Association of prealbumin with short-term and long-term outcomes in patients with acute ST-segment elevation myocardial infarction

BACKGROUND Prealbumin is considered to be a useful indicator of nutritional status. Furthermore, it has been found to be associated with severities and prognosis of a range of diseases. However, limited data on the association of baseline prealbumin level with outcomes of patients with acute ST-segment elevation myocardial infarction(STEMI) are available.METHODS We analyzed 2313 patients admitted for acute STEMI between October 2013 and December 2020. In-hospital outcomes and mortality during the 49 months(interquartile range: 26–73 months) follow-up period were compared between patients with the low prealbumin level(< 170 mg/L) and those with the high prealbumin level(≥ 170 mg/L).RESULTS A total of 114 patients(4.9%) died during hospitalization. After propensity score matching, patients with the low prealbumin level than those with the high prealbumin level experienced higher incidences of heart failure with Killip class Ⅲ(9.9%vs. 4.4%, P = 0.034), cardiovascular death(8.4% vs. 3.4%, P = 0.035) and the composite of major adverse cardiovascular events(19.2%vs. 10.3%, P = 0.012). Multivariate logistic regression analysis identified that the low prealbumin level(< 170 mg/L) was an independent predictor of in-hospital major adverse cardiovascular events(odds ratio = 1.918, 95% CI: 1.250–2.942, P = 0.003). The cutoff value of prealbumin level for predicting in-hospital death was 170 mg/L(area under the curve = 0.703, 95% CI: 0.651–0.754, P< 0.001;sensitivity = 0.544, specificity = 0.794). However, after multivariate adjustment of possible confounders, baseline prealbumin level(170 mg/L) was no longer independently associated with 49-month cardiovascular death. After propensity score matching, Kaplan-Meier survival curves revealed consistent results.CONCLUSIONS Decreased prealbumin level closely related to unfavorable short-term outcomes. However, after multivariate adjustment and controlling for baseline differences, baseline prealbumin level was not independently associated with an increased risk of long-term cardiovascular mortality in STEMI patients.

Beware of the serious harm of veterinary drug poisoning:a case report

Veterinary drugs are substances(including pharmaceutical feed additives)used to prevent,treat,and diagnose diseases or regulate the physiological functions of animals.Veterinary drug poisoning in humans is relatively rare both in China and the rest of the world.Here,we report a case of death from veterinary drug poisoning from avermectin-closantel.Avermectin-closantel is a broad-spectrum antiparasitic drug,which has high efficacy against a variety of trematodes and nematodes.

Role of PERK/eIF2α/CHOP Endoplasmic Reticulum Stress Pathway in Oxidized Low-density Lipoprotein Mediated Induction of Endothelial Apoptosis

Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum （ER） stress related with atherosclerosis. Oxidized LDL （ox-LDL） also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells （HUVECs） were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.

Bioactive compounds of sea cucumbers and their therapeutic effects

Abstract Sea cucumbers belong to the Class Holothuroidea of marine invertebrates. They are commercially valuable and prized as a food and folk medicine in Asia. Nutritionally, sea cucumbers have an impressive profile of valuable nutrients such as vitamins, minerals and amino acids. A number of unique biological and pharmacological activities/properties, including anticancer, anticoagulant/antithrombotic, antimicrobial, antioxidant, antihyperlipidemic, antihyperglycemic, anti-inflammatory, antihypertension and radioprotective, have been ascribed to various compounds isolated from sea cucumbers. The therapeutic properties and medicinal benefits of sea cucumbers can be linked to the presence of a wide array ofbioactives, especially triterpene glycosides, acid mucopolysaccharide, sphingoid bases, glycolipids, fucosylated chondroitin sulfate, polysaccharides, phospholipids, cerebrosides, phosphatidylcholines, and other extracts and hydrolysates. This review highlights the valuable bioactive components as well as the multiple therapeutic properties of sea cucumbers with a view to exploring their potential uses as functional foods and a natural source of new multifunctional drugs.

