OBJECTIVES: To establish a prognostic model for primary liver cancer (PLC) using bioinformatics methods. METHODS: Based on the data from 404 patients in the Cancer Genome Atlas (TCGA) database, we constructed a prognostic model integrating the differentially expressed genes, anoikis, and immune-related genes (DAIs) using univariate Cox regression and the LASSO-Cox approach. The predictive ability of the model was evaluated using Kaplan-Meier method and receiver-operating characteristic curves, and a nomogram was developed to facilitate its clinical applications. Gene set enrichment analysis (GSEA) was performed to explore the associated pathways and relationship between the DAIs and the tumor immune microenvironment, and the half-maximal inhibitory concentration (IC₅₀) of liver cancer drugs was calculated using the "pRRophetic" R package. We also detected the expression of SEMA7A in paired tumor and adjacent tissues from liver cancer patients. RESULTS: We constructed and validated a prognostic model based on 7 DAIs (NR4A3, SEMA7A, IL11, AR, BIRC5, EGF, and SPP1), and obtained consistent results in both the TCGA training cohort and GEO validation cohort (GSE14520), where the patients in the low-risk group were characterized by more favorable clinical outcomes and immune status. By integrating this prognostic signature with clinical information, a composite nomogram was generated. Somatic mutation analysis showed that TTN, TP53, and CTNNB1 mutations accounted for the largest proportion of total mutations, and the patients in the low-risk-low-TMB group had higher survival rate. Drug sensitivity analysis revealed differences in sensitivity to chemotherapeutic agents between high- and low-risk groups and between TP53 mutations and non-mutations. In clinical tissue specimens, SEMA7A expression was significantly higher in liver cancer tissues than in the adjacent tissues. CONCLUSIONS We established a new prognostic model based on DAIs for predicting clinical outcomes and therapeutic response of patients with primary liver cancer.
Humans ; Liver Neoplasms/diagnosis* ; Prognosis ; Anoikis ; Nomograms ; Computational Biology ; Tumor Microenvironment ; Semaphorins/metabolism*

Objective To explore the biological mechanism of radiation resistance in esophageal squamous cell carcinoma(ESCC)and search for effective sensitization targets.Methods We retrieved 186 signaling pathways and related gene information from the MSigDB database.We also obtained RNA transcriptome data of ESCC patients using the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.We collected clinical pathological characteristics and tissue samples of 97 ESCC patients in our hospital from 2013 to 2020.Gene set variation analysis(GSVA)was made to calculate KEGG signaling pathway score,radiotherapy resistance related signaling pathways were screened through random forest algorithm,key genes in the pathway were screened using DESeq2,and a radiotherapy efficacy prediction model was constructed based on support vector machine-recursive feature elimination(SVM-RFE).The results were validated through experiments such as Western blotting and clonogenic assay.Results Based on the KEGG signaling pathway and GSVA enrichment score,random forest analysis showed that in the TCGA and GSE45670 cohorts,the contribution of tryptophan metabolism pathway enrichment values to radiation resistance in ESCC was significantly better than that of the other pathways.DESeq2 analysis revealed that key molecules in the tryptophan metabolism pathway,namely,IDO1,ALDH1B1,AOC1,INMT,AFMID and ALDH7A1,were significantly differentially expressed in the resistant and sensitive groups of ESCC.Based on the SVM-RFE algorithm,the AUC was 0.77,which could accurately predict the radiotherapy efficacy of ESCC.Western blotting experiments showed that IDO1 was highly expressed in ESCC cells,and IDO1 inhibitor treatment significantly inhibited the survival ability and radiosensitivity of KYSE-410 cells.In the enrolled patients of our hospital,immunohistochemical studies showed that IDO1 was highly expressed in the radiotherapy resistant group of ESCC and was associated with poor radiotherapy prognosis in ESCC patients.In addition,further testing showed that the expression of IDO1 in patient samples from our hospital was positively correlated with its PD-L1 expression,but negatively correlated with the infiltration ratio of CD3/CD8 immune cells.Conclusion Tryptophan catabolism is associated with radiation resistance in ESCC,and the key enzyme IDO1 in tryptophan metabolism can be used as a therapeutic target for radiosensitization in ESCC.

