OBJECTIVE To systematically evaluate the efficacy and safety of thalidomide combined with aclacinomycin， granulocyte colony-stimulating factor and cytarabine （CAG） regimen in the treatment of elderly patients with acute myeloid leukemia （AML）. METHODS CNKI， Wanfang data， VIP， Sino Med， PubMed， Embase， the Cochrane Library and Web of Science were searched comprehensively from the inception to Aug. 27th， 2023. Randomized controlled trials （RCTs） about thalidomide combined with CAG regimen （trial group） versus CAG regimen （control group） in the treatment of elderly AML patients were collected， and RevMan 5.3 software was used for meta-analysis of included studies. RESULTS Finally， 7 RCTs were included， with a total of 601 patients， including 307 patients in the trial group and 294 patients in the control group. Meta-analysis results showed that the trial group was superior to the control group in enhancing the overall response rate [Z＝4.75， P＜0.000 01， OR＝2.80， 95%CI （1.83，4.28）]， complete remission rate [Z＝2.82， P＝0.005， OR＝1.61， 95%CI （1.16， 2.25）]， and improving platelet count [Z＝2.70， P＝0.007， MD＝64.02， 95%CI （17.53， 110.51）]， vascular endothelial growth factor [Z＝13.63，P＜0.000 01， MD＝－65.17， 95%CI（－74.54， －55.80）]， vascular endothelial growth factor receptor [Z＝12.03， P＜ 0.000 01， MD＝－499.01， 95%CI （－580.31， －417.71）] and basic fibroblast growth factor [Z＝4.17， P＜0.000 1，MD＝－0.23， 95%CI（－0.35， －0.12）]. And there was no statistical difference between the trial group and the control group in the incidence of adverse drug reaction [Z＝0.99， P＝0.32， OR＝0.52， 95%CI（0.14，1.89）]， nausea and vomiting [Z＝ 1.06， P＝0.29， OR＝0.66， 95%CI （0.30，1.43）]， constipation or diarrhea [Z＝0.92， P＝0.36， OR＝0.65， 95%CI（0.26， 1.63）]， drowsiness [Z＝1.38， P＝0.17， OR＝0.57， 95%CI（0.26， 1.27）] or myelosuppression [Z＝0.88，P＝0.38，OR＝0.68，95%CI（0.28， 1.62）]. CONCLUSIONS The combination of thalidomide and CAG regimen in the treatment of elderly AML patients can significantly improve clinical efficacy and has high safety.

BACKGROUND:The formation of Lewy bodies due to abnormal α-synuclein aggregation is a characteristic pathological change in Parkinson's disease.In recent years,several studies have revealed that the formation of α-synuclein aggregates is closely related to its post-translational modifications.The modification of α-synuclein such as phosphorylation,nitration,acetylation,and ubiquitination has attracted extensive attention in the pathogenesis and progression of Parkinson's disease. OBJECTIVE:To review the research progress in the effect of modification types and sites of α-synuclein on the characteristic pathological formation and progression of Parkinson's disease. METHODS:PubMed and CNKI databases were searched by the first author with the key words of"α-synuclein,Parkinson's disease,phosphorylation,acetylation,ubiquitination,nitration"in English and Chinese respectively to collect and sort out the literature related to abnormal modification of α-synuclein in recent years.Finally,61 articles were included for further review. RESULTS AND CONCLUSION:Abnormal modification of α-synuclein is closely related to its protein structure and its positive and negative charges.Its amino terminus is positively charged and prone to ubiquitination and acetylation modifications.The central hydrophobic region is prone to forming β-pleated sheet due to its hydrophobic property.The carboxyl terminus is negatively charged,which is the main phosphorylation modification region.Phosphorylation modification sites promote phosphorylation modification and are closely related to α-synuclein aggregation,while protein kinases can target the activation of translational modifications,which may help to promote or inhibit aggregate formation.The degradation pathway of α-synuclein mainly plays a role in removing pathological proteins.Various kinase catalysts contribute to impaired protein ubiquitination modifications that lead to abnormal protein accumulation,thereby exacerbating neurodegeneration.The amino-terminal acetylation of α-synuclein improves the shuttle ability of the protein to the cell membrane and slows down the protein aggregation,which may be the protection target of nerve cells.However,the acetylation modification of the mutant protein produces the opposite effect.The protein nitration modification is mainly related to oxidative stress.The aggregation tendency of the protein modified by nitration is enhanced under the action of reactive oxygen species.Different post-translational modifications have different effects.Therefore,elucidating the main mechanisms of their post-translational modifications and inhibiting the post-translational modifications that contribute to protein aggregation may provide a reference for new targets for early diagnosis and treatment of Parkinson's disease.

