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Objective: To compare the efficacy and safety of eravacycline and polymyxin drugs in the treatment of multidrug-resistant complicated intra-abdominal infections(cIAI). Methods: The cIAI patients diagnosed or highly suspected of multidrug resistant bacterial infection who received eravacycline treatment at Sir Run Run Shaw Hospital and Shulan (Hangzhou) Hospital from June to August 2023 were prospectively included as the elacycline group. The cIAI patients with cIAI caused by multidrug resistant bacteria who received treatment with polymyxin (B or E) from January 2021 to August 2023 were retrospectively collected. The acute physiology and chronic health scores and age were matched with those of the elacrinid group, and they were included in the polymyxin group. The study mainly analyzed the clinical efficacy, microbial clearance rate, comprehensive efficacy, and safety of the two groups at the end of treatment and discharge. Results: A total of 72 patients with cIAI were included in the study, including 53 males and 19 females, aged (56.0±15.4) years. Among them, there were 28 cases in the eravacycline group and 44 cases in the polymyxin group. There was no statistically significant differences in the baseline, the proportion of patients who used combined drugs, the strains, the infection sites and infection conditions of patients between the two groups(all P >0.05).The clinical efficacy rate at the end of treatment [89.3% (25/28) vs 56.8%(25/44), P =0.004] and discharge [(88.5%(23/26) vs 63.6%,(28/44), P =0.024], microbial clearance rate at the end of treatment [(88.9% (24/27) vs 47.6%(20/42), P =0.001] and discharge [(91.3%(21/23) vs 59.5%(25/42), P =0.007], and overall recovery rate at the end of treatment [(89.3%(25/28) vs 52.3%(23/44), P =0.001] and discharge [(88.5%(23/26) vs 63.6%(28/44), P =0.024] in the erythromycin group were higher than those in the polymyxin drug group. In terms of safety, only 2 cases of mild vasculitis were observed in the eravacycline group. Conclusions: Combined regimens based on eravacycline showed better clinical effect in the treatment of cIAI caused by multidrug-resistant bacteria. The clinical effective rate, microbial clearance rate and comprehensive efficacy were significantly higher than those of polymyxin drugs at the end of treatment and discharge with good safety.

Purpose: At present, various treatment strategies are available for pituitary adenomas, including medications, surgery and radiation. The guidelines indicate that pharmacological treatments, such as bromocriptine (BRC) and cabergoline (CAB), are important treatments for prolactinomas, but drug resistance is an urgent problem that needs to be addressed. Therefore, exploring the mechanism of drug resistance in prolactinomas is beneficial for clinical treatment., Methods: In our research, BRC-induced drug-resistant cells were established. Previous RNA sequencing data and an online database were used for preliminary screening of resistance-related genes. Cell survival was determined by Cell Counting Kit-8 (CCK-8) assay, colony formation assays and flow cytometry. Quantitative real-time polymerase chain reaction (qRT‒PCR), western blotting, immunohistochemistry, immunofluorescence and Co-immunoprecipitation (Co-IP) were used to assess the molecular changes and regulation. The therapeutic efficacy of BRC and FGFR4 inhibitor fisogatinib (FISO) combination was evaluated in drug-resistant cells and xenograft tumors in nude mice., Results: Consistent with the preliminary results of RNA sequencing and database screening, fibroblast growth factor 19 (FGF19) expression was elevated in drug-resistant cells and tumor samples. With FGF19 silencing, drug-resistant cells exhibited increased sensitivity to BRC and decreased intracellular phosphorylated fibroblast growth factor receptor 4 (FGFR4) levels. After confirming that FGF19 binds to FGFR4 in prolactinoma cells, we found that FGF19/FGFR4 regulated prolactin (PRL) synthesis through the ERK1/2 and JNK signaling pathways. Regarding the effect of targeting FGF19/FGFR4 on BRC efficacy, FISO and BRC synergistically inhibited the growth of tumor cells, promoted apoptosis and reduced PRL levels., Conclusion: Overall, our study revealed FGF19/FGFR4 as a new