Transmission Dynamics and Optimal Control Strategies of a Hand-Foot-Mouth Disease Model with Treatment and Vaccination Interventions

In this article, the transmission dynamics of a Hand-Foot-Mouth disease model with treatment and vaccination interventions are studied. We calculated the basic reproduction number and proved the global stability of disease-free equilibrium when R0 R0 > 1. Meanwhile, we obtained the optimal control strategies minimizing the cost of intervention and minimizing the infected person. We also give some numerical simulations to verify our theoretical results.

Evaluation of a protocol for rifaximin discontinuation in critically ill patients with liver disease receiving broad-spectrum antibiotic therapy

BACKGROUND Rifaximin is frequently administered to critically ill patients with liver disease and hepatic encephalopathy,but patients currently or recently treated with antibiotics were frequently excluded from studies of rifaximin efficacy.Due to overlapping spectrums of activity,combination therapy with broad-spectrum antibiotics and rifaximin may be unnecessary.A pharmacist-driven protocol was piloted to reduce potentially overlapping therapy in critically ill patients with liver disease.It was hypothesized that withholding rifaximin during broad-spectrum antibiotic therapy would be safe and reduce healthcare costs.AIM To determine the clinical,safety,and financial impact of discontinuing rifaximin during broad-spectrum antibiotic therapy in critically ill liver patients.METHODS This was a single-center,quasi-experimental,pre-post study based on a pilot pharmacist-driven protocol.Patients in the protocol group were prospectively identified via the medical intensive care unit(ICU)(MICU)protocol to have rifaximin withheld during broad-spectrum antibiotic treatment.These were compared to a historical cohort who received combination therapy with broadspectrum antibiotics and rifaximin.All data were collected retrospectively.The primary outcome was days alive and free of delirium and coma(DAFD)to 14 d.Safety outcomes included MICU length of stay,48-h change in vasopressor dose,and ICU mortality.Secondary outcomes characterized rifaximin cost savings and protocol adherence.Multivariable analysis was utilized to evaluate the association between group assignment and the primary outcome while controlling for potential confounding factors.RESULTS Each group included 32 patients.The median number of delirium-and coma-free days was similar in the control and protocol groups[3 interquartile range(IQR 0,8)vs 2(IQR 0,9.5),P=0.93].In multivariable analysis,group assignment was not associated with a reduced ratio of days alive and free of delirium or coma at 14 d.The protocol resulted in a reduced median duration of rifaximin use during broad-spectrum antibiotic therapy[6 d control(IQR 3,9.5)vs 1 d protocol(IQR 0,1);P<0.001].Rates of other secondary clinical and safety outcomes were similar including ICU mortality and 48-h change in vasopressor requirements.Overall adherence to the protocol was 91.4%.The median estimated total cost of rifaximin therapy per patient was reduced from$758.40(IQR$379.20,$1200.80)to$126.40(IQR$0,$126.40),P<0.01.CONCLUSION The novel pharmacist-driven protocol for rifaximin discontinuation was associated with significant cost savings and no differences in safety outcomes including DAFD.

Histone methylation in Huntington's disease:are bivalent promoters the critical targets?

Huntington’s disease（HD）is a currently incurable,late onset,progressive,ultimately fatal neurological disorder（Bates et al.,2015）.We have recently published the results of comprehensive genetic interaction tests aimed at identification of histone methyltransferases and demethylases involved in HD pathogenesis in a Drosophila model of the disease（Song et al.,2018）.

Critical respiratory failure due to pregnancy complicated by COVID-19 and bacterial coinfection:A case report

