OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

Objective To explore the effects and mechanisms of a traditional Chinese medicine (TCM) prescription, "Fang-gan Decoction" (FGD), in protecting against SARS-CoV-2 spike protein-induced lung and intestinal injuries in vitro and in vivo.Methods Female BALB/c mice and three cell lines pretreated with FGD were stimulated with recombinant SARS-CoV-2 spike protein (spike protein). Hematoxylin-eosin (HE) staining and pathologic scoring of tissues, cell permeability and viability, and angiotensin-converting enzyme 2 (ACE2) expression in the lung and colon were detected. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of inflammatory factors in serum and cell supernatant. The expression of NF-κB p65, p-NF-κB p65, p-IκBα, p-Smad2/3, TGF-β1, Caspase3, and Bcl-2 was evaluated by Western blotting.Results FGD protected against the damage to the lung and colon caused by the spike protein in vivo and in vitro according to the pathologic score and cell permeability and viability (P<0.05). FGD up-regulated ACE2 expression, which was reduced by the spike protein in the lung and colon, significantly improved the deregulation of inflammatory markers caused by the spike protein, and regulated the activity of TGF-β/Smads and NF-κB signaling.Conclusion Traditional Chinese medicine has a protective effect on lung and intestinal tissue injury stimulated by the spike protein through possible regulatory functions of the NF-κB and TGF-β1/Smad pathways with tissue type specificity.
Mice ; Animals ; Female ; Humans ; NF-kappa B/metabolism* ; Spike Glycoprotein, Coronavirus/pharmacology* ; Transforming Growth Factor beta1/metabolism* ; Angiotensin-Converting Enzyme 2/pharmacology* ; COVID-19 ; SARS-CoV-2/metabolism* ; Lung ; Antineoplastic Agents ; Transforming Growth Factor beta/pharmacology* ; Epithelial Cells/metabolism* ; Colon

OBJECTIVETo investigate the role of endoplasmic reticulum stress (ERS)-induced trophoblast apoptosis in the development of intrahepatic cholestasis during pregnancy (ICP).

METHODSTwenty pregnant women with ICP and 20 normal pregnant women undergoing cesarean section were enrolled in this study. The number of placenta syncytial knots in these women was determined using HE staining. The mRNA expressions of GRP78, CHOP, caspase-3, and caspase-7 were detected using RT-PCR in the placental tissues of the women and also in HTR-8/SVneo cells treated with different doses of deoxycholic acid (DCA). Caspase-3 and caspase-7 activities were also detected in DCA-treated HTR-8/SVneo cells using commercial assay kits, and the presence of apoptotic bodies in the cells were detected with electron microscopy.

RESULTSCompared with normal placental tissues, the placenta from women with ICP showed significantly increased syncytial knots (P<0.01) and obviously enhanced mRNA expressions of GRP78, CHOP, caspase-3, and caspase-7 (P<0.05). In HTR-8/SVneo cells treated with different doses of DCA (0, 10, 50, and 100 µmol/L), the mRNA expressions of GRP78, CHOP, caspase-3 and caspase-7 were significantly increased in a dose-dependent manner (P<0.05) and the protein levels of GRP78 and CHOP were also increased dose-dependently. Treatment with DCA at 50 µmol/L for 24 h significantly upregulated caspase-3 and caspase-7 activity in the cells (P<0.05), and the cells treated with 50 µmol/L DCA for 12 h showed the presence of apoptotic bodies.

CONCLUSIONThe activation of ERS and enhanced apoptosis of the trophoblasts occur in the placenta of women with ICP. DCA can significantly increase the expressions of ERS markers and thus lead to trophoblast apoptosis, suggesting that ERS-induced trophoblasts apoptosis may play a key role in the development of ICP.

OBJECTIVETo explore the clinical efficacy and toxicity of CLAT protocol (cladribine, cytarabine and topotecan) for treating patients with refractory acute myeloid leukemia (R-AML).

METHODSA total of 18 patients with R-AML (median age 37 years, range 18 to 58 years; male n = 16, female n = 2) were treated with CLAT protocol, which consisted of cladribine 5 mg/m(2)/d, i.v. on days 1-5, cytarabine 1.5 g/m(2)/d, i.v. on days 1-5, topotecan 1.25 mg/m(2)/d, i.v. on days 1-5 and G-CSF 300 µg/d subcutaneous injection on day 6 until neutrophile granulocyte recovery.

