ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption （HSCD） on chronic gouty arthritis （CGA） rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated， using the random number table， to a normal group （n=8） and a model group （n =33）. CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate （250 mg·kg^-1·d^-1） and hypoxanthine （300 mg·kg^-1·d^-1）， combined with intra-articular injection of a monosodium urate （MSU） crystal suspension （50 μL， 25 g·L^-¹） into the left ankle twice weekly. After 4 weeks of modeling， 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group， an HSCD group （10.35 g·kg^-1·d^-1， gavage once daily）， an M1 polarization agonist group （L-methionine sulfoximine， 300 mg·kg^-1， subcutaneous injection every other day）， an M1 polarization agonist + HSCD group， an M2 polarization inhibitor group （PD0325901， 10 mg·kg^-1·d^-1， gavage once daily）， and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment， whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium （CMC-Na） vehicle （10.35 g·kg^-1·d^-1， gavage once daily）. All interventions were continued for four weeks. During the intervention period， except for the normal group， potassium oxonate （250 mg·kg⁻¹） and hypoxanthine （300 mg·kg^-1） were co-administered by gavage every other day to maintain the model. At the end of treatment， serum uric acid （SUA）， ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， chemokine C-C motif ligand 2 （CCL2）， S100 calcium-binding protein A8/A9 （S100A8/A9）， interleukin-10 （IL-10） and arginase-1 （Arg-1） in serum and joint fluid were determined by enzyme-linked immunosorbent assay （ELISA）. High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin （HE） staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase （iNOS） and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 （CD163） in synovial tissue. ResultsCompared with the normal group， the model group showed significantly elevated SUA level and joint swelling index， and increased levels of pro-inflammatory cytokines， CCL2， and S100A8/A9 in both serum and joint fluid （P<0.05）， accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated （P<0.05）. Compared with model group， rats in HSCD group had significantly lower SUA levels， attenuated joint swelling， reduced serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid， accompanied with alleviated MSU deposition and synovial inflammation （P<0.05）. HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS （P<0.05）， whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group， the M1 polarization agonist + HSCD group showed significantly reduced joint swelling， lower serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in joint fluid （P<0.05）. In addition， synovial inflammatory cell infiltration and angiogenesis were attenuated， and iNOS mRNA and protein expression levels were significantly reduced （P<0.05）. Compared with the M2 polarization inhibitor group， the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling， decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation （P<0.05）， whereas the levels of anti-inflammatory mediators （IL-10， Arg-1） and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats， at least in part， by inhibiting macrophage polarization toward the M1 phenotype.

Objective To observe the effects of growth differentiation factor-15(GDF-15)on collateral circulation and cardiac function in rats with acute myocardial infarction(AMI)in relation to the nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)/protein kinase G(PKG)signaling pathway.Methods An AMI rat model was constructed by ligating the left anterior descending coronary artery.After modeling,the rats were divided randomly into Sham,Model,and GDF-15 groups(n=12 rats per group).Rats in the GDF-15 group were injected intraperitoneally with recombinant GDF-15 protein,and the other two groups were injected with the same amount of normal saline twice a week for 8 consecutive weeks.Cardiac function was detected by echocardiography.Pathological damage to rat myocardial tissue was detected by hematoxylin and eosin staining and the collateral circulation was observed by CD31 immunohistochemical staining.Vascular endothelial growth factor(VEGF)mRNA expression was detected by quantitative polymerase chain reaction.Transcriptomic sequencing of heart tissues in the model and GDF-15 groups was performed and differentially expressed genes(DEGs)were screened.Pathway enrichment analysis of the DEGS was carried out according to the Kyoto Encyclopedia of Genes and Genomes(KEGG).Nitric oxide(NO),reactive oxygen species(ROS),and cGMP were detected using kits,and VEGF,endothelial nitric oxide synthase(eNOS)monomer,p-eNOSser1177monomer,eNOS dimer,and PKG protein were detected by Western blot.Results Left ventricular end-systolic diameter(LVEDs)and left ventricular end-diastolic diameter(LVEDd)were increased(P＜0.001),and left ventricular ejection fraction(LVEF)and the short-axis shortening rate(FS)were decreased in the Model group compared with the Sham group(P＜0.001).Myocardial cell necrosis was more severe,vascular density in the infarcted area was decreased(P＜0.05),but VEGF mRNA and protein levels were no change(P＞0.05),and levels of NO,eNOS dimer,cGMP,and PKG protein were decreased(P＜0.05),and expression levels of ROS,eNOS monomer,and p-eNOSser1177 monomer were increased(P＜0.05).LVEDs and LVEDd decreased(P＜0.05),LVEF and FS increased(P＜0.01),myocardial cell necrosis was relieved,vascular density in the infarcted area increased significantly(P＜0.0001),and VEGF mRNA levels increased(P＜0.0001),compared with the Model group.Transcriptomic sequencing identified 324 DEGs,including 230 up-regulated and 94 down-regulated genes.According to KEGG enrichment analysis,the cGMP-PKG signaling pathway showed the most significant difference in the T20 pathway.VEGF,NO,eNOS dimer,cGMP,and PKG protein levels were all increased(P＜0.05),while ROS,eNOS monomer,and p-eNOSser1177 monomer were decreased in the GDF-15 group(P＜0.05).Conclusions GDF-15 can promote collateral circulation in ischemic myocardium and improve cardiac function by inhibiting eNOS decoupling and activating the NO/cGMP/PKG pathway.

