ObjectiveTo investigate the effect of phytoestrogen biochanin A （BCA） on liver fibrosis induced by CCl₄ in female mice with bilateral oophorectomy （ovariectomized） and its mechanism. MethodsA total of 50 ovariectomized Kunming mice were selected and given intraperitoneal injection of CCl₄ to establish a model of liver fibrosis， and then according to body weight， they were randomly divided into model group， positive control group， and low-， middle-， and high-dose BCA groups， with 10 mice in each group. In addition， 10 female mice in the same litter were given resection of a small amount of adipose tissue near both ovaries to establish the sham-operation group. The mice in the positive control group were given estradiol 2 mg/kg by gavage， and those in the low-， middle-， and high-dose BCA groups were given BCA by gavage at a dose of 25， 50， and 100 mg/kg， respectively， once a day for 7 consecutive weeks； the mice in the sham-operation group and the model group were given an equal volume of 0.5% sodium carboxymethyl cellulose solution by gavage. The mice were anesthetized and sacrificed after administration to collect samples. Liver index and uterus index were measured； HE staining and Masson staining were used to observe liver histopathological changes； the biochemical analysis was used to measure the activity of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； ELISA was used to measure the levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in liver tissue， and Western blot was used to measure the relative protein expression levels of collagen Ⅰ， transforming growth factor-beta 1 （TGF-β₁）， alpha-smooth muscle actin （α-SMA）， estrogen receptor beta （ERβ）， and p-NF-κBp65/NF-κBp65 in liver tissue. The t-test was used for comparison of continuous data between two groups； a one-way analysis of various was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. ResultsCompared with the sham-operated group， the model group had a significant increase in liver index and a significant reduction in uterus index， as well as significant increases in the activities of serum AST and ALT， the levels of IL-6 and TNF-α in liver tissue， and the protein expression levels of collagen Ⅰ， TGF-β₁， α-SMA， and p-NF-κBp65/NF-κBp65 in liver tissue （all P<0.05）， with no significant change in the expression of ERβ in liver tissue （P>0.05）， and the model group showed significant fibrosis lesions in the liver， such as hepatocyte edema， steatosis， and necrosis with inflammatory cell infiltration and hyperplasia， deposition， and staggered distribution of collagen fibers. Compared with the model group， the low-， middle-， and high-dose BCA groups had significant reductions in liver index， the activities of serum AST and ALT， the levels of IL-6 and TNF-α， and the protein expression levels of collagen Ⅰ， TGF-β₁， α-SMA， and p-NF-κBp65/NF-κBp65 in liver tissue （all P<0.05）， with no significant change in uterine index （P>0.05）， as well as a significant increase in the protein expression level of ERβ in liver tissue （P<0.05） and varying degrees of improvement in liver fibrosis lesions. ConclusionBCA can effectively improve CCL₄-induced liver fibrosis in ovariectomized female mice， possibly by upregulating ERβ to inhibit the NF-κB signaling pathway and then alleviating inflammatory response.

Objective To investigate the clinical efficacy of mitral valve repair technique in the treatment of rheumatic mitral valve lesions. Methods The clinical data of patients diagnosed with rheumatic mitral valve lesions and undergoing mitral valve repair under extracorporeal circulation in our department from 2021 to 2022 were retrospectively analyzed. Results A total of 100 patients were collected, including 78 females and 22 males with an average age of 52 years. There were no secondary open heart or death in the whole group. Extracorporeal circulation time was 136.3±33.1 min, aortic cross-clamping time was 107.6±27.5 min, ventilator use time was 12.9±5.9 h, ICU stay was 2.6±1.4 d, and vasoactive medication use was 823.4±584.4 mg. Before and after the surgery, there were statistical differences in the left ventricular end diastolic diameter, left atrial end systolic diameter, effective mitral valve orifice area, shortening rate of left ventricular short axis, mitral E-peak blood flow velocity, mean mitral transvalvular pressure difference, mitral pressure half-time, and cardiac function graded by New York Heart Association (P＜0.05). While there was no statistical difference in left ventricular ejection fraction or left ventricular end-diastolic volume (P>0.05). Conclusion Overall repair of rheumatic mitral valve lesions can significantly improve the cardiac function and hemodynamics of the patients, and is a good choice for patients with rheumatic mitral valve lesions.

