Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase

BACKGROUND Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B(CHB)patients were not previously conducted.AIM To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy.METHODS The clinical and laboratory data of 1532 untreated CHB patients were collected,and all patients had least once liver biopsy from January 2015 to December 2021.The significant differences among different phases of CHB infection were compared with t-test,and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis.RESULTS Among 1532 untreated CHB patients,814(53.13%)patients were in the indeterminate phase.Significant liver histological changes(defined as biopsy score≥G2 and/or≥S2)were found in 488/814(59.95%)CHB patients in the indete-rminate phase.Significant liver histological changes were significant differences among different age,platelets(PLTs),and alanine aminotransferase(ALT)subgroup in indeterminate patient.Multivariate logistic regression analysis indicated that age≥40 years old[adjust odd risk(aOR),1.44;95%confidence interval(CI):1.06-1.97;P=0.02],PLTs≤150×10^(9)/L(aOR,2.99;95%CI:1.85-4.83;P<0.0001),and ALT≥upper limits of normal(aOR,1.48;95%CI:1.08,2.05,P=0.0163)were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase.CONCLUSION Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase,and additional strategies are urgently required for the management of these patients.

Outcomes of ABO-incompatible liver transplantation in end-stage liver disease patients co-infected with hepatitis B and human immunodeficiency virus

BACKGROUND Human immunodeficiency virus(HIV)-positive patients coinfected with hepatitis B virus(HBV)are eligible for liver transplantation(LT)in Africa and Southeast Asia,particularly China.However,the outcome of HIV-HBV coinfected patients referred for ABO-incompatible LT(ABOi-LT)is unknown.AIM To clarify the outcome of ABOi-LT for HIV-HBV coinfected patients with endstage liver disease(ESLD).METHODS We report on two Chinese HIV-HBV coinfected patients with ESLD who underwent A to O brain-dead donor LT and reviewed the literature on HIV-HBV coinfected patients treated with ABO-compatible LT.The pretransplantation HIV viral load was undetectable,with no active opportunistic infections.Induction therapy consisted of two sessions of plasmapheresis and a single dose of rituximab in two split doses,followed by an intraoperative regimen of intravenous immunoglobulin,methylprednisolone,and basiliximab.Post-transplant maintenance immunosuppressive agents consisted of tacrolimus and mycophenolate mofetil,and prednisone.RESULTS At the intermediate-term follow-up,patients showed undetectable HIV viral load,CD4(+)T cell counts greater than 150 cells/μL,no HBV recurrence,and stable liver function.A liver allograft biopsy showed no evidence of acute cellular rejection.Both patients survived at 36-42 mo of follow-up.CONCLUSION This is the first report of ABOi-LT in HIV-HBV recipients with good intermediate-term outcomes,suggesting that ABOi-LT may be feasible and safe for HIV-HBV coinfected patients with ESLD.

Activation-induced pyroptosis contributes to the loss of MAIT cells in chronic HIV-1 infected patients

Background: Mucosal-associated invariant T(MAIT) cells are systemically depleted in human immunodeficiency virus type 1(HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy(cART).This study aimed to identify the mechanism underlying MAIT cell depletion.Methods: In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.Results: Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4+ T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D(GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory cytokines interleukin-12(IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro.Conclusions: Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients,which could potentiate disease progression and poor immune reconstitution.

Clinical efficacy of total laparoscopic splenectomy for portal hypertension and its influence on hepatic hemodynamics and liver function

