OBJECTIVE To explore the effect and mechanism of Zexie tang （ZXT） on reducing lipid accumulation through network pharmacology， and compare the difference of traditional decoction versus formula granules. METHODS The active components and targets of ZXT were identified using TCMSP and SwissTargetPrediction databases. GeneCards， OMIM， DisGeNET and TTD databases were used to analyze the related targets of non-alcoholic fatty liver disease （NAFLD）； protein-protein interaction network model was constructed by String database；“ ZXT-NAFLD target-pathway” network diagram was constructed by using CytoScape software； target enrichment analysis was performed by using Metascape platform. Fat accumulation model of human hepatocellular carcinoma HepG2 cells was established to observe the effects of traditional decoction and formula granules of ZXT on lipid accumulation of cells. RESULTS Alisol B， alisol C， 1-monolinolein and alisol B monoacetate were the key active components of ZXT in the treatment of NAFLD. The core targets included MDM2， MAPK1， PIK3CB， PRKCQ and MAPK14， etc. The core signaling pathways included endocrine resistance， insulin resistance and Th17 cell differentiation. Compared with model group， except for the Zexie formula granules group and Baizhu formula granules group， the absorbance values in all other administration groups were significantly decreased （P＜0.01）； the absorbance value of Baizhu traditional decoction group was significantly higher than that of ZXT traditional decoction group （P＜0.01）； the absorbance values of Zexie formula granule group and Baizhu formula granule group were significantly higher than that of ZXT formula granule group （P＜0.01）； the absorbance value of Zexie formula granule group was significantly higher than that of Zexie traditional decoction group （P＜0.01）； the absorbance value of Baizhu formula granule group was significantly higher than that of Baizhu traditional decoction group （P＜0.01）. CONCLUSIONS ZXT reduces lipid accumulation of human hepatocellular carcinoma cells through multiple components， multiple target and multiple pathways， and its traditional decoction and formula granules exhibit slightly different lipid-lowering effects.

Objective:To investigate the neural regulatory mechanism of parvalbumin-positive interneurons(PV-INs)in the dentate gyrus(DG)involved in the impairment of spatial recognition memory by exercise-induced chronic fatigue.Methods:Male Sprague-Dawley(SD)rats were divided into control group and fatigue group by random num-ber method.A three-level incremental load treadmill training program was selected to establish a chronic exhaustion exercise fatigue model.The spatial recognition memory ability of rats was tested by novel object recognition test.The ac-tivation levels and quantitative changes of astrocytes(AS)and PV-INs in the DG region was observed and quantified through immunofluorescence staining and immunohistochemical staining.The phosphorylation level of calcium/calmodu-lin-dependent protein kinase Ⅱ(CaMK Ⅱ)in the hippocampus was detected by Western blot.Results:In the test of novel object recognition,the exploration time of novel object was reduced in the fatigue group,and the discrimination index was significantly lower than that in the control group(P＜0.01).Immunohistochemical staining showed that PV-INs in the DG region of fatigue rats were lighter and fewer than those in the control group,the fibers were short and sparse,and the positive cell density and average optical density of cells were significantly lower than those in the control group(P＜0.01).Immunofluorescence staining showed that AS was significantly activated,glial fibrillary acidic pro-tein(GFAP)was stained deeply,and the cell processes were dense and elongated in the DG region of fatigue rats.The positive cell density and mean fluorescence intensity were significantly higher than those of the control group(P＜0.01).The results of Western blot showed that the phosphorylation level of CaMK Ⅱ protein in the hippocampus of the fatigue group was significantly reduced than that of the control group(P＜0.01).Conclusion:Exercise-induced chro-nic fatigue inhibited PV-INs in the rat hippocampal DG region.The excessive activation of AS following exercise fatigue may be a major contributor to this PV-INs suppression.Concurrently,reduced phosphorylation levels of CaMK Ⅱ protein were observed in hippocampal tissue.These alterations ultimately impaired spatial recognition memory in the rats.

