Steroid-induced avascular necrosis of femoral head（SANFH） is a bone and joint disease caused by prolonged and excessive steroid use. Its typical pathological features involve progressive circulatory disorders in the blood supply system of femoral head， leading to osteocyte apoptosis and bone tissue necrosis. As the disease progresses， it ultimately results in structural collapse and necrotic lesions of the femoral head， severely affecting patients' limb function and quality of life. Glucocorticoids mediate pathological damage through dual mechanisms， on the one hand， they disrupt the dynamic equilibrium between bone formation and resorption by suppressing osteoblast differentiation activity and activating osteoclastogenesis， on the other hand， they induce lipid metabolism disorders， inhibit angiogenesis， and impair endothelial cell function， thereby triggering microcirculatory disorders. Epimedii Folium and its active components exhibit multidimensional regulatory effects in SANFH prevention and treatment. Literature review reveals that it is rich in multiple active ingredients， primarily including total flavonoids of Epimedii Folium， icaritin， icariin， kaempferol， icariside Ⅱ， etc. These compounds exert multiple pharmacological effects（regulating bone metabolic homeostasis， modulating angiogenesis， correcting lipid metabolism disorders， and controlling cellular autophagy processes） through multiple signaling pathways， including Wnt/β-catenin， transforming growth factor（TGF）-β/bone morphogenetic protein（BMP）/Smad， mitogen-activated protein kinase（MAPK）， phosphoinositide 3-kinase/protein kinase B（PI3K/Akt）， osteoprotegerin/receptor activator of nuclear transcription factor-κB ligand/receptor activator of nuclear transcription factor-κB（OPG/RANKL/RANK）， etc. Based on existing research findings， this paper systematically elucidates the intervention mechanisms of active components in Epimedii Folium on key pathological processes of SANFH through the above pathways. It also deeply analyzes their regulatory roles in key nodes of different signaling pathways， aiming to provide valuable references for future clinical treatment and experimental research.

Neurofibromas are benign peripheral nerve sheath tumors. It is more common in neurofibromatosis type Ⅰ. However, isolated vagal nerve neurofibroma（VNN） of the neck is extremely rare, and only a few case reports have been reported. Its etiology and pathogenesis are not clear. The diagnosis is mainly based on pathological examination and immunohistochemistry, and surgical resection is the main treatment. This study reports a rare case of giant solitary vagus neurofibroma in the neck. The patient was a 29-year-old female who was found to have a mass on the right side of the neck by physical examination, which was considered to be a vagus nerve tumor by neck ultrasound and imaging examination. The tumor was completely removed during the operation, with the size of about 10.0 cm×2.5 cm, and the patient had no special discomfort. Postoperative pathology and immunohistochemistry confirmed neurofibroma. After surgery, the patient had right vocal cord paralysis, hoarseness, choking and paroxysmal cough. After swallowing function training and voice rehabilitation treatment in the department, the patient recovered satisfactorily. There was no complication and recurrence during the follow-up of 1 year. This article reviews the literature to improve the diagnosis and treatment of solitary vagus neurofibroma in the neck by combining its medical history, imaging features, pathology and immunohistochemistry, and surgical treatment.
Humans ; Female ; Adult ; Neurofibroma ; Vagus Nerve/pathology* ; Neck ; Cranial Nerve Neoplasms

In order to comprehensively deepen the reform of medical insurance payment methods and explore the establishment of a medical insurance payment system with Chinese features,five representative cities have been selected for analysis:Jinhua City in Zhejiang Province,Xiamen City in Fujian Province,Suixi City in Anhui Province,TianjinCity,and Zhenjiang City in Jiangsu Province.These regions have been chosen due to their typical ambulatory care payment reform.It summarises the features of ambulatory care payment reforms in different regions regarding implementing agencies,covered crowds and types of illnesses,and payment methods.It is recommended that a reasonable scope of implementation be selected and the reform purpose and basic conditions should be taken into account to explore an appropriate ambulatory care payment reform.It is proposed that an innovative payment method reform be implemented to promote healthcare and prevention integration,and to incorporate a value-oriented paradigm,thereby realizing the benefits of the doctor and patient insurance.

