[Expressions of MPV, P-LCR and NLR in patients with novel coronavirus disease 2019].

To provide new ideas for clinical diagnosis and treatment of coronavirus disease 2019 (COVID-19), this study explore the expression level and prognostic value of platelet parameters in mild, moderate and severe COVID-19. This is a retrospective analysis. From January to May 2020, a total of 69 patients who were diagnosed with COVID-19 in the Third Central Hospital and the Jinnan Hospital (both situated in Tianjin) were enrolled in the disease group. According to the severity, these patients were divided into mild group (15 cases), moderate group (46 cases), and severe group (8 cases). In the same period, 70 non-infected patients were enrolled in control group. The level of white blood cell count (WBC), absolute neutrophil count (NEU#), absolute lymphocyte count (LY#), neutrophil-lymphocyte ratio (NLR), red blood cell count (RBC), hemoglobin (Hb), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large contrast ratio (P-LCR) before and after treatment were analyzed. Binary logistic regression analysis is used to establish a mathematical model of the relationship between these indexes and the outcome of severe COVID-19 patients. The receiver operating characteristic(ROC) curve is used to further explore the prognosis value of MPV, P-LCR, NLR separately and jointly in COVID-19 patients. Compare to the control group, WBC and NE# increase (Z=-5.63, P<0.01;Z=-9.19,P<0.01) and LY# decrease (Z=-9.34, P<0.01) in the severe group; NLR increase with the aggravation of the disease, there is significant difference between groups (Z=17.61, P<0.01); PLT, PDW, MPV and P-LCR decrease with the aggravation of the disease, there is significant difference between groups (Z=9.47, P<0.01; Z=11.41, P<0.01; Z =16.76, P<0.01; Z=13.97, P<0.01). Binary logistic regression analysis shows MPV, P-LCR and NLR have predictive value for severe COVID-19 patients. There is a negative correlation between MPV, P-LCR and severe COVID-19 patients (OR=1.004, P=0.034; OR=1.097, P=0.046). There is a positive correlation between NLR and severe COVID-19 patients (OR=1.052, P=0.016). MPV and P-LCR of patients with good prognosis after treatment were significantly higher than those before treatment (Z=-6.47, P<0.01; Z=-5.36, P<0.01). NLR was significantly lower than that before treatment (Z=-8.13, P<0.01). MPV and P-LCR in poor prognosis group were significantly lower than those before treatment (Z=-9.46, P<0.01; Z=-6.81, P<0.01). NLR was significantly higher than that before treatment (Z=-3.24, P<0.01). There were significant differences between good and poor prognosis groups before and after treatment in MPV, P-LCR and NLR (P<0.01). Combination of these three indexes, ROC shows the AUC is 0.931, the sensitivity is 91.5%, the specificity is 94.1%, the positive predictive value is 88.9%, and the negative predictive value is 87.4%, which is better than any of these indexes separately. Changes in these parameters are closely related to clinical stage of COVID-19 patients. MPV, P-LCR and NLR are of great value in the prediction and prognosis of severe COVID-19 patients.

TIGAR mediates the inhibitory role of hypoxia on ROS production and apoptosis in rat nucleus pulposus cells.

OBJECTIVE: Hypoxia has been shown to inhibit reactive oxygen species (ROS) production in nucleus pulposus (NP) cells. The TP53-induced glycolysis and apoptosis regulator (TIGAR) has been reported to suppress oxidative stress. We sought to explore the role of TIGAR in the effect of hypoxia on ROS production and apoptosis. METHODS: An intervertebral disc degeneration (IDD) model of Sprague-Dawley (SD) rat caudal spine was established by puncturing the Co6-7 disc. TIGAR expression was detected by immunohistochemistry and western blotting in human and SD rat NP tissues of degenerated discs. Rat primary NP cells treated with hypoxia and cobalt chloride (CoCl2) were analyzed by western blotting for TIGAR expression. After TIGAR silence with TIGAR siRNA transfection, apoptosis percentage, mitochondrial and total intracellular ROS levels were measured. H2O2 was used to further check the effects of TIGAR on oxidative stress. Finally, NADPH/NADP+ and GSH/GSSH ratio were examined after TIGAR silencing under hypoxic conditions and after H2O2 treatment. RESULTS: A degree-dependent increase in TIGAR expression was observed in human and rat degenerated NP tissues. Hypoxia and hypoxia-inducer CoCl2 enhanced TIGAR and P53 expressions in rat NP cells. TIGAR silence reversed the inhibitory effects of hypoxia on intracellular and mitochondrial ROS production, as well as apoptosis percentage. However, TIGAR silence aggravated H2O2-induced ROS production. In addition, TIGAR increased NADPH/NADP+ and GSH/GSSH ratio in NP cells. CONCLUSIONS: These results suggested that TIGAR appears to mediate the protective role of hypoxia on ROS production and apoptosis percentage by enhancing NADPH/NADP+ and GSH/GSSH ratio.

