Objective: To investigate characteristics of colorectal cancer incidence and mortality in registration areas of Guangdong Province in 2020, so as to provide a basis for optimizing regional prevention and control strategies. Methods: Data on incidence and mortality of colorectal cancer in cancer registration areas of Guangdong Province in 2020 were collected from the Cancer Follow-up Registration System and the All-Cause Mortality Registration Reporting System of the Guangdong Provincial Center for Disease Control and Prevention. The crude incidence, crude mortality, truncated rate for 35 to 64 years, and cumulative rate for 0 to 64 years were calculated, and standardized using the Segi's world standard population. Descriptive epidemiological methods were applied to analyze the characteristics of colorectal cancer incidence and mortality by different genders, urban/rural areas and ages. Results: A total of 14 771 cases of colorectal cancer were reported in Guangdong Province in 2020. The crude incidence, world population-standardized incidence, truncated incidence for 35 to 64 years and cumulative incidence for 0 to 64 years were 35.18/100 000, 24.84/100 000, 38.87/100 000 and 1.37%, respectively. A total of 5 384 deaths of colorectal cancer were reported, with crude incidence, world population-standardized incidence, truncated incidence for 35 to 64 years and cumulative incidence for 0 to 64 years were 14.55/100 000, 8.83/100 000, 10.39/100 000 and 0.37%, respectively. The crude incidence and mortality were higher in males than in females (40.35/100 000 vs. 29.88/100 000, 16.51/100 000 vs. 12.54/100 000, both P<0.05). The crude incidence and mortality were higher in urban areas than in rural areas (38.94/100 000 vs. 26.10/100 000, 16.60/100 000 vs. 10.42/100 000, both P<0.05). The crude incidence of colorectal cancer initially increased with advancing age (P<0.05), reaching a peak of 239.36/105 in the 80-<85 age group, followed by a marked decline after 85 years. The crude mortality of colorectal cancer increased with advancing age (P<0.05), reaching a peak of 174.25/100 000 in the ≥85 years age group. Conclusions In 2020, the incidence and mortality of colorectal cancer in registration areas of Guangdong Province were higher than the national averages. There were differences in the characteristics of incidence and mortality among genders, urban/areas and age. Therefore, it is necessary to strengthen the comprehensive prevention and control efforts for colorectal cancer in males, urban areas, and the elderly population.

Objective: To investigate the epidemiological characteristics of lung cancer in cancer registration areas of Guangdong Province in 2020, so as to provide the evidence for improving prevention and control strategies of lung cancer. Methods: Data of incidence and mortality in 2020 from 30 cancer registries in Guangdong Province were collected from the Cancer Follow-up Registration System and the All-Cause Mortality Registration Reporting System of the Guangdong Provincial Center for Disease Control and Prevention. The crude incidence, crude mortality, and cumulative rate for 0 to 74 years were calculated. The Chinese population-standardized rate and world population-standardized rate were calculated using the age structure of the standard population from the Fifth National Population Census in 2000 and Segi's world standard population. The incidence and mortality characteristics of lung cancer in different genders, urban/rural areas and ages were described. Results: In 2020, there were 25 357 new cases of lung cancer in Guangdong Province. The crude incidence, Chinese population-standardized incidence, world population-standardized incidence, and cumulative incidence for 0 to 74 years were 60.40/100 000, 43.75/100 000, 43.26/100 000, and 5.30%, respectively. There were 14 366 lung cancer deaths. The crude mortality, Chinese population-standardized mortality, world population-standardized mortality, and cumulative mortality for 0 to 74 years were 38.82/100 000, 24.49/100 000, 24.36/100 000, and 2.88%, respectively. The crude incidence and crude mortality of lung cancer in males were higher than those in females (71.19/100 000 vs. 49.42/100 000, 52.94/100 000 vs. 24.36/100 000, both P<0.05). The crude incidence and crude mortality of lung cancer in urban areas were higher than those in rural areas (66.37/100 000 vs. 45.95/100 000, 40.68/100 000 vs. 35.07/100 000, both P<0.05). The crude incidence and crude mortality of lung cancer exhibited upward trends with increasing age (both P<0.05), peaking in the age of 80-<85 years (347.97/100 000 and 342.14/100 000). Conclusions Comparing to the national data, the incidence of lung cancer in registration areas of Guangdong Province remained relatively high, while mortality remained relatively low. Males, urban residents and the elderly constitute the key populations for lung cancer prevention and control. It is recommend to optimize the allocation of medical resources between urban and rural areas and strengthen lung cancer screening among high-risk groups.