BACKGROUND In the past 3 years,the global pandemic of coronavirus disease 2019(COVID-19)has posed a great threat to human life and safety.Among the causes of death in COVID-19 patients,combined or secondary bacterial infection is an important factor.As a special group,pregnant women experience varying degrees of change in their immune status,cardiopulmonary function,and anatomical structure during pregnancy,which puts them at higher risk of contracting COVID-19.COVID-19 infection during pregnancy is associated with increased adverse events such as hospitalisation,admission to the intensive care unit,and mechanical ventilation.Therefore,pregnancy combined with coinfection of COVID-19 and bacteria often leads to critical respiratory failure,posing severe challenges in the diagnosis and treatment process.CASE SUMMARY We report a case of COVID-19 complicated with Staphylococcus aureus(S.aureus)coinfection in a pre-gnant woman at 34 wk of gestation.Her rapid progression of pulmonary lesions caused severe respiratory failure,and she received noninvasive ventilator-assisted respiratory treatment.Subsequently,we delivered a foetus via emergency caesarean section after accelerating the maturity of the foetal pulmonary system,and the respiratory condition of the puerperant woman significantly improved after the delivery of the foetus.Lavage fluid was taken under tracheoscopy to quickly search for pathogens by the metagenomic nextgeneration sequencing(mNGS),and both COVID-19 and S.aureus were detected.After targeted anti-infective treatment,the maternal condition gradually improved,and the patient was discharged from the hospital.CONCLUSION The coinfection of pregnancy with COVID-19 and bacteria often leads to critical respiratory failure,which is a great challenge in the process of diagnosis and treatment.It is crucial to choose the right time to deliver the foetus and to quickly find pathogens by mNGS.

Clinical and neuroimaging features of enterovirus71 related acute flaccid paralysis in patients with hand-foot-mouth disease

Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012.Results:One extremity flaccid was found in four cases(3 with lower limb,1 with upper limb),two limbs flaccid in three cases(2 with lower limbs,1 with upper limbs),and four limbs flaccid in two cases.Spinal MRI studies showed lesion with high signal in T2-weighted images(T2WI) and low signal T1-weighted images(T1WI) in the spinal cord of all nine cases,and the lesions were mainly in bilateral and unilateral anterior hom of cervical spinal cord and spinal cord below thoracic 9(T9) level.In addition,the midbrain,pons, and medulla,which were involved in 3 cases with brainstem encephalitis,demonstrated abnormal signal.Moreover,spinal cord contrast MRI studies showed mild enhancement in corresponding anterior hom of the involved side,and strong enhancement in its ventral root.Conclusions: EV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior hom regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiendy show the characteristic pattern and extent of the lesions which correlated well with the clinical features.

Application of Seasonal Auto-regressive Integrated Moving Average Model in Forecasting the Incidence of Hand-foot-mouth Disease in Wuhan,China

Outbreaks of hand-foot-mouth disease（HFMD） have occurred many times and caused serious health burden in China since 2008. Application of modern information technology to prediction and early response can be helpful for efficient HFMD prevention and control. A seasonal auto-regressive integrated moving average（ARIMA） model for time series analysis was designed in this study. Eighty-four-month（from January 2009 to December 2015） retrospective data obtained from the Chinese Information System for Disease Prevention and Control were subjected to ARIMA modeling. The coefficient of determination（R^2）, normalized Bayesian Information Criterion（BIC） and Q-test P value were used to evaluate the goodness-of-fit of constructed models. Subsequently, the best-fitted ARIMA model was applied to predict the expected incidence of HFMD from January 2016 to December 2016. The best-fitted seasonal ARIMA model was identified as（1,0,1）（0,1,1）12, with the largest coefficient of determination（R^2=0.743） and lowest normalized BIC（BIC=3.645） value. The residuals of the model also showed non-significant autocorrelations（P_（Box-Ljung（Q））=0.299）. The predictions by the optimum ARIMA model adequately captured the pattern in the data and exhibited two peaks of activity over the forecast interval, including a major peak during April to June, and again a light peak for September to November. The ARIMA model proposed in this study can forecast HFMD incidence trend effectively, which could provide useful support for future HFMD prevention and control in the study area. Besides, further observations should be added continually into the modeling data set, and parameters of the models should be adjusted accordingly.

Current situation and prospect for the diagnosis and treatment of pediatric critical rare diseases in China

The onset of critical rare diseases(RDs)in children is rapid and dangerous,accompanied by a high mortality rate,which brings a heavy burden to both families and society.Multiple malformations,neuromuscular diseases,metabolic diseases,and heart diseases are the most common types of RDs in children of China,often manifesting with multiple organ dysfunction.At present,the diagnosis and treatment of critical RDs in children face challenges such as prolonged diagnosis time,a high misdiagnosis rate,limited treatment modalities,and a significant disease burden.However,with the progress in genetic testing technology,the establishment of multidisciplinary diagnosis and treatment platforms,and the implementation of relevant RD policies in China,children with critical RDs will received enhanced medical services,experience improved prognoses,and reintegrate into social life.

