Drug resistance is one of the key factors affecting the effectiveness of cancer treatment methods, including chemotherapy, radiotherapy, and immunotherapy. Its occurrence is related to factors such as mRNA expression and methylation within cancer cells. If drug resistance in patients can be accurately identified early, doctors can devise more effective treatment plans, which is of great significance for improving patients' survival rates and quality of life. Cancer drug resistance prediction based on artificial intelligence (AI) technology has emerged as a current research hotspot, demonstrating promising application prospects in guiding clinical individualized and precise medication for cancer patients. This review aims to comprehensively summarize the research progress in utilizing AI algorithms to analyze multi-omics data including genomics, transcriptomics, epigenomics, proteomics, metabolomics, radiomics, and histopathology, for predicting cancer drug resistance. It provides a detailed exposition of the processes involved in data processing and model construction, examines the current challenges faced in this field and future development directions, with the aim of better advancing the progress of precision medicine.

OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

Objective·To evaluate the clearance and pharmacokinetics/pharmacodynamics(PK/PD)of antibiotics from the perspective of protein binding rates in critically ill patients undergoing intermittent hemodialysis(IHD),in order to explore the association between protein binding rate and dialysis clearance of antibiotics,and to provide theoretical basis for developing antibiotic dosing regimens during hemodialysis.Methods·Nineteen patients undergone low-flux hemodialysis and received antibiotic therapy at the Department of Nephrology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,were enrolled and divided into the meropenem group(n=7),the vancomycin group(n=5)and the ceftriaxone group(n=7)according to the type of antibiotics.A liquid chromatography with tandem mass spectrometry(LC-MS/MS)method was established to detect meropenem,vancomycin,and ceftriaxone in human plasma/serum and dialysate.A two-compartment pharmacokinetic model was established using MATLAB.Instantaneous and total dialysis clearance rates were calculated,and PK/PD parameters were analyzed.Results·No significant differences were found in the clinical characteristics of subjects among the three groups.The dialysis clearance rates were as follows:meropenem group(5.14?5.97 L/h)>vancomycin group(2.87?3.77 L/h)>ceftriaxone group(1.21?1.90 L/h),with statistically significant differences(P<0.001).All three antibiotics showed good fit in the two-compartment pharmacokinetic model with a dialysate chamber(fval%<2),and the calculated PK/PD parameters were consistent with previous literature.For meropenem,the fraction of time that the free drug concentration remained above the minimal inhibitory concentration(%fT>MIC)values were 95.2%,60.8%and 32.4%at minimal inhibitory concentration(MIC)values of 2,8 and 16 μg/mL,respectively.For ceftriaxone(free concentration),the%fT>MIC values were all above 45.0%at MICs of 0.25,4 and 16 μg/mL.For vancomycin,only 14.0%of the trough concentrations reached the target range of 15?20 mg/L.Conclusion·The three antibiotics are well described by the two-compartment model.The plasma protein binding rate has a significant effect on the dialysis clearance of antibiotics in low-flux IHD,with higher protein binding associated with lower clearance.The regimens of meropenem(0.5 g/d)and ceftriaxone(2.0 g/d)are generally effective among patients undergoing low-flux IHD,while the vancomycin regimen with a loading dose of 1.0 g and a maintenance dose of 0.5 g/2 d carries a risk of treatment failure.

