Patients with Asian-type DEL can safely be transfused with RhD-positive blood.

Red blood cells (RBCs) of Asian-type DEL phenotype express few RhD proteins and are typed as serologic RhD-negative (D-) phenotype in routine testing. RhD-positive (D+) RBC transfusion for patients with Asian-type DEL has been proposed but has not been generally adopted because of a lack of direct evidence regarding its safety and the underlying mechanism. We performed a single-arm multicenter clinical trial to document the outcome of D+ RBC transfusion in patients with Asian-type DEL; none of the recipients (0/42; 95% confidence interval, 0-8.40) developed alloanti-D after a median follow-up of 226 days. We conducted a large retrospective study to detect alloanti-D immunization in 4045 serologic D- pregnant women throughout China; alloanti-D was found only in individuals with true D- (2.63%, 79/3009), but not in those with Asian-type DEL (0/1032). We further retrospectively examined 127 serologic D- pregnant women who had developed alloanti-D and found none with Asian-type DEL (0/127). Finally, we analyzed RHD transcripts from Asian-type DEL erythroblasts and examined antigen epitopes expressed by various RHD transcripts in vitro, finding a low abundance of full-length RHD transcripts (0.18% of the total) expressing RhD antigens carrying the entire repertoire of epitopes, which could explain the immune tolerance against D+ RBCs. Our results provide multiple lines of evidence that individuals with Asian-type DEL cannot produce alloanti-D when exposed to D+ RBCs after transfusion or pregnancy. Therefore, we recommend considering D+ RBC transfusion and discontinuing anti-D prophylaxis in patients with Asian-type DEL, including pregnant women. This clinical trial is registered at www.clinicaltrials.gov as #NCT03727230.

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease.

BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

The contribution of preoperative balanced halo-pelvic traction to severe rigid spinal deformity correction.

PURPOSE: The aim of this study was to assess the clinical efficacy of balanced halo-pelvic traction (HPT) and evaluate its contribution to the correction surgery in treating adult severe rigid spinal deformity. METHODS: One hundred and eight adult patients with severe rigid spinal deformity who underwent preoperative HPT and correction surgery were reviewed. The main coronal curve, segmental kyphotic angle, coronal balance (CB), sagittal balance (SVA), and the length of spine were measured before HPT, after HPT, post-operatively, and at final follow-up. The HPT contribution rates to deformity correction were calculated. RESULTS: The pre-HPT main coronal curve was 103.4 ± 10.6°, improved to 61.0 ± 13.4° after traction and further improved to 44.2 ± 10.2° after surgical correction, and maintained at 50.3 ± 9.9° at final follow-up. CB started at 4.2 ± 4.8 cm, improved to 2.1 ± 2.5 cm after HPT, 0.8 ± 1.2 cm after operation, and 0.7 ± 0.9 cm at final follow-up. The pre-HPT sagittal segmental kyphotic angle was 67.3 ± 17.7°, was then improved to 42.2 ± 27.5° after traction and further improved to 34.9 ± 10.2° after surgery, and maintained at 35.4 ± 10.4° at final follow-up. The length of spine improved from 35.9 ± 5.9 to 42.6 ± 6.0 cm via HPT, reached up to 45.0 ± 6.0 cm after operation, and maintained at 44.3 ± 5.2 cm at final follow-up. CONCLUSION: HPT is effective for the treatment of severe rigid spinal deformity. Balanced HPT can dramatically improve coronal and sagittal deformity as well as spinal length before corrective surgery.

Global realignment after posterior vertebral column resection in severe thoracolumbar post-tubercular kyphosis: correlation with patient-reported outcomes.

