Causal relationship between Type 1 diabetes and osteoporosis and fracture occurrence: a two-sample Mendelian randomization analysis.

We used two-sample Mendelian Randomization to reveal causal estimates of type 1 diabetes and bone. Type 1 diabetes was found to be a risk factor for bone metabolic health, although there was no clear evidence to support a genetic association between type 1 diabetes and osteoporosis and fracture risk. INTRODUCTION: Based on the random assignment of gametes at conception, Mendelian randomization (MR) analysis simulates randomized controlled trials in an observational setting. Therefore, we used MR to assess the association causality of type 1 diabetes (T1D) with fractures and osteoporosis. METHODS: From a genome-wide association meta-analysis, independent single nucleotide polymorphisms closely associated with T1D were selected as instrumental variables. Data on fracture and osteoporosis were obtained from the FinnGen Consortium. We performed a two-sample MR analysis, using inverse-variance weighted (IVW) as the primary analysis method, to assess possible causal associations between T1D and bone risk. The results were verified by MR-Egger regression and median weighted method (WME). MR-PRESSO and MR-Egger intercepts were used to evaluate the horizontal pleiotropy of instrumental variables, and the Q-test and "leave-one-out" methods were used to test the heterogeneity of MR results. RESULTS: IVW (OR=1.040, 95% CI=0.974-1.109, P=0.238), MR-Egger regression (OR=1.077, 95% CI=0.921-1.260, P=0.372) and WME (OR=1.021, 95% CI=0.935-1.114, P=0.643) all showed that there was no causal relationship between T1D and osteoporosis, but the direction was consistent. The indicative significance of IVW results in T1D and forearm fractures (OR=1.062, 95% CI=1.010-1.117, P=0.020), but the results are not robust enough. There was no causal effect in femur, lumbar and pelvis, or shoulder and upper arm fractures. CONCLUSIONS: After MR analysis, although T1D may be a risk factor for bone health, we do not have sufficient evidence to support a causal effect of T1D on osteoporosis and fractures at a genetically predicted level. More cases need to be included for analysis.

Propofol Inhibits Ferroptotic Cell Death Through the Nrf2/Gpx4 Signaling Pathway in the Mouse Model of Cerebral Ischemia-Reperfusion Injury.

Ferroptosis is characterized by excessive accumulation of iron and lipid peroxides, which are involved in ischemia, reperfusion-induced organ injury, and stroke. Propofol, an anesthetic agent, has neuroprotective effects due to its potent antioxidant, anti-ischemic, and anti-inflammatory properties. However, the relationship between propofol and ferroptosis is still unclear. In the current study, we elucidated the role of ferroptosis in the neuroprotective effect of propofol in mouse brains subjected to cerebral ischemia reperfusion injury (CIRI). Ferroptosis was confirmed by Western blotting assays, transmission electron microscopy, and glutathione assays. Propofol regulated Nrf2/Gpx4 signaling, enhanced antioxidant potential, inhibited the accumulation of lipid peroxides in CIRI-affected neurons, and significantly reversed CIRI-induced ferroptosis. Additionally, Gpx4 inhibitor RSL3 and Nrf2 inhibitor ML385 attenuated the effects of propofol on antioxidant capacity, lipid peroxidation, and ferroptosis in CIRI-affected neurons. Our data support a protective role of propofol against ferroptosis as a cause of cell death in mice with CIRI. Propofol protected against CIRI-induced ferroptosis partly by regulating the Nrf2/Gpx4 signaling pathway. These findings may contribute to the development of future therapies targeting ferroptosis induced by CIRI.

Analysis of Online Recruitment Intention Among 543 Hospitals: A Comprehensive Investigation of Influencing Factors and Current Situation.

