[Clinical application of a classification based on crucial curvature of coronal imbalance in degenerative lumbar scoliosis].

Objective: To present efficacy of clinical application of a classification based on crucial curvature of coronal imbalance in degenerative lumbar scoliosis (DLS). Methods: A case series study. Clinical data of 61 cases (8 males, 53 females) who underwent posterior correction surgery for DLS from January 2019 to January 2021 were retrospectively analyzed. The mean age was (71.7±6.2) years (ranged 60-82 years). According to the direction of C7 plumb line (C7PL) deviated from central sacral vertical line (CSVL) and orientation of L4 coronal tilt, the author determined which one was the crucial curve. If C7PL deviated from CSVL in the same direction as concave side of the thoracolumbar curve and L4 coronally tilts opposite direction of C7PL deviates from CSVL, then the crucial curve was thoracolumbar curve (type 1). On the contrary, if C7PL deviated from CSVL in the same direction as concave side of the lumbosacral curve and L4 coronally tilts consist with direction of C7PL deviates from CSVL, then the crucial curve was lumbosacral curve (type 2). According to absolute value of coronal balance distance (|CBD|), each type of patients was divided into two groups, respectively, namely coronal balance (CB) (|CBD|≤3 cm) and coronal imbalance (CIB) (|CBD|>3 cm). Changes of Cobb angles of thoracolumbar curve and lumbosacral curve and CBD were recorded and analyzed. Results: The rate of preoperative CIB was 55.7% (34/61) in all the patients. Of the patients, 23 cases were classified as type 1 and 38 cases as type 2. The rate of preoperative CIB was 34.8% (8/23) in type 1 patients and 68.4% (26/38) in type 2. The rate of postoperative CIB was 27.9% (17/61) in all the patients, with 13.0% (3/23) in type 1 and 36.8% (14/38) in type 2. The |CBD| of CB group in type 1 patients decreased from (2.6±1.4) cm before the operation to (1.5±1.0) cm after (P=0.015); and the correction rate of thoracolumbar curve (68.8%±18.4%) was significantly higher than that of lumbosacral curve (34.5%±23.9%) (P=0.005). The |CBD| of CB group in type 2 patients decreased from (2.6±3.0) cm before the operation to (1.6±1.2) cm after (P=0.027); the correction rate of lumbosacral curve (71.3%±18.6%) was higher than that of thoracolumbar curve (57.3%±21.1%), but the difference was not statistically significant (P=0.546). There was no significant difference in |CBD| of CIB group in type 2 patients before and after the operation (P=0.222); the correction rate of lumbosacral curve (38.3%±14.8%) was significantly lower than that of thoracolumbar curve (53.6%±16.0%) (P=0.001). There was a correlation between the change of CBD (3.8±1.5) cm and the difference in correction rate between thoracolumbar and lumbosacral curve (32.3%±19.6%) in CB group in type 1 patients after surgery (r=0.904, P<0.001). There was a correlation between the change of CBD (1.9±2.2) cm and the difference in correction rate between lumbosacral and thoracolumbar curve (14.0%±26.2%) in CB group in type 2 patients after surgery (r=0.960, P<0.001). Conclusion: Clinical application of a classification based on crucial curvature of coronal imbalance in DLS is satisfactory, and its combination with matching correction can effectively prevent the occurrence of coronal imbalance after spinal correction surgery.

[A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma].

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

[One-stage posterior correction and second-stage anterior debridement and fusion in treating children with thoracic tuberculosis complicated with kyphoscoliosis].

