Mantle cell lymphoma (MCL) is a rare B cell lymphoma, and its incidence rate is increasing year by year. MCL has the common characteristics of both inert lymphoma and aggressive lymphoma: rapid progress and poor prognosis. The latest research believes that the pathogenesis of MCL is a continuum, and many factors such as cell cycle disorder, SOX11 overexpression, epigenetic aberration play a role in different stages of the disease. This paper mainly reviews the pathogenesis of MCL and new findings of different subtypes from the perspective of molecular genetics,and further analyzes the clinical diversity of MCL. At the same time, the understanding of the pathogenesis of MCL aims to provide potential targets for future treatment of MCL.

Objective:To investigate the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma(NDMM)with thrombocytopenia.Methods:Clinical data of 529 patients with NDMM admitted to The Second Hospital of Shanxi Medical University between January 2012 and December 2021 were retrospectively analyzed.The patients were categorized into thrombocytopenia and nor-mal platelet count groups based on their platelet count levels.Results:A total of 529 patients with NDMM were included in this study,with 108(20.42%)patients in the thrombocytopenia group.The median progression-free survival(mPFS)was 30.64 months(95%confidence in-terval[CI]:23.43-37.85)in the thrombocytopenia group,which was shorter than that in the normal platelet count group(41.39 months[95%CI:37.37-45.39],P=0.002).The median overall survival(mOS)was 40.59 months(95%CI:30.61-50.57)in the thrombocytopenia group,which was shorter than that in the normal platelet count group(60.92 months[95%CI:54.54-67.29],P<0.001).Multivariate Cox regression analysis identified thrombocytopenia as a risk factor for OS in patients with NDMM(HR=1.238[95%CI:1.16-1.952],P=0.03).Conclusions:The prognosis of patients with NDMM with thrombocytopenia was worse than that of patients with NDMM who had normal platelet levels.Thrombocytopenia may serve as a poor prognostic indicator for NDMM.

Objective To explore the age-related biological properties of bone-derived mesenchymal stem cells(BMSCs)from mice of different age groups and their osteogenic differentiation induced by bone morphogenetic protein 2(BMP2).Methods Eight C57BL/6J mice were divided into a young group(4 weeks old,weighing 10～15 g,n=4)and an old group(12 months old,weighing 20～25 g,n=4),with half male and half female.MSCs were extracted from the whole bones of the 2 groups of mice.After the obtained cells were identified with flow cytometry for the surface markers,β-galactosidase staining was employed to compare the senescence level of BMSCs,MTT and EdU incorporation assays were conducted to compare the proliferation and self-renewal abilities of between the 2 groups.Western blotting was employed to analyze the expression of CyclinD1 and P21 in BMSCs.Then ALP staining,Alizarin Red staining and RT-qPCR were used to evaluate the osteogenic differentiation ability of the cells.RNA sequencing was performed to compare the differential gene expression in BMP2-induced BMSCs.Lastly,the sequencing results were re-confirmed by using flow cytometry.Results Flow cytometry showed that the sorted and cultured mouse BMSCs met the criteria for MSCs.The results of β-galactosidase staining indicated that the senescence level of BMSCs in the old group was significantly higher than that in the young group(P＜0.05).MTT and EdU doping experiments revealed that the cell viability and proliferation ability of BMSCs were significantly lower in the old group than the young group(P＜0.05).Western blotting displayed that the expression level of cell cycle protein CyclinD1 was lower,whereas that of cell cycle inhibitory factor P21 was significantly higher in the BMSCs from the old group than the cells from the young group(P＜0.05).ALP/Alizarin Red staining and RT-qPCR demonstrated that the BMSCs from the young group had stronger osteogenic differentiation capacity after BMP2 treatment when compared the cells of the old group(P＜0.05).RNA sequencing results displayed that the changing profile of CD51 expression was in opposite trends in the young and old BMSCs after BMP2 treatment.Finally,flow cytometry revealed that the percentage of CD51+cells within the CD45-cells was significantly higher in the young group than the old group.Conclusion The decrease in the percentage of CD51+cells among CD45-cells in aged BMSCs is closely associated with their decreased responsiveness to BMP2-induced osteogenic differentiation.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

Objective:To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods:A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses.Results:A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) ( χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months ( χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS ( χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group ( χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy ( HR=0.11, 95% CI 0.05-0.27), achievement of efficacy of partial response or better ( HR=0.47, 95% CI 0.34-0.66), and non-aggressive relapse ( HR=0.25, 95% CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion:In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

Humans ; Adult ; Invasive Pulmonary Aspergillosis ; Pneumonia, Viral/complications* ; Risk Factors ; Pulmonary Aspergillosis/complications*