PURPOSE: To investigate spinal realignment in patients with severe post-tubercular kyphosis (PTK) who underwent posterior vertebral column resection (PVCR) and its correlation with patient-reported outcomes (PROs). METHODS: Eighty-two patients were included in this study. Spinopelvic parameters (focal scoliosis (FS), coronal balance (CB), sagittal vertical axis (SVA), focal kyphosis (FK), C2-7 lordosis (CL), thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), and pelvic incidence minus lumbar lordosis (PI-LL)) and PROs (Visual Analog Scale (VAS) and Oswestry Disability Index (ODI)) were analyzed. The correlation between spinopelvic parameters and PROs was evaluated. RESULTS: FK, FS, CL, TK, LL, and PI-LL significantly changed after surgery. FK decreased from pre-operative 108.5 ± 16.4° to 31.8 ± 4.5° at three months after surgery and increased to 38.7 ± 6.6° at final follow-up (P < 0.001). FS decreased from pre-operative 20.9 ± 2.2° to 5.1 ± 2.2° at final follow-up (P < 0.001). CL decreased from pre-operative 7.2 ± 7.3° to 3.3 ± 8.3° at final follow-up (P = 0.002). TK improved from pre-operative - 5.6 ± 7.1° to 12.9 ± 8.2° at final follow-up (P < 0.001). LL decreased from pre-operative 75.5 ± 12.6° to 45.5 ± 7.9° at final follow-up (P < 0.001). PI-LL improved from pre-operative - 24.8 ± 13.4° to 4.8 ± 9.9° at final follow-up (P < 0.001). The improvement of PROs was found to be significantly correlated with the variations of FK, CL, TK, LL, and PI-LL. The multiple regression analysis revealed that FK was an independent predictor for the improvement of VAS and ODI. CONCLUSIONS: PVCR is effective in treating severe PTK, which can significantly improve patients' clinical and radiographic outcomes. Spine surgeons should pay more attention to reducing the residual kyphosis.

A novel classification of osteotomized debridement based on the range of focus in treating active thoracolumbar tuberculosis: a multicenter study.

INTRODUCTION: Osteotomized debridement (OD) is increasingly used in the treatment of active thoracolumbar tuberculosis (TB). So far, no nomenclature has been established to describe the patterns of OD, and thus the surgical outcomes cannot be directly analyzed and compared among the patients treated with different extents of OD. The purpose of this study was to establish a reliable classification of OD for further study of spinal TB. MATERIALS AND METHODS: This was a multicenter retrospective study. The proposed classification included 6 grades of OD based on sagittal range of vertebral body destruction: grade 0 involves single-level intervertebral disc and adjacent superficial endplates; grade 1 involves adjacent endplates and vertebral bodies, but no pedicle is involved; grade 2 involves adjacent endplates, vertebral bodies, and a lower or upper pedicle; grade 3 involves adjacent endplates, vertebral bodies, and both of lower and upper pedicles; grade 4 involves an entire vertebral body and an adjacent lower or upper pedicle; grade 5 involves two continuous entire vertebral bodies. Two hundred and five patients with active thoracolumbar TB who underwent OD surgery were included, and all ODs were classified. The reliability of this classification was evaluated twice by 10 readers, and Fleiss kappa coefficients were calculated. RESULTS: In the 205 patients, 208 ODs were performed. Grade 2 OD was the commonest type (98/208, 47.1%), followed by grade 1 (50/208, 24.0%), grade 3 (26/208, 12.5%), grade 0 (20/208, 9.6%), grade 4 (8/208, 3.8%), and grade 5 (6/208, 2.9%). The average accuracy of the two readings was 86.2% and 90.1%, respectively. The intra-rater reliability for the classification was "almost perfect agreement" with a Fleiss kappa coefficient average of 0.92. The inter-rater reliability was "almost perfect agreement" with a coefficient average of 0.89 for two readings. CONCLUSIONS: This classification proved to be intuitive and reliable. The graded OD provides a platform for preoperative evaluation and allows comparative analysis of clinical outcomes in different extents of OD.

Halo traction combined with posterior-only approach correction for cervical kyphosis with Neurofibromatosis-1: minimum 2 years follow-up.

