Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N⁶-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
DNA, Mitochondrial/metabolism* ; Mouth Mucosa/pathology* ; Hypoxia/immunology* ; Methyltransferases/metabolism* ; Blood Platelets/metabolism* ; Animals ; Periodontitis/immunology* ; Humans ; Platelet Activation ; Mice

Objective To investigate the medication characteristics of Professor Gu Shizh in the treatment of lumbar disc herniation based on various data mining techniques.Methods The outpatient case records of Professor Gu was collected from January 2018 to September 2024 in the Guoyitang outpatient department of Beijing University of Chinese Medicine(BUCM)and BUCM Famous Elderly TCM Inheritance Research Integrated Platform.Patients with lumbar disc herniation mentioned in Professor Gu Shizhe's book of Zhi Zhen Zhi Yao were also be screened.R Studio 2024.4.3.2 was used for descriptive analysis and Apriori was used for association rule analysis.SPSS Statistics 27.0 was used for clustering analysis,and chiplot website was used for visualize the properties,tastes and meridians of drugs.Cytoscape 3.10.2 was used to build a network of"high frequency drug association",and combined with the TCM theories characteristics and medicine law used by professor Gu Shine in the treatment of lumbar disc herniation were summarized.Results A total of 63 cases were collected,involving 194 prescriptions and 187 kinds of Chinese materia medica.The top 30 drugs with the highest frequency were extracted,and the top 6 drugs were Angelicae Pubescentis Radix,Taxilii Herba,salt Eucommiae Cortex,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Chuanxiong Rhizoma,Gentianae Macrophyllae Radix.The main tastes were sweet,bitter and pungent,the main properties were warm and neutral.The main meridians were liver,spleen,lung,kidney and stomach meridians.Three core medicinal combinations were obtained by clustering analysis,including Duhuo Jisheng Decoction,Gegeng Decoction,Zhijing Powder and Xuduan Pill.Conclusion The focus of Professor Gu's treatment for lumbar disc herniation is to nourish the liver and kidneys,warm and replenish qi and blood,reflecting the characteristics of"qi and blood are in harmony,essence and blood are equally emphasized"in medication

Objective To investigate the medication characteristics of Professor Gu Shizh in the treatment of lumbar disc herniation based on various data mining techniques.Methods The outpatient case records of Professor Gu was collected from January 2018 to September 2024 in the Guoyitang outpatient department of Beijing University of Chinese Medicine(BUCM)and BUCM Famous Elderly TCM Inheritance Research Integrated Platform.Patients with lumbar disc herniation mentioned in Professor Gu Shizhe's book of Zhi Zhen Zhi Yao were also be screened.R Studio 2024.4.3.2 was used for descriptive analysis and Apriori was used for association rule analysis.SPSS Statistics 27.0 was used for clustering analysis,and chiplot website was used for visualize the properties,tastes and meridians of drugs.Cytoscape 3.10.2 was used to build a network of"high frequency drug association",and combined with the TCM theories characteristics and medicine law used by professor Gu Shine in the treatment of lumbar disc herniation were summarized.Results A total of 63 cases were collected,involving 194 prescriptions and 187 kinds of Chinese materia medica.The top 30 drugs with the highest frequency were extracted,and the top 6 drugs were Angelicae Pubescentis Radix,Taxilii Herba,salt Eucommiae Cortex,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Chuanxiong Rhizoma,Gentianae Macrophyllae Radix.The main tastes were sweet,bitter and pungent,the main properties were warm and neutral.The main meridians were liver,spleen,lung,kidney and stomach meridians.Three core medicinal combinations were obtained by clustering analysis,including Duhuo Jisheng Decoction,Gegeng Decoction,Zhijing Powder and Xuduan Pill.Conclusion The focus of Professor Gu's treatment for lumbar disc herniation is to nourish the liver and kidneys,warm and replenish qi and blood,reflecting the characteristics of"qi and blood are in harmony,essence and blood are equally emphasized"in medication

