1.Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease
Tianzhong PAN ; Peng DING ; Aijie HUANG ; Baolin TANG ; Kaidi SONG ; Guangyu SUN ; Yue WU ; Shiying YANG ; Xingchi CHEN ; Dongyao WANG ; Xiaoyu ZHU
Chinese Medical Journal 2024;137(10):1207-1217
Background::With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods::A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results::The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year ( F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93; P = 0.031). Conclusions::Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.
2.TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD
Baokai SUN ; Xiaoqian DING ; Jie TAN ; Jie ZHANG ; Xueru CHU ; Shuimi ZHANG ; Shousheng LIU ; Zhenzhen ZHAO ; Shiying XUAN ; Yongning XIN ; Likun ZHUANG
Clinical and Molecular Hepatology 2024;30(4):863-882
Background:
s/Aims: Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood.
Methods:
The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC).
Results:
The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFDinduced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice.
Conclusions
The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.
3.Early neurological deterioration in patients with minor ischemic stroke caused by large vessel occlusion: risk factors and the impact of rescue endovascular thromboectomy on outcomes at discharge
Chenchen MA ; Mengmeng WANG ; Jian DING ; Ting WU ; Shiying SHENG ; Hanqing LI ; Meng LIU
International Journal of Cerebrovascular Diseases 2023;31(5):321-326
Objective:To investigate the risk factors of early neurological deterioration (END) in patients with minor ischemic stroke caused by large vessel occlusion (LVO) and the impact of rescue endovascular thromboectomy (REVT) on clinical outcomes of patients with END at discharge.Methods:Consecutive patients with acute minor ischemic stroke caused by LVO within 24 h of onset in the Third Affiliated Hospital, Soochow University from January 2021 to March 2023 were retrospectively enrolled. Minor ischemic stroke was defined as baseline National Institute of Health Stroke Scale (NIHSS) score ≤5 at admission. END was defined as an increase of ≥4 in the NIHSS score within 24 h after the best medical management. The modified Rankin Scale was used to evaluate the clinical outcomes of patients with END at discharge. 0-2 was defined as a good outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for END and the impact of REVT on clinical outcomes in patients with END. Results:A total of 75 patients with minor ischemic stroke caused by LVO were included, of which 31 (41.3%) developed END and 13 (41.9%) underwent REVT after END. Multivariate logistic regression analysis showed that internal carotid artery occlusion was an independent risk factor for END (odds ratio 4.304, 95% confidence interval 1.213-15.270; P=0.024), and REVT was an independent protective factor for good outcomes in patients with END (odds ratio 0.068, 95% confidence interval 0.006-0.774; P=0.030). Conclusions:The incidence of END is higher in patients with minor ischemic stroke caused by LVO, and internal carotid artery occlusion is an independent risk factor for the occurrence of END. Providing REVT after END may improve the clinical outcomes of patients with END at discharge.
4.Association of stress hyperglycemia with occurrence and prognosis of sepsis-associated encephalopathy
Shiying ZHANG ; Zhuo LI ; Hongguang DING ; Wenhong ZHONG ; Yin WEN ; Yongli HAN ; Xinqiang LIU ; Heng YOU ; Huishan ZHU ; Guoqiang DU ; Hongke ZENG
Chinese Journal of Emergency Medicine 2023;32(8):1070-1076
Objective:To investigate whether stress hyperglycemia (SH) is an independent risk factor for the occurrence and mortality of sepsis-associated encephalopathy (SAE).Methods:From August 2016 to October 2021, sepsis patients admitted to the ICU of Guangdong Provincial People's Hospital were selected as the study subjects. According to whether they developed to SH (RBG>11.1 mmol/L) within 7 days of enrollment, the pat ients were divided into the SH group and the non-SH group for analysis. Logistic regression was used to analyze whether SH was an independent risk factor for SAE occurrence, and ROC curve was used to analyze the predictive value of SH to SAE. Kaplan-Meier curve was used to compare the 90-day survival of SAE patients with or without SH. Cox regression analysis was used to analyze the risk factors of 28-day and 90-day death in SAE patients.Results:A total of 183 sepsis patients were included, including 62 patients in the SH group and 121 in the non-SH group. Logistic regression analysis demonstrated that SH was an independent risk factor for SAE ( OR=4.452, 95% CI: 2.021-9.808, P <0.001). ROC curve demonstrated that SH could accurately predict SAE (AUC=0.831; Sensitivity=78.4%; Specificity=76.8%; and Yoden index=0.553). Kaplan-Meier curve demonstrated that the 90-day survival of SAE patients with SH significantly declined (log-rank test: P<0.01). Cox regression analysis suggested that SH was a risk factor for death at day 28 and day 90 in SAE patients (28 d, HR=2.272, 95% CI: 1.212-4.260, P=0.010; 90 d, HR=2.456, 95% CI: 1.400-4.306, P<0.01). Conclusions:SH is an independent risk factor for SAE and can predict SAE occurrence. SH significantly reduces 90-day survival and increase mortality at 28 and 90 days in SAE patients.
