Improvement of proportion of days covered for denosumab under implementation of clinical pharmacist adherence management system: normal and COVID-19 period.

We established a clinical pharmacist adherence management system (CPAMS) led by clinical pharmacists to examine whether denosumab adherence could be improved. The results showed that CPAMS could effectively improve adherence to denosumab and the treatment of osteoporosis. However, this effect weakened during the spread of infectious diseases such as COVID-19. PURPOSE: Denosumab is currently one of the drugs that can effectively reduce the risk of clinical fracture. However, as a drug requiring long-term subcutaneous injection, patient adherence to denosumab is the most important factor affecting its therapeutic efficacy. Therefore, we established a clinical pharmacist adherence management system (CPAMS) led by clinical pharmacists and examined whether denosumab adherence could be improved. METHODS: Data were collected from patients receiving denosumab in our hospital between March 2021 and May 2022. The patients who participated in the CPAMS were in the intervention group, and the rest were in the control group. We analysed the proportion of days covered (PDC) value of denosumab, distribution of subsequent visits, and proportion of patients who continued participating during the normal and coronavirus (COVID-19) periods. RESULTS: Eighty-five patients were enrolled in this retrospective study: 32 in the intervention group and 53 in the control group. The PDC values were significantly higher in the intervention group (0.9875, 0.9025-1) than in the control group (0.5, 0.5-0.5) after 1 year. The subsequent visit rate in the intervention group was 93.80%. However, none of the patients in the control group returned. In the intervention group, the ratio of timely to delayed subsequent visits was 11:19. After the COVID-19 pandemic, the PDC value of the intervention group (0.957, 0.5-1) was lower than that before COVID-19, and the ratio of timely to delayed subsequent visits was 9:13. CONCLUSIONS: Clinical pharmacist-led CPAMS could effectively improve adherence to denosumab and the treatment of osteoporosis.

Efficacy of early clinical interventions for children with global developmental delay.

OBJECTIVE: To evaluate the efficacy of early clinical interventions for children with global developmental delay. METHODS: A total of 127 initial subjects with GDD met the complete inclusion criteria. Seven cases were excluded due to withdrawal or refusal for follow-up. Eventually, the remaining 120 children were divided into two groups based on different treatment regimens: an experimental group and a control group. Ninety children received individualized treatment in the experimental group, while 30 children, due to various reasons, did not receive inpatient treatment and only underwent home-based intervention therapy in the control group. The developmental progress under different intervention methods was compared, and their clinical effectiveness was analyzed. RESULTS: Both groups of patients showed no significant differences in general characteristics such as gender and age (p > 0.05), demonstrating comparability. The initial comparison of developmental quotient scores in all patients before treatment revealed no significant differences. Post-treatment, there was improvement observed in both groups. However, children in the experimental group exhibited significantly higher scores in gross motor skills, fine motor skills, adaptability, language, and personal-social skills compared to those in the control group (p < 0.05). Additionally, the clinical effective rate in the experimental group was notably higher than that in the control group (p < 0.05). CONCLUSION: The combined use of acupuncture with home-based intervention therapy demonstrates favorable therapeutic outcomes in young children with comprehensive developmental delays. This approach has the potential to enhance gross motor skills, fine motor skills, cognition, language, and overall intellectual development in affected children.

Co-transplantation of umbilical cord mesenchymal stem cells and peripheral blood stem cells in children and adolescents with refractory or relapsed severe aplastic anemia.

To evaluate the co-transplantation efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) and peripheral blood stem cells (PBSCs) as a novel approach for refractory or relapsed severe aplastic anemia (R/R SAA) in children and adolescents, thirty-two children and adolescents diagnosed with R/R SAA underwent a retrospective chart review. The patients were categorized into two groups based on the source of PBSCs: the matched sibling donor (MSD) group and the unrelated donor (UD) group. No adverse events related to UC-MSC infusion occurred in any of the patients. The median time for neutrophil engraftment was 13 days (range: 10-23 days), and for platelets, it was 15 days (range: 11-28 days). Acute GVHD of Grade I-II and moderate chronic GVHD were observed in 21.8 and 12.5% of cases, respectively. No statistically significant differences were found between the MSD and UD groups in terms of engraftment, GVHD, and complications, including infection and hemorrhagic cystitis. The median follow-up time was 38.6 months (range: 1.4-140.8 months). As of October 31, 2021, five patients had succumbed, while 27 (84.4%) survived. The 5-year OS rate showed no statistically significant difference between the MSD and UD groups (84.8 ± 10.0 vs. 82.4 ± 9.2%, p = 0.674). In conclusion, the application of UC-MSCs in the treatment of R/R SAA in PBSC transplantation is reliable and safe, they had no graft rejection, low incidence of severe GVHD which may have been contributed by the co-infusion of MSC.

