1.Clinical Characteristics and Outcomes in Children With Severe Multisystem Inflammatory Syndrome in Children in Malaysia: A Nationwide Cohort Study
Hing Cheong Kok1 ; Dinesh Nair1 , ; Ee Vien Low2 ; Mohd Nizam Mat Bah3 ; David Chun-Ern Ng4 ; Anis Siham Zainal Abidin5,6 ; Fu Lung Khiu7 ; Huong Nai Law7 ; Heng Kiat Pung6 ; Ke Juin Wong1 ; Kwee Ching See8 ; Putri Nor Baiti Mohamad Radzi8 ; Kwai Cheng Chan9 ; Lina Lim10 ; Deenish Muniandy11 ; Nik Khairulddin Nik Yusoff12 ; Lydia Toon Muhammad Nasrun Toon3 ; Emieliyuza Yusnita Alias3 ; Pheik Sian Choong13 ; Muhammad Syarhan Nor Hadid14 ; Haema Shunmugarajoo15 ; Prakash Rao Rama Rao16 ; Siew Moy Fong1
Malaysian Journal of Medicine and Health Sciences 2025;21(No. 1):18-26
Introduction: Early identification of patients at risk for severe multisystem inflammatory syndrome in children (MIS-C)
is essential for favourable clinical outcomes. This study aims to identify the clinical characteristics, factors and outcomes associated with severe MIS-C. Materials and methods: In this retrospective cohort study involving 14 major
hospitals in Malaysia, children <15 years who met the United States Centres for Disease Control and Prevention
case definition for MIS-C were included. Severe MIS-C was defined as children who required inotropic support,
ventilatory support (invasive or non-invasive ventilation), or left ventricular ejection fraction of <55%. The factors
investigated for severe MIS-C were demographic characteristics, the presence of comorbidities, clinical characteristics, and laboratory measures. Multivariable logistic regression was used to compute the adjusted odds ratio (aORs)
of factors associated with severe MIS-C. Results: Among the 155 patients, 91 (58.7%) presented with severe MIS-C.
Severe MIS-C was more likely in patients aged ≥5 years old (aOR 2.13, 95% confidence interval [CI] 1.08-4.21), with
dehydration (aOR 3.80, 95% CI 1.53-9.45), lethargy (aOR 2.02, 95% CI 0.97-4.18), tachycardia (aOR 8.33, 95% CI
3.27-21.22), albumin <30g/L (aOR 3.36, 95% CI 1.58-7.13), creatine kinase >200U/L (aOR 3.68, 95% CI 1.57-8.64),
D-dimer >3.0µg/mL (aOR 2.11, 95% CI 1.08-4.13), ferritin >500ng/mL (aOR 3.77, 95% CI 1.88-7.55), prothrombin
time >12.7 seconds (aOR 3.22, 95% CI 1.61-6.43), and urea >6mmol/L (aOR 5.09, 95% CI 2.04-12.71). Conclusion:
Identification of these associated factors of severity in MIS-C could aid in early recognition and prompt escalation of
care, leading to better outcomes.
3.Fexolone inhibits neuronal ferroptosis through the Nrf2/HO-1/GPX4 pathway to alleviates sepsis-associated brain injury.
Rao SUN ; Jinyao ZHOU ; Yang JIAO ; Kaixuan NIU ; Cheng YUAN ; Ximing DENG
Chinese Critical Care Medicine 2025;37(5):452-457
OBJECTIVE:
To observe the protective effect of Fisetin on sepsis-associated brain injury and explore its possible mechanism from the perspective of ferroptosis.
