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Renjie Li,1 Tingting Li,1 Yang Xie,1 Shuang Zhai,1 Yang Qu,1 Dan Zhang,1 Liwei Zou,2 Yajuan Yang,2 Xiaoyan Wu,1,2 Fangbiao Tao,1,2 Shuman Tao2,3 1Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2MOE Key Laboratory of Population Health Across Life Cycle; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei, 230032, People’s Republic of China; 3Department of Ophthalmology, The Second Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of ChinaCorrespondence: Shuman Tao, Email Shumantao@126.comPurpose: Smartphone use could lead to being physically inactive and a greater risk for health problems, such as inflammation. However, the associations between smartphone use, physical activity (PA), and systemic low-grade inflammation remained unclear. This study aimed to examine the potential mediating effect of PA on the association between smartphone use and inflammation.Patients and Methods: A two-year follow-up study was conducted between April 2019 and April 2021. Duration of smartphone use, smartphone dependence and PA were assessed by a self-administered questionnaire. Laboratory analysis of blood samples was performed to evaluate the levels of TNF-α, IL-6, IL-1β, and CRP as biomarkers of systemic inflammation. The correlations between smartphone use, PA, and inflammation were analyzed using Pearson correlation. Structural equation modelling was used to analyze the potential mediating effect of PA on the associations between smartphone use and inflammation.Results: A total of 210 participants were included with a mean (standard deviation) age of 18.7 (1.0) years, 82 (39%) of whom were males. Smartphone dependence was negatively associated with the total PA level (r=− 0.18, P< 0.01). PA mediated the associations between the duration of smartphone use and smartphone dependence with inflammatory markers. Specifically, as PA decreased, the duration of smartphone use was more negatively associated with TNF-α (ab=− 0.027; 95% CI: − 0.052, − 0.007) and more positively correlated to IL-6 (ab=0.020; 95% CI: 0.001, 0.046) and CRP (ab=0.038; 95% CI: 0.004, 0.086); smartphone dependency was more negatively associated with TNF-α (ab=− 0.139; 95% CI: − 0.288, − 0.017) and more positively related to CRP (ab=0.206; 95% CI: 0.020, 0.421).Conclusion: Our study illustrates that there are no direct associations between smartphone use and systemic low-grade inflammation, however, PA level plays a weak but significant mediating effect on the associations between smartphone use and inflammation among college students.Keywords: smartphone, inflammation, physical activity, mediating role, follow-up

1. This trial investigated the effect on embryo injected with ochratoxin A (OTA) and the growth performance, jejunal morphology and barrier of ducklings to 21 d old. 2. Two hundred forty, fertilised eggs were individually weighed and randomly assigned to two groups, a control (CON) and the OTA treatment, according to average egg weight. On d 13 of embryonic development, the treatment group was injected with 8 ng OTA/g egg and the CON group was injected with NaHCO3 solution as a placebo. All newly hatched ducklings were assigned to the CON or OTA group based on the different treatments. Each treatment consisted of six replicates and each included 10 ducklings and the experiment lasted until 21 d of age. 3. The results showed that embryos injected with OTA affected the 21 d body weight (BW) and average daily gain (ADG) of ducklings (p < 0.05). OTA exposure increased the relative weights of the liver, pancreas, gizzard, proventriculus and jejunum (p < 0.05); and decreased the relative length of the jejunum of ducklings (p < 0.05). Moreover, jejunal crypt depth increased (p < 0.05) and the villus height-to-crypt depth ratio (Vh/Cd) decreased in the OTA-injected group (p < 0.05). Compared with those in the CON group, the mRNA expression of Zonula Occludens-1; (ZO-1) (p = 0.0582) and Occludin; (p = 0.0687) in the OTA treatment group was downregulated. 4. The findings demonstrated that a single low-dose injection of OTA increased body weight and daily gain in ducklings. Moreover, embryo exposure to OTA had negative effects with increased relative weight of organs and the jejunal crypt depth, decreased relative length of the intestine and mRNA expression of tight junctions (ZO-1, Occludin). [ABSTRACT FROM AUTHOR]

