OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

BACKGROUND:The elastic modulus of traditional bone implants is large and does not match the elastic modulus of human bone,which will cause a stress shielding effect and lead to bone resorption.The trabecular scaffold of the triply periodic minimal surface with radial gradient has elastic modulus matching with human cancellous bone,and its yield strength is greater than that of human cortical bone,which provides a new choice for the design of bone scaffold. OBJECTIVE:Triply periodic minimal surface structure with radial gradient was constructed by the implicit surface method.The sample was manufactured by laser selective melting technology,and the quasi-static compression test was carried out to obtain trabecular scaffolds with mechanical properties matching human bones. METHODS:Four types of the trabecular scaffolds of the triply periodic minimal surface with a radial gradient of G,I,P and D were established by the implicit surface method.Samples were manufactured by laser selective melting technology.We observed the surface morphology of the molded sample,evaluated the molding quality,conducted a quasi-static compression test,and evaluated the mechanical properties of the samples. RESULTS AND CONCLUSION:The quasi-static compression test results showed that compared with the four triply periodic minimal surface scaffolds,the platform stress of the G scaffold had less fluctuation and no failure or fracture,indicating that the G scaffold had the best plasticity.The mechanical properties of the G scaffolds with 45%,55%and 65%porosities were analyzed.It was found that the elastic modulus of G scaffolds with 55%porosity was within the range of elastic modulus of human cancellous bone(0.022-3.7 GPa),and the yield strength was close to the maximum yield strength of human cortical bone(187.7-222.3 MPa).In conclusion,G triply periodic minimal surface scaffold with 55%porosity can reduce the stress shielding effect,bear a higher body load,improve the stability of the implant,and prolong the service life of the implant.

BACKGROUND:Vertebral compression fracture is a common disease in the current orthopedic field.However,the occurrence of re-fracture in neighboring vertebrae after surgery is a problem that cannot be ignored,which has a serious impact on the normal life of patients. OBJECTIVE:The aim of this study is to establish four postoperative models with different recovery heights using computed tomography images.By using finite element analysis,we derived the stresses on the neighboring vertebrae at different recovery heights and further explored the importance of postoperative recovery of the height of the injured vertebrae. METHODS:A finite element model of the thoracolumbar spine(T11-L3)was established and validated,on the basis of which four postoperative finite element models of L1 with different recovery heights of 100%,80%,60%,and 40%were constructed,in which the cement capacity varied with the recovery height.The specific models are as follows:Model 1 was the postoperative model with normal recovery height,and the cement capacity was 8.3 mL.Model 2 was the postoperative model in which 20%of the anterior height of the L1 was removed and the posterior convexity angle became 10.41°,and the cement capacity was 6.9 mL.Model 3 was the postoperative model in which 40%of the anterior height of the L1 was removed and the posterior convexity angle became 20.17°,and the cement capacity was 4.7 mL.Model 4 was a postoperative model with 60%of the L1 anterior height removed and the posterior convexity angle changed to 28.85°,with a cement capacity of 3.6 mL.For evaluation of the postoperative model,we applied a moment of 7 Nm and an axial force of 500 N.The followings were recorded and analyzed:peak stresses in the L2 upper endplate and T12 lower endplate;peak stresses in the L2 and T12 cancellous bone. RESULTS AND CONCLUSION:(1)The highest peak stresses for each condition of the L2 upper endplate,T12 lower endplate,L2 cancellous bone,and T12 cancellous bone occurred in Model 1 and Model 4.In particular,the T12 lower endplate,except for the posterior extension condition,the anterior flexion,left and right lateral bending,and left and right rotation conditions all reached their highest peak stresses in Model 4,with stresses of 50.3,33.1,44.9,34.3,and 31.9 MPa.(2)Based on the peak stresses in the adjacent vertebral endplates and cancellous bone,after excluding Model 1 and Model 4,the minimum peak stresses for most of the conditions appeared in the Model 2,and the minimum peak stresses appeared in the Model 2 in 66.6%of the cases,especially in the upper endplates of the L2 and cancellous bone except for the posterior extension condition,the minimum peak stresses all appeared on the Model 2.(3)Therefore,controlling the recovery height at about 100%and 40%of the original height was a dangerous recovery height,which had a greater impact on the neighboring vertebrae.Controlling the recovery height at about 80%of the original height may be a more ideal choice.With a recovery height of about 80%of the original height,the adjacent vertebrae are subjected to less stress,thus reducing the risk of re-fracture of the adjacent vertebrae in the patient.

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Objective To compare the results of accumulation and continuation methods in indoor radon measurement. Methods The radon concentrations in 30 households in 7 provincial capital cities of China were simultaneously measured using both accumulation and continuation methods. Results The radon concentration measured by accumulation method in 30 households ranged from 21 to 323 Bq/m³, with a median M(P₂₅, P₇₅) of 70.5 (43.8, 111). The radon concentration measured by the continuation method ranged from 16.1 to 258 Bq/m³, with a median M(P₂₅, P₇₅) of 100 (51.3, 141). The average relative percent deviation between the two measurement methods was 41.8%. There were significant differences among the measurement results at 8, 16, and 24 h by the continuation method. Pairwise comparisons showed there were statistical diffferences between 8 h and 16 h, as well as between 8 h and 24h; however, no statistical significance was found (P < 0.05), between 16 h and 24 h. Conclusion The overall continuous measurement results of the 30 households were higher than those of cumulation method. The comparison between accumulation and continuation measurement results did not show a high level of correlation (r=0.49). The continuation method is significantly affected by environmental factors, and the length of the measurement period can affect the measurement results. The selection of indoor radon measurement methods should consider the purpose, sample size, and environmental conditions.

