1.In vitro cultured calculus bovis alleviates cerebral ischemia/reperfusion injury through regulating microglial polarization and inhibiting NLRP3.
Tanlu CHU ; Wei ZHANG ; Jingwen CHEN ; Zeyue PAN ; Lingfeng WANG ; Xiaoming ZHONG ; Fengmei QIU ; Zhen HUANG
Journal of Zhejiang University. Medical sciences 2025;54(3):360-371
OBJECTIVES:
To investigate the effect of in vitro cultured calculus bovis (ICCB) on cerebral ischemia/reperfusion injury (CIRI) and its mechanism.
METHODS:
A CIRI rat model and a cell model were induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats and oxygen glucose deprivation/reperfusion (OGD/R) in BV2 cells, respectively. The CIRI rat model was evaluated using the modified neurological severity score (mNSS), brain water content, and cerebral infarction volume after 1.5 h of ischemia followed by 72 h of reperfusion. Histopathological changes in the cortex and hippocampal CA1 region were observed with hematoxylin and eosin staining. Microglial polarization and NOD-like receptor thermal protein domain associated protein (NLRP) 3 inflammasome expression in the cortex were examined by immunofluorescence. BV2 cell viability was measured via MTT assay after treatment with ICCB and Nigericin. The expressions of NLRP3, ASC, caspase-1 proteins and inflammatory cytokines were detected with Western blotting in OGD/R treated BV2 cells (0.5 h OGD+24 h reperfusion) and in cells pretreated with Nigericin for 24 h.
RESULTS:
ICCB treatment significantly improved neurological function, reduced cerebral infarct volume and brain water content, and mitigated pathological damage in the cortical and hippocampal CA1 regions of rats subjected to CIRI (all P<0.05). ICCB promoted the transition of cortical microglia from M1 to M2 phenotypes and suppressed NLRP3 activation in microglial cells (all P<0.01). ICCB significantly down-regulated the expression of NLRP3, ASC, and caspase-1 proteins, and reduced the secretion of IL-18 and IL-1β in BV2 cells of OGD/R model (all P<0.01). In addition, Nigericin significantly reversed the salvage effect of ICCB on model cells (both P<0.01) and the modulation of inflammatory cytokines (P<0.05).
CONCLUSIONS
ICCB exerts a protective effect against CIRI by mitigating neuroinflammation, through the reduction of M1 microglial polarization, promotion of M2 conversion, and suppression of the NLRP3/ASC/caspase-1 signaling pathway.
Animals
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Rats, Sprague-Dawley
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Reperfusion Injury/prevention & control*
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Microglia/metabolism*
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Rats
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NLR Family, Pyrin Domain-Containing 3 Protein
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Brain Ischemia/metabolism*
;
Male
2.Clinical characteristics and influencing factors of vestibular migraine patients with sleep disorders.
Qingchun PAN ; Bei LI ; Jing ZHANG ; Yuanling WANG ; Xiaoming TANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(9):817-823
Objective:To investigate the sleep characteristics and clinical features of patients with vestibular migraine(VM), and to explore the influencing factors of sleep disorder in VM patients. Methods:A cross-sectional study method was adopted to collect VM patients from Otolaryngology department and neurology department of our hospital from June 2022 to June 2024(divided into sleep disorder group and non-sleep disorder group according to whether there is sleep disorder) as the experimental group, and recruit non-VM volunteers with clinical characteristics matching with the experimental group during the same period as the control group. The clinical data of the subjects were collected, and the sleep quality of the subjects was assessed using the Pittsburgh Sleep Quality Index(PSQI). The influencing factors of sleep disorders in VM patients were analyzed by multivariate Logistic regression, and the correlation between sleep disorders and clinical features such as headache, vertigo and hearing in VM patients was analyzed by Spearman correlation coefficient. Results:A total of 530 individuals with VM were analyzed, including 332 with sleep disturbances(62.64%), 198 without sleep issues(37.36%), and 50 in the control group. The overall PSQI score and all its components were significantly higher in the VM group compared with the control group(P<0.05). A positive correlation was observed between PSQI and VAS, DHI-T, DHI-E, DHI-F and DHI-P(r=0.797, P<0.05; r=0.834, P<0.05; r=0.794, P<0.05; r=0.771, P<0.05; r=0.877, P<0.05), PSQI had no correlation with pure tone hearing(r=0.324, P=0.167). Multivariate logistic regression analysis showed that female, age ≥60 years, living alone, duration of disease ≥3 months, motion sickness history, and HADS-A were independent influencing factors for comorbidification of sleep disorder in VM patients(P<0.05). Conclusion:The prevalence of sleep disorders in patients with vestibular migraine(VM) was significantly higher compared to the control group. Moreover, the severity of sleep disorders was positively correlated with the intensity of headache and vertigo in VM patients. It is recommended that female VM patients aged 60 years or older, living alone, with a disease duration of three months or longer, a history of motion sickness, and anxiety symptoms undergo sleep assessments to determine the presence of sleep disorders. This approach provides a theoretical foundation for precise treatment and prevention strategies for VM.
