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.

OBJECTIVE: To observe the effects of electroacupuncture at the pterygopalatine region on nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated pyroptosis and inflammatory factors in rats with allergic rhinitis (AR). METHODS: Twenty-four SD rats were randomly divided into a blank group, a model group, an acupuncture group and an electroacupuncture group, 6 rats in each group. Except for the blank group, OVA-induced AR model was established in the remaining groups. In the electroacupuncture group, the rats were treated with electroacupuncture at the bilateral pterygopalatine region, with disperse-dense wave, in frequency of 2 Hz/100 Hz and current of 0.5-1 mA, 15 min each time, once every other day, for 3 times. In the acupuncture group, the rats were treated with acupuncture at bilateral pterygopalatine region simply, without electrical stimulation. The rhinitis symptom score was observed, the pathomorphology of the nasal mucosa was observed by HE staining; the serum levels of OVA-specific immunoglobulin E (OVA-sIgE), interleukin (IL)-4, IL-6 and IL-1β were detected by ELISA; the mRNA expression of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1) and IL-18 in the nasal mucosa was detected by real-time PCR; the protein expression of NLRP3, ASC, caspase-1 and IL-18 in the nasal mucosa was detected by Western blot. RESULTS: Compared with the blank group, in the model group, the rhinitis symptom score was increased (P<0.01), the serum levels of OVA-sIgE, IL-4, IL-6 and IL-1β were increased (P<0.05), the nasal mucosa showed pathomorphology of inflammatory infiltration; the mRNA and protein expression of NLRP3, ASC, caspase-1 and IL-18 in the nasal mucosa was increased (P<0.05). Compared with the model group, in the electroacupuncture group, the rhinitis symptom score was reduced (P<0.01), the pathology of the nasal mucosa was improved; the serum levels of OVA-sIgE, IL-4, IL-6 and IL-1β were decreased (P<0.05); the mRNA and protein expression of NLRP3, ASC, caspase-1 and IL-18 in the nasal mucosa was decreased (P<0.05). CONCLUSION Electroacupuncture at the pterygopalatine region can exerting the anti-inflammatory effect by inhibiting NLRP3-mediated pyroptosis and inflammatory factor imbalance, thus alleviate rhinitis symptoms in AR rats.
Animals ; Electroacupuncture ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Rats ; Rats, Sprague-Dawley ; Rhinitis, Allergic/physiopathology* ; Pyroptosis ; Male ; Acupuncture Points ; Humans ; Female ; Interleukin-1beta/genetics* ; Interleukin-18/immunology* ; Interleukin-6/genetics* ; Caspase 1/immunology*

Objective To explore the affective response and dynamic attributes of obese adolescents in high-and moderate-intensity interval training.Methods Between February and July 2023,a total of 42 obese adolescents(Age:12.3±0.5 years,BMI:24.0±1.1 kg/m2)were recruited and randomly divided into a high-intensity interval training group(HIIT),a moderate-intensity interval training group(MIIT),and a non-training control group.Before and after the intervention,all groups were measured and compared their weight,BMI,body composition(body fat percentage and visceral adipose fat),car-diorespiratory fitness(VO2max),and affective response during exercise(affect valence,perceived arousal,rating of perceived exertion),as well as post-exercise enjoyment.Results After the 12-week interven-tion,there were significant decrease in the average BMI,body fat percentage,and visceral adipose tis-sue in the HIIT group(P<0.05),but a significant increase in the average VO2max(P<0.05).Moreover,a-fter the training,the average VO2max of the HIIT group was significantly higher than the MIIT group(P<0.05).Meanwhile,both HIIT and MIIT had a positive effect on emotional valence and post-exercise enjoyment.However,MIIT participants had more positive affect responses than HIIT ones,while the arousal(P<0.01)and physical activity enjoyment scores(P<0.05)in the HIIT group were significantly higher than the MIIT group.Conclusions Interval training is effective in improving body composition and cardiorespiratory fitness of obese adolescents.Higher intensity and arousal are key to the improve-ment.Moreover,the positive affect response and exercise enjoyment after interval training may help them maintain high exercise adherence and play a long-term promoting role.

Objective:To investigate the prognostic factors for liver transplantation for hepatocellular carcinoma beyond UCSF criteria but without macrovascular invasion.Methods:A retrospective analysis was performed for the clinical data of the hepatocellular carcinoma patients without macrovascular invasion beyond UCSF criteria who underwent liver transplantation at our center from Jan 2018 to Jun 2023. The receiver operating characteristic curve analysis was performed to assess the predictive power of potential prognosis factors.Results:With this criteria, the 1-, 3-year overall survival rates were 94.1% and 75.0%, respectively, and the 1-, 3-year tumor free survival rates were 82.4% and 38.1%, respectively. The maximum tumor size, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and whether undergo pretransplant down-stage therapy were significant prognostic factors ( P<0.05). Combining the above prognostic factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.967, with a sensitivity and specificity of 0.932, 0.952, respectively. Further, the differentiation, MVI and Ki-67 were significant prognostic factors ( P<0.05). Combining pathological factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.927, with a sensitivity and specificity of 0.769, 1, respectively. Conclusion:The maximum tumor diameter, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and pretransplant down-stage therapy and tumor differentiation, MVI and Ki-67 are all prognostic factors of liver transplantation for hepatocellular carcinoma without macrovascular invasion beyond UCSF criteria.

