1.Heterogeneity of Adipose Tissue From a Single-cell Transcriptomics Perspective
Yong-Lang WANG ; Si-Si CHEN ; Qi-Long LI ; Yu GONG ; Xin-Yue DUAN ; Ye-Hui DUAN ; Qiu-Ping GUO ; Feng-Na LI
Progress in Biochemistry and Biophysics 2025;52(4):820-835
Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.
2.Vaccination against coronavirus disease 2019 in patients with pulmonary hypertension: A national prospective cohort study
Xiaohan WU ; Jingyi LI ; Jieling MA ; Qianqian LIU ; Lan WANG ; Yongjian ZHU ; Yue CUI ; Anyi WANG ; Cenjin WEN ; Luhong QIU ; Yinjian YANG ; Dan LU ; Xiqi XU ; Xijie ZHU ; Chunyan CHENG ; Duolao WANG ; Zhicheng JING
Chinese Medical Journal 2024;137(6):669-675
Background::Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH.Methods::In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients.Results::In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%). Conclusions::COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.
3.Research progress of celastrol in the treatment of stroke
Ronghui ZHU ; Li CHEN ; Yang CHEN ; Yue HUANG ; Yunhua ZHENG ; Tao QIU
China Pharmacist 2024;27(4):711-721
Celastrol is extracted from the traditional Chinese medicine Tripterygium wilfordii Hook.f..It is a kind of traditional Chinese medicine monomer with extensive pharmacological activity and has anti-tumor,anti-inflammation,anti-oxidation and neuroprotective effects.Studies have found that celastrol is not only closely related to obesity,tumor and cardiovascular diseases,but also plays a neuroprotective role in the cerebrovascular system by regulating various signaling pathways.At present,effective drugs for stroke are still limited,but with the deepening of the research on celastrol,its therapeutic potential in stroke has received more and more attention,especially in ischemic and hemorrhagic stroke,which has shown good therapeutic effects.Therefore,this is the first time to systematically summarize the therapeutic effects of celastrol on stroke and the underlying mechanisms involved,in order to provide further directions and references for the neuroprotective effects of celastrol.
4.Significance of 18F-PI-2620 PET imaging for diagnosing tau protein deposition in patients with different cognitive disorders alongside cognitive correlation analysis
Gan HUANG ; Yan ZHANG ; Cheng WANG ; Mei XIN ; Hongda SHAO ; Yue WANG ; Liangrong WAN ; Ju QIU ; Qun XU ; Jianjun LIU ; Xia LI ; Chenpeng ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(5):273-278
Objective:To evaluate the values of 18F-PI-2620 PET/CT brain imaging with SUV ratio (SUVR) in the assessment of tau protein deposition in the brain of patients with different cognitive disorders and its correlation with cognition. Methods:This was a cross-sectional study. From December 2019 to November 2022, a total of 67 subjects including 54 patients with Alzheimer′s disease (AD; 21 males, 33 females, age (68.6±7.8) years), 7 patients with mild cognitive impairment (MCI; 1 male, 6 females, age (63.1±11.2) years) and 6 healthy controls (HC; 4 males, 2 females, age (69.0±5.8) years) were enrolled retrospectively in Renji Hospital. All participants were examined by 18F-PI-2620 PET/CT. SUVRs of brain regions were obtained, including frontal lobe, temporal lobe, occipital lobe, parietal lobe, insular lobe, whole brain, as well as 10 independent brain ROIs (amygdala, orbitofrontal cortex, cingulate gyrus, superior occipital gyrus, superior parietal gyrus, inferior angular gyrus, precuneus, inferior temporal gyrus, entorhinal cortex and parahippocampal gyrus), with inferior cerebellum cortex as the reference region. All participants were estimated by cognitive scales(mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA)). One-way analysis of variance and the least significant difference t test were used to compare the differences of SUVR in each brain region among HC, MCI and AD groups. ROC curve analysis was used to determine the optimal cut-off values of SUVR in each brain region for the differential diagnosis of AD-MCI and AD-HC. Pearson correlation analysis was employed to examine the correlations of SUVR with cognitive scale scores. Results:The SUVR of whole brain was 1.40±0.31 in AD group, 1.08±0.19 in MCI group, and 1.01±0.12 in HC group. SUVR analysis in the whole brain and each brain region could distinguish AD from HC, AD from MCI ( F values: 1.76-10.09, t values: 2.98-7.47, all P<0.05), but could not distinguish HC from MCI ( t values: 0.17-1.53, all P>0.05). ROC curve analysis showed that the best cut-off value of SUVR was 1.18 for whole brain (AUC=0.89), 1.13 for amygdala (AUC=0.94) and 1.26 for parahippocampal gyrus (AUC=0.94) for differential diagnosis of AD and HC, which was 1.06 for whole brain (AUC=0.82), 1.18 for amygdala (AUC=0.88) and 1.28 (AUC=0.88) for infratemporal gyrus to differential diagnosis of AD and MCI. SUVRs of the whole brain, frontal, occipital, parietal, temporal and insula were significantly negatively correlated with MMSE and MoCA cognitive scale scores ( r values: from -0.64 to -0.40, all P<0.05). Conclusions:SUVR quantitative analysis in 18F-PI-2620 PET imaging can assist the differential diagnosis of AD and HC, AD and MCI. The SUVRs of whole brain and five lobes show negative correlations with MMSE and MoCA scores.
