Different subsets of haematopoietic cells and immune cells in bone marrow between young and older donors.

Young donors are reported to be associated with better transplant outcomes than older donors in allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the mechanism is still unclear. The current study compared the different subsets of haematopoietic stem cells (HSCs) and their progenitors as well as immune cells in bone marrow (BM) between young and older donors. The frequencies of HSCs, multipotent progenitors (MPPs) and myeloid progenitors, including common myeloid progenitors (CMPs) and megakaryocyte-erythroid progenitors (MEPs), were decreased, whereas those of lymphoid progenitors, including multi-potent lymphoid progenitors (MLPs) and common lymphoid progenitors (CLPs), were increased in the BM of young donors compared with in that of older donors. Lower reactive oxygen species (ROS) levels were observed in BM HSCs and six progenitor lines in young donors. Furthermore, young donors demonstrated higher frequencies of naive T cells and immune suppressor cells, such as alternative macrophages (M2) and lower frequencies of memory T cells and immune effectors, including T helper-1 and T cytotoxic-1 cells, in BM than older donors. Multivariate analysis demonstrated that donor age was independently correlated with BM HSC frequency. Although further validation is required, our results suggest that the differences in the frequency and immune differentiation potential of HSCs in BM between young donors and older donors may partly explain the different outcomes of allo-HSCT.

Gingko biloba extract EGB761 alleviates heat-stress damage in chicken heart tissue by stimulating Hsp70 expression in vivo in vascular endothelial cells.

1. This study aimed to investigate the protective effects of Gingko biloba extract EGB761 on heat-stressed chicken heart in vivo and its underlying relevance to Hsp70.2. A total of 50 one-day-old female chicks were randomly divided into five groups: control (Con), heat-stress (HS), 0.1% EGB761 plus heat-stress (0.1%EGB+HS), 0.3%EGB761 plus heat-stress (0.3%EGB+HS) and 0.6%EGB761 plus heat-stress (0.6%EGB+HS) groups. After administration of EGB761 for 45 days, the chickens in each group were exposed to a single heat-stress event at 38 ± 1°C for 3 h.3. EGB761 attenuated the abnormal symptoms and pathological scores of myocardium of heat-stressed chickens. Despite a reduction in the transcription and translation of the Hsp70 gene in heat-stressed myocardium, EGB761 induced the expression of Hsp70 in endothelial cells of the microarteries and venules into the blood, and reduced heat-stress damage in vascular endothelial cells.4. Supplementation with EGB761 before heat-stress exposure protected chicken myocardium from damage by increasing serum Hsp70 protein from myocardial cells and cardiac microvascular endothelial cells and protected the microvascular system from adverse injury.

Human papillomavirus infection and colorectal cancer in the Chinese population: a meta-analysis.

AIM: Human papillomavirus (HPV) infection has been reported in colorectal cancer in many studies. We conducted a meta-analysis to assess the association between HPV infection and colorectal cancer/adenomas in the Chinese population. METHOD: Relevant studies up to January 2018 were searched in PubMed, EMBASE, China National Knowledge Infrastructure and the Wanfang database. We used a random effects model to determine the prevalence of HPV and odds ratios (ORs) with 95% confidence intervals (CIs). The I2 statistic and P-value from the Cochrane Q-test were used to describe the heterogeneity. RESULTS: Ten case-control studies involving 766 colorectal cancer patients and 470 controls were included in the meta-analysis. Among the colorectal cancer patients, the pooled prevalence was 0.45 (95% CI 0.36-0.53). The pooled estimate for OR was 10.78 (95% CI 4.22, 27.53). Among the 193 patients with colorectal adenoma, the pooled prevalence and OR were 0.31 (95% CI 0.24-0.37) and 2.03 (95% CI 0.79, 5.26), respectively. The prevalence of HPV 16 and HPV 18 among HPV-positive cancers ranged from 57.9% to 100% and 0% to 39.7%, respectively. CONCLUSION: The results indicated that HPV infection, especially HPV 16 and HPV 18, is associated with colorectal cancer in the Chinese population.

