Prosthesis loosening is the leading cause of postoperative revision in unicompartmental knee arthroplasty (UKA). The deviation of medial and lateral translational installation of the prosthesis during surgery is a common clinical phenomenon and an important factor in increasing the risk of prosthesis loosening. This study established a UKA finite element model and a bone-prosthesis fixation interface micromotion prediction model. The predicted medial contact force and joint motion of the knee joint from a patient-specific lower extremity musculoskeletal multibody dynamics model of UKA were used as boundary conditions. The effects of 9 femoral component medial and lateral translational installation deviations on the Von Mises stress of the proximal tibia, the contact stress, and the micro-motion of the bone prosthesis fixation interface were quantitatively studied. It was found that compared with the neutral position (a/A of 0.492), the lateral translational deviation of the femoral component significantly increased the tibial Von Mises stress and the bone-prosthesis fixation interface contact stress. The maximum Von Mises stress and the maximum contact stress of the fixation interface increased by 14.08% and 143.15%, respectively, when a/A was 0.361. The medial translational deviation of the femoral component significantly increased the bone-prosthesis fixation interface micro-motion. The maximum value of micromotion under the conditions of femoral neutral and medial translation deviation was in the range of 20-50 μm, which is suitable for osseointegration. Therefore, based on considerations such as the micromotion range suitable for osseointegration reported in the literature, the risk of reducing prosthesis loosening, and factors that may induce pain, it is recommended that clinicians control the mounting position of the femoral component during surgery within the safe range of 0-4 mm medial translation deviation.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Finite Element Analysis ; Biomechanical Phenomena ; Knee Prosthesis ; Tibia/surgery* ; Femur/surgery* ; Stress, Mechanical ; Prosthesis Failure ; Knee Joint/surgery* ; Prosthesis Design

Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS). Using this newly developed method, we screened the RNA-binding proteins that regulate PABPN1 phase separation and identified the tumor suppressor QKI as a promoter of PABPN1 phase separation. Furthermore, QKI exhibits decreased expression levels and diminished nuclear localization in colorectal cancer cells, resulting in reduced PABPN1 phase separation, which, in turn, promotes alternative polyadenylation (APA), cell proliferation, and migration in colorectal cancer.
Humans ; Colorectal Neoplasms/genetics* ; RNA-Binding Proteins/genetics* ; Poly(A)-Binding Protein I/genetics* ; CRISPR-Cas Systems ; Flow Cytometry ; Cell Proliferation ; Cell Line, Tumor ; Cell Movement

Machine Learning ; Image Processing, Computer-Assisted/methods*

Objective:To investigate the characteristics of nasal flora and the pathogenic role of differential microbiome in patients with allergic rhinitis (AR) and non-allergic rhinitis (nAR).Methods:Thirty-five patients with AR who attended the rhinology outpatient clinic of the Second Hospital of Harbin Medical University from February to July 2022 were selected. A total of 35 nAR patients were selected as the test group, and 20 cases of healthy people with physical examination at the same period were selected as the control group, including 39 males and 51 females, aged 8 to 55 years. 16SrDNA High-throughput sequencing was used to analyze the relative abundance from nasal flora in the three groups of subjects. Alpha diversity index analysis was conducted with R software, and differences between groups were analyzed with LEfSe, Metastats, and t tests. At the same time, the role of microbiome and its relationship with environmental factors were analyzed with R software. Results:There was a significant difference in the bacterial composition of the samples from the three groups, with the relative abundance of Staphylococcus aureus ( P=0.032) and Corynebacterium proinquum ( P=0.032) within the AR group being significantly higher than that of the nAR group, and that of Lactobacillus murinus, Lactobacillus kunkeei, and Alcaligenes faecalis ( P value was 0.016, 0.005, and 0.001, respectively) being significantly lower than that of the nAR group. The relative abundance of Ackermannia muciniphila within the nAR group was higher than that of the control group ( P=0.009). Correlation analysis of environmental factors showed a negative correlation between Lactobacillus kunkeei and IgE ( P=0.044), and a positive correlation between Lactobacillus murinus and age ( P=0.019). AR and nAR random forest prediction models were constructed for the five genera, respectively, and the area under the curve (AUC) of the models of Streptococcus-SP-FF10, Pseudoalteromonas luteoviolacea, Pseudomonas parafulva, Acinetobacter ursingii, and Azotobacter chroococcum in the AR group was 100% (95%CI: 100% to 100%). The AUC for the Pseudomonas parafulva, Azotobacter chroococcum, Closoridium baratii, Turicibacter-SP-H121, and Streptococcus lutetiensis models in the nAR group was 98.4% (95%CI: 94.9% to 100%). Conclusions:The distribution of nasal flora in AR patients, nAR patients and healthy subjects is significantly different, and the changes of bacterial flora abundance are significantly related to the occurrence of AR and nAR. Combined detection of microbiota has the potential to diagnose AR and nAR patients.