Objective:To explore the correlation between the methylation of sclerostin (SOST) promoter and glucocorticoid-induced osteoporosis (GIOP) in children.Methods:Children with GIOP ( n=66) were selected as the experimental group. At the same time, children treated with glucocorticoid whose bone mass were selected as the control group ( n=72). The general clinical information of all children was compared, and the data collected by CT were detected by lumbar QCT, and the levels of bone metabolism related indexes were detected by biochemical analyzer. The mRNA expression of SOST was detected by fluorescence quantitative PCR, and the protein content of SOST was detected by enzyme-linked Immunosorbent Assay (ELISA). Methylation status of SOST gene promoter was detected by methylation-specific PCR (MSP), and the risk factors affecting GIOP were compared and analyzed, and the diagnostic and therapeutic value of each index for children with GIOP was evaluated. Results:Compared with the control group, the duration of hormone application and the current dose of hormone in the experimental group were higher, and the expression levels of bone metabolism indexes β-collagen carboxy terminal peptide ( β-CTX) ( t=9.87, P<0.01), typeⅠprocollagenamino-terminal peptide (P1NP) ( t=16.09, P<0.001), osteopontin (OPN) ( t=21.32, P<0.001) and N-MID ( t=15.21, P<0.01) were significantly increased, with statistical significance. However, in terms of bone mineral density, the related level of children in the experimental group was low ( t=22.49, P<0.001), and the expression of SOST mRNA ( t=9.48, P<0.01) and protein content ( t=7.70, P<0.01) was significantly decreased, and the children in the experimental group showed methylation status of SOST. Pearson analysis showed that the level of serum SOST protein in the experimental group was negatively correlated with the levels of β-CTX ( r=-0.16, P=0.012), P1NP ( r=-0.35, P=0.021), OPN ( r=-0.25, P=0.043) and N-MID ( r=-0.09, P=0.036). At the same time, the Logistic regression analysis showed that the high expression of P1NP ( SE=0.35, P<0.001), OPN (S E=0.37, P<0.001) and SOST ( SE=0.33, P<0.001) were risk factors for glucocorticoid-induced osteoporosis in children. The receiver operating characteristic (ROC) curve showed that the area under the curve of SOST was 0.874 (95% CI: 0.824-0.934), with higher sensitivity and specificity. Conclusions:There is a correlation between the methylation of SOST promoter and the GIOP of children. Besides, SOST can be used as a potential diagnostic index of GIOP with high value among many factors affecting children’s GIOP. In this case, the medical industry needs to further strengthen the prevention and treatment of children’s GIOP.

Objective:An artificial intelligence(AI)model based on deep learning algorithms was constructed using clinical data to evaluate the feasibility of predicting the efficacy of neoadjuvant immunotherapy combined with chemotherapy for non-small cell lung cancer(NSCLC).Methods:Clinical and pathological data of 132 patients with NSCLC who were diagnosed and treated with neoadjuvant immunotherapy combined with chemotherapy between January 2020 and January 2024 at Beijing Chest Hospital/Beijing Tuberculosis and Thoracic Tumor Research Institute were collected.Statistical analysis was conducted to identify the main factors affecting the efficacy of neoadjuvant im-munotherapy combined with chemotherapy.Variables were selected based on statistical results and relevant literature,and a variable data-set was constructed.A deep learning model was established using a multi-layer perceptron(MLP)algorithm with 5-fold cross-validation,and the performance of the model was evaluated using receiver operating characteristic curve(ROC).Results:Among the 132 patients,univari-ate analysis demonstrated statistically significant differences in sex(P=0.020),smoking history(P=0.004),carcinoembryonic antigen(CEA)(P=0.038)and programmed death-ligand 1(PD-L1)≥1%(P=0.038)between the major pathological response(MPR)and non-MPR groups.Patients in the complete pathological response(pCR)group and non-pCR groups showed statistical differences in tumor size(P=0.007)and CEA levels(P=0.010).After 5-fold cross-validation,the average area under the curve(AUC)of the MPR prediction model in the validation and test sets was 0.72 and 0.71,respectively.Conclusions:The deep learning model can effectively predict the efficacy of neoadjuvant chemoim-munotherapy in patients with NSCLC.

