[摘 要] 目的：探讨lncRNA核内富集丰富转录本1（NEAT1）调控miR-1287-5p/DNA损伤诱导转录本4（DDIT4）轴对卵巢癌SKOV3细胞增殖、凋亡和侵袭的影响及其机制。方法：收集2023年6月至2024年6月期间湖北医药学院附属随州医院手术切除的27例卵巢癌患者的癌及癌旁组织标本，以及正常人卵巢上皮细胞IOSE80和卵巢癌细胞系SKOV3、CAOV3和A2780，RT-qPCR检测卵巢癌组织与细胞中lncRNA NEAT1、miR-1287-5p及DDIT4 mRNA表达。将SKOV3细胞分为Ctrl组、si-NC组、si-NEAT1组、si-NEAT1 + anti-miR-NC组、si-NEAT1 + anti-miR-1287-5p组、si-NEAT1 + vector组、si-NEAT1 + OE-DDIT4组。CCK-8法、克隆形成实验、流式细胞术、Transwell实验分别检测各组细胞增殖、凋亡及侵袭能力，WB法检测细胞中DDIT4、细胞周期蛋白D1（cyclin D1）、p53、迁移侵袭增强子1（MIEN1）蛋白水平。双萤光素酶报告基因验证lncRNA NEAT1与miR-1287-5p/DDIT4靶向结合关系，RNA pull-down实验、RNA免疫沉淀实验分别验证lncRNA NEAT1与miR-1287-5p、miR-1287-5p与DDIT4的靶向结合关系。另设pcDNA组（转染空载体pcDNA3.1）和pc-NEAT1 组（转染pcDNA-NEAT1）以验证NEAT1过表达效应。结果：卵巢癌组织中lncRNA NEAT1、DDIT4 mRNA表达水平显著高于癌旁组织（P < 0.05），而miR-1287-5p表达显著低于癌旁组织（P < 0.05）。敲低lncRNA NEAT1后，与Ctrl组和si-NC组相比，si-NEAT1组lncRNA NEAT1表达、DDIT4 mRNA表达均显著降低（均P < 0.05），miR-1287-5p 表达显著升高（P < 0.05）；而过表达lncRNA NEAT1则下调miR-1287-5p表达并上调DDIT4表达，呈现与敲低实验相反的调控效应；敲低lncRNA NEAT1后，克隆形成数、细胞增殖活性、细胞侵袭数均显著降低（均P < 0.05），细胞凋亡率显著升高（P < 0.05）；DDIT4、cyclin D1、MIEN1蛋白表达均显著降低（均P < 0.05），p53蛋白表达显著升高（P < 0.05）。进一步实验证实，anti-miR-1287-5p或OE-DDIT4均可减弱si-NEAT1对SKOV3细胞增殖和侵袭的抑制作用，同时减弱其对细胞凋亡的促进作用。lncRNA NEAT1靶向调控miR-1287-5p/DDIT4。结论：lncRNA NEAT1通过靶向调控miR-1287-5p/DDIT4轴促进SKOV3细胞增殖和侵袭，抑制细胞凋亡。

Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the ag-gregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

Parkinson's disease is a neurodegenerative disease that mainly affects dopamine neurons in the substantia nigra region of the brain,and its clinical manifestations include shaking and slowness of movement.The means of clinical medicine treatment are limited,but traditional Chinese medicine,with its advantages of low cost and high safety,shows great potential in the prevention and treatment of Parkinson's disease.Our team proposed that the core pathogenesis of Parkinson's disease was"earth deficiency and wood multiplication",that is,spleen(soil)deficiency and liver(wood)dysfunction.Among them,"earth deficiency"was the basis of the disease,and"wood multiplication"was the core of the disease.The treatment advocated"strengthening spleen and soothing liver",the specific methods included strengthening spleen and resolving phlegm,Tonify qi and cultivate the middle and soothing liver and relieve depression,and subdue wind and unblock the meridians,etc.Representative recipes were Lianmei Siwu decoction,Zhengan Xifeng decoction,Huangya decoction and Shenzhu decoction.In the treatment,we should pay attention to the whole concept and syndrome differentiation and treatment,and combine the three factors to improve the clinical effect.At the same time,the advantages and mechanisms of TCM in the prevention and treatment of Parkinson's disease deserve further research and verification.

