Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Objective:To investigate the association between single nucleotide polymorphism (SNP) of the protein phosphatase 1 regulatory subunit 1B( PPP1R1B) gene and schizophrenia in the Han population of northern Henan province. Methods:Utilizing Psychiatric Genomics Consortium 3 (PGC3) data, the SNPs of PPP1R1B gene which were significantly associated with schizophrenia were screened.Subsequently, totally 1 721 schizophrenia patients and 6 726 healthy controls from the Han population in northern Henan province were recruited for further analysis. The SNP rs907094, located within the PPP1R1B gene was validated, and the clinical symptoms of 386 schizophrenia patients were evaluated using the positive and negative syndrome scale (PANSS). Additionally, expression quantitative trait loci (eQTL) association analysis was conducted to explore the relationship between the rs907094 polymorphism and PPP1R1B gene expression.The PLINK v1.9, Genetic Power Calculater, SPSS 20.0 softwares were used for data analysis. Results:Significant differences in genotype AA, AG, GG(schizophrenia group: AA, 489(28.4%); AG, 848(49.3%); GG, 384(22.3%); control group: AA, 1 450(21.6%); AG, 3 386(50.3%); GG, 1 890(28.1%), χ2=45.418, P<0.05) and allele frequency(schizophrenia group: A, 1 826(53.1%); G, 1 616(46.9%); control group: A, 6 286(46.7%); G, 7 166(53.3%), χ2=43.877, P<0.05) were observed for SNP rs907094 between the schizophrenia group and control group. Individuals carrying allele A were identified to have a higher risk of developing schizophrenia compared to those carrying allele G ( OR=1.288, 95% CI=1.195-1.388). Furthermore, the genotype PPP1R1B gene was found to be associated with the clinical features of schizophrenia. A statistically significant difference was observed in the excitement/hostility factor between AA and GG patients with rs907094 (13.62±5.65, 15.54±4.66)( P<0.05). Additionally, significant differences were noted in the cognitive factor scores between AA and GA genotypes (17.76±5.58, 19.43±5.73)( P<0.05). Conclusions:In the Han population from northern Henan province, the rs907094 polymorphism of the PPP1R1B gene is associated with schizophrenia.And the specific locus may be implicated in arousal/hostility symptoms and cognitive dysfunction.

Objective:To investigate the relationship between macrophage activation related factors and clini-cal symptoms of schizophrenia(SCZ).Methods:Outpatient or inpatient SCZ patients(n=166)and normal con-trols(n=71)meeting the diagnostic criteria of DSM 4th edition were selected as subjects.The psychopathological symptoms were assessed by the Positive and Negative Syndrome Scale(PANSS),and the concentrations of α-Na-Galases,MAF and IL-18 were determined by enzyme-linked immunosorbent assay(ELISA).The correlation be-tween biological indicators and clinical symptoms was analyzed and the mediation effect was tested.Results:The concentrations of α-NaGalases(P＜0.001)and MAF(P＜0.01)in SCZ group were lower than those in normal control group.In SCZ group,IL-18 was negatively correlated with α-NaGalases concentration(r=-0.24,P＜0.01).α-NaGalases was positively correlated with MAF concentration(r=0.67,P＜0.001),and the total score of PANSS positive symptom scale was positively correlated with IL-18(r=0.21,P＜0.05)and MAF concentration(r=0.22,P＜0.01).The mediating effect of α-NaGalases and MAF was statistically significant,and the relative mediating effect accounted for 25.47％.Conclusion:The increase of IL-18 level may indicate the occurrence of positive symptoms of schizophrenia,and α-NaGalases and MAF may negatively regulate the inflammatory damage effect of IL-18 on SCZ,thereby reducing the positive symptoms.

