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.

Based on the theory of "shaoyang（少阳） resembling the pivot" and collateral diseases， this article proposes that pulmonary fibrosis （PF） can be divided into three stages including wind bi （痹）， constraint bi， and atrophy bi. The core pathogenesis of PF is the obstruction of the pivot and pulmonary collateral obstruction. In terms of treatment， the basic principles are to harmonize and regulate the pivot， and to promote the circulation of the lung collaterals. Depending on the different characteristics of the "essence-attribute-function"， treatment methods such as harmonizing and regulating the pivot， resolving phlegm and removing stasis， supplementing deficiency and harmonizing collaterals are suggested. This approach ensures the regulation of the pivot， smooth circulation of qi and blood， unblocking of the lung collaterals and nourishing the lung body， achieving the goals of balancing the ascending and descending of qi， removing phlegm and stasis， and relieving cough and wheezing.

In this paper， by referring to ancient and modern literature， the textual research of Inulae Flos has been conducted to clarify the name， origin， production area， quality evaluation， harvesting， processing and others， so as to provide reference and basis for the development and utilization of famous classical formulas containing this herb. After textual research， it could be verified that the medicinal use of Inulae Flos was first recorded in Shennong Bencaojing of the Han dynasty. In successive dynasties， Xuanfuhua has been taken as the official name， and it also has other alternative names such as Jinfeicao， Daogeng and Jinqianhua. The period before the Song and Yuan dynasties， the main origin of Inulae Flos was the Asteraceae plant Inula japonica， and from the Ming and Qing dynasties to the present， I. japonica and I. britannica are the primary source. In addition to the dominant basal species， there are also regional species such as I. linariifolia， I. helianthus-aquatili， and I. hupehensis. The earliest recorded production areas in ancient times were Henan， Hubei and other places， and the literature records that it has been distributed throughout the country since modern times. The medicinal part is its flower， the harvesting and processing method recorded in the past dynasties is mainly harvested in the fifth and ninth lunar months， and dried in the sun， and the modern harvesting is mostly harvested in summer and autumn when the flowers bloom， in order to remove impurities， dry in the shade or dry in the sun. In addition， the roots， whole herbs and aerial parts are used as medicinal materials. In ancient times， there were no records about the quality of Inulae Flos， and in modern times， it is generally believed that the quality of complete flower structure， small receptacles， large blooms， yellow petals， long filaments， many fluffs， no fragments， and no branches is better. Ancient processing methods primarily involved cleaning， steaming， and sun-drying， supplemented by techniques such as boiling， roasting， burning， simmering， stir-frying， and honey-processing. Modern processing focuses mainly on cleaning the stems and leaves before use. Regarding the medicinal properties， ancient texts describe it as salty and sweet in taste， slightly warm in nature， and mildly toxic. Modern studies characterize it as bitter， pungent， and salty in taste， with a slightly warm nature. Its therapeutic effects remain consistent across eras， including descending Qi， resolving phlegm， promoting diuresis， and stopping vomiting. Based on the research results， it is recommended that when developing famous classical formulas containing Inulae Flos， either I. japonica or I. britannica should be used as the medicinal source. Processing methods should follow formula requirements， where no processing instructions are specified， the raw products may be used after cleaning.