CTLA-4 polymorphisms and haplotype correlate with survival in ALL after allogeneic stem cell transplantation from related HLA-haplotype-mismatched donor.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been established as an effective treatment for patients with hematological malignancies. Disease relapse remains a major cause of transplant failure. T cell homeostasis is critical to determine the potency of the GVT effect. Recent studies have shown the association of the CTLA-4 polymorphisms with the outcome after HLA-identical sibling allogeneic HSCT. METHODS: In this study, we focused on four CTLA-4 polymorphisms, and analyzed the impact of donor genotypes and haplotypes on the conditions of 152 acute leukemia patients (ALL 83) after related HLA-haplotype- mismatched transplantation. The four SNP genotypes (-1661, -318, CT60 and +49) were determined by TaqMan SNP genotyping assays. RESULTS: ALL recipients of donors with +49 GG showed significantly lower OS (67.7 vs. 90.3 %, P = 0.015) than those with GA+AA. Multivariate analyses showed that +49 GG was an independent risk factor for OS (HR: 0.306, 95 % CI 0.111-0.842, P = 0.022) .23 ALL patients receiving mDLI showed significantly lower OS with +49 GG donor than those with GA+AA (30.0 vs. 83.1 %, P = 0.003). The haplotype analysis revealed only three haplotypes in the donor population -1661/-318/CT60/+49 i.e., ACGG, ACAA and GTGA, the frequencies were 64.1, 19.4 and 16.5 %, respectively. Donors with and without the ACGG/ACGG haplotype had the same effect on transplant outcomes as those with +49 GG and +49 GA+AA. CONCLUSION: In summary, the CTLA-4 +49 GG and the haplotype ACGG/ACGG reduced the overall survival in ALL after allo-HSCT from the related HLA-haplotype-mismatched donor, knowledge of the CTLA-4 polymorphism and haplotype may provide useful information for donor selection and individual application of immunosuppressive agents and immunotherapy.

CD8(+) T cells with distinct cytokine-producing features and low cytotoxic activity in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: CD8(+) T cells are important effectors of cell-mediated immunity; however, their contribution to the pathogenesis of CRS is unclear. OBJECTIVE: This study aimed to characterize the cytokine-producing features and cytotoxic activity of CD8(+) T cells, and their correlation with inflammation patterns in CRS with nasal polyps. METHODS: The expression of IFN-γ, IL-4, IL-5, IL-17A, forkhead box P3 (FOXP3), perforin, and granzyme B in CD8(+) T cells was studied by means of flow cytometry, immunohistochemistry, and immunofluorescence. The expression of CD8(+) T-cell subset relevant chemokines and chemokine receptors was detected by means of real-time RT-PCR or ELISA. The cytotoxic activity of sorted CD8(+) T cells was defined by anti-CD3-redirected killing assay. RESULTS: Compared with controls, elevated percentages of total CD8(+) T cells and cytotoxic T lymphocyte (Tc) 1 (IFN-γ(+) ), Tc2 (IL-4(+) ), and Tc17 (IL-17A(+) ) cell subset, and decreased percentages of FOXP3(+) CD8(+) regulatory T cells, were found in both eosinophilic and non-eosinophilic polyps with a Tc2-skewed and Tc1/Tc17-dominated response in eosinophilic and non-eosinophilic polyps, respectively. Nasal CD8(+) T cells were found to produce similar or even higher levels of IFN-γ and IL-4 compared with CD4(+) T cells. Tc1 and Tc17, and Tc2 (IL-4(+) and IL-5(+) ) cell subset percentages positively correlated with neutrophil and eosinophil counts in sinonasal mucosa, respectively. Strikingly, the expression of perforin and granzyme B and cytotoxic activity were significantly reduced in nasal CD8(+) T cells compared with their counterparts in peripheral blood. The expression of CXCL16, CCL17, and CCL20 positively correlated with Tc1, Tc2, and Tc17 cell subset number in sinonasal mucosa, respectively. CONCLUSION AND CLINICAL RELEVANCE: CD8(+) T cells have low cytotoxic activity; nevertheless, they are a significant and previously underappreciated source of inflammatory cytokine production in polyps. Different Tc cell subset domination may contribute to distinctly biased granulocyte inflammation in eosinophilic and non-eosinophilic polyps.

Under-recognized pertussis in adults from Asian countries: a cross-sectional seroprevalence study in Malaysia, Taiwan and Thailand.

