Associations of change in body fat percentage with baseline body composition and diabetes remission after bariatric surgery.

OBJECTIVE: The objective of this study was to determine the role of body fat percentage (BFP) changes in diabetes remission (DR) and the association between baseline body composition and its changes after bariatric surgery. METHODS: We analyzed 203 patients with type 2 diabetes who underwent Roux-en-Y gastric bypass. Body composition was measured using a gold-standard-derived predictive equation and magnetic resonance imaging. Body composition changes were calculated as 100 × (baseline value - follow-up value)/baseline value. We verified the results in a laparoscopic sleeve gastrectomy cohort with 311 patients. RESULTS: Compared with non-remission patients in the Roux-en-Y gastric bypass cohort, those who achieved DR showed a higher baseline fat-free mass index (FFMI) and experienced the most significant changes in BFP (p < 0.001). In comparative analyses, BFP changes were significantly better than BMI changes in identifying short- and long-term DR. Linear regression analysis identified FFMI as the most significant baseline variable correlated with BFP changes (p < 0.001). Baseline BMI was positively correlated with changes in BFP but negatively correlated with changes in FFMI. These findings were replicated in the laparoscopic sleeve gastrectomy cohort. CONCLUSIONS: BFP changes determine DR after bariatric surgery, and baseline FFMI is crucial for BFP changes. A low initial BMI is associated with a smaller BFP reduction and greater FFMI loss after bariatric surgery.

Effective Treatment of Anlotinib Combined With Chemotherapy in Children With Desmoplastic Small Round Cell Tumor: A Case Series in a Single-center and Literature Review.

INTRODUCTION: Desmoplastic small round cell tumor (DSRCT) is a highly aggressive primitive sarcoma with a 5-year survival rate estimated at only 15% to 30%. Although few curative treatment options exist, patients are most often treated with a combination of aggressive chemotherapy, radiation, and surgery. Targeted therapy inhibitors of platelet-derived growth factor A, insulin-like growth factor receptor 1, and vascular endothelial growth factor receptor-2, which are almost uniformly overexpressed in DSRCT, have largely failed in clinical trials. Anlotinib is a multitarget receptor tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor α/ß, c-Kit, and Met. In this study, we presented 3 cases of DSRCT treated effectively with anlotinib combined with chemotherapy. CASE PRESENTATION: Three children DSRCT patients were enrolled from September 2020 to December 2021 and monitored until August 30, 2022. The clinical data were prospectively studied. The peritoneal cancer index classified all 3 patients as stage IV. After surgery, all 3 patients received anlotinib in combination with chemotherapy and reacted to the medication. For all 3 patients, clinical symptoms were substantially eased, and the size of the masses was reduced. Patient 1 and patient 3's progression-free survival had been extended, and anlotinib was continued as a maintenance medication in the 2 patients who were in good health at the end of the follow-up. Patient 2 died of postoperative complications 1 month after second-stage surgery. The main side effects of anlotinib were fatigue and hypertension. However, its toxicity was controllable and tolerable in children patients. CONCLUSIONS: This is the first report that anlotinib is effective in children with DSRCT. This report may provide an additional option for the treatment of metastatic DSRCT.

Compliant-Control-Based Assisted Walking with Mobile Manipulator.

In this paper, a new approach involving the use of a mobile manipulator to assist humans with mobility impairments to walk is proposed. First, in order to achieve flexible interaction between humans and mobile manipulators, we propose a variable admittance controller that can adaptively regulate the virtual mass and damping parameters based on the interaction forces and the human motion intention predicted using the fuzzy theory. Moreover, a feedforward velocity compensator based on a designed state observer is proposed to decrease the inertia resistance of the manipulator, effectively enhancing the compliance of the human-robot interaction. Then, the configuration of the mobile manipulator is optimized based on a null-space approach by considering the singularity, force capacity, and deformation induced by gravity. Finally, the proposed assisted walking approach for the mobile manipulator is implemented using the human-robot interaction controller and the null-space controller. The validity of the proposed controllers and the feasibility of assisted human walking are verified by conducting a set of tests involving different human volunteers.