Objective:To analyze the dose-response relationship of 99Tc m-dimercaptosuccinic acid (DMSA) in pediatric renal static imaging. Methods:A retrospective analysis of children (model group: n=199, 81 males, 118 females; validation group: n=30, 13 males, 17 females; all age: 1 month-14 years) who underwent 99Tc m-DMSA renal static imaging from January 2022 to November 2023 in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology were conducted. Post-administration radiation counts and related clinical data were collected. Imaging quality was evaluated using visual analogue scoring (VAS). ROC curve analysis was used to assess the relationship between radiation count intensity (RCI) and imaging quality. A nonlinear mixed-effects modeling method was employed to establish the dose-response relationship for 99Tc m-DMSA in pediatric renal static imaging. Internal and external validations of the model were performed. Final model was utilized to evaluate patient dosing protocols. Results:Body weight was considered as a significant determinant of the dose-response relationship in 99Tc m-DMSA renal static imaging( χ2 values: 120.79, 116.36, both P<0.05). ROC curve analysis showed that the quality of diagnostic images was acceptable when the anterior renal RCI was ≥32.61 (cut-point) and the posterior renal RCI was ≥35.46 (cut-point). Both internal and external validation results demonstrated that the dose-response model established exhibited good prediction performance. Based on the final model graph, the image quality could meet the requirements for clinical diagnosis. Conclusions:The 99Tc m-DMSA dose-response model for pediatric renal static imaging is successfully established. Individualized dosage based on the model can provide a reference for clinical individualized dosing decision-making.

Objective To investigate the effects of long-term exposure to three new types of light emitting diode (LED) sources on the behavior, learning, and memory of rats. Methods A total of 160 specific pathogen-free SD rats were divided into eight groups as followed, trichromatic fluorescent lamps color temperature control group, violet-chip full-spectrum white LED group, blue-chip white LED group, and blue-chip full-spectrum white LED group based on the light sources types, with color temperature of 4 000 K and 6 500 K groups in each group using the 4×2 factorial design. There were 20 rats in each group, with half of the rats were males and half females. Rats were exposed to artificial lighting, and the illumination was set at 750 lx. The rats in each group were exposed to different lighting environments for 12 hours per day for 24 weeks. The open-field and step-down tests were conducted in rats after 24 weeks exposure, followed by sacrifice of rats and measurement of organ coefficients. Differences in body weight, organ coefficients, and neurobehavioral indexes of rats in different groups were compared. Results The spleen coefficient of female rats decreased in blue-chip white LED of 6 500 K color temperature group, and the liver coefficient of male rats decreased in the violet-chip full-spectrum white LED of 4 000 K color temperature, blue-chip full-spectrum white LED of 4 000 K color temperature, and blue-chip full-spectrum white LED of 6 500 K color temperature groups, compared with the same-sex rats in trichromatic fluorescent lamps with same-color temperature control group (all P<0.05). The result of different types of light sources compared in the open-field test showed that the index of total distance and movement speed of female rats in the blue-chip full-spectrum white LED group were lower than those in the other three groups, and the time cost to the central area was longer than that in the blue-chip white LED group and the violet-chip full-spectrum white LED group (all P<0.05). The total distance and movement speed of male rats in the blue-chip full-spectrum white LED group were longer or higher than those in the violet-chip full-spectrum white LED group (all P<0.05). Based on the comparison of color temperature, the time and total distance of male rats in 6 500 K color temperature group were lower than that in the 4 000 K color temperature group (both P<0.05). In the step-down test, both male and female rats in the blue-chip full-spectrum white LED group made more errors compared with other three groups with the same gender (all P<0.05). Conclusion Based on the experimental conditions of this study, the blue-chip full-spectrum white light LED affects behavior, learning and memory of the rats, and trichromatic fluorescent lamp has the lowest effect on neurobehavior. The color temperature also affects behavior of the rats, and high color temperature has higher risk.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

