Objective:To explore the expression of family with sequence similarity 83 member A (FAM83A) in colorectal cancer, and the effect of FAM83A knockdown on the proliferation of colorectal cancer cells and the related mechanism.Methods:The expression of FAM83A in the tissues of 102 patients with colorectal cancer and its adjacent tissues was detected by immunohistochemistry. HCT116 cells were divided into experimental group and control group. The experimental group cells were transfected with FAM83A-siRNA plasmid, and the control group cells were transfected with MOCK-siRNA plasmid. The mRNA content of FAM83A in each group was detected by fluorescence quantitative PCR. The expressions of FAM83A, P13K, p-AKT and p-mTOR in each group were detected by Western blot. CCK8 assay and clonogenesis assay were used to detect cell proliferation.Results:The positive rate of FAM83A in colorectal cancer patients was 88.23% (90 cases /102 cases), and the expression rate of FAM83A in paracancer tissues was 10.78% (11 cases /102 cases). The expression rate of Fam83a in colorectal cancer tissues was significantly higher than that in paracancer tissues, with statistical significance ( P<0.001). After siRNA transfection, the mRNA expression levels of FAM83A in HCT116 cells of the experimental group and control group were 1.23±0.20 and 0.43±0.12, respectively, and the protein expression levels of FAM83A were 1.19±0.11 and 0.23±0.08, respectively. The expression levels of P13K were 1.21±0.17 and 0.28±0.09, the expression levels of p-AKT were 1.35±0.23 and 0.57±0.18, and the expression levels of p-mTOR were 1.48±0.20 and 1.05±0.14. The expression of P13K, p-Akt and p-mTOR was down-regulated (all P<0.05). The absorbance of HCT116 cells in the experimental group and the control group was 1.09±0.22 and 2.21±0.27, respectively. The cloning rate of HCT116 cells in the experimental group and the control group was 21.6%±2.4% and 62.7%±4.1%, respectively. The proliferation ability of HCT116 cells in the experimental group decreased significantly ( P<0.05) . Conclusions:The expression of FAM83A is significantly increased in colorectal cancer tissues, which may be related to the malignant degree of colorectal cancer. FAM83A affects the proliferation of colorectal cancer cells through the P13K/AKT/mTOR signaling pathway.

Objective:To explore the factors affecting changes of disc angle (ΔDA) during oblique lateral interbody fusion (OLIF) and establish a predictive model of ΔDA.Methods:This retrospective study included 119 patients with 174 segments undergoing OLIF procedures between July 2017 and August 2019 in Beijing Jishuitan Hospital. 45 males and 74 females with an average age of 62.1±9.8 years (33-86 years) were included. The lordotic cages were all 6 degrees. Radiographic parameters included preoperative and postoperative disc angle (DA), disc height (DH), ΔDA on flexion-extension views (ΔDA-FE), cage location and cage inclination. Pearson correlation coefficient and machine-learning techniques were utilized to identify factors related to ΔDA. Based on machine leaning techniques, ten-fold cross-validation for model training and validation were used to develop a predictive linear model for ΔDA.Results:The average ΔDA was 3.9°±4.8° with preoperative disc angle (preoperative DA) of 5.3°±5.0°. The average change of posterior DH (ΔPDH) was 3.1±2.1 mm with preoperative posterior DH of 6.6±1.9 mm. The average change of anterior DH was 6.1±3.2 mm. Pearson correlation analysis showed a significant negative correlation between ΔDA and preoperative DA ( r=-0.713, P<0.001), cage location ( r=-0.183, P=0.016), and ΔDA-FE ( r=-0.153, P=0.044). PDH changes were significantly negatively correlated with preoperative PDH ( r=-0.444, P<0.001) and positively correlated with cage location ( r=0.218, P=0.004). ΔDA was 10.8°±3.2° for negative preoperative DA (indicating kyphotic), 5.0°±3.7° for preoperative DA between 0° and 6°, and 1.0°±4.1° for preoperative DA>6°. A predictive model was developed using ten-fold cross-validation, resulting in the formula ΔDA=7.9°-0.8×preoperative DA ( R=0.707, MAE=2.837). Conclusion:Disc angle changes in OLIF primarily depend on the preoperative disc angle, secondly on cage location. The predicting model based on machine-learning techniques using preoperative disc angle facilitates preoperative planning for OLIF procedures.