Objective To explore the biological mechanism of radiation resistance in esophageal squamous cell carcinoma(ESCC)and search for effective sensitization targets.Methods We retrieved 186 signaling pathways and related gene information from the MSigDB database.We also obtained RNA transcriptome data of ESCC patients using the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.We collected clinical pathological characteristics and tissue samples of 97 ESCC patients in our hospital from 2013 to 2020.Gene set variation analysis(GSVA)was made to calculate KEGG signaling pathway score,radiotherapy resistance related signaling pathways were screened through random forest algorithm,key genes in the pathway were screened using DESeq2,and a radiotherapy efficacy prediction model was constructed based on support vector machine-recursive feature elimination(SVM-RFE).The results were validated through experiments such as Western blotting and clonogenic assay.Results Based on the KEGG signaling pathway and GSVA enrichment score,random forest analysis showed that in the TCGA and GSE45670 cohorts,the contribution of tryptophan metabolism pathway enrichment values to radiation resistance in ESCC was significantly better than that of the other pathways.DESeq2 analysis revealed that key molecules in the tryptophan metabolism pathway,namely,IDO1,ALDH1B1,AOC1,INMT,AFMID and ALDH7A1,were significantly differentially expressed in the resistant and sensitive groups of ESCC.Based on the SVM-RFE algorithm,the AUC was 0.77,which could accurately predict the radiotherapy efficacy of ESCC.Western blotting experiments showed that IDO1 was highly expressed in ESCC cells,and IDO1 inhibitor treatment significantly inhibited the survival ability and radiosensitivity of KYSE-410 cells.In the enrolled patients of our hospital,immunohistochemical studies showed that IDO1 was highly expressed in the radiotherapy resistant group of ESCC and was associated with poor radiotherapy prognosis in ESCC patients.In addition,further testing showed that the expression of IDO1 in patient samples from our hospital was positively correlated with its PD-L1 expression,but negatively correlated with the infiltration ratio of CD3/CD8 immune cells.Conclusion Tryptophan catabolism is associated with radiation resistance in ESCC,and the key enzyme IDO1 in tryptophan metabolism can be used as a therapeutic target for radiosensitization in ESCC.

Objective:To evaluate the effects of acupuncture combined with Tongbi Yinao Decoction in the treatment of isolated vertigo due to posterior circulation ischemia.Methods:A total of 78 elderly patients with isolated vertigo due to posterior circulation ischemia who were admitted to the Traditional Chinese Medicine Rehabilitation Department of Meishan People's Hospital from February 2019 to February 2022 were selected as the study subjects. They were divided into two groups by open randomized parallel control trail method, with 39 cases in each group. The control group was given conventional Western medicine treatment and oral administration of flunarizine hydrochloride capsules. On this basis, the observation group was treated with acupuncture combined with Tongbi Yinao Decoction. Both groups received 2 months of treatment. TCM syndrome scores before and after treatment were recorded. The Mini Mental State Examination (MMSE) was used to evaluate the patients' intelligence level. Transcranial Doppler ultrasound was used to detect blood flow velocity of the basilar artery, left vertebral artery and right vertebral artery. The blood rheometer was used to detect plasma viscosity, whole blood low shear viscosity and whole blood high shear viscosity. Adverse reactions that occurred during treatment were recorded, and clinical efficacy was evaluated.Results:The total effective rates in the observation group and the control group were 94.87% (37/39) and 76.92% (30/39), with statistical significance ( χ2=5.19, P=0.023). After treatment, the observation group in terms of vertigo and dizziness (1.05±0.12 vs. 2.14±0.74, t=9.08), chest distress and nausea (0.97±0.10 vs. 2.06±0.61, t=11.01), cyanosis of lip and nail (1.07±0.88 vs. 2.55±0.70, t=8.22), scaly dry skin (0.85±0.22 vs. 2.02±0.84, t=8.42) and the total score (3.94±1.32 vs. 8.77±2.89, t=9.49) were lower than those in the control group ( P<0.01). The MMSE score (26.39±2.20 vs. 24.20±2.37, t=4.01) was higher than that of the control group ( P<0.01). After treatment, blood flow velocity of the basilar artery [(37.55±3.61) cm/s vs. (33.50±2.96) cm/s, t=5.42], left vertebral artery [(34.27±4.87) cm/s vs. (30.58±3.74) cm/s, t=3.75] and right vertebral artery [(38.74±5.21) cm/s vs. (35.17±4.54) cm/s, t=3.23] in the observation group were higher than those in the control group ( P<0.01); The plasma viscosity [(1.32±0.19) mPa?s vs. (1.45±0.21) mPa?s, t=20.28], whole blood low shear viscosity [(8.71±0.35) mPa?s vs. (8.97±0.38) mPa?s, t=3.14] and whole blood high shear viscosity [(5.41±0.39) mPa?s vs. (5.92±0.43) mPa?s , t=5.49] were lower than those in the control group ( P<0.01). During treatment, the incidence rates of adverse reactions in the observation group and the control group were 28.2% (11/39) and 20.5% (8/39), without statistical significance ( χ2=0.63, P=0.429). Conclusion:Acupuncture combined with Tongbi Yinao Decoction can effectively maintain hemodynamics and cerebral blood flow of patients with isolated vertigo due to posterior circulation ischemia, and improve clinical efficacy, with good safety.