The rapid development of digital intelligence technologies is providing a powerful boost to the high-quality development of the healthcare system.Considering the current state of our healthcare services and guided by General Secretary Xi Jinping's insights on new quality productive forces and the directives from Third Plenary Session of Communist Party of China's 20th Central Committee,the high-quality development of the healthcare service system should focus on digital intelligence technologies such as cloud computing,big data,privacy computing,blockchain,Internet of Things(IoT),mobile computing,and AI.The key measures should include the optimization of production factors,services,and governance.Emphasis should be placed on enhancing the efficient and intensive development of the development model,ensuring the high-quality and continuous integration of the supply model,and transitioning to scientific and modern management methods.Herein,we analyzed the"factor optimization—service optimization—governance optimization"development mechanism driven by digital intelligence and proposed corresponding implementation pathways,intending to provide references for establishing a high-quality and efficient healthcare service system with Chinese characteristics.

Immune checkpoint inhibitors (ICIs) have ushered in a new era of tumor treatment; however, immunotherapy-related adverse events are critical issues that restrict the clinical application of ICIs and have attracted wide attention. The liver is one of the target organs that is easily affected. With the progress in research, scholars have found that besides hepatocytes, intrahepatic and extrahepatic bile ducts can also be attacked by the immune system, leading to the disease known as immune-related cholangitis. This article reviews the research advances in ICI-related cholangitis by summarizing related articles, in order to preliminarily reveal its clinical, pathological, and imaging features and provide clues for early identification, standard treatment, and subsequent research.

Objective To summarize the diagnosis and treatment experience of portal vein aneurysm after liver transplantation. Methods Clinical data of two recipients with portal vein aneurysm after liver transplantation were retrospectively analyzed. Clinical features, diagnosis, treatment and prognosis were summarized based on literature review. Results Both two cases were diagnosed with intrahepatic portal vein aneurysm complicated with portal vein thrombosis and portal hypertension after liver transplantation. Case 1 was given with targeted conservative treatment and he refused to undergo liver retransplantation. Physical condition was worsened after discharge, and the patient eventually died from liver graft failure, kidney failure, lung infection, and septic shock. Case 2 received high-dose glucocorticoid pulse therapy, whereas liver function was not improved, and the patient was recovered successfully after secondary liver transplantation. Conclusions Long-term complication of portal vein aneurysm (especially intrahepatic type) after liver transplantation probably indicates poor prognosis. Correct understanding, intimate follow-up and active treatment should be conducted. Liver retransplantation may be a potential treatment regimen.

Objective:To investigate the value of low-energy virtual monoenergetic image (VMI) at 45 keV in visualizing the primary tumor and T staging of hypopharyngeal squamous cell carcinoma.Methods:The clinical and imaging data of 58 patients with hypopharyngeal squamous cell carcinoma from April 2018 to January 2020 at Eye & ENT Hospital, Fudan University were analyzed retrospectively. All the patients underwent a venous phase contrast-enhanced dual-source dual-energy CT scan before treatment. The VMI at 45 keV and standard linearly blended image (30% 80 kV+70% 140 kV) were acquired from dual-energy post-processing software. One senior radiologist and one junior radiologist independently assessed the visibility of the tumor on the 45 keV VMI and standard linearly blended image using a 5-point Likert rating scale. Furthermore, the senior radiologist assessed the visibility of the tumor at each subsite (piriform fossa, posterior pharyngeal wall, postcricoid region) and determined the invasion depth of the tumor (extension to esophagus, invasion to strip muscles and prevertebral muscles) and performed the T staging of the primary tumor using the two sets of images blindly. The accuracy of T staging was calculated, using pathological T staging (surgical cases) or clinical T staging (non-surgical cases) as the gold standard. The image scores of the two sets of images were compared using Wilcoxon rank sum test. McNemar-Bowker test was used to compare the accuracy of T staging using the two sets of images.Results:The overall image scores of the 45 keV VMI and standard linearly blended image from the senior radiologist were 3.5 (3, 4) and 3 (2, 3) respectively ( Z=-7.03, P<0.001), and the scores from the junior radiologist were 3 (3, 4) and 2 (2, 3) ( Z=-6.93, P<0.001). The scores of the 45 keV VMI were significantly higher than those of the standard linearly blended image in visualizing tumors in the piriform fossa, posterior pharyngeal wall, and postcricoid region, as well as in detecting invasion to the strip muscles ( P<0.05). There was no significant difference in the scores of the two sets of images in determining whether the tumor extended to esophagus or invaded prevertebral muscles ( P>0.05). Referring to pathological and clinical T stage, the accuracy of T staging determined by the 45 keV VMI and standard linearly blended image was 87.9% (51/58) and 81.0% (47/58) respectively, and the difference was not significant (χ 2=3.33, P=0.189). Conclusions:The 45 keV VMI is superior to the standard linearly blended image in visualizing tumors and detecting invasion to the strip muscles of hypopharynx squamous cell carcinoma. However, the accuracy of determining T staging using 45 keV VMI is slightly improved than that of standard linearly blended image, and the difference is not statistically significant. In determining whether the tumor extends to esophagus or invades prevertebral muscles, 45 keV VMI shows no significant advantage over standard linearly blended image.

