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 investigate the effect of subanesthetic dose of esketamine on emergence agitation(EA)in patients undergoing laparoscopic hernia repair.Methods Seventy-two male patients who treated with lapa-roscopic hernia repair under general anesthesia were randomly divided into AS group(subanesthetic esketamine)and control group.In the AS group,0.2 mg/kg of esketamine was administered intravenously 30 minutes before the surgery ended,while the control group was given an equal volume of normal saline.Upon surgery completion,patients were transferred to PACU with endotracheal tube retained,and the time to extubation was recorded.Hemo-dynamic parameters were measured immediately after extubation and at 10 min,30 min,1 h,and 4 h thereafter.Patients' pain and sedation levels were assessed at the above time points using RASS and VAS,respectively.The incidence of EA was evaluated using the Confusion Assessment Method for the Intensive Care Unit(CAM-ICU).Observation duration in the PACU and recovery outcomes within 24 hours postoperatively were assessed via the QoR-40 and adverse events were recorded.Results Compared to those in the control group,patients in the AS group had higher HR and MAP at 10 min post-extubation,and the changes in HR and MAP over time were more stable(P<0.05).The RASS and VAS scores in the AS group were significantly lower than those in the control group at the time of extubation and all subsequent time points(P<0.05),both groups showed temporal changes in RASS and VAS scores(P<0.05),but the change process in the AS group was more stable(P<0.05).Postoperative extubation time,PACU observation duration,and adverse event rates(delirium,respiratory depression,nausea and vomiting)did not differ significantly between the two groups(P>0.05),while recovery quality was markedly better in the AS group(P<0.05).Conclusion Subanesthetic esketamine effectively alleviates pain and the incidence of EA,supports hemodynamic stability during PACU stay,and enhances recovery quality in patients undergoing laparo-scopic hernia repair,demonstrating clinical value.

OBJECTIVE To analyze the medication patterns of traditional Chinese medicine combinations for the treatment of pulmonary nodules in national patents using data mining and network pharmacology methods,providing a reference for the clinical treat-ment of pulmonary nodules.METHODS Patent data on traditional Chinese medicine compound prescriptions for the treatment of pul-monary nodules were collected from the China National Intellectual Property Administration Patent Inquiry System and the China Na-tional Knowledge Infrastructure(CNKI)patent database.Formula statistics were performed using Excel software.The Ancient and Modern Medical Case Cloud Platform was used to conduct high-frequency analysis of traditional Chinese medicine including frequency,properties and flavors,meridian tropism,efficacy categories,association rules,clustering,complex network analysis to screen out core drugs.Network pharmacology was then used to predict potential targets and pathways in patent prescriptions for the treatment of pulmo-nary nodules.RESULTS A total of 67 valid patents for the treatment of pulmonary nodules were included,involving 276 traditional Chinese medicines,with a cumulative total frequency of 859.The top five traditional Chinese medicines in terms of frequency of use were Glycyrrhiza uralensis Fisch,Astragalus membranaceus,Pinellia ternate,Curcuma zedoary and Hedyotis diffusa.These traditional Chinese medicines were primarily sweet and warm in property,primarily targeting the lung,liver,and spleen meridians,and their main effects were clearing heat,drying dampness and resolving phlegm,and promoting diuresis and reducing swelling.Association a-nalysis revealed that the top drug pairs were Scutellaria baicalensis Georgi-Pinellia ternate,Fagopyrum cymosum-Pinellia ternate,Ra-nunculus ternatus-Curcuma zedoary,Radix Angelicae Sinensis-Radix Paeoniae Alba,and Radix Angelicae Sinensis-Glycyrrhiza ura-lensis Fisch.Cluster analysis identified three drug combinations,and complex network analysis demonstrated that the core drug compo-nents were Scutellaria baicalensis Georgi,Pinellia ternate,Astragalus membranaceus,Curcuma zedoary,Fritillaria thunbergii,Fago-pyrum dibotryis,Hedyotis diffusa and Ranunculus ternatus.Network pharmacology analysis showed that the key targets for the treat-ment of lung nodules with patent prescriptions were GAPDH,IL6,TNF and so on.The core active ingredients were Baicalein,Moslosooflavone,and Norwogonin and so on.The main pathways involved were cancer pathways,lipids and arteriosclerosis,and viral carcinogenesis.CONCLUSION The inclusion of traditional Chinese medicine compound patent in this case is consistent with the eti-ology and pathogenesis of traditional Chinese medicine for treating lung nodules.Commonly used drug pairs and cluster prescriptions re-flect the flexible compatibility of traditional Chinese medicines in the treatment of pulmonary nodules,such as clearing away heat and toxic materials,resolving phlegm and eliminating swelling,regulating qi and strengthening spleen,promoting blood circulation and remo-ving blood stasis.The core drugs exert their effects on pulmonary nodules through multiple components,multiple targets and multiple pathways.

