Exploring the link between walking and lung cancer risk: a two-stage Mendelian randomization analysis.

BACKGROUND: Previous observational research showed a potential link between physical activities such as walking and the risk of lung cancer. However, Mendelian randomization (MR) studies suggested there was no association between moderate to vigorous physical activity and lung cancer risk. We speculated that specific physical activities may be associated with lung cancer risk. Consequently, we conducted an MR study to examine the potential relationship between walking and the risk of lung cancer. METHODS: We collected genetic summary data from UK Biobank. After excluding SNPs with F values less than 10 and those associated with confounding factors, we conducted a MR analysis to assess the causal effects between different types of walk and lung cancer. We also performed sensitivity analysis to validate the robustness of our findings. Finally, we analyzed the possible mediators. RESULTS: MR analysis showed number of days/week walked for 10 + minutes was associated with a reduced risk of lung cancer risk (OR = 0.993, 95% CI = 0.987-0.998, P = 0.009). Additionally, usual walking pace was identified as a potentially significant factor in lowering the risk (OR = 0.989, 95% CI = 0.980-0.998, P = 0.015). However, duration of walks alone did not show a significant association with lung cancer risk (OR = 0.991, 95%CI = 0.977-1.005, P = 0.216). The sensitivity analysis confirmed the robustness of these findings. And number of days/week walked for 10 + minutes could affect fed-up feelings and then lung cancer risk. There was a bidirectional relationship between usual walking pace and sedentary behaviors (time spent watching TV). CONCLUSION: The study unveiled a genetically predicted causal relationship between number of days/week walked for 10 + minutes, usual walking pace, and the risk of lung cancer. The exploration of potential mediators of walking phenotypes and their impact on lung cancer risk suggests that specific physical activities may reduce the risk of lung cancer.

Treatment patterns and clinical outcomes of patients with resectable non-small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World).

BACKGROUND: Neoadjuvant immunotherapy has ushered in a new era of perioperative treatment for resectable non-small cell lung cancer (NSCLC). However, large-scale data for verifying the efficacy and optimizing the therapeutic strategies of neoadjuvant immunochemotherapy in routine clinical practice are scarce. METHODS: NeoR-World (NCT05974007) was a multicenter, retrospective cohort study involving patients who received neoadjuvant immunotherapy plus chemotherapy or chemotherapy alone in routine clinical practice from 11 medical centers in China between January 2010 and March 2022. Propensity score matching was performed to address indication bias. RESULTS: A total of 408 patients receiving neoadjuvant immunochemotherapy and 684 patients receiving neoadjuvant chemotherapy were included. The pathologic complete response (pCR) and major pathologic response (MPR) rates of the real-world neoadjuvant immunochemotherapy cohort were 32.8% and 58.1%, respectively. Notably, patients with squamous cell carcinoma exhibited significantly higher pCR and MPR rates than those with adenocarcinoma (pCR, 39.2% vs 16.5% [P < .001]; MPR, 66.6% vs 36.5% [P < .001]), whereas pCR and MPR rates were comparable among patients receiving different neoadjuvant cycles. In addition, the 2-year rates of disease-free survival (DFS) and overall survival (OS) rate were 82.0% and 93.1%, respectively. Multivariate analyses identified adjuvant therapy as an independent prognostic factor for DFS (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.89; P = .018) and OS (HR, 0.28; 95% CI, 0.13-0.58; P < .001). A significantly longer DFS with adjuvant therapy was observed in patients with non-pCR or 2 neoadjuvant cycles. We observed significant benefits in pCR rate (32.4% vs 6.4%; P < .001), DFS (HR, 0.50; 95% CI, 0.38-0.68; P < .001) and OS (HR, 0.61; 95% CI, 0.40-0.94; P = .024) with immunotherapy plus chemotherapy compared to chemotherapy alone both in the primary propensity-matched cohort and across most key subgroups. CONCLUSIONS: The study validates the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy alone for NSCLC. Adjuvant therapy could prolong DFS in patients receiving neoadjuvant immunochemotherapy, and patients with non-pCR or those who underwent 2 neoadjuvant cycles were identified as potential beneficiaries of adjuvant therapy.