Surveillance data on the burden of pertussis in Asian adults are limited. This cross-sectional study evaluated the prevalence of serologically confirmed pertussis in adults with prolonged cough in Malaysia, Taiwan and Thailand. Adults (⩾19 years) with cough lasting for ⩾14 days without other known underlying cause were enrolled from outpatient clinics of seven public and/or private hospitals. Single blood samples for anti-pertussis toxin antibodies (anti-PT IgG) were analysed and economic impact and health-related quality of life (EQ-5D) questionnaires assessed. Sixteen (5·13%) of the 312 chronically coughing adults had serological evidence of pertussis infection within the previous 12 months (anti-PT IgG titre ⩾62·5 IU/ml). Three of them were teachers. Longer duration of cough, paroxysms (75% seroconfirmed, 48% non-seroconfirmed) and breathlessness/chest pain (63% seroconfirmed, 36% non-seroconfirmed) were associated with pertussis (P < 0·04). Of the seroconfirmed patients, the median total direct medical cost per pertussis episode in public hospitals (including physician consultations and/or emergency room visits) was US$13 in Malaysia, US$83 in Taiwan (n = 1) and US$26 in Thailand. The overall median EQ-5D index score of cases was 0·72 (range 0·42-1·00). Pertussis should be considered in the aetiology of adults with a prolonged or paroxysmal cough, and vaccination programmes considered.

Late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation: prognostic factors and treatments.

BACKGROUND: In this study, we aimed to evaluate the prognostic factors associated with and treatments for late-onset severe pneumonia (LOSP) in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Fifty consecutive patients who underwent non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and met the criterion of LOSP after allo-HSCT were enrolled. RESULTS: The median time from allo-HSCT to the occurrence of LOSP was 231 (90-1487) days. Twenty-eight patients harbored 1 or more pathogens (infectious LOSP, I-LOSP), whereas 22 did not harbor any pathogens (non-infectious LOSP, NI-LOSP). The 100-day survival rate of LOSP patients was 31.1%. Patients smoking before allo-HSCT (0% vs. 35.4%, P = 0.002) and male gender (20.0% vs. 61.9%, P = 0.026) had lower 100-day survival rate. Patients with a lower bronchoalveolar lavage fluid (BALF) neutrophil percentage had higher 100-day survival rate relative to those with higher BALF neutrophil percentage (45.5% vs. 16.7%, P = 0.012). The 100-day survival rate of patients with I-LOSP was lower than that of patients with NI-LOSP (19.1% vs. 46.9%, P = 0.043). Patients given late (≥1 week after LOSP diagnosis) and low-dose methylprednisolone (MP) therapy (≤2 mg/kg/day) had the best 100-day survival rate. In the multivariate analysis, nonsmoking before allo-HSCT and late and low-dose MP therapy were significantly associated with a better survival after LOSP. CONCLUSION: LOSP is a severe complication after allo-HSCT. The correct timing and corticosteroid dosage in the context of broad-spectrum antimicrobial therapy might further improve the outcomes of patients with LOSP.

Changes in erectile organ structure and function in a rat model of chronic prostatitis/chronic pelvic pain syndrome.

There is a growing recognition of the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED); however, most of the reports are based on questionnaires which cannot distinguish between organic and functional ED. The purpose of this study was to determine the exact relationship between CP/CPPS and ED, and to investigate the changes in erectile organ structure and function in a rat model of CP/CPPS. We established a rat model of experimental autoimmune prostatitis (EAP), which is a valid model for CP/CPPS. Erectile function in EAP and normal rats was comparable after cavernous nerve electrostimulation. The serum testosterone and oestradiol levels, ultrastructure of the corpus cavernosum and expression of endothelial nitric oxide synthase and neuronal nitric oxide synthase in the two groups were similar; however, there was a decrease in smooth muscle-to-collagen ratio and alpha-smooth muscle actin expression and an increase in transforming growth factor-beta 1 expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats. We speculate that ED complained by patients with CP/CPPS may be psychological, which could be caused by impairment in the quality of life; however, further studies are needed to fully understand the potential mechanisms underlying the penile fibrosis in EAP rats.

Changes in hematological parameters in α-thalassemia individuals co-inherited with erythroid Krüppel-like factor mutations.

