BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15％ of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5％?49.7％ of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3％?17.9％, which was significantly higher than that (6.9％?7.4％) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis

Objective To determine the influence of abiraterone acetate (AA) on neuroendocrine differentiation (NED) in metastatic castration-resistant prostate cancer (mCRPC) and the prognostic predicting value of the serum NED markers in mCRPC patients treated with AA.Methods We conducted an analysis in 115 chemotherapy-naive mCRPC patients who were treated with chemotherapy in Renji hospital from 2013 to 2017.The median age was 70,ranged from 65 to 76 years old.The median CgA,NSE and PSA levels were 101.1 ng/ml (78.5-150.0 ng/ml),13.4 ng/ml (10.5-17.6 ng/ml) and 38.8 ng/ml (11.2-123.2 ng/ml),respectively.Among them,48 cases were classified as the group without AA treatment.The other 67 cases were classified as group after AA failure.In group without AA treatment,the median CgA,NSE and PSA levels were 109.1 ng/ml(80-151.5 ng/ml);13.8 ng/ml(10.8-18.2 ng/ml) and 39.2 ng/ml (8.6-200 ng/ml),respectively.In group after AA failure,the median CgA,NSE and PSA levels were 105.4 ng/ml(78.8-175.5 ng/ml),13.8 ng/ml(10.8-17.6 ng/ml) and 39.0 ng/ml(8.4-219.8 ng/ml),respectively.In the group with serial evaluation of NED markers during AA treatment,the median serum CgA,NSE levels at baseline were 115.9 ng/ml(90.1-201.5 ng/ml),13.3 ng/ml (10.4-18.1 ng/ml),respectively.The endpoints were PSA PFS(progression-free survival) and radiographic PFS (rPFS).Results In 34 patients with serial evaluation,serum NED markers level in 19 patients increased after the failure of AA treatment.Median serum CgA and NSE levels were 115.9 ng/ml(90.1-201.5 ng/ml)and 13.25 ng/ml (10.37-18.14 ng/ml) at baseline.Median serum CgA and NSE levels were 129.6ng/ml (75.5-230.5 ng/ml) and 14.7 ng/ml (11.8-19.1 ng/ml) after 6 months treatment,respectively.The median serum CgA and NSE levels were 130.4 ng/ml (95.7-205.7 ng/ml) and 15.2 ng/ml(12.4-18.7 ng/ml) at the time of failure of AA treatment,respectively.There was no significant difference of NED markers between baseline and failure of AA treatment (P =0.243).In logistic univariate analysis,AA treatment and its duration were not independent factors influencing NED(P =0.30;P =0.52).Compared with the NED markers elevation group in the first 6 months of AA treatment and baseline supranormal NED markers group,the NED markers decline group(PSA PFS(17.1 vs.10.4 months,P ＜ 0.001) and rPFS (17.0 vs.10.4 months,P =0.003)) and baseline normal NED markers group(PSA PFS(14.1 vs.9.5 months,P =0.001) and rPFS(16.4 vs.10.5 months,P ＜ 0.001)) has a longer median PSA PFS and rPFS respectively.In multivariate Cox analysis,baseline NED markers level and NED markers variation during the first 6 months of AA treatment remained significant predictors of rPFS(P ＜ 0.05),and PSA-PFS (P ＜ 0.05).Conclusions We found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment,and AA might not significantly lead to progression of NED of mCRPC in general.Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.Serum NED markers elevation during the first 6 months of AA treatment and elevated baseline NED markers levels indicated poor prognosis in mCRPC treated with AA.

Objective To summarize the experiences of postoperative care of 7 patients with lung transplantation patients receiving high flow nasal cannulae oxygen therapy. Methods The key points to ensure the success of operation were oxygen therapy waiting for lung transplantation,sequential treatment after tracheal intubation, assisted by fiberoptic bronchoscopy, nasal high flow oxygen therapy failed to switch to non-invasive treatment or re intubation. Results All 7 patients got through the intensive care period successful. Conclusions High flow nasal cannulae can improve the comfort and compliance of lung transplant patients,and easy to operate.

