Laparoscopic posterior pelvic exenteration is safe and feasible for locally advanced primary rectal cancer in female patients: a comparative study from China PelvEx collaborative.

PURPOSE: Posterior pelvic exenteration (PPE) for locally advanced rectal cancer is a technical and challenging procedure. The safety and feasibility of laparoscopic PPE remain to be determined. This study aims to compare short-term and survival outcomes of laparoscopic PPE (LPPE) with open PPE (OPPE) in female patients. METHOD: From January 2015 to December 2020, data from 105 female patients who underwent PPE at three institutions were retrospectively analyzed. The short-term and oncological outcomes between LPPE and OPPE were compared. RESULTS: A total of 54 cases with LPPE and 51 cases with OPPE were enrolled. The operative time (240 vs. 295 min, p = 0.009), blood loss (100 vs. 300 ml, p < 0.001), surgical site infection (SSI) rate (20.4% vs. 58.8%, p = 0.003), urinary retention rate (3.7% vs. 17.6%, p = 0.020), and postoperative hospital stay (10 vs. 13 days, p = 0.009) were significantly lower in the LPPE group. The two groups showed no significant differences in the local recurrence rate (p = 0.296), 3-year overall survival (p = 0.129), or 3-year disease-free survival (p = 0.082). A higher CEA level (HR 1.02, p = 0.002), poor tumor differentiation (HR 3.05, p = 0.004), and (y)pT4b stage (HR 2.35, p = 0.035) were independent risk factors for disease-free survival. CONCLUSION: LPPE is safe and feasible for locally advanced rectal cancers and shows lower operative time and blood loss, fewer SSI complications, and better preservation of bladder function without compromising oncological outcomes.

The effectiveness of an unsupervised home-based pulmonary rehabilitation with self-management program in patients with chronic obstructive pulmonary disease.

AIMS: To assess the effectiveness of an unsupervised home-based pulmonary rehabilitation with self-management program in patients with chronic obstructive pulmonary disease (COPD). BACKGROUND: A few recent studies have shown that unsupervised home-based pulmonary rehabilitation can improve the clinical outcome of patients with COPD. More studies are needed to prove its benefits. DESIGN: This study used a quasi-experimental design. METHODS: Seventy-two admitted COPD patients were assigned to experimental group or control group through purposeful sampling. Data were collected from March 2016 to November 2017 in the Thoracic Intensive Care Unit of a Medical Center in Taiwan. The Medical Research Council dyspnea scale, the COPD Self-Efficacy Scale and the Clinical COPD Questionnaire were measured before education and at the first, second and third months after discharge. RESULTS: The Medical Research Council dyspnea scale and COPD Self-Efficacy Scale results in the experimental group were significantly improved compared with the control group in the third month after discharge. The Clinical COPD Questionnaire score continued to improve in both groups in the third month after discharge, and there was no difference between the two groups. CONCLUSION: A short-term unsupervised home-based pulmonary rehabilitation with self- management program had significant benefits for patients with COPD. The long-term effects need to be confirmed.

Cerebral arterial gas embolism and neurogenic stunned myocardium in a previously healthy freediver.

Cardiomyopathy is a known but rare sequelae of diving-related cerebral arterial gas embolism (CAGE). In previously reported cases, patient findings have been consistent with takotsubo cardiomyopathy (TCM) per the revised Mayo Clinic's diagnostic criteria. A lesser-known variant of stress-related cardiomyopathy is neurogenic stunned myocardium (NSM), which occurs after a neurological event such as subarachnoid hemorrhage and typically presents in younger patients. Presentation tends to differ slightly to TCM with non-specific left ventricular dysfunction and T wave inversions. This case adds to the rare numbers of reported cardiomyopathy from diving and is the first reported case of suspected NSM associated with CAGE.

[Analysis of clinical and genetic variation in neonatal intrahepatic cholestasis caused by citrin deficiency].

