OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).
Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19/epidemiology* ; COVID-19 Drug Treatment ; Aged ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/adverse effects* ; SARS-CoV-2 ; Treatment Outcome ; China/epidemiology* ; Adult

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts are still under-represented in genome-wide genetic studies. Here, we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combined with single-cell sequencing data from the developing human brain, we found that the expression of genes with de novo mutations was specifically enriched in the pre-, post-central gyrus (PRC, PC) and banks of the superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and healthy controls, we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls, suggesting the potential structural deficits associated with ASD. Finally, we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas, the insula, as well as the frontal lobes in ASD patients. This work indicated that combinatorial analysis with genome-wide screening, single-cell sequencing, and brain imaging data reveal the brain regions contributing to the etiology of ASD.
Humans ; Autism Spectrum Disorder/metabolism* ; Autistic Disorder ; Exome Sequencing ; DNA Copy Number Variations ; East Asian People ; Brain/metabolism* ; Mutation/genetics* ; Genetic Predisposition to Disease/genetics*

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.
Humans ; COVID-19 ; Algorithms ; Databases, Factual ; Prescriptions ; Plant Extracts

Genetic composition plays critical roles in the pathogenesis of autism spectrum disorder (ASD). Especially, inherited and de novo intronic variants are often seen in patients with ASD. However, the biological significance of intronic variants is difficult to address. Here, among a Chinese ASD cohort, we identified a recurrent inherited intronic variant in the CHD7 gene, which is specifically enriched in East Asian populations. CHD7 has been implicated in numerous developmental disorders including CHARGE syndrome and ASD. To investigate whether the ASD-associated CHD7 intronic variant affects neural development, we established human embryonic stem cells carrying this variant using CRISPR/Cas9 methods and found that the level of CHD7 mRNA significantly decreased compared to control. Upon differentiation towards the forebrain neuronal lineage, we found that neural cells carrying the CHD7 intronic variant exhibited developmental delay and maturity defects. Importantly, we found that TBR1, a gene also implicated in ASD, was significantly increased in neurons carrying the CHD7 intronic variant, suggesting the intrinsic relevance among ASD genes. Furthermore, the morphological defects found in neurons carrying CHD7 intronic mutations were rescued by knocking down TBR1, indicating that TBR1 may be responsible for the defects in CHD7-related disorders. Finally, the CHD7 intronic variant generated three abnormal forms of transcripts through alternative splicing, which all exhibited loss-of-function in functional assays. Our study provides crucial evidence supporting the notion that the intronic variant of CHD7 is potentially an autism susceptibility site, shedding new light on identifying the functions of intronic variants in genetic studies of autism.

OBJECTIVE: To observe the effect of acupoint application of gel plaster on quality of sleep and life in patients with insomnia. METHODS: A total of 63 patients with insomnia were randomized into a gel plaster group (32 cases, 1 case dropped off) and a placebo plaster group (31 cases). Acupoint application of gel plaster was applied at Yintang (GV 29) and Yongquan (KI 1) in the gel plaster group, placebo plaster was applied at the same acupoints in the placebo plaster group. The treatment was given from bedtime to early moming of the next day, 5 days were as one course, with 2-day interval, totally 4 courses were required in the both groups. Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS) and Flinders fatigue scale were used to evaluate the sleep quality and fatigue level of the patients in the both groups before and after treatment and at 2 weeks of follow-up. The variations of insomnia TCM syndrome score and the 36-item short-form health survey (SF-36) score before and after treatment were observed. RESULTS: Compared before treatment, the scores of PSQI, ESS and FFS after treatment and at follow-up were decreased in the both groups ( CONCLUSION Acupoint application of gel plaster can effectively improve the quality of sleep and life in patients with insomnia.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Sleep ; Sleep Initiation and Maintenance Disorders/therapy* ; Treatment Outcome

BACKGROUND: Resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for the study of brain function. Typically, rs-fMRI is performed on anesthetized animals. Although different functional connectivity (FC) in various anesthetics on whole brain have been studied, few studies have focused on different FC in the aged brain. Here, we measured FC under three commonly used anesthesia methods and analyzed data to determine if the FC in whole brain analysis were similar among groups. METHODS: Twenty-four male aged Wistar rats were randomly divided into three groups (n = 8 in each group). Anesthesia was performed under either isoflurane (ISO), combined ISO + dexmedetomidine (DEX) or α-chloralose (AC) according to the groups. Data of rs-fMRI was analyzed by FC in a voxel-wise way. Differences in the FC maps between the groups were analyzed by one-way analysis of variance and post hoc two-sample t tests. RESULTS: Compared with ISO + DEX anesthesia, ISO anesthesia caused increased FC in posterior brain and decreased FC in the middle brain of the aged rat. AC anesthesia caused global suppression as no increase in FC was observed. CONCLUSION ISO could be used as a substitute for ISO + DEX in rat default mode network studies if the left temporal association cortex is not considered important.
Anesthesia ; Animals ; Brain/diagnostic imaging* ; Brain Mapping ; Isoflurane ; Magnetic Resonance Imaging ; Male ; Rats ; Rats, Wistar

