BACKGROUND:Bone mineral density is the clinical gold standard for determining bone strength,but bone mineral density is less sensitive to changes in bone mass,with large changes in bone mineral density only occurring when bone mass is significantly reduced,so bone mineral density has limited ability to predict changes in bone strength and fracture risk. OBJECTIVE:A model of the normal and osteoporotic hip joint was developed to analyze the stresses and deformation in the hip of normal and osteoporotic patients under single-leg standing conditions. METHODS:A healthy adult female volunteer at the age of 36 years was selected as the study subject.The CT data of the hip joint of this volunteer were obtained and saved in DICOM format.The hip joint model was reconstructed in three dimensions,and the material properties were assigned by the gray value assignment method to obtain the normal and osteoporotic hip joint models according to the empirical formula.The same boundary conditions and loads were set to simulate the stresses and deformation in the normal and osteoporotic hip joints in the single-leg standing position. RESULTS AND CONCLUSION:(1)In the finite element model of the normal and osteoporotic hip,the stress distribution was more concentrated in the medial region of the femoral neck.(2)In the hip bone,the stress distribution was mainly concentrated in the upper part of the acetabulum.(3)The stress peaks in the medial femoral neck and upper acetabulum were larger in the normal hip model than in the osteoporotic hip model,probably due to the reduced bone strength of the osteoporotic bone.(4)The peak Von Mises of both normal and osteoporotic hip models were concentrated on the medial femoral neck,and the peak Von Mises of the hip bone was smaller,indicating that the overall effect of osteoporosis on hip bone stresses was relatively small.(5)In terms of deformation in the single-leg standing position,the maximum deformation in the normal hip model was located at the acetabulum and femoral head,and the maximum deformation was located at the upper part of the greater trochanter of the femur.(6)It is suggested that the finite element analysis method to model the values of parameters related to bone tissue in osteoporosis may improve clinical prediction of bone strength changes and fracture risk.It is explained from the biomechanical view that the intertrochanteric femur and femoral neck are good sites for osteoporotic hip fractures.

Objective:To investigate the application value of transanal endoscopic intersphincteric resection (taE-ISR) in sphincter preservation for low rectal cancer.Methods:The pro-pensity score matching and retrospective cohort study was conducted. The clinicopathological data of 278 patients with low rectal cancer who were admitted to 5 medical centers, including Ruijin Hospital of Shanghai Jiaotong University School of Medicine et al, from January 2017 to December 2021 were collected. There were 178 males and 100 females, aged 58 (range, 49-64)years. Of 278 pati-ents, 147 cases undergoing taE-ISR were divided into the taE-ISR group, and 131 cases undergoing intersphincteric resection (ISR) were divided into the ISR group. Observation indicators:(1) propen-sity score matching and comparison of general data of patients between the two groups after matching; (2) comparison of intraoperative and postoperative conditions between the two groups; (3) long-term follow-up of the two groups; (4) analysis of risk factors affecting sphincter preservation for low rectal cancer. Propensity score matching was done by the 1∶1 nearest neighbor matching method, with a caliper value of 0.05. Propensity score matching analysis was done using the Matching package. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the Student′s t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the Pearson chi-square test or Fisher exact probability. The Kaplan-Meier method was used to calculate survival rate and plot survival curve, and the Log-Rank test was used for survival analysis. Multivariate analysis was conducted using the Logistic regression model with the "glm2" package. The forest plot was used to show the risk factors affecting sphincter preservation for low rectal cancer. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 278 patients, 180 cases were successfully matched, including 90 cases in the taE-ISR group and 90 cases in the ISR group, respectively. After propensity score matching, the elimination of distance between ischial tuberosities and distance from ischial tuberosity to the skin of buttocks confounding bias ensured comparability between the two groups. (2) Comparison of intraoperative and postoperative conditions between the two groups. Cases with positive distal margins, cases with specimen integrity, cases with sphincter preservation were 1, 88, 88 in the taE-ISR group and 8, 78, 74 in the ISR group, showing significant differences between the two groups ( P<0.05). (3) Long-term follow-up of the two groups. The median follow-up time was 4.3(range, 3.8-5.0)years of the taE-ISR group and 4.1(range, 3.4-4.7)years of the ISR group. The overall survival rate, disease-free survival rate and cumulative recurrence rate were 100.0%, 95.6% and 2.2% of the taE-ISR group, versus 98.9%, 87.8% and 10.0% of the ISR group, showing no significant difference in overall survival rate between the two groups ( χ2=0.97, P>0.05) and significant differences in disease-free survival rate and cumulative recurrence rate between the two groups ( χ2=4.05, 5.26, P<0.05). (4) Analysis of risk factors affecting sphincter preservation for low rectal cancer. Results of multivariate analysis showed that taE-ISR, distance from the tumor to the anus, and adjacent organ damage were independent factors affecting sphincter preservation for low rectal cancer ( odds ratio=0.86, 0.88, 1.35, 95% confidence interval as 0.79-0.93, 0.83-0.92, 1.04-1.74, P<0.05). In further analysis, there were significant differences in sphincter preservation and defecatory dysfunction between the 21 cases with neoadjuvant therapy in the taE-ISR group and the 19 cases with neoadjuvant therapy in the ISR group ( P<0.05). Conclusions:The taE-ISR is safe and feasible for patients with low rectal cancer. Compared with ISR, taE-ISR can significantly improve surgical quality, sphincter preservation rate and patient prognosis.