BACKGROUND The liver hemodynamic changes caused by portal hypertension(PH)are closely related to various complications such as gastroesophageal varices and portosystemic shunts,which may lead to adverse clinical outcomes in these patients,so it is of great clinical significance to find treatment strategies with favorable clinical efficacy and low risk of complications.AIM To study the clinical efficacy of total laparoscopic splenectomy(TLS)for PH and its influence on hepatic hemodynamics and liver function.METHODS Among the 199 PH patients selected from October 2016 to October 2020,100 patients[observation group(OG)]were treated with TLS,while the remaining 99[reference group(RG)]were treated with open splenectomy(OS).We observed and compared the clinical efficacy,operation indexes[operative time(OT)and intraoperative bleeding volume],safety(intraperitoneal hemorrhage,ascitic fluid infection,eating disorders,liver insufficiency,and perioperative death),hepatic hemodynamics(diameter,velocity,and flow volume of the portal vein system),and liver function[serum alanine aminotransferase(ALT),serum aspartate aminotransferase(AST),and serum total bilirubin(TBil)]of the two groups.RESULTS The OT was significantly longer and intraoperative bleeding volume was significantly lesser in the OG than in the RG.Additionally,the overall response rate,postoperative complications rate,and liver function indexes(ALT,AST,and TBil)did not differ significantly between the OG and RG.The hepatic hemodynamics statistics showed that the pre-and postoperative blood vessel diameters in the two cohorts did not differ statistically.Although the postoperative blood velocity and flow volume reduced significantly when compared with the preoperative values,there were no significant inter-group differences.CONCLUSION TLS contributes to comparable clinical efficacy,safety,hepatic hemodynamics,and liver function as those of OS in treating PH,with a longer OT but lesser intraoperative blood loss.

Gut microbiome and metabolic-associated fatty liver disease:Current status and potential applications

Metabolic-associated fatty liver disease(MAFLD)is one of the most common chronic liver diseases worldwide.In recent years,the occurrence rate of MAFLD has been on the rise,mainly due to lifestyle changes,high-calorie diets,and imbalanced dietary structures,thereby posing a threat to human health and creating heavy social and economic burdens.With the development of 16S sequencing and integrated multi-omics analysis,the role of the gut microbiota(GM)and its metabolites in MAFLD has been further recognized.The GM plays a role in digestion,energy metabolism,vitamin synthesis,the prevention of pathogenic bacteria colonisation,and immunoregulation.The gut-liver axis is one of the vital links between the GM and the liver.Toxic substances in the intestine can enter the liver through the portal vascular system when the intestinal barrier is severely damaged.The liver also influences the GM in various ways,such as bile acid circulation.The gut-liver axis is essential in maintaining the body’s normal physiological state and plays a role in the onset and prognosis of many diseases,including MAFLD.This article reviews the status of the GM and MAFLD and summarizes the GM characteristics in MAFLD.The relationship between the GM and MAFLD is discussed in terms of bile acid circulation,energy metabolism,micronutrients,and signalling pathways.Current MAFLD treat ments targeting the GM are also listed.

Immediate and long-term outcomes after treat-all among people living with HIV in China:an interrupted time series analysis