Calcium Orthophosphate in Liposomes for Co-Delivery of Doxorubicin Hydrochloride/Paclitaxel in Breast Cancer.

Nanoparticles (NPs) show great advantages in cancer treatment by enabling controlled and targeted delivery of payloads to tumor sites through the enhanced permeability and retention (EPR) effect. In this study, highly effective pH-responsive and biodegradable calcium orthophosphate@liposomes (CaP@Lip) NPs with a diameter of 110 ± 20 nm were designed and fabricated. CaP@Lip NPs loaded with hydrophobic paclitaxel and hydrophilic doxorubicin hydrochloride achieved excellent drug loading efficiencies of 70 and 90%, respectively. Under physiological conditions, the obtained NPs are negatively charged. However, they switched to positively charged when exposed to weak acidic environments by which internalization can be promoted. Furthermore, the CaP@Lip NPs exhibit an obvious structural collapse under acid conditions (pH 5.5), which confirms their excellent biodegradability. The "proton expansion" effect in endosomes and the pH-responsiveness of the NPs facilitate the release of encapsulated drugs from individual channels. The effectiveness and safety of the drug delivery systems were demonstrated through in vitro and in vivo experiments, with a 76% inhibition of tumor growth. These findings highlight the high targeting ability of the drug-loaded NPs to tumor sites through the EPR effect, effectively suppressing tumor growth and metastasis. By combining CaP NPs and liposomes, this study not only resolves the toxicity of CaP but also enhances the stability of liposomes. The CaP@Lip NPs developed in this study have significant implications for biomedical applications and inspire the development of intelligent and smart drug nanocarriers and release systems for clinical use.

TIGIT/CD47 dual high expression predicts prognosis and is associated with immunotherapy response in lung squamous cell carcinoma.

BACKGROUND: Recent studies indicated that T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) and cluster of differentiation 47 (CD47) have emerged as new potential immunotherapy targets. However, the roles of TIGIT and CD47 in lung squamous cell carcinoma (LUSC) have not been fully illustrated. METHODS: The specimens and clinicopathological information from 190 LUSC patients who underwent surgeries in our center were retrospectively collected. Immunohistochemical staining for TIGIT and CD47 was conducted. Transcriptional and clinical data of 479 LUSC were downloaded from The Cancer Genome Atlas (TCGA). RESULTS: In the TCGA LUSC cohort, 142 (29.6%) cases were TIGIT/CD47 dual high expression at RNA level. The expression levels of TIGIT and CD47 were significantly correlated (p < 0.001). The proportions of patients with high TIGIT expression (p = 0.001) and high TIGIT/CD47 dual high expression (p = 0.049) were both higher in female cases. Advanced TNM stage (p = 0.006) and TIGIT/CD47 dual high expression (p = 0.047) were independent prognostic factors for LUSC. In the 190 LUSC cohort of our center, 75 (39.5%) cases were TIGIT/CD47 dual high expression at protein level. Cross-table analysis showed a correlation between TIGIT and CD47 expression. Older age (p = 0.001), advanced TNM stage (p < 0.001) and TIGIT/CD47 dual high expression (p = 0.046) were independent prognostic factors in our cohort. CONCLUSION: We found that TIGIT and CD47 dual high expression was associated with poor prognosis in LUSC. We speculated that patients with dual high expression of CD47/TIGIT might be suitable for new target immunotherapy in the future.

A four-gene prognostic signature for predicting the overall survival of patients with lung adenocarcinoma.

