Objective To detect the content of 5'-tRF-GlyGCC in peripheral blood and explore its applica-tion value in the early diagnosis of colorectal cancer(CRC).Methods Peripheral blood samples were randomly collected from 99 CRC patients,11 patients with enteritis,17 patients with colorectal polyps and 99 healthy indi-viduals in the same period at the Affiliated Hospital of Guizhou Medical University.The content of 5'-tRF-GlyGCC in total RNA of peripheral blood was detected by fluorescence RT-PCR.The receiver operating characteristic curve(ROC)was established to analyze the value of 5'-tRF-GlyGCC content in the early diagnosis of CRC and to explore the relationship between its content and the clinical and pathological characteristics of CRC patients.Results The content of 5'-tRF-GlyGCC in the peripheral blood of CRC patients and colorectal polyp patients was significantly higher than that of healthy individuals and patients with enteritis,and the differences were statistically significant(P<0.05).The area under the curve(AUC)of 5'-tRF-GlyGCC for diagnosing CRC was 0.817(95%CI:0.763～0.871),with a diagnostic sensitivity of 56.7%and a specificity of 99.9%.The content of 5'-tRF-GlyGCC in peripheral blood was significantly positively correlated with the levels of CEA and CA19-9 in CRC patients.Conclusion The detection of 5'-tRF-GlyGCC in peripheral blood has a high application value in the early diagnosis of CRC and can be used for clinical reference and research.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

Objective To detect the content of 5'-tRF-GlyGCC in peripheral blood and explore its applica-tion value in the early diagnosis of colorectal cancer(CRC).Methods Peripheral blood samples were randomly collected from 99 CRC patients,11 patients with enteritis,17 patients with colorectal polyps and 99 healthy indi-viduals in the same period at the Affiliated Hospital of Guizhou Medical University.The content of 5'-tRF-GlyGCC in total RNA of peripheral blood was detected by fluorescence RT-PCR.The receiver operating characteristic curve(ROC)was established to analyze the value of 5'-tRF-GlyGCC content in the early diagnosis of CRC and to explore the relationship between its content and the clinical and pathological characteristics of CRC patients.Results The content of 5'-tRF-GlyGCC in the peripheral blood of CRC patients and colorectal polyp patients was significantly higher than that of healthy individuals and patients with enteritis,and the differences were statistically significant(P<0.05).The area under the curve(AUC)of 5'-tRF-GlyGCC for diagnosing CRC was 0.817(95%CI:0.763～0.871),with a diagnostic sensitivity of 56.7%and a specificity of 99.9%.The content of 5'-tRF-GlyGCC in peripheral blood was significantly positively correlated with the levels of CEA and CA19-9 in CRC patients.Conclusion The detection of 5'-tRF-GlyGCC in peripheral blood has a high application value in the early diagnosis of CRC and can be used for clinical reference and research.

Objective:To construct an evaluation index system for rural order-oriented general practice residents based on Entrustable Professional Activities (EPAs) and conduct an empirical analysis. ?Methods:A mixed-methods study design was adopted (November 2022-April 2023). The preliminary draft of the index system was developed through literature review and group discussions, then refined and improved via two rounds of expert consultation using the Delphi method. The analytic hierarchy process (AHP) was applied to determine the weight of each index. Meanwhile, questionnaires were distributed to 181 participants, including general practitioners from general hospitals, general practitioners from community hospitals, and general practice residents. The scores of the three groups regarding the importance and feasibility of the indices were compared. Ten general practitioners of the above three types were selected for semi-structured interviews on their cognitive and practical aspects of the system. ?Results:The positive coefficients of the two rounds of expert consultation were 16/17 and 16/16, respectively. The expert authority degree was >0.70, and the test of coordination coefficient was statistically significant ( P<0.05). Finally, an index system consisting of 20 first-level indices and 56 second-level indices was established. In terms of weight, among the first-level indices,"EPA1: Information Acquisition"had the highest weight (0.11), while"EPA12: Clinical Research"had the lowest (0.02). Among the second-level indices, "Medical History Taking" and "Physical Examination" under EPA1 had the highest weight (both 0.056), while "Healthcare for Patients with Severe Mental Illness" and "Healthcare for Disabled and Handicapped Populations" under EPA15 had the lowest (both 0.003). The 181 participants gave scores ranging from 4.49 to 4.92 for the importance of the 20 first-level indices and from 4.16 to 4.81 for their feasibility. Only for" EPA19: Common Diseases in Primary Care and Health Management", the feasibility score given by general practitioners from community hospitals was higher than that from general hospitals ( t=2.157, P=0.032); no statistically significant differences were observed among the groups for the other indices ( P>0.05).The interview results showed that general practitioners have a relatively high level of recognition for this system, but there is still room for improvement in its practical application.? Conclusions:The evaluation index system for rural order-oriented general practice residents constructed based on EPAs has high reliability, and it is consistently recognized by different types of general practitioners. It can provide a reference for the cultivation of post competency of this group.?