Fei Zuo,1 Shaoguo Zhai2 1Department of Finance, Economics and Management School, Northwest University, Xi’an, Shaanxi Province, People’s Republic of China; 2Department of Social Security, Public Management School, Northwest University, Xi’an, Shaanxi Province, People’s Republic of ChinaCorrespondence: Fei ZuoDepartment of Finance, Northwest University, No. 1, Xuefu Road, Xi’an, Shaanxi Province, People’s Republic of ChinaTel +86 153-3907-9756Email grace.fiz@nwu.edu.cnBackground: While past experiences show that a health system financing mechanism can support resilience to shocks, the impact on the sustainability of the financing system is exceptionally important considering the magnitude of the COVID-19 pandemic. The role of Social Health Insurance (SHI) in responding to the pandemic brings about an influence on insurance system sustainability. This study investigates the impact of China’s COVID-19 treatment policy on the sustainability of its SHI system, explores influences of the policy on Wuhan’s system, and discusses the effects of an assumed equivalent emergency on SHI funds for five other provincial capital cities in China.Methods: The study was conducted using pay-as-you-go actuarial models of Urban Employee Basic Medical Insurance (UEBMI) and Urban and Rural Residents Basic Medical Insurance (URRBMI) funds, which constitute China’s basic health insurance system. Current and accumulated balances of the funds in 2020 are predicted and utilized to measure the sustainability of health insurance funds during emergencies.Results: The findings suggest a disparity in the capacities of insurance schemes and localities. If the surplus before 2018 is not considered, it is likely that the URRBMI fund of Wuhan would suffer a deficit, whereas the UEBMI would retain a considerable surplus. To maintain the current actuarial balance of the URRBMI fund, coverage for ordinary inpatient and outpatient expenses would have to be significantly reduced in Wuhan, potentially affecting enrollees’ wellbeing. A similar situation may occur in three other cities, some with underdeveloped economies and lower per capita income are likely to be encountered with worse situation than Wuhan.Conclusion: Concerning fragmentation of China’s SHI system, to strengthen longer-term preparedness to manage future emergencies, this study suggests the integration of insurance schemes and provincial pooling, fund balance adjusting and an emergency safety net are also advised. All options call for more public health investments.Keywords: public health emergency, COVID-19 pandemic, public health insurance, sustainability, disparity

Shuang Zhai,1 Shuman Tao,2,3 Xiaoyan Wu,1,3 Liwei Zou,1 Yajuan Yang,4 Yang Xie,1 Tingting Li,1 Dan Zhang,1 Yang Qu,1 Fangbiao Tao1,3 1Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 2Department of Nephrology, The Second Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3MOE Key Laboratory of Population Health Across Life Cycle/NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, People’s Republic of China; 4School of Nursing, Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Shuman TaoDepartment of Nephrology, The Second Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of ChinaTel +86 15077927106Email shumantao@126.comPurpose: Sleep insufficiency and circadian rhythm disturbances in college students have become prominent. Current findings show that sleep insufficiency is closely related to inflammation. Studies on the correlation between chronotype and inflammatory factors are still lacking. Therefore, this research intended to examine the relationships between sleep duration, chronotype and inflammatory cytokines in young adults, and to estimate the correlation between chronotype and inflammatory cytokines stratified by sleep duration.Patients and Methods: We conducted a cross-sectional study in April and May 2019. Participants were recruited from two colleges located in central China. The Pittsburgh Sleep Quality Index (PSQI) and the Morning and Evening Questionnaire-5 (MEQ-5) were administered to assess sleep duration and chronotype. Sleep duration less than 7 hours was defined as insufficient sleep. Fasting venous blood was collected to measure plasma levels of inflammatory markers including IL-1β, IL-6, TNF-α and IL-10.Results: A total of 723 participants were included in this study, with a mean age of 18.68 years (standard deviation=0.99). After adjusting for confounding factors, the results of generalized linear model showed that sleep insufficiency was positively correlated with IL-1β, TNF-α and IL-10; and evening-types (E-types) were positively associated with the levels of IL-1β and IL-6 (p< 0.05). Compared to the control group (sleep sufficiency and M-types), there were positive interaction effects of sleep insufficiency and neutral-types (N-types) on the levels of IL-1β, IL-6, TNF-α and IL-10 (p< 0.05). The hierarchical regression model showed that N-types and E-types were positively correlated to the levels of IL-1β, IL-6, TNF-α and IL-10 among college students with sleep insufficiency (p< 0.05).Conclusion: The levels of inflammatory markers were higher among college students with sleep insufficiency and E-types. N-types and E-types were positively correlated with IL-1β, IL-6, TNF-α and IL-10 among college students with sleep insufficiency.Keywords: sleep duration, circadian rhythm, chronic inflammation, young adults