Objective: To investigate the clinical outcomes of one-stage posterior correction surgery and second-stage anterior debridement and fusion in treating children with thoracic tuberculosis complicated with kyphoscoliosis. Methods: From January 2008 to December 2014, a total of 17 children with thoracic vertebral tuberculosis complicated with kyphoscoliosis who underwent a one-stage posterior correction and second-stage anterior debridement and complementary fusion were included. There were 8 males and 9 females with an average age of (8±4) years (5-14 years). All patients underwent posterior correction and anterior debridement and bone graft fusion surgery. The neurological function was determined by Frankel grade. The operation time, estimated blood loss (EBL), levels fused and numbers of screws were recorded. The following radiographic parameters were measured: Cobb angle of the coronal curve, regional kyphosis and sagittal vertical axis (SVA). The incidence of intraoperative and postoperative complications was recorded. The data before and after the operation were compared with paired sample t test. Results: The tuberculosis lesions located in the thoracic vertebrae, and the abscess involved 2 to 4 vertebral segments. The average operation time was (4.1±0.8) h, the EBL was (526±275) ml, the levels fused were 7.6±2.3, and 173 pedicle screws were placed. The preoperative coronal curve averaged 12.6°±6.2°, and it was corrected to 4.2°±1.9° postoperatively (t=4.628, P<0.01), the regional kyphosis was 67.2°±19.4°, and it was corrected to 15.7°±8.2° postoperatively (t=8.192, P<0.01). The SVA improved from (8.1±5.0) mm to (3.0±1.7) mm postoperatively. The mean duration of follow-up for all the patients were (38±11) months. At final follow-up, SVA was reduced to (2.4±2.0) mm and the other parameter kept stable. Thirteen patients had more than one grade improvement of Frankel grade. The VAS score for all patients improved from 4.7±2.8 to 2.2±0.5 postoperatively (t=3.973, P=0.01), and improved to 0.5±0.5 at final follow-up (t=-7.880, P<0.01). No recurrence of primary spinal tuberculosis was seen at final follow-up of all patients. Conclusions: One-stage posterior correction and second-stage anterior complementary debridement and fusion is an effective procedure for children with thoracic tuberculosis complicated with kyphoscoliosis. Significant postoperative deformity correction could be achieved with satisfactory improvement of neurological function. Solid fusion and satisfactory correction maintenance were observed at mid-to long-term follow-up.

[Correlation between syrinx resolution after posterior fossa decompression and cervical sagittal profile change in adolescents with Chiari malformation and syringomyelia].

Objective: To evaluate the long term change of the cervical sagittal profile in adolescent Chiari malformation type Ⅰ (CMI)/syringomyelia undergoing posterior fossa decompression (PFD) and to further evaluate the correlation between the syrinx resolution and cervical sagittal profile. Methods: A retrospective radiographic study was performed in 32 adolescents undergoing PFD for CMI/syringomyelia from October 2011 to August 2015 with a minimum 2-year follow-up. There were 23 males and 9 females, with a mean age of (13.7±2.8) years (range, 10-16 years). The following parameters including upper cervical angle (C(0)-C(2)), lower cervical angle (C(2)-C(7)), sagittal balance (C(2)-C(7)SVA), cervical curvature index (CCI), syrinx size and length were compared preoperatively and at the last follow-up. The correlation of syrinx resolution and cervical sagittal parameters were further analyzed with Pearson correlation analysis. Results: All patients received a followed-up for 2.0-6.5 years [mean (3.9±1.1) years]. The lower cervical angle and CCI were-29.8°±11.4° and 29.1%±7.1% at the last follow-up, respectively, which were significantly higher than those before surgery (-15.2°±8.8°, 13.4%±4.2%)(t=2.917, 2.902, both P<0.05). The syrinx size and length were also obviously decreased at the last follow-up. No significant difference was found in the upper cervical angle and C(2)-C(7)SVA before operation and at the last follow-up (t=0.302, 0.871, both P>0.05). There were significantly positive correlations between the differences of syrinx width and the lower cervical angle, and the CCI before and after surgery (r=0.611, 0.652, both P<0.05). Significantly positive correlations were also observed between the differences of syrinx length and the lower cervical angle, and the CCI before and after surgery (r=0.504, 0.514, both P<0.05). Conclusions: The cervical lordosis can be restored after PFD in adolescents with CMI/syringomyelia. The resolution of syrinx may play an important role in restoring the cervical sagittal alignment.

[Clinical features of adult patients with chronic active Epstein-Barr virus infection].

Objective: To investigate the clinical features of adult-onset chronic active Epstein-Barr virus infection (CAEBV). Methods: A total of 21 adult patients with CAEBV who were admitted to the department of General Internal Medicine at Peking Union Medical College Hospital from January 2006 to January 2016 were retrospectively analyzed. Demographic data, disease duration, clinical manifestations, laboratory findings, treatments and prognosis were reviewed. Results: Eighteen females and 3 males were enrolled with a mean age of 39 years. The most common clinical manifestations included fever in 20 patients, splenomegaly in 20 patients, lymphadenopathy in 18 patients, and hepatomegaly in 10 patients, followed by laryngopharyngeal disorders in 6 patients, pleural effusion and peritoneal effusion each in 5 patients, rash in 4 patients, interstitial lung disease in 3 patients, gastrointestinal hemorrhage in 2 patients, and peripheral neuropathy and pulmonary hypertension each in 1 patient. Six patients were complicated with hemophagocytic lymphohis-tioncytosis(HLH) that developed 5-17 (mean: 9) months following CAEBV onset, all of whom experienced hyperpyrexia, pancytopenia, lymphadenopathy, splenomegaly, and liver dysfunction, 3 with hepatomegaly. Nineteen of the 21 patients had received steroid therapy including 10 combined with immunosuppressive agents, 11 with antiviral therapy, and 8 with intravenous immunoglobulin. Thirteen patients died, including 10 of multiple organ failure, (including 6 of HLH) 2 of severe pulmonary infection, and 1 of lymphoma. Six patients remained on follow-up, yet 2 were missing. Conclusions: CAEBV is expected with severe condition and poor prognosis, which is likely to be complicated with HLH. Clinical physicians should pay attention to adult patients with fever, hepatosplenomegaly and lymphadenopathy, which suggests possible CAEBV.