Objective:To analyze the role of patient support system in multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment adherence and outcome, and provide evidence for deepening the patient-centered support system.Methods:Based on the stakeholder analysis, definite stakeholders (administrators from the Department of Medical Insurance, and those from the provincial CDC), expectant stakeholders (administrators from regional CDC, health workers from primary CDCs, medical workers from designated MDR/RR-TB hospitals and MDR/RR-TB patients), and latent stakeholders (MDR/RR-TB patient families and their neighbors or colleagues) were selected using a purposive sampling. These stakeholders were subject to a semi-structured interview on patient support. The inclusion of participants ceased after reaching code or thematic saturation and meaning saturation, while thematic framework analysis was applied in interview data.Results:The 25 interviewees included could be categorized into three groups of stakeholders, i. e., 4 definite stakeholders, 19 expectant stakeholders and 2 latent stakeholders. Three themes summarized in this regard were definite stakeholders providing policy support to advance these patients′ access to standardized diagnosis and treatment services; diagnosis and treatment and management support of expectant stakeholders of these patients to encourage their compliance to treatment and enable their access to high quality medical care; and support from latent stakeholders as a critical guarantee for the patients to welcome a desirable treatment outcome. Psychological support provided under MDR/RR-TB basic care program in some provinces contributed positively to raising patients′ compliance. Economic support, treatment support from family menmbers ccould help the patients to welcome desirable outcomes.Conclusions:MDR/RR-TB patient-centered support system operating in the Yangtze River delta provide the patients with MDR/RR-TB diagnostic and treatment services of some accessibility. Given the progress, there are still shortcomings for the respective stakeholders to enhance their attention and collaboration to improve the access and equity to medical service.

[Abstract] Objective: To investigate the expression of chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) in breast cancer tissues and its correlation with clinicopathological features and prognosis of patients. Methods:Atotal of 136 breast cancer tissue chips (purchased from Superchip Company), including 42 pairs of matched cancer and paracancerous tissues, were used for this study. The expression level of CMTM6 in cancer and paracancerous tissues was detected by immunohistochemistry. The comparison of CMTM6 expression between breast cancer and paracancerous tissues was conducted by paired χ2 test. The relationship between CMTM6 expression in breast cancer tissues and the clinicopathological characteristics of patients was analyzed by χ2 test. Kaplan-Meier and Log rank test analyses were used to analyze the relationship between CMTM6 expression and the survival of patients, and Cox model was used to evaluate the effect of different indicators on the prognosis of patients. Results: The expression of CMTM6 in breast cancer tissues was significantly higher than that in paracancerous tissues (P<0.01). The expression of CMTM6 was correlated with pathological type of breast cancer and HER2 positivity (P<0.05). The survival time of patients in CMTM6 high expression group was significantly shorter than that of patients in CMTM6 low expression group (P<0.05). Pathological type (HR=10.374, 95%CI: 3.529-30.497, P<0.01), TNM stage (HR=4.599, 95%CI: 1.784-11.856, P<0.01), triple-negative breast cancer (HR=3.370, 95%CI: 1.055-10.761, P<0.05) and high expression of CMTM6 (HR=0.195, 95%CI: 0.073-0.518, P<0.01) were independent risk factors for prognosis of breast cancer patients. Conclusion: CMTM6 is highly expressed in breast cancer tissues, which can be used as a risk factor for prognosis evaluation of breast cancer patients.

Objective:To investigate the effect of Lee Silverman voice therapy (LSVT) on the speech and life quality of Chinese persons with Parkinson′s disease (PD).Methods:A total of 16 Chinese PD patients were enrolled and given standard LSVT for 4 weeks. Their acoustic data were analyzed using PRAAT software before and after the treatment. Their voice quality was evaluated using the Japanese GRBAS voice scale and their quality of life was quantified using the Voice Handicap Index (VHI) scale.Results:After 4 weeks of LSVT the patients′ average voice and life quality had improved significantly. The average maximum duration of sustained vowel phonation had increased significantly, as had the vowels′ mean loudness, reading and monologue delivery. The GRBAS grading indicated that hoarseness had decreased significantly. The average total voice handicap index had also decreased significantly.Conclusion:Lee Silverman therapy can significantly improve maximum phonation time and loudness of Chinese-speakers, which enhances sensory feedback. The quality of their speech and of their life also improve significantly. This technique is recommended for clinical application.