Objective:To systematically analyze the risk factors for knee injury complicated with adolescent tibial tubercle fractures (ATTF).Methods:A retrospective study was conducted to analyze the clinical data of the 90 adolescent patients (the observation group) who had been treated and fully followed up for knee injury complicated with ATTF at Department of Pediatric Orthopedics, The Second General Hospital of Fuzhou from September 2017 to April 2024. There were 86 males and 4 females, with a mean age of 14.0 (13.0, 14.0) years. The injury was on the left side in 51 cases, on the right side in 34 ones, and on the bilateral sides in 5 ones. All their injuries resulted from sports activities. In addition, another contemporary 90 patients with knee injury but no exercise-induced ATTF were enrolled as the control group, including 54 males and 36 females with a mean age of 14.0 (13.0, 14.3) years. Their injury was on the left side in 45 cases, on the right side in 41 ones, and on the bilateral sides in 4 ones. Univariate analysis was conducted to compare gender, age, injury side, height, weight, body mass index, history of Osgood-Schlatter disease (OSD), and injury mechanism between the 2 groups. Variables with P<0.1 were included in a multivariate logistic regression analysis to screen independent risk factors for ATTF. The receiver operating characteristic (ROC) curve was used to evaluate their predictive values. The optimal cutoff value was determined by Youden index. Results:The univariate analysis showed that gender, height, weight, body mass index, and OSD history were significantly correlated with the occurrence of ATTF ( P<0.05). The multivariate logistic regression analysis further confirmed that male ( P=0.017), height ( P=0.021), weight ( P=0.014), body mass index ( P=0.032) and history of OSD ( P=0.003) were independent risk factors for ATTF. The ROC curve analysis showed that weight had the largest area under the curve (AUC) in prediction of the ATTF risk, suggesting that its predictive value was the most significant. Conclusion:Male, height, weight, body mass index, and prior OSD are independent risk factors for ATTF, with the highest predictive value in weight.

Objective:To analyze the risk factors for growth disturbance (GD) in children with distal femoral epiphyseal fracture (DFEF) after surgical treatment.Methods:A retrospective study was conducted to analyze the clinical data of the 72 children who had undergone surgery for DFEF at Department of Pediatric Orthopaedics, The Second General Hospital of Fuzhou between February 2013 and February 2024. There were 52 boys and 20 girls with an age of 11.0 (5.0, 13.0) years. The data collected included age at injury, gender, side affected, cause for injury, time from injury to surgery, the maximum fracture displacement, Salter-Harris fracture classification, and presence of high-energy trauma. The risk factors for GD after DFEF surgical treatment were determined through univariate analysis and logistic regression analysis.Results:Distal femur GD occurred in 40.2% (29/72) of the children treated surgically for DFEF. The univariate analysis showed that, compared with the children without GD, those with GD had a significantly significantly longer time from injury to surgery ( P=0.005), a significantly greater fracture displacement ( P=0.002), and more severe Salter-Harris fracture classification ( P=0.045). The logistic analysis showed that all the 3 factors were independent risk factors for GD ( P<0.05). Conclusion:After DFEF surgery, the GD risk is significantly increased by the 3 factors:longer time from injury to surgery, greater fracture displacement, and more severe fracture classification.

Objective·To evaluate the clearance and pharmacokinetics/pharmacodynamics(PK/PD)of antibiotics from the perspective of protein binding rates in critically ill patients undergoing intermittent hemodialysis(IHD),in order to explore the association between protein binding rate and dialysis clearance of antibiotics,and to provide theoretical basis for developing antibiotic dosing regimens during hemodialysis.Methods·Nineteen patients undergone low-flux hemodialysis and received antibiotic therapy at the Department of Nephrology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,were enrolled and divided into the meropenem group(n=7),the vancomycin group(n=5)and the ceftriaxone group(n=7)according to the type of antibiotics.A liquid chromatography with tandem mass spectrometry(LC-MS/MS)method was established to detect meropenem,vancomycin,and ceftriaxone in human plasma/serum and dialysate.A two-compartment pharmacokinetic model was established using MATLAB.Instantaneous and total dialysis clearance rates were calculated,and PK/PD parameters were analyzed.Results·No significant differences were found in the clinical characteristics of subjects among the three groups.The dialysis clearance rates were as follows:meropenem group(5.14?5.97 L/h)>vancomycin group(2.87?3.77 L/h)>ceftriaxone group(1.21?1.90 L/h),with statistically significant differences(P<0.001).All three antibiotics showed good fit in the two-compartment pharmacokinetic model with a dialysate chamber(fval%<2),and the calculated PK/PD parameters were consistent with previous literature.For meropenem,the fraction of time that the free drug concentration remained above the minimal inhibitory concentration(%fT>MIC)values were 95.2%,60.8%and 32.4%at minimal inhibitory concentration(MIC)values of 2,8 and 16 μg/mL,respectively.For ceftriaxone(free concentration),the%fT>MIC values were all above 45.0%at MICs of 0.25,4 and 16 μg/mL.For vancomycin,only 14.0%of the trough concentrations reached the target range of 15?20 mg/L.Conclusion·The three antibiotics are well described by the two-compartment model.The plasma protein binding rate has a significant effect on the dialysis clearance of antibiotics in low-flux IHD,with higher protein binding associated with lower clearance.The regimens of meropenem(0.5 g/d)and ceftriaxone(2.0 g/d)are generally effective among patients undergoing low-flux IHD,while the vancomycin regimen with a loading dose of 1.0 g and a maintenance dose of 0.5 g/2 d carries a risk of treatment failure.

