Blood Routine Indexes Research Articles

Research on early warning of renal damage in hypertensive patients based on the stacking strategy

BackgroundAmong the problems caused by hypertension, early renal damage is often ignored. It can not be diagnosed until the condition is severe and irreversible damage occurs. So we decided to screen and explore related risk factors for hypertensive patients with early renal damage and establish the early-warning model of renal damage based on the data-mining method to achieve an early diagnosis for hypertensive patients with renal damage.MethodsWith the aid of an electronic information management system for hypertensive out-patients, we collected 513 cases of original, untreated hypertensive patients. We recorded their demographic data, ambulatory blood pressure parameters, blood routine index, and blood biochemical index to establish the clinical database. Then we screen risk factors for early renal damage through feature engineering and use Random Forest, Extra-Trees, and XGBoost to build an early-warning model, respectively. Finally, we build a new model by model fusion based on the Stacking strategy. We use cross-validation to evaluate the stability and reliability of each model to determine the best risk assessment model.ResultsAccording to the degree of importance, the descending order of features selected by feature engineering is the drop rate of systolic blood pressure at night, the red blood cell distribution width, blood pressure circadian rhythm, the average diastolic blood pressure at daytime, body surface area, smoking, age, and HDL. The average precision of the two-dimensional fusion model with full features based on the Stacking strategy is 0.89685, and selected features are 0.93824, which is greatly improved.ConclusionsThrough feature engineering and risk factor analysis, we select the drop rate of systolic blood pressure at night, the red blood cell distribution width, blood pressure circadian rhythm, and the average diastolic blood pressure at daytime as early-warning factors of early renal damage in patients with hypertension. On this basis, the two-dimensional fusion model based on the Stacking strategy has a better effect than the single model, which can be used for risk assessment of early renal damage in hypertensive patients.

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.

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.

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.

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.

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.

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.

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.

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.

Discrimination of TCM constitutions by biochemical and routine urine indexes

To investigate whether the specific traditional Chinese medicine (TCM) constitution of individuals can be defined by certain biological indexes instead of answering the questionnaire, and to explore the possibility of discriminating nine TCM constitutions from each other simultaneously using biological indexes. Blood and urine samples from 152 individuals with nine TCM constitutions were collected, and the related biological indexes were analyzed combining ANOVA, multiple comparison, discriminant analysis, and support vector machine. We found that 4 out of 24 blood routine indexes, 7 out of 10 urine routine indexes, and 12 out of 32 biochemical indexes showed differences among the constitutions. High-sensitivity C-reactive protein, apolipoprotein A1, and alkaline phosphatase were potential candidates for screening out individuals with unbalanced constitutions. Combining uric acid, high-density lipoprotein, apolipoprotein A1, creatine kinase, total protein, aspartate aminotransferase, total bile acid, dehydrogenase, sodium, and calcium levels had the potential to directly distinguish the nine TCM constitutions from each other. Among these indexes, the highest ratio of discriminant analysis between two constitutions was 95.5%, while the lowest was 66.1%. Our results suggest that some biochemical and urine indexes are related to various TCM constitutions, and thus they have the potential to be used for TCM constitution classification.

Purification of novel polypeptides from bee pupae and their immunomodulatory activityin vivo andin vitro