BACKGROUND:C2 ceramide reduces the formation of Alpha-Synuclein(α-Syn)oligomers as the protein phosphatase 2A agonist,which has an important regulatory effect on cell aging in the central nervous system. OBJECTIVE:To investigate the protective mechanism of C2 ceramide on dopaminergic neurons. METHODS:Twenty-five C57BL/6 mice were randomly divided into control group,model group,C2 ceramide low-,medium-and high-dose groups(n=5 per group).Except for the control group,a mouse model of Parkinson's disease was established by injecting mutant A53T α-Syn oligomers into the left striatum in the other groups.On the 30th day after the striatal injection,three C2 ceramide groups were intragastrically administered with C2 ceramide(1,5,10 μg/g)dissolved in saline at one time,while the control and model groups were administered with the same amount of saline within 30-90 days after modeling,for a total of 60 days.Behavioral changes in each group of mice were observed during this period.On the 90th day after striatal injection,mouse brain tissue was extracted by perfusion under anesthesia,and the changes of dopaminergic neurons in the midbrain substantia nigra were analyzed by immunohistochemical staining.The levels of α-Syn oligomerization and phosphorylation in the midbrain of mice were detected by ELISA,and the changes of enzyme activities related to α-Syn phosphorylation were analyzed. RESULTS AND CONCLUSION:C2 ceramide had an ameliorating effect on Parkinson's disease-like dyskinesia in mice caused by the striatal injection of mutant A53T α-Syn oligomers.High-dose C2 ceramide showed better effects on dyskinesia in mice with Parkinson's disease(P<0.01).The mutant A53T α-Syn oligomers significantly reduced the number of dopaminergic neurons in the substantia nigra of mice(P<0.01),while the number of dopaminergic neurons in the substantia nigra increased significantly in the C2 ceramide high-dose group(P<0.01).The levels of α-Syn oligomers and phosphorylated α-Syn in the brain were significantly reduced in the C2 ceramide high-dose group compared with the model group(P<0.01),while the level of ceramide was increased(P<0.05)and the activity of protein phosphatase 2A was significantly upregulated(P<0.01).To conclude,C2 ceramide can attenuate the neurotoxic effects induced by oligomerized α-Syn by the phosphorylation modification environment of α-Syn in mouse midbrain tissue and protect against the reduction in the number of nigrostriatal dopaminergic neurons in mice,thereby reducing the degree of dyskinesia in Parkinson's disease.

Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.

Objectives:To examine the feasibility of using foundation model in computer vision for echocardiographic left ventricular ejection fraction measurement. Methods:Based on the most extensive publicly accessible repository of echocardiographic loops,EchoNet-Dynamic,featuring 10024 recordings from individual patients,a foundation model in computer vision,VideoMAE V2,was fine-tuned,validated,tested using 7460,1288,and 1276 echocardiographic loops,respectively. Results:The mean absolute error between left ventricular ejection fraction measurements of VideoMAE V2 and expert's measurements was 3.94％ (95％CI:3.79％-4.11％).The Pearson's correlation coefficient was 0.91 (95％CI:0.89-0.92).Additionally,VideoMAE V2 demonstrated exceptional accuracy in identifying patients with a left ventricular ejection fraction below 50％,achieving an AUC of 0.96 (95％CI:0.95-0.97). Conclusions:This study validates the feasibility of using foundation model in computer vision for measuring left ventricular ejection fraction in echocardiographic loops and lays the foundation for the development of a generalized multimodal automated interpretation system for echocardiography.

Objective To explore the medication law of Professor Wang Qingguo for the treatment of insomnia based on data mining technology.Methods Paper-based prescriptions for Professor Wang Qingguo's treatment of insomnia from December 2016 to August 2023 were collected and a database was constructed.The screened prescriptions were subjected to data mining such as frequency statistics,association rule analysis,and clustering analysis.Results Totally 399 effective outpatient prescriptions were screened-out,involving 276 kinds of Chinese materia medica,with a total frequency of 6738 times.There were 38 Chinese materia medica with a frequency of use≥50.The properties were mainly warm,cold and mild,the tastes were mainly sweet,bitter and pungent,and mainly belong to the lung,spleen and heart meridians.Association rule analysis showed that the most commonly used drug combinations were"Fructus Tritici Levis-Scutellariae Radix-Bupleuri Radix","Pericarpium Citri Reticulatae-Scutellariae Radix-Pinelliae Rhizoma",etc.Association rule network analysis obtained a core prescription containing 12 kinds of Chinese materia medica for insomnia.Four new drug combinations were obtained by clustering analysis.Conclusion Professor Wang's treatment of insomnia has the characteristics of following the original meaning of Huang Di Nei Jing and Nan Jing,making good use of the classical prescription,applying combined prescription,flexible use of prescription,combining ancient and modern prescriptions,using specific medicine.It deeply reflects the academic view of"Tongping Zhihe".