【Objective】 To explore the relationship between the methylation level of CNR1 and autism spectrum disorder (ASD), in order to provide a theoretical basis for the etiology of ASD. 【Methods】 A case-control study was conducted, recruiting 30 children with ASD from the Child Development and Behavior Research Center of Harbin Medical University and a rehabilitation facility, and 30 matched typically developed children from June 2017 to December 2018. The methylation levels of CNR1 in peripheral blood were measured by the Agena MassArray^® Mass Spectrometry System. A univariate conditional Logistic regression model was used to analyze the potential association between the methylation level of CNR1 and the risk of ASD with adjustment for age, BMI, body fat percentage and body fat. The correlations between the methylation level of CNR1 and the score of Social Responsiveness Scale (SRS) were evaluated by Pearson/Spearman correlation analysis. 【Results】 The methylation levels of the average methylation (t=2.224), CpG_3.4 (Z=2.187), CpG_9.10.11 (t=2.308), and CpG_28.29 (t=2.943) of the CNR1 promoter region in ASD children were significantly higher than controls (P<0.05). The methylation levels of the average methylation (OR=1.117, 95%CI: 1.003 - 1.245), CpG_9.10.11 (OR= 1.072, 95%CI:1.006 - 1.142), and CpG_28.29 (OR=1.078, 95%CI: 1.018 - 1.141) of the CNR1 promoter region were positively correlated with the risk of ASD (P<0.05). The methylation level of CpG_28.29 in ASD children was positively correlated with the scores of social motivation in SRS (r=0.421, P<0.05). 【Conclusions】 The methylation levels of CNR1 in peripheral blood are abnormal in ASD children and might be correlated with the risk of ASD and social function. The underlying mechanism needs to be further explored.

Postoperative thyroid scar not only causes itching, pain, and pulling, but also seriously affects the patient’s aesthetics, so it is important to study the prevention and treatment of postoperative thyroid scar. In the past 20 years, clinicians have made many innovative researches to alleviate postoperative thyroid scar growth, and the following progresses have been made: firstly, thyroid surgery methods and surgical accesses have been improved to a certain extent, resulting in more concealed and less traumatic accesses; secondly, the use of lasers and silicone and other drugs has significantly improved the scar treatment effect; thirdly, the concept of "cosmetic" is gradually gaining popularity, and related technical means are used throughout the treatment of postoperative scarring of the thyroid gland, and multiple treatment modalities are used "early" and "in combination" to "prevent" scar growth after surgery. The use of multiple treatment modalities to prevent scar growth in the early postoperative period has achieved twice the result with half the effort.

