The Role of Microglia with Mitochondrial Dysfunction and Its Therapeutic Prospects in Alzheimer's Disease.

Alzheimer's disease (AD), a primary cause of dementia, is rapidly emerging as one of the most financially taxing, lethal, and burdensome diseases of the 21st century. Increasing evidence suggests that microglia-mediated neuroinflammation plays a key role in both the initiation and progression of AD. Recently, emerging evidence has demonstrated mitochondrial dysfunction, particular in microglia where precedes neuroinflammation in AD. Multiple signaling pathways are implicated in this process and pharmaceutical interventions are potentially involved in AD treatment. In this review, advance over the last five years in the signaling pathways and pharmaceutical interventions are summarized and it is proposed that targeting the signaling pathways in microglia with mitochondrial dysfunction could represent a novel direction for AD treatment.

Artificial intelligence of digital morphology analyzers improves the efficiency of manual leukocyte differentiation of peripheral blood.

BACKGROUND AND OBJECTIVE: Morphological identification of peripheral leukocytes is a complex and time-consuming task, having especially high requirements for personnel expertise. This study is to investigate the role of artificial intelligence (AI) in assisting the manual leukocyte differentiation of peripheral blood. METHODS: A total of 102 blood samples that triggered the review rules of hematology analyzers were enrolled. The peripheral blood smears were prepared and analyzed by Mindray MC-100i digital morphology analyzers. Two hundreds leukocytes were located and their cell images were collected. Two senior technologists labeled all cells to form standard answers. Afterward, the digital morphology analyzer unitized AI to pre-classify all cells. Ten junior and intermediate technologists were selected to review the cells with the AI pre-classification, yielding the AI-assisted classifications. Then the cell images were shuffled and re-classified without AI. The accuracy, sensitivity and specificity of the leukocyte differentiation with or without AI assistance were analyzed and compared. The time required for classification by each person was recorded. RESULTS: For junior technologists, the accuracy of normal and abnormal leukocyte differentiation increased by 4.79% and 15.16% with the assistance of AI. And for intermediate technologists, the accuracy increased by 7.40% and 14.54% for normal and abnormal leukocyte differentiation, respectively. The sensitivity and specificity also significantly increased with the help of AI. In addition, the average time for each individual to classify each blood smear was shortened by 215 s with AI. CONCLUSION: AI can assist laboratory technologists in the morphological differentiation of leukocytes. In particular, it can improve the sensitivity of abnormal leukocyte differentiation and lower the risk of missing detection of abnormal WBCs.

[Expression of Ephrin-B2 after focal cerebral ischemia in rats].

OBJECTIVE: To explore the expression profile of Ephrin-B2 in the ischemic penumbra after transient focal cerebral ischemia in rats, and to clarify the mechanism of Ephrin-B2 triggering angiogenesis. METHODS: Sprague-Dawley rats were randomly divided into a normal group, a sham operation group and ischemic-reperfusion 1, 3, 7, 14, and 28 d groups. Suture-occluded method was used to establish the focal middle cerebral artery occlusion model and the ischemic brain was reperfused 2 h after the occlusion. Western blot and quantitative real-time reverse-transcription polymerase chain reaction were used to detect the dynamic expression profile of Ephrin-B2 in the penumbra cortex. Double immunofluorescence was used to speculate the location and the co-expression of Ephrin-B2 in blood vessels, neurons and astrocytes. Microvessel density was quantified by the number of CD31+ cells. Rats were subjected to neurologic functional tests by modified neurological severity scores (mNSS) before sacrifice. RESULTS: Compared with the sham group, Ephrin-B2 protein and mRNA level of the penumbra cortex in the ischemic group increased 3 days (P<0.05) after the reperfusion, peaked at day 7 and 14 (P<0.01), and declined at day 28. Double immunofluorescence indicated that Ehprin-b2 was expressed in the neurons, blood vessels and astrocytes; mNSS peaked at day 7, and gradually declined at day 14. The microvessel density of penumbra cortex in the ischemic group increased 3 days (P<0.05) after the reperfusion, peaked at day 14 (P<0.01), and gradually declined at 48 h. CONCLUSION: Cerebral ischemia reperfusion induces the over-expression of Ephrin-B2, with a dynamic trend, suggesting that Ehprin-b2 may improve post-stroke functional recovery by enhancing angiogenesis and neurogenesis.

Sevoflurane suppresses the malignant progression of breast cancer via the hsa_circ_0000129/miR-578/EPSTI1 axis.

