Machine learning framework develops neutrophil extracellular traps model for clinical outcome and immunotherapy response in lung adenocarcinoma.

Neutrophil extracellular traps (NETs) are novel inflammatory cell death in neutrophils. Emerging studies demonstrated NETs contributed to cancer progression and metastases in multiple ways. This study intends to provide a prognostic NETs signature and therapeutic target for lung adenocarcinoma (LUAD) patients. Consensus cluster analysis performed by 38 reported NET-related genes in TCGA-LUAD cohorts. Then, WGCNA network was conducted to investigate characteristics genes in clusters. Seven machine learning algorithms were assessed for training of the model, the optimal model was picked by C-index and 1-, 3-, 5-year ROC value. Then, we constructed a NETs signature to predict the overall survival of LUAD patients. Moreover, multi-omics validation was performed based on NETs signature. Finally, we constructed stable knockdown critical gene LUAD cell lines to verify biological functions of Phospholipid Scramblase 1 (PLSCR1) in vitro and in vivo. Two NETs-related clusters were identified in LUAD patients. Among them, C2 cluster was provided as "hot" tumor phenotype and exhibited a better prognosis. Then, WGCNA network identified 643 characteristic genes in C2 cluster. Then, Coxboost algorithm proved its optimal performance and provided a prognostic NETs signature. Multi-omics revealed that NETs signature was involved in an immunosuppressive microenvironment and predicted immunotherapy efficacy. In vitro and in vivo experiments demonstrated that knockdown of PLSCR1 inhibited tumor growth and EMT ability. Besides, cocultural assay indicated that the knockdown of PLSCR1 impaired the ability of neutrophils to generate NETs. Finally, tissue microarray (TMA) for LUAD patients verified the prognostic value of PLSCR1 expression. In this study, we focus on emerging hot topic NETs in LUAD. We provide a prognostic NETs signature and identify PLSCR1 with multiple roles in LUAD. This work can contribute to risk stratification and screen novel therapeutic targets for LUAD patients.

[5 cases of silicosis complicated with connective tissue diseases].

Long-term inhalation of silica dust can cause silicosis, but also may induce autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, anti-histidyl tRNA synthetase antibody (JO-1 antibody) syndrome. These two diseases can be isolated or combined. In this paper, the clinical characteristics of 5 cases of silicosis complicated with connective tissue diseases were analyzed and summarized to strengthen the clinical understanding of silicosis complicated with connective tissue diseases, so as to reduce its misdiagnosis and missed diagnosis, and provide reference for clinicians in diagnosis and treatment.

Clinical, imaging, and pathological characteristics of congenital infiltrating lipomatosis of the face.

Congenital infiltrating lipomatosis of the face (CILF) is a rare congenital disease of the head and neck region. In this study, the cases of 20 patients diagnosed with CILF were reviewed retrospectively to analyse the characteristics of the disease. The symptoms, signs, and clinical progression were investigated. Radiological changes were analysed according to the distribution of the trigeminal nerve. The pathological features of the fatty facial lesions, jaw hyperplasia, and lingual lesions were further identified. All 20 patients demonstrated hemifacial hypertrophy at birth. None had a family history of the disease. Significant radiological features of CILF (prevalence ≥90%) included thickened buccal subcutaneous fat, palatal submucosal fat, and temporal subcutaneous fat, maxillary tuberosity heteroplasia, and fatty infiltration of the masseteric intermuscular space. With regard to the trigeminal nerve, the frontal branch region (CNV1) was rarely affected, while the maxillary (CNV2) and mandibular (CNV3) branch regions showed considerable changes. Pathologically, CILF was observed to be characterized by the infiltration of mature adipose tissue into the adjacent buccal soft tissue, osteal remodelling surrounded by sheets of mature lipocytes and supporting fibrovascular stroma, and lingual hamartoma. In summary, CILF exhibits distinct characteristics that are related to the regions controlled by the maxillary and mandibular branches of the trigeminal nerve, suggesting that CILF may be associated with early neural development.

[Prognostic value of the Second Revision of the International Staging System in patients with newly diagnosed transplant-eligible multiple myeloma].

Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS (HR=2.37, 95%CI 1.30-4.30; HR=4.50, 95%CI 2.35-9.01) and OS (HR=4.20, 95%CI 1.50-11.80; HR=9.53, 95%CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

Factors influencing the occurrence of hyperuricemia and poor cardiac and renal outcomes in chronic kidney disease.