Piperine promotes PI3K/AKT/mTOR-mediated gut-brain autophagy to degrade α-Synuclein in Parkinson's disease rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum L., a medicinal and food homologous herb, has a traditional history of use in treating gastrointestinal and neurological disorders. Piperine (PIP) the main alkaloid of P. longum, exists neuroprotective effects on various animal models of Parkinson's disease (PD). Nevertheless, the underlying mechanism, particularly the role of PIP in promoting gut-brain autophagy for α-Synuclein (α-Syn) degradation in PD, remains incompletely understood. AIM OF THE STUDY: To explore the role of PIP in regulating the gut-brain autophagy signaling pathway to reduce α-Syn levels in both the colon and substantia nigra (SN) of PD model rats. MATERIALS AND METHODS: Behavioral experiments were conducted to assess the impact of PIP on 6-hydroxydopamine (6-OHDA)-induced PD rats. The intestinal microbiome composition and intestinal metabolites were analyzed by metagenomics and GC-MS/MS. The auto-phagosomes were visualized by transmission electron microscopy. Immunohistochemistry, immunofluorescence, and western blotting were performed to assess the levels of tyrosine hydroxylase (TH), α-Syn, LC3II/LC3I, p62, and the PI3K/AKT/mTOR pathway in both the SN and colon of the rats. The pathway-related inhibitor and agonist were used to verify the autophagy mechanism in the SH-SY5Y cells overexpressing A53T mutant α-Syn (A53T-α-Syn). RESULTS: PIP improved autonomic movement and gastrointestinal dysfunctions, reduced α-Syn aggregation and attenuated the loss of dopaminergic neurons in 6-OHDA-induced PD rats. After oral administration of PIP, the radio of LC3II/LC3I increased and the expression of p62 was degraded, as well as the phosphorylation levels of PI3K, AKT and mTOR decreased in the SN and colon of rats. The effect of PIP on reducing A53T-α-Syn through the activation of the PI3K/AKT/mTOR-mediated autophagy pathway was further confirmed in A53T-α-Syn transgenic SH-SY5Y cells. This effect could be inhibited by the autophagy inhibitor bafilomycin A1 and the PI3K agonist 740 Y-P. CONCLUSIONS: Our findings suggested that PIP could protect neurons by activating autophagy to degrade α-Syn in the SN and colon, which were related to the suppression of PIP on the activation of PI3K/AKT/mTOR signaling pathway.

Preparation, characterization, and anticancer effects of an inclusion complex of coixol with ß-cyclodextrin polymers.

CONTEXT: Coix [Coix lacryma-jobi L. var. mayuen (Roman.) Stapf (Poaceae)], a crop of medicinal and edible significance, contains coixol, which has demonstrated anticancer properties. However, the limited solubility of coixol restricts its potential therapeutic applications. OBJECTIVE: This study prepared a water-soluble coixol-ß-cyclodextrin polymer (CDP) inclusion compound and evaluated its anticancer effect. MATERIALS AND METHODS: The coixol-CDP compound was synthesized through a solvent-stirring and freeze-drying technique. Its coixol content was quantified using HPLC, and its stability was tested under various conditions. The anticancer effects of the coixol-CDP compound (4.129, 8.259, 16.518, and 33.035 mg/L for 24, 48, and 72 h) on the proliferation of non-small cell lung cancer (NSCLC) A549 cells were evaluated using an MTT assay; cell morphology was examined by Hoechst nuclear staining; apoptosis and cell cycle was detected by flow cytometry; and the expression of apoptosis-related proteins was assessed by Western blots. RESULTS: The water-soluble coixol-CDP inclusion compound was successfully prepared with an inclusion ratio of 86.6% and an inclusion yield rate of 84.1%. The coixol content of the compound was 5.63% and the compound remained stable under various conditions. Compared to coixol alone, all 24, 48, and 72 h administrations with the coixol-CDP compound exhibited lower IC50 values (33.93 ± 2.28, 16.80 ± 1.46, and 6.93 ± 0.83 mg/L) in A549 cells; the compound also showed stronger regulatory effects on apoptosis-related proteins. DISCUSSION AND CONCLUSIONS: These findings offer a new perspective for the potential clinical application of Coix in NSCLC therapy and its future research.

Effect of regional body composition changes on bone density remodeling after sleeve gastrectomy.

