Objective To observe the efficacy and safety of radiotherapy combined with programmed death receptor-1(PD-1)inhibitors and tyrosine kinase inhibitors(TKIs)for the treatment of microsatellite-stabilized(MSS)-type or mismatch-matched repair-normal(pMMR)-type colorectal cancer with liver metastases(CCLM).Methods Case data of 25 patients with MSS-type CCLM admitted to Jiangsu Provincial Cancer Hospital from April 2021 to August 2023 were retrospectively analyzed.They were divided into observation group(n = 12)and control group(n = 13).The observation group was given radiotherapy combined with PD-1 inhibitor and TKI treatment,and the control group was given TKI monotherapy.The baseline data,treatment effect,progression-free survival,and treatment-related adverse reactions of patients in the two groups were compared.Results The difference in baseline data between the two groups was not statistically significant(P＞0.05),the disease control rate(DCR)of the observation group was higher than that of the control group(P＜0.05),the progression-free survival(PFS)of the patients in the observation group was longer than that of the control group,but the difference was not statistically sig-nificant(P＞0.05),and the difference in the incidence of treatment-related adverse events(TRAE)between the two groups was not statistically significant(P＞0.05).Conclusion The treatment regimen of radiotherapy com-bined with PD-1 inhibitors and TKI drugs improved clinical efficacy and did not increase the incidence of adverse events when compared with TKI alone,which is a treatment regimen worthy of further validation.

Objective:To explore the development status, research hotspots, and frontiers of low value care (LVC) de-implementation in foreign countries.Methods:The literature on LVC de-implementation included in the Web of Science core collection from 1995 to 2023 was electronically searched. Excel software was used to organize literature. CiteSpace software was used to visually analyze the authors, institutions, countries, journals, co-citation status, and key terms included in the literature.Results:A total of 576 articles were included. The overall number of articles published from 1995 to 2023 showed an increase, with the highest in 2022 (150 articles). The top 10 research institutions with publication volume and centrality> 0.10 were the Harvard University and the United States Department of Veterans Affairs. Compared with other journals, Archives of Internal Medicine, Anesthesiology and American Review of Respiratory Disease had the highest number of indexed literature. The journals with a co-citation frequency greater than 50 and centrality>0.10 were Archives of Internal Medicine, The American Journal of Medicine, British Medical Journal and Annals of Internal Medicine. In addition to the key terms searched for in this study, the key terms frequently cited greater than 30 times in 576 articles were "impact" "management" "outcome" "health" "quality" "health care", and "guidelines". The clusters in keyword clustering analysis that extend the timeline to the past 5 years were "value based care" and "low value care". The analysis of burst words showed that the forefront was the accurate identification of LVC in clinical practice and the intervention strategies for LVC de-implementation. Conclusions:Through the analysis of key terms and burst terms, it is found that in recent years, research topics in this field focus on the relationship between LVC and medical insurance expenditures, the influencing factors of de-implementation, tools (checklists or manuals) for identifying LVC, clinical intervention pathways, de-implementation of different types of LVC, and evaluation of the effectiveness of de-implementation. In the future, domestic research needs to strengthen international cooperation and exchange, explore and construct a suitable implementation path for LVC in China, accurately formulate LVC lists and intervention strategies, optimize nursing measures, improve the effective utilization of medical resources, and provide effective and high-quality nursing services for patients.

Background and objective Video-assisted thoracoscopic surgery (VATS) lobectomy is generally ac-cepted for patients with lung cancer. hTe aim of this study is to explore the feasibility of the single-operation-hole thoraco-scopic lobectomy in the treatment of non-small cell lung cancer. Methods To review and analyze the single-operation-hole thoracoscopic lobectomy performed in our hospital for 113 non-small cell lung cancer (NSCLC) cases from October 2010 to October 2013. hTe incision for observation was 1.5 cm the eighth intercostal at the rear of the midaxillary line and the incision for operation was 2.0 cm-4.0 cm at the fourth or iftfh intercostal of the anterior axillary line. hTe operations were performed through the single-operation-hole. Result hTe operation processes were smooth for all the patients without any operative mor-tality occurrence. Only in 5 cases was the operation hole expanded because of the occurrence of massive hemorrhage during the operation;3 patients with postoperative complications underwent thoracoscopic lobectomy again, including 2 cases of de-layed hemorrhage and 1 case of chylothorax. hTe average surgical duration was (178.24±31.17) min, the average blood loss was (213.56±62.38) mL, and the number of lymph nodes dissected was from 5-22. All diagnose were conifrmed by pathology atfer operation. hTe average length of stay was (8.17±2.93) d. All cases recovered well during the follow-up of (2-38) months, only 5 cases had recurrence or metastasis. Conclusion hTe single-operation-hole thomcoscopic lobectomy for lung cancer is safe and feasible, further reducing the trauma, and can be used as a conventional treatment for early-or medium-term NSCLC.

Radiopharmaceuticals play an important role in the medical field,but they also carry certion risks and potential safety concerns.Medical institutions implement pharmacovigilance to ensure the safety of patients'drug use,including the safety of Radiopharmaceuticals.The operation and management of the pharmacovigilance system in the United States and the European Union are relatively mature.China can learn from their advanced concepts and establish our own radiopharmaciligence system.

Global Burden of Disease ; Risk Factors ; Quality-Adjusted Life Years

Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.