Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

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 deubiquitinases (DUBs), as the crucial peptidohydrolases in the ubiquitin system, can reverse and strictly regulate ubiquitination and play key roles in various biological processes, including the regulation of protein stability, cell signal transduction. Ubiquitin-specific protease 28 (USP28) involves multiple cancer-related signaling pathways by enhancing the stability of various cancer-related proteins, and is closely associated with the progression of colorectal, breast cancer, lung carcinomas, and pancreatic cancer. USP28 has been considered as a promising drug target in anticancer therapy, and the development of USP28 inhibitors has made some progress. In this article, we review the structure of USP28 and its interaction with substrates, discuss the research progress of USP28 in cancers and summarize the development of USP28 inhibitors.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

Aim To study the therapeutic effect of Balanophora polysaccharide(BPS)on gastric ulcer(GU)induced by acetic acid in rats and to investigateits mechanisms. Methods Sixty male SD rats were randomly divided into sham-operated group, GU model group, omeprazole positive group(3.6 mg·kg-1), and low, medium and high dose of BPS treatment groups(100, 200 and 400 mg·kg-1). The GU model group was prepared by acetic acid cautery method, and the morphology and pathological changes of ulcers were observed by visual observation combined with HE staining, and the ulcer area and inhibition rate were measured and calculated; superoxide dismutase(SOD)activity, malondialdehyde(MDA)content and glutathione peroxidase(GSH-PX)activity were measured by enzymatic assay; tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)content were detected by ELISA. The expression levels of epidermal growth factor(EGF)and epidermal growth factor receptor(EGFR)were measured by immunohistochemistry staining and Western blot. Results Compared with the sham-operated group, obvious ulcer damage was seen in the model group. Compared with the model group, the BPS-treated group showed a significant reduction in ulcer area, an increase in SOD and GSH-PX activity and EGF and EGFR expression levels, and a significant decrease in MDA, TNF-α and IL-6 content. Conclusions BPS has a therapeutic effect on GU in rats, and its mechanism may be related to the inhibition of oxidative stress, suppression of inflammatory stimuli and promotion of regenerative repair of gastric mucosa.

Objective: To construct chimeric antigen receptor (CAR) T cells targeting CD52 (CD52 CAR-T) and validate the effect of CD52 CAR-T cells on CD52-positive leukemia. Methods: A second-generation CD52-targeting CAR bearing 4-1BB costimulatory domain was ligated into a lentiviral vector through molecular cloning. Lentivirus was prepared and packaged by 293 T cells with a four-plasmid system. Fluorescein was used to label cell surface antigens to evaluate the phenotype of CD52 CAR-T cells after infection. Flow cytometry and ELISA were used to evaluate the specific cytotoxicity of CD52 CAR-T cells to CD52-positive cell lines in vitro. Results: ①A pCDH-CD52scFv-CD8α-4-1BB-CD3ζ-GFP expressing plasmid was successfully constructed and used to transduce T cells expressing a novel CD52-targeting CAR. ②On day 6, CD52-positive T cells were almost killed by CD52-targeted CAR-T post lentivirus transduction [CD52 CAR-T (4.48 ± 4.99) %, vs Vector-T (56.58±19.8) %, P=0.011]. ③T cells transduced with the CAR targeting CD52 showed low levels of apoptosis and could be expanded long-term ex vivo. ④The CD52 CAR could promote T cell differentiation into central and effector memory T cells, whereas the proportion of T cells with a CD45RA(+) effector memory phenotype were reduced. ⑤CD52 CAR-T cells could specifically kill CD52-positive HuT78-19t cells but had no killing effect on CD52-negative MOLT4-19t cells. For CD52 CAR-T cells, the percentage of residual of HuT78-19t cells was (2.66±1.60) % at an the E:T ratio of 1∶1 for 24 h, while (56.66±5.74) % of MOLT4-19t cells survived (P<0.001) . ⑥The results of a degranulation experiment confirmed that HuT78-19t cells significantly activated CD52 CAR-T cells but not MOLT4-19t cells[ (57.34±11.25) % vs (13.06± 4.23) %, P<0.001]. ⑦CD52 CAR-T cells released more cytokines when co-cultured with HuT78-19t cells than that of vector-T cells [IFN-γ: (3706±226) pg/ml, P<0.001; TNF-α: (1732±560) pg/ml, P<0.01]. Conclusions: We successfully prepared CD52 CAR-T cells with anti-leukemia effects, which might provide the foundation for further immunotherapy.
CD52 Antigen ; Cell Line, Tumor ; Humans ; Immunotherapy, Adoptive/methods* ; Lentivirus/genetics* ; Leukemia ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen/genetics*