Background: Sleeve gastrectomy (SG) results in bone mineral density (BMD) loss and varying body composition parameters. However, the effects of body compositions on bone health are controversial. In order to accurately demonstrate their relationship and provide new insights into the causes of BMD loss after sleeve gastrectomy, this study is aimed to investigate the role of changes in body composition in BMD loss 12 months after SG. Methods: 41 Chinese individuals with obesity (25 women and 16 men) who underwent SG were prospectively examined for at least 12 months. Measurements of anthropometrics, body composition, BMD and blood samples were collected. Results: For 12 months, the femoral neck (FN) BMD and total hip (TH) BMD decreased significantly compared with baseline in both sexes but not lumbar spine (LS) BMD. Greater TH BMD loss was observed in men than in women. For the first 6 months post-SG, the FN BMD loss was positively associated with the estimated fat free mass index (eFFMI) reduction in women (adjusted ß = 0.77, P = 0.004) and positively associated with reduction of subcutaneous fat area (SFA) in men (r = 0.931, P = 0.007). For 12 months post-SG, the FN BMD loss was negatively associated with visceral fat area (VFA) reduction in women (adjusted ß = -0.58, P = 0.027) and men (adjusted ß = -0.68, P = 0.032). TH BMD loss was positively associated with waist circumference reduction in women (r = 0.448, P = 0.028). Conclusion: FN and TH BMD decrease after SG in both women and men. The changes in body compositions are associated with BMD loss at different time points and bone sites. Our data emphasize the limitation of simply taking the total weight loss (% TWL) as an influencing factor of bone mineral density and the necessity of delineating body composition in relevant studies.

Astrocharis margarita sp. nov., a new snake star (Echinodermata, Ophiuroidea, Euryalidae) from a seamount in the Western Pacific.

During the scientific expedition of the R/V Kexue in 2014, a new species belonging to the genus Astrocharis Koehler, 1904 was collected from a seamount near the Yap Trench. Astrocharis margarita sp. nov. is distinguished from the other species of Astrocharis by the following characters: radial shields are partly naked or completely covered by polygonal ossicles, and the body color is uniformly light pink. Maximum Likelihood Tree and Bayesian Tree, based on a concatenated dataset of COI, 16S, and 18S genes analyses, indicated that the monophyly of Astrocharis was not supported, which suggested the genus needs to be revised.

Influence of temperature on the risk of gestational diabetes mellitus and hypertension in different pregnancy trimesters.

Previous studies have proved that exposure to extreme temperature in specific windows of pregnancy could cause some complications, such as pregnancy induced hypertension (PIH) and gestational diabetes mellitus (GDM), but differences in the effect of extreme temperature on the 2 complications are rarely studied. We carried a retrospective study on the impact of temperature on GDM/PIH in different trimesters based on data from a maternal and child health center in Beijing, China. Ambient temperatures (°C) were obtained from the China Meteorological Administration from January 1st, 2013 to May 15th, 2018. We use distributed lag non-linear models (DLNMs) combined with logistic regression to calculate the lag exposure-response relationships between the temperature and GDM/PIH from 1st to 24th/20th weeks of pregnancy. In both first and second trimesters, the risk of GDM was increased in summer with high temperatures; in second trimester, the risk of GDM increased in winter with low temperatures. In first half of pregnancy, risk of PIH was decreased in winter with low temperatures. These findings can provide the guideline for preventing the GDM and PIH induced by extreme temperature during pregnancy.

Effect of acute PM2.5 exposure on PTGS2 and RNA m6A modification.

Particulate matter 2.5 (PM2.5) is a prevalent risk factor in many diseases, but its molecular mechanism remains ambiguous and may be diverse. RNA m6A is an important epigenetic modification that regulates gene expression at the post-transcriptional level. Some previous animal exposure studies found that PM2.5 exposure up-regulated m6A RNA methylation in the lung, but there is no research on m6A RNA methylation in humans from PM2.5 exposure now. Here, in the present experiment, we performed a panel study of 65 students at the Chinese research academy of environmental sciences (CRAES) with 3 rounds of follow-up visits from August 2021 to January 2022. We examined m6A RNA modification profiles of peripheral blood mononuclear cells (PBMCs) from subjects after low and high concentrations of ambient PM2.5 exposure. We applied a linear mixed-effect (LME) model to investigate the association between PM2.5 exposure and global m6A RNA methylation and PTGS2 level in peripheral blood. We found that increased levels of global m6A RNA methylation and PTGS2 level were associated with higher PM2.5 exposure. Among the methylated mRNAs, PTGS2 was hyper-methylated after high concentrations of PM2.5 exposure, which coincided with the increased expression of PTGS2 mRNA. In the present study, we determined that PM2.5 exposure promoted RNA m6A modification, and PTGS2 in peripheral blood could serve as a novel regulatory factor of inflammation induced by PM2.5 exposure. Furthermore, RNA m6A modification may contribute to the altered expression of PTGS2 induced by PM2.5 exposure. Our finding provided a new perspective for the prevention and treatment of PM2.5 exposure-induced adverse health effects.

