R2-ISS staging combined with circulating plasma cells improves risk stratification for newly diagnosed multiple myeloma: a single-center real-world study.

We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.

Hyperuricemia as an independent risk factor for metabolic dysfunction-associated fatty liver disease in nonobese patients without type 2 diabetes mellitus.

According to the latest consensus statement, fatty liver complicated by specific metabolic abnormalities can be diagnosed as metabolic dysfunction-associated fatty liver disease (MAFLD) in nonobese patients without type 2 diabetes mellitus (T2DM). However, hyperuricemia (HUA), a manifestation of metabolic disorders, is excluded from diagnostic criteria. This study explored the association between HUA and MAFLD in nonobese patients without T2DM. A total of 28,187 participants were recruited from the Examination Center of the China-Japan Friendship Hospital from 2018 to 2022 and divided into four subgroups: nonobese patients without T2DM, obese patients without T2DM, nonobese patients with T2DM, and obese patients with T2DM. MAFLD was diagnosed by ultrasound combined with laboratory examinations. The association of HUA with MAFLD subgroups was performed by logistical regression analysis. The predictive ability of UA for MAFLD subgroups was assessed by receiver operating characteristics (ROC). HUA was positively associated with MAFLD in nonobese patients without T2DM in both males and females, even after adjusting for sex, BMI, dyslipidemia, and abnormal liver function. The association increased gradually with aging, especially in those over 40 yr old. HUA was an independent risk factor for MAFLD in nonobese patients without T2DM. We suggest that UA abnormalities might be considered in the diagnosis of MAFLD in nonobese patients without T2DM.NEW & NOTEWORTHY HUA is an independent risk factor for MAFLD in nonobese patients without T2DM. The association of HUA with MAFLD in nonobese patients without T2DM increased gradually with aging, especially in those over 40 yr old. In nonobese patients without T2DM, univariate analysis showed that females with HUA had a higher risk of MAFLD than males. However, the difference was narrowed after adjustment for confounders.

Risk-benefit ratio of percutaneous kyphoplasty and percutaneous vertebroplasty in patients with newly diagnosed multiple myeloma with vertebral fracture: a single-center retrospective study.

The indications for percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP) are painful vertebral compression fractures. Our study is to assess the risk-benefit ratio of PKP/PVP surgery in the patients with newly diagnosed multiple myeloma (NDMM) without receiving antimyeloma therapy. The clinical data of 426 consecutive patients with NDMM admitted to our center from February 2012 to April 2022 were retrospectively analyzed. The baseline data, postoperative pain relief, the proportion of recurrent vertebral fractures, and survival time were compared between the PKP/PVP surgical group and the nonsurgical group in the NDMM patients. Of the 426 patients with NDMM, 206 patients had vertebral fractures (206/426, 48.4%). Of these, 32 (32/206, 15.5%) underwent PKP/PVP surgery for misdiagnosis of simple osteoporosis prior to diagnosis of MM (surgical group), and the other 174 (174/206, 84.5%) did not undergo surgical treatment prior to definitive diagnosis of MM (non-surgical group). The median age of patients in the surgical and nonsurgical groups was 66 and 62 years, respectively (p = 0.01). The proportion of patients with advanced ISS and RISS stages was higher in the surgical group (ISS stage II + III 96.9% vs. 71.8%, p = 0.03; RISS stage III 96.9% vs. 71%, p = 0.01). Postoperatively, 10 patients (31.3%) never experienced pain relief and 20 patients (62.5%) experienced short-term pain relief with a median duration of relief of 2.6 months (0.2-24.1 months). Postoperative fractures of vertebrae other than the surgical site occurred in 24 patients (75%) in the surgical group, with a median time of 4.4 months postoperatively (0.4-86.8 months). Vertebral fractures other than the fracture site at the first visit occurred in 5 patients (2.9%) in the nonoperative group at the time of diagnosis of MM, with a median time of 11.9 months after the first visit (3.5-12.6 months). The incidence of secondary fractures was significantly higher in the surgical group than in the nonsurgical group (75% vs. 2.9%, p = 0.001). The time interval between the first visit and definitive diagnosis of MM was longer in the surgical group than in the nonsurgical group (6.1 months vs. 1.6 months, p = 0.01). At a median follow-up of 32 months (0.3-123 months), median overall survival (OS) was significantly shorter in the surgical group than in the nonsurgical group (48.2 months vs. 66 months, p = 0.04). Application of PKP/PVP surgery for pain relief in NDMM patients without antimyeloma therapy has a limited effect and a high risk of new vertebral fractures after surgery. Therefore, patients with NDMM may need to have their disease controlled with antimyeloma therapy prior to any consideration for PKP/PVP surgery.