Objective To compare the clinical outcomes between oblique lumbar interbody fusion(OLIF)and transforaminal lumbar interbody fusion(TLIF)for patients with degenerative spondylolisthesis during 2-year follow-ups.Methods Patients with symptomatic degenerative spondylolisthesis who underwent OLIF(46 cases)and TLIF(45 cases)between July 2017 and September 2020 with 2-year follow-ups were retrospectively reviewed.One level or two-level lumbar fusion were included.The primary outcomes were Visual Analogue Scale(VAS)and Oswestry Disability Index(ODI)at 2 years after surgery.The secondary outcomes included radiographic parameters,fusion rate,cage subsidence rate,and permanent nerve injury rate.Results No significantly different changes were noted in VAS-back[2(2,3)vs.2(2,2),P=0.943],VAS-leg[2(2,2)vs.2(2,2),P=0.988],and ODI[17％(10％,22％)vs.14％(10％,22％),P=0.417]between the OLIF group and the TLIF group,respectively.Greater restoration of disc height and segmental lordosis were obtained in the OLIF group[mean,(11.9±1.5)mm and 15.7°±7.2°]than in the TLIF group[mean,(9.2±2.0)mm and 12.5°±5.9°]at postoperative 2-year(P＜0.001 and P=0.029).The subsidence rate was lower in the OLIF group than in the TLIF group[19.6％(9/46)vs.40.0％(16/40),P=0.037].The fusion rates at postoperative 2-year were 93.5％(43/46)in the OLIF group and 87.5％(35/40)in the TLIF group,having no significant difference(P=0.562).The rates of permanent nerve injury were similar between the two groups[4.3％(2/46)vs.6.7％(3/45),P=0.980]at postoperative 2-year.Conclusion Short segment OLIF doesn't show better clinical outcomes and fusion rate than TLIF for degenerative spondylolisthesis,except for greater disc height restoration,greater segmental lordosis,and lower subsidence rate at postoperative 2-year.

Objective:To explore the correlation between early inflammation indicators and the severity of coronavirus disease 2019 (COVID-19).Methods:A retrospective study was conducted. Patients with COVID-19 admitted to Wenzhou Central Hospital from January 17 to February 14, 2020 were enrolled. The general information, chest CT before admission, the first laboratory parameters and chest CT within 24 hours after admission were collected. Patients were followed up for 30 days after the first onset of dyspnea or pulmonary imaging showed that the lesions progressed more than 50% within 24 to 48 hours (according to the criteria for severe cases) as the study endpoint. According to the endpoint, the patients were divided into two groups: mild type/common type group and severe/critical group, and the differences in general information and inflammation index of the two groups were compared. Logistic regression was used to analyze the inflammation index and the severity of COVID-19. Receiver operating characteristic (ROC) curve was draw to evaluate the predictive value of early inflammation indicators for severe/critical in patients with COVID-19.Results:A total of 140 patients with COVID-19 were included, 74 males and 66 females; the average age was (45±14) years old; 6 cases (4.3%) of mild type, 107 cases (76.4%) of common type, and 22 cases (15.7%) of severe type, 5 cases (3.6%) were critical. There were significantly differences in ages (years old: 43±13 vs. 57±13), the proportion of patients with one chronic disease (17.7% vs. 55.6%), C-reactive protein [CRP (mg/L): 7.3 (2.3, 21.0) vs. 40.1 (18.8, 62.6)], lymphocyte count [LYM (×10 9/L): 1.3 (1.0, 1.8) vs. 0.8 (0.7, 1.1)], the neutrophil/lymphocyte ratio [NLR: 2.1 (1.6, 3.0) vs. 3.1 (2.2, 8.8)] and multilobularinltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hyper-tension and age [MuLBSTA score: 5.0 (3.0, 5.0) vs. 5.0 (5.0, 7.0)] between mild/common group and severe/critical group (all P < 0.05). Univariate Logistic regression analysis showed that CRP, NLR, MuLBSTA score, age, and whether chronic diseases were associated with the severity of COVID-19 [odds ratio ( OR) and 95% confidence interval (95% CI) were 1.037 (1.020-1.055), 1.374 (1.123-1.680), 1.574 (1.296-1.911), 1.082 (1.042-1.125), 6.393 (2.551-16.023), respectively, all P < 0.01]. Further multivariate Logistic regression analysis showed that CRP and MuLBSTA score were risk factors for the development of COVID-19 to severe/critical cases [OR and 95% CI were 1.024 (1.002-1.048) and 1.321 (1.027-1.699) respectively, both P < 0.05]. ROC curve analysis showed that the area under the curve for CRP and MuLBSTA score to predict severe/critical cases were both 0.818, and the best cut-off points were 27.4 mg/L and 6.0 points, respectively. Conclusion:CRP and MuLBSTA score are related to the severity of COVID-19, and may have good independent predictive ability for the development of severe/critical illness.

