ObjectiveTo identify protein biomarkers and potential therapeutic targets associated with metabolic dysfunction-associated fatty liver disease （MAFLD） through an integrative multi-omics analysis. MethodsLarge-scale plasma protein quantitative trait locus data were integrated with MAFLD genome-wide association study data， and a proteome-wide Mendelian randomization analysis was performed. Summary data-based Mendelian Randomization （SMR）/heterogeneity in dependent instruments （HEIDI） test and colocalization analysis were used to assess significant proteins. The independent samples t-test was used for comparison of continuous data with homogeneity of variance between two groups， and the Welch-corrected t-test was used for comparison of continuous data with heterogeneity of variance. The transcriptomic validation results were compared with the Mendelian randomization results to evaluate the changing trends of gene expression， and boxplots were used to display the expression distribution of candidate genes between groups. ResultsAmong 7 130 proteins analyzed， 40 showed a causal relationship with MAFLD， among which 26 increased the risk of MAFLD and 14 exerted a protective effect against MAFLD （FDR<0.05）. Nine proteins were supported by SMR/HEIDI （P_SMR<0.05， P_HEIDI>0.05）， and 14 showed a strong colocalization signal （PPH₄>0.9）. The transcriptomic analysis identified 5 differentially expressed proteins （all P<0.05）， i.e.， adenosine diphosphate-ribosylation factor-like GTPase 2， insulin-like growth factor binding protein 2， casein kinase 1 delta （CSNK1D）， leucine-rich repeat neuronal 1， and moesin （MSN）. In vitro validation showed upregulated expression levels of MSN （1.612±0.346 vs 0.569±0.077， P<0.05）， 14-3-3 protein theta （YWHAQ） （1.267±0.126 vs 0.313±0.029， P<0.05）， and CSNK1D （0.871±0.025 vs 0.431±0.080， P<0.05） and a downregulated expression level of histone deacetylase 8 （0.637±0.059 vs 1.097±0.260， P<0.05） in the MAFLD cell model. Functional annotation showed that CSNK1D participated in circadian and metabolic regulation， YWHAQ modulated the Hippo pathway and lipid signal transduction， and MSN was associated with cytoskeletal remodeling and fibrogenic responses. ConclusionThe integrative proteogenomic analysis in this study shows that CSNK1D， YWHAQ， and MSN may be key mediators in the pathogenesis of MAFLD. These proteins have the potential to serve as novel biomarkers and therapeutic targets， providing new directions for research on disease mechanisms and the development of intervention strategies.

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 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.

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.?

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 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 incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore the short-term outcome and safety of 577 nm subthreshold micropulse laser(SML)in the treatment of central serous chorioretinopathy(CSC).Methods The clinical data of 22 patients(24 eyes)with CSC who were admitted to First Affiliated Hospital of Army Medical University from April 2023 to April 2024 were retrospectively analyzed.The 12 eyes had acute CSC,the 12 eyes had chronic CSC,and all of them were treated with SML.The changes of best-corrected visual acuity(BCVA),central macular thickness(CMT),subfoveal choroidal thickness(SFCT),subretinal fluid height(SRFH),and central macular sensitivity(CMS)before treatment and 1 month after treatment were analyzed.The absorption of subretinal fluid 1 month after treatment and related complications were observed.Results Compared with those before treatment,the CMT,SFCT,and SRFH 1 month after treatment significantly declined(P<0.05).The LogMAR BCVA and CMS 1 month after treatment were significantly improved compared with those before treatment(P<0.05).The CMS(r=-0.555,P=0.006)and LogMAR BCVA(r=0.439,P=0.032)before treatment were significantly correlated with SRFH before treatment.The change of SRFH was significantly correlated with CMT before treatment(r=0.616,P=0.001),but without correlation with SFCT before treatment(r=0.168,P=0.431).One month after treatment,11 eyes had complete absorption of subretinal fluid,12 eyes had varying degrees of absorption,and 1 eye had an increase in SRFH.No related adverse reactions were observed.Conclusion The 577 nm SML has a good therapeutic effect on CSC,which can significantly improve the macular structure and central visual function,with good safety.

Panax notoginseng is the dried root and rhizome of Panax notoginseng(Burk.)F.H.Chen,a perennial erect herb of the genus Ginseng of the family Wujiaceae.As a traditional Chinese medicine in our country,Panax notoginseng has a good tonic effect,and the Dictionary of Traditional Chinese Medicines has the words that Panax notoginseng is used to tonify the blood,remove the blood stasis and damage,and stop epistaxis.It can also be used to pass the blood and tonify the blood with the best efficacy,and it is the most precious one of the prescription med-icines.Eaten raw,it removes blood stasis and generates new blood,subdues swelling and stabilizes pain,stops bleeding with-out leaving stasis,and promotes blood circulation without hurting the new blood;taken cooked,it can be used to replenish and strengthen the body.Notoginsenoside R1 is a characteristic com-pound in the total saponin of Panax ginseng.In recent years,China's aging has been increasing,and the incidence of neuro-logical disorders has been increasing year by year.Meanwhile,reports on notoginsenoside R1 in the treatment of neurological disorders are increasing,and its neuroprotective effects have been exerted with precise efficacy.The purpose of this paper is to review the treatment of neurological diseases and the mecha-nism of action of notoginsenoside R1,so as to provide a certain theoretical basis for clinical use and new drug development.