mechanism involved in the drug resistance of prolactinomas, and combination therapy targeting the pathway could be helpful for the treatment of BRC-induced drug-resistant prolactinomas., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Needs arising at both current and future accelerator facilities call for the development of radiation-hardened position-sensing diagnostics that can operate with multi-GHz repetition rates. Such instruments are likely to also have applications in the diagnosis of rapid plasma behavior. Building on the recent work of our Advanced Accelerator Diagnostics Collaboration, we are exploring the development of integrated multi-GHz ionizing particle detection systems based on chemical-vapor deposition diamond sensors, with the initial goal of producing a quadrant detector that can determine the intensity and centroid position of a particle beam at a repetition rate between 5 and 10 GHz. Results from our initial high-speed characterization work are presented, including those from a single-channel sensor with a GHz response. Approaches to achieving multi-GHz (5-10 GHz) rate capability, including the design of a dedicated Application Specific Integrated Circuit and the use of 3D RF-solver computer aided design software, are presented and discussed in more detail. 3D RF simulations suggest clean pulses of duration less than 250 ps (FWHM less than 125 ps) can be achieved with the approaches developed by this work., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background and Aim: Preeclampsia, a pregnancy complication associated with significant maternal and perinatal mortality and morbidity, has been found to be closely linked to dysfunction in the blood coagulation-fibrinolysis system. However, the relationship between hematologic data and severity and onset time of preeclampsia remains unclear. This study aimed to identify specific hematologic parameters in both preeclamptic and normotensive pregnant women and determine their potential significance in the pathogenesis of preeclampsia., Materials and Methods: A total of 112 patients with gestational hypertension disease were divided into two groups: early-onset preeclampsia (32 cases) and late-onset preeclampsia (80 cases). A control group of 82 normotensive pregnant women matched for age and parity was also selected. Blood samples were collected from all participants to test for specific hematologic parameters., Results: Mild and severe preeclampsia were associated with lower hemoglobin level (P = 0.01 and P = 0.03, respectively), higher mean platelet volume (P = 0.01 and P = 0.01, respectively) and fibrinogen (P = 0.01 and P = 0.01, respectively), and shorter prothrombin time (P = 0.02 and P = 0.01, respectively) and activated partial thromboplastin time (P = 0.01 and P = 0.02, respectively)., Conclusion: These findings have provided evidence on the hematologic coagulative actors in the pathogenesis and severity of preeclampsia., (Copyright © 2024 Copyright: © 2024 Nigerian Journal of Clinical Practice.)

Microneedle patches are easy-to-use medical devices for transdermal administration. However, the insufficient insertion of microneedles due to the gap between planar patches and contoured skin affects drug delivery. Herein, we formulate a prepolymer for high-fidelity three-dimensional (3D) printed personalized transdermal patches. With the excellent photoinitiation ability of 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine (Tz), a high-fidelity and precise microneedle patch is successfully fabricated. Upon irradiation of the white illuminator, the doped gold nanoparticles (AuNPs) in the patch release heat and promisingly induce sweat production. With the introduction of Na + , the dominant component of sweat, the curvature of the produced transdermal patch is observed due to the ion-induced network rearrangement. The alkanethiol-stabilized AuNP with an end group of a carboxyl group causes controlled drug release behavior. Furthermore, the irradiation-induced photothermal heating of AuNP can facilitate the sustainability of drug release thanks to the substantially increased particle size of AuNP. These findings demonstrate that the developed prepolymer is a promising candidate for the production of transdermal patches fitting the curvature of the body surface.