Objective:To summarize the clinical symptoms of cyclic vomiting syndrome（CVS）in children and investigate its association with small intestinal bacterial overgrowth（SIBO）.Methods:A total of 89 children who were diagnosed as CVS and improved lactulose hydrogen breath test (LHBT) in the Pediatric Department of Beijing Tsinghua Changgung Hospital from June 2020 to June 2023 were selected as CVS group.Simultaneously，50 healthy children with physical examination in our hospital were selected as the control group. According to the results of LHBT,the children with CVS were divided into SIBO group (LHBT positive) and non-SIBO group (LHBT negative). The clinical data of children in each group were compared.Results:Among the 89 CVS patients，there were 42 males and 47 females，with a mean age of（7.50±3.54）years.Common accompanying symptoms included excessive sleepiness（76 cases，85.39%），anorexia(62 cases，69.66%），constipation（55 cases，61.80%），abdominal pain（34 cases,38.20%）and so on. There were no significant differences in age and gender between children in CVS group and control group ( P>0.05). The body mass index of CVS group was lower than that of control group.The positive rate of LHBT was higher than that of the control group (56.18% vs. 8.00%),the difference was statistically significant ( P<0.05),and the concentrations of hydrogen and methane in CVS group were higher than those of the control group at different time points( P<0.05).Among 89 children with CVS,there were 50 cases in SIBO group and 39 cases in non-SIBO group. There were no significant differences in gender,age and body mass index between the two groups ( P>0.05). The constipation rate and moderate/severe disease rate in SIBO group were higher than those in non-SIBO group (88.00% vs. 28.21%,94.00% vs. 43.59%),and the differences were statistically significant ( P<0.05). Conclusion:The incidence of SIBO in children with CVS is higher,and SIBO may play a key role in CVS. CVS children with SIBO have higher disease severity.

Objective:To investigate the characteristics of gut microbiota distribution in children with cyclic vomiting syndrome（CVS）complicated by constipation.Methods:The children with CVS, aged from 1 to 16 years, who were admitted to Beijing Tsinghua Changgung Hospital from June 2022 to January 2024, were divided into constipation group and normal group(non-constipation group) according to whether they were complicated with constipation or not.The clinical data and stool samples of children were collect. The abundance, diversity and composition of intestinal flora in fecal samples of two groups were detected by metagenomics sequencing.Results:A total of 20 children with CVS were collected, including 10 patients in constipation group and 10 patients in normal group.There were no significant differences in general demographic data between the two groups, including age at admission, age at first onset, body mass index, gender distribution, disease severity, endoscopic findings, and abdominal pain patterns.Microbiome analysis yielded 470 operational taxonomic units (OTUs), with 414 OTUs identified in normal group and 56 OTUs in constipation group. The abundance and diversity of intestinal flora in constipation group were significantly lower than those in normal group. Principal coordinate analysis and principal component analysis indicated significant structural differences in gut microbiota composition between the two groups. LEfSe analysis revealed distinct taxonomic patterns between the two groups, with the normal group demonstrating predominant representation of Firmicutes at the phylum level, while the constipation group showed higher relative abundance of Bacteroidetes and Actinobacteria. KEGG pathway analysis revealed that the carbon metabolism pathways was significantly enriched in the constipation group.Conclusion:There are significant differences in intestinal flora between CVS children with and without comorbid constipation.Bacteroides and Actinomycetes play an important role in constipation of children with CVS. The diversity and metabolic function of intestinal flora may be one of the pathological mechanisms of CVS complicated with constipation.