Objective To study the hearing intervention effects of the Shokz condyle-stimulated headband bone-conduction hearing aid on patients with conductive,mixed,and sensorineural hearing loss and to explore its clinical application prospects.Methods A total of 55 patients with hearing loss(age 18～82)participated in the study.Among them,9 had conductive hearing loss,15 had sensorineural hearing loss,and 31 had mixed hearing loss.Their bilat-eral bone conduction pure tone thresholds at 0.5,1,2,and 4 kHz were all ≤60 dB HL.The patients were fitted with the condyle-stimulated headband bone-conduction hearing aid.Hearing thresholds in sound field,single-syllable speech recogni-tion scores in quiet,and sentence recognition thresholds in quiet were assessed before fitting and on the day of 14±2 after fitting to compare differences in results.The effectiveness of the hearing aids on the day of 14±2 after fitting was also eval-uated using the IOI-HA questionnaire.Results After wearing the bone-conduction hearing aid,the average hearing thresh-old and sentence recognition threshold of the patients decreased significantly compared with before fitting(the average hear-ing threshold:56.5±8.2 dB HL before fitting,39.3±4.9 dB HL on the day of 14±2 after fitting;sentence recognition threshold:48.6±9.7 dB HL before fitting,34.3±5.6 dB HL on the day of 14±2 after fitting),and the difference was statistically significant(P＜0.001).The single-syllable speech recognition score before fitting was 29.8％±11.4％,and on the day of 14±2 after fitting,it was 72.4％±14.4％,the difference was statistically significant(P＜0.001).The av-erage total score of the IOI-HA questionnaire was 29.0±3.8 points.Conclusion Condyle-stimulated headband bone-con-duction hearing aids can significantly improve the hearing and speech recognition ability of patients with conductive,mixed and sensorineural hearing loss whose bone conduction pure tone thresholds at 0.5～4 kHz were ≤60 dB HL.It may poten-tially improve the quality of life for patients with hearing loss and holds substantial clinical application value.

Objective To observe the effects of growth differentiation factor-15(GDF-15)on collateral circulation and cardiac function in rats with acute myocardial infarction(AMI)in relation to the nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)/protein kinase G(PKG)signaling pathway.Methods An AMI rat model was constructed by ligating the left anterior descending coronary artery.After modeling,the rats were divided randomly into Sham,Model,and GDF-15 groups(n=12 rats per group).Rats in the GDF-15 group were injected intraperitoneally with recombinant GDF-15 protein,and the other two groups were injected with the same amount of normal saline twice a week for 8 consecutive weeks.Cardiac function was detected by echocardiography.Pathological damage to rat myocardial tissue was detected by hematoxylin and eosin staining and the collateral circulation was observed by CD31 immunohistochemical staining.Vascular endothelial growth factor(VEGF)mRNA expression was detected by quantitative polymerase chain reaction.Transcriptomic sequencing of heart tissues in the model and GDF-15 groups was performed and differentially expressed genes(DEGs)were screened.Pathway enrichment analysis of the DEGS was carried out according to the Kyoto Encyclopedia of Genes and Genomes(KEGG).Nitric oxide(NO),reactive oxygen species(ROS),and cGMP were detected using kits,and VEGF,endothelial nitric oxide synthase(eNOS)monomer,p-eNOSser1177monomer,eNOS dimer,and PKG protein were detected by Western blot.Results Left ventricular end-systolic diameter(LVEDs)and left ventricular end-diastolic diameter(LVEDd)were increased(P＜0.001),and left ventricular ejection fraction(LVEF)and the short-axis shortening rate(FS)were decreased in the Model group compared with the Sham group(P＜0.001).Myocardial cell necrosis was more severe,vascular density in the infarcted area was decreased(P＜0.05),but VEGF mRNA and protein levels were no change(P＞0.05),and levels of NO,eNOS dimer,cGMP,and PKG protein were decreased(P＜0.05),and expression levels of ROS,eNOS monomer,and p-eNOSser1177 monomer were increased(P＜0.05).LVEDs and LVEDd decreased(P＜0.05),LVEF and FS increased(P＜0.01),myocardial cell necrosis was relieved,vascular density in the infarcted area increased significantly(P＜0.0001),and VEGF mRNA levels increased(P＜0.0001),compared with the Model group.Transcriptomic sequencing identified 324 DEGs,including 230 up-regulated and 94 down-regulated genes.According to KEGG enrichment analysis,the cGMP-PKG signaling pathway showed the most significant difference in the T20 pathway.VEGF,NO,eNOS dimer,cGMP,and PKG protein levels were all increased(P＜0.05),while ROS,eNOS monomer,and p-eNOSser1177 monomer were decreased in the GDF-15 group(P＜0.05).Conclusions GDF-15 can promote collateral circulation in ischemic myocardium and improve cardiac function by inhibiting eNOS decoupling and activating the NO/cGMP/PKG pathway.

