Comparison of conventional mathematical model and machine learning model based on recent advances in mathematical models for predicting diabetic kidney disease.

Previous research suggests that mathematical models could serve as valuable tools for diagnosing or predicting diseases like diabetic kidney disease, which often necessitate invasive examinations for conclusive diagnosis. In the big-data era, there are several mathematical modeling methods, but generally, two types are recognized: conventional mathematical model and machine learning model. Each modeling method has its advantages and disadvantages, but a thorough comparison of the two models is lacking. In this article, we describe and briefly compare the conventional mathematical model and machine learning model, and provide research prospects in this field.

Protein kinase C: A potential therapeutic target for endothelial dysfunction in diabetes.

Protein kinase C (PKC) is a family of serine/threonine protein kinases that play an important role in many organs and systems and whose activation contributes significantly to endothelial dysfunction in diabetes. The increase in diacylglycerol (DAG) under high glucose conditions mediates PKC activation and synthesis, which stimulates oxidative stress and inflammation, resulting in impaired endothelial cell function. This article reviews the contribution of PKC to the development of diabetes-related endothelial dysfunction and summarizes the drugs that inhibit PKC activation, with the aim of exploring therapeutic modalities that may alleviate endothelial dysfunction in diabetic patients.

N6-methyladenosine RNA modification: an emerging molecule in type 2 diabetes metabolism.

Type 2 diabetes (T2D) is a metabolic disease with an increasing rate of incidence worldwide. Despite the considerable progress in the prevention and intervention, T2D and its complications cannot be reversed easily after diagnosis, thereby necessitating an in-depth investigation of the pathophysiology. In recent years, the role of epigenetics has been increasingly demonstrated in the disease, of which N6-methyladenosine (m6A) is one of the most common post-transcriptional modifications. Interestingly, patients with T2D show a low m6A abundance. Thus, a comprehensive analysis and understanding of this phenomenon would improve our understanding of the pathophysiology, as well as the search for new biomarkers and therapeutic approaches for T2D. In this review, we systematically introduced the metabolic roles of m6A modification in organs, the metabolic signaling pathways involved, and the effects of clinical drugs on T2D.

MicroRNA-126 Regulates Thrombosis Through Endothelial Progenitor Cells.

Thrombosis is a common problem with potentially severe consequences. Endothelial progenitor cells (EPCs) show great potential as a thrombosis therapy due to their angiogenesis-promoting, thrombus-relieving, and anticoagulant functions. However, cell therapies present more clinical challenges than small molecule solutions. MicroRNAs (miRNAs) are small noncoding single-stranded RNAs with wide-ranging regulatory activities. miRNA-126 is highly enriched in EPCs and endothelial cells. Although increasing research showed that mircoRNA-126 (miR-126) can regulate EPC functions through various pathways and cytokines, summaries of these interactions are rare. Therefore, this brief review of recent findings on the relationship between miRNA-126 and EPC function will attempt to clarify the role of miR-126 in thrombosis through regulation of EPCs, with the goal of exploring alternative therapies for thrombotic diseases.

NK4 Regulates Laryngeal Squamous Cell Carcinoma Cell Properties and Inhibits Tumorigenicity by Modulating the DKK1/Wnt/ß-Catenin Axis.

OBJECTIVE: To investigate the effects of NK4 gene on the properties and tumorigenicity in laryngeal squamous cell carcinoma cell. METHODS: Here, we used the attenuated Salmonella carrying the NK4 gene to transfect the AMC-HN-8 cells and detected the expression of NK4 by the real-time quantitative polymerase chain reaction (q RT-PCR). The properties of NK4 gene was determined by MTT method, cell scratch test, and flow cytometry. A nude mouse tumorigenesis model was used to evaluate the effect of NK4 gene on the growth of AMC-HN-8 cells in vivo. While a western blot assay was used to assess the expression of DKK1, Wnt1 and ß-Catenin in nude mouse tumors. RESULTS: qRT-PCR showed that the expression of NK4 in the transfection group was significantly higher than that in the control group (P<0.01), and the expression increased with the time of transfection. MTT results showed NK4 overexpression inhibited the proliferation of AMC-HN-8 cells, and the inhibitory activity no longer increased with increasing dose when 30% expression supernatant was added (P<0.01). Scratch experiment showed that NK4 overexpression decreased the cell migration ability (P<0.01). Annexin V/PI double staining experiment showed that NK4 gene induced AMC-HN-8 cell apoptosis (P<0.01), and cell cycle arrest in S phase (P<0.01). NK4 overexpression inhibited tumor formation ability of AMC-HN-8 cells in vivo (P <0.05). WB detection showed that the expression of DKK1 increased, Wnt1 and ß-Catenin protein decreased after the high expression of NK4. CONCLUSIONS: NK4 gene inhibit cell proliferation and migration, while promote cell apoptosis, and induce cell cycle arrest in S phase of laryngeal carcinoma AMC-HN-8 cells. NK4 overexpression inhibit the tumorigenesis ability of AMC-HN-8 cells, which may be related to the regulation of DKK1/Wnt1/ß-Catenin signal axis.