Objective:To investigate the efficacy of one-stage anterior debridement and bone graft fusion for the treatment of cervical pyogenic spondylodiscitis.Methods:This is a retrospective case series study. Retrospective analysis of clinical data from 23 patients with cervical pyogenic spondylodiscitis treated with one-stage anterior approach debridement and bone graft fusion was performed in the Department of Spinal Surgery, the First Affiliated Hospital of Xinjiang Medical University from January 2015 to January 2020. There were 14 males and 9 females,aged (51.9±12.8) years (range:26 to 82 years). Preoperatively, 14 patients had neurological deficits, classified according to the American Spinal Injury Association (ASIA) impairment scale as follows: grade A in 1 case, grade B in 1 case, grade C in 5 cases, and grade D in 7 cases . All patients underwent the one-stage anterior debridement and fusion procedure. The surgical time, blood loss, hospital stay, fusion time, and surgical complications were documented. Clinical efficacy was assessed using the visual analogue scale (VAS), the neck disability index (NDI), and the ASIA impairment scale. Preoperative and postoperative data were compared using paired sample t tests, repeated measures analysis of variance, and generalized estimating equations. Results:All the 23 patients underwent the operative procedures successfully. The operation time was (102.8±19.8) minutes (range:60 to 140 minutes), blood loss was (84.4±40.2) ml (range:30 to 160 ml), and the length of hospital stay was (17.4±6.0) days (range:10 to 30 days). Blood cultures were positive for the causative pathogen in 14 cases (60.8% positivity rate), while 9 cases had negative results. Irrigation fluid cultures yielded the causative pathogen in 19 cases (82.6% positivity rate), with 4 cases negative. All patients were followed up for more than 12 months, with a follow-up duration of (19.0±5.9) months (range:12 to 36 months). At the final follow-up, VAS improved from (5.9±1.1) points preoperatively to (0.8±0.3) points; NDI improved from (38.3±6.0)% preoperatively to (9.3±3.0)%, with statistically significant differences (both P<0.01). All patients experienced improvement in neurological function, with the exception of one patient in grade C and two in grade D, all other patients recovered to grade E. The C 2-7 Cobb angle and the affected segment Cobb angle were corrected. white blood cell, erythrocyte sedimentation rate and C-reactive protein levels returned to normal. All patients achieved bony fusion, with a fusion time of (8.9±1.9) months (range:6 to 12 months). Two diabetic patients developed postoperative incision infection; no other surgery-related complications occurred in the remaining patients. Conclusion:One-stage anterior debridement and bone graft fusion can correct kyphosis, restore normal alignment, and improve neurological function in the treatment of single and double segment cervical pyogenic spondylodiscitis, representing a viable treatment option for cervical pyogenic spondylodiscitis.

Objective To compare the application of main concept analysis(MCA)and story narration as-sessment(SNA)in aphasia discourse assessment,and study their clinical applicability.Methods A total of 8 apha-sic and 22 healthy control subjects were recruited.Local sequential picture materials were used to elicit language samples.The differences between groups in the assessment results of the MCA and the SNA were compared,the consistency of the assessment results of the two methods were also analyzed.The inter-rater and the intra-rater reli-ability of the two methods was discussed.Results The results of the MCA showed that the number of accurate and complete(AC)main concepts(P＜0.01),the number of accurate and complete main concepts per minute(AC/min)(P＜0.05)and main concept scores(MC scores)(P＜0.05)of the aphasia group were significantly lower than those of the healthy group.The number of absent(AB)main concepts(P＜0.05)were significantly higher than those of the control group.As for the result of SNA,the score of the content of sub picture description(P＜0.05),the total score of sub picture description(P＜0.05)and the total score of overall description(P＜0.05)in the aphasia group were significantly less than those in the control group(P＜0.05).No significant difference be-tween the standardized scores of the two methods were observed,and inter-rater and the intra-rater reliability were both in a good range.Conclusion The clinical applicability of the two methods is excellent and the evaluation results are conststent.The MCA has outstanding advantages in evaluating the quality and quantity of information,while SNA examines the syntax and content organization,which can reflect the overall discourse performance.