METHODS:
Sprague-Dawley (SD) rats (6-8-week-old male) were randomly divided into three groups: sham operation group (Sham group), colonic ligation and puncture (CLP) induced sepsis model group (CLP group) and Fisetin preprocessing group (CLP+Fisetin group), with 18 rats in each group (12 for observing survival rate and 6 for indicator testing). The CLP+Fisetin group was given Fisetin solution 50 mg×kg-1×d-1 by gavage continuously for 5 days before CLP, with dimethyl sulfoxide (DMSO) as the solute, while Sham group and CLP group were given the same dose of DMSO. The model was established at 2 hours after the last gavage. The general condition of each group of rats were observed, and the 10-day mortality were record. The behavioral testing (new object recognition experiment, elevated cross maze experiment) were performed after 7 days of modeling. After 24 hours of modeling, nerve reflex scoring was performed, and then the rats were euthanized and brain tissue was collected. The pathological changes of brain tissue were observed under a microscope by hematoxylin-eosin (HE) staining, the deposition of iron ion in brain tissue was observed by Prussian blue staining. The content of iron in brain tissue was determined by tissue iron kit, and the content of malondialdehyde (MDA) in brain tissue was determined by colorimetry. The expressions of tumor necrosis factor-α (TNF-α), neuron damage marker S100β, nuclear factor E2-related factor 2 (Nrf2), heme oxygenases-1 (HO-1) and glutathione peroxidase 4 (GPX4) were detected by Western blotting.
RESULTS:
On day 10 post-operation, 12, 3, and 7 animals survived in the Sham group, CLP group, and CLP+Fisetin group, respectively. Compared with the Sham group, rats in the CLP group showed significantly decreased nerve reflex score, new object discrimination index and open arm dwell time. HE staining showed arranged disorderly of neuronal cells, cytoplasm deep staining, nuclear condensation, unclear structures, neuron loss, and significant inflammation in the hippocampus in the hippocampus. Prussian blue staining showed iron ion deposition in the brain tissue. The contents of iron and MDA in brain tissue were elevated, and the expressions of TNF-α and S100β were up-regulated, while the expressions of Nrf2, HO-1, and GPX4 were down-regulated. Compared with the CLP group, the CLP+Fisetin group showed significantly increased neurological reflex score (7.33±1.15 vs. 4.67±1.53), improved new object discrimination index (0.44±0.02 vs. 0.32±0.04), and longer open arm dwell time (minutes: 78.33±9.29 vs. 41.15±9.64). Neuronal cells in the hippocampus were more organized, with less cytoplasmic staining, nuclear condensation, reduced neuronal loss, and fewer inflammatory cells. Iron ion deposition was reduced, and the contents of iron ions and MDA in brain tissue were decreased [iron ion (μg/g): 151.27±14.90 vs. 224.69±17.64, MDA (μmol/g): 470.0±44.3 vs. 709.3±65.4]. The expressions of TNF-α and S100β were significantly decreased (TNF-α/GAPDH: 0.651±0.060 vs. 0.896±0.022, S100β/GAPDH: 0.685±0.032 vs. 0.902±0.014), while the expressions of Nrf2, HO-1, and GPX4 were significantly increased (Nrf2/GAPDH: 0.708±0.108 vs. 0.316±0.112, HO-1/GAPDH: 0.694±0.022 vs. 0.538±0.024, GPX4/GAPDH: 0.620±0.170 vs. 0.317±0.039). All differences were statistically significant (all P < 0.05).
CONCLUSION
Fisetin pretreatment can inhibit ferroptosis and reduce sepsis-associated brain injury by Nrf2/HO-1/GPX4 pathway.