Effects of iguratimod in the treatment of palindromic rheumatism: Case report.

OBJECTIVE: Palindromic rheumatism (PR) is characterized by interstitial inflammation, redness, and pain in joints and periarticular tissues. However, the pathogenesis and treatment of PR remain unknown. Herein, we report on the first use of iguratimod (IGU) - a novel small-molecule compound with anti-inflammatory effects - in the treatment of refractory PR. CASE: A male patient aged 70 years was diagnosed with PR based on medical history, clinical manifestations, and ultrasound findings. The patient was treated with IGU (25 mg PO q.d.). The disease activity was measured by the frequency of PR flares and clinical symptoms. The patient's laboratory tests were monitored for safety reasons. RESULTS: The use of IGU significantly improved pain symptoms and reduced flare frequency. After 28 days of treatment, abnormal levels of glutamic-pyruvic transaminase were observed. One month after discontinuation of IGU, flares occurred in the patient's second toe of both feet. CONCLUSION: IGU provides a new treatment option for patients with refractory PR who cannot use hydroxychloroquine. The effective treatment with IGU suggests the potential pathogenesis of PR and provides a basis for physicians to choose a new drug for PR treatment.

Correction to: The predictive value of dynamic monitoring of peripheral blood lymphocyte to monocyte ratio in patients with extranodal NK/T cell lymphoma.

[This corrects the article DOI: 10.1186/s12935-019-0993-9.].

The predictive value of dynamic monitoring of peripheral blood lymphocyte to monocyte ratio in patients with extranodal NK/T cell lymphoma.

BACKGROUND: To investigate the value of dynamic monitoring peripheral blood lymphocyte-to-monocyte (LMR) ratio in evaluating the treatment response and prognosis of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: A total of 148 patients with ENKTL were retrospectively analyzed in the Affiliated Tumor Hospital of Zhengzhou University between March 2012 and March 2018. The optimal cut-off value of LMR was determined using the receiver operating characteristic curve (ROC) method, then patients were divided into low LMR group and high LMR group. The LMR level was dynamically measured at various time points, and the relationships between LMR and therapeutic response, and survival were analyzed. RESULTS: The complete remission rate (CR) was 85.7% in patients with high LMR at diagnosis, which was remarkably higher than that of patients with low LMR at diagnosis (64.9%) (P = 0.009). The 5-year overall survival (OS) and progression-free survival (PFS) were 49.28% and 44.89% in the low LMR group, respectively; 5-year OS and PFS in the high LMR group were 84.50% and 67.12%, respectively, significantly longer (P values were < 0.001 and 0.034, respectively). The OS and PFS of patients with elevated LMR after treatment were longer than those with decreased LMR after treatment (all P values < 0.05). The LMRs at relapse were significantly lower in both high and low LMR groups than those of the last follow-up (P values were 0.001 and 0.016, respectively). Univariate and multivariate analysis demonstrated that low LMR was an independent risk factor for poor prognosis in ENKTL patients (P values were < 0.001 and 0.009, respectively). CONCLUSIONS: Lymphocyte to monocyte ratio can be used as an indicator of treatment response, prognosis and recurrence in patients with ENKTL. Low LMR before and after treatment is a poor prognostic factor.

Synergistic effect of organic-inorganic hybrid monomer and polyhedral oligomeric silsesquioxanes in a boronate affinity monolithic capillary/chip for enrichment of glycoproteins.

