1.Evaluation of PEscore performance in predicting platelet transfusion efficacy in hematological patients
Jun LI ; Lan WANG ; Yihua XIE ; Ziqi CHEN ; Gang ZHAO
Chinese Journal of Blood Transfusion 2025;38(6):797-802
Objective: To evaluate the performance of platelet efficacy score (PEscore) in predicting platelet transfusion efficacy in hematological patients. Methods: A total of 485 patients with hematological diseases, including 298 males (62.09±15.45 years) and 187 females (59.17±16.52 years) who received platelet transfusion from January 1, 2021 to December 31, 2024 were enrolled in this study. Clinical data of the patients such as diagnosis, gender, age, number of platelet transfusion, and platelet antibody data were analyzed to investigate the incidence and influencing factors of platelet transfusion refractoriness in hematological patients at our hospital. ROC curve was used to evaluate the performance of PEscore model in predicting platelet transfusion efficacy. The predictive performance of PEscore model was validated by calculating its sensitivity, specificity, and accuracy in 115 clinical cases. Results: The incidence of platelet transfusion refractoriness in 485 cases was 29.90% (145/485). Significant differences (P<0.05) were observed between the effective and ineffective platelet transfusion groups regarding the following factors: diagnosis: lymphoma [55.32% (26/47) vs 44.68% (21/47)], the number of previous platelet transfusions [≥25: 60.78% (31/51) vs 39.22% (20/51)], platelet antibody screening result [positive: 33.76% (53/157) vs 66.24% (104/157)], and platelet transfusion volume (×10
/L) [>6: 62.71% (74/118) vs 37.29% (44/118)]. The area under the ROC curve of PEscore was 0.876. The cut-off points and corresponding sensitivity and specificity were 19.90.59% and 69.44%, respectively. The results of clinical application showed that the sensitivity, specificity and accuracy of the PEscore model for predicting platelet transfusion were 87.50%, 93.41% and 92.17%, respectively. Conclusion: The incidence of platelet transfusion refractoriness in hematological patients is relatively high. PEscore prediction model has a good performance in predicting the effect of platelet transfusion, which can provide a reliable basis for predicting the effect of platelet transfusion in hematological patients before blood transfusion.
2.Effect of recombinant glycoprotein hormone beta5/alpha2 on promoting lipolysis via regulation of cAMP/PKA/CREB pathway in 3T3-L1 adipocytes and its mechanism
Ai-Jun QIAN ; Geng-Miao XIAO ; Zhuang LI ; Xue TIAN ; Xiao-Hong LIU ; Yu-Ping SONG ; Zheng-Gang ZHAO ; Zi-Jian ZHAO ; Fang-Hong LI
Chinese Pharmacological Bulletin 2024;40(7):1272-1278
Aim To investigate the effect of recombi-nant glycoprotein hormone β5/α2(rCGH)on lipolysis in 3T3-L1 adipocytes,and explore the underlying mechanism.Methods 3T3-L1 preadipocytes were cultured and induced to differentiate into mature adipo-cytes,then treated with different concentrations of rCGH for 24 h in vitro.Cell viability of 3T3-L1 adipo-cytes was evaluated by CCK-8 assay,the levels of in-tracellular triglyceride(TG)and glycerol in the culture supernatant were measured by enzymatic method,and the changes of lipid droplets were observed by oil red O staining.The expression levels of HSL and ATGL lipo-lytic proteins in adipocytes were detected by Western blot.To carry out the intervention experiment with dif-ferent concentrations of rCGH with or without the PKA inhibitor,H89,on the mature 3T3-L1 adipocytes,the cultured cells were divided into the control group,H89 pre treatment group,1 μmol·L-1 rCGH group,and(1 μmol·L-1 rCGH+H89)combined intervention group.The contents of intracellular TG and free glycer-ol were measured by enzymatic method,and the ex-pression of CREB and lipolysis-related proteins was de-tected using Western blot.Results Different concen-trations of rCGH(0.25,0.5,1,and 2 μmol·L-1)had no significant effect on the cell viability of adipo-cytes(P>0.05).Compared with the control group,the treatment with rCGH significantly decreased the size of lipid droplets and intracellular TG content,while significantly elevated glycerol concentration in cell supernatant.rCGH treatment also stimulated the protein expression of p-HSL,ATGL,and p-PKA.In addition,the addition of a PKA inhibitor,H89,atten-uated the effects of rCGH on free glycerol level,intra-cellular TG content,and the expression of p-HSL,p-PLIN1,and p-CREB.Conclusions rCGH enhances the lipolysis of 3T3-L1 adipocytes by up-regulating the activities of HSL,ATGL and PKA,promoting glycerol release,inhibiting TG synthesis and lipid accumula-tion,and its mechanism of action is related to the acti-vation of cAMP/PKA/CREB signaling pathway.