Mutation, food-grade expression, and characterization of a lactonase for zearalenone degradation.

Zearalenone (ZEN) is a mycotoxin that causes serious threats to human health. People are exposed to ZEN contamination externally and internally through many ways, while environmental-friendly strategies for efficient elimination of ZEN are urgently needed worldwide. Previous studies revealed that the lactonase Zhd101 from Clonostachys rosea can hydrolyze ZEN to low toxicity compounds. In this work, the enzyme Zhd101 was conducted with combinational mutations to enhance its application properties. The optimal mutant (V153H-V158F), named Zhd101.1, was selected and introduced into the food-grade recombinant yeast strain Kluyveromyces lactis GG799(pKLAC1-Zhd101.1), followed by induced expression and secretion into the supernatant. The enzymatic properties of this mutant were extensively examined, revealing a 1.1-fold increase in specific activity, as well as improved thermostability and pH stability, compared to the wild-type enzyme. The ZEN degradation tests and the reaction parameters optimization were carried out in both solutions and the ZEN-contaminated corns, using the fermentation supernatants of the food-grade yeast strain. Results showed that the degradation rates for ZEN by fermentation supernatants reached 96.9% under optimal reaction conditions and 74.6% in corn samples, respectively. These new results are a useful reference to zearalenone biodegradation technologies and indicated that the mutant enzyme Zhd101.1 has potential to be used in food and feed industries. KEY POINTS: • Mutated lactonase showed 1.1-fold activity, better pH stability than the wild type. • The strain K. lactis GG799(pKLAC1-Zhd101.1) and the mutant Zhd101.1 are food-grade. • ZEN degradation rates by supernatants reached 96.9% in solution and 74.6% in corns.

Exposure to ambient air pollution from the preconceptional period and risk of gestational hypertension.

Although accumulative studies have revealed the associations between air pollutants and elevated risk of gestational hypertension (GH), evidence from developing countries with relatively higher levels of air pollutants remains limited. In this retrospective study, a total of 45,439 birth records were collected in Beijing, China from 2013 to 2018. For PM2.5, SO2, NO2, and O3, exposure windows from the 3rd month of preconception to the 6th month of conception and the averages of 3 months of preconception, trimester 1 and trimester 2 periods were all calculated for assessment of GH risks. The correlations between air pollutants and the risk of GH were analyzed by logistic regression model. Our results showed that exposure to PM2.5 and SO2 in the preconceptional and early pregnancy periods was related to the elevated risk of GH. Furthermore, 3 months preconceptional exposure to PM2.5 (PCPM2.5: OR = 1.134 (1.114, 1.155)) and SO2 (PCSO2: OR = 1.158 (1.135, 1.181)) showed a higher risk of GH than the results of the trimester 1 (T1PM2.5: OR = 1.131 (1.104, 1.159); T1SO2: OR = 1.164 (1.141, 1.187)) and the trimester 2 (T2PM2.5: OR = 1.154 (1.126, 1.182); T2SO2: OR = 1.121 (1.098, 1.144)). The study also found significant and higher OR values for PCPM2.5, and PCSO2 from 2013 to 2016 when air pollution was serious in Beijing compared with 2017 to 2018 when the air pollution was obviously improved. Subgroup analysis also found that during 3 months of preconception women with higher age and who exposure to higher temperatures showed higher GH risk from PM2.5 and SO2 than that of the younger group and who exposure to lower temperature, respectively. Collectively, our findings suggest that air pollution exposure was adversely associated with GH in pregnant women and the preconceptional period is a critical air pollution exposure window for GH. Improving air quality can benefit public health, especially for sensitive populations like pregnant women.

Apelin-36 alleviates LPS-induced trophoblast cell injury by inhibiting GRP78/ASK1/JNK signaling.