BACKGROUND: The prognosis of patients for lung adenocarcinoma (LUAD) is known to vary widely; the 5-year overall survival rate is just 63% even for the pathological IA stage. Thus, in order to identify high-risk patients and facilitate clinical decision making, it is vital that we identify new prognostic markers that can be used alongside TNM staging to facilitate risk stratification. METHODS: We used mRNA expression from The Cancer Genome Atlas (TCGA) cohort to identify a prognostic gene signature and combined this with clinical data to develop a predictive model for the prognosis of patients for lung adenocarcinoma. Kaplan-Meier curves, Lasso regression, and Cox regression, were used to identify specific prognostic genes. The model was assessed via the area under the receiver operating characteristic curve (AUC-ROC) and validated in an independent dataset (GSE50081) from the Gene Expression Omnibus (GEO). RESULTS: Our analyses identified a four-gene prognostic signature (CENPH, MYLIP, PITX3, and TRAF3IP3) that was associated with the overall survival of patients with T1-4N0-2M0 in the TCGA dataset. Multivariate regression suggested that the total risk score for the four genes represented an independent prognostic factor for the TCGA and GEO cohorts; the hazard ratio (HR) (high risk group vs low risk group) were 2.34 (p < 0.001) and 2.10 (p = 0.017). Immune infiltration estimations, as determined by an online tool (TIMER2.0) showed that CD4+ T cells were in relative abundance in the high risk group compared to the low risk group in both of the two cohorts (both p < 0.001). We established a composite prognostic model for predicting OS, combined with risk-grouping and clinical factors. The AUCs for 1-, 3-, 5- year OS in the training set were 0.750, 0.737, and 0.719; and were 0.645, 0.766, and 0.725 in the validation set. The calibration curves showed a good match between the predicted probabilities and the actual probabilities. CONCLUSIONS: We identified a four-gene predictive signature which represents an independent prognostic factor and can be used to identify high-risk patients from different TNM stages of LUAD. A new prognostic model that combines a prognostic gene signature with clinical features exhibited better discriminatory ability for OS than traditional TNM staging.

Elaboration on the architecture of pH-sensitive surface charge-adaptive micelles with enhanced penetration and bactericidal activity in biofilms.

BACKGROUND: Biofilm formation is one of the main reasons for persistent bacterial infections. Recently, pH-sensitive copolymers have fascinated incredible attention to tackle biofilm-related infections. However, the proper incorporation of pH-sensitive segments in the polymer chains, which could significantly affect the biofilms targeting ability, has not been particularly investigated. Herein, we synthesized three types of pH-sensitive copolymers based on poly (ß-amino ester) (PAE), poly (lactic-co-glycolic acid) (PLA) and polyethylene glycol (PEG), PAE-PLA-mPEG (A-L-E), PLA-PAE-mPEG (L-A-E) and PLA-PEG-PAE (L-E-A) to address this issue. RESULTS: The three copolymers could self-assemble into micelles (MA-L-E, ML-A-E and ML-E-A) in aqueous medium. Compared with MA-L-E and ML-A-E, placing the PAE at the distal PEG end of PLA-PEG to yield PLA-PEG-PAE (ML-E-A) was characterized with proper triggering pH, fully biofilm penetration, and high cell membrane binding affinity. Further loaded with Triclosan (TCS), ML-E-A/TCS could efficiently kill the bacteria either in planktonic or biofilm mode. We reasoned that PAE segments would be preferentially placed near the surface and distant from the hydrophobic PLA segments. This would increase the magnitude of surface charge-switching capability, as the cationic PAE+ would easily disassociate from the inner core without conquering the additional hydrophobic force arising from covalent linkage with PLA segments, and rapidly rise to the outermost layer of the micellar surface due to the relative hydrophilicity. This was significant in that it could enable the micelles immediately change its surface charge where localized acidity occurred, and efficiently bind themselves to the bacterial surface where they became hydrolyzed by bacterial lipases to stimulate release of encapsulated TCS even a relatively short residence time to prevent rapid wash-out. In vivo therapeutic performance of ML-E-A/TCS was evaluated on a classical biofilm infection model, implant-related biofilm infection. The result suggested that ML-E-A/TCS was effective for the treatment of implant-related biofilm infection, which was proved by the efficient clearance of biofilm-contaminated catheters and the recovery of surrounding infected tissues. CONCLUSIONS: In summary, elaboration on the architecture of pH-sensitive copolymers was the first step to target biofilm. The ML-E-A structure may represent an interesting future direction in the treatment of biofilm-relevant infections associated with acidity.

On-demand pH-sensitive surface charge-switchable polymeric micelles for targeting Pseudomonas aeruginosa biofilms development.