BACKGROUND: Sevoflurane (Sev) is a commonly used volatile anesthetic that might suppress the process of breast cancer. Also, circular RNAs (circRNAs) have been reported to partake in the pathogenesis of breast cancer. Accordingly, this research was designed to investigate the mechanism of hsa_circ_0005962 on Sev-mediated breast cancer development. METHODS: Sev was applied to treat breast cancer cells. Cell proliferation ability, migration, invasion, and apoptosis were detected using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), Transwell, and flow cytometry assay. Proliferating cell nuclear antigen (PCNA), Matrix metallopeptidase 9 (MMP9), B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), and Epithelial stromal interaction 1 (EPSTI1) were assessed using western blot assay. circ_0000129, microRNA-578 (miR-578), and EPSTI1 levels were determined using real-time quantitative polymerase chain reaction (RT-qPCR). Using bioinformatics software (Circinteractome and Targetscan), the binding between miR-578 and circ_0000129 or EPSTI1 were predicted, and proved using dual-luciferase reporter and RNA pull-down assay. The biological roles of circ_0000129 and Sevoflurane on tumor growth were analyzed using a xenograft tumor model in vivo. RESULTS: Sevoflurane blocked tumor cell proliferation, migration, invasion, and promoted apoptosis. Circ_0000129 and EPSTI1 expression were increased, and miR-578 was decreased in breast cancer cells. Also, they presented an opposite trend in Sev-treated tumor cells. Circ_0000129 upregulation might abolish Sev-mediated tumor progression in vitro. Mechanically, circ_0000129 can affect EPSTI1 expression by sponging miR-578. Sev might inhibit tumor growth by regulating circ_0000129 in vivo. CONCLUSION: Circ_0000129 relieved Sev-triggered suppression impacts on breast cancer development partly via the miR-578/EPSTI1 axis, which provides a new mechanism for studying mediated therapy of breast cancer treatment.

[Effect of lycopene on the apoptosis of human peripheral endothelial progenitor cells cultivated in high concentration of glucose].

OBJECTIVE: To investigate the effect of lycopene treatment on the proliferation and apoptosis of endothelial progenitor cells (EPCs) incubated in a culture medium with high concentration of glucose. METHODS: Mononuclear cells (MNCs) were isolated from human peripheral blood by Ficoll density gradient centrifugation. After being induced to differentiation, the endothelial progenitor cells (EPC) were identified by FITC-labeled Ulex europaeus agglutinin I and Dil labeled acetylated low density lipoprotein dual stain method. Then MTT assay and flow cytometry were used to assess the proliferation and apoptosis of EPCs. RESULTS: The glucose in a concentration of 33 mmol/L significantly inhibited the proliferation and promoted the apoptosis of EPCs (P < 0.05). The proliferation of EPCs in 10, 30 and 50 microg/ml lycopene groups were significantly higher than the 0 microg/ml group. The rate of apoptosis were significantly lower than the lycopene 0 microg/ml group (P < 0.05). CONCLUSION: High concentration of glucose attenuates the proliferative activity and increases the apoptotic rate of EPCs. Lycopene promotes the proliferation and reduces the apoptosis of EPCs cultivated in high glucose medium.

Application Value of Nutrition Support Team in Chemotherapy Period of Colon Cancer Based on Internet Multidisciplinary Treatment Mode.

Objective: To explore the application value of the nutrition support team in chemotherapy period of colon cancer based on the internet multidisciplinary treatment mode. Methods: For the method of retrospective study, 90 patients with colon cancer admitted to our hospital from August 2018 to August 2020 were selected as the study subjects. They were equally divided into the experimental group (n = 45) and the control group (n = 45) according to the order of initials and the method of parity group. The control group was given conventional nutrition support, and the experimental group was given the nutrition support under the internet multidisciplinary treatment mode. The serum tumor marker levels (CEA and CA19-9), immune function indexes, nutrition indicators, and the incidence of adverse reactions were compared between the two groups before and after intervention. Results: The serum tumor marker levels in the experimental group after intervention were significantly lower than those in the control group (P < 0.001). The immune function indexes in the experimental group after intervention were significantly better than those in the control group (P < 0.001). The nutrition indicators in the experimental group after intervention were significantly better than those in the control group (P < 0.001). The incidence of gastrointestinal adverse reactions above grade 2 in the experimental group was significantly lower than that in the control group (P < 0.05). There were 20 patients with myelosuppression, 2 patients with neurotoxicity, and 1 patient with hand and foot syndrome in the experimental group, while 22 patients with myelosuppression, 4 patients with neurotoxicity, and 2 patients with hand and foot syndrome in the control group, with no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion: The nutrition support team under the internet multidisciplinary treatment mode can improve the immune function of chemotherapy patients with colon cancer and enhance their nutritional level, thereby reducing the incidence of adverse reactions and improving the chemotherapy effects.

