BACKGROUND:Previous studies by our research group discovered that Jiawei Xiaoyao San has a significant anti-liver cancer effect,but the specific mechanism of action was unclear. OBJECTIVE:To investigate the regulatory effects of the traditional Chinese medicine formula Jiawei Xiaoyao San on the levels of miRNAs in plasma exosomes of rats with diethylnitrosamine chronically induced primary liver cancer,based on high-throughput sequencing combined with bioinformatics. METHODS:SD rats were randomly divided into a blank control group,a liver cancer model group,and a Jiawei Xiaoyao San treatment group.Liver cancer models were induced by continuous administration of diethylnitrosamine for 12 weeks.Starting from the 17th week,rats in the Jiawei Xiaoyao San treatment group were administered Jiawei Xiaoyao San once daily until the end of the 20th week,while rats in the blank control and liver cancer model groups were given an equivalent volume of saline.Anti-hepatocellular carcinoma effects were validated by assessing the morphological structure of rat liver tissues,along with the expression of the hepatocellular carcinoma markers,Glypican-3 protein and serum alpha-fetoprotein.Plasma exosomes from each group of rats were isolated using ultracentrifugation.High-throughput sequencing technology was used to screen for differentially expressed miRNAs in rat plasma exosomes.Bioinformatics was used to predict the potential biomarkers through which Jiawei Xiaoyao San exerts its anti-liver cancer effects via liver cancer-derived exosomal miRNAs,followed by functional analysis. RESULTS AND CONCLUSION:(1)Jiawei Xiaoyao San significantly improved the morphological structure of liver tissues in a rat model of liver cancer.Compared with the liver cancer model group,the expression of liver cancer markers Glypican-3 protein and serum alpha-fetoprotein was significantly reduced in the Jiawei Xiaoyao San treatment group.(2)Bioinformatics analysis showed that in the Jiawei Xiaoyao San group,upregulated miR-223-3p in the liver cancer model group had target binding sites with genes E2F1 and NCOA1,which were closely related to liver cancer survival and prognosis.Therefore,Jiawei Xiaoyao San has a therapeutic effect on liver cancer,possibly by targeting negative regulation of NCOA1/E2F1 through liver cancer plasma-derived exosomal miR-223-3p,thereby playing anti-liver cancer effect.

Objective To analyze the epidemiological characteristics of mumps in Guangxi from 2012 to 2024, and to provide a scientific basis for formulating prevention and control strategies. Methods Descriptive epidemiological methods were used to analyze the incidence data of mumps in Guangxi from 2012 to 2024. Results A total of 159 873 mumps cases were reported from 2012 to 2024 in Guangxi, with an average annual reported incidence of 25.41/100 000, and no death. Mumps occurred every month, with the peak incidence mainly concentrated in April to July and October to January of the next year. There were 96,118 male cases (29.43 /100 000), and 63 755 female cases (21.07 /100 000). The male to female ratio was 1.40:1, and the difference between male and female was significant (χ²=4 321.276，P＜0.05). The annual incidence of mumps showed a certain periodic change, with the incidence peak and trough alternating every 4 - 5 years. The majority of patients were under 15 years old, accounting for 85.32% of the total number of cases. The patients mainly included students, preschool children and scattered children. The highest average incidence was in Nanning City with 40 231 cases (42.08/100 000), and the lowest was in Qinzhou City with 3 466 cases (8.16/100 000). From 2012 to 2024, a total of 210 mumps outbreaks with 4 483 cases were reported in Guangxi. Conclusion The incidence of mumps in Guangxi from 2012 to 2024 shows a periodic change and obvious seasonality. People under 15 years old are the key group at risk of mumps. The prevention and control of the epidemic of mumps in schools and kindergartens should be strengthened. It is suggested to carry out long-term monitoring of mumps as well as immune effect research, and continue to maintain a high vaccination rate of 2 doses of mumps-containing vaccines.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of β-D-galactose into α-D-galactose (α-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), β-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and Aβ deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct α-D-G (20 mg/kg, i.p.) also inhibited Aβ deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards α-cleavage, preventing Aβ generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and α-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
Animals ; ADAM10 Protein/metabolism* ; Alzheimer Disease/pathology* ; Amyloid Precursor Protein Secretases/metabolism* ; Disease Models, Animal ; Humans ; Mice ; Amyloid beta-Peptides/metabolism* ; Male ; Mice, Transgenic ; Membrane Proteins/metabolism* ; Cognitive Dysfunction/pathology* ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/metabolism* ; Female ; Hippocampus/metabolism* ; Long-Term Potentiation/physiology*

