Objective To explore the influencing factors of early neurological deterioration(END)in patients with acute anterior circulation large-vessel occlusive mild stroke who were treated with medications alone within 72 h after onset.Methods Retrospective consecutive data were collected of patients with acute large-vessel occlusive mild stroke who presented to the Advanced Stroke Center of Linyi People's Hospital within 24 h of onset from January 2021 to December 2022.END was defined as an increase of ≥ 4 points in the National Institutes of Health stroke scale(N1HSS)score within 72 h after onset compared to the admission score.Patients were divided into the neurological deterioration group and the stable condition group(NIHSS score did not increase or increased by 1-3 points within 72 h after onset compared to the admission score).Baseline and clinical data of all patients were collected,including sex,age,cerebrovascular disease risk factors(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation,smoking,alcohol consumption,stroke history),NIHSS score at admission,time from onset to admission,systolic blood pressure at admission,diastolic blood pressure at admission,laboratory test indicators at admission(blood glucose,glycosylated hemoglobin,homocysteine,total cholesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,neutrophils,lymphocytes and neutrophil-to-lymphocyte ratio),responsible occlusion artery(internal carotid artery,middle cerebral artery,anterior cerebral artery),affected cerebral hemisphere,collateral circulation score,and medications used within 72 h after admission(intravenous thrombolysis+dual antiplatelet therapy,tirofiban+dual antiplatelet therapy,argatroban+dual antiplatelet therapy,argatroban alone,dual antiplatelet therapy alone).Variables with statistically significant differences in univariate analysis were included in multivariate Logistic regression analysis to explore the independent influencing factors for END in patients with acute anterior circulation large-vessel occlusive mild stroke treated with medications alone.Results A total of 208 patients with acute anterior circulation large-vessel occlusive mild stroke were included,with 143 males and 65 females,aged 38-85 years,with an average age of(64±9)years.Among them,86 patients were in the neurological deterioration group and 122 in the stable condition group.(1)There were statistically significant differences between the neurological deterioration group and the stable condition group in terms of history of diabetes mellitus(39.5％[34/86]vs.17.2％[21/122]),smoking history(43.0％[37/86]vs.29.5％[36/122]),left cerebral hemisphere lesion(57.0％[49/86]vs.41.0％[50/122]),collateral circulation score(4[3,5]vs.5[4,5]),time from onset to admission(7.0[3.0,17.0]hvs.4.3[2.0,11.0]h),blood glucose at admission(7.4[5.8,10.0]mmol/L vs.6.7[5.8,7.7]mmol/L),neutrophil-to-lymphocyte ratio(3.8[2.4,5.1]vs.3.0[2.1,4.3]),dual antiplatelet therapy alone(19.8％[17/86]vs.6.6％[8/122]),and argatroban+dual antiplatelet therapy(8.1％[7/86]vs.29.5％[36/122];all P＜0.05).There were no statistically significant differences in the results of the remaining univariate analyses(all P＞0.05).(2)Multivariate Logistic regression analysis showed that diabetes mellitus(OR,2.674,95％CI 1.121-6.377,P=0.027)and left cerebral hemisphere vessel occlusion(OR,2.030,95％CI I.083-3.806,P=0.027)were independent risk factors for END in acute anterior circulation large-vessel occlusive mild stroke.Argatroban+dual antiplatelet therapy(OR,0.267,95％CI 0.116-0.613,P=0.002)and high collateral circulation score(OR,0.551,95％CI 0.368-0.824,P=0.004)were independent protective factors for END in acute anterior circulation large-vessel occlusive mild stroke.Conclusions Acute anterior circulation large-vessel occlusive mild stroke patients with diabetes mellitus or left cerebral hemisphere lesions are prone to END.The combination of argatroban and dual antiplatelet therapy and good collateral circulation can reduce the risk of END.