3.Mechanism of quercetin inhibiting neutrophil extracellular trap formation based on LOX-1/NOX2 signaling pathway
Si LIU ; Gang LUO ; Jun-Chang WANG ; Lin-Yao YING ; Yan WANG ; Lin XIAO
Chinese Pharmacological Bulletin 2024;40(11):2047-2054
Aim To investigate the molecular mecha-nism of lysophosphatidylcholine(LPC)-induced neu-trophil extracellular trap formation and the intervening role of quercetin.Methods An in vitro model of NETs formation was constructed using LPC-induced primary rat neutrophils,and quercetin intervention was performed.The formation of NETs and the expression level of related pathway proteins were detected.Results 100 mg·L-1 LPC induced the formation of NETs in vitro,and NETs formation was associated with the up-regulation of LOX-1/NOX2 pathway protein expres-sion.Quercetin intervention effectively decreased LOX-1 and NOX2 protein expression,then inhibiting NETs formation.Conclusions Quercetin inhibits the forma-tion of NETs by regulating the LOX-1/NOX2 signaling pathway and exerting a protective effect against related inflammatory diseases.
4.Antimicrobial resistance and resistance gene carriage by Salmonella bacteria in environmental sewage in Guangzhou
Bi-Hui SU ; Guang-Hong DU ; Xiao-Ying WU ; Gang HE ; Jun YUAN ; Chao-Jun XIE
Chinese Journal of Zoonoses 2024;40(5):442-447
This study explored the antibiotic resistance and resistance gene carriage of 140 Salmonella strains isolated from environmental sewage in Guangzhou city between March 1,2022,and November 30,2022.The micro broth dilution method was used to select 17 antibiotics for susceptibility testing.According to whole genome sequencing results,the CARD resistance database was used to obtain corresponding resistance genes.High antimicrobial resistance rates above 80%were observed a-gainst ampicillin,tetracycline,streptomycin,chloramphenicol,and cotrimoxazole.The intermediation rate of polymyxin E and ciprofloxacin exceeded 60%.The multiple drug resistance status was severe,and the rate of multiple drug resistance was as high as 92.86%.The strains carried multiple types of resistance genes,particularly for aminoglycosides,with a carriage rate as high as 92.68%.The resistance of Salmonella in environmental wastewater in Guangzhou to one or more drugs was severe,and the overall multi-drug resistance rate gradually increased over time.The resistance spectrum was diverse,and the resistance mechanism,mediated by mobile genetic elements such as re-sistance genes,was found to be the main cause of resistance to one or more drugs.
5.Cancer Stem Cell-derived Exosomes Promote Drug Resistance and Invasion in Colorectal Cancer Cells
Xin-Yu GAO ; Zi-Jun MAO ; Sheng-Zhe HUANG ; Gang HUANG ; Hao YANG
Chinese Journal of Biochemistry and Molecular Biology 2024;40(8):1119-1131
Cancer stem cells,a small population of cells with self-renewal and multidirectional differenti-ation potential in tumor tissues,can initiate primary tumors and mediate treatment resistance,tumor re-currence,and metastasis,but the mechanism of how they affect colorectal cancer at the cellular level is unknown.Therefore,in this study,we explored the effect of cancer stem cells and their exosomes on the malignant phenotype of colorectal cancer.First,CD 166+CD44+cancer stem cells(CSCs)were isolated from colorectal cancer tumor tissues,and then cancer stem cell-derived exosomes(CSCexo)and colorec-tal cancer SW480 cell-derived exosomes(Sexo)were extracted by ultracentrifugation.Then,exosomes were subjected to NTA particle size analysis,electron microscopic observation and identification by West-ern blotting.Subsequently,the successfully isolated CSC and CSCexo were co-cultured with colorectal cancer SW480 cells.The apoptosis rate of SW480 cells after co-culture was found to decrease from 20%to about 13%by CCK-8,apoptosis assay(P<0.01)and the invasive ability was significantly increased(P<0.001)after co-culture with CSC or CSCexo.In addition,in vivo animal experiments revealed that the tumor growth rate of the S-exo treatment group was slower than that of the CSCexo treatment group,and that CSCexo inhibited the drug efficacy of 5-FU against colorectal cancer tumors.PET/CT imaging,immunohistochemical analysis,and Western blotting experiments showed that CSCexo enhanced the up-take of the glucose analog 18F-FDG and the expression of the glycolytic enzymes HK2,PFKFB2,PKM2,and LDHA in colorectal cancer.In addition,interfering with the expression of glycolytic enzymes with siRNAs blocked the drug resistance induced by CSCexo.In summary,this study demonstrates that color-ectal cancer stem cells deliver exosomes that affect tumor glucose metabolism pathways and promote chemotherapy resistance and invasive ability,revealing the mechanism of formation and dynamic changes in the malignant tumor microenvironment.