Bacterial biofilm is the complicated clinical issues, which usually results in bacterial resistance and reduce the therapeutic efficacy of antibiotics. Although micelles have been drawn attention in treatment of the biofilms, the micelles effectively permeate and retain in biofilms still facing a big challenge. In this study, we fabricated on-demand pH-sensitive surface charge-switchable azithromycin (AZM)-encapsulated micelles (denoted as AZM-SCSMs), aiming to act as therapeutic agent for treating Pseudomonas aeruginosa (P. aeruginosa) biofilms. The AZM-SCSMs was composed of poly(L-lactide)-polyetherimide-hyd-methoxy polyethylene glycol (PLA-PEI-hyd-mPEG). It was noteworthy that the pH-sensitive acylhydrazone bond could be cleaved in acidic biofilm microenvironment, releasing the secondary AZM-loaded cationic micelles based on PLA-PEI (AZM-SCMs) without destroying the micellar integrity, which could tailor drug-bacterium interaction using micelles through electrostatic attraction. The results proved that positively charged AZM-SCMs could facilitate the enhanced penetration and retention inside biofilms, improved binding affinity with bacterial membrane, and added drug internalization, thus characterized as potential anti-biofilm agent. The excellent in vivo therapeutic performance of AZM-SCSMs was confirmed by the targeting delivery to the infected tissue and reduced bacterial burden in the abscess-bearing mice model. This study not only developed a novel method for construction non-depolymerized pH-sensitive SCSMs, but also provided an effective means for the treatment of biofilm-related infections.

The value of multidisciplinary team (MDT) management in the diagnosis and treatment of primary intrathoracic synovial sarcomas: a single-center experience.

BACKGROUND: Synovial sarcoma (SS) is a rare malignant soft tissue tumor. Primary intrathoracic SS is extremely rare, with limited diagnosis and treatment experiences. The aim of our study was to retrospectively study the clinicopathological characteristics, treatment and prognosis of primary intrathoracic SS and the impact of multidisciplinary team (MDT) management in diagnosis and treatment on patient prognosis. METHODS: The clinical and pathological characteristics, treatment, survival and prognosis of patients with primary intrathoracic SS admitted to the National Cancer Center from January 1999 to December 2018, as well as MDT intervention during diagnosis and treatment, were retrospectively analyzed. RESULTS: Thirteen patients were enrolled, including 7 (53.8%) males and 6 (46.3%) females, with primary intrathoracic SS in the lung (8/13, 61.5%), mediastinum (4/13, 30.8%) and pleura (1/13, 7.7%) as confirmed by morphological observation, immunohistochemical (IHC) staining and fluorescence in situ hybridization (FISH). Overall, 10/13 (76.9%) patients underwent surgery, and 6/10 (60.0%) received postoperative adjuvant therapy. Only 23.1% of patients received nonsurgical therapy. The MDT discussed and managed seven patients before and/or after surgery and one patient who did not undergo surgery. The estimated 3- and 5-year overall survival (OS) rates were 50.0% and 30.0%, respectively. Patients who were managed by an MDT had a longer median OS time than those who were not (46.0 vs. 18.0 months). Age (P=0.018), tumor location (P=0.029), and Ki-67 (P=0.020) were found to be significantly related to OS. CONCLUSIONS: Monophasic morphology and fusion gene characteristics are the main features for the diagnosis of primary intrathoracic SS. MDT management can help obtain accurate diagnoses and provide reasonable therapeutic options.

Clinicopathological characteristics and prognostic factors of primary pulmonary lymphoma.

