ObjectiveTo investigate the regulatory effect of icariin （ICA） on transforming growth factor-β₁ （TGF-β₁）/Smad pathway in bone microvascular endothelial cells （BMECs） and the effect on autophagy in BMECs. MethodsBMECs were isolated and cultured， and the cell types were identified by immunofluorescence. Cells were divided into the control group， model group （0.1 g·L^-1 methyl prednisolone）， ICA group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA）， and TGF-β inhibitor group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA +1×10^-5 mol·L^-1 LY2157299）. Transmission electron microscopy was used to observe the ultrastructure and autophagosome number of BMECs. Autophagy double-standard adenovirus was used to monitor the confocal autophagy flow generation of each cell. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the gene and protein expression of autophagy in the TGF-β₁/ Smad pathway. ResultsAfter cell separation culture， platelet endothelial cell adhesion molecule （CD31） and von willebrand factor （vWF） immunofluorescence identified BMECs. Transmission electron microscopy showed that the cell membrane was damaged， and the nucleus was pyknotic and broken in the model group. Compared with the model group， the ICA group had complete cell membranes， clear structures， with autophagy-lysosome sparsely distributed. The confocal photo showed that BMECs had autophagosomes and autophagy-lysosomes， and the autophagy expression of the ICA group was similar to that of the blank group. Compared with the blank group， in the model group and the LY2157299 group， autophagosomes and autophagy-lysosomes were barely seen in the autophagy flow. Compared with the blank group， the mRNA and protein expressions of autophagy effector protein 1 （Beclin1） and microtubule-associated protein 1 light chain 3B （LC3B） in the model group were significantly decreased （P<0.01）， and those of ubiquitin-binding protein （p62） were significantly increased （P<0.01）. The mRNA expression of TGF-β₁， Smad homolog 2 （Smad2）， and Smad homolog 3 （Smad3） decreased （P<0.05， P<0.01）. The protein expressions of TGF-β₁， p-Smad2， and p-Smad3 were significantly decreased （P<0.01）. Compared with those of the model group， the mRNA and protein expression of Beclin1 and LC3B in BMECs of the ICA group increased （P<0.01）， and those of p62 significantly reduced （P<0.01）. The mRNA expression of TGF-β₁， Smad2， and Smad3 increased significantly （P<0.01）. The protein expression of TGF-β₁， p-Smad2， and p-Smad3 increased significantly （P<0.01）. Compared with those in the model group， the mRNA and protein expressions of Beclin1， LC3B， and p62 in the inhibitor group were not statistically significant. The expression of key genes and proteins of the TGF-β₁ pathway in the inhibitor group was not statistically significant. ConclusionICA can promote glucocorticoid-induced autophagy expression of BMECs， and its mechanism may be related to activating the TGF-β₁/Smad signaling pathway.

Steroid-induced osteonecrosis of the femoral head （SONFH） is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells， necrosis， and trabecular fractures， SONFH is accompanied by pain， femoral head collapse， and joint dysfunction， which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis， bone microvascular endothelial cell （BMEC） apoptosis， oxidative stress， and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation， thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts， promoting angiogenesis in BMECs， and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine （TCM） has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway， as well as its regulatory effects on osteoblasts， mesenchymal stem cells， osteoclasts， BMECs， and other cells. Additionally， the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings， this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM， it is expected to bring safer and more effective treatment options for patients with SONFH.

Objective To analyze the trend of heart disease death and the life expectancy without cause of death in Qidong City, Jiangsu Province from 1990 to 2019, and to provide reference for the prevention and control of heart disease. Methods Data on heart disease deaths among residents in Qidong City from 1990 to 2019 were collected through the Qidong City Death Registration and Monitoring System. The crude mortality rate (CR) and Chinese age-standardized mortality rate (CASR), potential years of life loss (PYLL), average years of life loss (AYLL), potential life loss years rate (PYLLR), life expectancy, and life expectancy without cause of death were calculated, and the annual percentage change (APC) was used to analyze the trend of heart disease death. Using SAS9.2 software, the death trend prediction was conducted by the ARIMA model in time series analysis. Results From 1990 to 2019, 27,762 residents died of heart disease in Qidong City, with a CR of 81.20/100 000 and an APC of 3.734%. There were 12 358 deaths of heart disease in men, with a CR of 73.24/100 000 and an APC of 3.86%, while there were 15 404 deaths of heart disease in women, with a CR of 88.95/100 000 and an APC of 3.63%. CR showed an upward trend (all P < 0.001). The PYLL for heart disease was 66 192.00 person-years, the AYLL was 13.23 person-years, and the PYLLR was 2.16‰. The life expectancy loss from heart disease was gradually increasing: 0.89 years in 1990 to 1.85 years in 2019, with an APC of 0.405% (P<0.001, a statistically significant trend). The prediction results showed that in 2029, the life expectancy after heart disease would reach 88.17 years. Conclusion From 1990 to 2019, the crude mortality rate of heart disease in Qidong City has showed an increasing trend, leading to an increasing loss of life due to heart disease year by year. The mortality rate and life loss of heart disease in women are higher than those in men. Targeted intervention measures should be further adopted to reduce the mortality rate of heart disease among residents in Qidong.