Objective: To investigate the clinical phenotype and gene variation conditions in neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), so as to provide a basis for genetic counseling and clinical diagnosis and treatment of the family. Methods: 11 cases of neonatal intrahepatic cholestasis who visited the Children's Hospital Affiliated to Zhengzhou University between February 2019 and March 2021 were selected as the study subjects. High-throughput sequencing technology was used to detect the gene variation condition in 11 neonatal patients and 100 normal control neonates. The suspicious loci and family members were verified by Sanger sequencing and QPCR technology. Results: All 11 children with NICCD had different degrees of jaundice and liver damage symptoms, combined with coagulation dysfunction and anemia (n = 7), cardiac malformation (n = 2), elevated myocardial enzymes (n = 4), hyperlipidemia (n = 1), hyperkalemia (n = 1), persistent diarrhea (n = 3), developmental delay (n = 1). A total of 10 different types of SLC25A13 gene mutations were detected in 11 cases, including three frameshift mutations, two splicing changes, two missense mutations, one intron insertion, one nonsense mutation, and one heterozygous deletion. After reviewing literature and databases, c.1878delG(p.I627Sfs*73) and exon11 deletion were novel mutations that had not been reported at home or abroad. Conclusion: The clinical features of NICCD are non-specific, and genetic testing aids in the early and accurate diagnosis of the disease, providing an important basis for clinical treatment and genetic counseling for family members. In addition, the detection of novel mutation sites has enriched the SLC25A13 gene variation spectrum.

Disease burden and treatment adherence among children and adolescent patients with asthma.

OBJECTIVE: To assess asthma burden and medication adherence in a US de-identified patient level claims database. METHODS: This retrospective observational study used the IQVIA PHARMETRICS PLUS database to identify patients aged 5-17 years, diagnosed with asthma between 01/01/2012-09/30/2017 (asthma cohort), and those initiating treatment with twice-daily inhaled corticosteroids (ICS) or twice-daily ICS/long-acting beta2 agonists (LABA) (treatment cohorts; index date = first dispensing). Patient characteristics, asthma medication, and healthcare resource utilization were assessed over a 12-month baseline period. Treatment cohort endpoints were assessed in a 12-month follow-up period, including: adherence using proportion of days covered (PDC); persistence (no gap >45 days between dispensings). RESULTS: The asthma cohort included 186,868 patients (112,689 children, mean age 7.9 years; 74,179 adolescents, mean age 14.3 years). During baseline, 34.5% used ICS or ICS/LABA, 24% used oral corticosteroids, 11.1% had ≥1 asthma-related emergency department visit, 2.2% had ≥1 asthma-related hospitalization. Among treatment cohorts, 47,276 and 10,247 patients initiated twice-daily ICS and ICS/LABA, respectively (mean ages: 9.9; 12.5 years). Mean PDC adherence to twice-daily ICS and ICS/LABA was 30% and 34% at 6 months (PDC ≥0.8: 4.3%; 6.1%); 21% and 24% at 12 months (PDC ≥0.8: 1.8%; 2.8%). Persistence with twice-daily ICS and ICS/LABA was 10.1% and 14.2% at 6 months; 5.6% and 8.0% at 12 months. CONCLUSIONS: A large disease burden and unmet need exist among US children/adolescent asthma patients, evidenced by low use of, and poor adherence to, ICS-containing medication, the notable proportion of oral corticosteroid users, and higher-than-expected asthma-related emergency department and hospitalization rates.

The cross-sectional study of depressive symptoms and associated factors among adolescents by backpropagation neural network.

OBJECTIVES: This study aimed to investigate the association between depressive symptoms and diet- and lifestyle-related behaviors among adolescents. STUDY DESIGN: Cross-sectional study. METHODS: Our study used stratified random cluster sampling method to recruit 6,251 adolescents aged 11-19 years as samples for research and analysis. The Center for Epidemiological Studies Depression Scale was used to assess depressive symptoms. Chi-squared test, t test, and logistic regression were used to explore the diet and lifestyle factors of depressive symptoms. Backpropagation (BP) neural network model was used to investigate the ranking of diet and lifestyle behaviors factors of depressive symptoms. RESULTS: The prevalence of depressive symptoms among adolescents was 32.1%. Multivariable logistic regression was used to determine 10 important variables of depressive symptoms. After ranking the importance by BP neural network, the top three important variables were found, which were sleep duration (100%), screen time (49.1%), and breakfast (23.6%). CONCLUSION: Sleep duration, screen time, and breakfast were associated factors with the most significant impacts on depressive symptoms.

Predicting Influenza and Rhinovirus Infections in Airway Cells Utilizing Volatile Emissions.