Objective To study the hearing intervention effects of the Shokz condyle-stimulated headband bone-conduction hearing aid on patients with conductive,mixed,and sensorineural hearing loss and to explore its clinical application prospects.Methods A total of 55 patients with hearing loss(age 18～82)participated in the study.Among them,9 had conductive hearing loss,15 had sensorineural hearing loss,and 31 had mixed hearing loss.Their bilat-eral bone conduction pure tone thresholds at 0.5,1,2,and 4 kHz were all ≤60 dB HL.The patients were fitted with the condyle-stimulated headband bone-conduction hearing aid.Hearing thresholds in sound field,single-syllable speech recogni-tion scores in quiet,and sentence recognition thresholds in quiet were assessed before fitting and on the day of 14±2 after fitting to compare differences in results.The effectiveness of the hearing aids on the day of 14±2 after fitting was also eval-uated using the IOI-HA questionnaire.Results After wearing the bone-conduction hearing aid,the average hearing thresh-old and sentence recognition threshold of the patients decreased significantly compared with before fitting(the average hear-ing threshold:56.5±8.2 dB HL before fitting,39.3±4.9 dB HL on the day of 14±2 after fitting;sentence recognition threshold:48.6±9.7 dB HL before fitting,34.3±5.6 dB HL on the day of 14±2 after fitting),and the difference was statistically significant(P＜0.001).The single-syllable speech recognition score before fitting was 29.8％±11.4％,and on the day of 14±2 after fitting,it was 72.4％±14.4％,the difference was statistically significant(P＜0.001).The av-erage total score of the IOI-HA questionnaire was 29.0±3.8 points.Conclusion Condyle-stimulated headband bone-con-duction hearing aids can significantly improve the hearing and speech recognition ability of patients with conductive,mixed and sensorineural hearing loss whose bone conduction pure tone thresholds at 0.5～4 kHz were ≤60 dB HL.It may poten-tially improve the quality of life for patients with hearing loss and holds substantial clinical application value.

Objective To explore the effect and mechanism of Baicalein in the treatment of hyperuricemia.Methods The mouse model of hyperuricemia was established by yeast extract combined with potassium oxazinate.The effect and potential mechanism of Baicalein in the treatment of hyperuricemia were studied by biochemical indexes,pathological changes,non-target metabonomics and network pharmacology.Results Baicalein could reduce the contents of serum uric acid,creatinine and blood urea nitrogen,reduce the inflammatory injury of renal tissue,up-regulate the expression level of uric acid excretion protein and down-regulate the expression level of uric acid reabsorption protein.Nine disease-related targets such as BCL2,SIRT1 and XDH were screened by network pharmacology.Six key metabolic pathways including nicotinic acid and nicotinamide metabolism,caffeine metabolism and purine metabolism were screened by metabonomics analysis.Conclusions Baicalein can treat hyperuricemia and reduce renal injury,and its mechanism may be related to the metabolic pathways of nicotinic acid and nicotinamide regulated by SIRT1 and quinolinate.