Objective:TP53-abnormal MDS/acute myeloid leukemia (AML) patients’ allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment’s effectiveness and influencing factors should be studied.Methods:42 patients with TP53 gene status change MDS/AML who underwent allo-HSCT from 2014.8.1 to 2021.7.31 at the Hematology Hospital of the Chinese Academy of Medical Sciences were the subject of a retrospective analysis. The 42 patients were divided into three groups: the TP53 deletion group (group A) , TP53 mono-alle mutation group (group B) , and TP53 multi-hit group (group C) . The differences in clinical features and prognostic factors after transplantation were analyzed.Results:There were 42 MDS/AML patients, including 21 patients with MDS, and 21 patients with AML. The median follow-up period was 34.0 (7.5-75.0) months and the median patient age at the time of transplantation was 41.5 (18-63) years old. The total OS was 66.3% (95% CI 53.4%-82.4%) in 3 years after transplantation, and EFS was 61.0% (95% CI 47.7%-78.0%) in 3 years. For 3 years after receiving hematopoietic stem cell transplantation, there were no statistically significant differences in 3-year OS and EFS in groups A, B, and C ( P≥0.05) . The 3 years OS was 82.5% (95% CI 63.1%-100.0%) in group A, 60.6% (95% CI 43.5%-84.4%) in group B, and 57.1% (95% CI 30.1%-100.0%) in group C. Univariate analysis revealed that the number of co-mutant genes, pre-HSCT treatment, and disease type did not affect prognosis, while age, karyotype, co-mutation, positive blast cell before transplantation, and positive blast cell after transplantation were common prognostic factors for OS and EFS ( P<0.1) . MRD levels before transplantation were found to be independent risk factors for OS ( P=0.037, HR=33.40, 95% CI 1.24-901.17) in a multivariate analysis. Conclusion:Patients with MDS/AML who have TP53 mutations can benefit from allo-HSCT, but patients with complex karyotypes have a worse prognosis. Meanwhile, the final flow cytometry (FCM) monitoring blast cell test before HSCT has a certain guiding significance for prognostic assessment.

Hepatitis B virus (HBV) infection is a key risk factor for the development and progression of hepatocellular carcinoma (HCC) and it promotes the progression of HCC by inducing liver fibrosis, genetic and epigenetic alterations, and the expression of active virally encoded proteins. Many studies have confirmed the influence of viral status on the prognosis of HCC, and effective antiviral therapy can help prevent or delay the recurrence of HBV-associated HCC, increase the overall survival time of patients undergoing radical or systemic, and improve the prognosis after multimodality therapy. Therefore, correct selection of antiviral drugs is crucial for the antiviral treatment of patients with HBV-associated HCC. This article briefly reviews the selection of antiviral drugs for patients with HBV-associated HCC, so as to provide a reference for clinical practice.

Objective:To investigate the predictive value of neutrophil to lymphocyte ratio (NLR) for hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS).Methods:Consecutive patients with AIS without performing intravenous thrombolysis and mechanical thrombectomy admitted to the Cerebrovascular Disease Treatment Center, the Affiliated Brain Hospital of Nanjing Medical University from December 2015 to December 2020 were enrolled. The clinical, imaging and laboratory examination data were collected. HT was defined as the first imaging examination of AIS patients without finding bleeding signs, but the imaging reexamination after hospitalization found intracranial hemorrhage. Multivariate logistic regression analysis was used to determine the independent correlation between NLR and HT. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of NLR for HT. Results:A total of 805 patients with AIS were included. The median age was 67 years (interquartile range, 63-71 years), the median National Institutes of Health Stroke Scale (NIHSS) score was 4 (interquartile range, 2-9), the median NLR was 3.84 (interquartile range, 2.66-5.30). Seventy-ywo patients (8.9%) had HT. There were significant differences in age, baseline systolic blood pressure, baseline NIHSS score, time from onset to admission, time from onset to blood collection, time from onset to imaging reexamination, NLR, atrial fibrillation, history of previous stroke and transient ischemic attack and stroke etiology between the HT group and the non-HT group (all P<0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for HT in patients with AIS after adjusting for confounding factors (odds ratio 1.355, 95% confidence interval 1.099-1.672; P=0.005). The ROC curve analysis showed that the area under the curve of NLR predicting HT was 0.852, and the optimal cut-off value was 4.75. Its sensitivity and specificity of predicting HT were 88.3% and 71.8% respectively. Conclusion:High NLR is an independent risk factor for HT in patients with AIS during hospitalization, and had better predictive value for HT risk.