Objective:To systematically analyze the risk factors for knee injury complicated with adolescent tibial tubercle fractures (ATTF).Methods:A retrospective study was conducted to analyze the clinical data of the 90 adolescent patients (the observation group) who had been treated and fully followed up for knee injury complicated with ATTF at Department of Pediatric Orthopedics, The Second General Hospital of Fuzhou from September 2017 to April 2024. There were 86 males and 4 females, with a mean age of 14.0 (13.0, 14.0) years. The injury was on the left side in 51 cases, on the right side in 34 ones, and on the bilateral sides in 5 ones. All their injuries resulted from sports activities. In addition, another contemporary 90 patients with knee injury but no exercise-induced ATTF were enrolled as the control group, including 54 males and 36 females with a mean age of 14.0 (13.0, 14.3) years. Their injury was on the left side in 45 cases, on the right side in 41 ones, and on the bilateral sides in 4 ones. Univariate analysis was conducted to compare gender, age, injury side, height, weight, body mass index, history of Osgood-Schlatter disease (OSD), and injury mechanism between the 2 groups. Variables with P<0.1 were included in a multivariate logistic regression analysis to screen independent risk factors for ATTF. The receiver operating characteristic (ROC) curve was used to evaluate their predictive values. The optimal cutoff value was determined by Youden index. Results:The univariate analysis showed that gender, height, weight, body mass index, and OSD history were significantly correlated with the occurrence of ATTF ( P<0.05). The multivariate logistic regression analysis further confirmed that male ( P=0.017), height ( P=0.021), weight ( P=0.014), body mass index ( P=0.032) and history of OSD ( P=0.003) were independent risk factors for ATTF. The ROC curve analysis showed that weight had the largest area under the curve (AUC) in prediction of the ATTF risk, suggesting that its predictive value was the most significant. Conclusion:Male, height, weight, body mass index, and prior OSD are independent risk factors for ATTF, with the highest predictive value in weight.

Objective:To analyze the risk factors for growth disturbance (GD) in children with distal femoral epiphyseal fracture (DFEF) after surgical treatment.Methods:A retrospective study was conducted to analyze the clinical data of the 72 children who had undergone surgery for DFEF at Department of Pediatric Orthopaedics, The Second General Hospital of Fuzhou between February 2013 and February 2024. There were 52 boys and 20 girls with an age of 11.0 (5.0, 13.0) years. The data collected included age at injury, gender, side affected, cause for injury, time from injury to surgery, the maximum fracture displacement, Salter-Harris fracture classification, and presence of high-energy trauma. The risk factors for GD after DFEF surgical treatment were determined through univariate analysis and logistic regression analysis.Results:Distal femur GD occurred in 40.2% (29/72) of the children treated surgically for DFEF. The univariate analysis showed that, compared with the children without GD, those with GD had a significantly significantly longer time from injury to surgery ( P=0.005), a significantly greater fracture displacement ( P=0.002), and more severe Salter-Harris fracture classification ( P=0.045). The logistic analysis showed that all the 3 factors were independent risk factors for GD ( P<0.05). Conclusion:After DFEF surgery, the GD risk is significantly increased by the 3 factors:longer time from injury to surgery, greater fracture displacement, and more severe fracture classification.