Prognosis and outcome of intrauterine treatment of fetuses with critical congenital heart disease

Background:Intrauterine valvuloplasty is an innovative therapy,which promotes ventricular growth and function in some congenital heart diseases(CHDs).The technique remains challenging and can only be performed in a few centers.This study aimed to assess the feasibility and mid-term outcomes of fetal cardiac intervention(FCI)in fetuses with critical CHD in an experienced tertiary center.Methods:Five fetal aortic valvuloplasty(FAV)or fetal pulmonary valvuloplasty(FPV)procedures were performed in our fetal heart center between August 2018 and May 2022.Technical success was defined as crossing the aortic or pulmonary valve and balloon inflation,followed by evidence of increased blood flow across the valve and/or new regurgitation.Follow-up clinical records and echocardiography were obtained during the prenatal and postnatal periods.Results:Five fetuses received FAV or FPV,including critical aortic stenosis(n=2)and pulmonary atresia with intact ventricular septum(n=3).The mean maternal age was 33.0±2.6 years.The median gestational age(GA)at diagnosis was 24 weeks(range,22-26 weeks).The median GA at intervention was 29 weeks(range,28-32 weeks).All five cases underwent successful or partially successful procedures.One patient had pulmonary valve perforation without balloon dilation.No procedure-related deaths or significant complications occurred.However,one neonatal death occurred due to heart and renal failure.The median follow-up period was 29.5 months(range,8.0-48.0 months).The four surviving patients had achieved biventricular circulation,exhibited improved valve,and ventricular development at the last follow-up visit.Conclusion:Intrauterine FCI could be performed safely with good prognosis in critical CHD.

Clinical observation on the treatment of severe hand-foot-mouth disease with antelope horn powder combined with auricular point application

Objective:To explore the Clinical observation on the treatment of severe hand-foot-mouth disease with antelope horn powder combined with auricular point application.Methods:From July 2016 to June 2018,90 children were randomly divided into control group(n=30),treatment group(n=30)and control group(n=30).The control group was treated with routine western medicine,the treatment group 1 was treated with oral antelope horn powder on the basis of control group,the second group was treated with auricular point application on the basis of treatment group 1,and the time of symptom relief and clinical cure were observed in each group.Related immune function and related inflammatory factors,serum neuron-specific enolase(NSE),safety index.Results:In treatment group 1,the time of herpes regression,antipyretic,antispasmodic time and clinical cure time were shorter than those of control group,and the time of treatment 2 group was shorter than that of group 1(P<0.05).The levels of CD3,CD4 and CD8 were increased after treatment in the three groups,especially in the treatment group(P<0.05),and the levels of TNF-毩αand IL-2,IL-6,IL-10 were decreased after treatment in the three groups,especially in the treatment group(P<0.05).NSE decreased after treatment in three groups,especially in treatment group 2(P<0.05).Conclusion:The application of antelope horn powder combined with auricular point application can obviously improve the severe hand,foot and mouth disease,and the clinical curative effect is definite.It is worth popularizing and applying in clinical practice.

Effect of interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy on inflammatory response and immune response in children with hand-foot-mouth disease

Objective: To investigate the effect of interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy on inflammatory response and immune response in children with hand-foot-mouth disease. Methods: A total of 116 children with hand-foot-mouth disease who were treated in this hospital between September 2016 and February 2018 were selected as the study subjects and divided into the control group (n=58) and the Potassium Sodium Dehydroandrograpolide Succinate group (n=58) by random number table method. Control group received symptomatic + interferon therapy, and Potassium Sodium Dehydroandrograpolide Succinate group received symptomatic + interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy, and they were treated for 1 week. The differences in the serum contents of inflammatory factors, adhesion molecules and humoral immunity indexes were compared between the two groups before and after treatment. Results:Before treatment, serum levels of inflammatory factors, adhesion molecules and humoral immunity indexes were not significantly different between the two groups. After 1 week of treatment, serum inflammatory factors IL-1β, IL-10, PCT and hs-CRP levels of Potassium Sodium Dehydroandrograpolide Succinate group were lower than those of control group;serum adhesion molecules CD44, ICAM-1 and VCAM-1 levels were lower than those of control group;serum humoral immunity indexes IgA, IgG, C3 and C4 levels were lower than those of control group. Conclusion: Interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy can effectively reduce the systemic inflammatory response and improve the humoral immune function in children with hand-foot-mouth disease.

