Malignant tumor metastasis is the key factor leading to poor prognosis of patients， and it is a difficult problem to be overcome in the field of tumor therapy. Metabolic reprogramming， as a key link in the regulation of tumor metastasis activity， affects the growth， invasion， and metastasis of tumor cells by changing the metabolic pathways of intracellular substances （such as glucose， amino acids， lipids， and nucleotides）. In particular， metabolic reprogramming plays a key role in the multistage linked steps related to tumor metastasis and can play a crucial role in several key stages of tumor tissue dissociation in situ， hematogenous metastasis， and remote colonization. Malignant tumor cells can selectively adjust their own metabolic state to adapt to the growth conditions of different metastatic microenvironments and colonization sites and then choose the most favorable growth and metabolism strategy. According to the holistic concept of traditional Chinese medicine （TCM）， the metastasis of malignant tumors is generally closely related to the metabolic state of the whole body. One of the advantages of TCM in the treatment of malignant tumors is systemic regulation. With its multi-pathway， multi-target， and multi-component therapeutic characteristics， TCM can effectively control the metastasis of malignant tumors by regulating the degradation of tumor epithelial mesenchymal transformation （EMT） and extracellular matrix （ECM）， anchoring the independent growth of tumor cells and the tumor microenvironment. In this paper， the potential regulatory effects of metabolic reprogramming on the metastasis of malignant tumors were discussed， and the latest research progress of the regulation of metabolic reprogramming by TCM on tumor metastasis was reviewed. At the same time， the key targets of TCM and its bioactive components in the process of tumor metastasis intervention were reviewed. This study aims to provide a more valuable basis and clearer idea for the treatment of malignant tumor metastasis by regulating metabolic reprogramming with TCM.

OBJECTIVE To evaluate the cost-effectiveness of the first-line treatment using the combination therapy of sugemalimab and chemotherapy （hereinafter referred to as the “combination therapy”） for advanced esophageal squamous cell carcinoma （ESCC） with high programmed death-ligand 1 （PD-L1） expression from the perspective of the Chinese healthcare system. METHODS A partitioned survival model was constructed based on data from the GEMSTONE-304 study. The model cycle was set at 3 weeks， with a study duration of 10 years and a discount rate of 5%. The primary output parameters of the model included total costs， quality-adjusted life year （QALY）， incremental costs， and incremental cost-effectiveness ratio （ICER）. Cost- utility analysis was employed to assess the economic feasibility of the combination therapy compared to chemotherapy alone. The robustness of the base case analysis results was evaluated through univariate sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis. RESULTS The ICER of the combination therapy compared to chemotherapy alone was 288 430.35 yuan/QALY， significantly exceeding the willingness-to-pay （WTP） threshold of 173 354.52 yuan/QALY which was set at 1.94 times the per capita gross domestic product （GDP） in 2023. The price of sugemalimab was the primary factor influencing the ICER. When the WTP threshold was set at 1.94 times the per capita GDP （173 354.52 yuan/QALY）， the probability of the combination therapy being cost-effective compared to chemotherapy alone was 0. The combination therapy only became cost-effective compared to chemotherapy alone when the price of the drug dropped to 6 107.41 yuan per box （600 mg）. CONCLUSIONS From the perspective of the Chinese healthcare system， the combination therapy for first-line treatment of advanced ESCC with high PD-L1 expression is not cost-effective； the combination therapy is cost-effective when the price of sugemalimab decreas by 50.65%.

Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis(PF).It is considered as a promising ther-apeutic target anti-PF.The well-documented against PF properties of Tanshinone ⅡA(Tan ⅡA)have been primarily attributed to its antioxidant and anti-inflammatory potency.Emerging evidence suggests that TanⅡA may target energy metabolism pathways,including glycolysis and tricarboxylic acid(TCA)cycle.However,the detailed and advanced mechanisms underlying the anti-PF activities remain obscure.In this study,we applied[U-13C]-glucose metabolic flux analysis(MFA)to examine metabolism flux disruption and modulation nodes of Tan ⅡA in PF.We identified that Tan ⅡA inhibited the glycolysis and TCA flux,thereby suppressing the production of transforming growth factor-β1(TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro.We further revealed that Tan ⅡA inhibited the expression of key metabolic enzyme hexokinase 2(HK2)by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)pathway activities,which decreased the accumulation of abnormal metabolites.Notably,we demonstrated that Tan ⅡA inhibited ATP citrate lyase(ACLY)activity,which reduced the collagen synthesis pathway caused by cytosol citrate consumption.Further,these results were validated in a mouse model of bleomycin-induced PF.This study was novel in exploring the mechanism of the occurrence and develop-ment of Tan ⅡA in treating PF using 13C-MFA technology.It provided a novel understanding of the mechanism of Tan ⅡA against PF from the perspective of metabolic reprogramming.

