Specific ACE2 expression in small intestinal enterocytes may cause gastrointestinal symptoms and injury after 2019-nCoV infection.

The coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China and rapidly spread in other countries in December 2019. The infected patients presented with fever, respiratory symptoms, sometimes with digestive and other systemic manifestations, and some progressed with a severe acute respiratory syndrome or even death. Associated digestive symptoms were frequently observed in the patients, with an unknown significance and mechanism. ACE2, as the major known functional receptor of the 2019 novel coronavirus (2019-nCoV) attracted our attention. We collected the clinical data of the 2019-nCoV-infected patients from published studies and extracted the data about the incidence of gastrointestinal symptoms. Furthermore, we used online datasets to analyze ACE2 expression in different human organs, especially in the small intestine, to explore the relationship between ACE2 expression patterns and clinical symptoms. We found that diarrhea accounted for a notable proportion of COVID-19 patients, ranging from 8.0% to 12.9%. The results reveal that ACE2 mRNA and protein are highly expressed in the small intestinal enterocytes but not in the goblet cells or intestinal immune cells. High expression of ACE2 on the surface cells in the digestive tract may lead to gastrointestinal symptoms and inflammation susceptibility. Overall, digestive symptoms were common in the COVID-19 patients. ACE2 expression on surface cells of the small intestine may mediate the invasion and amplification of the virus and activation of gastrointestinal inflammation. It is a possible mechanism of digestive symptoms in the COVID-19 patients and explains the presence of the virus in patients' stool samples. The study also highlights the necessity of taking stool samples for suspected patients to help in early diagnosis and assessment of disease status.

The role of microRNA-608 polymorphism on the susceptibility and survival of cancer: a meta-analysis.

The role of rs4919510 polymorphism in microRNA-608 (miR-608) and cancer susceptibility and prognosis remain controversial and debatable. We conducted a meta-analysis of twenty-four eligible publications on the association of rs4919510 polymorphism with cancer risk and/or prognosis. Odds ratios, hazard ratios, and 95% confidence interval were used to investigate the association between this polymorphism and susceptibility, overall survival, and recurrence-free survival of cancer. Overall, eighteen case-control studies and nine cohort studies evaluated the susceptibility and prognostic value of rs4919510 polymorphism in cancer, respectively. Pooled analysis showed that rs4919510 polymorphism was not associated with cancer risk in all five genetic models. When stratifying by different cancer sites, rs4919510 polymorphism was detected to have a significant association with a decreased risk of colorectal cancer in homozygous model (P = 0.006) and recessive model (P = 0.001), subgroup analysis also emerged a weakened correlation between rs4919510 polymorphism and an increased risk of papillary thyroid cancer in heterozygote model (P = 0.04). Furthermore, the prognosis of rs4919510 variant in cancer patients showed that rs4919510 GG genotype was significant association with poor recurrence-free survival in homozygous models (P = 0.04). The meta-analysis suggested that the microRNA-608 rs4919510 polymorphism maybe associate with a significantly decreased risk for colorectal cancer. Further investigations on larger populations are required to evaluate and confirm this relationship.

Effects of kaixin jieyu decoction on behavior and glial fibrillary acidic protein expression in cerebral hippocampus of a rat vascular depression model.

OBJECTIVE: To explore the effects and anti-depression mechanisms of Kaixin Jieyu Decoction (, KJD). METHODS: The rat vascular depression (VD) model was established by ligation of bilateral common carotid arteries (LBCCA) combined with chronic unpredictable mild stress (CUMS). Forty Wistar rats were randomly divided into sham, VD model, VD + high-dose KJD [15.4 g/(kg·d) of crude drug], VD + medium-dose KJD [7.7 g/(kg·d) of crude drug], and VD + fluoxetine [2.4 mg/(kg·d)] groups (n=8 in each group), and the treatments lasted for 21 days. Changes of behavior and hippocampus pathology were observed. The level of glial fibrillary acidic protein (GFAP) protein and mRNA in hippocampus was detected respectively by immunohistochemistry and real-time polymerase chain reaction. RESULTS: Compared with the sham group, rats in model group showed a variety of behavioral obstacles, including a significant reduction in sucrose consumption percentage, horizontal and vertical activity scores in open-field tests (P<0.05 or P<0.01), pathological damage like neuronal degeneration, necrosis, and a significant decrease of GFAP protein and mRNA in hippocampus (P<0.01); compared with the model group, rats in the high-dose KJD group, medium-dose KJD group and fluoxetine group obtained notable higher behavioral scores, and pathological injury lessened in hippocampus with a increased expression of GFAP protein and mRNA P<0.05 or P<0.01); compared with the medium-dose KJD group and fluoxetine group, GFAP mRNA in high-dose KJD group expressed higer (P<0.05). CONCLUSION: LBCCA combined with CUMS may cause depression-like behavioral changes resulting in the VD model of rats whose depression state can be ameliorated by KJD, and the mechanism of cerebral protection is related possibly with promoting expression of GFAP in hippocampus.

