A sex- and site-specific relationship between body mass index and osteoarthritis: evidence from observational and genetic analyses.

OBJECTIVE: We primarily aimed to investigate whether there are phenotypic and genetic links underlying body mass index (BMI) and overall osteoarthritis (OA). We then intended to explore whether the relationships differ across sexes and sites. METHOD: We first evaluated the phenotypic association between BMI and overall OA using data from the UK Biobank. We then investigated the genetic relationship leveraging summary statistics of the hitherto largest genome-wide association studies performed for BMI and overall OA. Finally, we repeated all analyses in a sex- (female, male) and site- (knee, hip, spine) specific manner. RESULTS: Observational analysis suggested an increased hazard of diagnosed OA per 5 kg/m2 increment in BMI (hazard ratio = 1.38, 95% confidence interval (CI) = 1.37-1.39). A positive overall genetic correlation was observed for BMI and OA (rg = 0.43, P = 4.72 × 10-133), corroborated by 11 significant local signals. Cross-trait meta-analysis identified 34 pleiotropic loci shared between BMI and OA, of which seven were novel. Transcriptome-wide association study revealed 29 shared gene-tissue pairs, targeting nervous, digestive, and exo/endocrine systems. Mendelian randomization demonstrated a robust BMI-OA causal relationship (odds ratio = 1.47, 95% CI = 1.42-1.52). A similar pattern of effects was observed in sex- and site-specific analyses, with BMI affecting OA comparably in both sexes and most strongly in the knee. CONCLUSION: Our work demonstrates an intrinsic relationship underlying BMI and overall OA, reflected by a pronounced phenotypic association, significant biological pleiotropy, and a putative causal link. Stratified analysis further reveals that the effects are distinct across sites and comparable across sexes.

Comparison of Anemia Screening Methods Using Paired Venous Samples in Women of Reproductive Age in Southern India.

BACKGROUND: Anemia is an important public health problem, and accurate estimates may inform policy and programs. Although hemoglobin (Hb) assessment of venous blood via automated hematology analyzers (AHAs) is recommended, most population-based surveys estimate anemia prevalence based on analysis of capillary blood via portable hemoglobinometers. OBJECTIVES: We aimed to evaluate screening methods for hemoglobin and anemia assessment using paired venous samples. METHODS: Participants were women 15-40 y who were not pregnant or lactating. Paired venous whole blood samples (n = 896) were analyzed for hemoglobin (Hb) via portable hemoglobinometer (HemoCue 301) and Coulter Counter AHA. Anemia and severe anemia were defined as Hb <12.0g/dL and <8.0 g/dL, respectively. Bland-Altman methods were used to assess the level of agreement for Hb results (mean difference, SD of differences, limits of agreement). Diagnostic accuracy parameters (sensitivity, specificity, positive predictive value, negative predictive value, accuracy) were calculated to evaluate HemoCue performance compared to the AHA reference, overall and by sociodemographic, nutritional, and metabolic characteristics. RESULTS: The estimated anemia prevalence was significantly lower via HemoCue vs. AHA (36.3% compared with 41.6%; P value < 0.0001). The HemoCue had 84.4% accuracy for anemia screening and 98.8% for severe anemia, compared to the AHA reference. The HemoCue had 74.8% sensitivity and 91.2% specificity, compared to AHA. HemoCue sensitivity was higher in women with iron deficiency [serum ferritin (SF) <15.0 µg/L: 81.6% compared with SF ≥15.0 µg/L: 41.3%], and lower in women with metabolic risk factors, including overweight [BMI ≥25.0 kg/m2: 63.9% vs. BMI <25.0 kg/m2: 78.8%], or elevated CRP (>1.0 mg/L: 67.2% vs. ≤1.0 mg/L: 82.9%), trunk fat (>35%: 62.7% vs. ≤35%: 80.1%), or whole-body fat (>35%: 63.9% vs. ≤35%: 80.3%). CONCLUSIONS: Findings suggest that women with anemia may be incorrectly identified as not anemic via portable hemoglobinometer, and anemia prevalence may be underestimated at the population level.This study was registered at clinicaltrials.gov as NCT04048330.

The Effect of Histogram Analysis of DCE-MRI Parameters on Differentiating Renal Tumors.