Objective To explore the correlation between the total burden of cerebral small vessel disease and poor prognosis of branch atheromatous disease(BAD)in elderly patients.Methods A total of 114 BAD patients admitted to Shanghai Eighth People's Hospital between January 2021 and March 2023 were enrolled,and according to mRS score at 90 d after onset,they were divided into a good prognosis group(mRS score ≤2,67 cases)and a poor prognosis group(mRS score＞2,47 cases).The clinical and imaging characteristics were analyzed,and the relationship between total cerebral small vessel disease burden and clinical prognosis of BAD was investigated using lo-gistic regression analysis.ROC curve analysis was used to determine the threshold of the total cere-bral small vessel disease burden for predicting adverse outcomes and to evaluate its sensitivity and specificity.Results The good prognosis group had younger age,smaller proportion of diabetes,lower SBP,NIHSS score at admission and white matter hyperintensities,and reduced ratio of cerebral microbleeds than the poor prognosis group(P＜0.05,P＜0.01).Statistical difference was observed in the total cerebral small vessel disease burden between the two groups(P＜0.01).Binary logistic regression analysis showed that the total cerebral small vessel disease burden score and NIHSS score at admission were independent predicators of poor prognosis in BAD patients(OR=3.350,95％CI:1.439-7.798,P=0.005;OR=2.814,95％CI:1.586-4.993,P=0.001).ROC curve analysis indicated that the total cerebral small vessel disease burden had a cut-off val-ue of 1.5,and the sensitivity and specificity for predicting poor prognosis was 63.8％and 86.6％,respectively,for BAD patients.Conclusion The total cerebral small vessel disease burden is an in-dependent predictor for poor prognosis of BAD patients.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Objective To investigate the association between dipstick hematuria and chronic kidney disease(CKD)in patients with diabetes mellitus(DM).Methods DM patients who underwent the first health examination among the working and retired employees of Kailuan General Hospital and 11 affiliated hospitals in Tangshan City,Hebei Province from 2006 to 2007 were included as the study objects.Test dipstick hematuria is defined by the level of urine occult blood on the test paper:negative dipstick hematuria(NH)<10 erythrocytes/μl,moderate dipstick hematuria(MH)trace～1+(10～49 erythrocytes/μl),severe dipstick hematuria(SH)2+～3+(≥50 erythrocytes/μl).CKD is diagnosed based on eGFR and urinary protein levels.Logistic regression model was used to analyze the association between paper hematuria and CKD in DM patients.Results A total of 8958 DM patients were included,including 2390 patients(26.68%)in the CKD group and 6568 patients(73.32%)in the DM group.The detection rates of moderate dipstick hematuria and severe dipstick hematuria in CKD group were 9.00%and 4.64%,respectively,higher than those in DM group(7.20%and 2.33%).The risk of CKD in MH and SH patients was 1.560(95%CI 1.260～1.940)and 3.080(95%CI 2.220～4.270)times that in NH patients,respectively.The odds ratios were 1.960(95%CI 1.530～2.510)and 3.430(95%CI 2.270～5.200)in males and 0.910(95%CI 0.580～1.430)and 2.760(95%CI 1.570～4.880)in females.The odds ratios were 1.650(95%CI 1.150～2.350)and 4.070(95%CI 2.240～7.400)in patients aged≥60 years,and 1.550(95%CI 1.170～2.040)and 2.860(95%CI 1.920～4.240)in patients aged<60 years.Conclusions Dipstick hematuria is a risk factor for CKD in DM patients.The association between dipstick hematuria and CKD in DM patients is not only independent of traditional risk factors,but also affected by age and gender.

Objective:To establish and optimize a detection method of dibutyryl cyclic adenosine phosphate related substances.Methods:On the basis of the JP,the experimental conditions were optimized to obtain the optimal detection conditions.The column was CAPCEILPAK C18;mobile phase was pH 6.0 phosphate buffer solution-meth-anol with gradient elution;detection wavelength was 258 mm.The method validation was carried out.Results:In the system applicability solution,the separation degree of the main peak and adjacent peaks in each destruction solution was greater than 1.5;the solution was stable within 48 h.The content of each impurity showed a good line-ar relationship with the peak area in the range of 50％-150％of the limit concentration,R2＞0.999 4.In the spike experiment,the average recovery rate of N6-butyryl 3',5-cyclophosphatin sodium was 99.4％-106.6％.The average recoveries of 2'-0 butyryl 3,5-cycloadenosine monophosphate sodium were 88.8％-103.6％,and the average recoveries of cyclophosphaminate sodium were 96.9％-102.5％,which met the requirements.Three bat-ches of samples were tested,and the above impurities were detected.Conclusion:This method has high sensitivi-ty,good separation effect,accuracy and durability,and can be used for the detection of bucladesine sodium,provi-ding a basis for its quality control.