Humans
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Migraine Disorders/complications*
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Sleep Wake Disorders/complications*
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Cross-Sectional Studies
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Vertigo
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Female
;
Male
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Vestibular Diseases/complications*
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Sleep Quality
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Adult
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Middle Aged
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Logistic Models
3.Analysis of the trend of mortality among residents of Fuling District, Chongqing from 2017 to 2022
Xiaoming CHEN ; Yu XIANG ; Qiyu RAN ; Chengyu HUANG ; Hong PAN ; Xuemei DAI ; Hongbo LIU
Shanghai Journal of Preventive Medicine 2024;36(6):602-605
ObjectiveTo understand the mortality trends among residents of Fuling District, Chongqing, before and after theCOVID-19 outbreak, and to provide references for the government to formulate disease prevention and control policies and measures. MethodsData on mortality and population in Fuling District from 2017 to 2022 were collected to analyze population mortality and standardized mortality rates, and to compare the changes in the causes of death by year and before and after the pandemic. ResultsFrom 2017 to 2022, the crude mortality rate in Fuling District showed an upward trend (APC=3.04%, P<0.05), while the standardized mortality rate showed a downward trend (APC=-6.47%, P<0.01). The mortality rate of males was higher than that of females (P<0.05), with different age groups having different causes of death composition. The highest proportion of deaths in 0-year-old group was from infectious diseases, maternal and neonatal diseases, and nutritional deficiencies, the highest proportion of deaths in the 1‒24 age group, with the exception of those aged 5‒9, was from injuries, and the main cause of death for residents aged 25 and above was chronic diseases. The mortality rate of mental and behavioral disorders rose from the 13th to the 9th place. According to the epidemic situation of COVID-19, there were no changes in the top five causes of death among the entire population. The motility rate of endocrine, nutritional and metabolic diseases rose from the sixth to the fifth place in male population, and the motility rate of malignant tumor rose from the 3rd to the 2nd place in female population. ConclusionThere are no changes in the top five causes of death among the entire population of Fuling District before and after the COVID-19 outbreak. Chronic diseases remain the main cause of death. It is necessary to control the risk factors for cardiovascular and cerebrovascular diseases such as hypertension, diabetes, and dyslipidemia, and to curb the rising trend of mortality rates from strokes and acute myocardial infarction. For deaths caused by accidental injuries, targeted health education should be conducted for different populations.
4.Median Effective Dose of Ciprofol Combined with Sufentanil for Gastroscope in Different Populations
Min PAN ; Zhengda FAN ; Xiaoming ZUO ; Cheng WANG ; Jing MA ; Weibin XIE
Chinese Journal of Modern Applied Pharmacy 2024;41(12):1717-1722
OBJECTIVE
To test and compare the median effective dose(ED50) of ciprofol for gastroscope in patients of different genders and ages.
METHODS
Patients who planed to undergo gastroscope examination and treatment from March 2023 to April 2023 were selected, and divided into four groups according to stratified random method: N1 group(non-elderly male patients), N2 group(non-elderly female patients), N3 group(elderly male patients), and N4 group(elderly female patients). All patients received intravenous injection of 0.1 μg·kg−1 sufentanil followed by injection of the test dose of ciprofol according to Dixon’s modified sequential method. Gastroscope was performed after the disappearance of the eyelash reflex. The initial dose of ciprofol in all four groups was 0.4 mg·kg−1, and the ratio of adjacent doses was 1∶1.1. The next patient would receive a 10% increase in the dose of ciprofol if the patient experienced positive reactions such as coughing, frowning, and body movements during the endoscopy process. Otherwise, it would be judged as a negative reaction, and the next patient would receive a 10% decrease in the dose of ciprofol. The transition from a positive reaction to a negative reaction was defined as a turning point, and the study was terminated when seven turning points occurred. Hemodynamic parameters, oxygen saturation and adverse reactions were recorded at different time points. The Probit regression analysis method was used to calculate the ED50 of ciprofol for four groups.