BACKGROUND: We aimed to assess the role of histogram analysis of DCE-MRI parameters for accurately distinguishing renal clear cell carcinoma from renal hamartoma with minimal fat. METHODS: Patients with renal tumors were enrolled from January 2013 to December 2015, including renal clear cell carcinoma (n = 39) and renal hamartoma (n = 10). Preoperative DCE-MR Imaging was performed, and whole-tumor regions of interest were drawn to obtain the corresponding histogram parameters, including skewness, kurtosis, frequency size, energy, quartile, etc. Histogram parameters differences between renal clear cell car-cinoma and renal hamartoma with minimal fat were compared. The diagnostic value of each significant parameter in predicting malignant tumors was determined. RESULTS: Histogram parameters of the DCE map contributed to differentiating the benign from malignant renal tumor groups. Histogram analysis of DCE maps could effectively present the heterogeneity of renal tumors and aid in differentiating benign and malignant tumors. ROC analysis results indicated that when frequency size = 1,732 was set as the threshold value, favorable diagnostic performance in predicting malignant tumors was achieved (AUC - 0.964; sensitivity - 84.6%; specificity - 100%), followed by skewness, Energy, Entropy, Uniformity, quartile 5, quartile 50, and kurtosis. CONCLUSIONS: Histogram analysis of DCE-MRI shows promise for differentiating benign and malignant renal tumors. Frequency size was the most significant parameter for predicting renal clear cell carcinoma.

Pulse Oximetry and Perfusion Index Screening for Congenital Heart Defects: A Systematic Review and Meta-analysis.

Congenital heart defects (CHDs) are the most common neonatal malformations and are a leading cause of infant death in developed countries. Finding safe and effective diagnostic methods to screen for CHDs is important. The aim of this study was to evaluate the effectiveness of pulse oximetry (PO) and perfusion index (PI) in screening CHD. We conducted a systematic review of studies in PubMed, Embase, and the Cochrane Library published on or before October 1, 2021. Studies based on PICOS were included in this systematic review. The flow chart is made by PRISMA software. The quality of included studies was assessed by RevMan5 software (QUADAS-2: Quality Assessment of Diagnostic Accuracy Studies-2). The sensitivity, specificity, and other measurements of accuracy were pooled using Stata/SE 12.0 software. Five studies containing 46,965 neonates were included in this study. A randomized-effects model was used for the meta-analysis because of significant heterogeneity. The combined sensitivity and specificity were 0.82 (95% confidence interval [CI], 0.53-0.95) and 0.97 (95% CI, 0.57-1.00), respectively. The area under the curve was 0.92 (95% CI, 0.89-0.94). The combination PO and PI was significant in CHD screening. Once diagnosed by the combined method, it means that the neonate is most likely to have a CHD. KEY POINTS: · Pulse oximetry and PI screening.. · Congenital heart defects.. · A systematic review and meta-analysis..

Recurrent Frameshift Neoantigen Vaccine Elicits Protective Immunity With Reduced Tumor Burden and Improved Overall Survival in a Lynch Syndrome Mouse Model.

BACKGROUND & AIMS: DNA mismatch repair deficiency drives microsatellite instability (MSI). Cells with MSI accumulate numerous frameshift mutations. Frameshift mutations affecting cancer-related genes may promote tumorigenesis and, therefore, are shared among independently arising MSI tumors. Consequently, such recurrent frameshift mutations can give rise to shared immunogenic frameshift peptides (FSPs) that represent ideal candidates for a vaccine against MSI cancer. Pathogenic germline variants of mismatch repair genes cause Lynch syndrome (LS), a hereditary cancer syndrome affecting approximately 20-25 million individuals worldwide. Individuals with LS are at high risk of developing MSI cancer. Previously, we demonstrated safety and immunogenicity of an FSP-based vaccine in a phase I/IIa clinical trial in patients with a history of MSI colorectal cancer. However, the cancer-preventive effect of FSP vaccination in the scenario of LS has not yet been demonstrated. METHODS: A genome-wide database of 488,235 mouse coding mononucleotide repeats was established, from which a set of candidates was selected based on repeat length, gene expression, and mutation frequency. In silico prediction, in vivo immunogenicity testing, and epitope mapping was used to identify candidates for FSP vaccination. RESULTS: We identified 4 shared FSP neoantigens (Nacad [FSP-1], Maz [FSP-1], Senp6 [FSP-1], Xirp1 [FSP-1]) that induced CD4/CD8 T cell responses in naïve C57BL/6 mice. Using VCMsh2 mice, which have a conditional knockout of Msh2 in the intestinal tract and develop intestinal cancer, we showed vaccination with a combination of only 4 FSPs significantly increased FSP-specific adaptive immunity, reduced intestinal tumor burden, and prolonged overall survival. Combination of FSP vaccination with daily naproxen treatment potentiated immune response, delayed tumor growth, and prolonged survival even more effectively than FSP vaccination alone. CONCLUSIONS: Our preclinical findings support a clinical strategy of recurrent FSP neoantigen vaccination for LS cancer immunoprevention.

