BACKGROUND:Parkinson's disease is a multifactorial neurological disorder characterized by progressive loss of dopaminergic neurons,and dimethyl fumarate(DMF)has potent neuroprotective and immunomodulatory effects in neurodegenerative diseases. OBJECTIVE:To explore the neuroprotective mechanism of DMF in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease. METHODS:Twenty-four C57BL/6 mice were selected and randomly divided into control group,model group,low-dose DMF,and high-dose DMF groups.An animal model of Parkinson's disease was established in the latter three groups by intraperitoneal injection of 30 mg/kg MPTP,once a day for 5 consecutive days.Intragastric administration was given 30 minutes after each injection of MPTP.Mice in the low-dose DMF group(30 mg/kg)and high-dose DMF group(50 mg/kg)were intragastrically administered once a day for 7 consecutive days.The control and model groups were initially administered the same dose of normal saline.Behavioral testing,western blot,oxidative stress marker detection,and immunohistochemical staining were used to analyze the regulatory effects of DMF on oxidative stress and Keap1/Nrf2 signaling pathway in MPTP-induced Parkinson's disease mice,as well as the protective mechanism of DMF on degeneration of dopamine neurons. RESULTS AND CONCLUSION:Compared with the model group,mice in the low-dose DMF group exhibited significant improvements in motor retardation and postural imbalance(P<0.01),with even more remarkable improvements observed in the high-dose DMF group(P<0.01).Compared with the control group,the model group showed a significant increase in the oxidative stress marker malondialdehyde and a decrease in superoxide dismutase expression(P<0.01).Compared with the model group,the low-dose DMF group reduced malondialdehyde production and increased superoxide dismutase expression(P<0.01),and similar improvements were observed in the high-dose DMF group(P<0.01).Immunohistochemical and western blot assays demonstrated a significant decrease in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra of mice in the model group compared with the control group(P<0.01).However,in the low-dose DMF group,there was an increase in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra(P<0.01),with even more significant improvements in the high-dose DMF group(P<0.01).Western blot results revealed that the model group exhibited elevated Keap1 protein expression and decreased Nrf2 protein expression.In contrast,the DMF groups showed reduced Keap1 protein expression and increased Nrf2 protein expression compared to the model group(P<0.01).To conclude,DMF regulates the Keap1/Nrf2 pathway in the substantia nigra of mice with Parkinson's disease,and this regulatory effect is positively correlated with the dose of DMF(P<0.01).Therefore,we infer that DMF exerts neuroprotective effects through the Keap1/Nrf2 signaling pathway.

ObjectiveTo understand the epidemiological distribution and gene evolutionary variation of influenza A (H3N2) viruses in Fengxian District, Shanghai, in the surveillance year of 2023, and to provide a reference basis for influenza prevention and control. MethodsThe prevalence of influenza virus in Fengxian District in the 2023 influenza surveillance year (April 2023‒March 2024) was analyzed. The hemagglutinin (HA) gene, neuraminidase (NA) gene, and amino acid sequences of 75 strains of H3N2 influenza viruses were compared with the vaccine reference strain for similarity matching and phylogenetic evolutionary analysis, in addition to an analysis of gene characterization and variation. ResultsIn Fengxian District, there was a mixed epidemic of H3N2 and H1N1 in the spring of 2023, with H3N2 being the predominant subtype in the second half of the year, and Victoria B becoming the predominant subtype in the spring of 2024. A total of 75 influenza strains of H3N2 with HA and NA genes were distributed in the 3C.2a1b.2a.2a.2a.3a.1 and B.4 branches, with overall similarity to the reference strain of the 2024 vaccine higher than that of the reference strain of the 2022 and 2023 vaccine. Compared with the 2023 vaccine reference strain, three antigenic sites and one receptor binding site were changed in HA, with three glycosylation sites reduced and two glycosylation sites added; where as in NA seven antigenic sites and the 222nd resistance site changed with two glycosylation sites reduced. ConclusionThe risk of antigenic variation and drug resistance of H3N2 in this region is high, and it is necessary to strengthen the publicity and education on the 2024 influenza vaccine and long-term monitoring of influenza virus prevalence and variation levels.

