Objective:To develop and validate machine learning-based radiomics models using preoperative CT images for individualized prediction of mitotic index (MI) in patients with gastrointestinal stromal tumors (GIST).Methods:The study was a case-control study. The data of 348 GIST patients confirmed by pathology were retrospectively collected from two independent medical centers: the Affiliated Hospital of Qingdao University (center 1) and Shandong Provincial Hospital Affiliated to Shandong First Medical University (center 2), covering the period from January 2013 to June 2018. Patients from center 1 were divided into a training cohort (176 cases) and an internal validation cohort (75 cases) at a ratio of 7∶3 using random sampling. Patients from center 2 served as an independent external validation cohort (97 cases). The primary endpoint was MI, categorized into high MI (145 cases) and low MI (203 cases) groups. Radiomic features were extracted from the portal venous phase images of preoperative contrast-enhanced CT scans. Five machine learning algorithms, including logistic regression, support vector machine, random forest, decision tree, and extreme gradient boosting (XGBoost),were employed to construct MI prediction models. The optimal model was identified using receiver operating characteristic curves. An individualized prediction model was developed by integrating the the optimal machine learning model combined with selected independent clinical factors, and the importance of features was visualized using Shapley Additive Explanation (SHAP) analysis. Patients were followed up, and Kaplan-Meier curves along with log-rank tests were used to evaluate recurrence-free survival (RFS) differences between the predicted high MI and low MI groups.Results:Among the five constructed machine learning models, the XGBoost model demonstrated the best predictive performance, with area under the curve (AUC) of 0.809 (95% CI 0.738-0.872), 0.693 (95% CI 0.571-0.809), and 0.718 (95% CI 0.605-0.822) in the training cohort, internal validation cohort, and external validation cohort, respectively. An individualized prediction model combining the XGBoost model with independent clinical factors (tumor location and tumor size) was developed. The model achieved AUC of 0.843 (95% CI 0.785-0.899), 0.791 (95% CI 0.680-0.894), and 0.777 (95% CI 0.678-0.861) in the training cohort, internal validation cohort, and external validation cohort, respectively. SHAP analysis indicated that radiomic features had the highest predictive impact. In both the training cohort and internal validation cohort, the RFS of patients predicted to be in the high MI group was lower than that of the low MI group, with statistically significant differences ( χ2=14.58, 9.52, both P<0.001). However, there was no statistically significant difference in RFS in the external validation set ( χ2=6.18, P=0.080). Conclusions:The optimal XGBoost model based on radiomic features extracted from preoperative portal venous phase CT images, when combined with clinical factors, can effectively predict the MI of GIST patients.

Objective To explore the effect of playing moderate-intensity table tennis and badminton on myo-pia prevention among children between 7 and 9 years old,so as to provide related theoretical basis.Methods A total of 536 myopic children were initially screened from two schools in Guangzhou via questionnaires and in-terviews.Among them,36 children(7-9 years old)were selected and randomly divided into a control group,a table tennis group and a badminton group,each of 12.All groups underwent 1.5-hour training three times a week for six months,covering training on dynamic visual acuity,sports vision and attention training and the ex-ercise intensity was adjusted according the heart rate,rating of perceived exertion(RPE)and blood oxygen lev-els.Moreover,the equivalent spherical degree(SED),ocular biology,and accommodative parameters were mea-sured before and after the intervention.Results After intervention,the left eye SEDs of the control and badmin-ton groups were lower than before intervention(P<0.05).Moreover,the axial length(AL)in the left and right eyes and the axial length/corneal radius of curvature(AL/CR)of all 3 groups after intervention were significant-ly higher than before that(P<0.05).The table tennis group showed significant improvement in accommodative fa-cility(AF)in both eyes(P<0.05),while the badminton group demonstrated significant increases in AF of both eyes,amplitude of accommodation(AMP)in the right eye,but a significant decrease in the positive relative adjustment(PRA)(P<0.05).Moreover,after intervention,SE and AF of both eyes in the table tennis group was significantly higher,with lower AL and AL/CR ratios in the left eye compared to the control group(P<0.05).The badminton group exhibited greater AMP in the right eye and AF improvements in both eyes com-pared to the control and table tennis groups(P<0.05),but lower PRA(P<0.05).Moreover,the left-eye SE of the badminton group was higher than the control group(P<0.05),while the right-eye corneal curvature and the left-eye AL/CR were lower than the latter(P<0.05).Meanwhile,after the intervention,the left-eye AL and PRA of the badminton group were significantly lower than the table tennis group(P<0.05).Conclusion Pupils can effectively increase their reserve of eye adjustment,improve the adjustment function of the eye,and delay the development of myopia by playing table tennis and badminton with moderate intensity.Playing table tennis excels in delaying refractive power changes,while doing badminton significantly improves PRA,AMP,and AF.

