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.Exploration on the Diagnosis and Treatment of Esophageal Carcinoma from the Perspective of "Failure of Spleen and Kidney Warming,Internal Accumulation of Phlegm-Toxin" Based on Lipid Metabolism Disorder-Mediated Tumor Microenvironmental Imbalance
Shangfeng YUE ; Jiafan CHEN-YUAN ; Xuyang LIU ; Yaxing LI ; Hongzhen YIN ; Shaobo HU ; Ying SU ; Jie LI
Journal of Traditional Chinese Medicine 2026;67(15):1613-1617
Based on the modern understanding that lipid metabolism disorders mediate tumor microenvironmental imbalance in esophageal carcinoma, this paper proposes that failure of spleen and kidney warming and internal accumulation of phlegm-toxin constitute the core pathogenesis of esophageal carcinoma. Deficiency of spleen and kidney yang qi serves as the root cause, while impaired transformation and transportation of lipids and the accumulation of phlegm-toxin represent the superficial manifestations. Phlegm originates from the transformation of lipids, while toxin arises from and attaches to phlegm. Their interaction forms a sticky and persistent pathological state that runs throughout the entire disease process. The evolution of pathogenesis follows a dynamic and progressive pattern. In the early stage, failure of spleen and kidney warming and dysfunction of lipid metabolism mediate abnormalities in a lipid-enriched microenvironment; in the middle stage, lipid turbidity condenses into phlegm, and phlegm-toxin stasis promotes the formation of an inflammatory and hypercoagulable microenvironment; in the late stage, dysfunction of the sanjiao (三焦) warming function and impaired qi transformation lead to an imbalance in the hypoxic and metabolically dysfunctional microenvironment. Accordingly, a staged therapeutic approach is proposed, including warming the kidney and strengthening the spleen, transforming phlegm and resolving toxin, and warming and unblocking the sanjiao. By regulating lipid metabolism to restore tumor microenvironmental homeostasis, this approach provides a new theore-tical perspective and practical strategy for the intervention of esophageal cancer progression through traditional Chinese medicine.
3.Exploration on the Diagnosis and Treatment of Esophageal Carcinoma from the Perspective of "Failure of Spleen and Kidney Warming,Internal Accumulation of Phlegm-Toxin" Based on Lipid Metabolism Disorder-Mediated Tumor Microenvironmental Imbalance
Shangfeng YUE ; Jiafan CHEN-YUAN ; Xuyang LIU ; Yaxing LI ; Hongzhen YIN ; Shaobo HU ; Ying SU ; Jie LI
Journal of Traditional Chinese Medicine 2026;67(15):1613-1617
Based on the modern understanding that lipid metabolism disorders mediate tumor microenvironmental imbalance in esophageal carcinoma, this paper proposes that failure of spleen and kidney warming and internal accumulation of phlegm-toxin constitute the core pathogenesis of esophageal carcinoma. Deficiency of spleen and kidney yang qi serves as the root cause, while impaired transformation and transportation of lipids and the accumulation of phlegm-toxin represent the superficial manifestations. Phlegm originates from the transformation of lipids, while toxin arises from and attaches to phlegm. Their interaction forms a sticky and persistent pathological state that runs throughout the entire disease process. The evolution of pathogenesis follows a dynamic and progressive pattern. In the early stage, failure of spleen and kidney warming and dysfunction of lipid metabolism mediate abnormalities in a lipid-enriched microenvironment; in the middle stage, lipid turbidity condenses into phlegm, and phlegm-toxin stasis promotes the formation of an inflammatory and hypercoagulable microenvironment; in the late stage, dysfunction of the sanjiao (三焦) warming function and impaired qi transformation lead to an imbalance in the hypoxic and metabolically dysfunctional microenvironment. Accordingly, a staged therapeutic approach is proposed, including warming the kidney and strengthening the spleen, transforming phlegm and resolving toxin, and warming and unblocking the sanjiao. By regulating lipid metabolism to restore tumor microenvironmental homeostasis, this approach provides a new theore-tical perspective and practical strategy for the intervention of esophageal cancer progression through traditional Chinese medicine.
