Nomogram-based risk assessment model for left ventricular hypertrophy in patients with essential hypertension: Incorporating clinical characteristics and biomarkers.

Left ventricular hypertrophy (LVH) is a hypertensive heart disease that significantly escalates the risk of clinical cardiovascular events. Its etiology potentially incorporates various clinical attributes such as gender, age, and renal function. From mechanistic perspective, the remodeling process of LVH can trigger increment in certain biomarkers, notably sST2 and NT-proBNP. This multicenter, retrospective study aimed to construct an LVH risk assessment model and identify the risk factors. A total of 417 patients with essential hypertension (EH), including 214 males and 203 females aged 31-80 years, were enrolled in this study; of these, 161 (38.6%) were diagnosed with LVH. Based on variables demonstrating significant disparities between the LVH and Non-LVH groups, three multivariate stepwise logistic regression models were constructed for risk assessment: the "Clinical characteristics" model, the "Biomarkers" model (each based on their respective variables), and the "Clinical characteristics + Biomarkers" model, which amalgamated both sets of variables. The results revealed that the "Clinical characteristics + Biomarkers" model surpassed the baseline models in performance (AUC values of the "Clinical characteristics + Biomarkers" model, the "Biomarkers" model, and the "Clinical characteristics" model were .83, .75, and .74, respectively; P < .0001 for both comparisons). The optimized model suggested that being female (OR: 4.26, P <.001), being overweight (OR: 1.88, p = .02) or obese (OR: 2.36, p = .02), duration of hypertension (OR: 1.04, P = .04), grade III hypertension (OR: 2.12, P < .001), and sST2 (log-transformed, OR: 1.14, P < .001) were risk factors, while eGFR acted as a protective factor (OR: .98, P = .01). These findings suggest that the integration of clinical characteristics and biomarkers can enhance the performance of LVH risk assessment.

Penetration of Calcium Silicate and Epoxy Resin Sealers Into the Lateral Canals.

OBJECTIVES: The aim of this research was to compare the penetration ability of calcium silicate-based sealers (iRoot SP and TotalFill BC HiFlow) and an epoxy resin-based sealer (AH Plus) into the lateral canals using the single-cone (SC) or continuous wave compaction (CW) obturation techniques. METHODS: Ninety single-rooted human teeth received canal instrumentation and diaphanisation before artificial lateral canals were created at 3 different root levels. The specimens were randomly allocated into 6 groups based on the combination of obturation technique and sealer used. Radiographic and photographic measurements evaluated the percentage of sealer penetration. Statistical analysis was performed to compare the penetration ability amongst different types of sealers, obturation methods, and root levels. RESULTS: Although TotalFill BC HiFlow sealer combined with the CW technique demonstrated greater sealer penetration at the coronal level (P < .05), the overall penetration ability of iRoot SP, TotalFill BC HiFlow, and AH Plus was not significantly different. The deepest sealer penetration was observed at the apical root level. CONCLUSIONS: All sealers showed similar penetration abilities into the lateral canals using the SC or CW techniques in vitro. Calcium silicate-based sealers have comparable penetration ability into lateral canals compared to epoxy resin-based sealers using SC or CW obturation techniques.

Chest compression quality and patient outcomes with the use of a CPR feedback device: A retrospective study.

Feedback devices were developed to guide resuscitations as targets recommended by various guidelines are difficult to achieve. Yet, there is limited evidence to support their use for in-hospital cardiac arrests (IHCA), and they did not correlate with patient outcomes. Therefore, this study has investigated the compression quality and patient outcomes in IHCA with the use of a feedback device via a retrospective study of inpatient code blue activations in a Singapore hospital over one year. The primary outcome was compression quality and secondary outcomes were survival, downtime and neurological status. 64 of 110 (58.2%) cases were included. Most resuscitations (71.9%) met the recommended chest compression fraction (CCF, defined as the proportion of time spent on compressions during resuscitation) despite overall quality being suboptimal. Greater survival to discharge and better neurological status in resuscitated patients respectively correlated with higher median CCF (p = 0.040 and 0.026 respectively) and shorter downtime (p < 0.001 and 0.001 respectively); independently, a higher CCF correlated with a shorter downtime (p = 0.014). Overall, this study demonstrated that reducing interruptions is crucial for good outcomes in IHCA. However, compression quality remained suboptimal despite feedback device implementation, possibly requiring further simulation training and coaching. Future multicentre studies incorporating these measures should be explored.