Objective:To investigate the association between single nucleotide polymorphism (SNP) of the protein phosphatase 1 regulatory subunit 1B( PPP1R1B) gene and schizophrenia in the Han population of northern Henan province. Methods:Utilizing Psychiatric Genomics Consortium 3 (PGC3) data, the SNPs of PPP1R1B gene which were significantly associated with schizophrenia were screened.Subsequently, totally 1 721 schizophrenia patients and 6 726 healthy controls from the Han population in northern Henan province were recruited for further analysis. The SNP rs907094, located within the PPP1R1B gene was validated, and the clinical symptoms of 386 schizophrenia patients were evaluated using the positive and negative syndrome scale (PANSS). Additionally, expression quantitative trait loci (eQTL) association analysis was conducted to explore the relationship between the rs907094 polymorphism and PPP1R1B gene expression.The PLINK v1.9, Genetic Power Calculater, SPSS 20.0 softwares were used for data analysis. Results:Significant differences in genotype AA, AG, GG(schizophrenia group: AA, 489(28.4%); AG, 848(49.3%); GG, 384(22.3%); control group: AA, 1 450(21.6%); AG, 3 386(50.3%); GG, 1 890(28.1%), χ2=45.418, P<0.05) and allele frequency(schizophrenia group: A, 1 826(53.1%); G, 1 616(46.9%); control group: A, 6 286(46.7%); G, 7 166(53.3%), χ2=43.877, P<0.05) were observed for SNP rs907094 between the schizophrenia group and control group. Individuals carrying allele A were identified to have a higher risk of developing schizophrenia compared to those carrying allele G ( OR=1.288, 95% CI=1.195-1.388). Furthermore, the genotype PPP1R1B gene was found to be associated with the clinical features of schizophrenia. A statistically significant difference was observed in the excitement/hostility factor between AA and GG patients with rs907094 (13.62±5.65, 15.54±4.66)( P<0.05). Additionally, significant differences were noted in the cognitive factor scores between AA and GA genotypes (17.76±5.58, 19.43±5.73)( P<0.05). Conclusions:In the Han population from northern Henan province, the rs907094 polymorphism of the PPP1R1B gene is associated with schizophrenia.And the specific locus may be implicated in arousal/hostility symptoms and cognitive dysfunction.

Objective To explore the effect of classroom pivotal response teaching(CPRT)-based fun-damental motor skills intervention on the motor coordination ability in children with autism spectrum disorder(ASD).Methods Seventeen boys with ASD(aged 5～9 years)were recruited from a leading au-tism rehabilitation center.According to the principle of convenience sampling,the school-age class 3(n=9)was taken as the experimental group,and class 1 and 2(n=8)were chosen as the control group.Before the intervention,there was no significant difference between the two groups in terms of social communication skills.The experimental group was given CPRT-based fundamental motor skills in-tervention 3 times/week,60 minutes/session,for 9 weeks,while the control group did not receive the intervention.Before and after the intervention,as well as 4 weeks after the intervention,both groups were evaluated their motor coordination skills(manual dexterity,aiming and catching,and balance)us-ing the movement assessment battery for children(Movement-ABC).Repeated measures ANOVA was used to compare the differences in the total Movement-ABC scores and scores across its subdomains between the experimental group and the control group during different intervention periods.Results(1)After the intervention,the scores of experimental group were significantly higher than the control group in total motor skills,aiming and catching,and balance[F(1,15)=14.308,P<0.01;F(1,15)=7.244,P<0.05;F(1,15)=9.362,P<0.01].Moreover,4 weeks after the intervention,the scores of the former group were also significantly higher than the latter in all the above measurements[F(1,15)=11.670,P<0.01;F(1,15)=5.549,P<0.05;F(1,15)=9.209,P<0.01].(2)After the intervention,there was an improvement in manual dexterity in the experimental group,but without significant differences compared with the control group[F(1.316,19.736)=4.795,P>0.05].Conclusion The CPRT-based fundamental motor skills inter-vention can improve and sustain motor coordination among children with ASD,primarily through en-hanced performance in aiming,catching and balancing.

Objective:To investigate the clinical characteristics and genetic etiology of Duchenne muscular dystrophy (DMD) with myogenic tumors.Methods:The clinical data of 2 children with DMD combined with myogenic tumors diagnosed in Children′s Hospital Affiliated to Zhengzhou University in July 2021 and February 2022 were collected. The relevant literature was reviewed to summarize the clinical characteristics and explore the mechanism of the dystrophin ( DMD) gene in myogenic tumors. Results:A 6-year and 10-month-old boy with DMD (deletion of exon 45) and a 12-year-old boy with DMD (deletion of exon 51) were diagnosed with tumors. They were diagnosed with DMD for delayed motor development in the Department of Neurology of Children′s Hospital Affiliated to Zhengzhou University. They presented with painless masses in the waist. Postoperative pathological diagnosis: the pathology and immunohistochemistry of case 1 showed an alveolar rhabdomyosarcoma (ARMS) and both myogenin and myogenic differentiation 1 positive; the pathology and immunohistochemistry of case 2 showed an alveolar soft part sarcoma(ASPS) and transcription factor enhancer 3 positive; both cases were myogenic tumors. Literature review (including this paper) showed that there were in total 14 cases with DMD combined with myogenic tumors including 13 cases of rhabdomyosarcoma (RMS) and 1 case of ASPS. All of them are male, and the age of onset of the tumors was 4-17 years. Pathological subtypes were described in 6 cases of ARMS and 5 cases of embryonal RMS, and were not described in 2 cases. The 9 cases described all had large deletions in the DMD gene which can change the reading frame of the DMD gene, and all gene mutations did not exceed exon 62. Conclusions:DMD gene with deletion may increase the risk of having myogenic tumors, and RMS is more common, which is manifested as painless mass in early stage. All DMD gene deletions do not exceed exon 62 and lead to change of the gene reading frame with severe clinical phenotype and degenerative changes in muscle function.

