Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.

Objective : To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods : An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results : Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.

Objective:To explore the clinical effectiveness of Masquelet technique combined with improved bone grafting in the treatment of open tibial fractures of Gustilo-Anderson ⅢB with segmental bone defects.Methods:A retrospective study was conducted to analyze the clinical data of 13 patients with open tibial fracture of Gustilo-Anderson ⅢB with segmental bone defects who had been admitted to Department of Orthopeadics, Xijing Hospital, Air Force Medical University from January 2021 to May 2023. There were 9 males and 4 females with an age of (36.9±9.3) years. The length of tibial defects after debridement was (8.1±2.8) cm, and the area of soft-tissue defects 95.0 (53.6, 202.0) cm 2. At the first stage, Masquelet technique was used, soft-tissue defects were covered simultaneously or step by step, skin grafting was conducted on the donor site surface simultaneously, and survival of the tissue and skin grafts was observed. At the second stage, intramedullary space occupation with bone cement rods was conducted using improved bone grafting for which iliac bone, artificial bone, platelet rich plasma (PRP), and recombinant human bone morphogenetic protein-2 (rhBMP-2) were mixed; internal fixation was replaced. The interval between 2 stages of surgery was 4 to 7 weeks. The occurrence of infection, bone defect healing time, knee Lysholm score, ankle Mazur score, and knee and ankle ranges of motion at the last follow-up were recorded. The knee and ankle function scores before the second stage bone grafting and at the last follow-up were compared. Results:After the first-stage surgery, all the 13 patients did not need any revision with fine wound healing. After the second-stage surgery, all patients were followed up for (14.9±4.4) months with no infection at all. The healing time for bone defects was 8.0 (6.0, 12.0) months. At the last follow-up, the knee Lysholm score and the ankle Mazur score were (77.2±5.2) points and (76.1±10.9) points respectively, significantly different from those before the second-stage bone grafting [(41.3±7.5) points and (37.4±5.2) points] ( P<0.05). In the 13 patients at the last follow-up, ankle dorsiflexion limitation was 5.0° (0, 10.0°), knee flexion 105.0°±9.6°, and knee extension limitation 5.0° (5.0°, 5.0°). Conclusion:In the treatment of open tibial fractures of Gustilo-Anderson ⅢB with segmental bone defects, Masquelet technique combined with improved bone grafting can effectively prevent infection, repair bone defects, and restore the function of lower extremities, leading to definite curative efficacy.

Bipolar disorder (BD) affects 1% of the global population. BD is a group of chronic psychiatric disorders characterized by recurrent manic or hypomanic episodes that may alternate with depressive episodes. Given the current diagnostic modalities, accurately diagnosing BD, particularly distinguishing it from unipolar depression (UD), is challenging. Biomarkers have emerged as potent instruments for establishing objective diagnostic criteria for BD, and their identification, which reflects the pathophysiological processes of BD, can facilitate the precise diagnosis of the disorder. In this review, the search terms "BD" and "diagnosis" or "biomarker" were used as the key search syntax. In total, 110 studies were included. This review systematically examines the research in the field and summarizes current studies on biomarkers of BD in omics and neuroimaging. We hope that this review will benefit research aimed at establishing objective diagnostic criteria for BD and developing novel therapeutic interventions.

