Over the past two decades, genome-wide association study(GWAS) has identified numerous genetic variants and loci associated with heritable diseases. With the gradual maturation and saturation of GWAS methodologies, transcriptome-wide association study(TWAS) offers a novel perspective by linkinggenetic phenotypes to gene expression levels. By integrating TWAS with other multi-omics analyses, researchers can gain a deeper understanding of heritable diseases. This article provides an overview of recent groundbreaking and representative TWAS methods and tools, analyzes their strengths and limitations, and discusses future trends in TWAS development.

To explore the variation laws of volatile oil during the extraction process of Artemisiae Argyi Folium and its impact on the quality of the medicinal solution, as well as to achieve precise control of the extraction process, this study employed headspace solid phase microextraction gas chromatography-mass spectrometry(HS-SPME-GC-MS) in combination with multiple light scattering techniques to conduct a comprehensive analysis, identification, and characterization of the changes in volatile components and the physical properties of the medicinal solution during the extraction process. A total of 82 volatile compounds were identified using the HS-SPME-GC-MS technique, including 21 alcohols, 15 alkenes, 14 ketones, 9 acids, 6 aldehydes, 5 phenols, 3 esters, and 9 other types of compounds. At different extraction time points(15, 30, 45, and 60 min), 71, 72, 64, and 44 compounds were identified in the medicinal solution, respectively. It was observed that the content of volatile components gradually decreased with the extension of extraction time. Through multivariate statistical analysis, four compounds with significant differences during different extraction time intervals were identified, namely 1,8-cineole, terpinen-4-ol, 3-octanone, and camphor. RESULTS:: from multiple light scattering techniques indicated that at 15 minutes of extraction, the transmittance of the medicinal solution was the lowest(25%), the particle size was the largest(0.325-0.350 nm), and the stability index(turbiscan stability index, TSI) was the highest(0-2.5). With the extension of extraction time, the light transmittance of the medicinal solution improved, stability was enhanced, and the particle size decreased. These laws of physicochemical property changes provide important basis for the control of Artemisiae Argyi Folium extraction process. In addition, the changes in the bioactivity of Artemisiae Argyi Folium extracts during the extraction process were investigated through mouse writhing tests and antimicrobial assays. The results indicated that the analgesic and antimicrobial effects of the medicinal solution were strongest at the 15-minute extracting point. In summary, the findings of this study demonstrate that the content of volatile oil in Artemisiae Argyi Folium extracts gradually decreases with the extension of extraction time, and the variation in volatile oil content directly influences the physicochemical properties and pharmacological efficacy of the medicinal solution. This discovery provides important scientific reference for the optimization of Artemisiae Argyi Folium extraction processes and the development and application of process analytical technologies.
Oils, Volatile/pharmacology* ; Artemisia/chemistry* ; Gas Chromatography-Mass Spectrometry ; Drugs, Chinese Herbal/pharmacology* ; Chlorogenic Acid/pharmacology* ; Solid Phase Microextraction ; Quality Control

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

The Ehlers-Danlos syndromes(EDS)are a group of rare hereditary connective tissue disorders characterized by joint hypermobility,skin hyperextensibility,and tissue fragility.The clinical and genetic hetero-geneity of EDS frequently leads to underdiagnosis and misdiagnosis.Genetic testing is an essential approach to clarify the underlying diagnosis.Recent research has preliminarily established genotype-phenotype correlations and introduced the novel concept of"disease spectrum"in some subtypes.These studies deepen our under-standing of EDS etiology and provide important insights into clinical management.Published in 2023,the Chinese Guidelines for Diagnosis and Treatment of the Ehlers-Danlos Syndromes(the Guidelines)recommend performing genetic testing with deep phenotyping for patients who meet the clinical diagnostic criteria or are sus-pected of having EDS.However,it should be noted that the clinical diagnosis might differ from the molecular diagnosis.Furthermore,cutting-edge approaches such as periodic data reanalysis,integration of RNA sequen-cing into family-based whole-genome sequencing,and third-generation sequencing may facilitate the reclassifi-cation of variants of uncertain significance or resolve undiagnosed cases.This article summarizes recent progress in the genetics research of EDS,with the hope of offering a valuable resource for clinical diagnosis,treatment and scientific research to optimize the quality of life of patients with EDS.

Although indigenous malaria has been eliminated in Wuhan since 2013,imported malaria remains a potential threat as an infectious source of local malaria transmission.The epidemiological and clinical characteristics of imported malaria are particularly important in areas where local malaria has been eliminated.This study was aimed at analyzing the epidemiological and clinical characteristics of imported malaria in Wuhan from 2012 to 2019,to provide a basis for further improving the preven-tion and control of imported malaria.Patients in Wuhan diagnosed with imported malaria from January 1,2012,to December 31,2019,were included in this study.A case-control study was con-ducted to analyze the features of patients with severe malaria.Uni-variate and multivariate logistic regression was used to identify risk factors for prolonged hospital length of stay(LOS).Among 229 imported malaria cases,212(92.6％)were in Chinese citizens,and most cases were in men(96.5％).The gender ratio is 28:1,and the age of cases is mainly concertrated between 18 and 50 years old(89.1％).More than 80％of patients were mi-grant workers,and most cases were infections from African countries(92.6％).Plasmodium falciparum(80.8％)was the dominant species.Fifty-three severe malaria cases were identified during the study period.Compared with uncomplicated cases,severe cases tended to occur in patients with no history of malaria(P=0.008),patients infected with Plasmodium falciparum(P=0.009),and patients who were initially misdiagnosed(P＜0.001).The median LOS was 6 days,and the species of infec-tion(Plasmodium falciparum),the use of antimalarial drugs(group B),antipyretic time(longer than 3 days),and the turn-around time of blood smear microscopy(longer than 3 days)were significantly associated with longer LOS(all P＜0.05).Al-though malaria has been eradicated in Wuhan for many years,imported cases continue to pose a threat.Efforts should be made to strengthen malaria knowledge education for outbound personnel.Additionally,medical institutions must enhance diagnosis and treatment capabilities for malaria,and adhere to standardized treatment processes,and the development of drug resistance and occurrence of severe malaria must be prevented.

