AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.

Objective: To examine the mediating effect of resilience on AIDS-related stress and patient-reported outcome among elderly cases with HIV/AIDS, so as to provide the basis for promoting mental health and improving health outcomes of this population. Methods: From June to July 2024, elderly cases with HIV/AIDS receiving treatment in the infectious diseases department of a tertiary-level hospital in Sichuan Province and undergoing follow-up management at 12 community health service centers in Wuhou District, Chengdu City, Sichuan Province, were selected as study participants using convenience sampling method. Data on demographic information, duration since confirmed diagnosis and the most recent CD4+T lymphocyte count were collected through questionnaire surveys. The Chinese versions of the HIV/AIDS Stress Scale, the Chinese versions of the 10-item Connor-Davidson Resilience Scale, and the Patient-Reported Outcome Scale for Elderly HIV/AIDS Patients were used to assess AIDS-related stress, resilience, and patient-reported outcome, respectively. Structural equation modeling was performed using Mplus 8.3 software to analyze the mediating effect of resilience on AIDS-related stress and patient-reported outcome. The Bootstrap method was employed to test the significance of the mediating effect. Results: A total of 424 elderly HIV/AIDS cases were included, with a mean age of (62.04±8.73) years. Among them, 315 (74.29%) were males and 109 (25.71%) were females. The median scores were 23.00 (interquartile range, 11.00) points for AIDS-related stress, 30.00 (interquartile range, 7.00) points for resilience, and 363.45 (interquartile range, 53.03) points for the total score of patient-reported outcome. Resultsof the mediation effect analysis revealed that AIDS-related stress had a direct negative effect on patient-reported outcome (β=-0.608, 95%CI: -0.742 to -0.465). It also exerted an indirect negative effect on patient-reported outcome through the mediating role of resilience (β=-0.258, 95%CI: -0.364 to -0.158), with the mediating effect accounting for 29.79% of the total effect. Conclusion AIDS-related stress among elderly cases with HIV/AIDS can directly or indirectly negatively affect patient-reported outcome through resilience.

AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.

OBJECTIVE To study the effects and mechanisms of serum containing Wenjing Tongluo Decoction on interleukin-1β(IL-1β)-induced mouse primary chondrocyte injury.METHODS The IL-1β-induced primary chondrocyte injury model was estab-lished,and the mRNA expression of inflammatory factors IL-1β,IL-6,TNF-α,cartilage degradation-related proteases matrix metal-loproteinase 3(MMP3),MMP9,MMP13,ADAM metallopeptidase containing thrombospondin 1 motif 4(ADAMTS4),and glycoly-sis-related enzymes lactate dehydrogenase A(LDHA),M2 pyruvate kinase(PKM2),reduced coenzyme Ⅱ oxidase 2(NOX2)and re-duced coenzyme Ⅱ oxidase 4(NOX4)in the cells was detected;the intracellular MMP3,MMP13,P65,IκB-ζ,hypoxia-inducible factor 1α(HIF-1α)and LDHA protein expression levels were determined;the concentrations of nitric oxide(NO),malondialdehyde(MDA)and lactic acid in the cell supernatant were further detected,and the ratio of the reduced state(NADH)and oxidized state(NAD+)of intracellular coenzyme Ⅰ(NAD),as well as intracellular reactive oxygen species(ROS)levels were assayed.RESULTS Serum containing Wenjing Tongluo Decoction significantly inhibited the mRNA expression of IL-1β,IL-6,and TNF-α in IL-1β chondrocytes(P＜0.01),reduced the NO concentration in the cell supernatant(P＜0.05,P＜0.01),and downregulated the protein ex-pression of IκB-ζ(P＜0.05)and P65(P＜0.05,P＜0.01).Serum containing Wenjing Tongluo Decoction significantly downregulated the mRNA expression of MMP3,MMP9,MMP13 and ADAMTS4(P＜0.01),and inhibited the protein expression of MMP13(P＜0.05,P＜0.01)and MMP3(P＜0.05).In terms of oxidative stress,it significantly suppressed the production of ROS in chondrocytes,increased the NADH/NAD+ratio,reduced the MDA concentration in the supernatant,and downregulated the expression of HIF-1α protein(P＜0.01).The serum containing Wenjing Tongluo Decoction significantly reduced the lactic acid concentration,downregulated the expression of LDHA,PKM2,NOX2 and NOX4,and reduced the level of intracellular glycolysis(P＜0.05,P＜0.01).CONCLU-SION The serum containing Wenjing Tongluo Decoction can alleviate IL-1β-induced mouse primary chondrocyte injury by inhibiting inflammation,cartilage degradation,oxidative stress and glycolysis,which may be related to the regulation of IκB-ζ/HIF-1α/LDHA axis.

