Predicting coronary heart disease in Chinese diabetics using machine learning.

Diabetes, a common chronic disease worldwide, can induce vascular complications, such as coronary heart disease (CHD), which is also one of the main causes of human death. It is of great significance to study the factors of diabetic patients complicated with CHD for understanding the occurrence of diabetes/CHD comorbidity. In this study, by analyzing the risk of CHD in more than 300,000 diabetes patients in southwest China, an artificial intelligence (AI) model was proposed to predict the risk of diabetes/CHD comorbidity. Firstly, we statistically analyzed the distribution of four types of features (basic demographic information, laboratory indicators, medical examination, and questionnaire) in comorbidities, and evaluated the predictive performance of three traditional machine learning methods (eXtreme Gradient Boosting, Random Forest, and Logistic regression). In addition, we have identified nine important features, including age, WHtR, BMI, stroke, smoking, chronic lung disease, drinking and MSP. Finally, the model produced an area under the receiver operating characteristic curve (AUC) of 0.701 on the test samples. These findings can provide personalized guidance for early CHD warning for diabetic populations.

A gender specific risk assessment of coronary heart disease based on physical examination data.

Large-scale screening for the risk of coronary heart disease (CHD) is crucial for its prevention and management. Physical examination data has the advantages of wide coverage, large capacity, and easy collection. Therefore, here we report a gender-specific cascading system for risk assessment of CHD based on physical examination data. The dataset consists of 39,538 CHD patients and 640,465 healthy individuals from the Luzhou Health Commission in Sichuan, China. Fifty physical examination characteristics were considered, and after feature screening, ten risk factors were identified. To facilitate large-scale CHD risk screening, a CHD risk model was developed using a fully connected network (FCN). For males, the model achieves AUCs of 0.8671 and 0.8659, respectively on the independent test set and the external validation set. For females, the AUCs of the model are 0.8991 and 0.9006, respectively on the independent test set and the external validation set. Furthermore, to enhance the convenience and flexibility of the model in clinical and real-life scenarios, we established a CHD risk scorecard base on logistic regression (LR). The results show that, for both males and females, the AUCs of the scorecard on the independent test set and the external verification set are only slightly lower (<0.05) than those of the corresponding prediction model, indicating that the scorecard construction does not result in a significant loss of information. To promote CHD personal lifestyle management, an online CHD risk assessment system has been established, which can be freely accessed at http://lin-group.cn/server/CHD/index.html .

Real-world study of antiresorptive-related osteonecrosis of jaw based on the US food and drug administration adverse event reporting system database.

Objective: This study aims to explore the risk signals of osteonecrosis of the jaw induced by antiresorptive drugs and provide references for the clinical safety application. Method: According to the FDA's Adverse Event Reporting System (FAERS), from January 2004 to September 2021, we chose "Osteonecrosis of the jaw (10064658)" and "Exposed bone in jaw (10071014)" as preferred terms, "antiresorptive drugs" as the target drugs, and primary suspect drug as the drug role code in the dataset. We evaluated the association between drugs and adverse events by using reporting odds ratio (ROR) based on disproportionality analysis. We took the High-Level Terms (HLT) of MedDRA® as the classification level of indications to calculate ROR to compare the signal difference of ONJ in different indications. In addition, patients with antiresorptive-induced osteonecrosis of the jaw and the time of onset of the condition following different antiresorptive medications were collected for the study. Results: The FAERS contained 18,421 reports relating to jaw osteonecrosis from January 2004 to September 2021. A total of eight antiresorptive agents were included in the analysis. From high to low, the ROR of ONJ induced by antiresorptive agents (regardless of indication) is pamidronate (ROR = 494.8), zoledronic acid (ROR = 431.9), denosumab (ROR = 194.8), alendronate (ROR = 151.2), risedronate (ROR = 140.2), etidronic acid (ROR = 64.5), ibandronate (ROR = 40.8), and romosozumab (ROR = 6.4). HLT ROR values for "metabolic bone disorders" were the lowest for each drug, while HLT ROR values were high for "tumor-related indications," including breast and nipple neoplasms malignant, plasma cell myelomas, and prostatic neoplasms malignant. The onset time for osteonecrosis of the jaw as median (Q1, Q3), osteoporosis-related indications, and the onset time for ONJ were 730 (368, 1268), 489.5 (236.3, 909.8), 722.5 (314, 1055), 761 (368, 1720), and 153 (50, 346) for zoledronic acid, denosumab, ibandronate, risedronate, and romosozumab, respectively. Cancer-related indications: the onset time for ONJ were 680.5 (255.3, 1283), 488 (245, 851), and 696.5 (347, 1087) for zoledronic acid, denosumab, and pamidronate, respectively. Conclusion: When antiresorptive drugs are used for metastasis, they have the largest risk signal, followed by malignancy, and the smallest is osteoporosis. The onset time of ONJ may not be related to the indications. The onset time of ONJ for BPs was about 2 years, denosumab about 1.3 years, and romosozumab less than 1 year, which may be related to sequential treatment. When used according to the instructions, the risk of ONJ caused by denosumab was higher than that of zoledronic acid, regardless of the indication. Based on these findings, researchers will continue to monitor and identify risk factors.

