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Recently, adeno-associated virus(AAV)vectors have been a hotspot in gene therapy and have shown great potential for rare diseases therapy, due to their low pathogenicity, mild immunogenicity and high tissue specificity. The safety and efficacy of AAV vectors, which are essentially infectious viruses, require new bioanalytical techniques to assess. At present, the relevant industry guidelines have specified the needs for the assessment of biodistribution, shedding, and immunogenicity, but the requirements related to bioassay are limited. In this paper, we reviewed the bioanalytical techniques and pharmacokinetics/pharmacodynamics(PK/PD)research of AAV vectors and their challenges from four aspects: biodistribution, shedding, immunogenicity and PK/PD research, with the hope of providing some reference for the clinical development of AAV vectors gene therapy products.

Despite the rapid development of antitumor drugs, the limited drug response rate and adverse drug reactions have severely limited their clinical application. In recent years, the concept of 'pharmacomicrobiomics' has emerged, and more and more studies have shown thatmicrobiota plays an important role in the treatment of antitumor drugs. Herein, the interaction between microbiota and antitumor drugs is reviewed from the aspects of chemotherapeutics, molecular targeted drugs and immunotherapy drugs. The mechanism involves immune regulation, hormone regulation, metabolite regulation, drug biotransformation and transmembrane transport regulation. The microbiota regulation strategies that can improve the efficacy and reduce adverse reactions of antitumor drugs are reviewed, in order to provide reference for the individualized treatment of clinical antitumor drugs.

The thermal management problem of IGBT is becoming more and more prominent, and it is urgent to develop a new cooling technology with high efficiency, stability and flexibility. Based on the main problems and bottlenecks in the current IGBT module cooling, was conducted a detailed analysis and evaluation of the widely used IGBT cooling technologies, as well as spray cooling, jet impingement cooling technology and micro-channel cooling technology, which are the hot spots of the current research. It shows that compared with other cooling technologies, micro-channel cooling technology, especially microchannel flow boiling cooling technology, has the advantages of compact structure, strong heat transfer capacity, high heat transfer coefficient, less working fluid charge, and good temperature uniformity performance, which have great development prospects in the field of thermal management of electronic devices. Thus, in this paper, it was proposed that microchannel flow boiling cooling is an optimal solution to the thermal management of new electronic devices, which provides an important reference for the design and application of IGBT module heat sinks.

Objective To explore the situation and characteristics of clinical trials of 121 rare diseases in the Chinese First List of Rare Diseases over the past 10 years and to provide reference for promoting the researchand development of orphan drugs in China. Methods The 121 rare diseases covered in the Chinese First List of Rare Diseases and Guidelines for Diagnosis and Treatment of Rare Diseases published in 2019 were retrieved as keywords on the National Medical Products Administration Registration and Information Disclosure Platform for Drug Clinical Studies (chinadrugtrials.org.cn) from November 1st, 2012 (Platform registration open time) to November 28th, 2021. The status and characteristics of rare disease clinical trials were analyzed from the perspectives of the number of registrations, geographical distribution, research fields, research design, and sample size. Results A total of 235 clinical trials were collected, including 41 items of phase Ⅰ, 22 items of phase Ⅱ, 74 items of phase Ⅲ, 15 items of phase Ⅳ, 77 items of bioequivalence clinical trials, and 6 clinical trials. During the past 10 years, the number of rare diseases clinical trials in China showed an increasing trend, with an annual average growth rate of about 54%. A total of 16 kinds of rare diseases in the Chinese First List of Rare Diseases were involved in the early phase (phase Ⅰ and phase Ⅱ) clinical trials, mainly focusing on hemophilia, idiopathic pulmonary fibrosis, multiple sclerosis, and neuromyelitis optica. The researchers of rare disease clinical trials were mainly in big cities such as Beijing, Tianjin, and Shanghai. Phase Ⅰ clinical trials of rare diseases listed in the Chinese First List of Rare Diseases in China were mainly single-center(61%, 25/41) parallel controlled studies (46%, 19/41), Phase Ⅱ clinical trials were mainly multi-center parallel controlled studies (65%, 13/22), and phase Ⅲ clinical trials were mainly multi-center (99%, 73/74) single-arm trials (64%, 47/74). The sample size in clinical trials increased with the study stage. Phase Ⅰ clinical trials were mainly restricted to 11~50 cases (83%, 34/41), 59% (13/22) of phase Ⅱ clinical trials were more than 50 cases, and 53%(39/74) of phase Ⅲ clinical trials involved 51~500 cases. Conclusions The research and development of orphan drugs in China is still at an early stage, covering few rare diseases in the Chinese First List of Rare Diseases, but it has shown a rapidly growing trend in recent years. At present, the development of rare disease drugs is still based on traditional clinical trial design. It is therefore necessary to explore more new clinical research strategies according to the disease and drug mechanism to promote the development of rare disease drugs.

