Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients (version 2022) / 中华创伤杂志

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

Efficacy and safety of CD19 chimeric antigen receptor T cells for the treatment of 22 patients with B-cell lymphoma / 中华血液学杂志

Objective: To investigate the efficacy and safety of CD19 chimeric antigen receptor T (CAR-T) lymphocytes for the treatment of B cell lymphoma. Methods: A total of 22 patients with B-cell lymphoma from February 1, 2017 to July 1, 2018 were reviewed to evaluate the efficacy and adverse reactions of CD19 CAR-T. Results: Of 22 patients with B-cell lymphoma received CD19 CAR-T cells, the median dose of CAR-T cells was 7.2 (2.0-12.0) ×106/kg. Nine of 12 cases of relapse refractory patients were overall response. Complete remission (CR) occurred in 2 of 12 patients, partial remission (PR) in 7 of 12 patients. The overall response in minor residual disease positive (MRD) group was 8 of 10 patients. CD19 CAR-T cells proliferated in vivo and were detectable in the blood of patients. The peak timepoints of CAR-T cells proliferated in the relapsed refractory and MRD positive groups were 12 (5-19) and 4.5 (1-12) days after treatment respectively, and among peripheral blood cells, CAR-T cells accounted for 10.10% (3.55%-24.74%) and 4.02% (2.23%-28.60%) of T lymphocytes respectively. The MRD positive patients achieved sustained remissions during a median follow-up of 8 months (rang 3-18 months) . None of all the patients relapsed during a median follow-up time of 10 months (3-18 months) . However, 7 PR responders of the relapsed refractory patients maintained a good condition for 1.5-6.0 months. One patient bridged to hematopoietic stem cell transplantation, another one sustained remission for 12 months. Cytokine-release syndrome (CRS) occurred in 14 patients with grade 1-2 CRS in MRD positive group and grade 3 CRS in relapsed refractory group. Conclusions: CAR-T cell therapy not only played a role in the rescue treatment of relapsed and refractory patients, but also produced a surprising effect in the consolidation and maintenance of B-cell lymphoma. CD19 CAR-T cells might be more effective in the treatment of MRD positive B-cell lymphoma patients than in the refractory or relapsed cases. High response rate was observed with fewer adverse reactions.

Efficacy and safety of CD19 chimeric antigen receptor T cells for the treatment of 22 patients with B-cell lymphoma / 中华血液学杂志

Objective@#To investigate the efficacy and safety of CD19 chimeric antigen receptor T (CAR-T) lymphocytes for the treatment of B cell lymphoma.@*Methods@#A total of 22 patients with B-cell lymphoma from February 1, 2017 to July 1, 2018 were reviewed to evaluate the efficacy and adverse reactions of CD19 CAR-T.@*Results@#Of 22 patients with B-cell lymphoma received CD19 CAR-T cells, the median dose of CAR-T cells was 7.2 (2.0-12.0) ×106/kg. Nine of 12 cases of relapse refractory patients were overall response. Complete remission (CR) occurred in 2 of 12 patients, partial remission (PR) in 7 of 12 patients. The overall response in minor residual disease positive (MRD) group was 8 of 10 patients. CD19 CAR-T cells proliferated in vivo and were detectable in the blood of patients. The peak timepoints of CAR-T cells proliferated in the relapsed refractory and MRD positive groups were 12 (5-19) and 4.5 (1-12) days after treatment respectively, and among peripheral blood cells, CAR-T cells accounted for 10.10% (3.55%-24.74%) and 4.02% (2.23%-28.60%) of T lymphocytes respectively. The MRD positive patients achieved sustained remissions during a median follow-up of 8 months (rang 3-18 months) . None of all the patients relapsed during a median follow-up time of 10 months (3-18 months) . However, 7 PR responders of the relapsed refractory patients maintained a good condition for 1.5-6.0 months. One patient bridged to hematopoietic stem cell transplantation, another one sustained remission for 12 months. Cytokine-release syndrome (CRS) occurred in 14 patients with grade 1-2 CRS in MRD positive group and grade 3 CRS in relapsed refractory group.@*Conclusions@#CAR-T cell therapy not only played a role in the rescue treatment of relapsed and refractory patients, but also produced a surprising effect in the consolidation and maintenance of B-cell lymphoma. CD19 CAR-T cells might be more effective in the treatment of MRD positive B-cell lymphoma patients than in the refractory or relapsed cases. High response rate was observed with fewer adverse reactions.