Many meta-analyses have assessed the efficacy of preventive interventions against ventilator-associated pneumonia (VAP) in critically ill patients. However, there has been no comprehensive analysis of the strength and quality of evidence to date. Systematic reviews of randomized and quasi-randomized controlled trials, which evaluated the effect of preventive strategies on the incidence of VAP in critically ill patients receiving mechanical ventilation for at least 48 h, were included in this article. We identified a total of 34 interventions derived from 31 studies. Among these interventions, 19 resulted in a significantly reduced incidence of VAP. Among numerous strategies, only selective decontamination of the digestive tract (SDD) was supported by highly suggestive (Class II) evidence (risk ratio (RR)=0.439, 95% CI: 0.362-0.532). Based on data from the sensitivity analysis, the evidence for the efficacy of non-invasive ventilation in weaning from mechanical ventilation (NIV) was upgraded from weak (Class IV) to highly suggestive (Class II) (RR=0.32, 95% CI: 0.22-0.46). All preventive interventions were not supported by robust evidence for reducing mortality. Early mobilization exhibited suggestive (Class III) evidence in shortening both intensive length of stay (LOS) in the intensive care unit (ICU) (mean difference (MD)=-0.85, 95% CI: -1.21 to -0.49) and duration of mechanical ventilation (MD=-1.02, 95% CI: -1.41 to -0.63). In conclusion, SDD and NIV are supported by robust evidence for prevention against VAP, while early mobilization has been shown to significantly shorten the LOS in the ICU and the duration of mechanical ventilation. These three strategies are recommendable for inclusion in the ventilator bundle to lower the risk of VAP and improve the prognosis of critically ill patients., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Serum lipid levels are associated with cancer risk. However, there still have uncertainties about the single and combined effects of low lipid levels on cancer risk., Methods: A prospective cohort study of 33,773 adults in Shanghai between 2016 and 2017 was conducted. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured. Cox proportional hazard models were used to assess the association of single and combined lipids with overall, lung, colon, rectal, thyroid gland, stomach, and female breast cancers. The effect of the combination of abnormal lipid score and lifestyle on cancer was also estimated., Results: A total of 926 incident cancer cases were identified. In the RCS analysis, hazard ratios (HRs) of overall cancer for individuals with TC < 5.18 mmol/L or with LDL-C < 3.40 mmol/L were higher. Low TC was associated with higher colorectal cancer risk (HR [95% CI] = 1.76 [1.09-2.84]) and low HDL-C increased thyroid cancer risk by 90%. Abnormal lipid score was linearly and positively associated with cancer risk, and smokers with high abnormal lipid scores had a higher cancer risk, compared to non-smokers with low abnormal lipid scores (P < 0.05)., Conclusions: Low TC levels were associated with an increased risk of overall and colorectal cancer. More attention should be paid to participants with high abnormal lipid scores and unhealthy lifestyles who may have a higher risk of developing cancer. Determining the specific and comprehensive lipid combinations that affect tumorigenesis remains a valuable challenge., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Objective: To assess the association between body mass index (BMI) and major adverse cardiovascular and cerebrovascular events (MACCE) among patients with acute coronary syndrome (ACS). Methods: This was a multicenter prospective cohort study, which was based on the Improving Care for Cardiovascular Disease in China (CCC) project. The hospitalized patients with ACS aged between 18 and 80 years, registered in CCC project from November 1, 2014 to December 31, 2019 were included. The included patients were categorized into four groups based on their BMI at the time of admission: underweight (BMI<18.5 kg/m 2 ), normal weight (BMI between 18.5 and 24.9 kg/m 2 ), overweight (BMI between 25.0 and 29.9 kg/m 2 ), and obese (BMI≥30.0 kg/m 2 ). Multivariate logistic regression models was used to analyze the relationship between BMI and the risk of in-hospital MACCE. Results: A total of 71 681 ACS inpatients were included in the study. The age was (63.4±14.7) years, and 26.5% (18 979/71 681) were female. And the incidence of MACCE for the underweight, normal weight, overweight, and obese groups were 14.9% (322/2 154), 9.5% (3 997/41 960), 7.9% (1 908/24 140) and 7.0% (240/3 427), respectively ( P< 0.001). Multivariate logistic regression analysis showed a higher incidence of MACCE in the underweight group compared to the normal weight group ( OR =1.30, 95% CI 1.13-1.49, P <0.001), while the overweight and obese groups exhibited no statistically significant difference in the incidence of MACCE compared to the normal weight group (both P >0.05). Conclusion: ACS patients with BMI below normal have a higher risk of in-hospital MACCE, suggesting that BMI may be an indicator for evaluating short-term prognosis in ACS patients.