Incidence,predictors and prognosis of acute kidney injury in acute ST-segment elevation myocardial infarction patients undergoing emergent coronary angiography/primary percutaneous coronary intervention

BACKGROUND Acute kidney injury(AKI) after coronary angiography(CAG) and primary percutaneous coronary intervention(PPCI) is frequently observed, and often interpreted as contrast induced-AKI. This study aimed to investigate the incidence, predictors and outcomes of AKI in acute ST-segment elevation myocardial infarction(STEMI) patients undergoing emergent CAG/PPCI using the control group of STEMI patients who were not exposed to contrast agents within the first 72 h.METHODS We performed a retrospective analysis of 1670 STEMI patients. Of them, 673 patients underwent emergent CAG/PPCI, and 997 patients treated with thrombolysis or no reperfusion therapy who were not exposed to contrast material during the first 72 h. AKI was defined as an increase of serum creatinine ≥ 44.2 mmol/L or ≥ 25% from baseline within 72 h. Patents were then followed up for the occurrence of all-cause mortality for 40 months(interquartile range: 24–55 months).RESULTS After propensity score matching, 505 pairs of patients were matched. Overall, the incidence of AKI was 27.4%, and AKI rates were not significantly different in patients with and without emergent CAG/PPCI procedure(27.5% vs. 27.3%, P = 0.944). Multivariate logistic regression analysis identified that the independent predictors of AKI were female, elevated interleukin-6 level,decreased lymphocyte count, left ventricular ejection fraction < 50% and use of diuretics in patients with emergent CAG/PPCI. Patients with AKI than those without AKI experienced higher incidence of acute heart failure with Killip class Ⅲ(9.4% vs. 3.3%, P =0.005;15.2% vs. 6.8%, P = 0.003, respectively) and mortality(5.8% vs. 1.4%, P = 0.014;12.3% vs. 4.6%, P = 0.002, respectively) in patients with and without emergent CAG/PPCI. Multivariate Cox regression analysis confirmed that AKI was independently associated with long-term mortality rate at 40 months follow-up in patients with and without emergent CAG/PPCI(HR = 1.867, 95% CI:1.086–3.210, P = 0.024;HR = 1.700, 95% CI: 1.219–2.370, P = 0.002, respectively).CONCLUSIONS Approximately 27.0% of STEMI patients experience AKI, which is strongly associated with an increased shortand long-term mortality regardless of emergent CAG/PPCI procedure. The development of AKI is mainly related to female gender, inflammation reaction, heart failure and use of diuretics in STEMI patients undergoing emergent CAG/PPCI.

Effects and Mechanism of Irbesartan on Tubulointerstitial fibrosis in 5/6 Nephrectomized Rats

Tubulointerstitial fibrosis(TIF)is a common pathological feature of end-stage kidney disease.Previous studies showed that upregulation of TGFβ1 notably contributed to the chronic renal injury and irbesartan halted the development of TIF in rats with 5/6 renal mass reduction.This study was to investigate the effects of irbesartan on chronic TIF and the mechanism involved TGFβ1 in the rodent model of chronic renal failure involving 5/6 nephrectomy.The results showed that irbesartan significantly attenuated th...

Performance of extracorporeal membrane oxygenation in patients with fatal paraquat poisoning:grasp for straws?

Dear editor,Paraquat(PQ)can cause acute lung injury and irreversible pulmonary fibrosis,without specific antidotes.Respiratory failure is the main cause of death among patients with PQ poisoning.Currently,the treatment involves the use of adsorbents,intensive hemoperfusion,antioxidants,immunosuppressive therapy,respiratory support by mechanical ventilation,and other symptomatic and supportive treatments.[1-3]The mortality of patients with severe PQ poisoning remains high.More eff ective and safer therapies remain to be explored.Few studies reported performing extracorporeal membrane oxygenation(ECMO)and subsequent lung transplantation with either successful or poor clinical outcome in extremely critical patients with PQ poisoning.[4,5]This study aims to summarize the clinical experience and refl ect on the therapeutic prospect of ECMO in respiratory failure or cardiopulmonary failure caused by fatal PQ poisoning.

