ObjectiveTo investigate the potential mechanism of Danggui Buxuetang （DBT） in the treatment of vascular dementia （VAD）. MethodsSixty male SD rats were randomly assigned to the sham-operated group， model group， DBT low-， medium-， and high-dose groups， and the donepezil group. Except for the sham-operated group， rats in all other groups underwent bilateral common carotid artery ligation. After successful modeling， DBT was administered at doses of 9.2， 18.4， 36.8 g·kg^-1 for the low-， medium-， and high-dose groups， respectively， while the donepezil group received 3 mg·kg^-1 donepezil solution by gavage once daily. After 4 consecutive weeks of drug treatment， rats underwent the Morris water maze test， novel object recognition test， Nissl staining to observe hippocampal neurons， and immunofluorescence staining to detect the expression of neuronal nuclear protein （NeuN） in the hippocampus. Western blot was used to assess the expression of PTEN-induced kinase 1 （PINK1）， Parkin， microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Transmission electron microscopy was used to observe hippocampal neuronal ultrastructure. Real-time PCR was used to detect the expression of NADPH oxidase subunits p22^phox and p47^phox in hippocampal tissues. The levels of malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase （SOD）， and total antioxidant capacity were measured to evaluate oxidative stress levels. ResultsIn the Morris water maze test， escape latency changed significantly over time in all groups except the model group. Compared with the sham-operated group， the model group showed significantly prolonged escape latency （P<0.01）. Compared with the model group， rats in the DBT groups and the donepezil group exhibited significantly shorter escape latency （P<0.05， P<0.01）. The number of crossings over the original platform was significantly reduced in the model group compared with the sham-operated group （P<0.01）， whereas rats in the DBT and donepezil groups showed significantly increased platform crossings compared with the model group （P<0.05， P<0.01）. Compared with the sham-operated group， exploration time of new objects was significantly reduced in the model group （P<0.01）. Compared with the model group， exploration time of new objects increased significantly in the medium- and high-dose DBT groups and the donepezil group （P<0.05， P<0.01）， while no significant change was observed in the low-dose DBT group. Compared with the high-dose DBT group， rats in the donepezil group had significantly prolonged escape latency and reduced platform crossings and new-object exploration time （P<0.05）. Nissl staining showed decreased density of healthy neurons in the CA1 and CA3 regions of the hippocampus in the model group， with loss of Nissl bodies and nuclear atrophy or disappearance. In the high-dose DBT group， neuronal density in CA1 and CA3 increased， with neurons arranged closely and displaying normal morphology. Immunofluorescence showed that compared with the sham-operated group， the hippocampal NeuN⁺ cell count in the VAD model group was significantly decreased（P<0.01）， compared with the VAD model group， the hippocampal NeuN⁺ cell count in the high-dose DBT group was significantly increased（P<0.01）. Compared with the sham-operated group， the expression of PINK1， Parkin， LC3Ⅱ， and Bax proteins was significantly increased（P<0.01）， while the expression of Bcl-2 was significantly decreased in the VAD model group（P<0.01）. Compared with the VAD model group， the high-dose DBT group showed significantly decreased expression of PINK1， Parkin， LC3Ⅱ， and Bax proteins（P<0.01）and significantly upregulated Bcl-2 expression（P<0.01）. The medium-dose DBT group exhibited significantly reduced expression of Parkin， LC3Ⅱ， and Bax proteins（P<0.05，P<0.01） and significantly increased Bcl-2 expression（P<0.01）， while no statistically significant differences were observed in the low-dose DBT group. Transmission electron microscopy showed mitochondrial pyknosis， thickened cristae， increased electron density， and the presence of mitochondrial autophagy in the model group. In contrast， hippocampal neurons in the high-dose DBT group contained abundant mitochondria with intact morphology， clear cristae， and uniform matrix. Compared with the sham-operated group， total antioxidant capacity， SOD activity， and GSH levels were significantly decreased， while MDA levels were significantly increased in the model group （P<0.01）. Compared with the model group， total antioxidant capacity and antioxidant levels （SOD， GSH） increased significantly， and MDA decreased significantly in the medium- and high-dose DBT groups （P<0.01）， while no significant changes were observed in the low-dose DBT group. Compared with the sham-operated group， mRNA expression of p22^phox and p47^phox was significantly increased in the model group （P<0.01）. Compared with the model group， expression of p22^phox and p47^phox was significantly decreased in the DBT groups （P<0.05， P<0.01）. ConclusionDBT may exert neuroprotective effects by regulating PINK1/Parkin-mediated mitochondrial autophagy， thereby improving learning and memory abilities and treating VAD.

