ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

Chronic hepatitis B virus (HBV) infection remains a major global public health concern. The persistent presence of intrahepatic covalently closed circular DNA (cccDNA) poses a major challenge to the complete cure of chronic HBV infection. Therefore, identifying reliable and effective serological surrogate markers for cccDNA holds great clinical significance in evaluating antiviral efficacy, predicting prognosis, and guiding the clinical management of chronic HBV-infected patients. In recent years, serum HBV RNA has emerged as a promising non-invasive alternative marker for cccDNA, offering the potential for monitoring disease progression and predicting prognosis in chronic HBV-infected patients. In this review, we summarize recent studies on HBV RNA, highlighting its ability to assess the immune and histological status of patients, and discussing its value in guiding the timing of antiviral therapy. Furthermore, we systematically summarize the clinical significance of HBV RNA in multiple domains: monitoring viral replication, evaluating antiviral treatment efficacy, predicting relapse after treatment cessation, and guiding new antiviral strategies. This review aims to provide clinicians with valuable insights for better utilizing this marker in the clinical management of chronic HBV infection.

Objective:To explore the mediating effect of dyadic coping between perceived social support and family cohesion and adaptability and happiness in spouses of patients with post-stroke motor impairments.Methods:From December 2023 to May 2024, a total of 366 spouses of patients with post-stroke motor impairments who received treatment at the First Affiliated Hospital of Zhengzhou University were recruited as study participants. Data were collected using the general information, perceived social support scale, dyadic coping inventory, Chinese version of the family cohesion and adaptability scale(FACESⅡ-CV), and memorial University of Newfoundland scale of happiness. The AMOS 21.0 software was utilized to construct a structural equation model to examine the mediating effect of dyadic coping between perceived social support, family cohesion and adaptability and happiness.Results:The spouses of patients with post-stroke motor impairments reported overall scores for perceived social support (62.80±12.80), dyadic coping (117.07±20.78), family cohesion and adaptability (115.96±19.51), and happiness (22.27±7.29). Family cohesion and adaptability was positively correlated with dyadic coping and perceived social support ( r=0.614, 0.520, both P<0.01).Spousal happiness was positively correlated with dyadic coping and perceived social support ( r=0.296, 0.202, both P<0.01).The spouses recognized that perceived social support had a positive correlation with dyadic coping ( r=0.479, P<0.01).Dyadic coping played a partial mediating effect between perceived social support and family cohesion and adaptability as well as happiness, accounting for 32.41% (0.211/0.651) and 44.39% (0.190/0.428) of the total effect, respectively. Conclusion:Dyadic coping is the mediating variable of family cohesion, adaptability and happiness of spouses of patients with post-stroke motor impairments. Medical staff should try to construct a dyadic coping intervention plan to improve the dyadic coping level of spouses of patients with post-stroke motor impairments, so as to improve their family happiness index.

Objective To establish the fingerprint of Xuemai Shutong granules by UPLC-ELSD and determine the contents of 9 components in the preparation simultaneously.Methods The UPLC-ELSD was used to establish the fingerprint of Xuemai Shutong granules,and determine the content of its 9 components.The similarity evaluation system,systematic,cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used to evaluate the quality of different batches of preparation.Results The similarity degrees of UPLC-ELSD fingerprints of 11 batches of Xuemai Shutong granules were from 0.929 to 0.978,17 common peaks were calibrated,of which 11 peaks were identified:peak 3(notoginsenoside R1),peak 4[ginsenoside Rg,(Re)],peak 5(notoginsenoside R2),peak 6(ginsenoside Rb,),peak 9(astragaloside Ⅳ),peak 10(ginsenoside Rk3),peak 11(ginsenoside Rh4),peak 12[20(S)-ginsenoside Rg3],peak 13[20(R)-ginsenoside Rg3],peak 14(ginsenoside Rk1),peak 15(ginsenoside Rg5).The stoichiometric analysis divided 11 batches of samples into 2 classes,and the 2 principal components in PCA analysis reflected the information of 17common peaks,10 peaks which affected the quality difference are screened out.The linear relationship of the 9 components was good in their respective quality ranges in the content analysis(r＞0.999 2),the average recovery rate were between 95.02％-97.78％and the RSD were 0.69％-1.70％(n=6).The contents of notoginsenoside R1,notoginsenoside R2,ginsenoside Rb1,astragaloside Ⅳ,ginsenoside Rh4,20(S)-ginsenoside Rg3,20(R)-ginsenoside Rg3,ginsenoside Rk1 ginsenoside Rg5 in the 11 batches of Xuemai Shutong granules were 0.087 5-0.187 6,0.494 3-0.688 6,0.448 1-0.705 5,0.192 2-0.270 8,1.492 5-2.077 6,0.316 0-0.463 8,0.254 5-0.382 0,0.117 6-0.163 9,3.407 7-4.706 4 mg·g-1,respectively.Conclusions The established fingerprint and content determination method was accurate and reliable,which can improve the quality standard of Xuemai Shutong granules,and provide reference for its overall quality evaluation.

