1.Predictive model for severe adverse reaction associated with bevacizumab based on the global trigger tool and machine learning
Yongfei FU ; Xin LONG ; Hongzhen XU ; Jian TANG ; Xiangqing LI ; Yucheng LONG ; Dong QIN
China Pharmacy 2026;37(4):497-503
OBJECTIVE To confirm trigger items for adverse drug reaction (ADR) induced by bevacizumab, to identify and analyze the occurrence of related ADR, and to establish a predictive model for severe adverse reaction (SAR) caused by this drug. METHODS Based on the global trigger tool (GTT) theory, and referencing the GTT White Paper, drug package inserts and relevant literature, trigger items for bevacizumab-related ADR were confirmed using a single-round Delphi method. Utilizing these established items, electronic medical records of relevant patients at Guilin People’s Hospital from January 2020 to September 2024 were actively screened via the China Hospital Pharmacovigilance System. Pharmacists then identified and tallied the occurrence of bevacizumab-induced ADR. Data from patients with any positive trigger item served as the study subjects (divided into training and test sets at a ratio of 7∶3), candidate feature variables were selected from 39 related variables using the Boruta algorithm, and the multivariable Logistic regression analysis was performed with the occurrence of SAR as the dependent variable. Based on these candidate features, Logistic Regression, Extreme Gradient Boosting, Light Gradient Boosting Machine, Random Forest, and Categorical Boosting models were constructed. Model performance was evaluated using metrics including the area under the curve (AUC) of receiver operating characteristic curve and recall rate. The Shapley Additive exPlanations (SHAP) method was applied to analyze and interpret the contribution of each variable. A nomogram was constructed based on the optimal model. RESULTS A total of 38 trigger items for active monitoring of bevacizumab-related ADR were determined, comprising 17 laboratory indicators, 13 clinical manifestations, and 8 intervention measures. In total, 483 patients with positive trigger items were included, and 318 patients with bevacizumab-induced ADR were identified, including 83 SARs. The positive predictive values for the trigger items and cases were 43.57% (708/1 625) and 63.84% (318/483), respectively. Bevacizumab-induced ADR involved 7 systems/organs, with the hematological system being the most frequently involved (64.15%). The Boruta algorithm selected 7 vari ables: serum potassium, hematocrit, albumin-to-globulin ratio, prealbumin, hypertension history, age and red blood cell count. Multivariable Logistic regression showed that elevated serum potassium levels were associated with a decreased risk of bevacizumab-induced SAR (OR=0.234, P =0.002), while a history of hypertension (OR=2.642, P =0.006) and increased age (OR=1.040, P =0.025) were associated with an increased risk. The Logistic Regression model demonstrated superior performance with higher AUC, F1 score and recall rate (0.761, 0.447, 0.607), compared to other models. SHAP evaluation results indicated that variables such as serum potassium, hematocrit, and age ranked highest in importance. CONCLUSIONS Totally 38 trigger entries have been successfully identified for active screening of bevacizumab-related ADR. Elevated serum potassium levels are a protective factor against bevacizumab-induced SAR, whereas the hypertension history and increased age are risk factors. The Logistic Regression model is the optimal predictive model.
2.Expression and diagnostic value of serine-threonine kinase 1 and isochorismatase domain-containing 1 in gastric cancer
Jiangqiao ZHAO ; Liping FU ; Long YANG ; Zhiqiang DONG ; Shuli SONG ; Benxin YANG
The Journal of Practical Medicine 2025;41(13):2033-2038
Objective To explore the expression of serine/threonine protein kinase 1(AKT1)and Isocho-rismatase Domain-Containing 1(ISOC1)in gastric cancer tissues and evaluate their diagnostic utility.Methods A total of 90 patients with gastric cancer who were diagnosed and treated in our hospital between March 2023 and September 2024 were recruited as the study subjects.The positive expression rates and positive scores of AKT1 and ISOC1 in cancer tissues and adjacent tissues were compared.The AKT1 and ISOC1 positive scores of gastric cancer patients with diverse characteristics were also compared.The Spearman correlation analysis was employed to exam-ine the relationship between the expression of AKT1 and ISOC1 in cancer tissues and the clinical features of gastric cancer patients.A diagnostic model for gastric cancer,integrating AKT1 and ISOC1,was established using the Logistic regression model.Receiver operating characteristic(ROC)curves were plotted to analyze the area under the curve(AUC)value,sensitivity,and specificity of AKT1,ISOC1,and their combined diagnosis for gastric cancer.Results The positive expression rates and positive scores of AKT1 and ISOC1 in cancer tissues were significantly higher than those in paracancerous tissues(P<0.05).In gastric cancer patients,the expressions of AKT1 and ISOC1 were notably higher in patients with low differentiation,clinical stage Ⅰ~Ⅱ,invasion depth T1-2,absence of lymph node metastasis,and no distant metastasis compared to those with moderate differentiation,clinical stage Ⅲ~Ⅳ,invasion depth T3-4,and presence of lymph node metastasis and distant metastasis(P<0.05).Spearman's correlation analysis indicated that AKT1 and ISOC1 were positively correlated with the degree of differ-entiation,clinical stage,lymph node metastasis,invasion degree,and distant metastasis(P<0.05).The area under the curve(AUC)values of AKT1,ISOC1,and their combined diagnosis for gastric cancer were 0.735,0.726,and 0.875 respectively(P<0.05).The sensitivities were 60.00%,56.70%,and 75.60%,while the speci-ficities were 85.60%,83.30%,and 87.80%.The AUC value of the combined detection of AKT1 and ISOC1 in the diagnosis of gastric cancer was higher than that of AKT1 or ISOC1 alone(Z=-3.003,-3.196,P<0.05).Conclusions AKT1 and ISOC1 are highly expressed in gastric cancer tissues,and their expressions are upregu-lated with the progression of the disease.The combined detection of their expression levels holds great significance for the diagnosis and prognosis assessment of gastric cancer.
