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Background Evidence on maintenance therapy following frontline induction is sparse in primary light-chain amyloidosis (AL), especially for those who do not undergo autologous haematopoietic stem cell transplantation (ASCT).Methods We enrolled primary AL patients who achieved at least haematologic very good partial response (VGPR) by the 4th month at the frontline from December 2008 to June 2023 at Zhongshan Hospital, Fudan University. Those who followed maintenance therapy were identified as the maintenance group (n = 44), whereas those entering the observational phase were classified as the observational group (n = 24).Results After 7.2(interquartile range, 4.7–18.6) months of maintenance therapy, 9(20.5%), 14(31.8%) and 5 (11.4%) patients achieved improvement in haematologic, cardiac and renal response respectively. Five (11.4%) patients had minimal residual disease (MRD) response conversion from positive to negative based on maintenance therapy. In the observation group, none of the patients had haematologic response improvement, with 3(12.5%) and 1(4.2%) patient showing cardiac and renal response improvement during follow-up.Conclusion This study identified the clinical benefits of maintenance therapy in patients with AL who did not undergo ASCT in real-world practice.

Abstract Background Obesity is a risk factor for multiple myeloma (MM). However, we still lack knowledge on the clinical course of obese MM patients in a broad view. Methods Here, we reviewed 568 MM patients recorded in the Multiple Myeloma Research Foundation (MMRF) coMMpass dataset. Patients were divided into the normal and obese groups according body mass index (BMI) at diagnosis, and then the baseline characteristics, cytogenetic abnormalities, treatment variability, and survival outcomes were evaluated in the obese cohort. Results We found no differences in the characteristics when comparing normal and obese MM patients other than more male in the obese part (50.4% vs. 59.9%, p = 0.024). Compared with the normal BMI patients, median overall survival (OS) was shorter for obese MM patients but without significant meaning (82.3 vs. 95.3 months, p = 0.25). However, in the subgroup analysis, obese MM patients younger than 65 years had significantly inferior OS than that in the normal category (p = 0.047). We also found obese MM patients had a higher overall response rate (ORR) compared with normal BMI patients (92.7% vs. 88.6%, p = 0.037). Additionally, obese patients seemed to achieve faster best response during first‐line therapy. Conclusions Obesity assumes a paradoxical function in the clinical trajectory of myeloma.

BackgroundAcute promyelocytic leukemia (APL) is rarely caused by the PLZF::RARα fusion gene. While APL patients with PLZF::RARα fusion commonly exhibit diverse hematologic symptoms, the presentation of myeloid sarcoma (MS) as an initial manifestation is infrequent.Case presentationA 61-year-old patient was referred to our hospital with 6-month history of low back pain and difficulty walking. Before this admission, spine magnetic resonance imaging (MRI) conducted at another hospital revealed multiple abnormal signals in the left iliac bone and vertebral bodies spanning the thoracic (T11-T12), lumbar (L1-L4), and sacral (S1/S3) regions. This led to a provisional diagnosis of bone tumors with an unknown cause. On admission, complete blood count (CBC) test and peripheral blood smear revealed a slightly increased counts of monocytes. Immunohistochemical staining of both spinal and bone marrow (BM) biopsy revealed positive expression for CD117, myeloperoxidase (MPO), and lysozyme. BM aspirate showed a significant elevation in the percentage of promyelocytes (21%), which were morphologically characterized by round nuclei and hypergranular cytoplasm. Multiparameter flow cytometry of BM aspirate revealed that blasts were positive for CD13, CD33, CD117, and MPO. Through the integrated application of chromosome analysis, fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), and Sanger sequencing, it was determined that the patient possessed a normal karyotype and a rare cryptic PLZF::RARα fusion gene, confirming the diagnosis of APL.ConclusionIn the present study, we report the clinical features and outcome of a rare APL patient characterized by a cryptic PLZF::RARα fusion and spinal myeloid sarcoma (MS) as the initial presenting symptom. Our study not only offers valuable insights into the heterogeneity of APL clinical manifestations but also emphasizes the crucial need to promptly consider the potential link between APL and MS for ensuring a timely diagnosis and personalized treatments.