To study the immunoregulatory effects of lycorine on mice infected with Toxoplasma gondii(T.gondii),BALB/c mice were treated with 20 mg/kg lycorine solution after peritoneal in-fection with T.gondii RH strain.The serum and spleen of mice were collected at the 1st,3rd,5th and 7th day,respectively,and the spleen index of mice was calculated.The proportion of T lympho-cyte subtypes and NK cells were detected in mice by flow cytometry,and the changes of cytokine levels in mice were measured using ELISA kit,so as to evaluate the immunomodulatory effect of lycorine on mice infected with T.gondii.At the same time,the heart,liver,spleen,lungs,and kid-neys of mice were collected at the 7th day,and the pathological changes of the mouse organs were observed through pathological tissue sections,and the amount of the parasite in the liver,lung,kid-ney,and brain of the mice was detected by fluorescence quantitative PCR.The results showed that the survival time of the mice treated with lycorine was significantly extended,and the survival rate reached 80％.The spleen index of mice treated with lycorine was lower than that of the control group.Lycorine up-regulates the ratio of the CD4+T lymphocytes and NK cells in the spleen of mice infected with T.gondii,and helps to improve the ability of mice to resist T.gondii infection.Lycorine can up-regulate the levels of anti-inflammatory cytokine IL-4 and down-regulate the lev-els of pro-inflammatory factors IFN-γ,IL-1β,and IL-9 in serum of mice infected with T.gondii,which is conducive to reducing the damage of inflammatory response and enhancing the ability of anti-T.gondii infection.In addition,lycorine can alleviate the pathological damage of T.gondii to the liver,lungs,spleen,and kidneys of mice,and significantly reduce the amount of the parasite in the lung of mice.The results showed that lycorine could up-regulate the proportion of immune cells CD4+T lymphocytes and NK cells,inhibit the inflammatory response of mice infected with T.gondii,reduce the pathological damage of mice organs,and enhance the ability of mice to resist T.gondii infection,which is expected to become a novel anti-T.gondii drug.

