The Relationship Between Small Dense Low-Density Lipoprotein Cholesterol and Metabolic Syndrome.

Background: Prior research has established an association between small dense low-density lipoprotein cholesterol (sdLDL-C) and dyslipidemia, serving as a significant marker for predicting cardiovascular diseases. Nevertheless, the connection between sdLDL-C and metabolic syndrome (MetS) remains unclear. Methods: This study retrospectively analyzed 23,187 individuals who underwent health checkups at Taizhou Hospital's health management center. Here, we investigated the relationship between sdLDL-C and MetS, along with its components, utilizing Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, logistic regression, and mediation analysis. Results: The MetS group exhibited significantly higher level of sdLDL-C compared to the non-MetS group (P<0.001). We observed a strong correlation between sdLDL-C and several key factors: TG (r = 0.711), TC (r = 0.672), LDL-C (r = 0.781), GGT (r = 0.420), and HDL-C (r = -0.417). After adjusting for age and gender, the odds ratio (OR) (95% confidence interval [CI]) for MetS incidence in the second, third, and fourth quartiles versus the first quartile of sdLDL-C concentration were 2.264 (95% CI: 1.851, 2.770), 4.053 (95% CI: 3.350, 4.903), and 9.034 (95% CI: 7.531, 10.837). The optimal cut-off value for diagnosing MetS using sdLDL-C was determined to be 0.98 mmol/L, with an area under the ROC curve (AUC) of 0.716 (95% CI: 0.705, 0.726). Additionally, mediation analysis revealed that sdLDL-C mediated a 12.8% correlation between GGT and TG concentration. Conclusion: The sdLDL-C is correlated with MetS and it can successfully mediate the relationship between GGT and TG. Our data suggests that sdLDL-c and GGT are suitable parameters for preventing and monitoring MetS.

Machine learning in the prediction of in-hospital mortality in patients with first acute myocardial infarction.

BACKGROUND: Persistent efforts are required to further reduce the in-hospital mortality of patients suffering from acute myocardial infarction (AMI), even in the face of a global trend of declining AMI-related fatalities. We investigated deep machine learning models for in-hospital death prediction in patients on their first AMI. METHOD: In this 2-center retrospective analysis, first AMI patients from Hospital I and Hospital II were included; 4783 patients from Hospital 1 were split in a 7:3 ratio between the training and testing sets. Data from 1053 AMI patients in Hospital II was used for further validation. 70 clinical information and laboratory examination parameters as predictive indicators were included. Logistic Regression Classifier (LR), Random Forests Classifier (RF), eXtreme Gradient Boosting (XGB), Support Vector Machine Classifier (SVM), Multilayer Perceptron (MLP), Gradient Boosting Machine (GBM), Bootstrapped Aggregation (Bagging) models with AMI patients were developed. The importance of selected variables was obtained through the Shapley Additive exPlanations (SHAP) method. The performance of each model was shown using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (Average Precision; AP). RESULT: The in-hospital mortality for AMI in the training, testing, and validation sets were 5.7 %, 5.6 %, and 6.0 %, respectively. The top 8 predictors were D-dimer, brain natriuretic peptide, cardiogenic shock, neutrophil, prothrombin time, blood urea nitrogen, cardiac arrest, and phosphorus. In the testing cohort, the models of LR, RF, XGB, SVM, MLP, GBM, and Bagging yielded AUROC values of 0.929, 0.931, 0.907, 0.868, 0.907, 0.923, and 0.932, respectively. Bagging has good predictive value and certain clinical value in external validation with AUROC 0.893. CONCLUSION: In order to improve the forecasting accuracy of the risk of AMI patients, guide clinical nursing practice, and lower AMI inpatient mortality, this study looked into significant indicators and the optimal models for predicting AMI inpatient mortality.

A novel feasible technique for rapid removal of broken proximal femoral nails: A case series.

Proximal femoral nail (PFN) fixation is a technique widely used to treat various femoral fractures, but femoral re-injury may occur, leading to PFN breakage. Broken nail removal, particularly removal of the distal broken nails, is usually challenging. Herein, we describe a feasible approach to successfully remove broken femoral intramedullary nails in three sites (proximal, middle, and distal section) of the PFN. Three patients required surgery for PFN breakage. We performed a novel technique using minimal exposure and a cerclage wire to remove the PFN fragment, which a distal knot on the wire was applied to hold the PFN fragment, and the removal trajectory was completed through the minimal exposure, a distal femoral bone window, and the marrow cavity. We successfully operated these three patients and removed the PFN fragments rapidly and effectively. In conclusion, this novel technique is rapid, feasible, and cost-effective, and can also be promising in removing intramedullary nail breakages in other long bones.