OBJECTIVE: To explore the rule of point selection in treatment of cerebral palsy with acupuncture in preschool children. METHODS: Based on the electronic medical records of Xi'an Encephalopathy Hospital of TCM, through structuring medical record text, acupuncture prescriptions were extracted. Using the data mining tools of the ancient and modern medical record cloud platform V2.2.3 and the clinical effective prescription and molecular mechanism analysis system of traditional Chinese medicine V2.0, the cluster analysis and complex network analysis were conducted on acupuncture prescriptions. RESULTS: Of 1584 acupuncture prescriptions for cerebral palsy in children, there were 84 acupoints and stimulating areas of scalp acupuncture, of which, foot-motor-sensory area, balance area and Sanyinjiao (SP 6) were the top 3 acupoints with the highest use rate. With cluster analysis, 5 groups of common supplementary acupoints and stimulating areas were found, named, Weizhong (BL 40) and Waiguan (TE 5), Shousanli (LI 10), Xingjian (LR 2), Xuanzhong (GB 39) and Chengfu (BL 36), foot-motor-sensory area, balance area and Sanyinjiao (SP 6), Xuehai (SP 10) and Fenglong (ST 40), Pishu (BL 20), motor area and Yanglingquan (GB 34). With complex network analysis on core prescriptions, 13 core acupoints and stimulating areas of scalp acupuncture were obtained, including 3 core main points, i.e. Sanyinjiao (SP 6), balance area and foot-motor-sensory area and 10 sub-core points, i.e. Taichong (LR 3), motor area, Xuehai (SP 10), Ganshu (BL 18), Pishu (BL 20), Yanglingquan (GB 34), Sishencong (EX-HN 1), Baihui (GV 20), Fengchi (GB 20) and Shenshu (BL 23). CONCLUSION In treatment of acupuncture for cerebral palsy in preschool children, the core prescriptions reveal the simultaneous treatment of exterior and interior, the mutual regulation of
Acupuncture Points ; Acupuncture Therapy ; Cerebral Palsy/therapy* ; Child, Preschool ; Data Mining ; Electronic Health Records ; Humans

To systematically evaluate the clinical efficacy and safety of Lianhua Qingwen in the treatment of adult pneumonia. The randomized controlled trial of Lianhua Qingwen combined with conventional Western medicine in the treatment of pneumonia were retrieved from PubMed, EMbase, Wanfang database, VIP database, and CNKI from the establishment of database to March 2020. Two researchers independently conducted literature screening and data extraction, and the third researcher was in charge of arbitration in case of any disagreement. Outcome indicators included total clinical effective rate, symptom improvement time, and incidence of adverse events. R 3.6.1 was used for Meta-analysis, and RevMan 5.3 was used for quality evaluation. Twenty-two studies were included, with a total of 2 007 patients, including 1 017 patients in the experimental group and 990 patients in the control group. The results showed that the total clinical effective rate of the experimental group was higher than that of the control group(RR=1.11, 95%CI[1.08, 1.15], P<0.001), and the antifebrile time(MD=-1.81, 95%CI[-2.42,-1.21], P<0.001), cough duration(MD=-2.32, 95%CI[-2.89,-1.76], P<0.001), rale duration(MD=-2.19, 95%CI[-2.74,-1.63], P<0.001), imaging recovery time(MD=-2.17, 95%CI[-2.76,-1.58], P<0.001) and post-treatment CRP(MD=-4.07, 95%CI[-6.39,-1.75], P<0.001] were all significantly lower than those of the control group. However, it did not proved that the experimental group was safer than the control group(RR=0.84, 95%CI[0.57, 1.24], P=0.382). The results confirmed that Lianhua Qingwen combined with conventional Western medicine in the treatment of pneumonia could improve the clinical treatment efficiency, shorten the time of fever, cough, rale disappearance and imaging recovery, improve CRP index and accelerate the recovery of pneumonia patients. However, the literatures included in this study had a low quality, and the conclusions still need to be further confirmed by more high-quality, multi-center, rigorously designed randomized controlled trial.
Adult ; Cough ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Pneumonia/drug therapy* ; Treatment Outcome

Objective:To study the protective effect of modified Sinisan on liver injury caused by chronic unpredictable mild stress (CUMS) combined with solitary nutrition method based on a depression model. Method:Forty-eight SD male rats were randomly divided into normal group, depression model group, fluoxetine group (1.58 mg·kg^-1·d^-1), and low, medium and high-dose modified Sinisan (3.67, 7.34, 14.68 g·kg^-1·d^-1) groups, with 8 rats in each group. After the administration of the model, the levels of alanine aminotransferase（ALT）, aspartate aminotransferase（AST） in serum and the levels of inflammatory factors tumor necrosis factor-α（TNF-α）, interleukin（IL）-1β, and IL-6 in liver tissues were measured by a biochemical kit method. Western blot was used to detect the expressions of cysteine aspastic acid-specific protease-3 (Caspase-3) and cleaved Caspase-3 in liver cells after intervention with modified Sinisan. Result:Compared with the normal group, the biochemical test showed that the levels of ALT and AST in the serum of the model group were significantly increased (P<0.05), and the levels of inflammatory factors TNF-α, IL-1β and IL-6 in liver tissue significantly increased (P<0.05). Compared with the model group, low, medium-dose modified Sinisan groups significantly reduced serum ALT, AST and inflammatory factors TNF-α, IL-1β and IL-6 levels (P<0.05). Western blot showed that compared with the normal group, the protein expression of Caspase-3 in model rat liver cells decreased, while the protein expression of cleaved Caspase-3 increased（P<0.05，P<0.01）. Compared with the model group, low, medium-dose modified Sinisan groups could up-regulate Caspase-3 protein expression, and down-regulated the expression of cleaved Caspase-3 protein（P<0.05，P<0.01）. Conclusion:Chronic stress-induced depression model can cause liver damage. Modified Sinisan can have the hepatoprotective effect by regulating the levels of various physiological, biochemical and inflammatory factor indicators, and inhibiting liver cell apoptosis.