RESULTS
The ED50 of ciprofol combined with 0.1 μg·kg−1 sufentanil for gastroscope in the non-elderly men, non-elderly women, elderly men, and elderly women were 0.409, 0.373, 0.356, 0.327 mg·kg−1, respectively. The ED50 of ciprofol in the N1 group was significantly higher compared with the N2 group and N3 group(P<0.05). The ED50 of ciprofol in the N4 group was significantly lower compared with the N2 group and N3 group(P<0.05).
CONCLUSION
The ED50 of ciprofol is significantly different among gastroscope patients of different genders and ages, which is lower in female patients than in male patients, and is lower in older patients than in non-elderly patients.
5.CAR-T Therapy for T-lineage Leukemia:Progress,Dilemmas,and Way Forward
Yajing HAN ; Liping ZHAO ; Kaiting TANG ; Qing NIU ; Jing PAN ; Xiaoming FENG
Cancer Research on Prevention and Treatment 2024;51(8):648-654
Tumor immunotherapy occupies a pivotal position in the field of hematological malignancies.Chimeric antigen receptor(CAR)T-cell therapy has established a new therapeutic pattern for hematological immunotherapy and achieved satisfactory clinical results in the treatment of B-lineage hematological malignancies.However,CAR T-cell therapy has some limitations in the treatment of T-cell acute lymphoblastic leukemia because of the presence of CAR T-cell fratricide,tumor cell contamination,T-cell aplasia,and other clinically relevant problems.Therefore,the current major challenge is overcoming the existing bottlenecks to optimize CAR-T therapy and improve its efficacy against T-ALL while improving the prognosis of patients.
6.Research progress on restarting anticoagulant therapy for anticoagulation related cerebral hemorrhage
Xufeng PAN ; Rong WU ; Haifei CHAI ; Jie WANG ; Xiaoming HU
Journal of Chinese Physician 2024;26(8):1273-1276
With the aging population, the burden of diseases such as atrial fibrillation and venous thrombosis is gradually increasing. Anticoagulant therapy has a positive significance in preventing ischemic stroke, pulmonary embolism, and other related conditions in these patients. However, anticoagulant therapy can have the opposite effect on diseases caused by intracranial hemorrhage, such as falls in the elderly, cerebrovascular accidents, and car accidents. It is still difficult to determine whether and when to restart anticoagulation after cerebral hemorrhage. Although most studies have shown that restarting anticoagulant therapy can reduce stroke risk without significantly increasing bleeding risk, they are mostly based on observational studies, so more high-quality research is needed to guide clinical decision-making. This article reviews the research progress on restart anticoagulation, aiming to provide some assistance for clinical applications.
7.A case report of Launois-Bensaude syndrome
Xiaoming WU ; Juan WANG ; Congqing PAN
Chinese Journal of Endocrinology and Metabolism 2024;40(10):884-886
Benign symmetric lipomatosis (BSL) is a rare syndrome. This article presents a 65-year-old female patient with symmetric fat accumulation in both upper arms, along with hypertension and diabetes. Whole-body dual-energy X-ray absorptiometry revealed significantly higher fat content in the upper arms compared to other areas. Localized fat imaging indicated that the proliferative fatty tissue was non-encapsulated. Considering the patient′s lack of history of alcohol consumption, type 2 BSL, also known as Launois-Bensaude syndrome, was diagnosed. This article aims to help clinicians differentiate between obesity and various types of BSL, providing the most appropriate treatment for patients.
8.Advances in the treatment of venous thromboembolism in the neurosurgery department
Xufeng PAN ; Rong WU ; Haifei CHAI ; Jie WANG ; Xiaoming HU
Chinese Journal of Primary Medicine and Pharmacy 2024;31(9):1433-1436
Venous thromboembolism is a common comorbidity in neurosurgery department that can lead to life-threatening pulmonary embolism, endangering patient health. The unique characteristics of neurosurgical conditions often present a high risk of bleeding, which complicates the treatment of venous thrombosis. Although numerous observational studies and meta-analyses support the feasibility of initiating early anticoagulation prevention or treatment after hemorrhage stabilization in intracranial hemorrhagic conditions such as traumatic brain injury and cerebral hemorrhage, there is a lack of high-quality clinical research. As a result, neurosurgeons tend to adopt a conservative approach regarding pharmacological prophylaxis and anticoagulant treatment for venous thromboembolism. Key aspects such as the timing of prevention, monitoring, and discontinuation of treatment still require high-quality research to establish definitive guidelines.
