Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

ObjectiveTo investigate the effects and mechanism of baicalin （BA） on lipopolysaccharide （LPS）-induced acute lung injury in rats. MethodEighty healthy male SD rats were randomly divided into the control group， model group， low-dose BA （BA-L） group， medium-dose BA （BA-M） group， high-dose BA （BA-H） group， dexamethasone （DEX） group， SB203580 group， and BA + SB203580 group， with 10 rats in each group. The rats in the BA-L， BA-M， and BA-H groups were injected intraperitoneally with different doses （10， 50， 100 mg·kg^-1） of BA solution， the ones in the DEX group with 5 mg·kg^-1 DEX solution， the ones in the SB203580 group with 0.5 mg·kg^-1 SB203580 solution， the ones in the BA + SB203580 group with 100 mg·kg^-1 BA solution and 0.5 mg·kg^-1 SB203580， and those in both the control group and model group with the same volume of normal saline， once per day， for seven successive days. One hour after the last administration， rats in all groups except for the control group were given 5 mg·kg^-1 LPS via intratracheal instillation for inducing the acute lung injury， whereas those in the control group received the same volume of normal saline solution. Twelve hours later， the lung tissues were sampled and stained with htoxylin-eosin （HE） for observing the pathological changes， followed by the counting of the total number of cells and neutrophils in bronchoalveolar lavage fluid （BALF）. The wet/dry weight ratio of the lung tissue and the contents of serum superoxide dismutase （SOD） and malondialdehyde （MDA） were measured. The activity of reactive oxygen species （ROS） in the lung tissue was detected by immunofluorescence and the levels of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in BALF by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was conducted to determine the relative expression of p-p38 mitogen-activated protein kinase （MAPK） and Western blotting was carried out to detect the protein expression levels of p-p38 MAPK， thioredoxin interacting protein （TXNIP）， NOD-like receptor protein 3 （NLRP3）， and cysteinyl aspartate specific protease-1 （Caspase-1） in the lung tissue. ResultCompared with the control group， the model group displayed inflammatory pathological changes in lung tissue， elevated wet/dry weight ratio， total number of cells and neutrophils in BALF， and ROS and MDA levels （P<0.01）， decreased SOD activity （P<0.01）， and up-regulated IL-1， IL-18， IL-6， TNF-α， p-p38 MAPK， NLRP3， and Caspase-1 expression （P<0.01）. Compared with the model group， BA at different doses， SB203580， and BA + SB203580 all effectively alleviated the pathological changes in lung tissue induced by LPS， reduce the lung wet/dry weight ratio， the total number of cells and neutrophils in BALF， and ROS and MDA levels （P<0.05，P<0.01）， enhanced the activity of SOD （P<0.05，P<0.01）， and down-regulated the expression of IL-1β， IL-18， IL-6，TNF-α， p-p38 MAPK， NLRP3， and Caspase-1 in lung tissue （P<0.05，P<0.01）. ConclusionBA has a protective effect against LPS-induced acute lung injury， which may be related to its inhibition of p38MAPK/NLRP3 signaling pathway and the improvement of inflammatory response.

OBJECTIVE: To preliminarily investigate the role of long non-coding RNA (lncRNA) MIR4697 host gene (MIR4697HG) in regulating the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: For adipogenic differentiation, BMSCs were induced in adipogenic media for 10 days. The mRNA expression levels of lncRNA MIR4697HG and adipogenic marker genes including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhanced binding protein α (CEBP/α) and adiponectin (ADIPQ) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) at different time points (0, 1, 2, 3, 5, 7, 10 days). The MIR4697HG stable knockdown-BMSC cell line was generated by infection of MIR4697HG shRNA-containing lentiviruses. To avoid off-target effect, two target sequences (shMIR4697HG-1, shMIR4697HG-2) were designed. And then cells were induced to differentiate in adipogenic medium. Oil red O staining, Western blot and qRT-PCR were used to detect the effect of MIR4697HG knockdown on adipogenic differentiation of BMSCs. RESULTS: The mRNA expression level of MIR4697HG was significantly increased during adipogenic differentiation (P < 0.01), and adipogenic differentiation of BMSCs was evidenced by upregulated mRNA levels of specific adipogenesis-related genes including PPARγ, CEBP/α and ADIPQ. Observed by fluorescence microscopy, more than 90% transfected target cells expressed green fluorescent protein successfully after shMIR4697HG-1 group, shMIR4697HG-2 group and shNC group transfection for 72 h. And the transfection efficiency of MIR4697HG examined by qRT-PCR was above 60%. Then the BMSCs were treated with adipogenic media for 7 days and showed that the mRNA expression levels of adipogenesis-related genes including PPARγ, CEBP/α and ADIPQ were significantly decreased in the MIR4697HG knockdown group (P < 0.01), while the expression levels of PPARγ and CEBP/α proteins were decreased remarkably as well (P < 0.01). Consistently, MIR4697HG knockdown BMSCs formed less lipid droplets compared with the control BMSCs, which further demonstrated that MIR4697HG knockdown inhibited adipogenic differentiation of BMSCs. CONCLUSION lncRNA MIR4697HG played a crucial role in regulating the adipogenic differentiation of BMSCs, and MIR4697HG knockdown significantly inhibited the adipogenic differentiation of BMSCs. These data may suggest that lncRNA MIR4697HG could serve as a therapeutic potential target for the aberrant adipogenic differentiation-associated disorders including osteoporosis.
Adipogenesis/genetics* ; Bone Marrow Cells/metabolism* ; Cell Differentiation ; Cells, Cultured ; Mesenchymal Stem Cells ; Osteogenesis ; PPAR gamma/pharmacology* ; RNA, Long Noncoding/genetics* ; RNA, Messenger/metabolism*

