Objective To evaluate the change of energy metabolism during cisplatin-induced acute kidney injury.Methods Adult CD-1 male mice were intraperitoneally injected with a single dose of cisplatin (20 mg/kg), and renal function and renal tissue pathology were tested;gene expression was analyzed and signaling pathways were en-riched in cisplatin-treated renal tubular epithelial cells using transcriptome; the contents of renal glycolysis and a-mino acid metabolites were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) .Re-sults Serum urea nitrogen and blood creatinine significantly increased in cisplatin-treated mice.Pathological his-tology observed swelling and shedding of renal tubular epithelial cells.Transcriptome analysis revealed that 2632 genes were upregulated and 2799 genes were downregulated in cisplatin-treated HK-2 cells.GO and KEGG analy-sis showed that differential genes were enriched in energy metabolism.The GSEA analysis results showed that cispl-atin caused an upregulation of the oxidative phosphorylation pathway and a downregulation of the glycolysis pathway in renal tubular epithelial cells, further KEGG analysis demonstrated that cisplatin caused changes in the expression of amino acid genes in renal cells.Metabolomics showed that the contents of glycolytic intermediates and several a-mino acids were altered in the kidney of cisplatin-treated mice.Conclusion Cisplatin-induced acute renal injury is accompanied by modification in renal tubular cell glycolysis and amino acid metabolism.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

On-site supervision is a risk-based regulatory system that requires the scientific development of supervision plans for quality risks and hidden dangers in pharmaceutical enterprises， the rational allocation of supervision resources based on their risk levels， and the implementation of classified supervision measures. In this study， the quality risk monitoring business support system is set up for pharmaceutical enterprises by establishing the quality risk expert database and quality risk monitoring index system for pharmaceutical enterprises based on the difficulty analysis of on-site drug supervision. Based on this support system， the quality risk classification method， the differentiated spot check strategy and business auxiliary visualization system are established. This support system is used to learn the risk level of pharmaceutical enterprises， so as to innovate supervision methods and optimize monitoring strategies. Taking Jiangxi Province as an example， it is verified that the support system can guide the risk assessment of sample enterprises， can improve the targeting of on-site drug supervision in the process of technical review， scheme editing， on-site implementation and comprehensive evaluation， and can effectively improve the quality and efficiency of supervision.

Objective To explore the prognostic value of hs-cTnⅠ in patients with suspected acute coronary syndrome(ACS)in emergency department.Methods A large-scale,prospective observa-tional study was conducted on totally 966 patients with suspected ACS admitted in Fuwai Hospi-tal from January 2017 to October 2020.Their baseline serum/plasma hs-cTnⅠ level was detected at admission,conventional treatment was performed,and relevant data were collected.Logistic regression analysis was used to predict the risk of primary and secondary endpoint events within 30 d by hs-TnⅠ concentration,and subgroup analysis was performed.Results Among the 966 patients,the time from chest pain to visit was 5.0(2.5,13.0)h,and 284 patients had primary end-point events within 30 d,including 283 cases of myocardial infarction(99.6％)at the first visit,1 case of recurrent myocardial infarction(0.4％),5 cases of cardiovascular death(1.8％),and 1 case of unplanned revascularization(0.4％).When hs-cTnⅠ was at the minimum detection limit of 2 ng/L,the incidence of adverse events was 5.8％,when the limit of 70 ng/L,the incidence was 49.2％,and when of 316 ng/L,the incidence reached 100％.The model could correctly classify 92.3％of the patients.Conclusion The hs-cTn sequence has a good predictive effect for the risk of short-term cardiovascular adverse events in Chinese population.

The aging process in China is accelerating, and geriatric care is facing daunting challenges. This paper reviews the concept, component factors, measurement methods of cognitive reserve, and its role in geriatric nursing, and elaborates on the necessity of personalized cognitive reserve intervention for the aged, so as to promote the application of cognitive reserve in geriatric nursing.