BACKGROUND: Respiratory viral infections are common and potentially devastating to patients with underlying lung disease. Diagnosing viral infections often requires invasive sampling, and interpretation often requires specialized laboratory equipment. Here, we test the hypothesis that a breath test could diagnose influenza and rhinovirus infections using an in vitro model of the human airway. METHODS: Cultured primary human tracheobronchial epithelial cells were infected with either influenza A H1N1 or rhinovirus 1B and compared with healthy control cells. Headspace volatile metabolite measurements of cell cultures were made at 12-hour time points postinfection using a thermal desorption-gas chromatography-mass spectrometry method. RESULTS: Based on 54 compounds, statistical models distinguished volatile organic compound profiles of influenza- and rhinovirus-infected cells from healthy counterparts. Area under the curve values were 0.94 for influenza, 0.90 for rhinovirus, and 0.75 for controls. Regression analysis predicted how many hours prior cells became infected with a root mean square error of 6.35 hours for influenza- and 3.32 hours for rhinovirus-infected cells. CONCLUSIONS: Volatile biomarkers released by bronchial epithelial cells could not only be used to diagnose whether cells were infected, but also the timing of infection. Our model supports the hypothesis that a breath test could serve to diagnose viral infections.

Excretory/secretory proteins of adult Toxocara canis induce changes in the expression of proteins involved in the NOD1-RIP2-NF-κB pathway and modulate cytokine production in mouse macrophages.

Dog roundworm (Toxocara canis) is the major causative agent of toxocarosis, a parasitic disease of both veterinary and medical importance. Knowledge gaps in fundamental and applied aspects hinder the control of this important zoonotic disease. To have a better understanding of Toxocara infection and host immune responses, mouse macrophages were exposed to excretory/secretory (ES) proteins released by adult worms of T. canis in vitro. The messenger RNA transcription and protein expression of nucleotide-binding oligomerization domain-containing protein 1 (NOD1), receptor interacting protein 2 (RIP2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in macrophages were analysed using quantitative real-time PCR (qRT-PCR) and Western blot. The levels of tumour necrosis factor alpha (TNF-ɑ), interleukin-1 beta (IL-1ß) and IL-6 released by the stimulated macrophages were analysed using enzyme-linked immunosorbent assay. It was found that 20 µg/mL ES proteins of adult T. canis induced the expression of NOD1, RIP2 and NF-κB in mouse macrophages at both transcriptional and translational levels after 9 h of incubation in vitro. Incubation with 20 µg/mL ES proteins also modulated the production of pro-inflammatory cytokines TNF-ɑ, IL-1ß and IL-6 by the macrophages. Taken together, ES proteins of adult T. canis appeared to be able to affect the macrophage NOD1-RIP2-NF-κB signalling pathway, which might play a role in regulating the production of proinflammatory cytokines. Further investigation of these aspects should lead to a better understanding of immune recognition of and modulation by Toxocara canis in host animals.

Changes in rumen fermentation and bacterial community in lactating dairy cows with subacute rumen acidosis following rumen content transplantation.

Rumen microbiota intervention has long been used to cure ruminal indigestion in production and has recently become a research hotspot. However, how it controls the remodeling of rumen bacterial homeostasis and the restoration of rumen fermentation in cows of subacute ruminal acidosis (SARA) remains poorly understood. This study explored changes in rumen fermentation and bacterial communities in SARA cows following rumen content transplantation (RCT). The entire experiment comprised 2 periods: the SARA induction period and the RCT period. During the SARA induction period, 12 ruminally cannulated lactating Holstein cows were selected and allocated into 2 groups at random, fed either a conventional diet [CON; n = 4; 40% concentrate, dry matter (DM) basis] or a high-grain diet (HG; n = 8; 60% concentrate, DM basis). After the SARA induction period, the RCT period began. The HG cows were randomly divided into 2 groups: the donor-recipient (DR) group and the self-recipient (SR) group, and their rumen contents were removed completely before RCT. For the DR group, cows received 70% rumen content from the CON cows, paired based on comparable body weight; for the SR group, each cow received 70% rumen content, self-derived. The results showed that nearly all rumen fermentation parameters returned to the normal levels that the cows had before SARA induction after 6 d of transplantation, regardless of RCT. The concentrations of acetate, valerate, and total volatile fatty acids (VFA) were not recovered in the SR cows, whereas all of them were recovered in the DR cows. The amplicon sequencing results indicated that both the SR and DR cows rebuild their rumen bacterial homeostasis quickly within 4 d after RCT, and the DR group showed a higher level of bacterial community diversity. At the genus level, the DR cows displayed an improved proportion of unclassified Ruminococcaceae and Saccharofermentans compared with the SR cows. Correlation analysis between the rumen bacteria and rumen fermentation suggested some potential relationships between the predominant transplantation-sensitive operational taxonomic units and VFA. Co-occurrence network analysis revealed that RCT affected only those rumen bacterial taxa that showed weak interactions with other taxa and did not affect the pivotal rumen bacteria with high levels of co-occurrence. Our findings indicate that RCT contributes to the restoration of rumen bacterial homeostasis and rumen fermentation in cows suffering from SARA without affecting the core microbiome.