Neurodegenerative diseases(NDs)are a series of disorders characterized by varying degrees of cognitive and mobility impairment,with increasing incidence in recent years.Currently,the treatment of these diseases is mainly based on drug therapy,and there are no effective methods for reversing the course of the diseases.Corni Fructus has the efficacy of tonifying the liver and kidney,and astringency and arresting,which is effective to various types of NDs.This article summarized the pharmacological effects of Corni Fructus,including anti-inflammatory,anti-oxidative stress,regulation of mitochondrial function,modulation of autophagy,inhibition of neuronal apoptosis,and epigenetic modulation,and sorted out the research progress of Corni Fructus and its active components in the treatment of NDs,such as Alzheimer disease,Parkinson disease,multiple sclerosis,and so on,with a view to providing a reference for further research and clinical application of Corni Fructus in NDs.

Objective To construct mouse models of vaccinia virus infection using C57BL/6N and BALB/C mice infected with vaccinia virus VR-1354(WR(NIH TC-adapted)),and to compare the differences between the models in the two mouse strains.Methods Vaccinia virus VR-1354 was amplified,concentrated,and titrated,according to conventional method.The median lethal doses(LD50)of vaccinia virus V R-1354 for C57BL/6N and BALB/C mice were determined,respectively,and mice from the two strains were infected with the respective LD50.Lung tissues from control and experimental mice were removed for hematoxylin and eosin staining on days 3,7,and 14,and changes in the virus load in the lung tissues were measured at the same times.Results The titer of the amplified vaccinia virus VR-1354 was 3×108 plaque forming units(PFU)/mL.The LD50 values in C57BL/6N and BALB/C mice were 2.5×103and BALB/C 2.8×103PFU,respectively.After infecting mice from both strains with 2.5× 103 PFU of vaccinia virus VR 1354,lung tissue lesions worsened with increasing infection time,but the symptoms of the mice tended to recover after day 7.The virus loads in lung tissues began to increase on day 3 in both strains,peaked on day 7,and then gradually decreased.Conclusions C57BL/6N and BALB/C mouse models infected with vaccinia virus VR-1354 were established successfully.The virus can cause obvious lesions in mouse lung tissues,including inflammatory cell infiltration and alveolar cavity fluid exudation.The degree of disease onset and susceptibility differed between the two mouse strains,with C57BL/6N mice showing higher susceptibility to this virus than BALB/C mice.

Objective To construct mouse models of vaccinia virus infection using C57BL/6N and BALB/C mice infected with vaccinia virus VR-1354(WR(NIH TC-adapted)),and to compare the differences between the models in the two mouse strains.Methods Vaccinia virus VR-1354 was amplified,concentrated,and titrated,according to conventional method.The median lethal doses(LD50)of vaccinia virus V R-1354 for C57BL/6N and BALB/C mice were determined,respectively,and mice from the two strains were infected with the respective LD50.Lung tissues from control and experimental mice were removed for hematoxylin and eosin staining on days 3,7,and 14,and changes in the virus load in the lung tissues were measured at the same times.Results The titer of the amplified vaccinia virus VR-1354 was 3×108 plaque forming units(PFU)/mL.The LD50 values in C57BL/6N and BALB/C mice were 2.5×103and BALB/C 2.8×103PFU,respectively.After infecting mice from both strains with 2.5× 103 PFU of vaccinia virus VR 1354,lung tissue lesions worsened with increasing infection time,but the symptoms of the mice tended to recover after day 7.The virus loads in lung tissues began to increase on day 3 in both strains,peaked on day 7,and then gradually decreased.Conclusions C57BL/6N and BALB/C mouse models infected with vaccinia virus VR-1354 were established successfully.The virus can cause obvious lesions in mouse lung tissues,including inflammatory cell infiltration and alveolar cavity fluid exudation.The degree of disease onset and susceptibility differed between the two mouse strains,with C57BL/6N mice showing higher susceptibility to this virus than BALB/C mice.