Objective:To investigate the clinical characteristics of encephalocraniocutaneous lipomatosis (ECCL) in pediatric patients.Methods:A retrospective analysis was conducted on the clinical data of 2 ECCL cases admitted to Children′s Hospital Affiliated to Zhengzhou University between January 2024 and December 2024. Additionally, a review of relevant literature was performed to summarize the clinical features of this condition.Results:Case 1 is a male patient aged 2 years and 10 months, while case 2 is a female patient aged 8 months. Both patients presented with seizures and exhibited nevus psiloliparus on the scalp, non-scarring alopecia, nodular skin tags around the eyes, and ocular choristomas. Brain magnetic resonance imaging revealed leptomeningeal angiomatosis in both cases, with case 1 also demonstrating an intracranial lipoma and case 2 showing localized cerebral atrophy and an arachnoid cyst. Whole-exome sequencing of peripheral blood and copy number variation analysis in both cases did not identify any pathogenic variants. Additionally, no relevant pathogenic variants were detected in the scalp lesion tissue of case 2. A review of the literature revealed that, to date, there have been 5 reported domestic cases, 132 reported foreign cases in pediatric populations, totally 139 cases including 2 cases described in this article. Among these patients, 86 are male, 49 are female, and the gender of 4 cases remains unspecified. Clinical manifestations observed included seizures in 79.0% (64/81) of cases and developmental delay in 64.7% (57/88). Cutaneous lesions were characterized by non-scarring alopecia in 100% (97/97) of cases,non-hair-bearing fatty tissue nevi in 98.3% (58/59), nodular skin tags in 96.5% (56/58), and subcutaneous lipomas in 94.8% (73/77). Ocular lesions predominantly involved choristomas, occurring in 91.8% (90/98) of cases. Central nervous system abnormalities were identified as ventricular dilatation or hydrocephalus in 85.0% (68/80) of cases, intracranial lipomas in 82.1% (69/84), localized cerebral atrophy in 80.9% (34/42), intracranial vascular anomalies in 74.1% (23/31), and spinal lipomas in 66.6% (30/45).Conclusions:ECCL is an uncommon neurocutaneous disorder with the potential to impact various organ systems, notably the integumentary, ocular, and central nervous systems. Pediatric patients may exhibit symptoms such as seizures, developmental delays, and additional clinical manifestations, necessitating vigilant monitoring and management.

Objective To analyze the use of anticholinergic medications at discharge among elderly patients with chronic heart failure(CHF)and its associated risk factors.Methods Clinical data of 240 elderly CHF patients admitted in our Department of Cardiovascular Diseases between January 1,2020,and December 31,2023 were colloected.Based on ACB score,they were divided into an an-ticholinergic group(ACB score≥1,223 cases)and a non-anticholinergic group(ACB score of 0,17 cases).Using the ACB score,the anticholinergic burden was quantified,and the relationship be-tween anticholinergic burden and various related factors was analyzed using logistic regression.Results The anticholinergic group had significantly younger age[(75.17±7.21)years vs(79.12±8.75)years,P＜0.05],and larger number of discharge medications[8(6,10)vs 5(4,7),P＜0.01]when compared with the non-anticholinergic group.Logistic regression analysis showed that the number of discharge medications was an independent risk factor for increased anticholinergic bur-den in the elderly CHF patients(OR=1.575,95％CI:1.249-1.986,P=0.001).Conclusion The proportion of elderly CHF patients using anticholinergic medications is relatively high.Clinically,special attention should be given to polypharmacy to reduce the incidence of adverse events caused by anticholinergic drugs.