Abstract Background To improve the early detection rate of multiple myeloma (MM), the M‐protein screening system has been performed in the hospital population at Zhongshan Hospital Fudan University since 2014, with electrophoretic‐based monoclonal immunoglobulin (M‐protein) screening integrated into the blood biochemistry panel. This study updated 7‐year follow‐up findings of MM patients diagnosed by screening‐driven and symptom‐driven approaches. Methods The retrospective study compared the characteristics and outcomes of patients diagnosed through two patterns by reviewing the plasma cell disease database from January 2014 to October 2021. The screening‐driven group included patients diagnosed through the screening system during workups of unrelated medical conditions or routine checkups. In contrast, patients who visited or were referred to the hematological department due to myeloma‐related end‐organ damage were categorized into the symptom‐driven group. Results There were 3,110,218 serum protein electrophoresis (SPEP) tests performed during 7 years, with 1.95% (60,609) patients yielding positive SPEP results. Of 911 confirmed MM cases (excluding concurrent amyloidosis), 366 were assigned to the screening‐driven group, while 545 were to the symptom‐driven group. Compared to the symptom‐driven group, the screening group had more IgG subtypes, earlier International Stage System stages, fewer disease‐related symptoms, lower ECOG scores, less extramedullary disease, a lower percentage of bone marrow plasma cells, and a lower level of lactate dehydrogenase. Frontline response results of two groups were similar. Patients detected through screening had a significantly improved median progression‐free survival (PFS) than the symptom‐driven group (62.2 vs. 24.9 months, p

ABSTRACTObjectives The clinical outcomes of multiple myeloma (MM) patients are highly variable in the real-world setting. Some MM patients may have clinical endings that do not abide by the book. We aim to describe features of MM patients with extreme survivals in real-world practice.Methods This retrospective study enrolled 941 patients consecutively visited a national medical center, China, between July 1995 and December 2021. Among patients, we identified two groups of MM patients with extreme survivals, 56 were in the long-term remission (LR) group with progression-free survival (PFS) ≥ 60 months, and 82 were in the rapid progression (RP) group with PFS ≤ 6 months.Results CRAB features, of which hypercalcemia, renal insufficiency, and anemia were more common in the RP group, except for bone disease, with a comparable incidence at diagnosis in both groups (88.8 vs 85.7%, P = 0.52). High-risk cytogenetics was detected in 45.7% of patients in the RP group. Of note, 14.3% of MM patients in the LR group harbored del (17p). According to the Revised International Staging System (R-ISS), 9% of patients belonged to stage I in the RP group, and 19% of patients in the LR group were found in stage III. There were 8 (15.7%) patients in the LR group only achieved partial response (PR) as the best response. Median time to best response (TBR) for LR and RP group patients was 4.6 and 1.4 months, respectively.Conclusions The disparities in the survivals of MM patients indicated that some unexpected factors have influenced the outcomes in the real-world setting.

Abstract Background Significant advances in multiple myeloma (MM) over the past 15 years led to exciting changes in the management of MM patients in China, which in turn brought about the early diagnoses, precise risk stratifications, and improved prognoses. Methods We summarized the dynamic changes in the management of newly diagnosed (ND) MM in a national medical center, crossing the old and novel drug era. Demographics, clinical characteristics, first‐line treatment, response rate, and survival were retrospectively collected among NDMMs diagnosed in Zhongshan Hospital Fudan University from January 2007 to October 2021. Results Of the 1256 individuals, median age was 64 (range 31–89) with 45.1% patients >65 years. About 63.5% were male, 43.1% were at ISS stage III and 9.9% had light‐chain amyloidosis. Patients with abnormal ratio of free light chain (80.4%), extramedullary disease (EMD, 22.0%), and high‐risk cytogenetic abnormalities (HRCA, 26.8%) were detected by novel detection techniques. The best confirmed ORR was 86.5%, including 39.4% with CR. Short‐ and long‐term PFS and OS rates persistently increased each year along with increasing novel drug applications. Median PFS and OS were 30.9 and 64.7 months. Advanced ISS stage, HRCA, light‐chain amyloidosis and EMD independently predicted an inferior PFS. First‐line ASCT indicated a superior PFS. Advanced ISS stage, elevated serum LDH, HRCA, light‐chain amyloidosis, and receiving PI/IMiD‐based regimen versus PI+IMiD‐based regimen independently indicated a poorer OS. Conclusions In brief, we illustrated a dynamic landscape of MM patients in a national medical center. Chinese MM patients evidently benefited from newly introduced techniques and drugs in this field.