Objective:To evaluate the effect of oblique lateral interbody fusion (OLIF) combined with posterior fixation on segmental alignment in the treatment of degenerative spondylolisthesis (DS).Methods:The clinical data of 40 patients with DS who underwent OLIF combined with posterior fixation from July 2017 to December 2019 were retrospectively analyzed. There were 7 males and 33 females, aged 45-81 years, with an average age of 65.7±9.06 years. The total number of slip segments was 43, including 37 levels at L 4, 5, 5 levels at L 3, 4, and 1 level at L 2, 3. According to the decompression methods, the patients were divided into two groups. 22 patients with 23 levels were treated with direct decompression combined with laminectomy, and 18 patients with 20 levels were treated with indirect decompression without laminectomy. All patients underwent preoperative and intraoperative imaging examination. The disc height (DH), slip ratio (SR) and segmental lordosis (SL) were measured by preoperative CT and intraoperative fluoroscopy images. One-way repeated measures ANOVA was used to compare the radiographic parameters of the segmental alignment prior to cage implantation, following cage insertion and posterior fixation. Bonferroni test was used to compare the radiographic parameters between groups. Results:In the OLIF combined with the posterior fixation, there were statistically significant differences in the radiographic parameters of segmental alignment at different stages of operation [DH ( F=147.786, P<0.001) , SR ( F=83.754, P<0.001) , SL ( F=38.296, P<0.001) ]. DH increased from 7.99±1.39 mm to 11.69±1.72 mm ( P<0.001), SR decreased from 10.67%±4.67% to 8.66%±4.50% ( P=0.001) and SL increased from 7.26°±2.73° to 7.85°±2.30° ( P=0.425). After combined posterior fixation, SR further decreased from 8.66%±4.50% to 2.07%±4.00% ( P<0.001), SL further increased from 7.85°±2.30° to 10.72°±3.08° ( P<0.001), and DH had no significant change ( P=1.000). There was no significant difference in radiographic parameters between the direct decompression group and the indirect decompression group when prior to cage implantation, following cage insertion and following posterior fixation, respectively. Conclusion:OLIF combined with posterior fixation in the treatment of DS can further reduce the slip rate of patients with lumbar degenerative spondylolisthesis and increase the lordosis angle of the surgical segment. At the same time, the direct decompression combined with laminectomy has no significant effect on the segmental alignment.