3.Transcriptomic and Metabolomic Investigations on the Effects of High Salt Stress on Hydroxyectoine Biosynthesis in Virgibacillus Salexigens
Meng-Yao DONG ; Qi-Fu LONG ; Jiang-Wa XING ; Xiang GAO ; Yong-Zhen LI
Chinese Journal of Biochemistry and Molecular Biology 2025;41(4):586-596
To investigate the impact of high salt stress on the metabolic pathways and regulatory mecha-nisms involved in synthesizing hydroxyectoine(5-HE)in Virgibacillus salexigens,cultures were supple-mented with 1.5 and 2.5 mol/L NaCl as control and experimental groups,respectively.High-perform-ance liquid chromatography(HPLC)was used to detect the difference in the amount of 5-HE synthesis.Transcriptomic and metabolomic analyses identified differential genes and metabolites under varying salt concentrations.Key differential gene expressions related to 5-HE synthesis were validated using qRT-PCR.Results showed that 5-HE synthesis reached 121.9 mg/L at 2.5 mol/L NaCl.Transcriptomic anal-ysis identified 652 differentially expressed genes across 348 KEGG pathways,with 210 upregulated and 442 downregulated,primarily enriched in pathways such as purine metabolism,amino acid biosynthesis,sulfur metabolism,and biotin metabolism.Validation of 13 genes,including lysC,asd,ectA,ectB,ectC,ectD,thrB,thrC,ilvA,ilvE,AGXT,YckA and GlnQ,showed expression trends consistent with transcriptome data.Metabolomic analysis identified 1153 metabolites predominantly enriched in histidine metabolism,lysine degradation,and arginine and proline metabolism.This study preliminarily elucidated the effect of high salt on the 5-HE synthesis pathway,and provided a basis for the subsequent construc-tion of 5-HE high-yielding strains.
4.Transcriptomic and Metabolomic Investigations on the Effects of High Salt Stress on Hydroxyectoine Biosynthesis in Virgibacillus Salexigens
Meng-Yao DONG ; Qi-Fu LONG ; Jiang-Wa XING ; Xiang GAO ; Yong-Zhen LI
Chinese Journal of Biochemistry and Molecular Biology 2025;41(4):586-596
To investigate the impact of high salt stress on the metabolic pathways and regulatory mecha-nisms involved in synthesizing hydroxyectoine(5-HE)in Virgibacillus salexigens,cultures were supple-mented with 1.5 and 2.5 mol/L NaCl as control and experimental groups,respectively.High-perform-ance liquid chromatography(HPLC)was used to detect the difference in the amount of 5-HE synthesis.Transcriptomic and metabolomic analyses identified differential genes and metabolites under varying salt concentrations.Key differential gene expressions related to 5-HE synthesis were validated using qRT-PCR.Results showed that 5-HE synthesis reached 121.9 mg/L at 2.5 mol/L NaCl.Transcriptomic anal-ysis identified 652 differentially expressed genes across 348 KEGG pathways,with 210 upregulated and 442 downregulated,primarily enriched in pathways such as purine metabolism,amino acid biosynthesis,sulfur metabolism,and biotin metabolism.Validation of 13 genes,including lysC,asd,ectA,ectB,ectC,ectD,thrB,thrC,ilvA,ilvE,AGXT,YckA and GlnQ,showed expression trends consistent with transcriptome data.Metabolomic analysis identified 1153 metabolites predominantly enriched in histidine metabolism,lysine degradation,and arginine and proline metabolism.This study preliminarily elucidated the effect of high salt on the 5-HE synthesis pathway,and provided a basis for the subsequent construc-tion of 5-HE high-yielding strains.