Objective: The primary objective of this study was to investigate the current state of online recruitment intention among hospitals and identify its key influencing factors. This research aims to provide valuable insights that can guide the development of recruitment and employment strategies for hospital departments and student management. Methods: This study employed a cross-sectional survey approach involving 543 hospitals. Data collection utilized both convenient offline recruitment methods and online recruitment information platforms. A total of 543 questionnaires were distributed, resulting in the collection of 543 valid responses. The participating hospitals comprised 225 tertiary hospitals and 318 secondary hospitals. Additionally, the sample included 430 general hospitals, 113 psychiatric hospitals, dental hospitals, and 406 specialized hospitals. Geographically, 137 hospitals were located in urban counties or towns. Furthermore, 333 hospitals targeted undergraduate graduates, while 210 focused on graduate students. Results: The analysis of the data revealed several significant findings. Among the included hospitals in the sample, 19.71% expressed online recruitment intention for candidates with neurasthenia. Factors contributing to a higher online recruitment intention among hospitals included a preference for recruiting undergraduates (P = .011), the belief that online recruitment is suitable for clinical positions (P = .002), challenges in assessing candidates' expertise online (P = .002), concerns about dishonesty in online recruitment (P = .028), and the perception that online recruitment requires less technical expertise for hospitals (P < .001). Conclusions: This study highlights the multifaceted nature of online recruitment intention within hospitals. The identified influential factors emphasize the need for customized strategies in recruitment and employment. Medical university recruitment and employment departments should adopt tailored measures that align with the unique dynamics of online recruitment to address these factors effectively. In this way, hospitals can enhance their recruitment processes and ensure the selection of candidates that meet their specific requirements.

[Endoscopic treatment of Mirizzi syndrome]. / Endoskopicheskoe lechenie sindroma Mirizzi.

Mirizzi syndrome is a complication of cholelithiasis occurring in 0.25-6% of cases [1]. Clinical pattern includes jaundice due to prolapse of a large calculus into the common bile duct following cholecystocholedochal fistula. Ultrasound, CT, MRI, MRCP data, as well as some pathognomonic signs provide preoperative diagnostics of Mirizzi syndrome. In most cases, treatment of this syndrome requires open surgery. We report successful endoscopic treatment of a patient with long-standing bile stone disease complicated by Mirizzi syndrome. Postoperative complications of surgery performed in acute period of disease and further staged treatment using retrograde access are illustrated. Endoscopic treatment demonstrated minimally invasive management of disease presenting diagnostic and technical difficulties.

[A follow-up study on the introduction of vegetables and fruits during infants aged 4-8 months in Beijing and Chenzhou City of Hunan Province].

OBJECTIVE: To investigate the introduction of vegetables and fruits in 4-8 months old infants, and to describe the maternal and infants' characteristics associated with the introduction of vegetables and fruits. METHODS: Mother-infant dyads (n=228) were recruited from 12 to 16 weeks postpartum and formally entered the study at 4 months of age. Data collected via face to face interview at 4-8 months postpartum, including the timing and types of added vegetables and fruits, as well as a variety of maternal and infant characteristics (n=204). Rank sum test and multiple linear regression were used to analyze the maternal and infant characteristics related to the introduction of vegetables and fruits. RESULTS: The time of introducing vegetables was concentrated at the age of 7 months, and the time of adding fruits was mainly at 6 months. Fruits were added earlier than vegetables (P < 0.001), and the variety of the added fruits was higher than that of vegetables (P=0.045). 48% (n=98) of infants had no more than three types of fruits and vegetables at 8 months. Only 9.8% (n=20) had added more than 10 kinds of fruits and vegetables at 8 months. Green leafy vegetables were the most commonly added vegetable, and apple was the most popular fruit. Compared with women who were 35 years of age or younger, women beyond 35 years old introduced vegetables to their babies 0.6 months later. 4-month-old exclusively breastfed infants had vegetables 0.4 months later than mixed-fed infants. Women with a bachelor's degree or above added 2-3 more types of fruits and vegetables to their babies than those with junior high school education and below. CONCLUSION: The adding time of fruits was earlier than that of vegetable. Apples and green leafy vegetables are commonly added. Women with lower educational backgrounds add fewer types of fruits and vegetables to their babies. Mothers who choose exclusive breastfeeding and those over 35 years of age at childbirth add vegetables to their babies later than others. They should be targeted for health promotion programs that aim to improve the intake of fruits and vegetables among infants.

[Clinical characteristics and prognosis of lymphoma-associated hemophagocytic syndrome].

