Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Objective To explore the relationship between the expression levels of adenosine triphosphate binds to the box transporter C4(ABCC4)and microRNA-125b-5p(miR-125b-5p)and survival 3 years after surgery in prostate cancer(PCa)tissue.Methods A total of 60 patients with PCa diagnosed in Huanghua People's Hospital from November 2017 to February 2020 were selected,and PCa tissues(PCa group)and pa-racancer tissues(control group)were collected intraoperatively.The expression levels of ABCC4 mRNA,miR-125b-5p and ABCC4 in the samples were detected;the patients were followed up for 3 years.The correlation between the expression levels of ABCC4 mRNA and miR-125b-5p in PCa tissues,their relationship with clini-copathological features and prognosis,and the factors affecting the prognosis of PCa patients,the predictive value of both for 3-year survival of patients were analyzed.Results The expression level and positive rate of ABCC4 mRNA in PCa group were higher than those in control group,and the expression level of miR-125b-5p was lower than that in control group,and the differences were statistically significant(P＜0.05).The expres-sion level of ABCC4 mRNA and miR-125b-5p in PCa tissue was negatively correlated(P＜0.05).The expres-sion level of ABCC4 mRNA and miR-125b-5p in PCa tissue was related to tumor stage,serum prostate specific antigen,Gleason score and tumor metastasis(P＜0.05).The 3-year cumulative survival rate of patients in the ABCC4 mRNA high expression group and the miR-125b-5p low expression group was lower than that in the ABCC4 mRNA low expression group and the miR-125b-5p high expression group,respectively,and the differ-ences were statistically significant(P＜0.05).The expression level of ABCC4 mRNA in the PCa tissue in death group was higher than that in survival group,and the expression level of miR-125b-5p was lower than that in survival group,and the differences were statistically significant(P＜0.05).High expression of ABCC4 mRNA and low expression of miR-125b-5p were independent risk factors for poor prognosis in PCa patients(P＜0.05).Compared to the area under the curve(AUC)predicted by ABCC4 mRNA and miR-125b-5p alone for 3-year survival in PCa patients,the combined prediction of the two had a higher AUC(P＜0.05).Conclu-sion ABCC4 is highly expressed and miR-125b-5p is low expressed in PCa patients'cancer tissues,and the combination of the two has a high predictive power for 3-year survival in PCa patients.

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.

Ketamine,an antagonist of the glutamate N-methyl-D-aspartate(NMDA)receptor,is cur-rently one of the most widely abused psychoactive substances.Prolonged abuse can result in damages to various systems in the body,making it crucial to investigate the regulatory mechanism of ketamine addic-tion and screening related biomarkers.In this study,zebrafish embryos/larvae were initially exposed a-cutely to ketamine.Then,a ketamine addiction model was established in 6-month-old zebrafish through conditioned place preference(CPP)experiments.The zebrafish brain transcriptome was analyzed using RNA-seq,while qPCR and Western blotting were employed to detect the expression of key genes.Results revealed significant reductions in the spontaneous tail coiling,embryo hatching rate,and survival rate of zebrafish embryos in the ketamine-treated group compared to the control group.The distance moved also decreased significantly,from 1904.2 mm in the control group to 319.0 mm in the high dose of ketamine group(300 μmol/L).Conditional positional preference experiments demonstrated that the control ze-brafish did not exhibit significant changes in activity in the CPP tank.In contrast,the ketamine-treated group increased their activity time in the light zone of the tank from 385.2 s before training to 706.4 s af-ter training,representing a 26.8％increase(***P＜0.001).This suggests a preference for ketamine stimulation in zebrafish.KEGG analysis indicated enrichment of differentially expressed genes in the neu-roactive ligand-receptor interaction pathway in the ketamine-treated samples.GSEA analysis further re-veals a significant upregulation of the glutamatergic synapse pathway(NES=1.5).In addition,compared with the control group,the mRNA levels of Grin2b and Gria2 in the ketamine group increased by 4.6 and 1.4 times,respectively,while the protein levels increased by 2.0 and 1.4 times,respectively.These findings suggest that ketamine can induce addiction in zebrafish,potentially through upregulation of the glutamatergic synaptic pathway.