Background In 2003,China implemented free antiretroviral therapy(ART)for people living with HIV(PLHIV),establishing an eligibility threshold of CD4<200 cells/μl.Subsequently,the entry criteria were revised in 2012(eligibility threshold:CD4≤350 cells/μl),2014(CD4≤500 cells/μl),and 2016(treat-all).However,the impact of treat-all policy on HIV care and treatment indicators in China is unknown.We aimed to elucidate the immediate and long-term impact of the implementation of treat-all policy in China.Methods Anonymized programmatic data on ART initiation and collection in PLHIV who newly started ART were retrieved between 1 January 2015 and 31 December 2019,from two provincial and municipal Centers for Disease Control and Prevention and ten major infectious disease hospitals specialized in HIV care in China.We used Poisson and quasi-Poisson segmented regression models to estimate the immediate and long-term impact of treat-all on three key indicators:monthly proportion of 30-day ART initiation,mean CD4 counts(cells/μl)at ART initiation,and mean estimated time from infection to diagnosis(year).We built separate models according to gender,age,route of transmission and region.Results Monthly data on ART initiation and collection were available for 75,516 individuals[gender:83.8%males;age:median 39 years,interquartile range(IQR):28-53;region:18.5%Northern China,10.9%Northeastern China,17.5%Southern China,49.2%Southwestern China].In the first month of treat-all,compared with the contemporaneous counterfactual,there was a significant increase in proportion of 30-day ART initiation[+12.6%,incidence rate ratio(IRR)=1.126,95%CI:1.033-1.229;P=0.007]and mean estimated time from infection to diagnosis(+7.0%,IRR=1.070,95%CI:1.021-1.120;P=0.004),while there was no significant change in mean CD4 at ART initiation(IRR=0.990,95%CI:0.956-1.026;P=0.585).By December 2019,the three outcomes were not significantly different from expected levels.In the stratified analysis,compared with the contemporaneous counterfactual,mean CD4 at ART initiation showed significant increases in Northern China(+3.3%,IRR=1.033,95%CI:1.001-1.065;P=0.041)and Northeastern China(+8.0%,IRR=1.080,95%CI:1.003-1.164;P=0.042)in the first month of treat-all;mean estimated time from infection to diagnosis showed significant increases in male(+5.6%,IRR=1.056,95%CI:1.010-1.104;P=0.016),female(+14.8%,IRR=1.148,95%CI:1.062-1.240;P<0.001),aged 26-35(+5.3%,IRR=1.053,95%CI:1.001-1.109;P=0.048)and>50(+7.8%,IRR=1.078,95%CI:1.000-1.161;P=0.046),heterosexual transmission(+12.4%,IRR=1.124,95%CI:1.042-1.213;P=0.002)and Southwestern China(+12.9%,IRR=1.129,95%CI:1.055-1.208;P<0.001)in the first month of treat-all.Conclusions The implementation of treat-all policy in China was associated with a positive effect on HIV care and treatment outcomes.To advance the work of rapid ART,efforts should be made to streamline the testing and ART initiation process,provide comprehensive support services,and address the issue of uneven distribution of medical resources.

Evolution of blood lipids and risk factors of dyslipidemia among people living with human immunodeficiency virus who had received first-line antiretroviral regimens for 3 years in Shenzhen

Background:Lipid abnormalities are prevalent among people living with human immunodeficiency virus(HIV)(PLWH)and contribute to increasing risk of cardiovascular events.This study aims to investigate the incidence of dyslipidemia and its risk factors in PLWH after receiving different first-line free antiretroviral regimens.Methods:PLWH who sought care at the Third People’s Hospital of Shenzhen from January 2014 to December 2018 were included,and the baseline characteristics and clinical data during the follow-up were collected,including total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C).The risk factors of dyslipidemia after antiretroviral therapy were analyzed with the generalized estimating equation model.Results:Among the 7623 PLWH included,the mean levels of TC,HDL-C and LDL-C were 4.23±0.85 mmol/L,1.27±0.29 mmol/L and 2.54±0.65 mmol/L,respectively,and the median TG was 1.17(IQR:0.85-1.68)mmol/L.Compared with that in PLWH receiving tenofovir disoproxil fumarate(TDF)+lamivudine(3TC)+ritonavir-boosted lopinavir(LPV/r),zidovudine(AZT)+3TC+efavirenz(EFV),and AZT+3TC+LPV/r,the incidence of dyslipidemia was lower in PLWH receiving TDF+3TC+EFV.In multivariate analysis,we found that the risks of elevations of TG,TC,and LDL-C were higher with TDF+3TC+LPV/r(TG:odds ratio[OR]=2.82,95%confidence interval[CI]:2.55-3.11,P<0.001;TC:OR=1.24,95%CI:1.14-1.35,P<0.001;LDL:OR=1.06,95%CI:1.00-1.12,P=0.041),AZT+3TC+EFV(TG:OR=1.41,95%CI:1.28-1.55,P<0.001;TC:OR=1.43,95%CI:1.31-1.56,P<0.001;LDL:OR=1.18,95%CI:1.12-1.25,P<0.001),and AZT+3TC+LPV/r(TG:OR=3.08,95%CI:2.65-3.59,P<0.001;TC:OR=2.40,95%CI:1.96-2.94,P<0.001;LDL:OR=1.52,95%CI:1.37-1.69,P<0.001)than with TDF+3TC+EFV,while treatment with TDF+3TC+LPV/r was less likely to restore HDL-C levels compared with TDF+3TC+EFV(OR=0.95,95%CI:0.92-0.97,P<0.001).In addition to antiretroviral regimens,antiretroviral therapy duration,older age,overweight,obesity and other traditional factors were also important risk factors for dyslipidemia.Conclusion:The incidence of dyslipidemia varies with different antiretroviral regimens,with TDF+3TC+EFV having lower risk for dyslipidemia than the other first-line free antiretroviral regimens in China.