Gallbladder cancer is the most common malignant tumor of the biliary system,characterized by insidious growth,rapid progression,and skip metastasis.The 5-year overall survival rate is only 5%.Although targeted immunotherapies have emerged in recent years,they are still in the exploratory phase for the treatment of gallbladder cancer,and radical surgical resection remains the only potentially curative treatment.The main goal of surgery is to completely remove the tumor and perform systematic lymph node dissection to reduce the risk of recurrence.Thanks to advances in surgical techniques and continuous optimization of perioperative management,postoperative complications,and hospital mortality in patients undergoing extended radical surgery for gallbladder cancer have decreased.However,the complex mechanisms of gallbladder cancer spread and metastasis make it challenging to determine the optimal scope of surgical resection.Clinical guidelines from different countries and hepatobiliary surgery centers often vary on surgical options,especially regarding the reasonable extent of liver resection,the scope of lymph node dissection and its impact on prognosis,and whether routine extrahepatic bile duct resection should be performed.There remains significant controversy in these areas.Future extensive prospective cohort studies are still needed to provide more evidence-based medical data for the surgical treatment of gallbladder cancer.When designing a surgical plan,surgeons must consider preoperative examination results,intraoperative findings,and pathological evaluation of frozen sections.A balance must be struck between radical treatment and safety and effectiveness.The most appropriate surgical method for each patient should be chosen while also emphasizing establishing a multidisciplinary collaborative system.Based on accurate tumor staging,postoperative adjuvant therapies should be integrated to continue making progress in improving patient prognosis.

Objective: To investigate the efficacy and safety of intelligent temperature-pressure-controlled flexible ureteroscopy combined with negative-pressure suction sheath lithotripsy in the treatment of upper urinary tract stones ≤2.5 cm. Methods: The clinical data of 225 patients with ≤2.5 cm upper urinary tract stones treated with this surgical method in our department during Aug. 2023 and Jul. 2024 were retrospectively analyzed. The patients were divided into the dual-control group (n=36) and conventional group (n=189) according to whether or not the intelligent temperature and pressure control device was used during operation. In the dual-control group，the intraoperative temperature and pressure in the renal pelvis were monitored and controlled in real time by the temperature and pressure sensors distributed at the end of the ureteral soft lens. The perioperative parameters，stone-removal rate，complication rate and renal function were compared between the two groups. Results: All operations were successfully completed in both groups. The postoperative procalcitonin (PCT) level [(22.75±5.85) ng/L vs. (29.08±6.60) ng/L，P=0.001]，difference in the white blood cell (WBC) level [(0.24±2.12)×10 cells/L vs. (1.19±2.17)×10 cells/L，P=0.016]，incidence of fever (2.8% vs. 16.9%，P=0.028) and overall complication rate (5.6% vs. 19.6%，P=0.042) were significantly lower in the dual-control group than in the conventional group，while the stone-clearance rate was slightly higher (88.9% vs. 82.5%，P=0.346)，with no significant difference. Conclusion: For upper urinary tract stones ≤2.5 cm，intelligent temperature-pressure-controlled ureteroscopy combined with negative-pressure suction sheath lithotripsy has a satisfactory stone-removal rate and a low rate of complications，which is worthy of clinical promotion.

Parkinson’s disease （PD） is a common chronic neurodegenerative disease with movement disorders as the main clinical manifestation. The nuclear factor-erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway is closely associated with the occurrence and progression of PD. TCM flavonoid monomers （luteolin， rutin， etc.）， alkaloids （camptothecin， sinomenine， and alkaloids extracted from Uncaria rhynchophylla）， terpenes （tanshinone ⅡA， carvacrol， paeoniflorin）， phenols （ellagic acid， rosmarinic acid）， saponins （ginsenoside RK1）， and traditional Chinese medicine compounds （Wuzi yanzong pill and PD formula-2） can resist oxidative stress damage， inhibit inflammatory responses and abnormal aggregation of α-synuclein， and regulate neurotrophic factors by activating the Nrf2/HO-1 signaling pathway， thereby alleviating dopaminergic neuronal damage.

ObjectiveCardiovascular diseases pose a major public health challenge in China. The burden of cardiovascular disease associated with high low-density lipoprotein cholesterol （LDL-C） has increased steadily nationwide. A comprehensive analysis of secular trends in cardiovascular disease burden and its determinants is crucial for developing targeted interventions and evidence-based health policies. MethodsBased on data from the Global Burden of Disease Study 2021， we analyzed the trends in deaths， disability-adjusted life years （DALYs）， age-standardized mortality rates （ASMR）， and age-standardized DALY rates （ASDR） of cardiovascular diseases attributable to high LDL-C in China from 1990 to 2021 using Joinpoint regression analysis. An age-period-cohort model was applied to assess the contributions of age， period， and cohort effects to changes in the cardiovascular disease burden attributable to high LDL-C. Projections of the high LDL-C-attributable cardiovascular disease burden in China from 2022 to 2030 were generated using a Bayesian age-period-cohort model. ResultsBetween 1990 and 2021， China saw a substantial rise in both deaths and disability-adjusted life years （DALYs） from cardiovascular disease linked to high LDL-C. Joinpoint regression revealed key turning points in this trend： an overall increase continued until 2004， after which the burden began to fall starting in 2011. Throughout this period， age-standardized mortality and DALY rates were consistently higher in males than in females. Age-period-cohort analysis further indicated that mortality and DALY rates due to high LDL-C increased almost exponentially with age， while period and cohort risks generally decreased over time. Projections suggest a continued decline in age-standardized mortality rates from LDL-C-related cardiovascular disease for both Chinese men and women by 2030. ConclusionRapid population growth and accelerated ageing in China emerge as primary drivers of the escalating cardiovascular diseases burden linked to elevated LDL-C. The burden of cardiovascular diseases is higher in men compared to women. By 2030， the burden of cardiovascular disease caused by high LDL-C in China will remain severe. These findings underscore the critical need for gender-specific screening protocols， age-tailored interventions， and personalized management frameworks to mitigate this public health challenge.