[Tri-dimensional omics analysis on effect of zhuanggu zhitong capsule against experimental postmenopausal osteoporosis].

To propose the new concept of multidimensional omics, and define that the multidimensional omics is a proper method for studying the material base and mechanism of traditional Chinese medicine (TCM) compounds. Zhuanggu Zhitong capsule was taken for example to study its effect against experimental postmenopausal osteoporosis. From the perspective of chemi-omics, genomics and proteomics of TCM, it systematically interpreted the efficacious materials and mechanisms of Zhuanggu Zhitong capsule in preventing and treating experimental postmenopausal osteoporosis, while taking the lead in designing a three dimensional form to intuitively exhibit the results of the multidimensional omics study. This study provides a new idea and solution for studies on the efficacious materials and mechanisms of TCM compounds.

[The effects of cytochrome P450 2C19 genetic polymorphism on clopidogrel resistance and recent prognosis of patients with acute coronary syndrome].

OBJECTIVE: To investigate the relationship between cytochrome P450 (CYP) 2C19 genetic polymorphism and clopidogrel resistance(CR) in patients with acute coronary syndrome(ACS), and to assess the effects of genetic polymorphism at CYP2C19 (681G>A) on the prognosis of ACS patients. METHODS: A total of 462 patients with ACS were enrolled and received loading dose clopidogrel(600 mg). The blood samples of patients were collected before and 24 hours after taking loading dose clopidogrel, then 5 µmol/L ADP-induced platelet aggregation ratio (PAR) was examined. Difference of two PAR ≤ 10% was defined as CR. Genomic DNA of patients were extracted from whole blood samples according to standard protocols and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to genotype the single nucleotide polymorphism of the CYP2C19 681G>A. According to whether the gene CYP2C19 681A was carried, patients were divided into two groups: wild type group and non-wild type group. After PCI treatment, patients were followed up for 6 months and major cardiac adverse events (MACE) happened during follow-up periods were recorded. RESULTS: Totally 127 enrolled cases were finally defined as CR (27.5%) , the frequency of CYP2C19 681A in patients with CR was higher than that in patients without CR (46.9% vs 28.1%, P < 0.01) . The ratio of CR in wild type group were lower than non-wide type group (17.4% vs 36.1%, P < 0.01) . Binary logistic regression analysis indicated that gene CYP2C19 681A was a strong independent predictor for CR in patients with ACS (OR 3.642, P < 0.05). After 6 months of follow-up, Kaplan-Meier survival analysis showed patients of wild type group and non-wild type group had significantly different cumulative non-events survival rates (94.8% vs 89.6%, Log rank = 4.296, P = 0.038) . CONCLUSIONS: The genetic polymorphism of CYP2C19 was associated with CR in patients with ACS. The mutation of CYP2C19 gene increased the risk of MACE in ACS patients undergoing PCI treatments and affected the patients' prognosis.