Protective effects of organic extracts of Alpinia oxyphylla against hydrogen peroxide-induced cvtotoxicitv in PC12 cells

Alpinia oxyphylla,a traditional herb,is widely used for its neuroprotective,antioxidant and memory-improving effects.However,the neuroprotective mechanisms of action of its active ingredients are unclear.In this study,we investigated the neuroprotective effects of various organic extracts of Alpinia oxyphylla on PC12 cells exposed to hydrogen peroxide-induced oxidative injury in vitro.Alpinia oxyphylla was extracted three times with 95%ethanol(representing extracts 1–3).The third 95%ethanol extract was dried and resuspended in water,and then extracted successively with petroleum ether,ethyl acetate and n-butanol(representing extracts 4–6).The cell counting kit-8 assay and microscopy were used to evaluate cell viability and observe the morphology of PC12 cells.The protective effect of the three ethanol extracts(at tested concentrations of 50,100 and 200μg/mL)against cytotoxicity to PC12 cells increased in a concentration-dependent manner.The ethyl acetate,petroleum ether and n-butanol extracts(each tested at 100,150 and 200μg/mL)had neuroprotective effects as well.The optimum effective concentration ranged from 50–200μg/mL,and the protective effect of the ethyl acetate extract was comparatively robust.These results demonstrate that organic extracts of Alpinia oxyphylla protect PC12 cells against apoptosis induced by hydrogen peroxide.Our findings should help identify the bioactive neuroprotective components in Alpinia oxyphylla.

^(99m)Tc-3P_4 -RGD_2 radiotracers for SPECT/CT of esophageal tumor

In recent years,several RGD(Arg-Gly-Asp)-based radiotracers have already been successfully tested in human for the visualization of integrin αvβ3,demonstrating its feasibility in tumor diagnosis.In this paper,we evaluated the 99mTc-3P4-RGD2 single photon emission computed tomography/computerized tomography(SPECT/CT)in patients suffering from space occupying disease of esophagus.40 patients(34 males and 6 female;mean age: 58.3 years) with a suspected space occupying lesion of esophagus were included,thus finally obtaining their definite pathologic diagnosis(malignant,n=32;benign,n=8).All patients underwent endoscopic,barium esophagography and SPECT/CT imaging preoperatively.The chest SPECT was performed at 4 h after administration of99mTc-3P4-RGD2 with a dose of 939±118 MBq.The diagnosis precision,sensitivity and specificity among these methods were compared.The relationship between radioactive uptake and clinical pathological stage of esophageal carcinoma was discussed by calculating the tumor to normal esophagus(T/N).Meanwhile,the integrin αvβ3 expression was assessed immunohistochemically in postoperative esophageal tissues.31 patients were diagnosed as esophageal carcinoma;and 1,leiomyosarcoma;and 6.leimyoma;and 2,esophageal tuberculosis.The accuracy,sensitivity and specificity of barium esophagography,endoscopic and SPECT/CT imaging are 92.5/93.8/87.5%,97.5/96.9/100%,and 90/90.6/87.5%,respectively.Abnormal accumulation of radiotracer in 29 malignant lesions is observed.The SPECT/CT imaging displayed the region of radioactive uptake and lesions matched extremely with the T/N ratio from 1.31 to 2.79(mean 2.04).A case with pulmonary metastases and a case with mediastinal lymph node metastases were found which were missed by barium esophagography and endoscopic.The99mTc-3P4-RGD2 uptake of the esophageal carcinoma masses had no relevance to the tumor pathologic classification(P>0.05).There was a significant positive correlation between T/N ratio and positive cell percentage of integrin αvβ3(r=0.976),demonstrating the certain clinical potential in the diagnosis of esophageal carcinoma.