Evidence that activation of ASIC1a by acidosis increases osteoclast migration and adhesion by modulating integrin/Pyk2/Src signaling pathway.

Activated acid-sensing ion channel 1a (ASIC1a) is involved in acid-induced osteoclastogenesis by regulating activation of the transcription factor NFATc1. These results indicated that ASIC1a activation by extracellular acid may cause osteoclast migration and adhesion through Ca2+-dependent integrin/Pyk2/Src signaling pathway. INTRODUCTION: Osteoclast adhesion and migration are responsible for osteoporotic bone loss. Acidic conditions promote osteoclastogenesis. ASIC1a in osteoclasts is associated with acid-induced osteoclastogenesis through modulating transcription factor NFATc1 activation. However, the influence and the detailed mechanism of ASIC1a in regulating osteoclast adhesion and migration, in response to extracellular acid, are not well characterized. METHODS: In this study, knockdown of ASIC1a was achieved in bone marrow macrophage cells using small interfering RNA (siRNA). The adhesion and migration abilities of osteoclast precursors and osteoclasts were determined by adhesion and migration assays, in vitro. Bone resorption was performed to measure osteoclast function. Cytoskeletal changes were assessed by F-actin ring formation. αvß3 integrin expression in osteoclasts was measured by flow cytometry. Western blotting and co-immunoprecipitation were performed to measure alterations in integrin/Pyk2/Src signaling pathway. RESULTS: Our results showed that blockade of ASIC1a using ASIC1a-siRNA inhibited acid-induced osteoclast precursor migration and adhesion, as well as osteoclast adhesion and bone resorption; we also demonstrated that inhibition of ASIC1a decreased the cell surface αvß3 integrin and ß3 protein expression. Moreover, blocking of ASIC1a inhibited acidosis-induced actin ring formation and reduced Pyk2 and Src phosphorylation in osteoclasts and also inhibited the acid-induced association of the αvß3 integrin/Src/Pyk2. CONCLUSION: Together, these results highlight a key functional role of ASIC1a/αvß3 integrin/Pyk2/Src signaling pathway in migration and adhesion of osteoclasts.

Modified Da Chengqi granules improvement in immune function in early severe acute pancreatitis patients.

We investigated the role of modified Da Chengqi granules in improving immune function in early severe acute pancreatitis patients. Early severe acute pancreatitis patients who agreed to receive combined treatment of traditional Chinese and Western medicine were randomly assigned to the experimental or control group. All subjects received conventional therapy to support organ function. The experimental group also received modified Da Chengqi granules. Cytokine (interleukin-6, interleukin-10, and tumor necrosis factor-α) levels, immunological markers (HLA-DR, Treg, and Th1/Th2), urinary lactulose/mannitol ratio, and endotoxin levels were measured at 1, 3, 7, and 14 days after hospital admission. The total mortality rate was 11.69% (9/77), which was significantly lower in the experimental group [4.88% (2/41)] than in the control group [19.44% (7/36); χ(2) = 3.940, P < 0.05]. Serum interleukin-6, interleukin-10, tumor necrosis factor-α and endotoxin levels and the lactulose/mannitol ratio were significantly lower on day 7 and day 14 than on day 1 in experimental and control groups (P < 0.01). Immunological indices were significantly lower in the experimental group than in the control group on day 14 (all P < 0.01 or 0.05). HLA-DR-positive cell ratio gradually increased over 14 days in experimental and control groups (P < 0.01 vs day 1), but was higher in the experimental group than in the control group by day 14 (P < 0.05). Notably, Treg cell prevalence and Th1/Th2 cell ratio deteriorated within 7 days in both groups (P < 0.01 vs day 1), but then returned to day 1 levels (P < 0.01 or 0.05 vs day 1). Significant differences in Treg levels and Th1/Th2 cell ratio between experimental and control groups were observed on day 14 (P < 0.01). These results show that modified Da Chengqi granules can improve immune function in early severe acute pancreatitis patients.