Objective: To evaluate the feasibility and safety of transcatheter tricuspid valve edge-to-edge repair guided by only transesophageal echocardiography (TEE). Methods: Patients with severe tricuspid regurgitation in Fuwai Yunnan Cardiovascular Hospital who met the inclusion criteria based on clinical and echocardiographic evaluationand underwent transcatheter tricuspid valve edge-to-edge repair between January 2022 and May 2023 were prospectively enrolled. The procedure was performed under general anesthesia with endotracheal intubation and solely guided by TEE. The patients underwent clinical evaluation, electrocardiogram and transthoracic echocardiography one month after the procedure. Results: A total of 22 patients (12 males and 10 females) were included, with an average age of (71.3±6.7) years. All 22 patients successfully underwent the transcatheter tricuspid valve edge-to-edge repair under TEE guidance, with an average of (1.5±0.6) clips implanted. Immediately after procedure, six patients had no or trace regurgitation, 15 patients had mild regurgitation, and one patient had moderate regurgitation. All 22 patients completed 30-day follow-up, with four patients having trace regurgitation, 17 patients having mild regurgitation, and one patient having moderate regurgitation. Echocardiographic measurements revealed that effective regurgitant orifice area, regurgitant volume, vena contracta width, and proximal isovelocity surface area radius significantly decreased after the procedure (all P <0.05). In addition, inferior vena cava width, right atrial volume, tricuspid annular diameter, and right ventricular end-diastolic diameter significantly improved (all P <0.05), but tricuspid annular plane systolic excursion and right ventricular fractional area change did not show significant differences compared with those before the procedure (both P> 0.05). Conclusion: It has been preliminarily confirmed that transcatheter tricuspid valve edge-to-edge repair solely guided by TEE is feasible and safe, but requires more large-scale studies for further validation.

Calcific aortic valve disease (CAVD) is the most common heart disease of the developed world. It has previously been established that metformin administration reduces arterial calcification via autophagy; however, whether metformin directly regulates CAVD has yet to be elucidated. In the present study we investigated whether metformin alleviates valvular calcification through the autophagy-mediated recycling of Runx2. Calcification was reduced in rat valve interstitial cells (RVICs) by metformin treatment (0.5-1.5 mM) (P < 0.01), with a marked decrease in Runx2 protein expression compared to control cells (P < 0.05). Additionally, upregulated expression of Atg3 and Atg7 (key proteins required for autophagosome formation), was observed following metformin treatment (1 mM). Blocking autophagic flux using Bafilomycin-A1 revealed colocalisation of Runx2 with LC3 puncta in metformin treated RVICs (P < 0.001). Comparable Runx2 accumulation was seen in LC3 positive autolysosomes present within cells that had been treated with both metformin and hydroxychloroquine in combination (P < 0.001). Mechanistic studies employing three-way co-immunoprecipitation with Runx2, p62 and LC3 suggested that Runx2 binds to LC3-II upon metformin treatment in VICs. Together these studies suggest that the utilisation of metformin may represent a novel strategy for the treatment of CAVD., (© 2023. The Author(s).)

Objective: To investigate the role of mucosal-associated invariant T (MAIT) cells in the regulatory mechanism of adipose browning., Methods: A mouse model with functional deficiency of MAIT cells was established for comparison with the wild-type mice for levels of brown adipose tissue markers in response to cold stimulation using Western blotting and RT-PCR. Flow cytometry was used to analyze the changes in the number, activation level and cytokine secretion ability of MAIT cells in mouse adipose tissue after cold stimulation. In a co-culture system of MAIT cells and adipocytes, the effect of interleukin-4 (IL-4) blocking antibodies on the expressions of brown adipose tissue markers in the adipocytes was evaluated using Western blotting and RT-PCR. In a mouse model of MAIT cell deficiency, the changes in adipose browning-related indicators in response to cold stimulation were analyzed using metabolic cages, immunohistochemistry, Western blotting and the Seahorse method., Results: In both the mouse models of functional deficiency of MAIT cells and wild-type mice, cold stimulation significantly increased the expression levels of brown adipose tissue markers UCP-1 and PGC1-α and upregulated CD69 and IL-4 expressions in the adipose tissue without significantly affecting the number of MAIT cells in the adipose tissue. In the coculture experiment, the adipocytes showed obviously increased browning level after co-culture with MAIT cells ( P < 0.05), but blocking IL-4 signaling strongly downregulated the browning level ( P < 0.05). The MAIT cell-deficient mice showed obviously lower levels of energy expenditure, adipose browning and metabolism of the adipocytes compared with the wild-type mice in response to cold stimulation ( P < 0.05)., Conclusion: MAIT cells participate in adipose browning in mice, and cold stimulation promotes MAIT cell secretion of IL-4 to positively regulate adipose browning.

