[Methodology and application of process analytical technology (PAT) for traditional Chinese medicine manufacturing:a review].

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the characteristics and status quo of the technology, we summed up the methodology for the continuous application and improvement of PAT during the whole life-cycle of traditional Chinese medicine. The five key procedures(process understanding, process detection, process modeling, process control, and continuous improvement) were summarized, and the application was reviewed. Finally, we proposed suggestions for the technical and regulatory challenges in implementing PAT in traditional Chinese medicine industry. This paper aims to provide a reference for development and application of PAT in advanced manufacturing, intelligent manufacturing, and continuous manufacturing of traditional Chinese medicine industry.

Residue analysis and dietary risk assessment of tebuconazole in loquat and sugarcane after open-field application in China.

Tebuconazole is an effective but potentially carcinogenic fungicide. Tebuconazole residues in loquat and sugarcane were investigated, together with an analysis of their dietary risk. Solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry showed fortified recoveries of 87% to 98%, with standard deviations ≤ 6.4%. The tebuconazole residues were below 6.34 mg kg-1 for whole loquat and 0.80 mg kg-1 for sugarcane. Based on the final residue test, the chronic hazard index was 90.74% in whole loquat and sugarcane, while the acute hazard index ranged from 66.32% to 109.49% for loquat and 33.37% to 76.93% for sugarcane. The assessment of potential dietary risk showed that while loquats may represent an acute risk to human health, whereas sugarcane consumption was safe. A 21-day pre-harvest interval is proposed to comply with maximum residue limit regulations and the observed risks when using 430 g/L tebuconazole for treating sugarcane. These findings offer guidance for tebuconazole formulation and use.

Clinical profile of cutaneous adverse drug reactions: a retrospective study of 1883 hospitalized patients from 2007 to 2016 in Shanghai, China.

BACKGROUND: Cutaneous adverse drug reactions (CADRs) are drug-induced skin reactions with or without systemic involvement, ranging from mild maculopapular exanthema (MPE) to life-threatening severe CADRs (S-CADRs). Due to their unpredictability and severity, early recognition of suspected causative drugs is highly recommended. However, the profile of CADRs remains unknown in China. OBJECTIVES: To assess the clinical profile, predominant causative drugs, and cost associated with CADRs in Shanghai, China. MATERIALS AND METHODS: Clinical records of inpatients admitted with a diagnosis of CADRs to the dermatology ward of Huashan Hospital from January 2007 to December 2016 were retrospectively studied. RESULTS: A total of 1,883 patients (1,231 female and 652 male), admitted with a diagnosis of CADR, were investigated. S-CADRs made up 21.99% of all cases (n=414), and urticaria (27.19%) was the most frequent reaction. Of the patients, 53.43% suffered from multiple drug-induced drug eruptions and the rest (45.83%) from single drug-induced drug eruptions. Overall, antimicrobials (28.85%) was the main drug group involved, and for S-CADRs, this was antiepileptic drugs (36.15%). The total cost for CADRs was RMB23,718,788.83 ($3,588,319.04). Both age and sex were related to admission cost (p=0.005 and p=7.84E-8, respectively). Antimicrobials were the most common treatment causing CADRs. CONCLUSION: The management of CADRs requires considerable medical cost. CADRs are not only a health problem but also a significant financial burden for affected individuals.

Comprehensive assessment of T cell receptor ß repertoire in Stevens-Johnson syndrome/toxic epidermal necrolysis patients using high-throughput sequencing.

Stevens-Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse drug reactions characterized by widespread epidermal necrosis. Recent studies have indicated that SJS/TEN is a specific immune reaction regulated by T cells. Certain drug serves as foreign antigens that are presented by major histocompatibility complex (MHC) and recognized by T cell receptors (TCRs), inducing adaptive immune responses. However, few studies have performed detailed characterization of TCR repertoire in SJS/TEN, and it remains unclear whether the particular types of TCRs expanded clonally are drug-specific, which would provide a potential underlying mechanism of SJS/TEN. In this study, using high-throughput sequencing, we comprehensively assessed the diversity, composition and molecular characteristics of the TCRß repertoires in 17 SJS/TEN patients associated with three different causative drugs including methazolamide (MZ), carbamazepine (CBZ) and allopurinol (ALP). Systematic analysis of the TCRß sequences revealed that SJS/TEN patients had more highly expanded clones and less TCR repertoire diversity, and the TCR repertoire diversity of these patients showed certain associations with the clinical severity of disease. Similar predominant clonotypes, shared-usage TRBV/TRBJ subtypes and combinations thereof were observed among different subjects with the same causative agent. Our observations provide enhanced understanding of the role of T lymphocytes in the pathogenesis of SJS/TEN and enumerate potential therapeutic targets.

Clinical, Viral and Genetic Characteristics of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in Shanghai, China.

DRESS is one of the most severe drug reactions. The aim of this retrospective study was to summarize the clinical presentation, genetic predisposition and prognostic factors of DRESS. A total of 52 patients with DRESS, who were inpatients at a medical referral centre in Shanghai, China, from January 2011 to December 2016, were analysed retrospectively. All the patients had skin eruption, 83% had liver involvement, and ≤10% had other organ involvement. Mean cost of hospitalization was US$5,511±3,050. The 3 most common causative agents were allopurinol (18/52; 35%), salazosulphapyridine (11/52; 21%) and carbamazepine (5/52; 10%). HLA-B*5801 and HLA-B*1302 were associated with allopurinol-induced DRESS. HLA-B*1301 was related to salazosulphapyridine-induced DRESS. The mortality rate was 6% (3/52). Epstein-Barr virus DNA was found in 10 patients (19%) and indicated a poor prognosis. Human herpes virus 6 DNA was detected in 17 patients (33%) and was associated with autoimmune sequelae. Due to its high medical cost and sometimes poor prognosis, prevention of DRESS should be a high priority.

Assessment and improvement of Indian-origin rhesus macaque and Mauritian-origin cynomolgus macaque genome annotations using deep transcriptome sequencing data.

BACKGROUND: The genome annotations of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques, two of the most common non-human primate animal models, are limited. METHODS: We analyzed large-scale macaque RNA-based next-generation sequencing (RNAseq) data to identify un-annotated macaque transcripts. RESULTS: For both macaque species, we uncovered thousands of novel isoforms for annotated genes and thousands of un-annotated intergenic transcripts enriched with non-coding RNAs. We also identified thousands of transcript sequences which are partially or completely 'missing' from current macaque genome assemblies. We showed that many newly identified transcripts were differentially expressed during SIV infection of rhesus macaques or during Ebola virus infection of cynomolgus macaques. CONCLUSIONS: For two important macaque species, we uncovered thousands of novel isoforms and un-annotated intergenic transcripts including coding and non-coding RNAs, polyadenylated and non-polyadenylated transcripts. This resource will greatly improve future macaque studies, as demonstrated by their applications in infectious disease studies.