Protective effects of Bushen Tiansui decoction on hippocampal synapses in a rat model of Alzheimer's disease

Bushen Tiansui decoction is composed of six traditional Chinese medicines：Herba Epimedii,Radix Polygoni multiflori,Plastrum testudinis,Fossilia Ossis Mastodi,Radix Polygalae,and Rhizoma Acorus tatarinowii.Because Bushen Tiansui decoction is effective against amyloid beta（Aβ） toxicity,we hypothesized that it would reduce hippocampal synaptic damage and improve cognitive function in Alzheimer＇s disease.To test this hypothesis,we used a previously established animal model of Alzheimer＇s disease,that is,microinjection of aggregated Aβ25–35 into the bilateral brain ventricles of Sprague-Dawley rats.We found that long-term（28 days） oral administration of Bushen Tiansui decoction（0.563,1.688,and 3.375 g/m L;4 m L/day） prevented synaptic loss in the hippocampus and increased the expression levels of synaptic proteins,including postsynaptic density protein 95,the N-methyl-D-aspartate receptor 2 B subunit,and Shank1.These results suggested that Bushen Tiansui decoction can protect synapses by maintaining the expression of these synaptic proteins.Bushen Tiansui decoction also ameliorated measures reflecting spatial learning and memory deficits that were observed in the Morris water maze（i.e.,increased the number of platform crossings and the amount of time spent in the target quadrant and decreased escape latency） following intraventricular injections of aggregated Aβ25–35 compared with those measures in untreated Aβ_（25–35）-injected rats.Overall,these results provided evidence that further studies on the prevention and treatment of dementia with this traditional Chinese medicine are warranted.

Prevalence and clinical implications of polypharmacy and potentially inappropriate medication in elderly patients with heart failure: results of six months' follow-up

OBJECTIVES To investigate the prevalence of polypharmacy and potentially inappropriate medication(PIM)in elderly patients with heart failure(HF)and their impact on readmission and mortality.METHODS We conducted a study of 274 participants aged 60 years or older with HF.The prevalence of polypharmacy(defined as the use of five or more medications)was calculated,and the 2019 American Geriatrics Society Beers criteria were applied to access PIMs.Medications and PIMs were characterized at admission and discharge,and changes in prescriptions during hospitalization were compared.The impact of polypharmacy and PIM on readmission and mortality were investigated.RESULTS The median age of this study population was 68 years old.The median number of prescribed drugs was 7 at admission and 10 at discharge.At discharge,99.27%of all patients were taking five or more drugs.The incidence of composite endpoint and cardiovascular readmission increased with the number of polypharmacy within 6 months.The use of guideline-directed medical therapy reduced the incidence of composite endpoint events and cardiovascular readmission,while the use of noncardiovascular medications increased the composite endpoint events.The frequency of PIMs was 93.79%at discharge.The incidence of composite endpoint events increased with the number of PIMs.“PIMs in older adults with caution”increased cardiovascular readmission and“PIMs based on kidney function”increased cardiovascular mortality.Several comorbidities were associated with cardiovascular mortality or non-cardiovascular readmission.CONCLUSIONS Polypharmacy and PIM were highly prevalent in elderly patients with HF,and their use was associated with an increased risk of composite endpoint events,readmission and mortality.Non-cardiovascular medications,“PIMs in older adults with caution”,“PIMs based on kidney function”and several comorbidities were important factors associated with hospital readmission and mortality.Our findings highlight the importance of medication optimization in the management of HF in elderly patients.