6.Association of Triglyceride Glucose-Derived Indices with Recurrent Events Following Atherosclerotic Cardiovascular Disease
Sha LI ; Hui-Hui LIU ; Yan ZHANG ; Meng ZHANG ; Hui-Wen ZHANG ; Cheng-Gang ZHU ; Yuan-Lin GUO ; Na-Qiong WU ; Rui-Xia XU ; Qian DONG ; Ke-Fei DOU ; Jie QIAN ; Jian-Jun LI
Journal of Obesity & Metabolic Syndrome 2024;33(2):133-142
Background:
Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indices of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction.
Methods:
This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed.
Results:
Distribution of the TyAG and TyAG-BMI indices shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance.
Conclusion
This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters.
7.Robotic visualization system-assisted microsurgical reconstruction of the reproductive tract in male rats
Zheng LI ; Jian-Jun DONG ; Ming LIU ; Xun-Zhu WU ; Ren-Feng JIA ; San-Wei GUO ; Kai MENG ; Chen-Cheng YAO ; Er-Lei ZHI ; Gang LIU ; Da-Xian TAN ; Zheng LI ; Peng LI
National Journal of Andrology 2024;30(8):675-680
Objective:To evaluate the safety and efficiency of robotic visualization system(RVS)-assisted microsurgical re-construction of the reproductive tract in male rats and the satisfaction of the surgeons.Methods:We randomly divided 8 adult male SD rats into an experimental and a control group,the former treated by RVS-assisted microsurgical vasoepididymostomy(VE)or vaso-vasostomy(VV),and the latter by VE or VV under the standard operating microscope(SOM).We compared the operation time,me-chanical patency and anastomosis leakage immediately after surgery,and the surgeons'satisfaction between the two groups.Results:No statistically significant difference was observed the operation time between the experimental and the control groups,and no anasto-mosis leakage occurred after VV in either group.The rate of mechanical patency immediately after surgery was 100%in both groups,and that of anastomosis leakage after VE was 16.7%in the experimental group and 14.3%in the control.Compared with the control group,the experimental group achieved dramatically higher scores on visual comfort(3.00±0.76 vs 4.00±0.53,P<0.05),neck/back comfort(2.75±1.16 vs 4.38±1.06,P<0.01)and man-machine interaction(3.88±1.55 va 4.88±0.35,P<0.05).There were no statistically significant differences in the scores on image definition and operating room suitability between the two groups.Conclusion:RVS can be used in microsurgical reconstruction of the reproductive tract in male rats and,with its advantages over SOM in ergonomic design and image definition,has a potential application value in male reproductive system micosurgery.