OBJECTIVE To analyze the medication patterns of traditional Chinese medicine combinations for the treatment of pulmonary nodules in national patents using data mining and network pharmacology methods,providing a reference for the clinical treat-ment of pulmonary nodules.METHODS Patent data on traditional Chinese medicine compound prescriptions for the treatment of pul-monary nodules were collected from the China National Intellectual Property Administration Patent Inquiry System and the China Na-tional Knowledge Infrastructure(CNKI)patent database.Formula statistics were performed using Excel software.The Ancient and Modern Medical Case Cloud Platform was used to conduct high-frequency analysis of traditional Chinese medicine including frequency,properties and flavors,meridian tropism,efficacy categories,association rules,clustering,complex network analysis to screen out core drugs.Network pharmacology was then used to predict potential targets and pathways in patent prescriptions for the treatment of pulmo-nary nodules.RESULTS A total of 67 valid patents for the treatment of pulmonary nodules were included,involving 276 traditional Chinese medicines,with a cumulative total frequency of 859.The top five traditional Chinese medicines in terms of frequency of use were Glycyrrhiza uralensis Fisch,Astragalus membranaceus,Pinellia ternate,Curcuma zedoary and Hedyotis diffusa.These traditional Chinese medicines were primarily sweet and warm in property,primarily targeting the lung,liver,and spleen meridians,and their main effects were clearing heat,drying dampness and resolving phlegm,and promoting diuresis and reducing swelling.Association a-nalysis revealed that the top drug pairs were Scutellaria baicalensis Georgi-Pinellia ternate,Fagopyrum cymosum-Pinellia ternate,Ra-nunculus ternatus-Curcuma zedoary,Radix Angelicae Sinensis-Radix Paeoniae Alba,and Radix Angelicae Sinensis-Glycyrrhiza ura-lensis Fisch.Cluster analysis identified three drug combinations,and complex network analysis demonstrated that the core drug compo-nents were Scutellaria baicalensis Georgi,Pinellia ternate,Astragalus membranaceus,Curcuma zedoary,Fritillaria thunbergii,Fago-pyrum dibotryis,Hedyotis diffusa and Ranunculus ternatus.Network pharmacology analysis showed that the key targets for the treat-ment of lung nodules with patent prescriptions were GAPDH,IL6,TNF and so on.The core active ingredients were Baicalein,Moslosooflavone,and Norwogonin and so on.The main pathways involved were cancer pathways,lipids and arteriosclerosis,and viral carcinogenesis.CONCLUSION The inclusion of traditional Chinese medicine compound patent in this case is consistent with the eti-ology and pathogenesis of traditional Chinese medicine for treating lung nodules.Commonly used drug pairs and cluster prescriptions re-flect the flexible compatibility of traditional Chinese medicines in the treatment of pulmonary nodules,such as clearing away heat and toxic materials,resolving phlegm and eliminating swelling,regulating qi and strengthening spleen,promoting blood circulation and remo-ving blood stasis.The core drugs exert their effects on pulmonary nodules through multiple components,multiple targets and multiple pathways.

Objective To investigate the effect of subanesthetic dose of esketamine on emergence agitation(EA)in patients undergoing laparoscopic hernia repair.Methods Seventy-two male patients who treated with lapa-roscopic hernia repair under general anesthesia were randomly divided into AS group(subanesthetic esketamine)and control group.In the AS group,0.2 mg/kg of esketamine was administered intravenously 30 minutes before the surgery ended,while the control group was given an equal volume of normal saline.Upon surgery completion,patients were transferred to PACU with endotracheal tube retained,and the time to extubation was recorded.Hemo-dynamic parameters were measured immediately after extubation and at 10 min,30 min,1 h,and 4 h thereafter.Patients' pain and sedation levels were assessed at the above time points using RASS and VAS,respectively.The incidence of EA was evaluated using the Confusion Assessment Method for the Intensive Care Unit(CAM-ICU).Observation duration in the PACU and recovery outcomes within 24 hours postoperatively were assessed via the QoR-40 and adverse events were recorded.Results Compared to those in the control group,patients in the AS group had higher HR and MAP at 10 min post-extubation,and the changes in HR and MAP over time were more stable(P<0.05).The RASS and VAS scores in the AS group were significantly lower than those in the control group at the time of extubation and all subsequent time points(P<0.05),both groups showed temporal changes in RASS and VAS scores(P<0.05),but the change process in the AS group was more stable(P<0.05).Postoperative extubation time,PACU observation duration,and adverse event rates(delirium,respiratory depression,nausea and vomiting)did not differ significantly between the two groups(P>0.05),while recovery quality was markedly better in the AS group(P<0.05).Conclusion Subanesthetic esketamine effectively alleviates pain and the incidence of EA,supports hemodynamic stability during PACU stay,and enhances recovery quality in patients undergoing laparo-scopic hernia repair,demonstrating clinical value.

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 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.

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.