OBJECTIVE To investigate the horizontal transfer mechanisms and genetic evolutionary characteristics of virulence genes in hypervirulent Klebsiella pneumoniae(HvKP)and resistance genes in carbapenem-resistant K.pneumoniae(CRKP).METHODS The donor strain was a CRKP strain harboring both VIM and KPC resist-ance genes.The positive control was a CRKP strain containing blaIMP-4.The recipient strain was Escherichia coli J53.The horizontal transfer capability of the resistance genes was verified by plasmid conjugation assay.Fifty HvKP strains were collected from the First Affiliated Hospital of Jinan University from 2017 to 2021 and conjuga-ted with the plasmids of five CRKP strains which could mediate the transmission of drug resistance genes.The conjugants were screened by selective medium containing meropenem,and polymerase chain reaction(PCR)was used to detect the resistance and virulence genes in the conjugation-successful strains.The lethality of conjugants was verified by Galleria mellonella larval assays.RESULTS The donor CRKP strain had the ability to mediate re-sistance gene transmission.Its blaKPC gene was successfully transferred to E.coli J53,but the transference of the VIM gene failed.Five CRKP strains with the ability to mediate resistance gene transmission were screened,of which one strain carried both VIM and KPC resistance genes,and the other four strains carried the IMP-4 resist-ance gene.Only one CRKP strain with the blaIMP-4 resistance gene was successfully conjugated with HvKP,carry-ing both virulence genes(aerobactin and RmpA)and the blaIMP-4 resistance gene,with positive wire drawing test result.The Galleria mellonella larvae test showed that the conjugation-successful strain caused the death of all lar-vae within 24 hours.CONCLUSIONS In the hospital environment,CRKP and HvKP can form"superbugs"with both drug resistance and high virulence through plasmid conjugation,posing a severe challenge to clinical an-ti-infection treatment.It is necessary to strengthen the prevention and control of hospital-acquired infections.

Objective To explore the application values of different detection methods in monitoring the decline pattern of syphilis-spe-cific antibody in the non-congenital syphilis children.Methods A total of 80 non-congenital syphilis children were included in the study.The serum specimens were collected after birth,and the syphilis-specific antibodies were detected using electrochemilumines-cence immunoassay(ECLIA),western blotting(WB),treponema pallidum particle agglutination assay(TPPA),enzyme-linked im-munosorbent assay(ELISA),and toluidine red unheated serum test(TRUST).Follow-up was conducted every three months until the positive results of ELISA and TRUST turned to negative.Results The results of ECLIA showed that the syphilis-specific antibody lev-els in the non-congenital syphilis children declined to 25％of the level at birth within 2 to 3 months,and the rate of decline was inde-pendent of the initial concentration.WB analysis indicated that the specific IgG bands in non-congenital syphilis children at birth were consistent with those of their mother,and the sequence of specific antibodies decline was as follows:TPN47,TPN15,TPN45,and TPN17.Due to methodological limitations,the absorbance values of ELISA showed no significant change during the first three months after birth when high concentrations of antibodies were present in the samples,but it showed high sensitivity in the detection for the samples with low-concentration of syphilis antibodies.The detection rates of ECLIA,TPPA,and WB were compared by using ELISA as the reference method.At birth,the detection rates of syphilis antibodies were 100％,100％,and 90％,respectively.In 3 months after birth,the detection rates were 100％,100％,and 75％.In 6 months after birth,,they were 100％,46％,and 15％.In 9 months after birth,they were 83％,33％,and 0％.The positive rate of TRUST was 17.5％at birth.and turned to negative in 3 month of follow-up.Conclusion Syphilis specific IgG antibodies may fully transferred to the fetus and decline in a predictable pattern after birth.The comprehensive analysis for the results of the four methods suggested that dynamic detection using ECLIA method could be used to pre-dict the risk of non-congenital syphilis or terminate the follow-up at 3 months,while the seroconversion detected by WB was earlier than that by TPPA,while ELISA required the longest follow-up period.