Tissue Stabilization, Bacterial Adhesion, and Stem Cell Viability in Trans-cinnamaldehyde-conditioned Dentin.

INTRODUCTION: This laboratory study aimed to evaluate the effect of trans-cinnamaldehyde (TC) conditioning on dentin tissue stabilization, bacterial adhesion, and stem cell toxicity. METHODS: Dentin beams (n = 204) from extracted human molars were demineralized in phosphoric acid and treated with TC (2.5, 5, and 7.5%), 50% ethanol-water mixture (vehicle control) or 2.5% glutaraldehyde (GA) (positive control) for 30 minutes. Demineralized but untreated specimens served as the negative control. After treatment, collagen crosslinking was characterized by measuring the elastic modulus (Er) and hardness (n = 5). Biodegradation resistance was examined by determining the loss of dry mass (n = 8), hydroxyproline release (n = 4) and scanning electron microscopy (n = 2), after exposure to bacterial collagenase. Inhibition of bacterial adhesion was investigated by colony counting assay (n = 12) and scanning electron microscopy (n = 2). Viability of stem cells of the apical papilla on TC-conditioned dentin was determined using the Cell Counting Kit-8 assay (n = 8). Data were statistically analyzed using one-way analysis of variance (ANOVA) test followed by Dunnett's multiple comparisons at a significance level of 5%. RESULTS: TC-conditioned dentin showed a concentration-dependent increase in Er and hardness. The Er and hardness of 5% and 7.5% TC-conditioned dentin were significantly greater than that of the negative control and vehicle control groups (P < .05). There was no significant difference in the biodegradation resistance between GA and 5% TC-conditioned dentin (P > .05). TC-conditioned dentin showed a well-preserved collagen fibril network with clear cross-banding, comparable to GA-conditioned dentin. All concentrations of TC inhibited bacterial adhesion on dentin, significantly greater than the negative control (P < .05). There was no reduction in viability of stem cells of the apical papilla viability on TC-conditioned dentin compared to the negative control (P > .05). CONCLUSIONS: TC conditioning stabilized the dentin and protected it from enzymatic degradation. TC prevented bacterial adhesion on the dentin but maintained stem cell viability.

Intracellular bacterial eradication using a novel peptide in vitro.

AIM: To determine the effect of a novel antimicrobial peptide (AMP; OP145) and cell-penetrating peptide (Octa-arginine/R8) conjugate on the killing of intracellular Enterococcus faecalis, compared to OP145 and an antibiotic combination recommended for regenerative endodontic procedures. METHODOLOGY: The biocompatible concentrations of OP145 and OP145-R8 were determined by assessing their cytotoxicity against human macrophages and red blood cells. Spatiotemporal internalization of the peptides into macrophages was investigated qualitatively and quantitatively by confocal laser scanning microscopy and flow cytometry respectively. Killing of extracellular and intracellular E. faecalis OG1RF by the peptides was determined by counting the colony-forming units (CFU). Intracellular antibacterial activity of the peptides was compared to a double antibiotic combination. Confocal microscopy was used to confirm the intracellular bacterial eradication. Significant differences between the different test groups were analysed using one-way analysis of variance. p < .05 was considered to be statistically significant. RESULTS: Peptides at a concentration of 7.5 µmol/L were chosen for subsequent experiments based on the results of the alamarBlue™ cell viability assay and haemolytic assay. OP145-R8 selectively internalized into lysosomal compartments and the cytosol of macrophages. Conjugation with R8 improved the internalization of OP145 into macrophages in a temporal manner (70.53% at 1 h to 77.13% at 2 h), while no temporal increase was observed for OP145 alone (60.53% at 1 h with no increase at 2 h). OP145-R8 demonstrated significantly greater extracellular and intracellular antibacterial activity compared to OP145 at all investigated time-points and concentrations (p < .05). OP145-R8 at 7.5 µmol/L eradicated intracellular E. faecalis after 2 h (3.5 log reduction compared to the control; p < .05), while the antibiotics could not reduce more than 0.5 log CFU compared to the control (p > .05). Confocal microscopy showed complete absence of E. faecalis within the OP145-R8 treated macrophages. CONCLUSIONS: The results of this study demonstrated that the conjugation of an AMP OP145 to a cell-penetrating peptide R8 eradicated extracellular and intracellular E. faecalis OG1RF without toxic effects on the host cells.

Consensus Statements on Precision Oncology in the China Greater Bay Area.