Prevention Effects of Chain Management on Pressure Ulcers of Hospitalized Patients.

The study focused on the preventive effects of the chain management model on pressure ulcers in the operating room. Sqoop big data collection module is used to collect patient information from various hospital information systems in a distributed manner. The data were from the clinical data center of the Zhongshan Hospital Xiamen University General Hospital, and 268 patients were selected as the research subjects. A chain management model is constructed, concerning the preventive measures, the management of each link, the perioperative pressure ulcer management, and the reporting of pressure ulcers. Then, the two groups were compared for the SAS and SDS scores before and after nursing, the pressure ulcer sites, pressure ulcer reporting rate, pressure ulcer staging, and nursing satisfaction. The results show that it is not that more collection modules will lead to better cluster performance and that the execution delay is caused by MapReduce requiring the JAVA virtual machine, and after reaching a certain point, the increase in the number of tasks will slow down the process, and as data size increases, DataNote has an expanded capability to analyze data. After nursing treatment, the SAS and SDS scores of the two groups of patients were significantly lower than before treatment (P < 0.05). The pressure ulcers were mainly distributed in the forehead, mandible, cheeks, front chest, and knees in the two groups, and the difference between the two groups was statistically significant (P < 0.05). The total satisfaction of the observation group was 93.28%, and the total satisfaction of the control group was 92.54%. The patients' satisfaction with the chain management model was higher than that of conventional nursing.

Characterization of the novel HLA-A*30:154 allele by next-generation sequencing.

A*30:154 differs from A*30:01:01:01 by one nucleotide substitution at codon 39 in exon 2 from C to A.

A meta-analysis of everolimus-eluting stents versus sirolimus-eluting stents and paclitaxel-eluting stents in diabetic patients.

OBJECTIVE: We performed this meta-analysis to determine which stent among everolimus eluting stents (EES), sirolimus eluting stents (SES) and paclitaxel eluting stents (PES) should be preferred for the treatment of DM patients. METHODS: A systematic search of publications about randomized controlled trials (RCTs) focused on diabetic patients received EES, SES or PES was conducted. We evaluated the following indicators: target vessel revascularization (TVR), target lesion revascularization (TLR), late luminal loss (LLL), stent thrombosis (ST), myocardial infarction (MI), all-cause mortality and cardiac mortality. RESULTS: EES showed obvious advantages over SES for DM patients, as it induced the lowest rate of target vessel revascularization and target lesion revascularization (TLR) (p = 0.04). In addition, EES induced lower in-segment LLL than PSE and SES and lower in-stent LLL than PES in DM patients (all p < 0.05). Moreover, EES effectively reduced all-cause mortality compared to SES (RR = 0.71, 95% CI: 0.52-0.99, p = 0.04) and MI rates compared to PES (RR = 0.44, 95% CI: 0.26-0.73, p = 0.0002). Furthermore, EES could reduce the ST rate compared with both SES (RR = 0.53, 95% CI: 0.28-0.98, p = 0.04) and PES (RR = 0.18, 95% CI: 0.07-0.51, p = 0.001). CONCLUSION: Among those three types of stents, EES should be the first recommended stent for DM patients.

Identification of the novel HLA-DQB1*03:13 allele by next-generation sequencing in a Chinese Han individual.

HLA-DQB1*03:13 differs from HLA-DQB1*03:01:01:01 by one nucleotide substitution in codon 67 in exon 2.

[Feasibility analysis on membrane-based right-sided approach of laparoscopic suprapancreatic lymph node dissection for advanced distal gastric cancer].