Real-World Adherence in Patients with Metastatic Colorectal Cancer Treated with Trifluridine plus Tipiracil or Regorafenib.

BACKGROUND: Trifluridine and tipiracil (FTD + TPI) and regorafenib (REG) are approved treatments for the treatment of refractory metastatic colorectal cancer (mCRC). This study assesses adherence and duration of therapy with FTD + TPI versus REG and explores the effect of sequencing on adherence. MATERIALS AND METHODS: Adults diagnosed with mCRC were identified in the IQVIA Real-World Data Adjudicated Claims: U.S. database (October 2014-July 2017). The observation period spanned from the index date (first dispensing of FTD + TPI or REG) to the earliest of a switch to another mCRC agent, the end of continuous enrollment, or the end of data availability. Medication possession ratio (MPR), proportion of days covered (PDC), and persistence and time to discontinuation (gap ≥45 days) were compared between FTD + TPI and REG users and among switchers (FTD + TPI-to-REG vs. REG-to-FTD + TPI). RESULTS: A total of 469 FTD + TPI and 311 REG users were identified. FTD + TPI users had higher compliance with an MPR ≥80% (odds ratio [OR], 2.47; p < .001) and PDC ≥80% (OR, 2.77; p < .001). FTD + TPI users had better persistence (82.8% vs. 68.0%; p < .001) and lower risk of discontinuation (hazard ratio [HR], 0.76; p = .006). Among switchers (96 FTD + TPI-to-REG; 83 REG-to-FTD + TPI), those switching from FTD + TPI to REG were more likely to have an MPR ≥80% (OR, 2.91; p < .001) and PDC ≥80% (OR, 4.60; p < .001) compared with REG-to-FTD + TPI switchers while treated with these drugs. Additionally, FTD + TPI-to-REG switchers had a lower risk of first treatment discontinuation (HR, 0.66; p = .009). CONCLUSION: FTD + TPI users had significantly higher adherence and persistence, and patients who were treated with FTD + TPI before switching to REG also had higher adherence and persistence outcomes. IMPLICATIONS FOR PRACTICE: Trifluridine plus tipiracil (FTD + TPI) and regorafenib (REG) prolong survival in refractory metastatic colorectal cancer (mCRC) but have different tolerability profiles. This study assessed real-world adherence to treatment with FTD + TPI versus REG and compared outcomes among patients who switched from FTD + TPI to REG and vice versa. FTD + TPI was associated with significantly higher medication adherence and longer time to discontinuation than REG. Patients treated with FTD + TPI prior to switching to REG also showed higher adherence outcomes. Findings could help inform decision making regarding the choice and sequencing of treatment with FTD + TPI versus REG in patients with mCRC.

Real-World Assessment of Clinical Outcomes Among First-Line Sunitinib Patients with Clear Cell Metastatic Renal Cell Carcinoma (mRCC) by the International mRCC Database Consortium Risk Group.