Pre-eclampsia (PE) is a type of hypertensive disorder of pregnancy that poses a serious threat to the health of both mother and fetus. Inhibition of the inflammatory environment on trophoblast cells is of great significance to improve PE. Apelin-36 is an endogenous active peptide with strong anti-inflammatory activity. Therefore, this study aims to investigate the effects of Apelin-36 on lipopolysaccharide (LPS)-induced trophoblast cells and its potential mechanism. The levels of inflammatory factors (TNF-α, IL-8, IL-6 and MCP-1) were detected by reverse transcription-quantitative PCR (RT-qPCR). The proliferation, apoptosis, migration and invasion capacities in trophoblast cells were detected by CCK-8, TUNEL staining, wound healing and Transwell assays, respectively. GRP78 was overexpressed by cell transfection. Western blot was applied for the identification of protein levels. Apelin concentration-dependently decreased the expression of inflammatory cytokines and p-p65 protein level in trophoblast cells induced by LPS. Apelin treatment reduced LPS-induced apoptosis and improved the proliferation, invasion and migration capacities of LPS-mediated trophoblast cells. Additionally, Apelin down-regulated GRP78, p-ASK1 and p-JNK protein levels. The inhibition on LPS-induced trophoblast cell apoptosis and the promotion on invasion and migration by Apelin-36 was counteracted by GRP78 overexpression. To sum up, Apelin-36 could alleviate LPS-induced cell inflammation and apoptosis and improve the invasion and migration of trophoblasts by inhibiting the GRP78/ASK1/JNK signaling.

Risk of ozone exposure-induced fracture.

Introduction: Ozone (O3) is known to induce oxidative stress that influences various cells and tissues, which may further lead to diminished bone mineral density. Nevertheless, few studies have investigated the association between O3 exposure and fractures. Considering the similar growing trends of O3 concentrations and fracture morbidity in recent years, in the present study, we aimed to examine whether O3 exposure is associated with the fracture morbidity. Methods: Using a retrospective cohort study design, we analyzed the records of 8,075 patients with fracture admitted in the warm season to Beijing Jishuitan Hospital from 2014 to 2019 and matched them to the corresponding exposure time and concentration of O3. Results: The results showed that increased odds of fracture were associated with increased O3 concentrations, presumably because O3 induces oxidative stress (OS) that leads to bone mineral density (BMD) loss. Discussion: Our findings suggest that O3 exposure is a risk factor for fractures, providing new evidence of the adverse health effect induced by air pollution. We can conclude that more intensive air pollution control is needed for the prevention of fracture occurrence.

Influence of different concentrations of ozone on the alteration of mitochondrial DNA copy numbers in human peripheral blood.

By now, O3 pollution has become a main environmental problem. O3 is a prevalent risk factor for many diseases, but the regulatory factors linking O3 and diseases remain ambiguous. Mitochondrial DNA (mtDNA) is the genetic material in mitochondria, which plays a key role in the production of respiratory ATP. Due to a lack of histone protection, mtDNA is easily damaged by ROS, and O3 is an important source to stimulate the production of endogenous ROS in vivo. Therefore, we logically speculate that O3 exposure can alter mtDNA copy number by the induction of ROS. In the present study, we performed a panel study of 65 MSc students at the Chinese research academy of environmental sciences (CRAES) with 3 rounds of follow-up visits from August 2021 to January 2022. We examined the mtDNA copy numbers in the peripheral blood of subjects using quantitative polymerase chain reaction. Linear mixed-effect (LME) model and stratified analysis were used to investigate the association between O3 exposure and mtDNA copy numbers. We found a dynamic process of the association between the concentration of O3 exposure and the mtDNA copy number in the peripheral blood. The lower concentration of O3 exposure did not affect the mtDNA copy number. As the concentration of O3 exposure increased, the mtDNA copy number also increased. While, when O3 exposure reached a certain concentration, a decrease in mtDNA copy number was found. This correlation between the concentration of O3 and the mtDNA copy number could be ascribed to the severity of cellular damage induced by O3 exposure. Our results provide a new perspective for the discovery of a biomarker of O3 exposure and health response, as well as for the prevention and treatment of adverse health effects caused by different concentrations of O3.

Incidence of postoperative hypothermia and shivering and risk factors in patients undergoing malignant tumor surgery: a retrospective study.

