OBJECTIVE: To investigate the clinical characteristics, curative effect and prognostic factors of patients with multiple myeloma (MM) complicated with light chain myocardial amyloidosis (AL-CA). METHODS: The data of 38 patients diagnosed with MM complicated with AL-CA in our hospital from January 2018 to December 2023 were retrospectively analyzed, and the data were comprehensively screened by multiple methods such as positive two-dimensional spot tracking echocardiography (2D-STE). Survival analysis was performed using the Kaplan-Meier method. Cox regression models were used to screen for independent prognostic factors. RESULTS: Among the 38 MM patients with AL-CA, 23 were male and 15 were female, with a median age of 60(50,75) years. The 1-year survival rate was 71.05%. Patients who underwent transplantation had significantly better survival outcomes than those who did not (P < 0.01). Additionally, the median survival time of patients with all-negative FISH results at the first visit was statistically different compared to patients with other mutations (P < 0.05). Multivariate Cox regression analysis showed that all negative FISH results at the first visit and the absence of autologous hematopoietic stem cell transplantation (ASCT) were not independent risk factor for the prognosis of patients with MM and AL-CA (P >0.05). CONCLUSION ASCT may improve the prognosis of MM patients with AL-CA, and negative FISH results may indicate poor prognosis, but the results still need to be verified by larger samples.
Humans ; Multiple Myeloma/complications* ; Retrospective Studies ; Aged ; Female ; Male ; Middle Aged ; Prognosis ; Hematopoietic Stem Cell Transplantation ; Amyloidosis/complications* ; Survival Rate ; Proportional Hazards Models

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

Objective:To investigate the mechanism of inhibition for Janus tyrosine kinase,signal transducer and activator of transcription(JAK/STAT)on ferroptosis,myocardial remodeling,and JAK/STAT melatonin receptor 1-nuclear factor E2-related factor 2-glutathione peroxidase 4(MT1-Nrf2-GPX4)signaling axis in rats with heart failure(HF)under echocardiography.Methods:Forty SD rats were selected,and they were randomly divided into blank control group,model group,interleukin-6(IL-6)group and tyrosine phosphorylation inhibitor(AG490)group according to random number table,with 10 rats in each group.HF rat models were established in three groups except the blank control group.The expression levels of JAK/STAT mRNA in myocardial tissue among 4 groups were compared and analyzed.The small animal ultrasound imaging system was used to measure a series of cardiac function indexes included interventricular septum(IVS)thickness,left ventricular posterior wall(LVPWs)thickness,left ventricular posterior wall(LVPWd)thickness,left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD)and ejection fraction(EF).The Fe2+concentration and lesions of myocardial tissue,as well as the expressions of MT1,Nrf2 and GPX4 proteins,in the four groups were compared and analyzed.Results:The increases of JAK1 and STAT3 mRNA levels,and Fe2+concentration in the model group,IL-6 group and AG490 group were higher than those in the blank control group,and the protein expression levels of MT1,Nrf2 and GPX4 in them were lower than those in the blank control group,and the differences of the above indicators between the model group and the blank control group were statistically significant(t=11.810,16.250,17.150,10.460,9.272,11.180,P＜0.05),and the differences of the above indicators between the IL-6 group and the blank control group were statistically significant(t=9.834,19.030,16.320,14.450,13.250,14.070,P＜0.05),and the differences of them between the AG490 group and the blank control group were statistically significant(t=8.025,11.050,17.590,4.173,4.179,4.183,P＜0.05),respectively.The levels of STAT3 mRNA level and Fe2+concentration in IL-6 group were higher than those in the model group,and the expression levels of MT1,Nrf2 