8.Clinical and electrophysiological analysis of 13 patients of temporal lobe epilepsy originating from the temporal pole
Jun ZHUANG ; Lingxia FEI ; Hua LI ; Shaochun LI ; Gang HUA ; Junxi CHEN ; Qiang GUO ; Meiling CAI
Chinese Journal of Neurology 2024;57(12):1317-1325
Objective:To summary the clinical and electrophysiological characteristics of temporal lobe epilepsy (TLE) originating from the temporal pole (TP), and to conduct brain network analysis based on stereo-electroencephalogram (SEEG) and head positron emission tomography- computed tomography (PET-CT).Methods:A retrospective analysis was conducted on patients with TLE who underwent SEEG implantation from January 1, 2019 to September 1, 2023 in Guangdong Sanjiu Brain Hospital. Based on anatomical-electrical-clinical analysis and SEEG findings, patients with seizures originating from the TP were selected. The clinical data, head magnetic resonance imaging (MRI), PET-CT, scalp electroencephalogram were reviewed, and the seizure-induced network was analyzed based on SEEG and head PET-CT.Results:A total of 108 cases of TLE were analyzed, of whom 13 cases had an epileptogenic zone located at the TP, accounting for 12% (13/108) of all TLE patients. Among them, 8 were males and 5 were females, and age of onset was (11.6±7.8) years. All of them were drug-resistant epilepsy patients, of whom 6 cases had normal cognitive function, 4 had mild cognitive abnormalities, and 3 had severe cognitive decline. A total of 59 seizures were recorded, and the occurrence rate of generalized tonic-clonic seizures (GTCS) was 42% (25/59). Seizure symptoms were classified into 3 types: the first type was hypermotor, seen in 9 patients; the second type was complex motor, seen in 2 patients; and the third type was automotor, seen in 2 patients. Head MRI showed that 9 cases had a blurring of the TP on one side, with or without hippocampal sclerosis; 2 cases had a mass at the TP without hippocampal sclerosis; 2 cases were negative on head MRI. Head PET-CT showed that 13 cases had TP hypometabolism on the lesion side, of whom 11 cases had hypometabolism involving the medial temporal lobe (mTL), posterior orbital gyrus (POG), anterior cingulate gyrus (ACG) and insular lobe at the same time, the other 2 cases combined with ipsilateral hypometabolism of the medial temporal lobe. Pathology showed that 7 cases had microcortical dysplasia of the TP; 3 had focal cortical dysplasia Ⅰ or focal cortical dysplasia Ⅱ; 2 had benign tumors. Scalp electroencephalogram showed that interictal phase was divided into 3 discharge patterns: bilateral temporal regions with prominent lesion side; bilateral anterior regions with prominent lesion side; lesion-side hemisphere with prominent temporal region. Ictal period showed 4 initial patterns: lesion-side hemispheric rhythmic spikes-slow waves or polyspikes-slow waves; lesion-side anterior region rhythmic slow waves; lesion-side anterior region low voltage fast (LVF) activities, and diffuse LVF with prominent lesion-side hemisphere. SEEG showed that 13 patients received electrode implantation with (9±2) electrodes per patient, divided into 3 seizure patterns: type 1: TP?adjacent temporal neocortex?POG, ACG and insula?mTL; type 2: TP?para hippocampal gyrus and the base of temporal lobe?ACG ,POG and insula?mTL; type 3: TP?mTL?insular lobe?POG.Conclusions:TLE originating from the TP is relatively rare, with hypermotor or complex motor as the main manifestations, and automotor being relatively less common, which is more likely to be followed by GTCS. The epileptogenic network analysis displays a tendency to spread from the TP to the frontal and insular lobes, as well as to the mTL, with the former pattern being more common. Common etiologies are cortical dysplasia and benign tumors of the TP without hippocampal sclerosis.
9.Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy
Linghu KE-GANG ; Zhang TIAN ; Zhang GUANG-TAO ; Lv PENG ; Zhang WEN-JUN ; Zhao GUAN-DING ; Xiong SHI-HANG ; Ma QIU-SHUO ; Zhao MING-MING ; Chen MEIWAN ; Hu YUAN-JIA ; Zhang CHANG-SHENG ; Yu HUA
Journal of Pharmaceutical Analysis 2024;14(3):401-415
Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.
10.Characterization of muscle synergy during sitting and standing in older adults with hallux valgus
Yanyan LIU ; Lei QIAN ; Ruiping LIU ; Jun OUYANG ; Gang LIU
The Journal of Practical Medicine 2024;40(10):1376-1381
Objective To analyze changes in neuromuscular control during sit-to-stand(STS)in older adults with hallux valgus(HV)through muscle synergy,and thus to explore the effect of falls in older adults with HV.Methods Four groups of subjects were included in this study,13 young controls(YC);12 young HVgroup(HVY);14 healthy elderly controls(EC);and 15 elderly HV group(HVE).All subjects completed the STS maneuver in an armless chair,and EMG data were integrated using non-negative matrix factorization to compare muscle synergies in the YC,HVY,EC,and HVE groups;plantar pressures(COP),ground reaction forces(GRF),and fall scores(FES-I)were collected.Results Compared with YC group,HVY,EC,and HVE groups had lower relative activation amplitude of abductor hallucis and lateral gastrocnemius in STS preparation phase;meanwhile,EC and HVE groups needed more muscle activation to maintain stability of trunk and foot-ankle joints in STS stabi-lization phase;and HVE group needed more co-contractions of thigh muscles to maintain stability of the knee joint.The COP,FES-I of HVE group was higher than that of the other groups(P<0.05).Conclusion In STS,healthy older adults and older adults with HV required more muscle activation to maintain trunk and ankle stability;older adults with HV required more co-contraction of the thigh muscles to maintain knee stability;in addition to this,older adults with HV were more prone to falls.

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