Objective:To investigate the differences in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 expressions between metastatic sites and primary sites in metastatic triple-negative breast cancer (TNBC) patients and to analyze their effects on the prognosis of patients.Methods:A retrospective cohort study was conducted. The clinicopathological data of 108 patients diagnosed with metastatic TNBC in Lianyungang Hospital Affiliated to Xuzhou Medical University from September 2018 to September 2023 were collected. Local metastatic sites included ipsilateral axillary lymph nodes and chest wall, while distant metastatic sites encompassed contralateral axillary lymph nodes and chest wall, bilateral supraclavicular lymph nodes, cervical lymph nodes, bone and viscera. The metastatic sites were identified as metastatic TNBC by using immunohistochemistry (IHC) and/or fluorescence in situ hybridization. The heterogeneity in ER, PR, HER2, and Ki-67 expression between primary sites and metastatic sites in all patients and those with local and distant metastases was analyzed, and the heterogeneity was defined as the inconsistency in the expression of markers including loss and gain expressions between primary sites and metastatic sites. The Kaplan-Meier method was used to analyze disease-free survival (DFS), and log-rank test was used for comparison among groups.Results:All patients were female, with an average age of (55±10) years; 51 cases had local metastases, and 57 cases had distant metastases. In metastatic sites, no ER and PR positivity were observed; in primary sites, 28.7% (31/108) of patients were ER positive and 21.3% (23/108) of patients were PR positive, and there were statistically significant differences in the proportion of patients with ER or PR positive between primary sites and metastatic sites (all P < 0.001). There were no statistically significant differences in the proportions of patients with different expression status including HER2 [positive: 0 (0/108) vs. 4.6%(5/108), low expression: 50.0% (54/108) vs. 45.4% (49/108), negative: 50.0% (54/108) vs. 50.0% (54/108)], Ki-67 [high expression: 86.1% (93/108) vs. 91.7% (99/108)] between metastatic sites and primary sites (all P > 0.05). The proportions of patients with inconsistent ER and PR expression between metastatic sites and primary sites were 28.7% (31/108) and 21.3% (23/108), respectively, all due to the expression loss in metastatic sites; the proportions of patients with inconsistent HER2 and Ki-67 expression between metastatic sites and primary sites were 42.6% (46/108) and 11.1% (12/108), respectively, with HER2 and Ki-67 expression loss of metastatic sites accounting for 22.2% (24/108) and 8.3% (9/108), respectively and expression gain accounting for 20.4% (22/108) and 2.8% (3/108), respectively. The proportions of patients with inconsistent ER [45.6% (26/57) vs. 9.8% (5/51)], PR [36.8% (21/57) vs. 3.9% (2/51)] and Ki-67 [17.5% (10/57) vs. 3.9% (2/51)] expression in distant metastatic sites and primary sites were higher than those with local metastatic sites and primary sites, and the differences were statistically significant (all P < 0.05). The proportions of patients with inconsistent HER2 between distant metastatic sites and primary sites and those with inconsistent HER2 between local metastatic sites and primary sites were 47.4% (27/57), 37.3% (19/51), respectively, and the difference was not statistically significant ( P = 0.300). Patients with inconsistent ER and Ki-67 expressions had better DFS than those with consistent expressions, with median DFS time of 30 months (95% CI: 22-40 months) vs. 22 months (95% CI: 22-24 months) for ER and 28 months (95% CI: 20-61 months) vs. 22 months (95% CI: 22-24 months) for Ki-67, and the differences were statistically significant (all P < 0.05). There were no significant differences in DFS between metastatic sites and primary sites with consistent expressions of PR and HER2 or not (all P > 0.05). Conclusions:There are differences in ER and PR expressions between primary sites and metastatic sites of metastatic TNBC patients, while the expressions of HER2 and Ki-67 seem to be no differences. The inconsistency of ER, PR and Ki-67 expressions with primary sites in distant metastatic sites are more common compared with in local metastatic sites. The differences in hormone receptor expression between primary sites and metastatic sites may impact patients' DFS.

The construction of county medical service community (medical community) is an important measure for building a hierarchical and integrated medical and health service system. The article takes Yinzhou District of Ningbo city as an example to elaborate the strengths and weaknesses of the internal environment and the opportunities and challenges of the external conditions using SWOT analysis in the construction of county medical community, also put forward corresponding countermeasures and suggestions to provide reference for the further improvement.