Objective To analyze the value of the potential risk factors on predicting primary graft dysfunction (PGD) after bilateral lung transplantation for the patients with idiopathic pulmonary fibrosis (IPF).Methods A retrospective study was conducted. Fifty-eight patients with IPF who underwent the bilateral lung transplantation admitted to Wuxi People's Hospital Affiliated to Nanjing Medical University from June 2014 to March 2017 were enrolled. The grade 3 PGD happened within 72 hours after transplantation was taken as the outcome event, and these patients were divided into PGD and non-PGD groups. The age, gender, body mass index (BMI), underlying disease, and N-terminal-probrain natriuretic peptide (NT-proBNP) before operation, pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), and mean pulmonary artery pressure (mPAP) before and after operation, duration of operation, the volume of blood transfusion during operation and postoperation, the use of extracorporeal membrane oxygenation (ECMO) during the operation, blood purification treatment after operation, and shock within 3 days after operation were recorded. The differences of parameters mentioned above between the two groups were compared. The predictive factors of PGD were searched by binary logistic regression analysis, and the receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of preoperative PADP for grade 3 PGD after transplantation.Results Among 58 patients who underwent the bilateral lung transplantation, 52 patients were enrolled. The rest patients were excluded because of incomplete clinical data. There were 17 patients in the PGDgroup, with a mortality rate of 47.06%. The non-PGD group included 35 patients with a mortality rate of 8.57%. PADP and mPAP ahead of operation, the dosage of red cells suspension after the operation, and the total amount of blood transfusion during and after the operation in PGD group were significantly higher than those in non-PGD group [PADP ahead of operation (mmHg, 1 mmHg = 0.133 kPa): 33.7±10.5 vs. 25.3±10.1, mPAP ahead of operation (mmHg): 40.4±14.1 vs. 32.8±11.1, the dosage of red cells suspension after the operation (mL): 700 (300, 1500) vs. 300 (300, 500), the total amount of blood transfusion during and after the operation (mL): 2250 (1850, 4275) vs. 1800 (1550, 2800)], with statistically significant differences (all P < 0.05). There were no significant differences in age, gender, BMI, underlying disease, NT-proBNP before operation, PASP before and after operation, PADP and mPAP after operation, duration of operation, amount of plasma and red cells suspension as well as total amount of blood transfusion during operation, plasma amount and total amount of blood transfusion after operation, amount of plasma and red cells suspension during and after operation, use of ECMO during operation, blood purification treatment after operation, and shock after operation between the two groups (all P > 0.05). It was shown by binary logistic regression analysis that the preoperative PADP was the independent risk factor of grade 3 PGD after lung transplantation [odds ratio (OR) = 1.084, 95% confidence interval (95%CI) = 1.016-1.156,P = 0.015]. It was shown by ROC curve that the area under the ROC curve (AUC) of the PADP before operation for predicting the grade 3 PGD after lung transplantation was 0.728. When the cut-off value was 36 mmHg, the sensitivity was 47.1%, and the specificity was 91.4%.Conclusions Compared with the non-PGD group, the patients with higher preoperative PADP were more common in the PGD group, and the patients in the PGD group were more likely to be characterized by grade 3 PGD after lung transplantation. The preoperative PADP was an effective predictor of grade 3 PGD after lung transplantation.

This paper summarized nursing care in intra-hospital transfer of 13 critically ill patients with extracorporeal membrane oxygenation. The key points to guarantee safety of critically ill patients were establishing a well-trained professional team and developing standardized procedures,and applying checklist for ECMO Transfer. The key points in nursing were assessment and pretreatment,homogenized nursing during transfer and effective handover after transfer. As a result,six cases of avian influenza patients successfully completed CT ex-amination,five cases of lung re-transplant patients and two cases of lung transplant patients were successfully trans-ferred to the operating room.

Aim To investigate the impact of CYP3 A5 genetic polymorphism on modified releasing tacrolimus pharmacokinetics in Chinese stable renal transplant re-cipients. Methods Pharmacokinetics of once daily-ta-crolimus( tac-q. d. ) and twice daily-tacrolimus( tac-b. i. d. ) were determined by CLIA, CYP3A5 genotype was measured by PCR-RFLP. Each 10 patients receiv-ing tac-q. d. and tac-b. i. d. respectively were en-rolled, and each 5 patients receiving tac-q. d. were matched to poor metabolizer ( PM ) and extensive me-tabolizer ( EM ) group respectively according to CYP3A5 genotypes. Results AUC0~24 h for tac-q. d. was 1. 78 folds higher than AUC0~12 h for tac-b. i. d. , and dose-adjusted C0 was 40% lower for tac-q. d. than for tac-b. i. d. There were no significant differences for other parameters between the two groups; Cmax, AUC0~24 h and C0 were 1. 75, 1. 96 and 2. 49 folds higher for PM than for EM, and dose-adjusted Cmax, AUC0~24 h and C0 were 1. 80, 2. 34 and 2. 64 folds higher for PM than for EM. There were good correla-tions between AUC0~24 h and C0 for tac-q. d. Conclu-sion Conversion from tac-b. i. d. to tac-q. d. results in requirement of increased tacrolimus dose and detec-tion of CYP3A5 genotype, which is necessary for ensu-ring C0 in the range of therapeutic window.

Objective To prepare a rabbit monoclonal antibody GCET 2 and to investigate its diagnostic value in the workup of diffuse large B-cell lymphoma ( DLBCL ) .Methods GCET2 rabbit monoclonal antibody was developed by using RabMAb ? technology , and its specificity was confirmed by ELISA, Western blot, immunohistochemistry ( IHC) and flow cytometry.A panel of immunomarkers including GCET2, CD10, bcl-6, MUM1, GCET1, FOXP1, Ki-67 and CMYC was evaluated in 81 cases of DLBCLs, 5 cases of follicular lymphomas ( FL) and 2 cases of Burkitt′s lymphomas.Results Rabbit monoclonal GCET2 antibody ( clone EP316 ) was developed with specificity for normal germinal center B-cells ( GCB ) and GCB origined lymphomas .In 81 cases of DLBCL , the positive rate of GCET2 was 43.2%( 35/81 ) , which was significantly higher than that of other germinal center markers .Moreover , among 81 DLBCLs, the proportions of high CMYC expression in GCET 2 negative and positive groups were 15.2%(7/46) and 2.8%(1/35), respectively.Conclusion GCET2 is a sensitive immunohistochemical marker for GCB derived lymphomas . Combined with other biomarkers , it may improve the diagnostic sensitivity of GCB-DLBCL.