Objective: To examine the associations between peer bullying and parental phubbing with executive function and their combined effect among primary and secondary school students, so as to provide scientific evidence for promoting healthy development of executive function among primary and secondary school students. Methods: In November 2024, a combining convenience with clustering method was used to select 3 547 primary and secondary school students in Shenzhen City. The Chinese versions of the Delaware Bullying Victimization Scale-Student (DBVS-S), the Parental Phubbing Scale (PPS), and the Teenage Executive Functioning Inventory (TEXI) were used to assess peer bullying, parental phubbing, and executive function, respectively. Generalized linear regression models were applied to analyze the associations of peer bullying and parental phubbing with executive function, and to assess their joint effects. Subgroup analyses were performed by ages and genders, and multiplicative interaction terms were used to test for interactions. Results: The score for peer bullying among primary and secondary school students was (15.27± 5.67 ), with verbal bullying, physical bullying, and relational bullying scores being (5.64±2.77) (4.70±1.62) (4.93±2.07), respectively. The score for parental phubbing was (13.98±5.00). Executive function score was (47.35±15.89), while inhibitory control and working memory scores were (26.44±9.00) (20.91±7.49), respectively. After adjusting for confounding factors such as age, gender, self reported family relationship, self reported family economic status, parental education level, both peer bullying ( β= 0.75, 95%CI =0.67-0.84), verbal bullying( β=1.41, 95%CI =1.23-1.58), physical bullying ( β=2.18, 95%CI =1.87- 2.49 ), relational bullying ( β=1.78, 95%CI =1.54-2.01) and parental phubbing ( β=0.88, 95%CI =0.79-0.98) were significantly positively associated with the degree of executive function impairment (all P <0.01). Joint effect analysis showed that, compared with the "no bullying low phubbing" group, the total executive function scores in other combined exposure groups were all higher ( β = 6.78-15.96, all P <0.01). Among them, the "bullying high phubbing" group exhibited the highest level of executive function impairment ( β=14.17, 95%CI=12.61-15.73, P <0.01). Subgroup analysis indicated significant interactions between verbal bullying and age on total executive function, inhibitory control, and working memory (all P interaction <0.01). The association of verbal bullying with executive function was slightly higher in primary and secondary school students younger than 13 years ( β=1.80, 95%CI = 1.45-2.16) than in those aged 13 years or older ( β=1.25, 95%CI =1.05-1.45) (both P <0.01). Other types of bullying and parental phone neglect showed no statistically significant interaction with age or gender in executive function, inhibitory control, and working memory(all P interaction >0.05). Conclusion Both peer bullying and parental phubbing are significantly associated with impaired executive function among primary and secondary school students, and there is a combined effect between them; among these, the association between verbal bullying and executive function impairment in younger primary and secondary school students is more pronounced.

Objective:To explore the technical focus of robotic-assisted laparoscopic surgery for the treatment of horseshoe kidney combined with renal tumor.Methods:The clinical data of a patient with horseshoe kidney combined with renal tumor treated by robot-assisted laparoscopic partial nephrectomy in the Second Hospital of Dalian Medical University in September 2021 were retrospectively analyzed. PubMed, CNKI, Wanfang and VIP databases were searched for all the literature on the use of robot-assisted laparoscopic nephrectomy or partial nephrectomy for the treatment of horseshoe kidney combined with renal tumor from the time of establishment to December 2022.Results:A total of 11 patients from 10 articles were retrieved and 12 patients were enrolled. Among the 12 patients, 4 cases used the retroperitoneal approach and 8 cases used the transperitoneal approach. Two cases were operated by traditional laparoscope, and the arteries were searched for and controlled before the robotic arm was placed to perform the partial nephrectomy and suture; and 10 cases were operated with the robotic-assisted laparoscopic approach throughout the whole procedure. Five cases of nephrectomy were performed on one side, and 7 cases were performed in the partial nephrectomy. Postoperative pathological diagnosis was clear cell carcinoma in 8 cases, chromophobe cell carcinoma in 1 case, eosinophilic cell carcinoma in 1 case, renal cell carcinoma in 1 case, and renal abscess in 1 case. The patient in the Second Hospital of Dalian Medical University was 38 years old female who was admitted to the hospital with a fever. After CT arteriography and three-dimensional reconstruction, robotic-assisted laparoscopic partial nephrectomy of right kidney and isthmus dissecting was performed. During the operation, tumor trophoblast vessels were ligated and dissected one by one by using single-use tissue closure clips, and the isthmus was dissected using endoscopic cutting anastomosis on the left side of the tumor, with the tumor edges sharply resected and completely dissected. The operation time was 240 min, without thermal ischemia time, and the bleeding volume was about 300 ml. The patient recovered well after the operation, and the postoperative pathological diagnosis was renal abscess.Conclusions:Robot-assisted laparoscopic treatment of horseshoe kidney combined with renal tumor is safe and effective, and has more advantages than traditional laparoscopic surgery. Preoperative CT arteriography or three-dimensional reconstruction examination should be applied to fully evaluate the variant vessels. The surgical access and plan should be decided according to the size and location of the tumor. The variant vessels should be properly handled during operation. The use of endoscopic cutting anastomosis to deal with the isthmus can be more conducive to the surgical operation.