Docking protein 1 and free fatty acids are associated with insulin resistance in patients with type 2 diabetes mellitus.

OBJECTIVE: Insulin resistance (IR) is a key defect in type 2 diabetes mellitus (T2DM); therefore, effective means of ameliorating IR are sought. METHODS: We performed a retrospective cohort study of 154 patients with T2DM and 39 with pre-diabetes (pre-DM). The effects of IR and a high concentration of FFA on gene expression were determined using microarray analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR) in patients with T2DM or pre-DM. RESULTS: Serum FFA concentration and homeostasis model assessment of IR (HOMA-IR) were significantly higher in patients with T2DM but no obesity and in those with pre-DM than in controls. HOMA-IR was significantly associated with T2DM. RT-qPCR showed that the expression of FBJ murine osteosarcoma viral oncogene homolog (FOS) and AE binding protein 1 (AEBP1) was much lower in the circulation of participants with obesity and diabetes. RT-qPCR showed that the expression of docking protein 1 (DOK1) was significantly lower in the blood of participants with diabetes but no obesity and in those with pre-DM than in controls. CONCLUSIONS: FFA and DOK1 are associated with IR in patients with T2DM but no obesity or pre-DM. The downregulation of DOK1 might inhibit lipid synthesis and induce lipolysis, inducing or worsening IR.

[Effects of altitude on circulating endothelial progenitor cells and hypoxia-inducible factor-1α in patients with type 2 diabetes].

Objective: To compare the changes in the number of circulating endothelial progenitor cells and hypoxia-inducible factors in patients with type 2 diabetes at different altitudes, and to provide a basis for the research and treatment of type 2 diabetes vascular complications. Methods: Selected Type 2 diabetes patients who were diagnosed in a low altitude area of 386 m (Xianyang City) and a high altitude area of 1 520 m (Lanzhou) (25 persons/29 persons) and healthy persons (20 persons/20 persons) were selected. An automatic biochemical analyzer was used to detect the indexes of blood lipids, blood glucose, and glycosylated hemoglobin of the two groups of people, and the concentration of Hypoxia inducible factor-1α (HIF-1α) was detected by enzyme-linked immunosorbent assay (ELISA). The number of circulating endothelial progenitor cells (EPCs) in peripheral blood was determined by a cytometer. Results: No matter in low or high altitude areas, the number of circulating EPCs in the diabetes group was lower than that in the healthy group (P＜0.01). The levels of body mass index (BMI), waist to hip ratio (WHR), triglyceride (TG), fasting blood glucose (FBG) and glycosylated hemoglobin (HbAlc) were increased (P＜0.05). Compared with the low-altitude group, the expression levels of HIF-1α in diabetic patients at high-altitude and healthy people were increased significantly (P＜0.05), while the number of circulating EPCs was decreased significantly (P＜0.05), and the number of circulating EPCs in healthy people or the patients with type 2 diabetes without vascular complications was higher than that of patients with type 2 diabetes with vascular complications (P＜0.05). Conclusion: With the increase in altitude, the expression level of HIF-1α in type 2 diabetes mellitus(T2DM)patients is increased, and the number of circulating EPCs is decreased, which is closely related to the degree of vascular disease. Therefore, it is possible through transplantation of EPCs for high altitude T2DM patients to achieve the prevention and improvement of diabetic vascular complications.

Development of Models to Predict Postoperative Complications for Hepatitis B Virus-Related Hepatocellular Carcinoma.

BACKGROUND: Surgical treatment remains the best option for patients with hepatocellular carcinoma (HCC) caused by chronic hepatitis B virus (HBV) infection. However, there is no optimal tool based on readily accessible clinical parameters to predict postoperative complications. Herein, our study aimed to develop models that permitted risk of severe complications to be assessed before and after liver resection based on conventional variables. METHODS: A total of 1,047 patients treated by hepatectomy for HCC with HBV infection at three different centers were recruited retrospectively between July 1, 2014, and July 1, 2018. All surgical complications were recorded and scored by the Comprehensive Complication Index (CCI). A CCI ≥26.2 was used as a threshold to define patients with severe complications. We built two models for the CCI, one using preoperative and one using preoperative and postoperative data. Besides, CCI and other potentially relevant factors were evaluated for their ability to predict early recurrence and metastasis. All the findings were internally validated in the Hangzhou cohort and then externally validated in the Lanzhou and Urumqi cohorts. RESULTS: Multivariable analysis identified National Nosocomial Infections Surveillance (NNIS) index, tumor number, gamma-glutamyltransferase (GGT), total cholesterol (TC), potassium, and thrombin time as the key preoperative parameters related to perioperative complications. The nomogram based on the preoperative model [preoperative CCI After Surgery for Liver tumor (CCIASL-pre)] showed good discriminatory performance internally and externally. A more accurate model [postoperative CCI After Surgery for Liver tumor (CCIASL-post)] was established, combined with the other four postoperative predictors including leukocyte count, basophil count, erythrocyte count, and total bilirubin level. No significant association was observed between CCI and long-term complications. CONCLUSION: Based on the widely available clinical data, statistical models were established to predict the complications after hepatectomy in patients with HBV infection. All the findings were extensively validated and shown to be applicable nationwide. Such models could be used as guidelines for surveillance follow-up and the design of post-resection adjuvant therapy.