5.Early-warning value of PCT/PLT ratio on sepsis-induced myocardial injury
Mengting LIU ; Wenhong ZHONG ; Yin WEN ; Shiying ZHANG ; Zhuo LI ; Heng YOU ; Yongli HAN ; Hongguang DING ; Hongke ZENG
Chinese Journal of Emergency Medicine 2022;31(8):1071-1076
Objective:To investigate the diagnostic and early-warning value of laboratory test indicators for sepsis-induced myocardial injury (SIMD).Methods:The clinical data of 183 patients with sepsis admitted to the Department of Emergency and Critical Care Medicine of Guangdong Provincial People's Hospital from August 2016 to October 2020 were collected. The patient's age, gender, past medical history, vital signs and pathogen culture results were extracted. Cardiac function, blood routine, liver function, renal function, inflammatory factors, coagulation function, APACHE Ⅱ and SOFA scores were recorded at enrollment and 72 h after admission. SIMD was defined as cTnT ≥300 pg/mL and NT-proBNP ≥1243 pg/mL twice in 72 h intervals between enrolled cases, and the early-warning factors of patients with SIMD were analyzed. The differences in various indicators between the two groups were compared, and Logistic regression analysis was used to explore the diagnostic efficacy of cTnT and NT-proBNP combined for SIMD, and the correlation between PCT/PLT ratio and the occurrence of SIMD.Results:Among 250 patients, 67 patients were excluded for lack of the main indicators, and 183 patients (including 62 patients with history of cardiac disease) were enrolled finally. Among 183 patients with sepsis, 105 patients (57.38%) with cTNT ≥300 pg/mL and NT-proBNP ≥1 243 pg/mL, were diagnosed as myocardial injury; after excluding 62 patients with history of cardiac disease, 59 patients (48.76%) with cTNT ≥300 pg/mL and NT-proBNP ≥1 243 pg/mL were diagnosed as myocardial injury. Logistic regression analysis showed that increased PCT/PLT ratio ( OR=1.585, 95% CI: 1.124-2.237, P=0.009) was an independent risk factor for early-warning of SIMD. The PCT/PLT ratio ( OR= 1.850, 95% CI: 1.103-3.102, P=0.020) could stably predict the occurrence of SIMD in patients without previous history of heart disease. ROC curve analysis showed that PCT/PLT ratio could effectively predict the occurrence of SIMD (AUC=0.693, 95% CI: 0.617-0.769, P<0.001), the optimal cut-off value was 0.177 (sensitivity: 65.7%, specificity: 66.7%). The PCT/PLT ratio was still effective in predicting the occurrence of SIMD after excluding patients with previous history of heart disease (AUC=0.733, 95% CI: 0.643-0.823, P<0.001), and the optimal cut-off value was 0.429 (sensitivity: 55.9%, specificity: 83.9%). Conclusions:The combination of cTnT and NT-proBNP has certain diagnostic value for SIMD, and the PCT/PLT ratio could warn the occurrence of SIMD.