Objective: This study aimed to reveal the potential clinical and biological functions of frizzled related protein (FRZB) mRNA expression in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Methods: We used the keyword “lung cancer” to search the data through Gene Expression Omnibus (GEO) database attached to NCBI(National Center of Biotechnology) and download the data of LUAD and LUSC from TCGA (The Cancer Genome Atlas) Database. A total of eight LUAD and six LUSC datasets were incorporated in this analysis. We defined cutoff value of FRZB using Cutoff Finder into the two groups to calculate hazard ratio (HR). Results: We found that high expression level of FRZB mRNA in tumor tissues was a positive prognostic factor for overall survival in LUAD [pooled HR（95%CI）=0.54（0.46-0.64）,P＜0.05 in univariate analysis; pooled HR（95%CI）=0.66（0.54-0.79）,P＜0.05 in multivariate analysis]. Interestingly, there was no similar results in LUSC [pooled HR（95%CI）=1.11（0.67-1.84）,P＞0.05 in univariate analysis; pooled HR（95%CI）=1.13（0.71-1.78）,P＞0.05 in multivariate analysis]. We also found that FRZB may inhibit WNT signal pathway by t-SNE and correlation analysis. By enrichment analysis, FRZB and its most correlated genes were involved in multiple immune-related pathways, such as complement and coagulation cascades, humoral immune response, etc. Conclusion High expression of FRZB mRNA in LUAD was associated with better prognosis of lung adenocarcinoma. These results suggest that FRZB may be used as a potential marker for favorable prognosis of lung adenocarcinoma.

Simulation-based medical education can ensure medical safety, reduce medical errors and improve students' clinical skills. At present, the main problems in medical teaching are the conflict between doctors and patients, the contradiction between medical teaching and ethics, the shortage of teaching resources and the lack of a universal assessment standard. The advantages of simulation-based medical education are its safety, repeatability, standardization, controllability, relative authenticity, and the cultivation of humanistic spirit and teamwork for students. Simulation-based medical education has two major limits. First, its teaching effect relies on the function and quality of each model. Second, simulation cannot replace clinical practice. This article proposes the following ways and means for promoting the simulation-based medical education: training of faculty is the core, establishment of courses is the focus, cooperation and communication is an important way to promote development, and phased and refined development is the future direction.

Objective To construct a prognostic nomogram for predicting the prognosis of patients with colorectal cancer ( CRC) , and verify its accuracy. Methods The clinical pathologic data from 438 CRC patients hospitalized in the Third Affiliated Hospital of Soo-chow University during January 2006 and May 2013 were retrospectively analyzed. The independent risk factors for predicting the prog-nosis of CRC were determined by the univariate and multivariate regression model. The prognostic nomogram was established by the R-language software. Then, the nomograms of postoperative 3-year and 5-year disease free survivals ( DFS) were drawn, and compared with the actual status. The internal validation and accuracy of the nomogram were determined by the Bootstrap method and the calculat-ed concordance index ( C-index) , respectively. The sensitivity and specificity of the nomogram for predicting the 3-year and 5-year DFS were compared with those of TNM system established by the American Joint Committee On Cancer (AJCC) (7th ed.) by using the time-dependent ROC curve. Results Among 438 CRC patients, the metastasis of CRC occurred in 233 patients, including 105 liver metas-tasis and 57 lung metastasis. Multivariate COX regression analysis showed that tumor differentiation degree, TNM stage, serum CEA level, serum CA19-9 level, neutrophil lymphocyte ratio ( NLR) and P53 level were the independent risk factors of CRC. The C-index of the constructed nomogram for predicting the survival rate of CRC patients was 0.678. The predicted 3-year and 5-year DFS by the no-mogram were highly coincident with the actual status. The analysis results of the time-dependent ROC curve showed that the sensitivity and specificity of the established nomogram for predicting the postoperative 3-year and 5-year DFS were higher than those of AJCC-TNM stage.Conclusion The established nomogram may accurately predict the prognosis of CRC patients, which may be helpful for clinicians to follow up or make beneficial treatment for CRC patients.