Population Pharmacokinetics of Intranasal Dexmedetomidine in Infants and Young Children.

BACKGROUND: Intranasal dexmedetomidine provides noninvasive, effective procedural sedation for pediatric patients, and has been widely used in clinical practice. However, the dosage applied has varied fourfold in pediatric clinical studies. To validate an appropriate dosing regimen, this study investigated the pharmacokinetics of intranasal dexmedetomidine in Chinese children under 3 yr old. METHODS: Intranasal dexmedetomidine 2 µg · kg-1 was administered to children with simple vascular malformations undergoing interventional radiological procedures. A population pharmacokinetic analysis with data from an optimized sparse-sampling design was performed using nonlinear mixed-effects modeling. Clearance was modeled using allometric scaling and a sigmoid postmenstrual age maturation model. Monte Carlo simulations were performed to assess the different dosing regimens. RESULTS: A total of 586 samples from 137 children aged 3 to 36 months were included in the trial. The data were adequately described by a two-compartment model with first-order elimination. Body weight with allometric scaling and maturation function were significant covariates of dexmedetomidine clearance. The pharmacokinetic parameters for the median subjects (weight 10 kg and postmenstrual age 101 weeks) in the authors' study were apparent central volume of distribution 7.55 l, apparent clearance of central compartment 9.92 l · h-1, apparent peripheral volume of distribution 7.80 l, and apparent intercompartmental clearance 61.7 l · h-1. The simulation indicated that at the dose of 2 µg · kg-1, 95% of simulated individuals could achieve a target therapeutic concentration of 0.3 ng · ml-1 within 20 min, and the average peak concentration of 0.563 ng · ml-1 could be attained at 61 min. CONCLUSIONS: The pharmacokinetic characteristics of intranasal dexmedetomidine were evaluated in Chinese pediatric patients aged between 3 and 36 months. An evidence-based dosing regimen at 2 µg · kg-1 could achieve a preset therapeutic threshold of mild to moderate sedation that lasted for up to 2 h.

A tetrapeptide class of biased analgesics from an Australian fungus targets the µ-opioid receptor.

An Australian estuarine isolate of Penicillium sp. MST-MF667 yielded 3 tetrapeptides named the bilaids with an unusual alternating LDLD chirality. Given their resemblance to known short peptide opioid agonists, we elucidated that they were weak (Ki low micromolar) µ-opioid agonists, which led to the design of bilorphin, a potent and selective µ-opioid receptor (MOPr) agonist (Ki 1.1 nM). In sharp contrast to all-natural product opioid peptides that efficaciously recruit ß-arrestin, bilorphin is G protein biased, weakly phosphorylating the MOPr and marginally recruiting ß-arrestin, with no receptor internalization. Importantly, bilorphin exhibits a similar G protein bias to oliceridine, a small nonpeptide with improved overdose safety. Molecular dynamics simulations of bilorphin and the strongly arrestin-biased endomorphin-2 with the MOPr indicate distinct receptor interactions and receptor conformations that could underlie their large differences in bias. Whereas bilorphin is systemically inactive, a glycosylated analog, bilactorphin, is orally active with similar in vivo potency to morphine. Bilorphin is both a unique molecular tool that enhances understanding of MOPr biased signaling and a promising lead in the development of next generation analgesics.

[Association study between the KCNE family gene polymorphisms of potassium channel gene and the susceptibility of atrial fibrillation].