5.Expression and diagnostic value of serine-threonine kinase 1 and isochorismatase domain-containing 1 in gastric cancer
Jiangqiao ZHAO ; Liping FU ; Long YANG ; Zhiqiang DONG ; Shuli SONG ; Benxin YANG
The Journal of Practical Medicine 2025;41(13):2033-2038
Objective To explore the expression of serine/threonine protein kinase 1(AKT1)and Isocho-rismatase Domain-Containing 1(ISOC1)in gastric cancer tissues and evaluate their diagnostic utility.Methods A total of 90 patients with gastric cancer who were diagnosed and treated in our hospital between March 2023 and September 2024 were recruited as the study subjects.The positive expression rates and positive scores of AKT1 and ISOC1 in cancer tissues and adjacent tissues were compared.The AKT1 and ISOC1 positive scores of gastric cancer patients with diverse characteristics were also compared.The Spearman correlation analysis was employed to exam-ine the relationship between the expression of AKT1 and ISOC1 in cancer tissues and the clinical features of gastric cancer patients.A diagnostic model for gastric cancer,integrating AKT1 and ISOC1,was established using the Logistic regression model.Receiver operating characteristic(ROC)curves were plotted to analyze the area under the curve(AUC)value,sensitivity,and specificity of AKT1,ISOC1,and their combined diagnosis for gastric cancer.Results The positive expression rates and positive scores of AKT1 and ISOC1 in cancer tissues were significantly higher than those in paracancerous tissues(P<0.05).In gastric cancer patients,the expressions of AKT1 and ISOC1 were notably higher in patients with low differentiation,clinical stage Ⅰ~Ⅱ,invasion depth T1-2,absence of lymph node metastasis,and no distant metastasis compared to those with moderate differentiation,clinical stage Ⅲ~Ⅳ,invasion depth T3-4,and presence of lymph node metastasis and distant metastasis(P<0.05).Spearman's correlation analysis indicated that AKT1 and ISOC1 were positively correlated with the degree of differ-entiation,clinical stage,lymph node metastasis,invasion degree,and distant metastasis(P<0.05).The area under the curve(AUC)values of AKT1,ISOC1,and their combined diagnosis for gastric cancer were 0.735,0.726,and 0.875 respectively(P<0.05).The sensitivities were 60.00%,56.70%,and 75.60%,while the speci-ficities were 85.60%,83.30%,and 87.80%.The AUC value of the combined detection of AKT1 and ISOC1 in the diagnosis of gastric cancer was higher than that of AKT1 or ISOC1 alone(Z=-3.003,-3.196,P<0.05).Conclusions AKT1 and ISOC1 are highly expressed in gastric cancer tissues,and their expressions are upregu-lated with the progression of the disease.The combined detection of their expression levels holds great significance for the diagnosis and prognosis assessment of gastric cancer.
6.A comparative study of different surgical method for stage ⅠA non-small cell lung cancer
Wang HE ; Tong-Xin LI ; Yu ZHOU ; Dong WANG ; Sheng-Yuan HUANG ; Xiao-Long ZHANG ; Yong FU
Journal of Regional Anatomy and Operative Surgery 2024;33(3):226-230
Objective To compare the clinical efficacies of video-assisted thoracoscopic segmentectomy versus lobectomy for early-stage non-small cell lung cancer.Methods The clinical data of 234 patients with stage ⅠA non-small cell lung cancer and undergoing different surgical methods under video-assisted thoracoscopy admitted to Chongqing Dianjiang General Hospital were retrospectively analyzed,and the patients were divided into the lung segment group and the lung lobe group according to their surgical methods.The clinical characteristics of the patients in the two groups were balanced by a 1-to-1 ratio matching through the propensity score matching method,and each group finally included 63 cases.The perioperative indicators containing operation time,intraoperative blood loss,postoperative thoracic drainage tube indwelling time,thoracic drainage volumes 24 hours and 48 hours after operation and postoperative hospital stay were compared of patients between the two groups.The incidence of postoperative complications such as air leakage>6 days,pulmonary infection,atelectasis,hemoptysis,and hoarseness in the two groups was collected.Results There was no significant difference in the operation time,intraoperative blood loss,thoracic drainage volumes 24 hours and 48 hours after operation,postoperative thoracic drainage tube indwelling time or incidence of postoperative complications of patients between the two groups(P>0.05).The postoperative hospital stay of patients in the lung segment group was shorter than that in the lung lobe group,with statistically significant difference(P=0.003).Conclusion For patients with stage ⅠA non-small cell lung cancer,video-assisted thoracoscopic segmentectomy has similar perioperative efficacy to lobectomy,while segmentectomy has a more significant advantage in shortening the hospital stay.