OBJECTIVE: The aim of our study was to analyze the factors influencing the occurrence of hyperuricemia and poor cardiac and renal outcomes in chronic kidney disease (CKD). PATIENTS AND METHODS: One hundred and sixteen patients with CKD admitted to our hospital from January 2022 to September 2022 were picked as the subjects. Fasting venous blood of these subjects was collected to value the serum uric acid (SUA) levels on an automatic biochemical analyzer. Patients were then grouped as the CKD-only group (n=80) and hyperuricemia group (n=36), according to the SUA results, or the good prognosis group (n=88) and poor prognosis group (n=28), according to the presence of cardiovascular diseases. The changes in laboratory indexes and clinical data were analyzed and compared. Multivariate logistic regression analysis was used to analyze the risk factors for combined hyperuricemia and the risk factors for poor cardiac and renal outcomes in patients with CKD. The correlation between SUA level and cardiac and renal indexes was analyzed by Pearson analysis. RESULTS: Patients in the CKD hyperuricemia group had markedly higher content of systolic blood pressure (SBP), diastolic blood pressure (DBP), B-type natriuretic peptide (BNP), urinary retinol-binding protein (RBP), urinary N-acetyl-ß-D glucosidase (NAG), much higher proportion of heart failure episodes history, and much lower content of total cholesterol (TC), albumin (Alb), hemoglobin (Hb), urinary α1-microglobulin (α1-MG), and glomerular filtration rate (eGFR) than the CKD-only group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for combined hyperuricemia in CKD patients (p < 0.05). Besides, eGFR, albumin, and hemoglobin were independent protective factors for combined hyperuricemia in CKD patients (p < 0.05). Compared with the good prognosis group, the content of BNP, SBP, DBP, urinary RBP, urinary NAG, and SUA was much higher, the proportion of heart failure episodes history was obviously higher, and the levels of Alb, Hb, TC, eGFR, and urinary α1-MG were sharply lower in the poor prognosis group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for poor cardiac and renal outcomes (p < 0.05), and eGFR was an independent protective factor for poor cardiac and renal outcomes in patients with CKD (p < 0.05). The SUA level in CKD patients was positively correlated with BNP and SBP (r=0.463, 0.215, p < 0.05), but negatively correlated with eGFR (r=0.463, 0.215, p < 0.05). CONCLUSIONS: The serum SUA level was elevated with the aggravation of the CKD stage. High serum SUA level is a risk factor for the development of hyperuricemia and poor cardio-renal outcomes in CKD patients, suggesting that early monitoring of changes in SUA levels may help assess the risk of cardio-renal outcomes in CKD patients.

[Epidemiological investigation of constipation in urban areas of Hangzhou, China].

Objective: To determine the prevalence and risk factors of constipation in Hangzhou urban areas by analyzing data from a recent epidemiological survey. Methods: From August 2022 to June 2023, a cross-sectional survey was conducted on 43 communities on eight streets in suburbs of Hangzhou, including Wangjiang, Sijiqing, Puyan, Changhe, Ziyang, Xiaoshanchengxiang, Zhuantang, and Banshan. Written questionnaires were filled out face to face by community doctors. The prevalence of constipation was investigated using a combination of the Bristol stool typing method and the Rome IV criteria. The risk factors for constipation were analyzed using multivariate logistic regression analysis. Results: The study cohort comprised 10,479 participants, 5551 of whom were male (53.0%) and 4928 female (47.0%). The overall prevalence of constipation was 10.6% (1107/10,479). The prevalence was 11.0% (613/5551) for male and 10.0% (494/4928) for female participants; this difference is not statistically significant (P>0.05).There were no significant differences in the prevalence of constipation between different categories of body mass index (P>0.05). The prevalence of constipation was highest in individuals aged 70 years and above, accounting for 15.4% (264/1717) of all cases. There were significant differences in the prevalence of constipation between different occupations, marital statuses, and educational levels (P<0.001). Patients with hypertension or diabetes mellitus had a higher prevalence of constipation than those without these conditions, those who had been taking long-term medication had a higher prevalence of constipation than those who did not, parents of children with constipation had a higher prevalence of constipation than those with children who did not have constipation, and there were other significant differences in various variables (P<0.001). Multivariate logistic regression analysis of modifiable factors revealed that eating less fruit (OR=1.284, 95%CI: 1.061-1.553, P=0.010), liking spicy and salty food (OR=1.234, 95%CI: 1.039-1.466, P=0.016), sleeping for too long (OR=1.644, 95%CI: 1.260-2.144, P<0.001), irregular sleep patterns (OR=1.370, 95%CI: 1.127-1.665, P=0.002) and minimal exercise (OR=1.388, 95% CI: 1.168-1.649, P<0.001) were all risk factors for constipation; whereas mix diets (OR=0.709,95%CI:0.608-0.826, P<0.001), meat diets (OR=0.604,95%CI: 0.495-0.736, P<0.001), moderate alcohol consumption (OR=0.659, 95% CI: 0.534-0.812, P<0.001), less or no drinking (OR=0.523, 95% CI: 0.428-0.638, P<0.001), and non-smoking (OR=0.819, 95%CI:0.674-0.995, P<0.001) protected against constipation. We found no association between dietary preferences and the risk of constipation (refined grains: OR=1.147, 95%CI:0.944-1.393, P=0.167; no specific preference: OR=0.935, 95%CI:0.783-1.117, P=0.459). The rate of agreement between self-evaluation of constipation by the respondents and objective criteria was higher for negatives (95.8%) than for positives (38.0%). Conclusion: The prevalence of constipation is relatively high in the urban population of Hangzhou. A good lifestyle and diet can significantly reduce its incidence. There should be more emphasis on preventive education, promotion of prevention of constipation, and advocacy for a healthy lifestyle.