Objective: To investigate the relationship between KCNE family gene polymorphisms of potassium channel gene and the susceptibility of atrial fibrillation (AF). Methods: In the case-control study, a total of 648 subjects were studied, of which 338 patients with atrial fibrillation were selected from the Department of Cardiovascular Medicine, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2019 to December 2019, and 310 healthy people were selected from the physical examination population during the same period. DNA sequencing technology and polymerase chain reaction (PCR) were used to detect the genotype and allele frequency of rs1805127 of KCNE1, rs9984281 of KCNE2, rs9516, rs626930 of KCNE3 and rs12621643 of KCNE4. Results: The ages of subjects in atrial fibrillation group and control group were (69±13) and (73±8) years, respectively (P=0.077). Men subjects accounted for 57.70% (195 men) and 40.00% (124 men) in the two groups, respectively (P=0.092). The distribution frequencies of the allele C at rs1805127 of gene KCNE1, the allele A at rs9984281 of gene KCNE2 and the allele G at rs12621643 of gene KCNE4 were significantly different between groups (P<0.05). After adjustment for sex, smoking, hypertension, cardiac insufficiency and other factors, it was found that the increase in the frequency of the above three loci would increase the risk of atrial fibrillation (rs1805127 OR=7.064, 95%CI:1.559-31.997; rs9984281 OR=4.210, 95%CI:1.118-15.850; rs12621643 OR=2.679, 95%CI:1.025-6.998). Conclusion: The rs1805127 of KCNE1, the rs9984281 of KCNE2,the rs12621643 of KCNE4 were significantly associated with the susceptibility to atrial fibrillation.

Litter Additions Reduce the Side Effects of Biocides on Soil Nematode Communities in Illicium Verum Forest.

The application of biocides may create unintended consequences on soil biota and ecosystem stability. The inputs of organic matter can increase biocides adsorption and reduction of non-target organisms influence. A field experiment was conducted to study the changes of soil abiotic and nematode communities resulting from biocides application in non-litter-added and litter-added soils in Illicium verum forest. Our results showed that litter addition could change the responses of soil nematodes to biocides. The influence of fungicide was evident mainly in litter-added plots in which it increased nematode abundance. Insecticide and its interaction with fungicide significantly decreased the diversity index and the abundance of omnivores-predators and herbivores in non-litter-added plots. While, insecticide had little effect on nematode diversity and abundance in litter-added plots. Litter addition may help to maintain the structure and stability of soil food web and result in bacteria dominant decomposition pathway. Our results suggest that litter addition may be a critical factor for maintaining soil ecosystem stability when biocides are applied in Illicium verum forest.

[Establishment and application of a nomogram model for prognostic risk prediction in patients with epithelial ovarian cancer].

Objective: To explore the prognostic factors of epithelial ovarian carcinoma (EOC), construct a nomogram model, and evaluate the prognosis of EOC patients. Methods: A retrospective analysis was performed on clinicopathological data of 208 cases of EOC patients who received initial treatment in the First Affiliated Hospital of Army Medical University from August 11, 2016 to July 11, 2018, including age, preoperative ascites, preoperative neoadjuvant chemotherapy, surgical method, pathological type, pathological differentiation degree, surgical pathology stage, preoperative and post-chemotherapy serum cancer antigen 125 (CA125) level, human epididymal protein 4 (HE4) level, platelet count and platelet/lymphocyte number ratio (PLR). The univariate and multivariate Cox risk ratio models were used to analyze the related factors affecting progression free survival (PFS) in EOC patients, and the prediction nomogram of PFS in EOC patients was established to evaluate its efficacy in predicting PFS. Results: Univariate analysis showed that preoperative neoadjuvant chemotherapy, pathological type, pathological differentiation degree, surgical pathology stage, serum CA125 and HE4 level before operation and after chemotherapy, platelet count and PLR before operation and after chemotherapy were significantly correlated with PFS in EOC patients (all P<0.05). Multivariate analysis showed that surgical pathology stage, preoperative PLR, serum CA125 and HE4 level after chemotherapy were independent prognostic factors affecting PFS of EOC patients (all P<0.01). The index coefficient of the prediction model for the prognosis of EOC patients established by this method was 0.749 (95% CI: 0.699-0.798), which had good prediction ability, and could help clinicians to more accurately evaluate the prognosis of EOC patients. Conclusion: The nomogram model constructed based on surgical pathology stage, preoperative PLR, serum CA125 and HE4 level after chemotherapy could effectively predict the PFS of EOC patients after initial treatment, could help clinicians to screen high-risk patients, provide individualized treatment, and improve the prognosis of EOC patients.

[Analysis on causes and influencing factors of sudden death on job of workers in a large oil field branch plant during 2014-2020].