AIM:To explore the effects of moderate-altitude exposure on intestinal flora in healthy individuals.METHODS:The aid-Tibet cadres,who were sent to work from Guangdong(average altitude<50 m)to Nyingchi(average altitude of 2 900 m),were recruited.A total of 76 samples were collected,including 42 samples from healthy adults with plateau living for 0 day and 34 samples from healthy adults with plateau living for 6 months.Fecal samples DNA were ex-tracted,sequenced by the 16S rDNA high-throughput sequencing technology and analyzed bioinformatically.RESULTS:Compared with the base group,α diversity was increased(P=4.00×10-4)and β diversity was decreased(P=1.00×10-3).After moderate altitude exposure,the relative abundance of phylum Proteobacteria(|LDA|>4,P<0.05),genus Escherich-ia-Shigella,species Enterococcus_faecalis,Haemophilus_influenzae and Helicobacter_sp._UNSW1.7sp decreased(adjust-ed P<0.05),wheras the relative abundance of phylum Bacteroidetes(|LDA|>4,P<0.05),genus Butyricimona,species Lactobacillus_sp._RA2113(s)and Butyricimonas_sp._Marseille-P2440(s)increased(adjusted P<0.05).The function-al prediction by PICRUSt showed a decrease in the relative abundance of pathway related to xenobiotics biodegradation and metabolism,membrane transport and amino acid metabolism(adjusted P<0.05).Conversely,the relative abundance of pathway related to biosynthesis of other secondary metabolites and nucleotide metabolism was increased(adjusted P<0.05).Finally,the results of microbiome phenotype prediction by BugBase showed that moderate altitude exposure im-proves the gut microbiota functions involving anaerobic oxygen tolerance and gram positive(adjusted P<0.05).And bacte-ria containing facultatively anaerobic oxygen tolerance,oxidative stress tolerance,gram negative and biofilm formation in the six-group decreased significantly compared with those in base group(adjusted P<0.05).CONCLUSION:Moderate altitude exposure impacts the diversity,abundance and function of intestinal flora in healthy population,suggesting that al-titude factors may have some influence on gut microbiota.

The geographical origin of forensic evidence provides important information for crime investigation and solving cases,and is one of the key elements of criminal cases.Previous studies have shown significant differences in the distribution of microorganisms in different regions.Detecting environmental DNA samples and inferring the geographical and spatial sources can provide clues and evidence for case handling.However,due to the diversity of criminal environments and the trace amount of frequently encountered exhibits,stable and reliable technical methods for inferring geographical origin from environmental DNA are not yet available.This article summarizes the sample collection and DNA extraction methods for four types of environmental samples:dust,soil,water,and air.It compares the differences between amplicon sequencing and metagenomic sequencing in studying environmental biological populations,outlines the full process of high-throughput sequencing-based data analysis,and focuses on reviewing the research progress in inferring geographical sources of environmental samples based on bacteria,fungi,and other eukaryotes,to provide references for establishing sequencing and analysis methods for environmental DNA in forensic DNA laboratories and exploring environmental DNA information for forensic applications.

Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.

Objective To analyze the publication profile and research hotspots of studies at home and abroad on postoperative cognitive dysfunction by bibliometric methods. Methods Literatures related to postoperative cognitive dysfunction published in the China National Knowledge Infrastructure (CNKI) and Web of Science databases from 2013 to 2023 were included, and statistical analysis was conducted by CiteSpace software. Results A total of 2 705 Chinese literatures and 2 412 English core literatures were included. The number of literatures on postoperative cognitive dysfunction showed an annual increase from 2013 to 2023; China was the country with the highest number of publications internationally, with Capital Medical University ranking the top among Chinese institutions; domestically, postoperative cognitive dysfunction researches predominantly focused on clinical studies, while overseas researches emphasized pathological mechanisms and basic investigations. Research hotspot analysis revealed an enhanced interest in the inflammatory mechanisms and anesthetic aspects of postoperative cognitive dysfunction. Conclusion From 2013 to 2023, the overall research at home and abroad interest in postoperative cognitive dysfunction has shown an upward trend, yet its pathophysiological mechanisms need further exploration. The risk factors for postoperative cognitive impairment and their correlations with anesthesia and mortality are being actively explored, and new methods for prevention and treatment such as percutaneous electrical stimulation are gradually emerging.