[Genetic analysis of posterior cranial fossa morphology in families of Chiari malformation type â ].

Objective: To explore genetic characteristic of posterior cranial fossa morphology in families of Chiari malformation type Ⅰ (CMI). Methods: From April 2010 to May 2016, a total of 47 cases of CMI families (CMI group) and their 94 parents (CMI-P group)collected were retrospectively reviewed in Department of Spinal Surgery, Drum Tower Hospital, School of Medicine, Nanjing University.Another cohort of 50 asymptomatic adults was enrolled to serve as the control group.Patients with skull fracture or other diseases which can lead to secondary CMI were excluded.On mid-sagittal T2-weighted magnetic resonance (MR) imaging, four measurements were evaluated and compared between these three groups, including the length of cerebellar tonsillar descent, the area of posterior cranial fossa(PCF area), the area of the brain tissue in posterior cranial fossa (PCF tissue area), and the PCF crowdedness indexes (PCF tissue area/ PCF area×100%). Results: Totally 47 CMI patients (21 males and 26 females; mean age, 16.4 years), 94 parents (47 males and 47 females; mean age, 39.2 years) and 50 controls (23 males and 27 females; mean age, 22.3 years) were recruited in this study.Significant differences in all four indexes were found between CMI group and the control group.The length of cerebellar tonsillar descent were much bigger in CMI-P group than in the control group (1.5±2.2 mm vs -0.9±1.1 mm), with 7 cases reach the diagnostic criteria of Chiari malformation(≥5 mm) and one with syingomyelia.Compared to the control group, CMI-P group had smaller PCF area, and its PCF crowdedness indexes averaged 90.0% as between the control group (85.3%) and the CMI group (93.6%). Conclusions: In CMI families, parents have similar posterior cranial fossa abnormalities with their CMI children, presenting obviously narrow and crowded.Their PCF crowdedness indexes are between normal subjects and CMI patients, and their cerebellar tonsils are lower, even some parents are also CMI patients, suggesting genetic mechanisms involved in the development of CMI.

[Effect of SET deficiency on the trichloroethylene-induced alteration of cell proliferation and cell apoptosis and DNA methylation in human hepatic L-02 cells].

OBJECTIVE: To compare the trichloroethylene (TCE) -induced alteration in cell proliferation, cell apoptosis, histone deacetylase activity and expression levels in human hepatic L-02 cells (L-02 cells) and SET deficient cells, and reveal the TCE-induced effect in histone modification and the role of SET on epigenetic pathway. METHODS: The L-02 cells and preestablished SET deficient cells were treated with different TCE concentrations. For the changes of cell proliferation level and apoptosis rate, The L-02 cells and SET deficiency cells without TCE treatment were served as the control group, the TCE treatment was in the concentration of 2.0 and 8.0 mmol/L for 24 h. For histone deacetylase activity and expression levels, the TCE treatment was in the concentration of 0.25, 0.50, 1.0, 2.0, 4.0, and 8.0 mmol/L for 24 h. RESULTS: After treatment with TCE for 24 h, the cell proliferation level was significantly decreased and the apoptotic rate was significantly increased in both cell lines. When concentration of TCE were reached to 8.0 mmol/L, the difference of cell proliferation level and apoptotic rate between two groups was statistically significant (t=-4.362 for proliferation level and t=23.950 for apoptotic rate, both P<0.05). After treatment with TCE for 24 h in various concentration (0, 0.25, 0.50, 1.00, 2.00, 4.00 and 8.00 mmol/L) , the activity of histone deacetylases was significantly increased in both cell lines. When the TCE concentration were high than 0.50 mmol/L, compared with control group of L-02 cells, the enzymes activity were significantly increased (F=403.26, P<0.001). When TCE concentration was reached 1.00 mmol/L, the enzyme activity is highest. Compared with control group of SET deficiency cells, the enzyme activity was significantly increased when TCE concentration was reached 1.00 mmol/L (F=44.01, P<0.001). When concentration of TCE reached 0.50 mmol/L, the difference of enzyme activity between two groups was statistically significant. For the protein expression, compared with control group of L-02 cells, TCE exposure can induced a significant increased expression level of HDAC2 in TCE-treated L-02 cells (F values were 79.99, P<0.001). But the alteration in SET deficiency cells was not significant. CONCLUSION: TCE exposure can induce a significant alteration on cell proliferation, apoptotic rate and, the activity and expression on histone deacetylases. SET deficiency can attenuate the TCE-induced alteration in histone modification in L-02 cells. Our results indicated that SET is involved in the mechanism of TCE-induced cytotoxicity and epigenetic regulation in L-02 cells.