Objective: To investigate the epidemiological characteristics of sudden death on job among workers in the large oil field, and to provide scientific basis for dealing with such incidents. Methods: In April 2021, the medical records of employees who died in a large oilfield from 2014 to 2020, and the occupational health examination data in the first year of life were collected, and 85 employees who died suddenly on duty were included in the study. According to whether the employees are exposed to the occupational disease hazards, they are divided into the injured type of work (66 persons) and the non injured type of work (19 persons) . The characteristics of the clinical data of the sudden death employees are analyzed retrospectively. The gender, age, length of service, type of work, distribution of causes of sudden death of the cases are analyzed. The detection of abnormalities in various occupational health examination indicators is analyzed. The chi square test is used to analyze the distribution of the types of work, length of service and abnormal physical examination indicators. Results: Among the 85 employees who died suddenly on duty, the ratio of men and women was 16∶1. The proportion of sudden death among employees aged 40 to 50 years was the highest (54.12%, 46/85) , which was mainly the first-line workers in the affected departments (43.53%, 37/85) and those with 20-30 years of service (57.64%, 49/85) . The main cause of sudden death was cardiogenic sudden death (78.82%, 67/85) . There were statistically significant differences in abnormal rates of blood pressure and blood glucose among workers of different types of work (χ(2)=7.24, 24.22, P<0.05) , and there were statistically significant differences in abnormal rates of blood lipid and blood glucose among workers of different ages of service (χ(2)=12.37, 31.44, P<0.05) Conclusion: Higher risks of sudden death on job are male, older than 40 years old, front-line workers in disaster receiving departments, worked for more than 30 years, and have abnormal cardiovascular indicators. Workers with these high risks are the major target population for the prevention and treatment of sudden death on the job. It's necessary to supervise enterprises to implement protective measures against risk factors, and to strengthen health education and reduce the incidence of cardiovascular and cerebrovascular diseases, in order to reduce the occurrence rate of sudden death in oilfield workers.

[Effect of exercise intervention on musculoskeletal disorders in nursing staff].

Objective: To evaluate the effects of exercise intervention on musculoskeletal disorders (MSD) in nursing staff. Methods: In september 2021, we searched the articles on exercise intervention for nurses with musculoskeletal diseases in Embase, PubMed, ClinicalTrails, Wanfang, CNKI and other databases in September 2021, and the search period was from database creation to August 2021. The quality of article was evaluated by Cochrane bias risk assessment tool and MINORS. The systematic review method with narrative synthesis was used to analyze the research results. Results: A total of 7 studies were included, including 6 randomized controlled trials and 1 quasi-experiment. The sample size of the experimental group was 276, and the control group was 273. Depending on the type of exercise intervention, muscle strength training, muscle strength training+stretch/flexibility training, Back School program can reduce the local pain of nursing staff. Among them, muscle strength training can improve the nursing staff's muscle function and quality of life, muscle strength training+stretching/flexibility training can increase muscle strength, range of physical activity and self-efficacy, the Back School program is effective for improving poor posture. Conclusion: Exercise intervention is effective on controlling musculoskeletal disorder symptoms in nursing staff, managers can develop exercise strategies for different MSD symptoms.

The association between vitamin D receptor FokI gene polymorphism and osteoporosis in postmenopausal women: a meta-analysis.

OBJECTIVE: This study aimed to quantitatively summarize the evidence for vitamin D receptor (VDR) FokI gene polymorphism and osteoporosis risk in Caucasian and Asian postmenopausal women. MATERIALS AND METHODS: The PubMed, EMBASE, Weipu, CNKI, and Wanfang databases were searched for eligible studies. Case-control studies containing available genotype frequencies for F/f were chosen, and the odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. RESULTS: In total, 3349 osteoporosis cases and 3202 controls were identified in our meta-analysis. In the stratified analysis, a significant association was observed between VDR FokI gene polymorphism and postmenopausal osteoporosis susceptibility in Asian subjects (additive model: OR = 1.529, 95% CI 1.053-2.219, p = 0.026; dominant model: OR 2.711, 95% CI 1.693-4.342 p < 0.001; co-dominant model: ff vs. FF, OR 2.796, 95% CI 1.439-5.433 p = 0.002), and we failed to find any significant relationship in Caucasian populations. CONCLUSION: The present meta-analysis suggests that the VDR FokI genotype is associated with increased risk of osteoporosis in Asian women but not in Caucasian women. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between VDR FokI polymorphism and osteoporosis.

[Clinicopathological characteristics of rectal neuroendocrine neoplasms].