Objective:To investigate the application value of the anatomically oriented "six steps with six windows" approach in laparoscopic radical total gastrectomy.Methods:The retros-pective cohort study was conducted. The clinicopathological data of 121 patients who underwent laparoscopic radical total gastrectomy in Henan Provincial People′s Hospital from January 2019 to February 2022 were collected. There were 53 males and 68 females, aged (68±12)years. Of the 121 patients, 72 patients using the traditional approach in the surgery were divided into the control group, and 49 patients using the "six steps with six windows" approach in the surgery were divided into the experiment group. Observation indicators: (1) surgical situations; (2) postoperative situations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolute numbers or percen-tages, and comparison between groups was conducted using the chi-square test. Results:(1) Surgical situations. All 121 patients underwent laparoscopic radical total gastrectomy successfully, without laparotomy conversion. The operation time, volume of intraoperative blood loss, number of lymph nodes dissected were (250±50)minutes, (150±34)mL, 41±6 in the control group, versus (180±16)minutes, (55±13)mL, 51±5 in the experiment group, showing significant differences in the above indicators between the two groups ( t=11.04, 21.47, 9.42, P<0.05). (2) Postoperative situations. The times of postoperative analgesic injection, time to postoperative ?rst ?atus, duration of postoperative hospital stay, postoperative pathological staging (stage Ⅰ, stage Ⅱ, stage Ⅲ), incidence of postoperative complication were 3.4±1.6, (4.0±1.4)days, (13.1±2.0)days, 9, 32, 31, 15.3%(11/72) in the control group, versus 3.5±1.7, (4.1±1.5)days, (13.1±1.7)days, 6, 25, 18, 16.3%(8/49), showing no significant difference in the above indicators between the two groups ( t=0.35, 0.18, 0.03, Z=0.55, χ2=0.02, P>0.05). There was no perioperative death in both groups of patients. Conclusion:Appli-cation of the anatomically oriented "six steps with six windows" approach in laparoscopic radical total gastrectomy is safe and feasible.

Objective: To clinically validate the feasibility and accuracy of cine images acquired through the multitasking method, with no electrocardiogram gating and free-breathing, in measuring left ventricular (LV) function indices by comparing them with those acquired through the balanced steady-state free precession (bSSFP) method, with multiple breath-holds and electrocardiogram gating. Materials and Methods: Forty-three healthy volunteers (female:male, 30:13; mean age, 23.1 ± 2.3 years) and 36 patients requiring an assessment of LV function for various clinical indications (female:male, 22:14; 57.8 ± 11.3 years) were enrolled in this prospective study. Each participant underwent cardiac magnetic resonance imaging (MRI) using the multiple breath-hold bSSFP method and free-breathing multitasking method. LV function parameters were measured for both MRI methods. Image quality was assessed through subjective image quality scores (1 to 5) and calculation of the contrast-to-noise ratio (CNR) between the myocardium and blood pool. Differences between the two MRI methods were analyzed using the Bland–Altman plot, paired t-test, or Wilcoxon signed-rank test, as appropriate. Results: LV ejection fraction (LVEF) was not significantly different between the two MRI methods (P = 0.222 in healthy volunteers and P = 0.343 in patients). LV end-diastolic mass was slightly overestimated with multitasking in both healthy volunteers (multitasking vs. bSSFP, 60.5 ± 10.7 g vs. 58.0 ± 10.4 g, respectively; P < 0.001) and patients (69.4 ± 18.1 g vs. 66.8 ± 18.0 g, respectively; P = 0.003). Acceptable and comparable image quality was achieved for both MRI methods (multitasking vs. bSSFP, 4.5 ± 0.7 vs. 4.6 ± 0.6, respectively; P = 0.203). The CNR between the myocardium and blood pool showed no significant differences between the two MRI methods (18.89 ± 6.65 vs. 18.19 ± 5.83, respectively; P = 0.480). Conclusion Multitasking-derived cine images obtained without electrocardiogram gating and breath-holding achieved similar image quality and accurate quantification of LVEF in healthy volunteers and patients.