Shengyong Zhai,1,* Xiaojing Sun,2,* Longfeng Du,1 Kai Chen,1 Shanshan Zhang,2 Yiran Shi,1 Fei Yuan1 1Department of Oncology Surgery, Weifang People’ s Hospital, Weifang Medical College, Weifang City, Shandong Province, 261041, People’s Republic of China; 2School of Management and Information, Shandong Transport Vocational College, Weifang City, Shandong Province, 261041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei YuanDepartment of Oncology Surgery, Weifang People’s Hospital, Weifang Medical College, NO.181, Guangwen Street, Kuiwen District, Weifang City, Shandong Province, 261041, People’s Republic of ChinaTel +86 13696360906Fax +86-536-8675792Email zsy-1985122@163.comPurpose: This study is a retrospective analysis of exploring the efficiency of surgical management on patients with synchronous colorectal liver metastasis (SCLM).Patients and Methods: Nine hundred fifty-three consecutive patients with SCLM from Weifang People’s Hospital of Shandong Province between January 2006 and December 2015 were reviewed. The values of different factors were analyzed, such as different surgical indications of liver metastases, simultaneous or staged resection of primary colorectal cancer and liver metastases, and primary tumor resection (PTR) of asymptomatic patients with unresectable liver metastases.Results: Median survival time (47.3 months) and 5-year survival rate (31%) for patients with resected liver metastases were significantly superior to that of with nonoperative treatment (17.2 months, 4%, P< 0.001); enlarging the standard of liver metastases resection can improve the resection rates (31.0% vs 13.6%, P< 0.001); for patients with resectable liver metastases, the in-hospital cost for simultaneous resection group was lower than that in the staged resection group (36,698 vs 45,134 RMB, P< 0.001); for patients of the asymptomatic primary tumor with unresectable liver metastases, PTR was associated with improved median survival (18.0 vs 15.0 months, P=0.006).Conclusion: For patients with SCLM, liver resection is considered the best treatment; expanding indications of liver resection can improve the resection rates. Simultaneous resection of the primary tumor and liver metastases were indicated in patients with resectable SCLM; PTR was recommended for asymptomatic patients with unresectable hepatic metastases.Keywords: surgical treatment, synchronous colorectal liver metastases, survival analysis, primary tumor resection

Yaping Li,1 Muqi Wang,1 Wenjun Wang,1 Dandan Feng,1 Huiling Deng,1,2 Yufeng Zhang,2 Shuangsuo Dang,1 Song Zhai1 1Department of Infectious Diseases, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an 710004, People’s Republic of China; 2Department of Infectious Diseases, Xi’an Children’s Hospital, Xi’an 710003, People’s Republic of ChinaCorrespondence: Shuangsuo Dang; Song ZhaiDepartment of Infectious Diseases, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an 710004, People’s Republic of ChinaTel/Fax +86-29-87679688; +86 18991307953Fax +86 29-87679273Email dangshuangsuo123@xjtu.edu.cn; zhaisong1103@xjtu.edu.cnIntroduction: Severe hand, foot, and mouth disease (HFMD) may lead to serious complications, which cause child mortality during outbreaks. The aim of this study was to determine whether neutrophil-to-lymphocyte ratio (NLR) can predict death risk in severe HFMD.Methods: Medical records for 664 severe HFMD patients were retrospectively examined, and NLR was calculated from blood counts. Youden’s index was calculated to determine the optimal NLR cutoff. Uni- and multivariate logistic regression were used to determine death risk factors associated with severe HFMD.Results: An NLR cutoff value of 2.01 and 2.50 respectively predicted mortality among all 664 severe HFMD and 137 critical HFMD. Among all 664 patients, the multivariate model identified the following as independently associated with death risk: high fever (OR 3.342, 95% CI 1.736– 6.432), EV71 infection (OR 3.200, 95% CI 1.529– 6.698), fasting glucose (OR 37.343, 95% CI 18.616– 74.909), and NLR (> 2.01) (OR 2.142, 95% CI 1.125– 4.079). Among 137 critical HFMD, EV71 infection (OR 3.441, 95% CI 1.132– 10.462), fasting glucose (OR 14.173, 95% CI 4.920– 40.827), and NLR (> 2.50) (OR 4.166, 95% CI 1.570– 11.051) were associated with death risk.Conclusion: In conclusion, NLR (> 2.01) in severe HFMD and NLR (> 2.50) in critical HFMD patients may be associated with increased death risk.Keywords: enterovirus 71, hand, foot and mouth disease, neutrophil-to-lymphocyte ratio, risk factor

