Objective:To analyze the clinical characteristics, treatment response, and prognosis of patients newly diagnosed with immunoglobulin A multiple myeloma (IgA MM), and to ascertain whether the IgA isotype remains a poor prognostic factor in the bortezomib era.Methods:This study retrospectively enrolled 155 patients newly diagnosed with IgA MM and 420 with non-IgA MM admitted to the Department of Hematology, the First Affiliated Hospital of Nanchang University from March 2014 to December 2021. We compared the two groups in terms of their clinical characteristics, prognoses, and progression-free survival (PFS) and overall survival (OS) following different treatment regimens.Results:Compared with the non-IgA group, the IgA group presented with more aggressive clinical features, including a higher proportion of patients with hemoglobin<85 g/L (61.3% vs 51.4%, P=0.035), extramedullary manifestations (20.0% vs 11.4%, P=0.008), and gain/amp (1q21) (48.6% vs 36.7%, P=0.032). Efficacy analysis revealed a lower overall response rate (ORR) in the IgA group than in the non-IgA group (83.2% vs 92.4%, P=0.001). Among patients treated with bortezomib-based regimens, the ORR was 91.2% in the IgA group and 94.8% in the non-IgA group, but the difference was nonsignificant ( P=0.146). Survival analysis showed that the median PFS and OS were significantly shorter in the IgA group compared with the non-IgA group[23.5 (95% CI: 17.4-29.5) months and 48.8 (95% CI: 30.1-67.5) months vs 40.7 (95% CI: 33.8 - 47.6) months and not reached, respectively; P<0.001 and P=0.002]. In the subgroup of patients who received bortezomib-based therapy without subsequent autologous hematopoietic stem cell transplantation (auto-HSCT), the PFS and OS were significantly shorter in the IgA group compared with the non-IgA group[25.4 (95% CI: 18.7-32.1) months and 53.5 (95% CI: 35.4-71.6) months vs 41.0 (95% CI: 33.7-48.3) months and not reached; P=0.001 and P=0.011]. In patients who underwent bortezomib-based induction therapy followed by auto-HSCT, the 1-, 3-, and 5-year OS rates for the IgA group were 96%, 81%, and 81%, respectively, compared with 93%, 89%, and 79% for the non-IgA group, but the difference was nonsignificant ( P=0.758) . Conclusion:In the bortezomib era, IgA MM is still associated with a poorer overall prognosis than non-IgA MM, likely due to its inherent high-risk biological characteristics. Although bortezomib-based regimens effectively improve the treatment response, they fail to completely bridge the survival gap between the two disease isotypes. Therefore, bortezomib-based therapy followed by auto-HSCT may be a key strategy to overcome the poor prognosis of IgA MM, potentially enabling these patients to achieve long-term survival comparable to that of their non-IgA counterparts.

Objective:To compare the effects of using cone beam CT (CBCT) and oral scanning registration on implant positional accuracy during robot-assisted implant surgery, and to provide a basis for selecting the appropriate registration for robot-assisted implant surgical options.Methods:One patient with dentition defect, specifically missing teeth at positions 21 and 26 and having natural teeth adjacent mesially and distally to the edentulous area, who visited the Department of Oral Implantology, School of Hospital of Stomatology Wuhan University in 2024 were selected. Based on reconstructed imaging data, 30 identical jaw models were printed. These models were divided into a CBCT registration group and an intra-oral scanning registration group (15 models per group). An associate chief physician with extensive experience in implant surgery performed preoperative registration using the implant robot and completed the implant surgeries. Postoperative CBCT scans were used to determine the three-dimensional position of the implants. The deviations between the planned implant position and the actual position were evaluated, including deviations at the implantation point, apical point, and angular deviation. The differences between the two groups were compared.Results:The implantation deviation was 0.675 (0.490) mm, apical deviation was (0.680±0.272) mm, and the angular deviation was 0.566°±0.147° in the CBCT registration group, and in the intra-oral scanning registration group, implantation deviation was 0.695 (0.313) mm, apical deviation was (0.667±0.217) mm, and the angular deviation was 0.523°±0.168°. There was no statistically significant error in implant precision between the two groups ( P>0.05). Conclusions:This in vitro experiment found that the use of intra-oral scanning registration in robot-assisted implant surgery can achieve similar implant placement accuracy as CBCT registration.