Fluorescence/Colorimetry/Smartphone Triple-Mode Sensing of Dopamine by a COF-Based Peroxidase-Mimic Platform.

Simple and accurate monitoring of urinary dopamine (DA) concentration is significant, which is helpful for the assessment or exclusion of catecholamine-producing tumors, such as pheochromocytoma and paraganglioma. Herein, a fluorescence/colorimetry/smartphone triple-mode sensing platform for DA determination was constructed using copper ion (Cu2+)-modified hydrazone-linked covalent organic frameworks (Cu-BTA-COF). Cu-BTA-COF with 21.67 wt % copper content exhibited peroxidase-mimic activity. After adding H2O2 and 1,3-dihydroxynaphthalene, the Cu-BTA-COF platform can sensitively and selectively detect DA in three modes with consistent results. In fluorescence/colorimetry/smartphone modes, the linear ranges of DA were 1-10, 0.2-40, and 1-10 µM, with related detection limits of 7.2, 8.6, and 23 nM, respectively. Moreover, the Cu-BTA-COF platform can be explored for DA determination in human urine samples with satisfactory recoveries (97.6-100.4%) in all the three modes, suggesting the potential practical application of the Cu-BTA-COF platform for DA detection in urine.

Ratiometric Fluorescent pH Sensor Based on a Tunable Multivariate Covalent Organic Framework.

Ratiometric detection of pH is always significant in environmental regulation, medical diagnosis, synthetic chemistry, and beyond. The construction of practical ratiometric pH sensors with reusability is still challenging. Herein, by exploiting a multivariate strategy, we first synthesized and reported a series of novel three-component covalent organic frameworks (COF-COOHX, X = 33, 50, and 67) through Schiff base reaction between 2-hydroxybenzene-1,3,5-tricarbaldehyde (HTA), 4,4'-diamino-3,3'-biphenyldicarboxylic acid (DBA), and 5,5'-diamino-2,2'-bipyridine (BPY) at various molar ratios (X = [DBA]/([BPY] + [DBA]) × 100 = 33, 50, and 67). COF-COOHX (X = 33, 50, and 67) displayed ratiometric pH sensing performance in acidic conditions with selectivity and repeatability. By tuning the molar ratio of DBA and BPY, the fluorescent properties, linear pH responsive ranges, and pKa values of COF-COOHX (X = 33, 50, and 67) can be regulated. Meanwhile, the two-component COF-COOH0 and COF-COOH100 did not exhibit ratiometric pH detection ability. Moreover, the constructed three ratiometric sensors can be applied to detect pH in drug solutions and carbonated drinks with satisfactory results. This work sheds new light on the design and fabrication of innovative ratiometric fluorescent sensors using COFs.

Addition of chemoradiotherapy to palliative chemotherapy in de novo metastatic nasopharyngeal carcinoma: a real-world study.

BACKGROUND: To determine whether concurrent chemotherapy is necessary during locoregional radiotherapy (RT) after palliative chemotherapy (PCT) in patients with de novo metastatic nasopharyngeal carcinoma (mNPC). METHODS: A total of 746 patients with mNPC from 2000 to 2017 at our hospital were retrospectively reviewed. Among them, 355 patients received PCT followed by RT. Overall survival (OS) and progression-free survival (PFS), including locoregional progression-free survival (LRPFS) and distant progression-free survival (DPFS) were estimated with the Kaplan-Meier method and log-rank test. Cox proportional-hazards models, landmark analyses, propensity score matching, and subgroup analyses were used to address confounding. RESULTS: Of the patients included in our study, 192 received radiotherapy alone after PCT (PCT + RT), and 163 received concurrent chemoradiotherapy after PCT (PCT + CCRT). The prognosis of PCT + CCRT was significantly better than that of PCT + RT (5 year OS, 53.0 vs 36.2%; P = 0.004). After matching, the 5 year OS rates of the two groups were 55.7 and 39.0%, respectively (P = 0.034) and the median DPFS were 29.4 and 18.7 months, respectively (P = 0.052). Multivariate Cox regression analysis indicated that PCT + CCRT was an independent favorable prognostic factor (P = 0.009). In addition, conducting concurrent chemoradiotherapy after 4-6 cycles of PCT or conducting concurrent chemotherapy with single-agent platinum was associated with significant survival benefit in the matched cohort (5 year OS rate, 60.4 or 57.4%, respectively). The survival difference between groups remained significant when evaluating patients who survived for ≥ 1 year (P = 0.028). CONCLUSIONS: The optimal treatment strategy of mNPC is the combination of PCT followed by concurrent chemoradiotherapy. More specifically, concurrent chemoradiotherapy with single-agent platinum after 4-6 cycles of PCT is suggested.