OBJECTIVE To evaluate the effects of different functional dyspepsia(FD)modeling methods and explore the thera-peutic effect and potential mechanism of Banxia Xiexin Decoction on FD.METHODS BALB/c mice were randomly divided into the blank group,iodoacetamide group,loperamide group,tail clamp group and vinegar group.After 1 week of intervention,the status of mice in each group was observed and their gastrointestinal motility,hormone levels and pathological changes were detected.A more i-deal FD modeling method was evaluated and determined.After modeling,different doses of Banxia Xiexin Decoction were given to in-tervene,and the changes in the gastrointestinal function of mice were observed.The expression of related proteins was studied by im-munohistochemistry,ELISA,Western Blot and other experimental methods.RESULTS Comparing the four modeling methods,it was found that the mice in the iodoacetamide group,loperamide group,and vinegar group showed weight loss compared to the blank group;the gastric emptying rate and small intestinal propulsion rate of mice in the iodoacetamide group and vinegar group decreased;changes in gastrointestinal hormones were found in the serum of mice in the tail clip group and vinegar group.Finally,the iodoacetamide meth-od was evaluated as the optimal FD modeling method.The administration results showed that Banxia Xiexin Decoction had no signifi-cant effect on the food intake and body weight of FD mice,while medium and high doses could improve the physical condition of FD mice,increase their gastric emptying rate and small intestine propulsion rate.The experimental results of immunohistochemistry,West-ern blotting,and ELISA confirmed that medium and high doses of Banxia Xiexin Decoction can significantly reduce the expression lev-els of TNF-α and IL-6 in the duodenum and serum of FD mice.CONCLUSION The iodoacetamide method is a better FD modeling method.Banxia Xiexin Decoction can improve the condition of FD mice,increase gastrointestinal motility,reduce the secretion of in-flammatory factor,thereby achieving the therapeutic effect of treating FD.

Intestinal fibrosis is a complication of inflammatory bowel disease,and its refractory and recurrent nature impose a serious disease burden on patients.The disease's pathogenes is not clear,and there is no effective treatment.Moreover,there is still a lack of recognized intestinal fibrosis models.In this paper,we review the method used to establish animal models of intestinal fibrosis both at home and abroad,and consider the clinical relevance,key characteristics,and advantages and disadvantages of the procedures.Intestinal fibrosis models were summarized according to the modeling period and method.

Objective:To investigate the association of WWP2 single nucleotide polymorphism (rs3790088, rs4247109) with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) , and explore the influences of DEACMP genetic predisposition. Methods:From November 2006 to December 2017, 235 DEACMP cases and 429 acute carbon monoxide poisoning (ACMP) cases were selected. All ACMP patients were followed up for more than 90 days without DEACMP. The DNA in all blood samples were extracted with the blood Genome DNA Extraction Kit. The method of Sequenom Mass Array SNP technique was used to detect the genotype and allele of WWP2. All DEACMP patients were assessed every 3 days after hospitalization by the Hasegawa Dementia Scale (HDS) and Activity of Daily Living Scale (ADL) . The distribution of genotypes in conformty with Hardy-Weinderg law was analyzed by goodness-of-fit χ 2 test, and χ 2 test was used for association analysis. Results:For rs3790088, there were 226 DEACMP cases and 414 ACMP cases. For rs4247109, there were 234 DEACMP cases and 428 ACMP cases. For rs3790088 and rs4247109 in WWP2 gene: there were not significant differences in the gene genotype distribution and allele frequency of both DEACMP group and ACMP group ( P>0.05) . According to gender, there were not significant differences in WWP2 gene genotype distribution and allele frequency between two female groups and two male groups ( P>0.05) . After analysis by genetic model, the genotype distributions in both DEACMP group and ACMP group were not significantly differences in three genetic models (codominant genetic model, recessive genetic model and dominant genetic model, P>0.05) . Conclusion:It has not confirmed the genetic correlation between the two gene single nucleotide polymorphisms (rs3790088, rs4247109) of WWP2 gene and the incidence of DEACMP.

Objective:To investigate the association of WWP2 single nucleotide polymorphism (rs3790088, rs4247109) with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) , and explore the influences of DEACMP genetic predisposition. Methods:From November 2006 to December 2017, 235 DEACMP cases and 429 acute carbon monoxide poisoning (ACMP) cases were selected. All ACMP patients were followed up for more than 90 days without DEACMP. The DNA in all blood samples were extracted with the blood Genome DNA Extraction Kit. The method of Sequenom Mass Array SNP technique was used to detect the genotype and allele of WWP2. All DEACMP patients were assessed every 3 days after hospitalization by the Hasegawa Dementia Scale (HDS) and Activity of Daily Living Scale (ADL) . The distribution of genotypes in conformty with Hardy-Weinderg law was analyzed by goodness-of-fit χ 2 test, and χ 2 test was used for association analysis. Results:For rs3790088, there were 226 DEACMP cases and 414 ACMP cases. For rs4247109, there were 234 DEACMP cases and 428 ACMP cases. For rs3790088 and rs4247109 in WWP2 gene: there were not significant differences in the gene genotype distribution and allele frequency of both DEACMP group and ACMP group ( P>0.05) . According to gender, there were not significant differences in WWP2 gene genotype distribution and allele frequency between two female groups and two male groups ( P>0.05) . After analysis by genetic model, the genotype distributions in both DEACMP group and ACMP group were not significantly differences in three genetic models (codominant genetic model, recessive genetic model and dominant genetic model, P>0.05) . Conclusion:It has not confirmed the genetic correlation between the two gene single nucleotide polymorphisms (rs3790088, rs4247109) of WWP2 gene and the incidence of DEACMP.