Objective:To analyze the effects of Mulligan technique combined with isokinetic exercise training (IET) on isokinetic muscle strength and neuromuscular control ability in patients with knee osteoarthritis (KOA).Methods:A retrospective case-control study was conducted. A total of 49 patients with KOA who underwent IET at Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2021 to January 2022 were included in the control group. An additional 49 patients with KOA who received Mulligan technique and IET at the same hospital from June 2022 to June 2023 were included in the observation group. Both groups were treated for 8 successive weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Lysholm score, proprioception metrics [including average track error (ATE) and test time execution (TTE)], isokinetic muscle strength [peak torque (PT) and average power (AP) for flexors and extensors at 60°/s, 90°/s, and 120°/s)]were compared between the two groups before and after 4 and 8 weeks of intervention. Additionally, Visual Analog Scale score was compared between the two groups at baseline and after 8 weeks of intervention.Results:There was no statistically significant difference in WOMAC score, Lysholm score, or PT and AP levels for flexor and extensor muscles at 60°/s, 120°/s, and 180°/s between the two groups before intervention (all P > 0.05). After 4 and 8 weeks of intervention, the levels of PT and AP for both flexors and extensors at 60°/s, 120°/s, and 180°/s, as well as the Lysholm scores, were significantly higher in the observation group compared with the control group [PT level: t = -0.10, -3.03, -3.85, -0.35, -3.62, -3.95, -0.27, -5.51, -6.52, -1.13, -2.74, -3.68, -0.09, -2.91, -5.79, -0.13, -4.66, -6.05; AP level: t = -0.23, -4.77, -6.15, 0.01, -3.10, -3.75, -0.13, -3.73, -3.44, 0.16, -2.09, -4.05, -0.17, -3.71, -3.51, -0.27, -3.26, -3.69; Lysholm score: t = -7.17, -6.44; all P < 0.05]. After 4 and 8 weeks of intervention, the WOMAC score, ATE, and TTE in the observation group were significantly lower than those in the control group [WOMAC score: t = 3.68, 0.64; ATE level: t = 3.88, 4.13; TTE level: t = 4.86, 4.60; all P < 0.05]. After 8 weeks of intervention, both groups had lower Visual Analog Scale scores compared with their scores before the intervention (U control group = -8.75, U observation group = -8.63), with the observation group showing significantly lower scores than the control group ( U = -5.95, P < 0.001). Conclusions:The Mulligan technique combined with IET can effectively alleviate knee joint pain in patients with KOA, promote the recovery of knee joint function, enhance proprioceptive recovery, and improve neuromuscular control abilities.

Objective:To explore the clinical and genetic characteristics of X-linked intellectual disability associated with HUWE1 gene variants.Methods:A cases series study retrospectively analyzed the clinical data of 6 children with HUWE1 gene variants. The children were identified from the Third Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Henan University of Chinese Medicine, and Guangzhou Women and Children′s Medical Center of Guangzhou Medical University between April 2021 and July 2023.The data included sex, age, dysmorphic features, intellectual and motor development, seizure history, neuroimaging findings, family history, and genetic results was analyzed.Results:A total of 6 children, including 5 boys and 1 girl. The age of onset ranged from 1 day to 3 years. All children presented with varying degrees of intellectual disability, with or without motor developmental delay. Dysmorphic features were observed in 4 children, including microcephaly in 3 children. Short stature were observed in 3 children. One child was diagnosed with autism spectrum disorders and 1 child had seizures. Two boys had relevant maternal family histories of febrile seizures and mild intellectual disability, respectively. Abnormal neuroimaging findings were presented in 4 children, including cerebral dysplasia (1 child), prominent supratentorial ventricles (1 child), and mild white matter demyelination (2 children). Whole-exome sequencing identified 5 missense variants and 1 in-frame deletion variant. Five variants were novel and previously unreported (c.12290C>T, c.12701T>C, c.9875C>T, c.9641A>T and c.10313_10315del). The variants in 4 boys were maternally inherited, while the remaining 2 children had de novo variants. The child with the in-frame deletion variant (c.10313_10315del) presented with the most severe phenotype, exhibiting symptoms from 1 day of age, absent cognitive development, feeding difficulties, and congenital laryngeal chondrodysplasia. He was lost to follow-up at 3 months of age after treatment was withdrawn. The age at the last follow-up for the remaining 5 children ranged from 2 years and 10 months to 17 years. A boy with seizures died at 2 years and 10 months of age. The remaining 4 children were able to walk independently at the last follow-up, although their developmental progress was slow. Conclusions:HUWE1 gene related X-linked intellectual disability is characterized by varying degrees of developmental delay and intellectual disability, frequently accompanied by microcephaly, short stature, and occasionally by seizures and autism spectrum disorders. Missense variants are more common and the in-frame deletion variant appears to be associated with a particularly severe phenotypic presentation.