Finite element analysis of vertebral column resection versus vertebral column decancellation in treatment of ankylosing spondylitis kyphosis / 中国组织工程研究

BACKGROUND: Sagittal imbalance makes significant effect on spinal biomechanics, and choosing osteotomy for ankylosing spondylitis depends on its biomechanics characteristics. OBJECTIVE: To establish a three-dimensional (3D) finite element model of kyphosis in ankylosing spondylitis treated by osteotomy on software, and to analyze its biomechanical properties, thus providing theoretical basis for clinical practice. METHODS: A 3D finite element model of kyphosis in ankylosing spondylitis was established based on CT data, and the predetermined angle of the osteotomy at L2was measured. Afterwards, vertebral column decancellation and vertebral column resection were stimulated, and then the biomechanical parameters were analyzed. RESULTS AND CONCLUSION: (1) The 3D finite element models of kyphosis in ankylosing spondylitis treated by vertebral column decancellation or vertebral column resection at L2were established successfully. (2) Finite element analysis on Ansys workbench 15.0 showed that the vertebral column decancellation (948 874, 1 564 477 nodes) and vertebral column resection (931 969, 1 548 812 nodes) were meshed and analyzed by 10-node tetrahedron solid element. (3) After loaded, the stress values of the vertebral column decancellation were higher than those of vertebral column resection; the equivalent stress on the screw was 40.946, 67.26, 493.64, 304.05, 75.359, and 146.31 MPa; the equivalent stress on the titanium rob was 391.01 MPa. (4) These results suggest that both two methods can reconstruct the sagittal balance, but vertebral column decancellation exhibits significantly higher stress values. Indeed, the incidence of internal fixation failure and complications in vertebral column decancellation is higher than that in vertebral column resection at the same segment and angle.

Finite element analysis of vertebral column decancellation for treatment of ankylosing spondylitis kyphosis / 中国组织工程研究

BACKGROUND: Kyphosis in ankylosing spondylitis is a kind of spinal sagittal imbalance; due to center of gravity displaced and complicated biomechanical properties of the spine, the spinal biomechanics after kyphosis correction is little reported. OBJECTIVE: To establish a three-dimensional finite element model of the spine after osteotomy for kyphosis. METHODS: A three-dimensional finite element model of kyphosis in ankylosing spondylitis was established, simulating three kinds of osteotomy orthopedic programs (osteotomy angle in 20°, 30° and 40°), and the orthopedic effect and biomechanics were analyzed.RESULTS AND CONCLUSION: (1) The three-dimensional finite element model of finite element model of kyphosis in ankylosing spondylitis was established successfully, and simulated three kinds of osteotomy orthopedic programs at the angles of 20°, 30°, and 40°. (2) The best osteotomy angle was 30°, the stress distribution was less, and the stress on the T12, L1, L2, L4, L5, S1and rod was 7.346 1, 11.952, 72.783, 81.368, 28.144, 41.114, and 109.69 MPa, respectively. (3) Under 30°osteotomy angle, the postoperative Cobb angle is 1.4°, which not only obtains better orthopedic effect, but also reduces the incidence of complications caused by stress concentration.

Virological characterization of influenza A(H3N2) virus in Mainland China during 2011-2012 / 病毒学报

To study the prevalence and variation of influenza A(H3N2) viruses, the antigenic and genetic characteristics of influenza A(H3N2) viruses circulating in Mainland China during April 2011 to March 2012 were analyzed. The results showed that influenza A(H3N2) viruses increased gradually since 2012 and became the dominant strain since March. The viruses were antigenically closely related to the vaccine strain A/PER/16/09 (87.2%) and the representative virus A/FJ/196/09 (76.0%) in Mainland China. The genetic characteristics analysis results showed that recently isolated viruses belonged to the Vic/208 clade, and most of the low reaction strains also fell into the same clade. Crystal structure analysis of HA protein found that, compared with the vaccine strain A/PER/16/09, the recently isolated viruses had amino acid substitutions in the antigenic site A, B and C areas, in addition to gaining potential glycosylation sites at the amino acid position of 45 of HA and 367 of NA. Although the majority of circulating influenza A (H3N2) viruses in 2011-2012 season in Mainland China were antigeniclly matched by current influenza vaccine strain and the selected representative viruses, low reaction strains have increased since 2012, therefore it is necessary to strengthen the surveillance on the variation of influenza virus and to provide solid information for the vaccine strain selection.