6.Research of the change of blood-brain barrier permeability in septic rats
Ya LI ; Mengting LIU ; Shiying ZHANG ; Zhuo LI ; Yin WEN ; Hongguang DING ; Hongke ZENG
Chinese Journal of Emergency Medicine 2021;30(6):699-703
Objective:To explore the change of blood-brain barrier (BBB) permeability in septic rats.Methods:A rat model of sepsis was established by cecal ligation and puncture. Rats were randomly (random number) grouped according to the intervention time: sham-operated group, sepsis 1-day group, sepsis 4-day group, and sepsis 7-day group. Fluorescein sodium was used to test the permeability of the BBB. Western blot and immunofluorescence methods were applied to detect the expression of tight junction proteins including Claudin-5, Occludin and ZO-1.Results:Compared with the sham-operated group, rats in the sepsis group presented quick breath, slow response, decreased intake of food and water, obvious abdominal distension and loose stools. After abdominal anatomy of sepsis rats, we found mesenteric adhesions, dilatation of proximal intestinal, black cecum ligation site with purulent exudate, enlarged liver and diffused bloody exudate. Compared with the sham-operated group, body weight of sepsis rats was reduced remarkably ( P < 0.05). The body weight of rats of sepsis 7-day group was the lowest, which was significantly lower than that of rats of sepsis 4-day group ( P< 0.05) and 1-day group ( P< 0.05). Compared with the sham-operated group, the content of fluorescein sodium in sepsis 1-day rats was increased remarkably ( P< 0.05). The content of fluorescein sodium in rats of sepsis 7-day group was the highest, which was significantly higher than that in rats of sepsis 4-day group ( P< 0.05) and 1-day group ( P< 0.05). Compared with the sham-operated rats, the expression of Claudin-5, Occludin and ZO-1 in sepsis rats were decreased remarkably (all P < 0.05). The expression of Claudin-5, Occludin and ZO-1 were the lowest in rats of the sepsis 7-day group, which were significantly decreased than those of rats in the sepsis 4-day group (all P< 0.05) and rats in sepsis 1-day group (all P < 0.05). Conclusions:Sepsis rats showed increased permeability of the BBB, and the permeability of BBB increased continuously along with the duration of sepsis.
7. Correlation analysis between Dx-pH monitoring and proton pump inhibitor test in the diagnosis of laryngopharyngeal reflux disease
Zhiling CHEN ; Huawei WU ; Xianwei MEI ; Wenhua YIN ; Shiying XU ; Suqin LIU ; Yanchun CHEN ; Gan WANG ; Chenjia ZHANG ; Xiaolong DING ; Jiani WU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2020;55(1):34-39
Objective:
The consistency of 24-hour oropharyngeal Dx-pH monitoring and proton pump inhibitor(PPI) test in the diagnosis of laryngopharyngeal reflux disease (LPRD) was investigated.
Methods:
Sixty patients with laryngopharyngeal reflux (LPR) related symptoms who had never received PPI treatment were assessed by reflux symptom index (RSI) and reflux finding score (RFS) between October 2017 and October 2018, including 28 males and 38 females, aged from 16 to 72 years, with a medium age of 38 years. Prior to treatment, all patients were evaluated with 24 hours oropharyngeal Dx-pH monitoring(Restech). After empiric therapy with PPI twice-daily for 8 weeks, the efficacy was evaluated according to posttreatment RSI score.The data was analysed with Kruskal-Wallis test, Student Newman Keuls test and consistency check.
Results:
(1)Among all 60 patients,13 patients (21.7%) had pathologic Ryan score and all resulted responsive to PPI;27 patients (45.0%) with a negative Ryan score were unresponsive to PPI; 20 patients (33.3%) despite a negative Ryan score resulted responsive to PPI therapy. Considering responsiveness to PPI therapy as the gold standard for the diagnosis of LPRD, the sensitivity, specificity, positive predictive value and negative predictive value of Ryan score were 39.4%, 100%, 100% and 57.4% respectively. The Kappa value was 0.369 (
8.Diagnosis and treatment of 40 cases of gastritis cystica profunda
Shuai GONG ; Shiying YANG ; Hanbing XUE ; Yunjia ZHAO ; Yao ZHANG ; Yunjie GAO ; Haiying CHEN ; Hui DING ; Xiaobo LI ; Zhizheng GE
Chinese Journal of Digestive Endoscopy 2019;36(7):483-486
Objective To investigate the clinical,endoscopic and pathological features of gastritis cystica profunda (GCP).Methods A total of 40 patients with GCP confirmed by pathology who received endoscopic or surgical treatment at Renji Hospital,School of Medicine,Shanghai Jiaotong University from May 2013 to May 2018,were included in the retrospective analysis.The clinical data such as population composition,clinical manifestations,endoscopic findings and pathological results were summarized and analyzed.Results Among the 40 patients were predominantly males (75.0%,30/40),and the mean age of onset was 61.2 years.The most common sites were cardia (32.5%,13/40) and gastric antrum (30.0%,12/40).The clinical symptoms of the patients were atypical and it was difficult to diagnose GCP with routine endoscopy examination.The endoscopic findings were mostly type 0-Ⅱ (50.0%,20/40).GCP with neoplastic lesions accounted for 55% (22/40).Unconditional logistic regression analysis showed that male (P =0.013,OR =31.093,95% CI:2.079-464.976) and Helicobacter pylori infection (P =0.041,OR =10.225,95% CI:1.096-95.411) were risk factors for GCP with neoplastic lesions.Conclusion GCP commonly occurs in middle-aged and elderly men,and varies in different manifestations under white light endoscopy.GCP is not a benign lesion,but can also coexist with neoplastic lesions,which are mostly differentiated intramucosal cancer.