Objective:To uncover the effect of circ0025847 on the proliferation of colorectal cancer cells and its molecular mechanisms.Methods:qRT-PCR was utilized to analyze the expression of circ0025847 and QK1 in human colorectal cancer cells (HCT116, SW480) and normal mucosa cells (NCM460) .CCK-8 was used to analyze the effect of circ0025847 and QK1 on proliferation in colorectal cancer cells. Bioinformatics method was used to screen RBP which could bind to circ0025847. RNA pulldown and RIP was utilized to confirm whether QK1 binds to circ0025847.Effects of circ0025847 over-expression on QK1 expression was analyzed by Western blot.NC group, circ0025847 overexpression group and circ0025847 overexpression+ QK1 inhibitor group were established and the proliferation effect was determined by CCK8.Results:circ0025847 (the expression levels in NCM460, HCT116 and SW480 cells were 1.01±0.05, 0.49±0.08, 0.45±0.10) and QK1 (the expression levels in NCM460, HCT116 and SW480 cells were 0.98±0.07, 0.50±0.07, 0.47±0.09) expression was significantly downregulated in colorectal cancer cells. Overpression of circ0025847 and QK1 suppressed colorectal cancer cells growth.RNA pull-down and RIP clarified that circ0025847 bind to QK1 and circ0025847 positively regulate QK1 expression (7 199.20±12.44 VS 3 889.80±11.03) . circ0025847 inhibiting the proliferation of colorectal cancer cells by promoting the expression of QK1 was confirmed by rescue experiment.Conclusion:circ0025847 inhibits colorectal cancer cells proliferation via positively regulating QK1 expression, indicating that circ0025847 may be potential therapeutic target of colorectal cancer.

Objective:To investigate the effect of exosomes (Exo) secreted by brain vascular endothelial cell bEnd.3 after ischemic preconditioning (IPC) on neurons suffering from oxygen and glucose deprivation (OGD).Methods:bEnd.3 was exposed to OGD for 3 h to simulate IPC in vivo. After 48 h of reoxygenation, the Exo (IPC Exo) in the conditioned medium were extracted and identified by Western blot and transmission electron microscopy. IPC Exo were incubated with primary cultured mouse cortical neurons for 24 h. Confocal microscope was used to observe whether Exo could be uptaked by primary cultured mouse cerebral cortical neurons. The primary cultured cortical neurons were divided into control group, OGD group, OGD+ IPC Exo (5 μg/ml, 10 μg/ml, 20 μg/ml) groups and sham OGD group (treated with Exo secreted by bEnd.3 cultured under normoxia conditions). The cell viability was detected by CCK-8 and cell survival/death detection kit.Results:Transmission electron microscopy showed that the extract of bend.3 culture medium showed typical morphology of Exo, i. e., a double concave disc-shaped vesicle with a diameter of 30-100 nm. Western blot analysis showed that the extract of bEnd.3 medium highly expressed Exo markers Alix and Tsg101. Confocal microscopy showed that Exo could be uptaked by primary cultured mouse cortical neurons, and the uptake of Exo was widely distributed in the cytoplasm and synapses. Compared with the OGD group, the addition of 10 and 20 μg/ml IPC Exo could significantly increased the neuronal viability ( P<0.05), while the addition of sham Exo had no neuroprotective effect. Conclusion:Exo released by cerebral vascular endothelial cells after IPC have protective effect on neurons suffering from OGD.