Objective To investigate the expression level of circular RNA circ-Tns3 in Alzheimer's disease(AD)mice and its role in Aβ-induced neuronal damage.Methods Five APP/PS1 transgenic AD mice and 5 wild-type(WT)mice,weighting of 23～26 g and aged 6 months were subjected in the study.Morris water maze test was used to assess learning and memory abilities,and immunohistochemical staining was performed to observe the number of Aβ plaques in the hippocampal tissue.Subsequently,total RNA was extracted from the brains to detect the differential expression of circRNAs between AD and WT mice,and the results were further analyzed with Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.The top 6 differentially expressed circRNAs were validated by real-time quantitative PCR(RT-qPCR).In in vitro experiments,Aβ1-42 was used to treat neuronal cells to establish AD cell model,and si-circ-Tns3 was transfected into Aβ1-42-treated neuronal cells to knock down circ-Tns3.RT-qPCR was used to determine the expression levels of circ-Tns3 and miR-671-5p.Cell viability and apoptotic rate were detected by CCK-8 assay and TUNEL staining,respectively.The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)were measured using corresponding kits,and the levels of inflammatory factors IL-6,IL-1β,and TNF-α were detected with ELISA.The interaction between circ-Tns3 and miR-671-5p was verified by dual-luciferase reporter assay and RNA-binding protein immunoprecipitation(RIP)assay.The expression level of Sirt1 protein was detected by Western blotting.Results The 6-month-old AD mice exhibited significant cognitive impairment and Aβ deposition(P<0.01).There were 269 differentially expressed circRNAs identified between AD and WT mice,of which 159 were up-regulated and 110 down-regulated.GO and KEGG enrichment analyses showed that these differentially expressed circRNAs were mainly involved in synaptic transmission,memory,and cholinergic synapse signaling pathways.The expression of circ-Tns3 was significantly increased not only in the brain tissue of AD mice but also in neuronal cells after Aβ1-42 treatment.In cellular experiments,knockdown of circ-Tns3 significantly reduced cell viability and number of apoptotic cells in Aβ1-42-treated neuronal cells,decreased MDA content,increased SOD activity,and reduced the levels of IL-6,IL-1β,and TNF-α(P<0.01).The starBase database predicted that circ-Tns3 and miR-671-5p have complementary sequences,and dual-luciferase reporter and RIP assays confirmed their interaction.The bioinformatics database predicted that miR-671-5p and sirt1 have complementary sequences.Western blotting indicated that in neuronal cells treated with Aβ1-42,the expression of sirt1 was increased after knockdown of circ-Tns3(P<0.01).In Aβ1-42-treated neuronal cells,after knockdown of circ-Tns3,addition of miR-671-5p inhibitor significantly decreased the expression level of sirt1 protein(P<0.01).Conclusions circ-Tns3 is highly expressed in AD mice and cell model of AD.Knocking circ-Tns3 down improves neuronal damage.circ-Tns3 may be involved in the neuronal damage through regulating sirt 1 protein by binding to miR-671-5p.

Objectives:To investigate the clinical efficacy of staged percutaneous endoscopic posterior decom-pression for treating multi-segment thoracic ossification of ligamentum flavum(mTOLF).Methods:The clinical data of 16 patients with mTOLF who were treated with staged percutaneous endoscopic posterior decompres-sion at our hospital between June 2021 and June 2023 were retrospectively analyzed,including 9 males and 7 females,aged 46-67(55.4±6.8)years old.The preoperative imaging examinations of the patients indicated multi-segment ossification of ligamentum flavum,including double segments in 14 cases and triple segments in 2 cases.The responsible segments were as follows:upper thoracic spine(T1-T4)in 4 cases,middle thoracic spine(T5-T9)in 6 cases,and lower thoracic spine(T10-T12)in 24 cases.Staged percutaneous endoscopic posterior decompression was performed for mTOLF,targeting only one responsible segment in each surgery.The operative time,blood loss,hospitalization days,and complications were recorded.The Oswestry disability index(ODI)and the modified Japanese Orthopaedic Association(mJOA)11-point scale scores were recorded preoperatively,on 3d postoperatively,and at the final follow-up,and the mJOA improvement rate at the final follow-up was calculated.Statistical analysis was performed to evaluate the clinical efficacy.The spinal canal area and the anterior-posterior spinal canal diameter were measured on CT images preoperatively,on 3d post-operatively,and at the final follow-up to evaluate the improvement of imaging findings.Results:All the 16 patients successfully completed the surgery,and no cerebrospinal fluid leakage or permanent lower limb paral-ysis occurred except for one dural tear during operation.The operative time was 80-205min(150.2±36.1min),blood loss was 30-70mL(50.3±12.4mL),hospitalization days were 9-15d(10.8±1.8d)and the follow-up time ranged from 9-20(14.3±3.2)months.The mJOA scores and ODIs before surgery,on 3d after surgery,and at the final follow-up were 5.7±1.3,7.1±1.3,8.5±1.4,and(41.4±1.8)％,(17.8±1.6)％,(15.6±1.3)％,respectively,which were both significantly improved on 3d postoperatively and at final follow-up compared with those val-ues before operation(P＜0.05).The mJOA recovery rate was 28.6％-100％[(56.1±19.3)％],and according to the mJOA evaluation criteria,the outcomes were classified as excellent in 3 cases,good in 9 cases,fair in 4 cases,and poor in no case,with an excellent and good rate of 75.0％.The spinal canal area and anterior-posterior diameter before surgery,on 3d after surgery,and at the final follow-up were 76.7±12.5mm2,159.9±22.1mm2,157.7±21.6mm2,and 7.4±0.5mm,15.5±0.9mm,15.3±0.9mm,respectively.Both the spinal canal area and anterior-posterior diameter on 3d postoperatively and at the final follow-up significantly increased com-pared to preoperative values(P＜0.05).Conclusions:Staged percutaneous endoscopic posterior decompression for treating mTOLF is safe and effective,and yields satisfactory clinical outcomes.