BACKGROUND: Surgical management of cervical kyphosis in patients with NF-1 is a challenging task. Presently, anterior-only (AO), posterior-only (PO) and combined anterior-posterior (AP) spinal fusion are common surgical strategies. However, the choice of surgical strategy and application of Halo traction remain controversial. Few studies have shown and recommended posterior-only approach for cervical kyphosis correction in patients with NF-1. The aim of this study is to evaluate the safety and the effectiveness of halo Traction combined with posterior-only approach correction for treatment of cervical kyphosis with NF-1. METHODS: Twenty-six patients with severe cervical kyphosis due to NF-1 were reviewed retrospectively between January 2010 and April 2018. All the cases underwent halo traction combined with posterior instrumentation and fusion surgery. Correction result, neurologic status and complications were analyzed. RESULTS: In this study, cervical kyphosis Cobb angle decreased from initial 61.3 ± 19.7 degrees to postoperative 10.6 ± 3.7 degrees (P<0.01), with total correction rate of 82.7%, which consist of 45.8% from halo traction and 36.9% from surgical correction. JOA scores were improved from preoperative 13.3 ± 1.6 to postoperative 16.2 ± 0.7 (P<0.01). Neurological status was also improved. There was no correction loss and the neurological status was stable in mean 43 months follow-up. Three patients experienced minor complications and one patient underwent a second surgery. CONCLUSION: Halo traction combined with PO approach surgery is safe and effective method for cervical kyphosis correction in patients with NF-1. A satisfied correction result, and successful bone fusion can be achieved via this procedure, even improvement of neurological deficits can also be obtained. Our study suggested that halo traction combined with PO approach surgery is another consideration for cervical kyphosis correction in patients with NF-1.

The clinical characteristics of patients with acute leukemia or stem cell transplantation exhibiting immune based platelet refractoriness.

BACKGROUND: To investigate the related factors influencing immune platelet transfusion refractoriness (PTR) in acute leukemia (AL) from induction to consolidation and compare management for immune PTR, so as to improve the Platelet increment in AL. METHODS: The primary analysis included 890 patients with AL, 225 of whom were the immune PTR (25 %).They are patients in our center from induction to consolidation or transplantation in the past 10 years. Flow cytometry, karyotype characteristics and other basic information were compared between the immune PTR vs control (no-PTR) groups. We analyzed the treatment outcomes of immune PTR including matched platelets, intravenous immunoglobulin (IVIG), increasing apheresis platelet does. RESULTS: Immune PTR is more likely to occur in patients with poor prognosis in acute lymphoblastic leukemia (ALL) (P = 0.01).There is a relation between NPM1 mutation and occurrence of immune PTR (P = 0.029).The incidence of PTR at 35-59Y was higher than that at <35Y(OR = 0.68, 95 % CI = 0.48-0.96) and ≥60Y(OR = 0.49,95 % CI = 0.28-0.83), and the difference was statistically significant(P = 0.03, P = 0.01).The Platelet increment with 1 unit (u) was 47.12 %, 2 u increased to 71.14 %, and the matched 2 u (75.11 %) had the best effect. IVIG improved the Platelet increment, but there was no difference between 0.4 g/kg IVIG and 1 g/kg IVIG. Immune PTR is more likely to occur in the ages of 35-60 years. CONCLUSION: There are specific AL patient characteristics which predispose to the phenomenon of immune based PTR. Meanwhile, increasing the IVIG dose could not improve Platelet increment obviously.

Aberrant Phenotype and Function of Dendritic Cells in Adult B Lineage Acute Lymphoblastic Leukemia.

Dendritic cells (DCs) play a major role in regulating immune responses, but the aberrant phenotype and function of defective DCs in adult acute lymphoblastic leukemia (ALL) remain unclear. Here, B lineage ALL (B-ALL) patients were divided into groups according to different standards. By course of disease: newly diagnosed (ND), complete remission (CR), consolidation (CONS). By stratification: high risk (HR), standard risk (SR). By minimal residual disease (MRD): MRD positive(MRD+), MRD negative (MRD-). The proportion of plasmacytoid DC(pDC) and myeloid DC(mDC) were compared within these standards. The costimulatory molecule levels of pDC, mDC in ND and CR were measured and the function of peripheral blood monocyte-derived DC(MoDC)s were examined. We found proportions of pDC and mDC in ND were both lower compared to control group and gradually increased after CR. In HR and MRD+, the proportions were also lower compared to SR and MRD- at CR stage, respectively; but there were no difference between these comparisons when newly diagnosed. In ND, both CD80, CD86 levels in pDC, mDC were higher while the levels in activated MoDCs were lower when compared to control and CR group, respectively. The dextran uptake of MoDCs, T cell proliferation promoting ability, IL-12, BAFF, INF-α levels in supernatant and their mRNA relative expression in activated MoDCs in ND were also lower than those in control and CR group. So, DCs in B-ALL display suppressed status in phenotype and function，which would be gradually restored after effective chemotherapy. pDC and mDC could respond to patient condition, DCs proportion may be useful for monitoring disease progression.