OBJECTIVES: To verify whether hesperetin (Hes) alleviates doxorubicin (DOX)-induced cardiotoxicity by reducing inflammation via regulating the AMPK/NLRP3 pathway. METHODS: C57/bl6 mice and H9c2 cells treated with DOX to mimic cardiotoxicity were randomly divided into Sham (or control) group, DOX group, DOX+Hes group, DOX+Hes+compound C (CC, an AMPK inhibitor) group. Cardiac function and myocardial pathologies of the mice were evaluated, and the changes in H9c2 cell morphology and viability were assessed. Lactate dehydrogenase (LDH) activity in mouse myocardial tissues and H9c2 cells was measured using ELISA, and H9c2 cell apoptosis was detected with TUNEL staining. In both H9c2 cells and the myocardial tissues of the mice, cellular expression levels of TNF-α, IL-6 and IL-1β mRNAs and cleaved caspase-3, Bcl2, Bax, IL-1β, IL-18, p-AMPK, AMPK, p-mTOR, mTOR, NLRP3, ASC and caspase-1 proteins were detected using RT-PCR and Western blotting. RESULTS: DOX treatment caused cell swelling, decreased cell viability and increased LDH activity in H9c2 cells, resulting also in significantly increased cell apoptosis and cleaved caspase-3 expression and decreased Bcl2/Bax ratio. The DOX-treated mice showed obvious myocardial fiber swelling and inflammatory infiltration, decreased cardiac function and significantly increased myocardial LDH activity. In H9c2 cells, DOX treatment significantly increased the mRNA expressions of TNF-α, IL-6 and IL-1β and protein expressions of IL-1β and IL-18, lowered the expressions of p-AMPK and p-mTOR, and increased the expressions of NLRP3, ASC and caspase-1. Hes treatment obviously reduced these toxic effects of DOX in H9c2 cells, but its protective effects were blocked by application of compound C. CONCLUSIONS Hes reduces DOX-induced cardiotoxicity by inhibiting inflammation via regulating the AMPK/NLRP3 pathway.
Animals ; Doxorubicin/toxicity* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice, Inbred C57BL ; Mice ; Signal Transduction/drug effects* ; Cardiotoxicity ; AMP-Activated Protein Kinases/metabolism* ; Apoptosis/drug effects* ; Cell Line ; Myocytes, Cardiac/drug effects* ; Rats

Objective To investigate the expression of ferritinophagy-related gene ELAV-like RNA binding protein 1(ELAVL1)in multiple myeloma(MM)and elucidate its diagnostic and prognostic value for MM.Methods First,we analyzed ELAVL1 expression level in healthy controls and MM patients using data from the GEO and TCGA databases.Subsequently,bone marrow specimens were collected from 28 newly diagnosed MM patients and 20 healthy controls,and qRT-PCR was employed to validate ELAVL1 expression.The diagnostic and prognostic potential of ELAVL1 was assessed using ROC curve analysis and Kaplan-Meier survival curves.Additionally,univariate and multivariate COX regression analyses were performed to identify independent risk factors for MM prognosis.Finally,KEGG and GO enrichment analyses were performed using the DAVID online platform.Results The level of ELAVL1 expression was significantly higher in newly diagnosed MM patients and refractory/relapsed MM patients than in the healthy controls(P＜0.001).Moreover,ELAVL1 expression was positively correlated with the International Staging System(ISS)stage of MM(P＜0.01).Furthermore,qRT-PCR validation confirmed that ELAVL1 expression was elevated in the 28 newly diagnosed MM patients compared to the 20 healthy controls(P＜0.001).ROC curve analysis demonstrated that ELAVL1 could effectively differentiate between newly diagnosed MM patients,healthy controls,and MGUS patients(P＜0.001 and P=0.000 2,respectively).Survival analysis revealed that high ELAVL1 expression was associated with shorter progression-free survival(P=0.0141)and overall survival(P=0.008 0).Univariate and multivariate COX regression analyses identified high ELAVL1 expression as an independent risk factor for poor MM prognosis(P=0.005 0).KEGG analysis suggested that ELAVL1 might be involved in the Hippo and MAPK signaling pathways.Conclusion High ELAVL1 expression in MM may serve as a biomarker for diagnosis and poor prognosis.ELAVL1 may promote MM initiation and progression via the Hippo and MAPK signaling pathways.

Apolipoprotein D(APOD)is a protein that is widely present in animal tissues and is in-volved in the reproductive regulation of the body.In order to investigate the expression regularity of APOD in bactrian camel epididymis and its regulation effect on sperm maturation,this study took the epididymis of bactrian camel during estrus and anestrus as materials,and first cloned the complete sequence of APOD coding sequence(CDS)region.The physicochemical properties of AP-OD were analyzed by ProParam,SOPMA,SWISS-MODEL and MEGA7.0 software.Meanwhile,the expression and distribution of APOD in epididymis were detected by qRT-PCR,Western blot and IHC.The cloning results showed that:the length of the CDS region of APOD gene was 624 bp,encoding 207 amino acids.The APOD sequence of Bactrian camel was highly conserved with the nucleotide and amino acid sequence of alpaca,and the homology of APOD sequence with elk was the lowest.The results of qRT-PCR showed that the mRNA levels of APOD in the head,body and tail of epididymis in estrus were significantly higher than those in estrus(P＜0.01).Western blot results showed that the APOD protein expression and mRNA expression trend was similar in the head and body of the epididymis during anestrus,but the APOD expression level in the tail of the epididymis during anestrus was opposite to the mRNA expression level(P＜0.05).The results of H&E and IHC showed that there were significant differences in epididymal tissue between estrus and anestrus.In addition,APOD showed positive reactions in epididymal epithelial cells,smooth muscle cells,sperm and connective tissue to varying degrees,suggesting that APOD may be in-volved in the maturation of sperm during estrus and anestrus,providing evidence for further explo-ring the regulatory mechanism of APOD's involvement in seasonal estrus.