The rehabilitation compliance of stroke patients is generally low.Evaluating the rehabilitation motivation of patients is helpful to promote the rehabilitation management of patients,enhance the rehabilitation enthusiasm and compliance of patients,and improve the rehabilitation outcome.This paper reviews the existing stroke patients rehabilitation motivation assessment tools,and expounds the main contents,application status,characteristics and limitations of stroke patients rehabilitation motivation assessment tools,in order to provide references for the appropriate selection of clinical assessment tools,the rehabilitation management of stroke patients and the development of domestic localized stroke rehabilitation motivation assessment tools.

Objective:To establish a set of artificial intelligence (AI) verification rules for blood routine analysis.Methods:Blood routine analysis data of 18 474 hospitalized patients from the First Hospital of Jilin University during August 1st to 31st, 2019, were collected as training group for establishment of the AI verification rules,and the corresponding patient age, microscopic examination results, and clinical diagnosis information were collected. 92 laboratory parameters, including blood analysis report parameters, research parameters and alarm information, were used as candidate conditions for AI audit rules; manual verification combining microscopy was considered as standard, marked whether it was passed or blocked. Using decision tree algorithm, AI audit rules are initially established through high-intensity, multi-round and five-fold cross-validation and AI verification rules were optimized by setting important mandatory cases. The performance of AI verification rules was evaluated by comparing the false negative rate, precision rate, recall rate, F1 score, and pass rate with that of the current autoverification rules using Chi-square test. Another cohort of blood routine analysis data of 12 475 hospitalized patients in the First Hospital of Jilin University during November 1sr to 31st, 2023, were collected as validation group for validation of AI verification rules, which underwent simulated verification via the preliminary AI rules, thus performance of AI rules were analyzed by the above indicators. Results:AI verification rules consist of 15 rules and 17 parameters and do distinguish numeric and morphological abnormalities. Compared with auto-verification rules, the true positive rate, the false positive rate, the true negative rate, the false negative rate, the pass rate, the accuracy, the precision rate, the recall rate and F1 score of AI rules in training group were 22.7%, 1.6%, 74.5%, 1.3%, 75.7%, 97.2%, 93.5%, 94.7%, 94.1, respectively.All of them were better than auto-verification rules, and the difference was statistically significant ( P<0.001), and with no important case missed. In validation group, the true positive rate, the false positive rate, the true negative rate, the false negative rate, the pass rate, the accuracy, the precision rate, the recall rate and F1 score were 19.2%, 8.2%, 70.1%, 2.5%, 72.6%, 89.2%, 70.0%, 88.3%, 78.1, respectively, Compared with the auto-verification rules, The false negative rate was lower, the false positive rate and the recall rate were slightly higher, and the difference was statistically significant ( P<0.001). Conclusion:A set of the AI verification rules are established and verified by using decision tree algorithm of machine learning, which can identify, intercept and prompt abnormal results stably, and is moresimple, highly efficient and more accurate in the report of blood analysis test results compared with auto-vefication.

Objective Compare and analyze the clinical efficacy and imaging differences of zero-profile interbody fusion cage and interbody fusion cage combined with titanium plate in anterior cervical discectomy and fusion(ACDF).Methods The clinical data of 40 patients who underwent ACDF in our hospital from February 2017 to November 2021 were retrospectively analyzed.Among them,22 patients were treated with zero-profile interbody fusion cage(zero-profile group),and 18 patients were treated with interbody fusion cage combined with titanium plate(titanium plate group).Record the operation time and intraoperative blood loss of the two groups.Japa-nese Orthopaedic Association(JOA)score,neck disability index(NDI)score and postoperative dysphagia were used to evaluate the clinical efficacy.Measure the cervical Cobb angle(C2-C7),fusion segment Cobb angle,aver-age intervertebral space height,and fusion segment height.Evaluate the fusion and subsidence of the cage by observ-ing the internal and external bone bridging of the cage through postoperative CT.Results There was no significant difference in operation time and intraoperative blood loss between the two groups(P>0.05).The JOA score,NDI score,average intervertebral space height,and fusion segment height of the two groups after operation were signifi-cantly improved compared with those before operation(P<0.05).The incidence of postoperative dysphagia in the zero-profile group was significantly lower than that in the titanium plate group(P<0.05).The Cobb angle of the fusion segment in the zero-profile group at 3 months after operation was significantly improved compared with that before operation(P<0.05).There was no significant difference in the other radiographic parameters between the two groups at each follow-up time point(P>0.05),except for the Cobb angle of the fusion segment at 3 months after operation and at the last follow-up(P<0.05)and the difference in the extra-fusion bone bridge(ExGBB)between the two groups at the last follow-up(P<0.05).Conclusions In ACDF,the clinical efficacy of zero-profile interbody fusion cage and interbody fusion cage combined with titanium plate is similar,both of which can significantly improve cervical function and postoperative imaging indicators.However,the zero-profile interbody fusion cage sig-nificantly reduced the incidence of dysphagia compared with the interbody fusion cage combined with titanium plate.In the end-stage follow-up,the former is better than the latter in improving the Cobb angle of the fusion segment and ExGBB,which is more conducive to promoting bone graft fusion.Both fuses have the risk of sinking.

Objective To conduct the evaluation and comparison on the application effects of the 5-D Pruritus Assessment Scale and the Multidimensional Uremic Pruritus Assessment Scale in the patients with maintenance hemodialysis.Methods A total of 154 maintenance hemodialysis patients with pruritus symptom in this hospital from February to June 2023 were selected as the study subjects.The 5-D Pruritus Assessment Scale and the Multidimensional Uremic Itch Assessment Scale were used to evaluate the dimensions such as the pruritus degree,duration and itching location.After standardization treatment by aiming at the evaluation results of the two kinds of scales,the Bland-AItman method was adopted to conduct the consistency compari-son.The Spearman correlation coefficient was adopted to test the correlation between the two kinds of scales. Results The consensus limit (LoA) confidence interval of the 5-D Pruritus Assessment Scale was-0.1578 to 0.1603,the Multidimensional Uremic Pruritus Assessment Scale was-0.1592 to 0.1592.The Spearman correlation results showed that the two scales had the positive correlation (r=0.472,P<0.001).In the 5-D Pruritus Assessment Scale,the area under the curve(AUC) of the fractal dimensions such as duration,degree,development direction,disability and distribution were 0.674 (95％CI:0.557-0.790),0.799 (95％CI:0.700-0.899),0.637 (95％CI:0.528-0.747),0.951 (95％CI:0.905-0.997) and 0.786(95％CI:0.701-0.872),respectively.In the Multidimensional Uremic Pruritus Assessment Scale,AUC of the fractal dimen-sions such as symptom and sign,psychological society and sleep were 0.989 (95％CI:0.978-1.000),0.931 (95％CI:0.878-0.985),and 0.951 (95％CI:0.909-0.994),respectively.Conclusion The consistency of the two scales is good,and both scales can be used to evaluate uremia skin pruritus.The Multidimensional Uremic Pruritus Assessment Scale is more targeted in the assessment of sleep dimension,which is more suitable for the evaluation of maintenance hemodialysis patients.

In recent years,the incidence and mortality rates of cancer have been rising steadily,with drug resistance becoming a major challenge in cancer treatment.Traditional monolithic treatment approaches have proven ineffective in addressing the heterogeneity of tumor cells and their multiple resistance mechanisms,leading to suboptimal therapeutic outcomes.Drug combination therapy,as a critical strategy,aims to enhance efficacy and delay the development of drug resistance through the synergistic action of multiple drugs.However,conventional methods for screening drug combinations are time-consuming and costly.With the accumulation of data and advances in computational methods,artificial intelligence,particularly deep learning,has demonstrated great potential in predicting synergistic drug combinations for cancer treatment.Artificial intelligence technologies allow researchers to efficiently predict whether drug combinations exhibit synergistic effects,reducing experimental costs and identifying novel potential synergistic combinations.Nevertheless,artificial intelligence models still face challenges such as poor interpretability,insufficient feature integration,and a lack of labeled data.This paper provided a comprehensive review of the advancements in artificial intelligence applications for predicting synergistic drug combinations in cancer therapy.First,it discussed the mechanisms of drug resistance and the challenges of combination therapy,highlighting the limitations of traditional drug combination screening methods.Then,it presented the advantages and disadvantages of various deep learning models used for predicting synergistic drug combinations,including feedforward neural networks,graph neural networks,autoencoders,visible neural networks,Transformer and their extended models.In response to the common issues in current deep learning models,this review proposed several solutions,such as leveraging multimodal data to enhance model generalization,employing transfer learning and multitask learning to address data scarcity,and designing more interpretable models to facilitate clinical application.In the future,the field of synergistic drug combination prediction is expected to benefit from the development of standardized synergy metrics,improvements in model interpretability,integration of multimodal data,and effective handling of data limitations,further advancing the transition of models from laboratory research to clinical practice,ultimately providing more effective solutions for cancer treatment.

AIM:To explore the roles and associations of hepatocyte nuclear factor 4 alpha(HNF4A)and mu-protocadherin(MUCDHL)in the kidney of diabetic mice.METHODS:(1)A cohort of six 12-week-old db/m mice and six db/db mice were selected and maintained on a standard diet until 16 weeks.The protein levels of fibronectin(FN),collagen type III(Col-III),E-cadherin,α-smooth muscle actin(α-SMA),HNF4A,Snail and MUCDHL in renal tissues were scrutinized using Western blot.Immunohistochemical staining was conducted to observe the distribution and expres-sion of FN,HNF4A and MUCDHL.(2)Mouse renal tubular epithelial cells(mRTEC)were cultured in vitro and catego-rized into groups:normal glucose(NG)group,high glucose(HG)group,overexpression control groups(NG+vector and HG+vector),overexpression groups(NG+OE-MUCDHL,HG+OE-MUCDHL,NG+OE-HNF4A and HG+OE-HNF4A),knockdown control groups(NG+control and HG+control),and knockdown groups(NG+si-MUCDHL,HG+si-MUCDHL,NG+si-HNF4A and HG+si-HNF4A).The relevant protein levels were also detected by Western blot.RESULTS:(1)In db/db group,elevated body weight,blood glucose and urine albumin-to-creatinine ratio(UACR)indicated significant re-nal injury.Compared with db/m group,the mice in db/db group exhibited increased expression of FN,Col-III,α-SMA and Snail,and decreased expression of E-cadherin,HNF4A and MUCDHL.MUCDHL was predominantly expressed in the apical membrane of renal tubular epithelial cells,FN in the tubular mesenchyme,and HNF4A in the plasma and nu-cleus of renal tubular cells.(2)In HG group,there was an up-regulation in the expression of fibrosis-related proteins and a down-regulation in the expression of E-cadherin,HNF4A and MUCDHL compared with NG group.Overexpression of MUCDHL led to a decrease in the expression of FN,Col-III,α-SMA and Snail proteins,an increase in the expression of E-cadherin and MUCDHL proteins,and unaltered expression of HNF4A.Knockdown of MUCDHL resulted in a reversal of the aforementioned effects,with HNF4A expression remaining unaltered.Overexpression of HNF4A led to an increased ex-pression of MUCDHL,and the expression changes of the remaining indicators were consistent with the overexpression of MUCDHL.Knockdown of HNF4A reversed the aforementioned effects.MUCDHL may represent a downstream target gene of HNF4A.CONCLUSION:The diminished expression of HNF4A and MUCDHL in the renal tubules of diabetic mice implies their involvement in the progression of renal fibrosis in diabetic kidney disease(DKD).HNF4A may potentially impede the progression of renal fibrosis in DKD by up-regulating the expression of MUCDHL.