Abstract We considered various non‐uniformities such as branch faults, rotation of stress field directions, and changes in tectonic environments to simulate the dynamic rupture process of the 6 February 2023 Mw 7.8 Kahramanmaraş earthquake in SE Türkiye. We utilized near‐fault waveform data, GNSS static displacements, and surface rupture to constrain the dynamic model. The results indicate that the high initial stress accumulated in the Kahramanmaraş‐Çelikhan seismic gap leads to the successful triggering of the East Anatolian Fault (EAF) and the supershear rupture in the northeast segment. Due to the complexity of fault geometry, the rupture speed along the southeastern segment of the EAF varied repeatedly between supershear and subshear, which contributed to the unexpectedly strong ground motion. Furthermore, the triggering of the EAF reminds us to be aware of the risk of seismic gaps on major faults being triggered by secondary faults, which is crucial to prevent significant disasters.

In a neutral solution, we investigated the effects of Na2[ZnEDTA] concentrations at 0, 6, 12, 18, and 24 g/L on surface morphology, chemical composition, degradation resistance, and in vitro cytocompatibility of micro-arc oxidation (MAO) coatings developed on WE43 (Mg-Y-Nd-Zr) magnesium alloys. The results show that the enhanced Na2[ZnEDTA] concentration increased the Zn amount but slightly decreased the degradation resistance of MAO-treated coatings. Among the zinc-containing MAO samples, the fabricated sample in the base solution added 6 g/L Na2[ZnEDTA] exhibits the smallest corrosion current density (6.84 × 10−7 A·cm−2), while the sample developed in the solution added 24 g/L Na2[ZnEDTA] and contains the highest Zn content (3.64 wt.%) but exhibits the largest corrosion current density (1.39 × 10−6 A·cm−2). Compared to untreated WE43 magnesium alloys, zinc-containing MAO samples promote initial cell adhesion and spreading and reveal enhanced cell viability. Coating degradation resistance plays a more important role in osseogenic ability than Zn content. Among the untreated WE43 magnesium alloys and the treated MAO samples, the sample developed in the base solution with 6 g/L Na2[ZnEDTA] reveals the highest ALP expression at 14 d. Our results indicate that the MAO samples formed in the solution with Na2[ZnEDTA] promoted degradation resistance and osseogenesis differentiation of the WE43 magnesium alloys, suggesting potential clinic applications.

Abstract Background Multiple myeloma (MM) is an incurable hematological malignancy. Although proteasome inhibitors and immunomodulators have significantly improved patient outcomes, some patients respond poorly to treatment and almost all patients will relapse. Mechanisms of proteasome inhibitor resistance in multiple myeloma have not been fully elucidated. ZHX2 is a transcription regulator degraded via proteasome and presents both oncogenic or tumor suppressive effect in different cancers, however, it is still unknown that the role of ZHX2 in myeloma. In this study, we aim to demonstrate the effect and mechanism of ZHX2 on proteasome inhibitor resistance in MM. Methods GSE24080 gene expression profile datasets from Gene Expression Omnibus (GEO) were analyzed to evaluate the relationship between ZHX2 expression level and survival in MM. Expression of ZHX2 in human MM cell lines at baseline and after bortezomib (BTZ) treatment was determined by Western blotting (WB). The proliferation and apoptosis rate of MM cells treated with BTZ after the knockdown of ZHX2 were analyzed by flow cytometry. Nuclear translocation of NF‐κB after the knockdown of ZHX2 was evaluated by WB and immunofluorescence, and the expression of NF‐κB target genes was measured by real‐time quantitative PCR. Co‐immunoprecipitation (Co‐IP) and WB were used to detect the interaction of ZHX2 with NF‐κB. Results We found that higher ZHX2 expression was correlated with poorer clinical outcomes of patients. In addition, ZHX2 expression was relatively higher in RPMI‐8226 and MM.1S cell lines and the level of ZHX2 protein was upregulated after BTZ treatment. Knockdown of ZHX2 significantly enhanced the sensitivity of MM cells to BTZ, inhibited nuclear translocation of NF‐κB, and reduced mRNA expression of NF‐κB target genes. It was also revealed that ZHX2 directly binds to NF‐κB. Conclusion Our study showed that ZHX2 can promote proteasome inhibitor resistance in MM cells by regulating the nuclear translocation of NF‐κB.

Most patients with multiple myeloma (MM) will eventually relapse and current treatments have limited effect. Herein, we demonstrate that succinate dehydrogenase subunit A (SDHA) was low expressed in MM patients, and patients with SDHA relatively high expression had long overall survival and progression-free survival. Furthermore, SDHA high expression inhibited proliferation and invasion in MM cell lines and enhanced the anti-tumor and synergistic effect of chemotherapeutics. More importantly, chidamide was proved effective in MM by targeting SDHA, and expression of SDHA was increased by chidamide through acetylating H3K27 site of SDHA. Collectively, high expression of SDHA, which was regulated by histone acetylation and targeted by chidamide, might become a good prognostic factor of MM patients.

