Correlation analysis of norepinephrine dose on enteral nutrition tolerance and prognosis in patients with septic shock.

BACKGROUND: To explore correlation between the dose of norepinephrine and the timing of starting enteral nutrition in septic shock (SS) patients. METHODS: Totally 150 SS patients treated with enteral nutrition (EN) in Shiyan People's Hospital from Dece20 to July 2022 were included in this retrospective analysis. Patients were divided into tolerance group (n = 97) and intolerance group (n = 53) according to whether EN was tolerated or not. The study indexes include baseline characteristics [gender, age, weight, body mass index (BMI), scores of acute physiology and chronic health evaluation II system (APACHE II), comorbidity, time in-hospital, prognosis], clinical indexes [mean arterial pressure (MAP), time of mechanical ventilation (MV), norepinephrine dose at the time of starting EN, using of sedative drug, gastrointestinal motility drugs and cardiotonic drugs], EN indexes (timing of starting EN, speed of EN infusion, calorie of EN per day, EN target percent), and gastrointestinal intolerance index [residual gastric volume > 250 ml, vomiting, aspiration, gastrointestinal bleeding, blood lactic acid (BLA)]. Student-t test and Mann-Whitney test were used for test of measurement data. Chi-square test and fisher exact test were used for comparison of categorical data. RESULTS: There were 51 (52.58%) male and 46 (47.42%) female patients with a median age of 66.4 ± 12.8 years old in tolerance group. There were 29 (54.72%) male and 24 (45.28%) female patients with a median age 67.3 ± 12.5 years old in intolerance group. The weight and BMI were significantly higher in intolerance group than those of tolerance group (both P < 0.001). There was no significant difference of comorbidity rate between two groups (all P > 0.05). Before the overlapping time of EN and norepinephrine, there were significantly more patients receiving gastrointestinal motility drugs in intolerance group compared with tolerance group (58.49% vs. 20.62%, P < 0.001). Patients in tolerance group had significantly less residual volume in gastric than that of intolerance group (188.00 ± 52.32 vs. 247.83 ± 34.95, P < 0.001). The rate of residual volume in gastric > 250ml (9.28% vs. 37.74%, P < 0.001), vomiting (15.46% vs. 35.85%, P = 0.004) and aspiration(16.49% vs. 33.96%, P = 0.018) were significantly lower in tolerance group than those of intolerance group. The BLA in tolerance group was significantly lower than that of intolerance group (1.84 ± 0.63 vs. 2.90 ± 1.5 3mmol/L,P < 0.001). There were significantly more patients with increased BLA (75.47% vs. 30.93%, P < 0.001) and > 2mmol BLA rising (43.40% vs. 8.25%, P < 0.001) in intolerance group than those of tolerance group. Patients in tolerance group had significantly lower time of starting EN (40.97 ± 9.53 vs. 49.85 ± 11.61 h, P < 0.001), dose of NE(0.23 ± 0.07 vs. 0.28 ± 0.10 ug/kg/min, P = 0.049), mortality in hospital (18.56% vs. 49.06%, P < 0.001) and mortality in ICU (16.49% vs. 37.74%, P < 0.001) compared with intolerance group. The EN target percent (92.78% vs. 56.60%, P < 0.001) and calorie of EN during overlapping period (20.22 ± 5.99 vs. 16.21 ± 2.52 kcal/kg/day, P < 0.001) in tolerance group were significantly higher than those of intolerance group. CONCLUSIONS: SS patients should be comprehensively evaluated according to their condition. Obese patients are more prone to EN intolerance, and those who can tolerate EN should be implemented as soon as possible. The use dose of NE is significantly related to EN tolerance. When the use dose is low, EN tolerance is greater.

Contributions of HOTAIR polymorphisms to the susceptibility of cancer.