Subjective To investigate clinical characteristics, treatment, and prognosis of lymphoma-associated hemophagocytic syndrome (LAHS) patients. Methods: The clinical data of patients diagnosed with LAHS from January 2010 to October 2021 in West China Hospital were retrospectively analyzed. Clinical characteristics, treatment, overall response rate (ORR), and overall survival (OS) were investigated. Univariate and multivariate analysis of potential factors were conducted. Results: Of all 94 patients included, 59 were male and 35 were female. The age at hemophagocytic lymphohistiocytosis (HLH) diagnosis was (40.5±17.3) years. Seventy-four cases were T/NK cell lymphoma; 15 were B cell lymphoma; 5 were Hodgkin lymphoma. The age at HLH diagnosis of T/NK cell LAHS patients was (37.9±16.2) years, while that of B cell LAHS patients was (55.9±14.0) years. T/NK cell LAHS patients were significantly younger than B cell LAHS patients (P<0.001). Baseline fibrinogen of T/NK cell LAHS patients was 1.34 (0.86, 2.44) g/L, while that of B cell LAHS patients was 2.20 (1.75, 4.25) g/L. T/NK cell LAHS patients showed significantly lower fibrinogen levels than B cell LAHS patients (P=0.008). Combined treatment of anti-HLH and anti-lymphoma treatment was conducted in 35 patients; anti-HLH treatment was conducted in 31 patients; anti-lymphoma treatment was conducted in 8 patients; glucocorticoid treatment was conducted in 7 patients. ORR was 49.4%, and the median OS was 61 days for overall patients. Patients who received anti-HLH treatment and turned to anti-lymphoma treatment early displayed the best ORR and OS, significantly higher than those of anti-HLH patients (69.0 vs 38.7%, P=0.019, and 192.0 vs 24.5 days, P=0.028, respectively), which were also insignificantly higher than those of anti-lymphoma patients. Extranodal NK/T-cell lymphoma or aggressive natural killer cell leukemia was the risk factor of LAHS prognosis (HR=0.113, 95%CI: 0.018-0.728, P=0.022). Conclusions: Prognosis of LAHS patients is poor. Anti-lymphoma treatment should be initiated as soon as HLH is rapidly controlled.

[Efficacy and safety of daratumumab in patients with relapsed/refractory multiple myeloma].

Objective: To investigate the efficacy and safety of daratumumab in relapsed/refractory multiple myeloma (RRMM) patients. Methods: Fifty-two RRMM patients treated with daratumumab from September 2019 to November 2021 in West China Hospital were retrospectively enrolled, including 31 males and 21 females. The mean age of these patients at the first diagnosis of multiple myeloma was (58±10) years. According to the dosage of daratumumab, patients were divided into low dosage group (n=10) and high dosage group (n=42). Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse event rates were investigated. Univariate and multivariate analysis of potential factors were conducted. Results: Of the 52 patients, 8 received daratumumab monotherapy, 27 received daratumumab plus immuno-modulatory drug (IMiD) treatment, 4 received daratumumab plus proteosome inhibitor (PI) treatment, and 11 received daratumumab plus dexamethasone treatment. The diagnosis age of high dosage group patients was (57±9) years, which was significantly younger than that of low dosage group [(66±10) years] (P=0.009). The baseline creatinine level of high dosage group patients [M (Q1, Q3)] was 91 (68, 196) µmol/L, which was significantly higher than that of low dosage group [66 (51, 76) µmol/L] (P=0.021). There was no significant difference in other baseline clinical characteristics, previous treatment regimens, previous lines of treatment, and regimen and cycles of daratumumab between the high dosage group and low dosage group (all P>0.05). The ORR for the 52 patients was 71.2% (37/52). The ORR for daratumumab plus IMiD group was 81.5% (22/27), which was significantly higher than that in monotherapy or dexamethasone group [ORR: 52.6% (10/19), P=0.036). With a median follow-up [M (Q1, Q3)] of 7 (5, 26) months, the median PFS for overall cohort was 17 (95%CI: 9.6-24.4) months. The median PFS for daratumumab plus IMiD group was 26 (95%CI: 6.0-46.0) months, which was significantly better than that in monotherapy or dexamethasone group [12 (95%CI: 3.5-20.5) months] (HR=0.231, 95%CI: 0.075-0.715, P=0.011). Higher diagnosis age was the risk factor of progression (HR=1.085, 95%CI: 1.016-1.158, P=0.014), while more cycles of daratumumab treatment was the protective factor of progression (HR=0.669, 95%CI: 0.495-0.904, P=0.009). There was no significant influence of daratumumab dosage on progression (high dosage vs low dosage, HR=1.016, 95%CI: 0.221-4.668, P=0.984). The median OS for overall cohort was 26 (95%CI: 13.1-38.9) months. Higher serum calcium was the independent risk factor of death (HR=12.190, 95%CI: 1.170-127.048, P=0.037). There was no significant influence of daratumumab dosage on death (high dosage vs low dosage, HR=0.818, 95%CI: 0.171-3.917, P=0.802). Adverse events included infections (43.2%, 16/37), infusion-associated reactions (29.7%, 11/37), and thrombocytopenia (27.0%, 10/37). Conclusions: Daratumumab is effective to treat RRMM. The dosage of daratumumab has no significant influence on prognosis when used in combined treatment. The incidence of adverse events is relatively low, with a favorable safety profile.