FGF-induced LHX9 regulates the progression and metastasis of osteosarcoma via FRS2/TGF-ß/ß-catenin pathway.

BACKGROUND: Fibroblast growth factor (FGF) and tumor growth factor-ß (TGFß) have emerged as pivotal regulators during the progression of osteosarcoma (OS). LHX9 is one crucial transcription factor controlled by FGF, however, its function in OS has not been investigated yet. METHODS: The expression of LHX9, FRS2, BMP4, TGF-beta R1, SMAD2, beta-catenin and metastasis-related proteins was measured by real-time quantitative PCR (RT-qPCR) and Western blot. CCK-8 assay and colony formation assay were employed to determine the proliferation of OS cells, while scratch wound healing assay and transwell assay were used to evaluate their migration and invasion, respectively. In vivo tumor growth and metastasis were determined by subcutaneous or intravenous injection of OS cells into nude mice. RESULTS: LHX9 expression was evidently up-regulated in OS tumor tissues and cell lines. Knockdown of LHX9 impaired the proliferation, migration, invasion and metastasis of OS cells. Mechanistically, LHX9 silencing led to the down-regulation of BMP-4, ß-catenin and metastasis-related proteins, which was also observed in beta-catenin knockdown OS cells. By contrast, FRS2 knockdown conduced to the up-regulation of LHX9, BMP4, ß-catenin and TGF-ßR1, while TGF-beta inhibition repressed the expression of LHX9 and metastasis-related proteins. Additionally, let-7c modulates LHX9 and metastasis-related proteins by suppressing TGF-beta R1 expression on transcriptional level. CONCLUSIONS: This study revealed LHX9 was essential for the proliferation, migration, invasion, and metastasis of OS cells via FGF and TGF-ß/ß-catenin signaling pathways.

Intraocular pressure elevation and choroidal thinning.

PURPOSE: To evaluate changes in subfoveal choroidal thickness (SFCT) and peripapillary choroidal thickness (PPCT) after acute intraocular pressure (IOP) elevation provoked by a dark room prone provocative test (DRPPT). METHODS: The prospective cohort study included 114 eyes from 65 individuals who had an IOP elevation ≥2 mm Hg during the DRPPT. The participants stayed in a dark room for 2 h with the forehead placed on a desk. At baseline and within 5 min after the end of the DRPPT, tonometry and enhanced depth imaging by spectral-domain optical coherence tomography were carried out. RESULTS: During the DRPPT, IOP increased by 10.1±10.9 mm Hg, SFCT decreased significantly (p<0.001) from 280±80 µm to 267±76 µm and PPCT decreased significantly (p<0.001) from 177±74 to 169±70 µm. In multivariate analysis, a more marked SFCT thinning was associated with higher IOP increase (p<0.001) and shallower anterior chamber depth at baseline (p=0.01). In a similar manner, a higher PPCT change was correlated with a higher IOP increase (p<0.001), and a thicker choroidal thickness at baseline (p<0.001). CONCLUSIONS: Choroidal thickness in the subfoveal region and in the peripapillary region decreased parallel to an acute increase in IOP in individuals 2 h after a dark room test. Choroidal thickness depends on the actual IOP, which may be noted when choroidal thickness is measured.