BACKGROUND: Perioperative hypothermia and shivering are common and can cause adverse outcomes. The aim of this study was to investigate the incidence of postoperative hypothermia and shivering and their risk factors in patients undergoing malignant tumor surgery. METHODS: This retrospective study collected data from patients with American Society of Anesthesiologists physical status (ASA) I or II who underwent scheduled surgery from November 2020 to March 2021 at Fudan University Shanghai Cancer Center. Each patient's core body temperature was measured at three time points: time point 1 (arrival at the postanesthesia care unit (PACU)), time point 2 (after 30-min care in the PACU), and time point 3 (at discharge from the PACU). At time point 1, if the patient's body temperature was below 36 ℃, we provided an active forced-air warmer. At time point 2, if it was still below 36 ℃, the forced-air warmer was still applied until the patient was discharged from the PACU. If it reached 36 ℃, the forced-air warmer would be switched off. Univariate and multivariate logistic regression combined with stepwise methods and linear regression were used to explore risk factors for postoperative hypothermia and shivering. RESULTS: The numbers (percentage) of 202 patients who developed postoperative hypothermia at the different time points were 52 (25.7%), 37 (18.3%) and 28 (13.9%). Eight patients (4.0%) experienced shivering. Multivariate logistic regression showed that high weight (OR = 0.923, 95% CI: 0.884 to 0.964, P = 0.0003) and low estimated blood loss (OR = 0.252, 95% CI: 0.115 to 0.550, P = 0.0005) were protective factors against hypothermia, while long surgical duration (OR = 3.339, 95% CI: 1.675 to 6.655, P = 0.0006) was an independent risk factor for hypothermia at time point 1. There was no risk factor associated with the occurrence of shivering (P > 0.05). There was a significant difference between the hypothermia and normothermia groups in the median length of stay in the PACU (59.0 vs. 49.0 min, P = 0.0123). CONCLUSIONS: Postoperative hypothermia occurred frequently. Weight, estimated blood loss and surgical duration were significantly associated with hypothermia on arrival at the PACU.

Air pollution exposure and the risk of macrosomia: Identifying specific susceptible months.

Birth weight is an important indicator of future growth and development for newborns. Few studies investigated the potential effects of air pollutants on macrosomia and their susceptible windows. We included 38,971 singleton full-term births from Beijing HaiDian Maternal and Child Health Hospital between 2014 and 2018, and assessed the associations of air pollutants exposure during preconception and pregnancy with macrosomia as well as the corresponding susceptible windows. The concentrations of air pollutants (PM2.5, PM10, SO2, NO2, CO and O3) for participants were calculated by the data from the nearest monitoring stations. Distributed lag models (DLM) incorporating logistic regression models were used to estimate the associations between air pollutants exposure during the 3 months before conception and pregnancy period and the risk of macrosomia, identifying susceptible windows of air pollutants. Weighted quantile sum (WQS) regression was applied to estimate the joint effect of air pollutants. A 10 µg/m3 increase in PM2.5 exposure from 3rd to 8th gestational month was positively associated with the risk of macrosomia, with the strongest effect in the 6th month (OR = 1.010, 95 % CI: 1.002-1.019). For a 10 µg/m3 increase in SO2, the windows of significant exposure were from the 1st preconception month to the 3rd gestational month, with the strongest effect in the 2nd month (OR = 1.030, 95 % CI: 1.010-1.049). We also observed the significant positive associations were in the 5th-8th gestational months for PM10, the 8th-9th gestational months for NO2 and the 3rd-7th gestational months for CO respectively. WQS regression also indicated a positive association between co-exposure to air pollutants and macrosomia. Our results suggest air pollution exposure is associated with increased risk of macrosomia. The windows of exposure for susceptibility to the risk of macrosomia vary between air pollutants. The susceptible exposure windows were middle and late pregnancy for PM, CO and NO2, while for SO2, early pregnancy is the window of vulnerability. Our findings provide the evidence that air pollution exposure is an independent risk factor for macrosomia and a basis for targeted environment policy.

Evaluation of Combined use of Fecal Multigene Mutation Test and Fecal Immunochemical Test for Colorectal Cancer Screening.