[Relationship between nutrients intake during pregnancy and the glycemic control effect in pregnant women with gestational diabetes mellitus].

OBJECTIVE: To explore the relationship between nutrients intake during pregnancy and the glycemic control effect in pregnant women with gestational diabetes mellitus (GDM). METHODS: Pregnant women for 25-35 gestational weeks who underwent prenatal examination and completed GDM diagnostic test in two third-class hospitals in Beijing from October 2015 to October 2017 were recruited to participate in the cohort study, and were investigated at enrollment, 2 weeks after enrollment, and delivery. The cross-sectional survey data 2 weeks after enrollment was used for this study. Among them, dietary survey used the 24 h dietary records to collect the food intake of the subjects for the past day, and the intake of energy, macronutrients and micronutrients, was calculated according to the Chinese Food Composition Table. Using the data of fasting blood glucose (FBG) collected by clinical information system and referring to the Chinese Guidelines for the Diagnosis and Treatment of Pregnancy Diabetes (2014), the GDM patients with FBG ≤5.3 mmol/L were divided into the well-control group, those with FBG >5.3 mmol/L were divided into poorly-control group, and pregnant women with normal glucose tolerance were consi-dered as the normal group. Binary Logistic regression was used to analyze the association between the nutrients intake and glycemic control effect in pregnant women with GDM. RESULTS: A total of 227 pregnant women were enrolled, including 104 GDM patients and 123 normal pregnancy women. Among them, 76 subjects in the well-control group (73.1%, 76/104) and 28 subjects in the poorly-control group (26.9%, 28/104). Compared with the well-control group and the normal group, the protein intake and its energy ratio of the poorly-control group were significantly higher, while carbohydrate energy ratio was significantly lower. In terms of micronutrients, there was no significant difference between the well-control group and the poorly-control group. After adjusting for age, gestational age and physical activity level, with the well-control group as the control group, binary Logistic regression model showed that higher protein energy ratio was positively correlated with poorly glycemic control effect in pregnant women with GDM (OR=6.12, 95%CI: 1.44-25.98), while higher carbohydrate energy ratio was negatively correlated with poorly glycemic control (OR=0.54, 95%CI: 0.32-0.91). CONCLUSION: Reduced protein intake and increased carbohydrate intake were associated with better glycemic control in pregnant women with GDM. It is suggested that GDM patients should adjust their dietary pattern further to achieve good glycemic control effect.

[Study on lung injury induced by rare earth samarium oxide particles in rats].

Objective: To study the effect of samarium trioxide (Sm(2)O(3)) particles on rat lung tissue and compare it with the same dose of silica (SiO(2)) particles, in order to find the reference index for early screening of pneumoconiosis. Methods: In October 2018, 72 SPF healthy male rats were randomly divided into control group, SiO(2) group and Sm(2)O(3) group. The lungs of rats in each group were perfused with 2.0 ml/kg normal saline and 280 mg/kg SiO(2) and Sm(2)O(3) particle suspension by one-time non exposed tracheal perfusion. The lungs of rats were stained with hematoxylin eosin (HE) staining, and the pathological changes of lung tissues were observed. The concentrations of SNAIL homologue 1 (SNAI1) , SNAIL homologue 2 (SNAI2) , and heat shock protein-27 (HSP-27) in rat serum were detected by enzyme-linked immunosorbent assay. 0.5 g of lung tissue from rats in Sm(2)O(3) group and control group exposed to dust for 56 days was screened for long-chain noncoding RNA (lncRNA) and circular RNA (circRNA) . Results: After 7 days of dust exposure, the alveoli in SiO(2) group and Sm(2)O(3) group were disordered, and lymphoid tissue aggregation and proliferation were observed around the bronchial wall. At 14 days, a large number of lymphocytes infiltrated in SiO(2) group, and a small number of macrophages containing Sm(2)O(3) and fibrotic nodules scattered in Sm(2)O(3) group. At 28 days, a small amount of lymphocyte infiltration appeared in SiO(2) group, and fibrotic nodules were seen in some areas of Sm(2)O(3) group. At 56 days, there was a small amount of fibroblast proliferation in SiO(2) group, and a large number of fibrotic nodules containing gray black matter were seen in Sm(2)O(3) group. There was no significant difference in lung organ coefficient among groups at different dust exposure time (P>0.05) . After 14 days of dust exposure, the contents of SNAI1 and SNAI2 in serum of rats in SiO(2) group were lower than those in control group, the content of SNAI2 in serum of Sm(2)O(3) group was lower than that in control group, and the contents of SNAI1 and SNAI2 in serum of Sm(2)O(3) group were higher than those in SiO(2) group (P<0.05) . The content of HSP-27 in SiO(2) group was lower than that in control group (P<0.05) . After 56 days of dust exposure, the content of HSP-27 in Sm(2)O(3) group was lower than that in control group (P<0.05) . At 56 days, lncRNA in Sm(2)O(3) group was up-regulated by 148 and down regulated by 725, circRNA was up-regulated by 16 and down regulated by 153. Conclusion: Sm(2)O(3) can cause lung injury in rats, and the change of SNAI2 content can be detected in the early stage, which can be used as a reference index for early screening of pneumoconiosis. There are differences in the expression of lncRNA and circRNA after 56 days of dust exposure in rats, which may be related to the pathogenesis of pneumoconiosis.

