1.Research progress on endogenous small-molecule phenolics and the proposal of "phenolomics"
Hong-qian KUI ; Chuan-xin LIU ; Qiang WANG ; Hai-feng ZHAI ; Jian-mei HUANG
Acta Pharmaceutica Sinica 2024;59(2):336-349
Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.
2.Mechanism study on S-allylmercaptocysteine promoting CD8+T cell killing function
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(2):74-78
OBJECTIVE To investigate the effect of SAMC on the killing function of CD8+T cells against nasopharyngeal carcinoma cells and its mechanism.METHODS HK-1 and C666-1 are divided into 0,25,50,and 100 mol/L SAMC group,Western blot was used to detcet PD-L1 expression in tumor cells.CD8+T cells were co-cultured with HK-1 and C666-1 cells in a ratio of 10∶1,and 0,25,50,and 100 μmol/L SAMC were added and detect the killing ability of CD8+T on HK-1 and C666-1.ELISA was used to detect INF-γ and TNF-α concentration.Construct a subcutaneous transplant tumor model of nasopharyngeal HK-1 cells,and divide it into a control group,CD8+T cell group,SAMC group,and SAMC+CD8+T cell group.The tumor volume was measured during treatment in each group of mice.Western blot was used to detect the expression of PD-L1 in the tumor tissue,ELISA was used to detect INF-γ and TNF-α concentration of mouse serum.RESULTS Compared to 0 μmol/L SAMC group,the expression of PD-L1 in 25,50,100μmol/L SAMC group were significantly downregulated(P<0.05).Compared to 0 μmol/L SAMC+CD8+T group,the INF-γ and TNF-α concentration were significantly increased in 25,50,100 μmol/L SAMC+CD8+T group,the lysis rates of HK-1 and C666-1 cells were significantly increased.Compared with the control group,the tumor volume and weight in the CD8+T cell group and SAMC+CD8+T cell group were significantly reduced(P<0.05),the concentration of INF-γ and TNF-α were significantly increased.Compared with the CD8+T cell group,the tumor volume and weight in the SAMC+CD8+T cell group mice significantly decreased(P<0.05),while the serum INF-γ and TNF-α concentration significantly increased(P<0.05),and the expression of PDL-1 in tumor tissue was significantly downregulated(P<0.01).CONCLUSION SAMC can promote the killing function of CD8+T cells by inhibiting the expression of PD-L1 in human nasopharyngeal carcinoma cells.
3.Clinical Consistency Evaluation of Quetiapine Kit Based on Liquid Chromatography Tandem Mass Spectrometry Technology
LI Xuanwei ; LIN Meihua ; ZHAI You ; XU Nana ; LI Xiao ; LYU Duo ; ZHAO Qingwei ; LIU Jian
Chinese Journal of Modern Applied Pharmacy 2024;41(13):1803-1807
OBJECTIVE
To evaluate the consistency between the quetiapine LC-MS/MS kit and the laboratory-built method(reference method) in the detection results of quetiapine therapeutic drug monitoring.
METHODS
A total of 120 remaining plasma samples were collected from patients receiving quetiapine therapeutic drug monitoring from March to October in 2021. The plasma concentration of quetiapine was detected by kit and reference method respectively. The analysis of correlations and consistency was performed by outlier analysis, linear regression and Bland-Altman method.
RESULTS
No outliers were detected. The linear regression equation was Y=1.018X+4.400(r=0.998), indicating a good correlation. The Bland-Altman plot analysis showed good agreement between the two measurements.
CONCLUSION
The detection results of quetiapine LC-MS/MS kit and reference method are in good agreement. The kit can be used for clinical quetiapine treatment drug monitoring.
4.A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children
Li SONG ; Ling JIN ; Yonghong ZHANG ; Xiaomei YANG ; Yanlong DUAN ; Mincui ZHENG ; Xiaowen ZHAI ; Ying LIU ; Wei LIU ; Ansheng LIU ; Xiaojun YUAN ; Yunpeng DAI ; Leping ZHANG ; Jian WANG ; Lirong SUN ; Rong LIU ; Baoxi ZHANG ; Lian JIANG ; Huixia WEI ; Kailan CHEN ; Runming JIN ; Xige WANG ; Haixia ZHOU ; Hongmei WANG ; Shushuan ZHUANG ; Chunju ZHOU ; Zifen GAO ; Xiao MU ; Kaihui ZHANG ; Fu LI
Chinese Journal of Pediatrics 2024;62(10):941-948
Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.
