor size, the effect of WIT on postoperative eGFR was significantly different among the three groups ( F=3.864, P=0.022). The postoperative eGFR in the WIT<20 min group was significantly higher than that in 20 min≤WIT<30 min group( P=0.009) and WIT≥30 min group( P=0.017). There was no significant difference in postoperative eGFR between the two groups with longer WIT( P=0.806). Conclusions:In partial nephrectomy, patients with WIT less than 20 minutes had higher postoperative eGFR levels than those with WIT greater than 20 minutes. However, when WIT exceeded 20 minutes, prolonged ischemia time did not lead to further decline in renal function.

Objective:To investigate the correlation of intratumoral fibrosis with the prognosis of clear cell renal cell carcinoma (ccRCC).Methods:The correlation of the transcriptional expression of the primary collagen with the prognosis in ccRCC was evaluated using the Cancer Genome Atlas (TCGA) database, including 530 ccRCC patients with complete information. Of them, 344 cases were male, 186 cases were female. The age of 264 cases was ≤ 60 years, and the age of 266 cases was > 60 years. The pathology grade of 241 patients was G 1-2 grade, and the pathology of 281 cases were G 3-4 grade, 8 cases were undetermined grade. There were 322 cases with AJCC stage Ⅰ-Ⅱ and 205 cases with AJCC stage Ⅲ-Ⅳ, and 3 cases with undetermined stage. There were 420 cases in M 0 and 78 cases in M 1, and 32 cases without distant metastases information. Furthermore, the paraffin sections of 158 non-cystic ccRCC patients confirmed by pathology from November 2005 to November 2017 were further used to evaluate the level of collagen of ccRCC and the status of the pseudocapsule by the Masson staining, Sirius red staining and multicolor immunofluorescence staining of collagen Ⅰ and collagen Ⅲ. Of them, 112 cases were male, 46 cases were female. There were 100 cases with age ≤ 60 years, and 58 cases with age > 60 years. The pathology grade of 111 cases were G 1-2, and the pathology grade of 47 cases were G 3-4. There were 144 cases with AJCC stage Ⅰ-Ⅱ, 14 cases with AJCC stage Ⅲ-Ⅳ. Kaplan-Meier survival curve were used to analyze the relationship between tumor collagen parameters and the overall survival prognosis of patients with ccRCC. Results:The transcriptome results of the TCGA database indicated that the expression level of COL1A1 in ccRCC tissues was significantly higher than that in adjacent normal tissues ( P<0.001). The high expression of collagen suggested a worse overall survival prognosis ( HR=1.165, P=0.002). In addition, the high ratio of COL1A1/COL3A1 indicated a worse overall survival prognosis ( HR=1.901, P<0.001) compared with the low ratio. We further confirmed that the abundance of collagen in tumor was significantly increased compared with the normal adjacent tissues by the Masson staining [41.0 (14.0-75.0) vs.15.0 (3.0-57.0), P<0.001] and the Sirius red staining [42.5 (10.0-90.0) vs.10.0 (2.5-60.0), P<0.001] on 30 ccRCC tissues and adjacent normal tissues. Based on the Masson staining, we found that high collagen abundance in tumor tissue was associated with more G 3-4 grade of tumor compared with low collagen abundance (38.5% vs.21.3%, OR=2.316, 95% CI 1.146-4.681, P=0.023). Kaplan-Meier survival curve showed that higher collagen abundance was associated with a worse overall survival prognosis in ccRCC ( HR=2.630, P=0.007). However, incomplete fibrous pseudocapsule was associated with a worse overall survival prognosis ( HR=11.140, P<0.001). Conclusions:In ccRCC, intratumoral collagen fiber level was overexpressed. High intratumoral collagen level and incomplete fibrous pseudocapsule may indicate a poor overall survival prognosis.

Objective : To explore the effect of sericin on podocyte epithelial-mesenchymal transition induced by high glucose． Methods : Conditional immortalized mouse podocytes were used as the research object to construct podocyte injury model by high glucose stimulation．The podocytes were divided into normal (NG) group ，hyperton- ic control (MG) group ，high glucose injury ( HG) group ，low ，medium and high dose sericin ( LS ，MS ，HS) group．CCK-8 method was used to determine the viability of podocytes in each group ; the morphological structure of podocytes in each group was observed by ordinary optical inverted microscope．The migration ability was detected by Transwell and cell scratch test．Western blot was used to detect the expression levels of EMT-related mesenchy- mal phenotype factors Snai1，α-SMA，FSP-1，MMP-9 and epithelial phenotype factors Nephrin，E-cadherin，and WT-1 in podocytes of each group. Results : Compared with NG group，HG group showed lower podocyte activity (P＜0. 01) ，worse podocyte status and enhanced podocyte migration ability，up-regulated Snai1，α-SMA，FSP-1 and MMP-9 protein expressions (P ＜0. 01) ，and down-regulated Nephrin，E-cadherin and WT-1 protein expres- sions (P＜0. 01) ．Compared with HG group，the viability of podocytes in sericin group increased (P＜0. 05) ，the state of podocytes was improved ，the migration ability of podocytes was weakened ，the expression of Snai1 ，α - SMA，FSP-1 and MMP-9 was down-regulated (P＜0. 05) ，and the expression of Nephrin，E-cadherin and WT-1 was up-regulated (P ＜0. 05 ) ． Conclusion Sericin can alleviate podocyte epithelial-mesenchymal transition in- duced by high glucose.