and GPX4 proteins in that were lower than those in the model group,and the differences were statistically significant(t=2.224,2.582,3.550,3.078,2.624,P＜0.05),respectively.The levels of JAK1,STAT3 mRNA and Fe2+concentration in the AG490 group were lower than those in the model group,and the levels of MT1,Nrf2 and GPX4 in that were higher than those in the model group,and the differences were statistically significant(t=4.052,6.930,8.598,6.247,5.055,6.799,P＜0.05),respectively.The IVS,LVPWs,LVPWd and EF of the model group,IL-6 group and AG490 group were lower than those of the blank control group,and the LVEDD and LVESD of them were higher than those of the blank control group,and the differences of these indicators between the model group and the blank control group were statistically significant(t=13.740,11.100,5.654,7.049,13.440,14.260,P＜0.05),and the differences of them between the IL-6 group and the blank control group were statistically significant(t=16.090,13.140,8.103,9.174,15.940,17.010,P＜0.05),and the differences of them between the AG490 group and the blank control group were statistically significant(t=5.474,4.947,2.682,4.071,8.608,13.300,P＜0.05),respectively.The LVPWd and EF in the IL-6 group were lower than those in the model group,and the LVEDD and LVESD in the IL-6 group were higher than those in the model group,and the differences of them were statistically significant(t=2.417,2.327,2.236,2.818,P＜0.05),respectively.The IVS,LVPWs,LVPWd and EF in the AG490 group were higher than those in the model group,and the LVEDD and LVESD in that were lower than those in the model group,and the differences were statistically significant(t=8.598,7.147,3.514,3.361,4.914,2.970,P＜0.05),respectively.Conclusion:Inhibition of JAK/STAT expression can improve the cardiac structure of HF rats,and relieve ventricular remodeling,and inhibit ferroptosis of cardiomyocyte,and promote the expression of MT1,Nrf2 and GPX4 proteins.

Objective To evaluate the efficacy and safety of obinutuzumab(OBZ)in the treatment of refractory primary membranous nephropathy(pMN).Methods The clinical data of 15 patients with refractory pMN who received OBZ treatment in Department of Nephrology of The First Affiliated Hospital of Naval Medical University between Jan.2022 and Sep.2024 were retrospectively analyzed,and they included basic information,relevant laboratory indexes,clinical and immunological outcomes,and adverse events.Results Among the 15 patients with refractory pMN,14(93.3％)were phospholipase A2 receptor(PLA2R)-associated membranous nephropathy(10 cases with positive PLA2R by renal biopsy and 4 cases with no recorded PLA2R results by renal biopsy but with positive serum PLA2R antibodies).During the follow-up period,all 15 patients achieved clinical remission,with 4(26.7％)patients achieving complete remission and 11(73.3％)patients achieving partial remission.Of the 12 patients with positive serum PLA2R antibodies,11 patients had continuously positive serum PLA2R antibodies before OBZ treatment,and 9(81.8％)patients achieved immunological remission after OBZ treatment.All the 15 patients had previously received immunosuppressive therapy,and all of them were classified as refractory pMN,with 7(46.7％)patients having been treated with cyclophosphamide combined with corticosteroids,2(13.3％)patients having been treated with calcineurin inhibitor combined with corticosteroids,11(73.3％)patients having received rituximab.During the treatment,2(13.3％)cases of adverse events were observed:1 patient experienced transient liver dysfunction,and the transaminase returned to normal after discontinuing atorvastatin;another patient developed a positive T-cell spot test for Tuberculosis infection during the intertreatment interval and successfully completed the subsequent OBZ treatment and achieved clinical remission after treatment with isoniazid and rifampicin.Conclusion OBZ demonstrates favorable clinical efficacy in the treatment of refractory pMN,with a low incidence of adverse events.