Edible insects have been proposed as an understudied food whose cultivation could be increased with global population growth. However, the bioactivators and bioactivities of bee pupae are poorly studied. In this paper, the active ingredients of bee pupa powder were analysed, and novel bee pupa polypeptides (BPP) were obtained through protein hydrolysis with alkaline protease. Two purified polypeptide components (BPP-21 and BPP-22) were isolated and purified on a diethylaminoethyl-sepharose fast flow column and a Sephadex G-25 column, and identified using size exclusion chromatography-high performance liquid chromatography and amino acid composition analyses. Due to its higher cell proliferation activity, BPP-22 was selected for further study of its immunomodulatory activity and mechanismin vivo andin vitro. The analysis of immunomodulatory activity showed that BPP-22 significantly increased the body weight growth rate, organ index, macrophage phagocytosis, delayed-type hypersensitivity reaction, cytokine level (interleukin (IL)-2 and interferon (IFN)-γ), immunoglobulin (Ig) levels (IgA, IgG, and IgM), and routine blood indexes in cyclophosphamide-treated immunosuppressed mice (P&lt;0.01). Mechanistic research in RAW264.7 cells showed that BPP-22 might promote the secretion of cytokines (IL-2, tumour necrosis factor-α and IFN-γ) and the production of nitric oxide by increasing homologous mRNA expression and could exert immunomodulatory activity by increasing the phosphorylation of ERK and p38, and modulating the expression of intranuclear transcription factors (EIK-1, MEF-2 and CREB) in the MAPK signalling pathway. These findings are helpful for promoting the application of bee pupae as potential immunomodulatory agents and protein supplements.

The Clinical Efficacy of Double Plasma Molecular Absorption System Combined with Plasma Exchange in the Treatment of Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis.

Objective This study aims to investigate the clinical efficacy of plasma exchange in treating acute-on-chronic liver failure (ACLF) through meta-analysis. Method PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched using a computer for all relevant Chinese and English literature from 2000 to 2021 in each database. At the same time, a large number of related papers and materials were manually consulted. Randomized controlled trials of plasma exchange (PE, control group) and combined double plasma molecular absorption system (DPMAS + PE, observation group) for the treatment of ACLF were collected. Meta-analysis was performed with Stata16.0 software. Result A total of 474 articles were retrieved, and 11 papers were finally included for research after screening. Meta-analysis results showed that the effective rate of treatment in the experimental group was significantly higher than that in the control group. At the same time, the observation group's prothrombin activity (PTA) level was better than that of the control group after treatment. After treatment, there was no significant difference in prothrombin time (PT) and international normalized ratio (INR) between the two groups. In addition, after treatment, the alanine aminotransferase (ALT) level of the observation group was significantly lower than that of the control group. However, TBIL levels and albumin (ALB) levels did not change significantly between the two groups. Regarding blood routine indexes, there were no significant changes in creatinine (Cr) levels and platelet counts (PLT) in the two groups after treatment, but hemoglobin (HGB) levels in the observation group were significantly lower than those in the control group. Conclusion DPMAS combined with plasma exchange therapy can improve liver function, coagulation function, and blood routine level of ACLF patients and increase the effective rate of treatment. It is an effective treatment for acute-on-chronic liver failure.

Metabolomic strategies and biochemical analysis of the effect of processed Rehmanniae radix extract on a blood-deficient rat model

BackgroundRehmanniae Radix (RR), an herb with numerous pharmacological effects, is widely used in traditional Chinese medicine for the treatment of blood deficiency syndrome, either alone or in combination with other herbs. However, the mechanism by which processed Rehmanniae Radix (PRR) improves blood enrichment efficacy has not been clearly defined.MethodsUltra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) and biochemical methods were combined to explore the hematopoietic functional mechanisms of PRR on blood deficiency in a rat model, as well as the potential active ingredient for blood enrichment efficacy. The pharmacological effects of PRR were evaluated on a rat blood deficiency model induced by cyclophosphamide in combination with 1-acetyl-2-phenylhydrazine. The blood routine index, including white blood cell (WBC), red blood cell (RBC), and platelet (PLT) counts, as well as hemoglobin (HGB) level, and the changing metabolite profile based on urine and serum were assessed. Nontargeted metabolomic studies, combined with biochemical analyses, were employed to clarify pharmacological mechanisms.ResultsPRR significantly increased the blood routine index levels and reversed the levels of SOD, GSH, and ATP. The PRR group was similar to the control group, as determined from the metabolic profile. All of the 60 biomarkers, representing the typical metabolic characteristics of the blood-deficient rat model, mainly involved energy metabolism dysfunction, the peripheral circulation system, and oxidative damage in the body. This improvement may be attributed to changes in polysaccharide and sixteen non-polysaccharide compounds in PRR, which were caused by processing RR with rice wine.ConclusionsThe strategies of integrated metabolomic and biochemical analyses were combined, revealing the biological function and effective mechanism of PRR.