Correlation study between bone metabolic markers, bone mineral density, and sarcopenia.

OBJECTIVE: To investigate the correlation between bone metabolism markers, bone mineral density (BMD), and sarcopenia. METHODS: A total of 331 consecutive patients aged ≥ 60 years who were hospitalized between November 2020 and December 2021 were enrolled. Participants were divided into sarcopenia and non-sarcopenia groups according to the Asian Working Group on Sarcopenia criteria (AWGS, 2019). The clinical data, bone metabolism markers (ß-CTX, N-MID, and TP1NP), and BMD were compared between the two groups. RESULTS: Age, ß-CTX, and N-MID of the sarcopenia group were higher than those of the non-sarcopenia group (P < 0.05), but the BMD T values were lower than those of the non-sarcopenia group (P < 0.05). Binary logistic regression analysis showed that increased femoral neck BMD (FNBMD) was a protective factor for sarcopenia, while increased ß-CTX was a risk factor. Pearson/Spearman correlation analysis showed that the diagnostic indices of sarcopenia were positively correlated with FNBMD and negatively correlated with ß-CTX and N-MID. Multiple linear regression analysis revealed that BMI and FNBMD significantly positively affected muscle strength and appendicular skeletal muscle mass (ASM). The FNBMD significantly positively affected physical performance, while ß-CTX significantly negatively affected muscle strength, ASM, and physical performance. CONCLUSION: Increased FNBMD may be a protective factor against sarcopenia, and increased ß-CTX may be a risk factor. The FNBMD significantly positively affected the diagnostic indices of sarcopenia, while ß-CTX significantly negatively affected them. BMD and bone metabolism marker levels may be considered in early screening for sarcopenia.

Burnout and turnover intention of primary health care providers during the COVID-19 pandemic in China.

OBJECTIVES: This study explored the changes and new characteristics of burnout and turnover intention of primary health care (PHC) providers during the COVID-19 pandemic in China. STUDY DESIGN: This was a cross-sectional study. METHODS: This study investigated 1326 PHC providers during the COVID-19 outbreak in 2022 in one district of Shanghai, China. Independent t-test or one-way analysis of variance (ANOVA) test were used to analyse the between-group variation of variables associated to burnout and turnover intention. Then, hierarchical regression analysis was used to further determine the impact of certain variables on burnout and turnover intention, the relationship of burnout on turnover intention and the possible moderating effect. RESULTS: The results showed that there was no significant change in the prevalence of overall burnout of PHC providers compared to the pre-epidemic period; however, there was a significant increase in high-level burnout. No significant change in turnover intention at the moderate level and above was observed. During the COVID-19 pandemic, PHC providers who were older, married, local and had a higher skill level had higher burnout, while PHC providers who were male, unmarried, non-local and separated from their family had a higher turnover intention. It was shown that burnout, with its three sub-dimensions, was a good predictor of turnover intention. The impact of burnout on turnover intention was shown to be alleviated by certain variables, including being married, living locally and receiving benefit packages, including the preferential education policy for children and talent incentive policies. CONCLUSIONS: Results from this study have highlighted the importance of paying attention to vulnerable groups of PHC providers, for example those who are separated from their families, during emergency situations. Various incentive tools could be comprehensively used to ensure the stability and efficiency of PHC human resources.