OBJECTIVE: To analyze the phenotype and genetic basis for a pedigree affected with hereditary coagulation factor XI deficiency. METHODS: Activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), FXI activity (FXI:C) and the antigen of FXI (FXI:Ag) were determined for the proband and members from his pedigree. Sanger sequencing was used to analyze all exons, exon-intronic boundaries, as well as the 5'- and 3'- untranslated regions of the F11 gene. Suspected variants were verified in her family members and confirmed by reverse sequencing. The impact of the variants on the protein function was predicted by using PolyPhen-2 and SIFT software. The protein structure and amino acid interaction were analyzed by using Swiss-PdbViewer. RESULTS: The APTT, FXI:C and FXI:Ag of the proband and her sister were significantly reduced to 73.0 s, 10.0%, 15.0% and 87.1 s, 2.0% and 11.5%, respectively. APTT of some family members was slightly prolonged, and FXI:C and FXI:Ag also decreased to various extents. DNA sequencing revealed that the proband and her sister have carried compound heterozygous variants of c.738G>A (p.Trp228stop) and c.938G>T (p.Ser295Ile) respectively in exons 7 and 9 of the F11 gene. Her father, sister and daughter were heterozygous for the c.738G>A (p.Trp228stop) variant, while her mother and nephew were heterozygous for the c.938G>T (p.Ser295Ile). Both PolyPhen-2 and SIFT predicted that the p.Ser295Ile variant is likely to be deleterious and can affect the protein function. Modeling analysis indicated that the p.Ser295Ile variant may lead to disruption of a hydrogen bond, resulting in alteration of protein structure and instability. CONCLUSION The compound heterozygous c.738G>A (p.Trp228stop) and c.938G>T (p.Ser295Ile) variants of the F11 gene probably underlie the decreased FXI level in this pedigree.
Factor XI Deficiency ; genetics ; Female ; Genetic Variation ; Heterozygote ; Humans ; Mutation ; Pedigree

Since December 2019, the corona virus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (2019-nCoV) has been reported in Wuhan, Hubei Province. Almost 70% of patients susceptible to 2019-nCoV are over age of 50 years, with extremely large proportion of critical illness and death of the elderly patients. Meanwhile, the elderly patients are at high risk of osteoporotic fractures especially osteoporotic vertebral compression fractures (OVCF). During the prevention and control of COVID-19 epidemic, orthopedists are confronted with the following difficulties including how to screen and protect OVCF patients, how to accurately diagnose and assess the condition of OVCF patients with suspected or confirmed COVID-19, and how to develop reasonable treatment plans and comprehensive protective measures in emergency and outpatient clinics. In order to standardize the diagnosis and treatment of patients with OVCF diagnosed with COVID-19, the authors jointly develop this expert consensus. The consensus systematically recommends the standardized emergency and outpatient screening and confirmation procedures for OVCF patients with suspected or confirmed COVID-19 and protective measures for emergency and outpatient clinics. Moreover, the consensus describes the grading and classification of OVCF patients diagnosed with COVID-19 according to the severity of illness and recommends different treatment plans and corresponding protective measures based on the different types and epidemic prevention and control requirements.

Objective:To explore the genetic characteristics, clinical features, and prognostic values of RAS mutations in patients with myelofibrosis (MF) .Methods:We analyzed 112-gene targeted sequencing data from 226 patients who had a diagnosis of either primary myelofibrosis (PMF) or post-polycythemia vera/post-essential thrombocythemia (post-PV MF and post-ET MF) from December 2011 to December 2019. A retrospective analysis of the genetic characteristics, clinical features, and prognosis of RAS mutations was performed.Results:Among 266 patients diagnosed PMF or post-PV/ET MF, RAS mutations were found in 14 (6.2%) cases, including 9 (4.0%) cases of NRAS mutations, 8 (3.5%) cases of KRAS mutations, and 3 (1.3%) cases of both NRAS and KRAS mutations. All of the NRAS mutations were located in codons 12 and 13. The median VAFs of RAS mutations were significantly lower than those of the driver mutations, confirming that they represent sub-clonal events that are acquired during the disease course. SETBP1, SRSF2, and MPL tended to be clustered with RAS mutations. Patients with RAS mutations had a higher number of additional oncogenic mutations (median, 3.36 vs 1.17, P<0.001) . RAS mutations had a statistically significant association with elevated monocyte cell counts ( P=0.003) , lower platelet counts ( P=0.026) , higher bone marrow blasts ( P=0.022) , splenomegaly ( P=0.005) , and very high-risk (VHR) karyotype abnormality percentage ( P=0.031) . In univariate analysis, the OS of patients with NRAS mutations were significantly inferior in the entire MF and PMF cohorts ( P=0.001, P=0.008) . In a multivariate model, NRAS retained an independent negative prognostic factor in PMF. Conclusion:RAS gene mutations were constantly related to elevated monocyte cell counts, lower platelet counts, higher bone marrow blasts, and VHR karyotype abnormality percentage that usually defined high-risk disease and often occurred as sub-clonal events. NRAS mutation is an independent poor prognostic factor in PMF.