Investigation of the optimal duration of bed rest in the supine position to reduce complications after lumbar puncture combined with intrathecal chemotherapy: a multicenter prospective randomized controlled trial.

PURPOSE: This randomized, open-label trial was conducted to investigate the optimal duration of bed rest after intrathecal chemotherapy to reduce the incidence of complications without increasing patients' tolerance to long-term bed rest. METHODS: A total of 390 patients receiving intrathecal chemotherapy were randomly assigned 1:1:1 to undergo bed rest for 6, 8, or 10 h after intrathecal chemotherapy. The primary outcome was the rate of complications after intrathecal chemotherapy. The analysis was per protocol. RESULTS: A total of 359 patients among the 390 patients in our study completed follow-up with 120 patients in the 6-h group, 120 in the 8-h group, and 119 in the 10-h group. The complications among the three groups differed significantly (P = 0.005). The 6-h group had significantly more complications than the 8- (50, 41.7% vs 29, 24.2%, P = 0.004) and 10-h groups (50, 41.7% vs 31, 26.1%, P = 0.011), whereas the difference between the 8- and 10-h groups was not significant (29, 24.2% vs 31, 26.1%, P = 0.737). CONCLUSIONS: The overall results support that the optimal time interval for bed rest in the supine position after intrathecal chemotherapy is 8 h. This trial is registered with the Chinese Clinical Trial Registry (number ChiCTR-IOR-17011671).

Management of eosinophilic granuloma in pediatric patients: surgical intervention and surgery combined with postoperative radiotherapy and/or chemotherapy.

BACKGROUND: Eosinophilic granuloma (EG) of spine in pediatric patients presents kinds of clinical manifestation and a difficult management scenario. The choice of treatment, issues of surgical intervention versus conservative treatment, combination therapy or single treatment, all these factors, including neurological deficits, spinal stability, long-term complications, and continued skeletal growth, must be considered. METHODS: From 2008 to the 2015, 31 pediatric patients of spinal EG were retrospectively reviewed. They were 17 males and 14 females, with a mean age 8.89 ± 2.84 years old (range, 3.5-14 years old). All the cases were divided into two groups. Twenty-three cases (Group S) accepted surgical interventions and surgery combined with local low-dose radiotherapy and/or chemotherapy. Eight patients (Group C) accepted radiotherapy and/or chemotherapy. All the patients had imaging studies of the lesion including standard radiography, three-dimensional computed tomography (CT) scan, and magnetic resonance imaging (MRI) prior to and after treatment. Cases in group S underwent surgery-related treatment, which include six patients accepted surgery only, nine patients accepted postoperative low-dose radiotherapy, four patients accepted additional chemotherapy, and four patients accepted both. Cases in group C accepted radiotherapy and/or chemotherapy, which include five patients accepted radiotherapy, one patient accepted chemotherapy, and two patients accepted both radiotherapy and chemotherapy. Clinical symptoms, neurologic status, radiologic manifestations, treatment, outcome, and/or complications were recorded and analyzed. RESULTS: All the 31 patients had pain relief (both in group S and group C) but the patients in group S obtained more prompt pain relief. All the patients in group S obtained local kyphosis correction, reconstruction of stability of spine, and recovery of neurological deficit after treatment. They have no surgery-related complications after treatment and in follow-up. Seventeen patients who received additional postoperative radiotherapy and/or chemotherapy also had good outcomes. There were no severe radiation and chemotherapy complications in procedure. The patients (group C) who accepted non-surgical treatment also have no severe complications, and a new femur lesion was found in one patient in follow-up. CONCLUSION: Surgical intervention, including anterior and/or posterior approach with bone graft or surgery combined with postoperative low-dose radiotherapy and/or chemotherapy is a safe and effective way for treatment of the spinal EG. Compared with radiotherapy and/or chemotherapy, more prompt pain relief can be achieved via surgical intervention or surgery combined radiotherapy and/or chemotherapy.