Objective To analyze the efficacy and safety of unilateral laminectomy and bilateral decompression under unilateral biportal endoscopy(UBE)and microendoscope(MED)in lumbar spinal stenosis.Methods 80 patients with lumbar spinal stenosis from January 2021 to December 2022 were selected and divided into two groups by numerical table method,the control group and the study group,and the number of cases was 40.The grouping method was random number table method.The control group was treated with unilateral laminectomy and bilateral decompression under MED,while the study group was treated with unilateral laminectomy and bilateral decompression under UBE.Operation time,intraoperative blood loss,Oswestry disability index(ODI)and visual analogue scale(VAS)of lumbago and leg pain were obtained before surgery,1,3 months after surgery and at the last follow-up,efficacy and complications were compared between the two groups.Result There were no significant differences in operative time and blood loss between the study group and the control group(P>0.05).1,3 months after surgery and at the last follow-up,ODI in both groups were lower than those before surgery(P<0.05),but there was no difference between the study group and the control group(P>0.05).The VAS of lumbago and leg pain in both groups were lower than those before surgery(P<0.05),at 1,3 months after surgery and the last follow-up,and the study group was significantly lower than the control group(P<0.05).The excellent and good rate of clinical treatment in the study group was 97.50%,and there was no difference compared with 92.50%in the control group(P>0.05).The complication rate of the study group was 2.50%,significantly lower than that of the control group(15.00%)(P<0.05).Conclusion Unilateral laminectomy and bilateral decompression under the UBE and MED have similar efficacy in the treatment of lumbar spinal stenosis,both of which can effectively promote functional recovery,but UBE can reduce pain more effectively and has fewer postoperative complications.

Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQ-containing regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients. Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM. Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups. Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To evaluate the influence of different teaching modes in the creativity of nursing students in China.Methods:A systematic search of PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database and VIP Database were carried out. Randomized control trials (RCTs) examining the influence of different teaching modes in the creativity of nursing students were included from inception to March 5, 2023. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies according to the Cochrane Handbook for Systematic Reviews of Interventions and combined with the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE), then network Meta-analysis with random effects was performed by using WinBugs 1.4.3 and Stata 17.0 software.Results:A total of 63 studies involving 22 teaching modes were included. The network Meta-analysis showed that Case-based Learning Mode, Evidence-based Nursing Teaching Mode, 3D Printing Model Teaching Mode, Hands-on Inquiry Based Learning, Quality Control Circle Teaching Mode, Six Thinking Hats Teaching Mode, Theory, Drill, Practice, Combine (TDPC, T:theory; D:drill; P:practice; C:combine) Teaching Mode were more effective than Lecture-based Learning Mode ( SMD values were 4.61-22.51, all P<0.05). Sensitivity analysis showed the effectiveness of TDPC Teaching Mode was the greatest in nursing theoretical teaching[surface under the cumulative ranking (SUCRA)=98.08%], the Quality Control Circle Teching Mode was the second most effective (SUCRA=83.13%). The effectiveness of Six Thinking Hats Teaching Mode was the greatest in nursing practical teaching (SUCRA=95.73%), followed by the 3D Printing Model Teching Mode (SUCRA=86.97%). Conclusions:TDPC Teaching Mode, Six Thinking Hats Teaching Mode, 3D Printing Model, Quality Control Circle Teaching Mode were superior to other teaching modes in improving creativity of nursing students.

Objective To evaluate the reliability and validity of the Chinese version of the hyperacusis scale and estimate its applicability in the Chinese population.Methods The patients admitted to the Department of Oto-laryngology of Xijing Hospital from June 2017 to December 2017 were surveyed.A total of 300 questionnaires were sent out and 293 valid questionnaires were collected with effective response rate of 97.67％.All participants comple-ted a basic information survey,pure tone audiometry and fill in the Chinese version of the hyperacusis scale.The re-liability and validity of this scale were evaluated.Results Among the 293 respondents,243(82.93％)were compli-cated with tinnitus.A total of 181 cases(61.77％)were subjectively diagnosed with hyperacusis through question-naire survey.According to the scale evaluation,174 cases(59.39％)were diagnosed with hyperacusis,and the Kappa value of conformity test of the two methods was 0.81(P＜0.001).Reliability analysis indicated a Cronbach'sα coefficient of 0.93 for the entire scale.Each dimension had a Cronbach's α coefficient＞0.60.The split-half relia-bility coefficient for the entire scale was 0.86,and for each dimension,it was＞0.60.Exploratory factor analysis of validity suggested that 25 items could be grouped under 4 factors,such as functional part,social part,emotional part and harmonic sensitivity part.These factors had eigenvalues greater than 1,accounting for 59.42％of the total variance.Post-rotation,the 25 items were distributed across the 4 components,with each item having a factor load-ing＞0.40.Confirmatory factor analysis of validity showed model fit parameters as:x2/df=1.98,GFI=0.91,AGFI=0.83,CFI=0.92,TLI=0.89,RMSEA=0.08.Each item had a standardized factor loading＞0.40.Con-clusion The Chinese version of the hyperacusis scale demonstrated strong reliability and validity,making it suitable for use among the Chinese population.