Phenotypic variations in α-thalassemia mainly depend on the defective α-globin gene number. Genetic modifiers of the phenotype of Hemoglobin H (HbH) disease were poorly reported, apart from ß-thalassemia allele that was identified ameliorating the severity of α-thalassemia. Because erythroid Krüppel-like factor (KLF1) mutations can modulate the red blood phenotype, we evaluated its effect on the α-thalassemia phenotype. Overall, we identified 72 subjects with five different KLF1 heterozygous mutations in 1468 individuals, including 65 out of 432 α-thalassemia carriers with fetal hemoglobin (HbF) levels ≥1%, 0 out of 310 carriers with HbF levels <1% and 7 out of 726 HbH disease patients. We firstly established the link between KLF1 mutations and relatively elevated hemoglobin A2 (HbA2 ) and HbF levels, along with lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) values in a group of α-thalassemia carriers. However, we concluded that KLF1 mutations were not significantly linked to HbH disease severity. On the basis of HBA or HBB genotype and gender, clinical severity of patients with HbH disease was correctly predicted in 73.3% cases. It may improve the screening and diagnostic assessment of α-thalassemia.

Detection of human cytomegalovirus (CMV) DNA in feces has limited value in predicting CMV enteritis in patients with intestinal graft-versus-host disease after allogeneic stem cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) enteritis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is difficult to diagnose. We aimed to evaluate the sensitivity and specificity of the detection of CMV DNA in feces for predicting CMV enteritis. METHODS: HSCT patients with intestinal graft-versus-host disease (GVHD) were enrolled if they met the following criteria: (i) underwent a colonoscopy and (ii) peripheral blood and feces specimens were available for CMV DNA detection within 24 h of colonoscopy. The colonoscopy histology was used as the gold standard for diagnosing CMV enteritis. RESULTS: Fifty-six patients underwent 58 colonoscopy examinations, and 7 were diagnosed as having CMV enteritis. Within 24 h of colonoscopy, 9 patients had detectable CMV in the feces and 19 patients had detectable CMV in the plasma, respectively. In the 7 patients with CMV enteritis, only 2 had detectable CMV in the stool, resulting in a sensitivity of 28.6%. In the 51 patients without CMV enteritis, 44 had no detectable CMV in the stool, with a specificity of 86.3%. CONCLUSION: We concluded that CMV detection in the feces was not a good predictor of CMV enteritis in patients with intestinal GVHD after allo-HSCT.

HLA and KIR genotyping correlates with relapse after T-cell-replete haploidentical transplantation in chronic myeloid leukaemia patients.

BACKGROUND: Conflicting results have been reported regarding the predicative roles of alloreactive natural killer (NK) cells on the outcomes of transplantation in leukaemia patients. METHODS: We prospectively analysed the human leukocyte antigen (HLA) typing of donor-recipient pairs and the KIR typing of the donors in 97 CML patients to address the predictive roles of NK cells in relapse undergoing T-cell-replete haploidentical transplantation. RESULTS: Patients with class I ligands for the donor-inhibitory KIR gene exhibited decreased molecular and haematologic relapse rates (P=0.003 and P=0.015, respectively). There was a significantly reduced risk of molecular and haematologic relapse in patients with HLA-C1C2 or C2C2 who accepted donors with KIR2DS1 or in patients with HLA-Bw4 who accepted donors with KIR3DS1 ('recipient with relevant KIR ligand for donor-activating KIR', n=25), compared with the remaining transplants (n=72, P=0.009 and P=0.009, respectively). In addition, the presence of class I ligand in the recipients of donor-activating KIR contributed to a decreased relapse rate in patients lacking class I ligand in the recipient of donor-inhibitory KIR (P=0.04 and P=0.03, respectively). CONCLUSIONS: This study suggests that the presence of class I ligands for the donor-activating or donor-inhibitory KIR gene in the recipient might confer some protection against leukaemic relapse in T-cell-replete haploidentical transplantation.

CYP2C9 polymorphism analysis in Han Chinese populations: building the largest allele frequency database.