Objective: Clinicopathological characteristics of neuroendocrine neoplasms are highly heterogeneous based on variable origins.Our study aims to explore the clinical features of rectal neuroendocrine neoplasm (RNEN). Methods: Patients with histologically diagnosed rectal neuroendocrine neoplasms were retrospectively analyzed between January 2012 and December 2020. Epidemiological characteristics, clinical manifestations, complete blood count, endoscopy findings, and pathological features were recorded and analyzed. T-test was used for measurement data analysis, Chi-square test was performed for classification data analysis, and Binary logistic regression was applied for analyzing risk factors of metastasis. Results: Among 172 patients, the male to female ratio was 107 to 65 with an average age of (52±12) years (16-77 years). Altered bowel habit was the most common initial symptom (58/172, 33.7%), followed by abdominal pain (36/172, 20.9%) and loss of body weight (27/172, 15.7%). One hundred and sixty-one cases were neuroendocrine tumors, 9 were neuroendocrine carcinomas and 2 were mixed neuroendocrine-non-neuroendocrine neoplasms. Most endoscopic presentations were polypoid lesions (147/172, 85.5%), mainly limited to mucosa (48/172, 27.9%) and submucosa (96/172, 55.8%). Twenty-nine patients developed lymph node invasion or distant metastasis at diagnosis. There were statistical difference of neutrophil-to-lymphocyte ratios (NLR) among groups with different tumor size (<10 mm vs. 10-20 mm vs.>20 mm, mean NLR 1.79±0.55 vs. 2.27±1.23 vs. 2.95±0.66, P<0.01. Compared with non-metastatic group, the metastatic group presented higher NLR(2.61±0.81 vs. 1.89±0.80, P<0.01). Tumor size (<10 mm vs. 10-20 mm vs.>20 mm, OR 1.00 vs. 2.10 vs. 5.25×109, P =0.001), invasion to bowel wall (mucosa vs. submucosa vs. muscularis vs. serosa invasion,OR 1.00 vs. 3.26 vs. 14.11 vs. 39.42, P=0.008), and NLR (NLR<2.25 vs. NLR≥2.25, OR 1.00 vs. 5.19, P =0.024) were risk factors for metastasis. Conclusion: Metastasis of RNEN is related with tumor size, degree of bowel invasion and NLR. High NLR is a poor prognostic factor of RNEN.

[Evaluation on effectiveness of community-based comprehensive intervention and internet-based intervention for vaccination among patients with chronic diseases].

To evaluate the effectiveness of community-based comprehensive intervention and internet-based intervention on influenza and pneumococcal vaccination in patients with diabetes or chronic obstructive pulmonary disease (COPD) in communities. Before the onset of influenza in 2015 and 2016, five demonstration areas for comprehensive prevention and control of chronic diseases were selected in the study. Patients aged 35 years old and above with diabetes and COPD were selected from selected demonstration areas as study participants. Two communities were selected from each demonstration area and randomly divided into Group A with the community-based comprehensive intervention and Group B with the combination of community-based comprehensive intervention and internet-based intervention within 6 months. The differences of vaccination knowledge, vaccination intention and vaccination proportion in study participants between the two groups before and after interventions were analyzed and compared. A total of 15 226 patients were included in the study. After the intervention the increase in the vaccine knowledge score, vaccination intention and vaccination proportion of patients in the two groups were all higher than those before the intervention. After intervention, the increase of the median score of vaccine knowledge in group B (50.00 points) was higher than that in Group A (42.86 points). The increase of influenza vaccination intention in Group B (6.91%) was higher than that in Group A (4.16%). The increase of proportion of influenza vaccination in Group B (7.35%) was lower than that in Group A (16.61%). The increase of pneumococcal vaccination intention in Group B (7.90%) was lower than that in Group A (9.08%). The proportion of pneumococcal vaccination in Group B (3.37%) was lower than that in Group A (4.06%). Community-based comprehensive intervention could improve the level of vaccine knowledge, vaccination intention and vaccination proportion of patients in this study. Combined with community-based intervention, internet-based intervention could have a better effect on improving vaccine knowledge and influenza vaccination intention, but its impact on vaccination proportion needs to be further explored.

Identification of genetic loci associated with growth traits at weaning in yak through a genome-wide association study.

A multilocus GWAS was performed to explore the genetic architecture of four growth traits in yak. In total, 354 female yaks for which measurements of body weight (BW), withers height (WH), body length (BL) and chest girth (CG) at weaning were available underwent genotyping with the Illumina BovineHD BeadChip (770K). After quality control, we retained 98 688 SNPs and 354 animals for GWAS analysis. We identified seven, 18, seven and nine SNPs (corresponding to seven, 17, seven and eight candidate genes) associated with BW, WH, BL and CG at weaning respectively. Interestingly, most of these candidate genes were reported to be involved in growth-related processes such as muscle formation, lipid deposition, feed efficiency, carcass composition and development of the central and peripheral nervous system. Our results offer novel insight into the molecular architecture underpinning yak growth traits. Further functional analyses are thus warranted to explore the molecular mechanisms whereby these genes affect these traits of interest.

