ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

The development of forensic medicine is crucial to the national welfare,people's livelihood,social stability,and the construction of a Safe China.It plays an indispensable role in the comprehen-sive promotion of the rule of law.The establishment of forensic medicine as a first-level discipline,along with the transformation brought by the fifth research paradigm,makes the construction of forensic medicine stand at a new historical starting point.This paper reviews the current status and challenges of forensic medicine development,outlines the characteristics of the fifth research paradigm and its im-pact on the construction of forensic medicine,and proposes strategies for addressing these challenges.

Objective To analyze the literature in the field of body fluid identification collected in the Web of Science Core Collection(WoSCC)database from 2000 to 2023,and explore the research sta-tus,hotspots and development trends in this field.Methods The CiteSpace software was utilized to conduct a visual analysis of the literature in the field of body fluid identification included in the WoSCC database from 2000 to 2023.Meanwhile,a bibliometric analysis of the annual publication vol-ume,journal distribution,national contribution,research institutions,author collaboration,and keywords of the literature was conducted.Results A total of 715 papers on forensic body fluid identification were included,and the annual publication volume showed a continuous and stable growth.Among the 55 countries(regions)that published papers,the United States ranked first with 174 papers,followed by China with 107 papers.In terms of journal distribution,Forensic Science International:Genetics had the largest number of papers,which accounted for 20%of the total papers.In terms of author collaboration,a total of 2 079 authors participated in body fluid identification research,and the author collaboration network showed a clearly clustered distribution.The keywords analysis revealed that re-search hotspots focused on traditional methods,specific RNA molecular markers,DNA methylation,spectroscopy,and the application of microbiomics.Conclusion Research in the field of forensic body fluid identification is thriving,and research institutions and teams should strengthen their collaboration.Establishing unified result interpretation standards and systems and exploring the multiple biomarkers combined application methods will be the research hotspots and important directions for future research in this field.

Objective:To explore the effect and mechanism of CD147 on differentiation of circulating fibrocytes and its pro-inflammatory and pro-fibrotic function.Methods:Circulating fibrocytes were extracted from peripheral blood of asthma patients,stimu-lated with CD147,and intervened with CD147 antagonist AP-9 or p38/MAPK inhibitor SB203580.Cell viability was detected by CCK-8 method,cell migration was assessed by Transwell method,expressions of collagen type Ⅰ(COL-Ⅰ),CD45 and α-SMA were detected by immunofluorescence staining.Levels of cytokines such as TGF-β1,IL-4,IL-5 and IL-13 were detected by ELISA,and expression levels of COL-Ⅰ,fibronectin(FN),α-SMA,p-TAK1,p-P38 and other proteins were detected by Western blot.Results:Low dose of CD147 increased cell viability of circulating fibrocytes.CD147 significantly promoted migration of circulating fibrocytes and induces their differentiation into myofibrocytes.CD147 significantly increased secretion of cytokines such as TGF-β1,IL-4,IL-5 and IL-13 in circulating fibrocytes.CD147 significantly increased expressions of COL-Ⅰ,FN,α-SMA,p-TAK1,p-P38 in circulating fibrocytes.AP-9 or SB203580 significantly inhibited effect of CD147 on circulating fibrocytes.Conclusion:CD147 can promote proliferation,mi-gration,differentiation and pro-inflammatory and profibrotic function of circulating fibrocytes in vitro,and TAK1-p38/MAPK signaling pathway is involved in CD147-mediated regulation of circulating fibrocytes.

Patients with advanced pregnancy complicated by acute ST-segment elevation myocardial infarction are relatively rare both domestically and internationally,and there are currently no relevant guidelines to guide clinical treatment.In this case,a 39-year-old pregnant woman was admitted to the hospital with sudden chest pain,and the electrocardiogram showed extensive anterior ST-segment elevation myocardial infarction.Coronary angiography showed subtotal subtotal occlusion of the proximal left anterior descending artery.Reperfusion and revascularization were given,and the blood flow grade of the trial of thrombolytic in myocardial infarction was restored.Complete intravascular ultrasonography to determine the cause of occlusion due to spontaneous hematoma of the left anterior descending artery.After the operation,a reasonable antiplatelet and anticoagulant treatment regimen was selected according to the coronary artery lesion,and the pregnancy was terminated at the appropriate time,and 1 live male baby was successfully delivered.Maternal and fetal health was followed up after 1、3 and 6 months.Through the experience and summary of the treatment process,combined with the literature,the pathogenesis of this disease is discussed,and the strategy of revascularization,the selection of antithrombotic drugs and the timing of pregnancy termination are discussed in depth for clinical reference.