BACKGROUND: Primary pulmonary lymphoma (PPL) is a rare extranodal lymphoma originating from the lung, accounting for 0.5-1.0% of primary lung malignant tumors. Previous case reports or cohort studies included a limited sample size; therefore, the understanding of the disease remains inadequate, and clinical data regarding PPL are limited. METHODS: Patients with PPL diagnosed histologically and radiologically between January 2000 and December 2019 at our center were retrospectively analyzed. RESULTS: In total, 90 consecutive cases were included in this research. Forty-seven (52.2%) patients were female, and the median age was 54 years old. Non-Hodgkin's lymphoma (PPNHL) was the most common type of PPL (71/90, 78.9%), and mucosa-associated lymphoid tissue (MALT) lymphoma was the most common pathological subtype of PPNHL (56.3%) followed by diffuse large B-cell lymphoma (DLBCL) (32.4%). Thirty-nine (43.3%) patients underwent surgical treatment, and the others received chemotherapy alone or combined with radiotherapy. The estimated 5-year overall survival (OS) rates of MALT lymphoma and non-MALT lymphoma were 68.9% and 65.9%, respectively. Univariate analysis of PPL showed that clinicopathological features that significantly correlated with worse OS were age over 60 years (P=0.006<0.05), elevated LDH (P=0.029<0.05) and ß2-MG (P=0.048<0.05) levels, clinical stage II2E and greater (P=0.015<0.05), and nonsurgical treatment (P=0.046<0.05). Age (P=0.013<0.05) was an independent prognostic factor for the 5-year OS of patients through multivariate analysis. CONCLUSIONS: Age over 60 years old, elevated LDH and ß2-MG levels, clinical stage II2E disease or higher, and nonsurgical treatment were associated with poor prognosis in patients with PPL. Age can be used as a potential independent prognostic factor for PPL.

A rare case of primary pulmonary inflammatory pseudotumor-like follicular dendritic cell sarcoma successfully treated by lobectomy.

Primary pulmonary inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is extremely rare. Here, we report a case of a 64-year-old female with primary pulmonary IPT-like FDCS. The patient was found to have a solid nodule in the right lower lobe (RLL) of the lung incidentally without any symptoms or signs of discomfort. The chest computed tomography (CT) showed that there was an irregular nodule in the basal segment of the RLL, approximately 2.0 cm × 1.1 cm × 1.0 cm in size, of 15 HU in CT value. While the result of the fiberoptic bronchoscope-guided biopsy of the mass showed that there was inflammatory cell infiltration, no evidence of malignancy was found. After a thorough discussion of the multidisciplinary team, lobectomy of the RLL and systematic lymph node dissection were performed for the patient. Histologic analysis of the resected mass revealed infiltration of a large number of lymphocytes and plasma cells with the expression of CD21, CD23, CD35 were positive. In addition, the Epstein-Barr virus (EBV) probe in situ hybridization were positive. As a result, the diagnosis of EBV-positive IPT-like FDCS was strongly supported. No recurrence or any signs of metastasis were found during a 10-month follow-up time. As we have reported in this rare case, the diagnosis of primary pulmonary IPT-like FDCS should be considered even when there is only lymphoplasmacytic infiltration and no evidence of malignant tumor cells in the lung.

Three-dimensional reconstruction/personalized three-dimensional printed model for thoracoscopic anatomical partial-lobectomy in stage I lung cancer: a retrospective study.

BACKGROUND: Considering the complexity of vascular or bronchial variations and the difficulty of nodule localization during segmental resection, the three-dimensional (3D) reconstruction and printing model can provide a guarantee for safe operation and, to some extent, can simplify the surgical procedure. We conducted this study to estimate the avail of 3D reconstruction and personalized model in anatomical partial-lobectomy (APL). METHODS: We prospectively collected and retrospectively reviewed the data of 298 cases who underwent APL in our institute from April 2017 to May 2019. The patients were divided into "3D-reconstruction" group (131 patients), "3D model" group (31 patients) and "non-3D" group (136 patients). We adopted the ANOVA analysis and Chi-square test to compare the perioperative data between the three groups. Subjective satisfaction questionnaires for surgeons were provided to evaluate the value of personalized 3D printed model. RESULTS: The proportion of complex segmentectomy in 3D model group (87.1%) was significantly higher than that in the 3D-reconstruction group (60.3%) and non-3D group (55.9%) (P=0.006), and the average operation time of complex segmentectomy in 3D model group (99.56 minutes) was significantly shorter than that of the other group (all P<0.05). The average intraoperative blood loss in the 3D model group (12.9 mL) was significantly lower than that in the 3D reconstruction group (20.9 mL) (P=0.001) and non-3D group (18.2 mL) (P=0.022). For simple segmentectomy, the operation time, postoperative drainage, and postoperative hospital stay were similar among the three groups. The questionnaire survey showed that most surgeons were satisfied with the clinical effectiveness of the personalized 3D printed model. CONCLUSIONS: 3D printing technology can improve understanding of the anatomy, decrease the operation time, and reduce the potential risk of thoracoscopic anatomical partial lobectomy in stage I lung cancer. A pre-operative rating scale was designed to standardize the application of this technology.