In this paper， by referring to ancient and modern literature， the textual research of Inulae Flos has been conducted to clarify the name， origin， production area， quality evaluation， harvesting， processing and others， so as to provide reference and basis for the development and utilization of famous classical formulas containing this herb. After textual research， it could be verified that the medicinal use of Inulae Flos was first recorded in Shennong Bencaojing of the Han dynasty. In successive dynasties， Xuanfuhua has been taken as the official name， and it also has other alternative names such as Jinfeicao， Daogeng and Jinqianhua. The period before the Song and Yuan dynasties， the main origin of Inulae Flos was the Asteraceae plant Inula japonica， and from the Ming and Qing dynasties to the present， I. japonica and I. britannica are the primary source. In addition to the dominant basal species， there are also regional species such as I. linariifolia， I. helianthus-aquatili， and I. hupehensis. The earliest recorded production areas in ancient times were Henan， Hubei and other places， and the literature records that it has been distributed throughout the country since modern times. The medicinal part is its flower， the harvesting and processing method recorded in the past dynasties is mainly harvested in the fifth and ninth lunar months， and dried in the sun， and the modern harvesting is mostly harvested in summer and autumn when the flowers bloom， in order to remove impurities， dry in the shade or dry in the sun. In addition， the roots， whole herbs and aerial parts are used as medicinal materials. In ancient times， there were no records about the quality of Inulae Flos， and in modern times， it is generally believed that the quality of complete flower structure， small receptacles， large blooms， yellow petals， long filaments， many fluffs， no fragments， and no branches is better. Ancient processing methods primarily involved cleaning， steaming， and sun-drying， supplemented by techniques such as boiling， roasting， burning， simmering， stir-frying， and honey-processing. Modern processing focuses mainly on cleaning the stems and leaves before use. Regarding the medicinal properties， ancient texts describe it as salty and sweet in taste， slightly warm in nature， and mildly toxic. Modern studies characterize it as bitter， pungent， and salty in taste， with a slightly warm nature. Its therapeutic effects remain consistent across eras， including descending Qi， resolving phlegm， promoting diuresis， and stopping vomiting. Based on the research results， it is recommended that when developing famous classical formulas containing Inulae Flos， either I. japonica or I. britannica should be used as the medicinal source. Processing methods should follow formula requirements， where no processing instructions are specified， the raw products may be used after cleaning.

ObjectiveTo investigate the association of the single nucleotide polymorphism （SNP） of the insulin-like growth factor binding protein-3 （IGFBP3） gene at rs10225396 （A>G） locus with the susceptibility to hepatocellular carcinoma， as well as its potential molecular regulatory mechanisms， and to provide novel genetic biomarkers and a theoretical basis for early screening and precise targeted therapy for hepatocellular carcinoma. MethodsA total of 192 patients with hepatocellular carcinoma who were admitted to The Affiliated Hospital of Yanbian University and Yanbian Cancer Hospital from January 2009 to August 2016 were enrolled as experimental group， and 190 healthy individuals who underwent physical examination in Physical Examination Center of Yanbian Hospital during the same period of time were enrolled as control group. Peripheral blood samples were collected from all subjects， and after DNA was extracted from whole blood， the DNA samples meeting quality standards were sent to Beijing Genomics Institute Research Center Co.， Ltd.， for Mass ARRAY mass spectrometry， while genotyping was completed. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. A binary Logistic regression model was used to analyze the association of the SNP of the IGFBP3 gene at rs10225396 locus with the susceptibility to hepatocellular carcinoma， and odds ratio （OR） and 95% confidence interval （CI） were calculated to assess the risk of developing hepatocellular carcinoma in individuals carrying different genotypes. ResultsThere were two alleles （G and A） at the rs10225396 locus of the IGFBP3 gene， yielding the three genotypes of AA， AG， and GG， and its genotype distribution was consistent with the Hardy-Weinberg equilibrium （χ²=0.072， P=0.789）. The stratified genetic analysis showed that carriers of the IGFBP3 rs10225396 AA genotype had a significant increased risk of hepatocellular carcinoma among individuals of age <63 years， male sex， smoking history， drinking history， and the Chinese Korean population （all P<0.001）. The binary Logistic regression analysis showed that after adjustment for related risk factors in the codominant model， the population with genotype AG and GG had a significant reduction in the risk of hepatocellular carcinoma compared with the population with genotype AA （P<0.001）， and in the dominant model， the population with genotype AG+GG had a significant reduction in the risk of hepatocellular carcinoma compared with the population with genotype AA （P<0.001）. ConclusionThrough a genotyping analysis of hepatocellular carcinoma patients and healthy individuals in Yanbian Korean Autonomous Prefecture of Jilin Province， China， this study shows that genotype AA at rs10225396 locus of the IGFBP3 gene is significantly associated with the susceptibility to hepatocellular carcinoma， and this genotype can significantly increase the risk of developing hepatocellular carcinoma with the presence of specific risk factors， which provides a potential genetic marker for early screening and precise treatment of hepatocellular carcinoma.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］