5.Diagnostic efficiency of 18F-FDG PET for Alzheimer′s disease in patients with memory impairment
Yan ZHANG ; Chenpeng ZHANG ; Gan HUANG ; Cheng WANG ; Mei XIN ; Hongda SHAO ; Yue WANG ; Liangrong WAN ; Ju QIU ; Qun XU ; Xia LI ; Jianjun LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(12):712-717
Objective:To assess the diagnostic efficiency of 18F-FDG PET for Alzheimer′s disease (AD) in patients with memory impairment. Methods:A retrospective analysis was conducted on 96 patients (40 males, 56 females, age: 69.0(62.8, 74.0) years) initially diagnosed with memory impairment in Renji Hospital, School of Medicine, Shanghai Jiao Tong University between August 2019 and September 2023. The amyloid-tau-neurodegeneration (ATN) criteria, based on 18F-AV45+ 18F-PI-2620 PET/CT+ MRI imaging results, were used as the diagnostic standard for AD. Visual analysis (temporoparietal or posterior cingulate cortex (PCC) hypometabolism) and semi-quantitative analysis methods (PET-SCORE and NeuroQ software analysis (SUV ratio, SUVR)) were applied to evaluate the diagnostic efficiency of 18F-FDG PET imaging for AD. Diagnostic efficiencies of visual assessment and semi-quantitative parameters were compared by χ2 test. Additionally, Pearson correlation analysis was performed to examine the relationship between results of PET-SCORE and cognitive scales. Results:Of the 96 patients initially diagnosed with memory impairment, 61 were clinically diagnosed with AD, while 35 were non-AD patients. Visual assessment of temporoparietal hypometabolism showed the highest sensitivity (91.80%, 56/61), which was significantly different from the sensitivities of PET-SCORE (40.98%(25/61); χ2=29.03, P<0.001) and visual assessment of PCC hypometabolism (77.05%(47/61); χ2=5.82, P=0.016). While semi-quantitative assessment using PET-SCORE demonstrated the highest specificity (100%, 35/35), which was significantly different from the specificities of visual assessment methods (temporoparietal hypometabolism: 17.14%(6/35), χ2=27.03, P<0.001; PCC hypometabolism: 54.29%(19/35), χ2=14.06, P<0.001). PET-SCORE exhibited statistically significant correlations with Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL) scores ( r values: -0.38, -0.36, 0.31, all P<0.01). Conclusions:Among patients initially diagnosed with memory impairment, visual assessment in 18F-FDG PET imaging analysis demonstrates higher sensitivity, while semi-quantitative analysis using PET-SCORE exhibits higher specificity. PET-SCORE shows statistically significant correlation with the severity of cognitive decline.
6.The efficacy and safety of protein A immunoadsorption combined with rituximab treatment for highly sensitized patients undergoing haplo-hematopoietic stem cell transplantation
Ling LI ; Wenjuan ZHU ; Qian ZHU ; Shiyuan ZHOU ; Chao MA ; Jun WANG ; Xiaohui HU ; Yue HAN ; Ying WANG ; Xiaowen TANG ; Xiao MA ; Suning CHEN ; Huiying QIU ; Luyao CHEN ; Jun HE ; Depei WU ; Xiaojin WU
Chinese Journal of Hematology 2024;45(5):468-474
Objective:To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) .Methods:The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured.Results:After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) ( P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) ( P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0–15 989) ( P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 ( P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions:The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.