4.Exploration on the mechanism of lung cancer treatment from the perspective of phlegm pathogen theory based on inflammatory-metabolic-immune microenvironment
Yuanjiafan CHEN ; Yaxing LI ; Shaobo HU ; Hongzhen YIN ; Chongyang QU ; Shuzhen DUAN ; Yinghua LI ; Jie LI
International Journal of Traditional Chinese Medicine 2025;47(10):1341-1346
The tumor microenvironment (TME) is the cellular milieu in which tumor cells thrive, comprising interacting cells and associated factors that form a complex network of interactions, directly or indirectly influencing the initiation, progression, and metastasis of lung cancer. Through TCM pattern identification, it has been observed thatphlegm-pathogen is closely associated with disorder in the inflammatory-metabolic-immune microenvironments of lung cancer. This involves three key pathological mechanisms: "phlegm-stasis complicated by toxin, qi deficiency with exuberant phlegm, and phlegm-pathogen impairing healthy qi". Molecular mechanism studies have revealed that phlegm-resolving agents can extensively modulate multiple targets or pathways, thereby remodeling the inflammatory-metabolic-immune microenvironments of lung cancer. Consequently, a comprehensive therapeutic strategy integrating "resolving phlegm, dispelling stasis, and detoxifying; supplementing qi, warming yang, and resolving phlegm; and reinforcing healthy qi, tonifying the lung, and eliminating phlegm" is essential to reshape the lung cancer TME and enhance antitumor efficacy.
5.Optimization of clinical target volume delineation for prostate cancer radiotherapy based on prostate bed occurrence patterns in prostate-specific membrane antigen positron emission tomography
Huan ZHANG ; Xin QI ; Xuhe LIAO ; Cheng CHEN ; Jingyun WU ; Jianhua ZHANG ; Yan FAN ; Xianshu GAO ; Hongzhen LI
Chinese Journal of Radiological Medicine and Protection 2025;45(10):966-972
Objective:To explore the optimization potential of clinical target volume (CTV) delineation proposed in the guidelines of the Oncology Group (RTOG), the Francophone Group of Urological Radiotherapy (GFRU), and the European Society for Radiotherapy and Oncology (ESTRO) based on prostate bed local occurrence patterns after radical prostatectomy identified using prostate-specific membrane antigen positron emission tomography (PSMA PET).Methods:A retrospective analysis was conducted on patients with local prostate bed recurrence after radical prostatectomy who underwent PSMA PET at the Department of Nuclear Medicine, Peking University First Hospital from September 2021 to February 2024. The central point of each recurrence was marked. A six-zone method was established based on prostate bed anatomy and the characteristics of cross-sectional imaging. Then, the positional relationships (within or outside) were recorded with respect to recurrences and CTV defined by the RTOG, GFRU, and ESTRO (CTV RTOG, CTV GFRU, and CTV ESTRO), followed the analysis of the recurrence rates and distribution characteristics of various zones. Results:A total of 63 patients with prostate bed recurrence after radical prostatectomy were enrolled in this study, including 97 recurrences. The recurrence rates in the six zones were as follows: 10% of zone 1, 22% of zone 2, 29% of zone 3, 2% of zone 4, 12% of zone 5a, 18% of zone 5b, and 7% of zone 6. Among these zones, zones 2 and 3 showed the highest and second-highest recurrence rates, respectively. CTV GFRU and CTV ESTRO completely covered zones 2 and 3, while CTV RTOG covered zone 2 completely and zone 3 partially. Zone 4, characterized by a low recurrence rate, was not covered by CTV GFRU and CTV ESTRO but was entirely covered by CTV RTOG. Zone 5a, with a recurrence rate of 12%, was completely covered by CTV RTOG but was partially covered by CTV GFRU and CTV ESTRO. The range of 1.3 cm in front of the posterior wall of the bladder covered all recurrences in zone 5a. Conclusions:For CTV delineation of the prostate cancer surgical bed, zone 4, the anterior half of the bladder above the pubic symphysis midpoint, should be contracted due to the low recurrence rate in this zone. In contrast, the anterior boundary above the pubic symphysis midpoint should extend to 1.3 cm in front of the posterior wall of the bladder to completely cover the recurrence zones.
6.Discussion on the Treatment of Radiation Enteritis Based on the Principle of"Stabilizing the Zhongzhou,Regulating the Intestines"
Yuanjiafan CHEN ; Yaxing LI ; Yuanyuan GUO ; Hongzhen YIN ; Shaobo HU ; Chunfang TIAN ; Min LIU ; Jie LI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(10):169-173
Radiation enteritis(RE)is an inflammatory reaction caused by radiation exposure,commonly observed following radiotherapy for malignancies in the abdominal,pelvic and retroperitoneal regions.The authors believe that the pathogenesis of RE is complex,involving factors such as deficiency and excess,cold and heat,as well as qi and blood.The general pathogenesis can be summarized as"instability of the Zhongzhou,depletion of essence and blood,dysregulation of ascending and descending,and accumulation of heat-toxins".And"the instability of the Zhongzhou and subsequent malnutrition of the intestines"are the key drivers of disease progression.Based on theoretical exploration and clinical observations,this article proposed a comprehensive diagnostic and therapeutic approach centered on"stabilizing the Zhongzhou,replenishing essence and blood,regulating ascending and descending functions,and clearing heat-toxins".These four methods are often applied simultaneously,with"stabilizing the Zhongzhou and regulating the intestines"serving as the core of treatment.The approach is tailored according to the individual patient's condition of blood,qi and body fluids.A medical case was attached as evidence for verification.
