BACKGROUND:At present,the pathogenesis of osteoarthritis is still unclear,and there is a lack of effective means to control the disease.Research on osteoarthritis is mostly concentrated in the field of immunity,and there are few studies in the field of oxidative stress. OBJECTIVE:To explore the roles of oxidative stress and immune infiltration in osteoarthritis and to predict related miRNAs and therapeutic agents. METHODS:The GSE55235 dataset(10 samples of osteoarthritis and 10 healthy control samples)and the GSE55457 dataset(10 samples of osteoarthritis and 10 healthy control samples)were obtained from the GEO database for merging to obtain their differentially expressed genes that were combined with oxidative stress genes to get the differentially expressed genes of oxidative stress.The differentially expressed genes of oxidative stress were analyzed for KEGG and GO enrichment,and the osteoarthritis pathways and biological processes were evaluated using GSEA enrichment analysis.The protein-protein interaction network was constructed using the STRING online website and Cytoscape software,and the Degree algorithm was run to get the key genes.The GSE1919 dataset was obtained from the GEO database as a validation dataset,and the key genes were analyzed by variance analysis and receiver operating characteristic curve analysis to get the core genes.In addition,immune infiltration was evaluated by CIBERSORT and the correlation between core genes and immune cells was explored.miRNA prediction of core genes was performed using TargetScan and target drugs were predicted using the DSigDB database. RESULTS AND CONCLUSION:Sixty-five differentially expressed genes and five core genes(IL1B,CXCL8,MYC,NFKBIA,JUN)associated with oxidative stress were identified.Enrichment analysis showed that differentially expressed genes associated with oxidative stress were concentrated in the pathways of oxidative stress,interleukin-17,osteoclast differentiation,fluid shear stress and atherosclerosis.The area under the receiver operating characteristic curve for the five core genes exceeded 0.85,indicating their excellent specificity and sensitivity in diagnosing bone and joint conditions,as well as their close association with immune cells.The predicted miRNA was has-miR-3937,and the therapeutic small-molecule drugs were metformin,ionomycin and celecoxib.To conclude,oxidative stress and immune infiltration exist in osteoarthritis,and immune infiltration is involved in activating oxidative stress.The core genes and predicted miRNAs can be used as novel markers for the diagnosis of osteoarthritis,and small molecule drugs are predicted to treat osteoarthritis.

Objective: To explore the efficacy of vonoprazan fumarate in the treatment of laryngopharyngeal reflux disease（LPRD） evaluated by the Chinese version of the RSS-12 scale. Methods:A total of 100 LPRD patients treated in the otolaryngology-head and neck surgery outpatient clinic of our hospital were randomly divided into two groups（50 cases each）. The observation group was treated with vonoprazan fumarate（20 mg, once daily）, and the control group was treated with esomeprazole enteric-coated capsules（20 mg, twice daily） for 12 weeks. The selected observation indicators in this study included RSI, the Chinese version of RSS-12, and RFS scores before and after treatment. Results:Prior to treatment, there was no statistically significant difference in the Chinese version of RSS-12, RSI, and RFS between the two groups（P>0.05）. After 8 and 12 weeks of antacid treatment, both the Chinese version of RSS-12 and RSI significantly decreased in both group （P<0.05）. The changes in symptoms were particularly noticeable between 0-8 weeks of treatment according to the Chinese version of RSS-12 and RSI. After 12 weeks of treatment, the RFS scores significantly decreased compared to pretreatment levels （P<0.05）. After 12 weeks of antacid treatment, according to the Chinese version of RSS-12, 80% of patients in the observation group showed a good therapeutic response, compared to 64% in the control group; according to RSI, 90% of patients in the observation group showed a good therapeutic response, compared to 84% in the control group. There was no statistically significant difference in the treatment effect between the two groups after 12 weeks of treatment（P>0.05）. Conclusion:Vonoprazan fumarate can significantly improve the symptoms and signs of laryngopharyngeal reflux, and their treatment effect is not inferior to proton pump inhibitors. Compared with RSI, the Chinese version of RSS-12 can serve as a new screening tool for clinical diagnosis of LPRD in China.
Humans ; Sulfonamides/therapeutic use* ; Male ; Pyrroles/therapeutic use* ; Female ; Laryngopharyngeal Reflux/drug therapy* ; Treatment Outcome ; Middle Aged ; Esomeprazole/therapeutic use* ; Proton Pump Inhibitors/therapeutic use* ; Adult