Peng Men,1,2 Tianbi Liu,1,3 Suodi Zhai1,2 1Department of Pharmacy, Peking University Third Hospital, Beijing, People’s Republic of China; 2Institute for Drug Evaluation, Peking University Health Science Center, Beijing, People’s Republic of China; 3Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Suodi Zhai Department of Pharmacy, Peking University Third Hospital, No. 49 North Huayuan Road, Haidian District, Beijing, People’s Republic of ChinaTel +86-13401169143Fax +86-10-82266686Email zhaisuodi@163.comPurpose: To evaluate the cost-utility of empagliflozin, in addition to best available standard care (BASC), for the treatment of adult patients with T2DM at high cardiovascular risk from the Chinese healthcare system perspective.Methods: A Microsoft Excel-based patient-level simulation model, based on the EMPA-REG OUTCOME trial data, was adapted and used to project individual’s clinical and economic outcomes over a lifetime horizon. The cost and utility values were derived from databases and published studies. Numbers and rates of diabetes-related events, life-years (LYs), quality-adjusted life-years (QALYs), costs (¥ 2019) as well as incremental cost-utility ratios (ICURs) were calculated. Deterministic and probabilistic sensitivity analyses were conducted to test the robustness of the model results.Results: Compared with BASC, empagliflozin plus BASC was predicted to result in an additional 1.01 QALYs (8.05 QALYs vs 7.04 QALYs) at an incremental cost of ¥ 4002 per patient. The modeled ICUR was ¥ 3988 per QALY gained, which was considered highly cost-effective in China compared to both one and three times the GDP per capita in 2019 (¥ 70,892 and ¥ 212,676). The deterministic and probabilistic sensitivity analyses confirmed the robustness of base-case results.Conclusion: This is the first cost-utility analysis regarding the use of empagliflozin in patients with T2DM in China, the world’s most affected country by the T2DM pandemic. The economic evaluation suggests that empagliflozin added to BASC was estimated to be a highly value-for-money option for the treatment of adult patients with T2DM at high cardiovascular risk in the Chinese healthcare setting.Keywords: diabetes, China, sodium-glucose transporter 2 inhibitors, cost-effectiveness

Na He,1,2 Fei Dong,3 Wei Liu,1 Suodi Zhai1 1Department of Pharmacy, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Science, Peking University, Beijing, People’s Republic of China; 3Department of Hematology, Peking University Third Hospital, Beijing, People’s Republic of ChinaCorrespondence: Suodi Zhai; Wei LiuDepartment of Pharmacy, Peking University Third Hospital, 49 Huayuan North Road, Haidian District, Beijing 100191, People’s Republic of ChinaTel +86 10-82266686; +86 10-82265740Email zhaisuodi@163.com; andthen0023@163.comObjective: To provide a comprehensive review of vancomycin dosing in patients with hematologic malignancies or neutropenia.Methods: PubMed, Embase and the Cochrane Library were searched through April 2, 2020. Original studies relevant to vancomycin dosing regimen in adults with hematologic malignancies or neutropenia were included. No restriction was applied in study design and language. A descriptive analysis was performed.Results: Twenty-three studies were included eventually, of which eighteen were case series studies, four were cohort studies and another one was a randomized controlled trial. Five case series studies made a clinical audit of conventional vancomycin dosing in patients with malignancies or neutropenia, showing that the proportion of patients with sub-therapeutic trough levels remained high, ranging from 32% to 88%. Seven case series studies and four cohort studies demonstrated that vancomycin clearance (CLva) tended to be higher in patients with hematologic malignancies or neutropenia, whereas volume of distribution (V) seemed to be comparable to the control group. Five studies proposed individualized initial dosing regimen per the pharmacokinetic changes; however, no prospective validation has been conducted in clinical setting. Additionally, four case series studies suggested that the correlation between vancomycin clearance and estimated creatinine clearance was relatively poor, bringing a great challenge to proper dosing strategy. A randomized controlled trial stated that therapeutic drug monitoring (TDM) of vancomycin could decrease the incidence of nephrotoxicity in immunocompromised febrile patients with hematologic malignancies.Conclusion: The available evidence indicates that conventional vancomycin dosing leads to suboptimal concentration in patients with hematologic malignancy or neutropenia. TDM accompanied by pharmacokinetic interpretation can decrease the risk of nephrotoxicity. The individualization of the initial dosing regimen and mechanisms of augmented clearance require further research.Keywords: vancomycin, hematologic malignancy, neutropenia, pharmacokinetics, evidence-based practice