Development and clinical evaluation of a rapid antibody lateral flow assay for the diagnosis of SARS-CoV-2 infection.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has quickly spread worldwide since its outbreak in December 2019. One of the primary measures for controlling the spread of SARS-CoV-2 infection is an accurate assay for its diagnosis. SARS-CoV-2 real-time PCR kits suffer from some limitations, including false-negative results in the clinic. Therefore, there is an urgent need for the development of a rapid antibody test kit for COVID-19 diagnosis. METHODS: The nuclear capsid protein (N) and spike protein 1 (S1) fragments of SARS-CoV-2 were expressed in Escherichia coli, and rapid antibody-based tests for the diagnosis of SARS-CoV-2 infection were developed. To evaluate their clinical applications, the serum from COVID-19 patients, suspected COVID-19 patients, recovering COVID-19 patients, patients with general fever or pulmonary infection, doctors and nurses who worked at the fever clinic, and health professionals was analyzed by the rapid antibody test kits. The serum from patients infected with Mycoplasma pneumoniae and patients with respiratory tract infection was further analyzed to test its cross-reactivity with other respiratory pathogens. RESULTS: A 47 kDa N protein and 67 kDa S1 fragment of SARS-CoV-2 were successfully expressed, purified, and renatured. The rapid antibody test with recombinant N protein showed higher positive rate than the rapid IgM antibody test with recombinant S1 protein. Clinical evaluation showed that the rapid antibody test kit with recombinant N protein had 88.56 % analytical sensitivity and 97.42 % specificity for COVID-19 patients, 53.48 % positive rate for suspected COVID-19 patients, 57.14 % positive rate for recovering COVID-19 patients, and 0.5-0.8 % cross-reactivity with other respiratory pathogens. The analytical sensitivity of the kit did not significantly differ in COVID-19 patients with different disease courses (p < 0.01). CONCLUSIONS: The rapid antibody test kit with recombinant N protein has high specificity and analytical sensitivity, and can be used for the diagnosis of SARS-CoV-2 infection combined with RT-PCR.

Protective effect of rhodioloside and bone marrow mesenchymal stem cells infected with HIF-1-expressing adenovirus on acute spinal cord injury.

Rhodioloside has been shown to protect cells from hypoxia injury, and bone marrow mesenchymal stem cells have a good effect on tissue repair. To study the effects of rhodioloside and bone marrow mesenchymal stem cells on spinal cord injury, a rat model of spinal cord injury was established using the Infinite Horizons method. After establishing the model, the rats were randomly divided into five groups. Rats in the control group were intragastrically injected with phosphate buffered saline (PBS) (5 µL). PBS was injected at 6 equidistant points around 5 mm from the injury site and at a depth of 5 mm. Rats in the rhodioloside group were intragastrically injected with rhodioloside (5 g/kg) and intramuscularly injected with PBS. Rats in the mesenchymal stem cell (MSC) group were intramuscularly injected with PBS and intramuscularly with MSCs (8 × 106/mL in a 50-µL cell suspension). Rats in the Ad-HIF-MSC group were intragastrically injected with PBS and intramuscularly injected with HIF-1 adenovirus-infected MSCs. Rats in the rhodioloside + Ad-HIF-MSC group were intramuscularly injected with MSCs infected with the HIF-1 adenovirus and intragastrically injected with rhodioloside. One week after treatment, exercise recovery was evaluated with a modified combined behavioral score scale. Hematoxylin-eosin staining and Pischingert's methylene blue staining were used to detect any histological or pathological changes in spinal cord tissue. Levels of adenovirus IX and Sry mRNA were detected by real-time quantitative polymerase chain reaction and used to determine the number of adenovirus and mesenchymal stem cells that were transfected into the spinal cord. Immunohistochemical staining was applied to detect HIF-1 protein levels in the spinal cord. The results showed that: (1) compared with the other groups, the rhodioloside + Ad-HIF-MSC group exhibited the highest combined behavioral score (P < 0.05), the most recovered tissue, and the greatest number of neurons, as indicated by Pischingert's methylene blue staining. (2) Compared with the PBS group, HIF-1 protein expression was greater in the rhodioloside group (P < 0.05). (3) Compared with the Ad-HIF-MSC group, Sry mRNA levels were higher in the rhodioloside + Ad-HIF-MSC group (P < 0.05). These results confirm that rhodioloside combined with bone marrow mesenchymal stem cells can promote the recovery of spinal cord injury and activate the HIF-1 pathway to promote the survival of bone marrow mesenchymal stem cells and repair damaged neurons within spinal cord tissue. This experiment was approved by the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine, China (approval No. 2015KYLL029) in June 2015.