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Abstract Heart failure (HF) is a terminal stage of cardiovascular diseases, classified based on ejection fraction. Serum uric acid (SUA) has been implicated in the pathogenesis and progression of coronary artery disease (CAD) with HF, yet its predictive value remains unclear. This study aimed to evaluate the predictive role of SUA in the progression of HF in CAD patients and its potential to differentiate HF types. A retrospective analysis was conducted on 342 CAD patients, including 29 with CAD alone and 313 with CAD complicated by varied HF types. Biochemical parameters and HF severity were assessed, and logistic regression analyses were performed to identify independent predictors of HF progression. Significant differences were observed in biochemical parameters, including glutamic–pyruvic transaminase (ALT), glutamic oxalacetic transaminase (AST), alkaline phosphatase (ALP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), creatine kinase–MB (CK–MB), SUA, lactate dehydrogenase (LDH), myoglobin (MTO), between groups. SUA levels were significantly higher in CAD patients with HF, particularly in those with reduced ejection fraction. Univariate and multivariate logistic regression analyses identified history of hypertension, AST, and SUA as independent predictors of HF progression, with SUA showing the highest odds ratio. In addition, SUA levels were positively correlated with Gensini scores, indicating its association with CAD severity. SUA is a strong predictor of HF progression in CAD patients, especially for patients with HFrEF, which can serve as a diagnostic and prognostic marker for HF progression in CAD patients.

Repeated low-intensity noise exposure is prevalent in industrialized societies. It has long been considered risk-free until recent evidence suggests that the temporary threshold shift (TTS) induced by such exposure might be a high-risk factor for hearing loss. This study was conducted to further investigate the manner in which repeated low-intensity noise exposure contributed to hearing damage. Two-month-old C57BL/6 J mice were exposed to white noise at 96 dB SPL for 8 h per day over 7 days to induce TTS. Auditory brainstem response (ABR) was monitored to assess changes in hearing thresholds, tracking the effects of noise exposure until the mice reached 12 months of age. Our results indicated that noise-exposed mice exhibited accelerated age-related hearing loss spanning from high to low frequencies. Proteomics analysis revealed an upregulation in the receptor for the advanced glycation end-products (RAGE) signaling pathway, which was associated with an activated inflammatory response, vascular injury, and mitochondrial and synaptic dysfunction. Further analysis confirmed increased levels of inflammatory cytokines in the cochlear lymph fluid and significant macrophages infiltration in the cochlear lateral wall, accompanied by hyperpermeability of the blood-labyrinth barrier. Additionally, degenerated mitochondria in the outer hair cells and decreased synaptic ribbons in the inner hair cells were also observed. These pathological changes indicated that noise exposure damages the cochlear cellular components, increasing the cochlear susceptibility to age-related stress. Our findings suggest that TTS caused by repeated low-intensity noise exposure correlates with a severe sensorineural hearing loss during aging; targeting the RAGE signaling pathway may be a promising strategy to mitigate damage from low-intensity noise and slow down the progression of age-related hearing loss.

ObjectiveThis study aimed to analyze the correlation between gestational diabetes mellitus and postpartum metabolic indicators and inflammatory factors, and explore the role of inflammatory factors, so as to provide evidence for the early prevention of postpartum CVD risk in gestational diabetes mellitus.MethodsThis prospective study was based on the pregnant women cohort study established in Peking University International Hospital from December 2017 to March 2019. A total of 120 women were enrolled sequentially, including 60 cases of gestational diabetes mellitus (GDM group) and 60 cases of non-gestational diabetes mellitus (non-GDM group) after 4-7 years. The general information, inflammatory factors and metabolic indicators of the women were collected and analyzed.Results(1)The TyG and siMS levels in the GDM group were higher than those in the non-GDM group (p

The digital economy is an important driving force for China’s economic transformation and upgrading, while “carbon peaking and carbon neutrality” is the goal to be achieved in China. Based on the panel data of 30 Chinese provinces (cities and districts) from 2012 to 2019, the article empirically investigates the impact of the digital economy on regional carbon emissions and its mechanism of action by using a two-way fixed-effects model and mediated-effects model. The study shows that, firstly, the digital economy has a significant carbon emission reduction effect, and the conclusion still holds after robustness testing. Secondly, the emission reduction effect of industry digitization in the digital economy dimension is the most obvious. Again, the carbon emission reduction effect of digital economy development on different regions varies, with the strongest carbon emission reduction effect on western regions and regions with high carbon emission levels. Finally, the analysis of mediating effects shows that the energy structure is an important mechanism for the digital economy to suppress regional carbon emissions. The findings of the study provide a feasible path and policy reference for the digital economy to contribute to the goal of “carbon peaking and carbon neutrality.”