Amp 1q21 is more predictable with dismal survival than gain 1q21 of newly diagnosed multiple myeloma in real-world analysis.

INTRODUCTION: The gain/amplification (amp) of 1q21 is one of the most common high-risk chromosome abnormality (HRCA) in multiple myeloma (MM). The prognostic value of 1q21+ remains to be controversial on the status of gain or amp and the combination of other HRCAs. METHODS: In this retrospective study, we included 318 newly diagnosed MM (NDMM) patients who had fluorescence in situ hybridization (FISH) data and treated with novel agents in our department. RESULTS: Our study noted MM patients with amp 1q21 were more likely accompanied with t(4;14), t(14;16), and t(14;20). Patients with amp 1q21 presented with elder age, advanced Revised International Staging System (R-ISS) stages, anemia, and more plasma cells in bone marrow compared to patients with gain 1q21 alone and no 1q21+. Moreover, amp 1q21 alone correlated with shorter progression-free survival (PFS) (22.8m vs. 40.5m vs. 39.6m) and overall survival (OS) (45.2m vs. NA vs. 83.5m) compared with gain 1q21 alone and no FISH abnormalities. Although the high ratio of proteasome inhibitor and immunomodulatory drugs used in patients with amp 1q21, the overall response (ORR) was the lowest compared with no 1q21+ and gain 1q21. Multivariate analysis defined amp 1q21 as an independent prognostic marker for NDMM patients, rather than gain 1q21. CONCLUSION: The amp 1q21 predict inferior treatment response and survival, especially coexisted with high-risk IgH translocation.

[Pharmacokinetic study of Polydopamine Guttate Pills loaded with active components of Sarcandrae Herba in rats].

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established for the determination of active components of Sarcandrae Herba, and applied to the pharmacokinetics study of multiple dosage forms. After SD rats were administered by gavage with three dosage forms [Sarcandrae Herba extract, commercial Sarcandrae Herba Guttate Pills, and polydopamine guttate pills loaded with active components of Sarcandrae Herba(PDA-Sg Guttate Pills)], blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC C_(18) column(2.1 mm×100 mm, 1.7 µm). The mobile phase consisted of water containing 0.2% formic acid and acetonitrile in gradient elution. The negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 2.0. All four components could be detected in the plasma of rats in each group at each time point except the neochlorogenic acid and cryptochlorogenic acid in the Sarcandrae Herba extract group. The guttate pills group showed a significant increase in drug content at each time point. The exposure of the main components of Sarcandrae Herba in blood was effectively increased by PDA-drug loading effect in PDA-Sg Guttate Pills(The AUC_(0-24 h) of neochlorogenic acid, cryptochlorogenic acid, isaziridin and rosmarinic acid reached 2.45, 32.90, 1.54, 4.81 times that of the commercial guttate pills). This study proves the measurability of the above-mentioned multi-component in vitro-in vivo delivery process. The pharmacokinetic study has shown that PDA-Sg Guttate Pills can effectively delay the elimination time and improve the bioavailability of the four components, which can provide theoretical data for the production of the drug.