Objective:To analyze the clinical characteristics of children with head and neck rhabdomyosarcoma (RMS) and to summarize the mid-long term efficacy of Beijing Children′s Hospital Rhabdomyosarcoma 2006 (BCH-RMS-2006) regimen and China Children′s Cancer Group Rhabdomyosarcoma 2016 (CCCG-RMS-2016) regimen.Methods:A retrospective cohort study. Clinical data of 137 children with newly diagnosed head and neck RMS at Beijing Children′s Hospital, Capital Medical University from March 2013 to December 2021 were collected. Clinical characteristic of patients at disease onset and the therapeutic effects of patients treated with the BCH-RMS-2006 and CCCG-RMS-2016 regimens were compared. The treatments and outcomes of patients with recurrence were also summarized. Survival analysis was performed by Kaplan-Meier method, and Log-Rank test was used for comparison of survival rates between groups.Results:Among 137 patients, there were 80 males (58.4%) and 57 females (41.6%), the age of disease onset was 59 (34, 97) months. The primary site in the orbital, non-orbital non-parameningeal, and parameningeal area were 10 (7.3%), 47 (34.3%), and 80 (58.4%), respectively. Of all patients, 32 cases (23.4%) were treated with the BCH-RMS-2006 regimen and 105 (76.6%) cases were treated with the CCCG-RMS-2016 regimen. The follow-up time for the whole patients was 46 (20, 72) months, and the 5-year progression free survival (PFS) and overall survival (OS) rates for the whole children were (60.4±4.4)% and (69.3±4.0)%, respectively. The 5-year OS rate was higher in the CCCG-RMS-2016 group than in BCH-RMS-2006 group ((73.0±4.5)% vs. (56.6±4.4)%, χ2=4.57, P=0.029). For the parameningeal group, the 5-year OS rate was higher in the CCCG-RMS-2016 group (61 cases) than in BCH-RMS-2006 group (19 cases) ((57.3±7.6)% vs. (32.7±11.8)%, χ2=4.64, P=0.031). For the group with meningeal invasion risk factors, the 5-year OS rate was higher in the CCCG-RMS-2016 group (54 cases) than in BCH-RMS-2006 group (15 cases) ((57.7±7.7)% vs. (30.0±12.3)%, χ2=4.76, P=0.029). Among the 10 cases of orbital RMS, there was no recurrence. In the non-orbital non-parameningeal RMS group (47 cases), there were 13 (27.6%) recurrences, after re-treatment, 7 cases survived. In the parameningeal RMS group (80 cases), there were 40 (50.0%) recurrences, with only 7 cases surviving after re-treatment. Conclusions:The overall prognosis for patients with orbital and non-orbital non-parameningeal RMS is good. However, children with parameningeal RMS have a high recurrence rate, and the effectiveness of re-treatment after recurrence is poor. Compared with the BCH-RMS-2006 regimen, the CCCG-RMS-2016 regimen can improve the treatment efficacy of RMS in the meningeal region.