BACKGROUND: Acinetobacter baumannii (A. baumannii) has become one of the most important opportunistic pathogens inducing nosocomial pneumonia and increasing mortality in critically ill patients recently. The interaction between A. baumannii infection and immune response can influence the prognosis of A. baumannii related pneumonia. The target of the present study was to investigate the role of immunodeficiency in A. baumannii induced pneumonia. METHODS: Male BALB/c mice were randomly divided into the normal immunity control (NIC) group, normal immunity infection (NIA) group, immune compromised control (CIC) group, and immune compromised infection (CIA) group (n = 15 for each group). Intraperitoneal injection of cyclophosphamide and intranasal instillation of A. baumannii solution were used to induce compromised immunity and murine pneumonia, respectively. The mice were sacrificed at 6 and 24 h later and the specimens were collected for further tests. Seven-day mortality of mice was also assessed. RESULTS: After A. baumannii stimulation, the recruitment of neutrophils in mice with normal immunity increased sharply (P = 0.030 at 6 h), while there was no significant raise of neutrophil counts in mice with compromised immune condition (P = 0.092 at 6 h, P = 0.772 at 24 h). The Th cell polarization presented with pulmonary interleukin (IL)-4 and interferon (IFN)-γ level in response to the A. baumannii in CIA group were significantly depressed in comparison with in NIA group (IFN-γ: P = 0.003 at 6 h; P = 0.001 at 24 h; IL-4: P < 0.001 at 6 h; P < 0.001 at 24 h). The pulmonary conventional dendritic cell accumulation was even found to be inhibited after A. baumannii infection in immunocompromised mice (P = 0.033). Correspondingly, A. baumannii associated pneumonia in mice with compromised immunity caused more early stage death, more severe histopathological impairment in lung. CONCLUSION A. baumannii could frustrate the immune response in immunocompromised conditions, and this reduced immune response is related to more severe lung injury and worse outcome in A. baumannii induced pneumonia.

OBJECTIVE: To investigate whether there is necessity for carrying out pharmaceutical care for advanced maternal aged multiparous women as the number of this special population in our country growing greatly under the "universal two-child" policy. METHODS: We compared the pregnancy outcomes of the advanced maternal aged multipara with advanced maternal aged primipara and right aged multipara to investigate the characteristics of advanced maternal aged pregnancy outcomes. Through analyzing the importance and urgency of pharmaceutical care for advanced maternal aged multipara, we explored current status and challenges, and analyzed pregnancy drug risk category and pregnancy drug registry. RESULTS: Compared with advanced maternal aged primipara and right aged multipara, pregnancy outcomes and exposure risk are different in advanced maternal aged multipara. Pregnancy drug risk category and pregnancy drug registry are crucial measures in observing study of pharmaceutical care. CONCLUSION: It is necessary to carry out pharmaceutical care for advanced maternal aged multipara. Pregnancy drug risk category and pregnancy drug registry can provide basis for designing interventional study of pharmaceutical care.

OBJECTIVE: To analyze 13 judicial precedents involving off-label drug use and explore the legal interpretation on off-label drug use in China in order to provide experience for establishment of off-label drug use and clinical application. METHODS: Based on the law databases (China Judgements Online, Chinalawinfo, Jufaanli, Itslaw), 13 cases were searched and screened involving legal off-label drug use. The relationship was investigated and discussed between different results and characteristics of the 13 cases. RESULTS: In 13 cases, there are 2 cases probably reasonable for off-label use, 2 cases unreasonable but not correlated with patients′ outcomes, 9 unreasonable and with a causal relationship with patients′ outcomes. In the 9 unreasonable cases, there are 4 cases without sufficient evidence, 3 cases without informed consent, 1 case lack of monitoring after off-label use, 1 case with idiosyncratic reaction, and 1 case not consistent with the label of the drug used. CONCLUSION: Major deficiencies of off-label drug use in China are without sufficient evidence, lack of informed consent and with uncompleted system on off-label drug use. Establishing more completed and detailed system, investigating enough clinical evidence, better informed consent and monitoring after off-label use are important measurements to ensure safety on off-label drug use.

OBJECTIVE: The aim of this study is to investigate labelings on dermatologic drugs for pregnant women and provide qualitative and quantitative pharmaceutical support for clinical use. METHODS: Labelings and formularies on pregnancy of topical drugs were analyzed and sorted according to classification on pregnancy use. Transdermal abilities of the drugs not forbidden nor avoided were evaluated through ACD/LAB 6.0 software and Potts-Guy formulation. Through TOXNET database and dose conversion equation, toxicities on animals were collected and human doses for pregnant women were calculated. RESULTS: In dermatologic drugs, there are 16 drugs forbidden, 8 not recommended/avoided/should not be used, 14 used with caution/weighed pros and cons, 7 used under instruction, 16 unclear or with no statement. In topical drugs not forbidden nor avoided, there are 9 drugs' logKp above-5, butenafine and sertaconazole with strongest transdermal abilities, 7 drugs' logKp influenced under pH5.5 or pH7.0, with a decline in logK'p compared with logKp, still 15 drugs not influenced by pH, 7 drugs' toxicities on animals unknown, 14 drugs' pregnancy human doses under 10 mgkg-1. CONCLUSION: Currently,only a few topical drugs' instructions on pregnancy are clear. With properties and animal experiments, better pharmaceutical support can be provided for clinical use on qualitative or quantitative reference.