5.One-year outcomes of D-shant atrial shunt device for patients with heart failure with reduced ejection fraction
Yi-Wei WANG ; Ping JIN ; Meng-En ZHAI ; Xin MENG ; Yu-Xi LI ; Yu MAO ; Yuan-Zhang LIU ; Jian YANG ; Yang LIU
Chinese Journal of Interventional Cardiology 2024;32(8):434-442
Objective To assess the clinical short-term outcomes of implanting D-shant atrial shunt device(aSD)in a single center for patients with heart failure with reduced ejection fraction(HFrEF).Methods From January 2022 to January 2023,a retrospective analysis was conducted on 12 patients with HFrEF who underwent percutaneous implantation of a D-shant aSD.We assessed cardiac chamber size and ventricular function using echocardiography,right heart catheterization measurements and patient clinical indicators were collected,follow up data of 12 months postoperative and pre-implantation D-shant were compared.The primary endpoint of the study was the cumulative occurrence of adverse cardiac,neurologic,or renal events during the follow-up period.Secondary endpoints were improvements in functional status included cardiac function,quality of life,and exercise capacity.Results All 12 patients underwent successful percutaneous inter-atrial shunting procedures using the D-shant.Postoperative immediately fluoroscopy and echocardiography confirmed accurate localization and patency of the atrial shunt devices in all cases.Postoperative hemodynamic assessment revealed a significant decrease in pulmonary capillary wedge pressure[(29.8±3.4)mmHg vs.(17.8±0.8)mmHg,P<0.001].During 12 months follow-up,the cumulative adverse event rate was 8.3%(one patient received a heart transplant),a significant reduction in left atrial diameter from(65.8±6.5)mm to(48.0±4.5)mm(P<0.001)was observed.Furthermore,there was notable improvement in clinical cardiac function indices quality of life,and exercise capacity of the patients.Conclusions This single-center retrospective study found that the use of a D-shant aSD to perform percutaneous interatrial shunting in patients with HFrEF is safe and effective.Short-term follow-up demonstrated sustained patency of the shunt and that the intervention was associated with improved functional status.
6.Study on the safety and efficacy of novel portable extracorporeal membrane oxygenation in animal experiments in vivo
Meng-En ZHAI ; Jian-Chao LUO ; Lin-He LU ; Yu-Chao REN ; Ping JIN ; Zhen-Hua LIU ; Jian YANG ; Zhen-Xiao JIN ; Jin-Cheng LIU ; Yang LIU
Chinese Journal of Interventional Cardiology 2024;32(8):447-450
Objective To verify the safety and efficacy of a new portable extracorporeal membrane oxygenation(ECMO)system(Xijing Advanced Life Support System JC-Ⅲ)in large animals.Methods A total of 10 healthy small fat-tail sheep underwent veno-arterial extracorporeal membrane oxygenation(VA-ECMO)support by carotid arterial-jugular catheterization to evaluate the performance of the JC-Ⅲ ECMO system.Systemic anticoagulation was achieved by continuous infusion of heparin.Active coagulation time(ACT)was recorded every 2 hours during the experiment,and the ACT was maintained between 200-250 s.Centrifugal pump speed is set at 3 000-3 500 r/min.The changes of hemoglobin,blood cell counts,hematocrit,liver and kidney function were monitored before and 24 h after ECMO initiation,respectively.After the experiment,the pump and oxygenator were dissected to probe the thrombosis.Results The success rate of VA-ECMO operation was 100%,and there was no hemolysis,pump thrombosis and oxygenator thrombosis after 24 h of ECMO.Before and after the operation,there were no significant changes in indicators such as hemoglobin content,white blood cell counts,platelet counts,alanine aminotransferase concentration,aspartate aminotransferase concentration,urea,creatinine,high-sensitivity troponin Ⅰ,and N-terminal pro-brain natriuretic peptide(all P>0.05).Conclusions This in vivo study confirms that Xijing Advanced Life support System JC-Ⅲ is safe and effective.