Objective To investigate the protective effects and potential mechanisms of tetrahydrocurcumin(THC)on thoracic aortic aneurysm and dissection(TAAD)in mice.Methods TAAD was induced in 3-week-old C57BL/6J mice by oral administration of β-aminopropionitrile(BAPN)(diluted in drinking water,1 g/(kg·d)).Eighty mice were divided randomly into Con,BAPN,BAPN+THC,and BAPN+THC+3-TYP(SIRT3 inhibitor)groups(n=20 mice per group).The survival rate of mice in each group was recorded after 4 weeks.The maximum diameter of the aorta was measured and the histomorphology and aortic wall elastin integrity were evaluated by hematoxylin and eosin and elastin van Gieson staining.Macrophage infiltration was detected by immunohistochemical staining and α-smooth muscle actin(α-SMA)and osteopontin(OPN)expression were detected by immunofluorescence staining.The production of reactive oxygen species(ROS)was measured by dihydroethidium staining and superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were determined using kits.Protein expression levels of matrix metalloproteinase(MMP)2,MMP9,interleukin(IL)-6,tumor necrosis factor(TNF)-α,nuclear factor erythroid 2-related factor 2(NRF2),NADPH oxidase 2(NOX2),α-SMA,OPN,sirtuin 3(SIRT3),Ac-SOD2,and SOD2 were measured by Western Blot.Results Mice in the BAPN+THC group showed significantly higher survival and a lower incidence of TAAD compared with the BAPN group and the degree of aortic dilatation and morphology and structure were improved(P＜0.05).Infiltration of CD68-positive macrophages and MMP2,MMP9,IL-6,and TNF-α expression levels were lower(P＜0.05),ROS generation,MDA content,and NOX2 expression in aortic tissue were also significantly decreased,while SOD activity and NRF2 expression were increased(P＜0.05).α-SMA expression was also increased,while OPN expression was reduced(P＜0.05).SIRT3 expression was increased while the Ac-SOD2/SOD2 ratio was decreased(P＜0.01).Treatment with the SIRT3-specific inhibitor and silencing of SIRT3 counteracted the ability of THC to resist TAAD via the SIRT3 signaling pathway(all P＜0.05).Conclusions THC alleviated inflammation and oxidative stress in aortic tissues by activating the SIRT3 signaling pathway,thus inhibiting the phenotypic transformation of vascular smooth muscle cells and resisting the formation of TAAD in mice.

Objective To investigate the protective effects and potential mechanisms of tetrahydrocurcumin(THC)on thoracic aortic aneurysm and dissection(TAAD)in mice.Methods TAAD was induced in 3-week-old C57BL/6J mice by oral administration of β-aminopropionitrile(BAPN)(diluted in drinking water,1 g/(kg·d)).Eighty mice were divided randomly into Con,BAPN,BAPN+THC,and BAPN+THC+3-TYP(SIRT3 inhibitor)groups(n=20 mice per group).The survival rate of mice in each group was recorded after 4 weeks.The maximum diameter of the aorta was measured and the histomorphology and aortic wall elastin integrity were evaluated by hematoxylin and eosin and elastin van Gieson staining.Macrophage infiltration was detected by immunohistochemical staining and α-smooth muscle actin(α-SMA)and osteopontin(OPN)expression were detected by immunofluorescence staining.The production of reactive oxygen species(ROS)was measured by dihydroethidium staining and superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were determined using kits.Protein expression levels of matrix metalloproteinase(MMP)2,MMP9,interleukin(IL)-6,tumor necrosis factor(TNF)-α,nuclear factor erythroid 2-related factor 2(NRF2),NADPH oxidase 2(NOX2),α-SMA,OPN,sirtuin 3(SIRT3),Ac-SOD2,and SOD2 were measured by Western Blot.Results Mice in the BAPN+THC group showed significantly higher survival and a lower incidence of TAAD compared with the BAPN group and the degree of aortic dilatation and morphology and structure were improved(P＜0.05).Infiltration of CD68-positive macrophages and MMP2,MMP9,IL-6,and TNF-α expression levels were lower(P＜0.05),ROS generation,MDA content,and NOX2 expression in aortic tissue were also significantly decreased,while SOD activity and NRF2 expression were increased(P＜0.05).α-SMA expression was also increased,while OPN expression was reduced(P＜0.05).SIRT3 expression was increased while the Ac-SOD2/SOD2 ratio was decreased(P＜0.01).Treatment with the SIRT3-specific inhibitor and silencing of SIRT3 counteracted the ability of THC to resist TAAD via the SIRT3 signaling pathway(all P＜0.05).Conclusions THC alleviated inflammation and oxidative stress in aortic tissues by activating the SIRT3 signaling pathway,thus inhibiting the phenotypic transformation of vascular smooth muscle cells and resisting the formation of TAAD in mice.

