Chronic heart failure （CHF） refers to a clinical syndrome in which the function or structure of the heart is changed due to damage to the original myocardium， resulting in reduced pumping and/or filling functions of the heart. In recent years， the mechanisms， pathways， and targets of traditional Chinese medicine （TCM） in the treatment of CHF have been continuously confirmed， and the application of TCM theories in guiding the syndrome differentiation and precise treatment of CHF is currently a research hotspot. On the basis of the syndrome differentiation and treatment in TCM， Professor LI Candong innovatively proposed the thinking of five differentiation： Disease differentiation， syndrome differentiation， pathogenesis differentiation， symptom differentiation， and individual differentiation. This article explores the clinical diagnosis and treatment of CHF from this thinking， emphasizing comprehensive syndrome differentiation， objective analysis， dynamic assessment， and individualized treatment. In terms of diagnosis， the first is to identify the disease name， cause， location， severity， and type of CHF， determine the type and its evolution， and clarify the process of transmission and transformation between deficiency and excess. Secondly， it is necessary to distinguish the authenticity， severity， primary and secondary， urgency and complexity of CHF syndromes， providing scientific guidance for syndrome differentiation and treatment. Thirdly， according to the symptoms and the principles of deficiency and excess， the physician should identify the core pathogenesis of CHF from the perspectives of Qi， blood， Yin， Yang， deficiency， stasis， phlegm， water， and toxins. Fourthly， from the macro， meso and micro levels， the physician should carefully distinguish the presence or absence， severity， authenticity， and completeness of the symptoms to guide the diagnosis and treatment process of CHF. Finally， personalized medication for CHF should be promoted based on the patient's gender， age， constitution， and living habits. In terms of treatment， based on the thinking of five differentiation， we propose that the treatment of CHF should integrate the disease and syndrome， clarify the pathogenesis， and apply precise treatment. The treatment should be people-oriented， staged， and typed， and the medication should be adjusted according to symptoms. This diagnostic and therapeutic approach is based on the holistic concept and syndrome differentiation and treatment， and combines the three causes for appropriate treatment， providing new ideas and insights for the diagnosis and treatment of CHF.

OBJECTIVE To explore the in vitro and in vivo inhibitory effects and mechanism of metformin on the malignant biological behavior of esophageal squamous cell carcinoma （ESCC） cells by the hypoxia inducible factor-1α （HIF-1α）/interleukin-8 （IL-8） signaling pathway. METHODS Human ESCC TE1 cells were assigned into blank group， metformin low-， medium-， and high-dose groups （0.5， 1， 2 mmol/L）， IDF-11774 （HIF-1α inhibitor） group （20 μmol/L）， and high-dose metformin+HIF-1α activator dimethyloxalylglycine （DMOG） group. After 24 h treatment， cell proliferation [measured by the positive rate of 5-ethynyl- 2′-deoxyuridine （EdU） and optical density at 450 nm （OD450 value）]， apoptosis， invasion and migration as well as mRNA expressions of proliferating cell nuclear antigen （PCNA）， Bcl-2 interacting mediator of cell death （Bim）， migration and invasion enhancer 1 （MIEN1）， and matrix metalloproteinase-9 （MMP-9）， and protein expressions of HIF-1α and IL-8 in the cells were detected. The xenograft tumor model of nude mice was established. Thirty nude mice were randomly divided into blank group， metformin low-， medium-， and high-dose groups （i.g. administration of metformin 62.5， 125， 250 mg/kg+i.p. administration of equal volume of normal saline）， IDF-11774 group （i.g. administration of 50 mg/kg IDF-11774+i.p. administration of equal volume of normal saline） and high-dose metformin+DMOG group （i.g. administration of metformin 250 mg/kg+i.p. administration of DMOG 250 mg/kg）， with 5 mice in each group. They were given relevant medicine， once a day， for 4 consecutive weeks； the mass and volume of the tumor and protein expressions of HIF-1α and IL-8 in the tumor tissue were determined. RESULTS The EdU positive rate， OD450 value， cell invasion number， scratch healing rate， mRNA expressions of PCNA， MIEN1 and MMP-9， protein expressions of HIF-1α and IL-8， as well as the mass and volume of transplanted tumors and protein expressions of HIF-1α and IL-8 in tumor tissues were decreased by metformin in concentration/dose-dependent manner （P＜0.05）. Additionally，metformin increased the apoptosis rate and mRNA expression of Bim in cells （P＜0.05）. The trend of changes in corresponding indicators in the IDF-11774 group was consistent with that in the metformin groups， whereas DMOG could significantly attenuate the aforementioned effects of high-concentration/high-dose metformin （P＜0.05）. CONCLUSIONS Metformin can inhibit the proliferation， invasion， migration of TE1 cells， and tumor growth of nude mice， and induce cell apoptosis， the mechanism of which may be related to the inhibition of HIF-1α/IL-8 signaling pathway.

