Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Objective:To evaluate the prognostic value of Epstein-Barr virus (EBV)-DNA level in plasma and whole blood in treatment of children with EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH).Methods:Clinical data of 66 children with EBV-HLH, who were admitted to the Hematology and Oncology Center of Beijing Children′s Hospital, Capital Medical University from January 2016 to December 2017 were retrospectively reviewed and analyzed.The data included the dynamic changes of the EBV-DNA level in plasma (P-EBV-DNA) and whole blood (W-EBV-DNA) at the time of admission, 2 and 4 weeks after treatment.P-EBV-DNA was divided into the positive group and the negative group according to the copy number of EBV-DNA, and W-EBV-DNA was divided into the high and the low level group by the receiver operating characteristic curve(ROC); the incidence of poor prognosis was compared between different groups by Chi- Square test; the event-free survival (EFS)was evaluated by the Log- Rank test to identify its prognostic significance. Results:The analysis showed that both P-EBV-DNA and W-EBV-DNA at admission could not be associated with a poor outcome; P-EBV-DNA (≥500 copies/mL) or W-EBV-DNA [>(5.04-5.09)×10 5 copies/mL]after 2 and 4 weeks of treatment could be a good marker of a poor outcome and progression-free survival ( P<0.001). Besides, central nervous system (CNS) involvement ( P=0.025), sever leukopenia(WBC≤3×10 9/L, P=0.031), neutropenia (ANC ≤0.5×10 9/L, P=0.041), albumin reduction (≤26 g/L, P=0.012) and hemoglobin decrease (≤90 g/L, P=0.023) at diagnosis are also associa-ted with worse outcomes.In multivariate analysis, only P-EBV-DNA at 4 th week and CNS involvement were indepen-dent prognostic factors ( HR=7.139, P=0.032 and HR=6.455, P=0.042, respectively). The prognostic value of W-EBV-DNA at different time points and P-EBV-DNA after 2 weeks of treatment had a lower prognostic value. Conclusions:The P-EBV-DNA level after 4 weeks of treatment is a promising risk indicator for early diagnosis of disease and early recognition of poor prognosis in EBV-HLH children, so it provides the guidance for optimal treatment.

Objective To evaluate the effectiveness and safety of gefitinib retreatment beyond progression(GRBP)in non-small cell lung cancer(NSCLC)patients with rare EGFR mutations.Methods We retrospectively analyzed six rare-EGFR-mutation NSCLC patients from Jan 2011 to Dec 2015.Those patients had previous disease control and then disease progression according to Response Evaluation Criteria in Solid Tumors version 1.1(RECIST v1.1)after taking oral gefitinib 250 mg once a day.After that,continuing gefitinib was decided by clinicians′ experience at the same treatment option.The primary endpoints were response rate(RR),overall survival(OS),the first and second progression-free survival(PFS-1 and PFS-2).Safety was assessed according to the NCI-CTCAE version 4.0.Results After initial treatment of gefitinib,4 patients achieved partial response(PR)and 2 patients showed stable disease(SD),with RR being 66.7％.The median PFS-1 and PFS-2 were 10 months(95％CI 6.6-13.4)and 9 months(95％CI 6.9-11.1),respectively.The median OS time was 28 months(95％CI 10.4-45.6).The most common treatment-related adverse events were fatigue,diarrhea,rash,itching and elevated transaminases.Conclusion In our study,gefitinib retreatment beyond disease progression is effective with a manageable tolerability profile.

Proteomics has been widely used in the last few years to look for new biomarkers and decipher the mechanism of HIV-host interaction.Herein,we review the recent developments of HIV/AIDS proteomic research,including the samples used in HIV/AIDS related research,the technologies used for proteomic study,the diagnosis biomarkers of HIV-associated disease especially HIV-associated neurocognitive impairment,the mechanisms of HIV-host interaction,HIV-associated dementia,substance abuse,and so on.In the end of this review,we also give some prospects about the limitation and future improvement of HIV/AIDS proteomic research.

Influenza A virus (HINI) 2009, a new swine-origin influenza A virus, has been spread worldwidely and causedgreat public fear. High-throughput transcriptomics and proteomies methods are now being used to identify H1N1and H1N1-host interaction. This article reviews recent transcriptomics and proteomics research in H1N1 diagnosis,treatment, and H1N1 virus-host interaction, to offer some help for further understanding the infection mechanismand controlling H1N1 transmission.

Objective To investigate the protective effect and its mechanism of prescription Zu Zhong 1 Hao (a traditional Chinese medical prescription, including Astragalus membranaceus, Atractylodes macrocephala, Arisaema cure Bile, Rhizoma pinelliae, the seed of Prunus persiea , Angelica sinensis , Ligusticum Chuanxiong, Paeonia lactiflora , and Pueraria ,etc) pretreatment on focal cerebral ischemia-reperfusion in rats. Methods Sixty SD rats were randomly divided into sham-operation, ischemia-reperfusion, flunarizine and prescription Zu Zhong 1 Hao low-, medium-and high-dose groups (n=10 in each group). A rat model of focal cerebral ischemia-reperfusion was induced by suture method (ischemia for 3 hours followed by reperfusion for 24 hours). Nitric oxide (NO) was measured by the nitrate reductase method; superoxide dismutase (SOD) activity was assessed by the xanthine oxidase method; maiondialde-hyde (MDA) was determined by the thiobarbiturie acid method; and tumor necrosis factor-a(TNF-α) was detected by the enzyme-linked immunosorbent assay (ELISA) method. Results Prescription Zu Zhong 1 Hao significantly improved neurological deficits in focal cerebral ischemia-reperfusion in rats, reduced the content of NO and MDA in brain tissue, increased SOD activity, and down-regulated the expression of TNF-α. Among them, the role of the high-dose group was more significant (P<0. 01). There were also significant differences between the low-and medium-dose groups and the ischemia-reperfusion group (P<0. 05). Conclusions The pretreatment of prescription Zu Zhong 1 Hao has the protective effect on focal cerebral ischemia-reperfusion injury, and its mechanism may be associated with the decreased content of NO and MDA in brain tissue, increased SOD activity, and down-regulated TNF-α expression.