Development of a real-time reverse transcriptase PCR assay for detection of E119V amino acid change in neuraminidase of influenza A (H3N2) using the TaqMan-MGB probe / 中华预防医学杂志

<p><b>OBJECTIVE</b>To develop a rapid duplex Real-time reverse transcription PCR (rRT-PCR) method to detect E119V mutation on neuraminidase (NA) of influenza A(H3N2) subtype with drug resistance to oseltamivir.</p><p><b>METHODS</b>Twenty-six NA genes of influenza A(H3N2) virus between 2000 and 2012 in GenBank database were selected as the target genes, and specific TaqMan-MGB probe was designed to target the E119V amino acid change in neuraminidase protein. rRT-PCR was then performed and evaluated for the sensitivity, specificity and reproducibility using virus with E119V mutation and clinical samples.</p><p><b>RESULTS</b>This study described the validation of a highly sensitive and specific duplex rRT-PCR for detection of substitutions leading to the E119V amino acid change in NA protein of influenza A(H3N2). Fluorescence signals could be detected even when diluted a A (H3N2) virus (HA = 8) into 10(-5) and linear correlation between the logarithm of the viral titer with the Ct values was observed. In addition, the assay was highly specific in that there was no cross-react with other respiratory viruses, nor did two TaqMan-MGB probes. E119V substitution in quasispecies with both sensitive and resistant viruses could be detected as well. The limit of detection was 5% for quasispecies with high concentrations and 50% for quasispecies with low concentrations. The average coefficient of variation (CV) for within-run assays was 2.32% and 0.57% for H3N2-119E and H3N2-119V primer/probe sets separately, 1.77% and 0.97% for average CV of between-run assays, which exhibited good repeatability. Sequence analysis of twenty NA genes verified glutamic acid (E) at amino acid site 119, which was in consistent with the results from our rRT-PCR method.</p><p><b>CONCLUSION</b>The assay developed in this study is highly sensitive and specific, and easy to operate; thereby it could be used for identification of A(H3N2) virus with E119V amino acid change in NA protein.</p>

Virological characterization of influenza B virus in mainland China during 2011-2012 / 病毒学报

In order to understand the prevalence and variation of influenza B viruses, the antigenic and genetic characteristics of influenza B viruses circulating in Mainland China during April, 2011 to March, 2012 were analyzed. The results showed the B Victoria lineage viruses were much more prevalent than B Yamagata lineage during this period, phylogenetic analysis showed vast majority of Victoria lineage viruses belong to genetic group 1, intra-clade reassortant between HA1 and NA gene was identified in a minor proportion of the viruses. 72.8% of the B/Victoria-lineage viruses were antigenically closely related to the vaccine strain B/Brisbane/60/2008. B Yamagata component was not included in the trivalent influenza vaccine in China during the study period, however vast majority of B Yamagata lineage viruses were antigenically and genetically closely related to the representative virus B/Hubei-Wujiagang/158/2009(97.8%) and B/Sichuan-Anyue/139/2011(85.2%) in China, reassortant between HA1 and NA was not identified in B Yamagata lineage viruses. Overall, the predominant circulating influenza B viruses in 2011-2012 season in China were matched by current influenza vaccine and the selected representative viruses were proved to represent the antigenic and genetic characteristics of the circulating viruses.

Emerged Pdm09 influenza virus increased purifying selection of seasonal H1N1 influenza virus / 病毒学报

Pdm09 virus outbreak occurred in Mainland China in May 2009, a few months later, the prevalence of seasonal H1N1(sH1N1) influenza virus that already circulated in human for tens of years began to decline and disappeared afterwards. To identify the reason for the rapid decline of sH1N1 in mainland China, we sequenced the HA1 of sH1N1 during 2006-2011, and then analyzed the selective pressure in different phases. Our results showed before Pdm09 outbreak, the omega value was 0. 36 while after Pdm09 outbreak the omega value was 0. 28 and significant difference (t test, P<0. 05) was identified. We concluded that sH1N1 obtained stronger purifying selection after Pdm09 outbreak in China. This might one of the major reasons causing the disappearance of sH1N1 in human.

Development of multi-pathogen detection techniques for respiratory viruses / 病毒学报

Viral respiratory tract infection is among the leading causes of mortality and morbidity worldwide. Rapid screening methods for multiple detection of a wider range of pathogens become very important for diagnosis of respiratory infection. This article describes conventional detection technologies and several emerging multiplex assays that have potential applications in the diagnosis and monitoring of respiratory viral infections. These techniques include new rapid culture system, multiplex reverse transcription-PCR, real-time reverse transcription PCR, solid and suspension microarrays, mass spectrometry as well as metagenomics methods. The development and application of these techniques will not only improve the ability of rapid detection and control of viral respiratory infection, but play pivotal roles in the rapid characterization of new viral pathogens.