Objective:To investigate the clinicopathological features,differential diagnosis,treatment and prognosis of Burkitt-like lymphoma with 11q aberration (BLL-11q).Methods:The clinical manifestations,histological morphology,immunophenotype and molecular genetic changes of 2 cases of BLL-11q admitted to the department of pathology of The First People's Hospital of Lianyungang in 2020 and 2021 were analyzed retrospectively,and the relevant literatures were reviewed.Results:Patients were found with right neck masses inadvertently and grew rapidly. They presented with localized disease with Ann Arbor stages IA and IIA. Microscopically, the normal structure of the lymph node disappeared and was replaced by a diffuse proliferation of lymphocytes, with consistent morphology and medium size. And the presence of "star-sky" phenomenon was obvious, the morphological characteristics were similar to Burkitt lymphoma. Immunophenotypically, tumor cells were diffusely positive for CD20, CD79α, PAX5, CD10 and Bcl-6, partly moderately positive for C-MYC and MUM-1, however, CD3, Bcl-2, CD30 and TDT were negative,Ki-67 positive index was more than 95%, and EBER was negative. FISH detection showed that MYC, Bcl-2, and Bcl-6 were negative. Both cases had the 11q23.3 gain and 11q24.3 loss. Both patients were treated with chemotherapy and followed up for 10-22 months,and achieved complete remission and disease-free survival.Conclusion:BLL-11q is a rare germinal center B-cell lymphoma with abnormal long arm of chromosome 11 and lack of MYC gene rearrangement. It should be distinguished from Burkitt lymphoma, diffuse large B-cell lymphoma, B-lymphoblastic lymphoma, large B-cell lymphoma with IRF4 rearrangement and high-grade B-cell lymphoma. On the basis of morphology and immunophenotype, the diagnosis depends on genetic detection. There may be a better prognosis.

Objective This study examined the research status and development process of FU Qingzhu’s Obstetrics and Gynecology (Fu Qing Zhu Nv Ke,《傅青主女科》, FQZNK) in the past 40 years with bibliometrics and visual analysis. Methods Retrieved all related literature in the research field of FQZNK from the domestic and foreign databases: China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database, and Web of Science (WOS) core database, including Science Citation Index Expanded (SCIE), Social Sciences Citation Index (SSCI), and Arts & Humanities Citation Index (A&HCI). The search range was from January 1, 1980 to March 10, 2021. In addition, bibliometrics and CiteSpace 5.7.R2 software were used to analyze literature types, published journals, cited literature, the number of author publications, co-author networks, co-institution networks, keyword co-occurrence networks, keyword clusters, and keyword bursts. Results A total of 678 valid records were included in the final dataset. Literature types, high publication journals, highly cited literature, high-yield institutions, high-yield research teams, and high-productivity scholars in this research field were found through bibliometrics. Literature types can be divided into four categories, among which 451 are theoretical studies on academic thoughts of FQZNK, accounting for 66.5% of the included journals. The Journal of Shanxi Traditional Chinese Medicine had the largest volume of published articles (61), accounting for 9.0% of the total number of the included journals. The most cited literature was ZHOU Mingxin’s article “Using the quantitative method to discuss author’s authenticity and formula characteristics of FU Qingzhu’s Obstetrics and Gynecology”, which was cited 94 times. Hunan University of Chinese Medicine, the institution with the most publications, published 45 articles, and YOU Zhaoling, the most published author, published 33 articles. Moreover, it was found that most high-yield researchers came from high-yield institutions and that Hunan University of Chinese Medicine had the most research on FQZNK. Keyword co-occurrence analysis revealed that the keyword “FQZNK” had the highest frequency (597 times) and the highest centrality (1.00). Keyword cluster analysis used the Log-Likelihood Ratio (LLR) algorithm to form eleven important clusters: #0 treatment aiming at its root causes, #1 gynecopathy, #2 Siwu Decoction (四物汤), #3 FU Qingzhu, #4 post-partum, #5 infertility, #6 dysmenorrhea, #7 sterility, #8 coordinate the heart and kidney, #9 Danggui Buxue Decoction (当归补血汤), and #10 treatment. It was found that the prescriptions of FQZNK were studied mainly before 2000, the theoretical studies were mainly conducted before 2010, and its clinical application was mainly explored from 2010 until now. Diseases such as dysmenorrhea, morbid vaginal discharge, infertility, metrorrhagia, and polycystic ovarian syndrome (PCOS) have recently become popular topics in this field. Conclusion The current study provides more scientific, accurate, and comprehensive scientific support for further research and development of traditional Chinese medicine (TCM) in FQZNK. With this foundation, people can use burst detection to ascertain the current hotspots in research, get their development trends, and forecast future research directions. In addition, infertility, morbid vaginal discharge, flooding, and PCOS treatments based on TCM syndrome differentiation are currently popular research topics for FQZNK.