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

BACKGROUND: The association between uric acid-albumin ratio (UAR) with different diseases has been evaluated before. However, the association between UAR with spontaneous reperfusion (SR) in patients with ST-segment elevation myocardial infarction (STEMI) has not been explored. METHODS: STEMI patients admitted to our department and underwent primary coronary angiography between 1^st November 2018 and 31^st December 2020 were retrospectively enrolled. The patients were divided into the SR group and the non-SR group according to the index coronary angiography results. The association between UAR and SR was evaluated by uni-variable and multi-variable logistic analysis. Receiver operating characteristic curve analysis was used to determine the optimum cut-off level of UAR in predicting SR. RESULTS: Three hundred and fifty-seven patients were finally enrolled in our study, 55 patients were divided into the SR group and 302 patients were divided into the non-SR group. In uni-variable analysis, patients with SR were older (P = 0.032), with higher red blood cell distribution width (P < 0.001) and red blood cell distribution width-to-platelet ratio (P < 0.001), higher level of C-reactive protein (P = 0.046), higher level of uric acid (P < 0.001) compared with patients without SR. Patients with SR had a lower level of platelets (P = 0.008), lower level of on-admission B-type natriuretic peptide (P < 0.001). As for the level of UAR, STEMI patients with SR had significantly higher levels of UAR compared with STEMI patients without SR [11.1 (8.9-13.4) vs. 8.3 (6.6-10.0), P < 0.001]. Further multi-variable logistic analysis reveals that UAR was the independent risk factor of SR in different models after adjusting different variables. Receiver operating characteristic analysis showed that UAR had good predictive value in SR (AUC = 0.75, 95% CI: 0.702-0.794, P < 0.01). CONCLUSIONS Our study shows that UAR is an independent risk factor for predicting SR in STEMI patients.

OBJECTIVE: This study aimed to identify high-risk areas for type 2 diabetes mellitus (T2DM) mortality to provide relevant evidence for interventions in emerging economies. METHODS: Empirical Bayesian Kriging and a discrete Poisson space-time scan statistic were applied to identify the spatiotemporal clusters of T2DM mortality. The relationships between economic factors, air pollutants, and the mortality risk of T2DM were assessed using regression analysis and the Poisson Log-linear Model. RESULTS: A coastal district in East Guangdong, China, had the highest risk (Relative Risk [RR] = 4.58, P < 0.01), followed by the 10 coastal districts/counties in West Guangdong, China (RR = 2.88, P < 0.01). The coastal county in the Pearl River Delta, China (RR = 2.24, P < 0.01), had the third-highest risk. The remaining risk areas were two coastal counties in East Guangdong, 16 districts/counties in the Pearl River Delta, and two counties in North Guangdong, China. Mortality due to T2DM was associated with gross domestic product per capita (GDP per capita). In pilot assessments, T2DM mortality was significantly associated with carbon monoxide. CONCLUSION High mortality from T2DM occurred in the coastal areas of East and West Guangdong, especially where the economy was progressing towards the upper middle-income level.
Diabetes Mellitus, Type 2/epidemiology* ; China/epidemiology* ; Humans ; Risk Factors ; Spatio-Temporal Analysis ; Air Pollutants/analysis* ; Socioeconomic Factors ; Bayes Theorem ; Female ; Male ; Middle Aged