Hybrid Exercise Program Enhances Physical Fitness and Reverses Frailty in Older Adults: Insights and Predictions from Machine Learning.

PURPOSE: The declining physical condition of the older adults is a pressing issue. Wu Qin Xi exercise, despite being low-intensity, is highly effective among older adults. Inspired by its characteristics, we designed a new exercise program for frail older adults, combining strength, endurance, and Wu Qin Xi. Furthermore, we employed machine learning to predict whether frailty can be reversed in older adults after the intervention. METHODS: A total of 181 community-dwelling frail older adults aged 65 years or older participated in this single-center, randomized controlled study, with 54.7% (n=99) being female. The study assessed the effectiveness of several exercise modalities in reversing frailty. The Fried's frailty criterion was used to assess the degree of frailty of the subjects. Participants were assigned a three-digit code 001-163 and randomly assigned (1:1:1) by computer to three different groups based on the study participant number: the Wu Qin Xi group (WQX), the strength exercise mixed with endurance exercise training group (SE), and the WQXSE hybrid exercise group incorporated the above two. Body composition and frailty-related physical fitness factors were measured before and after a 24-week intervention. The measurements included Body height, Body mass, Timed Up and Go Test (TUGT), grip strength assessment (GS), 6min walk test (6 min WT), and 10 m maximum walk speed (10 m MWS). Data were analyzed using repeated measures ANOVA to determine group and time interaction effects and machine learning models were used to predict program effectiveness. RESULTS: A total of 163 participants completed the study, with 53.9% (n=88) of them being female. The two items, 10 m maximum walking speed (10 m MWS) and grip strength, were significantly affected by the interaction of group and time. Compared to the other two groups, the WQXSE group showed the most improvement in the item 10 m MWS. In addition, following 24 weeks of training, 68 (41.7%) of the initially frail older adults had reversed their frailty status. Among them, 19 (36.5%) were in the WQX group, 24 (44.4%) were in the WQXSE group, and 25 (43.9%) were in the SE group. The stacking model exhibited superior performance when compared to other algorithms. CONCLUSION: A hybrid exercise regimen comprising the Wu Qin Xi routine and exercises focused on both strength and endurance holds the potential to yield greater improvements in the physical fitness of older adults, as well as reducing frailty. Leveraging a stacking model, it is possible to forecast the likelihood of older adults successfully reversing their frailty status following participation in a prevention exercise program.

[Genome sequence analysis of two SARS-CoV-2 virus infections in Inner Mongolia, 2022].

The target gene sequences of the novel coronaviruses obtained by sequencing were compared with the reference sequences to analyze the genetic variation of the two cases of the novel coronaviruses from Inner Mongolia Autonomous Region in 2022 and to explore the sources of infection. The results showed that the two sequences belonged to different evolutionary branches, Delta (AY.122) and Omicron (BA.1.1), respectively. hCoV-19/Inner Mongolia/IVDC-591/2022 had 48 single nucleotide polymorphisms on the genome sequences, sharing 40 nucleotide mutation sites with a Mongolian strain; hCoV-19/Inner Mongolia/IVDC-592/2022 genome shared 57 nucleotide mutation sites with a UK strain, and the nucleotide mutation site identity was 100% (57/57). Phylogenetic analysis showed that the target gene sequences were not directly related to domestic novel coronavirus sequences during the same period, but were related to isolates from Europe and Mongolia.

TNF inhibitors associated with cardiovascular diseases and cardiometabolic risk factors: a Mendelian randomization study.