Shufen Xu,* Shengping Zhai,* Tiantian Du,* Zhan Li Respiratory Department, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai City, Shandong Province 264000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhan LiRespiratory Department, Yantai Yuhuangding Hospital Affiliated to Qingdao University, NO. 20 Yuhuangding East Road, Zhifu District, Yantai City, Shandong Province 264000, People’s Republic of ChinaEmail gvjycert0951@126.comIntroduction: LncRNA MIR503HG has been reported to participate in liver cancer and ALK-negative anaplastic large-cell lymphoma, while its role in non-small cell lung cancer (NSCLC) is unknown. We therefore investigated the functions of lncRNA MIR503HG in NSCLC.Methods: MIR503HG expression in paired cancer and non-cancer tissues from NSCLC patients was analyzed by RT-qPCR. The interaction between cyclin D1 and MIR503HG was analyzed by overexpression experiments. Cell cycle analysis was performed by flow cytometry. Cell proliferation was analyzed by CCK-8 assay.Results: MIR503HG was downregulated in NSCLC and low levels of MIR503HG were associated with poor survival. In contrast, cyclin D1 was upregulated in NSCLC, and cyclin D1 and MIR503HG were inversely correlated. In NSCLC cells, overexpression experiments revealed that MIR503HG functioned as an upstream inhibitor of cyclin D1. MIR503HG overexpression led to G1 cell cycle arrest, while overexpression of cyclin D1 attenuated the effects of MIR503HG overexpression. Similarly, MIR503HG overexpression resulted in reduced cell proliferation rate, while overexpression of cyclin D1 caused the increased cell proliferation rate and attenuated effects of MIR503HG overexpression.Conclusion: MIR503HG inhibits NSCLC cell proliferation by inducing cell cycle arrest through the downregulation of cyclin D1.Keywords: non-small cell lung cancer, lncRNA MIR503HG, cyclin D1, cell cycle, survival

Background: The To discuss the application value of ultrasonography (US) and 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy in hyperparathyroidism (HPT), so as to provide a more reliable guarantee for surgery or thermal ablation. Materials and Methods: Sixty-four HPT patients admitted to our hospital and the Tenth People's Hospital of Tongji University from January 2018 to February 2023 were selected as research participants. All patients underwent cervical US, dual-phase 99mTc-MIBI planar scintigraphy, single photon emission computed tomography (SPECT), and pathological examination. The diagnostic efficiency of the above three imaging modalities was evaluated with pathological findings as the gold standard. In addition, the influence of parathyroid position, size and histological type on imaging results was evaluated. Results: Among the 64 patients, 71 positive lesions were pathologically confirmed. The analysis showed that 99mTc-MIBI SPECT/CT (Kappa=0.806) and US (Kappa=0.686) had high consistency with pathological findings, while dual-phase 99mTc-MIBI planar scintigraphy had moderate consistency with pathological examination results (Kappa=0.594). Conclusions: 99mTc-MIBI scintigraphy can significantly improve the diagnostic rate of parathyroid lesions. US is first recommended for patients suspected of HPT, followed by 99mTc-MIBI scintigraphy for confirmation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to investigate the protective effect of recombinant erythropoietin at different doses on brain injury in premature infants and the related effects on blood routine, liver function, intellectual development, mental development index (MDI), psychomotor development index (PDI), etc. PATIENTS AND METHODS: A total of 120 premature infants were divided into four groups, including experimental group A (n=30), experimental group B (n=30), experimental group C (n=30) and control group (n=30). The experimental group was treated with different doses of recombinant erythropoietin for brain injury protection of premature infants, while the control group with conventional methods. RESULTS: There was no statistical significance in all test indicators of the four groups of patients before the intervention. After the intervention experiment, the S-100B index was p<0.05, and the erythropoietin (EPO) index was p<0.05. In the comparison of IL-6 indicators, the indicators of the experimental group were reduced after the comparison experiment, and there were significant differences, p<0.05. In neonatal behavior evaluation, there was a statistical difference between groups A and B and the control group (p<0.05), and no statistical significance was shown between group C and the control group (p>0.05). In the intelligence test comparison, the F value of the experimental group was 3.113 three months after treatment. After six months, the F value was 3.654. After nine months, the F value was 3.392 with p<0.05. In the comparison of blood routine indicators, the p-values of four indicators between groups were more than 0.05. In the comparison of liver function indexes, the indexes of groups A, B, and C were significantly changed before and after treatment, and the data after treatment were significantly different from those before treatment, p<0.05. In the comparison of development, there were no significant differences observed in the p-values of the two indicators of vigorous exercise and language in the experimental group. CONCLUSIONS: Recombinant erythropoietin has a protective effect on infants with brain injury and can improve the intellectual development of premature infants, but has no significant effect on blood routine indicators. It can effectively improve the MDI, PDI, and related cytokines of premature infants, and has certain significance for the treatment of brain injury. [ABSTRACT FROM AUTHOR]