9.Intraoperative ultrasound added with neuronavigation in resection of intracranial gliomas
Wei CHENG ; Chaoshi NIU ; Wanhai DING ; Chi XIONG ; Ying JI ; Xiaofeng JIANG ; Shiying LING
Chinese Journal of Neuromedicine 2014;13(7):663-666
Objective To conclude the application experience of intraoperative ultrasound added with neuronavigation in resection of intracranial gliomas.Methods A retrospective analysis was performed on the clinical data of 60 patients with intracranial gliomas,performed resection in our hospital from January 2010 to June 2013 by intraoperative ultrasound added with neuronavigation; 32 of them had high-grade gliomas and 28 low-grade ones.Ultrasonoscopy of different grade gliomas was studied.Results The accuracy of localization was 100% in 60 patients with intracranial gliomas.Ultrasonic image of high-grade gliomas enjoyed obvious hyperechogenicity and the boundaries were clear usually; ultrasonic image of low-grade ones were slightly hyperechogenic or isoechogenic and the boundaries were indistinct usually.Inhomogeneous hyperechogenic of the ultrasonoscopy of intracranial gliomas before resection and hypoechogenic of residual cavity after resection were noted,respectively.Total removal was achieved in 50 patients,subtotal resection in 6 and partial resection in 4.Brain swelling happened postoperatively in 1 and was remitted by decompressive craniectomy.Hemiplegia happened in 2,and no death occurred postoperatively.Conclusions Intraoperative ultrasound is important to the correct of brain shift,and has clear and important value to the choice of operation approach and incising cortex.Ultrasonic image of high-grade gliomas and calcified lesions enjoys the best view.Intraoperative ultrasound added with neuronavigation can raise resection rate of intracranial gliomas.
10.Lung ventilation/perfusion imaging in the diagnosis of chronic thromboembolic pulmonary hypertension in comparison with CT pulmonary angiography
Chun ZHANG ; Tie WANG ; Zhanhong MA ; Yi DING ; Shiying QU ; Jingwei HUANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2013;33(4):254-257
Objective To evaluate the lung V/Q imaging in the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH).Methods Seventy-six patients (46 males,30 females,age 27-84 y) with clinically suspected CTEPH who had undergone lung V/Q imaging,CT pulmonary angiography (CTPA),pulmonary angiography (PA) and right heart cardiac catheterization were studied.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of lung V/Q imaging in detecting CTEPH were calculated and compared with those of CTPA.The x2 test was used for statistical analysis with SPSS 11.5.The distribution of involvement of segments in 47 patients with CTEPH was analyzed.Results Forty-seven patients had a final diagnosis of CTEPH and 29 had non-CTEPH etiology.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of lung V/Q imaging were 97.9% (46/47),86.2% (25/29),93.4% (71/76),92.0% (46/50) and 96.2% (25/26),while those of CTPA were 78.7% (37/47),93.1% (27/29),84.2% (64/76),94.9% (37/39) and 73.0% (27/37),respectively.The sensitivity (x2 =5.818,P=0.012) and negative predictive value (x2 =5.693,P =0.017) for lung V/Q imaging were significantly higher than those of CTPA.V/Q imaging could identify patients with CTEPH from those with idiopathic PAH and familial PAH based on the almost normal ventilation imaging.The lung perfusion SPECT imaging detected 585 (62.2%) of involved segments among 940 segments in 47 patients with CTEPH,with an average of 12.4 involved segments in each patient.The number of involved segments in the right lung was significantly higher than that in the left lung (36.2% (340/940) vs 26.1% (245/940) ; x2 =40.85,P<0.01).Conclusions Lung V/Q imaging plays an important role in diagnosis of CTEPH and in identification of CTEPH from other types of PAH.A normal V/Q imaging can effectively exclude CTEPH.In addition,V/Q imaging can provide more diagnostic information in patients with a clinical suspicion of CTEPH who had negative results by CTPA and PA.

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