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.

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 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 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 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.

Objective:To compare treatment effect of the new multi-dimensional cross locking plate-II (MDC-LP-II) and locking compression plate (LCP) as additional plates in the treatment of nonunion after intramedullary nailing treatment of subtrochanteric fractures.Methods:A retrospective analysis was performed on 23 patients with nonunion after subtrochanteric fractures treated with intramedullary nails from January 2019 to January 2021. According to the type of additional plate, it was divided into MDC-LP-II group and LCP group. There were 12 patients in MDC-LP-II group, including 10 males and 2 females, with an age of 36.83±12.61 years, a body mass index (BMI) of 25.09±2.37 kg/m 2, the time from the last operation to this treatment was 12.25±2.93 months, the number of previous operations was 1.33±0.65, 5 cases of hypertrophic nonunion, 7 cases of atrophic nonunion, and the length of bone nonunion defect was 1.19±0.78 cm. In the LCP group, there were 11 cases, 9 males and 2 females, aged 30.55±8.85 years, BMI was 26.74±5.05 kg/m 2, a time of 12.82±4.40 months after the last operation, the number of previous operations was 1.36±0.96, 5 cases of hypertrophic nonunion, 6 cases of atrophic nonunion, and the length of bone nonunion defect was 1.20±0.57 cm. The incision length, additional plate length, number of screws, number of bicortical screws, intraoperative blood loss, blood transfusion, healing time of nonunion, Harris hip score, lower extremity functional scale (LEFS) and the medical outcomes study item short from health survey-36 (SF-36) were compared between the two groups. Results:All 23 patients were followed up. The follow-up time of MDC-LP-II group was 14.17±2.55 months, and that of LCP group was 14.45±3.75 months, with no significant difference ( t=0.22, P=0.834). In MDC-LP-II group, the incision length was 7.25±2.01 cm, the plate length was 9.25±0.62 cm, the number of screws was 7.17±0.94, the number of bicortical screws was 7.17±0.94, the intraoperative blood loss was 279.17±169.84 ml, and the blood transfusion was 166.67±187.05 ml. In LCP group, the incision length was 15.45±4.72 cm, the plate length was 15.51±2.38 cm, the number of screws was 5.09±0.95, the number of bicortical screws was 1.82±1.72, the intraoperative blood loss was 481.82±227.24 ml, and the blood transfusion was 685.45±299.95 ml. There were significant differences in incision length ( P<0.05), plate length ( P<0.05), number of screws ( P<0.05), number of bicortical screws ( P<0.05), intraoperative blood loss ( P<0.05), and blood transfusion volume ( P<0.05) between the two groups. The fracture healing rate was 100% in MDC-LP-II group and 64% in LCP group at 6 months after operation, and the difference was statistically significant ( P<0.05). At 12 months after operation, the healing rate of LCP group was 91%, and the difference was not statistically significant ( P=0.478). The Harris score 92.83±8.04 and LEFS 74.92±6.68 at the last follow-up in MDC-LP-II group and the Harris hip score 83.36±9.89 and LEFS 66.27±7.68 at the last follow-up in LCP group were significantly different between the two groups ( P<0.05). In terms of SF-36, scores of physical function, physical pain, general health status, vital vitality and mental health of MDC-LP-II group were higher than those of LCP group. No complications related to the use of MDC-LP-II or LCP fixation were observed in both groups. Conclusion:On the basis of preserving the original intramedullary nail, MDC-LP-II compared with LCP as additional plates in the rebuilding of nonunion after intramedullary nailing treatment of subtrochanteric fractures, it can effectively enhance the stability of the broken ends in a much smaller operating range, reduce the surgical trauma, protect the local blood supply and accelerate the healing of the broken end of the fracture. The patients who received MDC-LP-II treatment had better lower limb function recovery and quality of life.

Maili moxibustion can alleviate cancer pain, reduce bone marrow suppression, alleviate gastrointestinal reaction of chemotherapeutic drugs, alleviate cancer-related fatigue, inhibit neurotoxic reaction, improve quality of life and prolong patients' survival. It plays therapeutic effects by regulating immunity, inhibiting tumor cell proliferation and regulating tumor microenvironment. The researches of Maili moxibustion for tumor focus on reducing the toxic or side effects of radiotherapy or chemotherapy. In the future, we should continue to study the combination of Maili moxibustion and other therapies on the treatment of tumor.

Objective:To investigate the radiation dosimetry and biodistribution of 68Ga-FAPI-04 PET/CT in patients with hepatobiliary tumor. Methods:A total of six patients with hepatic lesions who underwent PET/CT examination in Peking Union Medical College Hospital were enrolled. After intravenous injection of radiotracer 68Ga-FAPI-04 at (170.57 ± 14.43) MBq, whole-body imaging were performed at the time points of 3, 10, 15, 20, 30 and 60 min, respectively. Biodistribution pattern was observed. Regions of interest were manually delineated. Radiation dosimetry of all target organs were calculated by Olinda/EXM software. Results:The radioactive uptake dissipated gradually in liver whereas it was relatively stable in tumor lesions. The average SUV max of tumor lesions reached the maximum value (13.87± 2.55) at 20 min after injection. The target-to-background ratio increased with time, reaching the maximum value (10.09 ± 8.17) at 30 min after injection. The average effective dose in total body was (0.020 ± 0.002) mSv/MBq and organ with the highest effective dose was bladder wall at (0.146 ± 0.035) mSv/MBq. Conclusions:The effective dose in total body of 68Ga-FAPI-04 was similar to that of 18F-FDG. 68Ga-FAPI-04 is expected to be a PET/CT radiotracer for hepatobiliary tumors in consideration of rapid tumor uptake, low accumulation of liver background, and no influence of blood sugar levels.

Objective:To assess the effect and safety of bone-filling mesh container (BFC) and percutaneous kyphoplasty (PKP) in treatment of osteoporotic vertebral compression fractures (OVCF).Methods:PubMed, Web of Science, Cochrane Library, CNKI, VIP, CBM and Wanfang database were searched by computer from inception to September 2019, for the randomized controlled trial (RCT) or case-control trial (CCT) that compared the treatment of OVCF using BFC and PKP. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the quality of the included studies. Then meta-analysis was performed using RevMan 5.3. The literature search results, basic characteristics of the included studies, operation time, postoperative visual analogue score (VAS), Oswestry disability index (ODI), Cobb's angle, leakage rate of the bone cement and publication bias were evaluated.Results:Only 5 RCTs and 5 CCTs involving 668 patients were included. Compared with the PKP group, the BFC group showed no significant difference in postoperative VAS ( MD=-0.06, 95% CI -0.24-0.37), ODI ( MD=-0.20, 95% CI-1.13-0.73) and Cobb's angle ( MD=0.18, 95% CI-0.05-0.91), while there were significant differences in operation time ( MD=-3.07, 95% CI-5.53--0.60) and leakage rate ( OR=0.21, 95% CI 0.12-0.36). Funnel plots showed that there was no significant asymmetry among the above indicators, suggesting that publication bias had little effect on the results. Conclusion:BFC is as effective as PKP in the postoperative efficacy of OVCF, but is superior in operation time and leakage rate of bone cement.