[Significance of IgH Gene Rearrangement in Surveillance of Minimal Residual Disease after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma].

OBJECTIVE: To investigate the value of immunoglobulin heavy chain (IgH) gene rearrangement in monitoring minimal residual disease (MRD) in multiple myeloma (MM) received autologous hematopoietic stem cell transplantation(auto-HSCT). METHODS: The clinical data of 26 MM patients who received auto-HSCT in the Department of Hematology, Wuhan First Hospital from 2018 to 2022 were collected. IgH rearrangement was detected by multiplex PCR combined with capillary electrophoresis fragment analysis to evaluate minimal residual disease (MRD), and the outcome of the disease was analyzed statistically. RESULTS: Among the 26 MM patients, 18 were males and 8 were females, with a median age of 59(41-70) years. The median follow-up time after transplantation was 33 (7-52) months. Compared with the IgH rearrangement negative group (n=17), the proportion of CR and sCR of patients with IgH rearrangement positive in bone marrow samples before auto-HSCT at 3 months after transplantation was lower （1/9 vs 14/17）, and the duration of remission (DOR) after transplantation was shorter（10.78±4.35 vs 15.88±5.22 months）, with statistically significant difference in DOR between the two groups(P < 0.05). Compared with IgH rearrangement negative group (n=21), the proportion of CR and sCR of patients with positive IgH rearrangement results from peripheral blood stem cell collection at 3 months after transplantation was lower（0/5 vs 15/21）, the duration of remission (DOR) after transplantation was shorter（9.60±4.83 vs 15.19±5.11 months）, and the difference in DOR between the two groups was statistically significant (P < 0.05). During the follow-up period, 5 patients (5/9) with positive IgH rearrangement results in bone marrow specimens died, and all patients with negative IgH rearrangement results survived. Four patients (4/5) with positive IgH rearrangement results by peripheral blood stem cell samples died, while one patient (1/21) with negative IgH rearrangement results died. In both bone marrow and peripheral blood stem cell samples, the survival time of IgH rearrangement-positive patients after transplantation was shorter than that of IgH rearrangement-negative patients(P < 0.05). Logistic regression analysis showed that gender, disease stage, the proportion of bone marrow smear plasma cells at initial diagnosis, stem cell mobilization plan, efficacy evaluation before transplantation (≥CR and 0.05). CONCLUSION: By detecting IgH rearrangement of MM patients receiving auto-HSCT, the depth of MRD can be further evaluated, which has a certain guiding significance for the efficacy and prognosis of the disease.

Age differences in the impact of dietary salt on metabolism, blood pressure and cognitive function in male rats.

The influence of salt consumption on physiological processes, especially blood pressure (BP), metabolism, and cognition, remains a topical concern. While guidelines endorse reduced salt diets, there are gaps in understanding the age-specific implications and challenges in adherence. The present study delved into the differential effects of salt intake on young adult and aged male rats over a 12-week period, using control, low-, and high-salt diets. Key metrics, such as BP, cognition, and general parameters, were monitored. Our findings revealed significant age-dependent effects of salt intake on survival rates, body weight, blood sodium, blood glucose, blood lipids, BP, heart rates, and cognition. Notably, young adult rats did not show significant sodium level changes on a high-salt diet, whereas aged rats experienced increased sodium levels even on a normal salt diet. Blood glucose levels decreased significantly in aged rats on a high-salt diet but remained stable in young adults. Aged rats had the highest survival rates on low-salt diets. Low-salt diets led to reduced BP in both age groups, more significantly in young adults. Young adult rats displayed increased BP variability on both high- and low-salt diets, while a decrease in BP variability was exclusive to aged rats on a low-salt diet. There were significant differences across age groups in short-term memory, but not in long-term memory. The study provides a nuanced understanding of the age-dependent physiological effects of salt intake, suggesting the necessity of age-specific guidelines for public health.

The safety of digestive tract cancer surgery during COVID-19: A living systematic review and meta-analysis.