Objective:To evaluate and summary the relevant evidence of emergency target blood pressure management in acute aortic dissection, so as to provide guidance for the evidence-based practice of emergency target blood pressure management.Methods:According to the "6S" evidence pyramid model, the evidence about emergency target blood pressure management of acute aortic dissection in various databases and professional association websites at home and abroad was retrieved, including clinical decision, guidelines, expert consensus, systematic evaluation, randomized controlled trial, cohort study, case series, etc. Two researchers used corresponding literature quality evaluation tools to evaluate the quality of the included literature, extracted and summarized the evidence of the literature above grade B.Results:A total of 22 articles were included in this study, including 6 clinical decisions, 5 guidelines, 7 expert consensus, 1 systematic evaluation, 1 randomized controlled trial, 1 cohort study and 1 case series, forming 37 best evidences, including 9 topics such as target value setting, management strategies, disease observation, medical history collection, monitoring methods, vasoactive drugs, non vasoactive drugs, auxiliary examination, health education.Conclusions:The summarized best evidence provides a reference for emergency medical staff to manage the emergency target blood pressure of acute aortic dissection. It is recommended that emergency medical staff follow the summarized best evidence to formulate an individualized target blood pressure management scheme for patients.

OBJECTIVE：To study the effects of Modified liuwei dihuang decoction on kidney/bone injury of chronic kidney disease-mineral and bone disorder（CKD-MBD）model rats. METHODS ：The male SD rats were randomly divided into normal group（n＝10），high phosphorus group （n＝30），model group （n＝30），calcitriol group （positive control ，0.09 μg/kg，n＝30）， Modified liuwei dihuang decoction group （10 g/kg by crude drug ，n＝30）. CKD-MBD model was established by high phosphorus and adenine diet for 6 weeks. After modeling ，normal group and model group were given normal diet/high phosphorus diet and intragastric administration of water. Administration groups were fed with normal diet and given corresponding solution intragastrically（water as solvent ），0.1 mL/kg，once a day ，for consecutive 6 weeks. Blood sample of rats in the normal group were collected ，and they were sacrificed after the last administration. Blood sample of 10 rats in each other group were collected ， and they were sacrificed at 2，4 and 6 weeks after administration. The contents of blood urea nitrogen （BUN），serum creatinine （Scr），calcium，phosphorus，iPTH，FGF-23，RANKL and osteocalcin in serum were detected in each group. The bone mineral density（BMD）of femoral was measured ，the morphological changes of renal tissue and bone tissue were observed ，and the percentage of renal tubular injury and the score of renal interstitial fibrosis were calculated. RESULTS ：Compared with normal group，above indexes in high phosphorus group had no significant change at different time points （P＞0.05）. There was no abnormal change in renal/bone tissue. Compared with high phosphorus group at the same time point ，the contents of BUN ，Scr， phosphorus，iPTH，FGF-23，RANKL and osteocalcin in serum ，the percentage of renal tubular injury and the score of renal interstitial fibrosis in the model group were significantly increased ，while the contents of calcium in serum and the BMD of femoral were significantly decreased （P＜0.05 or P＜0.01）. The renal tissue showed diffuse fibrosis. The width of trabecular bone was increased and the number of osteoblasts was decreased. Compared with the model group at the same time point ，the contents of BUN（except for Modified liuwei dihuang decoction group after 2 weeks of administration ），Scr，serum phosphorus ，iPTH， FGF-23，RANKL and osteocalcin ，the percentage of renal tubular injury and the score of renal interstitial fibrosis in Modified liuwei dihuang decoction group and calcitriol group were decreased significantly at each time point ；serum calcium content and BMD（except for 2 weeks of administration ）were significantly increased （P＜0.05 or P＜0.01），and the pathological changes of renal/bone tissue were significantly improved ；there was no statistical significance in above indexes between Modified liuwei dihuang decoction group and calcitriol group （P＞0.05）. CONCLUSIONS ：Modified liuwei dihuang decoction can improve kidney/ bone injury of CKD-MBD model rats ，and improve BMD and regulate disorder of calcium and phosphorus metabolism.