Immunodeficiencies are widely becoming known as important features of multiple myeloma (MM) and may promote the proliferation of malignant cells as well as confer resistance to therapy. Few studies focus on the immunomodulatory effects of the complement system on MM. This study aims to explore the role of C1q in MM patients. Plasma C1q was found to be significantly reduced in MM patients, and the amount of C1q deposited around the CD138+ cells in bone marrow (BM) biopsy sections was observed to be much higher, especially in the subgroup with 1q21 amplification (Amp1q21). CD138+ cells expressed higher levels of C1q receptors (C1qRs) than CD138− cells. Patients with Amp1q21 expressed higher levels of globular C1qR (gC1qR), whereas patients without Amp21 expressed higher levels of collagen tail C1qR (cC1qR). Additionally, gC1qR was noted to suppress the MM-inhibiting role of C1q in H929, U266, and MM1S. gC1qR interacts with insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), which also suppressed the function of C1q and regulated CDC28 protein kinase regulatory subunit 1B (CKS1B) mRNA. In summary, gC1qR suppressed the MM-inhibiting role of C1q and regulated CKS1B mRNA in promoting tumor proliferation via IGF2BP3 in 1q21-amplified MM. Our findings provide novel evidence on how MM cells evade the immune system and promote survival as well as suggest possible novel targets for future therapies of MM.

LaFeO perovskite was synthesized mechanochemically through ball milling of LaO and FeO in stoichiometric ratio. X-ray powder diffraction (XRPD), simultaneous differential scanning calorimetry and thermogravimetry analysis (DSC-TGA), Mössbauer spectroscopy, scanning electron microscopy (SEM), and optical diffuse reflectance spectroscopy were combined for a detailed study of the growth mechanism of LaFeO perovskite during the ball milling process. The XRPD results showed that LaO is unstable when exposed to air. Both LaO and La(OH) phases coexist under the ball milling process, indicating that LaO or La(OH) can be used to produce LaFeO. The formation of LaFeO perovskite was evident after only 2 h of milling and the amount of LaFeO gradually increased with the increase of ball milling time. After 12 h of ball milling, single phase LaFeO was formed. The Mössbauer spectroscopy studies show that the spectrum of the formed LaFeO phase consists of three sextets and one doublet, indicating the wide distribution of LaFeO particle sizes and some of the smaller particles having superparamagnetic properties. This is in good agreement with the SEM images, which show that the formed LaFeO phase consists of nanometer-sized particles and micrometer-sized agglomerates. The formation of LaFeO phase was mainly caused by the La substitution of Fe in FeO lattice. Optical diffuse reflectance spectroscopy studies show that the formed LaFeO phase has semiconductor properties, with the band gap energy ~2.67 eV. [ABSTRACT FROM AUTHOR]

Indium oxide-doped hematite xInO·(1 − x)α-FeO ( x = 0.1-0.7) nanostructure system was synthesized using mechanochemical activation by ball milling and characterized by XRD, simultaneous DSC-TGA, and UV/Vis/NIR. The microstructure and thermal behavior of as obtained system were dependent on the starting InO molar concentration x and ball milling time. XRD patterns yielded the dependence of lattice parameters and grain size as a function of ball milling time. After 12 h of ball milling, the completion of In substitution of Fe in hematite lattice occurs for x = 0.1, indicating that the solid solubility of InO in hematite lattice is extended. For x = 0.3, 0.5, and 0.7, the substitutions between In and Fe into hematite and InO lattice occur simultaneously. The lattice parameters a and c of hematite and lattice parameter a of indium oxide vary as a function of ball milling time. The changes of these parameters are due to ion substitutions between In and Fe and the decrease in the grain sizes. Ball milling has a strong effect on the thermal behavior and band gap energy of the as-obtained system. The hematite decomposition is enhanced due to the smaller hematite grain size. The crystallization of hematite and InO was suppressed, with drops of enthalpy values due to the stronger solid-solid interactions after ball milling, which caused gradual In-Fe substitution in hematite/InO lattices. The band gap for hematite shifts to higher energy value, while that of indium oxide shifts to lower energy value after ball milling. [ABSTRACT FROM AUTHOR]