Surgery is the primary curative treatment of solid cancers. However, its safety has been compromised by the outbreak of COVID-19. Therefore, it is necessary to evaluate the safety of digestive tract cancer surgery in the context of COVID-19. We used the Review Manager software (v.5.4) and Stata software (version 16.0) for meta-analysis and statistical analysis. Sixteen retrospective studies involving 17,077 patients met the inclusion criteria. The data indicates that performing digestive tract cancer surgery during the COVID-19 pandemic led to increased blood loss(MD = -11.31, 95%CI:-21.43 to -1.20, P = 0.03), but did not increase postoperative complications(OR = 1.03, 95%CI:0.78 to1.35, P = 0 0.86), anastomotic leakage (OR = 0.96, 95%CI:0.52 to1.77, P = 0 0.89), postoperative mortality (OR = 0.65, 95%CI:0.40 to1.07, P = 0 0.09), number of transfusions (OR = 0.74, 95%CI:0.30 to 1.80, P = 0.51), number of patients requiring ICU care(OR = 1.37, 95%CI:0.90 to 2.07, P = 0.14), postoperative 30-d readmission (OR = 0.94, 95%CI:0.82 to 1.07, P = 0 0.33), total hospital stay (MD = 0.11, 95%CI:-2.37 to 2.59, P = 0.93), preoperative waiting time(MD = - 0.78, 95%CI:-2.34 to 0.79, P = 0.33), postoperative hospital stay(MD = - 0.44, 95%CI:-1.61 to 0.74, P = 0.47), total operation time(MD = -12.99, 95%CI:-28.00 to 2.02, P = 0.09) and postoperative ICU stay (MD = - 0.02, 95%CI:-0.62 to 0.57, P = 0.94). Digestive tract cancer surgery can be safely performed during the COVID-19.

[Chemotherapy Combined with Venetoclax Followed by Allo-Hematopoietic Stem Cell Transplantation for Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm].

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.

[Ixazomib-Based Regimen Followed by Autologous Hematopoietic Stem Cell Transplantation in the Treatment of POEMS Syndrome].

OBJECTIVE: To investigate the safety and efficacy of a new proteasome inhibitor Ixazomib followed by autologous hematopoietic stem cell transplantation (AHSCT) in the treatment of POEMS syndrome. METHODS: The clinical manifestations, diagnosis and treatment process and follow-up results of 4 patients with POEMS syndrome who were treated with Ixazomib-based regimen combined with AHSCT in Wuhan No.1 Hospital from February 2018 to July 2020 were analyzed retrospectively. All patients were male, aged from 37-54 years old, with varying degrees of peripheral neuropathy, organ enlargement (liver, spleen or lymph nodes), circulatory overload (peripheral edema and/or pleural effusion), osteosclerosis, endocrine diseases (thyroid, gonads, etc.), skin changes (pigmentation, hemangioma, white nails, etc.), M protein, papilledema and other clinical manifestations and characteristics at the time of initial treatment. Two patients were pathologically diagnosed as hyaline vascular Castleman disease by lymph node biopsy. Three patients underwent lumbar puncture examinations and all showed elevated cerebrospinal fluid protein. All patients received at least 2 cycles of sequential AHSCT after induction chemotherapy based on ixazomib. The follow-up time was 10-28 months, and the median follow-up time was 16 months. RESULTS: All cases survived. The complications were controllable during the treatment. Moreover, the clinical symptoms related to the disease were improved to a certain extent after the treatment. The levels of vascular endothelial growth factor (VEGF) showed a gradual decline. CONCLUSION: Ixazomib combined with AHSCT is safe and effective in the treatment of POEMS syndrome.

Plasmonic nanoreactors regulating selective oxidation by energetic electrons and nanoconfined thermal fields.

Optimizing product selectivity and conversion efficiency are primary goals in catalysis. However, efficiency and selectivity are often mutually antagonistic, so that high selectivity is accompanied by low efficiency and vice versa. Also, just increasing the temperature is very unlikely to change the reaction pathway. Here, by constructing hierarchical plasmonic nanoreactors, we show that nanoconfined thermal fields and energetic electrons, a combination of attributes that coexist almost uniquely in plasmonic nanostructures, can overcome the antagonism by regulating selectivity and promoting conversion rate concurrently. For propylene partial oxidation, they drive chemical reactions by not only regulating parallel reaction pathways to selectively produce acrolein but also reducing consecutive process to inhibit the overoxidation to CO2, resulting in valuable products different from thermal catalysis. This suggests a strategy to rationally use plasmonic nanostructures to optimize chemical processes, thereby achieving high yield with high selectivity at lower temperature under visible light illumination.

Cerium caused life span shortening and oxidative stress resistance in Drosophila melanogaster.

To investigate the effects of the rare earth element cerium (Ce) on the life span and biomarkers of oxidative stress in the fruit fly (Drosophila melanogaster). Fruit flies were fed on media with different dose of ceric sulfate (1, 4, 16, 64, 256, 1024mg/L, corresponding to cerium concentrations of 0.45, 1.65, 6.91, 26.3, 104, and 429microg/g culture medium). Mean life span, maximum life span, and fertility were calculated. There was a significant decrease in mean life span and maximum life span with increasing doses of cerium. At some concentrations, there was a decrease in reproductive output, especially concentrations >6.91microg/g. We also measured superoxide dismutase (SOD) activity, catalase (CAT) activity, and lipid peroxidation product levels (malondialdehyde (MDA) content). Cerium caused a significant increase in MDA content and decrease in SOD and CAT activities at concentrations >6.91microg/g. These results suggest that cerium may result in oxidative toxicity to D. melanogaster.