Serum-derived three-circRNA signature as a diagnostic biomarker for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common tumor characterized by high morbidity and mortality rates. The importance of circRNA in cancer diagnosis has been established. The study aimed to identify differentially-expressed circRNAs (DECs) in human blood exosomes from patients with HCC and to investigate their diagnostic value. METHODS: The circRNA expression profiles of HCC and normal human blood samples were downloaded and processed from the exoRBase database. At the cutoff criteria of a fold change (FC) > 2.0 and P < 0.05, DECs were screened utilizing the limma package in the R software. A receiver operator characteristic curve (ROC) was used to study its diagnostic value. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis was performed to confirm the three-circRNAs expression in the blood samples with HCC. Various bioinformatics tools were used to characterize the potential biological pathways induced by circRNAs. RESULTS: Compared with the normal samples, seven up-regulated and five down-regulated circRNAs were determined in the HCC samples. ROC analyses demonstrated that hsa_circ_0004001, hsa_circ_0004123, hsa_circ_0075792, and a combination of the three biomarkers exhibited higher sensitivity and specificity. The qRT-PCR confirmed that the three circRNAs were upregulated in the blood samples with HCC. Chi squared tests implied that the expression of three circRNAs was positively correlated with the TNM stage and tumor size. The circRNAs participated in VEGF/VEGFR, PI3K/Akt, mTOR, and Wnt signaling pathways by targeting miRNAs. CONCLUSIONS: The study established the existence of seven up-regulated and five down-regulated circRNAs in HCC. Additionally, hsa_circ_0004001, hsa_circ_0004123, hsa_circ_0075792, and a combination of the three were utilized as valuable diagnostic biomarkers in HCC.

Changes of mechanoreceptors in different-state remnants of ruptured anterior cruciate ligament.

OBJECTIVE: To observe the changes in the quantity and morphology of mechanoreceptors in different-state remnant stumps of ruptured anterior cruciate ligaments (ACLs). METHODS: Specimens of completely ruptured ACL remnants were collected from 57 patients. The injury time from injury to surgery was recorded. According to the degree of pre-operative anterior displacement of knee joint, these patients were divided into two groups: group 1 (≤ 6 mm) and group 2 (> 6 mm). The morphology type of ligament remnant in each patient was identified. The correlations of mechanoreceptor number in the remnant stumps with the morphology of ligament stump, injured knee stability, and injury time were analyzed. Subsequently, based on ACL lesion type, patients were divided into four groups including groups A, B, C, and D, and then, the items above were compared among the four groups. RESULTS: Group 1 contained 20 specimens including three with type B and 17 with type C. Group 2 contained 37 specimens including 20 with type A, 1 with type B, 2 with type C, and 14 with type D. The distributions of four-type remnant morphologies (X2 = 49.406, P = 0.000) and mechanoreceptors (X2 = 13.84, P = 0.002) were all significantly different between the two groups. The number of mechanoreceptors was positively correlated with the injured knee stability (r = 0.63,P = 0.018). The number of the mechanoreceptors was not obviously correlated with the injury time in group 1 (r = - 0.37,P = 0.136), while it was negatively correlated with the injury time in group 2 (r = - 0.51,P = 0.022). There was a significant difference in pre-operative anterior displacement of knee joint among groups A, B, C, and D (F = 85.59, P = 0.000), and the pre-operative anterior displacement of knee joint was less in groups B and C than in groups A and D. There was a significant difference in the distribution of typical and atypical mechanoreceptors among groups A, B, C, and D (X2 = 68.16, P = 0.032). CONCLUSIONS: The ruptured ACL remnants connecting the femur to tibia can still play a role in maintaining knee stability; thus, the mechanoreceptors can persist in these remnants for a long time.

Aberrant T cell responses in the bone marrow microenvironment of patients with poor graft function after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, whether abnormalities of T cell subsets in the bone marrow (BM) immune microenvironment, including Th17, Tc17, Th1, Tc1, Th2, Tc2 cells and regulatory T cells (Tregs), are involved in the pathogenesis of PGF remains unclear. METHODS: This prospective nested case-control study enrolled 20 patients with PGF, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD). Th17, Tc17, Th1, Tc1, Th2, Tc2 cells, Tregs and their subsets were analyzed by flow cytometry. RESULTS: A significantly higher proportion of stimulated CD4+ and CD8+ T cells that produced IL-17 (Th17 and Tc17) was found in the BM of PGF patients than in the BM of GGF patients and HD, whereas the percentages of Tregs in PGF patients were comparable to those in GGF patients and HD, resulting in a dramatically elevated ratio of Th17 cells/Tregs in the BM of PGF patients relative to those in GGF patients. Moreover, both CD4+ and CD8+ T cells were polarized towards a type 1 immune response in the BM of PGF patients. CONCLUSIONS: The present study revealed that aberrant T cell responses in the BM immune microenvironment may be involved in the pathogenesis of PGF after allo-HSCT. These findings will facilitate the optimization of immune regulation strategies and improve the outcome of PGF patients post-allotransplant.