7.Analysis of risk factors for cardiovascular diseases in patients with obstructive sleep apnea hypopnea syndrome
Jing SUN ; Li CHEN ; De HUAI ; Yue QIU ; Qiao-Ling GUO ; Rong-Fang LI
Chinese Journal of cardiovascular Rehabilitation Medicine 2024;33(5):546-549
Objective:To investigate the risk factors of cardiovascular diseases(CVD)in patients with obstructive sleep apnea hypopnea syndrome(OSAHS).Methods:A total of 281 OSAHS patients admitted in Second People's Hospital of Huai'an City between May 2020 and March 2022 were selected and divided into CVD group(n=63)and no CVD group(n=218)according to presence of CVD.The OSAHS general data questionnaire designed by the re-search group was used to investigate the patients and univariate analysis was carried out,and the clinically significant single factors were included in the multivariate Logistic regression analysis.Influencing factors for CVD in OSAHS patients were analyzed.Results:Compared with no CVD group,patients in CVD group had significant higher age,body mass index(BMI),fasting plasma glucose(FPG)level,proportions of CVD family history,dyslipidemia and severe OSAHS(P<0.05 or<0.01).Multivariate Logistic regression analysis indicated that age,BMI,dyslipi-demia,FPG and severe OSAHS were independent risk factors for CVD in OSAHS patients(OR=2.213~2.482,P<0.05 or<0.01).Conclusion:Age,BMI,dyslipidemia,FPG and severe OSAHS are independent risk factors of CVD in OSAHS patients.Individualized prevention and control strategies can be formulated according to above fac-tors in clinic,which is of great significance for prevention of CVD occurrence.
8.Predictive value of systemic immune inflammation index(SII)on long-term survival of patients with stage Ⅲ squamous lung cancer treated with radical radiotherapy
Jingchen HUO ; Yue WANG ; Hua LI ; Rong QIU ; Jingwei SU ; Zhuofan WANG ; Jie YANG
Tianjin Medical Journal 2024;52(6):634-638
Objective To investigate the predictive value of systemic immune inflammation index(SII)scores in long-term survival of patients with stage Ⅲ squamous lung cancer treated with radical radiotherapy.Methods Clinical data of stage Ⅲ squamous lung cancer patients who underwent radical radiotherapy at the Radiotherapy Department of the Fourth Hospital of Hebei Medical University from January 2010 to December 2018 were retrospectively analyzed.The peripheral hematological indexes one week before radiotherapy were collected and recorded.X-Tile software was applied to determine the best cut-off values for continuous variables.Kaplan-Meier method was used to analyze overall survival(OS)and progression-free survival(PFS).Results A total of 453 patients were included in this study.There were 336 patients in the low SII group(<1 277.3),and other 117 patients were in the high SII group(≥1 277.3).The median OS and median PFS in the high SII group were shorter than those in the low SII group(OS:20.8 months vs.31.0 months,Log-rank χ2=18.015,P<0.01;PFS:13.0 months vs.21.0 months,Log-rank χ2=15.062,P<0.01).Multivariate Cox regression analysis showed that high SII was associated with OS(HR=1.628,95%CI:1.294-2.047,P<0.001)and PFS(HR=1.559,95%CI:1.240-1.961,P<0.001).Other influencing factors included late TNM stage,poor radiotherapy efficacy and decreased HALP score.Conclusion SII can be used to evaluate the long-term survival of patients with stage Ⅲ lung squamous cell carcinoma receiving radical radiotherapy,and the increase of SII indicates a poor prognosis.