Objective To construct N6-methyladenosine related long non-coding RNA(LncRNA)pairing model for renal cell carcinoma based on bioinformatics analysis of the cancer ganome atlas(TCGA)database and to explore its prognosis value.Methods Transcriptome data of RNA-sep for renal cell carcinoma and its related clinical information were downloaded from the TCGA database.Perl software was used to organize and separate LncRNA and messenger RNA(mRNA)from the transcriptome data.A total of 564 tissues from renal cell carcinoma cases and 72 normal tissues were obtained,and thus 540 renal cancer patients were eventually included.Random data table method was used to divide 540 patients with renal cancer into a training group(n=275)and a validation group(n=265)by caret.M6A related LncRNA pairing models were established based on the single factor and multivariate COX regression analysis.The risk assessment equation was obtained using the LASSO regression algorithm.The risk scores were calculated based on this equation,and the optimal critical point of the median risk value was applied to divide all patients into high-risk and low-risk groups.Kaplan-Meier survival analysis was used to make a survival curve for the differences between high and low risk groups in the overall sample.The gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses were conducted using the Cluster Profiler software package.The relationship between N6-methyladenosine related LncRNA pairing model and immune cell infiltration was analyzed by R software.Results Kaplan-Meier survival analysis showed the total survival time of patients in the low-risk group was significantly higher than that of patients in the high-risk group of the training group(P<0.05).Compared with high risk group,the overall survival time of patients(G1～2,G3～4,Ⅰ～Ⅱ,or Ⅲ～Ⅳ,age≤65 years,or patients>65 years old)in low risk group was higher(P<0.05).Differential gene enrichment analysis was obtained for high and low risk groups,which mainly enriched with many differential genes such as muscle contraction,rhabdomytic cell differentiation,myofibril,receptor activation activity,and vascular smooth muscle contraction.The highest driver genes in high risk group and low risk group exhibited mutation frequency and mutation information,and their risk score was positively correlated with the degree of T cell and plasma cell infiltration(r=0.638,P=0.001).Conclusion Bioinformatics-based analysis of the N6-methyladenosine related LncRNA pairing models can be helpful to predict the prognosis of patients with renal cancer.It provides new ideas for the prognosis evaluation and optimal treatment strategy of renal cancer,and contributes to further analyzing the molecular mechanism of the occurrence and development of gastric cancer in the future.

Objective:To compare the therapeutic effects of cannulated screws and Kirschner wires in the treatment of medial malleolar fractures of Salter-Harris types Ⅲ and Ⅳ in children.Methods:A retrospective study was conducted to analyze the data of 48 and 16 children who had been treated respectively at Department of Pediatric Orthopaedics, Fuzhou Second General Hospital, and Department of Pediatric Orthopaedics, Foshan Hospital of Traditional Chinese Medicine for medial malleolar fractures of Salter-Harris types Ⅲ and Ⅳ from June 2016 to June 2022. There were 32 males and 32 females with an age of 12 (10, 14) years; 31 left and 33 right sides were affected. By the Salter-Harris classification: type Ⅲ in 45 cases, and type Ⅳ in 19 cases. The patients were divided into 2 groups according to their internal fixation methods. Group A (44 cases) was subjected to internal fixation with cannulated screws and group B (20 cases) to internal fixation with Kirschner wires. At the last follow-up, anteroposterior and lateral X-ray films of their ankle joints were taken for imaging evaluation. Functional recovery of the affected limbs was evaluated based on the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scoring, and related complications were recorded.Results:The 2 groups were comparable because there were no significant differences in their preoperative general data except laterality ( P>0.05). All the patients were followed up for (37.3±21.5) months and achieved bony union. At the last follow-up, for groups A and B respectively, the distal lateral angle of the tibia was 89.0° (89.0°, 90.0°) and 89.0° (89.0°, 90.0°), the range of ankle motion was 73.5° (67.8°, 76.0°) and 70.0° (70.0°, 75.0°), and the good and excellent rate by the AOFAS ankle-hindfoot scoring was 97.7% (43/44) and 95.0% (19/20), showing no significant difference between the 2 groups ( P>0.05). There was a significant difference between the 2 groups in the incidence of premature physeal closure [36.4% (16/44) versus 65.0% (13/20)] ( P=0.033). Conclusions:In the treatment of medial malleolar fractures of Salter-Harris types Ⅲ and Ⅳ in children, internal fixation with both cannulated screws and Kirschner wires can lead to comparable efficacy in good functional recovery and imaging evaluation. However, fixation with cannulated screws may be more advantageous in reducing the risk of early closure of the epiphysis.