7.Malignancy risk assessment and cause analysis of the Bethesda class Ⅰ/Ⅲ cytolo-gy diagnosis due to insufficient cell volume in thyroid solid nodule
Hongzhen YU ; Ming LI ; Xiang XIE ; Xiaofeng LAN ; Tianyu XU ; Shan HUANG ; Xian WANG ; Zhenzhong FENG
Chinese Journal of Clinical and Experimental Pathology 2025;41(1):44-50
Purpose To investigate the incidence and risk of malignancy(ROM)of the Bethesda class Ⅰ/Ⅲ di-agnosis of thyroid nodules due to insufficient number of follicular cells,and to analyze the correlation between their in-sufficient cell volume and the characteristics of the nodules themselves from the perspective of ultrasound and histology.Methods Clinical data were collected from fine needle aspiration cytology(FNAC)of the thyroid gland.Review and statistical analysis was performed on cases with the Bethesda class Ⅰ/Ⅲ diagnosis due to insufficient cell volume.The incidence and the ROM of Bethesda class Ⅰ/Ⅲ diagnosis were calculated.BRAF V600E(+)or postoperative patho-logical indicating papillary thyroid carcinoma(PTC)was used as the criterion for malignancy.Then,we matched the Bethesda class Ⅱ/Ⅵ cases with sufficient cell volume as the control group.The ultrasound characteristics and histo-logical images of the two groups were compared and analyzed in order to reveal the correlation between the insufficient amount of penetrating cells and the objective characteristics of the nodule itself.Results There were 39 solid thyroid nodules with the Bethesda class Ⅰ diagnosis,with an incidence of 3.3%and a ROM of 38.5%,and 160 nodules with the Bethesda class Ⅲ diagnosis,with an incidence of 13.5%and a ROM of 59.4%.The incidence and ROM of nod-ules with C-TIRADS ≥4b(22.4%,67.6%)were higher than those of C-TIRADS ≤4a(12.7%,39.8%),and the differences were statistically significant(P<0.001).Compared to the Bethesda class Ⅱ/Ⅵ nodules with sufficient cell volume,occurrence of the Bethesda class Ⅰ/Ⅲ nodules were significantly correlated with small nodules(maximal diameter<5 mm),vertical growth(aspect ratio ≥ 1)and poor blood supply(no or little blood flow signals)(r=0.131,-0.230,0.237,P=0.008,<0.001,<0.001).They were also significantly correlated with the pathologic histologic structure of diffuse significant fibrosis of the interstitium and low parenchyma/interstitium composition ratio(about 1:1)(r=-0.269,-0.396,P=0.019,<0.001).Conclusion Thyroid Bethesda class Ⅰ/Ⅲ nodules have a high ROM,and BRAF V600E detection is recommended as a tool of tiered management.Bethesda class Ⅰ/Ⅲ diagnosis of insufficient cell volume is more likely when the nodules are too small,grow vertically and lack blood sup-ply,presumably associated with extensive interstitial fibrosis and sparse parenchymal cells.
8.Development and application of a healthcare quality evaluation system for national regional medical centers based on the structure-process-outcome Theory
Lizhong LIANG ; Hongzhen ZHOU ; Yan LI ; Tong LI ; Yingzhe LIU ; Hong LI ; Jie ZHENG ; Chao YANG
Modern Hospital 2025;25(11):1651-1655
Objective To develop a scientific,systematic,and operable healthcare quality evaluation system for Nation-al Regional Medical Centers(NRMCs),providing a theoretical basis and practical tool for objectively assessing their construction outcomes and guiding high-quality development.Methods Based on the classic"Structure-Process-Outcome"(SPO)quality management model,and aligned with national policy directives and the functional positioning of regional medical centers,a pre-liminary set of evaluation indicators was screened and an indicator system was constructed through literature review,policy analy-sis,and field investigations.Guangxi Hospital Division of The First Affiliated Hospital,Sun Yat-sen University was selected as the study subject,and cross-sectional data from March 2023 to June 2025 were collected for empirical application.Results A healthcare quality evaluation system for NRMCs was established,comprising 3 first-level dimensions(Structure Quality,Process Quality,Outcome Quality),10 second-level indicators,and 66 third-level indicators.This system covers multiple aspects,inclu-ding resource allocation,healthcare service efficiency,clinical practices,patient outcomes,and social benefits.Empirical results indicated that the center demonstrated a consistent upward trend in key indicators such as"Proportion of Discharged Patients Un-dergoing Level-4 Surgeries"(O1.2)and"DRG-CMI Value"(O2.1),while"Average Length of Hospital Stay"(P3.1)and"Cost Consumption Index"(O2.3)showed a steady decline.The indicator system effectively revealed the center's progress in en-hancing regional influence and operational efficiency.Conclusion The developed healthcare quality evaluation system is well-grounded in theory and practice,combining scientific rigor with policy relevance,and can serve as a decision-support tool for quality assessment and improvement in National Regional Medical Centers.