Objective:To investigate the efficacy of one-stage anterior debridement and bone graft fusion for the treatment of cervical pyogenic spondylodiscitis.Methods:This is a retrospective case series study. Retrospective analysis of clinical data from 23 patients with cervical pyogenic spondylodiscitis treated with one-stage anterior approach debridement and bone graft fusion was performed in the Department of Spinal Surgery, the First Affiliated Hospital of Xinjiang Medical University from January 2015 to January 2020. There were 14 males and 9 females,aged (51.9±12.8) years (range:26 to 82 years). Preoperatively, 14 patients had neurological deficits, classified according to the American Spinal Injury Association (ASIA) impairment scale as follows: grade A in 1 case, grade B in 1 case, grade C in 5 cases, and grade D in 7 cases . All patients underwent the one-stage anterior debridement and fusion procedure. The surgical time, blood loss, hospital stay, fusion time, and surgical complications were documented. Clinical efficacy was assessed using the visual analogue scale (VAS), the neck disability index (NDI), and the ASIA impairment scale. Preoperative and postoperative data were compared using paired sample t tests, repeated measures analysis of variance, and generalized estimating equations. Results:All the 23 patients underwent the operative procedures successfully. The operation time was (102.8±19.8) minutes (range:60 to 140 minutes), blood loss was (84.4±40.2) ml (range:30 to 160 ml), and the length of hospital stay was (17.4±6.0) days (range:10 to 30 days). Blood cultures were positive for the causative pathogen in 14 cases (60.8% positivity rate), while 9 cases had negative results. Irrigation fluid cultures yielded the causative pathogen in 19 cases (82.6% positivity rate), with 4 cases negative. All patients were followed up for more than 12 months, with a follow-up duration of (19.0±5.9) months (range:12 to 36 months). At the final follow-up, VAS improved from (5.9±1.1) points preoperatively to (0.8±0.3) points; NDI improved from (38.3±6.0)% preoperatively to (9.3±3.0)%, with statistically significant differences (both P<0.01). All patients experienced improvement in neurological function, with the exception of one patient in grade C and two in grade D, all other patients recovered to grade E. The C 2-7 Cobb angle and the affected segment Cobb angle were corrected. white blood cell, erythrocyte sedimentation rate and C-reactive protein levels returned to normal. All patients achieved bony fusion, with a fusion time of (8.9±1.9) months (range:6 to 12 months). Two diabetic patients developed postoperative incision infection; no other surgery-related complications occurred in the remaining patients. Conclusion:One-stage anterior debridement and bone graft fusion can correct kyphosis, restore normal alignment, and improve neurological function in the treatment of single and double segment cervical pyogenic spondylodiscitis, representing a viable treatment option for cervical pyogenic spondylodiscitis.

ObjectiveTo construct rehabilitation competency framework (RCF) of the speciality of education and rehabilitation (SER-RCF) based on World Health Organization RCF, to innovate the curriculum system. MethodsThe competency for undergraduate level professionals in the speciality of education and rehabilitation were analyzed to develop curriculum using RCF theory and methodology. ResultsTalent training was a kind of competency-based and outcome-based education. SER-RCF integrated the competencies and activities in the areas of professionalism, practice, learning and development, management and leadership, and research required for professional work in education and rehabilitation around core values and beliefs. It also designed the training objectives of the speciality of education and rehabilitation: to be ethical and correct, to be physically and mentally healthy, to have a solid foundation, to be sustainable, to be co-operative and enjoyable, and to be reflective and enquiring. SER-RCF played a central role in developing the curriculum system of rehabilitation, education and psychology, and practice. ConclusionReshaping the undergraduate level curriculum system of education and rehabilitation based on RCF is not only the implementation of the construction concept of new medicine and new liberal arts, but also can effectively connect with the international standard of rehabilitation higher education.