Objective:To evaluate the clinical value of cognitive and motor function in predicting conversion to neurodegenerative disorders in patients with isolated rapid eye movement sleep behavior disorder (iRBD).Methods:Forty-seven patients with iRBD were collected from the Department of Neurology of Tianjin Medical University General Hospital and Tianjin Medical University General Hospital Airport Site during October 2018 and June 2022. All participants received comprehensive evaluations of cognitive and motor function at baseline. The visuospatial function was evaluated by Rey-Osterrieth Complex Figure Test (ROCF)-copy, the memory function was evaluated by Auditory Verbal Learning Test and ROCF-recall, the attention-executive function was evaluated by Trail Making Test (TMT) and Stroop Color-Word Test, and the language function was evaluated by Boston Naming Test. The motor function was evaluated by Unified Parkinson′s Disease Rating Scale-Ⅲ, Alternate-tap Test (ATT), and 3-meter Timed Up and Go Test. The iRBD patients with phenoconversion were identified during follow-up. Receiver operating characteristic curve and generalized linear model Logistic regression were applied to identify the optimal combination of cognitive and motor tests in distinguishing the converters from non-converters in patients with iRBD. Multivariate Cox regression analyses were applied to evaluate the independent risk factors in predicting conversion to neurodegenerative diseases in patients with iRBD.Results:The median follow-up duration was 3 years. Forty-five iRBD patients were included in the analysis eventually, as 2 dropped out at follow-up. Twenty-one iRBD patients developed neurodegenerative disorders, with 14 presenting motor phenotype and 7 cognitive phenotype. Baseline ROCF-copy, TMT-A and ATT were best combination in identifying iRBD patients with phenoconversion [sensitivity: 90.0%, specificity: 87.5%, area under curve (AUC): 0.931, P<0.001]. Baseline TMT-A and ATT were best combination in identifying iRBD patients with motor phenotype conversion (sensitivity: 100.0%, specificity: 66.7%, AUC: 0.872, P<0.001); Baseline TMT-A performed best in identifying iRBD patients with cognitive phenotype conversion (sensitivity: 83.3%, specificity: 91.7%, AUC: 0.917, P<0.001). Multivariate Cox regression analysis showed that individuals with poorer performance of TMT-A (cut-off value: 63.0 s) and ATT (cut-off value: 205.5 taps/min) than the cut-off values at baseline had higher risks for developing to neurodegenerative disorders, with HR values of 5.455 (95% CI 1.243-23.941, P=0.025) and 11.279 (95% CI 1.485-85.646, P=0.019), respectively. Conclusions:In iRBD, ROCF-copy, TMT-A and ATT served as optimum combination in predicting phenoconversion, whereas TMT-A and ATT served as optimum combination in predicting motor phenotype, and TMT-A performed best in predicting cognitive phenotype. The performance in TMT-A and ATT in iRBD could predict the risk of developing to neurodegenerative disorders independently.

Objective:To explore the predictive value of single high-sensitivity cardiac troponin I (hs-cTnI) concentration of 30-day cardiovascular adverse events in patients with suspected acute coronary syndrome (ACS).Methods:This is a multicenter, prospective and observational clinical study. Patients with suspected ACS who were admitted into the emergency department of Fuwai Hospital, the First Affiliated Hospital of Sun Yat-sen University and Nanjing First Hospital from January 2017 to September 2020 were enrolled. hs-cTnI result at the time of visit was obtained from patients with suspected ACS. Patients were followed up for 30 days and patients were divided into no events group and events group according to the presence or absence of 30-day cardiovascular adverse events (acute myocardial infarction (including index), unplanned revascularization and cardiovascular death). The predictive value of single Hs-cTnI at different concentration thresholds on the adverse event was evaluated in terms of sensitivity, negative predictive value (NPV) and 95% confidence interval ( CI). The best threshold was defined as: missed diagnosis rate <2% and NPV >99%. Patients were sub-grouped according to the confounders of hs-cTnI (sex, age, chest pain duration, estimated glomerular filtration rate), and Chi-square test was used to compare sensitivity and NPV among various subgroups. Results:A total of 1 461 patients were included. Among them, 387 patients (26.5%) had 30-day adverse cardiovascular events and 1 074 patients (73.5%) had no adverse cardiovascular events. Mean age was (62±12) years old and 905 were males (61.9%). When the concentration of hs-cTnI was less than 2 ng/L (limit of detection), the missed diagnosis rate of 30-day cardiovascular adverse events was 0.8% (3/387), the sensitivity was 99.2% (95% CI 97.6%-99.8%), and NPV was 98.7% (95% CI 96.0%-99.7%). When hs-cTnI concentration was less than 6 ng/L, the missed diagnosis rate was 1.8%, the sensitivity was 98.2% (95% CI 96.1%-99.2%), and NPV was 99.0% (95% CI 97.9%-99.6%). Subgroup analysis showed that the sensitivity and NPV of single hs-cTnI concentration <6 ng/L for 30-day cardiovascular adverse events were lower in patients with chest pain less than 3 h than those with chest pain time>3 hours ( P<0.05). Conclusions:Single hs-cTnI concentration less than 6 ng/L can predict the risk of 30-day cardiovascular adverse events in suspected ACS patients, but continuous monitoring is recommended for patients with chest pain onset≤3 hours.

