1.Signal mining and analysis of adverse drug reactions for polatuzumab vedotin based on FAERS database
Zaiwei SONG ; Xinya LI ; Peng MEN ; Dan JIANG ; Fei DONG ; Rongsheng ZHAO ; Jun YANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(7):752-761
AIM:To evaluate and analyze the post-marketing adverse drug reaction(ADR)signals of polatuzumab vedotin,so as to provide reference for clinical safety management.METHODS:Using the FDA adverse drug event reporting system(FAERS)database and OpenVigil data platform,the ADR reports of polatuzumab vedotin were collect-ed from June 10,2019(FDA approval for market-ing)to the March 31,2023.The ADR signals were detected by using the reporting odds ratio(ROR)and proportional reporting ratio(PRR)in the pro-portional imbalance method.To increase the threshold and obtain stronger and more frequently occurring ADRs,a second screening of signals was performed.RESULTS:A total of 2 408 ADR reports related to polatuzumab vedotin were collected,and 83 ADR signals were detected after secondary screening.26 ADR signals were not mentioned in the drug instructions such as abnormal spinal mag-netic resonance imaging,increased bone resorp-tion,osteolysis,decreased aspartate aminotransfer-ase,decreased alanine aminotransferase,hypofibri-nogenemia,and pulmonary embolism.The system organ classes with a high signal counts or cumula-tive number of cases included infections and inva-sive diseases(24 signals,632 cases),various exami-nations(17 signals,675 cases),blood and lymphat-ic system diseases(11 signals,734 cases),various nervous system diseases(7 signals,153 cases),im-mune system diseases(3 signals,95 cases),system-ic diseases and various reactions at the site of ad-ministration(2 signals,145 cases),and systemic dis-eases and various reactions at the site of adminis-tration(2 signals,87 cases),etc.CONCLUSION:In addition to the common ADRs suggested by the in-structions,this study identified new ADR risk sig-nals for polatuzumab vedotin.In the clinical appli-cation of polatuzumab vedotin,in addition to the ADR mentioned in the instructions such as infec-tions,myelosuppression,peripheral neuropathies,infusion-related reactions,and abnormal liver func-tion,attention should also be paid to the risk sig-nals not mentioned such as abnormal spinal mag-netic resonance imaging,and increased bone re-sorption.
2.Characteristics and clinical predictive value of gut microbiota and metabolites related to neoadjuvant chemotherapy effect in patients with colorectal cancer liver metastases
Xinya ZHANG ; Yifan WANG ; Jinming LI ; Shujun ZHANG ; Peilong LI ; Chuanxin WANG ; Lutao DU
Chinese Journal of Laboratory Medicine 2024;47(7):779-788
Objective:To screen the characteristic gut microbiota and fecal metabolites related to the efficacy of oxaliplatin-based neoadjuvant chemotherapy in patients with colorectal cancer liver metastasis, to analyze the relationship between gut microbiota and fecal metabolites, and to evaluate the predictive value of relevant markers for the efficacy of neoadjuvant chemotherapy in patients with colorectal cancer liver metastasis.Methods:This is a case-control study, 34 patients with colorectal cancer liver metastasis who were treated in Qilu Hospital of Shandong University from October 2021 to July 2022 were selected as the research objects, and were divided into chemotherapy effective group (20 cases) and chemotherapy ineffective group (14 cases) according to the efficacy evaluation criteria. Logistic regression was used to construct a prediction model to screen the microbiota and metabolic markers capable of predicting the effect of chemotherapy, and the receiver operating characteristic (ROC) curve and survival analysis curve were plotted to evaluate the predictive effect of related microbiota and metabolites on the efficacy of neoadjuvant chemotherapy.Results:There was no significant difference in the α and β diversity of gut microbiota between the patients in the chemotherapy effective group and in the ineffective group (all P>0.05). In terms of species, the relative abundance of 5 species was up-regulated and 10 species were down-regulated in the chemotherapy-effective group compared with the chemotherapy-ineffective group, and the difference was statistically significant (all P<0.05), among which Prevotella salivae could effectively predict the chemotherapy effect (AUC=0.750, P=0.007), with a sensitivity of 80.0% and a specificity of 71.4%. The overall survival of patients with high abundance (17 cases) was lower than that of patients with low abundance (17 cases) ( χ 2=5.239, P=0.022). In terms of metabolites, 20 metabolites were up-regulated and 4 metabolites were down-regulated in the chemotherapy-effective group compared with the chemotherapy-ineffective group, and the difference was statistically significant (all P<0.05), among which threonine and prostaglandin F2α-1-ethanolamide could distinguish between patients who responded to chemotherapy and those who did not respond to chemotherapy (AUC=0.743, 0.707, all P<0.05), and the overall survival of patients with high levels of relative abundance (17 cases) was higher than that of patients with low levels (17 cases) ( χ 2=4.748, 5.407, all P<0.05). The Logistic regression model of Prevotella salivae and prostaglandin F2α-1-ethanolamide was obtained through screening analysis, and the ROC curve results showed that the model had a good predictive value (AUC=0.836, sensitivity: 90.0%, specificity: 78.6%), and the overall survival of patients with high predict probability (17 cases) predicted by the model was higher than that of patients with low predict probability (17 cases) ( χ 2=9.260, P=0.002). Conclusion:Prevotella salivae and prostaglandin F2α-1-ethanolamide can be used as predictive biomarkers of neoadjuvant chemotherapy for colorectal cancer liver metastasis, and the model has good clinical reference value for prognosis assessment of patients in this cohort.