Objective In recent years, the trend of tunnel blasting construction extending to depth is becoming more and more significant, and the influence of layered rock mass in deep buried diversion tunnel on cutting quality in blasting construction is the key to blasting construction. Methods In order to study the influence of the location of blasting in deep layered surrounding rock on the cut blasting, a three-dimensional finite element numerical calculation model was established by using ANSYS/LS-DYNA, based on the blasting excavation project of the diversion tunnel of San Gabán hydropower station in Peru. The damage area caused by cut blasting was analyzed, and the optimization scheme was put forward for field test. Results The results show that the boundary area of layered surrounding rock has a certain influence on the range of rock damage caused by cutting blasting. The closer to the boundary area of layered surrounding rock, the smaller the range of rock damage. In order to increase the damage area of cut blasting, the location of blasting should keep a certain distance from the boundary area of layered surrounding rock. Conclusion The optimized blasting scheme was tested on site and good blasting effect was achieved. In this study, numerical simulation was used to optimize the position of the cutting hole accroding to the law of rock damage evolution, which can improve the economy and safety of tunnel construction.

Abstract Background Iatrogenic facial nerve injury is one of the severest complications of middle ear surgery, this study aims to evaluate surgical management and prognosis in the era of improved surgical instruments. Methods Patients suffered from facial nerve paralysis after middle ear surgery between January 2000 and December 2019 were retrospectively collected. Demographic characters, primary disease and surgery, details of revision surgery were analyzed. Results Forty-five patients were collected, of whom 8 were injured at our center and 37 were transferred. For 8 patients injured at our center, seven (87.5%) ranked House-Brackmann (H-B) grade V and one (12.5%) ranked H-B VI before revision surgery; postoperatively, two (25.0%) patients recovered to H-B grade I, four (50.0%) recovered to H-B II, and the other two (25.0%) recovered to H-B III. For 37 patients transferred, thirteen (35.1%) ranked H-B grade V and 24 (64.9%) ranked H-B VI preoperatively, final postoperative grade ranked from H-B grade I to grade V, with H-B I 6 (16.2%) cases, H-B II 6 (16.2%) cases, H-B III 18 (48.6%) cases, H-B IV 5 (13.5%) cases and H-B V 2 (5.4%) cases. The most vulnerable site was tympanic segment (5, 62.5% and 27, 73.0% respectively). Twenty-one (46.7%) patients suffered from mild injury and 24 (53.3%) suffered from partial or complete nerve transection. For surgical management, twenty-one (46.7%) patients received decompression, nineteen (42.2%) received graft and 5 (11.1%) received anastomosis. Those decompressed within 2 months after paralysis had higher possibility of H-B grade I or II recovery (P = 0.026), those received graft within 6 months were more likely to get H-B grade III recovery (P = 0.041), and for patients underwent anastomosis within 6 months, all recovered to H-B grade III. Conclusions Tympanic segment is the vulnerable site. If facial nerve paralysis happens, high-resolution computed tomography could help identify the injured site. Timely treatment is important, decompression within 2 months after paralysis, graft and anastomosis within 6 months lead to better recovery.

In the context of flight test planning, numerous uncertainties exist, encompassing aircraft status, number of flights, and weather conditions, among others. These uncertainties ultimately manifest significantly in the actual number of flight sorties executed, rendering high significance to engineering problems related to the execution of flight test missions. However, there is a dearth of research in this specific aspect. To address this gap, this paper proposes an opportunity-constrained integer programming model tailored to the unique characteristics of the problem. To handle the uncertainties, Sample Average Approximation (SAA) is employed to perform oversampling of the uncertain parameters, followed by the Adaptive Large Neighborhood Search (ALNS) algorithm to solve for the optimal solution and objective function value. Results from numerical experiments conducted at varying scales and validated with diverse sampling distributions demonstrate the effectiveness and robustness of the proposed methodology. By decoding the generated execution sequences, comprehensive mission planning schemes can be derived. This approach yields sequences that exhibit commendable feasibility and robustness for the flight test planning problem with sorties uncertainty (FTPPSU), offering valuable support for the efficient execution of future flight test missions.

BackgroundAutoimmune thyroid disease (AITD) is the main cause of hypothyroidism in women of childbearing age. Bisphenol A (BPA) is an environmental factor affecting AITD. This study aims to investigate relationship between BPA and AITD in women of childbearing age, thereby contributing novel evidence for the prevention of hypothyroidism in this specific demographic.MethodsA total of 155 women of childbearing age were enrolled in this study, including the euthyroid group comprised 60 women with euthyroidism and thyroid autoantibodies negativity and the AITD group consisted of 95 women with euthyroidism and at least one thyroid autoantibody positivity. The general information, thyroid function, thyroid autoantibodies, and thyroid ultrasound results of the two groups of women of childbearing age were recorded. Urinary BPA and urinary BPA/creatinine were detected. The difference of BPA levels between the two groups was compared. logistic regression was used to analyze the correlation between BPA and AITD.ResultsThe proportion of multiparous and serum thyroid stimulating hormone levels were significantly higher in the AITD group compared to the euthyroid group. Logistic regression analysis revealed that BPA levels did not exhibit a statistically significant association with AITD. Spearman correlation analysis revealed a statistically significant correlation between BPA and urinary iodine levels (r=0.30, P < 0.05), as well as a correlation between urinary BPA and free tetraiodothyronine (FT4) levels (r=0.29, P < 0.05).ConclusionThis study revealed a correlation between urinary BPA levels and FT4 levels. However, it did not establish a relationship between BPA and AITD in women of childbearing age.