Cholinesterase is a Potential Biomarker with High Accuracy for the Nephrotic Syndrome Diagnosis in Minors.

Background: Serum Cholinesterase (CHE) levels have been found to be elevated in individuals with nephrotic syndrome (NS); nevertheless, it is unknown whether CHE can serve as a biomarker for NS diagnosis and what its diagnostic relevance is for NS in minors. Methods: In this study, 138 minors aged 1-17 years with NS were enrolled, including 101 patients with the first episode of NS and 37 patients with relapsing NS. One hundred and four minors suffering from nephritis and 109 healthy minors were included as control groups. The clinical information and laboratory data of all NS patients and the control group were obtained. Logistic regression, correlation analyses and receiver operator characteristic curve were used to examine the value of CHE for NS patients. Results: Compared to patients diagnosed with nephritis and healthy minors in the control group, the serum CHE levels of total/first episode/relapsing NS patients were substantially higher (P < 0.05). The CHE was an independent risk predictor of total (adjusted odds ratio [OR] = 2.23, 95% confidence interval [CI]: 1.57-3.18)/first episode (adjusted OR = 4.02, 95% CI: 1.47-11.08)/relapsing (adjusted OR = 2.04, 95% CI: 1.42-2.93) NS, and was positively correlated with total cholesterol in total/first episode/relapsing NS patients, respectively. The optimal cutoff for total/first episode/relapsing NS all was 11 KU/L, but the diagnostic accuracy in first episode NS (area under the curve [AUC] = 0.96, 95% CI: 0.94-0.98) was higher than the total NS (AUC = 0.93, 95% CI: 0.91-0.96) and relapsing NS (AUC = 0.85, 95% CI: 0.78-0.92). Conclusion: CHE is a possible biomarker for NS and has good diagnostic accuracy for NS in minors, particularly for the first episode of NS in minors.

Adenosine Deaminase is a Potential Molecular Marker for Diagnosis and Prognosis of Haemorrhagic Fever with Renal Syndrome.

Objective: Haemorrhagic fever with renal syndrome (HFRS) is a serious zoonotic disease which seriously endangers physical health and mainly occurs in China. To date, there is still a lack of early and novel biomarkers to detect the severity of disease and prognosis of HFRS. This study was aimed to examine the value of the serum Adenosine deaminase (ADA) concentrations in the patients with HFRS. Methods: The clinical and laboratory data of 124 adult patients with HFRS and 131 patients with similar clinical symptoms to HFRS were analyzed. A receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of ADA in HFRS. Results: The ADA levels in the serum of HFRS patients were significantly higher than those in control patients (P < 0.001), and ADA has a strong positive correlation with HFRS (r = 0.785, P < 0.001). The optimal cut-off value of ADA for diagnosis of HFRS was 18 U/L and the area under the curve (AUC) was 0.953 (95% CI: 0.925, 0.981). The sensitivity was 84.8%, the specificity was 93.1%, the positive predictive value was 92.2%, the negative predictive value was 86.5% and the Youden index was 77.9%. Serum ADA levels in patients with HFRS tended to decrease at discharge compared with those at admission. Conclusion: ADA could be a potential molecular marker for diagnosis and prognosis of HFRS patients.

Intraoperative periarticular injection can alleviate the inflammatory response and enhance joint function recovery after hip arthroplasty in elderly patients with osteoporotic femoral neck fractures.

PURPOSE: This study aimed to investigate the potential beneficial effects of periarticular injection (PAI) of multimodal drugs on the inflammatory response and joint function after hip arthroplasty in elderly patients with osteoporotic femoral neck fractures. METHODS: Fifty six elderly patients with unilateral osteoporotic femoral neck fractures were randomly allocated to 2 groups: the PAI group, which received the multimodal drug PAI intraoperatively before incision closure, and the control group, which received an injection of saline at the same time as placebo. The C-reactive protein (CRP), interleukin-1ß (IL-1ß), and IL-6 levels as well as the erythrocyte sedimentation rate (ESR) in peripheral venous blood samples were measured, along with the Visual Analogue Scale (VAS) score with activity and Harris hip score preoperation at 1, 2, 4, 7, and 14 days as well as 1 and 3 months post-operation. RESULTS: The 2 groups were comparable in sex and age, and no significant differences were observed in the preoperative CRP, IL-1ß, and IL-6 levels, ESR, VAS score, or Harris hip score between the 2 groups (all P > .05). However, during the postoperative period, the PAI group exhibited significantly lower levels of CRP, IL-1ß, and IL-6 as well as a lower ERS and VAS score compared with the control group (P < .05), while the Harris hip score was significantly higher postoperatively in the PAI group (P < .05). CONCLUSION: Multimodal drug PAI can alleviate the inflammatory response and enhance hip function recovery after hip arthroplasty in elderly patients with osteoporotic femoral neck fractures.