Thyroid-associated ophthalmopathy (TAO) is the ocular manifestation of thyroid autoimmune dysfunction.Its clinical feathers mainly include eyelid retraction, proptosis, and ocular movement disorders.TAO is the most common orbital diseases.The pathogenesis of TAO has not been fully elucidated, but researchers generally believe that T cells play an important role in the pathogenesis of TAO.In the early stage of TAO development, a large number of T cells are activated and infiltrated into the retroorbital soft tissue.T cells can be divided into CD4 + T cells and CD8 + T cells.CD4 + T cells play a more central role in TAO.CD4 + T cells include Th1, Th2, Treg and recently discovered Th17, Th22 and Tfh cells.In target tissues, the complete activation and later function of T cells largely rely on the costimulatory pathways, there needs to unravel the mechanism of these costimulatory pathways in TAO.This paper reviews the recent research progress of T cells and costimulatory signals required for their activation in the pathogenesis of TAO.

Objective To analyze anesthetic and analgesic effect of perioperovtive administration of esketamine in patients undergoing off-pump coronary artery bypass grafting(OPCABG).Methods The clinical data of 120 patients who underwent OPCABG under gene-ral anesthesia were retrospectively collected.Patients were divided into an esketamine group(n=60)and a non-esketamine group(n=60)according to whether esketamine was used perioperatively.The patients in the esketamine group received esketamine(1 mg/kg)during anesthesia induction and postoperative patient-controlled analgesia with sufentanil(3 μg/kg)plus esketamine(2 mg/kg).Those in the non-esketamine group received sufentanil(2 μg/kg)during anesthesia induction and postoperative patient-controlled analgesia with sufentanil(3 μg/kg).The mean arterial pressure(MAP)and heart rate(HR)were recorded at the time point of entering the room(T0),after anesthesia induction/before intubation(T1),1 min after intubation(T2),skin incision(T3),sternotomy(T4),after surgery and skin suture(T5),entering the ICU(T6),extubation(T7),24 hours after surgery(T8),and 48 hours after surgery(T9).The extubation time,Ramsay sedation scores,visual analog scale(VAS)scores,and adverse reactions were compared.Results There were no statistically significant differences in the baseline characteristics and MAP and HR at T0 and T1 between the two groups(P＞0.05).From T2 to T9,MAP and HR in the esketamine group were significantly lower than those in the non-esketamine group(P＜0.05).The postoperative extubation time,Ramsay sedation score,and VAS score were significantly lower in the esketamine group than in the non-esketamine group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion The perio-perative administration of esketamine in OPCABG can stabilize the hemodynamics,shorten the extubation time,and promote the recovery of patients undergoing OPCABG without increasing postoperative adverse reactions.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

AIM:To explore whether microRNA-30a-3p(miR-30a-3p)is involved in the pathogenesis of non-alcoholic fatty liver disease(NAFLD)by regulating autophagy and promoting lipid deposition.METHODS:Eight-week-old C57BL/6 mice were randomly divided into a normal control group and a high-fat diet(HFD)group.Mice in the HFD group were fed with 60％high fat diet for 10 weeks to induce the NAFLD phenotype.Some mice were injected with adeno-virus overexpressing miR-30a-3p via the tail vein and subsequently fed with high-fat diet for 4 weeks.Glucose tolerance and insulin resistance tests were performed at the end of the treatments.In addition,the concentrations of hepatic alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG)and total cholesterol(TC)were mea-sured.Hematoxylin-eosin staining and oil red O staining were conducted to examine morphological changes and lipid depo-sition in the liver tissue.The expression levels of microtubule-associated protein light chain 3(LC3),autophagy-related protein 5(ATG5),beclin-1 and p62 were quantified through Western blot.In addition,NAFLD models were established in AML12 hepatocytes by incubating the cells with palmitic acid and oleic acid(PO).The AML12 cells were transfected with miR-30a-3p shRNA to knock down miR-30a-3p expression.The concentration levels of TG and TC after miR-30a-3p knockdown were measured by the kits.Nile red staining was performed to examine lipid droplet aggregation and dual fluo-rescent recombinant adenovirus Ad-mCherry-GFP-LC3B was transfected into AML12 cells to observe changes in autopha-gic flow.RESULTS:HFD-fed mice exhibited significant insulin resistance and reduced glucose tolerance,significant lip-id deposition in the liver tissue,coupled with increased hepatic ALT,AST,TG and TC levels.The expression levels of au-tophagy-related proteins LC3-Ⅱ,beclin-1,and ATG5 were decreased,while that of p62 was increased(P<0.01).More-over,miR-30a-3p overexpression significantly increased blood glucose and insulin resistance in HFD-fed mice.However,it aggravated lipid droplets deposition in liver tissue and enhanced hepatic TG,TC,AST and ALT levels.Western blot re-vealed that the expression levels of LC3-Ⅱ,beclin-1 and ATG5 were further reduced,while that of p62 was significantly in-creased(P<0.01).In vitro,we observed that the TG and TC levels,as well as lipid accumulation in PO-treated AML12 cells were increased significantly.Similarly,the expression levels of LC3-Ⅱ,beclin-1 and ATG5 were decreased,whereas that of p62 increased in PO-treated AML12 cells(P<0.01).Notably,knockdown of miR-30a-3p resulted in a significant reduction in the TG content in PO-treated AML12 cells and lipid droplet aggregation was significantly suppressed.Further-more,the expression of LC3-Ⅱ,beclin-1 and ATG5 proteins was increased,while that of p62 was decreased significantly and the autophagy flow was improved(P<0.01).CONCLUSION:The miR-30a-3p exacerbates hepatic lipid deposi-tion,inducing severe hepatic steatosis and liver damage,to promote the occurrence and development of NAFLD in mice.Mechanistically,its effects involve inhibition of hepatic autophagy level.