Animals
;
Ferroptosis/drug effects*
;
Rats, Sprague-Dawley
;
NF-E2-Related Factor 2/metabolism*
;
Sepsis/complications*
;
Male
;
Rats
;
Phospholipid Hydroperoxide Glutathione Peroxidase
;
Neurons/drug effects*
;
Signal Transduction
;
Brain Injuries/metabolism*
;
Flavonols
;
Flavonoids/pharmacology*
;
Heme Oxygenase-1/metabolism*
;
Heme Oxygenase (Decyclizing)
4.Ten-gene panel detection for cytological specimens of lung adenocarcinoma
Xuelian ZHANG ; Kai CHENG ; Qiu RAO
Chinese Journal of Clinical and Experimental Pathology 2024;40(10):1033-1040
Purpose To explore the application and clini-cal significance of molecular detection in cell block specimens of lung adenocarcinoma.Methods A total of 200 cell block spec-imens of lung adenocarcinoma were collected.Among them 49 specimens underwent multi-gene panel detection(including EG-FR,EML4-ALK,ROS1,KRAS,HER2,BRAF,RET,MET,NRAS,and PIK3CA),while 151 specimens underwent EGFR single-gene detection.In addition,97 specimens were tested for EML4-ALK fusion gene alterations using the Ventana method,and the results were compared with that by PCR detection.The mutation characteristics were summarized,and the cytological features of the mutations and fusions were observed.Results The positive rate of driver gene mutations in 49 cases of multi-gene panel detection was 65.31%,which indicated no statisti-cally significant difference from that of 99 lung adenocarcinoma tissue specimens(P>0.05).The positive rates of ALK,ROS1,and RET fusion mutations were 4.08%,4.08%,and 2.04%,respectively,and the positive rates of EGFR,KRAS,HER2,MET,and BRAF mutations were 38.78%,6.12%,4.08%,4.08%,and 2.04%,respectively.The mutation rate of EGFR in 151 cases of single-gene detection was 54.97%,with a mutation rate of 42.86%in males and 67.57%in fe-males,showing a statistically significant difference between gen-ders(P<0.05).Exon 19 deletion mutation(19-Del)and exon 21 point mutation(21-L858R)in the EGFR gene took the high-est proportions,accounting for 54.22%and 37.35%,respec-tively,significantly higher than other mutation types(P<0.001).The positive rate of EML4-ALK fusion gene immuno-histochemistry(IHC)in 97 cytological paraffin-embedded speci-mens was 15.46%,among which 6 cases with weak positivity(+)showed negative results in molecular detection,and 9 ca-ses with diffuse positivity(+++)showed positive results in molec-ular detection.The results of immunohistochemistry were highly consistent with molecular detection in cases with diffuse strong positivity(Kappa=1).It was found from the cytological mor-phology of cases with gene alterations that KARS mutation carri-ers were born with unique characteristics,with tumor cells scat-tered or arranged in small clusters and more cytoplasmic vacu-oles were commonly seen.Conclusion Molecular detection in cytological specimens of lung adenocarcinoma is feasible with higher sensitivity.Multi-gene panel detection is superior to sin-gle-gene detection.Immunohistochemistry can be used for screening EML4-ALK fusion gene,and lung adenocarcinoma with KRAS mutation that exhibits distinct cytological morpholo-gy.
5.Impact of autonomic nerve function on motor function in patients with post-stroke depression
Minglan ZHANG ; Lingling ZHANG ; Lisha WANG ; Li LIU ; Run GAO ; Jiang RAO ; Wan LIU ; Zi'an XIA ; Chuanwen ZHANG ; Xinxin CHENG
Chinese Journal of Rehabilitation Theory and Practice 2024;30(2):223-231
ObjectiveTo explore the impact of autonomic nerve function on motor function in patients with post-stroke depression (PSD) from the perspective of regional homogeneity (ReHo). MethodsFrom January to December, 2020, a total of 60 inpatients and outpatients with cerebral infarction in the Affiliated Brain Hospital of Nanjing Medical University were divided into control group (n = 30) and PSD group (n = 30). Two groups were assessed using Fugl-Meyer Assessment (FMA), modified Barthel Index (MBI) and Hamilton Depression Scale (HAMD). Heart rate variability (HRV) was measured. Ten patients in each group were selected randomly to undergo resting state functional magnetic resonance imaging (rs-fMRI) to calculate ReHo. ResultsAll HRV indices were lower in PSD group than in the control group (|t| > 2.092, P < 0.05). In PSD group, FMA and MBI scores showed positive correlations with 24-hour standard deviation of normal-to-normal R-R intervals (SDNN), the root mean square of successive differences between normal heartbeats over 24 hours (RMSSD), the percentage of differences between adjacent normal R-R intervals over 24 hours that were greater than 50 ms (PNN50), total power (TP), very low frequency power (VLF) and low frequency power (LF) (r > 0.394, P < 0.05), and showed negative correlations with HAMD scores (|r| > 0.919, P < 0.001). HAMD scores in PSD group were negatively correlated with SDNN, RMSSD, PNN50, TP and VLF (|r| > 0.769, P < 0.001). Compared with the control group, the ReHo increased in PSD group in the right rectus gyrus (142 voxels, t = 6.575), the left medial and paracingulate gyri (204 voxels, t = 4.925) (GRF correction, P-Voxel < 0.005,P-Cluster < 0.05); and reduced in the right cerebellum (191 voxels, t = -6.487), the left middle temporal gyrus (140 voxels, t = -5.516), and the left precentral gyrus (119 voxels, t = -4.764) (GRF correction, P-Voxel < 0.005,P-Cluster < 0.05) in PSD group. ConclusionAutonomic nerve function is related to motor dysfunction in patients with PSD. The modulation of emotional, cognitive and motor brain regions by the autonomic nervous system may play a role in influencing the motor function in patients with PSD.
6.Clinical value of abdominal adipose volume in predicting early tumor recurrence after resec-tion of hepatocellular carcinoma
Guojiao ZUO ; Mi PEI ; Zongqian WU ; Fengxi CHEN ; Jie CHENG ; Yiman LI ; Chen LIU ; Xingtian WANG ; Xuejuan KONG ; Lin CHEN ; Xiaoqin YIN ; Hongyun RAO ; Wei CHEN ; Ping CAI ; Xiaoming LI
Chinese Journal of Digestive Surgery 2024;23(1):140-146
Objective:To investigate the clinical value of abdominal adipose volume in predicting early tumor recurrence after resection of hepatocellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 132 HCC patients with tumor diameter ≤5 cm who were admitted to The First Affiliated Hospital of Army Medical University from December 2017 to October 2019 were collected. There were 110 males and 22 females, aged (51±4)years. All patients underwent resection of HCC. Preoperative computer tomography scanning was performed and the visceral and subcutaneous fats of patients were quantified using the Mimics Research 21.0 software. Based on time to postoperative tumor recurrence patients were divided to two categories: early recurrence and non-early recurrence. Observation indicators: (1) consistency analy-sis; (2) analysis of factors influencing early tumor recurrence after resection of HCC and construction of prediction model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribu-tion were represented as M( Q1,Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Consistency analysis was conducted using the intragroup correlation coefficient (ICC) test. Multivariate analysis was performed using the binary Logistic regression model forward method. Independent risk factors influencing early tumor recurrence after resection of HCC were screened. The area under curve (AUC) of receiver operating characteristic (ROC) curve was applied to select the optimal cut-off value to classify high and low risks of recurrence. The Kaplan-Meier method was used to draw survival curve and calculate survival time. The Log-Rank test was used for survival analysis. Results:(1) Consistency analysis. The consistency ICC of abdominal fat parameters of visceral fat volume (VFV), subcutaneous fat volume, visceral fat area, and subcutaneous fat area measured by 2 radiologists were 0.84, 1.00, 0.86, and 0.94, respectively. (2) Analysis of factors influencing early tumor recurr-ence after resection of HCC and construction of prediction model. All 132 patients were followed up after surgery for 662(range, 292-1 111)days. During the follow-up, there were 52 patients with non-early recurrence and 80 patients with early recurrence. Results of multivariate analysis showed that VFV was an independent factor influencing early tumor recurrence after resection of HCC ( odds ratio=4.07, 95% confidence interval as 2.27-7.27, P<0.05). The AUC of ROC curve based on VFV was 0.78 (95% confidence interval as 0.70-0.85), and the sensitivity and specificity were 72.2 % and 77.4 %, respectively. The optimal cut-off value of VFV was 1.255 dm 3, and all 132 patients were divided into the high-risk early postoperative recurrence group of 69 cases with VFV >1.255 dm 3, and the low-risk early postoperative recurrence group of 63 cases with VFV ≤1.255 dm 3. The disease-free survival time of the high-risk early postoperative recurrence group and the low-risk early post-operative recurrence group were 414(193,702)days and 1 047(620,1 219)days, showing a significant difference between them ( χ2=31.17, P<0.05). Conclusions:VFV is an independent factor influen-cing early tumor recurrence of HCC after resection. As a quantitative indicator of abdominal fat, it can predict the prognosis of HCC patients.