Objective:To develop a network-structured clinical pathway grouping rule based on the principles and methods of China healthcare security diagnosis related groups(CHS-DRG), for references for optimizing clinical pathway management.Methods:From August to November 2024, this study constructed a network-structured clinical pathway management framework, followed the grouping principles of CHS-DRG, and developed a network-structured clinical pathway grouping rule through literature analysis and expert discussions. 54 clinical specialists from the sample hospital were organized and grouped according to the rule for the normal magnification cases(139 218 cases) of DRG medical insurance settlement in the hospital in 2023. Using a stratified random sampling method, 205 physicians from 54 clinical specialties in the hospital were selected to quantitatively evaluate the rationality, homogeneity, and clarity of the grouping results. The Likert 5-level scoring method was wsed to assign scores.Results:The network-structured clinical pathway grouping rule and nomenclature was established. A total of 341 main pathways and 35 sub-pathways covering 169 adjacent diagnosis related groups were formed. The quantitative assessment scores for rationality, homogeneity, and clarity were 4.90, 4.87 and 4.87 points, respectively.Conclusions:The network-structured clinical pathway grouping rule based on CHS-DRG had good, feasibility and standardization, and could meet the practical needs of clinical applications.

Objective:To conduct consistency analysis of antinuclear antibody (ANA) anti-cell type 2 (AC-2) fluorescence pattern based on HEp-2 cells and monkey liver matrix, and to investigate the clinical significance of the AC-2 and anti-dense fine speckled 70 (DFS70) antibody.Methods:This study is a cross-sectional study. Retrospective analysis of the results of 33 921 ANA tests detected by indirect immunofluorescence assay (IIFA) from January 2024 to December 2024 in Shengjing Hospital of China Medical University. A total of 457 patients with AC-2 positive were taken from the cohort as the research objectives, then the positive rate of AC-2 in ANA among the 457 patients and its distribution in different diseases were counted. One hundred cases were selected from 457 AC-2 positive cases, whose AC-2 fluorescence pattern were analyzed using HEp-2 cells and HEp-2 cells combined with monkey liver matrix and the anti-DFS70 antibody was detected to help identifying the AC-2 fluorescence pattern. Finally, the consistency of the two methods in identifying the AC-2 fluorescence pattern was compared and the clinical significance of the AC-2 and anti-DFS70 antibody was discussed. Spearman correlation analysis was used to compare the correlation between the reciprocals of ANA titer of AC-2 positive samples and the levels of anti-DFS70 antibody.Results:AC-2 positive cases accounted for 1.15% (457/33 921) and 3.64% (457/12 555) of the all cases and ANA positive cases, respectively. The positive rate of AC-2 in females (394/457) was higher than that in males (63/457), P<0.01. Totally 87.09% of the AC-2 positive patients aged 40 and below. Moreover, the most positive cases of AC-2 occured in female infertility, adverse pregnancy history, pregnancy status and patients with connective tissue disease or joint pain/arthritis, accounting for 57.33% of the total positive cases. AC-2 positive patients were mostly distributed in women with infertility, bad pregnancy history, pregnancy status, connective tissue disease or patients manifested with joint pain/arthritis, accounting for 57.33% (262/457) of the total positive cases.The consistency analysis of AC-2 fluorescence pattern based on HEp-2 cells and HEp-2 cells combined with monkey liver matrix showed that among 100 serum samples, 97 cases were unanimously determined to be AC-2 fluorescence pattern, suggesting that HEp-2 cells can identify most AC-2 fluorescent pattern.The other three cases were identified as AC-1 and AC-5, and these AC-2 miscible pattern could be identified by monkey liver matrix and DFS70 antibody. In addition, the positive rate of anti-DFS70 antibody was 92.78% (90/97) in AC-2 fluorescent pattern, and the titer of ANA was positively correlated with the concentration of anti-DFS70 antibody in 62 cases with single positive anti-DFS70 antibody ( r=0.441, P<0.05). Among 62 cases of single positive anti-DFS70 antibody, 5 patients with connective tissue disease and 57 patients with non-autoimmune diseases; among the 25 cases of positive DFS70 antibody combined with non-positive ANA spectrum antibody, 4 cases were pregnant, and 16 cases had infertility or bad pregnancy history. All of them were combined with anti-thyroid globulin or thyroid peroxidase antibody positive, lupus anticoagulant positive, phospholipid antibody and herpes virus, rubella virus or cytomegalovirus antibody positive. Two cases were arthritis patients with positive anti-cyclic citrulline colypeptide antibody. One patient was Hashimoto′s thyroid, and 1 case was antiphospholipid syndrome. Three autoimmune diseased patients with positive DFS70 antibody were combined with positive ANA spectrum antibody, which were anti-Sjogren′s syndrome A antigen, polymyositis-scleroderma antigen antibody. Conclusion:Most AC-2 fluorescent pattern can be identified by HEp-2 cells, monkey liver matrix and anti-DFS70 antibody are helpful to identify AC-2, AC-2 fluorescent pattern and DFS70 antibodies can be positive alone or combined with ANA spectrum antibodies and other non-ANA spectrum antibodies in different diseases, which account for a high proportion of female infertility patients, patients with bad pregnancy history and pregnancy status.