9.Tislelizumab monotherapy for the treatment of recurrent/metastatic head and neck squamous cell carcinoma.
Pan SONG ; Faya LIANG ; Yuchu YE ; Yongsheng HUANG ; Taowei WU ; Xiaoming HUANG ; Ping HAN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(10):778-785
Objective:The aim of this retrospective study is to evaluate the safety and efficacy of tislelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Methods:Six patients with recurrent/metastatic head and neck squamous cell carcinoma who received tislelizumab monotherapy in our hospital from 2018 to 2020 were retrospectively analyzed. The information of sex, age, TNM stage, efficacy, and adverse reactions were collected. All patients were recruited from the RATIONALE 102 study. The primary end point was the objective response rate, and other end points included progression-free survival and overall survival. We performed tumor immune-related gene sequencing and transcriptome sequencing analysis on the tumor tissues of the patient, and used bioinformatics methods to enrich immune cells and analyze signaling pathways. All analyses were performed using R 4.1. 0 software, SPSS Statistics 24.0 software and GraphPad Prism 8. Results:As of May 31, 2020, the median follow-up time was 26.35 months. The objective response rate with tislelizumab was 50.0%, the median progression-free survival was 6.44 months, and the estimated median survival was 20.07 months. The incidence of grade 3 or higher adverse reactions was 66.7%, including hyponatremia, hypokalemia, hypercalcemia, etc. The expression of macrophage, Treg and neutrophil-related genes are higher in immune-sensitive patients, and the signaling pathways of the intestinal immune network for IgA production, graft versus host disease and autoimmune thyroid disease are significantly activated. Conclusion:Tislelizumab was found to be controllable and tolerable in patients with recurrent/metastatic head and neck squamous cell carcinoma. The response to tislelizumab is related to immune cell infiltration and activation of immune-related signaling pathways.
Humans
;
Squamous Cell Carcinoma of Head and Neck/etiology*
;
Retrospective Studies
;
Carcinoma, Squamous Cell/pathology*
;
Neoplasm Recurrence, Local/pathology*
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Head and Neck Neoplasms
;
Antineoplastic Combined Chemotherapy Protocols
10.Case-problem-based learning of pathophysiology based on inquiry-based learning and process management
Xinfu LIN ; Mingzhou YUAN ; Haiyin ZHENG ; Xiaoming PAN ; Jianfeng WANG ; Sujuan CHEN ; Yao LIN ; Lufen HUANG ; Jun CHEN
Chinese Journal of Medical Education Research 2023;22(7):1004-1008
Based on the teaching concept of constructivism, this study aims to promote independent inquiry-based learning and clinical thinking among students and establish the guiding ideology of "full participation, process control, in-depth discussion, and expansion of thinking". A blending learning model was adopted with offline inquiry-based group learning and in-class defense and comment, as well as online teacher-student interaction and supervision to promote learning. Case-problem-based learning (CPBL) of pathophysiology was carried out among the medical students in the class of 2017, and process management was strengthened to effectively manage the two key links of data retrieval and group discussion. The analysis of 176 teaching evaluations collected at the end of the semester show that in terms of the overall evaluation of CPBL teaching, 162 students (92.05%) had high evaluation on teaching objectives, organization, cases, and personal gains and held a very or relatively favorable attitude. There were more negative feedbacks on "appropriate time allocation"; 21 students (11.93%) held a relatively or very disapproving attitude, and 149 students (84.66%) "felt very tired". In terms of teaching effect evaluation, 150 students (85.23%) strongly or relatively agreed that CPBL teaching may help to understand professional knowledge, stimulate learning enthusiasm and initiative, improve problem solving ability, emphasize clinical practice to cultivate clinical thinking, supervise and promote learning, and enhance team cooperation and teacher-student communication. In terms of the evaluation of teachers, 167 students (94.89%) thought that teachers were rigorous, responsible, and enthusiastic in teaching, attached importance to process management, and did well in effective guidance and thinking inspiration (strongly or relatively agree). The above results suggest that the CPBL teaching reform of pathophysiology based on process management can effectively promote in-depth inquiry-based independent learning and the cultivation of clinical thinking and improve teaching effectiveness, but further improvement is needed for teaching arrangement and time allocation.


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