Handgrip strength and health outcomes: Umbrella review of systematic reviews with meta-analyses of observational studies

Purpose:The aim of the present study was to assess both the credibility and strength of evidence arising from systematic reviews with meta-analyses of observational studies on handgrip strength and health outcomes.Methods:An umbrella review of systematic reviews with meta-analyses of observational studies was conducted.We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p values,95%prediction intervals,heterogeneity,small-study effects,and excess significance.We graded the evidence from convincing(Class I)to weak(Class IV).Results:From 504 articles returned in a search of the literature,8 systematic reviews were included in our review,with a total of 11 outcomes.Overall,nine of the 11 of the outcomes reported nominally significant summary results(p<0.05),with 4 associations surviving the application of the more stringent p value(p<106).No outcome presented convincing evidence.Three associations showed Class II evidence(i.e.,highly suggestive):(1)higher handgrip values at baseline were associated with a minor reduction in mortality risk in the general population(n=34 studies;sample size=1,855,817;relative risk=0.72,95%confidence interval(95%CI):0.670.78),(2)cardiovascular death risk in mixed populations(n=15 studies;relative risk=0.84,95%CI:0.780.91),and(3)incidence of disability(n=7 studies;relative risk=0.76,95%CI:0.660.87).Conclusion:The present results show that handgrip strength is a useful indicator for general health status and specifically for early all-cause and cardiovascular mortality,as well as disability.To further inform intervention strategies,future research is now required to fully understand mechanisms linking handgrip strength scores to these health outcomes.

Intracranial malignant solitary fibrous tumor metastasized to the chest wall:A case report and review of literature

BACKGROUND Solitary fibrous tumor(SFT)is a rare fibroblastic mesenchymal neoplasm that affects spindle cell soft tissues with broad-spectrum biological behavior;it is predominantly benign,and rarely metastasizes.SFT occurs mainly in the tissue structure of the serosa in the pleura and the thorax,and can be found throughout the body,though extra-thoracic localization,including the cephalic region,is uncommon.We reported the first case of intracranial malignant SFT metastasized to the chest wall.CASE SUMMARY An 81-year-old Japanese man was referred to our hospital due to progressive gait disturbance and appetite loss.His medical history included partial resection due to brain tumor,four times,and 50-Gray radiation therapy at another hospital,starting when he was 74 years old.An unenhanced head computed tomography(CT)scan revealed an 8 cm×5.1 cm×6.5 cm mixed-density mass at the left frontal lobe,accompanying a midline shift,and an unenhanced chest-abdomen CT scan revealed a 6 cm×4.1 cm×6.5 cm low-density mass in the left chest wall.A CT-guided percutaneous lung biopsy was performed,and the pathological findings were SFT corresponding to brain tumor.Finally,the correct diagnosis of his brain tumor in history of past illness revealed to be SFT,and the unremovable tumor,namely present brain lesions enlarged and metastasized to the chest wall.We established a definitive diagnosis of intracranial malignant SFT metastasized to the chest wall.We notified him and his family of the disease,and offered palliative care.He passed away on the 29 th hospital day.CONCLUSION This case suggests the need for careful,detailed examination,and careful followup when encountering patients presenting with a mass.

Exploring the use of transcranial photobiomodulation in Parkinson's disease patients

Parkinson＇s disease is a neurological disorder with distinct motor signs of resting tremor,akinesia and/or lead-pipe rigidity,together with non-motor symptoms of impaired smell,cognition and autonomic function.These manifest after a major degeneration of neurones mainly within the brainstem,particularly among the dopaminergic neurones.

Alpha-1-antitrypsin deficiency resulting in a hitherto unseen presentation of hepatocellular carcinoma:Polycythemia but with normal alpha fetoprotein

Polycythemia is a known paraneopastic manifestation of hepatoma, but only in the presence of alpha-fetopro （AFP）. We present a case of polycythemia in the absence of AFP, and suggest concurrent alpha-1-antitrypsin deficiency as the cause for breaking this rule. We also suggest a reason for the apparent constant conjunction between polycythemia and AFP in hepatoma.