BACKGROUND: International Metastatic Renal Cell Carcinoma (mRCC) Database Consortium (IMDC) risk groups are important when considering therapeutic options for first-line treatment. MATERIALS AND METHODS: Adult patients with clear cell mRCC initiating first-line sunitinib between 2010 and 2018 were included in this retrospective database study. Median time to treatment discontinuation (TTD) and overall survival (OS) were estimated using Kaplan-Meier analysis. Outcomes were stratified by IMDC risk groups and evaluated for those in the combined intermediate and poor risk group and separately for those in the intermediate risk group with one versus two risk factors. RESULTS: Among 1,769 patients treated with first-line sunitinib, 318 (18%) had favorable, 1,031 (58%) had intermediate, and 420 (24%) had poor IMDC risk. Across the three risk groups, patients had similar age, gender, and sunitinib initiation year. Median TTD was 15.0, 8.5, and 4.2 months in the favorable, intermediate, and poor risk groups, respectively, and 7.1 months in the combined intermediate and poor risk group. Median OS was 52.1, 31.5, and 9.8 months in the favorable, intermediate, and poor risk groups, respectively, and 23.2 months in the combined intermediate and poor risk group. Median OS (35.1 vs. 21.9 months) and TTD (10.3 vs. 6.6 months) were significantly different between intermediate risk patients with one versus two risk factors. CONCLUSION: This real-world study found a median OS of 52 months for patients with favorable IMDC risk treated with first-line sunitinib, setting a new benchmark on clinical outcomes of clear cell mRCC. Analysis of intermediate risk group by one or two risk factors demonstrated distinct clinical outcomes. IMPLICATIONS FOR PRACTICE: This analysis offers a contemporary benchmark for overall survival (median, 52.1 months; 95% confidence interval, 43.4-61.2) among patients with clear cell metastatic renal cell carcinoma who were treated with sunitinib as first-line therapy in a real-world setting and classified as favorable risk according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group classification. This study demonstrates that clinical outcomes differ between IMDC risk groups as well as within the intermediate risk group based on the number of risk factors, thus warranting further consideration of risk group when counseling patients about therapeutic options and designing clinical trials.

New Roles for the Nucleolus in Health and Disease.

Over the last decade, our appreciation of the importance of the nucleolus for cellular function has progressed from the ordinary to the extraordinary. We no longer think of the nucleolus as simply the site of ribosome production, or a dynamic subnuclear body noted by pathologists for its changes in size and shape with malignancy. Instead, the nucleolus has emerged as a key controller of many cellular processes that are fundamental to normal cell homeostasis and the target for dysregulation in many human diseases; in some cases, independent of its functions in ribosome biogenesis. These extra-nucleolar or new functions, which we term "non-canonical" to distinguish them from the more traditional role of the nucleolus in ribosome synthesis, are the focus of this review. In particular, we explore how these non-canonical functions may provide novel insights into human disease and in some cases new targets for therapeutic development.

New Opportunities and Challenges for Forensic Medicine in the Era of Artificial Intelligence Technology.

ABSTRACT: Traditional forensic identification relies on forensic experts to manually extract information and provide identification opinions based on medicine, biology and other fields of knowledge combined with personal work experience, which is not only time-consuming and require great effort, but also affected by subjective factors that are difficult to overcome. In the era of big data, the booming development of artificial intelligence brings new ideas to forensic medicine. In recent years, forensic researchers at home and abroad have conducted many studies based on artificial intelligence technology, such as face recognition, age and gender identification, DNA analysis, postmortem interval estimation, injury and cause of death identification, showing the feasibility and advantages of using artificial intelligence technology to solve forensic identification problems. As a new means of technology that has adapted to the development of the times, artificial intelligence has brought new vitality to forensic medicine, but at the same time also some new challenges. How to deal with these challenges scientifically and form a new mode of 'artificial intelligence plus forensic medicine' with artificial intelligence and forensic medicine developing collaboratively is a new direction for the development of forensic medicine in the era of big data.

Assessment of change in quality of life, carcinoid syndrome symptoms and healthcare resource utilization in patients with carcinoid syndrome.