The use of immune checkpoint inhibitors(ICIs) in advanced non-small cell lung cancer(NSCLC) significantly improves survival, but it has clinical problems such as low response rate. Treatment of tumor with ICIs is a dynamic change that involves the process of tumor-immune system interaction. Vertical monitoring of dynamic changes of biomarkers is helpful to eliminate individual differences and to provide information on spatiotemporal heterogeneity of tumors. This paper reviews the biomarkers of advanced NSCLC, covering the aspects of treatment with ICIs from tumor cell origin, immune microenvironmental source and joint indicators.

This study explored family function as a key factor of loneliness, hope, and emotion related to secondary vocational school students during the novel coronavirus pandemic. Chinese versions of the Olson Family Function Scale, Russell Loneliness Scale, Snyder Hope Scale, and Gross Emotion Regulation Scale were completed by 5,138 participants. Guardian type significantly predicted family function and loneliness. Family function significantly and positively correlated with loneliness. The relationship between family function and loneliness was mediated by hope, and expressive suppression concurrently moderated the relationship between hope and loneliness. Our study offers meaningful insights into the family function of Chinese secondary vocational school students. The findings supported a moderated mediation model that exemplifies the relationship between family function, loneliness, expressive suppression, and hope. Although the results showed that high hope mediated lower family functioning and loneliness, low expressive suppression led to intense loneliness immediately. This study confirms that emotional strategy is important and associated with mental health. It also suggests that schools should pay more attention to students' emotion regulation and help them rebuild hope or appropriate cognition to relieve loneliness during crisis events.

Abstract Aichi virus is a positive-sense and single-stranded RNA virus, which demonstrated to be related to diarrhea of Children. In the present study, phylogenetic and recombination analysis based on the Aichi virus complete genomes available in GenBank reveal a mosaic genome sequence [GenBank: FJ890523], of which the nt 261-852 region (the nt position was based on the aligned sequence file) shows close relationship with AB010145/Japan with 97.9% sequence identity, while the other genomic regions show close relationship with AY747174/German with 90.1% sequence identity. Our results will provide valuable hints for future research on Aichi virus diversity. Aichi virus is a member of the Kobuvirus genus of the Picornaviridae family 12 and belongs to a positive-sense and single-stranded RNA virus. Its presence in fecal specimens of children suffering from diarrhea has been demonstrated in several Asian countries 3456, in Brazil and German 7, in France 8 and in Tunisia 9. Some reports showed the high level of seroprevalence in adults 710, suggesting the widespread exposure to Aichi virus during childhood. The genome of Aichi virus contains 8,280 nucleotides and a poly(A) tail. The single large open reading frame (nt 713-8014 according to the strain AB010145) encodes a polyprotein of 2,432 amino acids that is cleaved into the typical picornavirus structural proteins VP0, VP3, VP1, and nonstructural proteins 2A, 2B, 2C, 3A, 3B, 3C and 3D 211. Based on the phylogenetic analysis of 519-bp sequences at the 3C-3D (3CD) junction, Aichi viruses can be divided into two genotypes A and B with approximately 90% sequence homology 12. Although only six complete genomes of Aichi virus were deposited in GenBank at present, mosaic genomes can be found in strains from different countries.