Effects of simvastatin on lipid levels and platelet activation in elderly patients with hypercholesterolemia

Background and Objective To investigate the effects of simvastatin on lipid lowering therapy and platelet activation in elderly patients with hypercholesterolemia. Methods Fasting serum lipids, CD63, CD41a, serum glucose, hepatic and renal function, routine urine analysis (UA) were measured in 50 healthy subjects, and in 50 elderly patients with hypercholesterolemia before and after 4 weeks treatment with simvastatin (20mg daily for 4 weeks). Results 1. After simvastatin treatment for 4 weeks, the fasting serum level of lipids in elderly patients with hypercholesterolemia was significantly lower than before treatment (P<0.01). 2. CD63 and CD41a were decreased after treatment compared with before, respectively (1.36 0.34) vs (4.26 1.06), (P<0.01) and (123.54 19.73) vs (253.78 16.75), (P<0.01). 3. Changes in serum lipid level tended to be positively correlated with the declines in CD63 and CD41a, but there was no statistical significance (P>0.05). Conclusions The results suggested that lipid lowering therapy with simvastatin inhibit platelet activity.(J Geriatr Cardiol 2007;4:215-217.)

Opportunistic screening for atrial fibrillation with a single lead device in geriatric patients

Objective To determine the diagnostic yield of repeated screening for atrial fibrillation(AF)among geriatric patients.Methods A pragmatic prospective cohort study into applying opportunistic screening for AF with a handheld single lead ECG device(SLD)in a geriatric cohort.Consecutive patients of 65 years old and older visiting the geriatric outpatient clinic were eligible for inclusion.A 12 lead ECG was performed,followed by measurements with the SLD during every visit to the geriatric outpatient clinic.A frailty index was based on the accumulation of deficits model.Results 478 patients were eligible.Patients were excluded if they did not give informed consent(17 patients),had a pacemaker or implantable cardioverter defibrillator(20 patients),or had incomplete medical files(two patients).After exclusion,439 patients participated in this study.The mean age was 78 years(range 65 to 100 years),54%were female.AF was known in 89 patients(20%),first detected on the baseline ECG in four patients(1%)and first detected with the SLD in 20 patients(5%)during follow up visits.Sensitivity of the SLD was 90.0%,specificity 99.0%,negative predictive value 99.7%,and positive predictive value 73.5%.Most patients(82%)with AF were frail and 53%were severely frail.Conclusion Repeated screening in geriatric patients has a five times higher diagnostic yield than usual care.It was easily combined with usual care.Because of the positive predictive value of 73.5%,it remains necessary to confirm AF with a 12 lead ECG or 24-h Holter monitoring.

Clinical, laboratory and radiological features and outcomes of moderate to severe COVID-19 patients: A descriptive retrospective study

Objective:To describe the clinical,laboratory and radiological characteristics and outcomes of moderate-to-severe coronvirus disease 2019(COVID-19)patients.Methods:We retrospectively analyzed 43 RT-PCR confirmed moderate-to-severe COVID-19 patients who were admitted to a tertiary care center.The primary composite outcomes were admission to intensive care unit,requirement of mechanical ventilation,and death.Results:The median age of the patients was 50 years,and 62.8%of the patients were male.Out of 43 patients,15(34.88%)were categorized as severe.A total of 26(60.47%)patients had 1 or more comorbidities[diabetes(34.88%)and hypertension(30.23%)].The median duration from the onset of symptoms to admission was 3 days,and the most common symptoms were dyspnoea(90.7%),cough(79.07%),fever(69.77%),and body ache(46.51%).Leucopenia was presented in 14(32.56%)patients,lymphopenia in 26(60.47%)patients,and monocytosis in 7(16.28%)patients.Besides,40(93.02%)patients had bilateral patchy nodular or interstitial infiltration on chest X-ray.The primary outcomes occurred in 20 patients(46.5%),among whom 8 required mechanical ventilation.The patients who had met the primary outcomes were older.They were prone to have at least 1 comorbidity(P=0.004),diabetes(P=0.01),hypertension,higher sequential organ failure assessment score,more tachycardia,lower SpO2,lower PaO2/FiO2,more thrombocytopenia,and more pancytopenia.Conclusions:This retrospective study identified several risk factors for poor outcomes in adults with COVID-19.In particular,older age,tachycardia,high SOFA score,low SpO2,low PaO2/FiO2,presence of comorbidities in form of diabetes and hypertension,thrombocytopenia,and pancytopenia at admission were associated with higher odds of ICU admission,a requirement of mechanical ventilation and in-hospital death.