ObjectiveTo investigate the comprehensive spoken communication performance of children with disabilities, and explore the related individual and environmental factors. MethodsFrom August to November, 2022, questionnaires of Communication Function Scale for Children based on ICF-CY were distributed online to parents of healthy children and children with disabilities aged two years to five years and eleven months in Shanghai, Nanjing and other areas. ResultsA total of 500 copies were sent out, and 407 valid questionnaires were returned, including 84 healthy children, 85 with hearing impairment, 119 with mental retardation, 35 with cerebral palsy and 84 with autism. There were significant differences in the comprehensive spoken communication function performance among the children with different impairment types (F = 127.618, P < 0.001). The comprehensive spoken communication ability was significantly poorer in the children with disabilities than in the healthy children (P < 0.05), and the ability was better in hearing-impaired children than in the children with other disabilities (P < 0.05). The higher the education of mother (r = -0.311, P < 0.001) and father (r = -0.280, P < 0.001), and family annual income (r = -0.228, P < 0.001), the better the children's comprehensive spoken communication performance; the children's comprehensive spoken communication performance was better when the family used Putonghua as unified communication language (r = 0.210, P < 0.001). ConclusionThe comprehensive spoken communication performance for children with disabilities is heterogeneous among different impairment types, and is affected by parents' education, family annual income, and family communication language.

Objective:To investigate the effect of the transcriptional coactivator Mediator 1 (Med1) on mouse hair regeneration, and to explore potential mechanisms.Methods:Med1 flox/flox C57BL/6J mice were mated with K14-Cre mice, and the mice with epidermis-specific knockout of Med1 gene, namely K14-Cre-expressing Med1 flox/flox mice (knockout group) , were obtained by using the Cre-Loxp system, while Med1 flox/flox mice without K14-Cre expression served as control group. Mice in the two groups (3 mice in each group) were raised together for 8 weeks followed by dorsal hair removal. Hair regeneration was observed for 12 consecutive days after hair removal. After 12 days, all mice in the two groups were sacrificed, their depilated and non-depilated dorsal skin tissues were resected, and total RNA was extracted from the tissues. Real-time quantitative PCR was performed to determine the mRNA expression of hair keratin genes, vitamin D receptor/β-catenin pathway-related genes, and genes associated with maintenance of hair follicle stem cell proliferation and quiescence. Paraffin-embedded sections of depilated and non-depilated mouse skin tissues were prepared, and immunofluorescence staining was conducted to determine the number of stem cells in the hair follicle bulge. Two-independent-sample t test was used for comparisons between two groups. Results:From days 0 to 12 after depilation, hair regeneration was delayed in the depilated skin area in the knockout group compared with the control group. Real-time quantitative PCR showed significantly decreased mRNA relative expression levels of hair keratin genes Ha1 and Krt2-16, vitamin D receptor/β-catenin pathway-related genes S100a3, Dlx3 and Tubb3, and genes associated with maintenance of hair follicle stem cell proliferation and quiescence including Lhx2, Sox9 and Nfatc1 in the depilated skin tissues in the knockout group (22.09 ± 12.32, 2.07 ± 0.20, 0.02 ± 0.01, 12.36 ± 2.12, 1.75 ± 0.46, 0.39 ± 0.02, 4.42 ± 0.76, 0.44 ± 0.07, respectively) compared with the control group (70.53 ± 9.46, 7.76 ± 0.49, 0.05 ± 0.01, 26.16 ± 2.96, 2.60 ± 0.14, 0.71 ± 0.09, 11.93 ± 0.42, 0.75 ± 0.04, respectively; t = 5.40, 18.64, 3.89, 6.57, 3.04, 6.10, 15.03, 6.18, respectively, all P < 0.05) . Immunofluorescence staining showed that the number of CD34 +K15 + hair follicle stem cells in the hair follicle bulge in both depilated and non-depilated skin tissues was significantly lower in the knockout group than in the control group. Conclusion:Med1 gene knockout may down-regulate the expression of downstream genes of the vitamin D receptor/β-catenin pathway and genes associated with maintenance of hair follicle stem cell proliferation and quiescence (Sox9, Nfatc1 and Lhx2) , and reduce the number of hair follicle stem cells, leading to hair follicle differentiation disorder and hair regeneration delay.