OBJECTIVE: Hox transcript antisense intergenic RNA (HOTAIR), a lncRNA, functions as a critical regulator in cancer development. A plenty of case-control studies were conducted to assess the actual relationship of HOTAIR gene generic variants on cancer susceptibility, yet conflicting conclusions remain. Herein, we carried out this up-to-date meta-analysis to get a better understanding of such relationship by incorporating all eligible case-control studies. MATERIALS AND METHODS: Six widely investigated polymorphisms were included in this meta-analysis: rs920778, rs4759314, rs7958904, rs874945, rs1899663, and rs12826786. We retrieved relevant studies from databases PubMed, EMBASE, Medline, CNKI and Wanfang update to June 2020. We applied odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the relationship strengths. RESULTS: Our findings indicate that rs920778, rs4759314, rs874945, rs12826786 polymorphism significantly increased with susceptibility to overall cancer. However, rs7958904, rs1899663 under any five genetic models could not impact susceptibility to overall cancer. Furthermore, altered cancer risk was detected when the data were stratified by cancer type, ethnicity, the source of controls, and HWE in all the SNPs. CONCLUSIONS: These findings of the meta-analysis suggest that HOTAIR polymorphisms may predispose to cancer susceptibility.

Contributions of PARP-1 rs1136410 C>T polymorphism to the development of cancer.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear chromatin-associated enzyme involved in the DNA damage response. SNP rs1136410 C>T, the most studied polymorphism in PARP-1 gene, is highly implicated in the susceptibility of cancer. However, the roles of PARP-1 rs1136410 C>T on cancer risk vary from different studies. We comprehensively screened all qualified publications from several databases, including PubMed, EMBASE, MEDLINE, CNKI and Wanfang. The searching was updated to April 2020. Our meta-analysis included 60 articles with 65 studies, comprised of a total of 23 996 cases with cancer and 33 015 controls. Overall, pooled data showed that the PARP-1 rs1136410 C>T polymorphism was significantly but a border-line associated with an increased risk of overall cancer (CC vs. TT/TC: OR = 1.11, 95% CI = 1.00-1.24; C vs T: OR = 1.07, 95% CI = 1.01-1.14). Subgroup analysis indicated that rs1136410 C allele contributed to high risk among gastric, thyroid, and cervical cancer, but lower risk among brain cancer. Furthermore, increased cancer risk was detected in the subgroups of Asian, controls from population-based design studies, and HWE ≤ 0.05 studies. Sensitivity analysis and Egger's test showed that results of the meta-analysis were fairly stable. The current study indicated that PARP1 rs1136410 C>T polymorphism may have an impact on certain types of cancer susceptibility.

Corticosteroid therapy in critically ill patients with COVID-19: a multicenter, retrospective study.

BACKGROUND: Corticoid therapy has been recommended in the treatment of critically ill patients with COVID-19, yet its efficacy is currently still under evaluation. We investigated the effect of corticosteroid treatment on 90-day mortality and SARS-CoV-2 RNA clearance in severe patients with COVID-19. METHODS: 294 critically ill patients with COVID-19 were recruited between December 30, 2019 and February 19, 2020. Logistic regression, Cox proportional-hazards model and marginal structural modeling (MSM) were applied to evaluate the associations between corticosteroid use and corresponding outcome variables. RESULTS: Out of the 294 critically ill patients affected by COVID-19, 183 (62.2%) received corticosteroids, with methylprednisolone as the most frequently administered corticosteroid (175 accounting for 96%). Of those treated with corticosteroids, 69.4% received corticosteroid prior to ICU admission. When adjustments and subgroup analysis were not performed, no significant associations between corticosteroids use and 90-day mortality or SARS-CoV-2 RNA clearance were found. However, when stratified analysis based on corticosteroid initiation time was performed, there was a significant correlation between corticosteroid use (≤ 3 day after ICU admission) and 90-day mortality (logistic regression adjusted for baseline: OR 4.49, 95% CI 1.17-17.25, p = 0.025; Cox adjusted for baseline and time varying variables: HR 3.89, 95% CI 1.94-7.82, p < 0.001; MSM adjusted for baseline and time-dependent variants: OR 2.32, 95% CI 1.16-4.65, p = 0.017). No association was found between corticosteroid use and SARS-CoV-2 RNA clearance even after stratification by initiation time of corticosteroids and adjustments for confounding factors (corticosteroids use ≤ 3 days initiation vs no corticosteroids use) using MSM were performed. CONCLUSIONS: Early initiation of corticosteroid use (≤ 3 days after ICU admission) was associated with an increased 90-day mortality. Early use of methylprednisolone in the ICU is therefore not recommended in patients with severe COVID-19.