Correlation of serum NSE and S100β levels with inflammatory response and immune response in children with hand-foot-mouth disease complicated by encephalitis

Objective:To study the correlation of serum NSE and S100β levels with inflammatory response and immune response in children with hand-foot-mouth disease (HFMD) complicated by encephalitis.Methods:Children who were diagnosed with hand-foot-mouth disease in Yulin Third Hospital between May 2015 and February 2017 were selected, children who were combined with central nervous system were selected as severe group, and children who were not combined with central nervous system were selected as mild group;children who received physical examination during the same period were selected as the control group. Serum was collected to determine the contents of NSE, S100β and inflammatory response mediators, and peripheral blood was collected to determine the contents of T cell subsets and NK cells.Results: Serum NSE and S100β levels of severe group and mild group were significantly higher than those of control group, and serum NSE and S100β levels of severe group were significantly higher than those of mild group;serum TNF-α, IL-6, IL-10, IL-17 and PCT levels as well as peripheral blood HLA-DR+CD4+, HLA-DR+CD8+, CD38+CD4+ and CD38+CD8+ levels of severe group and mild group were significantly higher than those of control group while peripheral blood CD3+T cell, CD4+T cell, CD8+T cell and NK cell levels were significantly lower than those of control group;serum TNF-α, IL-6, IL-10, IL-17 and PCT levels as well as peripheral blood HLA-DR+CD4+, HLA-DR+CD8+, CD38+CD4+ and CD38+CD8+ levels of severe group were significantly higher than those of mild group and positively correlated with NSE and S100β levels while peripheral blood CD3+T cell, CD4+T cell, CD8+T cell and NK cell levels were significantly lower than those of mild group and negatively correlated with NSE and S100β levels.Conclusion: The increase of serum NSE and S100β levels in children with HFMD complicated by encephalitis is closely related to inflammatory response activation and immune response disorder.

Critical illness polyneuropathy and myopathy:a systematic review

Critical illness polyneuropathy and critical illness myopathy are frequent complications of severe illness that involve sensorimotor axons and skeletal muscles, respectively. Clinically, they manifest as limb and respiratory muscle weakness. Critical illness polyneuropathy/myopathy in isolation or combination increases intensive care unit morbidity via the inability or difficulty in weaning these patients off mechanical ventilation. Many patients continue to suffer from decreased exercise capacity and compromised quality of life for months to years after the acute event. Substantial progress has been made lately in the understanding of the pathophysiology of critical illness polyneuropathy and myopathy. Clinical and ancillary test results should be carefully interpreted to differentiate critical illness polyneuropathy/myopathy from similar weaknesses in this patient population. The present review is aimed at providing the latest knowledge concerning the pathophysiology of critical illness polyneuropathy/myopathy along with relevant clinical, diagnostic, differentiating, and treatment information for this debilitat- ing neurological disease.

Utility of flexible fiberoptic bronchoscopy for critically ill pediatric patients:A systematic review

AIM: To investigate the diagnostic yield, therapeutic efficacy, and rate of adverse events related to flexible fiberoptic bronchoscopy(FFB) in critically ill children. METHODS: We searched Pub Med, SCOPUS, OVID, and EMBASE databases through July 2014 for English language publications studying FFB performed in the intensive care unit in children < 18 years old. We identified 666 studies, of which 89 full-text studies were screened for further review. Two reviewers independently determined that 27 of these studies met inclusion criteria and extracted data. We examined the diagnostic yield of FFB among upper and lower airway evaluations, as well as the utility of bronchoalveolar lavage(BAL). RESULTS: We found that FFB led to a change in medical management in 28.9%(range 21.9%-69.2%) of critically ill children. The diagnostic yield of FFB was 82%(range 45.2%-100%). Infectious organisms were identified in 25.7%(17.6%-75%) of BALs performed, resulting in a change of antimicrobial management in 19.1%(range: 12.2%-75%). FFB successfully reexpanded atelectasis or removed mucus plugs in 60.3%(range: 23.8%-100%) of patients with atelectasis. Adverse events were reported in 12.9%(range: 0.5%-71.4%) of patients. The most common adverse effects of FFB were transient hypotension, hypoxia and/or bradycardia that resolved with minimal intervention, such as oxygen supplementation or removal of the bronchoscope. Serious adverse events were uncommon; 2.1% of adverse events required intervention such as bag-mask ventilation or intubation and atropine for hypoxia and bradycardia, normal saline boluses for hypotension, or lavage and suctioning for hemorrhage. CONCLUSION: FFB is safe and effective for diagnostic and therapeutic use in critically ill pediatric patients.