OBJECTIVE: There is still disagreement about whether anti-tumor necrosis factor (TNF) therapy is beneficial or detrimental to cardiovascular conditions. This two-sample Mendelian randomization (MR) study aimed to evaluate the effects of long-term tumor necrosis factor (TNF) inhibition on cardiovascular diseases (CVDs) and cardiometabolic risk factors via genetically proxied inhibition of tumor necrosis factor receptor 1 (TNFR1) and TNF. MATERIALS AND METHODS: Two genetic instruments were examined to mimic the long-term effect of TNF inhibitors. The first were single-nucleotide polymorphisms (SNPs) within or nearby drug-target genes TNFRSF1A and TNF (encoding TNFR1 and TNF) associated with circulating CRP levels. The other instruments were the expression quantitative trait loci (eQTLs) near the genes. Inverse variance-weighted MR (IVW-MR) and summary-based MR (SMR) methods were employed to estimate causal effects. RESULTS: In IVW-MR analysis, TNF-mediated circulating CRP levels were significantly associated with 4 out of 12 CVDs, including hypertension [odds ratio (OR) = 1.13; 95% CI, 1.09-1.18], coronary artery disease (OR = 3.18; 95% CI, 1.77-5.71), coronary atherosclerosis (OR = 1.05; 95% CI, 1.02-1.08) and type 2 diabetes (OR = 3.48; 95% CI, 1.98-6.10). These findings were also validated in the FinnGen study. Moreover, TNF inhibition was also associated with total cholesterol, triglycerides, apolipoprotein B, systolic blood pressure, serum cystatin C, height, weight, and body mass index. CONCLUSIONS: In this study, the decrease in several CVDs and cardiometabolic risk factors has been found to be causally associated with genetically proxied TNF inhibitors.

[Curative effects of ultrathin anterolateral femoral flap in one-stage split-finger repair of palmar combined with multiple finger wounds].

Objective: To explore the curative effects of ultrathin anterolateral femoral flap in one-stage split-finger repair of palmar combined with multiple finger wounds. Methods: A retrospective observational study was conducted. From October 2016 to June 2018, 20 patients with wounds on palms and multiple fingers who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 15 males and 5 females, aged 18 to 77 years. After debridement, the wound area was 8 cm×4 cm-17 cm×12 cm. The wound was repaired by ultrathin anterolateral femoral flap with area of 9 cm×5 cm to 19 cm×13 cm. According to the wound condition of finger, the finger division was performed in one stage, and the length-to-width ratio of the split-finger flap was 2.0:1.0-2.5:1.0. During the surgery, the descending branches of lateral circumflex femoral artery and accompanying vein of flap were anastomosed end-to-end to the radial artery and vein in the recipient area, respectively, and the anterolateral femoral cutaneous nerve of flap was bridged with the superficial branch of radial nerve in the recipient area. The wounds in the donor area of flap in 14 patients were sutured directly, the wounds in the donor area of flap in 3 patients were repaired by relay superficial iliac circumflex artery perforator flap, and the wounds in the donor area of flap in 3 patients were covered by free trunk medium-thick skin graft. The survival of flap, occurrence of vascular crisis and other complications, and healing of wounds in the donor area of flap were recorded. The appearance of flap, scar hyperplasia in the donor and recipient areas and the patients' satisfaction with the shape and function of the donor and recipient areas were followed up. In 1 year after surgery, the two-point discrimination distance of the flap was measured, and the recovery of hand function was evaluated by the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association. Results: The flaps of 17 patients survived without vascular crisis or other complications after surgery. The flap of 1 patient had poor blood circulation and partial necrosis, and the wound was healed 14 days after dressing change and grafting of split-thickness skin graft from head. Two patients had mild cyanosis at the margin of flap after surgery, which disappeared spontaneously 5 days later. Incisions at donor site, relay flaps, and skin grafts of all patients survived well. After surgery, the color and texture of flap were basically the same as that of the normal skin of hand, and linear scars were observed in the donor and recipient areas. The patients were satisfied with the recovery of appearance and function of donor and recipient areas. After 1 year of follow-up, the patients' hand sensory function recovered well, the two-point discrimination distance of flap was 4-6 mm, and the recovery of hand function was evaluated as excellent in 18 cases and good in 2 cases. Conclusions: The ultrathin anterolateral femoral flap in repairing the palmar combined with multiple finger wounds in one-stage split-finger can significantly reduce the number of surgeries and improve the function and beauty of the hand, so it is worthy of clinical promotion.

Using CT imaging features to predict visceral pleural invasion of non-small-cell lung cancer.