Fallot Tetralogy with Dissected Pulmonary Artery Aneurysm: A Rare Case Report.

Pulmonary artery dissection is a rare and extremely dangerous disease with high mortality rates. It is one of the most serious complications of chronic pulmonary hypertension. It may be related to chronic pulmonary hypertension and pulmonary artery dilatation. Early diagnosis of pulmonary dissection is particularly important because of its high mortality. Once the symptoms worsen or severe deterioration of the disease occurs, imaging examination should be performed promptly for early diagnosis and timely treatment.

Full neurological recovery from severe nonexertional heat stroke with multiple organ dysfunction: A case report.

BACKGROUND: We report a rare case of full neurological recovery from severe nonexertional heat stroke in a 67-year-old woman with an initial Glasgow Coma Scale of 3. This report raises awareness among doctors that when heatstroke is diagnosed, comprehensive treatment should be implemented as soon as possible. Moreover, targeted temperature management, combination therapy with hemodialysis and hemoperfusion, and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke. CASE SUMMARY: A previously healthy 67-year-old woman with an initial Glasgow Coma Scale of 3 was found lying prone on the road at noon on a summer day. Laboratory tests revealed multiorgan failure. As soon as heatstroke was diagnosed, comprehensive treatment was implemented. On hospital Day 3, the patient was extubated. Her initial Sequential Organ Failure Assessment score at hospitalization was 14 and decreased to 2 on hospital Day 4. On the seventh day following hospital admission, as the patient's general condition improved, the levels of laboratory test findings decreased rapidly. Finally, the patient gradually recovered with no other neurological symptoms (the Glasgow Coma Scale at discharge was 15, and her ability to walk independently was restored). CONCLUSION: This case demonstrated that targeted temperature management, combination therapy with hemodialysis and hemoperfusion, and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.

Effects of vasoactive drugs on hepatic and intestinal circulation and intestinal barrier in patients with septic shock.

In this study, 60 patients with septic shock were selected over the course of 1 year, and the effects of dopamine and norepinephrine combined with dobutamine on hepatic and intestinal circulation and intestinal barrier in patients with septic shock were studied by comparison between the control group and the experimental group. All patients received mechanical ventilation to maintain breathing at 14 to 20 times/min. The experimental group was treated with vascular active drugs after adequate rehydration, and the control group only received adequate rehydration. There were extremely significant differences (p<0.01) in the total effective rate of each group. There were significant differences in the hemodynamic indexes in each group (p<0.05). There was a significant difference in total 24-hour bile output (p<0.01). There were significant differences in liver function and blood lipid values in patients (p<0.01). There were significant differences in the repair of epithelial injury at 0 hour, 48 hours and 96 hours (p<0.01). There were significant differences in the transmembrane resistance of monolayer cells (p<0.01). The expression differences of three proteins ZO-1, occludin and ß-actin were also significant, among which the three proteins in the control group were weak, while those in groups A and B were strong. The expression of tight junction protein in monolayer cells was weakly positive in expression and strong in other proteins. In conclusion, vasoactive drugs had significant effects on hepatic and intestinal circulation and intestinal barrier in patients with septic shock.

Depleting microRNA-183-3p improves renal tubulointerstitial fibrosis after acute kidney injury via SIRT1/PUMA/FOXO3a deacetylation.