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective To investigate the effects of chronic intermittent hypoxia(CIH)on hippocampal neuronal injury in rats,and to clarify the role of endoplasmic reticulum(ER)stress-related apoptotic pathways.Methods Male Sprague-Dawley rats were randomly assigned to a control group(n=8)or a CIH group(n=8).The CIH group was exposed to intermittent hypoxia for 8 h/day over 8 weeks.Hippocampal neuronal morphology was examined by hematoxylin-eosin staining and transmission electron microscopy.Neuronal apoptosis was assessed using the TUNEL assay.Intracellular Ca2? levels were measured by flow cytometry.The mRNA and protein expression of ER stress-related factors(GRP78,CHOP)and the apoptotic effector Caspase-3 were quantified by qPCR and Western blot.Results Compared with controls,rats in the CIH group exhibited marked hippocampal neuronal damage,including disrupted cytoarchitecture,cytoplasmic dissolution,and swollen rough ER.Ultrastructural analysis revealed nuclear deformation and organelle disruption.TUNEL assay demonstrated a significant increase in apoptotic cells(P<0.05).Flow cytometry showed elevated intracellular Ca2? levels(P<0.05).GRP78,CHOP,and Caspase-3 were significantly upregulated at both mRNA and protein levels in the CIH group(all P<0.05).Conclusion CIH induces pronounced hippocampal neuronal injury and apoptosis in rats,associated with Ca2? dysregulation and activation of ER stress-mediated apoptotic pathways.These findings provide experimental evidence for elucidating the mechanisms of OSAHS-related neuronal injury and identifying potential therapeutic targets.

Objective:To compare the effects of using cone beam CT (CBCT) and oral scanning registration on implant positional accuracy during robot-assisted implant surgery, and to provide a basis for selecting the appropriate registration for robot-assisted implant surgical options.Methods:One patient with dentition defect, specifically missing teeth at positions 21 and 26 and having natural teeth adjacent mesially and distally to the edentulous area, who visited the Department of Oral Implantology, School of Hospital of Stomatology Wuhan University in 2024 were selected. Based on reconstructed imaging data, 30 identical jaw models were printed. These models were divided into a CBCT registration group and an intra-oral scanning registration group (15 models per group). An associate chief physician with extensive experience in implant surgery performed preoperative registration using the implant robot and completed the implant surgeries. Postoperative CBCT scans were used to determine the three-dimensional position of the implants. The deviations between the planned implant position and the actual position were evaluated, including deviations at the implantation point, apical point, and angular deviation. The differences between the two groups were compared.Results:The implantation deviation was 0.675 (0.490) mm, apical deviation was (0.680±0.272) mm, and the angular deviation was 0.566°±0.147° in the CBCT registration group, and in the intra-oral scanning registration group, implantation deviation was 0.695 (0.313) mm, apical deviation was (0.667±0.217) mm, and the angular deviation was 0.523°±0.168°. There was no statistically significant error in implant precision between the two groups ( P>0.05). Conclusions:This in vitro experiment found that the use of intra-oral scanning registration in robot-assisted implant surgery can achieve similar implant placement accuracy as CBCT registration.

Objective To investigate the effects of chronic intermittent hypoxia(CIH)on hippocampal neuronal injury in rats,and to clarify the role of endoplasmic reticulum(ER)stress-related apoptotic pathways.Methods Male Sprague-Dawley rats were randomly assigned to a control group(n=8)or a CIH group(n=8).The CIH group was exposed to intermittent hypoxia for 8 h/day over 8 weeks.Hippocampal neuronal morphology was examined by hematoxylin-eosin staining and transmission electron microscopy.Neuronal apoptosis was assessed using the TUNEL assay.Intracellular Ca2? levels were measured by flow cytometry.The mRNA and protein expression of ER stress-related factors(GRP78,CHOP)and the apoptotic effector Caspase-3 were quantified by qPCR and Western blot.Results Compared with controls,rats in the CIH group exhibited marked hippocampal neuronal damage,including disrupted cytoarchitecture,cytoplasmic dissolution,and swollen rough ER.Ultrastructural analysis revealed nuclear deformation and organelle disruption.TUNEL assay demonstrated a significant increase in apoptotic cells(P<0.05).Flow cytometry showed elevated intracellular Ca2? levels(P<0.05).GRP78,CHOP,and Caspase-3 were significantly upregulated at both mRNA and protein levels in the CIH group(all P<0.05).Conclusion CIH induces pronounced hippocampal neuronal injury and apoptosis in rats,associated with Ca2? dysregulation and activation of ER stress-mediated apoptotic pathways.These findings provide experimental evidence for elucidating the mechanisms of OSAHS-related neuronal injury and identifying potential therapeutic targets.