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City,China. Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed. Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52％. The male:female ratio was 2.8:1. 75.3％ of patients were aged between 16 and 60 years old,75.3％ of patients were farmers,and 11.6％ had both "three red" and "three pain" symptoms. The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak. Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity. The typical symptoms of "three red" and"three pain" in patients with HFRS were not obvious.

Objective To explore the correlations of serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) with grading of myelofibrosis (MF) in patients with myeloproliferative neoplasms (MPN). Methods Ninety patients with Philadelphia chromosome negative (Ph-)MPN were selected as MPN group. According to the grading criteria for myelofibrosis by the World Health Organization (WHO) in 2016, MPN patients were divided into pre-fibrosis or early fibrosis group with 54 cases and significant fibrosis group with 36 cases; another 50 healthy volunteers were selected as the control group. Levels of serum VEGF, MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay, and the ratio of TIMP-1 to MMP-9 (TIMP-1/MMP-9) was calculated. Spearman rank correlation test was used to analyze the correlations of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 with MF grading. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of each indicator alone or their combination for diagnosing MPN or distinguishing MF grading. Results Compared with the control group, the serum levels of VEGF, MMP-9 and TIMP-1 in the MPN group increased significantly (P < 0.05). Values of area under the curve (AUC) of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for diagnosing MPN were 0, 834, 0.745, 0.923 and 0.618 respectively; the AUC of the combined diagnosis of MPN by VEGF, MMP-9 and TIMP-1 was 0.960; when the optimal cut-off value was 0.627, the sensitivity was 85.56%, and the specificity was 92.00%. Compared with the pre-fibrosis or early fibrosis group, the serum levels of VEGF, TIMP-1 and TIMP-1/MMP-9 in the significant fibrosis group increased significantly (P < 0.05). Spearman correlation analysis showed that VEGF (r=0.378, P=0.001), TIMP-1 (r=0.512, P < 0.001) and TIMP-1/MMP-9 (r=0.353, P=0.001) were positively correlated with the MF grading of MPN patients (P < 0.05). ROC curve analysis showed that the values of AUC of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis were 0.723, 0.523, 0.802 and 0.708 respectively; the AUC of the combined detection of VEGF, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis was 0.838; when the optimal cut-off value was 0.530, the sensitivity was 72.22%, and the specificity was 85.19%. Conclusion Serum VEGF, TIMP-1 and TIMP-1/MMP-9 can reflect the MF progression of MPN patients, and the combined detection of these indicators can predict the MF degree of MPN patients.

Objective To establish a method for simultaneous determination of 14 components in Cinnamomi Cortex;To comprehensively evaluate its quality by multivariate statistical analysis technology.Methods HPLC method was used to establish the relative correction factors(RCF)between protocatechuic acid and 13 other components of coumalic acid,coumarin,cinnamyl alcohol,cinnamic acid,2-methoxycinnamic acid,cinnamaldehyde,o-methoxycinnamaldehyde,vanillic,syringic acid,4-hydroxybenzoic acid,procyanidin B2,epicatechin and procyanidin C1 to be measured,and the content of each component was calculated.The QAMS method was validated using external standard method(ESM),and the comprehensive quality of Cinnamomi Cortex was evaluated using PCA,OPLS-DA and EW-TOPSIS methods.Results The methodological verification results of ESM were in accordance with the requirements;the RCF established with protocatechuic acid as the reference had good durability under different experimental conditions,and the difference in content of each component between ESM and QAMS was not significant(P>0.05);the results of multivariate statistical analysis showed that accumulative contribution rate of former 2 principle components was 90.312%.Cinnamaldehyde,2-methoxycinnamic acid,procyanidin B2 and 4-hydroxybenzoic acid had a significant impact on the quality of Cinnamomi Cortex.The results of EW-TOPSIS showed that the Pi value of 16 batches of Cinnamomi Cortex ranged from 0.147 2 to 0.768 1.The quality of Cinnamomi Cortex from different producing areas varied greatly,and the overall quality of Cinnamomi Cortex from Guangxi Province was the best,followed by that from Guangdong Province and Yunnan Province,and the quality of Cinnamomi Cortex from Fujian Province was relatively poor.Conclusion The established QAMS multi-component quantitative method combined with multivariate statistical analysis technology can be used for comprehensive quality evaluation of Cinnamomi Cortex.