Objective To explore the relationship between aural pre-attentive processing and non-rapid eye movement(NREM) sleep interictal epileptiform discharge (IED) in children with benign childhood epilepsy with central-temporal spikes (BECTS),in order to provide objective electrophysiological basis for early assessment of cognitive function lesion of BECTS children and intervention.Methods Twenty-nine children diagnosed as BECTS in the Second Affiliated Hospital of Xinxiang Medical University from February 2012 to November 2015 were selected,including 17 males and 12 females,and they were 4-14 years old with average age of (9.17 ±2.42) years,and the course of disease was 0.5-4.0 years.Twenty healthy children who had hospital routine check-up were selected as healthy control group,containing 14 males and 6 females,and they were 5-13 years old with average age of (8.55 ±3.09) years.Mismatch negativity (MMN) test was carried out in both groups,and the MMN amplitudes and latencies were analyzed.The long-term video electroencephalogram (VEEG) monitoring was conducted in the BECTS group to analyze the discharge phases (waking,sleep),locations and the IED indexes.The intergroup MMN indexes and the correlation between MMN and VEEG in the BECTS group were compared.Results The VEEG showed that the sleep structure of BECTS children did not change obviously.All children's epileptiform discharges were located in the Rolandic area,including 11 cases on the left side,8 cases on the right side,and 10 cases on both sides.Epilepsy discharge time:17 patients showed epileptiform discharges in sleep stages only and 12 patients showed epileptiform discharge in both sleep and waking stages.Epileptiform discharges of the 12 patients increased more significantly in sleep stage than thatin waking stage [(40.24 ± 25.15) times/min vs.(1.92 ± 1.38) times/rmin],and the difference was statistically significant (t =5.270,P =0.000).The sample IED index in stage 1 and 2 of NREM was (40.73 ± 10.69) times/min,in which 2 cases had IED indexes ＜ 5 times/min,the IED indexes of 3 cases ＞ 80 times/min who reached electrical status epilepticus during sleep,and others were 17.2-64.6 times/min.Clinical seizures in sleep stages were monitored in only 4 cases,which showed an electro-clinical segregation phenomenon from large quantities of sleep IED.The MMN amplitude was lower in the BECTS group than that in the healthy control group [(6.06 ± 1.89) μV vs.(7.28 ±1.64) μV],and the difference was statistically significant (t =2.346,P =0.025).Latency of BECTS group was longer than that in the healthy control group [(191.37 ±40.13) ms vs.(179.35 ±39.80) ms],but the difference was not statistically significant(t =1.037,P =0.355).Correlation analysis showed that the MMN amplitude was negatively related to discharge phases (r =-0.407,P ＜ 0.05) and the IED indexes (r =-0.644,P ＜ 0.01),and latency was positively related to the IED indexes (r =0.386,P ＜ 0.05),while the other VEEG indexes were not correlated with MMN.Conclusions The BECTS children have aural pre-attentive processing disturbance,especially unconscious automatic processing ability impairment,which weakenattention switch action of automatic processing switching to focused attention processing and fail to filter irrelevant information effectively.Sleep IED is an important factor in impairing the formation and reinforcement of acoustic discrimination and memory trace,interfering the acquisition,processing,storage and matching of new information,which induces children pre-attentive processing disturbance.The MMN may discover the electrophysiological changes of children pre-attentive processing disturbance in early stage.

OBJECTIVEBy explore the role of serum soluble Fas (sFas) in occurrence and progression of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP).

METHODSEnzyme-linked immunosorbent assay (ELISA) was used to detect serum sFas levels in 40 patients with DEACMP in acute stage and convalescent stage, with 36 healthy elderly subjects as the control group.

RESULTSSerum sFas levels of the patients with DEACMP in both the acute and convalescent stages showed no significant difference from those in the control group (P=0.737 and 0.137, respectively), nor was any significant difference found between the patients in acute and exacerbation stages (P=0.059).

CONCLUSIONSerum sFas is not involved in the occurrence and progression of DEACMP.

Adult ; Aged ; Aged, 80 and over ; Brain Diseases ; etiology ; Carbon Monoxide Poisoning ; blood ; complications ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; fas Receptor ; blood