Objective:To construct an evaluation index system for rural order-oriented general practice residents based on Entrustable Professional Activities (EPAs) and conduct an empirical analysis. ?Methods:A mixed-methods study design was adopted (November 2022-April 2023). The preliminary draft of the index system was developed through literature review and group discussions, then refined and improved via two rounds of expert consultation using the Delphi method. The analytic hierarchy process (AHP) was applied to determine the weight of each index. Meanwhile, questionnaires were distributed to 181 participants, including general practitioners from general hospitals, general practitioners from community hospitals, and general practice residents. The scores of the three groups regarding the importance and feasibility of the indices were compared. Ten general practitioners of the above three types were selected for semi-structured interviews on their cognitive and practical aspects of the system. ?Results:The positive coefficients of the two rounds of expert consultation were 16/17 and 16/16, respectively. The expert authority degree was >0.70, and the test of coordination coefficient was statistically significant ( P<0.05). Finally, an index system consisting of 20 first-level indices and 56 second-level indices was established. In terms of weight, among the first-level indices,"EPA1: Information Acquisition"had the highest weight (0.11), while"EPA12: Clinical Research"had the lowest (0.02). Among the second-level indices, "Medical History Taking" and "Physical Examination" under EPA1 had the highest weight (both 0.056), while "Healthcare for Patients with Severe Mental Illness" and "Healthcare for Disabled and Handicapped Populations" under EPA15 had the lowest (both 0.003). The 181 participants gave scores ranging from 4.49 to 4.92 for the importance of the 20 first-level indices and from 4.16 to 4.81 for their feasibility. Only for" EPA19: Common Diseases in Primary Care and Health Management", the feasibility score given by general practitioners from community hospitals was higher than that from general hospitals ( t=2.157, P=0.032); no statistically significant differences were observed among the groups for the other indices ( P>0.05).The interview results showed that general practitioners have a relatively high level of recognition for this system, but there is still room for improvement in its practical application.? Conclusions:The evaluation index system for rural order-oriented general practice residents constructed based on EPAs has high reliability, and it is consistently recognized by different types of general practitioners. It can provide a reference for the cultivation of post competency of this group.?

Objective To investigate the activated phenotype and the expression of the receptor of advanced glycation endproducts(RAGE)of astrocytes after hypoxic-ischemic brain damage(HIBD)in neonatal rats and the effects of gastrodin(GAS)intervention on them.Methods Totally 48 neonatal 3 days SD rats were used to construct HIBD model and randomly divided into sham group,HIBD group and HIBD+GAS group(100 mg/kg),and the expressions of Al type astrocyte marker C3,A2 type astrocyte marker S100A10,RAGE,tumor necrosis factor-α(TNF-α),brain-derived neurotrophic factor(BDNF),and insulin-like growth factor(IGF-1)in the corpus callosum of the ischemic side were detected by Western blotting and immunohistochemical staining on day 1 and day 3 after HIBD.TNC-1 cells were divided into control group,oxygen glucose deprivation(OGD)group,OGD+GAS(0.34 mmol/L)group and GAS group,and then the protein expressions of RAGE,TNF-α,BDNF and IGF-1 were detected by Western blotting and immunofluorescence.Results In vivo,Western blotting showed that compared with the sham group,the protein expression levels of C3,S100A10,RAGE,TNF-α and IGF-1 in the 1 day and 3 days groups after HIBD group in 1 day group were significantly higher than those in the sham group(P＜0.05),but the protein expression level of BDNF decreased in 1 day group and increased in 3 days group(P＜0.05).Compared with the HIBD group,the C3,RAGE and TNF-α protein expression levels were significantly attenuated in the HIBD+GAS group(P＜0.05),and the protein expression levels of BDNF and IGF-1 further increased(P＜0.05).The protein expression of S100A10 in the 3 days group was higher than that in the HIBD group after GAS treatment(P＜0.05).The immunohistochemical staining results of C3,S100A10,and RAGE in the 1 day and 3 days groups after HIBD were consistent with Western blotting results.Furthermore,the protein expressions of RAGE and TNF-α were significantly enhanced in OGD-stimulated astrocytes(P＜0.05).After GAS intervention,while the expressions of both RAGE and TNF-α decreased significantly(P＜0.05),the expressions of BDNF and IGF-1 increased significantly(P＜0.05).Conclusion With inhibiting the up-regulation of RAGE signal in astrocyte after HIBD and expressions of A1 astrocyte and neuroinflammatory factors,gastrodin can promot the expressions of A2 astrocyte and nutritional factors,which play an important role in neuro-protective effect.