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

ObjectiveTransfusion-Related Acute Lung Injury （TRALI） is a common fatal transfusion adverse reaction. Major Histocompatibility Complex （MHC） class I is an important factor involved in the pathogenesis of TRALI； however， the role of complement in itspathogenesis has not been fully elucidated. This study aims to explore the role of complement in MHC class I antibody-mediated TRALI， so as to provide a theoretical basis for clinical prevention and treatment. MethodsThis study established a murine model of transfusion-related acute lung injury （TRALI） based on the "two-hit" theory， with lipopolysaccharide （LPS） as the first hit and MHC class I antibody as the second hit. Male Balb/c mice were randomly divided into seven groups （n=5 per group per experiment）： Naive （blank control）， LPS （first hit only）， Isotype （isotype antibody control）， TRALI （model group）， C5aR1 inhi （C5aR1 antagonist intervention）， C5aR2 inhi （C5aR2 antagonist intervention）， and Anti-C5 （anti-complement C5 antibody intervention）. Rectal temperature was monitored after MHC class I antibody injection. After sample collection， the severity of pulmonary edema was assessed by measuring the lung wet-to-dry weight ratio， histological analysis， and immunohistochemistry. Serum and bronchoalveolar lavage fluid were collected to measure cytokine and complement levels. ResultsMice in the TRALI group exhibited a significant decrease in rectal temperature， an increased lung wet-to-dry weight ratio， elevated serum cytokine levels， and markedly heightened complement C5a levels in bronchoalveolar lavage fluid （P＜0.000 1）. Histopathological examination revealed substantial infiltration of inflammatory cells， predominantly neutrophils accompanied by fewer lymphocytes， plasma cells， and monocytes， along with increased deposition of the membrane attack complex C5b-9 in lung tissues. In contrast， mice treated with anti-C5 antibody demonstrated no significant decrease in rectal temperature. The lung wet-to-dry weight ratio in this group showed no statistical difference compared to either the Naive or Isotype control groups （P＞0.05）. Furthermore， these mice displayed reduced serum cytokine levels， a significant attenuation of inflammatory cell infiltration in the lungs， and a 100% survival rate at the 2-hour time point. However， mice administered either the C5aR1 antagonist or the C5aR2 antagonist failed to be protected and subsequently developed TRALI. ConclusionComplement activation， which forms the membrane attack complex C5b-9， plays a critical role in MHC class I antibody-mediated TRALI. Blocking complement C5 activation can effectively prevent the occurrence of TRALI.

Liver ischemia-reperfusion injury (IRI) is a significant factor contributing to liver dysfunction following surgical procedures such as liver transplantation and hepatectomy, and its pathogenesis is closely associated with oxidative stress and immune responses. However, effective prevention and therapeutic strategies are still lacking. Short-chain fatty acids (SCFAs), primarily produced by the fermentation of gut microbiota, are the major source of these acids in the human body. Research has indicated that SCFAs play a significant role in oxidative stress and immune response. This review primarily focuses on the advancements on the role of SCFAs, the main metabolic byproducts of gut microbiota, in liver IRI, with a view to provide insights for the development of prevention and treatment strategies for liver IRI.

Liver ischemia reperfusion injury (IRI) is one of the main causes of liver dysfunction or functional failure after liver transplantation or liver resection. As the main organ of lipid metabolism, liver is closely related to lipid metabolic balance. Lipoxygenase is a non-heme iron-containing oxidases that oxidizes polyunsaturated fatty acids to produce hydroxy-eicosanotetraenoic acid. Lipoxygenase is excessively expressed during liver ischemia, causing lipid metabolic disorders. High expression of several proinflammatory cytokines induced by lipoxygenase during liver reperfusion. Lipid peroxidation induced by lipoxygenase leads to the production of lipid oxygen free radicals, which induces iron death mainly characterized by lipid peroxidation, thus affecting apoptosis and tissue damage. This review mainly introduces the latest progress of lipoxygenase in liver IRI.