Altered serum creatine kinase level and cardiac function in ischemia-reperfusion injury during percutaneous coronary intervention.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) resulting from primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is considered harmful to the patient, but its clinical significance remains unclear. This study explored the relationship of cardiac function examined by echocardiography and serum creatine kinase (CK) and CK-MB levels with MIRI in a cohort of Chinese AMI patients. MATERIAL/METHODS: We retrospectively analysed the clinical and angiographic data in 228 AMI patients in whom the infarct-related artery (IRA) was successfully recanalized by primary PCI. Cardiac function was evaluated by use of echocardiography before discharge from hospital. RESULTS: The in-hospital mortality rate in the MIRI group was 13.4% (16/119), which was significantly higher than the 4.6% (5/109) mortality rate in the non-MIRI group (P=0.021). The median of peak serum CK level was remarkably lower in the suppression-type MIRI group than in the non-MIRI group. There were no significant differences in the peak serum CK or CK-MB levels between the irritation-type MIRI group and the non-MIRI group. The peak CK and CK-MB levels were significantly higher in the no-reflow-type MIRI group than in the non-MIRI group. Left ventricular ejection fraction in the no-reflow-type MIRI group was significantly lower than in the non-MIRI group; left ventricular end-diastolic volume was significantly higher than in the irritation-type MIRI subgroup; and left ventricular end-systolic volume was greater than that in non-MIRI group and suppression-type MIRI group. CONCLUSIONS: MIRI (especially the no-reflow type) may lead to acute hemodynamic disorders and increase the mortality rate. However, suppression- and irritation-type MIRI may imply the existence of surviving myocardium.

[Fas and TNFR1 expressions after cerebral ischemia and reperfusion in rats: association with cell apoptosis and the effects of Bcl-2 overexpression].

OBJECTIVE: To investigate the effect of Bcl-2 overexpression on Fas and TNFR1-mediated apoptosis and its possible mechanism in rat hippocampus following global ischemia/reperfusion (IR). METHODS: Ninety healthy male SD rats were randomly divided into sham operated group, IR group and Bcl-2 overexpression group (BT group). Rat model of global IR was established by the 4-V0 method. The expressions of Bcl-2, Fas and TNFR1 and the cell apoptosis in the CA1 and CA3 regions were examined by HE staining, immunohistochemistry and TUNEL method. RESULTS: In IR group, the neurons in the CA1 region showed an obvious reduction in number with disordered arrangement and interstitial edema 48 h after global IR. Such changes were not obvious in BT group. Immunohistochemistry showed that Fas expression in the CA1 region reached the peak level at 6 h in IR group with a greater expression intensity than that in BT group (P<0.05). TNFR1 was expressed at a higher level in IR group than in BT group (P<0.05), reaching the peak level at 24 h. In the sham group, the expression of Fas and TNFR1 was not detected the in CA1 and CA3 regions. Global IR caused increased cell apoptosis in the CA1 and CA3 regions, starting at 6 h and reached peak at 24 to 48 h. The cell apoptosis was less obvious in BT group (P<0.05). CONCLUSION: Fas and TNFR1 are expressed in the CA1 and CA3 regions after global IR in rats, suggesting the involvement of death receptor in cerebral IR injury. Bcl-2 overexpression decreases the expression of Fas and TNFR1 and cell apoptosis after global IR, thus offering protective effect against cerebral IR injury.

[Observation on therapeutic effect of moxibustion and exercise for children with short stature of deficience of the kidney essence].

OBJECTIVE: To observe the therapeutic effect of moxibustion and exercise comprehensive scheme intervention for children with short stature of deficience of the kidney essence. METHODS: Twenty four cases of children in 12 to 14 years old were selected, 12 male and 12 female, they were treated with comprehensive therapy of exercise therapy and moxibustion. Running and jumping were selected as main exercise therapy, it became a suitable exercise amount when the heart rate reach to 150 to 170 times per minute, thrice each week, 35 to 45 minutes each time. After exercises they were treated with moxibustion, Qihai (CV 6), Guanyuan (CV 4), Zusanli (ST 36), Dazhu (BL 11), Xuanzhong (GB 39), Geshu (BL 17) etc. were selected. After treatment for half a year, the changes of the body height, body weight, bone age(BA), growth hormone (GH), testosterone (T) and estradiol (E2) were compared before and after treatment. RESULTS: The body height and bone age of the boys and girls were significantly higher than those before treatment (all P<0.05), the growth of body height was more than 4 cm, the growth of bone age was more than 0.5 years old in half a year; the testosterone of all children was significantly increased (all P<0.05), and there were no significant differences in body weight, GH and E2 compared to those before treatment (all P>0.05). CONCLUSION: Moxbustion and exercise comprehensive scheme can effectively improve the children with short stature of deficience of the kidney essence, the mechanism is related to the improving of the testosterone level.