Objective To investigate the effect of PKM2 on the invasive ability of bladder urothelial carcinoma cells by regulating the reactive oxygen species(ROS)-dependent PI3K/Akt signaling pathway.Methods Human bladder cancer T24 cells were divided into the control,si-NC,si-PKM2,and si-PKM2+IGF-1 groups.PKM2mRNA expression,proliferation,invasion and migration,and apoptosis of T24 cells were detected using real-time PCR,CCK-8 assay,Transwell assay,and Hoechst 33342 fluorescence staining and flow cyto-metry,respectively.The ROS level in the cells was measured using ROS fluorescence probe staining.Western blotting was used to detect the expression of PI3K,Akt,mTOR,caspase-3,Bax,and Bcl-2 proteins.Results The expression of PKM2 mRNA in human bladder cancer T24 cells was significantly higher than in normal bladder SV-HUC-1 cells(P<0.05).Compared to the control group,the expres-sion of PKM2mRNA,cell proliferation ability,number of invading cells,p-PI3K/PI3K ratio,p-Akt/Akt ratio,p-mTOR/mTOR ratio,and Bcl-2 protein expression in T24 cells in the si-PKM2 group were significantly decreased(P<0.05),whereas the apoptosis rate,relative ROS level,and expression of Bax and caspase-3 proteins were significantly increased(P<0.05).Compared to the si-PKM2 group,the expression of PKM2mRNA,cell proliferation ability,number of invading cells,p-PI3K/PI3K ratio,p-Akt/Akt ratio,p-mTOR/mTOR ratio,and Bcl-2 protein expression in T24 cells in the si-PKM2+IGF-1 group were significantly increased(P<0.05),whereas the apoptosis rate,relative ROS level,and expression of Bax and caspase-3 proteins were significantly decreased(P<0.05).Conclusion Knockdown of PKM2can increase the level of ROS in bladder urothelial carcinoma cells and inhibit the activation of the PI3K/Akt/mTOR signaling pathway,thus inhibiting cell invasion and promoting cell apoptosis.

OBJECTIVE: To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI). METHODS: The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed. RESULTS: The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M₂). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections. CONCLUSION Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; Dexamethasone/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Bortezomib/therapeutic use* ; Renal Insufficiency/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

As the disease with high morbidity and mortality in the world, heart failure affects the development of human society. Due to its complicated pathology and limited treatment options, it is urgent to discover new disease targets and develop new treatment strategies. As innate immune cells accompanied by the evolution of heart failure, macrophages play an important role in cardiac homeostasis and stress. In recent years, the role of macrophages in the heart has attracted more and more attention as a potential target for heart failure intervention, and the research on cardiac macrophages has made important progress. Traditional Chinese medicine(TCM) has significant effects on regulating inflammatory response, treating heart failure, and maintaining homeostasis. In this article, researches on the functions of cardiac macrophages and application of TCM were reviewed from the source and classification of cardiac macrophages and the relationship of macrophages and cardiac inflammation, myocardial fibrosis, cardiac angiogenesis, and cardiac electrical conduction, which provided a basis for further basic research and clinical applications.
Humans ; Medicine, Chinese Traditional ; Heart Failure/drug therapy* ; Macrophages ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Ebola virus disease (EVD) is a severe infectious disease caused by Ebola virus in humans and primates. The main clinical features are fever and bleeding. The disease was first identified in Zaire and Sudan in Africa in 1976. Since then, it has caused many large-scale epidemics in Africa. One of the largest and most complex Ebola outbreaks in history was the 2014-2016 outbreak in West Africa, which caused more cases and deaths than all previous outbreaks combined. As of 2022, about 35 000 EVD cases and 15 000 deaths have been reported. During the African pandemic, EVD also spread to other regions outside the African continent, such as the Americas and Europe, and became a public health issue of worldwide concern. In Africa, the re-emergence of the disease in Uganda and the Republic of Congo in 2022 has attracted much attention from the world. This article systematically summarizes the history, epidemiological distribution, route of infection, clinical symptoms, diagnosis, treatment, prevention and control of Ebola virus disease, so as to provide reference for relevant workers in China.

Recent advances in multimodality treatment offer excellent opportunities to rethink the paradigm of perioperative management for locally advanced esophageal squamous cell carcinoma. One treatment clearly doesn't fit all in terms of a broad disease spectrum. Individualized treatment of local control of bulky primary tumor burden (advanced T stage) or systemic control of nodal metastatic tumor burden (advanced N stage) is essential. Given that clinically applicable predictive biomarkers are still awaited, therapy selection guided by diverse phenotypes of tumor burden (T vs. N) is promising. Potential challenges regarding the use of immunotherapy may also boost this novel strategy in the future.
Humans ; Esophageal Squamous Cell Carcinoma/surgery* ; Carcinoma, Squamous Cell/pathology* ; Esophageal Neoplasms/pathology* ; Combined Modality Therapy ; Immunotherapy