7.Quantitative CT abdominal fat parameters combined with clinical-imaging comprehensive model for predicting recurrent acute pancreatitis
Hui LUO ; Yuxuan WANG ; Qian ZHANG ; Chunyu LIU ; Chao REN ; Jian ZHAI
Chinese Journal of Medical Imaging Technology 2024;40(7):1036-1040
Objective To observe the value of quantitative CT(QCT)abdominal body fat parameters combined with clinical-imaging model for predicting recurrent acute pancreatitis(RAP).Methods Data of 468 patients with acute pancreatitis(AP),including 207 cases of RAP(RAP group)and 261 cases of non-RAP(non-RAP group)were retrospectively analyzed.Clinical information,conventional CT manifestations and QCT parameters such as abdominal subcutaneous fat area(SFA),visceral fat area(VFA),total abdominal fat area(TFA),hepatic fat content and pancreatic fat content at the first visit were recorded or measured.Clinical characteristics,CT manifestations and QCT parameter values were compared between groups,and the independent factors for predicting RAP were selected with multivariate logistic regression analysis.Then a clinical-imaging model and a comprehensive model combining with QCT parameters were constructed,and their efficacies for predicting RAP were evaluated with receiver operating characteristic(ROC)curves,and the area under the curves(AUC)were calculated.Results Compared with non-RAP group,patients in RAP group were younger,had higher percentage of alcohol consumption,biliary stones and hyperlipidemia,as well as of distinct pancreatic margins on CT images,also higher VFA,TFA,liver fat content and pancreatic fat content(all P<0.05).Alcohol consumption,hyperlipidemia,biliary stones,pancreatic margins and pancreatic fat content were all independent predictors of RAP,and the comprehensive model constructed based on these five had higher AUC(0.860)than clinical-imaging model constructed based on the previous 4 factors(0.701)and pancreatic fat content alone(0.770)(both P<0.001).Conclusion QCT abdominal body fat parameters combined with clinical-imaging comprehensive model was effective for predicting the risk of RAP.
8.Quantitative CT parameters related to abdominal and dorsal fat content for predicting early postoperative complications of esophageal cancer
Jiajia QIAN ; Jian ZHAI ; Yuxuan WANG ; Tong WU ; Zhiqiang WANG ; Kaidi QIU ; Hui LUO
Chinese Journal of Medical Imaging Technology 2024;40(11):1725-1729
Objective To investigate the value of quantitative CT(QCT)parameters related to abdominal and dorsal fat content for predicting early postoperative complications of esophageal cancer.Methods A total of 184 patients who underwent radical esophageal cancer surgery were retrospectively collected and divided into complication group(n=76)and control group(n=108)according to whether early postoperation complication(within 30 days after surgery)occurred or not.QCT was used to obtain parameters related to abdominal and dorsal fat content,including visceral fat area(VFA),subcutaneous fat area(SFA),VFA/SFA and the degree of muscle fat infiltration(MFI)of posterior vertebral muscles based on L3 central-level CT images.Univariate analysis and multivariate logistic regression were used to analyze clinical and pathological data as well as QCT parameters related to abdominal and dorsal fat content to screen independent risk factors for early postoperative complications of esophageal cancer.Then receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of each independent risk factor alone and their combination for predicting early postoperative complications of esophageal cancer.Results VFA/SFA and MFI degree of posterior vertebral muscles were both independent risk factors for early postoperative complications of esophageal cancer(OR=5.121,1.110,both P<0.05).The AUC of VFA/SFA and MFI degree of posterior vertebral muscle was 0.81 and 0.77,respectively,while of their combination was 0.84.Conclusion QCT parameters related to abdominal and dorsal fat content could be used to effectively predict early complications of esophageal cancer after surgery.
9.Value of intravoxel incoherent motion diffusion-weighted imaging quantitative parameters in different regions of kidney in the diagnosis of IgA nephropathy
Xue ZHAI ; Pu CHEN ; Shaopeng ZHOU ; Xu BAI ; Jian ZHAO ; Yong WANG ; Li ZHANG ; Guangyan CAI ; Song WANG ; Haiyi WANG
Chinese Journal of Radiology 2024;58(6):640-646
Objective:To explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in different regions of the kidney in distinguishing IgA nephropathy (IgAN) patients from healthy volunteers.Methods:This study was a cross-sectional study. Eighty-four patients diagnosed with IgAN (IgAN group) who underwent renal biopsy (lower pole of the left kidney) and were pathologically confirmed at the First Medical Center of PLA General Hospital from February 2022 to September 2023 and thirty-four healthy volunteers (control group) were included prospectively. The regions of interest were outlined in the right renal cortex, medulla, and parenchyma for all subjects, and the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D *), and perfusion fraction (f) were measured in the corresponding regions. The differences in IVIM-DWI parameters between the IgAN group and the control group were compared using the student′s t-test or the Mann-Whitney U test. Receiver operating characteristic curve analysis was performed on the parameters with statistically significant differences, and the area under the curve (AUC) was calculated. Results:There were statistically significant differences in renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values between the IgAN group and the control group ( Z=-3.03, -2.21, -2.62, -2.03, -2.03; P=0.002, 0.027, 0.009, 0.043, 0.042). The AUCs (95% CI) for diagnosing IgAN using renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values were 0.679 (0.586-0.762), 0.630 (0.537-0.717), 0.654 (0.535-0.774), 0.619 (0.497-0.742), and 0.620 (0.495-0.745), respectively. There were no statistically significant differences in renal medullary ADC, D, renal cortex, medulla and parenchyma D *, renal cortical and renal parenchymal f values between the two groups ( P>0.05). Conclusion:The quantitative parameters of renal IVIM-DWI are influenced by different measurement regions, among which the ADC, D of renal cortex and parenchyma, and f of renal medulla can be used for the initial diagnosis of IgAN.
