Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Nonalcoholic fatty liver disease (NAFLD) is regarded as the most common liver disease with no approved therapeutic drug currently. Silymarin, an extract from the seeds of Silybum marianum, has been used for centuries for the treatment of various liver diseases. Although the hepatoprotective effect of silybin against NAFLD is widely accepted, the underlying mechanism and therapeutic target remain unclear. In this study, NAFLD mice caused by methionine-choline deficient (MCD) diet were orally administrated with silybin to explore the possible mechanism and target. To clarify the contribution of peroxisome proliferator-activated receptor α (PPARα), PPARα antagonist GW6471 was co-administrated with silybin to NAFLD mice. Since silybin was proven as a PPARα partial agonist, the combined effect of silybin with PPARα agonist, fenofibrate, was then evaluated in NAFLD mice. Serum and liver samples were collected to analyze the pharmacological efficacy and expression of PPARα and its targets. As expected, silybin significantly protected mice from MCD-induced NAFLD. Furthermore, silybin reduced lipid accumulation via activating PPARα, inducing the expression of liver cytosolic fatty acid-binding protein, carnitine palmitoyltransferase (Cpt)-1a, Cpt-2, medium chain acyl-CoA dehydrogenase and stearoyl-CoA desaturase-1, and suppressing fatty acid synthase and acetyl-CoA carboxylase α. GW6471 abolished the effect of silybin on PPARα signal and hepatoprotective effect against NAFLD. Moreover, as a partial agonist for PPARα, silybin impaired the powerful lipid-lowering effect of fenofibrate when used together. Taken together, silybin protected mice against NAFLD via activating PPARα to diminish lipid accumulation and it is not suggested to simultaneously take silybin and classical PPARα agonists for NAFLD therapy.

Aging ; Animals ; Galactose ; Kidney/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Xanthophylls

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Based on literature research and Delphi expert consensus method, the important acupoints for cancer pain was summarized to provide evidence basis for the formulation of
Acupuncture Points ; Acupuncture Therapy ; Cancer Pain/therapy* ; Humans ; Meridians ; Neoplasms/therapy* ; Publications

Huosu Yangwei (HSYW) Formula is a traditioanl Chinese herbal medicine that has been extensively used to treat chronic atrophic gastritis, precancerous lesions of gastric cancer and advanced gastric cancer. However, the effective compounds of HSYW and its related anti-tumor mechanisms are not completely understood. In the current study, 160 ingredients of HSYW were identified and 64 effective compounds were screened by the ADMET evaluation. Furthermore, 64 effective compounds and 2579 potential targets were mapped based on public databases. Animal experiments demonstrated that HSYW significantly inhibited tumor growth in vivo. Transcriptional profiles revealed that 81 mRNAs were differentially expressed in HSYW-treated N87-bearing Balb/c mice. Network pharmacology and PPI network showed that 12 core genes acted as potential markers to evaluate the curative effects of HSYW. Bioinformatics and qRT-PCR results suggested that HSYW might regulate the mRNA expression of DNAJB4, CALD, AKR1C1, CST1, CASP1, PREX1, SOCS3 and PRDM1 against tumor growth in N87-bearing Balb/c mice.
Animals ; Biomarkers ; China ; Drugs, Chinese Herbal ; Mice ; Network Pharmacology ; Stomach Neoplasms/genetics*

Objective: To study the therapeutic effect of Huoxue Tongluo Decoction (HXTLD) on erectile dysfunction caused by ischemic stroke and identify the mechanisms involved. Methods: Network pharmacology was used to predict the key active ingredients and targets of HXTLD. Surgical methods were used to create a rat model of ischemic stroke. The rats were then given a suspension of HXTLD by ig administration. Erectile function was evaluated by Apomorphine (APO) induction. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (Real-time PCR) and Western blotting were used to detect the expression of related mRNAs and proteins in rat penile corpus cavernous tissue and brain tissue. Hematoxylin & Eosin (HE) staining was used to investigate structural changes in the penile cavernous tissue. Results: Network pharmacology showed that tumor necrosis factor (TNF), nitric oxide synthase 3 (eNOS), and vascular endothelial growth factor (VEGF) were the key targets of HXTLD in the treatment of erectile dysfunction caused by ischemic stroke. Experimental studies showed that HXTLD improved erectile dysfunction caused by ischemic stroke. HE results showed that HXTLD improved the structure of the corpus cavernosa. HXTLD also inhibited the expression of TNF and VEGF proteins in penile tissue (P < 0.05) and enhanced the expression of eNOS protein in penile tissue (P < 0.05). Conclusion: HXTLD improved the erectile function of rats with erectile dysfunction caused by ischemic stroke by regulating the mRNA and protein levels of TNF, eNOS and VEGF.