BACKGROUND: Next-generation sequencing comprehensive genomic panels (NGS CGPs) have enabled the delivery of tailor-made therapeutic approaches to improve survival outcomes in patients with cancer. Within the China Greater Bay Area (GBA), territorial differences in clinical practices and health care systems and strengthening collaboration warrant a regional consensus to consolidate the development and integration of precision oncology (PO). Therefore, the Precision Oncology Working Group (POWG) formulated standardized principles for the clinical application of molecular profiling, interpretation of genomic alterations, and alignment of actionable mutations with sequence-directed therapy to deliver clinical services of excellence and evidence-based care to patients with cancer in the China GBA. METHODS: Thirty experts used a modified Delphi method. The evidence extracted to support the statements was graded according to the GRADE system and reported according to the Revised Standards for Quality Improvement Reporting Excellence guidelines, version 2.0. RESULTS: The POWG reached consensus in six key statements: harmonization of reporting and quality assurance of NGS; molecular tumor board and clinical decision support systems for PO; education and training; research and real-world data collection, patient engagement, regulations, and financial reimbursement of PO treatment strategies; and clinical recommendations and implementation of PO in clinical practice. CONCLUSION: POWG consensus statements standardize the clinical application of NGS CGPs, streamline the interpretation of clinically significant genomic alterations, and align actionable mutations with sequence-directed therapies. The POWG consensus statements may harmonize the utility and delivery of PO in China's GBA.

Gut Microbiota Control the Bioavailability and Metabolism of Organoarsenicals of Seaweeds in Mice after Oral Ingestion.

Edible seaweed consumption is an essential route of human exposure to complex organoarsenicals, including arsenosugars and arsenosugar phospholipids. However, the effects of gut microbiota on the metabolism and bioavailability of arsenosugars in vivo are unknown. Herein, two nori and two kelp samples with phosphate arsenosugar and sulfonate arsenosugar, respectively, as the predominant arsenic species, were administered to normal mice and gut microbiota-disrupted mice treated with the broad-spectrum antibiotic cefoperazone for 4 weeks. Following exposure, the community structures of the gut microbiota, total arsenic concentrations, and arsenic species in excreta and tissues were analyzed. Total arsenic excreted in feces and urine did not differ significantly between normal and antibiotic-treated mice fed with kelp samples. However, the total urinary arsenic of normal mice fed with nori samples was significantly higher (p < 0.05) (urinary arsenic excretion factor, 34-38 vs 5-7%), and the fecal total arsenic was significantly lower than in antibiotic-treated mice. Arsenic speciation analysis revealed that most phosphate arsenosugars in nori were converted to arsenobetaine (53.5-74.5%) when passing through the gastrointestinal tract, whereas a large portion of sulfonate arsenosugar in kelp was resistant to speciation changes and was excreted in feces intact (64.1-64.5%). Normal mice exhibited greater oral bioavailability of phosphate arsenosugar from nori than sulfonate arsenosugar from kelp (34-38 vs 6-9%). Our work provides insights into organoarsenical metabolism and their bioavailability in the mammalian gut.

Identification of Inflammatory Endotypes by Clinical Characteristics and Nasal Secretion Biomarkers in Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION: The emergency of biologics and surgical techniques targeting the specific inflammatory endotype in chronic rhinosinusitis with nasal polyps (CRSwNP) asks for efficient identification of patients with different endotypes. Although mucosal IL-4, IL-5, IL-13, and IgE have been used to define type 2 (T2) inflammation, the optimal one remains unclear. In this study, we aimed to determine the optimal anchor for T2 inflammation and identify clinical characteristics and nasal secretion biomarkers predicting different endotypes in CRSwNP. METHODS: Six mediators in sinonasal tissue and 36 mediators in nasal secretion samples were detected by the Bio-Plex suspension array system. Mucosal IFN-γ and IL-17A levels were used to define the T1 and T3 endotype, respectively. The efficacy of mucosal IL-4, IL-5, IL-13, and IgE to define the T2 endotype was compared. The power of clinical characteristics and nasal secretion biomarkers to predict the T1, T2, and T3 endotype was analyzed. RESULTS: Among mucosal IL-4, IL-5, IL-13, and IgE, IL-13 was the best one to coincide with the expression of other T2 biomarkers. A combination of atopy, facial pain symptom score, ethmoid/maxillary computed tomography score ratio, and blood eosinophil percentage had a moderate predictive performance for T2 endotype (area under the receiver operating curve [AUC] = 0.815), comparable to that of nasal secretion IL-5 (AUC = 0.819). For the T3 endotype, nasal secretion IL-1Rα identified it with an AUC value of 0.756. No efficient marker for the T1 endotype was found. CONCLUSION: IL-13 is a primary anchor for the T2 endotype in CRSwNP. Clinical characteristics and nasal secretion biomarkers are helpful for identifying the T2 and T3 endotype of CRSwNP.