Exploring the Mechanism on the Medullary Visceral Zone Inhibiting the Cholinergic Anti-inflammatory Pathway Induced by Sepsis.

Inflammatory storm is an important pathological mechanism of multiple organ dysfunction, and it is associated with most deaths in septic patients, deserving to be studied. Recent findings have confirmed that the Medullary Visceral Zone (MVZ) regulates inflammation and immunity through the cholinergic anti-inflammatory pathway (CAP), but how sepsis affects the MVZ and leads to uncontrolled inflammation remain unclear. The current study reported that sepsis induced MVZ to inhibit CAP which underlies the inflammation storm. Our studies have shown that the rat models of sepsis prepared by cecal ligation and puncture had a higher inflammatory level, higher mortality, and higher Murine Sepsis Score. In septic rats, some indicators of heart rate variability (HRV) such as SDNN, HF band, RMSSD, SD1, and SD2 significantly reduced. In MVZ of septic rats, many cholinergic and catecholaminergic neurons showed apoptotic, with low expressions of tyrosine hydroxylase and choline acetyltransferase. The α7nAChR agonist GTS-21 can improve these pathologies, while the α7nAChR antagonist MLA is the opposite. Our study demonstrates for the first time that cholinergic and catecholaminergic neurons in MVZ went through significant apoptosis and inactiveness in sepsis, which contributes to the inhibition of CAP and acceleration of the inflammation storm in early sepsis. Intervening with CAP has a significant effect on the activity and apoptosis of MVZ neurons while altering systemic inflammation and immunity; in addition, for the first time, we confirmed that some indicators of HRV such as SDNN, HF band, RMSSD, SD1, and SD2 can reflect the activity of CAP, but the CAP interference had little effect on these indicators.

[Research on consistency of different measurement methods for saliva 1,5-anhydroglucitol].

Objective: To evaluate the consistency of different measurement methods of saliva 1,5-anhydroglucitol (1,5-AG) in different glucose metabolism populations. Methods: From January 2018 to June 2019, 175 healthy volunteers (21-65 years, 58 males and 117 females) with normal glucose tolerance (NGT) and 80 diabetic patients (18-70 years, 44 males and 36 females) were enrolled in Shanghai Jiao Tong University Affiliated Sixth People's Hospital. Saliva was collected by saliva collection tube, and 1,5-AG was measured using both enzymatic and mass spectrometry methods. Serum 1,5-AG was determined by enzymatic method. Results: In NGT subjects, both serum and saliva 1,5-AG levels detected by enzymatic method were positively correlated with the saliva 1,5-AG levels detected by liquid chromatography-mass spectrometry (r=0.247 and 0.523, respectively, both P<0.05). However, there was no significant correlation between saliva and serum 1,5-AG levels detected by enzymatic method (r=-0.074, P=0.333). In diabetic patients, both serum and saliva 1,5-AG levels detected by enzymatic method were positively correlated with the saliva 1,5-AG levels detected by gas chromatography-mass spectrometry (r=0.284 and 0.423, respectively, both P<0.05). However, there was no significant correlation between saliva and serum 1,5-AG levels detected by enzymatic method (r=-0.079, P=0.487). Conclusions: Both serum and saliva 1,5-AG levels detected by enzymatic method have a good consistency with saliva 1,5-AG levels detected by mass spectrometry method. The saliva and serum 1,5-AG levels detected by enzymatic method are not well correlated, and thus the enzymatic detection of saliva 1,5-AG needs further improvement in clinical practice.

