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1. chinaXiv:201907.00014 [pdf]

Remedial dosing recommendations for delayed or missed doses of valproic acid in patients with epilepsy based on Monte Carlo simulations

Chenyu,Wang; Jun-jie Ding; Zheng Jiao; Er-qian Yu; Guo-xing Zhu
Subjects: Medicine, Pharmacy >> Clinical Medicine

Objective: Delayed or missed doses are unavoidable in the pharmacotherapy of epilepsy and significantly compromise the efficacy of antiepileptic drug treatment. An inappropriate remedial regimen can cause seizure relapse or serious adverse events. This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of valproic acid (VPA) in patients with epilepsy and established remedial dosing recommendations for nonadherent patients. Methods: Monte Carlo simulations are based on all previous population pharmacokinetic models for pediatric, adult and elderly patients with epilepsy. The following four remedial strategies were investigated for each delayed dose: A) A partial dose or a regular dose is taken immediately; a regular dose is taken at the next scheduled time. B) The delayed dose was administered immediately, followed by a partial dose at the next scheduled time. C) The delayed dose and a partial dose are taken; the next scheduled time is skipped, and the regular regimen is resumed. D) Double doses are taken when missed one dose or two doses, and the regular regimen at the subsequent scheduled time is resumed. Results: The recommended remedial dose was related to the delay duration and daily dose. Remedial dosing strategies A and B were almost equivalent, whereas Strategy C was recommended when the delayed dose was close to the next scheduled dose. Strategy D was only suggested for delayed two doses. Conclusion: Simulations provide quantitative insight into the remedial regimens for nonadherent patients, and clinicians should select the optimal regimen for each patient based on the individual's status.

submitted time 2020-09-07 Hits20876Downloads884 Comment 1

2. chinaXiv:202007.00041 [pdf]

BRAF mutation predicts survival after immunotherapy across multiple cancer types

Ge, Weiting; Cai, Wen; Wu, Dehao; Hu, Wangxiong; Han, Weidong; Zheng, Shu; Hu, hanguang
Subjects: Medicine, Pharmacy >> Clinical Medicine

Recently studies in selected tumors suggested that BRAF mutation may associates with survival benefit from immune checkpoint inhibitor (ICI) therapy. To broadly investigate this association at a pan-cancer level, we analyzed two independent ICI treatment cohorts (MSKCC: n = 1630, and Dana-Farber: n = 249). BRAF-mutant patients exhibit better overall survival in the MSKCC cohort (Hazard ratio [HR] = 0.55, 95% confidence interval [CI]: 0.43-0.72; P <.001) and the result is validated by the Dana-Farber cohort (HR = 0.68, 95% CI: 0.46-0.99; P = .045). A multivariate analysis adjusting tumor mutational burden, mismatch repair status, cancer type, age and sex confirmed the results (adjusted HR = 0.58, 95% CI = 0.43-0.78; P < .001). Immunogenomic features analysis of TCGA dataset indicated that patients may respond to immunotherapy in various mechanisms. This finding substantially improve the therapeutic prospects for a sizeable fraction of patients who benefit from immunotherapy.

submitted time 2020-07-21 Hits4335Downloads340 Comment 0

3. chinaXiv:202003.00054 [pdf]


张文杰; 熊巧华; 陈思超; 朱家永; 张冉; 翁鸿; 曾宪涛
Subjects: Medicine, Pharmacy >> Clinical Medicine