A boronate affinity monolith with improved affinity and selectivity for glycoproteins was prepared starting from two monomers. The first is 3-aminopropyltriethoxysilane-methacrylic acid (APTES-MAA), and the other is a polyhedral oligomeric silsesquioxane (POSS) monomer. In the next step, 3-(acrylamido)benzeneboronic acid was adopted as boronate affinity ligand, and ethylene glycol dimethacrylate as the crosslinker, and iso-propanol and octanol as binary porogens. The synergistic effect of APTES-MAA and POSS warrants good affinity and selectivity for glycoproteins, which results in a number of attractive features including (a) a wide operation pH range (from 5 to 8); (b) higher enrichment factors ranging from 19.3 to 20.6; (c) greater recoveries of glycoproteins between 95.8 and 107.1%; (d) lower relative standard deviations of ≤4.2%. Compared to the corresponding APTES-MAA/POSS-free monolith, the new boronate material had 1.7-fold increased glycoprotein recovery from complex samples. Glycoproteins in 500-fold diluted serum samples can be enriched by the boronate monolith. Graphical abstractSchematic representation of the preparation of 3-aminopropyltriethoxysilane-methacrylic acid/polyhedral oligomeric silsesquioxanes boronate affinity monolith. This sorbent exhibits high selectivity and wide pH operation range for capturing glycopeptides.

Mycelium Polysaccharides from Termitomyces albuminosus Attenuate CCl4-Induced Chronic Liver Injury Via Inhibiting TGFß1/Smad3 and NF-κB Signal Pathways.

A major fraction (MPT-W), eluted by deionized water, was extracted from mycelium polysaccharides of Termitomyces albuminosus (MPT), and its antioxidant, anti-fibrosis, and anti-inflammatory activities in CCl4-induced chronic liver injury mice, as well as preliminary characterizations, were evaluated. The results showed that MPT-W was a polysaccharide of α- and ß-configurations containing xylose (Xyl), fucose (Fuc), mannose (Man), galactose (Gal), and glucose (Glc) with a molar ratio of 0.29:8.67:37.89:35.98:16.60 by gas chromatography-mass spectrometry (GC-MS), Fourier transform infrared (FT-IR) spectroscopy. Its molecular weight (Mw), obtained by high-performance gel permeation chromatography (HPGPC), was 1.30 × 105 Da. The antioxidant assays in vitro showed that MPT-W displayed scavenging free-radical abilities. Based on the data of in vivo experiments, MPT-W could inhibit TGFß1/Smad3 and NF-κB pathways; decrease the level and activity of cytochrome P4502E1 (CYP2E1), malonaldehyde (MDA) and serum enzyme; activate the HO-1/Nrf2 pathway; and increase antioxidant enzymes to protect the liver in CCl4-induced chronic liver injury mice. Therefore, MPT-W could be a potentially natural and functional resource contributing to antioxidant, hepatoprotective, and anti-inflammatory effects with potential health benefits.

Characterization, Antioxidant, Anti-Aging and Organ Protective Effects of Sulfated Polysaccharides from Flammulina velutipes.

As an irreversible and complex degenerative physiological process, the treatment for aging seems strategically necessary, and polysaccharides play important roles against aging owing to their abundant bioactivities. In this paper, the antioxidant and anti-aging activities of Flammulina velutipes polysaccharides (FPS) and its sulfated FPS (SFPS) on d-galactose-induced aging mice were investigated. The in vitro antioxidant activities demonstrated that SFPS had strong reducing power and superior scavenging effects on 2, 2-diphenylpicrylhydrazyl (DPPH), hydroxyl radicals and the chelating activities of Fe2+. The in vivo animal experiments manifested that the SFPS showed superior antioxidant and protective abilities against the d-galactose-induced aging by increasing the antioxidant enzyme activities, decreasing lipid peroxidation, improving the inflammatory response and ameliorating the anile condition of mice. Furthermore, the structural analysis of SFPS was investigated through FT-IR, NMR, and HPLC analysis, and the results indicated that SFPS was a homogeneous heteropolysaccharide with a weight-average molecular weight of 2.81 × 103 Da. Furthermore, SFPS has also changed in characteristic functional groups and monosaccharide composition compared to FPS. These results suggested that sulfated modification could enhance the anti-oxidation, anti-aging and protective activities of F. velutipes polysaccharides, which may provide references for the development of functional foods and natural medicines.

The Antioxidant and Anti-Aging Effects of Acetylated Mycelia Polysaccharides from Pleurotus djamor.