3.Analysis of causes and solutions for vacuum suction weakness of dental units
Xinya LI ; Yichen WANG ; Yansong LIU ; Anjia ZHENG ; Shubin WU ; Baolin FAN ; Jianxia WANG
China Medical Equipment 2024;21(2):193-195,199
An efficient vacuum suction system is a necessary prerequisite for the smooth operation of the oral diagnosis and treatment.During the use of the dental units,there is often a situation of vacuum suction weakness,resulting in the inability to discharge the mixture of blood,saliva,dental tissue and other mixtures in time,which affects the doctor's treatment field and increases the risk of aspiration pneumonia and cross-infection in patients.The working principle,pipeline system,filters and other aspects of the vacuum suction system that may affect the suction efficiency was analyzed.The causes and solutions of vacuum suction weakness were discussed,and operation suggestions were proposed to ensure the safe and effective use of equipment and ensure the safety of diagnosis and treatment.
4.Risk factors for poor prognosis in patients with extracorporeal cardiopulmonary resuscitation
Junjun WANG ; Shuai TONG ; Ruyi LEI ; Xinya JIA ; Xiaodong SONG ; Tangjuan ZHANG ; Hong WANG ; Yan ZHOU ; Renjie LI ; Xingqiang ZHU ; Chujun YANG ; Chao LAN
Chinese Journal of Emergency Medicine 2024;33(2):215-221
Objective:To analyze the clinical characteristics of patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR), and to explore the risk factors leading to poor prognosis.Methods:The clinical data of 95 patients with ECPR admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to May 2023 were retrospectively analyzed. According to the survival status at the time of discharge, the patients were divided into the survival group and death group. The difference of clinical data between the two groups was compared to explore the risk factors related to death and poor prognosis. Risk factors associated with death were identified by Binary Logistic regression analysis. Results:A total of 95 patients with ECPR were included in this study, 62 (65.3%) died and 33 (34.7%) survived at discharge. Patients in the death group had longer low blood flow time [40 (30, 52.5) min vs. 30 (24.5, 40) min ] and total cardiac arrest time[40 (30, 52.5) min vs. 30(24.5, 40) min], shorter total hospital stay [3 (2, 7.25) d vs. 19 (13.5, 31) d] and extracorporeal membrane oxygenation (ECMO) assisted time [26.5 (17, 50) h vs. 62 (44, 80.5) h], and more IHCA patients (56.5% vs. 33.3%) and less had spontaneous rhythm recovery before ECMO (37.1% vs. 84.8%). Initial lactate value [(14.008 ± 5.188) mmol/L vs.(11.23 ± 4.718) mmol/L], APACHEⅡ score [(30.10 ± 7.45) vs. (25.88 ± 7.68)] and SOFA score [12 (10.75, 16) vs. 10 (9.5, 13)] were higher ( P< 0.05). Conclusions:No spontaneous rhythm recovery before ECMO, high initial lactic acid and high SOFA score are independent risk factors for poor prognosis in ECPR patients.