Preoperative systemic immune-inflammation index and prognostic nutritional index predict prognosis of patients with pulmonary neuroendocrine tumors after surgical resection.

BACKGROUND: Pulmonary neuroendocrine tumors (PNETs) are a special subtype of lung cancer with treatment methods are limited and prognostic indicators are insufficient. The preoperative systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) are effective tumor biomarkers that have important significance for the prognosis of many malignant tumors. However, there is no similar research on the predictive value of SII and PNI for operable PNETs. Our study aimed to clarify the predictive value of SII and PNI in PNETs patients after surgical resection. METHODS: This study retrospectively analysed the relevant clinical data of PNETs patients who received surgical treatment from 2005 to 2015, which was obtained from patient's clinical records, blood test results recorded on admission before surgical treatment, and follow-up by hospital records. RESULTS: A total of 381 PNETs patients were enrolled in this study. Preoperative PNI was associated with age (P=0.001), T stage (P=0.001), tumor length (P=0.002), drinking status (P=0.013) and smoking status (P=0.049), while SII was significantly associated with T stage (P=0.001), tumor length (P=0.001) and TNM stage (P=0.001). There was significant difference between high SII and low PNI and worse OS of PENTs (P=0.001 and P<0.001). SII (P=0.002), neutrophil/lymphocyte ratio (NLR) (P<0.001), platelet/lymphocyte ratio (PLR) (P=0.001), lymph node metastasis (P<0.001), operation time (P=0.034<0.05), treatment (P<0.001) and PNI (P=0.044<0.05) were independent prognostic factors for PNETs identified by multivariate Cox regression analysis. CONCLUSIONS: High SII and low PNI indicated poor prognosis of patients with PNETs. Both of SII and PNI can predict the prognosis of PNETs and stratify patients for better treatment.

Primary pulmonary epithelioid malignant peripheral nerve sheath tumor in a child: a case report.

Primary pulmonary malignant peripheral nerve sheath tumors (MPNSTs) are uncommon sarcomas originating from intrapulmonary nerve sheath and have been rarely observed in children. Here, we report a case of a 16-year-old child who presented with a mass located in the upper lobe of right lung. The patient underwent a sleeve lobectomy and the pathological diagnosis of the tumor was primary pulmonary epithelioid MPNST. Despite the radical resection, multiple suspected metastasis occurred in heart, lung and muscles less than 2 years after the operation and the patient died 6 months after the metastasis.

Clinicopathological characteristics and prognosis of lung cancer in young patients aged 30 years and younger.

BACKGROUND: Lung cancer is one of the most common malignant tumors in the world and mainly occurs in elderly patients, but rarely in young patients. The purpose of this retrospective study was to examine the clinicopathological features and prognosis of lung cancer patients aged 30 years and younger. METHODS: Patients aged 30 years and younger with lung cancer admitted to our center from November 2013 to October 2018 were retrospectively identified. Data included sex, age, smoking history, family history of cancer, high resolution computed tomography results, size and location of tumors, histology of tumors, lymph node status, stage of tumors, treatment methods and prognosis of patients. RESULTS: The patient group included more females (56.3%) than males (43.7%) among lung cancer patients aged 30 and younger. Some patients had a history of tobacco inhalation and family cancer (17.5% and 22.3%, respectively). The most common tumors were in the left lower lobe (27.2%). Nearly half (49.5%) of the patients had pathological adenocarcinomas and 59.3% of the patients were showed early clinical stage and had no lymph node metastasis. All patients received surgical treatment; 47.1% received lobectomy and only 17.9% received adjuvant therapy such as radiotherapy, chemotherapy or targeted therapy after operation. Only seven (7.4%) of the successful follow-up patients died. Local recurrence occurred in two cases and distant metastasis in six cases. CONCLUSIONS: The main clinicopathological type of lung cancer in young lung cancer patients aged 30 years and younger is adenocarcinoma, and most cases were at the early stage. Surgical treatment based on lobectomy is still the main treatment method and the prognosis of these patients is very good. Early screening of lung cancer should be actively promoted for young people.