Genetic polymorphisms of CYP2C9 significantly influence the pharmacokinetics and pharmacodynamics of some drugs, which might result in adverse drug effects and therapeutic failure. Several studies have been performed on CYP2C9 genetic polymorphisms in Han Chinese populations. However, these studies only focused on two commonly investigated alleles, *2 and *3, in relatively small sample sizes. To scale up the gene-scanning region and determine relatively precise data on the genetic distribution pattern in Chinese populations, unrelated healthy Han Chinese volunteers from Zhejiang Province (n=1127) and Hebei (n=1000) Province were recruited as subjects for the direct sequencing of all exons of CYP2C9. As a result, 14 previously reported alleles were detected in this work, and 8 of these alleles (*14, *16, *19, *23, *27, *29, *33 and *34) were described for the first time in Chinese populations. In addition, 37 novel mutations were also detected, of which 22 variants were non-synonymous, and 21 new alleles, *36-*56, were designated by the Human CYP Allele Nomenclature Committee. In vitro functional analysis of these 22 novel CYP2C9 variants revealed that 17 mutations had a significant influence on the protein's catalytic activity. Our study provides the most accurate data on CYP2C9 polymorphisms in Han Chinese populations and detects the largest number of novel allelic variants existing to date. These new alleles will greatly enrich the current knowledge of naturally occurring CYP2C9 variants in Chinese populations.

Oridonin inhibits tumor growth in glioma by inducing cell cycle arrest and apoptosis.

Glioma is the most common malignant intracranial tumors. Despite newly developed therapies, these treatments mainly target oncogenic signals, and unfortunately, fail to provide enough survival benefit in both human patients and mouse xenograft models, especially the first-generation therapies. Oridonin is purified from the Chinese herb Rabdosia rubescens and considered to exert extensive anti-cancer effects on human tumorigenesis. In this study, we systemically investigated the role of Oridonin in tumor growth and the underlying mechanisms in human glioma. We found that Oridonin inhibited cell proliferations in a dose- and time-dependent manner in both glioma U87 and U251 cells. Moreover, these anti-cancer effects were also confirmed in a mouse model bearing glioma. Furthermore, cell cycle arrest in S phase was observed in Oridonin-mediated growth inhibition by flow cytometry. Cell cycle arrest in S phase led to eventual cell apoptosis, as revealed by Hoechst 33342 staining and annexin V/PI double-staining. The cell apoptosis might be accomplished through a mitochondrial manner. In all, we were the first to our knowledge to report that Oridonin could exert anti-cancer effects on tumor growth in human glioma by inducing cell cycle arrest and eventual cell apoptosis. The identification of Oridonin as a critical mediator of glioma growth may potentiate Oridonin as a novel therapeutic strategies in glioma treatments.

Mutations of flagellar genes fliC12, fliA and flhDC of Edwardsiella tarda attenuated bacterial motility, biofilm formation and virulence to fish.

AIMS: The aim of this study was to investigate functions of flagellar genes fliC2, fliC12, fliA and flhDC in a bacterial fish pathogen Edwardsiella tarda. METHODS AND RESULTS: In this study, functions of flagellar genes, fliC2, fliC12 (fliC1 + fliC2), fliA and flhDC (flhD + flhC) of Edw. tarda H1 were analysed by constructing in-frame deletion mutants respectively and complementary strains fliC2(+) and fliA(+) . Electron microscopy revealed that in-frame deletion of fliC12, fliA and flhDC significantly impaired the number and length of flagellar filaments, resulting in loss of both swimming and swarming motilities of the bacteria. In addition, compared to the wild-type strain and complementary strains, the flagellum-impaired mutants exhibited reduced biofilm formation ability, showed decreased ability in adherence and internalization to Epithelioma papulosum cyprini (EPC) cells and reduced pathogenicity to zebrafish. CONCLUSIONS: These results indicated that fliC12, fliA and flhDC of Edw. tarda played essential roles in flagellar filaments structure, bacteria motility, biofilm formation, adherence, internalization and pathogenicity of this bacterium. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed that flagella function in facilitating virulence and it may provide a new target for vaccines against Edw. tarda infection.

Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study.