9.A Systematic Review of Case Reports/Case Series on Rituximab Rapid Desensitization
Mo CHEN ; Xue MA ; Chao LI ; Yue QIU ; Ya CHEN
Herald of Medicine 2024;43(8):1259-1269
Objective To systematically evaluate the efficacy and safety of rituximab rapid desensitization therapy.Methods PubMed,Embase,Cochrane,Web of Science,Scopus,CNKI,Wanfang,and VIP databases were searched,and the search time frame was from the establishment of the database to February 2023.Two evaluators independently screened the literature,extracted data,and evaluated the quality of the included literature,and the resulting data were analyzed descriptively or statistically.The systematic review protocol was registered on PROSPERO(CRD:42022306557).Results Twenty-five studies(11 case reports and 14 case series)were included,with 138 patients desensitized,of whom 129 were successfully desensitized(i.e.,completed at least one target dose administration).The pretreatment regimen prior to desensitization was a combination of 2 or more of several classes of drugs,including H1 and H2 receptor antagonists,glucocorticoids,sedatives,NSAIDs,and acetaminophen,and 88%of the pretreatment regimens included H1 receptor antagonists or glucocorticoids.Sixteen studies(64.0%)reported on skin testing prior to desensitization,with positive rates of 12.50%for skin prick tests(n=16)and 49.15%for intradermal tests(n=59).Seventeen studies(68.0%)used the 3 bags-12 steps rapid desensitization protocol,the rest were for multiple desensitization methods such as 4 bags-16 steps or 2 bags-8 steps.The initial administration concentration of rituximab(i.e.,the concentration of the first desensitizing solution)was 1/10 X-1/10,000 X in most of the included studies,the first step infusion rate was 1.5-5 mL·min-1,and the total duration of single desensitization was approximately 4-10.5 h.Twenty-three studies(92%)reported the occurrence of anaphylactic reactions during patient desensitization,of which five studies had no anaphylactic reactions at the time of desensitization,and the majority of patients in the other 18 studies were able to continue to complete desensitization after being given symptomatic treatment or a modified desensitization regimen.Conclusions Current evidence suggests that rituximab rapid desensitization therapy has certain effectiveness and safety.However,there is still a lack of high-quality evidence or execution standards with strong operability and more large-sample,multicenter studies are needed to further explore the aspects of skin testing before desensitization,pretreatment,individualized desensitization steps,and management of allergic reactions during desensitization.
10.Vaccarin alleviates mitochondrial damage and endothelial dysfunction in type 2 diabetes by regulating miR-570-3p/BNIP3 pathway
Chenyang ZHAO ; Xuexue ZHU ; Xinyu CHEN ; Tianxiao CHEN ; Jinpeng XU ; Tai-Yue LI ; Xingyu CAO ; Yuan ZHANG ; Liying QIU
Chinese Journal of Pathophysiology 2024;40(5):872-881
AIM:To investigate the effect of vaccarin(VAC)on endothelial dysfunction in type 2 diabetes mellitus(T2DM),and to uncover the underlying mechanisms.METHODS:(1)C57BL/6 mice received intraperitoneal injection of streptozotocin and were fed with a high-fat diet(21.8 kJ/kg,60%of the energy source was fat)to construct a T2DM mouse model.Thirty mice were randomly divided into control,T2DM and T2DM+VAC groups,with 10 mice in each group.The mice in T2DM+VAC group were given 1 mg/kg VAC via oral gavage for 6 weeks,while those in control and T2DM groups were given the same volume of PBS.The mRNA and protein expression levels of BCL2-interacting pro-tein 3(BNIP3),PTEN-induced kinase 1(PINK1)and parkin in the thoracic aorta were detected by RT-qPCR and West-ern blot.(2)Human umbilical vein endothelial cells(HUVECs)were stimulated by high glucose(HG;35 mmol/L glu-cose).Mitochondrial membrane potential,autophagy and mitochondrial superoxide levels were detected using JC-1,acri-dine orange(AO)and MitoSOX staining,respectively.RESULTS:Compared with control group,the mRNA and protein levels of BNIP3,PINK1 and parkin were significantly increased in the thoracic aorta of T2DM mice(P<0.05).Compared with T2DM group,the mRNA and protein levels of BNIP3,PINK1 and parkin in the thoracic aorta were significantly re-duced in T2DM+VAC group(P<0.05).The results of JC-1,AO and MitoSOX staining showed that VAC attenuated the decrease in mitochondrial membrane potential and the increase in autophagy and mitochondrial superoxide levels in HG-in-duced HUVECs.Treatment with VAC also inhibited HG-mediated mitochondrial damage in HUVECs after BNIP3 overex-pression.The effect of miR-570-3p mimic on mitochondrial damage was similar to VAC.RT-qPCR and Western blot showed that both miR-570-3p mimic and VAC significantly reduced the mRNA and protein levels of BNIP3,PINK1 and parkin.In contrast,inhibition of miR-570-3p exhibited the opposite effects.CONCLUSION:Treatment with VAC alle-viated endothelial dysfunction in T2DM by inhibiting HG-induced mitochondrial dysfunction through miR-570-3p/BNIP3.

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