Objective To determine the blood physiological and biochemical indexes in the inbred SHANXI MU strain of spontaneous type 2 diabetes(T2DM)Chinese hamsters.Methods Chinese hamsters with spontaneously developed T2DM and normal hamsters(n=10 hamsters per group),aged 12 months,were selected for the study.Fasting blood samples were collected and 15 physiological parameters and 16 biochemical indicators were analyzed using a Sysmex XT automated hematology analyzer and Hitachi fully automatic biochemical analyzer.Results The white cell count,red cell count,platelet count,hemoglobin level,alanine transaminase,aspartate transaminase,glutamate,total cholesterol,triglycerides,and uric acid all differed significantly between the diabetic and control groups(P＜0.05).Conclusions The change of blood physiological and biochemical indexes in the Chinese hamster spontaneous T2DM model were in line with the trend in human T2DM incidence,thus providing basic data for the application of this model.

The clinical data of a patient with Klinefelter syndrome (KS) complicated by partial androgen insensitivity syndrome (PAIS) was retrospectively analyzed.The patient, a 2-month-and-22-day-old baby, was admitted to Children′s Hospital Affiliated to Zhengzhou University due to abnormal external genitalia in October 2021.Upon birth, the patient exhibited abnormal external genitalia, manifested as clitoral hypertrophy.Hormonal examinations were consistent with those of peers, while chromosomal analysis revealed 47, XXY.Due to the severe undermasculinization, whole exome sequencing was conducted, indicating a heterozygous variant of the AR gene (c.1847G>A, p.Arg616His). The patient was diagnosed with PAIS, and her elder sister was diagnosed with complete androgen insensitivity syndrome.For further treatment, a multidisciplinary comprehensive evaluation is needed.This is a rare case of KS combined with PAIS, suggesting the possibility of AR gene mutations in KS children with severe undermasculinization.

OBJECTIVE To enrich the polymethoxyflavonoid-rich fraction from Citri Reticulatae Pericarpium using D101 macro-porous resin,and further to analyse the chemical constituents using High-Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry(HPLC-Q-TOF-MS).METHODS Citri Reticulatae Pericarpium extract was adsorbed on D101 macro-porous resin and then eluted with different concentrations of ethanol to enrich the polymethoxyflavonoid-rich fraction;the content of the major flavonoid components was determined by high-performance liquid chromatography(HPLC);and the components were further an-alysed by HPLC-Q-TOF-MS.RESULTS The established HPLC method for the simultaneous determination of seven flavonoids in Citri Reticulatae Pericarpium extract was accurate and reliable.The contents of compounds such as nobiletin and tangeritin were signifi-cantly increased in the polymethoxyflavonoid-rich fraction.Using high resolution mass spectrometry(HRMS),70 and 60 compounds were identified from the Citri Reticulatae Pericarpium extract and the polymethoxyflavonoid-rich fraction,respectively,with 53 polyme-thoxyflavonoids being detected in these two extracts.CONCLUSION The results of this study provide an experimental basis for fur-ther identification of the pharmacological substance basis of the polymethoxyflavonoids in Citri Reticulatae Pericarpium and the estab-lishment of quality control methods.

Background:Endoscopic submucosal dissection(ESD)is a common minimally-invasive endoscopic treatment for early esophageal cancer.However,it still entails risks such as a narrow operative field,high difficulty in surgical operation,long operation time,and a high incidence of complications like bleeding and perforation.Therefore,precise visualization is of great importance for the safe completion of esophageal ESD.Aims:To explore the value of different traction techniques-assisted ESD in the treatment of early esophageal cancer and compare the application effects of different traction techniques.Methods:The en bloc resection rate and complete resection rate in all three groups were 100%.The dissection speeds of both the dental floss traction group and the snare traction group were significantly faster than that of the traditional ESD treatment group,with a statistically significant difference(P<0.05).There was no statistically significant difference in the dissection speed between the dental floss traction group and the snare traction group(P>0.05).No complications such as oropharyngeal or esophageal mucosal damage caused by the traction devices occurred in the three groups of patients during the peri-operative period.Results:The en bloc resection rate and complete resection rate in all three groups were 100%.The dissection speeds of both the dental floss traction group and the snare traction group were significantly faster than that of the traditional ESD treatment group,with a statistically significant difference(P<0.05).There was no statistically significant difference in the dissection speed between the dental floss traction group and the snare traction group(P>0.05).No complications such as oropharyngeal or esophageal mucosal damage caused by the traction devices occurred in the three groups of patients during the peri-operative period.Conclusions:The dental floss and snare traction techniques can significantly increase the dissection speed of early esophageal cancer.Moreover,the snare traction technique has the advantage of adjustable traction direction,making it safe and effective for clinical promotion.