OBJECTIVES: To study the mechanism mediating the protective effect of asiaticoside (AS) against myocardial ischemia-reperfusion injury (MIRI) in rats. METHODS: Fifty SD rats were randomized into sham-operated group, MIRI model group and AS treatment group. AS treatment was administered at low, moderate and high doses by daily gavage for 2 weeks before MIRI modeling (n=10). Serum levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), interleukin-18 (IL-18) and IL-1β, the volume of myocardial infarction and ischemia, and myocardial pathologies of the rats were determined or observed. The protein expression levels of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the myocardial tissues were detected using Western blotting. The changes in the expression levels of these proteins were also detected in H9C2 cells with AS pretreatment prior to hypoxia-reoxygenation (H/R) injury. RESULTS: The rats models of MIRI exhibited significant myocardial infarction and ischemia with increased serum levels of LDH and CK-MB and myocardial expressions of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18. AS pretreatment effectively reduced myocardial infarction volume in the rat models and significantly reduced serum LDH and CK-MB levels and the protein levels in the myocardial tissue in a dose-dependent manner. In the H9C2 cell model of H/R injury, AS pretreatment significantly suppressed the elevation of the protein expressions of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18. Molecular docking studies showed that AS had a strong binding affinity with NLRP3. CONCLUSIONS Asiaticoside can alleviate MIRI in rats possibly by inhibiting NLRP3 inflammasome-mediated pyroptosis.
Animals ; Myocardial Reperfusion Injury/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Inflammasomes/metabolism* ; Triterpenes/pharmacology* ; Interleukin-18/metabolism* ; Male ; Interleukin-1beta/metabolism* ; Caspase 1/metabolism*

Humans ; Female ; Receptors, Estrogen/metabolism* ; Breast Neoplasms/metabolism* ; Receptors, Progesterone/metabolism* ; Immunohistochemistry ; Estrogen Receptor alpha

BACKGROUND:Haploidentical hematopoietic stem cell transplantation is associated with a higher rate of graft rejection and therefore often requires a higher CD34+ cell dose,but the findings reported in existing studies regarding the relationship between CD34+ cell dose and study endpoints after allogeneic hematopoietic stem cell transplantation are controversial. OBJECTIVE:To investigate the effect of CD34+ cell dose on clinical outcomes of haploidentical hematopoietic stem cell transplantation for malignant hematological diseases. METHODS:135 patients who underwent haploidentical hematopoietic stem cell transplantation at Hematopoietic Stem Cell Transplantation Center,Department of Hematology,First Affiliated Hospital of Zhengzhou University between January 2019 and December 2021 were included.Combining the results of previous studies and our center's experience,the cohort was divided into two groups using a CD34+ cell count of 5.0×106/kg as the cut-off point.Clinical outcomes related to graft implantation,relapse incidence,non-relapse mortality,overall survival and progression-free survival were evaluated in both groups. RESULTS AND CONCLUSION:(1)CD34+ cell dose correlated with platelet engraftment,with platelets implanted earlier in the high-dose group than in the low-dose group(14 days vs.16 days,P=0.013).(2)There was no significant difference in 3-year overall survival between the two groups(67.5%vs.53.8%,P=0.257);nor was there a significant difference in progression-free survival between the two groups(65.6%vs.44.2%,P=0.106),but stratified analysis based on disease risk index revealed an association with elevated 3-year progression-free survival in the high-dose group among low-risk patients(72.0%vs.49.3%,P=0.036).(3)The cumulative 3-year relapse incidence was smaller in the high-dose group than in the low-dose group(16.0%vs.33.5%,P=0.05).(4)The rate of non-relapse mortality within 100 days was greater in the high-dose group than in the low-dose group,but there was no significant difference(17.3%vs.6.7%,P=0.070);stratified analysis revealed that non-relapse mortality within 100 days was significantly higher in the high-dose group than in the low-dose group(20.0%vs.3.3%,P=0.046).(5)In conclusion,CD34+ cell doses>5.0×106/kg promote early platelet implantation,improve 3-year progression-free survival in low-risk patients at transplantation and reduce the cumulative relapse incidence.However,in high-risk patients,high-dose CD34+ cells result in increased non-relapse mortality within 100 days after transplantation,which is considered to be possibly associated with an increased occurrence of severe acute graft versus host disease in the early post-transplantation period.Therefore,it is considered that graft versus host disease monitoring should be enhanced in patients who transfused high-dose CD34+ cells.

BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an effective and even the only way to cure various hematological diseases,but the short-term mortality rate is relatively high after transplantation. OBJECTIVE:To investigate the risk factors affecting the overall survival of patients with hematological diseases in the short term(within 100 days)after allogeneic hematopoietic stem cell transplantation,so as to reduce mortality and effectively prevent related risks in the short term(within 100 days)after allogeneic hematopoietic stem cell transplantation. METHODS:Clinical data of 585 patients with hematological diseases who underwent allogeneic hematopoietic stem cell transplantation at the Hematopoietic Stem Cell Transplantation Center of First Affiliated Hospital of Zhengzhou University from January 1,2018 to June 30,2021 were retrospectively analyzed.The risk factors that affected overall survival within 100 days after allogeneic hematopoietic stem cell transplantation were explored. RESULTS AND CONCLUSION:A total of 585 patients with hematologic diseases underwent allogeneic hematopoietic stem cell transplantation.92 patients died within 100 days after transplantation,with a mortality rate of 15.7%(92/585).The median age of death cases was 26.5 years old(1-56 years),and the median survival time of death cases was 48 days(0-97 days).Univariate analysis exhibited that age≥14 years old,acute graft-versus-host disease,grade IV acute graft-versus-host disease,bacterial bloodstream infection,as well as carbapenem-resistant organism bloodstream infection,were risk factors for overall survival within 100 days after allogeneic hematopoietic stem cell transplantation(P<0.05).Multivariate regression analysis showed that age≥14 years old,grades Ⅲ-Ⅳ acute graft-versus-host disease,bacterial bloodstream infection,and carbapenem-resistant organism bloodstream infections were independent risk factors for overall survival(within 100 days)in patients after allogeneic hematopoietic stem cell transplantation.Hazard ratios were 1.77(95%CI 1.047-2.991),7.926(95%CI 3.763-16.695),2.039(95%CI 1.117-3.722),and 3.389(95%CI 1.563-7.347),respectively.In conclusion,all-cause mortality rate after allogeneic hematopoietic stem cell transplantation is relatively high in the short term.A timely diagnosis and effective treatment of bacterial bloodstream infection and acute graft-versus-host disease are essential to improving allogeneic hematopoietic stem cell transplantation outcomes.

Objective To observe the effects of brain-computer interface-controlled pedal training system on bal-ance function and serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)levels in ischemic stroke pa-tients.Methods Forty patients with ischemic stroke who were hospitalized from September 2022 to September 2023 were selected as observation subjects.The patients were equally divided into stroke control group and stroke experimental group according to the random number table method.At the same time,20 healthy subjects with similar gender and age were recruited as the healthy control group to collect relevant plantar pressure data.Patients in the stroke control group received conventional rehabilitation training including the upper and lower extremity active and passive motor training system,and the stroke experimental group replaced the upper and lower extremity active and passive motor training system in the stroke control group with the brain-computer interface-controlled pedal training system for rehabilitation treatment,and other things remained unchanged.Bilateral plantar pressure symmetry index(SI)and center of body pressure(COP)swing area were collected from both groups of stroke patients with eyes open and closed using the plantar pressure assessment system before and after 4 weeks of treatment.Fugl-meyer low-er extremity motor function score(FMA-LE)and berg balance scale(BBS)were used to evaluate the two groups of stroke patients.Serum IL-6 and TNF-α levels were also compared between the two groups before and after treat-ment.Results ① The SI value and COP swing area in the eyes open and closed state improved in both groups of stroke patients after treatment compared with that before admission,and the results of the stroke experimental group were better than those of the stroke control group(P＜0.05),but there was still a gap with the healthy control group(P＜0.05).②The BBS and FMA-LE scores of stroke patients in both groups were higher after treatment than before treatment,and the scores of the stroke experimental group were greater than those of the stroke control group,with statistically significant differences(all P＜0.05).③Serum IL-6 and TNF-α levels decreased in both groups of stroke patients after treatment compared with before,and the degree of decrease in serum IL-6 and TNF-αlevels in the stroke experimental group was greater than that in the stroke control group,and the difference was sta-tistically significant(P＜0.001,P＜0.05).Conclusion Brain-computer interface-controlled pedal training sys-tem has a facilitating effect on the recovery of balance function in hemiplegic patients with ischemic stroke,and its mechanism may be related to the reduction of serum IL-6 and TNF-α levels.