Effect of ice slurry ingestion on thermoregulatory responses during fixed-intensity cycling in humid and dry heat.

PURPOSE: This study examined the thermoregulatory response and ergogenic effects of ice slurry (ICE) ingestion in hot environments with high and low relative humidity (RH). METHODS: Eight males completed four trials in a crossover manner in dry (DRY: 34.7 ± 0.2 °C, 38 ± 2%RH) and humid heat (HUM: 34.8 °C ± 0.2 °C, 80 ± 1%RH). They ingested 8.0 g·kg-1 of ICE (0.0 °C) or 37.5 °C water (CON) during 30 min before exercise, and three aliquots (3.2 g·kg-1) of ICE or CON during 45-min cycling at 50%[Formula: see text]O2peak, followed by cycling to exhaustion at 80%[Formula: see text]O2peak (TTE). Body core temperature (Tcore), mean skin temperature (Tsk), heart rate (HR), thermal comfort, thermal sensation and rating of perceived exertion (RPE) were measured. RESULTS: Relative to CON, ICE improved TTE by 76.5 ± 96.5% in HUM and 21.3 ± 44.9% in DRY (p = 0.044). End-exercise Tcore was lower in ICE versus CON in DRY (37.8 ± 0.4 °C versus 38.1 ± 0.3 °C, p = 0.005) and HUM (38.8 ± 0.4 °C versus 39.3 ± 0.6 °C, p = 0.004). ICE decreased HR, heat storage and heat strain index only in DRY (p < 0.001-0.018). ICE improved thermal sensation and comfort in DRY and HUM (p < 0.001-0.011), attenuated RPE in HUM (p = 0.012) but not in DRY (p = 0.065). CONCLUSION: ICE tended to benefit performance in humid heat more than in dry heat. This is likely due to the reduced extent of hyperthermia in dry heat and the relative importance of sensory inputs in mediating exercise capacity.

Effect of MMP Inhibitors on the Bond Strength of Fibre Posts After Ageing.

AIM: This in vitro study aimed to evaluate the effect of matrix metalloproteinase (MMP) inhibitors on the bond strength of resin-cemented fibre posts to radicular dentin under an aged-loaded condition. MATERIALS AND METHODS: Radicular dentin was prepared and irrigated by MMP inhibitor solution after root canal obturation in 60 extracted single-rooted teeth based on 6 groups: (1) 2% chlorhexidine (CHX) + loaded; (2) CHX + unloaded; (3) 0.5% benzalkonium chloride (BAC) + loaded; (4) BAC + unloaded; (5) 17% ethylenediaminetetraacetic acid (EDTA) + loaded; and (6) EDTA + unloaded. After final rinsing, all specimens were sliced cross-sectionally and kept in a water bath for 12 months of ageing. Groups 1, 3, and 5 were subjected to cyclic loading. Push-out tests were conducted using a universal testing machine, and failure mode was examined. The data were analysed using 3-way analysis of variance and post hoc tests at α = 0.05. RESULTS: BAC + unloaded demonstrated the highest mean bond strength (3.12 ± 0.18 MPa; P < .001), while the BAC + loaded and CHX + loaded groups showed a significantly lower push-out bond strength than their unloaded counterparts. Mixed adhesive-cohesive failure was the most common failure mode observed. CONCLUSIONS: Without cycling loading, BAC was superior to CHX and EDTA in preserving the bond strength of resin-cemented fibre posts after 12 months of ageing. Loading significantly weakened the effectiveness of BAC and CHX in preserving the bond strength.

Fracture Resistance of Endodontically Treated Maxillary Premolars with Non-carious Cervical Lesions Restored with Different Post Systems.