Inhibitory effect of 5-FU loaded ultrasound microbubbles on tumor growth and angiogenesis.

The anti-neovascularization treatment is one of the effective strategies for tumor molecular target therapy. At present, the target and effect of the anti-neovascularization treatment is limited, and it is urgent to establish a new vascular targeting strategy to effectively treat tumors. In this work, we used high intensity focused ultrasound (HIFU) combined with targeted microbubbles to establish a molecular targeted ultrasound response microbubble for neovascular cells. Furthermore, the effects of drug loaded microbubbles on neovascularization and tumor cells were studied. The tumor vascular targeted and ultrasound-responsive microbubbles of 5-FU@DLL4-MBs were prepared by the thin-film dispersion method. The size and zeta potential of 5-FU@DLL4-MBs was about 1248 nm and -9.1 mV. 5-FU@DLL4-MBs released 5-FU showed an ultrasound-responsive manner, and had better vascular-targeting ability. Furthermore, the 5-FU@DLL4-MBs showed the strongest cytotoxic effect on HUVECs or HepG-2 cells and can be effectively internalized into the HUVECs cells. Thus, 5-FU@DLL4-MBs combined with HIFU can be considered as a potential method for antitumor angiogenesis in the future.

Clinical efficacy and safety of drug interventions for primary and secondary prevention of osteoporotic fractures in postmenopausal women: Network meta-analysis followed by factor and cluster analysis.

We aimed to evaluate the comparative efficacy and safety of drugs respectively for primary prevention and secondary prevention of osteoporotic fractures in postmenopausal women (PMW), and to further identify the optimal intervention(s) respectively for the two groups when efficacy and safety both considered. We searched three databases. Bayesian network meta-analyses were conducted for two efficacy outcomes (vertebral fractures and nonvertebral fractures) and two safety outcomes (tolerability and acceptability) respectively in primary prevention group and secondary prevention group. We synthesized hazard ratios (HRs) and 95% confidence intervals (CIs) for nonvertebral fractures, and risk ratios (RRs) for three others. Factor and cluster analyses on surface under the cumulative ranking curve (SUCRA) values were conducted to identify the best intervention(s) with efficacy and safety both considered. The study protocol has been registered in PROSPERO. We included 57 randomized trials involving fifteen anti-osteoporotic interventions and 106320 PMW. For primary prevention, only zoledronate (once per 18 months) reduced both vertebral (RR 0.46, 95% CI 0.28-0.74) and nonvertebral (HR 0.66, 95% CI 0.51-0.85) fractures. For secondary prevention, abaloparatide, alendronate, denosumab, lasofoxifene, risedronate, romosozumab, teriparatide, and zoledronate (once per 12 months) reduced both vertebral (RRs: from 0.17 to 0.62) and nonvertebral (HRs: from 0.54 to 0.81) fractures. PTH (1-84) and abaloparatide increased withdrawal risk. Romosozumab, teriparatide, denosumab and risedronate, with the greatest composite scores, constituted the optimal cluster having both superior efficacy and superior safety. Zoledronate used at 5 mg per 18 months, with the similar safety as placebo, is the only drug intervention which has been shown to significantly reduce both vertebral and nonvertebral fractures for primary prevention of osteoporotic fractures in PMW; while romosozumab, teriparatide, denosumab, and risedronate are the optimal treatments for secondary prevention when efficacy and safety both considered. A limitation is that safety outcomes failed to consider the severity of adverse effects.

Efficacy and Safety of First- and Second-Line Drugs to Prevent Glucocorticoid-Induced Fractures.