[目的] 探究Rac GTP酶活性蛋白1(RACGAP1)基因在膀胱癌组织中的表达情况及临床意义。 [方法] 从NCBI的基因表达汇编(GEO)数据库下载膀胱癌组织RACGAP1的表达数据和临床病理参数。分析RACGAP1基因在膀胱癌组织与正常组织中的表达差异,结合随访信息使用SPSS软件对RACGAP1表达与临床病理特征进行卡方检验,采用Kaplan-Meier法进行生存分析,并利用基因富集分析(GSEA)法分析受RACGAP1调控的相关基因。 [结果] RACGAP1在正常膀胱组织中的表达水平为7.557±0.020,低于膀胱癌组织的7.790±0.028,差异有统计学意义(P<0.05)。膀胱癌组织中RACGAP1表达水平与年龄、侵袭性、T分期、N分期、疾病分级和复发有关(P<0.05)。RACGAP1低表达组和高表达组的5年总生存率分别为73.9%和56.6%(HR=0.47,95%CI:0.29-0.77,P<0.01),肿瘤5年特异生存率分别为91.6%和70.9%(HR=0.33,95%CI:0.17-0.67,P<0.01)。RACGAP1高表达样本富集了MYC信号通路、精子发生、未折叠蛋白反应、G2M检查点、E2F转录因子、MTORC1信号、有丝分裂纺锤体、PI3K/AKT/mTOR途径和DNA修复修复相关的基因集。 [结论] RACGAP1在膀胱癌组织中高表达,与膀胱癌患者的临床病理及预后显著相关,可作为反映膀胱癌患者预后的生物学标志物和潜在的膀胱癌防治靶点。

submitted time 2020-03-16 Hits10023Downloads969 Comment 0

4. chinaXiv:202003.00008 [pdf]

Germline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome-Wide Association Study in Multiple Cohorts

Yun-Miao Guo; Jie-Rong Chen; Yan-Chun Feng; Chua, Melvin L. K. ; Zeng, Yanni ; Edwin Pun Hui; Allen K. C. Chan; Lin-Quan Tang; Lin Wang; Qian Cui; Hui-Qiong Han; Chun-Ling Luo; Guo-Wang Lin; Yan Liang; Yang Liu; Zhong-Lian He; Yu-Xiang Liu; Pan-Pan Wei; Chu-Jun Liu; Wan Peng
Subjects: Medicine, Pharmacy >> Clinical Medicine

Germline polymorphisms have been linked with differential survival outcomes in cancers but have not been well studied in nasopharyngeal carcinoma (NPC). Here, two-phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China. Exome-wide genotypes at 246,173 single nucleotide polymorphisms (SNPs) are determined, followed by survival analysis for each SNP under Cox proportional hazards regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta-analysis of all samples (n = 5,553) confirm that the presence of rs1131636-T, located in the 3′-UTR of RPA1, confers an inferior overall survival (HR = 1.33, 95% CI = 1.20-1.47, P = 6.31 × 10-8). Bioinformatics and biological assays show that rs1131636 has regulatory effects on upstream RPA1. Functional studies further demonstrate that RPA1 promoted the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR-1253 has been identified as a suppressor for RPA1 expression, likely through regulation of its binding affinity to rs1131636 locus. Collectively, these findings provide a promising biomarker aiding in stratifying patients with poor survival, as well as a potential drug target for NPC.

submitted time 2020-03-06 Hits23299Downloads1336 Comment 0

5. chinaXiv:202003.00026 [pdf]

Effective Treatment of Severe COVID-19 Patients with Tocilizumab

Xu, Xiaoling; Han, Mingfeng; Li, Tiantian; Sun, Wei; Wang, Dongsheng; Fu, Binqing; Zhou, Yonggang; Zheng, Xiaohu; Yang, Yun; Li, Xiuyong; Zhang, Xiaohua; Pan, Aijun; Wei, Haiming
Subjects: Medicine, Pharmacy >> Clinical Medicine

Background: In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China, which spread rapidly and has become a world-wide public health challenge. We aimed to assess the efficacy of tocilizumab in severe patients with Corona Virus Disease-19 (COVID-19) and seek a new therapeutic strategy. Methods: The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People’s Hospital were given tocilizumab in addition to routine therapy between February 5 and February 14, 2020. The changes of clinical manifestations, CT scan image, and laboratory examinations were retrospectively analyzed. Findings: Within a few days, the fever returned to normal and all other symptoms improved remarkably. Fifteen of the 20 patients (75.0%) had lowered their oxygen intake and one patient need no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% patients (16/19). No obvious adverse reactions were observed. Nineteen patients (90.5%) have been discharged on average 13.5 days after the treatment with tocilizumab and the rest are recovering well. Interpretation: Tocilizumab is an effective treatment in severe patients of COVID-19, which provided a new therapeutic strategy for this fatal infectious disease.