ObjectiveInsufficient thyroid hormone levels during pregnancy, especially in the first trimester, adversely affect maternal and fetal health. However, the impact of isolated hypothyroxinemia (IH) on adverse pregnancy outcomes remains controversial. Therefore, this study aimed to investigate the association between IH during the first trimester and adverse pregnancy outcomes.MethodsThis prospective cohort study included 1236 pregnant women. Thyroid-stimulating hormone and free thyroxine levels were measured before 13 weeks of gestation. Logistic regression analysis and the Cochran-Armitage trend test were used to assess the association between IH in the first trimester and adverse pregnancy outcomes.ResultsIH during the first trimester was associated with an increased risk of macrosomia. After adjusting for confounding factors, including age, body mass index, parity, abnormal pregnancy history, fasting blood glucose, and total cholesterol, multivariate logistic regression analysis showed that IH in the first trimester remained an independent risk factor for macrosomia. In addition, the risk of macrosomia increased with IH severity. However, no significant relationship was found between IH during the first trimester and gestational diabetes mellitus, hypertensive disorders of pregnancy, spontaneous abortion, premature rupture of membranes, placental abruption, oligohydramnios, premature delivery, fetal distress, or low birth weight.ConclusionIH during the first trimester did not increase the risk of adverse pregnancy outcomes, except for macrosomia.

IntroductionSoil microorganisms are essential for crop growth and production as part of soil health. However, our current knowledge of microbial communities in tobacco soils and their impact factors is limited.MethodsIn this study, we compared the characterization of bacterial and fungal communities in tobacco soils and their response to regional and rootstock disease differences.Results and discussionThe results showed that the diversity and composition of bacterial and fungal communities responded more strongly to regional differences than to rootstock diseases, while bacterial niche breadth was more sensitive than fungi to regional differences. Similarly, the core bacterial and fungal taxa shared by the three regions accounted for 21.73% and 20.62% of all OTUs, respectively, which was much lower than that shared by RD and NRD in each region, ranging from 44.87% to 62.14%. Meanwhile, the differences in topological characteristics, connectivity, and stability of microbial networks in different regions also verified the high responsiveness of microbial communities to regions. However, rootstock diseases had a more direct effect on fungal communities than regional differences.ConclusionThis provided insight into the interactions between microbial communities, regional differences, and rootstock diseases, with important implications for maintaining soil health and improving tobacco yield and quality.

AbstractObjective This study aims to explore the correlation between central and peripheral thyroid resistance indices and diabetic retinopathy(DR) in patients with type 2 diabetes mellitus (T2DM), so as to provide a clinical basis for the prevention and treatment of diabetic retinopathy.Methods This study retrospectively analyzed 1249 euthyroid patients with T2DM hospitalized in the Department of Endocrinology, Peking University International Hospital from January 2017 to June 2022, including 852 males and 397 females, with an average age of 54.73 ± 13.40 years. According to the degree of DR, the patients were divided into three groups including the no diabetic retinopathy (NDR) group, non-proliferative diabetic retinopathy (NPDR) group and proliferative diabetic retinopathy (PDR) group.Results Free thymidine (FT4), thyroid stimulating hormone (TSH), thyroid feedback quantile index (TFQI), thyrotropin-T4 resistance index (TT4RI), thyroid stimulating hormone index (TSHI) and free triiodothyronine/free thyroxine (FT3/FT4) levels among the three groups were significantly different, with the NDR group having lowest TSH, TFQI, TT4QI, TSHI and the highest in the PDR group (all p

BackgroundTo explore the association between thyroid hormones and gestational diabetes mellitus in euthyroid pregnant women, with the aim of preventing the occurrence of gestational diabetes mellitus.MethodsIn this prospective study, a total of 1222 euthyroid pregnant women in their first trimester were recruited at Peking University International Hospital between December 2017 and March 2019. These participants underwent an oral glucose tolerance test during the 24-28 weeks of gestation.ResultsDuring early pregnancy, the gestational diabetes mellitus group displayed lower levels of free thyroxine when compared to the non-gestational diabetes mellitus group. Additionally, the ratio of free triiodothyronine to free thyroxine in the gestational diabetes mellitus group during early pregnancy was significantly higher (p