Differences of microRNA expression profiles between monozygotic twins' blood samples.

Monozygotic (MZ) twins are widely regarded as genetically identical, and traditional DNA typing methods are insufficient in identifying MZ twins. So the discrimination of MZ twins become a forensic problem. MicroRNAs (miRNAs) are a class of small, endogenous, non-protein-coding RNA molecules of approximately 22 nucleotides in length, and exist extensively in a variety of eukaryotic cells. MiRNAs regulate gene expression and play fundamental roles in multiple biological processes, including cell differentiation, proliferation and apoptosis as well as aging and disease processes. The goal of this study is to explore the differential expression of miRNAs within MZ twin pairs, and aimed to find new biomarkers for distinguishing MZ twins. Thus, the miRNA expression profiles of seven pairs of healthy MZ twins of different sex and age were analyzed by miRNA microarray. A total of 545 miRNAs were found to be differentially expressed in these MZ twin pairs, and 2, 5, 22, 53 and 132 differentially expressed miRNAs were shared across six, five, four, three and two pairs of MZ twins respectively. These findings had been confirmed by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays on select miRNAs, including miR-151a-3p, miR-3653-3p, miR-142-3p, miR-4325, miR-16-5p, let-7i-5p, miR-222-3p, miR-550b-3p, miR-4791 and miR-27a-3p. The results demonstrated that there are differences in the expression of miRNAs within MZ twin pairs, suggesting a role of miRNAs in identifying MZ twins.

Obesity and lipid-related parameters for predicting metabolic syndrome in Chinese elderly population.

BACKGROUND: The present study evaluated the predictive ability of five known "best" obesity and lipid-related parameters, including body mass index (BMI), waist-to-height ratio (WHtR), triglyceride-to-high-density-lipoprotein-cholesterol (TG/HDL-C), lipid accumulation product (LAP) and visceral adiposity index (VAI), in identifying metabolic syndrome (MetS) in Chinese elderly population. METHODS: A total of 6722 elderly Chinese subjects (≥60 years) were recruited into our community-based cross-sectional study from April 2015 to July 2017. The anthropometrics, blood pressure, fasting plasma glucose, blood lipid profiles, family history and health-related behaviours were assessed. RESULTS: The prevalence of MetS was 40.4% (32.5% in males and 47.2% in females). With the increase in the number of MetS components (from 0 to 5), all the five parameters showed an increase trend in both genders (all P for trend < 0.001). According to receiver operating characteristic curve (ROC) analyses, all the five parameters performed high predictive value in identifying MetS. The statistical significance of the areas under the curves (AUCs) differences suggested that the AUCs of LAP were the greatest among others in both genders (AUCs were 0.897 in males and 0.875 in females). The optimal cut-off values of LAP were 26.35 in males and 31.04 in females. After adjustment for potentially confounding factors, LAP was strongly associated with the odds of having MetS in both genders, and ORs for MetS increased across quartiles using multivariate logistic regression analysis (P < 0.001). CONCLUSION: LAP appeared to be a superior parameter for predicting MetS in both Chinese elderly males and females, better than VAI, TG/HDL-C, WHtR and BMI.

Body mass index, waist circumference, and waist-to-height ratio for prediction of multiple metabolic risk factors in Chinese elderly population.