Diabetic osteoporosis （DOP） is a kind of bone complication caused by diabetes， which is characterized by the decrease of bone mineral density， the change of bone microstructure and the increase of bone fragility. The process of DOP is closely related to high glucose， insulin resistance， oxidative stress and other mechanisms. The Wnt/β-catenin signaling pathway plays an important role in mediating insulin resistance and bone metabolic balance in diabetes. Regulation of Wnt signal transduction promotes the expression of glycogen synthase kinase-3β（GSK-3β）phosphorylation and improves glucose and lipid metabolism. The Wnt/β-catenin signaling pathway is also an important way regulating osteocyte-driven bone remodeling， which not only plays an important regulatory role in the balance between osteoblasts and osteoclasts and improve bone metabolic homeostasis， but also promotes the expression of osteopontin， osteocalcin and type Ⅰ collagen， and improves bone proliferation and osteogenic differentiation by regulating the Wnt pathway. In recent years， the research of traditional Chinese medicine （TCM） in the prevention and treatment of DOP has gradually increased， and the exploration of TCM to interfere with the Wnt pathway to improve DOP has made some progress. This paper collects and summarizes the studies on the Wnt signaling pathway in glucose metabolism， bone metabolism and DOP worldwide in the past decade， as well as the related literature on the intervention of DOP by TCM compounds （classical and other compounds）， single Chinese medicine and TCM monomers based on the Wnt pathway， in order to provide a reference and direction for the development of new drugs for clinical prevention and treatment of DOP.

Objective To evaluate factors associated with prognosis of tonsil squamous cell carcinoma (TSCC) patients and analyze the competing risks of death in TSCC patients. Methods Data tonsil malignant tumors cases diagnosed between 1975 and 2020 were obtained from the SEER database, and records confirmed as squamous cell carcinoma were selected. A Cox proportional hazards regression model was used to investigate the relationships of gender, race, age, marital status, year of diagnosis, lesion location, pathological evidence, treatment regimen with overall survival rate as well as cause-specific mortality outcomes. The competing risks of cause-specific death outcomes among TSCC patients with different clinical characteristics were assessed. Results This study included 14, 805 TSCC patients, including 11, 650 males, accounting for 78.69%. 93.99% of TSCC cases were diagnosed after the age of 45, with the highest incidence occurring in 45 to 64 age group. Radiotherapy was the most commonly used treatment modality (81.78%), compared to surgery (49.47%) and chemotherapy (47.10%). By the end of the follow-up period, 8, 003 (54.06%) TSCC patients had died, with a median survival time of 2.33 years. Cox proportional hazards regression analysis showed that the HR (95%CI) for TSCC-related deaths among patients not receiving surgery, radiotherapy and chemotherapy were 2.101 (1.972 to 2.239), 1.829 (1.702 to 1.966) and 1.023(0.951 to 1.100), respectively, compared to those who did receive these treatments; the HR (95%CI) for deaths due to other causes were 1.630 (1.513 to 1.756), 1.438 (1.318 to 1.570) and 1.328 (1.212 to 1.456), respectively. Compared to patients < 45 years old, the HR (95%CI) for TSCC-related deaths among patients ≥65 years old were 2.218 (1.933 to 2.545), and for deaths due to other causes were 6.178 (5.133 to 7.436). Conclusion Radiotherapy, surgery and chemotherapy all contribute to improving the prognosis of TSCC patients. For elderly TSCC patients, particular attention should be paid to non-TSCC-related death risks.