Objective:To investigate the relationship between macrophage activation related factors and clini-cal symptoms of schizophrenia(SCZ).Methods:Outpatient or inpatient SCZ patients(n=166)and normal con-trols(n=71)meeting the diagnostic criteria of DSM 4th edition were selected as subjects.The psychopathological symptoms were assessed by the Positive and Negative Syndrome Scale(PANSS),and the concentrations of α-Na-Galases,MAF and IL-18 were determined by enzyme-linked immunosorbent assay(ELISA).The correlation be-tween biological indicators and clinical symptoms was analyzed and the mediation effect was tested.Results:The concentrations of α-NaGalases(P＜0.001)and MAF(P＜0.01)in SCZ group were lower than those in normal control group.In SCZ group,IL-18 was negatively correlated with α-NaGalases concentration(r=-0.24,P＜0.01).α-NaGalases was positively correlated with MAF concentration(r=0.67,P＜0.001),and the total score of PANSS positive symptom scale was positively correlated with IL-18(r=0.21,P＜0.05)and MAF concentration(r=0.22,P＜0.01).The mediating effect of α-NaGalases and MAF was statistically significant,and the relative mediating effect accounted for 25.47％.Conclusion:The increase of IL-18 level may indicate the occurrence of positive symptoms of schizophrenia,and α-NaGalases and MAF may negatively regulate the inflammatory damage effect of IL-18 on SCZ,thereby reducing the positive symptoms.

BACKGROUND:Apoptosis and autophagy imbalance in the hippocampal region of perimenopausal depressed rats are closely related to cognitive decline.Whether aerobic exercise can reduce apoptosis by promoting hippocampal autophagy and thus improve the learning and memory abilities of perimenopausal depressed rats is not clear.OBJECTIVE:To investigate the possible mechanism by which 4-week moderate-intensity treadmill exercise improves learning memory ability in ovariectomized stressed rats.METHODS:Forty Sprague-Dawely rats were randomly divided into four groups,namely,sham operation group(n=10),ovariectomized group(n=10),ovariectomized stress group(n=10)and ovariectomized stress exercise group(n=10).Except for the sham operation group,the ovaries were removed in the other three groups to establish a perimenopausal rat model,and then a depressed rat model was established by chronic unpredictable stress in the latter two groups.The rats in the ovariectomized stress exercise group underwent a 4-week moderate-intensity treadmill exercise.Tail suspension test and sucrose preference test were performed to text depression-like behaviors in rats after exercise and stress.The eight-arm maze experiment was used to test the learning and memory behaviors of rats after exercise and stress.Western blot was used to detect the protein levels of AMP-activated protein kinase/UNC-51 like autophagy activating kinase 1/mammalian target of rapamycin(AMPK/mTOR/ULK1),hippocampus apoptotic factor Caspase-3 and the protein expression of autophagy markers LC-3II/Beclin-1 in the hippocampus.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,rats in the ovariectomized and ovariectomized stress groups had prolonged resting time in the tail suspension test and decreased sugar-water intake and sugar-water preference in the sucrose preference test.(2)Ovary removal reduced the learning memory capacity of rats,as evidenced behaviorally by a significant increase in the number of working memory errors,the number of reference memory errors,and the completion time,and an even more pronounced increase in the above measures in the ovariectomized stress group.(3)Compared with the ovariectomized group,there was a significant reduction in the number of working memory errors,the number of reference memory errors,and the completion time in the ovariectomized stress group.(4)Compared with the sham operation group,in the ovariectomized and ovariectomized stress groups,the expression of hippocampal apoptotic factor Caspase 3 protein was significantly elevated,the expression of autophagy-related factors proteins Beclin-1 and LC3II,as well as the protein expression of AMPK and ULK1,was decreased,whereas the expression of mTOR protein was elevated.Changes in the above indicators were more significant in the ovariectomized stress group.(5)Compared with the ovariectomized stress group,in the ovariectomized stress exercise group,the protein expression of Caspase 3 was significantly decreased,the protein expression of Beclin-1 and LC3II was significantly increased,the protein expression of AMPK and ULK1 was significantly increased,and the protein expression of mTOR was significantly reduced.To conclude,4-week moderate-intensity treadmill exercise may promote cellular autophagy and reduce apoptosis through the AMPK/mTOR/ULK1 autophagy signaling pathway,thereby enhancing the learning and memory capacity of rats with ovariectomized depression