Huang Bai Jian Pi decoction alleviates diarrhea and represses inflammatory injury via PI3K/Akt/NF-κB pathway: In vivo and in vitro studies

Ethnopharmacological relevanceHuang Bai Jian Pi (HBJP) decoction, a Chinese herbal formula based on the Pulsatilla decoction (PD) and Si Junzi decoction, is efficacy to treat clinical diarrhea in calves. Aim of the studyThe mechanism of HBJP decoction to treat calf diarrhea remains unclear. This study was to investigate the therapeutic effect and anti-inflammatory mechanism of HBJP decoction on diarrhea in rats. Materials and methodsThirty-six Sprague Dawley rats were randomly divided into control group, model group, PD group and three treated groups with HBJP decoction. The diarrheal model in rats was established by multiple factors including high-sugar and fat diet, high temperature and dampness environment, biological pathogenic factors. The diarrheal animals were treated with HBJP decoction or PD for 5 days. The inflammatory model of the intestinal epithelioid cell line 6 (IEC-6) was induced by TNF-α. The clinical symptoms, blood routine and biochemistry parameters, histopathology of main organs were detected. The proteins associated with PI3K/Akt/NF-κB pathway and the expression levels of cytokines associated with inflammation were detected in vivo and in vitro by Western blot and ELISA. ResultsThe model rats showed obvious diarrheal symptoms, and the obvious systemic inflammatory response accompanied with abnormal change in blood routine, biochemistry parameters and histopathology. HBJP decoction alleviated obviously the clinical symptoms, and pathological changes of the liver, colon and lung, and abnormal blood routine and biochemistry indexes in rats. The expression of P-PI3K, P-Akt, P–NF-κB, IL-1β, IL-6 was significantly increased, and the expression of IL-10 was markedly decreased in diarrheal rats and IEC-6 with inflammation. HBJP decoction significantly inhibited the PI3K/AKT/NF-κB signal pathway and adjusted the expression of these inflammatory cytokines. ConclusionsThe finding suggested that HBJP decoction alleviate the inflammation in diarrhea through inhibiting the PI3K/Akt/NF-κB signal pathway, which provides scientific evidences for the clinical application of HBJP decoction in diarrhea.

Quality Analysis of Autologous Platelet-Rich Plasmapheresis.

To summarized the technology of autologous platelet-rich plasmapheresis and analyzed the product quality, in order to provide safe and effective product guarantee service for clinical treatment. Technical parameters were set according to patient age, weight, height, and preoperative routine blood indices. Autologous platelet-rich plasma (PRP) was collected, and the product quality and adverse reactions of patients were statistically analyzed. Autologous PRP had platelet (PLT), white blood cell (WBC), and red blood cell (RBC) counts of (1250.26 ± 435.88) × 109/L, (1.19 ± 1.95) × 109/L, and (0.05 ± 0.04) × 1012/L, respectively. The PLT enrichment ratio in PRP was 5.66 ± 1.66. There was no significant difference in PLT, RBC, WBC, or hematocrit before and after apheresis (P > 0.05). The incidence of adverse reactions was 8%, and all were mild. When clinical patients use PRP in the treatment of diseases, autologous platelet-rich plasmapheresis technology was used to apheresis PRP, which has good product quality and few adverse reactions, and thus can be adopted more widely.