OBJECTIVE:To systematically review the effectiveness and safety of olanzapine in the prevention and treatment of chemotherapy-induced nausea and vomiting(CINV),and provide evidence-based reference for clinical treatment. METHODS:Re-trieved from Medline,PubMed,EMBase,Cochrane Library,Clinical Trials.gov,CBM,CJFD,VIP and Wanfang Database,ran-domized controlled trials (RCT) about olanzapine (test group) versus other drugs or conventional antiemetic regimen (control group)in the prevention and treatment of CINV were collected,Meta-analysis was performed by using Rev Man 5.3 software after data extraction and quality evaluation by modified Jadad. RESULTS:Totally 19 RCTs were included,involving 1 794 patients. Re-sults of Meta-analysis showed,olanzapine can significantly improve the complete control rate of patients with acute CINV [RR=1.12,95%CI(1.06,1.18),P<0.001],delayed CINV[RR=1.26,95%CI(1.14,1.39),P<0.001],overall CINV [RR=1.62,95%CI (1.32,1.99),P<0.001] and breakthrough CINV[RR=2.05,95%CI(1.47,2.86),P<0.001],there were significant differences be-tween 2 groups;there were no significant differences in the incidence of tiredness,dizziness,lethargy and constipation(P>0.05). CONCLUSIONS:Olanzapine is safe and effective in the prevention and treatment of CINV and can be recommended in treating breakthrough and refractory CINV. Besides,olanzapine in the prevention and treatment of CINV belongs to“off-label use”,so the clinicians should have a comprehensive consideration of chemotherapy and patients’consent.

Inorganic layered materials with the open structure of low dimension and good biological compatibility and stability are considered as one of the most promising materials for immobilizing biomolecules, which can not only adjust the spacing of layers according to guest molecular size to prevent leakage of guest molecule, but also reduce the effects of surrounding elements on immobilized molecules significantly. Moreover, they can promote electron transfer between enzyme and the electrode. Therefore, the inorganic layered materials have great application potential in electrochemical sensors. This paper reviews the ways of immobilizing guest molecules of inorganic layered materials and the applications and development prospects of the different types of inorganic layered materials including cationic, anionic and nonionic inorganic layered materials in electrochemical sensor.

Objective To explore the physiological characteristics of synaptic transmission of anterior horn early development in thorac-ic spinal cord mediated byα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in rats. Methods 36 Wistar rats were divided into embryonic 17 days group (E17, n=12), embryonic 20 days group (E20, n=12) and postnatal 7 days group (P7, n=12). Immuno-fluorescent staining of calmodulin-dependent protein kinaseⅡ(CaMKⅡ) was used to test the distribution of AMPA receptors. Multi-elec-trode array technique (MED-64 system) was used to test the changes of field excitatory post-synaptic potential (fEPSP) of synaptic transmis-sion mediated by AMPA receptor. Results There was small amount of CaMKⅡ-positive neurons existing in gray matter of spinal cord at E17, CaMKⅡ-positive neurons migrated to the center, and the number of neurons became more and more in E20 and P7 rats. The number of evoked fEPSP gradually increased in rats from E17 to P7, and could be blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The range of synaptic connection in spinal cord gray matter significantly reduced (P<0.001). Conclusion AMPA receptors participate in the early development of spinal cord in rats and act as the main excitatory receptor of functional synaptic connection in neural network of ventricornu.

OBJECTIVETo explore the role of myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) in myocardial injury induced by hind-limb ischemia-reperfusion (IR) in rats.

METHODSRat models of bilateral hindlimb IR established using a tourniquet were randomized into 9 groups, including a normal control group normal, 2 ischemic groups with hindlimb ischemia for 2 and 4 h, and 6 IR groups with a 4-h ischemia followed by reperfusion for 0.5, 2, 4, 6, 12, and 24 h. The plasma and myocardial levels of MPO and TNF-α in each group were measured, and the myocardial expression of TNF-α was determined with immunohistochemistry.

RESULTSCompared with the normal control group, the rats with a 2-h ischemia showed significantly increased levels of MPO and TNF-α in the plasma and myocardium. Compared with those in rats with a 4-h ischemia, the plasma and myocardial MPO levels increased significantly at 0.5 and 2 h of reperfusion, respectively; the plasma TNF-α level increased significantly at 4 h of reperfusion and myocardial TNF-α level decreased obviously at 12 h; plasma levels of MPO and TNF-α both significantly decreased at 24 h. The plasma MPO and TNF-α and myocardial TNF-α reached the peak levels at 4 h of reperfusion, and the peak myocardial MPO level occurred at 6 h. Immunohistochemistry showed that TNF-α positivity moderately increased after hindlimb ischemia, and further increased at 4 h of reperfusion but obviously reduced at 24 h.

CONCLUSIONThe activation of systemic and local neutrophils and inflammatory cytokines may play an important role in myocardial injury induced by hindlimb IR in rats.

Animals ; Disease Models, Animal ; Hindlimb ; blood supply ; Ischemia ; metabolism ; Male ; Myocardium ; metabolism ; Peroxidase ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism