Transalveolar technique for sinus floor elevation(TSFE)offers the advantages of minimal invasiveness,reduced postoperative reaction,and shorter operative time for vertical bone augmentation in the maxillary posterior region.The clinical data of one patient with severe deficiency of residual bone height(RBH)in the maxillary posterior region,a blood vessel visible in the lateral wall of the maxillary sinus and a visible septum at the floor of the maxillary sinus were reported,and two-stage flexible TSFE was used to improve the vertical bone height of the operated area while reducing trauma,the risk of Schneiderian membrane rupture and maxillary sinus infection,etc.,and the relevant literatures were reviewed.The patient,male,26 years old,complained of missing left maxillary posterior teeth for more than 1 year and requested restoration.The patient had 27 missing teeth,normal keratinized gingiva,full alveolar ridge,no elongation of the opposing teeth,fair width of the proximal and normal occlusal distance.The results of cone beam CT(CBCT)showed that the distance between the sinus crests at the site of the 27 teeth was about 3 mm,the width of the alveolar bone was about 12.8 mm,the bone density was normal,and there were no residual roots or other abnormalities;no cyst-like lesions were seen in the walls of the maxillary sinuses bilaterally,and separation was seen at the floor of the maxillary sinus on the left side and a blood vessel was seen in the lateral wall of the maxillary sinus.A diagnosis of Kennedy class Ⅱ maxillary tooth defects was made.After two stages of TSFE,the Schneiderian membrane was intact and the bone height of the implant area was elevated to 9.6 mm from 3 mm preoperatively after the completion of the restoration,with stable bone augmentation,good osseointegration,and restoration of normal occlusal function.For the patients with severe bone height deficiency in the maxillary posterior region,flexible two-stage TSFE should be considered,which can help to reduce the risk of maxillary sinus infection and Schneiderian membrane rupture while minimizing the damage and obtaining the ideal bone augmentation results.

Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.

Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Objective To investigate the value of monocyte to lymphocyte ratio(MLR)and neutrophil percentage to albumin ratio(NPAR)in predicting diabetic macular edema(DME).Methods One hundred and one diabetic retinopathy patients admitted to the Third Affiliated Hospital of Xinxiang Medical University from January 2018 to February 2023 were selected as the research subjects,and they were divided into DME group(n=56)and non-DME group(n=45)based on fun-dus examination results.The general data such as gender,age,course of diabetes and laboratory indicators were collected by consulting medical records.Fasting elbow venous blood was collected early in the morning of the next day after the diagnosis of DME in both groups,the monocytes(MONO)count,lymphocyte(LYM)count,white blood cell(WBC)count,percentage of neutrophils(NEUT),plasma albumin(ALB),glycosylated haemoglobin(HbA1c)were measured by full automatic blood routine analyzer,and MLR,NPAR were calculated.General information and laboratory indexes of patients in the two groups were compared,and risk factors for DME were analyzed by multivariate logistic regression,and receiver operator characteristic(ROC)curve was applied to evaluate the predictive value of MLR and NPAR for DME.Results The course of diabetes,MONO count,NEUT,MLR,NPAR,WBC count,and HbA1c level of patients between the DME group were significantly higher than those in the non-DME group(P＜0.05);there was no statistically significant difference in gender,age,LYM count,and ALB level of patients between the two groups(P＞0.05).Multivariate logistic regression analysis showed that increased levels of WBC,MLR,and NPAR were independent risk factors for the occurrence of DME(P＜0.05).The ROC curve showed that the best cut-off value of MLR was 0.192,and the area under the curve(AUC)for the prediction of DME was 0.729(95％confidence interval:0.631-0.826),with a sensitivity of 58.9％and a specificity of 82.2％;while the best cut-off value of NPAR was 1.404,and the AUC for predicting DME occurrence was 0.884(95％confidence interval:0.820-0.949),with a sensitivity of 75.0％and a specificity of 91.1％;the AUC of MLR and NPAP for predicting the occurrence of DME was 0.906(95％confidence interval:0.851-0.906),with a sensitivity of 69.6％and a specificity of 93.3％.With MLR＞0.192 as positive and NPAR＞1.404 as positive,the parallel test of MLR and NPAR predicted the occurrence of DME with a sensitivity of 87.5％,a specificity of 71.1％,and an accuracy of 80.2％;while the tandem test of MLR and NPAR predicted the occurrence of DME with a sensitivity of 46.4％,a specificity of 97.8％,and an accuracy of 69.3％.Conclusion Increased levels of MLR and NPAR are independent risk factors for the occurrence of DME and have certain predictive value for DME.The predictive value of combined MLR and NPAR test for DME is higher than that of separate test,and parallel experiment is more helpful for the early prediction of DME.

Objective:To predict the short-term postoperative recurrence status of patients with refractory temporal lobe epilepsy (TLE) by analyzing preoperative 18F-FDG PET images and patients′ clinical characteristics based on deep residual neural network (ResNet). Methods:Retrospective analysis was conducted on preoperative 18F-FDG PET images and clinical data of 220 patients with refractory TLE (132 males and 88 females, age 23.0(20.0, 30.2) years)) in the First Affiliated Hospital of Jinan University between January 2014 and June 2020. ResNet was used to perform high-throughput feature extraction on preprocessed PET images and clinical features, and to perform a postoperative recurrence prediction task for differentiating patients with TLE. The predictive performance of ResNet model was evaluated by ROC curve analysis, and the AUC was compared with that of classical Cox proportional risk model using Delong test. Results:Based on PET images combined with clinical feature training, AUCs of the ResNet in predicting 12-, 24-, and 36-month postoperative recurrence were 0.895±0.073, 0.861±0.058 and 0.754±0.111, respectively, which were 0.717±0.093, 0.697±0.081 and 0.645±0.087 for Cox proportional hazards model respectively ( z values: -3.00, -2.98, -1.09, P values: 0.011, 0.018, 0.310). The ResNet showed best predictive effect for recurrence events within 12 months after surgery. Conclusion:The ResNet model is expected to be used in clinical practice for postoperative follow-up of patients with TLE, helping for risk stratification and individualized management of postoperative patients.

Objective:To explore the spatial support capacity and its influence in osteogenic effect of composite biofilm based on poly(propylene carbonate)(PPC)/poly(butylene succinate)(PBS)in rabbit tibial bone defect models,and to clarify its barrier functional reliability and osteogenetic effect in vivo.Methods:The composite biofilms of PPC/PBS and PPC/PBS/collegen type Ⅰ(Col-Ⅰ)(PPC/PBS/Co)were prepared.Eighteen Japanese big-ear rabbits were selected and two bone defects were prepared on each side of the tibia of the rabbits.Six rabbits were randomly selected to place PPC/PBS composite biofilm on the bone defects,2 rabbits were executed at 2,4,8 and 12 weeks after operation,and the surface microstructures of PPC/PBS composite biofilm in the rabhit bone defect area were observed by scanning electron microscope(SEM).The experiment was divided into blank control group,PPC/PBS composite biofilm group,BME-10X collagen membrane group,and PPC/PBS/Co composite biofilm group.The above biofilms were placed on the corresponding bone defects of rabbits by operation,while no biofilm was placed in the rabbits in blank control group.Three rabbits were killed at 2,4,8 and 12 weeks after operation respectively,and the gray values of regenerated bone in the bone defect areas of the rabbits in varrous groups were detected by soft X-ray;the fluorescence intensities of regenerated bone tissue in the bone defect areas of the rabbits in various groups were observed by laser scanning confocal microscope after fluorescence labeling.The pathomorphology of regenerated bone tissue in the bone defect areas of the rabbits in various groups were observed by HE staining and modified Gomori staining,and the expression levels of bone morphogenetic protein 2(BMP-2)and osteopontin(OPN)in the regenerated bone tissue in bone defect areas of the rabbits in various groups were detected by immunohistochemical staining.Results:In general,the PPC/PBS composite biofilm was tightly covered in the bone defect area without displacement and collapse.The SEM results showed that the porous surface of PPC/PBS composite biofilm appeared micropore structure and the number of micropores was increased with the prolongation of time,while the smooth surface of biofilm basically did not form the micropore-like structure.The results of soft X-ray detection showed that the gray values of regenerated bone tissue in bone defect areas of the rabbits in various groups were increased with the prolongation of time,and the gray value of regenerated bone tissue in bone defect areas of the rabbits in PPC/PBS/Co composite biofilm group was significantly higher than those in other groups(P＜0.05).The confocal micrscope results showed that the fluorescence intensity of regenerated bone tissue in bone defect areas of the rabbits in PPC/PBS/Co composite biofilm group was similar to those in blank control group at 4,8,and 12 weeks;compared with PPC/PBS composite biofilm group and BME-10X collagen membrane group,the fluoresence intensity of regenerated bone tissue in bone defect areas of the rabbits in PPC/PB/Co composite biofilm group at 4 weeks was increased(P＜0.05),and the fluoresence intensity of regenerated bone tissue in bone defect areas of the rabbits at 8 and 12 weeks were decreased(P＜0.05).The results of HE staining and modified Gomori staining showed that compared with PPC/PBS composite biofilm group and BME-10X collagen membrane group,the new bone formed faster in PPC/PBS/Co composite biofilm group and blank control group at 2 and 4 weeks,and the lamellar bone mineralization was higher at 12 weeks.The immunohistochemical staining results showed that compared with blank control group,PPC/PBS composite biofilm group and BME-10X collagen membrane group,the expression levels of BMP-2 and OPN proteins in the regenerated bone tissue in bone defect areas of the rabbits in PPC/PBS/Co composite biofilm group at 2 and 4 weeks were increased(P＜0.05 or P＜0.01);compared with blank control group and PPC/PBS composite biofilm group,the expression levels of BMP-2 and OPN proteins in the regenerated bone tissue in bone defect areas of the rabbits in BME-10X collage membrane group were decreased(P＜0.05 or P＜0.01).Conclusion:PPC/PBS composite biofilm has excellent spatial support capacity and reliable physical barrier function.The PPC/PBS/Co composite biofilm has a good effect in guiding bone regeneration in vivo.

Objective To explore the risk factors of chemotherapy-induced adverse reactions(CIAEs)caused by capecitabine in colorectal cancer(CRC)patients and to construct a risk prediction model for CIAEs.Methods We retrospectively collected data from postoperative CRC patients treated with capecitabine tablets at our hospital between January 2021 and December 2023.Patients were divided into CIAEs and NCIAEs groups based on the presence or absence of CIAEs.Variable differences were screened using t-tests and chi-square tests.Stepwise multivariate logistic regression was employed to identify independent factors influencing CIAEs in CRC patients.Based on these independent risk factors,a risk prediction model for CIAEs in CRC patients was constructed using R software.The model's predictive ability,calibration,and clinical net benefits were evaluated using receiver operating characteristic(ROC)analysis,calibration curves,and decision curves.Results A total of 253 postoperative CRC patients treated with capecitabine were included in this study.Among them,201 patients developed CIAEs,with nausea and vomiting being the most common(69.96％).Multiple logistic regression results indicated that age[OR=3.018,95％CI(1.404,6.487),P=0.005],prognosis nutrition index[OR=0.129,95％CI(0.06,0.278),P＜0.001],and systematic inflammation index[OR=4.074,95％CI(1.316,12.615),P=0.015]were independent risk factors for CIAEs in CRC patients.The constructed risk prediction model demonstrated good predictive ability,calibration,and clinical net benefit.Conclusion The risk prediction model for CIAEs can be used for individualized prediction of CIAEs in CRC patients and serves as a simple and practical tool for CIAE prevention and nursing management.

Objective To explore the rules of acupoint selection and manipulation application of Tuina in the treatment of diabetes peripheral neuropathy(DPN)with data mining technology.Methods The clinical research literature of Tuina for DPN from October 2022 was selected by searching four Chinese databases that CNKI,WanFang,VIP and Chinese Biomedical Literature Database.Using the traditional Chinese medicine inheritance assistance platform software,analyze and summarize the rules of selecting acupoints and applying manipulations in the treatment of DPN with Tuina.Results A total of 110 articles were included,including 65 acupoints and 33 manipulations.The acupoints with the highest frequency are Zusanli(ST 36),Sanyinjiao(SP 6),Taixi(KI 3),Yongquan(KI 1),Taichong(LR 3),Yanglingquan(GB 34),etc.The meridians mainly include Taiyin Spleen Meridian of Foot,Yangming Stomach Meridian of Foot,Taiyang Bladder Meridian of Foot and Shaoyin Kidney Meridian of Foot.Five-shu Points,Lower He-sea Points and Yuan-primary Points are commonly used specific points.The acupoints are mostly distributed in the lower limbs.The categories of Tuina manipulations mainly include squeezing-pressing manipulations,pushing rolling manipulations and composite manipulations.The Tuina manipulations mainly include kneading manipulation,pressing manipulation,point-pressing manipulation,pressing-kneading manipulation and twisting manipulation with both palms.Conclusion The acupoint selection and manipulation application of Tuina in treating DPN have certain rules,and the main treatment principles are to regulate the organs and dredge collaterals,and to replenish qi and promote blood circulation,which can provide objective basis for clinical treatment.