CONTEXT: The evidence about benefits and harms of drugs for glucocorticoid (GC)-induced osteoporosis (GIOP) is limited, and the comparative efficacy and safety of first-line and second-line agents to prevent GC-induced (GI) fractures remains unclear. OBJECTIVE: To assess the comparative clinical efficacy, safety, and tolerability of first-line and second-line agents in preventing GI fractures. DATA SOURCES: We searched 3 different databases through March 5, 2019. STUDY SELECTION: We included randomized controlled trials enrolling patients receiving long-term GCs and compared a first-line and second-line agent with one another and with placebo. DATA EXTRACTION: Two reviewers independently extracted study and participant characteristics and outcome data. DATA SYNTHESIS: We performed multivariate random-effects network meta-analyses including base, 3 subgroups, and 12 sensitivity analyses. We included 22 papers from 19 unique trials involving 4328 patients receiving GCs. Teriparatide (risk ratio [RR] 0.11, 95% confidence interval [CI] 0.03-0.47), denosumab (RR 0.21, 95% CI 0.09-0.49), and risedronate (RR 0.33, 95% CI 0.19-0.58) reduced the risk of GI vertebral fractures, and the former 2 were the most efficacious according to violin plots including the surface under the cumulative ranking curve values calculated by base and sensitivity analyses. Oral alendronate (RR 0.33, 95% CI 0.12-0.93) reduced this risk in patients receiving GCs with at least 7.5 mg/day, while intravenous ibandronate (RR 0.25, 95% CI 0.06-0.99) was efficacious for the primary prevention of GIOP. Six drugs were similar in terms of the 5 other outcomes. CONCLUSIONS: In terms of clinical efficacy and safety, second-line teriparatide and denosumab pose a challenge to first-line oral bisphosphonates for prevention of GI fractures.

[Application of wire reduction technique guided by minimally invasive wire introducer in treatment of difficult-reducing intertrochanteric fractures].

OBJECTIVE: To investigate the application effect of wire reduction technique guided by minimally invasive wire introducer in the treatment of difficult-reducing intertrochanteric fractures. METHODS: Between April 2016 and April 2018, 30 patients with intertrochanteric fractures who had difficulty in closed reduction under the traction bed were treated. There were 17 males and 13 females, aged from 60 to 93 years (mean, 72 years). The causes of injury included falls in 22 cases and traffic accidents in 8 cases. The fractures were classified according to AO/Orthopaedic Trauma Association (AO/OTA) classification: 12 cases of type A1, 12 cases of type A2, and 6 cases of type A3. Intramedullary nail incision and self-made minimally invasive wire introducer were used to assist reduction of intertrochanteric fracture, and then intramedullary nail internal fixation was performed. RESULTS: The operation time was 30-70 minutes, with an average of 45 minutes. The intraoperative blood loss was 100-210 mL, with an average of 160 mL. One case died of cerebrovascular accident at 3 months after operation; the remaining 29 cases were followed up 6-18 months, with an average of 8.3 months. Postoperative DR reexamination showed that all patients had a good reduction in the fracture end, no retraction, fracture displacement, hip valgus deformity, and other serious complications occurred. The fracture was completely healed and the healing time was 3-8 months, with an average of 6 months. At 3 months after operation, the visual analogue scale (VAS) score was 1-3, with an averge of 1.7. According to Harris functional score of hip joint, 26 cases were excellent and 3 cases were good. CONCLUSION: For the difficult-reducing intertrochanteric fractures, minimally invasive wire introducer is used to insert steel wire into the incision of head and neck nail for assisted reduction, which can achieve satisfactory reduction results and improve the effectiveness of intertrochanteric fracture.

COL2A1 mutation (c.3508G>A) leads to avascular necrosis of the femoral head in a Chinese family: A case report.

Avascular necrosis of the femoral head (ANFH) is a consequence of ischemia. Although the majority of cases of ANFH are sporadic, certain familial cases of ANFH have been reported to be associated with collagen type II α1 chain (COL2A1) mutations, which lead to COL2A1 gene dysfunction. The structure of secreted type II collagen contains a core area with a triple helical glycine (Gly)­X­Y domain, and the replacement of Gly in this region as a result of COL2A1 mutations may damage the structure of type II collagen. In the present study, a Chinese family with ANFH was recruited and genetic analysis was conducted to determine whether COL2A1 mutations were implicated in this familial ANFH. A three­generation family containing 31 members, as well as 20 patients with sporadic ANFH, were recruited for investigation. The diagnosis was performed by independent surgeons and radiologists according to internationally recognized criteria. In the present study, a heterozygous c.3508G>A mutation in exon 50 of the COL2A1 gene was identified, which results in the substitution of Gly with serine at codon 1,170. Furthermore, genetic pedigree analysis indicated that this mutation was inherited in an autosomal dominant manner. The present study revealed that a heterozygous c.3508G>A mutation in the COL2A1 gene was involved in ANFH development in one Chinese family. Therefore, it is proposed that individuals who carry this c.3508G>A mutation in the COL2A1 gene should receive genetic counseling and early intervention for ANFH.

Antitumor effect of FP3 on a patient-derived tumor tissue xenograft model of rectal carcinoma.