Objective To explore the impact of smoking on coronary plaque characteristics on optical coherence tomography(OCT) in young patients with acute coronary disease(ACS).Methods We assessed the atherosclerotic plaque characteristics and vulnerability by OCT and coronary angiography in 60 ACS patients aged 45 years or younger in Beijing Anzhen Hospital, from June 2014 to June 2017. The patients were divided into the smoking group(n=33) and the non-smoking group(n=27) to compare the plaque characteristics and vulnerability.Results Smoking patients showed a less extent of fibrosis(48.55％vs. 77.8％,P=0.032)and microchannels(18.2％vs. 44.4％,P=0.033), and a greater extent of plaque rupture (24.2％vs. 3.7％,P=0.033) compared with non-smoking patients. In multivariate analysis, smoking was the only independent predictors of plaque rupture(OR 8.320, 95％CI 0.969-71.435,P=0.027) and less fibrosis (OR 0.269, 95％CI 0.086-0.837,P=0.020). Conclusions Patients who are smokers have less extensive fibrosis and a greater extent of plaque rupture, showing more extensive vulnerable plaque phenotype. Therefore, smoking is one of the major risk factors of advanced cardiovascular events in young patients.

OBJECTIVE: To study the effects and mechanisms of curcumin alleviating oxidative stress induced by overtraining and inhibiting renal apoptosis in rats. METHODS: Male Wistar rats of 7 weeks old were divided into control group (C group, 12), overtraining group (OM group, 11), curcumin + overtraining group (COM group, 14). Group C did not undergo any exercise intervention. Rats in OM group and COM group underwent 8-week incremental load swimming training. During the training, the COM group was treated with curcumin at the dose of 200 mg/(kg·d) in the volume as 5 ml/kg by intragastric administration, and the other groups was treated with an equal volume of 0.5% carboxymethylcellulose. Twenty-four hours after the last training, renal histopathological changes were observed by light microscopy, related biochemical indicators in blood and renal tissue were detected. RESULTS: The results showed that after 8 weeks of incremental load swimming training, the renal tissue structure of group C was normal under light microscope; histopathological changes were observed in OM group; COM group was significantly relieved compared with OM group. Compared with group C, serum levels of corticosterone (Cor), creatinine (Cr) and blood urea nitrogen (BUN) in OM group were increased (<0.01), serum level of testosterone (T) was lower (<0.01); the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) was not changed significantly (>0.05), while the expression of heme oxygenase-1 (HO-1) was decreased (<0.05), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were decreased (<0.01), malondialdehyde (MDA) concentration was increased (<0.01); the renal apoptosis was increased (<0.01), the expression of anti-apoptotic B cell lymphoma-2 protein (Bcl-2) was decreased (<0.01), and the expression of proapoptotic Bcl-2 associated X protein (Bax) was increased (<0.01). Compared with the OM group, Cor level was decreased (<0.01) in the COM group, T level was increased (<0.01), Cr and BUN levels were lower (<0.05); the expression of Nrf2 and HO-1 were increased (<0.05), T-AOC and SOD activity were increased (<0.01), MDA concentration was decreased (<0.05); the renal apoptosis was decreased (<0.05), the expression of Bcl-2 was increased (<0.05), and the expression of Bax was decreased (<0.01). The trend of testosterone/corticosterone ratio between groups was consistent with testosterone change, and the change trend of Bcl-2/Bax ratio was consistent with the change of Bcl-2. CONCLUSIONS The 8-week incremental load swimming training triggered excessive training in rats, aggravated oxidative stress and accelerated renal apoptosis, leading to pathological changes and dysfunction of kidney. Curcumin can up-regulate expression of Nrf2 and HO-1, effectively alleviates oxidative stress induced by overtraining, thereby increasing Bcl-2 expression, decreasing Bax expression, inhibiting renal apoptosis and protecting renal tissue structure and function properly.
Animals ; Apoptosis ; Curcumin ; Kidney ; Male ; Oxidative Stress ; Rats ; Rats, Wistar

Objective To improve the biological fidelity of the thorax flexible body in the original MADYMO child human model,so as to further study pediatric thorax injuries of child occupant.Methods The finite element model of six-year-old pediatric thorax was built by the method of reverse modeling based on CT images.By replacing the thorax model with flexible body in MADYMO six-year-old human model,an improved human model containing biomechanical thorax model was developed.The model was verified by joint validation of two tests,including Irwin and Mertz's method of scaling channel reported in Kroell's adult chest impact experiment and Ouyang's thoracic impact test on pediatric cadavers.Results The response of this established thorax model was in good agreement with scaling channel method and cadaver test data,and the thorax model was much more accurate than the original flexible body model.The resilience of simulation model was consistent with cadaver test.Conclusions The validity of the model is verified,and the results can be further used for occupant injury analysis in vehicle frontal crash.