[Objective] To explore the key factors affecting the efficiency and safety of hematopoietic stem cell apheresis. [Methods] The clinical data of 59 healthy donors who underwent allogeneic hematopoietic stem cell donation in the First Affiliated Hospital of Anhui Medical University from January 2021 to June 2024 were retrospectively analyzed. The number of CD34⁺ cells was used to evaluate the eligibility of stem cell collection. The effects of donor gender, age, patient weight, as well as the number of WBC, MNC, RBC, Hb, HCT, PLT, CD34⁺ cells, CD34⁺ percentage and instrument operating parameters on collection efficiency were analyzed. [Results] A total of 59 donors were enrolled, and 68 occasions of stem cell apheresis were performed, with a qualified collection rate of 56%. Donor gender, age, patient weight, total blood circulation volume, anticoagulant dosage, collection time, calcium gluconate dosage and RBC, Hb, HCT levels were not significantly correlated with the collection effect (P>0.05). Multivariate logistic regression analysis showed that the number of MNC cells, CD34⁺ cells and stem cell product volume were the key factors affecting the efficiency and safety. A total of 12 donors had mild adverse reactions during the collection process, and all of them were improved after treatment. [Conclusion] Optimizing apheresis strategy based on the three factors of MNC, WBC count and stem cell product volume on the day of collection will help to achieve high-quality collection and improve the success rate of transplantation.

Recent studies have revealed a significant association between Porphyromonas gingivalis(P.gingivalis)infection and poor prognosis in esophageal squamous cell carcinoma(ESCC).Although cer-tain circular RNAs(circRNA)have been shown to suppress ESCC tumorigenesis and progression,their regulatory mechanisms in P.gingivalis infection-associated ESCC remain elusive.In this study,RT-qPCR analysis demonstrated that P.gingivalis infection downregulated hsa_circ_0057552 expression in ESCC cells and tissues in a time-and dose-dependent manner.Actinomycin D assays further confirmed that P.gingivalis infection reduced the RNA stability of hsa_circ_0057552 in ESCC cells(P＜0.05).Functional assays in vitro and a subcutaneous tumor xenograft model in vivo revealed that hsa_circ_0057552 overexpression significantly inhibited ESCC cell proliferation,migration,invasion,and tumor growth(P＜0.05).Additionally,PCR array screening combined with RT-qPCR and Western blotting in-dicated that P.gingivalis infection markedly upregulated human antigen R(HuR)expression at both RNA and protein levels(P＜0.05).Mechanistic investigations demonstrated that HuR knockdown signifi-cantly increased hsa_circ_0057552 expression(P＜0.01),whereas hsa_circ_0057552 overexpression had no regulatory effect on HuR.Finally,si-HuR treatment reversed the inhibitory effect of P.gingivalis on hsa_circ_0057552 transcription.This study demonstrated that P.gingivalis may promote the progression of ESCC through a novel mechanism involving the regulation of HuR/hsa_circ_0057552,thereby identif-ying a novel therapeutic target and molecular marker for P.gingivalis-associated ESCC.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Recent studies have revealed a significant association between Porphyromonas gingivalis(P.gingivalis)infection and poor prognosis in esophageal squamous cell carcinoma(ESCC).Although cer-tain circular RNAs(circRNA)have been shown to suppress ESCC tumorigenesis and progression,their regulatory mechanisms in P.gingivalis infection-associated ESCC remain elusive.In this study,RT-qPCR analysis demonstrated that P.gingivalis infection downregulated hsa_circ_0057552 expression in ESCC cells and tissues in a time-and dose-dependent manner.Actinomycin D assays further confirmed that P.gingivalis infection reduced the RNA stability of hsa_circ_0057552 in ESCC cells(P＜0.05).Functional assays in vitro and a subcutaneous tumor xenograft model in vivo revealed that hsa_circ_0057552 overexpression significantly inhibited ESCC cell proliferation,migration,invasion,and tumor growth(P＜0.05).Additionally,PCR array screening combined with RT-qPCR and Western blotting in-dicated that P.gingivalis infection markedly upregulated human antigen R(HuR)expression at both RNA and protein levels(P＜0.05).Mechanistic investigations demonstrated that HuR knockdown signifi-cantly increased hsa_circ_0057552 expression(P＜0.01),whereas hsa_circ_0057552 overexpression had no regulatory effect on HuR.Finally,si-HuR treatment reversed the inhibitory effect of P.gingivalis on hsa_circ_0057552 transcription.This study demonstrated that P.gingivalis may promote the progression of ESCC through a novel mechanism involving the regulation of HuR/hsa_circ_0057552,thereby identif-ying a novel therapeutic target and molecular marker for P.gingivalis-associated ESCC.