ATM-mediated KDM2A phosphorylation is required for the DNA damage repair.

The ataxia-telangiectasia mutated (ATM) protein is a key signaling molecule that modulates the DNA damage response. However, the exact mechanism by which ATM regulates DNA damage repair has not yet been elucidated. Here, we report that ATM regulates the DNA damage response by phosphorylating lysine-specific demethylase 2A (KDM2A), a histone demethylase that acts at sites of H3K36 dimethylation. ATM interacts with KDM2A, and their interaction significantly increases in response to DNA double-stranded, but not single-stranded, breaks. ATM specifically phosphorylates KDM2A at threonine 632 (T632) following DNA damage, as demonstrated by a mutagenesis assay and mass spectrometric analysis. Although KDM2A phosphorylation does not alter its own demethylase activity, T632 phosphorylation of KDM2A largely abrogates its chromatin-binding capacity, and H3K36 dimethylation near DNA damage sites is significantly increased. Consequently, enriched H3K36 dimethylation serves as a platform to recruit the MRE11 complex to DNA damage sites by directly interacting with the BRCT2 domain of NBS1, which results in efficient DNA damage repair and enhanced cell survival. Collectively, our study reveals a novel mechanism for ATM in connecting histone modifications with the DNA damage response.

Atomistic origin of lattice strain on stiffness of nanoparticles.

Lattice strain plays a crucial role on the properties of nanoparticles. Although the effect of lattice strain on nanoparticles has been widely studied in experimental measurements and calculations, its physical mechanism from the perfective of bond identities is still poorly understood. Herein we put forward an analytical solution of the size effect and external stimuli such as pressure and temperature dependence of lattice strain and bulk modulus of a nanoparticle from the perspective of atomistic origin. A shell-core configuration has been considered for the nanoparticle structure. It has been found that the lattice strain as well as quantum trapping and energy storage exerted by the compressive stress and thermal stress would be responsible for the mechanical behavior of nanoparticles. The theoretical predictions were well consistent with the experimental data and ab initio calculations, implying that the model could be expected to be a general approach to understand mechanical behavior in nanomaterials.

A novel HLA-B*54 allele, B*5417, identified in a Northern Chinese Han individual.

The full-length sequence of HLA-B*5417 differs from HLA-B*5401 only by single-nucleotide change at nt 709 where A-->C resulting in a amino acid substitution from Ile (ATC) to Val (GTC) at codon 213 in exon 4.

A novel HLA-Cw*0124 allele found in a Chinese Han patient from Southern China.

The sequence of novel HLA-Cw*0124 allele differs from Cw*0103 by one nucleotide change at nt 806 from C to A, resulting in an amino acid change at codon 245 from Ala to Glu.

Full length sequence of the HLA-Cw*0361 allele identified in a Chinese Han potential bone marrow donor from Northern China.

HLA-Cw*0361 allele differs from Cw*030301 by one nucleotide substitution at nt 566 from T to A, resulting in an amino acid change at codon 165 from Val to Glu.

Genomic sequence of HLA-Cw*1222 allele identified in a Chinese Han patient from Southern China.

The genomic sequence of HLA-Cw*1222 allele is identical to Cw*120202 except for a single-nucleotide substitution at codon 87 (CAG-->CGG) resulting in an amino acid change from Gln to Arg.

Full length sequence of a novel HLA-B*3818 allele differs from HLA-B*380201 allele in exon 4 and intron 5.

The full length sequence of HLA-B*3818 differs from HLA-B*380201 at nt 660 in exon 4 (C-->A) and genomic position 2133 in intron 5 (A-->C).

Complete genomic sequence of a novel HLA-B*1325 allele observed in a Chinese Han individual.

The complete genomic sequence of HLA-B*1325 allele shows one nucleotide difference from B*130101 at nt 302 where A --> G resulting in an amino acid substitution from Asn(AAC) to Ser(AGC) at codon 77 in exon 2.