Increased Incidence of Severe Adverse Events in Non-Small Cell Lung Cancer Patients with Previous Tuberculosis Episode Treated with PD-1 Inhibitors

Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if past pulmonary tuberculosis(TB)affects ICIs’effectiveness and safety in lung cancer treatment.We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022.

Lactobacillus plantarum A3 attenuates ulcerative colitis by modulating gut microbiota and metabolism

Antibiotics are widely used to treat various diseases.However,growing evidence indicates that antibiotic therapy in human life increases the incidence of inflammatory bowel disease(IBD).Therefore,we need appropriate methods to reduce the incidence or symptoms of IBD.In this study,we used lincomycin hydrochloride to construct a gut micro-bial dysbiosis model in mice,and then,constructed an ulcerative colitis(UC)model.Meanwhile,we used Lactobacillus plantarum A3 from equine to treat UC in mice with gut microbial dysbiosis.The results showed that lincomycin hydro-chloride had little effect on the small gut microbiota in mice,but had a more destructive effect on the large intestin.Lactobaillus plantarum A3 alleviated the symptoms of UC in mice,which was reflected in its significantly reduced spleen index and disease activity index(DAl)(p<0.05),inhibited the shortening of colon and alleviated the invasion of inflammatory cells in the colon.Moreover,we found that it played a mitigatory role by inhibiting oxidative stress and regulating inflammatory cytokines in mice.At the same time,it restored the diversity and composition of the colonic microbiota and significantly increased the abundance of beneficial bacteria such as Blautia and Akkermansia(p<0.05);Notably,it significantly increased the concentrations of arachidonoyl ethanolamide phosphate(AEA-P)and cortisone(p<0.05)which have analgesic and anti-inflammatory effects.In conclusion,our study found that Lactobacillus plan-tarum A3 has the potential to regulate UC in mice with gut microbial dysbiosis.

数字资本对阅读素养影响的机理阐释:认识、路径与模式

数字阅读影响到数字时代国民阅读素养、国家知识文化力量的提升。文章基于国际学生评估项目2018年调查数据,通过结构方程模型研究数字资本、数字阅读对17个国家参与调查的中学生阅读素养的影响及传导路径,发现数字资本、数字阅读频率对阅读素养有显著的影响;数字阅读频率在数字资本与阅读素养之间起着十分重要的中介作用,但会因国家而改变,存在以韩国为代表的数字阅读完全中介—理智型、以斯洛文尼亚为代表的数字阅读部分削弱—理智型、以法国为代表的数字访问主因—理智型、以新加坡为代表的数字阅读强化—效能型、以爱尔兰为代表的数字阅读部分削弱—效能型、以芬兰为代表的数字能力主因—效能型6种模式。数字资本对阅读素养具有直接增益作用,数字阅读在数字资本对阅读素养的影响过程中具有中介效应,国家的经济社会文化背景对影响机制具有调节作用。

Evaluation of Reverse Transcription Loop-Mediated Isothermal Amplification assays for Rapid Detection of Human Enterovirus 71 and Coxsackievirus A16 in Clinical Samples

A sensitive reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for human enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) infection was further evaluated. The one step reaction was performed in a single tube at 65?C for 45 min for EV71 and 35 min for CVA16. The detection limits of RT-LAMP assays for both EV71 and CVA16 were 0.1 of a 50% tissue culture infective dose (TCID50) per reaction, based on 10—Fold dilutions of a titrated EV71 or CVA16 strain. The specific assay showed there were no cross-reactions with Coxsackievirus A (CVA) viruses (CVA 2, 4, 5, 7, 9, 10, 14, and 25), Coxsackievirus B (CVB) viruses (CVB 1, 2, 3, 4, and 5) or ECHO viruses (ECHO 3, 6, 11, and 19). In parallel with commercial quantitative real-time polymerase chain reaction (qRT-PCR) diagnostic kits for EV71 and CVA16, the RT-LAMP assay was evaluated with 515 clinical specimens, the results showed the RT-LAMP assay and the qRT-PCR assay were in complete agreement for 513/515 (99.6%) of the specimens. Two samples with discrepant results from two methods were further verified by nested reverse transcription polymerase chain reaction (nRT-PCR) assay and sequencing to be true positives for CVA16. In conclusion, RT-LAMP assay is demonstrated to be a sensitive and specific assay and have a great potential for the rapid and visual screening of EV71 and CVA16 in China, especially in those resource-limited hospitals and rural clinics of provincial and municipal regions.