5.Prognostic value of CAR combined with CPR duration in patients with cardiac arrest
Yan ZHOU ; Chao LAN ; Ruyi LEI ; Qiang ZHANG ; Qing LYU ; Tangjuan ZHANG ; Xinya JIA ; Renjie LI
Chinese Journal of Emergency Medicine 2024;33(7):955-962
Objective:Explore the predictive value of the C-reactive protein to albumin ratio (CAR) and combined indicators for the prognosis of cardiac arrest (CA) patients.Methods:Retrospective analysis was conducted on patients who recovered spontaneous circulation after cardiopulmonary resuscitation (CPR) admitted to the First Affiliated Hospital of Zhengzhou University from January 2021 to May 2023. Patients were divided into survival and non-survival groups based on their status at discharge. Baseline characteristics, CPR data, and laboratory indicators were compared between the two groups. Statistically significant indicators were further analyzed using multivariate logistic regression to identify independent risk factors affecting the prognosis of CA patients. Receiver operating characteristic (ROC) curves were constructed to assess the predictive value of each independent factor and combined indicators for the prognosis of CA patients.Results:A total of 145 patients were included in the study, including 33 patients in the survival group and 112 patients in the non-survival group. There were statistically significant differences between the survival group and the non-survival group in terms of CPR duration, the dosage of vasopressor drugs used, ICU length of stay, Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) score at ICU admission, lactate, fibrinogen, aspartate aminotransferase, albumin, procalcitonin, C-reactive protein, CAR, myoglobin, and creatine kinase isoenzyme (all P < 0.05). Multivariate logistic regression analysis revealed that CAR and CPR duration were independent risk factors affecting the prognosis of CA patients (CAR: OR=2.372, 95% CI: 1.094~5.146, P=0.029; CPR duration: OR=1.170, 95% CI: 1.020~1.342, P=0.025). ROC curve analysis showed that the areas under the curve for CAR, CPR duration, and their combination in predicting patient prognosis were 0.792, 0.731, and 0.859, respectively. The cut-off values for CAR and CPR duration were 1.455 and 11.5 minutes, respectively. Conclusions:The CAR and CPR duration are independent risk factors affecting the prognosis of CA patients, and the predictive value is higher when both CAR and CPR duration are combined. A CAR greater than 1.455 and a CPR duration longer than 11.5 minutes suggest a poorer prognosis for the patients.
6.Construction of pharmacogenomics-guided individualized medication list for elderly patients
Xinya LI ; Jingjing WU ; Liwei JI ; Qingxia ZHANG ; Li YANG ; Hui LI ; Shuang LIU ; Ting LI ; Rongsheng ZHAO ; Zhanmiao YI
China Pharmacy 2023;34(3):257-262
OBJECTIVE To develop an individualized medication list for elderly patients by evidence-based pharmacy method, and to support clinical decisions on rational use of METHODS Firstly, drugs with risk genetic information were screened out by systematically reviewing evidence-based pharmacy information. Secondly, researchers investigated the included drugs in lists from different data E- sources. Drugs included in three or more data sources and drugs proposed by the expert committee were then included in the medication list. Thirdly, for the drugs included in two data sources, researchers designed questionnaires to investigate the necessity of drug-related gene testing. According to the scoring results of the expert questionnaire, drugs with higher scores were included in the list. Data sources included real-world data (list of high frequency medication in hospitals, high frequency medication for elderly outpatients and inpatients in National Health Care Claims Data, drugs related to frequent medication errors and so on) and evidence-based pharmacy evidence (the websites of Clinical Pharmacogenomics Implementation Consortium, Dutch Pharmacogenetics Working Group, Food and Drug Administration and so on). RESULTS The study obtain 68 drugs with risk genetic information which were included in three data sources. Combined with 23 drugs proposed by the expert committee, a list containing 74 drugs was preliminarily formed after de-duplication. A total of 37 drugs included in two databases with risk genetic information were scored through the questionnaire survey to form a supplementary list of 26 drugs. This is the final composition of the list of 100 drugs developed in this study. Among them, there are 43 drugs for the central nervous system, 15 drugs for the cardiovascular system, 12 anti-tumor drugs and so on. Twelve drugs were included in six or more data sources, which mainly consisted of drugs for digestive system, all proton pump inhibitors. CONCLUSION In this study, a list of 100 commonly used drugs which require individualized medication for the elderly was developed by evidence-based pharmacy method. The drug list will be updated in time as available evidence changes, and can provide guidance for rational use of medicines for elderly patients.