Objective:To analyze the clinical characteristics, treatment response, and prognosis of patients newly diagnosed with immunoglobulin A multiple myeloma (IgA MM), and to ascertain whether the IgA isotype remains a poor prognostic factor in the bortezomib era.Methods:This study retrospectively enrolled 155 patients newly diagnosed with IgA MM and 420 with non-IgA MM admitted to the Department of Hematology, the First Affiliated Hospital of Nanchang University from March 2014 to December 2021. We compared the two groups in terms of their clinical characteristics, prognoses, and progression-free survival (PFS) and overall survival (OS) following different treatment regimens.Results:Compared with the non-IgA group, the IgA group presented with more aggressive clinical features, including a higher proportion of patients with hemoglobin<85 g/L (61.3% vs 51.4%, P=0.035), extramedullary manifestations (20.0% vs 11.4%, P=0.008), and gain/amp (1q21) (48.6% vs 36.7%, P=0.032). Efficacy analysis revealed a lower overall response rate (ORR) in the IgA group than in the non-IgA group (83.2% vs 92.4%, P=0.001). Among patients treated with bortezomib-based regimens, the ORR was 91.2% in the IgA group and 94.8% in the non-IgA group, but the difference was nonsignificant ( P=0.146). Survival analysis showed that the median PFS and OS were significantly shorter in the IgA group compared with the non-IgA group[23.5 (95% CI: 17.4-29.5) months and 48.8 (95% CI: 30.1-67.5) months vs 40.7 (95% CI: 33.8 - 47.6) months and not reached, respectively; P<0.001 and P=0.002]. In the subgroup of patients who received bortezomib-based therapy without subsequent autologous hematopoietic stem cell transplantation (auto-HSCT), the PFS and OS were significantly shorter in the IgA group compared with the non-IgA group[25.4 (95% CI: 18.7-32.1) months and 53.5 (95% CI: 35.4-71.6) months vs 41.0 (95% CI: 33.7-48.3) months and not reached; P=0.001 and P=0.011]. In patients who underwent bortezomib-based induction therapy followed by auto-HSCT, the 1-, 3-, and 5-year OS rates for the IgA group were 96%, 81%, and 81%, respectively, compared with 93%, 89%, and 79% for the non-IgA group, but the difference was nonsignificant ( P=0.758) . Conclusion:In the bortezomib era, IgA MM is still associated with a poorer overall prognosis than non-IgA MM, likely due to its inherent high-risk biological characteristics. Although bortezomib-based regimens effectively improve the treatment response, they fail to completely bridge the survival gap between the two disease isotypes. Therefore, bortezomib-based therapy followed by auto-HSCT may be a key strategy to overcome the poor prognosis of IgA MM, potentially enabling these patients to achieve long-term survival comparable to that of their non-IgA counterparts.