Clinical characteristics of lip infantile haemangiomas and main risk factors for ulceration: an 8-year retrospective study of 69 Chinese infants.

BACKGROUND: Infantile haemangiomas (IHs) involving the lip are of special concern because of the susceptibility of complications, including ulceration, obstruction and disfigurement. The available data for the relationship between their clinical characteristics and ulcerations are limited. OBJECTIVES: To describe the clinical characteristics of lip IHs and to evaluate the main risk factors for ulceration. METHODS: A retrospective study was designed that included infants with lip IHs during an 8-year period, the clinical data of participants were collected, and univariable and multivariable logistic models were used to determine the relationships between the clinical characteristics of lip IHs and ulcerations. Location, size and type were investigated as potential independent factors influencing the development of ulceration. RESULTS: A total of 69 lip IHs were identified including 40 girls and 29 boys. Ulcerations were found in 37 (53.6%) lip IHs. Lip haemangiomas experiencing ulceration had a mean size (SD) of 3.49 (2.82) cm2 compared with 1.08 (0.96) cm2 for those without ulceration. Twenty-eight (52.8%) of the 53 localized haemangiomas and 9 (56.3%) of the 16 segmental haemangiomas experienced ulcerations. Univariable analyses of all investigated factors revealed significant associations of location and size with increased risk of ulceration, and these significant associations remained after adjusting for sex and age [OR 8.61 (95% CI, 2.24-33.13) and 2.62 (95% CI, 1.46-4.72), respectively]. The duration before ulceration was between 4 and 70 days after the occurrence of lip IHs, with a median of 28 (19.41) days. Most ulcers occurred within 45 days of IH occurrence. CONCLUSIONS: Ulceration is a common complication of lip IHs at an earlier stage. A swollen with pale or bright crimson appearance of the lip IH surface could be an important signal of subsequent ulceration. Location of the IH on the lower lip and lip IH size are risk factors for the occurrence of ulceration.

(Phospho)proteomic Profiling of Microsatellite Unstable CRC Cells Reveals Alterations in Nuclear Signaling and Cholesterol Metabolism Caused by Frameshift Mutation of NMD Regulator UPF3A.

DNA mismatch repair-deficient colorectal cancers (CRCs) accumulate numerous frameshift mutations at repetitive sequences recognized as microsatellite instability (MSI). When coding mononucleotide repeats (cMNRs) are affected, tumors accumulate frameshift mutations and premature termination codons (PTC) potentially leading to truncated proteins. Nonsense-mediated RNA decay (NMD) can degrade PTC-containing transcripts and protect from such faulty proteins. As it also regulates normal transcripts and cellular physiology, we tested whether NMD genes themselves are targets of MSI frameshift mutations. A high frequency of cMNR frameshift mutations in the UPF3A gene was found in MSI CRC cell lines (67.7%), MSI colorectal adenomas (55%) and carcinomas (63%). In normal colonic crypts, UPF3A expression was restricted to single chromogranin A-positive cells. SILAC-based proteomic analysis of KM12 CRC cells revealed UPF3A-dependent down-regulation of several enzymes involved in cholesterol biosynthesis. Furthermore, reconstituted UPF3A expression caused alterations of 85 phosphosites in 52 phosphoproteins. Most of them (38/52, 73%) reside in nuclear phosphoproteins involved in regulation of gene expression and RNA splicing. Since UPF3A mutations can modulate the (phospho)proteomic signature and expression of enzymes involved in cholesterol metabolism in CRC cells, UPF3A may influence other processes than NMD and loss of UPF3A expression might provide a growth advantage to MSI CRC cells.

[Clinical value of p16INK4a immunocytochemistry in cervical cancer screening].