The review focuses upon the mechanism of exosome derived from mesenchymal stem cells in hepatic ischemia-reperfusion injury(IRI)to provide references for clinical application of exosomes in alleviating hepatic IRI.

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.
Male ; Mice ; Animals ; Cellular Reprogramming/genetics* ; Tetraploidy ; Pluripotent Stem Cells/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; DNA Methylation ; Spermatogonia/metabolism* ; Germ Cells/metabolism*

Objective:To evaluate the clinical efficacy and safety of high-selective laparoscopic high ligation of spermatic vein for the treatment of varicocele.Methods:A retrospective analysis was performed about 419 cases clinical data which have received high-selective laparoscopic high ligation of spermatic vein in Nanyang Second General Hospital from January 2010 to December 2018. The patients were divided into endoscopy group ( n=289) and open group ( n=130). the patients of endoscopy group were treated with laparoscopic high ligation of spermatic vein, the patients of open group were treated with high ligation of spermatic vein according inguinal incision. The operation time, hospital stay, intraoperative blood loss, postoperative analgesic application, postoperative complications, recurrence, and postoperative semen quality improvement were compared between the two groups. Measurement data were presented as mean±standard deviation ( Mean± SD), and comparison between groups was performed by t-test; count data groups using Chi-square test. Results:This group of 419 patients were all successful operation, all patients with intraoperative and postoperative stable vital signs. The operation time [(26.78±5.14) min vs (61.45±9.75) min], hospitalization time [(4.14±0.39) d vs (10.62±1.19) d] of the patients in the endoscopy group was better than that of the open group, and the difference were statistically significant ( P<0.01). Comparison of intraoperative blood loss between the two groups [(18.32±3.05) mL to (29.14±2.41) mL], the difference was not statistically significant ( P=0.053). The postoperative analgesic application rate, complication rate, and recurrence rate of patients in the endoscopic group were 12.5% (36/289), 2.1% (6/289), and 0.7% (2/289), respectively. The control group was 13.8%(18/130), 7.7% (10/130), 5.4% (7/130), the difference between the two groups were statistically significant ( P<0.05). The postoperative semen quality of the two groups of patients improved to varying degrees. There were 357 cases with definite improvement in postoperative semen quality, including 231 cases in the endoscopic group and 126 cases in the open group, but the difference between the two groups was not statistically significant ( P>0.05). Conclusions:High-selective laparoscopic high ligation of the spermatic vein for the treatment of varicocele, the operation is quick, the high ligation of the varicocele does not damage the blood supply of the testicular artery, the complication rate is low, and the recurrence rate is low. It is worthy of clinical application.

Objective To evaluate the clinical effect of iliac artery interventional chemotherapy combination with bladder perfusion for high level of bladder urothelial carcinoma after transurethral bladder tumor electricity cut operation for those who intend to retain the bladder.Methods From February 2010 to December 2016,a total of 74 cases high-grade urothelial carcinoma of the bladder,giving chemotherapy and suitted support were retrospectively analyzed.The patients were divided into two groups according to different chemotherapy methods.Artery perfusion chemotherapy group:43 cases treated by transurethral bladder tumor cutting + bilateral iliac artery interventional perfusion chemotherapy + bladder perfusion in combination therapy;Intravenous chemotherapy group:31 cases underwent transurethral bladder tumor cut method + cisplatin,vein gemcitabine + bladder perfusion chemotherapy combined therapy.According to the ((x) ± s) between the groups.The method of count data is represented by chi-square test.Kaplan-meier method was used to describe the survival time of two groups of patients after operation.Results Two groups of patients with postoperative there was no statistically significant difference in disease-free survival time.In the bone marrow suppression (x2 =4.956,P =0.029);gastrointestinal tract reaction (x2 =5.912,P =0.012);dermatitis,mucositis (x2 =4.276,P =0.013),etc.,has the advantages in the iliac artery interventional perfusion chemotherapy (P ＜ 0.05).Conclusion Via efficient iliac arterial infusion chemotherapy in patients with venous chemotherapy patients,to the retention of the bladder has a certain value,and the incidence of adverse reactions after surgery is low,have certain advantages.