[Investigation of the screening interval for population with negative colonoscopy examinations].

Objective: To investigate the colonscopy screening interval among patients with negative colonscopy. Methods: We selected 14 606 participants who completed the baseline and 3-year or 5-year colonoscopy examinations in the American Prostate, Lung, Colorectal, and Ovarian (PLCO) dataset as the target population. Sociodemographic characteristics (i.e., sex, age, marital status, race, and smoking), lifestyle, family history of cancer, and family history of colorectal cancer were collected. Cochran-Armitage trend analysis was used to examine whether the rate of positive cases (colorectal cancer, advanced adenoma, adenoma, and hyperplastic polyp) was increased with the length of screening interval. We compared the differences in number of detected cases, positive rates, and proportions of 3-year and 5-year screening interval strategies using internal standardization method. Results: The age of the population was （61.9±5.2） years and over half of them were males (54.4%) and 46.2% had family cancer history. The mean screening interval between the first and second endoscopies was （1 639.1±320.9） days. A total of 1 716 cases had positive endoscopic findings. With the screening interval extended, rate of the screened positive cases was also increased (P for trend<0.001). After standardized by the internal standardized population (14 606), 17.99 and 11.57 colorectal cancer cases and 177.37 and 240.35 advanced adenoma cases were detected by 3-year and 5-year screening interval strategies, respectively. Conclusion: Based on the initial screening negative population of colonoscopy in the United States, the 3-year screening interval strategy could detect a relatively large number of colorectal cancer cases, but its health and economic evaluation needs to be further explored.

[Study on the relationship between dietary quality and the risk of diabetes and prediabetes in urban women].

Objective: To explore the relationship between dietary quality and the risk of diabetes and prediabetes among urban women based on alternative healthy eating index-2010（AHEI-2010). Methods: From March to July 2016, a total of 1 061 female residents from 8 cities, Beijing, Guangzhou, Chengdu, Lanzhou, Xuchang, Jilin, Wuhu and Chenzhou in China, were selected by using the multi-stage sampling method. The basic characteristics of all participants were collected by using self-made questionnaire, and the dietary status of the subjects was collected by using 24-hour dietary recall method. AHEI-2010 scores were calculated and the diet was divided into low, medium and high dietary quality group according to the third quartile. All participants received physical examination, systolic blood pressure test, fasting blood glucose test and glycosylated hemoglobin test. Unconditional logistic regression model was used to analyze the relationship between dietary quality and the risk of diabetes and prediabetes. Results: The age of all participants was（48.0±17.5) years old. The median（P25, P75) of AHEI-2010 score was 46.52（40.04, 54.88). The prevalence of diabetes and prediabetes were 13.3%（141 cases) and 50.0%（530 cases), respectively. Unconditional logistic regression analysis showed that after adjusting for age, city, education, diet control, physical activity, energy intake and waist circumference, compared with the low diet quality group, the OR（95%CI) values of medium, high dietary quality group and diabetes risk were 0.96（0.57-1.62) and 0.63（0.36-1.09), respectively; the OR（95%CI) values of medium, high dietary quality group and prediabetes risk were 0.93（0.64-1.35) and 1.28（0.87-1.88), respectively. Conclusion: The dietary quality of urban women based on AHEI-2010 evaluation is not related to the risk of diabetes and prediabetes.

Recurrent Extra-gastrointestinal Stromal Tumor of the Vagina: A Case Report and Review of the Literature.

Gastrointestinal tumors are uncommonly found outside the gastrointestinal tract, and extremely rare in the vaginal wall. In this case report, a 39-year-old female, she was finally diagnosed with an extra gastrointestinal stromal tumor (EGIST) when she presented with a recurrent vaginal tumor, while misdiagnosed after the first surgery. She had definitive surgical clearance and was taking targeted drug therapy with no sign of recurrence after follow-up for 13 months. Immunohistochemistry and cytogenetic's remain the most definitive method to diagnose EGISTs. Surgical resection and postoperative adjuvant targeted therapy are the optimum treatment options.

Discovery of potential biomarkers for osteoporosis using LC-MS/MS metabolomic methods.