Objective To compare animal models of chronic heart failure(CHF)prepared by three different protocols,to establish a stable,reliable,and reproducible mouse model of CHF.Methods Twenty-five male C57BL/6J mice were divided randomly into four groups:a blank group,model A group(MA group),model B group(MB group),and model C group(MC group).The model groups adopted different preparation protocols for continuous injection of isoprenaline.The MA group and MB group were dose-decreasing models:MA group:subcutaneous injection of 10 mg/kg on day 1,5 mg/kg on day 2,2.5 mg/(kg·d)on days 3～30,total 30 days;and MB group:subcutaneous injection of 20 mg/kg on day 1,10 mg/kg on day 2,5 mg/(kg·d)on days 3～14,total 14 days.The MC group used a constant dose of intraperitoneal injection of 7.5 mg/(kg·d)for 28 days.The day after the final injection,the survival and model-formation rates for each group of mice were calculated.Cardiac function was measured by cardiac ultrasound and serum levels of N-terminal pro B-type natriuretic peptide,interleukin-6,and tumor necrosis factor-α were measured.Results CHF was successfully induced in all the model groups after all injections at the end of the fourth week.However,comprehensive test result showed that the MC model was the most stable.Conclusions An isoprenaline-induced mouse model of CHF using constant intraperitoneal injection of 7.5 mg/(kg·d)for 28 days may be the most suitable model for subsequent research on traditional Chinese medicine.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To investigate the epidemiological characteristics of chronic pain patients based on the the 11th edition of International Classification of Diseases (ICD-11) chronic pain classification in pain clinics.Methods:A retrospective study was conducted on chronic pain patients who visited the pain department outpatient clinics of the Third Xiangya Hospital of Central South University and Anfu Street Health Center in Linli County from July 2021 to July 2024. The general situation and epidemiological characteristics of chronic pain of the survey subjects were understood through outpatient medical records, and the differences in chronic pain composition ratio, gender, age, and season between the two hospitals were compared.Results:A total of 15 783 patients with chronic pain were enrolled. The constituent ratio of patients with chronic pain was as follows: chronic cancer-related pain (5.33%, n=841), chronic secondary musculoskeletal pain (80.98%, n=12 781), chronic secondary visceral pain (3.14%, n=496), chronic secondary headache or orofacial pain (1.30%, n=205), chronic neuropathic pain (5.08%, n=801), chronic postsurgical or post traumatic pain (1.93%, n=305) and chronic primary pain (2.24%, n=354). There were statistically significant differences in the constituent ratio of chronic pain classification, season, gender and age in the two hospitals (all P<0.001). Conclusions:In general, chronic secondary musculoskeletal pain had the highest proportion in this study, followed by chronic cancer-related pain and chronic neuropathic pain. Gender, age, and season were important influencing factors of chronic pain. There were certain differences between the two hospitals.

Prostate cancer(PCa)is one of the common tumors in the genitourinary system,with an increasing morbidity and mortality in China.Recent studies show that autophagy plays an important pathophysiological role in many diseases,including cancers.Besides,some miRNAs are also key regulatory factors for autophagy in PCa cells,and play an important role in the development,pro-gression,diagnosis and treatment of PCa.In-depth studies of miRNAs may contribute to the discovery of some valuable diagnostic methods and novel treatment strategies.This article reviews the progress in researches on the role of autophagy-related miRNAs in PCa,aiming to provide some reference for the diagnosis and treatment of the malignancy.

Objective:To study the effects of poly adenosine diphosphate ribose polymerase (PARP) inhibitors niraparib and pamiparib on the radiosensitivity of breast cancer cell lines MCF-7 and MDA-MB-436, and to explore its mechanism.Methods:MCF-7 and MDA-MB-436 cells were divided into control group, niraparib group, pamiparib group, radiation group, combination group treated with niraparib and radiation, and combination group treated with pamiparib and radiation, respectively. The effects of drugs on cell proliferation and radiosensitivity were measured by CCK-8 assay and colony formation assay, respectively. The effect of drugs combined with radiation on cell cycle and apoptosis were detected by flow cytometry. Immunofluorescence method was used to detect the changes of γ-H2AX focal number of cells. The expressions of FANCG, Bax and Bcl-2 mRNA and protein were detected by qPCR and Western blot, respectively.Results:Both niraparib and pamiparib inhibited the proliferation of breast cancer cells MCF-7 and MDA-MB-436 in a time-dose dependent manner. With the increase of irradiation dose, D0, Dq, SF2 value of MCF-7 and MDA-MB-436 cells decreased, and SER D0 and SER Dq value increased. Compared with control group, the percentages of cells in G 2/M phase were increased ( tMCF-7=41.66, 44.08, P<0.05; t436=24.69, 18.91, P<0.05), the percentage of cells in G 0/G 1 phase were decreased ( tMCF-7=8.67, 29.61, P<0.05; t436=26.39, 29.12, P<0.05), and the cell apoptosis rate was significantly increased ( tMCF-7=11.17, 11.71, P<0.05; t436=42.68, 15.89, P<0.05) in the combination group. Compared with control group, the number of γ-H2AX foci of MCF-7 cells in the radiation group and combination group treated with niraparib and radiation increased significantly at 2 h after irradiation ( t=8.89, 21.72, P<0.05). At 24 h after irradiation, the number of γ-H2AX foci basically returned to normal level in the radiation group but remained at a higher level in the combination group ( t=8.82, P<0.05). Compared with control group, the expressions of FANCG and Bcl-2 mRNA decreased ( tFANCG=14.07, P<0.05; tBcl-2=29.21, P<0.05), the expression of Bax mRNA increased ( t=8.90, P<0.05), and the expression of FANCG and Bcl-2 proteins decreased ( tFANCG=7.09, P<0.05; tBcl-2=10.24, P<0.05), while the expression of Bax protein increased ( t=2.90, P<0.05) in the combination group. Conclusions:PARP inhibitors niraparib and pamiparib can increase the radiosensitivity of breast cancer MCF-7 and MDA-MB-436 cells probably through down-regulating the expression of FANCG in FA-BRCA pathway, up-regulating apoptosis-related genes and inhibiting DNA damage repair.