Objective:Using Mendelian randomization analysis to investigate the unidirectional causal effects of gut microbiota on gout and serum uric acid levels.Methods:The Mendelian randomization analysis was conducted using summary statistics from genome-wide association studies (GWAS). The gut microbiota was used as the exposure factor, with gout and serum uric acid levels as the outcomes, utilizing the MiBioGen Consortium, FinnGen GWAS, and CKDGen Consortium meta-analysis databases. The analysis was performed using inverse variance weighted (IVW) method, MR-Egger, and weighted median (WM) approach. Additionally, sensitivity analysis was conducted by excluding heterogeneity and horizontal pleiotropy. This study used RStudio 4.3.1 software for analysis.Results:The IVW results confirmed that 17 microbiota taxa were associated with gout, including class Verrucomicrobiaceae [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], family Verrucomicrobiaceae [ OR(95% CI)=1.161(1.004, 1.344), P=0.044], genus Akkermansia [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], genus Collinsella [ OR(95% CI)=1.257(1.043, 1.516), P=0.016], genus Eubacterium hallii group [ OR(95% CI)=1.226(1.022, 1.471), P=0.027], genus Howardella [ OR(95% CI)=1.094(1.001, 1.195), P=0.046], genus Ruminococcaceae UCG010 [ OR(95% CI)=1.317(1.089, 1.593), P=0.004], order Clostridiales [ OR(95% CI)=1.182(1.007,1.387), P=0.041], order Verrucomicrobiales [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], class Melainabacteria [ OR(95% CI)=0.894(0.804, 0.994), P=0.038], family Streptococcaceae [ OR(95% CI)=0.851(0.727, 0.996), P=0.044], unknown family [ OR(95% CI)=0.890(0.800, 0.989), P=0.030], genus Streptococcus [ OR(95% CI)=0.836(0.710, 0.983), P=0.030], unknown genus [ OR(95% CI)=0.890(0.800, 0.989), P=0.030], genus Victivallis [ OR(95% CI)=0.857(0.736, 0.998), P=0.046], order Gastranaerophilales [ OR(95% CI)=0.890(0.800,0.989), P=0.030], and phylum Bacteroidetes [ OR(95% CI)=0.827(0.692, 0.989), P=0.037]. Additionally, 5 microbiota taxa were associated with serum uric acid levels: phylum Actinobacteria [ OR(95% CI)=0.963(0.925, 0.992), P=0.027], family ⅩⅢ [ OR(95% CI)=0.965(0.932, 1.008), P=0.035], genus Escherichia Shigella [ OR(95% CI)=1.047(1.005,1.089), P=0.034], genus Lachnospiraceae FCS020 group [ OR(95% CI)=0.974(0.941, 1.003), P=0.028], and genus Lachnospiraceae NC2004 group [ OR(95% CI)=0.966(0.943, 0.995), P=0.018]. No abnormalities in SNPs were found in the sensitivity analysis. Conclusion:An increase in the levels of class Verrucomicrobiae, family Verrucomicrobiaceae, genus Akkermansia, and genus Escherichia Shigella is associated with an increased risk of gout or serum uric acid levels, while an increase in the levels of class Melainabacteria, family Streptococcaceae, unknown family, phylum Actinobacteria, and family ⅩⅢ is associated with a decreased risk of gout or serum uric acid levels.