IntroductionSymptoms induced by arachnoid cysts in the fallopian canal are uncommon, and facial nerve paralysis without cerebrospinal fluid otorrhea is comparatively rarer.MethodsHerein, we present two cases of arachnoid cysts in the fallopian canal with acute severe facial nerve paralysis and review the relevant literature.ResultsThe symptoms and imaging findings of these two cases resembled those of facial nerve schwannomas. Cerebrospinal fluid otorrhea occurred upon removal of the arachnoid cyst, and the facial nerve was observed to be separated into multiple filaments or compressed and atrophied. Facial-hypoglossal nerve anastomosis and decompression were conducted after packing the dehiscence of cerebrospinal fluid otorrhea for the two cases.ConclusionArachnoid cysts of the fallopian canal rarely cause facial nerve paralysis. Enhanced magnetic resonance imaging is vital for differentiating schwannomas. Different treatment strategies should be adopted for patients with different degrees of facial nerve paralysis; however, concurrent repair of cerebrospinal fluid otorrhea and facial nerves during surgery can occasionally be challenging.

Abstract. Background:. Time in range (TIR) refers to the time an individual spends within their target glucose range, which now has been popularized as an important metric to classify glycemic management and also recognized as an important outcome of current diabetes therapies. This study aimed to investigate the association between TIR and the severity of the urinary albumin excretion rate (UAER) in patients with type 2 diabetes mellitus (T2DM). Methods:. We retrospectively analyzed the data of 1014 inpatients with T2DM at the Department of Endocrinology and Metabolism of Peking University International Hospital, China. TIR was defined as the percentage of blood glucose within the target range of 3.90–10.00 mmol/L. Urine samples for assessment of UAER were collected for 3 consecutive days from the start of hospitalization. Results:. The TIR values for patients with normal urine levels of albumin, microalbuminuria, and macroalbuminuria were 70% ± 20%, 50% ± 20%, and 30% ± 20%, respectively (all P 83%. The incidences of microalbuminuria in Q1, Q2, Q3, and Q4 were 41.1%, 21.6%, 7.1%, and 5.5% (all P

Abstract Background Macrosomia is closely associated with poor maternal and fetal outcome. But there is short of studies on the risk of macrosomia in early pregnancy. The purpose of this study is to establish a nomogram for predicting macrosomia in the first trimester. Methods A case-control study involving 1549 pregnant women was performed. According to the birth weight of newborn, the subjects were divided into macrosomia group and non-macrosomia group. The risk factors for macrosomia in early pregnancy were analyzed by multivariate logistic regression. A nomogram was used to predict the risk of macrosomia. Results The prevalence of macrosomia was 6.13% (95/1549) in our hospital. Multivariate logistic regression analysis showed that prepregnancy overweight (OR: 2.13 95% CI: 1.18–3.83)/obesity (OR: 3.54, 95% CI: 1.56–8.04), multiparity (OR:1.88, 95% CI: 1.16–3.04), the history of macrosomia (OR: 36.97, 95% CI: 19.90–68.67), the history of GDM/DM (OR: 2.29, 95% CI: 1.31–3.98), the high levels of HbA1c (OR: 1.76, 95% CI: 1.00–3.10) and TC (OR: 1.36, 95% CI: 1.00–1.84) in the first trimester were the risk factors of macrosomia. The area under ROC (the receiver operating characteristic) curve of the nomogram model was 0.807 (95% CI: 0.755–0.859). The sensitivity and specificity of the model were 0.716 and 0.777, respectively. Conclusion The nomogram model provides an effective mothed for clinicians to predict macrosomia in the first trimester.

Background: Numerous studies have found that subclinical hypothyroidism (SCH) may increase adverse pregnancy outcomes; however, the benefit of levothyroxine (LT4) treatment remains controversial. The 2017 guidelines of the American Thyroid Association weakly recommended LT4 therapy for serum antithyroi d peroxidase antibody (TPOAb)-negative women with thyroid-stimulating hormone (TSH) concentrations greater than the pregnancy-specific reference range and below 10.0 mU/L. Therefore, the primary goal of this study was to investigate the correlation between thyroid autoantibody-negative SCH with or without LT4 treatment and adverse pregnancy outcomes. Methods: We prospectively enrolled 1868 consecutive pregnant women. Finally, 1344 women were involved in the study according to the inclusion and exclusion criteria. Assays for TSH, free thyroxine (FT4), TPOAb, anti-thyroglobulin antibody, and laboratory indicators were performed. The participants were divided into the euthyroid (ET) group (n = 1250) and the SCH group(n = 94). The SCH group was further divided into LT4 group (n = 40) and non-LT4 group(n = 54). The laboratory indicators and pregnancy outcomes were evaluated during follow-ups. Results: Maternal age, BMI, parity, and the history of spontaneous abortion did not differ significantly between the ET group and the different SCH gr oups. There were no significant differences in lipid profile and homocysteine levels b etween ET and SCH group in the first and third trimester of pregnancy. After adjus ting the confounding factors, the non-LT4 group was a risk factor for spontaneous abortion (odds ratio: 3.141, 95% CI: 1.060–9.302). Survival analysis showed that the time of abortion was different between the ET group and SCH group (log-rank P = 0.042). The spontaneous abortion in SCH, especially in non-LT4, group mainly occurred in the first t rimester of pregnancy. Conclusions: Thyroid autoantibody negative-SCH seems to be associated with increased risk of spontaneous abortions during the first trimester of preg nancy. LT4 therapy in this patient population might be beneficial to reduce adverse pregnan cy outcomes.