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

Objective To explore the influencing factors of early neurological deterioration(END)in patients with acute anterior circulation large-vessel occlusive mild stroke who were treated with medications alone within 72 h after onset.Methods Retrospective consecutive data were collected of patients with acute large-vessel occlusive mild stroke who presented to the Advanced Stroke Center of Linyi People's Hospital within 24 h of onset from January 2021 to December 2022.END was defined as an increase of ≥ 4 points in the National Institutes of Health stroke scale(N1HSS)score within 72 h after onset compared to the admission score.Patients were divided into the neurological deterioration group and the stable condition group(NIHSS score did not increase or increased by 1-3 points within 72 h after onset compared to the admission score).Baseline and clinical data of all patients were collected,including sex,age,cerebrovascular disease risk factors(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation,smoking,alcohol consumption,stroke history),NIHSS score at admission,time from onset to admission,systolic blood pressure at admission,diastolic blood pressure at admission,laboratory test indicators at admission(blood glucose,glycosylated hemoglobin,homocysteine,total cholesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,neutrophils,lymphocytes and neutrophil-to-lymphocyte ratio),responsible occlusion artery(internal carotid artery,middle cerebral artery,anterior cerebral artery),affected cerebral hemisphere,collateral circulation score,and medications used within 72 h after admission(intravenous thrombolysis+dual antiplatelet therapy,tirofiban+dual antiplatelet therapy,argatroban+dual antiplatelet therapy,argatroban alone,dual antiplatelet therapy alone).Variables with statistically significant differences in univariate analysis were included in multivariate Logistic regression analysis to explore the independent influencing factors for END in patients with acute anterior circulation large-vessel occlusive mild stroke treated with medications alone.Results A total of 208 patients with acute anterior circulation large-vessel occlusive mild stroke were included,with 143 males and 65 females,aged 38-85 years,with an average age of(64±9)years.Among them,86 patients were in the neurological deterioration group and 122 in the stable condition group.(1)There were statistically significant differences between the neurological deterioration group and the stable condition group in terms of history of diabetes mellitus(39.5％[34/86]vs.17.2％[21/122]),smoking history(43.0％[37/86]vs.29.5％[36/122]),left cerebral hemisphere lesion(57.0％[49/86]vs.41.0％[50/122]),collateral circulation score(4[3,5]vs.5[4,5]),time from onset to admission(7.0[3.0,17.0]hvs.4.3[2.0,11.0]h),blood glucose at admission(7.4[5.8,10.0]mmol/L vs.6.7[5.8,7.7]mmol/L),neutrophil-to-lymphocyte ratio(3.8[2.4,5.1]vs.3.0[2.1,4.3]),dual antiplatelet therapy alone(19.8％[17/86]vs.6.6％[8/122]),and argatroban+dual antiplatelet therapy(8.1％[7/86]vs.29.5％[36/122];all P＜0.05).There were no statistically significant differences in the results of the remaining univariate analyses(all P＞0.05).(2)Multivariate Logistic regression analysis showed that diabetes mellitus(OR,2.674,95％CI 1.121-6.377,P=0.027)and left cerebral hemisphere vessel occlusion(OR,2.030,95％CI I.083-3.806,P=0.027)were independent risk factors for END in acute anterior circulation large-vessel occlusive mild stroke.Argatroban+dual antiplatelet therapy(OR,0.267,95％CI 0.116-0.613,P=0.002)and high collateral circulation score(OR,0.551,95％CI 0.368-0.824,P=0.004)were independent protective factors for END in acute anterior circulation large-vessel occlusive mild stroke.Conclusions Acute anterior circulation large-vessel occlusive mild stroke patients with diabetes mellitus or left cerebral hemisphere lesions are prone to END.The combination of argatroban and dual antiplatelet therapy and good collateral circulation can reduce the risk of END.