More preoperative flexibility implies adequate neural pliability for curve correction without prophylactic untethering in scoliosis patients with asymptomatic tethered spinal cord, a retrospective study.

BACKGROUND: Tethered spinal cord is frequently associated with scoliosis. It is still controversial whether a prophylactic untethering is necessary before correction procedure in scoliosis patients with tethered spinal cord. In this study we determined the clinical outcome of a one-stage posterior scoliosis correction without a prophylactic untethering for treating scoliosis with an asymptomatic tethered spinal cord. METHODS: Seventeen (5 males and 12 females) scoliosis patients with tethered spinal cords were retrospectively reviewed. All patients underwent a one-stage posterior scoliosis correction without preventive untethering. Parameters of radiograph were used to assess correction result. The Scoliosis Research Society (SRS)-22 questionnaire was analyzed pre- and post-operatively to evaluate the clinical outcomes. The modified Japanese Orthopaedic Association (mJOA) score was used to assess the pre- and post-operative spinal cord function. RESULTS: The post-operative coronal Cobb angle was significantly decreased compared with preoperative. (23.8 ± 6.4° vs. 58.4 ± 12.6°, P < 0.01). The coronal Cobb angle was 22.4 ± 6.8° at the final follow-up evaluation. The apical vertebral translation (AVT) was also decreased significantly. (27.5 mm vs. 60.9 mm, P < 0.01). The SRS-22 total score was improved at the 1-year follow-up evaluation compared with the pre-operative SRS-22 total score (87 ± 4 vs. 70 ± 5, p < 0.05). The functional activities, pain, self-image, mental health, and surgery satisfactory scores at the final follow-up evaluation were all improved compared with the corresponding pre-operative scores, especially the self-image and mental health scores (p < 0.05). The spinal cord function was stable and there was no new neurological symptoms after scoliosis correction. No difference existed between the pre- and post-operative total mJOA score (26 ± 2 vs. 27 ± 2, p = 0.39), which including subjective symptom (p = 0.07), clinical symptom (p = 0.33), daily activities (p = 0.44) and bladder function (p = 0.67). CONCLUSION: One-stage posterior scoliosis correction is a safe and effective surgical procedure for scoliosis patients combined with asymptomatic tethered spinal cord who have adequate spinal cord function reserve.

ZNF606 interacts with Sox9 to regulate chondrocyte differentiation.

SRY-related high-mobility-group box 9 (Sox9) gene is a transcription factor that plays an essential role in chondrocyte differentiation and cartilage formation. In this study, we identified the transcriptional factor ZNF606 as an interacting partner for Sox9 in cells. We further demonstrated that overexpression of ZNF606 inhibited the transcriptional activity of Sox9, while knockdown of ZNF606 increased Sox9-mediated transcription. Chromatin immunoprecipitation analysis revealed that ZNF606 prevents Sox9 binding to the enhancers of its target gene col2a1. Importantly, the interaction between ZNF606 and Sox9 was decreased during chondrocyte differentiation. Consistent with these findings, ZNF606 inhibited chondrocyte differentiation. Thus, our results demonstrate that ZNF606 acts as a novel Sox9 co-regulator that inhibits Sox9-mediated chondrocyte differentiation.

One-stage posterior focus debridement, fusion, and instrumentation in the surgical treatment of lumbar spinal tuberculosis with kyphosis in children.