BACKGROUND: There is limited information on changes over time in carcinoid syndrome (CS) symptoms and quality of life (QoL). This study assessed change in CS symptoms and QoL in patients treated with somatostatin analogs (SSAs) using the Functional Assessment of Cancer Therapy-General (FACT-G) and Patient-Reported Outcomes Measurement Information System (PROMIS)-29 instruments. METHODS: Patients ≥18 years old with CS symptoms and treated with SSA or non-SSA agents in the United States were recruited through a patient advocacy group to complete a two-part, anonymous online survey. Time point (T) 1 survey was fielded from July-October 2016, and T2 survey followed 6 months later. Clinical characteristics and SSA treatment duration were assessed at T1. FACT-G and PROMIS-29 QoL surveys were administered and CS symptoms were assessed at T1 and T2; proportions of patients not experiencing symptoms were compared by McNemar's test. Healthcare resource utilization (HRU) was assessed for the T1-T2 interval, and mean difference in QoL score from T1 to T2 by SSA duration was calculated. RESULTS: Of 117 participants at T1, 89 (76%) completed the T2 survey and served as the study sample; 11 (13%) were treated with SSAs for > 0-2 years, 37 (42%) for > 2-5 years, and 39 (45%) for > 5 years. A higher proportion of patients at T2 vs. T1 reported the following symptoms as not applicable: diarrhea (16% vs. 7%, p < 0.05), flushing (28% vs. 18%, p < 0.05), wheezing (78% vs 66%, p = 0.008). Most patients (89%) had a physical exam and a mean of 7.2 healthcare provider visits between T1 and T2. Patients treated with SSAs for ≤2 years had a mean positive change of 3.7 in their FACT-G total score between surveys, and 6.0 in an additional set of CS-specific questions. Patients receiving SSAs for > 2 years did not appear to associate with a clinically meaningful improvement in QoL score as assessed by FACT-G between T1 and T2; patients also had no clinically meaningful improvement as assessed by PROMIS-29. CONCLUSIONS: There may be clinically important improvement in QoL as measured by FACT-G in patients in earlier years of receiving SSA, which may not appear in later years of SSA treatment.

Treatment patterns and overall survival among patients with unresectable, stage III non-small-cell lung cancer.

Aim: To analyze treatment patterns and overall survival (OS) across time (2009-2014) among patients with unresected, stage III non-small-cell lung cancer (NSCLC). Patients & methods: Stage III NSCLC patients aged ≥65 years who initiated therapy were identified using SEER-Medicare data. Results: Among 4564 patients, 84% received chemotherapy (with or without radiotherapy), and 59% received chemoradiotherapy (CRT). Carboplatin + paclitaxel was the most frequent regimen. Median (interquartile range) OS among chemotherapy patients was 13.2 (6.0-28.9) months, and 14.8 (6.7-33.4) months among CRT patients. Among CRT patients, there was no difference in OS across years of CRT initiation. Conclusion: OS remained static across 2009-2014, indicating stagnancy in clinical outcomes for stage III NSCLC patients and a need for more effective therapeutic options.

SPME-based mobile field device for active sampling of volatiles.

Monitoring plant volatile organic compound (VOC) profiles can reveal information regarding the health state of the plant, such as whether it is nutrient stressed or diseased. Typically, plant VOC sampling uses sampling enclosures. Enclosures require time and equipment which are not easily adapted to high throughput sampling in field environments. We have developed a new, easily assembled active sampling device using solid phase microextraction (SPME) that uses a commercial off the shelf (COTS) hand vacuum base to provide rapid and easy mobile plant VOC collection. Calibration curves for three representative plant VOCs (α-pinene, limonene, and ocimene) were developed to verify device functionality and enable the quantification of field-samples from a Meyer lemon tree. We saw that the active sampling allowed us to measure and quantify this chemical in an orchard setting. This device has the potential to be used for VOC sampling as a preliminary diagnostic in precision agriculture applications due to its ease of manufacturing, availability, and low cost of the COTS hand vacuum module.

Detection of Ancestry Information of Urumqi Mongolians Based on the AIM-InDels Loci Multiplex System.

ABSTRACT: Objective To explore the genetic background and structure of Urumqi Mongolians, the previously developed 39-AIM-InDels panel for ancestry inference was utilized in the present study. Methods The blood samples of 145 unrelated healthy Urumqi Mongolian individuals were collected and genotyped. The compositions of ancestry information of Urumqi Mongolians were studied with 17 different populations from three continents （East Asia, Europe and Africa） as reference populations. Then, multiple population genetics and bioinformatics analysis methods were applied, the Fst and DA values between matched populations were compared and analyzed, PCA analysis was performed and a phylogenetic tree was constructed. The proportions of ancestry information components of Urumqi Mongolians were analyzed with Structure software, etc. Results The ancestry information components of Urumqi Mongolian group in different intercontinental populations accounted for 89%, 7%, and 3% of East Asian, European, and African populations, respectively. Compared with other intercontinental populations, Urumqi Mongolian group and East Asian populations have lower Fst and DA values, and they were in the same cluster in PCA analysis as well. In a phylogenetic tree, the Urumqi Mongolian group was in the same branch as East Asian populations. Conclusion Urumqi Mongolian group had relatively close genetic relationships with East Asian populations, and the proportion of its East Asian ancestry was about 89%.