Objective To explore the role of β-1,3-galactosyltransferase 2(B3galt2)in mice with cerebral ischemic injury.Methods Adult male C57BL/6J mice were randomly divided into the sham,suture-occluded middle cerebral artery occlusion(MCAO)model,MCAO model+lentiviral vector control(LV-GFP),and MCAO model+lentiviral vector overexpression B3galt2(LV-B3galt2)groups,with six mice in each group.Neurological deficit scoring and rotating rod experiments were performed 24 h after ischemia in each group,and 2,3,5-triphenyltetrazolium chloride(TTC)staining was used to determine the infarction volume.The number of neurons in the ischemic cerebral cortex was determined in each group using Nissl staining.The levels of oxidative stress-related factors in the brain tissues were detected using the relevant kits.Results Compared with the sham group,the MCAO model group showed increased infarct volume and neurological deficits(P<0.05),significantly decreased number of neurons in the ischemic cerebral cortex and levels of super-oxide dismutase(SOD)and glutathione peroxidase(GSH)(all P<0.05),and significantly increased levels of reactive oxygen species(ROS)and malondialdehyde(MDA)(all P<0.05).Compared with the MCAO model group,the LV-B3galt2 group had reduced volume of cerebral infarction,significantly improved neurological deficits(all P<0.05),significantly increased number of neurons in the ischemic cerebral cortex of mice,significantly decreased levels of ROS and MDA(P<0.05),and significantly elevated levels of SOD and GSH(all P<0.05).Conclusion B3galt2 overexpression can reduce brain injury in an ischemic damage mouse model,and its mechanism may be through the inhibition of oxidative stress reactions.

Objective To evaluate the differences in chemical composition and pharmacological effects between Angelica-Astragalus medicine pair decoction(DGD)and traditional decotion,and to provide a reference for the rational clinical application of Danggui Buxue decoction.Methods With the two comparison methods of unified and non-uniform raw material source batches,we set up different sample groups,established characteristic maps by HPLC,and evaluated the chemical components based on the similarity of characteristic maps,component types,index component content,common peak area,and other factors.The efficacy of the drug was evaluated in the hemorrhagic blood deficiency model mice.Results ①The similarity of the feature map between the DGD and TD was high(similarity was greater than 0.87).②The number of chromatographic peaks was inconsistent.Traditional decoction from self-purchased decoction pieces,or traditional decoction-Factory A decoction pieces had a total of 12 chromatographic peaks each.The DGD of Factory A had a total of 15 chromatographic peaks.There were 10 chromatographic peaks in the DGD of Factory B.③The contents of ferulic acid and calycosin 7-O-glucoside(CG)in DGD of Factory A were higher than those in traditional decoction(P<0.05,n=3).There was no significant difference between DGD and TD ferulic acid content in Factory B,but the content of CG was lower than that in traditional decoction(P<0.05).④The total area of common peaks in DGD was different from that in TD.The relative total ratios of the contents of the components in the self-purchased traditional decoction pieces,the traditional decoction pieces of Factory A,the formula granules of Factory A,and the formula granules of Factory B were 1.00,0.96,2.14,0.60,respectively.⑤Both DGD and traditional decoction could significantly promote the recovery of hemoglobin and red blood cells in hemorrhagic anemia model mice(P<0.01);Compared with the model control group,there was a significantly difference(P<0.05)except for the DGD group of Plant B.There was no significant difference between DGD and TD of Plant A,but there was a very significant difference between DGD and TD of Plant B(P<0.01).Conclusion Whether the raw material source batch is consistent or not,DGD and TD have certain differences in chemical composition.In terms of pharmacological effect,DGD,prepared from a unified batch of decoction pieces,has similar efficacy to traditional decoction in alleviating hemorrhagic anemia.There are certain differences in the pharmacological effects between DGD prepared from different batches of decoction pieces and traditional decoctions.The differences caused by the different preparation processes of the same source batch of prepared slices were compared,and the quality differences of the formula granules from different manufacturers were caused by the different source batches of prepared slices and different preparation processes,indicating the necessity and urgency of the country to formulate a unified quality standard for formula granules and related process specifications.

Objectives:This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) .Methods:From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy.Results:The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients.Conclusion:Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.