7.Accuracy of portable hemoglobinometer in maintenance hemodialysis patients
Xiaohao ZHANG ; Fanglin TANG ; Jialing RAO ; Yuanqing LI ; Wei LI ; Cailian CHENG ; Hui PENG
Chinese Journal of Nephrology 2024;40(1):49-52
This study aims to evaluate the accuracy of portable hemoglobinometer (Hemocue Hb 201+ hemoglobin analyzer) in patients with maintenance hemodialysis (MHD) and its diagnostic value for anemia. The data of venous hemoglobulin (Hb) and fingertip capillary hemoglobulin (DHb) in MHD patients from Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed, and the correlation and difference between DHb and Hb and the accuracy of DHb in the diagnosis of anemia were evaluated. A total of 105 patients were included in the study. There was no significant difference between the paired DHb and Hb [(109±21) g/L vs. (108±20) g/L, t=-1.284, P=0.202]. Pearson correlation analysis showed that DHb was positively correlated with Hb ( r=0.929, P<0.001). Linear regression analysis showed that DHb and Hb met the regression equation Hb=0.88×DHb+12.23, and P<0.001. Bland-Altman analysis showed that the differences between the paired DHb and Hb was (1.0±7.8) g/L with the limit of agreement as (-14.2, 16.2) g/L. The mean percentage of the differences in Hb was 1% with limit of agreement as (-13.7%, 15.7%). A DHb of >110 g/L was 0.90 sensitive and 0.83 specific to identify patients with an Hb >110 g/L and its positive and negative predictive values were 0.84 and 0.90, respectively. It suggests that, in MHD patients, Hemocue Hb 201+ analyzer shows good accuracy, and can be used to monitor the Hb trend and serve as a screen method for those reaching target Hb.
8.Role of fatty acid metabolism-related genes in periodontitis based on machine learning and bioinformatics analysis
Yuxiang CHEN ; Anna ZHAO ; Haoran YANG ; Xia YANG ; Tingting CHENG ; Xianqi RAO ; Ziliang LI
West China Journal of Stomatology 2024;42(6):735-747
Objective This study aims to investigate the role of genes related to fatty acid metabolism in periodon-titis through machine learning and bioinformatics methods.Methods Periodontitis datasets GSE10334 and GSE-16134 were downloaded from the GEO database,and the fatty acid metabolism-related gene sets were obtained from the GeneCards database.Differentially expressed fatty acid metabolism-related genes(DEFAMRGs)in periodontitis were screened using the"limma"R package.Functional enrichment and pathway analyses were conducted.Recursive Feature Elimination,Least Absolute Shrinkage and Selection Operator,and Boruta algorithm were used to determine hub DEFAMRGs and construct diagnostic models with internal and external validation.Subtypes of periodontitis relat-ed to hub DEFAMRGs were constructed using consis-tency clustering analysis.CIBERSORT was used to ana-lyze immune cell infiltration in gingival tissues and ex-plore the correlation between hub DEFAMRGs and im-mune cells.Results A total of 113 periodontitis DE-FAMRGs were screened out as a result.The enrichment analysis results indicate that DEFAMRGs are mainly associat-ed with immune inflammatory responses and immune cell chemotaxis.Finally,8 hub DEFAMRGs(BTG2,CXCL12,FABP4,CLDN10,PPBP,RGS1,LGALSL,and RIF1)were identified and a diagnostic model(AUC=0.967)was con-structed,based on which periodontitis was divided into two subtypes.In addition,there is a significant correlation be-tween hub DEFAMRGs and different immune cell populations,with mast cells and dendritic cells showing higher cor-relation.Conclusion This study provides new insights and ideas for the occurrence and development mechanism of periodontitis and proposes a diagnostic model based on hub DEFAMRGs to provide new directions for diagnosis and treatment.