AIMS: Transformed small cell lung cancer (T-SCLC) is a highly aggressive clinical disease with a notably poor prognosis. It most often arises from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) following treatment. To date, no standard treatment has been established for T-SCLC. Platinum-etoposide was the most commonly used regimen, but progression-free survival remains unsatisfactory. Therefore, there is an urgent unmet need to develop novel and effective strategies for this population. Our study, a multicentre, open-label, single-arm phase II clinical trial (NCT05957510), aims to evaluate the efficacy and safety of serplulimab plus chemotherapy in untreated T-SCLC patients after histological transformation. MATERIALS AND METHODS: In total, 36 eligible participants experiencing SCLC transformation from EGFR-mutant NSCLC will be enrolled to receive combination therapy of serplulimab, etoposide and carboplatin for four to six cycles, followed by maintenance therapy with serplulimab for up to 2 years. The primary endpoint is progression-free survival; secondary endpoints include objective response rate, overall survival and safety. RESULTS: Enrolment started in July 2023 and is ongoing, with an estimated completion date of December 2025. CONCLUSIONS: This study aims to provide valuable insights into the efficacy and safety of combining serplulimab with chemotherapy for treating patients with T-SCLC originating from EGFR-mutant NSCLC.

Invasin of Edwardsiella tarda is essential for its haemolytic activity, biofilm formation and virulence towards fish.

AIMS: The aim of this study was to investigate the role of invasin in a bacterial fish pathogen Edwardsiella tarda. METHODS AND RESULTS: In this study, an in-frame deletion mutant of invasin (Δinv) in Edw. tarda H1 was constructed through double crossover allelic exchange to explore the function of invasin in virulence to fish. Meanwhile, an invasin overexpression strain (inv(+)) was obtained by electrotransformation of a low-copy plasmid pACYC184 carrying the intact invasin into the Δinv mutant. Several virulence-associated characters of the mutants and wild-type strain were tested. Compared with the wild-type H1, haemolytic activity and biofilm formation were decreased in Δinv, while increased significantly in inv(+). In addition, the invasin overexpressing strain inv(+) exhibited increased internalization into Epithelioma Papulosum Cyprini (EPC) cells. Moreover, in zebrafish model, Δinv showed decreased virulence compared with H1, while inv(+) restored the virulence of wild type completely. CONCLUSIONS: The results demonstrated that invasin of Edw. tarda plays essential roles in haemolytic activity, biofilm formation, adherence, internalization and pathogenicity of this bacterium. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed the role of invasin in Edw. tarda infection and provided useful information for further unveiling the pathogenesis of Edw. tarda.

Serum N-terminal pro-brain natriuretic peptide level is a significant prognostic factor in patients with severe sepsis among Southwest Chinese population.

BACKGROUND: This study aimed to determine the predictive value of elevated N-terminal pro-brain natriuretic peptide (NTproBNP) for mortality in patients with severe sepsis. PATIENTS AND METHODS: This was a retrospective study in Emergency Department of Sichuan Provincial People's Hospital, and patients were screened between January 1, 2009 and December 31, 2011. Demographic and clinical data as well as Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sepsis Organ Failure Assessment (SOFA) scores were collected within the first day of admission. Survival was determined to establish its association with the NT-proBNP using logistic regression and receiver operating characteristic (ROC) curve. RESULTS: A total of 171 patients with severe sepsis were analyzed. The median APACHE IIⅡ and SOFA scores were 11 (IQR, 7-16) and 3 (IQR, 1-5), respectively. The median C-reactive protein (CRP), procalcitonin (PCT) and NT-proBNP was 10.3 mg/dL (IQR, 3.4-21.4 mg/dL), 0.4 ng/mL (IQR, 0.2-3.6 ng/mL), and 954 (321-1576) pg/mL, respectively. The median NT-proBNP in survivors was 584 pg/mL (IQR, 321-875 pg/mL) versus 1271 (IQR, 851-1576 pg/mL) in nonsurvivors (p < 0.001). In the ROC curves, the area value was 0.89 for serum NT-proBNP, and its potent cutoff value was 1500 pg/mL. After multivariate regression analysis, NT-proBNP was significantly correlated with the mortality of severe sepsis (OR = 1.58, 95% CI 1.36-1.77). CONCLUSIONS: Serum NT-proBNP is frequently increased in severe sepsis patients, and non-survivors have higher levels than survivors. High levels of admission NT-proBNP are associated with mortality.

Comparison of clinical outcomes between posterolateral approach and modified Hardinge approach in salvage total hip arthroplasty after medial buttress plate failure for femoral neck fractures.