Objective To evaluate the application value of the blastocysts derived from non-pronucleus (0PN) zygotes by the good quality blastocyst formation rate and the clinical outcomes of frozen-thawed blastocyst transfers. Methods The good quality blastocyst formation rate derived from 0PN zygotes was compared with that derived from2 pronucleus(2PN)zygotes in in vitro fertilization(IVF)or intracytoplasmic sperm injection (ICSI) cycles from January 2015 to December 2016. In addition, the clinical pregnancy, embryo implantation and live birth rates of frozen-thawed blastocyst transfers with blastocysts derived from 0PN and 2PN zygotes were analyzed on corresponding dates. Results (1)In IVF cycles, the high quality blastocysts formation rate of 2PN embryos was significantly higher than that of 0PN (46.64% versus 42.42%, P<0.01). In ICSI cycles, the high quality blastocysts formation rate of 2PN embryos was markedly higher than that of 0PN(41.96% versus 21.73%, P<0.01).(2)In frozen-thawed embryo transfer cycles for IVF, the clinical pregnancy, implantation and live birth rates of D5 0PN blastocysts were significantly higher than those of D6 2PN(52.64% versus 46.78%, 49.91% versus 41.20%, 46.54% versus 39.56%, all P<0.05), however, the abortion and newborn abnormal rates of D5 0PN blastocysts were lower than those of D6 2PN blastocysts(17.37% versus 23.36%, 1.31% versus 4.21%, both P<0.05); the clinical pregnancy, implantation and livebirth rates of D5 2PN blastocysts were significantly higher than those of D5 0PN(59.73% versus 52.64%, 55.95% versus 49.91%, 53.03% versus 46.54%, all P<0.05), but newborn abnormal rate was a little higher than that of D5 0PN(3.90% versus 1.31%, P<0.05);the clinical pregnancy, implantation and live birth rates of D5 2PN blastocysts were significantly higher than those of D6 2PN(59.73% versus 46.78%, 55.95% versus 41.20%, 53.03% versus 39.56%, all P<0.05), and the abortion rate of D5 2PN blastocysts was lower than that of D6 2PN blastocysts(18.23% versus 23.36%, P<0.05). Conclusions Although the blastocysts derived from 0PN could be transffered, the blastocysts derived from 2PN zygotes are preferred in all cycles. In IVF cycles, the good quality blastocysts derived from 2PN or 0PN zygotes will be transferred.

Objective To study nursing countermeasures for the brain tumor surgery patients with intracranial hypotension syndrome (IHS).Methods A total of 68 IHS patients in our hospital after brain tumor operation were divided into study group (n =34) and control group (n =34) with random number table method.Control group took routine nursing intervention,and comprehensive nursing intervention was given to study group on the basis of control group.Intracranial pressure recovery time,length of hospital stay,and the changes of quality of life after 6 months of two groups were compared.Results The intracranial pressure recovery time and hospital stay time were lower than that in control group (P ＜ 0.05).Psychological function,life condition,social function and physical function score after 6 months were higher than that in control group (P ＜ 0.05).Conclusion Comprehensive nursing intervention can effectively shorten intracranial pressure recovery time for IHS patients and hospital stay time,and improve the quality of life,so it is suitable for clinical application.