9.Routes to collection of reexamination data under the new evaluation standard in a tertiary hospital
Shaofeng RAO ; Botao JIANG ; Yueli YANG ; Ning HU ; Fan LU ; Xiu FENG ; Cheng CHEN
Modern Hospital 2024;24(5):747-749
In compliance with the data requirements for monitoring medical service capacity and quality safety in the sec-ond part of the"Rules for the Implementation of Evaluation Standards for Tertiary General Hospitals in Hubei Province(2023 Edition)",this paper,in conjunction with the specific circumstances of a tertiary hospital,carried out a brief overview of the da-ta collection process and the challenges faced during the reevaluation of the tertiary hospital.By accurately addressing the prob-lems and challenges in medical services,this paper aimed to enhance medical quality management and advance the hospital's high-quality development.
10.Prevalence of seven zoonotic pathogens in small mammals in the Qinghai plateau region
Hong-Bing CHENG ; Yi-Ping LIU ; Jia CUI ; Hua-Xiang RAO ; Dong-Mei LI ; Juan YU
Chinese Journal of Zoonoses 2024;40(9):880-886
This study investigated the prevalence of Borrelia burgdorferi,Anaplasma phagocy tophilum,Rickettsia typhi,Orientia tsutsugamushi,Leptospira interrogans,Francisella tularensis,and Babesia spp.in small mammals in the Qinghai plateau region,to provide a scientific basis for the prevention and control of local zoonotic diseases.Small mammals were cap-tured with snap traps at six sampling sites in the Qinghai plateau region.Liver,spleen,and kidney tissues were collected for detection of six bacterial pathogens with real-time PCR.Conventional PCR(cPCR)was used for Babesia detection,and the positive PCR products were sequenced and analyzed.The differences in pathogen detection rates among species and habitats were analyzed with x2 test or Fisher's exact test.In to-tal,235 small mammals from 15 species were captured.B.burgdorferi,L.interrogans,and Babesia were detected in 11 spe-cies of small mammals,whereas A.phagocytophilum,R.typhi,O.tsutsugamushi,and F.tularensis were not detected.B.burgdorferi was detected in 41 small mammals from nine species(Cricetulus longicaudatus,Apodemus peninsulae,Ochotona curzoniae,Mus m usc ulus,Meriones meridians,Microtus arvalis,Cricetidae,Ochotona cansus,and Allactaga sibirica),with an infection rate of 17.45%(41/235).L.interrogans was detected in eight small mammals from four species(C.longicaudatus,M.musculus,M.arvalis,and Microtus oeconomus),with an infection rate of 3.40%(8/235).Babesia was detected in only one Mustela altaica,with an infection rate of 0.85%(1/235).Statistically significant differences were ob-served in the detection rates of pathogens among small mammal species(x2=200.54,P<0.05).Among habitats,the detection rate of B.burgdorferi was highest in the forest(Fisher's exact test,P<0.05).B.burgdorferi and L.interrogans co-infection was observed in three M.arvalis and two C.longicaudatus.In addition,one Babesia sequence was obtained,which clustered with Babesia vulpes in the phylogenetic tree.B.burgdorferi,L.interrogans,and Babesia were the main pathogens prevalent in small mammals in the Qinghai plateau region and have potential to cause human diseases.Local authori-ties should strengthen the surveillance of corresponding zoonotic diseases,and formulate corresponding prevention and control measures.


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