Objective: To identify the phenotypes, antibodies and explore the molecular mechanisms of a patient who carries antibodies to RBC high-frequency antigens and his family members. Methods: The antibody identification test was performed for the proband by serological methods, and targeted NGS was subsequently used to detect mutations that occurred in blood group genes. Blood samples were collected from the proband and his family members. Sanger sequencing was used to verify the mutation of the XK gene. The expression of Kell blood group antigens was detected by serological methods and flow cytometry. K cells were used to detect the antibody specificity of the proband. The morphology of red blood cells was detected by the scanning electron microscopy. The serum creatine kinase levels of the proband and his family members were analyzed by colorimetric methods. Results: The results of the antibody identification test suggested that the proband might have antibodies to high-frequency antigens. NGS results suggested a homozygous mutation (c. 107G>A) in exon 1 of the XK gene in the proband, resulting in a truncated XK protein. The Sanger sequencing results of the proband were consistent with the NGS results, and the mutation was not found in other family members. The expression of Kell blood group antigens of the proband was not found by serological methods and flow cytometry. The results of the antibody specificity test showed that the proband had anti-Km antibodies. Spike-like changes were identified on red blood cells, and serum creatine kinase level was elevated in the proband. Conclusion: In this study, the McLeod phenotype caused by homozygous mutation (c. 107G>A) of XK gene was identified in Chinese individuals for the first time by the phenotype and molecular mechanism studies. The results of genotyping and phenotyping suggested that the McLeod phenotype caused by the mutation was compatible with the phenotypes of McLeod and K .

Objective:To analyze the electroencephalogram features of visual working memory in the delay stage based on microstate analysis.Methods:In this cross-sectional study, ten healthy male subjects aged 19-29 years old from Tianjin Medical University were selected from January to July 2015. The 32-channel electroencephalogram experimental data were recorded from these subjects during the visual working memory eye-open state for 10 min (resting-state) and the delayed matching-to-sample (DMS) task (task-state) conditions, respectively. After data pre-processing, a short-time Fourier transform was applied for time-frequency analysis to extract the characteristic time periods and frequency bands, and electroencephalogram microstates of the resting and task states of visual working memory were computed separately, using an improved k-means clustering algorithm. The Mann-Whitney U test was used to analyze the statistical differences between resting-state and task-state microstate parameters, including global field power (GFP), global explained variance (GEV), time proportion, mean spatial correlation, frequency of occurrence and duration. Results:The time-frequency distribution of the Fz channel in the responsible brain region in DMS task visual working memory showed that the energy was mainly concentrated in the theta band (4-8 Hz) during the delay stage (4.039-7.039 s). The bipolar locations of microstates A, B, C, and D were prefrontal and occipital, central frontal and occipital, right occipital and left frontal, and left occipital and right frontal, respectively. In microstates A and C, the mean spatial correlation of the task-state was both higher than that of the resting state. The comparison results for microstate A were (0.632 5±0.105 8 vs 0.624 5±0.461 4, P<0.05), and the results for microstate C were (0.589 4±0.233 4 vs 0.561 3±0.066 8, P<0.01). The parameters of the task-state microstate D were lower than those of the resting-state, including GFP (1.125±0.061 vs 1.277±0.741, P<0.05), GEV (0.077±0.061 vs 0.101±0.057, P<0.05), and time proportion (0.191±0.165 vs 0.224±0.094, P<0.05) and mean spatial correlation (0.561 2±0.211 6 vs 0.612 1±0.315 2, P<0.01). Conclusions:The critical period of visual working memory is the delay stage and the critical frequency band is the theta band. Microstate D is the characteristic feature of visual working memory in the delay stage of the theta band, and microstates A and C can also serve as its potential features.