MiR-410 affects the proliferation and apoptosis of lung cancer A549 cells through regulation of SOCS3/JAK-STAT signaling pathway.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-410 affects the proliferation and apoptosis of lung cancer A549 cells through regulation of SOCS3/JAK-STAT signaling pathway, by M. Li, R. Zheng, F.-L. Yuan, published in Eur Rev Med Pharmacol Sci 2018; 22 (18): 5987-5993-DOI: 10.26355/eurrev_201809_15933-PMID: 30280781" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15933.

Tra2ß protects against the degeneration of chondrocytes by inhibiting chondrocyte apoptosis via activating the PI3K/Akt signaling pathway.

OBJECTIVE: Osteoarthritis (OA) is a common disease in the elderly and seriously affects the quality of life of patients. Tra2ß is a protein that has been found to activate PI3K/Akt in recent years. The purpose of this study was to explore the protective effects of Tra2ß on chondrocytes and its mechanisms. PATIENTS AND METHODS: The expression of Tra2ß in knee cartilage tissue of patients with OA and normal people was compared. In addition, human primary chondrocytes were cultured, the expression of Tra2ß in chondrocytes by cell transfection was changed, and its effects on extracellular matrix, inflammation, and apoptosis in chondrocytes were examined. LY294002 was also used to inhibit the activity of PI3K/Akt signaling pathway to verify the mechanism of Tra2ß to protect chondrocytes. RESULTS: The expression of Tra2ß in the cartilage tissue of the OA group was significantly lower than that of the control group, and the IL-1ß-induced chondrocytes also expressed the lower Tra2ß. The overexpression of Tra2ß increased the expression of extracellular matrix collagen II and decreased the expressions of MMP3/13, inflammatory factors (IL-6, IL-8 and TNF-α), and apoptotic factors (caspase3/9, Bax). In addition, the overexpression of Tra2ß also increased expression and phosphorylation of PI3K and Akt. However, LY294002 attenuated the protective effect of Tra2ß on chondrocytes by inhibiting the PI3K/Akt signaling pathway. CONCLUSIONS: Tra2ß activates the PI3K/Akt signaling pathway, reduces the degradation of extracellular matrix of chondrocytes, reduces the level of inflammation and apoptosis of chondrocytes, and thus, plays a role in the treatment of OA.

MiR-410 affects the proliferation and apoptosis of lung cancer A549 cells through regulation of SOCS3/JAK-STAT signaling pathway.

OBJECTIVE: Janus kinase (JAK) - signal transducer and activator of transcription (STAT) signal pathway participates in regulating cell proliferation, differentiation, and apoptosis, and is correlated with non-small cell lung cancer (NSCLC) onset. Suppressors of cytokine signaling 3 (SOCS3) negatively regulates JAK-STAT pathway. SOCS3 is down-regulated in NSCLC tissues, with an elevation of miR-410 expression. This study thus intends to investigate if miR-410 plays a role in mediating NSCLC onset and underlying mechanism in this regulatory process. PATIENTS AND METHODS: NSCLC patients were collected for tumor and adjacent tissues, among which, miR-410 and SOCS3 expression were measured. Dual luciferase reporter gene assay was employed to confirm the targeting relationship between miR-410 and SOCS3. Their expression levels were compared between A549 and BEAS-2B cells. Cultured A549 cells were treated with anti-miR-410 and/or SOCS3. Expression levels of SOCS3, p-JAK1/2, p-STAT3, and Bcl-2 were compared along with the apoptotic rate of cells. RESULTS: Bioinformatics analysis revealed targeted binding site between miR-410 and 3'-UTR of SOCS3 mRNA. Compared to those in tumor tissues, a significant increase of miR-410 and reduction of SOCS3 were found in NSCLC tissue (p < 0.05). Dual luciferase reporter gene assay indicated that SOCS3 was targeted regulated by miR-410. Significantly higher miR-410 and lower SOCS3 levels were shown in A549 cells, compared to those in BEAS-2B cells. Transfection of anti-miR-410 and/or SOCS3 in A549 cells, SOCS3 expression and apoptosis were significantly induced, while JAK1, JAK2, and STAT3 phosphorylation were statistically decreased with the reduction of the Bcl-2 level (p < 0.05). CONCLUSIONS: miR-410 level was increased while SOCS3 expression was declined in NSCLS tissues. MiR-410 induces the apoptosis of A549 cells through downregulating JAK/STAT3/SOCS3 signaling pathway, which provides new insights for the therapy of pulmonary carcinoma in clinic.