RESULTSOut of 18 patients 2 died of severe infection before the assessment. Among 16 evaluated patients, 10 (55.6%) achieved complete remission (CR), and 2 (11.1%) achieved partial remission (PR), the overall response rate was 66.7%, the rest 4 patients did not respond (NR). The median overall survival time and DFS for the CR patients was 9.5 months (95%CI: 6.7-16.64) and 9.5 months (95%CI: 6.1-16.7) respectively. The 1 year OS and DFS rates were 45% and 46.9%, respectively. All patients developed grade 4 of granulocytopenia and thrombocytopenia, the median duration was 13 (range 2 to 21) days and 12 days (range 2 to 21), respectively, all patients developed infection, 2 patients died of severe infection. The most common non-hematological side effects included nausea, vomiting, diarrhoea, rash, aminotransferase or bilirubin elevation and were grade 1 to 2.

CONCLUSIONThe CLAT protocol seems to have promising for the treatment of refractory AML patients, and patients well tolerated. This CLAT protocol offers an alternative treatment for R-AML patients who received severe intensive treatment, especially with anthracycline-containing chemotherapy.

Adolescent ; Adult ; Agranulocytosis ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cladribine ; therapeutic use ; Cytarabine ; therapeutic use ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Remission Induction ; Thrombocytopenia ; Topotecan ; therapeutic use ; Young Adult

The type 1 insulin-like growth factor receptor (IGF-1R) and its downstream signaling components have been increasingly recognized to drive the development of malignancies, including non-small cell lung cancer (NSCLC). This study aimed to investigate the effects of IGF-1R and its inhibitor, AG1024, on the progression of lung cancer. Tissue microarray and immunohistochemistry were employed to detect the expressions of IGF-1 and IGF-1R in NSCLC tissues (n=198). Western blotting was used to determine the expressions of IGF-1 and phosphorylated IGF-1R (p-IGF-1R) in A549 human lung carcinoma cells, and MTT assay to measure cell proliferation. Additionally, the expressions of IGF-1, p-IGF-1R and IGF-1R in a mouse model of lung cancer were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (FQ-PCR), respectively. The results showed that IGF-1 and IGF-1R were overexpressed in NSCLC tissues. The expression levels of IGF-1 and p-IGF-1R were significantly increased in A549 cells treated with IGF-1 as compared to those treated with IGF-1+AG1024 or untreated cells. In the presence of IGF-1, the proliferation of A549 cells was significantly increased. The progression of lung cancer in mice treated with IGF-1 was significantly increased as compared to the group treated with IGF-1+AG1024 or the control group, with the same trend mirrored in IGF-1/p-IGF-1R/IGF-1R at the protein and/or mRNA levels. It was concluded that IGF-1 and IGF inhibitor AG1024 promotes lung cancer progression.
Adult ; Aged ; Animals ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Cell Proliferation ; Disease Models, Animal ; Disease Progression ; Female ; Humans ; Insulin-Like Growth Factor I ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Middle Aged ; Receptor, IGF Type 1 ; antagonists & inhibitors ; physiology ; Tyrphostins ; pharmacology

OBJECTIVETo investigate the effect of everolimus(RAD001)combined with all-trans retinoid acid(ATRA) on drug resistance of ATRA-resistance acute promyelocytic leukemia(APL) cell line NB4-R1 and its molecular mechanism.

METHODSAPL NB4-R1 cells were treated with different concentrations of RAD001(1 nmol/L, 10 nmol/L and 100 nmol/L) with ATRA(1μmol/L) for 24, 48 and 72 h, respectively. The differentiation of NB4-R1 cells was analyzed by flow cytometry with CD11b staining and nitro blue tetrozolium(NBT) reduction test. Cell cycle was detected by cell cycle staining kit and apoptosis was detected by flow cytometry with Annexin V/PI staining. Protein expressions of LC-3II, PML-RARα, P-P70S6K and P-4E-BP1 were determined by Western blotting.

RESULTSRAD001 combined with ATRA significantly induced NB4-R1 cells differentiation, but RAD001 or ATRA alone did not enhance NB4-R1 differentiation. The co-treatment induced accumulation of cells in G1 phase and decreased the proportion of cells in S phase. The combined treatment had no effect on cell apoptosis. The differentiation rate of NB4-R1 cells in 100 nmol/L RAD001, 1μmol/L ATRA, RAD001 combined with ATRA and control groups was(2.29±0.57)%,(17.06±2.65)%,(54.47±4.91)% and(2.54±0.53)%, respectively; the proportion of cells in G1 phase was(35.20±11.97)%,(33.54±6.25)%,(53.70±8.73)% and(27.40±6.01)%, respectively; cells apoptosis rate was(2.30±0.14)%,(2.25±0.21)%,(2.40±0.28)% and(1.95±0.07)%, respectively. The combination of RAD001 with ATRA significantly inhibited mTOR signaling downstream proteins P-P70S6K, P-4E-BP1 and enhanced autophagy-related protein LC3-II and Beclin 1. The co-treatment also induced degradation of fusion protein PML-RARα.