10.Prognostic value of serum adenosylhomocysteinase in patients with hepatitis E related acute liver failure
Hong YAN ; Ze XIANG ; Jiaqi CHEN ; Chun JIANG ; Shuxiang LI ; Guanghua ZHAI ; Jian WU
Chinese Journal of Laboratory Medicine 2024;47(8):888-894
Objective:To investigate the prognostic value of serum adenosylhomocysteinase (AHCY) in patients with hepatitis E virus acute liver failure (HEV-ALF).Methods:From 1 January 2017 to 31 December 2022, 100 patients each with HEV-ALF and acute hepatitis E (AHE) from the First Affiliated Hospital of Medical School of Zhejiang University and Affiliated Suzhou Hospital of Nanjing Medical University were included in this case-control study. The HEV-ALF group was 58.56±11.16 years old, including 71 men. The AHE group was 56.04±14.30 years old, including 61 men. All serum samples were obtained before the patient had an acute onset and were obtained without treatment. Firstly, the serum AHCY levels in patients with HEV-ALF and AHE were analyzed by ELISA. Secondly, the serum AHCY levels in HEV-ALF patients with different organ failure and disease condition were compared. According to the number of organ failure, 100 HEV-ALF patients were divided into organ failure number=2 group ( n=58), number=3 group ( n=24) and number>3 groups ( n=18). According to the disease condition, 100 patients were divided into improvement group ( n=49), disease fluctuation group ( n=37), and deterioration group ( n=14). Thirdly, the survival times between the high serum AHCY level group ( n=50) and the low serum AHCY level group ( n=50) were compared. Finally, the independent risk factors to predict mortality using the multivariate Logistic regression analysis, and evaluated the predictive and decision-making abilities of serum AHCY levels were explored using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results:Serum AHCY levels in HEV-ALF patients were significantly higher than those in AHE patients [326.92 (295.37-385.84) pg/ml vs. 222.88 (188.04-246.78) pg/ml, Z=-12.217, P<0.001]. Serum AHCY levels in group 2 were significantly lower than those in group 3 [303.44 (284.40-330.15) pg/ml vs. 335.36 (306.30-385.84) pg/ml, Z=-3.353, P=0.001]. Serum AHCY level in group 3 were significantly lowerthan those in group>3 [335.36 (306.30-385.84) pg/ml vs. 549.89 (423.35-660.22) pg/ml, P<0.001]. The serum AHCY levels in the fluctuation group were lower than those in the deterioration group [322.17 (283.92-423.74) pg/ml vs. 458.26 (374.66, 593.89) pg/ml, Z=-4.016, P=0.009]. The survival time of high serum AHCY level group was significantly lower than that of low serum AHCY level group [23.11 (20.25-25.96) days vs. 29.49 (28.79-30.20) days, Z=-2.596, P<0.001]. The multivariate Logistic regression analysis showed that the levels of serum AHCY and total bilirubin were independent risk factors to predict mortality in HEV-ALF patients [AHCY, OR (95% CI): 1.008 (1.002-1.015), P=0.008; total bilirubin, OR (95% CI): 1.011 (1.005-1.018), P=0.001]. Serum AHCY level predicting the area under the curve (AUC) of 30-day mortality in HEV-ALF patients was 0.912, with a sensitivity of 90.00% and a specificity of 93.75%. DCA results demonstrated that serum AHCY level had good decision-making power for predicting 30-day mortality in HEV-ALF patients. Conclusion:Serum AHCY has an important prognostic value for HEV-ALF patients. Higher serum AHCY levels indicate the worse prognosis of HEV-ALF patients.


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