Zhan-Miao Yi,1 Ting-Ting Qiu,1,2 Yuan Zhang,3 Zhi-Yan Liu,1 Suo-Di Zhai1 1Department of Pharmacy, Peking University Third Hospital, Beijing, 2Department of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 3Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada Objective: We compared prophylactic effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on upper gastrointestinal bleeding (UGIB) associated with dual antiplatelet therapy (DAPT) and explored this influence on platelet function. Methods: Randomized controlled trials and cohort studies comparing PPIs with H2RAs in adults receiving DAPT were collected from PubMed, EMBASE and Cochrane databases. Dichotomous data were pooled to obtain risk ratios (RRs) for UGIB, major adverse cardiovascular events (MACEs), poor responders to clopidogrel and rehospitalization, and continuous data were pooled to obtain mean differences (MDs) for P2Y12 reaction units (PRUs), with 95% confidence intervals (CIs). Results: Twelve clinical trials (n=3,301) met the inclusion criteria. Compared to H2RAs, PPIs lessened UGIB (RR =0.16, 95% CI: 0.03–0.70), and there was no significant difference in the incidence of PRUs (MD =18.21 PRUs, 95% CI: -4.11–40.54), poor responders to clopidogrel (RR =1.21, 95% CI: 0.92–1.61), incidence of MACEs (RR =0.89, 95% CI: 0.45–1.75) or rehospitalization (RR =1.76, 95% CI: 0.79–3.92). Subgroup analysis confirmed fewer PRUs in the H2RAs group compared to the omeprazole group (2 studies, n=189, MD =31.80 PRUs, 95% CI: 11.65–51.96). However, poor responder data for clopidogrel and MACEs might be unreliable because few studies of this kind were included. Conclusion: Limited evidence indicates that PPIs were better than H2RAs for prophylaxis of UGIB associated with DAPT and had no effect on platelet function. Further study is needed to confirm these observations. Keywords: proton pump inhibitors, histamine-2 receptor antagonists, dual-antiplatelet therapy, upper gastrointestinal bleeding, platelet function, meta-analysis

Chao Zhang,1 Haiyan Li,2 Xin Xiong,1 Suodi Zhai,1 Yudong Wei,2 Shuang Zhang,2 Yuanyuan Zhang,1 Lin Xu,2 Li Liu1 1Department of Pharmacy, 2Institute of Clinical Trial, Peking University Third Hospital, Beijing, People’s Republic of China Abstract: We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet®) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax), extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration–time curve (AUCs) of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations. Keywords: pharmacokinetics, safety, ethinylestradiol/gestodene, transdermal contraceptive patch

We present the results of photometric and spectroscopic monitoring campaigns of the changing look AGN NGC 2617 carried out from 2016 until 2022 and covering the wavelength range from the X-ray to the near-IR. The facilities included the telescopes of the SAI MSU, MASTER Global Robotic Net, the 2.3-m WIRO telescope, Swift , and others. We found significant variability at all wavelengths and, specifically, in the intensities and profiles of the broad Balmer lines. We measured time delays of ∼6 d (∼8 d) in the responses of the Hβ (Hα) line to continuum variations. We found the X-ray variations to correlate well with the UV and optical (with a small time delay of a few days for longer wavelengths). The K -band lagged the B band by 14 ± 4 d during the last three seasons, which is significantly shorter than the delays reported previously by the 2016 and 2017–2019 campaigns. Near-IR variability arises from two different emission regions: the outer part of the accretion disc and a more distant dust component. The HK -band variability is governed primarily by dust. The Balmer decrement of the broad-line components is inversely correlated with the UV flux. The change of the object's type from Sy1 to Sy1.8 was recorded over a period of ∼8 yr. We interpret these changes as a combination of two factors: changes in the accretion rate and dust recovery along the line of sight. [ABSTRACT FROM AUTHOR]