Objective To explore the impact of preoperative fibrinogen levels on the 1-year adverse outcomes after endovascular revascularization in patients with diabetes complicated with lower extremity arteriosclerosis obliterans(LEASO).Methods We collected the baseline clinical data of 289 patients with diabetes complicated with LEASO,who were admitted to The First Affiliated Hospital of Xi'an Jiaotong University from May 2020 to December 2022 for endovascular revascularization.All patients were followed up for 13 to 24 months after interventional therapy,with the follow-up information including major adverse cardiovascular events(MACEs)such as all-cause death,acute myocardial infarction and acute stroke,as well as major adverse lower extremity events(MALEs)such as rest pain in the lower extremities,ulcers or skin defects,gangrene,reocclusion and amputation.A multivariable Cox regression model was used to analyze the related risk factors for adverse outcomes 1 year after endovascular revascularization in patients with diabetes complicated with LEASO,and receiver operating characteristic(ROC)curves were constructed to evaluate the predictive efficacy and optimal cutoff value of fibrinogen levels for endpoint events,and Kaplan-Meier survival curves were drawn.Sensitivity analysis was made to assess the differences in the impact of fibrinogen on endpoint events across various subgroups.Results We recruited a total of 289 patients(55 patients in MACEs and 234 in non-MACEs;68 patients in MALEs and 221 in non-MALEs),with a mean age of 67.6±9.3 years,including 215 males.Multivariate Cox regression analysis showed that elevated plasma fibrinogen was an independent risk factor for MACEs(HR=1.250,95％CI:1.053-1.484,P=0.011)and all-cause death(HR=1.297,95％CI:1.030-1.633,P=0.027)in the cohort followed up 1 year after interventional therapy,but had no significant impact on the occurrence of MALEs(P=0.625).Baseline plasma fibrinogen level 4.32 g/L was the optimal cutoff value for predicting MACEs(sensitivity=0.673,95％CI:0.582-0.767;specificity=0.688,95％CI:0.562-0.775)and all-cause death(sensitivity=0.679,95％CI:0.483-0.880;specificity=0.651,95％CI:0.465-0.755).The AUC for predicting MACEs and all-cause death after interventional therapy was 0.652(95％CI:0.564 2-0.739 1)and 0.619(95％CI:0.507-0.733),respectively.After a median follow-up of 14.03 months,patients with preoperative fibrinogen level ≥ 4.32 g/L had a significantly higher risk of MACEs and all-cause death compared to patients with preoperative fibrinogen＜4.32 g/L(P＜0.001),and there were no significant differences in different subgroups,including gender(male/female,interaction P=0.836),age(＜65 years/≥65 years,interaction P=0.211),smoking status(never smoked/current or former smoker,interaction P=0.779),chronic kidney disease(yes/no,interaction P=0.360),and heart failure(yes/no,interaction P=0.114).Conclusion Preoperative plasma fibrinogen≥4.32 g/L is an effective indicator for predicting MACEs and all-cause mortality following endovascular revascularization in patients with diabetes and LEASO.

ObjectiveTo investigate the role of mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in the ferroptosis phenotype of ovarian cancer （OC） cells and the regulatory mechanism of gypenoside L （Gyp-L） on mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in OC cells. MethodsThe proliferation of human ovarian adenocarcinoma OVCAR3 cells was detected by cell counting kit-8 （CCK-8） assay， and the half-maximal inhibitory concentration （IC₅₀） values of cisplatin （DDP）， Gyp-L， and DDP in the presence of Gyp-L were calculated to determine the intervention concentration for subsequent experiments. Cell cloning assay and scratch assay reflected the proliferation and migration ability of OVCAR3 cells. PANDORA-seq small RNA sequencing was used to detect the differentially expressed transfer RNA-derived small RNAs （tsRNAs） in the cells after Gyp-L intervention， and the corresponding target genes of the tsRNAs were found by the RNAhybrid software. Malondialdehyde （MDA）， glutathione （GSH）， and lipid peroxide （LPO） levels were measured by colorimetry