Objective To explore the mechanism of lepirudine in inhibiting thrombin activation by regulating the Notch signaling pathway for the treatment of acute pulmonary embolism.Methods SD rats were randomly divided into sham group,model group and experimental group,with 10 rats in each group.Acute pulmonary embolism model was established by autologous thrombosis in model group and experimental group.Experimental group was intraperitoneally injected with lepiludine(2.0 mg·kg-1)at 24 h,0.5 h before and 24 h after modeling,respectively,while sham group and model group were intraperitoneally injected with 0.9％NaCl at the same time point.The contents of platelet P-selectin 62(CD62P),platelet granule membrane protein-140(GMP-140),N-terminal pro-brain natriuretic peptide(NT-proBNP)and cardiac troponin T(cTnT)in rat plasma were detected by enzyme-linked immunosorbent assay(ELISA).The contents of thromboxane B2(TXA2)and prostacyclin(PGI2)in rat plasma were detected by RIA.The protein expression levels of Notch receptor protein 1(Notch1)and Notch ligand protein 1(JAGGED1)in lung tissue of rats were detected by Western blot.Results The plasma CD62P content in sham group,model group and experimental group were(9.31±1.31),(25.03±2.66)and(11.42±2.21)ng·mL-1;the contents of GMP-140 were(43.23±5.61),(114.33±14.02)and(73.44±6.97)ng·mL-1;the contents of NT-proBNP were(14.71±1.93),(20.57±3.46)and(11.07±3.06)ng·mL-1;cTnT content were(81.07±9.77),(233.24±27.61)and(134.76±15.00)pg·mL-1;TXA2 content were(231.06±17.33),(378.69±29.10)and(268.61±24.15)pg·mL-1;PGI2 content were(147.25±16.44),(104.37±11.62)and(136.09±13.40)pg·mL-1;the relative expression levels of Notch1 protein in lung tissue were 1.24±0.21,0.51±0.06 and 0.87±0.09;the relative expression levels of JAGGED1 protein were 1.02±0.15,0.17±0.02 and 0.28±0.06.Compared with sham group and experimental group,there were statistically significant differences in the above indexes in model group(P＜0.01,P＜0.001).Conclusion Lepirudine can inhibit thrombin activation in the treatment of acute pulmonary embolism by activating the Notch signaling pathway.

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Major depressive disorder (MDD) is one of the most disabling illnesses, and approximately one-third of patients with MDD fail to show significant improvement after multiple courses of antidepressants, eventually progressing to treatment-resistant depression (TRD), a more severe and complex subtype that is difficult to treat. Obsessive-compulsive disorder (OCD) is a type of mental disorder characterized by repetitive obsessions and/or compulsive behaviors, and the high rate of comorbidity with other psychiatric disorders has been identified as a hallmark feature of OCD. In particular, OCD frequently co-occurs with MDD, and when these two conditions overlap, the resulting comorbidity is characterized by more severe symptoms and an increased risk of suicide. Magnetic seizure therapy (MST) is a novel, non-invasive neuromodulation technique that is safe and effective in the treatment of TRD with less cognitive impairment. This paper describes a case of significant symptom improvement following 100 Hz accelerated MST treatment in a patient with comorbid TRD and OCD. As a novel treatment option, MST requires further large-scale clinical trials to explore in the future.