7.Research progress of critical illness rehabilitation
Xinya LI ; Yong DAI ; Huai HUANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2023;30(5):636-640
Critical care medicine is an important component of clinical medicine,including multiple aspects such as screening,monitoring,treatment,and rehabilitation of the critical illness.With the formation of the critical care discipline system and the updating of rehabilitation medicine concepts,the early rehabilitation of critically ill patients has become a clinical concern.More and more evidence suggests that moderate sedation,early activity,and exercise in critically ill patients have a positive impact on cognitive function,physical function,mental health,and quality of life.Based on comprehensive rehabilitation assessment,following contraindications and indications,and appropriate and personalized rehabilitation treatment techniques are the key points.Combining artificial intelligence and information technology to assist rehabilitation may be the future development direction.However,there are still problems and obstacles in clinical practice such as low accessibility and uneven management of critical care rehabilitation.Therefore,by reviewing relevant literature on critical care rehabilitation in recent years,this article summarizes the evolution of critical care rehabilitation concepts,the composition and workflow of the multidisciplinary rehabilitation team,indications and contraindications,evaluation and commonly used technologies,the application of artificial intelligence,obstacles and countermeasures for carrying out critical care rehabilitation from the perspective of evaluation and treatment.To provide reference for the early clinical implementation of critical care rehabilitation.
8.A nomogram based on clinical factors and gadobenate dimeglumine-enhanced MRI for prediction of GPC-3 expression in hepatocellular carcinoma
Hui MA ; Li WANG ; Zhi SUN ; Zijian SHEN ; Chuanxi WANG ; Xinya ZHAO
Chinese Journal of Radiology 2022;56(11):1230-1236
Objective:To investigate the predictive value of a nomogram based on clinical factors and gadobenate dimeglumine (Gd-BOPTA)-enhanced MRI for predicting the expression of Glypican-3 (GPC-3) in hepatocellular carcinoma (HCC).Methods:The clinical and imaging data of 85 patients with HCC confirmed by pathology in the Provincial Hospital of Shandong First Medical University from July 2018 to June 2021 were retrospectively collected. All the patients underwent Gd-BOPTA-enhanced MRI scan before operation. According to the expression of GPC-3 by immunohistochemistry, the patients were divided into GPC-3 positive group (55 cases) and GPC-3 negative group (30 cases). The clinical data of patients were collected, including gender, age, hepatitis, cirrhosis, alpha-fetoprotein (AFP), alanine aminotransferase, aspartate aminotransferase, and glutamine transferase levels. The MRI qualitative signs including tumor margin, ring enhancement, intratumoral hemorrhage, enhanced capsule, and satellite nodules were reviewed. MRI quantitative parameters including the largest tumor diameter, Gd-BOPTA-enhanced tumor-to-liver parenchyma signal ratio (TLR) and tumor enhancement ratio (TER) in arterial phase (AP), portal venous phase (PP), and hepatobiliary phase (HBP) were calculated. The independent sample t-test or Mann-Whitney U test were used to compare the quantitative data between the two groups, and the χ2 test was used to compare the qualitative data between the two groups. Multivariate logistic regression analysis was used to identify the independent predictors of GPC-3 expression, and a nomogram model was established. The receiver operating characteristic (ROC) curves were used to evaluate the predictive performance of each independent factor and nomogram, and DeLong test was used to compare differences in area under the curve (AUC). Results:There were significant differences in AFP, tumor margin, intratumoral hemorrhage, and TLR-AP, TLR-PP and TLR-HBP between GPC-3 positive and negative groups (all P<0.05). Multivariate logistic regression results showed that AFP≥20 μg/L, intratumoral hemorrhage and TLR-HBP were independent predictors of GPC-3 positive expression in HCC (OR=3.816, 4.788, 0.001, all P<0.05). The preoperative clinical and Gd-BOPTA-enhanced MRI nomogram model for predicting GPC-3 expression in hepatocellular carcinoma was established. The AUC of AFP≥20 μg/L, intratumoral hemorrhage, TLR-HBP and nomogram model in predicting GPC-3 positive expression were 0.688, 0.697, 0.808, and 0.879, respectively. The AUC of nomogram model was significantly better than those of the other three single indicator ( Z=3.82, 4.13, 2.04, P<0.001,<0.001,=0.042). Conclusion:The nomogram model based on indicators of clinical and qualitative and quantitative Gd-BOPTA-enhanced MRI has better performance in predicting the expression of HCC GPC-3 before surgery, which is higher than those of each single indicator.