Study on Cisplatin Aggravating DNA Damage and Causing a High Apoptosis Rate on Breast Cancer MCF-7 Cells

[Objectives] To investigate the mechanism of DNA damage of cisplatin( DDP),a broad spectrum anticancer drug on breast cancer MCF-7 cells,and to study the mechanism of apoptosis induced by DDP.[Methods]MCF-7 cells were treated by DDP( 0 mg/L,2 mg/L,4 mg/L,6 mg/L,6 mg/L,and 10 mg/L) for 48 hours. MTT assay was used to detect the inhibitory effect of DDP on MCF-7 cells and IC50 value was calculated. Western blot was adopted to detect the expression of γ-H2 AX,which was the marker of DNA double stranded breaks( DSBs) and ATM( sensory molecules of DSBs),the apoptotic signal transduction molecule cleaved caspase-3,and the proteins associated with apoptosis calpain.[Results]DDP inhibited MCF-7 cell activity in a concentration-dependent manner and IC50 was 7. 57 mg/L. In contrast to the control group( without DDP treatment),MCF-7 cells with DDP treatment expressed more γ-H2 AX,ATM,cleaved caspase-3 and calpain.[Conclusions] DDP could inhibit the activity of breast cancer MCF-7 cells. Its mechanisms may be associated with inhibition of MCF-7 cell apoptosis,induction of DNA double strand breaking and the expression of pro-apoptotic protein up-regulation.

Safety and immunogenicity of a mosaic vaccine booster against Omicron and other SARS-CoV-2 variants:a randomized phase 2 trial

An ongoing randomized,double-blind,controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate,named NVSI-06-09,as a booster dose in subjects aged 18 years and older from the United Arab Emirates(UAE),who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment.The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV.The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant,and the exploratory outcome was cross-immunogenicity against other circulating strains.Between May 25 and 30,2022,516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group.Interim results showed a similar safety profile between two booster groups,with low incidence of adverse reactions of grade 1 or 2.For immunogenicity,by day 14 post-booster,the fold rises in neutralizing antibody geometric mean titers(GMTs)from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain(19.67 vs 4.47-fold),Omicron BA.1.1(42.35 vs 3.78-fold),BA.2(25.09 vs 2.91-fold),BA.4(22.42 vs 2.69-fold),and BA.5 variants(27.06 vs 4.73-fold).Similarly,the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV.Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants,including Omicron and its sub-lineages.

Cold-chain transportation in the frozen food industry may have caused a recurrence of COVID-19 cases in destination:Successful isolation of SARS-CoV-2 virus from the imported frozen cod package surface

Coronavirus disease 2019(COVID-19)pandemic has spread in 220 countries/regions towreak havoc to human beings around theworld.At present,the second wave of COVID-19 has begun in many European countries.The complete control of COVID-19 is very urgent.Although China quickly brought the virus under control,there have been eight sporadic outbreaks in China since then.Both in Xinfadi of Beijing and Dalian outbreak of COVID-19,environmental swab samples related to imported cold chain food were tested nucleic acid positive for SARS-CoV-2.In this outbreak in Qingdao,we directly isolated SARS-CoV-2 from the cod outer package's surface swab samples.This is the first time worldwide,SARS-CoV-2 were isolated from the imported frozen cod outer package's surface,which showed that imported frozen food industry could import SARS-CoV-2 virus.

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV:a phase 2 trial

The increased coronavirus disease 2019(COVID-19)breakthrough cases pose the need of booster vaccination.We conducted a randomised,double-blinded,controlled,phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine(BBIBP-CorV)followed by a recombinant protein-based vaccine(NVSI-06-07),using homologous boost with BBIBP-CorV as control.Three groups of healthy adults(600 individuals per group)who had completed two-dose BBIBP-CorV vaccinations 1–3 months,4–6 months and≥6 months earlier,respectively,were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost.Immunogenicity assays showed that in NVSI-06-07 groups,neutralizing antibody geometric mean titers(GMTs)against the prototype SARS-CoV-2 increased by 21.01–63.85 folds on day 28 after vaccination,whereas only 4.20–16.78 folds of increases were observed in control groups.For Omicron variant,the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14,however,a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster.Similar results were obtained for other SARS-CoV-2 variants of concerns(VOCs),including Alpha,Beta and Delta.Both heterologous and homologous boosters have a good safety profile.Local and systemic adverse reactions were absent,mild or moderate in most participants,and the overall safety was quite similar between two booster schemes.Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs,including Omicron.