Association of variants m.T16172C and m.T16519C in whole mtDNA sequences with high altitude pulmonary edema in Han Chinese lowlanders

BackgroundHigh altitude pulmonary edema (HAPE) is a hypoxia-induced non-cardiogenic pulmonary edema that typically occurred in un-acclimatized lowlanders, which inevitably leads to life-threatening consequences. Apart from multiple factors involved, the genetic factors also play an important role in the pathogenesis of HAPE. So far, researchers have put more energy into the nuclear genome and HAPE, and ignored the relationship between the mitochondrion DNA (mtDNA) variants and HAPE susceptibility.MethodsWe recruited a total of 366 individuals including 181 HAPE patients and 185 non-HAPE populations through two times. The first time, 49 HAPE patients and 58 non-HAPE individuals were performed through whole mtDNA sequences to search the mutations and haplogroups. The second time, 132 HAPE patients and 127 non-HAPE subjects were collected to apply verifying these mutations and haplogroups of mtDNA with the routine PCR method.ResultsWe analyzed and summarized the clinical characteristics and sequence data for the 49 HAPE patients and 58 non-HAPE individuals. We found that a series of routine blood indexes including systolic arterial blood pressure (SBP), heart rate (HR), white blood cell (WBC), and C-reactive protein (CRP) in the HAPE group presented higher and displayed significant differences compared with those in the non-HAPE group. Although the average numbers of variants in different region and group samples were not statistically significant (P > 0.05), the mutation densities of different regions in the internal group showed significant differences. Then we found two mutations (T16172C and T16519C) associated with the HAPE susceptibility, the T16172C mutation increased the risk of HAPE, and the T16519C mutation decreased the HAPE rating. Furthermore, the two mutations were demonstrated with 132 HAPE patients and 127 non-HAPE individuals. Unfortunately, all the haplogroups were not associated with the HAPE haplogroups.ConclusionsWe provided evidence of differences in mtDNA polymorphism frequencies between HAPE and non-HAPE Han Chinese. Genotypes of mtDNA 16172C and 16519C were correlated with HAPE susceptibility, indicating the role of the mitochondrial genome in the pathogenesis of HAPE.

Predictive and Prognostic Role of Peripheral Blood T-Cell Subsets in Triple-Negative Breast Cancer.

BackgroundTriple-negative breast cancer (TNBC), as a highly aggressive and metastatic tumor, can still not contain the medical needs. It has become an urgent problem to develop prognostic markers further and realize precision medicine. The predictive and prognostic significance of peripheral blood lymphocytes, as well as the clinicopathological factors affecting them, were explored in the present study.MethodsThe clinicopathological data of 278 patients with TNBC were collected and analyzed retrospectively. Peripheral blood lymphocytes (pBL) and blood routine indexes before treatment were quantified by flow cytometry analysis. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier curve and Cox hazard proportion regression model. The associations between hematologic parameters and treatment response and clinicopathological characteristics were estimated by the Mann-Whitney test and Spearman test.ResultsCompared with all blood routine indexes, only a significant correlation between better treatment efficacy and higher peripheral CD4 +/CD8 + ratio of TNBC patients was observed (P=0.059), particularly those treated with chemotherapy combined with immune checkpoint inhibitors (P=0.048). Among the pBL subsets, CD4 + T lymphocyte was the only independent factor that could predict the prognosis of metastatic TNBC. Patients presenting higher values of peripheral CD4 + T lymphocytes showed longer PFS (median PFS 9 months vs. 5 months; HR =0.65, 95%CI: 0.440-0.973, P = 0.032) and OS (median OS 31 months vs. 16 months; HR=0 .63, 95%CI: 0.417-0.940, P< 0.01). Especially CD4+ was found predictive for prognosis in TNBC patients who received chemotherapy (P<0.05). Finally, the older age, higher clinical stage, and more advanced treatment lines were related to the lower level of CD4 +. The older age and having received neoadjuvant therapy were related to the lower CD4 +/CD8 + ratio (P<0.05).ConclusionThe baseline CD4+/CD8+ cell ratio in peripheral blood is associated with therapeutic response, especially for chemotherapy combined with immunotherapy. Peripheral CD4+ cells can steadily predict all clinical outcomes for patients with mTNBC, and this clinical prognosis prediction is significantly related to chemotherapy. Peripheral CD4+ and CD4+/CD8+ are both closely associated with clinicopathological parameters.