Objective: To analyze the incidence and survival rate of liver cancer cases in the entire population in the Qidong region from 1972 to 2019, so as to provide a basis for prognosis evaluation, prevention, and treatment. Methods: The observed survival rate (OSR) and relative survival rate (RSR) of 34 805 cases of liver cancer in the entire Qidong region population from 1972 to 2019 were calculated using Hakulinen's method with SURV3.01 software. Hakulinen's likelihood ratio test was used for statistical analysis. Age-standardized relative survival (ARS) was calculated using the International Cancer Survival Standard. The Joinpoint regression analysis was performed with Joinpoint 4.7.0.0 software to calculate the average annual percentage change (AAPC) of the liver cancer survival rate. Results: 1-ASR increased from 13.80% in 1972-1977 to 50.20% in 2014-2019, while 5-ASR increased from 1.27% in 1972-1977 to 27.64% in 2014-2019. The upward trend of RSR over eight periods was statistically significant (χ (2) = 3045.29, P < 0.001). Among them, male 5-ASR was 0.90%, 1.80%, 2.33%, 4.92%, 5.43%, 7.05%, 10.78%, and 27.78%, and female 5-ASR was 2.33%, 1.51%, 3.35%, 3.92%, 3.84%, 7.18%, 11.45%, and 29.84%, respectively. There was a statistically significant difference in RSR between males and females (χ (2) = 45.68, P < 0.001). The 5-RSR for each age group of 25-34 years old, 35-44 years old, 45-54 years old, 55-64 years old, 65-74 years old, and 75 years old were 4.92%, 5.29%, 8.17%, 11.70%, 11.63%, and 9.60%, respectively. There were statistically significant differences in RSR among different age groups (χ (2) = 501.29, P < 0.001). The AAPC in Qidong region from 1972 to 2019 for 1-ARS, 3-ASR, and 5-ARS were 5.26% (t = 12.35, P < 0.001), 8.10% (t = 15.99, P < 0.001), and 8.96 % (t = 16.06, P < 0.001), respectively. The upward trend was statistically significant in all cases. The AAPC of 5-ARS was 9.82% in males (t = 14.14, P < 0.001), and 8.79% in females (t = 11.48, P < 0.001), and the upward trend was statistically significant in both. The AAPC of 25-34 years old, 35-44 years old, 45-54 years old, 55-64 years old, 65-74 years old, and 75 years old were 5.37% (t = 5.26, P = 0.002), 5.22% (t = 5.66, P = 0.001), 7.20% (t = 6.88, P < 0.001), 10.00% (t = 12.58, P < 0.001), 9.96% (t = 7.34, P < 0.001) and 8.83% (t = 3.51, P = 0.013), and the upward trend was statistically significant. Conclusion: The overall survival rate of registered cases of liver cancer in the Qidong region's entire population has greatly improved, but there is still much room for improvement. Hence, constant attention should be paid to the study on preventing and treating liver cancer.
Male ; Humans ; Female ; Adult ; Middle Aged ; Aged ; Survival Rate ; Liver Neoplasms/epidemiology* ; Prognosis ; Incidence ; Software ; China/epidemiology*

【Objective】 To construct an easy-to-use individual survival prognostic tool based on competing risk analyses to predict the risk of 1-, 2- and 3- year recurrence for patients with non-muscle invasive bladder cancer (NMIBC). 【Methods】 The follow-up data of 419 NMIBC patients were obtained. The patients were randomly divided into training cohort (n=293) and validation cohort (n=126). The variables included age at diagnosis, sex, history of smoking, tumor number, tumor size, histolo-gic grade, pathological stage, and bladder perfusion drug. The cumulative incidence function (CIF) of recurrence was estimated using all variables in the training cohort and potential prognostic variables were determined with Gray’s test. The Fine-Gray subdistribution proportional hazard approach was used as a multivariate competitive risk analysis to identify independent pro-gnostic variables. A competing risk nomogram was developed to predict the recurrence. The performance of the competing risk model was evaluated with the area under the receiver operating characteristic curve (AUC), calibration curve, and Brier score. 【Results】 Five independent prognostic factors including age, number of tumors, tumor size, histologic grade and pathological stage were used to construct the competing risk model. In the validation cohort, the AUC of 1-, 2- and 3- year recurrence were 0.895 (95%CI: 0.831-0.959), 0.861(95%CI: 0.774-0.948) and 0.827(95%CI: 0.721-0.934), respectively, indicating that the model had a high predictive performance. 【Conclusion】 We successfully constructed a competing risk model to predict the risk of 1-, 2- and 3-year recurrence for NMIBC patients. It may help clinicians to improve the postoperative management of patients.

【Objective】 To share the technical key points and experience of transvesical robot-assisted radical prostatectomy (TvRARP). 【Methods】 The clinical data of 13 patients with prostate cancer (PCa) receiving TvRARP during Nov.2021 and May 2022 were collected. The operation time, estimated blood loss, blood transfusion rate, catheter removal time, postoperative length of hospital stay, immediate urinary continence rate, postoperative IIEF-5 score and perioperative complications were evaluated. 【Results】 The operation time was (142±39) min, estimated intraoperative blood loss was (76±40) mL, and no transfusion was needed. The median postoperative IIEF-5 score was 16 (12-22), hospital stay 3 (2-5)days, and catheter removal time 7(5-14)days. Of all 13 patients, 12(92.3%) achieved immediate urinary continence at the removal of catheter. There were no postoperative complications of Clavien Ⅲ and above. Clavien Ⅰ-Ⅱ complications were observed in 4 patients (30.8%). 【Conclusion】 TvRARP is feasible and safe for selected patients with clinically localized PCa, which can ensure promising postoperative urinary continence and preserve erectile functional.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

The major challenges in drug therapy for prostate cancer are the ineffectiveness and resistance to androgen deprivation therapy, the low response to immunotherapy and the poor efficacy of small molecule targeted drugs. As a brand-new drug design concept, proteolysis targeting chimera (PROTAC) reveals its strength in the field of cancer treatment by connecting the target protein to the ubiquitin-proteasome system and triggering the degradation of the target protein. In recent years, basic medical research on targeting androgen receptors, cell proliferation, and transcriptional regulation proteins for the treatment of prostate cancer has achieved significant progress. Meanwhile, clinical trials related to PROTAC for the treatment of prostate cancer are gradually being carried out. In an era of big data and precision medicine, PROTAC is a breakthrough in the field of prostate cancer drug therapy. This article summarizes the fundamental principles of PROTACs and the basic and clinical research advances in the field of prostate cancer treatment.