Hollow Cobalt-Based Bimetallic Sulfide Polyhedra for Efficient All-pH-Value Electrochemical and Photocatalytic Hydrogen Evolution.

The development of highly active, universal, and stable inexpensive electrocatalysts/cocatalysts for hydrogen evolution reaction (HER) by morphology and structure modulations remains a great challenge. Herein, a simple self-template strategy was developed to synthesize hollow Co-based bimetallic sulfide (MxCo3-xS4, M = Zn, Ni, and Cu) polyhedra with superior HER activity and stability. Homogenous bimetallic metal-organic frameworks are transformed to hollow bimetallic sulfides by solvothermal sulfidation and thermal annealing. Electrochemical measurements and density functional theory computations show that the combination of hollow structure and homoincorporation of a second metal significantly enhances the HER activity of Co3S4. Specifically, the homogeneous doping in Co3S4 lattice optimizes the Gibbs free energy for H* adsorption and improves the electrical conductivity. Impressively, hollow Zn0.30Co2.70S4 exhibits electrocatalytic HER activity better than most of the reported nobel-metal-free electrocatalysts over a wide pH range, with overpotentials of 80, 90, and 85 mV at 10 mA cm(-2) and 129, 144, and 136 mV at 100 mA cm(-2) in 0.5 M H2SO4, 0.1 M phosphate buffer, and 1 M KOH, respectively. It also exhibits photocatalytic HER activity comparable to that of Pt cocatalyst when working with organic photosensitizer (Eosin Y) or semiconductors (TiO2 and C3N4). Furthermore, this catalyst shows excellent stability in the electrochemical and photocatalytic reactions. The strategy developed here, i.e., homogeneous doping and self-templated hollow structure, provides a way to synthesize transition metal sulfides for catalysis and energy conversion.

Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation.

Poor graft function (PGF) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched patients with good graft function after allo-HSCT, and 15 healthy donors were enrolled in this nested case-control study. The Th1, Th2, Tc1, Tc2, and active phenotypes were analyzed by flow cytometry. IFN-γ and IL-4 levels in BM plasma were evaluated using cytometric beads assay. Relative to other subjects, patients with PGF had significantly higher proportions of stimulated CD4(+) and CD8(+) T cells that produced IFN-γ (Th1 and Tc1 cells) but notably decreased proportions of IL-4-producing T cells (Th2 and Tc2 cells), resulting in a shift of the IFN-γ/IL-4 ratio towards a type 1 response and an elevated percentage of activated CD8(+) T cells. Changes in IFN-γ and IL-4 levels in BM plasma were consistent with the cellular results. Our results suggest that dysregulated T cell responses may contribute to the occurrence of PGF after HSCT.

Abnormalities of the bone marrow immune microenvironment in patients with immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an acquired autoimmune disease. Although antiplatelet antibodies are considered as the primary immunologic defect in these patients, dysfunctional cellular immunity is also important in the pathophysiology of ITP. Peripheral T cell abnormalities have been demonstrated in patients with ITP; however, whether the impaired bone marrow (BM) microenvironment, specifically the BM immune microenvironment, is involved in the pathogenesis of ITP remains unknown. In this study, the compartments of the BM immune microenvironment and BM vascular microenvironment were analyzed in 26 untreated patients with ITP and 26 healthy donors (HD). Subsets of T cells in the BM immune microenvironment, including Th1, Th2, Tc1, Tc2, Th17, and Treg cells, were analyzed via flow cytometry. BM endothelial cells and perivascular cells, which are key elements of the vascular microenvironment, were analyzed via flow cytometry as well as hematoxylin-eosin (H&E) and immunohistochemical (IHC) staining in situ. Elements of the BM vascular microenvironment were found to be normal in patients with ITP, but abnormal characteristics of the BM immune microenvironment, including excessive polarization in Th1, Tc1, and Th17 cells and a remarkable decrease in Treg cells, were observed in patients with ITP. Therefore, a deregulated T cell response in the BM microenvironment might play an important role in the pathogenesis of ITP.