Effect of low-dose glucocorticoid on corticosteroid insufficient patients with acute exacerbation of chronic obstructive pulmonary disease

BACKGROUND: This study aimed to investigate the prevalence rate of critical illness-related corticosteroid insuffi ciency(CIRCI) and the effect of low-dose glucocorticoid on prognosis of CIRCI in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).METHODS: Since January 2010 to December 2012, 385 patients, who met the criteria of AECOPD, were enrolled in the Intensive Care Unit(ICU) of the First People's Hospital and Municipal Central Hospital of Xiangtan City. The AECOPD patients complicated with CIRCI screened by an adrenalcorticotrophic hormone test within 12 hours after admission to ICU were divided into a treatment group(n=32) and a control group(n=31) for a prospective, randomized and controlled clinical trial. Hydrocortisone(150 mg/d) or normal saline was injected intravenously for 7 days. The patients were followed up for 28 days after injection. The endpoint included 28-day survival time, non-shock time, ICU stay and the period of non-mechanical ventilation. The markers ofinfl ammation C-reactive protein, tumor necrosis factor-α, interleukin 6 and procalcitonin were measured at baseline and 7 days after treatment. The variables were analyzed by Student's t test, the non-parametric statistical test, the Chi-square test or the Kaplan-Meier method with SPSS18.0 statistic software. A P value <0.05 was considered statistically signifi cant.RESULTS: Totally 63 patients were diagnosed with CIRCI by an adrenalcorticotrophic hormone test and the prevalence rate was 16.4%. The shock rate of the AECOPD patients complicated with CIRCI was higher than that of the AECOPD patients without CIRCI(23.8% vs. 8.7%, P<0.01). KaplanMeier analysis revealed that the 28-day survival time of the treatment group was obviously longer than that of the control group(P<0.05). Compared with the control group, shock-free days within 28 days was longer in the treatment group(18.2±9.5 vs. 25.8±4.1, P<0.05). Treatment with low-dose glucocorticoid obviously decreased the markers ofinfection and inflammation(P<0.01), such as C-reactive protein(13.2±5.5 mg/L vs. 8.3±3.1 mg/L for the control group; 13.5±5.9 mg/L vs. 5.1±2.3 mg/L for the treatment group), tumor necrosis factor-α(26.1±16.2 g/L vs. 17.5±11.7 g/L for the control group; 25.0±14.8 g/L vs. 10.4±7.8 g/L for the treatment group) and procalcitonin(3.88 g/L vs. 2.03 g/L for the control group; 3.77 g/L vs. 1.26 g/L for the treatment group). Furthermore, the markers in the treatment group decreased more obviously than those in the control group(P<0.01).CONCLUSION: The prevalence rate of CIRCI was higher in the patients with AECOPD in the department of critical medicine, and low-dose glucocorticoid treatment for one week reduced the 28-day mortality, shock time and markers ofinfection and infl ammation.

Risk factors and prognosis of critically ill cancer patients with postoperative acute respiratory insufficiency