OBJECTIVE: The purpose of this study was to investigate the clinical outcomes of salvage total hip arthroplasty (THA) after medial buttress plate surgery for femoral neck fractures via the modified Hardinge approach (MHA) and posterolateral approach (PLA) through a retrospective analysis. PATIENTS AND METHODS: From October 2016 to October 2020, a total of 41 patients with failed femoral neck fractures treated with cannulated screws and medial buttress plates underwent unilateral salvage THA, and a retrospective study was conducted. According to the surgical approach, patients were divided into PLA group and MHA group. Clinical and radiological data were evaluated. The primary outcome indicators were the Pain Visual Analog Scale (VAS) and Hip Harris Score (HHS). Secondary outcome indicators include hemoglobin (HGB), hematocrit (HCT), creatine kinase (CK), creatine kinase-MB (CK-MB), etc. The occurrence of postoperative complications was also recorded. RESULTS: There were no differences in demographic or clinical characteristics before surgery. There were no differences in postoperative HGB, HCT, CK-MB and radiological parameters. The surgical approach had no effect on the hospitalization period. The PLA group had earlier ambulation time, and the serum level of CK was also low. Analysis of the HHS and VAS showed that on postoperative day 3, the PLA group had superior scores. The incidence of complications did not significantly differ between groups. CONCLUSIONS: The posterolateral approach for salvage THA provides better functional recovery with less muscle damage in the early postoperative period.

Correlation research of serum substance P, CCK-8, and 5-HT values with depression levels in stroke survivors.

OBJECTIVE: This study aimed to investigate the correlation of serum octapeptide cholecystokinin-8 (CCK-8), substance P (SP), and 5-hydroxytryptryptamine (5-HT) values with depression levels in patients with post-stroke depression (PSD). It also aimed to explore the potential approach for the early diagnosis of PSD. PATIENTS AND METHODS: A correlation research between patients' biochemical indicators and depression levels was performed among 70 stroke patients during hospitalization from June 2021 to February 2022. The 70 stroke patients were selected and divided into post-stroke depression and non-depression groups according to the Hamilton Depression Scale (HAMD) score. The concentrations of CCK-8, SP, and 5-HT in both groups were measured, and the relationship between the values of CCK-8, SP, 5-HT and the depression levels was analyzed. RESULTS: Among the 70 stroke survivors, 35 were in the depression group and 35 were in the non-depression group. Significant differences were observed in the concentration of CCK-8, SP, and 5-HT between the patients in the depression and non-depression group (p < 0.05). Accompanied by an increase in the depression level, the SP value gradually increased, but the CCK-8 and 5-HT values gradually decreased. Spearman correlation analysis indicated that the order of the correlation between CCK-8, 5-HT, SP, and the depression levels was CCK-8 > SP > 5-HT. CONCLUSIONS: All the CCK-8, SP and 5-HT values were correlated with the depression levels in stroke survivors. Furthermore, the correlation between CCK-8, SP, and post-stroke depression levels was higher than that of 5-HT, suggesting that the early diagnosis of PSD may be reflected more precisely through the detection of CCK-8, and SP values, thus providing potential priority for biochemical detection in the diagnosis of PSD.

Overexpression of mltA in Edwardsiella tarda reduces resistance to antibiotics and enhances lethality in zebra fish.

AIMS: The aim of this study was to investigate the role of membrane-bound lytic murein transglycosylase A (MltA) in a bacterial fish pathogen Edwardsiella tarda. METHODS AND RESULTS: An mltA in-frame deletion mutant (ΔmltA) and an mltA overexpression strain (mltA(+)) of Edw. tarda were constructed through double-crossover allelic exchange and by transformation of a low-copy plasmid carrying the intact mltA into the ΔmltA mutant, respectively. Either inactivation or overexpression of MltA in Edw. tarda resulted in elevated sensitivity to ß-lactam antibiotics and lower viability in oligotrophic or high osmotic environment than wild-type strain. Autolysis induced by EDTA was reduced in ΔmltA strain, while mltA(+) strain was virtually flimsy, indicating that MltA is responsible for the lysis effect. Moreover, mltA(+) strain exhibited significant increases in lipopolysaccharide (LPS) biosynthesis and virulence to zebra fish compared with wild-type strain. CONCLUSIONS: The results indicated that MltA plays essential roles in ß-lactam antibiotics and environmental stresses resistance, autolysis, LPS biosynthesis and pathogenicity of Edw. tarda. This is the first report that MltA has a virulence-related function in Edw. tarda. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provided useful information for further studies on pathogenesis of Edw. tarda.