Objective:To investigate the mechanism of inhibition for Janus tyrosine kinase,signal transducer and activator of transcription(JAK/STAT)on ferroptosis,myocardial remodeling,and JAK/STAT melatonin receptor 1-nuclear factor E2-related factor 2-glutathione peroxidase 4(MT1-Nrf2-GPX4)signaling axis in rats with heart failure(HF)under echocardiography.Methods:Forty SD rats were selected,and they were randomly divided into blank control group,model group,interleukin-6(IL-6)group and tyrosine phosphorylation inhibitor(AG490)group according to random number table,with 10 rats in each group.HF rat models were established in three groups except the blank control group.The expression levels of JAK/STAT mRNA in myocardial tissue among 4 groups were compared and analyzed.The small animal ultrasound imaging system was used to measure a series of cardiac function indexes included interventricular septum(IVS)thickness,left ventricular posterior wall(LVPWs)thickness,left ventricular posterior wall(LVPWd)thickness,left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD)and ejection fraction(EF).The Fe2+concentration and lesions of myocardial tissue,as well as the expressions of MT1,Nrf2 and GPX4 proteins,in the four groups were compared and analyzed.Results:The increases of JAK1 and STAT3 mRNA levels,and Fe2+concentration in the model group,IL-6 group and AG490 group were higher than those in the blank control group,and the protein expression levels of MT1,Nrf2 and GPX4 in them were lower than those in the blank control group,and the differences of the above indicators between the model group and the blank control group were statistically significant(t=11.810,16.250,17.150,10.460,9.272,11.180,P＜0.05),and the differences of the above indicators between the IL-6 group and the blank control group were statistically significant(t=9.834,19.030,16.320,14.450,13.250,14.070,P＜0.05),and the differences of them between the AG490 group and the blank control group were statistically significant(t=8.025,11.050,17.590,4.173,4.179,4.183,P＜0.05),respectively.The levels of STAT3 mRNA level and Fe2+concentration in IL-6 group were higher than those in the model group,and the expression levels of MT1,Nrf2 and GPX4 proteins in that were lower than those in the model group,and the differences were statistically significant(t=2.224,2.582,3.550,3.078,2.624,P＜0.05),respectively.The levels of JAK1,STAT3 mRNA and Fe2+concentration in the AG490 group were lower than those in the model group,and the levels of MT1,Nrf2 and GPX4 in that were higher than those in the model group,and the differences were statistically significant(t=4.052,6.930,8.598,6.247,5.055,6.799,P＜0.05),respectively.The IVS,LVPWs,LVPWd and EF of the model group,IL-6 group and AG490 group were lower than those of the blank control group,and the LVEDD and LVESD of them were higher than those of the blank control group,and the differences of these indicators between the model group and the blank control group were statistically significant(t=13.740,11.100,5.654,7.049,13.440,14.260,P＜0.05),and the differences of them between the IL-6 group and the blank control group were statistically significant(t=16.090,13.140,8.103,9.174,15.940,17.010,P＜0.05),and the differences of them between the AG490 group and the blank control group were statistically significant(t=5.474,4.947,2.682,4.071,8.608,13.300,P＜0.05),respectively.The LVPWd and EF in the IL-6 group were lower than those in the model group,and the LVEDD and LVESD in the IL-6 group were higher than those in the model group,and the differences of them were statistically significant(t=2.417,2.327,2.236,2.818,P＜0.05),respectively.The IVS,LVPWs,LVPWd and EF in the AG490 group were higher than those in the model group,and the LVEDD and LVESD in that were lower than those in the model group,and the differences were statistically significant(t=8.598,7.147,3.514,3.361,4.914,2.970,P＜0.05),respectively.Conclusion:Inhibition of JAK/STAT expression can improve the cardiac structure of HF rats,and relieve ventricular remodeling,and inhibit ferroptosis of cardiomyocyte,and promote the expression of MT1,Nrf2 and GPX4 proteins.