submitted time 2020-03-05 Hits147722Downloads47333 Comment 0

6. chinaXiv:202002.00078 [pdf]

Confirmed asymptomatic carrier of SARS-CoV-2

Luo, Sihui; Liu, Wei; Liu, Zhenjun; Zheng, Xueying; Ling, Ping; Ding, Yu; Hong, Changxing; Liu, Zhirong; Liu, Jian; Weng, Jianping
Subjects: Medicine, Pharmacy >> Clinical Medicine

Here we reported a case of asymptomatic carrier of SARS-CoV-2 infection. A 50-year old woman, lived with her husband in Anqing(Anhui, China) with no significant past medical history, travel history to Wuhan or adjacent area, or exposure to wild animals. She took throat swab test for SARS-CoV-2 nucleic acid due to her husband’s close contact with patients who had SARS-CoV-2 infection. Her results were confirmed positive on February 6, 2020. But she did not report elevation of temperature measurement, nor respiratory or gastrointestinal symptoms and her chest CT scan showed no significant abnormalities. She was hospitalized on February 6 and treated with antiviral agents. During her hospitalization, apart from a mild elevation of liver enzymes after 10-day treatment of lopinavir/ritonavir, she was asymptomatic, with her blood cell count, live and renal function largely normal. Her subcutaneous oxygen saturation stayed above 97%. Chest CT scan was repeated on February 11 and 20, and both were negative for signs of viral pneumonia. Notably, a second set of throat swabs and anal swabs were sent to test for SARS-CoV-2 on February 19, and the results were still confirmed positive. This is a confirmed case of asymptomatic carrier of SARS-CoV-2 infection. Her persistent positive findings in both throat and anal swabs suggested the possibility of healthy carrier of the virus, which adds to the difficulty in preventing transmission of the disease.

submitted time 2020-02-28 Hits24725Downloads2720 Comment 0

7. chinaXiv:202002.00080 [pdf]

Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia

Zikuan Leng; Rongjia Zhu; Wei Hou; Yingmei Feng; Yanlei Yang; Qin Han; Guangliang Shan; Fanyan Meng; Dongshu Du; Shihua Wang; Junfen Fan; Wenjing Wang; Luchan Deng; Hongbo Shi; Hongjun Li; Zhongjie Hu; Fengchun Zhang; Jinming Gao; Hongjian Liu; Xiaoxia Li
Subjects: Medicine, Pharmacy >> Clinical Medicine

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China, Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improve the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China from Jan 23, 2020. to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients with COVID-19 pneumonia in 14 days without observed adverse effect. The pulmonary function and symptoms of all patients with COVID-19 pneumonia were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased and the overactivated cytokine-secreting immune cells CXCR3 CD4 T cells, CXCR3 CD8 T cells, and CXCR3 NK cells were disappeared in 3-6 days. And a group of CD14 CD11c CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level TNF-α is significantly decreased while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

submitted time 2020-02-28 Hits29496Downloads5953 Comment 0

8. chinaXiv:202002.00084 [pdf]

Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells

Bing Liang; Junhui Chen; Tao Li; Haiying Wu; Wenjie Yang; Yanjiao Li; Jianchun Li; Congtao Yu; Fangang Nie; Zhaoxia Ma; Mingxi Yang; Panrong Nie; Yanfeng Gao; Chuanyun Qian; Min Hu
Subjects: Medicine, Pharmacy >> Clinical Medicine