7.A retrospective study of occlusal reconstruction in patients with old jaw fractures and dentition defects
Ming-Chao DING ; Bo-Ya JING ; Jin SHI ; Liu YANG ; Xiang-Dong LIU ; Jing-Fu WANG ; Shuang QU ; Jia-Wu LIANG ; Zi-Hao TANG ; Jin-Long ZHAO ; Lei TIAN
Chinese Journal of Traumatology 2024;27(5):272-278
Purpose::This study evaluated the methods and clinical effects of multidisciplinary collaborative treatment for occlusal reconstruction in patients with old jaw fractures and dentition defects.Methods::Patients with old jaw fractures and dentition defects who underwent occlusal reconstruction at the Third Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2022 were enrolled. Clinical treatment was classified into 3 phases. In phase I, techniques such as orthognathic surgery, microsurgery, and distraction osteogenesis were employed to reconstruct the correct 3-dimensional (3D) jaw position relationship. In phase II, bone augmentation and soft tissue management techniques were utilized to address insufficient alveolar bone mass and poor gingival soft tissue conditions. In phase III, implant-supported overdentures or fixed dentures were used for occlusal reconstruction. A summary of treatment methods, clinical efficacy evaluation, comparative analysis of imageological examinations, and satisfaction questionnaire survey were utilized to evaluate the therapeutic efficacy in patients with traumatic old jaw fractures and dentition defects. All data are summarized using the arithmetic mean ± standard deviation and compared using independent sample t-tests. Results::In 15 patients with old jaw fractures and dentition defects (an average age of 32 years, ranging from 18 to 53 years), there were 7 cases of malocclusion of single maxillary fracture, 6 of malocclusion of single mandible fracture, and 2 of malocclusion of both maxillary and mandible fractures. There were 5 patients with single maxillary dentition defects, 2 with single mandibular dentition defects, and 8 with both maxillary and mandibular dentition defects. To reconstruct the correct 3D jaw positional relationship, 5 patients underwent Le Fort I osteotomy of the maxilla, 3 underwent bilateral sagittal split ramus osteotomy of the mandible, 4 underwent open reduction and internal fixation for old jaw fractures, 3 underwent temporomandibular joint surgery, and 4 underwent distraction osteogenesis. All patients underwent jawbone augmentation, of whom 4 patients underwent a free composite vascularized bone flap (26.66%) and the remaining patients underwent local alveolar bone augmentation. Free gingival graft and connective tissue graft were the main methods for soft tissue augmentation (73.33%). The 15 patients received 81 implants, of whom 11 patients received implant-supported fixed dentures and 4 received implant-supported removable dentures. The survival rate of all implants was 93.82%. The final imageological examination of 15 patients confirmed that the malocclusion was corrected, and the clinical treatment ultimately achieved occlusal function reconstruction. The patient satisfaction questionnaire survey showed that they were satisfied with the efficacy, phonetics, aesthetics, and comfort after treatment.Conclusion::Occlusal reconstruction of old jaw fractures and dentition defects requires a phased sequential comprehensive treatment, consisting of 3D spatial jaw correction, alveolar bone augmentation and soft tissue augmentation, and implant-supported occlusal reconstruction, achieving satisfactory clinical therapeutic efficacy.