Objective: To evaluate the value of p16INK4a detected by p16INK4a immunostaining as a new generation of cervical cytology for primary screening and secondary screening in population-based cervical cancer screening, and in improving cytological diagnosis. Methods: Between 2016 and 2018, 5 747 non-pregnant women aged 25-65 years with sexual history were recruited and underwent cervical cancer screening via high-risk (HR)-HPV/liquid-based cytological test (LCT) test in Shenzhen and surrounding areas. All slides were immuno-stained using p16INK4a technology, among them, 902 cases were offered p16INK4a detection during primary screening, and the remaining 4 845 cases were called-back by the virtue of abnormal HR-HPV and LCT results for p16INK4a staining. Participants with complete LCT examination, HR-HPV test, p16INK4a staining and histopathological examination results were included in this study. The performance of p16INK4a in primary and secondary screening, and in assisting cytology to detect high grade squamous intraepithelial lesion [HSIL, including cervical intraepithelial neoplasia (CIN) Ⅱ or Ⅲ] or worse [HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+] were analyzed. Results: (1) One-thousand and ninety-seven cases with complete data of p16INK4a and histology were included. Pathological diagnosis: 995 cases of normal cervix, 37 cases of low grade squamous intraepithelial lesion (LSIL), 64 cases of HSIL and one case of cervical cancer were found. Among them, 65 cases of HSIL (CIN Ⅱ)+ and 34 cases of HSIL (CIN Ⅲ)+ were detected. The positive rate of p16INK4a in HSIL (CIN Ⅱ)+ was higher than that in CINⅠ or normal pathology (89.2% vs 10.2%; P<0.01). (2) p16INK4a as primary screening for HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+ was equally sensitive to primary HR-HPV screening (89.2% vs 95.4%, 94.1% vs 94.1%; P>0.05), but more specific than HR-HPV screening (89.8% vs 82.5%, 87.7% vs 80.2%; P<0.05). p16INK4a was equally sensitive and similarly specific to cytology (≥LSIL; P>0.05). (3) The specificity of LCT adjunctive p16INK4a for detecting HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+ were higher than that of LCT alone or adjunctive HR-HPV (P<0.01), while the sensitivity were similar (P>0.05). (4) p16INK4a staining as secondary screening: p16INK4a was significantly more specific (94.1% vs 89.7%, 91.9% vs 87.4%; P<0.01) and comparably sensitive (84.6% vs 90.8%, 88.2% vs 91.2%; P>0.05) to cytology for triaging primary HR-HPV screening. HPV 16/18 to colposcopy and triage other HR-HPV with p16INK4a was equally sensitive (88.2% vs 94.1%; P=0.500) and more specific (88.3% vs 83.0%; P<0.01) than HPV 16/18 to colposcopy and triage other HR-HPV with LCT≥ atypical squamous cells of undetermined significance (ASCUS), and the referral rate decreased (14.0% vs 19.4%; P=0.005). Conclusions: For primary screening, p16INK4a is equally specific to cytology and equally sensitive to HR-HPV screening. p16INK4a alone could be an efficient triage after primary HR-HPV screening. In addition, p16INK4a immunostaining could be used as an ancillary tool to cervical cytological diagnosis, and improves its accuracy in cervical cancer screening.

[The value of p16(INK4a) cytology for early diagnosis of cervical cancer].

Objective: To investigate the use of p16(INK4a) immuno-stained cytology as the primary screening for cervical cancer prevention. Methods: From March to August 2018, 902 women from Shenzhen and surrounding area were recruited for cervical cancer screening with ThinPrep Cytologic Test (TCT), cobas4800 HPV test, and p16(INK4a) co-test. Colpo/biopsies were performed using the point of interest biopsy protocol of directed and random cervical biopsies plus endocervical curettage for all women, any of whose tests was positive. Two senior cytopathologists interpreted TCT and p16(INK4a) test. The performance of p16(INK4a) for early detection of CIN2+ and inter-observer reproducibility of the interpretation of p16(INK4a) were evaluated. Results: The positive rates of HPV test, p16(INK4a) co-test and TCT diagnosed as LSIL/AGC or higher grade were 8.1% (73/902), 6.8% (61/902) and 4.7% (42/902), respectively. Colposcopy referring rate was 79.6% (109/137), among which 10 cases were diagnosed as CIN2+ (5 cases of CIN2 and 5 cases of CIN3). The sensitivity and specificity for CIN2+ of p16(INK4a) test, TCT (LSIL/AGC or higher grade) and HPV test were 90.0%, 80.0%, 100.0% and 90.9%, 91.9%, 82.5%, respectively. Compared to TCT and HPV test, there was no significant difference in sensitivity and specificity between p16(INK4a) and TCT/HPV test (P>0.05). The Kappa value of the 2 cytopathologists in interpreting p16(INK4a) and TCT was 0.944 and 0.425, respectively (P<0.05). Conclusions: p16(INK4a) for cervical cancer screening is equally sensitive to HPV test and specific to TCT while subjective difference of cytopathologists' interpretation of p16(INK4a) is small. Therefore, p16(INK4a) can be used as a new cervical cancer screen method for its better diagnostic performance.