CONCLUSIONRAD001 combined with ATRA can induce cell differentiation, inhibit cell cycle, resulting the reverse of drug resistance in NB4-R1 cells, which is associated with increase of autophagy level and degradation of PML-RARα.

Adaptor Proteins, Signal Transducing ; metabolism ; Antineoplastic Agents ; pharmacology ; Apoptosis ; Cell Cycle ; Cell Differentiation ; Cell Line, Tumor ; drug effects ; Drug Resistance, Neoplasm ; Everolimus ; pharmacology ; Humans ; Leukemia, Promyelocytic, Acute ; pathology ; Oncogene Proteins, Fusion ; metabolism ; Phosphoproteins ; metabolism ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Signal Transduction ; Tretinoin ; metabolism

Objective: To investigate the effect of everolimus ( RAD001 ) combined with all-trans retinoid acid ( ATRA ) on drug resistance of ATRA-resistance acute promyelocytic leukemia ( APL ) cell line NB4-R1 and its molecular mechanism . Methods: APL NB4-R1 cells were treated with different concentrations of RAD 001 (1 nmol/L, 10 nmol/L and 100 nmol/L) with ATRA (1 μmol/L) for 24, 48 and 72 h, respectively .The differentiation of NB4-R1 cells was analyzed by flow cytometry with CD11b staining and nitro blue tetrozolium ( NBT) reduction test.Cell cycle was detected by cell cycle staining kit and apoptosis was detected by flow cytometry with Annexin V/PI staining.Protein expressions of LC-3II, PML-RARα, P-P70S6K and P-4E-BP1 were determined by Western blotting .Results: RAD001 combined with ATRA significantly induced NB 4-R1 cells differentiation , but RAD001 or ATRA alone did not enhance NB 4-R1 differentiation .The co-treatment induced accumulation of cells in G1 phase and decreased the proportion of cells in S phase .The combined treatment had no effect on cell apoptosis .The differentiation rate of NB 4-R1 cells in 100 nmol/L RAD001 , 1 μmol/L ATRA, RAD001 combined with ATRA and control groups was (2.29 ±0.57)%, (17.06 ±2.65)%, (54.47 ±4.91)% and (2.54 ±0.53)%, respectively;the proportion of cells in G 1 phase was ( 35 .20 ±11 .97 )%, ( 33 .54 ± 6.25)%, (53.70 ±8.73)% and (27.40 ±6.01)%, respectively; cells apoptosis rate was ( 2.30 ±0.14 )%, ( 2.25 ±0.21 )%, ( 2.40 ±0.28 )% and (1.95 ±0.07)%, respectively.The combination of RAD001 with ATRA significantly inhibited mTOR signaling downstream proteins P-P70S6K, P-4E-BP1 and enhanced autophagy-related protein LC3-II and Beclin 1. The co-treatment also induced degradation of fusion protein PML-RARα.Conclusion:RAD001 combined with ATRA can induce cell differentiation , inhibit cell cycle , resulting the reverse of drug resistance in NB4-R1 cells, which is associated with increase of autophagy level and degradation of PML-RARα.

OBJECTIVETo evaluate the effect of short-course kidney-invigorating therapy on near-term semen quality in asthenozoospermic men with kidney deficiency.

METHODSBased on the differential types in traditional Chinese medicine, 121 asthenozoospermia patients received at our clinic of andrology were divided into groups A (kidney-yin deficiency), B (kidney-yang deficiency) and C (spleen and kidney deficiency), and treated with Yougui Decoction plus Wuziyanzong Pills, Jinkuishenqi Pills plus Wuziyanzong Pills, and Shizi Decoction plus Liujunzi Decoction, respectively, all given once daily for 4 weeks. Sperm parameters of the patients were analyzed with the computer-assisted sperm analysis system before and after treatment and compared among the three groups.