Objective To investigate the clinical features,etiological features and prognosis of patients with hematologic diseases complicated with candidemia for improving clinical diagnosis and treatment.Methods A retrospective analysis was conducted for 107 hematological patients complicated with candidemia who were treated in the First Affiliated Hospital of Zhengzhou University,Henan Cancer Hospital,Henan Provincial People's Hospital,or Zhengzhou People's Hospital from June 2022 to May 2024.The clinical data and pathogenic bacteria were analyzed by univariate and multivariate analyses.Results The Candida pathogen of the 107 cases of candidemia were mostly Candida tropicalis(73.8％),followed by Candida parapsilosis,Candida glabrata,and Candida albicans.Antifungal susceptibility testing showed that 43.9％,47.7％,and 48.6％of the Candida strains were resistant voriconazole,fluconazole and itraconazole,respectively.Logistic regression analysis found that disease not in remission(OR=7.795,95％CI:2.274-26.723),septic shock(OR=10.376,95％CI:1.129-95.388),multiple organ dysfunction syndrome(MODS)(OR=9.107,95％CI:1.789-46.361),and inappropriate antifungal treatment(OR=3.422,95％CI:1.153-10.153)were risk factors for 30-day mortality in hematological patients with candidemia.Conclusions Candidemia in patients with hematological diseases is associated with high mortality rate,the major pathogen of which is Candida tropicalis.The Candida isolates showed high resistance rates to azoles.Disease not in remission,septic shock,MODS,and inappropriate antifungal treatment are the risk factors for mortality.

The neonatal Fc receptor(FcRn)prolongs the half-life of immunoglobulin G(IgG)and promotes its recycling by binding to and making it an important receptor for maintaining serum IgG homeostasis.However,the abnormal accumulation of pathogenic IgG is closely related to the occurrence of various neuroimmune diseases.FcRn antagonists can significantly reduce the level of pathogenic IgG by blocking the binding of FcRn to IgG,thereby effectively alleviating the clinical symptoms of related diseases.As an emerging targeted therapeutic drug,FcRn antagonists have shown their potential in treating IgG-mediated neuroimmune diseases.This article summarizes the mechanism of action,types and clinical research progress of FcRn antagonists with the aim of providing new ideas for the precise treatment of IgG-mediated neuroimmune diseases.Future research should focus on the long-term safety of drugs,expansion of indications and individualized treatment strategies to further enhance their clinical application value.