Spontaneous spinal epidural hematoma(SSEH)is a rare clinical disease characterized by acute onset of neck,shoulder,or lumbar back pain accompanied by compression of the spinal nerve roots or spinal cord.This article reports a 71 year old female patient with SSEH who was admitted to the hospital with"neck and shoulder pain accompanied by right limb weakness for 3 hours",and was diagnosed with SSEH by cervical magnetic resonance imaging(MRI).After drug treatment,the patient achieved good clinical outcomes.The early symptoms of SSEH lack specificity and are prone to misdiagnosis or missed diagnosis.This case report discribe its diagnosis and treatment strategies in combination of relevant literature in order to improve clinical workers'understanding and diagnosis and treatment capabilities of this disease.

Spontaneous spinal epidural hematoma(SSEH)is a rare clinical disease characterized by acute onset of neck,shoulder,or lumbar back pain accompanied by compression of the spinal nerve roots or spinal cord.This article reports a 71 year old female patient with SSEH who was admitted to the hospital with"neck and shoulder pain accompanied by right limb weakness for 3 hours",and was diagnosed with SSEH by cervical magnetic resonance imaging(MRI).After drug treatment,the patient achieved good clinical outcomes.The early symptoms of SSEH lack specificity and are prone to misdiagnosis or missed diagnosis.This case report discribe its diagnosis and treatment strategies in combination of relevant literature in order to improve clinical workers'understanding and diagnosis and treatment capabilities of this disease.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Malignant tumors are a major health problem in current society. With the improvement of people's living standards and the changes in diet structure， the development trend of gastrointestinal tumors in China is gradually similar to that in developed countries. The incidence and mortality of colorectal cancer （CRC） remain high in China. Although targeted therapy and immunotherapy have greatly improved the prognosis of patients in recent years， chemotherapy is still the main means in clinical practice. However， the adverse reactions of chemotherapy often seriously affect the quality of life of patients， and even lead to treatment interruption， thereby affecting the efficacy. Oral Chinese medicine shows unique advantages in enhancing efficiency and reducing toxicity in CRC patients during chemotherapy， but its poor drug experience not only makes it difficult for patients to take it consistently but also affects the popularization of Chinese medicine at this stage. Medicinal and edible herbs （MEHs） are an important part of Chinese medicine and they are mild， delicious， convenient， affordable， nutritious， and safe. Therefore， they may be more suitable for patients with CRC chemotherapy to adhere to treatment. However， their efficacy is often criticized by clinical practitioners. They are only used in the food and health products industry， and their role as Chinese medicines has not been fully utilized. This paper summarized the common traditional Chinese medicine （TCM） syndromes and treatment methods during CRC chemotherapy， sorted out the nature， flavor， meridian tropism， and efficacy of MEHs， and reviewed the modern pharmacological research results of MEHs by the method of literature statistics. This study finds that the nature， flavor， meridian tropism， and efficacy of MEHs are in good agreement with the common TCM syndromes and treatment methods during CRC chemotherapy. Moreover， many MEHs have the effects of resisting CRC and alleviating the adverse reactions of chemotherapy. Furthermore， the effectiveness and superior efficacy of MEHs in CRC chemotherapy are initially demonstrated from the theoretical level， but high-quality clinical evidence is still needed to support it. The present study discussed the efficiency-enhancing and toxicity-reducing effects and application advantages of MEHs in CRC patients during chemotherapy to provide references for the clinical promotion of MEHs.

BACKGROUND: Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy. METHODS: We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses. RESULTS: Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant. CONCLUSIONS The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.