BACKGROUND/AIM: Emerging studies have revealed the mechanism of microRNAs (miRNAs) in acute kidney injury (AKI). However, almost no research focuses on miR-183-3p in AKI. Therefore, this study is started to explore the potential role of miR-183-3p from the perspective of Sirtuin (SIRT1)/forkhead box O3a (FOXO3a)/p53 up-regulated modulator of apoptosis (PUMA) in AKI. METHODS: AKI rat models were established. miR-183-3p, SIRT1, deacetylated FOXO3a and PUMA expression in AKI were detected. The targeting relationship between miR-183-3p and SIRT1 was tested. AKI modeled rats were injected with miR-183-3p- or SIRT1-related sequences to identify their effects on AKI. Rat renal tubular epithelial cells NRK-52E were transfected with miR-183-3p- or SIRT1-related sequences for further exploration of their roles in vitro. RESULTS: Decreased SIRT1 and deacetylated FOXO3a and increased miR-183-3p and PUMA were found in AKI. SIRT1 was targeted by miR-183-3p. Down-regulated miR-183-3p or up-regulated SIRT1 attenuated renal tissue damage and fibrosis, and suppressed renal tubular epithelial cell apoptosis in renal tissues of AKI rats. Down-regulated miR-183-3p or up-regulated SIRT1 promoted proliferation and impaired fibrosis and apoptosis of renal tubular epithelial cells. CONCLUSION: Our study provides evidence that down-regulated miR-183-3p or up-regulated SIRT1 attenuates AKI via PUMA inhibition induced by FOXO3a deacetylation. Thus, miR-183-3p and SIRT1 can be the candidates for therapy of AKI.

Extracorporeal Membrane Oxygenation for SARS-CoV-2 Acute Respiratory Distress Syndrome: A Retrospective Study From Hubei, China.

Background: The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available. Methods: A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected. Results: The 73 ECMO-treated patients had a median age of 62 (range 33-78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO2/FiO2 of 71.9 [interquartile range (IQR), 58.6-87.0] mmHg and a median PCO2 of 62 [IQR, 43-84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15-25] days, and 23 [IQR, 19-31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12-30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively. Conclusions: In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.

miR­146a­5p suppresses ATP­binding cassette subfamily G member 1 dysregulation in patients with refractory Mycoplasma pneumoniae via interleukin 1 receptor­associated kinase 1 downregulation.

In the present study, we examined the function of microRNA (miR)­146a­5p in patients with refractory Mycoplasma pneumoniae pneumonia. In brief, the expression of miR­146a­5p was reduced in patients with refractory Mycoplasma pneumoniae pneumonia. Downregulation of miR­146a­5p reduced inflammation in an in vitro model of refractory Mycoplasma pneumoniae pneumonia, whilst overexpression of miR­146a­5p promoted inflammation. Downregulation of miR­146a­5p induced the protein expression of ATP­binding cassette subfamily G member 1 (ABCG1) and interleukin 1 receptor­associated kinase 1 (IRAK­1), while suppressed expression was observed of the aforementioned proteins following overexpression of miR­146a­5p in an in vitro model of refractory Mycoplasma pneumoniae pneumonia. The administration of small interfering RNA against RXR or IRAK­1 attenuated the effects of miR­146a­5p on inflammation in an in vitro model of refractory Mycoplasma pneumoniae pneumonia. Collectively, these results suggested that miR­146a­5p reduced ABCG1 expression in refractory Mycoplasma pneumoniae pneumonia via downregulation of IRAK­1.

HIF-1α rs11549465 C>T polymorphism contributes to increased cancer susceptibility: Evidence from 49 studies.

HIF-1α (hypoxia-inducible factor-1α) is a transcriptional factor that participates in the regulation of oxygen homeostasis. Despites numbers of case-control studies working on this area, the actual relationship of HIF-1α gene generic variant rs11549465 C>T imposing on cancer susceptibility remains unveiled. To get a better understanding of such relationship, this meta-analysis was carried out by incorporating all eligible case-control studies. Qualified articles were acquired from PubMed, CNKI, EMBASE, PMC, and Wanfang database update to April 2019. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were employed to estimate the relationship of interest. Heterogeneity tests, sensitivity analyses and publication bias assessments were also carried out to ensure the strength of our conclusion. A total of 46 articles with 49 studies including 12920 cases and 13363 controls were included. The results indicated that HIF-1α rs11549465 C>T was significantly related to the increased risk of overall cancer under four genetic models (TT vs. CC: OR=2.06, 95% CI=1.34-3.16; TT vs. CC/CT: OR=2.42, 95% CI=1.60-3.65; CT/TT vs. CC: OR=1.21, 95% CI=1.04-1.40; T vs. C: OR=1.29, 95% CI=1.12-1.48). Furthermore, enhanced cancer risk was detected after stratification by cancer type, ethnicity, the source of controls and HWE. These results suggest that HIF-1α rs11549465 C>T polymorphism may predispose to cancer susceptibility.