Efficacy and safety of two different low-dose rituximab regimens for Chinese adult patients with immune thrombocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy of two different regimens of low doses rituximab for the treatment of adult patients with immune thrombocytopenia (ITP).</p><p><b>METHODS</b>Fifty-one patients were enrolled in this study and was non-randomly assigned to receive 100 mg rituximab weekly for 4 weeks (group A, 31 cases) or a single dose of 375 mg/m2 rituximab (group B, 20 cases).</p><p><b>RESULTS</b>For group A: Overall and complete response (OR and CR) rates were 58% and 29% , respectively. In responders, the median time to response was 42 (10 -101) days, with a median follow-up time of 15 (10 - 16) months, 3 of 18 responders (17%) relapsed. For group B: OR and CR rates were 50% and 35% , respectively. In responders, the median time to response was 35 (18 - 108) days, with a median follow-up time of 13 (6 -17) months, 1 of 9 responders (11%) relapsed. No significant difference in the OR, CR, the relapse rate and relapse free survival was observed in patients between the two groups.</p><p><b>CONCLUSION</b>The low dose rituximab regimen (100 mg weekly for 4 weeks or a single close of 375 mg/m2) may be a useful alternative therapy in patients with ITP.</p>

Combined deficiency of factors V and VIII caused by a novel compound heterozygous mutation of gene Lman1 / 中国实验血液学杂志

Combined deficiency of factor V and VIII (F5F8D) is a rare, autosomal recessive disorder caused by mutations of either lman1 or mcfd2. To identify mutations of these two genes in a Chinese F5F8D family, the samples of peripheral blood were collected from the proband and her parents. Coagulation tests were carried out, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg) and coagulate activity of FV, FVIII (FV:C, FVIII:C). The genomic DNA was extracted, then all the exons and intron/exon boundaries of these two genes were amplified by polymerase chain reaction (PCR). The products were finally analyzed by direct sequencing. The results showed that the proband's APTT, PT, TT, Fg, FV:C and FVIII:C were 82.2 sec, 19.6 sec, 18.6 sec, 2.9 g/L, 7.1% and 18.7% respectively, while those parameters of the parents were all within the normal range. Two pathogenic mutations were identified in lman1 gene of the proband: one was the heterozygous c.912_913insA in exon 8 resulting in a frameshift of p.Glu305fsX20; the other was the heterozygous c.1366C > T in exon 11 resulting in p.Arg456X. The proband's father and mother were heterozygous for c.1366C > T and c.912_913insA respectively. It is concluded that F5F8D of the proband is caused by a novel compound heterozygous mutation of the lman1 gene, which has never been reported.

Efficacy of lower dose rituximab therapy for idiopathic thrombocytopenic purpura / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness, safety as well as the immunological change (peripheral T cell subpopulation) in patients with idiopathic thrombocytopenic purpura (ITP) treated with lower dose rituximab.</p><p><b>METHODS</b>Twenty-six patients with refractory ITP which were unresponsive to or relapse after steriod and IVIG treatment were treated with rituximab (100 mg per week for four weeks) and intravenous immunoglobulin (IVIG) treatment. Whole blood cell count, serum concentrations of IgG, IgM and IgA, platelet associated (PA)-IgG, PAIgA and PAIgM, peripheral T cell subpopulations, and B cells of CD19(+)/CD20(+) were detected before and after rituximab therapy.</p><p><b>RESULTS</b>Complete response (CR) was achieved in 6 patients (23.1%), response (R) in 10 (38.5%), and non-response (NR) in 10 (38.5%). One patient relapsed after R. The median follow-up time was 5.5 (0.8 - 8) months. The median response and CR time were 27 (1 - 104) and 41 (4 - 109) days, respectively. After the therapy, the serum concentrations of IgG, IgA, IgM, T cells of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(-)CD56(+), CD4(+)CD25(+) and CD4(+)CD25(+)FOXP3(+) were not changed, the number of CD4(+)CD25(+)FOXP3(-) T cells decreased (P < 0.05) and CD19(+)CD20(+) B cells significantly decreased (P < 0.01). PAIgG was lower after treatment compared with that before treatment (P < 0.05). There were no severe adverse effects during rituximab therapy.</p><p><b>CONCLUSION</b>Lower dose rituximab may be an effective and safe modality for patients with ITP.</p>

Genetic analysis of an inherited afibrinogenemia family caused by a novel frameshift mutation in FGA / 中国实验血液学杂志

Inherited afibrinogenemia is a rare autosomal recessive bleeding disease characterized by complete absence of fibrinogen in blood. To identify the genotype in a Chinese family with inherited afibrinogenemia, the samples of peripheral blood were collected from 6 members of 3 generations. The activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (Fg, clauss) were tested. Fg was also analyzed by using immunoturbidimetry method. DNAs of six members were extracted by using a DNA extract kit. All the exons and exon-intron boundaries of the three fibrinogen genes were amplified by using PCR and analyzed by direct sequencing. The results showed that the parents of proband were 3 degree consanguinity. A homozygous c.934_935insA in FGA was found in proband which results in the change of protein p.Ser312fsX42. The parents, grandmother, maternal grandmother and father's sister were all detected with heterozygous mutation which was same as that in proband. In conclusion homozygous c.934_935insA in FGA is a cause of inherited afibrinogenemia and a novel mutation being reported.