Comparison of clinical laboratory tests between bacterial sepsis and SARS-CoV-2-associated viral sepsis

Sepsis is a life-threatening condition that is characterized by multiple organ dysfunction due to abnormal host response to various pathogens,like bacteria,fungi and virus.The differences between viral and bacterial sepsis are indeed of great significance to deepen the understanding of the pathogenesis of sepsis,especially under pandemics of SARS-CoV-2 infection.

Development of septic shock and prognostic assessment in critically ill patients with coronavirus disease outside Wuhan, China

BACKGROUND: The study aims to illustrate the clinical characteristics and development of septic shock in intensive care unit(ICU) patients confirmed with severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) infection, and to perform a comprehensive analysis of the association between septic shock and clinical outcomes in critically ill patients with coronavirus disease(COVID-19).METHODS: Patients confirmed with SARS-Co V-2 infection, who were admitted to the ICU of the Third People's Hospital of Shenzhen from January 1 to February 7, 2020, were enrolled. Clinical characteristics and outcomes were compared between patients with and without septic shock.RESULTS: In this study, 35 critically ill patients with COVID-19 were included. Among them, the median age was 64 years(interquartile range [IQR] 59-67 years), and 10(28.4%) patients were female. The median ICU length of stay was 16 days(IQR 8-23 days). Three(8.6%) patients died during hospitalization. Nine(25.7%) patients developed septic shock in the ICU, and these patients had a significantly higher incidence of organ dysfunction and a worse prognosis than patients without septic shock.CONCLUSIONS: Septic shock is associated with a poor outcome in critically ill COVID-19 patients and is one of the hallmarks of the severity of patients receiving ICU care. A dysregulated immune response, uncontrolled infl ammation, and coagulation disorders are strongly associated with the development and progression of COVID-19-related septic shock.

Electroacupuncture at Dazhui(GV14) and Mingmen(GV4) protects against spinal cord injury:the role of the Wnt/β-catenin signaling pathway

Electroacupuncture at Dazhui（GV14） and Mingmen（GV4） on the Governor Vessel has been shown to exhibit curative effects on spinal cord injury; however, the underlying mechanism remains poorly understood. In this study, we established rat models of spinal cord injury using a modified Allen＇s weight-drop method. Ninety-nine male Sprague-Dawley rats were randomly divided into three equal groups： sham（only laminectomy）, SCI（induction of spinal cord injury at T10）, and EA（induction of spinal cord injury at T10 and electroacupuncture intervention at GV14 and GV4 for 20 minutes once a day）. Rats in the SCI and EA groups were further randomly divided into the following subgroups： 1-day（n = 11）, 7-day（n = 11）, and 14-day（n = 11）. At 1, 7, and 14 days after electroacupuncture treatment, the Basso, Beattie and Bresnahan locomotor rating scale showed obvious improvement in rat hind limb locomotor function, hematoxylin-eosin staining showed that the histological change of injured spinal cord tissue was obviously alleviated, and immunohistochemistry and western blot analysis showed that Wnt1, Wnt3 a, β-catenin immunoreactivity and protein expression in the injured spinal cord tissue were greatly increased compared with the sham and SCI groups. These findings suggest that electroacupuncture at GV14 and GV4 upregulates Wnt1, Wnt3 a, and β-catenin expression in the Wnt/β-catenin signaling pathway, exhibiting neuroprotective effects against spinal cord injury.

A Prospective Randomized Trial of Selective versus Nonselective Esophagogastric Devascularization for Portal Hypertension

Cirrhosis with portal hypertension is a common disease which has a significant impact on the quality of patients＇ life. Esophagogastric devascularization（EGDV） has been demonstrated to be an effective method to treat portal hypertension, however certain complications are associated with it. The purpose of this study was to evaluate the effectiveness and clinical outcome of the selective EGDV（sEGDV） for the treatment of portal hypertension. The study was conducted prospectively from Jan. 1 2011 to Dec. 31, 2012, and 180 patients were randomized to the sEGDV group（n=90） or the non-sEGDV（n-sEGDV） group（n=90）. Patients＇ demographics, preoperative lab test results and operative details were comparable between the two groups. Postoperative and short-term complications were analyzed in two groups. There was statistically significant difference（P〈0.01） in the PVF reduction between the two groups. Post-operative complications showed no statistically significant difference between the two groups in the incidence of bleeding, ascites, acute portal vein thrombosis, fever and hepatic encephalopathy. Mortality between two groups was comparable. The incidence of splenic fossa effusion after the surgery was lower in sEGDV group than in n-sEGDV group. There were no significant differences in the short-term follow-up data such as esophageal varices and portal hypertensive gastropathy（P〉0.05）. It is suggested that sEGDV is a safe, simple and effective surgical procedure. It has both the advantages of the shunt and devascularization because it preserves body＇s voluntary diversion. With the advantage of low incidence of postoperative complications, it is an ideal surgical approach for the treatment of portal hypertension.

Reconstructing the portal vein through a posterior pancreatic tunnel:New choice for portal vein thrombosis during liver transplantation

BACKGROUND Thrombectomy and anatomical anastomosis(TAA)has long been considered the optimal approach to portal vein thrombosis(PVT)in liver transplantation(LT).However,TAA and the current approach for non-physiological portal reconstructions are associated with a higher rate of complications and mortality in some cases.AIM To describe a new choice for reconstructing the portal vein through a posterior pancreatic tunnel(RPVPPT)to address cases of unresectable PVT.METHODS Between August 2019 and August 2021,245 adult LTs were performed.Forty-five(18.4%)patients were confirmed to have PVT before surgery,among which seven underwent PV reconstruction via the RPVPPT approach.We retrospectively analyzed the surgical procedure and postoperative complications of these seven recipients that underwent PV reconstruction due to PVT.RESULTS During the procedure,PVT was found in all the seven cases with significant adhesion to the vascular wall and could not be dissected.The portal vein proximal to the superior mesenteric vein was damaged in one case when attempting thrombolectomy,resulting in massive bleeding.LT was successfully performed in all patients with a mean duration of 585 min(range 491-756 min)and mean intraoperative blood loss of 800 mL(range 500-3000 mL).Postoperative complications consisted of chylous leakage(n=3),insufficient portal venous flow to the graft(n=1),intra-abdominal hemorrhage(n=1),pulmonary infection(n=1),and perioperative death(n=1).The remaining six patients survived at 12-17 mo follow-up.CONCLUSION The RPVPPT technique might be a safe and effective surgical procedure during LT for complex PVT.However,follow-up studies with large samples are still warranted due to the relatively small number of cases.

Potential therapy strategy: targeting mitochondrial dysfunction in sepsis

Recently, the definition of sepsis was concluded to be a life-threatening organ dysfunction caused by a dysregulated host response to infection. Severe patients always present with uncorrectable hypotension or hyperlactacidemia, which is defined as septic shock. The new definition emphasizes dysregulation of the host response and multiple organ dysfunction, which is partially attributed to metabolic disorders induced by energy crisis and oxidative stress. Mitochondria are a cellular organelle that are well known as the center of energy production, and mitochondrial damage or dysfunction is commonly induced in septic settings and is a predominant factor leading to a worse prognosis. In the present review, we determine the major mitochondrial disorders from morphology to functions in sepsis. In the following, several clinical or pre-clinical assays for monitoring mitochondrial function are demonstrated according to accumulated evidence, which is the first step of specific therapy targeting to modulate mitochondrial function. Accordingly, various reagents used for regulating mitochondrial enzyme activities and promoting biogenesis have been documented, among which mitochondriatargeted cation, TPP-conjugated antioxidants are the most valuable for future trials and clinical treatment to improve mitochondrial function as they may take advantage of the prognosis associated with septic complications.

Diagnostic Value of Dual-Energy CT in Differentiating Malignant and Benign Thyroid Nodules: A Systematic Review and Meta-Analysis

Objectives: To evaluate the diagnostic performance of the quantitative iodine parameters, including Iodine Concentration (IC), Normalized Iodine Concentration (NIC), and λHU, in distinguishing malignant and benign thyroid nodules. Methods: Relevant studies were searched from Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure database and other complementary sources from inception to May 20, 2020. Study selection, data extraction, quality assessment, and data analyses were performed following the Cochrane standards and the PRISMA-DTA guideline. Results: Eight studies were included (595 patients with 737 thyroid nodules). The pooled sensitivity, specificity and summary diagnostic odds ratio of IC were 79% (95% CI: 69% - 86%), 76% (95% CI: 65% - 84%) and 11 (95% CI: 5 - 27) respectively;those of NIC were 78% (95% CI: 70% - 85%), 80% (95% CI: 74% - 85%) and 15 (95% CI: 9 - 24) respectively;those of λHU were 80% (95% CI: 71% - 87%), 77% (95% CI: 70% - 83%) and 14 (95% CI: 8 - 24) respectively. Conclusion: DECT can be a potential evaluation tool for thyroid nodules. The NIC may be the most sensitive iodine parameter and could be comparable between different DECT machines in thyroid nodule assessment.

Virus load and virus shedding of SARS-CoV-2 and their impact onpatient outcomes

BACKGROUND Understanding a virus shedding patterns in body fluids/secretions is importantto determine the samples to be used for diagnosis and to formulate infectioncontrol measures.AIM To investigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)shedding patterns and its risk factors.METHODS All laboratory-confirmed coronavirus disease 2019 patients with completemedical records admitted to the Shenzhen Third People’s Hospital from January28, 2020 to March 8, 2020 were included. Among 145 patients (54.5% males;median age, 46.1 years), three (2.1%) died. The bronco-alveolar lavage fluid(BALF) had the highest virus load compared with the other samples. The viralload peaked at admission (3.3 × 108 copies) and sharply decreased 10 d afteradmission.RESULTS The viral load was associated with prolonged intensive care unit (ICU) duration.Patients in the ICU had significantly longer shedding time compared to those inthe wards (P < 0.0001). Age > 60 years [hazard ratio (HR) = 0.6;95% confidenceinterval (CI): 0.4-0.9] was an independent risk factor for SARS-CoV-2 shedding,while chloroquine (HR = 22.8;95%CI: 2.3-224.6) was a protective factor.CONCLUSION BALF had the highest SARS-CoV-2 load. Elderly patients had higher virus loads,which was associated with a prolonged ICU stay. Chloroquine was associatedwith shorter shedding duration and increased the chance of viral negativity.

Susceptibility-weighted imaging is suitable for evaluating signal strength in different brain regions of a rabbit model of acute hemorrhagic anemia

Acute hemorrhagic anemia can decrease blood flow and oxygen supply to brain, and affect its physiological function. While detecting changes in brain function in patients with acute hemorrhagic anemia is helpful for preventing neurological complications and evaluating therapeutic effects, clinical changes in the nervous systems of these patients have not received much attention. In part, this is because current techniques can only indirectly detect changes in brain function following onset of anemia, which leads to lags between real changes in brain function and their detection.

Value of Contrast-enhanced Ultrasound in Evaluating Synovitis and Predicting Recurrent Joint Bleeding of Hemophilia

Objective Contrast-enhanced ultrasound(CEUS)is advantageous for evaluating microcirculation,and has been applied to assess arthritis in previous studies.However,CEUS examinations have not been studied for hemophilia arthritis.Hemophilia arthritis is different from other arthritis,because it is induced by spontaneous joint bleeding.Hence,CEUS may have special value in evaluating hemophilia arthritis.The present study assessed the value of CEUS in evaluating synovial hypertrophy and predicting recurrent joint bleeding in severe hemophilia A patients.Methods From August 2016 to January 2017,81 severe hemophilia A patients,who were referred to our hospital for ultrasound joint assessment with conventional ultrasound,were enrolled.Among these 81 patients,46 patients consented for CEUS examinations on the same day.Results Compared to color Doppler flow imaging(CDFI),four more joints presented with a blood flow signal under CEUS mode.In addition,the synovial hypertrophy measured by CEUS was thicker than that measured by conventional ultrasound.The ultrasound scores(including the total grey-scale ultrasound score,joint effusion/hemarthrosis,synovial hypertrophy,CDFI semi-quantitative score,and CEUS semi-quantitative score)were significantly higher in the joint bleeding group than in the no joint bleeding group(P<0.05).Furthermore,these ultrasound scores were positively correlated with the joint bleeding frequency,and had the highest correlation with the CEUS score(r=0.620,P<0.05).Conclusion CEUS can more accurately assess the degree of synovial hypertrophy and vascularization,and diagnose synovitis,when compared to conventional ultrasound.In addition,CEUS appears to be essential for evaluating the possibility of recurrent joint bleeding,and providing more reliable evidence for individualized treatment.

Comparison of acute pneumonia caused by SARS-CoV-2 and other respiratory viruses in children:a retrospective multi-center cohort study during COVID-19 outbreak

Background:Until January 18,2021,coronavirus disease-2019(COVID-19)has infected more than 93 million individuals and has caused a certain degree of panic.Viral pneumonia caused by common viruses such as respiratory syncytial virus,rhinovirus,human metapneumovirus,human bocavirus,and parainfluenza viruses have been more common in children.However,the incidence of COVID-19 in children was significantly lower than that in adults.The purpose of this study was to describe the clinical manifestations,treatment and outcomes of COVID-19 in children compared with those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak.Methods:Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study.A total of 64 children with COVID-19 were defined as the COVID-19 cohort,of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort.Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort.The epidemiologic,clinical,and laboratory findings were compared by Kolmogorov-Smirnov test,t-test,Mann-Whitney U test and Contingency table method.Drug usage,immunotherapy,blood transfusion,and need for oxygen support were collected as the treatment indexes.Mortality,intensive care needs and symptomatic duration were collected as the outcome indicators.Results:Compared with the viral pneumonia cohort,children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19(53/64 vs.23/284),were of older median age(6.3 years vs.3.2 years),and had a higher proportion of ground-glass opacity(GGO)on computed tomography(18/40 vs.0/38,P<0.001).Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases(1/40 vs.38/284,P=0.048),and lower cases with high fever(3/40 vs.167/284,P<0.001),requiring intensive care(1/40 vs.32/284,P<0.047)and with shorter symptomatic duration(median 5d vs.8d,P<0.001).The proportion of cases with evaluated inflammatory indicators,biochemical indicators related to organ or tissue damage,D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than those in the viral pneumonia cohort(P<0.05).No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs(lopinavir-ritonavir,ribavirin,and arbidol)as compared with duration in 39 children without antiviral therapy(median 10d vs.9d,P=0.885).Conclusions:The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonia.Lopinavir-ritonavir,ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19.During the COVID-19 outbreak,attention also must be given to children with infection by other pathogens infection.