[Transurethral resection of the prostate combined with 2-micron continuous-wave laser vaporesection for benign prostatic hyperplasia with the prostate volume > 80 ml].

OBJECTIVE: To sum up the clinical experience in the management of benign prostatic hyperplasia (BPH) with the prostate weighing over 80 ml by transurethral resection of the prostate (TURP) combined with 2 µm continuous-wave laser vaporesection (LVR). METHODS: We retrospectively analyzed the clinical effects of TURP combined with 2 µm LVR in the treatment of 46 cases of BPH with the prostate volume > 80 ml. RESULTS: All the operations were successfully accomplished. The operation time and intraoperative blood loss were (112.0 ± 20.0) min (range 86-176 min) and (77.9 ± 25.9) ml (range 50-200 ml), respectively. The catheters were withdrawn at 7 days after surgery. Transient urinary incontinence occurred in 6 cases and secondary hemorrhage was found in 2 postoperatively. Six-month follow-up revealed no urethral stricture or other complications. Compared with the baseline, the international prostate symptom score (IPSS) was significantly decreased at 6 months after operation (26.3 ± 1.8 vs 11.6 ± 1.7, P <0.05), and so were the quality of life (QOL) score (5.3 ± 0.7 vs 1.3 ± 1.1, P <0.05) and post-void residual urine (PVR) ([115.5 ± 55.6] ml vs [19.9 ± 11.6] ml, P <0.05). However, the maximum urinary flow rate (Qmax) was remarkably increased from (4.1 ± 2.6) ml/s to (16.2 ± 1.7) ml/s (P <0.05). CONCLUSION: TURP combined with 2 µm LVR is safe and effective for the treatment of BPH with the prostate volume >80 ml.

Determination of cetirizine in human plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a bioequivalence study.

A rapid, sensitive and selective HPLC-MS/ MS method was developed and validated for the quantification of cetirizine dihydrochloride (CAS 83881-51-0) in human plasma using mosapride citrate as internal standard (IS, CAS 112885-42-4). Following liquid-liquid extraction, the analytes were separated using a mobile phase consisting of methanol and aqueous ammonium acetate solution (10 mM) (60:40, v/v) on a reverse phase C18 column and analyzed by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode using the respective [M+H]+ ions, m/z 398 --> 201 for cetirizine and m/z 422 --> 198 for mosapride. The analysis time for each run was 8.0 min. The assay exhibited a linear dynamic range of 0.5-500 ng/ml for cetirizine dihydrochloride in human plasma. The lower limit of quantification (LLOQ) was 0.5 ng/ml with a relative standard deviation of less than 15% (all the concentration data in this study related to the salt (cetirizine dihydrochloride)). Acceptable precision and accuracy were obtained for concentrations over the standard curve range. It is the first time that the validated HPLC-MS/MS method has been successfully applied to a bioequivalence study in 20 healthy male Chinese volunteers.

[Comparision study pharmacokinetics of different source cinnamon acid].

OBJECTIVE: To study relatively pharmacological activities of cinnamon acid in blood serum of rabbit administered cinnamon acid, cinnamon and Jingui Shenqi pills. METHOD: RP-HPLC determine and analysis blood serum sample from rabbits administered cinnamon acid, cinnamon and Jingui Shenqi pills. Condition of colour spectrum was Symmetry C18 (3.9 mm x 150 mm, 5 microm) chromato bar, mobile phase was methanol-1% glacial acetic acid water-solution (45:55), flow rate was 0.8 mL x min(-1), temperature of bar was 35 degrees C, detection wave length was 285 nm. The serum pharmacokinetic parameters were calculated with 3p87. RESULT: Linear range of cinnamon acid is from 0.06-15 microg x mL(-1) (r = 0.9997), the lowest detectability is 0.054 microg x mL(-1). Pharmacokinetic process of cinnamon acid in rabbit could be all fitted to two-compartment model. CONCLUSION: Sensitive and exclusive HPLC that adopt can exactly detect serum concentration in rabbits administerd cinnamon acid. Pharmacokinetic parameters of three conditions can reveal pharmacokinetics regularity of cinnamon acid in rabbit.