BACKGROUND:This study aimed to investigate the risk factors and outcome of critically ill cancer patients with postoperative acute respiratory insufficiency.METHODS:The data of 190 critically ill cancer patients with postoperative acute respiratory insufficiency were retrospectively reviewed.The data of 321 patients with no acute respiratory insufficiency as controls were also collected.Clinical variables of the first 24 hours after admission to intensive care unit were collected,including age,sex,comorbid disease,type of surgery,admission type,presence of shock,presence of acute kidney injury,presence of acute lung injury/acute respiratory distress syndrome,acute physiologic and chronic health evaluation(APACHE Ⅱ) score,sepsis-related organ failure assessment(SOFA),and PaO_2/FiO_2 ratio.Duration of mechanical ventilation,length of intensive care unit stay,intensive care unit death,length of hospitalization,hospital death and one-year survival were calculated.RESULTS:The incidence of acute respiratory insufficiency was 37.2%(190/321).Multivariate logistic analysis showed a history of chronic obstructive pulmonary diseases(P=0.001),surgeryrelated infection(P=0.004),hypo-volemic shock(P<0.001),and emergency surgery(P=0.018),were independent risk factors of postoperative acute respiratory insufficiency.Compared with the patients without acute respiratory insufficiency,the patients with acute respiratory insufficiency had a prolonged length of intensive care unit stay(P<0.001),a prolonged length of hospitalization(P=0.006),increased intensive care unit mortality(P=0.001),and hospital mortality(P<0.001).Septic shock was shown to be the only independent prognostic factor of intensive care unit death for the patients with acute respiratory insufficiency(P=0.029,RR:8.522,95%CI:1.243-58.437,B=2.143,SE=0.982,Wald=4.758).Compared with the patients without acute respiratory insufficiency,those with acute respiratory insufficiency had a shortened one-year survival rate(78.7%vs.97.1%,P<0.001).CONCLUSION:A history of chronic obstructive pulmonary diseases,surgery-related infection,hypovolemic shock and emergency surgery were risk factors of critically ill cancer patients with postoperative acute respiratory insufficiency.Septic shock was the only independent prognostic factor of intensive care unit death in patients with acute respiratory insufficiency.Compared with patients without acute respiratory insufficiency,those with acute respiratory insufficiency had adverse shortterm outcome and a decreased one-year survival rate.

Chinese herbal medicine for hand-foot-and-mouth disease in children: An overview of systematic reviews

Objective:To summarize the use of Chinese herbal medicines (CHM) for the treatment of hand-foot-and-mouth disease (HFMD) in children and to provide high-level evidence for clinical decision-making.Methods:We conducted an overview of systematic reviews (SRs).Two English-language and four Chinese-language electronic databases were searched from inception to March 31,2018.Published SRs and meta-analyses evaluating CHM use in children with HFMD and reporting clinically-relevant outcomes such as time to fever resolution were eligible for inclusion in this overview.Reviews were accepted if the intervention featured CHM with or without other treatment.Two authors evaluated the methodological quality of the included SRs by using ASMTAR and ROBIS.Results:Thirty SRs comprising 90 244 children with HFMD were included in this overview of SRs.All SRs were published in Chinese between 2011 and 2017.All intervention arms received CHM with or without conventional treatment and were compared against control arms receiving no treatment,conventional treatment alone,or placebo.All 30 reviews reported the time to fever resolution and results demonstrated that CHM had a greater benefit in reducing fever compared with controls.Twenty-three reviews reported the time to rash resolution which presented similar results.Fourteen SRs reported the time to oral ulcer healing and CHM demonstrated a significantly reduced time to resolution compared to controls.The quality of the included SRs was low to moderate as assessed by the AMSTAR tool.Conclusion:Published reviews demonstrated potential benefits of CHM in children with HFMD.Overall,the methodological quality of reviews included in this overview of SRs was low and our findings should be interpreted with caution.We would strongly recommend that future SRs be designed and reported rigorously following PRISMA in order to provide more robust evidence on which to base clinical guidance.

A Systematic Review of the Literature on the Relationships between Chronic Diseases and Food Insecurity

Background: The association between food insecurity (FI) and obesity is now so well documented that scholars have dubbed it the “‘new’ food insecurity” and cited it as a leading cause of increased chronic disease (CD) risk. Here, the chain of causality is assumed to be FI → obesity → CD. However, this model overlooks the possible direct associations between FI and CD independent of obesity. Aim: This study assessed the literature on relationships between FI and CD. Methods: We conducted a systematic literature review of electronic databases. Selection criteria were designed to elicit studies that assessed FI and CD using a measure of CD other than obesity. Results: Fifty-one articles met the inclusion criteria. Forty-five studies (87%) reported a statistically significant association between FI and CD, but only 15 adjusted for obesity. The association was less consistent for asthma and dyslipidemia than for diabetes, hypertension, and other dietrelated CDs, and most were conducted in the USA or Canada. Conclusion: There is a body of literature documenting relationships between FI and CD, but it is heavily biased toward Western nations, ecological study designs, and type 2 diabetes as the CD of focus. A small subset of the literature controls for BMI, demonstrating that a portion of the FI-CD relationship cannot be fully explained by obesity. Possible direct pathways linking FI and CD include systematic effects of poverty that accompanies FI, micronutrient deficiencies, and environmental exposure to toxins;however, exploration of these alternative pathways is limited by study designs that fail to include obesity as a control variable.

Revisiting endovascular treatment in below-the-knee disease. Are drug-eluting stents the best option？

Patients with below-the-knee arterial disease are primarily individuals suffering from critical limb ischemia(CLI), while a large percentage of these patients are also suffering from diabetes or chronic renal failure or both. Available data from randomized controlled trials and their meta-analysis demonstrated that the use of infrapopliteal drug-eluting stents(DES), in short-to medium-length lesions, obtains significantly better results compared to plain balloon angioplasty and bare metal stenting with regards to vascular restenosis, target lesion revascularization, wound healing and amputations. Nonetheless, the use of this technology in every-day clinical practice remains limited mainly due to concerns regarding the deployment of a permanent metallic scaffold and the possibility of valid future therapeutic perspectives. However, in the majority of the cases, these concerns are not scientifically justified. Large-scale, multicenter randomized controlled trials, investigating a significantly larger number of patients than those already published, would provide more solid evidence and consolidate the use of infrapopliteal DES in CLI patients. Moreover, there is still little evidence on whether this technology can be as effective for longer below-the-knee lesions, where a considerable number of DES is required. The development and investigation of new, longer balloon-expanding or perhaps selfexpanding DES could be the answer to this problem.

Prevalence analysis of hand,foot and mouth disease in China,2008-2018

Objective:To analyze the prevalence of hand,foot and mouth disease(HFMD)in China during 2008-2018 and to provide reference for the prevention and control of HFMD.Methods:Literature eligible for selection was retrieved from the China's national knowledge infrastructure project(CNKI),and data from 2008-2018 Chinese HFMD reports were systematically analyzed.Excel and SPSS 20.00 were used for statistical analysis,and GraphPad Prism 6 was used for mapping.Results:The analysis showed that the average incidence rate of HFMD in China from 2008 to 2018 was 123.37±93.14 cases per 100,000 people,with a male-to-female ratio of(1.50±0.15):1,and the vast majority of cases were concentrated in the under-5 age group,mainly in scattered children.The time of onset of HFMD showed obvious seasonal characteristics,in which single-peak provinces were higher than double-peak provinces,with double-peak trends in April-July and October-November,respectively,and single-peak trends mainly in May-July.Based on the spatial distribution study,the incidence pattern showed obvious regional differences(P<0.05),with high incidence concentrated in the southeastern part of the country,and a gradual increase in incidence from west to east and north to south of China.EV71,CA16 and other enteric viruses were the main pathogens of HFMD,with EV71 accounting for 53.5%,CA16 is accounting for 14.3%and other enteric viruses accounting for 32.2%of the pathogens.Conclusions:The incidence of HFMD in China is high,with obvious geographical,seasonal,gender and age distribution characteristics.According to the pattern of HFMD incidence in the region,early prevention and control of key areas and groups is an effective way to cut off the spread of the disease.

COVID-19: Lymphocyte Subpopulations Monitoring in Critically Ill Patients

Background: The alteration of lymphocyte subpopulations can help to predict the severity and the prognosis of severe Coronavirus disease 2019 (COVID-19). Our goal was to describe the kinetics of lymphocyte subsets, and their impact on the severity and mortality in critically ill COVID-19 patients. Methods: We collected demographic data, comorbidities, clinical signs on admission, laboratory findings on admission then a follow-up during hospitalization. Lymphocyte subsets including CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and natural killer (NK) cells were counted by flow cytometer. Results: On admission, we observed lymphopenia in 57% of cases, decreased CD3+ T cells in 76% of cases, decreased CD4+ T cells in 81% of cases, decreased CD8+ T cells in 62% of cases, decreased B cells in 52% of cases, and decreased natural killer (NK) cells in 33% of cases. After treatment, decreased CD3+ T cells, decreased CD4+ T cells, decreased CD8+ T cells, and decreased natural killer cells were predictor factors of mortality, in the univariable analysis. Conclusion: CD3+ T cells, CD4+ T cells, CD8+ T cells, and natural killer cells were predictor factors of severity, ICU mortality, and also a useful tool for predicting disease progression.