or enzyme linked immunosorbent assay （ELISA） method， Fe²⁺ content by FerroOrange fluorescent probe， and reactive oxygen species （ROS） content by DCFH-DA fluorescent probe to reflect the occurrence of ferroptosis in OVCAR3 cells. OVCAR3 cells were divided into a control group， a 50 µmol·L^-1 Gyp-L group， and a 100 µmol·L^-1 Gyp-L group. Quantitative real-time polymerase chain reaction （PCR） was performed to detect the expression of mature-tRNA-Asp-GTC， mature-tRNA-Leu-CAA， mature-mt_tRNA-Tyr-GTA_5_end， mature-tRNA-Val-CAC， mature-mt_tRNA-Glu-TTC， pre-tRNA-Arg-TCT， mature-tRNA-Asn-GTT， hydroxymethylbilane synthase （HMBS）， Wnt， β-catenin， glutathione peroxidase 4 （GPX4）， Kelch-like ECH-associated protein 1 （KEAP1）， nuclear factor erythroid 2-related factor 2 （Nrf2）， activating transcription factor 3 （ATF3）， cystine/glutamate antiporter xCT， lysophosphatidylcholine acyltransferase 3 （LPCAT3）， and arachidonate 15-lipoxygenase （ALOX15）. Western blot was performed to detect the expression of HMBS， Wnt， β-catenin， GPX4， KEAP1， Nrf2， ATF3， xCT， LPCAT3， and ALOX15 proteins. ResultsThe 50 µmol·L^-1 Gyp-L， 100 µmol·L^-1 Gyp-L， DDP， 50 µmol·L^-1 Gyp-L+DDP， and 100 µmol·L^-1 Gyp-L+DDP groups showed significantly inhibited proliferation and migration of OVCAR3 cells （P<0.05） and exacerbated cell ferroptosis as reflected by the increase in the content of ROS， MDA， LPO， and Fe²⁺， as well as a decrease in the content of GSH （P<0.05）. Compared with the control group， Gyp-L effectively interfered with the expression of 25 tsRNAs in OVCAR3 cells （P<0.05， |log₂Fc|>1）. Pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4， pre-tRNA-Arg-TCT/KEAP1/NRF2/xCT， mature-tRNA-Asp-GTC/ATF3/KEAP1/NRF2/xCT， and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 axial expression was significantly aberrant after Gyp-L intervention （P<0.05）. ConclusionThe pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4， pre-tRNA-Arg-TCT/KEAP1/Nrf2/xCT， mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT， and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling pathways are involved in OC development. Gyp-L inhibits OC development by activating OVCAR3 cell ferroptosis onset mainly through the mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling axes.

ObjectiveTo investigate the role of mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in the ferroptosis phenotype of ovarian cancer （OC） cells and the regulatory mechanism of gypenoside L （Gyp-L） on mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in OC cells. MethodsThe proliferation of human ovarian adenocarcinoma OVCAR3 cells was detected by cell counting kit-8 （CCK-8） assay， and the half-maximal inhibitory concentration （IC₅₀） values of cisplatin （DDP）， Gyp-L， and DDP in the presence of Gyp-L were calculated to determine the intervention concentration for subsequent experiments. Cell cloning assay and scratch assay reflected the proliferation and migration ability of OVCAR3 cells. PANDORA-seq small RNA sequencing was used to detect the differentially expressed transfer RNA-derived small RNAs （tsRNAs） in the cells after Gyp-L intervention， and the corresponding target genes of the tsRNAs were found by the RNAhybrid software. Malondialdehyde （MDA）， glutathione （GSH）， and lipid peroxide （LPO） levels were measured by colorimetry or enzyme linked immunosorbent assay （ELISA） method， Fe²⁺ content by FerroOrange fluorescent probe， and reactive oxygen species （ROS） content by DCFH-DA fluorescent probe to reflect the occurrence of ferroptosis in OVCAR3 cells. OVCAR3 cells were divided into a control group， a 50 µmol·L^-1 Gyp-L group， and a 100 µmol·L^-1 Gyp-L group. Quantitative real-time polymerase chain reaction （PCR） was performed to detect the expression of mature-tRNA-Asp-GTC， mature-tRNA-Leu-CAA， mature-mt_tRNA-Tyr-GTA_5_end， mature-tRNA-Val-CAC， mature-mt_tRNA-Glu-TTC， pre-tRNA-Arg-TCT， mature-tRNA-Asn-GTT， hydroxymethylbilane synthase （HMBS）， Wnt， β-catenin， glutathione peroxidase 4 （GPX4）， Kelch-like ECH-associated protein 1 （KEAP1）， nuclear factor erythroid 2-related factor 2 （Nrf2）， activating transcription factor 3 （ATF3）， cystine/glutamate antiporter xCT， lysophosphatidylcholine acyltransferase 3 （LPCAT3）， and arachidonate 15-lipoxygenase （ALOX15）. Western blot was performed to detect the expression of HMBS， Wnt， β-catenin， GPX4， KEAP1， Nrf2， ATF3， xCT， LPCAT3， and ALOX15 proteins. ResultsThe 50 µmol·L^-1 Gyp-L， 100 µmol·L^-1 Gyp-L， DDP， 50 µmol·L^-1 Gyp-L+DDP， and 100 µmol·L^-1 Gyp-L+DDP groups showed significantly inhibited proliferation and migration of OVCAR3 cells （P<0.05） and exacerbated cell ferroptosis as reflected by the increase in the content of ROS， MDA， LPO， and Fe²⁺， as well as a decrease in the content of GSH （P<0.05）. Compared with the control group， Gyp-L effectively interfered with the expression of 25 tsRNAs in OVCAR3 cells （P<0.05， |log₂Fc|>1）. Pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4， pre-tRNA-Arg-TCT/KEAP1/NRF2/xCT， mature-tRNA-Asp-GTC/ATF3/KEAP1/NRF2/xCT， and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 axial expression was significantly aberrant after Gyp-L intervention （P<0.05）. ConclusionThe pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4， pre-tRNA-Arg-TCT/KEAP1/Nrf2/xCT， mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT， and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling pathways are involved in OC development. Gyp-L inhibits OC development by activating OVCAR3 cell ferroptosis onset mainly through the mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling axes.

Infectious chronic refractory wounds are common in the department of dermatology,and have a great influence on the quality of life of patients.Their incidence is increasing year by year.The pathogensis of infectious chronic refractory wounds is due to the exuberance of pathogenic heat and toxin,disharmony between nutritive qi and defensive qi,and imbalance of zang-fu organs,which is related with the theory of qi-fluid and sweat pores.Therefore,it is proposed that stagnation and obstruction of sweat pores contribute to the pathological basis for the onset of infectious chronic refractory wounds,and therapeutic principle of opening sweat pores was presented.In the medication view of treating the skin diseases with the skin-related Chinese medicinals,skin-related Chinese medicinals are good at treating skin diseases,and consequently the application of skin-related Chinese medicinals to open sweat in treating infectious chronic refractory wounds was discussed.It is suggested that for the treatment of infectious chronic refractory wounds due to pathogenic fire-toxin accumulation in sweat pores,therapy of clearing heat and expelling fire to open sweat pores should be exployed,and skin-related Chinese medicinals such as Phellodendri Chinensis Cortex,Dictamni Cortex and Fraxini Cortex can be selected;for the treatment of infectious chronic refractory wounds due to blood-stasis stagnation in sweat pores,therapy of cooling and activating blood to open sweat pores should be exployed,and skin-related Chinese medicinals such as Moutan Cortex and Lycii Cortex can be selected;for the treatment of infectious chronic refractory wounds due to wind and dampness obstructing sweat pores,therapy of expelling wind and eliminating dampness to unblock sweat pores should be exployed,and skin-related Chinese medicinals such as Acanthopanacis Cortex,Citri Reticulatae Pericarpium,and Poriae Cutis can be selected;for the treatment of infectious chronic refractory wounds due to healthy qi deficiency resulting in the obstruction of sweat pores,therapy of invigorating spleen and tonifying kidney to nourish sweat pores should be exployed,and skin-related Chinese medicinals such as Cinnamomi Cortex,Eucommiae Cortex,and black soybean testa(Testa Glycinea Macids)can be chosen.Guided by the theory of qi-fluid and sweat pores,this paper explored the application of skin-related Chinese medicinals in the treating infectious chronic refractory wounds,which provides theoretical basis for such an approach,enriches the theory of traditional Chinese medicine for the treatment of infectious chronic refractory wounds,and expands the clinical application of the theory of sweat pores.