Objective To investigate the mechanism by which Yangmai Tongluo formula improves microcirculation disorders induced by high homocysteine(Hcy)levels via regulation of the acid sphingomyelinase(ASM)and endoplasmic reticulum(ER)stress pathways.Methods Fifty male C57BL/6J mice were divided randomly into a control group,Hcy model group,Yangmai Tongluo formula low-/high dose groups(5.3,10.4 g/kg,respectively),and a folic acid group(0.08 g/kg).Except for the control group,microcirculation disorders were induced in all mice using drinking water containing 1.8 g/L Hcy for 6 weeks.After modeling for 2 weeks,mice were administered the corresponding treatments by gavage for 4 weeks.Serum Hey concentrations and the blood perfusion volume of the lower extremity microvessels were measured.Protein expression levels of zonula occludens ZO-1,ZO-2,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),ASM,glucose-regulated protein 78(GRP78),and C/EBP homologous protein(CHOP)in the cardiac microvascular endothelium were analyzed using immunofluorescence.Results Serum Hcy levels were significantly increased in the Hcy model group compared with the control group(P＜0.05).Yangmai Tongluo formula did not significantly reduce Hey levels compared with the Hey model group,but blood perfusion in the lower extremities was significantly increased(P＜0.01)and expression levels of ZO-1 and ZO-2 in the cardiac microvascular endothelium were restored(P＜0.001)in the Yangmai Tongluo formula high dose group.It also inhibited the expression of ICAM-1,VCAM-1,ASM,GRP78,and CHOP(P＜0.05),with comparable effects to folic acid.Conclusions Yangmai Tongluo formula improves Hcy-induced microcirculation disorders and endothelial dysfunction by inhibiting ASM activity and alleviating ER stress,via a mechanism closely related to the regulation of endothelial inflammation and barrier stability.These result provide experimental evidence to support the use of traditional Chinese medicine to treat microvascular diseases.