9.Optimization of clinical target volume delineation for prostate cancer radiotherapy based on prostate bed occurrence patterns in prostate-specific membrane antigen positron emission tomography
Huan ZHANG ; Xin QI ; Xuhe LIAO ; Cheng CHEN ; Jingyun WU ; Jianhua ZHANG ; Yan FAN ; Xianshu GAO ; Hongzhen LI
Chinese Journal of Radiological Medicine and Protection 2025;45(10):966-972
Objective:To explore the optimization potential of clinical target volume (CTV) delineation proposed in the guidelines of the Oncology Group (RTOG), the Francophone Group of Urological Radiotherapy (GFRU), and the European Society for Radiotherapy and Oncology (ESTRO) based on prostate bed local occurrence patterns after radical prostatectomy identified using prostate-specific membrane antigen positron emission tomography (PSMA PET).Methods:A retrospective analysis was conducted on patients with local prostate bed recurrence after radical prostatectomy who underwent PSMA PET at the Department of Nuclear Medicine, Peking University First Hospital from September 2021 to February 2024. The central point of each recurrence was marked. A six-zone method was established based on prostate bed anatomy and the characteristics of cross-sectional imaging. Then, the positional relationships (within or outside) were recorded with respect to recurrences and CTV defined by the RTOG, GFRU, and ESTRO (CTV RTOG, CTV GFRU, and CTV ESTRO), followed the analysis of the recurrence rates and distribution characteristics of various zones. Results:A total of 63 patients with prostate bed recurrence after radical prostatectomy were enrolled in this study, including 97 recurrences. The recurrence rates in the six zones were as follows: 10% of zone 1, 22% of zone 2, 29% of zone 3, 2% of zone 4, 12% of zone 5a, 18% of zone 5b, and 7% of zone 6. Among these zones, zones 2 and 3 showed the highest and second-highest recurrence rates, respectively. CTV GFRU and CTV ESTRO completely covered zones 2 and 3, while CTV RTOG covered zone 2 completely and zone 3 partially. Zone 4, characterized by a low recurrence rate, was not covered by CTV GFRU and CTV ESTRO but was entirely covered by CTV RTOG. Zone 5a, with a recurrence rate of 12%, was completely covered by CTV RTOG but was partially covered by CTV GFRU and CTV ESTRO. The range of 1.3 cm in front of the posterior wall of the bladder covered all recurrences in zone 5a. Conclusions:For CTV delineation of the prostate cancer surgical bed, zone 4, the anterior half of the bladder above the pubic symphysis midpoint, should be contracted due to the low recurrence rate in this zone. In contrast, the anterior boundary above the pubic symphysis midpoint should extend to 1.3 cm in front of the posterior wall of the bladder to completely cover the recurrence zones.
10.Radiotherapy for undifferentiated spindle cell sarcoma of the prostate: a case report
Yuyang ZHAO ; Hongzhen LI ; Wei YU ; Huan ZHANG ; Shuai HU ; Xuhe LIAO ; Xin QI
Chinese Journal of Urology 2025;46(10):788-790
Undifferentiated spindle cell sarcoma of the prostate is clinically rare. This article reports a case of a 29-year-old male who presented on February 7,2022,with a two-week history of localized pain in the perineal area and spermatic cord. The diagnosis of prostatic undifferentiated spindle cell sarcoma was confirmed by imaging studies and prostate needle biopsy pathology. After consultation by the urologic oncology multidisciplinary team and considering the patient's preference,a treatment plan of radical radiotherapy combined with chemotherapy,immunotherapy,and targeted therapy was adopted,Partial stereotactic body radiotherapy(P-SBRT)was delivered to the tumor center with a total dose of 74.4 Gy,combined with cisplatin and pembrolizumab. Lung metastasis progression occurred 1.5 months after radiotherapy,and treatment was switched to a combination of pirarubicin,ifosfamide,pembrolizumab,and bevacizumab. After 39 months of follow-up,the disease remained well-controlled with preserved organ function and long-term survival. This case,utilizing a multidisciplinary comprehensive diagnosis and treatment model,provides a reference for organ-preserving non-surgical management in patients with prostate soft tissue sarcoma.

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