BackgroundHypoxia is involved in tumor biological processes and disease progression. Ferroptosis, as a newly discovered programmed cell death process, is closely related to breast cancer (BC) occurrence and development. However, reliable prognostic signatures based on a combination of hypoxia and ferroptosis in BC have not been developed.MethodWe set The Cancer Genome Atlas (TCGA) breast cancer cohort as training set and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) BC cohort as the validation set. Least Absolute Shrinkage and Selection Operator (LASSO) and COX regression approaches were used to construct ferroptosis-related genes (FRGs) and hypoxia-related genes (HRGs) prognostic signature (HFRS). The CIBERSORT algorithm and ESTIMATE score were used to explore the relationship between HFRS and tumor immune microenvironment. Immunohistochemical staining was used to detect protein expression in tissue samples. A nomogram was developed to advance the clinical application of HFRS signature.ResultsTen ferroptosis-related genes and hypoxia-related genes were screened to construct the HFRS prognostic signature in TCGA BC cohort, and the predictive capacity was verified in METABRIC BC cohort. BC patients with high-HFRS had shorter survival time, higher tumor stage, and a higher rate of positive lymph node. Moreover, high HFRS was associated with high hypoxia, ferroptosis, and immunosuppression status. A nomogram that was constructed with age, stage, and HFRS signature showed a strong prognostic capability to predict overall survival (OS) for BC patients.ConclusionWe developed a novel prognostic model with hypoxia and ferroptosis-related genes to predict OS, and characterize the immune microenvironment of BC patients, which might provide new cures for clinical decision-making and individual treatment of BC patients.

Objective: This study aims to explore the correlation between the free-triiodothyronine (FT3)-to-free-thyroxine (FT4) ratio (FT3/FT4) and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: This study retrospectively analyzed 1729 patients with T2DM hospitalized in the Department of Endocrinology, Peking University International Hospital, from January 2017 to August 2021, including 1075 males and 654 females. In accordance with the FT3/FT4, the patients were divided into three groups. Results: (1) The levels of glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG) and postprandial blood glucose (PBG) among the three groups were significantly different, with the low FT3/FT4 group having the highest HbA1c, FBG and PBG among the three groups (F = 39.39, p < 0.01; F = 27.04, p < 0.01; F = 5.76, p = 0.03; respectively). (2) The proportion of DKD is the highest in the low FT3/FT4 group and the lowest in the high FT3/FT4 group (χ2 = 25.83, p < 0.01). (3) Logistic regression showed that low FT3/FT4 were independent risk factors for DKD (OR = 2.36, 95 CI% 1.63, 3.43; p = 0.01). Conclusion: A decrease in the FT3/FT4 is an independent predictor of DKD occurrence in patients with T2DM.

Abstract The physical and mechanical properties of the reservoir bank slope are affected by the water–rock interaction. However, few studies considered the impact of long-term water–rock interaction on the evolution law of mesostructure. Therefore, in this study, the water–rock interaction test was conducted on a slightly weathered red-bed soft rock from the Three Gorges Reservoir area, considering the fluctuation in the reservoir water level. The corresponding pore structure parameters were measured and analyzed based on a scanning electron microscope (SEM) and digital image processing technology. The study showed that: (1) The pore size has been gradually increased, while the number of pores was increased initially and then decreased. Within 12 cycles, the maximum and average pore radius of the rock specimens was increased by 101.02% and 43.32%, respectively, and the porosity has been increased by 26.59%, whereas the number of pores decreased by 22.65%. This indicates the effect of water–rock interaction on the propagation of pores. (2) The pores were changed from oblate to slender by the water–rock interaction. The shape factor was decreased by about 15.79% within 12 cycles. In the meantime, the fractal dimension was increased from 1.20 to 1.28, and more complex structures of pores were observed. (3) The porosity evolution model for the red-bed soft rock was established based on the curve fitting technique. The results can be used as a reference to conceptualize the mesostructure damage of rocks under water–rock interaction.