Red cell distribution width: A predictor of the severity of hypertriglyceridemia-induced acute pancreatitis

BACKGROUND Compared with patients with other causes of acute pancreatitis,those with hypertriglyceridemia-induced acute pancreatitis(HTG-AP)are more likely to develop persistent organ failure(POF).Therefore,recognizing the individuals at risk of developing POF early in the HTG-AP process is a vital for improving outcomes.Bedside index for severity in acute pancreatitis(BISAP),a simple parameter that is obtained 24 h after admission,is an ideal index to predict HTG-AP severity;however,the suboptimal sensitivity limits its clinical application.Hence,current clinical scoring systems and biochemical parameters are not sufficient for predicting HTG-AP severity.AIM To elucidate the early predictive value of red cell distribution width(RDW)for POF in HTG-AP.METHODS In total,102 patients with HTG-AP were retrospectively enrolled.Demographic and clinical data,including RDW,were collected from all patients on admission.RESULTS Based on the Revised Atlanta Classification,37(33%)of 102 patients with HTG-AP were diagnosed with POF.On admission,RDW was significantly higher in patients with HTG-AP and POF than in those without POF(14.4%vs 12.5%,P<0.001).The receiver operating characteristic curve demonstrated a good discrim-inative power of RDW for POF with a cutoff of 13.1%,where the area under the curve(AUC),sensitivity,and specificity were 0.85,82.4%,and 77.9%,respectively.When the RDW was≥13.1%and one point was added to the original BISAP to obtain a new BISAP score,we achieved a higher AUC,sensitivity,and specificity of 0.89,91.2%,and 67.6%,respectively.CONCLUSION RDW is a promising predictor of POF in patients with HTG-AP,and the addition of RDW can promote the sensitivity of BISAP.

Safety and effectiveness of an iris hook assisted phacoemulsification in vitrectomized eyes

AIM:To introduce a simple iris hook assisted phacoemulsification(PE)procedure and evaluate the safety and efficacy of it in completely vitrectomized eyes.METHODS:A single centre study which included 65 previously completely vitrectomized eyes of 62 patients who underwent cataract surgery.Patients were randomly divided into 3 groups.Patients received PE,and intraocular lens(IOL)implantation with the assistance of iris hook(SynergetiesTM)as group A(25 eyes);patients who received PE assisted with a 25 G pars plana irrigation as group B(20 eyes),and patients who received PE performed without the help of any instrument as group C(20 eyes).Main outcome measures were surgery duration,Ultrasound(U/S)total time,endothelial cell density(ECD),cumulative dissipated energy(CDE)and complications of the procedures.RESULTS:With the help of iris hook,the patients in group A had the lowest ECD loss rate(0.07±0.03,0.09±0.03,and 0.10±0.03,P<0.05),shortest CDE(12.2±4.1,15.8±6.0,and 16.0±6.0,P<0.05)and U/S total time(36.6±13.0 s,46.3±16.4 s,and 47.6±16.1 s,P<0.05),and minimal incidence of complications.The longest surgery duration was in group B(19.4±1.6 min)and maximum complications rate in group C(20%miosis,10%posterior capsular tears,5%zonular dialysis,5%cystoid macular edema).While best-corrected visual acuity(BCVA),intraocular pressure(IOP)and ECD did not show a significant difference among the three groups.CONCLUSION:Without prolonged surgery duration,the iris hook assistant method can minimize heat generation during surgery and incidence of complications,which transfer the challenged PE in vitrectomized eyes into a regular surgery.It does not need any change in the hydrodynamic parameters and in the bag PE technique,easy to operate even for junior surgeons.

Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China

Background:Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and coronavirus disease 2019(COVID-19)development.Currently,it is unclear whether mitochondrial DNA(mtDNA)variants,which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production,are associated with COVID-19 risk.Methods:A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls(n=615)and COVID-19 patients(n=536).COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning.The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment.MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny.Student’s t-test was used for continuous variables,and Pearson’s chi-squared test or Fisher’s exact test was used for categorical variables.To assess the independent effect of each mtDNA variant defining mtDNA haplogroups,multivariate logistic regression analyses were performed to calculate the odds ratios(OR)and 95%confidence intervals(CI)with adjustments for possible confounding factors of age,sex,smoking and diseases(including cardiopulmonary diseases,diabetes,obesity and hypertension)as determined through clinical and radiographic examinations.Results:Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations(>10%in the control population)at C5178 a(in NADH dehydrogenase subunit 2 gene,ND2)and A249 d(in the displacement loop region,D-loop)/T6392 C(in cytochrome c oxidase I gene,CO1)/G10310 A(in ND3)were associated with a reduced risk of severe COVID-19(OR=0.590,95%CI 0.428–0.814,P=0.001;and OR=0.654,95%CI 0.457–0.936,P=0.020,respectively),while A4833 G(ND2),A4715 G(ND2),T3394 C(ND1)and G5417 A(ND2)/C16257 a(D-loop)/C16261 T(D-loop)were related to an increased risk of severe COVID-19(OR=2.336,95%CI 1.179–4.608,P=0.015;OR=2.033,95%CI 1.242–3.322,P=0.005;OR=3.040,95%CI 1.522–6.061,P=0.002;and OR=2.890,95%CI 1.199–6.993,P=0.018,respectively).Conclusions:This is the first study to explore the association of mtDNA variants with individual’s risk of developing severe COVID-19.Based on the case–control study,we concluded that the common mtDNA variants at C5178 a and A249 d/T6392 C/G10310 A might contribute to an individual’s resistance to developing severe COVID-19,whereas A4833 G,A4715 G,T3394 C and G5417 A/C16257 a/C16261 T might increase an individual’s risk of developing severe COVID-19.

The Role of 5-Aminolevulinic Acid (5-ALA) and Sleep

Objective: To determine if there is a relationship between the administration of the dietary supplement containing 5-Aminolevulinic Acid (5-ALA) and sleep. Methods: A double-blind, randomized parallel-group study was conducted. It was a 4-month study of 40 participants between the ages of 40 and 70. Males and females were recruited equally. There were 20 in each group who had existing sleep disorders. The tool used to measure participant sleep improvement included the Pittsburgh Insomnia Rating Scale-20 Question (PIRS-20). Improved sleep is reflected when the total PIRS-20 score is lower. Results: Improvement in sleep in the group taking 50 mg 5-ALA, compared to controls, was significant. The mean change, from baseline through week 6, was -5.67 units less on the sleep scale than the control group with a p value of 0.001. The mean change from week 6 to week 10 when the participant was no longer taking the supplement was 4.55 units higher than the control group with a p value of 0.062, which is of borderline significance. Conclusions: There is a relationship between the administration of dietary supplements containing 5-ALA and sleep. The results of this study suggest that 5-ALA is associated with improved sleep. The mechanism for sleep improvement needs to be explored. Further research is warranted.