OBJECTIVE: The purpose of this study is to investigate the clinical efficacy and feasibility of one-stage posterior focus debridement, fusion, and instrumentation in the surgical treatment of lumbar spinal tuberculosis with kyphosis in children. METHODS: From December 2007 to May 2012, 13 patients (six males and seven females) suffering from lumbar spinal tuberculosis with kyphosis were admitted. All patients were treated with one-stage posterior focus debridement, fusion, and instrumentation. Then, the clinical efficacy was estimated by statistical analysis based on the data about Frankel grade, the Cobb angle of kyphosis, and erythrocyte sedimentation rate (ESR), which were collected at certain time. RESULTS: The age of all patients ranged from 5 to 13 years (average, 8.8 years). Operation time ranged from 120 to 190 min (average, 165 min). Intraoperative blood loss ranged from 200 to 800 ml (average, 460 ml). All patients were followed up for 24 to 57 months postoperatively (average, 33.5 months). The Cobb angle was changed significantly between preoperation and postoperation (P < 0.05), and there was no significant loss at the last follow-up. The preoperation ESR (62.5 ± 15.7) returned to normal (16.6 ± 8.1) within 3 months postoperatively in all patients (P < 0.05). Bone fusion was achieved within 3-5 months (average, 3.5 months). In the 13 cases, no postoperative severe complications occurred and neurologic function improved in various degrees. CONCLUSION: The outcomes of follow-up showed that one-stage posterior focus debridement, fusion, and instrumentation can be an effective treatment method for the lumbar spinal tuberculosis with kyphosis in children.

Leptin Receptor Metabolism Disorder in Primary Chondrocytes from Adolescent Idiopathic Scoliosis Girls.

To investigate the underlying mechanisms of low metabolic activity of primary chondrocytes obtained from girls with adolescent idiopathic scoliosis (AIS); AIS is a spine-deforming disease that often occurs in girls. AIS is associated with a lower bone mass than that of healthy individuals and osteopenia. Leptin was shown to play an important role in bone growth. It can also regulate the function of chondrocytes. Changes in leptin and Ob-R levels in AIS patients have been reported in several studies. The underlying mechanisms between the dysfunction of peripheral leptin signaling and abnormal chondrocytes remain unclear; The following parameters were evaluated in AIS patients and the control groups: total serum leptin levels; Ob-R expression in the plasma membrane of primary chondrocytes; JAK2 and STAT3 phosphorylation status. Then, we inhibited the lysosome and proteasome and knocked down clathrin heavy chain (CHC) expression in primary chondrocytes isolated from girls with AIS and evaluated Ob-R expression. We investigated the effects of leptin combined with a lysosome inhibitor or CHC knockdown in primary chondrocytes obtained from AIS patients; Compared with the controls, AIS patients showed similar total serum leptin levels, reduced JAK2 and STAT3 phosphorylation, and decreased cartilage matrix synthesis in the facet joint. Lower metabolic activity and lower membrane expression of Ob-R were observed in primary chondrocytes from the AIS group than in the controls. Lysosome inhibition increased the total Ob-R content but had no effect on the membrane expression of Ob-R or leptin's effects on AIS primary chondrocytes. CHC knockdown upregulated the membrane Ob-R levels and enhanced leptin's effects on AIS primary chondrocytes; The underlying mechanism of chondrocytes that are hyposensitive to leptin in some girls with AIS is low plasma membrane Ob-R expression that results from an imbalance between the rate of receptor endocytosis and the insertion of newly synthesized receptors into the membrane.

Hepatitis B virus infection status is an independent risk factor for multiple myeloma patients after autologous hematopoietic stem cell transplantation.

The purposes of this study were to evaluate the infection by hepatitis B virus (HBV) and its impact on survival and to provide a clinical reference for monitoring and treating HBV during and after autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A retrospective analysis of HBV infections was performed in 70 MM patients who received a sequential bortezomib-containing induction therapy and ASCT in our department from June 2006 to February 2012. Among the 70 patients in our study, 11 cases (15.7 %) were hepatitis B surface antigen positive (HBsAg+), and 23 cases (33.3 %) were hepatitis B core antibody positive (HBcAb+). Eight cases were HBsAg, hepatitis B e antibody (HBeAb), and HBcAb positive, while one case was HBsAg, hepatitis B e antigen (HBeAg), and HBcAb positive. The median follow-up times for the HBsAg+ group and the HBsAg-negative (HBsAg-) group were 27.0 (7.6-85.2) months and 28.7 (7.1-111.0) months, respectively. The 1-year, 2-year, and 3-year overall survival rates of the HBsAg+ group were 90.9, 80.8, and 34.6 %, respectively, and the median survival time was 31.2 months (95 % CI, 24.8-37.6). The 1-year, 2-year, and 3-year overall survival rates of the HBsAg- group were 98.2, 94, and 84.6 %, respectively, while the median survival time was not yet available. There was a statistically significant difference (p=0.008) in the overall survival rate between the two groups. By Cox regression analysis, we found that the HBsAg+ status was a prognostic factor, which could independently influence the overall survival rate for ASCT. In conclusion, the HBsAg+ status is an independent risk factor for patients with MM receiving ASCT. The application of standard antiviral treatment might help to overcome this risk factor.