The effects of deferoxamine on inhibition for microglia activation and protection of secondary nerve injury after intracerebral hemorrhage in rats.

To investigate the effects of the iron chelatordeferoxamine (DFA) on inhibition formicroglia activation and protection of secondary nerve injury after intracerebral hemorrhage (ICH) in rats. The rats were randomly divided into sham operation group, ICH group and DFA treatment group. The collagenase was used to prepare ICH model of basal gangliain rats and 1h after the beginning of the operation, the intraperitoneal injection with DFA was arranged every 12 h and for a total of 7d. The changes of Iron ion concentration were measured at perihematomaat different time points after the medicine was given. OX42 immunohistochemical staining observed microglia change at perihematoma. ELISA method determined the changes of IL-1ß and TNF-ß content of brain tissue. Neurological deficit scores and Nissl staining were used to observe the situation of neurological function and neuronal loss of rats after DFA treatment. 1 d After the start of ICH, the concentration of iron in perihematoma was significantly higher than that of animalsin sham-operated group and could sustain for28 d. At the same time, the quantities of local microglial cells were significantly increased. After applying DFA, the concentration of iron ions in the brain tissue around the hematoma was significantly reduced, so did the number of microglial cells and activation of neurotoxic cytokines (IL-1ß and TNF-α content) secreted by microglial cells was significantly reduced. At the same time, the loss of neurons in the tissue around of the hematoma was significantly reduced and neurological deficit scores were significantly reduced. Iron ions which were sustainedly released by hematoma after ICH can activate the local microglia and cause secondary brain injury. DFA curb excessive activation of microglia and reduce neuronal death of ICH by means of clearinf away iron ions of brain tissue surrounding the hematoma, thus improve secondary neurological dysfunction.

Higher frequency of regulatory T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood grafts.

BACKGROUND: Regulatory T cells (Treg) in allografts are important for the prevention of graft-versus-host disease (GVHD) post-transplantation. The aim of this study was to compare the contents of Tregs and effector T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts (G-BM) and peripheral blood grafts (G-PB). METHOD: G-BM and G-PB were obtained from 20 allogeneic donors. T-cell subgroups, including conventional T cells and different types of Treg cells, as well as the percentage of Ki67 expression on CD4(+)CD25(high)Foxp3(+) Treg cells, were analyzed using flow cytometry. The levels of interferon-γ (IFN-γ) and interleukin-17 (IL-17) secreted by T cells stimulated with PMA and ionomycin were also determined by flow cytometry. RESULTS: The percentage of CD4(+)CD25(high)CD127(-/dim)CD62L(+) Treg cells was significantly higher in the G-BM group, with higher proportions of CD45RA(+) naïve Treg cells and higher expression of CD69 on Treg cells in G-BM (P < 0.05). The percentage of Ki67 expression in CD4(+)CD25(high)Foxp3(+) Treg cells in G-BM was significantly higher than that on G-PB. The suppressive functions of Treg cells in inhibiting T-cell activation were comparable between G-BM and G-PB. The proportions of CD4(+)CD25(-)CD69(+) Treg subsets as well as Th1 cells in G-BM were also significantly higher than those in G-PB (P < 0.001). The proportions of conventional T cells and Th17 effector cells were comparable in G-BM compared with those in G-PB. Thus, the ratio of conventional T cells and CD4(+)CD25(high)CD127(-/dim) regulatory T cells were lower in G-BM than that in G-PB (P = 0.014). CONCLUSION: In addition to the much higher T-cell counts in G-PB grafts that may contribute to more severe GVHD, the higher frequency of Treg cells and lower ratio of conventional T cells to Treg cells in G-BM compared with G-PB grafts might reduce GVHD post-transplantation in G-BM compared with G-PB transplantation.

The impact of donor characteristics on the immune cell composition of mixture allografts of granulocyte-colony-stimulating factor-mobilized marrow harvests and peripheral blood harvests.