AIM: To examine the diagnostic performance of different models based on computed tomography (CT) imaging features in differentiating the invasiveness of non-small-cell lung cancer (NSCLC) with multiple pleural contact types. MATERIALS AND METHODS: A total of 1,573 patients with NSCLC (tumour size ≤3 cm) were included retrospectively. The clinical and pathological data and preoperative imaging features of these patients were investigated and their relationships with visceral pleural invasion (VPI) were compared statistically. Multivariate logistic regression was used to eliminate confounding factors and establish different predictive models. RESULTS: By univariate analysis and multivariable adjustment, surgical history, tumour marker (TM), number of pleural tags, length of solid contact and obstructive inflammation were identified as independent risk predictors of pleural invasiveness (p=0.014, 0.003, <0.001, <0.001, and 0.017, respectively). In the training group, comparison of the diagnostic efficacy between the combined model including these five independent predictors and the image feature model involving the latter three imaging predictors were as follows: sensitivity of 88.9% versus 77% and specificity of 73.5% versus 84.1%, with AUC of 0.868 (95% CI: 0.848-0.886) versus 0.862 (95% CI: 0.842-0.880; p=0.377). In the validation group, the sensitivity and specificity of these two models were as follow: the combined model, 93.5% and 74.3%, the imaging feature model, 77.4% and 81.3%, and their areas under the curve (AUCs) were both 0.884 (95% CI: 0.842-0.919). The best cut-off value of length of solid contact was 7.5 mm (sensitivity 68.9%, specificity 75.5%). CONCLUSIONS: The image feature model showed great potential in predicting pleural invasiveness, and had comparable diagnostic efficacy compared with the combined model containing clinical data.

Fluorapatite nanorod arrays with enamel-like bundle structure regulated by iron ions.

Pigmented rodent tooth enamel is mainly composed of parallel hydroxyapatite nanorods and a small amount of organic matrix. These hydroxyapatite nanorods tend to be carbonated and contain traces of iron, fluorine, and magnesium. The pigmented rodent tooth enamel which contains trace iron is stronger and more resistant to acid corrosion than unpigmented rodent enamel, which could provide inspiration for the preparation and synthesis of high performance and corrosion resistant artificial materials. However, the regulatory role and mechanical enhancement of iron ions in enamel growth are unclear. Here, we synthesized enamel-like fluorapatite nanorod arrays in vitro using a mineralization technique at room-temperature. To investigate the regulatory effect of iron ions on the fluorapatite nanorod arrays (FAP-Fe), the phosphate solution is slowly transfused dropwise in the calcium ion solution, and different concentrations of iron ions are added to the calcium ion solution in advance. We demonstrated that fluorapatite nanorod arrays (FAP) can be epitaxially grown from amorphous calcium phosphate nanoparticles and iron ions can improve the microstructure of FAP nanorod arrays and obtain the same enamel bundle structure as the natural enamel. Moreover, high concentration of iron ions can inhibit the crystallization of fluorapatite. The FAP-Fe nanorod arrays controlled by 0.02 mM Fe3+ have good mechanical properties. Their hardness is 1.34 ± 0.02 GPa and Young's modulus is 65.3 ± 0.4 GPa, respectively. This work is helpful to understand the role of trace elements in natural enamel in the regulation of enamel formation and to provide a theoretical foundation for the preparation of high strength artificial composites, which can play a greater role in the fields of biological alternative materials, anti-oil coating, oil/water separation, anti-bioadhesion and so on.

CREB3L2 Regulates Hemidesmosome Formation during Epithelial Sealing.

The long-term success rate of dental implants can be improved by establishing a favorable biological sealing with a high-quality epithelial attachment. The application of mesenchymal stem cells (MSCs) holds promise for facilitating the soft tissue integration around implants, but the molecular mechanism is still unclear and the general application of MSC sheet for soft tissue integration is also relatively unexplored. We found that gingival tissue-derived MSC (GMSC) sheet treatment significantly promoted the expression of hemidesmosome (HD)-related genes and proteins in gingival epithelial cells (GECs). The formation of HDs played a key role in strengthening peri-implant epithelium (PIE) sealing. Further, high-throughput transcriptome sequencing showed that GMSC sheet significantly upregulated the PI3K/AKT pathway, confirming that cell adhesion and HD expression in GECs were regulated by GMSC sheet. We observed that the expression of transcription factor CREB3L2 in GECs was downregulated. After treatment with PI3K pathway inhibitor LY294002, CREB3L2 messenger RNA and protein expression levels were upregulated. Further experiments showed that overexpression or knockdown of CREB3L2 could significantly inhibit or promote HD-related genes and proteins, respectively. We confirmed that CREB3L2 was a transcription factor downstream of the PI3K/AKT pathway and participated in the formation of HDs regulated by GMSC sheet. Finally, through the establishment of early implant placement model in rats, we clarified the molecular function of CREB3L2 in PIE sealing as a mechanical transmission molecule in GECs. The application of GMSC sheet-implant complex could enhance the formation of HDs at the implant-PIE interface and decrease the penetration distance of horseradish peroxidase between the implant and PIE. Meanwhile, GMSC sheet reduced the length of CREB3L2 protein expression on PIE. These findings elucidate the potential function and molecular mechanism of MSC sheet regulating the epithelial sealing around implants, providing new insights and ideas for the application of stem cell therapy in regenerative medicine.