[Reperfusion arrhythmias in acute myocardial infarction do not enhance myocardial injury].

OBJECTIVE: To investigate the clinical implications of reperfusion arrhythmias during primary percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI). METHODS: Data from 228 AMI patients in whom the infarct-related artery (IRA) were successfully recanalized by primary PCI were retrospectively analyzed. The 228 patients were divided into 2 groups: myocardial ischemia-reperfusion injury (MIRI) group (n=119) in whom MIRI events occurred within minutes after successful recanalization of IRA, and non-MIRI group (n=109). The 119 patients in MIRI group were further divided into 3 subgroups: severe bradycardia with hypotension (brady-arrhythmia subgroup), lethal ventricular arrhythmias requiring electrical cardioversion (tachy-arrhythmia subgroup), and IRA antegrade flow less than or equal to TIMI 2 grade without angiographic evidence of abrupt closure (no-reflow subgroup). RESULTS: (1) Clinical and angiographic data: Compared with non-MIRI group, MIRI group was characterized by more inferior infarct location, shorter ischemic duration, more frequently right coronary artery as IRA, more diseased vessels, more often TIMI 0 grade of initial antegrade flow in IRA, less pre-infarction angina, more renal insufficiency, and higher in-hospital mortality (13.4% vs. 4.6%, P=0.021). (2) The peak CK level was remarkably lower in brady-arrhythmia subgroup than that in non-MIRI group (2010 IU/L vs. 2521 IU/L, P=0.039). The peak CK or CK-MB level was notably higher in no-reflow subgroup than in non-MIRI group (4573 IU/L, 338 IU/L, respectively, P=0.000). (3) Left ventricular ejection fraction in no-reflow subgroup was significantly lower than in non-MIRI group (38.7% +/- 8.3% vs. 51.2% +/- 8.1%, P=0.000), left ventricular end-diastolic volume in no-reflow subgroup was greater than that in tachy-arrhythmia subgroup [(135 +/- 32) ml vs. (105 +/- 19) ml, P=0.029]. CONCLUSION: Reperfusion arrhythmias may imply the existence of much survived myocardium and do not enhance myocardial damage, while no-reflow increases myocardial injury and induces permanent impairment of cardiac function.

[Analysis on correlative factors for occurrence of myocardial ischemia-reperfusion injury during primary percutaneous coronary intervention for acute myocardial infarction].

OBJECTIVE: To explore the risk and protective factors for the occurrence of myocardial ischemia-reperfusion injury (MIRI) during primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). METHODS: Clinical and angiographic data of 228 AMI patients in whom the infarct-related arteries (IRA) were successfully revascularized by primary PCI were analyzed retrospectively. MIRI was defined if the following conditions existed after PCI: severe bradycardia with hypotension, or lethal ventricular arrhythmias requiring electrical cardioversion, or IRA antegrade flow < or = TIMI 2 grade flow without angiographic evidence of thrombus, emboli, dissection or spasm. Multivariate logistic regression was used to identify independent relative factors among 18 clinical and angiographic factors for occurrence of MIRI. RESULTS: Multivariate logistic regression analysis showed that independent risk factors for MIRI were the time intervals from AMI onset to IRA reflow < or = 6 h (P = 0.014), inferior infarction localization (P = 0.006), IRA antegrade flow prior to PCI < or = TIMI 1 grade (P = 0.028), multivessel lesions (P = 0.063) and renal insufficiency (P = 0.067). Pre-infarction angina was found to be an independent protective factor (P = 0.005). CONCLUSIONS: Short time intervals from AMI onset to IRA revascularization, inferior wall infarction location, low IRA antegrade flow prior to PCI, multivessel lesions and renal insufficiency may promote the occurrence of MIRI during primary PCI, whereas pre-infarction angina may be a cardioprotective factor attenuating MIRI.