Determining the optimal time for bortezomib-based induction chemotherapy followed by autologous hematopoietic stem cell transplant in the treatment of multiple myeloma.

In our study, we determined the efficacy of bortezomib-based induction therapy followed by autologous stem cell transplant (ASCT) in newly diagnosed and relapsed/refractory (R/R) multiple myeloma (MM) patients and compared the advantages of early versus late transplant. We used a retrospective analysis to examine 62 patients, including 46 cases of newly diagnosed MM (early transplant group) and 16 cases of relapsed/refractory MM (late transplant group). All of these patients received bortezomib-based induction therapy followed by ASCT. The efficacy and side effects of the treatment regimen were analyzed. Patients' overall survival (OS) and progression-free survival (PFS) times were determined. The ratio of complete remission to near-complete remission (CR/nCR) was 69.5% versus 56.2% (P=0.361), respectively, for the early transplant group versus the late transplant group, respectively, after receiving bortezomib-based induction therapy; the overall response rates of the two group were 91.3% and 81.2%, respectively (P=0.369). After receiving ASCT, the CR/nCR of the two groups increased to 84.8% and 81.3%, respectively. The median time required for neutrophil engraftment of the early transplant group and the late transplant group was 11 and 14.5 days, respectively (P=0.003); the median time required for platelet engraftment was 13 and 21.5 days (P=0.031), respectively. There were no significant differences in the toxic side effects observed during induction therapy and ASCT between the two groups. The OS of the two groups was not statistically different (P=0.058). The PFS of the early transplant group and the late transplant group was 41.6 and 26.5 months, respectively (P=0.008). Multivariate analysis demonstrated that the time of receiving ASCT, the types of M protein, and the International Staging System (ISS) stage were all independent factors that influenced PFS. In conclusion, patients in a suitable condition for ASCT should be recommended to have an early ASCT immediately after diagnosis.

The Correlation of Global Spinal Realignment With the Quality of Life After Corrective Surgery for Delayed Thoracolumbar Osteoporotic Fracture-Related Kyphosis.

BACKGROUND AND OBJECTIVES: Few studies have been conducted to evaluate the precise impact of corrective surgery on sagittal spinal realignment and clinical outcomes in cases of delayed thoracolumbar osteoporotic fracture-related kyphosis. To assess the efficacy of corrective surgery on sagittal spinal alignment and investigate the relationship between spinal alignment and health-related quality of life (HRQoL) in patients with delayed thoracolumbar osteoporotic fracture-related kyphosis. METHODS: A total of 78 patients were enrolled. The characteristics and surgical variables were meticulously documented. The sagittal spinal parameters were measured, and the HRQoL was evaluated using Oswestry Disability Index (ODI), SF-12 Physical Component Score (SF-12 PCS), and Scoliosis Research Society-22 Patient Questionnaire (SRS-22) before and after surgery. The changes in spinal parameters and HRQoL were analyzed through the paired t -test. The Pearson correlation analysis was performed to analyze the correlation of parameters with HRQoL. Then, a multiple stepwise regression analysis was performed with HRQoL scores as the dependent variable and spinal parameters as the independent variable. RESULTS: The operative time was 185.9 ± 33.2 min, and the estimated blood loss was 782.8 ± 145.2 mL. The results of the paired t -test revealed a significant difference preoperatively and at the final follow-up in the thoracic kyphosis, thoracolumbar kyphosis (TLK), lumbar lordosis, T9 tilt, pelvic tilt, sacral slope, sagittal vertical axis, and spinosacral angle as well as the ODI, SF-12 PCS, and SRS-22 ( P < .05). Multiple stepwise regression analysis revealed that TLK and pelvic tilt, TLK and sagittal vertical axis, and TLK were the primary parameters affecting the ODI, SF-12 PCS, and SRS-22, respectively. CONCLUSION: Corrective surgery can effectively realign the global spine and improve HRQoL in patients with delayed thoracolumbar osteoporotic fracture-related kyphosis. The change of TLK is a driving factor to realign the global spine.