Context Huoxiangzhengqi oral liquid (HXZQ-OL), a traditional Chinese medicine formula, has antibacterial, anti-inflammation and gastrointestinal motility regulation effects. Objective The study investigates the anti-allergic activity and underlying mechanism of HXZQ-OL. Materials and methods IgE/Ag-mediated RBL-2H3 cells were used to evaluate the anti-allergic activity of HXZQ-OL (43.97, 439.7 and 4397 μg/mL) in vitro. The release of cytokines and eicosanoids were quantified using ELISA. RT-qPCR was used to measure the gene expression of cytokines. The level of intracellular Ca2+ was measured with Fluo 3/AM. Immunoblotting analysis was performed to investigate the mechanism of HXZQ-OL. In the passive cutaneous anaphylaxis (PCA), BALB/c mice (5 mice/group) were orally administrated with HXZQ-OL (263.8, 527.6 and 1055 mg/kg/d) or dexamethasone (5 mg/kg/d, positive control) for seven consecutive days. Results HXZQ-OL not only inhibited degranulation of mast cells (IC50, 123 μg/mL), but also inhibited the generation and secretion of IL-4 (IC50, 171.4 μg/mL), TNF-α (IC50, 88.4 μg/mL), LTC4 (IC50, 52.9 μg/mL) and PGD2 (IC50, 195.8 μg/mL). Moreover, HXZQ-OL suppressed the expression of IL-4 and TNF-α mRNA, as well as the phosphorylation of Fyn, Lyn and multiple downstream signalling proteins including MAPK and PI3K/NF-κB pathways. In addition, HXZQ-OL (527.5 mg/kg) attenuated the IgE-mediated PCA with 55% suppression of Evans blue exudation in mice. Conclusions HXZQ-OL attenuated the activation of mast cell and PCA. Therefore, HXZQ-OL might be used as an alternative treatment for allergic diseases.

Abstract Background Thyroid autoimmunity (TAI) and subclinical hypothyroidism (SCH) have been associated with poor pregnancy and fetal outcomes. However, whether euthyroid women with anti-thyroid peroxidase antibody (TPOAb) positivity have a higher risk of poor pregnancy and fetal outcomes is debatable. Therefore, this study aimed to investigate the association between TPOAb positivity and pregnancy-related and fetal outcomes in euthyroid women. Methods In total, 938 pregnant women participated in this prospective cohort study. The euthyroid group included 837 pregnant women and the TPOAb-positive group included 101 euthyroid pregnant women. Serum TPOAb, thyroglobulin antibody (TGAb), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels were assessed. Pregnancy and fetal outcomes included gestational diabetes mellitus, spontaneous abortion, premature rupture of membranes, hypertensive disorders of pregnancy, preterm birth, fetal distress, low birth weight, fetal macrosomia, and small for gestational age infant. Results Logistic regression analysis showed TPOAb positivity was not associated with an increased risk of poor pregnancy or fetal outcomes in euthyroid women. However, TPOAb-positive euthyroid women pregnant with a female fetus were independently associated with preterm births (OR: 4.511, 95% CI: 1.075–18.926) after adjustment for potential confounding factors. Conclusions TPOAb positivity was not found to be associated with poor pregnancy-related or fetal outcomes in euthyroid women. However, in euthyroid women with a female fetus, TPOAb positivity was strongly associated with preterm births. The risk of preterm birth in the euthyroid women with TPOAb positivity should be emphasized in clinical practice. Trial registration ClinicalTrials.gov Identifier: NCT02966405 . Registered on October 24th 2016 - Retrospectively registered.

Abstract Background Different fixation methods have been used to treat posterior malleolar fractures (PMFs), but the clinical efficacy of different fixation methods in the treatment of PMF with different fragmentation has rarely been reported. The purpose of this study was to investigate the efficacy of posterior-anterior (PA), anterior-posterior (AP) screws and PA plate in the fixation of PMFs with a fragment size of ≥15 and 0.05). In fragment size 0.05). Conclusion For PMFs with fragment size ≥15%, there was no significant difference in the outcomes between the three fixation methods. For PMF with fragmentation

(1) Background: To explore the correlation between central and peripheral thyroid sensitivity indices and macrosomia in euthyroid pregnant women and to provide clinical basis for the prevention and treatment of macrosomia. (2) Methods: This study is a prospective study. A total of 1176 euthyroid women in early pregnancy in the obstetrics department of Peking University International Hospital from December 2017 to March 2019 were enrolled. The women were divided into two groups, namely the macrosomia and non-macrosomia groups, according to birth weight. (3) Results: The level of free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid feedback quantile-based index (TFQI), thyrotropin-T4 resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), and free triiodothyronine/free thyroxine (FT3/FT4) in the macrosomia group was higher than that in the non-macrosomia group (p < 0.05). The multivariate logistic regression model showed that FT3, TFQI, TT4RI, TSHI, and FT3/FT4 were independent risk factors for macrosomia in early pregnancy after adjusting for age, body mass index, parity, blood pressure, blood glucose, and blood lipid levels (p < 0.05, respectively). (4) Conclusions: TFQI, TT4RI, TSHI, and FT3/FT4 are independent risk factors for fetal macrosomia in early pregnancy in euthyroid women.