The present work mainly describes the preparation of acetylated mycelia polysaccharides (AMPS) from Pleurotus djamor and investigates the antioxidant and anti-aging effects in d-galactose-induced aging mice. The optimized procedure indicates the acetyl substitution degree of AMPS is 0.54 ± 0.04 under the conditions of a reaction time of 56 h, a reaction temperature of 37 °C, and 4 mL of added acetic anhydride. The in vitro analysis and in vivo animal experiments indicate that the AMPS could alleviate the aging properties by scavenging the radicals, elevating the enzyme activities, and reducing the lipid contents. As for serum levels, the AMPS can improve the serum biochemical indices and enhance immunological activity. The histopathological observations indicate that the injuries to the liver, kidney, and brain can be remitted by AMPS intervention. The characterization showed that AMPS was one kind of ß-pyranose with the weight-average molecular weights of 3.61 × 105 Da and the major monosaccharides of mannose and glucose. The results suggest that AMPS can be used as a dietary supplement and functional food for the prevention of aging and age-related diseases.

Top-cited articles in digestive system disease from 1950 to 2013.

BACKGROUND AND AIM: Examination of top-cited articles is a tool that can help to identify and monitor outstanding scientific researches and landmark papers. We aimed to identify the 100 most cited published papers in peer-reviewed biomedical journals in the field of digestive diseases and to examine their characteristics. METHODS: The Web of Science (including Science Citation Index) was searched for the most cited papers related to digestive diseases, published from 1955 to the present. The top 100 most cited articles were identified. The number of citations, countries, and institutions of origin, year of publication, study design, topic, and levels of evidence of the articles were noted and analyzed. RESULTS: The most top-cited articles had a mean of 1375 citations. These articles were published between 1978 and 2009 in 29 high-impact journals, with the New England Journal of Medicine (n = 22) topping the list. Of the 100 articles, 34 were clinical studies, 15 were review articles, and 34 were concerned basic science. These articles came from 18 countries, with the USA contributing most of the top-cited articles (n = 53). Eighty-seven institutions produced these 100 top-cited articles, led by the University of Barcelona (n = 4). Seven persons authored two or more of these top-cited articles. The mostly represented specialty was gastrointestinal oncology (n = 49). CONCLUSIONS: Our study can give a historical perspective on the scientific progress of digestive diseases, as well as allow for recognition of most important advances in this area and provide useful information to guide future researches.

[Clinical analysis of grand glass opacity on CT as the first change of lung infection accompanied by hematologic malignancies].

OBJECTIVE: To evaluate the value of grand glass opacity(GGO) on CT as a diagnostic sign of pulmonary fungal infection. METHODS: The clinical data of 143 patients treated in department of hematology from January 2007 to June 2015 were analyzed retrospectively, and GGO or other attendant signs were observed. RESULTS: The cases of fungal infection secondary to acute leukemia(AL), myelodysplastic syndromes(MDS), non-Hodgkin's lymphoma(NHL), multiple myeloma(MM), Hodgkin's lymphoma(HL) were 83, 23, 18, 10, 9, respectively, including 23 patients with hematopoietic stem cell transplantation.Ninety percent(128/143) of patients with GGO changes was accompanied with the presence of neutropenia.GGO was mostly accompanied by funicular inflammatory infiltrating shadows or nodules.The cases of possible invasive pulmonary fungal infections(IPFI), probable IPFI, proven IPFI, undefined IPFI were 56, 15, 4, 26, respectively.The total effective cases after anti-fungal therapy was 92. CONCLUSIONS: Ground glass opacity as sign of pulmonary infection of CT mostly occurred in neutropenia and is more common in patients with acute leukemia or hematopoietic stem cell transplantation.GGO is a diagnostic sign of pulmonary fungal infection and it's indicating that anti-fungal medicine should be considered.

Heatstroke induces liver injury via IL-1ß and HMGB1-induced pyroptosis.

BACKGROUND & AIMS: Liver injury is a common complication of heat stroke (HS), and often constitutes a direct cause for patient death. The cellular and molecular mechanism underlying HS-induced liver injury remains unclear. Recent evidence indicates that inflammasome plays an important role in mediating sterile inflammation triggered by tissue damage. Using a rat HS model, we identified a novel mechanism by which inflammasome-dependent interleukin-1ß (IL-1ß) activation and hepatocyte pyroptosis mediate HS-induced liver injury. METHODS: To induce HS, rats were subjected to heat exposure. Inhibition of inflammasomes was achieved by RNA silencing and pharmacologic inhibitor prior to heat exposure. Inflammasome assembly, caspase-1 activation, histological changes, as well as serum levels of liver enzymes were measured. RESULTS: We demonstrated that the onset of HS activated inflammasome in the liver as evidenced by increased capase-1 activity and the association of inflammasome components NOD-like receptor family pyrin domain containing 3 (Nlrp3) and apoptosis speck-like protein containing a caspase-recruitment domain (ASC); and the activated inflammasome, in turn, induced IL-1ß activation and hepatocyte pyroptosis, and subsequent augmented liver injury. HS-induced hepatocyte inflammasome activation seems to be high-mobility group box 1 (HMGB1) dependent. Inhibition of Nlrp3, caspase-1, or HMGB1 prevented HS-induced liver inflammation and ameliorated liver injury. CONCLUSIONS: These findings demonstrate an important role of HMGB1 in mediating inflammasome activation in the development of liver injury following HS, and suggest that targeting inflammasome may represent a novel therapeutic strategy to limit cell death and prevent liver failure after HS.