Objective:To investigate the detection status of pulmonary tuberculosis (PTB) among patients aged ≥65 years in China and provide evidence for improving PTB prevention and control in this population.Methods:The data were collected from the tuberculosis subsystem of Chinese Disease Control and Prevention Information System, and the case information of elderly PTB patients aged ≥65 years old who were registered in designated tuberculosis medical institutions nationwide from January 1, 2015 to December 31, 2023.Descriptive epidemiological methods were used to analyze trends in detection status, regional differences, and demographic characteristics.Results:From 2015 to 2023, 1 567 047 elderly PTB detection were identified, accounting for 25.1% of all PTB patients (1 567 047/6 243 215). The average registration rate for elderly PTB patients was 96.9 per 100 000, approximately twice that of the general population. The registration rate declined over the years ( Z=-2.61, P=0.009) but increased in 2018 and 2023. The proportion of elderly PTB patients rose annually, from 21.3% in 2015 to 32.4% in 2023 ( Z=2.30, P=0.022). Active case-finding accounted for only 3.0% (47 049/1 567 047) of patients on average during the study period, peaking at 7.3% (14 123/194 615) in 2018 before declining. The registration rates of elderly tuberculosis patients are relatively higher in central and western regions. In the central region, the average registration rate was 113.8 per 100 000, with a proportion of active case detection of 0.4% (2 532/570 059). In the western region, the average registration rate was 130.0 per 100 000, and the proportion of active case-finding was 7.6% (41 973/549 998). Subgroups with notably lower active detection proportions included males (2.5%, 27 443/1 101 091), those aged 80-84 years (2.2%, 2 978/133 855), and migrant populations (0.5%, 1 635/307 673). Conclusions:The burden of PTB among the elderly aged ≥65 years in China remains high, with a low proportion of active case-finding from 2015-2023. There is an urgent need to strengthen health education and active screening to improve the early diagnosis and prevention of tuberculosis in the elderly.

OBJECTIVE: To investigate the safety and efficacy of avatrombopag（AVA） combined with rhIL-11 in treating thrombocytopenia induced by chemotherapy in acute myeloid leukemia. METHODS: The clinical information of 8 patients in the real world who received avatrombopag combined with rhIL-11 in cancer treatment-induced thrombocytopenia(CTIT) after AML chemotherapy were retrospectively analyzed, and at the same time, 8 patients who received rhIL-11 only in CTIT after AML chemotherapy served as the control group, A preliminary observation was to summarize and compare the therapeutic efficacy and adverse effects between the two groups. RESULTS: D3 and D7 platelet counts were not significantly different between the observation group and the control group after treatment. The platelet counts in the observation group was significantly higher than those of the control group on the 10th day after treatment (P < 0.01). The adverse reactions, such as weakness, abdominal pain, fatigue, nausea and edema after treatment were mild in the observation group and the control group. Except for one patient in the observation group who had a history of cerebral infarction before the onset of the disease and was routinely taking antiplatelet drugs, no thrombosis events occurred in the patients in the observation and control groups during the period of administration of the drug, and the total incidence rate of adverse reactions was not significantly different between the two groups. CONCLUSION The combination of AVA and rhIL-11 can enhance platelet recovery in CTIT of AML patients after chemotherapy. Compared with the rhIL-11 alone group, the platelet recovery time in AVA+rhIL-11 group was significantly shorter, the platelet count on the 10th day after drug administration was significantly higher. No statistically significant difference in the total incidence rate of adverse reactions was observed between rhIL-11 alone group and AVA+rhIL-11 group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Thrombocytopenia/chemically induced* ; Interleukin-11/therapeutic use* ; Retrospective Studies ; Adult ; Thiophenes/therapeutic use* ; Platelet Count ; Female ; Male ; Middle Aged ; Thiazoles

OBJECTIVE: To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: From September 2021 to September 2023, we enrolled LDH patients (LDH group, n=31) and age- and sex-matched healthy controls (HCs, n=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2). SMT was administered once every other day for 30 min per session, totally 14 treatment sessions over a span of 4 weeks. HCs did not receive SMT treatment and underwent only one fMRI scan. Additionally, participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale (VAS) and the Japanese Orthopedic Association (JOA) score, whereas HCs did not undergo clinical scale assessments. The effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Correlation analyses were conducted between specific brain regions and clinical scales. RESULTS: Following SMT treatment, pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the brain. In comparison to TP1, TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L (voxelwise P<0.005; clusters >30; FDR correction). Additionally, the most substantial enhancement in ReHo values was observed for the Cuneus_R, while the most prominent reduction was noted for the Olfactory_R (voxelwise P<0.005; clusters >30; FDR correction). Moreover, a comparative analysis revealed that, in contrast to HCs, LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L (voxelwise P<0.005; clusters >30; FDR correction). Furthermore, the most significant enhancement in ReHo values was observed for Postcentral_L, while the most prominent reduction was identified for ParaHippocampal_L (voxelwise P<0.005; clusters >30; FDR correction). Notably, correlation analysis with clinical scales revealed a robust positive correlation between the Cuneus_R score and the rate of change in the VAS score (r=0.9333, P<0.0001). CONCLUSIONS Long-term chronic lower back pain in patients with LDH manifests significant activation of the "AUN-DMN-S1-SAN" neural circuitry. The visual network, represented by the Cuneus_R, is highly likely to be a key brain network in which the analgesic efficacy of SMT becomes effective in treating LDH patients. (Trial registration No. NCT06277739).
Humans ; Magnetic Resonance Imaging ; Intervertebral Disc Displacement/diagnostic imaging* ; Male ; Female ; Brain/diagnostic imaging* ; Adult ; Manipulation, Spinal/methods* ; Middle Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management ; Rest ; Case-Control Studies

OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats