Routine Indexes Research Articles

Routinization of work processes, de-routinization of job structures

Abstract This article investigates changes in routine tasks and computer use in European jobs in the period 1995–2015, putting them in the context of the debates on the future of work and the impact of automation. Digital technologies not only affect employment shifts but also shape work organization. A shift-share analysis combining European Working Conditions Survey and European Labour Force Survey data assesses to what extent recent changes in tasks are the result of changes in the structure of employment (shifts in employment across jobs) or changes in the content of work itself (transformation in the task contents and methods within jobs). The results suggest contrasting trends between observed changes in tasks measures within jobs and compositional shifts in employment for routine tasks indexes. Employment structures are de-routinizing while work itself is becoming more routine. These results seem also related to the increased use of computers at work during the same period.

Novel index for the prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B patients in China.

BACKGROUNDNoninvasive, practical, and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed. AIMTo develop a precise noninvasive test to stage liver fibrosis and cirrhosis. METHODSWith liver biopsy as the gold standard, we established a new index, [alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)/platelet (109/L) (AGPR)], to predict liver fibrosis and cirrhosis. In addition, we compared the area under the receiver operating characteristic curve (AUROC) of AGPR, gamma-glutamyl transpeptidase to platelet ratio, aspartate transaminase to platelet ratio index, and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis. RESULTSCorrelation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage (P < 0.001). In the training cohort, the AUROC of AGPR was 0.83 (95%CI: 0.78-0.87) for predicting fibrosis (≥ F2), 0.84 (95%CI: 0.79-0.88) for predicting extensive fibrosis (≥ F3), and 0.87 (95%CI: 0.83-0.91) for predicting cirrhosis (F4). In the validation cohort, the AUROCs of AGPR to predict ≥ F2, ≥ F3 and F4 were 0.83 (95%CI: 0.77-0.88), 0.83 (95%CI: 0.77-0.89), and 0.84 (95%CI: 0.78-0.89), respectively.CONCLUSIONThe AGPR index should become a new, simple, accurate, and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.

Interhospital transfer of patients with malignant brain tumors undergoing resection is associated with routine discharge

IntroductionNeurosurgical patients often undergo interhospital transfer (IHT) for specialized care. While IHT is often associated with worse outcomes in emergent neurosurgical conditions, less is known about patient outcomes after IHT for urgent diagnoses such as brain tumors. We sought to evaluate patient outcomes after IHT for malignant brain tumor resection. MethodsPatients hospitalized for resection of malignant brain tumor resections were analyzed from the Nationwide Readmissions Database (NRD) from 2016 to 2018. Multivariate regression analyses were conducted to determine associations between transfer status and routine disposition, mortality index, and length of stay. ResultsAmong 13,173 patients with non-elective admissions for malignant brain tumor resection, 1583 (12.0%) were transferred from another facility. In comparison to non-transferred patients, IHT patients were more likely to be male (53.8% vs. 51.1%, p < 0.04), older (rates of age ≥60 64.0% vs. 58.9%, p < 0.001), and had greater Elixhauser comorbidity scores (≥3: 75.0% vs. 56.1%, p < 0.0001). After adjustment for comorbidity burden, transfer status was associated with increased likelihood of routine discharge (OR 1.35, 95% CI 1.18–1.55, p < 0.0001). Mortality was similar for IHT patients compared to non-transferred patients (OR 0.87, CI 0.62–1.22, p = 0.405). Transfer status was associated with increased length of stay (incident rate ratio [IRR] 1.41, 95% CI 1.34–1.48, p < 0.0001). ConclusionIHT for malignant brain tumor resection was not associated with worse patient outcomes with respect to discharge disposition and mortality. Length of stay was greater for IHT patients. Further research is needed to determine which patients will benefit from IHT for malignant brain tumor resection.

Analysis of hepatic pathological inflammation and fibrosis condition and its influencing factors in 721 patients with chronic hepatitis B with normal ALT

Objective: To analyze the hepatic pathological inflammation and fibrosis condition in order to explore the relationship with related clinical indicators in patients with chronic hepatitis B patients with normal alanine aminotransferase (ALT). Methods: 721 cases of chronic hepatitis B with normal ALT who were initially diagnosed in the Department of Infectious Diseases of Henan Provincial People's Hospital from August 2016 to December 2019 were retrospectively collected. Liver biopsy was performed in all patients. General data of patients such as gender, age, liver function indexes, blood routine indexes, HBsAg level, HBeAg status, HBV DNA level, spleen thickness and prothrombin time were collected. Univariate and multivariate analysis methods were used to determine the influencing factors of inflammation and fibrosis degree with liver biopsy. A receiver operating characteristic curve (ROC) was used to evaluate the established multi-factor prediction model. Alpha=0.05 was considered as a standard orientation of test. Results: The average age of 721 cases with chronic hepatitis B was 36.1±9.7 years, and the male to female ratio was 1.28/1, with inflammation and fibrosis grade mainly concentrated in G1S1 (349 cases), G1S2 (132 cases), G2S2 (119 cases), and G2S1 (57 cases). Among them, there were 349 (48.4%) cases of G1S1, and 372 (51.6%) cases of G/S≥2. The main manifestations were mild to moderate inflammation and fibrosis, and only 64 (8.88%) cases had severe G/S≥3. HBsAg level (stratified with 4 log10 IU/ml as the boundary) analyzed in 721 cases were correlated with the relevant clinical indicators stratification and liver pathological inflammation and fibrosis, and the difference was statistically significant (inflammation grade, χ2=6.182, P=0.013; Fibrosis grade, χ2=36.534, P=0.001). Univariate analysis of the relevant clinical indicators that may influence the patient's liver pathological G/S ≥2 showed the patient's age, albumin, γ- glutamyltransferase (GGT), platelet, prothrombin time (PT), spleen thickness and HBsAg level were all statistically significant (P<0.05), while multivariate analysis showed that age, GGT, PT, and spleen thickness had statistical differences (P<0.05). The prediction model was established in accordance to multivariate analysis, and the area under the ROC curve was 0.642. Maximization of the sum of sensitivity and specificity as cut-off value of Logit P=0.497, the diagnostic sensitivity, specificity, and Youden's index were 60.6%, 64.5%, and 0.252, respectively. Conclusion: More than half of patients with chronic hepatitis B with normal ALT have significant inflammation and fibrosis and require timely antiviral therapy. Age, GGT, PT and spleen thickness can help comprehensively evaluate the liver inflammation and fibrosis status among patients, but the lack of accurate prediction models suggests that more effective indicators that can help predict the inflammation and fibrosis status of such patients have yet to be discovered. Therefore, liver biopsy should still be actively performed in patients with normal ALT to confirm the diagnosis and timely treatment.

Current approaches to risk assessment of chronic heart failure after myocardial infarction

In the last decade, there has been an increase in the number of survivors of myocardial infarction (MI). However, the risk of developing chronic heart failure (CHF) remains high in this category of patients. Population aging and comorbidity further contribute to adverse outcomes. Optimization of approaches to identify predictors of postinfarction CHF is an important clinical task of modern medicine.The aim of the investigation is to develop a method to assess the risk of CHF development after MI.Material and Methods. The present analysis included 186 patients who underwent MI from January 2019 to January 2020: 86 patients with signs of CHF above functional class (FC) 2 (NYHA) (mean age 64.3 years) and 100 patients without signs of CHF or with CHF 1 (NYHA) (mean age 62.6 years) by day 30 of MI. A mathematical model of CHF risk after MI was built by factor and correlation analysis methods.Results. A method for assessing CHF risk after a previous MI was developed. The proposed formula is programmed in Excel table processor and includes 5 indicators: presence of atrial fibrillation, Killip class of acute heart failure, triglycerides level, ST-segment elevation of electrocardiogram, left ventricular ejection fraction less than 45 %. The authors’ approach allows long-term personalized monitoring, taking into account the ranked contribution of each factor in a particular patient; it is characterized by high sensitivity, specificity, and accuracy.Conclusion. The present study investigated the factors of formation of postinfarct chronic heart failure syndrome. An original mathematical formula for CHF risk estimation, including routine indices of MI patients, has been proposed. The approach allows personalized management of selected cohorts of patients – with increased and standard risk of postinfarction CHF.

Safety and immunogenicity of an Escherichia coli-produced bivalent human papillomavirus type 6/11 vaccine: A dose-escalation, randomized, double-blind, placebo-controlled phase 1 trial

ABSTRACT A dose-escalation, randomized, double-blind, placebo-controlled phase 1 clinical trial enrolled 145 eligible participants aged 18–55 years in March 2015 in Liuzhou, China. Stratified by age and sex, the participants were randomly assigned to receive either 30, 60, or 90 μg of the HPV-6/11 vaccine (n = 41/40/40) or the parallel placebo vaccine (n = 8/8/8) with a 0/1/6-month dose-escalation schedule. Participants were actively followed-up to record local and systemic AEs occurring within 30 days after each vaccination, and SAEs occurred in 7 months. Blood and urine samples of each participant were collected before and 2 days after the first and third vaccination to determine changes in routine blood, serum biochemical, and urine indexes. Serum HPV-6/11-specific IgG and neutralizing antibody levels at month 7 were analyzed. A total of 79 adverse events were reported, and no SAEs occurred. The incidences of total adverse reactions in the 30 μg, 60 μg, and 90 μg HPV vaccine groups and the control group were 31.7%, 50.0%, 42.5%, and 62.5%, respectively. All but one of the adverse reactions was mild or moderate with grade 1 or 2. No vaccine-related changes with clinical significance were found in paired blood and urine indexes before and after vaccinations. All the participants in the per-protocol set seroconverted at month 7 for both IgG and neutralizing antibodies. The candidate novel Escherichia-coli-produced bivalent HPV-6/11 vaccine has been preliminarily proven to be well tolerated and with robust immunogenicity in a phase 1 clinical study, supporting further trials with larger sample size. The study has been registered at ClinicalTrials.gov (NCT02405520)

Prediction of the severity of acute pancreatitis using machine learning models

ABSTRACT Background Acute pancreatitis (AP) is the most common pancreatic disease. Predicting the severity of AP is critical for making preventive decisions. However, the performance of existing scoring systems in predicting AP severity was not satisfactory. The purpose of this study was to develop predictive models for the severity of AP using machine learning (ML) algorithms and explore the important predictors that affected the prediction results. Methods The data of 441 patients in the Department of Gastroenterology in our hospital were analyzed retrospectively. The demographic data, blood routine and blood biochemical indexes, and the CTSI score were collected to develop five different ML predictive models to predict the severity of AP. The performance of the models was evaluated by the area under the receiver operating characteristic curve (AUC). The important predictors were determined by ranking the feature importance of the predictive factors. Results Compared to other ML models, the extreme gradient boosting model (XGBoost) showed better performance in predicting severe AP, with an AUC of 0.906, an accuracy of 0.902, a sensitivity of 0.700, a specificity of 0.961, and a F1 score of 0.764. Further analysis showed that the CTSI score, ALB, LDH, and NEUT were the important predictors of the severity of AP. Conclusion The results showed that the XGBoost algorithm can accurately predict the severity of AP, which can provide an assistance for the clinicians to identify severe AP at an early stage.

Novel Insights into the Predictors of Obstructive Sleep Apnea Syndrome in Patients with Chronic Coronary Syndrome: Development of a Predicting Model.

Background Obstructive sleep apnea syndrome (OSAS) is common in patients with chronic coronary syndrome (CCS); however, a predictive model of OSAS in patients with CCS remains rarely reported. The study aimed to construct a novel nomogram scoring system to predict OSAS comorbidity in patients with CCS. Methods Consecutive CCS patients scheduled for sleep monitoring at our hospital from January 2019 to September 2020 were enrolled in the current study. Coronary CT angiography or coronary angiography was used for the diagnosis of CCS, and clinical characteristics of the patients were collected. Significant predictors for OSAS in patients with moderate/severe CCS were estimated via logistic regression analysis, and a clinical nomogram was constructed. A calibration plot, examining discrimination (Harrell's concordance index) and decision curve analysis (DCA), was applied to validate the nomogram's predictive performance. Internal validity of the predictive model was assessed using bootstrapping (1000 replications). Results The nomograms were constructed based on available clinical variables from 527 patients which were significantly associated with moderate/severe OSAS in patients with CCS, including body mass index, impaired glucose tolerance, hypertension, diabetes mellitus, nonalcoholic fatty liver disease, and routine laboratory indices such as neutrophil to lymphocyte ratio, platelet-to-lymphocyte ratio, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The C-index (0.793) and AUC (0.771, 95% CI: 0.731–0.811) demonstrated a favorable discriminative ability of the nomogram. Moreover, calibration plots revealed consistency between moderate/severe OSAS predicted by the nomogram and validated by the results of sleep monitoring. Clinically, DCA showed that the nomogram had good discriminative ability to predict moderate/severe OSAS in patients with CCS. Conclusions The risk nomogram constructed via the routinely available clinical variables in patients with CCS showed satisfying discriminative ability to predict comorbid moderate/severe OSAS, which may be useful for identification of high-risk patients with OSAS in patients with CCS.

Blood routine examination: a simple way for differential diagnosis of immunoglobulin A vasculitis with abdominal involvement and appendicitis in children.

To explore the value of blood routine examination indexes in the differential diagnosis of immunoglobulin A vasculitis (IgAV) with abdominal involvement and appendicitis in children. Forty-seven patients with IgAV and abdominal involvement, 95 cases with appendicitis, and 48 healthy children were enrolled in this study. Demographic and laboratory data were retrospectively recorded from medical files. The levels of serum percentage of lymphocytes (LYM%), percentage of eosinophils (E%), red cell volume distribution width (RDW) and platelet (PLT) count were higher, while blood cells (WBC) count, percentage of neutrophils (N%), percentage of monocytes (M%), mean platelet volume (MPV), platelet distribution width and C-reactive protein were lower in the group of IgAV with abdominal involvement compared to appendicitis group (P < 0.05). Multivariate logistic regression analysis showed LYM% (odds ratio (OR) = 1.34, P = 0.001) and RDW (OR = 2.96, P = 0.045) were independent risk factors for IgAV with abdominal involvement. N% (OR = 1.270, P = 0.006) and MPV (OR = 51.15, P = 0.042) were independently associated with appendicitis. Using receiver operating characteristic analysis, the optimal cut-off values (sensitivity and specificity) respectively were 42.17% (95.7%, 100.0%) for LYM%, 12.65% (83.0%, 83.2%) for RDW, 61.5% (91.6%, 97.9%) for NE% and 10.1fL (78.9%, 75.4%) for MPV, with the AUC values of 0.989, 0.881, 0.985, 0.810, respectively. Blood routine examination indices, especially the N%, LYM%, RDW, and MPV, can be used for simple differential diagnosis of IgAV with abdominal involvement and appendicitis.

Treatment of Hyperlactatemia in Acute Circulatory Failure Based on CO2-O2-Derived Indices: Study Protocol for a Prospective, Multicentric, Single, Blind, Randomized, Superiority Study (The LACTEL Study).

BackgroundHyperlactatemia is a biological marker of tissue hypoperfusion with well-known diagnostic, prognostic, and therapeutic implications in shock states. In daily clinical practice, it is difficult to find out the exact mechanism underlying hyperlactatemia. Central venous to arterial CO2 difference (pCO2 gap) is a better parameter of tissue hypoperfusion than the usual ones (clinical examination and mixed venous saturation). Furthermore, the ratio between the pCO2 gap and p(v–a)CO2/C(a–v)O2 may be a promising indicator of anaerobic metabolism, allowing for the identification of different causes of tissue hypoxia and hyperlactatemia. The main aim of the study is to demonstrate that initial hemodynamic resuscitation based on an algorithm integrating the pCO2 gap and p(v–a)CO2/C(a–v)O2 ratio vs. usual clinical practice in acute circulatory failure improves lactate clearance.MethodsLACTEL is a randomized, prospective, multicentric, controlled study. It compares the treatment of hyperlactatemia using an algorithm based on the pCO2 gap and P(v–a)CO2/C(a–v)O2 ratio vs. usual clinical practice in acute circulatory failure. A total of 90 patients were enrolled in each treatment group. The primary endpoint is the number of patients with a lactate clearance of more than 10% 2 h after inclusion. Lactate levels were monitored during the first 48 h of treatment as hemodynamic parameters, biological markers of organ failure, and 28-day mortality.DiscussionpCO2 derivate indices may be of better interest than routine clinical indices to differentiate causes of hyperlactatemia and diagnose anaerobiosis. LACTEL results will provide clinical insights into the role of these indices in the early hemodynamic management of acute circulatory failure in the ICU.Clinical Trial Registrationwww.clinicaltrials.gov; identifier: NCT05032521.

Role of CD4 + T and CD8 + T Lymphocytes-Mediated Cellular Immunity in Pathogenesis of Chronic Obstructive Pulmonary Disease.

This work was to explore the changes of T lymphocyte subsets in peripheral blood of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) (AECOPD) and the role of cellular immunity mediated in the disease process. Eighty-six patients with AECOPD who visited Qingdao Hiser Medical Center from June 2020 to December 2021 and 30 healthy people (controls) who underwent health examination in the same period were selected. The differences of pulmonary function (PF), arterial blood gas (ABG), blood routine inflammatory indexes, T lymphocyte and T lymphocyte subsets were compared between the two groups, and the correlation between T lymphocyte subsets and each index was analyzed. There were clear differences in PF, ABG, and PB inflammation indexes between AECOPD patients and the controls (P <0.05). Compared with the controls, the CD4+ and CD4+/CD8+ ratio in PB of AECOPD group were obviously decreased, and the CD8+ level was clearly increased (P <0.05); Th1 of CD4+ cell subsets and Tc1 of CD8+ cell subsets were significantly increased, while Th2 of CD4+ cell subsets and Tc2 of CD8+ cell subsets were obviously decreased (P <0.05). However, CD4+ was significantly positively correlated with lung function indexes, and significantly negatively correlated with neutrophils/lymphocytes and high-sensitivity C-reactive protein (P <0.05) and significantly positively correlated with Hs-CRP (P <0.05). In summary, CD4+ and CD8+ T lymphocytes were involved in the occurrence and occurrence of AECOPD, the decrease of CD4+ and the increase of CD8+ may promote the deterioration of COPD.

Factor analysis of effective platelet-producing ability of fetal liver-derived cells

Objective: To study the different factors affecting platelet production post transplantation of hematopoietic stem cells (HSCs) isolated from different sources in order to explore novel options for treating platelet depletion following HSCs transplantation. Methods: HSCs and their downstream derivatives including myeloid and lymphoid cells (i.e., collective of mononuclear cells (MNCs)), were isolated from E14.5 fetal liver (FL) and bone marrow (BM) of 8-week-old mice by Ficoll separation technique. These cells were subsequently transplanted into the tibia bone marrow cavity of recipient mice post lethal myeloablative treatment in order to construct the FL-MNCs and BM-MNCs transplantation mouse model. Routine blood indices were examined in these recipient mice. The chimeric rate of donor cells in recipient peripheral blood cells were determined by flow cytometry. Different groups of cells involved in platelet reconstruction were analyzed. CD41+megakaryocytes were sorted from fetal liver or bone marrow using magnetic beads, which were then induced to differentiate into platelets in an in vitro assay. Quantitative RT-PCR was used to detect the expression of platelet-related genes in CD41+megakaryocytes from the two sources. Results: Both the FL-MNCs and the BM-MNCs transplantation groups resumed normal hematopoiesis at the 4th week after transplantation, and the blood cells of the recipient mice were largely replaced by the donor cells. Compared with the mice transplanted with BM-MNCs, the platelet level of mice transplanted with FL-MNCs recovered faster and were maintained at a higher level. At week 4, the PLT level of the FL-MNCs group was (1.45±0.37)×1012/L, and of the BM-MNCs group was (1.22±0.24)×1012/L, P<0.05. The FL-MNCs contain a higher proportion of hematopoietic stem cells (Lin-Sca-1+c-Kit+)(7.60%±1.40%) compared to the BM-MNCs (1.10%±0.46%), P<0.01; the proportion of the megakaryocyte progenitor cells (Lin-Sca-1-c-Kit+CD41+CD150+) and mature megakaryocyte cells (CD41+CD42b+), also differ significantly between the FL-MNCs (3.05%±0.22%, 1.60%±0.06%, respectively) and the BM-MNCs (0.15%±0.02%, 0.87%±0.11%, respectively) groups, both P<0.01. In vitro functional studies showed that FL-MNCs-CD41+megakaryocytes could produce proplatelet-like cells more quickly after induction, with proplatelet-like cells formation on day 3 and significant platelet-like particle formation on day 5, in contrast to bone marrow-derived BM-MNCs-CD41+megakaryocytes that failed to form proplatelet-like cell on day 5. In addition, FL-MNCs-CD41+cells expressed higher levels of platelet-related genes, Mpl (3.25-fold), Fog1 (3-fold), and Gata1 (1.5-fold) (P<0.05). Conclusion: Compared with the BM-MNCs group, the FL-MNCs transplantation group appears to have a more efficient platelet implantation effect in the HSCs transplantation recipient in vivo, as well as a higher platelet differentiation rate in vitro. This might be related to a higher proportion of megakaryocytes and higher expression levels of genes such as Mpl, Fog1, and Gata1 that could be important for platelet formation in FL-MNCs-CD41+cells. Further exploration of the specific functions of these genes and the characteristics of the different proportions of the donor cells will provide valuable clues for the future treatment of platelets reconstitution after HSCs transplantation clinically.

Effect and Mechanism of Cxcr4 Gene-Modified BMSC-Derived Exosomes on Aplastic Anemia

To explore the improvement effect of CXC chemokine receptor 4 (Cxcr4) gene-modified bone marrow mesenchymal stem cell (BMSC)-derived exosomes on aplastic anemia (AA), and make a preliminary exploration of the mechanism. Mouse BMSCs were isolated and cultured, then infected by recombinant lentivirus carrying Cxcr4 gene. The expression of green fluorescence was observed through fluorescence microscope, the expression of Cxcr4 mRNA was detected by real-time fluorescence quantitative PCR, and the BMSC-derived exosomes modified with Cxcr4 gene were extracted. Mouse models of AA were constructed, and control group, model group (AA), AA+BMSC group, AA+NC-BMSC group, AA+Cxcr4-BMSC group were set up. Except control group and model group, the other three groups of mice were injected 400 μl exosomes from different sources via the tail vein, after 2 weeks, the routine blood indices and the number of bone marrow nucleated cells were detected, the pathological changes of bone marrow were observed by HE staining, and the expression level of Treg cells was detected by flow cytometry. Mouse BMSCs were successfully isolated, and BMSCs with high expression of Cxcr4 and their exosomes were obtained. Compared with the control group, the number of red blood cell (RBC), white blood cell (WBC), and platelet (PLT), the hemoglobin (Hb) content and proportion of Treg cells in the peripheral blood of mice in the model group significantly decreased (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01). The proliferation level of nucleated cells was low, and the medullary cavity was filled with a large number of fat cells. Compared with the model group, the number of RBC, WBC, PLT, the Hb content and proportion of Treg cells in the peripheral blood of mice in the AA+BMSC group, AA+NC-BMSC group, and AA+Cxcr4-BMSC group significantly increased (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01), and pathological changes of bone marrow were improved. In addition, the number of RBC, WBC, PLT, the Hb content and proportion of Treg cells in the peripheral blood of mice in the AA+Cxcr4-BMSC group were significantly higher than those in the AA+BMSC group (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01). Injection of Cxcr4 gene-modified BMSC-derived exosomes has a certain improvement effect on AA mice, and the mechanism may be related to an increase of the proportion of Treg cells.

Efficacy and safety of glucocorticoids in treatment of COVID-19: a retrospective study.

Novel coronavirus pneumonia is a novel kind of highly contagious disease without any specific drugs. Considering the successful experience of antiviral therapy combined with glucocorticoids (GCs) in severe acute respiratory syndrome, this study was designed to evaluate the clinical efficacy of GCs in treating patients with coronavirus disease 2019 (COVID-19). A cohort of 42 patients with COVID-19 admitted to The First Hospital of Jiaxing from January 4, 2020, to February 16, 2020, were included and grouped into a test group (n=20) and control group (n=22) based on their therapeutic regimens. There were no significant differences in baseline characteristics between patients in the two groups. Conventional treatment (antiviral therapy) was given to patients in both groups, while an additional hormone drug (GCs) was used in patients in the test group. Indices including body temperature, blood routine indices [white blood cell (WBC), lymphocyte, monocyte, and C-reactive protein (CRP)], blood biochemical indices [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)], and complications were recorded during the treatment. Time to achieve negative virus nucleic acid (nCoV-RNA) testing, and hospital stays were also observed and compared between the two groups. All included patients completed the trial. After treatment, superior therapeutic efficacy was achieved in patients in the test group, with body temperature dropping more significantly with a much shorter recovery time compared to the control group (P=0.0412). Simultaneously, the percentage of patients with abnormal blood routine indices (WBC), monocyte, and (CRP) in the test group was reduced more sharply, while no noticeable difference was observed in the number of patients who developed abnormal blood biochemical indices during treatment between the two groups. Additionally, a shorter duration of hospital stays was found in the test group relative to the control group (14.84±8.76 vs. 18.25±7.42 days, P>0.05). Patients who received GCs had a shorter recovery time for body temperature and inflammation. Hormonotherapy with GCs can accelerate the recovery time for body temperature as well as inflammation in patients with COVID-19. It deserves promotion and application in the clinical treatment of coronavirus disease as a form of adjuvant medicine. The ongoing focus of research is on long-term adverse events in GCs.

Inorganic mercury induces liver oxidative stress injury in quails by inhibiting Akt/Nrf2 signal pathway

Mercury is widely used in human life and production. Excessive mercury can accumulate in livestock and poultry through air, drinking water, and food, which causes a serious threat to natural environment and human food safety. However, the exact mechanism of hepatotoxicity caused by mercuric chloride (HgCl2) is still unclear. The purpose of this study is to explore the mechanism of HgCl2 poisoning in the liver. Based on the above background, 28 quails were randomly and equally divided into 4 groups to establish a hepatotoxicity model by oral administration of HgCl2 once daily (0 mg/kg, 2 mg/kg, 4 mg/kg, and 8 mg/kg, respectively). The experiment period was 84 d. The assay results of blood routine and biochemical indexes showed liver injury in quails. Further research found that mRNA and protein levels of nuclear factor-erythroid related factor 2 (Nrf2) and its key promoter protein kinase B (Akt) were significantly decreased, suggesting HgCl2 treatment led to liver oxidative stress injury in a dose-dependent manner by inhibiting the antioxidant signal pathway Akt/Nrf2. Besides, the increase of nuclear factor-κB and tumor necrosis factor-alpha levels as well as the activation of tumor protein 53 indicated the occurrence of inflammation and apoptosis. Moreover, the inhibition of multidrug resistance protein 2 (Mrp2) which participates in HgCl2-mediated toxicant metabolism resulted in toxicity accumulation. Thus, a vicious circle was formed to further aggravate the liver injury. In conclusion, our results demonstrated that HgCl2 leads to liver inflammation, apoptosis, and detoxification dysfunction by inhibiting the antioxidant pathway Akt/Nrf2. Among them, Akt and Mrp2 may be effective therapeutic targets for the treatment of HgCl2-triggered hepatotoxicity.

Cofilin‐1 participates in the hyperfunction of myeloid dendritic cells in patients with severe aplastic anaemia

Cofilin‐1 interacts with actin to regulate cell movement. The importance of cofilin‐1 in immunity has been established, and its involvement in a number of autoimmune diseases has been confirmed. However, its role in severe aplastic anaemia (SAA) remains elusive. Thus, the aim of the current study was to investigate the role of cofilin‐1 in patients with SAA. Flow cytometry, Western blotting and real‐time quantitative reverse transcription‐polymerase chain reaction were performed to detect the mRNA and protein expression of cofilin‐1 in myeloid dendritic cells (mDCs) from patients with SAA. The expression of cofilin‐1 was then suppressed via siRNA, and its effects on mDCs and downstream effector T‐cell function were evaluated. Cofilin‐1 expression was higher in mDCs from patients with SAA and correlated with routine blood and immune indexes. Moreover, cofilin‐1 knockdown in mDCs from patients with SAA reduced their phagocytic capacity, migration capacity, and CD86 expression through F‐actin remodelling, downregulating the stimulatory capacity of mDCs on CD4+ and CD8+ T lymphocytes. Collectively, these findings indicate that cofilin‐1 participates in the hyperfunction of mDCs in patients with SAA and that the downregulation of cofilin‐1 in mDCs from patients with SAA could be a novel treatment approach for SAA.

Distribution of FIB-4 index in the general population: analysis of 75,666 residents who underwent health checkups

BackgroundFatty liver is frequently found in a general population, and it is critical to detect advanced fibrosis. FIB-4 index is considered a useful marker for evaluating liver fibrosis but the distribution of FIB-4 index in the general population remains unknown.MethodsThis cross-sectional study included residents who underwent ultrasonography at health checkups in Hiroshima or Iwate prefectures. The distribution of FIB-4 index in the total study population (N = 75,666) as well as in non-alcoholic fatty liver disease (NAFLD) populations (N = 17,968) and non-drinkers without fatty liver populations (N = 47,222) was evaluated. The distribution of aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT) levels was also evaluated.ResultsThe mean FIB-4 index in the total study population was 1.20 ± 0.63. FIB-4 index ≥ 2.67, which indicates a high risk of liver fibrosis, was found in 16.4% of those aged ≥ 70 years. In the NAFLD population, 58.1% of those in their 60 s and 88.1% of those ≥ 70 years met the criteria for referral to hepatologists by using the recommended FIB-4 index cutoff value (≥ 1.3). The mean FIB-4 index in the NAFLD population (1.12 ± 0.58) was significantly lower than in the non-drinkers without fatty liver (1.23 ± 0.63, p < 0.0001). The non-drinkers without fatty liver tended to have higher AST relative to ALT levels (60.0% with AST/ALT > 1.0), whereas the results in the NAFLD population were opposite (14.8% with AST/ALT > 1.0). AST > ALT resulted in a higher FIB-4 index in non-drinkers without fatty liver due to the nature of FIB-4 index formula.ConclusionsThe cutoff value of FIB-4 index (≥ 1.3) for triaging the elderly people with fatty liver for referral to hepatologists should be reconsidered to avoid over-referral. Due to the impact of age and characteristics of AST/ALT ratios, there is no prospect of using FIB-4 index for primary screening for liver fibrosis in a general population of unknown presence or absence of liver disease, even though it can be easily calculated using routine clinical indices. It is desired to develop a non-invasive method for picking up cases with advanced fibrosis latent in the general population.

Diagnostic Value of DCE-MRI and Tofts Model in Children with Unilateral Hydronephrosis.

Hydronephrosis is a common condition, and the correct diagnosis of hydronephrosis is necessary to improve the early diagnosis rates of pediatric hydronephrosis. The objective of this study is to explore and analyze the diagnostic value of dynamic contrast- enhanced magnetic resonance imaging (DCE-MRI) analyzed using the Tofts model in children with unilateral hydronephrosis. We retrospectively selected data from 88 children with unilateral hydronephrosis treated in our hospital from September 2018 to October 2020. Routine and DCE-MR renal image indexes were collected and their pharmacokinetic variables were calculated based on the Tofts model to compare kinetic parameters of affected and normal kidney. We compared the renal parenchymal thickness and other renal function indexes in children with different degrees of hydronephrosis, and drew receiver operating characteristic (ROC) curves to evaluate the diagnostic value of this approach in children with hydronephrosis. The Ktrans, Kep, and Ve values in the diseased kidneys were lower than those in the normal ones (P<0.05). The thickness of the healthy renal parenchyma in children with severe hydronephrosis was higher than in children with moderate and mild hydronephrosis, but the renal parenchyma thickness and the thickness ratio of renal parenchyma on the affected side were lower than those in children with moderate and mild hydronephrosis (P<0.05). Sensitivity, specificity and accuracy of DCE-MRI and Tofts model in the diagnosis of hydronephrosis in children were higher than those of a single DCE-MRI (P<0.05). The area under the ROC curve for the DCE-MRI and Tofts model approach for the diagnosis of hydronephrosis in children was 0.789 (95% CI, 0.72-0.859), and the sensitivity and specificity were 86.36% and 71.59%, respectively. DCE-MRI and Tofts model can provide a clear picture of renal morphology, and renal function evaluation parameters. They have high sensitivity and specificity in the diagnosis of hydronephrosis in children.

A Cohort Study of Rivaroxaban Combined with D-Dimer Dynamic Monitoring in the Prevention of Deep Venous Thrombosis after Knee Arthroplasty.

Objective To explore the cohort study of rivaroxaban combined with D-dimer dynamic monitoring in the prevention of deep venous thrombosis (DVT) after knee arthroplasty. Methods Eighty-four patients with knee osteoarthritis who went through total knee arthroplasty from June 2019 to June 2021 in our hospital were arbitrarily assigned into the study group and the control group. The patients in the control group were cured with rivaroxaban anticoagulation after operation, and the study group was cured with dynamic monitoring of D-dimer on the basis of the control group. The incidence of postoperative DVT, pulmonary embolism (PE), and bleeding complications (incision ecchymosis and bleeding events) were compared. The related indexes such as drainage volume and blood transfusion volume were compared. The levels of activated partial prothrombin time (APPT), prothrombin time (PT), and D-dimer were dynamically monitored before and after operation. Visual analogue scale (VAS) was adopted to assess the degree of postoperative incision pain, the level of limb swelling before and after operation was measured, the circumference difference of affected limb was calculated, the ecchymosis area was assessed in the form of nine-palace grid, and the scores were compared. Results According to the comparison of VAS score, there exhibited no remarkable difference before operation and on the first day after operation, but the VAS score decreased after operation, and the VAS score of the study group on the 3rd day, 7th day, and 14th day after operation was remarkably lower compared to the control group (P < 0.05). There exhibited no remarkable difference in drainage volume (P > 0.05), but the blood transfusion volume and total blood loss in the study group were remarkably lower (P < 0.05). There exhibited no remarkable difference in the level of PT on the 3rd day before operation and on the 3rd day after operation, but on the 7th day and 14th day after operation, the level of PT in the study group was remarkably higher (P < 0.05). The level of PT in the study group was remarkably higher (P < 0.05). There exhibited no remarkable difference in the level of APPT on the 3rd day before operation and on the 3rd day after operation, but on the 7th day and 14th day after operation, the level of APPT in the study group was remarkably higher (P < 0.05). The level of APPT in the study group was remarkably higher (P < 0.05). There exhibited no remarkable difference in the level of plasma D-dimer before operation (P > 0.05). The level of plasma D-dimer in the study group was lower (P < 0.05). In terms of the postoperative ecchymosis area score, the ecchymosis area score decreased remarkably after operation. Furthermore, the ecchymosis area score of the study group was remarkably lower (P < 0.05). In terms of the swelling degree of the affected limb, there exhibited no remarkable difference in thigh circumference and calf circumference before operation (P > 0.05), but after operation, the thigh circumference difference and calf circumference difference decreased, and the thigh circumference difference and calf circumference difference in the study group were lower (P < 0.05). The incidence of DVT in the study group was 16.67%, while that in the control group was 38.10%. No PE occurred in the two groups at the early stage after operation. There were 3 cases of incision ecchymosis, 1 case of bleeding event (incision oozing) in the study group, 11 cases of incisional ecchymosis, and 2 cases of bleeding event in the control group. In 3 patients with incisional bleeding, there were no obvious abnormalities in routine blood examination and blood coagulation indexes. The patients were given wound pressure bandaging and stopped using anticoagulants and changing wound dressings every day, all of which disappeared within 5 days. The incidence of early postoperative DVT and bleeding complications in the study group was lower (P < 0.05). Conclusion Rivaroxaban combined with D-dimer dynamic monitoring has high clinical value in preventing DVT after knee arthroplasty and can effectively reduce the amount of blood loss during operation and the incidence of postoperative DVT, PE, and bleeding complications, which is worth popularizing to reduce the area of ecchymosis and the degree of pain after operation and shorten the recovery process.

Efficacy and Safety of Lactobacillus reuteri CCFM1040 in Allergic Rhinitis and Asthma: A Randomized, Placebo-Controlled Trial.

The coexistence of allergic rhinitis (AR) and asthma reinforces the concept of “one airway, one disease,” which has prompted the exploration for a single intervention to treat both diseases. Lactobacillus reuteri CCFM1040 (CCFM1040) was found to be an inhibitor of the common pathogenesis of AR and asthma in our previous studies. This study presented a randomized, placebo-controlled trial to investigate the clinical effects of CCFM1040 on both diseases. The total symptom score (TSS), the quality of life (QoL), and the modulation in the gut microbiota of patients with AR, the Asthma Control and Test (ACT) of patients with asthma, and the safety of both AR and asthma were measured. In patients with AR, CCFM1040 numerically decreased TSS, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), 3 nasal scores in TSS (nasal congestion, watery eyes, and rhinorrhea), and sleep and significantly improved (P = 0.014) non-nose/eye symptoms. The ACT score was numerically increased in patients with asthma (from partially controlled to well-controlled). Significant microbial (from class level to genus level) and metabolic differences (P < 0.05) were found in patients with AR. No adverse reactions were observed. No effect on the blood and urine routine indexes. CCFM1040 has a potential benefit on both diseases. Further studies based on these findings will help to optimize the management of AR and asthma.