Risk factors and mortality of carbapenem-resistant Pseudomonas aeruginosa bloodstream infection in haematology department: A 10-year retrospective study.

OBJECTIVES: This study aims to investigate the risk factors for carbapenem-resistant Pseudomonas aeruginosa bloodstream infection (CRPA-BSI) and identify predictors of outcomes among patients with P. aeruginosa bloodstream infection (PA-BSI). METHODS: A retrospective cohort study was conducted on patients with PA-BSI at Henan Cancer Hospital from 2013 to 2022. RESULTS: Among the 503 incidences analysed, 15.1% of them were CRPA strains. Age, ANC < 100/mmc, receiving antifungal prophylaxis, exposure to carbapenems within the previous 90 days to onset of BSI, and allogeneic HSCT (allo-HSCT) were associated with the development of CRPA-BSI. CRPA-BSI patients experienced significantly higher 28-day mortality rates compared to those with carbapenem-susceptible P. aeruginosa bloodstream infection. Multivariate logistic regression analysis identified age at BSI, active stage of haematological disease, procalcitonin levels, prior corticosteroid treatment, isolation of CRPA, and septic shock as independent predictors of 28-day mortality. CONCLUSIONS: Risk factors for CRPA-BSI include age, ANC < 100/mmc, antifungal prophylaxis, exposure to carbapenems, and allo-HSCT. Additionally, age at BSI, active haematological disease, procalcitonin levels, prior corticosteroid treatment, CRPA isolation, and septic shock contribute to increased mortality rates among patients with PA-BSI.

Comparison of the burden of digestive diseases between China and the United States from 1990 to 2019.

Introduction: China has experienced unprecedented transformations unseen in a century and is gradually progressing toward an emerging superpower. The epidemiological trends of digestive diseases in the United States (the US) have significant prescient effects on China. Methods: We extracted data on 18 digestive diseases from the Global Burden of Diseases 2019 Data Resource. Linear regression analysis conducted by the JoinPoint software assessed the average annual percentage change of the burden. We performed subgroup analyses based on sex and age group. Results: In 2019, there were 836.01 and 180.91 million new cases of digestive diseases in China and the US, causing 1558.01 and 339.54 thousand deaths. The age-standardized incidence rates of digestive diseases in China and the US were 58417.87/100,000 and 55018.65/100,000 respectively, resulting in age-standardized mortality rates of 81.52/100,000 and 60.88/100,000. The rates in China annually decreased by 2.149% for mortality and 2.611% for disability-adjusted life of year (DALY). The mortality and DALY rates of the US, respectively, had average annual percentage changes of -0.219 and -0.251. Enteric infections and cirrhosis and other chronic liver diseases accounted for the highest incidence and prevalence in both counties, respectively. The burden of multiple digestive diseases exhibited notable sex disparities. The middle-old persons had higher age-standardized prevalence rates. Conclusion: China bore a greater burden of digestive diseases, and the evolving patterns were more noticeable. Targeted interventions and urgent measures should be taken in both countries to address the specific burden of digestive diseases based on their different epidemic degree.

Clinical Characteristics and Prognosis of Bloodstream Infection with Carbapenem-Resistant Pseudomonas aeruginosa in Patients with Hematologic Malignancies.