9.The predictive value of extra pulmonary multiple factors including creatine kinase-isoenzyme MB in prognosis of patients with acute paraquat poisoning
Chao LAN ; Nengyuan XU ; Xing MENG ; Xinya JIA ; Zhongshi LI ; Qing LYU ; Jinran YANG ; Huan LU
Chinese Journal of Emergency Medicine 2020;29(1):112-120
Objective To investigate the predictive value of extra pulmonary multiple factors including creatine kinase-isoenzyme MB (CK-MB) for the prognosis of patients with acute paraquat poisoning.Methods A retrospectively analysis were conducted on 641 patients who were treated at the First Affiliated Hospital of Zhengzhou University due to oral paraquat poisoning from October 2002 to April 2017.The observation end point was that the patients died from paraquat poisoning within 3 months after admission or were still alive within 3 months after paraquat poisoning.The patients' data were retrieved,including general information,the dose of poison,urinary paraquat concentration,arterial blood gas analysis,alanine transaminase (ALT),total bilirubin (TBIL),uric acid (UA),aspartate transaminase (AST),creatine kinase (CK),CK-MB,B type natriuretic peptide (BNP),lactic dehydrogenase (LDH),high sensitivity troponin T (hsTnT),C-reaction protein (CRP) and procaicitonin (PCT).According to the patient's prognosis within 3 months,the patients were divided into a survival group and a non-survival group.The above indicators were compared between the two groups and the diagnostic value of CK-MB for acute paraquat poisoning was analyzed according to the receiver operating characteristics (ROC) curve.Collect the last arterial blood gas analysis,and laboratory test results were analyzed by binary logistic regression analysis to determine the risk factors for death in patients with acute paraquat poisoning.Results Among the 641 patients with acute paraquat poisoning,315 (49.1%) patients survived and 326 (50.9%) died.Compared with the survival group,patients in the non-survival groupthere were older,had a shorter hospital stay,and had a higher oral paraquat dose and urinary paraquat concentration;Lac,TBIL,UA,AST,CK,CK-MB,BNP,LDH,CRP and PCT were higher,while blood gas analysis index were lower in the non-survival group (P<0.05).Binary logistic regression analysis showed that the dose of paraquat,CK-MB and AST were closely related to the prognosis of patients with acute paraquat poisoning.The optimal cut-off value of ingestion dose,the first urinary paraquat concentration on admission and CK-MB in predicting the prognosis of patients with acute paraquat poisoning were 7 g (AUC=0.918,sensitivity 80.6%,specificity 87.5%,Yoden index 0.681,P<0.01),5.16 μg/mL (AUC=0.879,sensitivity 93.8%,specificity 70.1%,Yoden index 0.639,P<0.01),and 18.2 U/L (AUC=0.846,sensitivity 83.9%,specificity 71.9%,Yoden index 0.558,P<0.01),respectively.Binary logistic regression analysis of the last biochemical indicators of paraquat poisoning showed that the dose of poison,the last CK-MB,the last SCr,urinary paraquat concentration,and the last blood Na+ were closely related to the prognosis of patients with acute paraquat poisoning.Among them,the last CK-MB>18.05 U/L often indicated poor prognosis (AUC=0.808,sensitivity 79.7%,specificity 65.8%,Yoden index 0.455,P<0.01).Conclusions In the treatment of patients with acute paraquat poisoning,there are significant differences in extra pulmonary factors such as heart,liver,kidney,electrolytes and inflammatory markers in patients with different prognosis,so the monitoring and follow-up should be improved,in addition to focusing on the presence and treatment of pulmonary fibrosis.In particular,CK-MB is an independent risk factor for the prognosis of acute paraquat poisoning.In the late stage of poisoning,CK-MB,SCr,and blood Na+ have a strong predictive value for the prognosis of the patients,and we should pay attention to the regular follow-up of the above mentioned laboratory items.
10.Detection of MSX1 gene mutations in patients with congenital tooth loss in Van der Woude syndrome
DU Xinya ; LI Xiaoyu ; XIE Chun ; WU Bin ; SONG Guangbao ; DU Ye
Journal of Prevention and Treatment for Stomatological Diseases 2020;28(1):47-51
Objective:
To explore the relationship between MSX1 gene detection and tooth loss in a Van der Woude syndrome (VWS) family
Methods :
DNA was extracted from the venous blood of 2 patients with dental hy⁃podontia in the 9th family of Van der Woude syndrome (VWS) families and 62 controls with complete dentition. Primers were designed for the MSXl gene. The coding regions of exons 1 and 2 of the MSX1 gene were amplified by PCR. The purified products of exons 1 and 2 of the MSX1 gene were sequenced and analyzed by sequence alignment
Results:
The ivs2+68 C>T polymorphism in the MSX1 gene was found in the VWS9 members with tooth loss, and the VWS pa⁃tients with IRF6 gene mutations had increased tooth loss
Conclusion
Congenital tooth loss in the patients with con⁃genital missing teeth in VWS family 9 may be related to the ivs2 + 68 C> T polymorphism of the MSX1 gene.


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