Objective:Regulatory quantitative trait loci (regQTL) theory can help to evaluate the regulation function of single nucleotide polymorphisms (SNPs) on crucial biological signals from a three-dimensional perspective. The aim of this study was to investigate the effect of these regQTL-SNPs on the susceptibility of lung cancer.Methods:Based on the regQTL theory, using the database of identified lung cancer regQTL-SNPs, we screened the SNPs that may function as regQTL in the reported susceptible regions of lung cancer by genome-wide association study(GWAS), and a two-stage case-control study was conducted (screening stage: 2 331 lung cancer cases and 3 077 healthy controls; validation stage: 626 lung cancer cases and 667 healthy controls) to definite the association of related regQTL-SNPs with the susceptibility of lung cancer.Results:A total of 8 regQTL-SNPs were screened in the reported susceptible regions of lung cancer by GWAS. Among which, 3 SNPs were significantly associated with the risk of lung cancer ( P<0.05) in the screening stage. Further validation results indicated that the variant T allele of rs6998591 in ADRA1A was significantly associated with increased risk of lung cancer (additive model: OR=1.33, 95% CI:1.01-1.74, P=0.040). In addition, the variant G allele of rs11202916 in ACTA2 was significantly associated with decreased risk of lung cancer (recessive model: OR=0.71, 95% CI:0.52-0.96, P=0.026). Stratified analysis indicated that the variant T allele of rs6998591 significantly increased lung squamous cell carcinoma risk (additive model: OR=1.53, 95% CI: 1.01-2.32, P=0.043), while the variant G allele of rs11202916 significantly decreased lung adenocarcinoma risk (additive model: OR=0.83, 95% CI: 0.69-0.98, P=0.031). Gene-environment interaction analysis indicated that the risk of developing lung cancer increased by 235% in smoking individuals carrying rs6998591 variant T allele compared with those non-smoking individuals carrying no rs6998591 variant T allele( OR=3.35,95% CI:2.10-5.34, P<0.001). Conclusion:There are two regQTL-SNPs that could significantly affect the susceptibility of lung cancer in the GWAS reported susceptible regions of lung cancer.

Alzheimer′s disease (AD) is an incurable disease in the field of major chronic diseases. Subjective cognitive decline (SCD) is a clinical risk factor for AD. The standardized screening and intervention in individuals with SCD are of great importance in early prevention and treatment of AD. According to the clinical criteria proposed by The characterisation of subjective cognitive decline, which was published online in Lancet Neurology, the article summarized the definition of SCD, the latest perspective of clinical standards in SCD, and the results of AD preclinical SCD research. The purpose of this work was to provide concrete guidance and recommendations for making clinical decisions in diagnosis and scientific research on SCD.

Objective:To investigate the clinicopathological characteristics and cost-effectiveness of endoscopic resection and surgical resection for gastric schwannomas arising from the muscularis propria layer.Methods:Thirty-eight consecutive cases of gastric schwannomas diagnosed by histopathology between October 2011 and July 2016 were divided into the endoscopy group(including endoscopic submucosal excavation and endoscopic full-thickness resection) and the surgery group. Complications, complete resection rate and cost-effectiveness were analyzed.Results:The age was 52±10 years (range, 41-63 years) with 11(28.9%) males and 27(71.1%) females. The most common site of gastric schwannomas was the body (71.1%) and the antrum (21.1%). All 38(100%) lesions were protruded. The maximum diameter of the lesions was 2.5±1.2 cm (range 0.6-4.5 cm). Under endoscopic ultrasonography (EUS), 60.5% lesions were heterogeneous hypoechoic, and 15 (39.5%) hypoechoic. The complete resection rate of endoscopy group was 100.0% (17/17). The median operation time of the endoscopy group was 54 minutes. Perforations occurred in 11 patients (64.7%, 11/17), and metal clips or the nylon rope combined with metallic clips were used to close the defect in the endoscopy group. Compared with the surgery group, the length of hospital stay was significantly shorter (4.6±0.6 d VS 9.6±4.4 d, P<0.001); the time to the first fluid diet was significantly shorter (1.2±0.4 d VS 2.7±0.7 d, P<0.001), and the costs were significantly lower (21 965.0±9 342.4 yuan VS 34 253.3±10 520.9 yuan, P<0.001) in the endoscopy group. S100 immunoreactivity was present in all tumors. Local recurrence and distant metastasis did not occur during the median 34 months of follow-up. Conclusions:Endoscopic resection appears to be safe and effective for diagnosis and treatment of gastric schwannomas from the muscularis propria layer. The cost-effectiveness of endoscopic resection is significantly higher than surgical resection.

OBJECTIVETo investigate the influence of renal function on the level of β₂-microglobulin (β₂-MG) as prognostic factor in newly diagnosed multiple myeloma (MM) patients, and to analyze the overall survival (OS) in different level of β₂-MG with relatively normal or abnormal renal function in MM patients.

METHODSAccording to the level of β₂-MG, 666 newly diagnosed MM patients were divided into three groups as β₂-MG<3.5, 3.5-<5.5, ≥5.5 mg/L. According to the level of serum creatinine, these patients were divided into two groups:serum creatinine <177 μmol/L as relatively normal group, serum creatinine ≥177 μmol/L as abnormal group.

RESULTSAmong 666 patients, there were 416 male and 250 female, the median age was 58 (25-86) years old. Comparison of OS among β₂-MG<3.5, 3.5-<5.5, ≥5.5 mg/L groups indicated that the median OS of the three groups were 85.75 (95% CI 70.99-100.50), 47.25 (95% CI 40.98-53.53) and 35.05 (95% CI 30.75-39.35) months, respectively (P<0.01). Comparison of OS between serum creatinine <177 and ≥177 mmol/L groups, the median OS of the two groups were 64.67 (95% CI 56.57-72.77) and 32.74 (95% CI 27.74-37.73) months, respectively (P<0.01). In β₂-MG≥5.5 mg/L, the median OS of relatively normal and abnormal groups were 37.25 (95% CI 31.45-43.06) and 32.55 (95% CI 26.26-38.83) months, respectively (P=0.142).

CONCLUSIONHigh level of β₂-MG and renal function correlated with shorter survival of MM patients. Higher level of β₂-MG with abnormal renal function can't change the prognostic value of β₂-microglobulin on MM.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Kidney ; Kidney Function Tests ; Male ; Middle Aged ; Multiple Myeloma ; Neoplasm Staging ; Prognosis ; beta 2-Microglobulin