Objective To investigate the effects of calcitriol intervention on PI3K/AKT signaling pathway and wound healing in rats with diabetic foot ulcer(DFU).Methods Thirty-two male SD rats were divided into normal control(Con)group,DFU group,calcitriol low dose(L)group and calcitriol high dose(H)group.A circular wound of 5 mm in diameter and deep to the fascia was made on the dorsum of the left foot of rats in each group.HE staining was used to evaluate the histopathological changes of the wounds.Immunohistochemical method was selected to compare the distribution of CD34-positive cells and the expression of p-PI3K and p-AKT in traumatic tissues of each group.ELISA was adopted in the detection of serum IL-6,IFN-γ,TNF-α and IL-7.RT-PCR was used to detect the mRNA expression of PI3K and AKT in each group,and western blot was used to detect the protein expression of PI3K,p-PI3K,AKT,p-AKT and VEGF.Results Compared with Con group,the expressions of IL-6,IFN-γ,TNF-α,IL-7,CD34,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K,p-AKT/AKT increased,while PI3K protein expression decreased in DFU,L and H groups(P<0.05),VEGF and AKT protein expression decreased in DFV and L groups(P<0.05).Compared with DFU group,the expressions of VEGF,AKT and PI3K protein increased(P<0.05),while the expressions of p-PI3K/PI3K,p-AKT/AKT decreased in L and H groups(P<0.05),IL-6 decreased in L group(P<0.05),and CD34 expression increased in H group(P<0.05),while IL-6,IFN-γ,TNF-α and IL-7,PI3K mRNA,AKT mRNA,p-AKT protein and p-PI3K protein expression decreased(P<0.05).Compared with L group,the expressions of CD34,VEGF,AKT and PI3K protein increased(P<0.05),while IL-6,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K and p-AKT/AKT decreased in H group(P<0.05).Conclusions Calcitriol intervention may reduce the activity of the PI3K/AKT signaling pathway,inhibit inflammation,promote neovascularization,and facilitate wound healing in rats with DFU.

Objective To evaluate the effects of total intravenous anesthesia on the circadian rhythms in the patients undergoing cardiac transcatheter closure.Methods Thirty patients undergoing cardiac transcathe-ter closure under elective intravenous anesthesia were included in this study.Paired t-tests were performed to com-pare the mRNA levels of the genes encoding circadian locomotor output cycles kaput(CLOCK),brain and mus-cle ARNT-1 like protein-1(BMAL1),cryptochrome1(CRY1),and period circadian clock 2(PER2),the Munich Chronotype Questionnaire(MCTQ)score,and the Pittsburgh Sleep Quality Index(PSQI)score be-fore and after anesthesia.Multiple stepwise regression analysis was performed to screen the factors influencing sleep chronotype and PSQI total score one week after surgery.Results The postoperative mRNA level of CLOCK was higher[1.38±1.23 vs.1.90±1.47;MD(95％CI):0.52(0.20-0.84),t=3.327,P=0.002]and the postoperative mRNA levels of CRY1[1.56±1.50 vs.1.13±0.98;MD(95％CI):-0.43(-0.81--0.05),t=-2.319,P=0.028]and PER2[0.82±0.63 vs.0.50±0.31;MD(95％CI):-0.33(-0.53--0.12),t=-3.202,P=0.003]were lower than the preoperative levels.One week after surgery,the pa-tients presented advanced sleep chronotype[3:03±0:59 vs.2:42±0:37;MD(95％CI):-21(-40--1),t=-2.172,P=0.038],shortened sleep latency[(67±64)min vs.(37±21)min;MD(95％CI):-30.33(-55.28--5.39),t=-2.487,P=0.019],lengthened sleep duration[(436±83)min vs.(499±83)min;MD(95％CI):62.80(26.93-98.67),t=3.581,P=0.001],increased sleep efficiency[(87.59±10.35)％vs.(92.98±4.27)％;MD(95％CI):5.39(1.21-9.58),t=2.636,P=0.013],decreased sleep quality score[1.13±0.78 vs.0.80±0.71;MD(95％CI):-0.33(-0.62--0.05),t=-2.408,P=0.023],and declined PSQI total score[6.60±3.17 vs.4.03±2.58;MD(95％CI):-2.57(-3.87--1.27),t=-4.039,P＜0.001].Body mass index(BMI)(B=-227.460,SE=95.475,t=-2.382,P=0.025),anesthesia duration(B=-47.079,SE=18.506,t=-2.544,P=0.017),and mRNA level of PER2(B=2815.804,SE=1080.183,t=2.607,P=0.015)collectively influenced the sleep chronotype,and the amount of anesthesia medicine(B=0.067,SE=0.028,t=2.385,P=0.024)independently influenced the PSQI one week after surgery.Conclusions Total intravenous anesthe-sia can improve sleep habits by advancing sleep chronotype.BMI,anesthesia duration,and mRNA level of PER2 collectively influence sleep chronotype one week after surgery.The amount of anesthesia medicine independently influences the PSQI total score one week after surgery.