Objective The mechanism of Huazhuo xingxue decoction(HZXXD)in the treatment of ischemic stroke was explored through network pharmacology,molecular docking and cell validation.Methods TCMSP,TCMID,BATMAN-TCM database and literature search were used to get the chemical components and related target proteins of Huazhuo Xingxue Decoction,and the targets of dementia,stroke and amnesia were obtained from Genecards database and OMIM database.The traditional Chinese medicine-active components-target-network and protein interaction map were constructed by using Cytoscape,and the target was enriched by KEGG pathway by David database.Western blot was used to investigate the effect of HZXXD on inflammation-related core targets expression using oxygen and glucose deprivation/reoxygenation cell model.Finally,Autodock was used for molecular docking of key active ingredients and important targets to evaluate their binding activity.Results 76 active molecules and 33 common targets of herb-disease were screened out.KEGG bioaccumulation results involve multiple inflammatory signal pathways such as TNF,chemical carcinogenesis-reactive oxygen species and HIF-1.TNF-α was found to be the core target of HZXXD by oxygen glucose deprivation/reoxygenation cell experiments.Five compounds with the strongest binding ability to TNF-α,kaempferol,apigenin,aloe-emodin,baicalein and stigasterol,were screened by traditional Chinese medicine-active ingredient-target network map and molecular docking.Conclusion Huazhuo Xingxue Decoction may down regulate the expression of core target TNF-α,kaempferol,apigenin,aloe emodin,baicalein and stigasterol may be the main active substances for TNF-α binding.

OBJECTIVE Aimd to investigate the prevalence of olfactory dysfunction among healthy elderly individuals in China using a large sample size and to explore its correlations with demographic and other factors.METHODS A total of 5 258 participants who aged 60 and above underwent the T&T olfactometer test and completed questionnaires.The prevalence of olfactory dysfunction was reported,and logistic regression analyses were performed to assess the associations between olfactory dysfunction and other factors.RESULTS The overall prevalence of olfactory dysfunction in the study was 26.5%.Independent risk factors for olfactory dysfunction included advanced age,rural residence(OR=1.88,95%CI:1.60-2.22,P<0.01),current smoking(OR=1.45,95%CI:1.15-1.83,P<0.01),and self-reported olfactory dysfunction(OR=10.12,95%CI:8.44-12.14,P<0.01).In contrast,female gender(OR=0.70,95%CI:0.58-0.85,P<0.01)and high educational attainment were independently associated with a lower prevalence of olfactory dysfunction.CONCLUSION The prevalence of olfactory dysfunction among individuals aged 60 and above increased with age.Male gender,rural residence,low educational attainment,current smoking,and self-reported decline in olfactory function were independently associated with olfactory dysfunction.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Thymoma is a malignant tumor originating from thymus epithelial cells, with an incidence of 1.3-2.6 per million. Due to its low incidence, lack of cells and animal models, there are relatively few studies on thymoma, and its diagnosis and treatment progress is relatively slow. The update of 5th edition of WHO Classification of Thoracic Tumors in 2021 and the NCCN( National Comprehensive Cancer Network) Clinical Practice Guidelines in Oncology: Thymoma and Thymoma Cancer in 2024 put forward many new views and suggestions on the diagnosis and treatment strategy of thymoma. This article reviews the research and treatment of thymoma based on the latest research progress in recent years, aiming to improve the clinician's understanding of thymoma, provide reference for treatment, and promote the research of thymoma.