OBJECTIVE: To investigate the feasibility and safety of membrane-based right-sided approach of laparoscopic suprapancreatic lymph node dissection for advanced distal gastric cancer. METHODS: The clinical data of 41 patients with advanced distal gastric cancer who underwent laparoscopic gastrectomy using membrane-based right-sided approach for laparoscopic suprapancreatic lymph node dissection at the Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University from January 2016 to January 2018 were retrospectively analyzed. There were 24 males and 17 females with a mean age of 56.8 years and a mean body mass index of 22.6 kg/m². Membrane-based right-sided approach of laparoscopic suprapancreatic lymph node dissection contained 4 steps briefly: (1) dissection of mesenteria above the head of pancreas: the tri-junction of pancreas-duodenum was cut to expose and identify the logo of Benz;clearance of the membrane of No.5a was performed towards the left, and then expanded to the posterior layer of No.12a. (2) dissection of the V shape dorsal mesogastrium: membrane bridge at splenic artery trunk root was cut; in suprapancreatic space, clearance was performed towards to the left to the middle of the splenic artery trunk and expanded to the posterior Tolds plane upwards to the posterior phrenic angle and retroperitoneal esophagus, then the surrounding tissue of anterior abdominal aorta. (3) dissection of the U shape mesenteria:membrane bridge at common hepatic artery root was cut; mesentery was separated; the left gastric vein was freed and ligated at its root; in posterior pancreatic space, the mesentery of No.7, No.9 and No.8 was dissected in turns; the left gastric artery was high ligated and cut; the portal vein and posterior dorsal mesogastrium Toldt plane was routinely exposed; clearance was performed to right for No.8a and upward to the hepatic portal meeting at posterior mesentery No.12 plane. (4) dissection of the upper triangular area of pylorus: the trigone mesentery was cut along the upper edge of the pylorus; No.12a was swept upward along the gastric ventral mesentery; the upper boundary(No.8a) on the right side of the U-shaped membrane was joined. Intraoperative and postoperative presentations were analyzed. RESULTS: Laparoscopic gastrectomy for advanced distal gastric cancer with membrane-based right-sided approach of laparoscopic suprapancreatic lymph node dissection was successfully carried out in all the 41 patients. Distal gastric mesenteria en bloc resection was successfully performed. The operation time was (145.2±25.4) minutes and intraoperative blood loss was (53.3±18.3) ml without massive bleeding and severe complication. Number of lymph nodes dissected was 41.1±6.4, and number of suprapancreatic lymph node dissected was 23.3±3.7 without residual cancer at cut margin by pathology. Postoperative drainage volume was (65.8±21.7) ml; time to withdraw of catheter was (7.0±1.7) days; time to fluid intake was (3.5±1.8) days; postoperative hospital stay was (10.4±2.8) days; time to postoperative anal exhaust was (3.3±1.1) days. No complications, such as chyle leakage, postoperative massive bleeding, anastomotic leakage, abdominal cavity infection or gastroplegia occurred within 30 days after surgery. CONCLUSION: Membrane-based right-sided approach of laparoscopic suprapancreatic lymph node dissection for advanced distal gastric cancer can achieve en bloc resection and conform to the radical principle of oncology, and is safe and feasible.

Protective effect and mechanism of lycopene on endothelial progenitor cells (EPCs) from type 2 diabetes mellitus rats.

Endothelial progenitor cells (EPCs), widely existing in bone marrow and peripheral blood, are involved in the repair of injured vascular endothelium and angiogenesis which are important to diabetic mellitus (DM) patients with vascular complications. The number and the function of EPCs are related to the advanced glycation end products (AGEs) generated in DM patients. Lycopene (Lyc) is an identified natural antioxidant that protects EPCs under the microenvironment of AGEs from damage. However, the underlying mechanism remains unclear. To investigate the effect of Lyc on EPCs, we isolated EPCs from DM rat bone marrow and determined cell proliferation, cell cycle,apoptosis and autophagy of EPCs. The present study showed that 10µg/mL Lyc improved cell proliferation and had low cytotoxicity in the presence of AGEs. In addition, Lyc rescued S phase of the cell cycle arrest, reduced apoptosis rate and decreased autophagic reaction including ROS and mitochondrial membrane potential (MMP) of EPCs. Moreover, Lyc combined use of autophagy inhibitors, 3-MA, had better protective effects. Taken together, our data suggests that Lyc promotes EPCs survival and protect EPCs from apoptosis and oxidative autophagy induced by AGEs, further remaining the number and function of EPCs. This study provides new insights into Lyc protective mechanism of AGEs-induced oxidative autophagy in EPCs from DM patients and offers a new therapy for DM vascular complications.

Immunoglobulin A nephropathy: current progress and future directions.