Objective: To analyze the clinical characteristics and prognostic risk factors of carbapenem-resistant Pseudomonas aeruginosa (CRPA) bloodstream infections in patients with hematologic malignancies. Methods: Medical records and drug susceptibility data of patients with hematologic malignancies complicated by CRPA bloodstream infections admitted to the Cancer Hospital of Zhengzhou University between January 1, 2018, and December 31, 2022, were retrospectively analyzed. Results: A total of 64 patients were included in the study, with a mortality rate of 37.5% (24/64) at 28 days after the occurrence of CRPA bloodstream infection. In Cox regression analysis, an absolute neutrophil count <0.5×109/L at discharge (HR 0.039, 95% CI 0.006 ~ 0.258, p=0.001), admission to the intensive care unit (HR 7.546, 95% CI 1.345 ~ 42.338, p= 0.022), and a higher Pitt bacteremia score (HR 0.207, 95% CI 0.046 ~ 0.939, p = 0.041) were independent risk factors associated with 28-day mortality. Survival analysis showed that patients receiving ceftazidime-avibactam-based (HR 0.368, 95% CI 0.107~ 1.268, p = 0.023) or polymyxin B (HR 2.561, 95% CI 0.721 ~ 9.101, p = 0.015) therapy had a higher survival rate. Conclusion: Patients with hematologic neoplasms had high mortality from CRPA bloodstream infections, and admission to the intensive care unit, higher Pitt bacteremia score (PBS) scores, granulocyte deficiency, and granulocyte deficiency at discharge were independently associated with higher mortality. Early anti-infective treatment with ceftazidime-avibactam or polymyxin B may improve the clinical prognosis of patients.

Haploidentical Cord Blood Transplantation with 8 mg/kg Antithymocyte Globulin as Graft-versus-Host Disease Prophylaxis Compared to Haploidentical Transplantation with 10 mg/kg Antithymocyte Globulin in the Treatment of Acute Leukemia.

Clinical outcomes of the transplantation strategy combined with a haploidentical stem cell graft and an unrelated umbilical cord blood unit (haplo-cord HSCT) with low-dose antithymocyte globulin (ATG) as graft-versus-host disease (GVHD) prophylaxis for the treatment of acute leukemia remains unclear. This study aimed to explore the clinical outcomes of haplo-cord HSCT in acute leukemia patients with the GVHD prevention strategy of 8 mg/kg ATG compared with haploidentical transplantation with 10 mg/kg ATG. A total of 130 patients with acute leukemia who underwent allogeneic HSCT between January 2016 and December 2020 were included in this study, including 70 patients who received haploidentical stem cell grafts and unrelated umbilical cord blood units (haplo-cord HSCT) with 8 mg/kg ATG (haplo-cord-ATG8 group) and haploidentical HSCT with 10 mg/kg ATG (haplo-ATG10 group) in 60 patients. Clinical data were collected and analyzed retrospectively. Patients in the haplo-cord-ATG8 group were significantly older compared with the haplo-ATG10 group (P = .000). Haplo-cord HSCT with reduced ATG to 8 mg/kg results in more rapid neutrophil recovery (P = .036). No between-group differences were observed in platelet recovery or the incidences of Epstein-Barr virus viremia, bloodstream infection, or hemorrhagic cystitis. The rate of grade II-IV acute GVHD by day 100 post-transplantation was higher in the haplo-ATG10 group (27.16% versus 11.48%; P = .033), as was the rate of chronic GVHD at 1 year (14.60% versus 3.36%; P = .048). The rate of cytomegalovirus reaction was higher in the haplo-ATG10 group (48.31% versus 26.30%; P = .022). With a median follow-up of 27.4 months for the haplo-cord-ATG8 group and 27.5 months for the haplo-ATG10 group, overall survival (OS) at 2 years was 79.4% versus 62.8% (P = .005), event-free survival (EFS) was 76.3% versus 55.9% (P = .001), the cumulative incidence of relapse was 10.11% versus 25.97% (P = .164), and nonrelapse mortality (NRM) was 14.33% versus 24.43% (P = .0040). Multivariate analysis identified Center for International Blood and Marrow Transplant Research Disease Risk Index was the sole significant predictor of relapse, NRM, OS, and EFS. Haplo-cord HSCT supported by cord blood with 8 mg/kg ATG as GVHD prophylaxis results in better outcomes compared with haplo-HSCT with 10 mg/kg ATG.

Clinical observation on the safety and efficacy of umbilical cord mesenchymal stem cells in the treatment of bronchiolitis obliterans after allogeneic haematopoietic stem cell transplantation.