BACKGROUND/AIMS: FP3 is an engineered protein which contains the extracellular domain 2 of VEGF receptor 1 (Flt-1) and extracellular domain 3 and 4 of VEGF receptor 2 (Flk-1, KDR) fused to the Fc portion of human immunoglobulin G1. Previous studies demonstrated its antiangiogenic and antitumor effects in vitro and in vivo. METHODOLOGY: In this study, a PDTT xenograft model of rectal carcinoma was established for assessment of the antitumor activity of FP3. Xenografts were treated with FP3 or bevacizumab (Avastin). After tumor growth was confirmed, volume and microvessel density in tumors were evaluated. Levels of VEGF and PCNA in the tumor were examined by immunohistonchemical staining and western blotting. RESULTS: FP3 showed significant antitumor activity in the PDTT xenograft model of rectal carcinoma. The microvessel density in tumor tissues treated with FP3 was lower than that of the control. Antitumor activity of FP3 was similar to that of bevacizumab in the PDTT xenograft model of rectal carcinoma. CONCLUSIONS: This study indicated that FP3 could be used as an effective antiangiogenic and antitumor agent in treatment of colorectal carcinoma.

[Effect of leptin on inducible NO and MMP-13 in rabbit articular chondrocytes in vitro].

OBJECTIVE: To observe the in vitro effect of leptin, alone or in combination with tumor necrosis factor-alpha (TNF-alpha) on inducible nitric oxide(NO)and on inducible matrix metalloproteinase-13 (MMP-13) in rabbit articular chondrocytes. METHODS: The chondrocytes from the articular cartilage of 2-month-old rabbits were cultivated and identified, and the second filial generation chondrocytes were cocultured on plates with different concentrations of leptin alone or in combination with TNF-alpha for 48 h or 96 h after 12 h starvation. The concentration of NO and MMP-13 was measured in the chondrocytes culture supernatant fluid. The results were statistically analyzed. RESULTS: There was no significant difference in the concentrations of NO between the different concentrations of leptin alone groups and the blank control group (P>0.05). In combination with the same concentration of TNF-alpha (10 ng/mL), leptin could dose-dependently increase the concentration of NO in the chondrocytes culture supernatant fluid in vitro. There was significant value in average concentration of MMP-13 on the main effect of both time and dose (P<0.05). No MMP-13 was detected in the blank control group. CONCLUSION: Leptin can induce MMP-13 and have synergistic induction effect on NO with TNF-alpha in rabbit articular chondrocytes in vitro.

[Effect of IGF-1 on NO and PGE2 in rabbit articular chondrocytes induced by IL-1].

OBJECTIVE: To explore the effect of insulin-like growth factor (IGF-1) on the concentration of NO and PGE(2) in the supernatant of rabbit articular chondrocytes induced by IL-1, and to explore the mechanism of IGF-1 in the development of osteoarthritis (OA). METHODS: The samples were divided into 7 groups: IL-1beta 10 microg/L group, IL-1beta 10 microg/L+IGF-1 1 microg/L group, IL-1beta 10 microg/L+IGF-1 10 microg/L group, IL-1beta 10 microg/L+IGF-1 50 microg/L group, IL-1beta 10 microg/L+IGF-1 100 microg/L group, IGF-1 50 microg/L group, and a blank control group. The chondrocytes from the articular cartilage of 2 month old rabbits were cultivated and identified, and then co-cultured in the second filial generation chondrocytes on plates with or without recombinant human IGF-1 or IL-1. The concentration of NO was detected by nitrate reductase kit, and that of PGE(2) by enzyme-linked immunosorbent assay (ELISA). The results were analyzed by statistical method. RESULTS: The average value of NO and PGE(2) was (89.971+/-10.224) micromol/L and (22.028+/-8.731) micromol/L in the IL-1beta 10 microg/L group, and (12.404+/-8.809) micromol/L and (1.900+/-0.227) ng/L in the blank control group. The concentration of NO and PGE(2) in IL-1beta 10 microg/L group was significantly higher than that in the blank control group (P<0.05). At the same concentration of 10 microg/L, IGF-1 could dose-dependently decrease the increase of NO and PGE(2) concentration induced by IL-1beta in the chondrocytes supernatant in vitro, and the optimum concentration of IGF-1 was 50 microg/L. CONCLUSION: IL-1 can significantly increase the concentration of NO and PGE(2), and IGF-1 can dose-dependently decrease the concentration of NO and PGE(2) in the chondrocytes supernatant in vitro. The optimum concentration of IGF-1 was 50 microg/L.