A polymorphic MYC response element in KBTBD11 influences colorectal cancer risk, especially in interaction with an MYC-regulated SNP rs6983267.

Background: MYC is a well-established cancer driver gene regulating the expression of numerous genes, indicating that polymorphisms in MYC response elements could affect tumorigenesis through altering MYC regulation. We performed integrative multistage study to evaluate the effects of variants in MYC response elements and colorectal cancer (CRC) risk. Patients and methods: We systematically integrated ChIP-Seq, DNase-Seq and transcription factor motif data to screen variants with potential ability to affect the MYC binding affinity. Then, we conducted a two-stage case-control study, totally consisting of 4830 CRC cases and 4759 controls in Chinese population to identify risk polymorphisms and interactions. The effects of risk variants were confirmed by functional assays in CRC LoVo, SW480 and HCT15 cells. Results: We identified a novel polymorphism rs11777210 in KBTBD11 significantly associated with CRC susceptibility (P = 2.43 × 10-12). Notably, we observed a significant interaction between rs11777210 and MYC nearby rs6983267 (P-multi = 0.003, P-add = 0.005), subjects carrying rs6983267 GG and rs11777210 CC genotypes showing higher susceptibility to CRC (2.83-fold) than those carrying rs6983267 TT and rs11777210 TT genotypes. We further demonstrated that rs6983267 T > G increased MYC expression, and MYC bound to and negatively regulated KBTBD11 expression when the rs11777210 C risk allele was present. KBTBD11 was downregulated in tumor tissues, and KBTBD11 knockdown promoted cell proliferation and inhibited cell apoptosis. Conclusion: The rs11777210 is a potential predictive biomarker of CRC susceptibility, and KBTBD11 functions as a putative tumor suppressor in tumorigenesis. Our study highlighted the high CRC risk of people carrying rs6983267 G and rs11777210 C alleles, and provided possible biological mechanism of the interaction.

Platelet-rich fibrin/aspirin complex promotes alveolar bone regeneration in periodontal defect in rats.

BACKGROUND AND OBJECTIVES: The efficacy and outcomes of aspirin in local defects and the use of platelet-rich fibrin (PRF) in periodontal defects were investigated. Whether the PRF/aspirin complex is a suitable scaffold and delivery system to carry sustained-release aspirin/salicylic acid to promote periodontal bone regeneration was determined. MATERIAL AND METHODS: PRF and PRF/aspirin complex were prepared. The concentrations of aspirin/salicylic acid released from the PRF/aspirin complex were calculated at 37°C. Periodontal ligament mesenchymal cells were cultured on six-well plates with PRF or PRF/aspirin complex gel to analyze proliferation and migration. The alveolar bone between the inferior buccal mesial root and anterior buccal distal root of the first maxillary molar was removed in 15 rats randomly divided into three groups: no treatment, PRF or PRF/aspirin complex. Twelve weeks post-transplantation, 2D/3D micro-computed tomography and histomorphometric technique were used for quantitative analyses. RESULTS: The PRF/aspirin complex provided a sustained-release aspirin/salicylic acid. Peak concentrations occurred 4 hours after transplantation and were sustained to 48 hours at 37°C; the total concentration of released aspirin/salicylic acid was 83.5 mg/mL, respectively. The sustained-release promoted the proliferation and migration of periodontal ligament mesenchymal cells. Micro-computed tomography and histological data showed that both the PRF and PRF/aspirin complex enhanced periodontal bone formation (P<.05). Moreover, the new bone formation was two times greater in the PRF/aspirin complex group than the PRF group. CONCLUSION: Aspirin/salicylic acid could be sustained-released from PRF/aspirin complex, which could inhibit inflammation and improve the function of mesenchymal cells. The data might provide a new safe and easy clinical therapeutic strategy to promote periodontal bone reparation.