The purpose of this study was to compare the predictive ability of five obesity indices, including body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHpR) and body adiposity index (BAI), to predict multiple non-adipose metabolic risk factors, including elevated blood pressure (BP), elevated fasting plasma glucose (FPG), elevated triglyceride (TG), reduced high-density lipoprotein cholesterol (HDL-C), elevated serum uric acid (SUA) and non-alcoholic fatty liver disease (NAFLD), in an elderly Chinese population. A total of 5685 elderly Chinese subjects (≥60 years) were recruited into our community-based cross-sectional study. Receiver operating characteristic curve (ROC) analyses were used to compare the predictive ability as well as determine the optimal cut-off values of the obesity indices for multiple metabolic risk factors. According to the areas under the receiver operating characteristic curve (AUC), BMI, WC and WHtR were able to similarly predict high metabolic risk in males (0.698 vs. 0.691 vs. 0.688), while in females, BMI and WC were able to similarly predict high metabolic risk (0.676 vs. 0.669). The optimal cut-off values of BMI, WC and WHtR in males were, respectively, 24.12 kg/m2, 83.5 cm and 0.51, while in females, the values were 23.53 kg/m2 and 77.5 cm.

Comparison of different methods for repairing damaged DNA from buffered and unbuffered formalin-fixed tissues.

Formalin fixation is considered an important process for preservation of human tissue samples for long periods. However, this process not only results in cross-linking complicating isolation of nucleic acid but also introduces polymerase "blocks" during polymerase chain reaction (PCR). At present, many protocols have already been developed aiming at extracting high amounts of amplifiable DNA from formalin-fixed tissues (FFTs). However, there are few methods for repairing formalin-damaged DNA. In this study, we compared the effectiveness of several post-extraction enzymatic repair techniques, including Taq DNA polymerase, DNA polymerase I and T4 DNA ligase, the PreCR™ Repair Mix and Restorase® DNA Polymerase, in restoring STR profiles from formalin-damaged DNA. Our results indicated that formalin-damaged DNA may be repaired partly with Taq DNA polymerase and the Restorase® DNA Polymerase, and lost alleles may be restored and STR peak heights may increase upon repair with them. Moreover, the repair ability of the protocol 2 with Taq DNA polymerase surpasses the Restorase® DNA Polymerase.

Glioblastoma multiforme in conus medullaris with intracranial metastasis after postoperative adjuvant therapy.

Spinal glioblastoma multiforme is not common among spinal cord tumors. According to our literature review, only 27 cases originating from the conus medullaris were reported. We herein reported a case of a 10-year-old child diagnosed with glioblastoma multiforme. The patient received adjuvant radiotherapy and standard temozolomide chemotherapy after total excision. Intracranial lesions were found 1 month after postoperative adjuvant therapy. We described the clinical characteristics and postoperative therapy of the patient, and reviewed all of the published cases of conus medullaris glioblastoma. Location, age, leptomeningeal spread, and secondary hydrocephalus may be predictive factors. Immunohistochemical factors such as p53 and Ki-67 are also important. Combined treatment of surgery and postoperative adjuvant therapy is commonly used, but is controversial.

Brain Stem and Entire Spinal Leptomeningeal Dissemination of Supratentorial Glioblastoma Multiforme in a Patient during Postoperative Radiochemotherapy: Case Report and Review of the Literatures.

Glioblastoma multiforme (GBM) is the most common primary malignancy of the central nervous system in adults. Macroscopically evident and symptomatic spinal metastases occur rarely. Autopsy series suggest that approximately 25% of patients with intracranial GBM have evidence of spinal subarachnoid seeding, although the exact incidence is not known as postmortem examination of the spine is not routinely performed. Herein, we present a rare case of symptomatic brain stem and entire spinal dissemination of GBM in a 36-year-old patient during postoperative adjuvant radiochemotherapy with temozolomide and cisplatin. Visual deterioration, intractable stomachache, and limb paralysis were the main clinical features. The results of cytological and immunohistochemical tests on the cerebrospinal fluid cells were highly suggestive of spinal leptomeningeal dissemination. After 1 month, the patient's overall condition deteriorated and succumbed to his disease. To the best of our knowledge, this is the first reported case of GBM dissemination presenting in this manner. Because GBM extracranial dissemination is rare, we also reviewed pertinent literature regarding this uncommon entity. Although metastases to spinal cord from GBM are uncommon, it is always important to have in mind when patients with a history of GBM present with symptoms that do not correlate with the primary disease pattern.