Objective: to analyze the association between blood lipid metabolism and osteoporosis (OP) in older adults with type 2 diabetes mellitus (T2DM). Methods: a total of 1158 older patients with T2DM treated by the Department of Endocrinology, Peking University International Hospital, were retrospectively analyzed, including 541 postmenopausal women and 617 men. Results: (1) Levels of low-density lipoprotein cholesterol (LDL-C) were significantly higher in the OP group, while levels of high-density lipoprotein cholesterol (HDL-C) were higher in the non-osteoporotic group (both p < 0.05). (2) Age, parathyroid hormone (PTH), total cholesterol (TC) and LDL-C were negatively linked to the patients’ bone mineral density (BMD) (all p < 0.05), while the body mass index (BMI), uric acid (UA) level, HDL-C level and glomerular filtration rate (eGFR) were positively related to their BMD (all p < 0.05). (3) In postmenopausal women, after adjustment for other indexes, raised LDL-C is an independent risk factor for OP (OR = 3.38, 95% CI 1.64, 6.98, p < 0.05) while raised HDL-C is protective (OR = 0.49, 95% CI 0.24, 0.96, p < 0.05). However, raised HDL-C was protective against OP (OR = 0.07, 95% CI 0.01, 0.53, p < 0.05). Conclusion: In older T2DM patients, the effect of blood lipid levels is related to sex. Our study conducted a detailed sex stratification. In addition to seeing the traditional risk factors of OP, such as age, sex, and BMI, we comprehensively analyzed the correlation between the blood glucose level, complications, and blood lipids with OP. HDL-C is a protective factor for OP in both men and women, while LDL-C independently predicts OP in postmenopausal women.

ABSTRACTDynamic changes of RNA and antibodies in SARS-CoV-2 infected patients remain largely unknown, and influence factors for antibody production have not been fully clarified. In this study, consecutive throat swabs specimens (n = 1875) from 187 patients were collected to analyse the dynamic changes of RNA. Moreover, 162 serial serum samples from 31 patients were tested for seroconversion of IgM and IgG. Meanwhile, IgM and IgG were also detected in 409 COVID-19 patients and 389 controls. Additionally, the logistic regression analysis was executed to identify the possible influence factors for antibody production. The median positive conversion time for RNA was day 7 (IQR, 3–11), and the positive rate was highest in day 1–5 (74.59 %) and then gradually decreased. The median time of seroconversion for IgM and IgG were both day 12 (IQR, 10–15). The sensitivity and specificity for IgM (or IgG) was 87.04% and 96.92%, respectively. Multivariate logistic regression indicated that reduced lymphocytes and short positive conversion time for SARS-CoV-2 RNA were independent factors for negative results of IgM and IgG. In conclusion, RNA and antibodies should be combined for COVID-19 diagnosis, and delayed seroconversion was influenced by the decreased lymphocytes and short positive conversion time for RNA.

Background: Urea, the end product of protein metabolism, has been considered to have negligible toxicity for a long time. Our previous study showed a depression phenotype in urea transporter (UT) B knockout mice, which suggests that abnormal urea metabolism may cause depression. The purpose of this study was to determine if urea accumulation in brain is a key factor causing depression using clinical data and animal models. Methods: A meta-analysis was used to identify the relationship between depression and chronic diseases. Functional Magnetic Resonance Imaging (fMRI) brain scans and common biochemical indexes were compared between the patients and healthy controls. We used behavioural tests, electrophysiology, and molecular profiling techniques to investigate the functional role and molecular basis in mouse models. Findings: After performing a meta-analysis, we targeted the relevance between chronic kidney disease (CKD) and depression. In a CKD mouse model and a patient cohort, depression was induced by impairing the medial prefrontal cortex. The enlarged cohort suggested that urea was responsible for depression. In mice, urea was sufficient to induce depression, interrupt long-term potentiation (LTP) and cause loss of synapses in several models. The mTORC1-S6K pathway inhibition was necessary for the effect of urea. Lastly, we identified that the hydrolysate of urea, cyanate, was also involved in this pathophysiology. Interpretation: These data indicate that urea accumulation in brain is an independent factor causing depression, bypassing the psychosocial stress. Urea or cyanate carbamylates mTOR to inhibit the mTORC1-S6K dependent dendritic protein synthesis, inducing impairment of synaptic plasticity in mPFC and depression-like behaviour. CKD patients may be able to attenuate depression only by strict management of blood urea. Keywords: Urea, Depression, LTP, Carbamylation, mTOR