Our study focused on the associations of metabolites with BMD and osteoporosis, finding that several metabolites are associated with BMD, and metabolites combined with bone turnover markers tend to be more sensitive in distinguishing osteoporosis in both males and postmenopausal females, which might be meaningful for the early diagnosis of osteoporosis. INTRODUCTION: Our study aimed to evaluate the association of metabolites with bone, trying to find new metabolic markers that are distinguishing for low bone mineral density (BMD). METHODS: Our study recruited 320 participants, including 138 males and 182 postmenopausal females from the Shanghai area. Bone turnover markers (BTMs), including osteocalcin, PINP and ß-CTX, and other biochemical traits were tested. BMD values of the lumber spine (L1-4), femoral neck and total hip were determined using dual-energy X-ray absorptiometry and the serum metabolome profiles including 221 metabolites from five groups (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids and hexose) were assessed by mass spectrometry. RESULTS: No visual separation in the metabolic profiles between different BMD groups was observed in principal component analysis (PCA) or partial least squares discriminant analysis (PLS-DA) models. We compared metabolites in three groups with different BMD levels in males and postmenopausal females separately and further filtering these metabolites via random forest-based feature selection, a commonly applied machine learning algorithm which could select the features with the greatest impact on osteoporosis, then metabolites with the highest importance (≥ 5%) (5 in males and 9 in postmenopausal females) were selected to construct better models for osteoporosis classification. After adding these selected metabolites to the model, the area under the curve (AUC) of receiver operating characteristic (ROC) curves increased significantly (BTMs: AUC 0.729, 95% CI 0.647-0.802, p < 0.0001, model 1: AUC = 0.828, 95% CI 0.754-0.888, p < 0.0001; model 1 versus model of BTMs: p = 0.0158) compared to the AUC of the BTM-only model in males. Similar results were also observed in postmenopausal females (BTMs: AUC = 0.638, 95% CI 0.562-0.708, p = 0.0025; model 2: AUC = 0.741, 95% CI 0.669-0.803, p < 0.0001; model 1 versus model of BTMs: p = 0.0182). CONCLUSION: Metabolites combined with traditional BTMs tend to better markers for distinguishing osteoporosis in both males and postmenopausal females than BTMs alone.

Associations of maternal upper respiratory tract infection/influenza during early pregnancy with congenital heart disease in offspring: evidence from a case-control study and meta-analysis.

BACKGROUND: Evidences regarding the associations between maternal upper respiratory tract infection/influenza during pregnancy and the risk of congenital heart disease (CHD) is still controversial. This study was specifically designed to examine the associations by a case-control study and a meta-analysis of the published evidences and our finding. METHODS: A hospital-based case-control study involving 262 children with simple CHD and 262 children with complex CHD, along with 262 control children, was conducted through June, 2016 to December, 2017. All children were aged 0-2 years old. Furthermore, a meta-analysis based on both previously published studies and our case-control study was performed. RESULTS: In the case-control study, after adjusting for possible confounders, maternal upper respiratory tract infection/influenza during early pregnancy was found to be related to an increased risk of CHD (OR = 3.40 and 95% CI: 2.05-5.62 for simple CHD; OR = 2.39 and 95% CI: 1.47-3.88 for complex CHD). After a meta-analysis, the adverse impact was still kept significant (OR = 1.47 and 95% CI: 1.28-1.67 for simple CHD; OR = 1.44 and 95% CI: 1.14-1.75 for complex CHD). The very similar associations were also observed among single type of CHD, herein, ventricular septal defects (VSD) and tetralogy of fallot (TOF) in the case-control study. In the subsequent meta-analysis, however, the significant association only existed in VSD. CONCLUSIONS: Although there is still conflicting in TOF, the results are overall consistent, which provide new enforced evidence that maternal upper respiratory tract infection/influenza during early pregnancy, in general, play an important role in the occurrence of CHD.

[Effect of GPX4 on proliferation and metastasis of renal clear cell carcinoma and its relationship with expression of IGF-1R and COX-2].