Objectives:To investigate the clinical efficacy of staged percutaneous endoscopic posterior decom-pression for treating multi-segment thoracic ossification of ligamentum flavum(mTOLF).Methods:The clinical data of 16 patients with mTOLF who were treated with staged percutaneous endoscopic posterior decompres-sion at our hospital between June 2021 and June 2023 were retrospectively analyzed,including 9 males and 7 females,aged 46-67(55.4±6.8)years old.The preoperative imaging examinations of the patients indicated multi-segment ossification of ligamentum flavum,including double segments in 14 cases and triple segments in 2 cases.The responsible segments were as follows:upper thoracic spine(T1-T4)in 4 cases,middle thoracic spine(T5-T9)in 6 cases,and lower thoracic spine(T10-T12)in 24 cases.Staged percutaneous endoscopic posterior decompression was performed for mTOLF,targeting only one responsible segment in each surgery.The operative time,blood loss,hospitalization days,and complications were recorded.The Oswestry disability index(ODI)and the modified Japanese Orthopaedic Association(mJOA)11-point scale scores were recorded preoperatively,on 3d postoperatively,and at the final follow-up,and the mJOA improvement rate at the final follow-up was calculated.Statistical analysis was performed to evaluate the clinical efficacy.The spinal canal area and the anterior-posterior spinal canal diameter were measured on CT images preoperatively,on 3d post-operatively,and at the final follow-up to evaluate the improvement of imaging findings.Results:All the 16 patients successfully completed the surgery,and no cerebrospinal fluid leakage or permanent lower limb paral-ysis occurred except for one dural tear during operation.The operative time was 80-205min(150.2±36.1min),blood loss was 30-70mL(50.3±12.4mL),hospitalization days were 9-15d(10.8±1.8d)and the follow-up time ranged from 9-20(14.3±3.2)months.The mJOA scores and ODIs before surgery,on 3d after surgery,and at the final follow-up were 5.7±1.3,7.1±1.3,8.5±1.4,and(41.4±1.8)％,(17.8±1.6)％,(15.6±1.3)％,respectively,which were both significantly improved on 3d postoperatively and at final follow-up compared with those val-ues before operation(P＜0.05).The mJOA recovery rate was 28.6％-100％[(56.1±19.3)％],and according to the mJOA evaluation criteria,the outcomes were classified as excellent in 3 cases,good in 9 cases,fair in 4 cases,and poor in no case,with an excellent and good rate of 75.0％.The spinal canal area and anterior-posterior diameter before surgery,on 3d after surgery,and at the final follow-up were 76.7±12.5mm2,159.9±22.1mm2,157.7±21.6mm2,and 7.4±0.5mm,15.5±0.9mm,15.3±0.9mm,respectively.Both the spinal canal area and anterior-posterior diameter on 3d postoperatively and at the final follow-up significantly increased com-pared to preoperative values(P＜0.05).Conclusions:Staged percutaneous endoscopic posterior decompression for treating mTOLF is safe and effective,and yields satisfactory clinical outcomes.

Objective To investigate the mechanism by which Yangmai Tongluo formula improves microcirculation disorders induced by high homocysteine(Hcy)levels via regulation of the acid sphingomyelinase(ASM)and endoplasmic reticulum(ER)stress pathways.Methods Fifty male C57BL/6J mice were divided randomly into a control group,Hcy model group,Yangmai Tongluo formula low-/high dose groups(5.3,10.4 g/kg,respectively),and a folic acid group(0.08 g/kg).Except for the control group,microcirculation disorders were induced in all mice using drinking water containing 1.8 g/L Hcy for 6 weeks.After modeling for 2 weeks,mice were administered the corresponding treatments by gavage for 4 weeks.Serum Hey concentrations and the blood perfusion volume of the lower extremity microvessels were measured.Protein expression levels of zonula occludens ZO-1,ZO-2,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),ASM,glucose-regulated protein 78(GRP78),and C/EBP homologous protein(CHOP)in the cardiac microvascular endothelium were analyzed using immunofluorescence.Results Serum Hcy levels were significantly increased in the Hcy model group compared with the control group(P＜0.05).Yangmai Tongluo formula did not significantly reduce Hey levels compared with the Hey model group,but blood perfusion in the lower extremities was significantly increased(P＜0.01)and expression levels of ZO-1 and ZO-2 in the cardiac microvascular endothelium were restored(P＜0.001)in the Yangmai Tongluo formula high dose group.It also inhibited the expression of ICAM-1,VCAM-1,ASM,GRP78,and CHOP(P＜0.05),with comparable effects to folic acid.Conclusions Yangmai Tongluo formula improves Hcy-induced microcirculation disorders and endothelial dysfunction by inhibiting ASM activity and alleviating ER stress,via a mechanism closely related to the regulation of endothelial inflammation and barrier stability.These result provide experimental evidence to support the use of traditional Chinese medicine to treat microvascular diseases.

Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.