OBJECTIVE: To test the hypothesis that the (i) presence of non-carious cervical lesions (NCCLs) and (ii) type of post system have no effect on the fracture resistance and pattern in endodontically treated maxillary premolars. METHODS: Human maxillary first premolars (n=60) with two root canals were randomly allocated into four groups (n=15). Buccal wedge-shaped NCCLs were prepared in 45 teeth specimens. Following root canal treatment, the specimens were randomly divided into (i) composite resin core (CRC); (ii) NCCLs + composite resin core (NCCL+CRC); (iii) NCCLs+prefabricated fibre-reinforced composite post + composite resin core (NCCL+PFRC+CRC); (iv) NCCLs+custom fibre posts + composite resin core (NCCL+CFP+CRC). All specimens were subjected to thermocycling (5°C to 55°C/5000 cycles). The compressive load was applied non-axially to the palatal cusp with a universal testing machine at a crosshead speed of 0.5 mm/min at a 30° angle until fracture. Fracture patterns were examined using a loupe magnification (2.5×) under transillumination. Statistical analyses were performed using non-parametric tests and pairwise comparisons of the load-to-fracture among the groups. Chi-square test was used to analyse the fracture patterns (P=0.05). RESULTS: Fracture resistance of NCCL+PFRC+CRC was significantly higher than NCCL+CRC (P=0.011), while NCCL+CFP+CRC did not show any significant difference when compared to NCCL+CRC (P=0.089). No statistical difference was found between CRC, NCCL+PFRC+CRC and NCCL+CFP+CRC (P=1.000). The frequencies of favourable fracture patterns in descending orders were as follows: CRC (80%), NCCL+CFP+CRC (73%), NCCL+PFRC+CRC (60%), and NCCL+CRC (40%). Chi-square test did not show significant differences in fracture patterns among all groups (P=0.110). CONCLUSION: Restoration of the endodontically treated maxillary premolars with NCCLs, with or without post, resulted in similar fracture resistance as their counterparts without NCCLs. Placement of a prefabricated fibre-reinforced composite post exhibited greater fracture resistance to the maxillary premolars with restored NCCLs than those without a post. (EEJ-2022-06-077).

Study on Computer Screening and Drug Properties of Herbs Intervening in Copper Death.

Objective: The objective of this study was to explore the medicinal properties of herbal medicines that can interfere with the copper death pathway. Methods: The Human Gene Database, Chemical Interactions in Comparative Toxicogenomics Database, Encyclopedia of Traditional Chinese Medicine, China Medical Information Platform, and Cytoscape software were used to find target and chemicals that interfere with copper death targets, as well as herbal medicines containing these chemicals and their four natures and five flavors (basic properties of herbal medicines). Results: 27 copper death-related targets were finally retrieved, as well as 2143 chemicals that could interfere with them, including 180 herbal compounds. The compounds with the highest degree values (number of nodes connected to this node) were folic acid, resveratrol, and quercetin. The 180 compounds were related to 278 herbs; those with the highest degree values (number of nodes connected to this node) were Jujubae Fructus, Ginkgo biloba L, and Acanthopanax senticosus. The 27 copper death targets were indirectly associated with 278 herbs; those with the highest degree values (number of nodes connected to this node) were Achyranthis Bidentatae Radix, Polygonum cuspidatum Sieb. et Zucc, and Mori Folium. Among the 278 herbs, 6 had incomplete information. A pharmacological analysis showed that among the 272 Chinese herbs, the most frequent meridians were the liver (133), lung (104), and spleen (91). Of the four natures, the most frequent were cold (73), warm (68), and flat (45). Of the five flavors, the most frequent were bitter (165), pungent (116), and sweet (99). Conclusion: This study preliminarily discussed the material basis and medicinal properties of herbs that can intervene in copper death, which can provide reference for the theoretical discussion, drug development, and clinical research of Chinese medicine regulating copper death.

Effects of L-Chg10-Teixobactin on Viability, Proliferation, and Osteo/Odontogenic Differentiation of Stem Cells from Apical Papilla.