Parkinson's disease is a neurodegenerative disease that mainly affects dopamine neurons in the substantia nigra region of the brain,and its clinical manifestations include shaking and slowness of movement.The means of clinical medicine treatment are limited,but traditional Chinese medicine,with its advantages of low cost and high safety,shows great potential in the prevention and treatment of Parkinson's disease.Our team proposed that the core pathogenesis of Parkinson's disease was"earth deficiency and wood multiplication",that is,spleen(soil)deficiency and liver(wood)dysfunction.Among them,"earth deficiency"was the basis of the disease,and"wood multiplication"was the core of the disease.The treatment advocated"strengthening spleen and soothing liver",the specific methods included strengthening spleen and resolving phlegm,Tonify qi and cultivate the middle and soothing liver and relieve depression,and subdue wind and unblock the meridians,etc.Representative recipes were Lianmei Siwu decoction,Zhengan Xifeng decoction,Huangya decoction and Shenzhu decoction.In the treatment,we should pay attention to the whole concept and syndrome differentiation and treatment,and combine the three factors to improve the clinical effect.At the same time,the advantages and mechanisms of TCM in the prevention and treatment of Parkinson's disease deserve further research and verification.

Deficiency, stasis, water and toxin are of great significance in the pathogenesis and pathologic evolution of chronic heart failure (CHF). Based on "deficiency, blood stasis, water and toxin", the pathogenesis and treatment of CHF were discussed in this article. It was found that in the pathogenesis, deficiency--deficiency of heart qi and deficiency of heart yang were the origin of the disease, and blood stasis, water and toxin were the markers of the disease. Among them, blood stasis was the central pathological link, and also an important mechanism that could aggravate the disease and cause a vicious cycle; water-phlegm and water dampness were the basic pathological products; toxin-heat toxin, water toxin, and stasis toxin were the final results of disease progress and product accumulation. In terms of treatment, CHF can be divided into four stages: early, middle, late and end. In the early stage, tonifying qi and regulating heart can be used for the treatment of root cause, and promoting blood circulation and water can be used for the treatment of symptoms; tonifying qi and yin and reinforcing the healthy qi, reducing blood stasis, purging turbid, and eliminating pathogenic factors can be used in the middle stage; reducing blood stasis and removing toxic materials should be used in the late stage, supplemented with warming yang and increasing urine excretion; astringing yang,generating body fluids, tonifying qi and yang should be used in the end stage. At the same time of treating by stages, attention should be paid to adhering to a holistic concept and dialectical treatment; pay attention to timing and flexible medication; adopting a combination of Chinese and Western approaches and integrating them.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Contrast-enhanced ultrasound (CEUS) is a new form of ultrasound (US) that can dynamically display microvessels in a highly sensitive manner. The purpose of this study was to investigate the efficacy of CEUS for characterizing testicular lesions in comparison with conventional US. Forty-seven patients with testicular lesions were enrolled. The histopathology results revealed that 31 cases were neoplastic (11 cases of seminomas, 8 nonseminomatous germ cell tumors, 8 lymphomas, 2 Leydig cell tumors, and 2 nonspecific tumors), and 16 cases were nonneoplastic (8 cases of infarctions, 3 epidermoid cysts, and 5 inflammation). The indicators of shallow lobulated morphology and cystic-solid echogenicity on conventional US were suggestive of germ cell tumors. More indicators on CEUS were found to be useful for characterizing testicular lesions. All the neoplastic lesions showed hyperenhancement on CEUS. Moreover, germ cell tumors presented with heterogeneous enhancement (73.7%, 14/19), a twisted blood vessel pattern, rapid wash-in and wash-out, and peripheral rim hyperenhancement signs. Lymphoma was characterized by nonbranching linear vessel patterns (87.5%, 7/8), rapid wash-in and slow wash-out. In nonneoplastic lesions, infarction and epidermoid cysts showed no enhancement, and abscesses were observed with marginal irregular enhancement. The sensitivity, specificity, and accuracy of CEUS for differentiating between neoplastic and nonneoplastic lesions were 100%, 93.8%, and 97.9%, respectively, and these values were higher than those for conventional US (90.3%, 62.5%, and 80.9%, respectively). CEUS can sensitively reflect the microvascular perfusion in testicular lesions and offers high accuracy for characterizing them.
Contrast Media ; Diagnosis, Differential ; Epidermal Cyst ; Humans ; Lymphoma ; Male ; Neoplasms, Germ Cell and Embryonal/diagnostic imaging* ; Sensitivity and Specificity ; Testicular Neoplasms/diagnostic imaging* ; Ultrasonography/methods*