ObjectiveTo observe the effects of electroacupuncture with "tonifying the kidney and dispelling stasis" acupoint prescription on sexual function in diabetic erectile dysfunction （DMED）model rats， and to explore its possible mechanism of action. MethodsSPF male SD rats were randomly divided into 10 each in blank group， model group， Tadalafil group， and electroacupuncture group. DMED rat model was prepared by high glucose and high fat diet combined with intraperitoneal injection of streptozotocin. After successful modelling， rats in the electroacupuncture group were given electroacupuncture intervention of "tonifying the kidney and dispelling stasis" acupoint prescription once every other day； Tadalafil group was given Tadalafil solution 0.5 mg/kg·d by gavage， and the blank group， model group and electroacupuncture group were given 10 ml/kg pure water by gavage once a day. Each group was intervened for 30 days. The body mass and blood glucose level of the rats were detected on the 1st， 8th， 15th， 22nd days and at the end of the intervention， respectively. At the end of the intervention， the penile erection of the rats was observed by using the apomorphine test； the level of plasma endothelial cell microparticles （EMPs）was detected by flow cytometry； the histopathological morphology of the penile cavernous body was observed by HE staining， and the pathological morphology of the endothelial cells of the penile vasculature was observed by electron microscopy. Serum sex hormones including testosterone （T）， follicle stimulating hormone （FSH）， luteinising hormone （LH） and vascular endothelial function-related factors including vascular endothelial growth factor （VEGF）， endothelin-1 （ET-1）， lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1）， soluble E-selectin （sE-selectin）， and soluble intercellular adhesion molecule-1 （sICAM-1） were measured by ELISA method. ResultsCompared with blank group， the model group， Tadalafil group， and electroacupuncture group all had lower body mass and higher blood glucose levels at each time of testing （P＜0.01）. Compared with the blank group， the number of penile erections reduced in the model group， the level of CD31⁺ EMPs increased， the levels of serum T， FSH， LH， and VEGF reduced， and the levels of serum ET-1， LOX-1， sE-selectin， and sICAM-1 increased （P＜0.01）. Compared with the model group， the Tadalafil group and the electroacupuncture group showed an increased number of penile erections decreased level of CD31⁺ EMPs， increased levels of serum T， FSH， LH， and VEGF， and decreased levels of serum ET-1， LOX-1， sE-selectin， and sICAM-1 （P＜0.01）. Compared with the Tadalafil group， serum T， FSH， LH， VEGF levels increased and ET-1， LOX-1 levels decreased in the electroacupuncture group （P＜0.05 or P＜0.01）. HE staining and electron microscopic observation revealed that there was severe pathological damage to the cavernous tissue of the penis and vascular endothelial cells of the rat in the model group， which was ameliorated to a certain degree in both Tadalafil group and electroacupuncture group. ConclusionThe electroacupuncture prescription of "tonifying the kidney and dispelling stasis" can improve the erectile dysfunction of DMED rats， which is comparable to the effect of Tadalafi. Its mechanism of action may be related to the regulation of vascular endothelial function.

The objective of this study was to develop a rapid and precise detection technique for por-cine Senecavirus A(SVA)employing reverse transcription recombinase polymerase amplification(RT-RAA)in conjunction with CRISPR Cas13a technology.Additionally,the study aimed to opti-mize the assay's reaction conditions to enhance amplification efficiency.Eight RT-RAA primer sets were designed based on the conserved gene sequence of porcine SVA,and a series of reaction condi-tions were evaluated to refine the RT-RAA reaction system.Subsequently,CRISPR-derived RNA(crRNA)sequences were developed and selected to construct the RT-RAA-CRISPR reaction sys-tem.The method's specificity was determined by examining six prevalent porcine pathogenic nucleic acids,while its sensitivity was assessed using SVA cRNA standards quantified by digital PCR.The method's stability and the consistency of clinical sample analysis were also evaluated.The findings revealed that the optimized RT-RAA and CRISPR reaction systems exhibited the highest amplifi-cation efficiency at a reaction temperature of 37 ℃.Among the eight crRNAs,five were identified as exhibiting the strongest detection signals.The formulated RT-RAA-CRISPR Cas13a method demonstrated exceptional specificity,showing no cross-reactivity with other common porcine disea-ses,including ASFV,PRRSV,PEDV,PCV2,CSFV,and PRV.The method achieved high sensitivi-ty,detecting as low as 0.86 copies/μL of SVA,and exhibited stable fluorescence output,robust re-producibility,and the ability to complete clinical sample analysis within 50 minutes.Consistency e-valuation with six positive and 58 negative samples indicated 100％agreement in outcomes.These results substantiate that the study successfully established a rapid and specific RT-RAA-CRISPR Cas13a detection method for the on-site identification of porcine Senecavirus A,demonstrating high specificity and sensitivity,and holds promise for application in SVA monitoring and control initia-tives.