RESULTSThe baseline sperm concentrations in groups A, B and C ([70.4 +/- 38.6], [73.5 +/- 40.2] and [56.0 +/-34.4] x 10(6)/ml) showed no significant differences from those after medication ([74.4 +/- 32.6], [67.0 +/- 30.8] and [58.6 +/- 24.6] x 10(6)/ml) (P > 0.05). The percentages of grade a sperm in the three groups were (12.9 +/- 5.3)%, (13.7 +/- 7.7)% and (12.9 +/- 6.4)% respectively after treatment, significantly higher than (9.9 +/- 6.7)%, (9.3 +/- 5.4)% and (9.0 +/- 6.8)% before treatment (P < 0.05), and so were the percentages of grade a + b sperm ([37.4 +/- 10.2 ]%, [35.7 +/- 13.7]% and [35.9 +/- 12.3]% after treatment versus [29.6 +/- 13.2]%, [27.5 +/- 10.4]% and [28.3 +/- 12.1]% before treatment, P < 0.05). All the three groups showed significantly increased sperm motility after treatment ([53.8 +/- 10.5]%, [52.6 +/- 15.2]% and [51.1 +/- 13.1]%) as compared with the baseline levels ([44.3 +/- 14.0]%, [43.5 +/- 15.0]% and [42.4 +/- 14.9]%) (P < 0.05). The cure rate and total effectiveness rate were significantly higher in group B than in A (P < 0.05), but had no significant differences between either A and C or B and C (P > 0.05).

CONCLUSIONShort-course kidney-invigorating therapy can significantly improve near-term semen quality in asthenozoospermic men with kidney asthenia, especially in those with kidney-yang deficiency, and it has no obvious adverse effects.

Adult ; Asthenozoospermia ; diagnosis ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Oligospermia ; diagnosis ; drug therapy ; Phytotherapy ; Semen Analysis ; Yang Deficiency ; Young Adult

Objective To investigate the prevalence ofperioperative depression and anxiety in patients who underwent acoustic neuroma resection (ANR) and to analyze their associated factors.Methods This survey recruited 62 patients who accepted ANR from June 2010 through June 2011 in our department. Participants were interviewed one day preoperation and one day pre-discharge with 2questionnaires:the Zung self-rating depression scale (SDS) and the Zung self-rating anxiety scale (SAS).Personal information and clinical data were also documented. Facial nerve outcomes were reported according to the House-Brackmann scale.Statistical analysis was performed with the SPSS,version 13.0,using two-sample t-test,paired t-test,pearson Chi-square test and Binary classification unconditional logistic regression analysis.Significance was accepted at P＜0.05. Results Thirteen patients (20.9％)had depression and/or anxiety preoperation while 24 patients (38.7％) had postoperation.Patients with a long preoperative hospital stay,young in age (Wald=5.958,OR=0.910,P=0.015) and associated with chronic diseases (Wald=6.578,OR=14.591,P=0.010) were prone to preoperative depression and/or anxiety.Female patients (Wald=4.258,OR =4.572,P=0.039),young patients (Wald=8.152,OR=0.913,P=0.004) and patients with facial paralysis of H-B grade Ⅳ-Ⅵ (Wald=6.310,OR=7.630,P=0.012) had a higher incidence of postoperative depression and/or anxiety.Occupation,educational level,economic status,hearing loss or balance dysfunction of the patients showed no statistically significant impact on the incidence of the condition. Conclusions Patients undergoing ANR tend to have a high incidence of perioperative depression and/or anxiety.Surgeons should pay special attention to and take effective measures for female,young patients and those with facial dysfunction because they,in particular,are prone to postoperative depression and/or anxiety.

OBJECTIVE: To investigate the changes of collagen fibers and the expression of osteopontin in the left ventricle in cases of hypertrophic cardiomyopathy (HCM), along with the significance of their potential forensic application. METHODS: Fifteen cases of HCM, 15 cases of coronary heart disease with cardiac hypertrophy and 20 cases of traffic accidents were selected as HCM group, coronary heart disease group and control group, respectively. Collagen volume fraction and osteopontin expression were observed and compared by HE staining, Masson trichrome staining and immunohistochemistry methods. Imaging and statistical methods were used for quantitative analysis. RESULTS: Collagen volume fraction in left ventricle of HCM and coronary heart disease were significantly higher than that in the control group (P < 0.05), which was not significantly different between the HCM group and the coronary heart disease group. The integral light density value of osteopontin in left ventricular cardiomyocytes of the HCM group and the coronary heart disease group were significantly higher than that of the control group (P< 0.05), and the value of the HCM group was also significantly higher than that of coronary heart disease group (P < 0.05). CONCLUSION The increased contents of collagen fibers and the overexpression of osteopontin may play an important role in myocardial fibrosis, and they can be used as markers in aid of diagnosing sudden death due to HCM.
Cardiomyopathy, Hypertrophic/physiopathology* ; Case-Control Studies ; Collagen/metabolism* ; Coronary Disease/physiopathology* ; Death, Sudden, Cardiac/etiology* ; Female ; Fibrosis ; Forensic Pathology ; Heart Ventricles/pathology* ; Humans ; Immunohistochemistry ; Male ; Myocardium/pathology* ; Osteopontin/metabolism* ; Staining and Labeling