Background: Platelet-rich plasma (PRP) has been suggested as an emerging treatment for bone defects. However, whether PRP could enhance the therapeutic efficacy of autologous bone grafting for long bone delayed union or non-union remains unknown. A meta-analysis of randomized and non-randomized controlled trials (RCT and NRCT) was performed to summarize current evidence.Methods: Relevant RCTs and NRCTs comparing the influences of autologous bone grafting on healing of long bone delayed union or non-union with and without PRP were obtained by searching PubMed, Embase, Cochrane's Library, China National Knowledge Infrastructure, and WanFang databases from inception to September 10, 2020. A random-effect model was applied to pool the results with the incorporation of the potential heterogeneity. Subgroup analysis according to study design was also performed.Results: Six RCTs and two NRCTs with 420 patients were included. Compared to patients allocated to autologous bone grafting alone, those allocated to combined treatment with PRP and autologous bone grafting were not associated with higher rates of radiographic bone healing [risk ratio (RR): 1.06, 95% confidence interval (CI): 0.99–1.13, P = 0.09; I2 = 24%] or excellent/good posttreatment limb function (RR: 1.14, 95% CI: 0.95–1.37, P = 0.37; I2 = 0%) but was associated with a shorter healing time (mean difference: −1.35 months, 95% CI: −1.86 to −0.84, P < 0.001; I2 = 58%). Subgroup analysis according to study design showed similar results for the above outcomes (P-values for subgroup difference all >0.10).Conclusions: Combined treatment with PRP and autologous bone grafting may be effective to accelerate the healing of long bone delayed union or non-union compared to autologous bone grafting alone.

ObjectiveWe aimed to explore the role and possible mechanism of leptin in lower-extremity artery calcification in patients with type 2 diabetes mellitus (T2DM).MethodsWe recruited 59 male patients with T2DM and 39 non-diabetic male participants. All participants underwent computed tomography scan of lower-extremity arteries. The calcification scores (CSs) were analyzed by standardized software. Plasma leptin level was determined by radioimmunoassay kits. Human vascular smooth muscle cells (VSMCs) calcification model was established by beta-glycerophosphate and calcium chlorideinduction. Calcium deposition and mineralization were measured by the o-cresolphthalein complexone method and Alizarin Red staining. The mRNA expression of bone morphogenic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and osteopontin (OPN) was determined by quantitative RT-PCR. The protein levels of BMP2, Runx2, α-smooth muscle actin (α-SMA) and (p)-Akt was determined by Western-blot analysis, and α-SMA was also measured by immunofluorescence analysis.ResultsCompared with controls, patients with T2DM showed higher median calcification score in lower-extremity artery [286.50 (IQR 83.41, 1082.00) vs 68.66 (3.41, 141.30), p

This study was aimed at exploring the predictive value of first-trimester glycosylated hemoglobin (HbA1c) levels in the diagnosis of gestational diabetes mellitus (GDM). A total of 744 pregnant women registered at the Peking University International Hospital between March 2017 and March 2019 were included in this study. Data on personal characteristics and biochemical indicators of the pregnant women were collected during the first trimester. The International Association of Diabetes and Pregnancy Study Groups has adopted specific diagnostic criteria as the gold standard for the diagnosis of GDM. Receiver operating characteristic (ROC) curve statistics were used to assess the predictive value of first-trimester HbA1c levels in the diagnosis of GDM. HbA1c levels in the first trimester were significantly higher in the GDM group than in the non-GDM group (5.23%±0.29% vs. 5.06±0.28%, P5.9%. There was no statistical difference between first-trimester HbA1c and fasting blood glucose levels in predicting GDM.

The belief rule base (BRB) uses the “IF-THEN” rule to handle different types of information under uncertainty, and then transforms them into a unified result in the same belief structure as the input. In this paper, the BRB space is analyzed from a new topological perspective, based on which three conclusions are derived: 1) the BRB space is an attribute product measure space; 2) a rule in BRB is a vector in the BRB space and the rule integration process by any input is a vector calculation process, and 3) the vector calculation follows from the commutative and associative laws of addition while the dot product of the vectors reflects their distance in the BRB space. An illustrative example is given to better clarify the proposed topological analysis on the BRB space. The limitations and future work are investigated as a conclusion.

This paper aims to develop a hierarchical risk assessment model using the newly-developed evidential reasoning (ER) rule, which constitutes a generic conjunctive probabilistic reasoning process. In this paper, we first provide a brief introduction to the basics of the ER rule and emphasize the strengths for representing and aggregating uncertain information from multiple experts and sources. Further, we discuss the key steps of developing the hierarchical risk assessment framework systematically, including (1) formulation of risk assessment hierarchy; (2) representation of both qualitative and quantitative information; (3) elicitation of attribute weights and information reliabilities; (4) aggregation of assessment information using the ER rule and (5) quantification and ranking of risks using utility-based transformation. The proposed hierarchical risk assessment framework can potentially be implemented to various complex and uncertain systems. A case study on the fire/explosion risk assessment of marine vessels demonstrates the applicability of the proposed risk assessment model.