Graft-versus-host disease (GVHD) is caused by a pathologic and destructive response of the organism as a result of the interaction between donor immunocompetent T lymphocytes and the recipient tisular antigens1. Graft-versus-host disease is considered a serious complication of hematopoietic stem cell transplantation. The skin, oral cavity and lungs are commonly affected organs. Among these complications bronchiolitis obliterans syndrome is a serious complication, which even can be life-threatening. Therefore, this research aims to do a clinical observation on the safety and efficacy of umbilical cord mesenchymal stem cells in the treatment of bronchiolitis obliterans after allogeneic haematopoietic stem cell transplantation. Fifteen patients were included in this study, who received allogeneic hematopoietic stem cell transplantation. Among these patients, both of them were treated with azithromycin, montelukast, glucocorticoid and pirfenidone. Two of them did not receive second line anti-rejection treatment due to economic reasons, and three of them were treated with mesenchymal stem cells. These bronchiolitis obliterans syndrome-related symptoms such as shortness of breath, chest tightness and wheezing have improved. Two of them died due to bronchiolitis obliterans syndrome related complications such as respiratory failure. Two of them not only improve the symptoms but also increased the FEV1/FVC, who were treated with mesenchymal stem cells. The comprehensive treatment regimen containing imatinib and ruxolitinib is safe and effective and mesenchymal stem cell is a promising treatment option to improve the prognosis of post-HSCT BOS.

Iguratimod efficacy in palindromic rheumatism treatment.

BACKGROUND: As a new immunomodulator for rheumatoid arthritis, iguratimod (IGU) also has therapeutic potential in other immune diseases. In this study, we determined the effects of IGU on disease control in patients with palindromic rheumatism (PR). METHODS: Patients with PR were divided into Control group (Ctrl group) and an IGU treatment (IGU group) groups. Drug efficacy was evaluated according to the frequency of PR attacks (monthly), the visual analog scale (VAS) score of patient pain, and clinical symptoms. RESULTS: The drug positivity and disease control rates of the IGU group (100.00% and 90.91%, respectively) were significantly higher than those of the Ctrl group (61.11% and 5.56%; p = .002 and p < .001, respectively). The median number of PR flares and the VAS score of patients in the Ctrl group decreased from 3.00 (1.00-15.00) to 0.83 (0.00-12.00) and from 5 (4-6) to 4 (1-6), respectively. In the IGU group, the median number of PR attacks decreased from 4.50 (2.00-15.00) to 0.00 (0.00-0.33), and the VAS score decreased from 5 (4-6) to 0 (0-2). The IGU group exhibited a significant reduction in PR flare frequency and improvement in the VAS value (p < .001 and p < .001, respectively). CONCLUSION: Our study is the first to describe the efficacy of IGU in PR treatment. IGU can significantly reduce the number of PR flares and improve the clinical symptoms of patients with PR.

Endothelial glycocalyx injury is involved in heatstroke-associated coagulopathy and protected by N-acetylcysteine.

Introduction: Damage to endothelial glycocalyx (EGCX) can lead to coagulation disorders in sepsis. Heat stroke (HS) resembles sepsis in many aspects; however, it is unclear whether EGCX injury is involved in its pathophysiology. The purpose of this study was to examine the relationship between the damage of EGCX and the development of coagulation disorders during HS. Methods: We retrospectively collected 159 HS patients and analyzed coagulation characteristics and prognosis of HS patients with or without disseminated intravascular coagulation (DIC). We also replicated a rat HS model and measured coagulation indexes, pulmonary capillary EGCX injury in HS rats. Finally, we evaluated the effect of the antioxidant N-acetylcysteine (NAC) on HS-initiated EGCX injury and coagulation disorders. Results: Clinical data showed that HS patients complicated with DIC had a higher risk of death than HS patients without DIC. In a rat HS model, we found that rats subjected to heat stress developed hypercoagulability and platelet activation at the core body temperature of 43°C, just before the onset of HS. At 24 h of HS, the rats showed a consumptive hypo-coagulation state. The pulmonary capillary EGCX started to shed at 0 h of HS and became more severe at 24 h of HS. Importantly, pretreatment with NAC substantially alleviated EGCX damage and reversed the hypo-coagulation state in HS rats. Mechanically, HS initiated reactive oxidative species (ROS) generation, while ROS could directly cause EGCX damage. Critically, NAC protected against EGCX injury by attenuating ROS production in heat-stressed or hydrogen peroxide (H2O2)-stimulated endothelial cells. Discussion: Our results indicate that the poor prognosis of HS patients correlates with severe coagulation disorders, coagulation abnormalities in HS rats are associated with the damage of EGCX, and NAC improves HS-induced coagulopathy, probably through its protection against EGCX injury by preventing ROS generation.