INTRODUCTION: Intracanal medicament is one of the essential steps for ensuring success in regenerative endodontic procedures. L-Chg10-teixobactin is a novel antimicrobial agent that exhibited potent antibacterial and antibiofilm effects against Enterococcusfaecalis at low concentrations compared with ampicillin. At the same time, its cytotoxicity on dental stem cells has not been studied. This study aimed to investigate the effects of L-Chg10-teixobactin on the viability, proliferation, migration, and osteo/odontogenic differentiation of stem cells from apical papilla (SCAPs). MATERIALS AND METHODS: SCAPs isolated from immature human third molars were treated with various concentrations of L-Chg10-teixobactin, calcium hydroxide, and dimethyl sulfoxide. The viability and proliferation of SCAPs were assessed using the LIVE/DEAD Viability/Cytotoxicity Kit and Cell Counting Kit-8. A scratch wound healing test was used to evaluate the lateral migration capacity of SCAPs. Alkaline phosphatase (ALP) activity, calcium mineralization ability tests -ie, ALP staining and alizarin red S staining, and quantitative real-time polymerase chain reaction were performed to assess the osteo /odontogenic differentiation of SCAPs. RESULTS: The tested concentrations of L-Chg10-teixobactin (0.01, 0.02, and 0.03 mg/mL), 1 mg/mL calcium hydroxide, and 0.03% dimethyl sulfoxide had no significant cytotoxic effect on SCAPs at any time point (P > .05). Besides, there were no significant differences between the control and experimental groups in SCAPs' viability, proliferation, and migration. L-Chg10-teixobactin upregulated the gene expression of osteo/odontogenic markers in SCAPs, while no significant difference was found in the ALP activity and alizarin red S staining. CONCLUSIONS: L-Chg10-teixobactin demonstrated excellent biocompatibility on SCAPs at concentrations from 0.01 to 0.03 mg/mL and potentially enhance the osteo/odontogenic differentiation of SCAPs; suggesting its promising role as root canal medicament for regenerative endodontic procedures.

PROMs Following Root Canal Treatment and Surgical Endodontic Treatment.

The FDI is currently working on developing a tool to encompass patient-reported outcome measures (PROMs) within the overall assessment of outcomes of endodontic treatment. The outcome of endodontic treatment has traditionally been determined by various clinical and radiographic criteria. However, these parameters do not address the impact of treatment on a patient's oral health-related quality of life (OHRQoL). OHRQoL, a crucial PROM, can be used to understand treatment outcome from a patient-centred perspective, thus improving clinician-patient communication whilst guiding decision-making. This focussed review aims to recount the OHRQoL of patients following nonsurgical root canal treatment and surgical endodontic treatment, with a specific focus on the minimal important difference (MID; the minimum score changes of an outcome instrument for a patient to register a clinically significant change in their OHRQoL and/or oral condition) and the methods used to determine it. The current evidence indicates that the OHRQoL of patients requiring root canal treatment is poorer than those without such need. Accordingly, the literature suggests that OHRQoL improves following nonsurgical or surgical endodontic treatment. However, study methodologies vary widely, and conclusions cannot be drawn with high confidence, nor can MID recommendations be provided. Well-designed clinical studies with baseline measurements and appropriate follow-up time frames are therefore needed. Despite that the literature is rife with outcome studies, research on PROMs is an area that deserves greater attention, particularly in relation to the MID. Determining the MID will facilitate the understanding of changes in outcome scores from the patients' perspective, thus allowing for more informed decision-making in clinical practice.

A new form of familial platelet disorder caused by germline mutations in RUNX1 in a pedigree / 中华内科杂志

Objective: To investigate the clinical and biological characteristics of familial platelet disorder (FPD) with germline Runt-related transcription factor (RUNX) 1 mutations. Methods: Patients diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with RUNX1 mutations from February 2016 to December 2021 in Wuhan No.1 Hospital underwent pedigree analysis and were screened for gene mutations (somatic and germline). Patients diagnosed with FPD with germline RUNX1 mutations were enrolled and evaluated in terms of clinical characteristics and biological evolution. Bioinformatics analysis was used to assess the pathogenicity of mutations and to analyze the effect of mutated genes on the function of the corresponding protein. Results: Germline RUNX1 mutations were detected in three out of 34 patients suffering from MDS/AML who had RUNX1 mutations. A pedigree of FPD with RUNX1 (RUNX1-FPD) c.562A>C and RUNX1 c.1415T>C mutations was diagnosed, and the mutations were of patrilineal origin. Bioinformatics analysis indicated that the locus at positions 188 and 472 in the AML-1G type of RUNX1 was highly conserved across different species, and that variations might influence functions of the proteins. The mutations were evaluated to be highly pathogenic. Of the nine cases with germline RUNX1 mutations: two patients died due AML progression; one case with AML survived without leukemia after transplantation of hemopoietic stem cells; four patients showed mild-to-moderate thrombocytopenia; two cases had no thrombocytopenia. During the disease course of the proband and her son, mutations in RUNX1, NRAS and/or CEBPA and KIT appeared in succession, and expression of cluster of differentiation-7 on tumor cells was enhanced gradually. None of the gene mutations correlated with the tumor were detected in the four cases not suffering from MDS/AML, and they survived until the end of follow-up. Conclusions: RUNX1-FPD was rare. The mutations c.562A>C and c.1415T>C of RUNX1 could be the disease-causing genes for the family with RUNX1-FPD, and these mutations could promote malignant transformation. Biological monitoring should be carried out regularly to aid early intervention for family members with RUNX1-FPD.

Effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis / 中国血吸虫病防治杂志

Objective To evaluate the effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis. Methods A “admission-hospitalization-discharge” whole-process health education model was created, 101 inpatients with ascites type of advanced schistosomiasis were given the whole-process health education. The scores of schistosomiasis control knowledge, attitudes towards schistosomiasis control and healthy behaviors, and awareness of schistosomiasis control knowledge, correct rate of attitudes towards schistosomiasis control and correct rate of healthy behaviors were compared among inpatients with ascites type of advanced schistosomiasis before and after implementation of the whole-process health education. Results The scores of schistosomiasis control knowledge, schistosomiasis control attitudes and healthy behaviors were all significantly higher among inpatients with ascites type of advanced schistosomiasis after implementation of the whole-process health education than before implementation (Z = −7.688, −3.576 and −4.328, all P values < 0.01). In addition, the awareness of schistosomiasis control knowledge increased from 54.3% to 82.7% (χ2 = 188.886, P < 0.01), and the correct rate of attitudes towards schistosomiasis control increased from 88.4% to 98.0% (χ2 = 22.001, P < 0.01), while the correct rate of healthy behaviors increased from 48.2% to 59.7% (χ2 = 11.767, P < 0.01). Conclusions The whole-process health education model may remarkably improve the awareness of schistosomiasis control knowledge and promote the formation of positive attitudes towards schistosomiasis control and correct behaviors among inpatients with ascites type of advanced schistosomiasis, which is of great significance to facilitate patients’ cure.

Clinical Analysis of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#Clinical data of 5 patients diagnosed with BPDCN in Wuhan First Hospital and Wuhan Tongji Hospital from June 2016 to November 2021 were retrospectively analyzed.@*RESULTS@#Among the 5 patients, 3 were male and 2 were female, with a median age of 28(10-52) years old. Four patients showed obvious skin damage at the initial diagnosis; the other one showed clinical manifestations of acute leukemia rather than obvious skin damage at the initial diagnosis, but infiltrated skin when the disease relapsed after treatment. Other infiltration sites of lesions included bone marrow (2/5), peripheral blood (2/5), lymph nodes (3/5), liver and spleen (2/5). All patients had no clinical manifestation of central nervous system infiltration. Tumor cell specific immune markers CD4, CD56, CD123 were all positive, and the median Ki-67 index was 70%. TET2, ASXL1 and NRAS gene mutations were found respectively in 3 patients by next-generation sequencing technique (NGS). ALL-like, AML-like and invasive NK/T cell lymphoma-like first-line induction chemotherapy regimens were used for the patients. One patient died of severe complications during the early stage of chemotherapy, 3 patients were evaluated as CR, and 1 patient was evaluated as PR. 2 patients were recurred and progressed after induction of chemotherapy, and one of them was evaluated as CR after re-treatment. One patient received autologous hematopoietic stem cell transplantation (auto-HSCT) and got long-term survival (OS 87 months). 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which one died of transplantation related complications, and 2 cases survived. The median follow-up time of 4 patients with evaluable efficacy was 28.5(9-84) months, the median OS time was 31.5(10-87) months.@*CONCLUSION@#BPDCN is a highly heterogeneous malignant tumor with a poor prognosis. HSCT, especially allo-HSCT can significantly improve the prognosis of BPDCN patients.

Regulation of Neuro-Microenvironment on Mitochondrial Mass of Hematopoietic Stem and Progenitor Cells / 中国实验血液学杂志