Ferrostatin-1 facilitated neurological functional rehabilitation of spinal cord injury mice by inhibiting ferroptosis.

BACKGROUND: To seek the potential therapy for spinal cord injury, Ferrostatin-1, the first ferroptosis inhibitor, was administrated in spinal cord injury mice to identify the therapeutic effect. METHODS: Spinal cord injury model was established by a modified Allen's method. Then, ferrostatin-1 was administrated by intraspinal injection. Cortical evoked motor potential and BMS were indicated to assess the neurological function rehabilitation. H&E, Nissl's staining, NeuN, and GFAP immunofluorescence were used to identify the histological manifestation on the mice with the injured spinal cord. Spinosin, a selective small molecule activator of the Nrf2/HO-1 signaling pathway, was administrated to verify the underlying mechanism of ferrostatin-1. RESULTS: Ferrostatin-1 promoted the rehabilitation of cortical evoked motor potential and BMS scores, synchronized with improvement in the histological manifestation of neuron survival and scar formation. Spinosin disturbed the benefits of ferrostatin-1 administration on histological and neurobehavioral manifestation by deranging the Nrf2/HO-1 signaling pathway. CONCLUSIONS: Ferrostatin-1 improved the rehabilitation of spinal cord injury mice by regulating ferroptosis through the Nrf2/HO-1 signaling pathway.

Improvement of pulmonary function and reconstructed 3D lung volume after deformity correction for thoracic spinal posttubercular kyphosis: a multicenter study.

OBJECTIVE: The aim of this study was to investigate the influence of corrective surgery on thoracic spinal posttubercular kyphosis (PTK) with respect to lung volume and pulmonary function. METHODS: This was a retrospective study of 126 patients (72 males and 54 females) who underwent posterior vertebral column resection (PVCR) for severe thoracic spinal PTK between September 2013 and June 2020. The patients' spinal parameters, results of their pulmonary function test (PFT), and CT-based 3D lung volume were recorded and analyzed preoperatively and at final follow-up. The correlation of kyphosis correction with the PFT and lung volume was evaluated. RESULTS: The mean local kyphosis decreased from 112.5° to 37.2°, and the mean local scoliosis decreased from 20.9° to 5.2°; C2-7 lordosis, thoracic kyphosis, and lumbar lordosis also significantly improved after surgery. The mean CT-based lung volume significantly increased from 2.9 L preoperatively to 3.6 L at the final follow-up. The indices of PFT, including forced vital capacity (FVC), percent predicted FVC, total lung capacity, and forced expiratory volume in 1 second, were also significantly improved, and 60 patients with pulmonary dysfunction recovered to normal at the final follow-up. The correlation analysis revealed that the correction of local kyphosis was closely correlated with the improvement in PFT and the increase in lung volume. CONCLUSIONS: PVCR cannot only effectively realign the spine in patients with severe thoracic spinal PTK deformity but also significantly improve pulmonary function. Adequate local kyphosis correction should be highly valued, as it is a key factor in increasing lung volume.

Online sex-seeking behaviors among men who have sex with men: implications for investigation and intervention.

To investigate factors associated with online sex-seeking behaviors among men who have sex with men (MSM) in Beijing, China. MSM participants were recruited from two cohort studies with multiple enrollment methods from November 2006 to February 2007 and from March to June 2008, respectively. Data collected included demographics and sexual behaviors. Of the 901 participants, 68.1% were single; 69.3% were non-Beijing residents; 94.4% considered themselves to be homosexual; 65.2% received college or higher levels of education; the median age was 26 years; 73.0% sought male sex partners via the Internet in the past 3 months; 66.2% had ≥2 sex partners. Younger age, higher levels of education and having had ≥2 male sex partners in the past 3 months were independently associated with seeking sex partners on the Internet. These findings indicate that Internet-based intervention programs could encourage younger high-risk MSM to use condoms and reduce their numbers of sexual partners.