Objective: To investigate the effect of human glutathione peroxidase 4 (GPX4) on the proliferation and metastasis of renal clear cell carcinoma and its relationship with the expression of IGF-1R and COX-2. Methods: Culture of human normal tubular cell line HK-2 and human renal clear cell carcinoma Caki-1, A498, Caki-2, 786-o in vitro. Detection of GPX4 mRNA and protein expression in different cell lines by quantitative real-time PCR (RT-PCR) and Western blot assay. Overexpression of GPX4 cell lines, including blank carrier (Vector) and overexpress GPX4 (oeGPX4) group, and interference with GPX4 renal clear cell carcinoma cell lines, including random sequence (shControl), interference GPX4#1 (shGPX4#1) and interference GPX4#2 (shGPX4#2) group by lentiviral transfection. RT-PCR technology and Western blot were used to detect the expression of GPX4, IGF-1R and COX-2 mRNA and protein. CCK-8 assay was used to detect the relative proliferation of cells at 0, 24, 48, 72 and 96 h in each group. Transwell invasion and migration assay to detect the invasion and migration ability of cells of each group. Results: GPX4 is highly expressed in renal clear cell carcinoma cell lines compared to human normal tubular cell lines; The expression of GPX4, IGF-1R and COX-2 mRNA was significantly increased in oeGPX4 cells compared with Vector cells, the expression of GPX4,IGF-1R and COX-2 mRNA was significantly decreased in shGPX4#1 and shGPX4#2 compared with shControl cells; oeGPX4 cells significantly increased proliferative capacity compared to Vector cells at 72 and 96 h, the proliferation of shGPX4#1 and shGPX4#2 cells was significantly lower than that of shControl cells at 72 and 96 h; The number of invading and migrating cells of oeGPX4 cells was significantly higher than that of Vector cells, the number of invasive and migrating cells in shGPX4#1 and shGPX4#2 cells was significantly lower than that in shControl cells. Conclusion: GPX4 is highly expressed in renal clear cell carcinoma cells, which is positively correlated with the expression of IGF-1R and COX-2, and can promote cell proliferation and metastasis in vitro.

Transgenic characterization of two silkworm tissue-specific promoters in the haemocyte plasmatocyte cells.

Haemocytes play crucial roles in insect metabolism, metamorphosis, and innate immunity. As a model of lepidopteran insects, the silkworm is a useful model to study the functions of both haematopoiesis and haemocytes. Tissue-specific promoters are excellent tools for genetic manipulation and are widely used in fundamental biological research. Herein, two haemocyte-specific genes, Integrin ß2 and Integrin ß3, were confirmed. Promoter activities of Integrin ß2 and Integrin ß3 were evaluated by genetic manipulation. Quantitative real-time PCR and western blotting suggested that both promoters can drive enhanced green fluorescent protein (EGFP) specifically expressed in haemocytes. Further evidence clearly demonstrated that the transgenic silkworm exhibited a high level of EGFP signal in plasmatocytes, but not in other detected haemocyte types. Moreover, EGFP fluorescence signals were observed in the haematopoietic organ of both transgenic strains. Thus, two promoters that enable plasmatocytes to express genes of interest were confirmed in our study. It is expected that the results of this study will facilitate advances in our understanding of insect haematopoiesis and immunity in the silkworm, Bombyx mori.

Solid pseudopapillary neoplasm of pancreas in pregnancy treated with tumor enucleation: Case report and review of the literature.

Solid pseudopapillary neoplasm of pancreas (SPN) during pregnancy is rare and presents a threat both to the mother and the fetus. We report a case of SPN in a 26-year-old woman diagnosed at 21 weeks of gestation. Tumor enucleation was successfully performed by a general surgeon. A healthy female infant was delivered at 39 weeks and 5 days of gestation vaginally without complications. Our report provides an example that tumor enucleation of SPN during the second trimester could be successfully performed during pregnancy. A multidisciplinary approach with respect to the pregnant patient's diagnosis, indications, and timing of surgery is necessary in ensuring the best possible outcomes for both the mother and the child.

Densoviruses in oyster Crassostrea ariakensis.

Densoviruses have short ssDNA genomes and mainly infect arthropods. To characterize viral nucleic acid in shellfish, oysters (Crassostrea ariakensis) were analyzed using viral metagenomics. Two large de novo assembled contigs, CaaDV1 and CaaDV2, consisting of nearly complete densovirus genomes (5860 nucleotides (nt) and 4034 nt) with two major ambisense protein coding regions were identified. Several potential non-structural proteins and capsid proteins were encoded by these genomes, but these were divergent from the existing densoviral species. The NS1 protein of the two CaaDVs shared 43.3%~61.5% amino acid identities with the sea star-associated densovirus and cherax quadricarinatus densovirus, with the four species clustering by phylogenetic analysis. This is the first report of densovirus detection in shellfish, increasing the potential host range of densoviruses and the genetic diversity of the genus Ambidensovirus.