Objective:To explore the understanding on health-related quality of life(HRQoL)among the Chinese populations and to develop a HRQoL conceptual framework that can be used to guide the development of Chinese HRQoL instruments.Methods:Respondents of Chinese general population and patients populations were recruited from 31 provinces in China.One-to-one semi-structured qualitative interviews were conducted to collect the views and perceptions on HRQoL.Based on the grounded theory,multi-level coding of qualitative interviews was carried out,and the framework method was used to sort out and summarize the coding to develop the HRQoL conceptual framework in China.Results:A total of 68 respondents were included in the study.The study extracted 1 558 open coding from the qualitative interview,which were analyzed and sorted into 180 axial coding and 31 selective coding(dimensions).The HRQoL conceptual framework for the Chinese population with 6 themes was finally summarized.Conclusions:The HRQoL conceptual framework based on the health concepts and preferences of the Chinese population contains 6 themes,refers to symptoms,physical function,emotion,cognition,activities and social function.In particular,the items of appetite,sleep and fatigue identifies may reflect Chinese cultural specific perceptions on important aspects of HRQoL.

Zona Incerta ; Prefrontal Cortex ; Fear ; Neural Pathways

Humans ; Anniversaries and Special Events ; Hypersensitivity

Establish a production line with controllable process and high intelligence, contribute to improve the quality and production efficiency of aconite processed by microwave, and promote the transformation and application of aconite processed by microwave. According to the principle of aconite detoxification and the characteristics of industrial microwave equipment, an industrial production line of aconite processed by microwave was established with diester alkaloids and monoester alkaloids as indicators, and pilot production was carried out. At the same time, the content of active constituents and efficacy were compared with that of the main processed products, such as Shengfupian, Baifupian and Heishunpian. The results showed that the industrial production of aconite processed by microwave can be divided into two stages: "Liquid seal to detoxification - drying and puffing". The content of monoester alkaloids in 10 batches of aconite processed by microwave was 0.071%-0.166% and the content of diester alkaloids was 0.004%-0.016%, which met the relevant requirements of the Chinese Pharmacopoeia in 2020. Compared with Heishunpian and Baifupian, the retention rate of the effective components of aconite processed by microwave was higher. Pharmacological experiments showed that aconite processed by microwave not only retained the anti-inflammatory and analgesic activities of Heishunpian and Baifupian, but also significantly increased the levels of leukocytes and lymphocytes in mice with liver cancer chemotherapy, enhanced the CD4/CD8 ratio in spleen cells of mice (P < 0.05), thus regulating the body's immunity. However, this effect of Baifupian was weak, while Heishunpian and Shengfupian had no such effect. Through the above research, this study established microwave processing line with controllable process and high intelligence, as well produced the aconite processed by microwave with low toxicity and stable quality. It laid a foundation for the industrialized continuous production and clinical positioning of aconite by microwave processed, and provided scientific support for the development and application of microwave technology in the field of traditional Chinese medicine. All animal experiments in this study were reviewed and approved by the Experimental Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine before being carried out (Approval No. 2020-28).

The present study explored the kinetics and variation of volatile components of Atractylodis Macrocephalae Rhizoma during the hot-air drying process to obtain the optimal process parameters under multiple goals such as drying efficiency and drying quality. The dry basis moisture content and drying rate curves along with the change of drying time of Atractylodis Macrocephalae Rhizoma were investigated at five levels of drying air temperatures(30, 40, 50, 60, and 70 ℃). The relationship between moisture ratio and time in the drying process of Atractylodis Macrocephalae Rhizoma was fitted and verified by Midilli model, Page model, Overhults model, Modified Page model, Logaritmic model, Two terms Exponential model, and Newton model. Meanwhile, the effective diffusion coefficient of moisture(D_(eff)) and activation energy(E_a) in Atractylodis Macrocephalae Rhizoma were calculated under different drying air temperatures. GC-MS was used to determine the volatile components and content changes of the fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures. The dry basis moisture content and drying rate of Atractylodis Macrocephalae Rhizoma were closely related to the temperature of the drying medium, and the moisture of the Atractylodis Macrocephalae Rhizoma decreased with the prolonged drying time. As revealed by the drying rate curve, the drying rate increased with the increase in hot air temperature, and the migration of moisture was accelerated. The comparison of the correlation coefficient(R~2), chi-square(χ~2), and root mean standard error(RMSE) of each model indicated that the parameter average of the Midilli model had the highest degree of fit, with R~2=0.999 2, χ~2=8.78×10~(-5), and RMSE=8.20×10~(-3). Besides, the D_(eff) at 30-70 ℃ was in the range of 1.04×10~(-9)-6.28×10~(-9) m~2·s~(-1), and E_a was 37.47 kJ·mol~(-1). The volatile components of fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures were determined by GC-MS, and 18, 18, 18, 17, 17, and 18 compounds were identified respectively, which accounted for more than 84.76% of the volatile components. In conclusion, the hot-air drying of Atractylodis Macrocephalae Rhizoma can be model-fitted and verified and the variation law of the moisture and volatile components of Atractylodis Macrocephalae Rhizoma with temperature is obtained. This study is expected to provide new ideas for exploring the drying characteristics and quality of aromatic Chinese medicine.
Atractylodes ; Drugs, Chinese Herbal ; Hot Temperature ; Kinetics ; Rhizome