Objective Based on the secreted frizzled-related protein 2(SFRP2)-Wnt/β-catenin signaling pathway,this study explored the effect and mechanism of Cuiru Keli(CRKL)in the treatment of postpartum hypogalactia.Methods A rat model of postpartum hypogalactia was established by gavaging 2 mL of 1.6 mg/mL bromocriptine mesylate to female rats on the third day after delivery.Female rats with a delivery time difference of less than 48 hours were selected and randomly assigned to 7 groups,including a normal group(without any modeling or medication),a model group,a CRKL low-dose group of model group model rats receiving CRKL at the dose of 3 g/kg,a CRKL medium-dose group of model rats receiving CRKL at the dose of 6 g/kg,a CRKL high-dose group of model rats receiving CRKL at the dose of 9 g/kg,a positive drug group of model rats receiving domperidone at the dose of 3 mg/kg,and a negative control(NC)group of model rats receiving normal saline.Each group contained 6 rats.Except for the normal and model groups,the remaining 5 groups were continuously administered with the respective intervention drugs at the specified doses by gavage once a day for 10 days.Changes in the total litter mass of the offspring in the 7 groups within 10 days were measured,and HE staining was performed to identify pathological changes in the mammary tissue(MT).Six groups of rats(excluding the positive control group)were used to observe the pathological changes of eosinophils in pituitary tissue.ELISA was performed to determine the content of prolactin(PRL)in serum,immunohistochemical staining was used to determine the expression of prolactin receptor(PRLR)in MT,and RT-qPCR was used to determine the mRNA expression of genes related to lactation in MT.Network pharmacology and molecular docking were used to study the therapeutic effect and mechanism of CRKL on postpartum hypogalactia,particularly whether it acted through the SFRP2-Wnt/β-catenin signaling pathway.The mechanism of CRKL treatment was further validated by detecting mRNA(RT-qPCR)and protein expression(Western blot)of related pathway genes.Cell experiments were conducted using primary culture rat mammary epithelial cells(RMEC)from rat MT.RMEC were divided into four groups,including a normal group(primary culture RMEC,untreated),SFRP2 overexpression group(primary cultured RMEC treated with SFRP2 overexpression vector),SFRP2 overexpression+CRKL group(receiving treatment for SFRP2 overexpression group plus 10% drug-containing serum),and negative control group(primary culture RMEC treated with empty vector).The effect of CRKL on the expression of lactation-related genes FASN,CSN2,and GLUT1 mRNA after SFRP2 overexpression was detected by RT-qPCR.Results In this study,CRKL was administered at a dose of 3 g/kg in the CRKL low-dose group,6 g/kg in the medium-dose group,and 9 g/kg in the high-dose group(P<0.05 or P<0.01).Compared with the model group,CRKL at all doses significantly increased the total litter weight gain of the offsprings within 10 days(P<0.05 or P<0.01),and effectively increased lactation(P<0.01),the area of mammary lobules,and the size and filling of acinar cavities.CRKL at all doses also increased the number of eosinophils that secreted PRL in the pituitary gland of the postpartum hypogalactia rat model,and increased the content of PRL in the serum(P<0.05 or P<0.01).CRKL promoted the secretion and expression of PRL in postpartum hypogalactic model rats.In addition,it significantly promoted the expression of genes related to milk fat,milk protein,and lactose synthesis in MT(P<0.05 or P<0.01).Network pharmacology predicted that the Wnt signaling pathway might be a key pathway for CRKL in treating postpartum hypogalactia.The molecular docking results showed that related chemical components in CRKL had good binding ability with CCND1 and SFRP2.Compared with the model group,CRKL at all doses inhibited the expression of SFRP2 gene in vivo(P<0.01)and activated the mRNA and protein expression of CCND1 and c-Myc in the Wnt/β-catenin signaling pathway in MT(P<0.05 or P<0.01).Cell experiments showed that,compared to the normal group,SFRP2 overexpression reduced the mRNA expression of milk synthesis-related genes FASN,CSN2,and GLUT1 in RMEC(P<0.01).The CCK8 results indicated that 10% of the drug-containing serum was the effective concentration administered to cells(P<0.01).After administering drug-containing serum,the expression of the lactation-related genes FASN,CSN2,and GLUT1 were up-regulated(compared with the SFRP2 overexpression group,P<0.01).Conclusion CRKL alleviates postpartum hypogalactia through the SFRP2-Wnt/β-catenin signaling pathway.SFRP2 might be a potential new target for the diagnosis and treatment of postpartum hypogalactia.This reveals a new mechanism of CRKL in treating postpartum hypogalactia and promotes its clinical application.

Objective To compare the difference in dose of general anesthesia between pastoral patients and urban pa-tients.Methods The patients who performed abdominal surgery under general anesthesia in Peoples hospital of Bortala Mongo-lian Autonomous Prefecture from January 1st to April 30th 2022 were included and divided into pastoral patient group and ur-ban patient group according to the residential place of patients.Anesthesia and surgery were carried out according to hospital regulations.The general characteristics of all patients were recorded and the dosages of general anesthesia drugs were compared between the two groups.Results There was no significant difference between the two groups in general and intraoperative con-ditions.Patients'performances were stable,and no severe adveres reaction was observed.The dosages of Propofol,Remifen and Rocuronium in pastoral patients were higher than that in urban patients(all P＜0.05).Conclusion The dosage of general anes-thesia for patients in pastoral areas is higher,which ensures the stability of anesthesia depth and vital signs of patients,creates good conditions for surgery and promotes rapid recovery of patients.

Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl₂ at designed doses (0, 0.5, 1.0, and 1.5 μmol·L⁻¹). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L⁻¹ dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.