8.Performance test of high-flow nasal cannula oxygen therapy device at different altitudes
Chun-Wei HE ; Ya-Ting WANG ; Yi-Long ZHOU ; Hui WANG ; Zi-Yu FU ; De-Dong MA
Chinese Medical Equipment Journal 2024;45(6):49-58
Objective To investigate the performance of brands and types of high-flow nasal cnnula oxygen therapy(HFNC)devices at different altitudes.Methods Four different models of HFNC devices,including R-80S bi-level non-invasive ventilator integrated with HFNC device,HF-60A HFNC device,HFT-300 HFNC device and H-80A HFNC device,were connected with the gas flow meter,simularted head and QuickLung and then put into a low-pressure chamber.The flow rates of the HFNC devices were set to 10,15,20,25,30,35,40,45,50,55 and 60 L/min,and the simulated altitudes of the low-pressure chamber were set to 6 000,5 000,4 000,3 000,2 000,1 000 and 0 m.The actual output airway flow rates,airway pressure changes and trends of the four HFNC devices were recorded at different setting altitudes and flow rates.SPSS 25.0 software was used for statistical analysis.Results The actual output airway flow rates of the four HFNC devices showed an increasing trend as the altitude rose with the simulated altitude of 6 000 m and the setting flow rate kept constant,which increased slowly and even went to decrease when the altitude and flow rate exceeded some limits.The degree of changes in the flow rate with the increasing altitude varied,and there was no uniform pattern.With the rising of altitude,the actual output airway pressure of the four HFNC devices with the flow rate raning from 10 to 35 L/min also increased gradually,which showed a decreasing trend(turning point)after going up to some certain value when the flow rate exceeded 35 L/min,and the altitude where the turning point appeared was lowered as the flow rate increased.Conclusion The actual output airway flow rates and airway pressure during HFNC rise at a high-altitude environment,and generally considerations have to be taken on required airway pressure,patient comfort and the altitude of the patient's usual place of residence when setting the flow rates of the HFNC device.[Chinese Medical Equipment Journal,2024,45(6):49-58]
9.Interpretation of the Interim Measures for the Management of Surplus Drugs in Medical Institutions in Hubei Province
Guangxin DU ; Wei FU ; Xuehong ZHOU ; Dong LIU ; Juan LI ; Ping LONG
Herald of Medicine 2024;43(9):1376-1380
This article introduced the background,drafting process,and main content of the Interim Measures for the Management of Surplus Drugs in Medical Institutions of Hubei Province(referred as the Measures).It focused on explaining the definition of surplus drugs and analyzing the requirements for drug dismantling,surplus drug billing,recovery and use procedures,special fund management,and duties and responsibilities of management departments.This paper aimed to guide readers to learn the Measures,understand the Measures and implement the Measures.It would help to improve the efficiency of medical resources,ensure medication safety,reduce patients'medication burden,and promote the rational use of medical insurance funds.
10.A cohort study of incidence of club drug abuse in men who have sex with men in Qingdao.
Gui Hua HUANG ; Li Min ZHU ; Xin SONG ; Yong FU ; Lin GE ; Pei Long LI ; Dong Min LI
Chinese Journal of Epidemiology 2023;44(5):802-808
Objective: To understand and analyze the incidence of club drug abuse and influencing factors in men who have sex with men (MSM) in Qingdao, and provide reference for the AIDS prevention and intervention in this population. Methods: From March 2017 to July 31, 2022, MSM who did not abuse club drug were recruited by snowball sampling of MSM social organizations in Qingdao, a prospective cohort was established, and a follow-up survey was conducted every 6 months. The survey collected the information about the MSM's demographic characteristics, sexual characteristics, club drug abuse and others. The incidence of club drug abuse was the outcome dependent variable and the interval between the recruitment into the cohort and the incidence of club drug abuse was the time dependent variable. Cox regression analysis was conducted to identify the influencing factors for club drug abuse. Results: A total of 509 MSM were recruited at baseline survey, and 369 eligible MSM were enrolled in this cohort. A total of 62 MSM began to abuse club drug during the study period, and the cumulative follow-up time was 911.54 person-years, the incidence of club drug abuse was 6.80/100 person-years. All the club drug abusers shared drugs with others in the first club drug abuse, and 16.13% (10/62) had mix-use of club drugs. The multivariate Cox proportional risk regression analysis showed that being students (aHR=2.17, 95%CI: 1.15-4.10), receiving no HIV testing or receiving 1 HIV testing during past 6 months (aHR=4.57, 95%CI:1.80-11.60; aHR=5.15, 95%CI: 2.83-9.36), having sex only with regular sexual partners during past 6 months (aHR=4.75,95%CI:2.32-9.75), having more than 4 homosexual partners (aHR=1.70, 95%CI:1.01-2.87) and abuse of club drug of sexual partners during past 6 months (aHR=12.78, 95%CI:3.06-53.35) were significantly associated with club drug abuse in the MSM. Conclusions: The incidence of club drug abuse was at a high level in the MSM cohort in Qingdao, indicating a high risk for HIV infection. Being student, receiving less HIV testing, having sex only with regular sexual partners, having more homosexual partners and abuse of club drug of sexual partners during past 6 months were risk factors for the incidence of club drug abuse in the MSM. Targeted surveillance and intervention measures should be strengthened to reduce the risk of club drug abuse in MSM.
Male
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Humans
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Homosexuality, Male
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Cohort Studies
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Illicit Drugs
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Incidence
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HIV Infections
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Prospective Studies
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Sexual and Gender Minorities
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Substance-Related Disorders

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