BACKGROUND: The aim was to investigate the value of concomitant use of fecal KRAS-APC-p53-BRAF mutation test and a fecal immunochemical test (FIT) for colorectal cancer (CRC) screening. METHODS: Stool samples of 279 subjects were collected from the Fujian provincial hospital and divided into five groups: CRC (n = 82); advanced adenoma (AA, n = 76); non-advanced adenoma (NAA, n = 24); healthy control (n = 85); and interference group (n = 12). All stool samples were tested using a fecal multigene mutation (KRAS-APC-p53-BRAF) Kit and FIT. RESULTS: The sensitivity of combined use of fecal multigene mutation test and FIT for detecting CRC [84.15% (69/ 82)] was significantly higher than that of fecal multigene mutation test [47.56% (39/82), p < 0.001] or FIT [71.95% (59/82), p < 0.001] alone. The sensitivity of combined use for detection of AA [48.68% (37/76)] was also significantly higher than that of multigene mutation test [26.32% (20/76), p < 0.001] or FIT [28.95% (22/76), p < 0.001] alone. The specificity of combined use for detection of NAA and healthy control was 87.16%. CONCLUSIONS: The combination of fecal multigene (KRAS-APC-p53-BRAF) mutation test and FIT has greater sensitivity than alone and may be a useful noninvasive method for CRC screening.

Sex-specific differences in bone mineral density loss after sleeve gastrectomy.

Background: Sleeve gastrectomy is an effective bariatric procedure; however, sleeve gastrectomy-related adverse skeletal outcomes have been increasingly reported. High levels of sex hormone-binding globulin (SHBG) have been documented to be a risk factor of bone mineral density (BMD) loss with different effects observed between sexes. The aim of this study was to identify sex-specific changes in BMD following sleeve gastrectomy and to evaluate the role of SHBG in this process. Methods: This retrospective study included 19 middle-aged men and 30 non-menopausal women with obesity who underwent sleeve gastrectomy in China. Anthropometrics, bone turnover markers, calciotropic hormones, BMD, SHBG, and gonadal steroids were measured preoperatively and at 6 and 12 months postoperatively. Longitudinal changes in BMD, bone turnover markers and SHBG were compared between sexes by linear mixed models. Multiple stepwise regression analysis was used to identify the predictors of BMD loss at the investigated bone sites. Results: Over the 12-month study period, total hip and femoral neck BMD decreased, while lumbar spine BMD remained largely unchanged in both sexes. Linear mixed models revealed significant sex × time interaction effects in total hip BMD and SHBG, showing that men had a significantly greater reduction in total hip BMD and less increase in SHBG after sleeve gastrectomy than women. In the multivariate model, SHBG was significantly associated with total hip BMD loss in men (adjusted ß = -0.533, P = 0.019) but not women while total estrogen was significantly associated with total hip BMD loss in women (adjusted ß = 0.508, P = 0.01) but not men. Conclusion: Significant sex-specific BMD changes were observed after sleeve gastrectomy in the current study. Sleeve gastrectomy-related increase in SHBG may be a specific risk factor for total hip BMD loss in men. Our results indicate that sex-specific screening may be warranted to facilitate personalized postoperative bone care in this population.

An Improved Isotope Labelling Method for Quantifying Deamidated Cobratide Using High-Resolution Quadrupole-Orbitrap Mass Spectrometry.

Protein deamidation can severely alter the physicochemical characteristics and biological functions of protein therapeutics. Cobratide is a non-addictive analgesic with wide clinical acceptance. However, the Asn residue at position 48 from the N-terminus of the cobratide amino acid sequence (N48) tends to degrade during purification, storage, and transport. This characteristic could severely affect the drug safety and clinical efficacy of cobratide. Traditional methods for quantitating deamidation reported in previous research are characterised by low efficiency and accuracy; the quality control of cobratide via this method is limited. Herein, we developed an improved 18O-labelling method based on the detection of a unique peptide (i.e., the protein fragment of cobratide containing the N48 deamidation hotspot after enzymolysis) using an Orbitrap high-resolution mass spectrometer to quantify deamidated cobratide. The limits of detection and quantification of this method reached 0.02 and 0.025 µM, respectively, and inter- and intra-day precision values of the method were <3%. The accuracy of the 18O-labelling strategy was validated by using samples containing synthesised peptides with a known ratio of deamidation impurities and also by comparing the final total deamidation results with our previously developed capillary electrophoresis method. The recoveries for deamidation (Asp), deamidation isomerisation (iso-Asp), and total deamidation were 101.52 ± 1.17, 102.42 ± 1.82, and 103.55 ± 1.07, respectively. The robustness of the method was confirmed by verifying the chromatographic parameters. Our results demonstrate the applicability of the 18O-labelling strategy for detecting protein deamidation and lay a robust foundation for protein therapeutics studies and drug quality consistency evaluations.