Immunoglobulin A (IgA) nephropathy is the most prevalent form of primary glomerulonephritis that often leads to end-stage kidney failure, thereby representing a major health challenge worldwide. Tremendous effort has been dedicated to the diagnosis, monitoring, and treatment of the disease, and the past several years have witnessed exciting advances that have enriched our understanding of the biology, etiology, and pathology of IgA nephropathy. The disease is characterized by predominant deposition of IgA immune complexes that progressively causes activation of mesangial cells, glomerular inflammation, and ultimately renal injury. Multiple recent independent high-throughput studies in cohorts have identified key susceptibility alleles, such as the major histocompatibility complex loci that are significantly associated with the risk of disease occurrence. Notably, a fraction of these risk loci encode proteins that participate in immune defense against mucosal pathogens, particularly intestinal nematodes, indicating a linkage between IgA-mediated antihelminth immunity and the pathogenesis of IgA nephropathy. The emerging "omics" technology also allows for systemic analysis of urinary and serum samples as a noninvasive procedure for diagnosis and prognosis, as demonstrated by several studies implicating the proteomic signature and microRNA profile as promising diagnostic and prognostic parameters. In the clinic, the current treatment protocol relies on suppression of the renin-angiotensin system to control blood pressure and proteinuria. This review scrutinizes and summarizes recent relevant findings that aim to translate researchers' benchside knowledge of disease initiation and development into patients' bedside diagnosis and therapy.

Effects of lycopene on number and function of human peripheral blood endothelial progenitor cells cultivated with high glucose.

BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the effects of lycopene on the migration, adhesion, tube formation capacity, and p38 mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor cells (EPCs) cultivated with high glucose (HG) and as well as explore the mechanism behind the protective effects of lycopene on peripheral blood EPCs. MATERIALS/METHODS: Mononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation. EPCs were identified after induction of cellular differentiation. Third generation EPCs were incubated with HG (33 mmol/L) or 10, 30, and 50 µg/mL of lycopene plus HG. MTT assay and flow cytometry were performed to assess proliferation and apoptosis of EPCs. EPC migration was assessed by MTT assay with a modified boyden chamber. Adhesion assay was performed by replating EPCs on fibronectin-coated dishes, after which adherent cells were counted. In vitro vasculogenesis activity was assayed by Madrigal network formation assay. Western blotting was performed to analyze protein expression of both phosphorylated and non-phosphorylated p38 MAPK. RESULTS: The proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs treated with 10, 30, and 50 µg/mL of lycopene plus HG were all significantly higher comapred to the HG group (P < 0.05). Rates of apoptosis were also significantly lower than that of the HG group. Moreover, lycopene blocked phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal relationship between MAPK inhibition and the protective effects of lycopene against HG-induced cellular injury, we treated cells with SB203580, a phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC injury. CONCLUSIONS: Lycopene promotes proliferation, migration, adhesion, and in vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the underlying molecular mechanism of the protective effects of lycopene against HG-induced EPC injury may involve the p38 MAPK signal transduction pathway. Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting p38 MAPKs.

[Correlation of the polymorphism of HLA-A, B and DRB1 alleles with nasopharyngeal carcinoma in the south of China].

AIM: To explore the correlation between and nasopharyngeal carcinoma the polymorphism of HLA-A, B and DRB1 alleles in the south of China. METHODS: The genotypes of HLA-A, B and DRB1 alleles in 35 patients with NPC and 60 healthy controls were determined by PCR-sequence-specific primer (PCR-SSP). RESULTS: The frequency of HLA-A * 02, HLA-B * 58 and HLA-DRB1 * 03 in the patients with NPC was higher than that in healthy controls (P < 0.05) while the frequency of HLAB * 40 was lower than that in NPC patients (P<0.05). CONCLUSION: HLA-A * 02, HLA-B * 58 and HLA-DRB1 * 03 might be the susceptible genes of NPC patients while HLA-B * 40 might be the protective gene of NPC patients.

Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated malignancy with high prevalence in Southern Chinese. In order to assess whether defects of EBV-specific immunity may contribute to the tumor, the phenotype and function of circulating T-cells and tumor infiltrating lymphocytes (TILs) were investigated in untreated NPC patients. Circulating naïve CD3+CD45RA+ and CD4+CD25- cells were decreased, while activated CD4+CD25+ T-cells and CD3-CD16+ NK-cells were increased in patients compared to healthy donors. The frequency of T-cells recognizing seven HLA-A2 restricted epitopes in LMP1 and LMP2 was lower in the patients and remained low after stimulation with autologous EBV-carrying cells. TILs expanded in low doses of IL-2 exhibited an increase of CD3+CD4+, CD3+CD45RO+ and CD4+CD25+ cells and 2 to 5 fold higher frequency of LMP1 and LMP2 tetramer positive cells compared to peripheral blood. EBV-specific cytotoxicity could be reactivated from the blood of most patients, whereas the TILs lacked cytotoxic activity and failed to produce IFNgamma upon specific stimulation. Thus, EBV-specific rejection responses appear to be functionally inactivated at the tumor site in NPC.