Objective To explore the effect and mechanism of Chaihu Longgu Muli Decoction (柴胡龙骨牡蛎汤, CHLGMLD) in rats with temporal lobe epilepsy (TLE). Methods A total of 80 Sprague-Dawley (SD) male rats were randomized into control (CON), model (MOD), carbamazepine (CBZ, 0.1 g/kg), CHLGMLD low dose (CHLGMLD-L, 12.5 g/kg), and high dose (CHLGMLD-H, 25 g/kg) groups, with 16 rats in each group. TLE rat models were established in the four groups with the use of lithium-pilocarpine except for the CON group. After the successful establishment of TLE models, all drugs were administered through gavage, and distilled water was given to rats in the CON and MOD groups for four weeks. The frequency and duration of seizures before and after treatment were recorded for the evaluation of the alleviation degree. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-146a-3p and miR-146a-5p. The expression levels of toll-like receptor 4 (TLR4), interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), TAK1-binding protein (TAB), nuclear factor-kappa B (NF-κB), and interleukin-1 beta (IL-1β) in hippocampus were tested by immunofluorescence assay. Correlation analysis between the above factors and expressions of miR-146a-3p and miR-146a-5p were performed separately. Results CHLGMLD decreased the frequency (P < 0.05) and duration (P < 0.01) of seizures in rats. CHLGMLD down-regulated the expression levels of miR-146a-5p and miR-146a-3p (P < 0.05), and inhibited the expression levels of TLR4, IRAK1, TRAF6, TAB, NF-κB, and IL-1β (P < 0.01). The correlation analysis revealed that the expression levels of TLR4, IRAK1, TRAF6, TAB, NF-κB, and IL-1β were positively correlated with the expression levels of miR-146a-3p and miR-146a-5p detected by qRT-PCR, respectively (P < 0.01). Conclusion CHLGMLD can inhibite the TLR4 signaling pathway by lowering the expression levels of miR-146a-3p and miR-146a-5p to alleviate hippocampal dentate gyrus inflammation in TLE rats, thus relieving seizures.

Objective:To investigate the function and mechanism of long noncoding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1)-mediated epigenetic regulation of Th2 cell differentiation and development in pregnant women with systemic lupus erythematosus (SLE).Methods:This study involved 11 women with normal singleton pregnancy (control group) and 15 pregnant women with SLE who delivered in the Henan Provincial People′s Hospital from July 1, 2014 to July 1, 2019. Peripheral blood mononuclear cells (PBMCs) were collected and analyzed by qPCR to detect the expression of NEAT1 at mRNA level. ELISA and flow cytometry were used to detect the expression of IFN-γ and IL-4 at protein level. Na?ve CD4 + T cells were sorted out by flow cytometry. RNA binding protein immunoprecipitation (RIP) was performed to detect the binding of EZH2 to NEAT1. After knockdown of NEAT1 expression, Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the expression of itchy E3 ubiguitin protein ligase(ITCH) at mRNA and protein levels. Chromatin immunoprecipitation (ChIP) was used to detect the abundance of EZH2 at ITCH promoter in pregnant patients with SLE. ELISA was used to detect IL-4 level after overexpression of NEAT1 and ITCH. Statistical data analysis was performed with t test. Results:The expression of NEAT1 at mRNA level in peripheral blood of pregnant women with SLE was significantly higher than that in controls. IFN-γ levels were significantly reduced, while IL-4 levels were significantly increased in pregnant women with SLE than in controls. RIP analysis revealed that there was a great enrichment of NEAT1 in the na?ve CD4 + T cells using anti-EZH2 compared to the control group. After knocking down the expression of NEAT1, the mRNA and protein levels of ITCH were significantly increased. ChIP assay demonstrated that EZH2 was recruited to the promoter of ITCH in pregnant women with SLE. ITCH significantly inhibited the production of IL-4 by na?ve CD4 + T cells, while overexpression of NEAT1 upregulated the expression of IL-4 at protein level. Conclusions:LncRNA NEAT1 was significantly up-regulated in pregnant women with SLE. It recruited EZH2 to the promoter of ITCH and promoted the differentiation of na?ve CD4 + T cells to Th2 cells, resulting Th1/Th2 imbalance and affecting disease progression.