Objective To establish a pediatric rare disease catalog,analyze the current status of therapeutic drugs and their coverage of the medical insurance in China,and propose strategies to enhance drug accessibility.Methods Pediatric rare diseases were identified from China's two national rare disease catalogs combined with the EU Orphanet database,US FDA orphan drug database,and the Diagnosis and Treatment Standards for Rare Diseases in Children.We created a specialized drug catalog for pediatric rare diseases,then analyzed drug types(ATC classification),pricing,and medical insurance coverage using descriptive statistics based on Yaozhi.com drug bidding prices and the 2024 Drug of List National Basic Medical Insurance(NBMIDL).Drug affordability was assessed through annual treatment cost calculations.Results The national catalogs included 151 pediatric rare diseases(72.95%of listed conditions),spanning 13 disease systems.We identified 94 dedicated orphan drugs(by generic name)for these conditions,among which 43 were approved internationally but unavailable in China.The average unit price per package was 6 113.53 yuan.Overall NBMIDL coverage was 68.83%,but drugs priced above 7 000 yuan per unit had only 7.69%coverage.Annual treatment costs reached 4.54 million for laronidase(mucopolysaccharidosis).Conclusions Critical gaps persist in China's pediatric rare disease treatment landscape,including catalog deficiencies,inadequate coverage for high-cost drugs and insufficient domestic innovation.It is recommended to establish a list of orphan drugs for pediatric rare diseases,accelerate the import of foreign drugs and the local innovative drugs through policy incentives,optimizing medical insurance reimbursement mechanisms for pediatric rare disease drugs to comprehensively improve therapeutic accessibility.

Objective:To explore the mediating effect of dyadic coping between perceived social support and family cohesion and adaptability and happiness in spouses of patients with post-stroke motor impairments.Methods:From December 2023 to May 2024, a total of 366 spouses of patients with post-stroke motor impairments who received treatment at the First Affiliated Hospital of Zhengzhou University were recruited as study participants. Data were collected using the general information, perceived social support scale, dyadic coping inventory, Chinese version of the family cohesion and adaptability scale(FACESⅡ-CV), and memorial University of Newfoundland scale of happiness. The AMOS 21.0 software was utilized to construct a structural equation model to examine the mediating effect of dyadic coping between perceived social support, family cohesion and adaptability and happiness.Results:The spouses of patients with post-stroke motor impairments reported overall scores for perceived social support (62.80±12.80), dyadic coping (117.07±20.78), family cohesion and adaptability (115.96±19.51), and happiness (22.27±7.29). Family cohesion and adaptability was positively correlated with dyadic coping and perceived social support ( r=0.614, 0.520, both P<0.01).Spousal happiness was positively correlated with dyadic coping and perceived social support ( r=0.296, 0.202, both P<0.01).The spouses recognized that perceived social support had a positive correlation with dyadic coping ( r=0.479, P<0.01).Dyadic coping played a partial mediating effect between perceived social support and family cohesion and adaptability as well as happiness, accounting for 32.41% (0.211/0.651) and 44.39% (0.190/0.428) of the total effect, respectively. Conclusion:Dyadic coping is the mediating variable of family cohesion, adaptability and happiness of spouses of patients with post-stroke motor impairments. Medical staff should try to construct a dyadic coping intervention plan to improve the dyadic coping level of spouses of patients with post-stroke motor impairments, so as to improve their family happiness index.