Objective:To investigate the clinicopathological characteristics of early gastric cancer with mixed histological staging, and to analyze the prognostic effect of endoscopic submucosal dissection (ESD) for early gastric cancer.Methods:Clinical data of early gastric cancer patients treated with ESD in Gansu Wuwei Cancer Hospital from January 2011 to March 2020 were collected, and clinicopathological characteristics of patients with mixed-type early gastric cancer were analyzed by descriptive statistical methods. The clinical effects and influencing factors of ESD on early gastric cancer were analyzed by logistic regression. Kaplan-Meier was used to estimate the survival rate, and log-rank test was used to compare the survival rate.Results:A total of 269 patients (280 lesions) were included in this study, including 216 males (80.30%) and 53 females (19.70%), with age of 60.43±8.01 years. There were 25 lesions (8.93%) of mixed early gastric cancer, 248 lesions (88.57%) of differentiated early gastric cancer, and 7 lesions (2.50%) of undifferentiated early gastric cancer. Compared with differentiated and undifferentiated early gastric cancer, the lesion site of mixed early gastric cancer was mainly located in the upper 1/3 of the stomach [64.00% (16/25), 40.73% (101/248) VS 0.00% (0/7), χ2=10.211, P=0.006], the proportion of the lesion size ≤2 cm was relatively small [52.00% (13/25), 80.65% (200/248) VS 85.71% (6/7), χ2=11.173, P=0.004], and the proportion of infiltration depth in the mucosa was lower [52.00% (13/25), 85.48% (212/248) VS 57.14% (4/7), χ2=20.019, P<0.001], the proportion of positive vertical resection margin was relatively high [20.00% (5/25), 2.82% (7/248) VS 0.00% (0/7), χ2=16.657, P<0.001], the proportion of vascular invasion was higher than that of differentiated carcinoma but lower than that of undifferentiated carcinoma [36.00% (9/25), 2.42% (6/248) VS 42.86% (3/7), χ2=58.413, P<0.001], the complete resection rate was lower [76.00% (19/25), 93.15% (231/248) VS 100.00% (7/7), χ2=9.497, P=0.009], the curative resection rate was lower than that of differentiated early gastric cancer, but higher than that of undifferentiated early gastric cancer [48.00% (12/25), 89.52% (222/248) VS 42.86% (3/7), χ2=39.757, P<0.001], and the proportion of eCura grade C2 was higher than that of differentiated cancer, but lower than that of undifferentiated cancer [48.00% (12/25), 5.65% (14/248) VS 57.14% (4/7), χ2=58.766, P<0.001]. The results of multivariate analysis showed that the larger lesions ( P=0.004, OR=0.539, 95% CI: 0.354-0.822) was the risk factor for curative resection. In terms of infiltration depth, mucosal ( P=0.001, OR=51.799, 95% CI: 5.535-84.768) and submucosal 1 ( P<0.001, OR=29.301, 95% CI: 24.694-73.972) were protective factors for curative resection compared with submucosal 2. In terms of differentiation degree, compared with mixed type, differentiated type ( P=0.024, OR=3.947, 95% CI: 1.195-13.032) was the protective factor for curative resection, while undifferentiated type ( P=0.443, OR=0.424, 95% CI: 0.048-3.788) showed no difference between curative resection and mixed type. During the follow-up, 7 patients died. The overall survival time was 114.42±0.97 months, and the 5-year survival rate was 97.10%. There was no significant difference in the survival rate of early gastric cancer patients with different degrees of differentiation ( χ2=0.434, P=0.805). The survival rate of early gastric cancer patients with or without curative resection was significantly different ( χ2=4.081, P=0.043). Conclusion:Mixed early gastric cancer patients show high margin positive rate, vascular infiltration, and less curative resection than differentiated early gastric cancer. Therefore, the process of treating mixed early gastric cancer should be more rigorous. The long-term survival prognosis of early gastric cancer after ESD treatment is promising.

To investigate the epidemiology of avian infectious bronchitis virus(IBV)and study the pathogenicity of IBV isolate,we isolated the IBV field strain from a clinical sample of chickens sus-pected to be infected with infectious bronchitis virus(IBV)from Hefei,Anhui Province,named HF210416.Sequencing analysis of the S1 gene showed that HF210416 belonged to the GI-22 geno-type,which was significantly differed from that of the reference GI-22-type strains,with homology ranging only from 84.5％to 87.8％.Recombinant analysis showed that HF210416 was a recombi-nant strain,with YX10(GI-19)as the major parent and YN(GI-19)as the minor parent.2-day-old SPF chicks infected with the HF210416 isolate showed clinical symptoms such as breathing with difficulty,depression and excreting watery droppings;the infected chicks had a rapid onset of dis-ease,with mortality occurring on the second day of inoculation,and mortality persisted until the fifth day,with 33.33％(5/15)mortality rate.The infected chicks recovered the 14th day after inoculation.RT-PCR detection of pharyngeal-anal swabs showed that the virus shedding by infected chicks could be continuously detected within 14 days of the test period;Enlarged and pale kidney as well as urate deposition in the kidney were observed in infected dead and undead chicks;and the HE staining of histopathological slices showed that the cilia of trachea were removed.Immunohis-tochemistry showed that obvious viral signals were observed in the trachea,lungs,and kidneys.The viral load of various tissues was detected by RT-qPCR and it showed that HF210416 had the high-est replication efficiency in kidney tissues,then in cecum tonsils and trachea.The results of serum neutralization test showed that HF210416 had a better neutralization effect on GI-22 homologous strains,but poorer neutralization effect on other genotypes strains,suggesting that HF210416 is not suitable for vaccine candidate.In conclusion,the GI-22 isolate HF210416 is highly pathogenic and nephrotropic to chicks,and its genomic genetic characteristics and immunogenicity are differ-ent from those of other strains.This study enriches the resources of IBV strains and provides refer-ence data for understanding of the prevalence and pathogenicity of GI-22 genotypes in China.