New concept for cancer screening.

Prevention of cancer mortality can be achieved by two main routes: (1) detection of precancerous lesions and preventing their progression to cancer, and (2) detecting cancers at an early stage when they are still amenable to curative treatment. Early detection of cancer is dependent on the population being well-informed about cancer, and about how to carry out self-examination as a preliminary screen (followed by a full clinical examination in the event of suspicious symptoms). In this paper the warning signs that the population should be taught to look out for are discussed. Superficial observation and palpation can be used for surface tumours (which comprise 10-15% of the total). A further 60-70% of tumours are of the digestive tract, respiratory tract or urogenital tract. For these, it is argued that a simple occult blood test could be used as a self-administered screening test. Data are presented to show that this is a practicable way for the general population to detect early signs of cancer or pre-cancer, with a high yield of clinically significant results in the occult blood positive persons.

[Occult blood detector for the upper G-I tract. I. A preliminary application in cancer screening].

The traditional chemical detection of small amount of blood in the stool can not tell whether the original bleeding site is in the upper or lower part of the G-I tract. The occult blood detector, designed by the authors, having a diameter of 8 mm, can easy be swallowed into the stomach with 30 to 50 ml of water. After remaining for 3 minutes in the stomach, it is pulled out by the patient himself and its coloration read to reveal the degree of bleeding. It can be used either by the medical personnel or the patient himself, at home, for the purpose of detecting minute bleeding in the upper G-I tract and for cancer screening in the high risk population. This detector gave a positive rate of 95% in patients with malignancies in the upper gastrointestinal tract. It is highly acceptable for its lack of discomfort during application. In cancer screening, it gave a positive rate of 5% to 10% in 10000 high risk persons. Those positive in this test showed a high incidence of gastric or esophageal cancers as proved by gastroscopy. This detector is being manufactured and sold by the Baiyunshan Pharmaceutical Factory, Guangzhou, Guangdong Province. Other papers concerning this topic are to be published.

Screening for upper digestive tract cancer with an occult blood bead detector. Investigation of a normal north China population.

Screening of the general population for cancer of the upper digestive tract using an occult blood bead detector supplemented by fibergastroscopy was able to detect 126 cancers of the esophagus, gastric cardia, and stomach. This screening was carried out in two of the high-risk areas, Yangzhong and Wun counties, located in central eastern and north China. The occult blood bead detector, swallowed and retained in the stomach for 3 minutes, was able to sort out the suspected persons by its coloration from sky blue (+) to dark blue ( ) on removal. The subsequent fibergastroscopy could make a definite diagnosis by biopsy specimen. A preliminary trial performed on patients with established cancers was 100% (18 of 18) positive for stomach cancer and 81% (13 of 16) positive for esophageal cancer. A public survey of the high-risk areas, screening 38,073 normal persons ranging in age from 35 to 70 years, showed positive results in 9204 (24.2%) persons. Subsequent fibergastroscopy carried out in 4023 occult blood bead detector positive persons showed 126 cancers (41 of the esophagus, 46 of the gastric cardia, and 39 of the stomach). Factors influencing the cancer detection rate were sex, age, and degree of positivity of the occult blood bead detector test. Seventy per cent (89 of 126) of the cancers discovered were in an early stage. The occult blood bead detector costs the primary screened person only 30 cents and may be practical for the large-scale screening of cancer of the upper digestive tract in developing areas.

Screening of esophageal and gastric cancer by occult blood bead detector.

A previously described bead method used to detect blood is simple, cheap, and effective; it can be repeated periodically. In 11 provinces in China, 233,825 persons (age range, 30-70 years) were screened. A positive occult blood test result was found in 28,557 persons (12%). Of these, 16,918 underwent a gastroscopy, resulting in the detection of 581 cancers that were located in similar frequencies in the esophagus, gastric cardia, and gastric body; 70% of the lesions were in an early or moderately advanced stage. Among 119 patients with early-stage cancer, the 3-year survival rate was 98.3%. After preliminary screening of cancer, the 4-year follow-up found a mortality rate in the group with negative occult blood test results that was only 25% of that of the positive group. Preliminary yearly screening would detect more early cancers and fewer advanced cancers. The mortality rate of esophageal and gastric cancer might be reduced drastically.