[Long term follow-up evaluation of combined surgery for congenital tibial pseudarthrosis in children].

Objective: To explore the long-term effect of combined surgery for the treatment of congenital tibial pseudarthrosis in children. Methods: The clinical data of 44 children with congenital tibial pseudarthrosis who underwent combined surgery (tibial pseudarthrosis tissue resection, intramedullary rod fixation, Ilizarov external fixator fixation, wrapped autologous iliac bone graft) from August 2007 to October 2011 at the Department of Pediatric Orthopedics, Hunan Children's Hospital were collected retrospectively. There were 33 males and 11 females. The age at the time of surgery was (3.7±2.2)years (range:0.6 to 12.4 years), including 25 cases under 3 years old and 19 cases above 3 years old.Among them, 37 cases were complicated with neurofibromatosis type 1.The operation status, postoperative complications and follow-up results were recorded. Results: The follow-up time after surgery was (10.9±0.7)years (range:10 to 11 years).Thirty-nine out of 44 patients (88.6%) achieved initial healing of tibial pseudarthrosis, with an average healing time of (4.3±1.1)months (range:3 to 10months).In the last follow-up, 36 cases (81.8%) had unequal tibial length, 20 cases (45.4%) had refractures, 18 cases (40.9%) had ankle valgus, 9 cases (20.4%) had proximal tibial valgus, and 11 cases (25.0%) had high arched feet.Nine cases (20.4%) developed distal tibial epiphyseal plate bridging.17 cases (38.6%) had abnormal tibial mechanical axis.Seven cases (15.9%) developed needle infection, and one case (2.3%) developed tibial osteomyelitis. 21 patients (47.7%) had excessive growth of the affected femur.Five patients (11.3%) had ankle stiffness, and 34 patients (77.2%) had intramedullary rod displacement that was not in the center of the tibial medullary cavity.Among them, 8 cases (18.1%) protruded the tibial bone cortex and underwent intramedullary rod removal.18 children have reached skeletal maturity, while 26 children have not been followed up until skeletal maturity. Conclusion: Combined surgery for the treatment of congenital pseudarthrosis of the tibia in children has a high initial healing rate, but complications such as unequal tibia length, refracture, and ankle valgus occur during long-term follow-up, requiring multiple surgical treatments.

Effects of water-sodium balance and regulation of electrolytes associated with antidiabetic drugs.

As the prevalence of diabetes rises, the use of antidiabetic drugs becomes more frequent. Thus, focusing on the effects of these drugs on water-sodium balance and electrolyte regulation is necessary. This review discusses the effects and the mechanisms behind them. Several sulfonylureas, such as chlorpropamide, methanesulfonamide, and tolbutamide, exhibit water-retaining properties. Other sulfonylureas, such as glipizide, glibenclamide, acetohexamide, and tolazamide, are not antidiuretic or even diuretic. Numerous clinical studies showed that metformin can reduce serum magnesium concentrations and may have an effect on the cardiovascular system, but the specific mechanism remains to be discussed. Different opinions exist about the mechanisms of thiazolidinedione-induced fluid retention. Sodium-glucose cotransporter 2 inhibitors can cause osmotic diuresis and natriuresis and elevated serum potassium and magnesium concentrations. Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors can enhance urine sodium excretion. At the same time, increased urinary sodium caused by sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors reduce blood pressure and plasma volume, thereby protecting the heart. Insulin has a sodium-retaining effect and is also associated with hypokalemia, hypomagnesemia, and hypophosphatemia. Several of the aforementioned pathophysiological changes and mechanisms have been discussed, and conclusions have been drawn. However, further investigation and discussion are still warranted.