BackgroundThe COVID-19 cases increased very fast in the last two months. The mortality among critically ill patients, especially the elder ones, was relatively high. Considering that most of the dead patients were caused by severe inflammation response, it is very urgent to develop effective therapeutic agents and strategies for these patients. The human umbilical cord mesenchymal stem cells (hUCMSCs) have shown very good capability to modulate immune response and repair the injured tissue with good safety. Case PresentationHere, we reported the treatment process and clinical outcome of a 65-year-old female critically ill COVID-19 patient infected with 2019-nCoV (now called SARS-CoV-2). The significant clinical outcome and well tolerance was observed by the adoptive transfer of allogenic hUCMSCs.ConclusionsOur results suggested that the adoptive transfer therapy of hUCMSCs might be an ideal choice to be used or combined with other immune modulating agents to treat the critically ill COVID-19 patients.

submitted time 2020-02-27 Hits33055Downloads5938 Comment 0

9. chinaXiv:202002.00065 [pdf]

Potential of Arbidol for Post-exposure Prophylaxis of COVID-19 Transmission

Jinnong,Zhang; Wenjing,Wang; Bo,Peng; Wei,Peng; Yisheng,Zhang; Yaling,Wang; Yan,Wan; Jiang,Chang; Ling,Mao; Xiaoping,Miao; Yifan,Zhou; Yanan,Li; Yu,Hu; Bo,Hu
Subjects: Medicine, Pharmacy >> Clinical Medicine

Background: The efficient transmission of Severe Acute Respiratory Syndrome-2 Coronavirus (SARS-CoV-2) from patients to healthcare workers or family members has been a worrisome and prominent feature of the ongoing outbreak. On the basis of clinical practice and in-vitro studies, we postulated that post-exposure prophylaxis (PEP) using Arbidol is associated with decreased infection among individuals exposed to confirmed cases of COVID-19 infection. Methods: We conducted a retrospective case-control study on family members and health care workers who were exposed to patients confirmed to have SARS-CoV-2 infection by real-time RT-PCR and Chest CT from January 1 to January 16, 2020. We collected demographic information, work location of exposure, post-exposure prophylaxis information, and symptoms, if any, 24 days after exposure. The relation between post-exposure prophylaxis and infection in household contacts and healthcare workers were respectively analyzed. Results: 27 families and 124 health care workers had evidence of close exposure to patients with confirmed COVID-19. There were no differences in age, profession and sex distribution in the two groups with different post-exposure prophylaxis, table 1. Logistic regression based on the data of the family members and health care workers with Arbidol or Oseltamivir prophylaxis showed that Arbidol PEP was a strong protective factor against the development of COVID-19 (Odds ratio 0·011 , 95% CI 0·001-0·125, P=0·0003 for family members and Odds ratio 0·049, 95%CI 0·003-0·717), P= 0·0276 for health care workers). On the contrary, Oseltamivir was associated with an increase in COVID-19 infection (Odds ratio 20·446, 95% CI 1·407-297·143, P= 0·0271). Conclusions: Our findings suggest Arbidol could reduce the infection risk of the novel coronavirus in hospital and family settings. This treatment should be promoted for PEP use and should be the subject of further investigation.

submitted time 2020-02-26 Hits31457Downloads3439 Comment 0

10. chinaXiv:201912.00031 [pdf]


庄楠; 李文波; ?朱庆莉
Subjects: Medicine, Pharmacy >> Clinical Medicine

肠腔狭窄是一类常见的克罗恩病并发症 肠腔狭窄是一类常见的克罗恩病并发症 ,15 %的CD 患者在首诊十年内可 发展为肠腔狭窄。 CD并发肠腔狭窄 根据病理类型可分为炎症、纤维及混合 型, 炎症为主型的患者可通过 药物治疗缓解状,而纤维只能介入或者手术 治疗病变肠段。所以,影像学手全面评估狭窄的数目、部 位、 形态,并且区分肠壁炎症和纤维化程度对于临床决策十重要。 本文 将 综述 主要 影像学手段 包括 内镜、 CT、MRI 、经腹超声等 对肠腔狭窄的诊断敏感性 和特异性。近年来,多项影像学新技术在鉴别狭窄肠壁炎症及纤维化方面取得 了很大的进展, 有望在临床广泛应用进一步提高 CD并发肠腔狭窄 的诊疗

submitted time 2019-12-22 From cooperative journals:《协和医学杂志》 Hits1318Downloads623 Comment 0

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