OBJECTIVE@#To study the effects of the neuro-microenvironment on the mass of mitochondria in hematopoietic stem and progenitor cells (HSPC), and to understand the potential mechanisms how nerve regulates HSPC.@*METHODS@#6-hydroxydopamine (6-OHDA) and capsaicin were used to interfere with the function of sympathetic nerve and nociceptive nerve in mitochondria-GFP reporter mice, respectively. The fluorescence intensity of GFP in bone marrow and spleen was measured by flow cytometry. The GFP median fluorescence intensity (MFI) of HSPC in normal bone marrow and spleen was analyzed and compared. The changes of the mitochondrial mass in HSPCs in each group after denervation were compared.@*RESULTS@#Hematopoietic stem cells (HSC) had the highest mito-GFP MFI in steady-state (49 793±1 877), and the mito-GFP MFI gradually decreased during the differentiation of HSCs. Compared with control group, pharmaceutical nociceptive denervation significantly increased the mito-GFP MFI of bone marrow multipotent progenitor-1 (MPP1, 50 751±420 vs 44 020±510) and LKS- cells (15 673±65 vs 13 979±103); pharmaceutical sympathetic denervation significantly reduced the mito-GFP MFI of bone marrow LKS+ cells (21 667±351 vs 29 249±973).@*CONCLUSION@#Sympathetic and nociceptive nerves can regulate the mass of mitochondria in HSPC and affect the function of HSPCs.

Chemotherapy Combined with Venetoclax Followed by Allo-Hematopoietic Stem Cell Transplantation for Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of chemotherapy combined with venetoclax followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).@*METHODS@#The clinical data of 3 patients with BPDCN undergoing allo-HSCT in Department of Hematology, Wuhan First Hospital from July 2017 to November 2021 were collected and retrospectively analyzed.@*RESULTS@#Among the 3 patients, there were 1 male and 2 females, aged 27-52 years old. Skin lesions were observed during initial diagnosis, and it could also be characterized by acute leukemia. Characteristic molecular markers of tumor cells, such as CD4, CD56, CD123, and CD303 were positive. In addition, the expression detection of Bcl-2 in 3 patients were positive. Chemotherapy combined with venetoclax in the initial induction of chemotherapy (1 case) or disease recurrence and progress (2 cases) was performed. There were 2 cases evaluated as complete remission (CR) and 1 case as partial remission (PR) before allo-HSCT. The patients all received a nonmyeloablative conditioning without total body irradiation (TBI). The prevention programme of graft-versus-host disease (GVHD) was antithymocyte globulin + mycophenolate mofetil + cyclosporin A/FK506 ± methotrexate. The number of mononuclear cell (MNC) count was (16.73-18.35)×108/kg, and CD34+ cell count was (3.57-4.65)×106/kg. The 3 patients were evaluated as CR after allo-HSCT (+21 to +28 d), the donor-recipient chimerism rate was 100%, and Ⅲ-Ⅳ GVHD was not observed. One patient died at +50 d after transplantation, two patients were followed up for 28 months and 15 months, respectively, and achieved disease-free survival (DFS).@*CONCLUSIONS@#BPDCN is a highly aggressive malignant tumor with poor prognosis. Chemotherapy combined with venetoclax followed by allo-HSCT may lead to long-term DFS or even cure. Post-transplant maintenance is still unclear.

Clinical analysis of seven cases of hemophagocytic lymphohistiocytosis secondary to cutaneous T-cell lymphoma / 中华皮肤科杂志

Objective:To investigate clinical and laboratory characteristics of secondary hemophagocytic lymphohistiocytosis (sHLH) associated with secondary cutaneous T-cell lymphoma (CTCL) .Methods:CTCL patients with clinically suspected sHLH were collected from Department of Hematology, Wuhan No.1 Hospital from January 2016 to October 2021, and were evaluated according to the HLH-2004 diagnostic criteria and HScore.Results:Seven CTCL patients were confirmedly diagnosed with sHLH, including 2 with primary cutaneous γδT-cell lymphoma (PC-GDTCL) , 3 with cutaneous extranodal natural killer/T-cell lymphoma (C-ENKTCL) , and 2 with primary cutaneous anaplastic large cell lymphoma (PC-ALCL) . All the 7 patients received chemotherapy, but 6 died finally, and the median overall survival duration was 26.5 days (range: 14 - 60 days) after the confirmed diagnosis of CTCL complicated by sHLH. HLH-related gene mutations, which were located in the PRF1 and LYST genes, were identified in 2 patients; lymphoma-related gene mutations were identified in the KRAS and KMT2D genes in 1 PC-GDTCL patient,and in the JAK3 and SAMHD1 genes in another PC-GDTCL patient.Conclusions:CTCL complicated by sHLH usually progresses rapidly, so early diagnosis and treatment are needed. Bone marrow biopsy and mutation screening of lymphoma- and HLH-related genes at initial diagnosis and during disease progression may facilitate early diagnosis.