BACKGROUND: The association of donor characteristics with immune cell composition in allografts remains poorly understood. In this retrospective study, the effects of donor characteristics on immune cell composition in allografts were investigated. STUDY DESIGN AND METHODS: The correlations of donor characteristics with the immune cell composition in mixture allografts of granulocyte-colony-stimulating factor-mobilized marrow harvests and peripheral blood harvests of 390 healthy donors (male, 240; female, 150; median age, 40 years old) were analyzed. RESULTS: The median doses of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD3+CD4-CD8- T cells, and monocytes in mixture allografts were 160.57 × 10(6), 89.29 × 10(6), 56.16 × 10(6), 10.87 × 10(6), and 137.94 × 10(6)/kg, respectively. Multivariate analysis showed that younger donor age was associated with a higher dose of CD3+ T cells (p = 0.006), CD3+CD8+ T cells (p < 0.001), CD3+CD4-CD8- T cells (p = 0.004), and monocytes (p = 0.014), as well as a higher ratio of CD3+CD4-CD8- T cells/CD3+ T cells (p < 0.001) in the mixture allografts. A negative association of donor weight with CD3+ T cells (p < 0.001), CD4+ T cells (p = 0.002), CD8+ T cells (p < 0.001), and CD3+CD4-CD8- T cells (p = 0.044) was observed. The count of peripheral blood lymphocyte pre-peripheral blood apheresis was correlated with the yield of CD3+ T cells (p < 0.001) and CD4+ T cells (p = 0.001). The peripheral blood monocyte count before marrow harvest predicted the monocyte dose (p = 0.002). CONCLUSION: The results suggested that older and overweight donors should not be chosen. The monocyte and lymphocyte counts before harvest could predict the yield of immune cells in allografts.

Solitary bone plasmacytoma: Long-term clinical outcomes in a single center.

BACKGROUND: A solitary plasmacytoma is classified into a solitary plasmacytoma of the bone (SBP) and a solitary extramedullary (soft tissue mass) plasmacytoma, based on the site of the lesion. Despite the high local control rate with radiotherapy, approximately half of patients' conditions progress to multiple myeloma (MM) within 3-5 years after diagnosis, with SBP having a worse prognosis. PATIENTS AND METHODS: We retrospectively assessed the treatment and outcomes of patients with SBP in a hospital in China from 2008 to 2021. Twenty-four patients treated over 13 years with SBP were enrolled in this retrospective study. RESULTS: The most common sites for SBP were the axial skeleton and femur. The M protein was detected in 11 patients (46 %), of which 8 (33 %) had light chains, 2 (8 %) had immunoglobulin G kappa and 1 (4 %) had immunoglobulin D kappa. Flow cytometry revealed that 5 patients (21 %) had minimal bone marrow involvement. The treatment included chemotherapy, surgery, and radiotherapy in 18 (75 %), 12 (50 %), and 9 (38 %) patients, respectively, of whom 13 (54 %) received combined treatment. Over a median follow-up period of 67.2 months, 9 patients (38 %) developed MM in a median time of 101.5 months. The 5- and 10-year progression-free survival rates were 67.3 % and 37.4 %, respectively. One patient died due to pneumonia without progression and the other died due to relapse. CONCLUSION: This study confirmed the high rate of progression of SBP to MM, indicating a need for adjunct chemotherapy for the management of SBP.

Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in Chinese Patients with Early Breast Cancer: A Single-Institution Study.

Objective: This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2 (HER2)-low early breast cancer (BC) and HER2-IHC0 BC. Methods: Patients diagnosed with HER2-negative BC ( N = 999) at our institution between January 2011 and December 2015 formed our study population. Clinicopathological characteristics, association between estrogen receptor (ER) expression and HER2-low, and evolution of HER2 immunohistochemical (IHC) score were assessed. Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes (5-year follow-up) between the HER2-IHC0 and HER2-low groups. Results: HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor (PgR) positivity than HER2-IHC0 BC group ( P < 0.001). The rate of HER2-low status increased with increasing ER expression levels (Mantel-Haenszel χ 2 test, P < 0.001, Pearson's R = 0.159, P < 0.001). Survival analysis revealed a significantly longer overall survival (OS) in HER2-low BC group than in HER2-IHC0 group ( P = 0.007) in the whole cohort and the hormone receptor (HR)-negative group. There were no significant differences between the two groups in terms of disease-free survival (DFS). The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion: HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Ixazomib-based frontline therapy followed by ixazomib maintenance in frail elderly newly diagnosed with multiple myeloma: a prospective multicenter study.

Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).