Objective:To investigate the efficacy of venetoclax-based combined regimen in treatment of adult patients with acute myeloid leukemia (AML).Methods:The data of 50 adult AML (non-acute promyelocytic leukemia) who received venetoclax-based combined regimen in the First Affiliated Hospital of Xiamen University, Dongguan People's Hospital, the First Hospital of Longyan City, Jieyang People's Hospital from December 2018 to May 2021 were retrospectively analyzed. Different doses venetoclax combined with demethylation drugs or low-dose chemotherapy regimen were used to analyze the therapeutic efficacy. The related factors influencing efficacy were analyzed by using logistic regression.Results:The composite complete remission (CR) rate of 50 AML patients was 62.0% (31/50), the overall response rate (ORR) was 76.0% (38/50); 28 patients achieved effectiveness [CR and partial remission (PR)] after the first cycle and could achieve effectiveness by 3 courses of treatment at the latest. Among 50 patients, 28 cases were newly diagnosed AML, the composite CR rate was 60.8% (17/28), ORR was 78.6% (22/28); 22 cases were recurrent and relapsed, the composite CR rate was 63.6% (14/22), ORR was 72.7% (16/22); and there was no statistically significant difference of ORR between the both groups ( χ2 = 0.23, P = 0.743). Logistic regression multivariate analysis showed age was the only independent influencing factor for the treatment effectiveness ( OR = 8.451, 95% CI 1.306-54.697, P = 0.025). The median duration time of patients receiving venetoclax treatment regimen was 4.5 months (1.1-15.0 months); 16 cases who had treatment effectiveness finally relapsed, the median time of maintaining effectiveness was 5 months (1.1-11.0 months). Additionally, the common treatment-related adverse reactions included bone marrow suppression after treatment, followed by some gastrointestinal reactions like nausea, vomiting and stomachache. In addition, no patient stopped medication for more than 1 week due to bone marrow suppression related complications. Conclusion:Venetoclax-based combined regimen shows a good short-term efficacy in treatment of AML. It is also effective and tolerable for elderly patients receiving reduced dose therapy.

OBJECTIVE: To investigate the treatment and prognosis of multiple primary malignant neoplasms (MPMN) complicated with renal cell carcinoma (RCC), and to make risk stratification. METHODS: A retrospective study of 27 cases of MPMN with RCC in two centers, including the different tumors of MPMN, specific treatment methods, and the interval between primary cancers. At the same time, the survival conditions, including recurrence, metastasis and survival, were followed up for statistical analysis. The interval between the two kinds of primary cancer within 6 months was simultaneous MPMNs, and more than 6 months was metachronous MPMNs. For simple risk stratification of cases, as long as one of the MPMNs had a stage Ⅲ or higher malignancy, which was defined as high risk. RESULTS: Among the 27 patients, 20 were male and 7 were female, with age at the time of diagnosis was 42-82 years, with an average age of (61.3±11.7) years. The age at the diagnosis of renal cancer was 43-87 years, with an average age of (66.0±11.3) years. There were 21 cases with duplex primary malignant neoplasms, 4 cases with triple primary malignant neoplasms, and 2 cases with quadruple primary malignant neoplasms. The interval between first cancer and second cancer was 0-360 months, with a median of 18 months. There were 17 cases of metachronous multiple primary malignant neoplasms and 10 cases of simultaneous multiple primary malignant neoplasms. The most common system of MPMN with comorbid RCC involved urologic system, digestive system and respiratory system. The most common locations of MPMN with comorbid RCC were bladder cancer, lung cancer and colon cancer. Follow-up time calcu- lated from the last cancer was 2-156 months, with a median of 32 months. And 14 cases survived and 13 cases died, with 11 cases being tumor related. Tumor stage was the risk factor of prognosis. Any kind of tumor stage in stage Ⅲ or above had a relatively poor prognosis. CONCLUSION MPMN complicated with RCC is relatively rare. Standard treatment should be used for each cancer type during the treatment process. The prognosis mainly depends on the highest stage of each tumor. Simple risk stratification shows that the prognosis of the high-risk group is worse. This simple stratification method may be helpful to predict the prognosis.
Aged ; Carcinoma, Renal Cell/therapy* ; Female ; Humans ; Kidney Neoplasms/therapy* ; Male ; Middle Aged ; Neoplasms, Multiple Primary/therapy* ; Prognosis ; Retrospective Studies