Based on the research literatures of Passiflora incarnata and the theory of traditional Chinese medicine, the paper discussed the traditional Chinese medicinal properties of P. incarnate, so as to provide a theoretical basis for the compatibility and application of P. incarnata. The literature databases of CNKI, Wanfang, VIP, Web of Science, PubMed and Scopus were selected, and the literatures relating to P. incarnata were reviewed to screen out the scientific research literatures with a high credibility, rational design and reliable conclusions. Foreign pharmacopoeia was consulted, and the listed products were summarized. The traditional Chinese medicine properties of P. incarnata were studied based on 32 clinical trials, 66 pharmacological researches, 64 chemical constituents researches as well as the theory of traditional Chinese medicine. It was preliminarily concluded that the medicinal properties of P. incarnata are sweet, cool, and enter heart, liver channels. The function is mainly to calm the heart and tranquilizing the mind, and calm the liver wind. It is used for hyperactivity of liver-Yang, stagnation of liver-Qi, restlessness of mind, depression, nervousness, insomnia. This paper summarized the source, characteristics of natures, tastes and channel tropism, usage and dosage, function indications of P. incarnata, and defined its clear traditional Chinese medicine property, which lays a theoretical foundation for the compatibility and clinical application of P. incarnata and Chinese medicine.
Anti-Anxiety Agents ; Anxiety ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Passiflora ; Sleep Initiation and Maintenance Disorders/drug therapy*

Aspalathus linearis is a needle-shaped shrub that grows in the Cedarberg mountains in southern South Africa, with an extremely high medicinal value. In 2014, China has approved A. linearis as a new food material. Through retrieval in CNKI, Wanfang, VIP, Web of Science, PubMed and Scopus databases, the literatures were excluded, classified and summarized.On the basis of Chinese medicine theory, the traditional Chinese medicine properties were deducted. Finally, 264 relevant li-teratures were included and classified into 6 categories: review, planting, chemical composition, clinical study, pharmacological effects and safety. The traditional Chinese medicinal properties were deducted as sweet flavor and neutral property. It enters kidney, spleen, heart and liver channels. The major functions are to tonify the kidney and benefit the essence, nourish Qi and spleen, nourish Yin and prompt the production of body fluid, tranquilize mind, and relieve pain. It can be used for soreness of the waist and fatigue, sexual disinterest, limbs heaviness, thirst due to insufficiency of fluid and internal heat, irritability and insomnia, forget fulness, stomachache, joint pain, dysmenorrhea, headache. Preparation for external use can treat eczema itching. Water decoction(2-15 g) can also be used as tea directly. This paper defined the traditional Chinese medicine properties of A. linearis, so as to provide the theoretical basis for further clinical application.
Aspalathus ; China ; Drugs, Chinese Herbal ; Female ; Medicine, Chinese Traditional

The present study analyzed the current Chinese medicinal health products and Chinese patent medicines effective in boosting memory,aiming at providing references for the formulation and development of memory-boosting health products. The information on memory-boosting health products published by the Department of Special Food Safety Supervision and Management,the State Administration for Market Regulation( SAMR) was collected and the Chinese patent medicines on DRUGDATAEXPY were searched. Microsoft Excel and the TCMISS were used to statistically analyze the characteristics of formulations. A total of 212 memory-boosting health products were obtained from SAMR,including 83 ones containing Chinese medicinal materials. Twelve Chinese herbal medicines showed a usage frequency ≥ 8,with 151 times in use. In DRUGDATAEXPY,258 similar Chinese patent medicines were collected.Twelve Chinese herbal medicines showed a usage frequency ≥ 58,with 907 times in use. Through unsupervised hierarchical entropybased clustering of the above-mentioned Chinese medicinal health products and Chinese patent medicines separately,5 and 12 new formulas were obtained. The selection of Chinese herbal medicines for the new formulas was consistent with the principles of traditional Chinese medicine( TCM) theories,i. e.,tonifying kidney and marrow,benefiting Qi,nourishing Yin,resolving phlegm,and eliminating stasis. According to TCM theories,syndrome differentiation of the users was conducted,and the formulas were designed following the correspondence of syndromes with formulas and Chinese herbal medicines. This study is expected to provide new ideas and methods for the development of Chinese medicinal health products and accurately guide practical applications to exert the advantages of TCM in health care based on syndrome differentiation and improve the effect of Chinese medicinal health products.
China ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Syndrome

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

BACKGROUND: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. METHODS: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. RESULTS: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). CONCLUSIONS IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.
Albumins/analysis* ; Antiviral Agents/administration & dosage* ; Betacoronavirus ; C-Reactive Protein/analysis* ; COVID-19 ; Case-Control Studies ; China ; Coronavirus Infections/drug therapy* ; Glucocorticoids/pharmacology* ; Hospitalization ; Humans ; Interferon alpha-2/administration & dosage* ; Nasal Sprays ; Pandemics ; Pneumonia, Viral/drug therapy* ; Propensity Score ; Retrospective Studies ; SARS-CoV-2 ; Sodium/blood* ; Virus Shedding/drug effects* ; COVID-19 Drug Treatment