Aim: To present an integrated 2-[ 18 F]-fluoro-2-deoxy-d-glucose ( 18 F-FDG) positron-emission tomography (PET)/computed tomography (CT) radiomic characterisation of programmed death-ligand 1 (PD-L1) status in non-small-cell lung cancer (NSCLC)., Materials and Methods: In this retrospective study, 18 F-FDG PET/CT images and clinical data of 394 eligible patients were divided into training (n=275) and test sets (n=119). Next, the corresponding nodule of interest was segmented manually on the axial CT images by radiologists. After which, the spatial position matching method was used to match the image positions of CT and PET, and radiomic features of the CT and PET images were extracted. Radiomic models were built using five different machine-learning classifiers and the performance of the radiomic models were further evaluated. Finally, a radiomic signature was established to predict the PD-L1 status in patients with NSCLC using the features in the best performing radiomic model., Results: The radiomic model based on the PET intranodular region determined using the logistic regression classifier preformed best, yielding an area under the receiver operating characteristics curve (AUC) of 0.813 (95% CI: 0.812, 0.821) on the test set. The clinical features did not improve the test set AUC (0.806, 95% CI: 0.801, 0.810). The final radiomic signature for PD-L1 status was consisted of three PET radiomic features., Conclusion: This study showed that an 18 F-FDG PET/CT-based radiomic signature could be used as a non-invasive biomarker to discriminate PD-L1-positive from PD-L1-negative in patients with NSCLC., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To evaluate and compare the short-term efficacy of domestic mechanical-locked (Clip2Edge) and elastic self-locked (ValveClip) transcranial mitral valve edge-to-edge interventional repair (TEER) devices in the treatment of functional mitral regurgitant valves. Methods: In this retrospective non-randomized comparative study, patients underwent TEER procedure in Fuwai Yunnan Cardiovascular Disease Hospital from May 2022 to April 2023 for heart failure combined with moderate to severe or severe functional mitral valve were divided into Clip2Edge and ValveClip groups based on the TEER system used. Baseline, perioperative, and postoperative 30 d follow-up data were collected and compared between the two groups. The primary outcome was the success rate on the 30 d post operation, while secondary outcomes included immediate postoperative technical success rate and the incidence of all-cause mortality on the 30 d post operation, readmission rate of acute heart failure, cerebral infarction, severe bleeding, and other serious adverse events rates. Results: A total of 60 patients were enrolled, 34 patients were in the Clip2Edge group and 26 in the ValveClip group, mean age was (63.8±9.3) years, and 24 patients (40%) were female. There were no significant differences in baseline data of age, cardiac function, comorbidities, mitral regurgitation 4+(19(73%) vs. 29(85%)), the end-diastolic volume of left ventricle ((220.8±91.2) ml vs. (210.8±71.7) ml) between the two groups (all P> 0.05). The technical success rate immediately after the procedure was 100%. There were no readmission of acute heart failure, death, cerebral infarction, severe bleeding, and other serious adverse events up to the 30 d follow-up. Device success rate was similar between the ValveClip group (24 cases (100%)) and the Clip2Edge group (27 cases (96%)) ( P >0.05). Conclusion: Both types of novel domestic TEER devices are safe and feasible in treating patients with functional mitral regurgitation.

Objective: To explore the optimal intensity of anticoagulation therapy for Chinese patients after mechanical heart valve replacement. Methods: This is a prospective, multicenter, cohort study. The anticoagulation data from in-hospital patients of 35 medical centers and patients in outpatient clinic of 11 medical centers from Anticoagulation Therapy Database of Chinese Patients after Heart Valve Replacement between January 2011 and December 2015 were analyzed. The anticoagulation-relevant complications among different coagulation intensities were compared, and the optimal value of anticoagulation intensity for Chinese patients after mechanical heart valve replacement were analyzed. Results: A total of 24 433 patients were in the final analysis, including 13 634 females and 10 799 males, with a median age of 49.0 (3-80) years. International normalized ratio (INR) values of in-hospital patients were recorded 94 286 times, with the mean value of 1.8±0.7, and 87.6% (82 595/94 286) of them were within the range of 1.5 to 2.5. During a median follow-up time of 19.2 (1.0-58.8) months, a total of 17 331 outpatient clinic patients were followed up, with the follow-up rate of 89.1% (17 331/19 452) and a total of 27 803 patient-years (Pty), including 4 038 aortic valve replacement (AVR), 8 215 mitral valve replacement (MVR), 4 437 AVR plus MVR (double valve replacement, DVR) replacement and 641 tricuspidvalve replacement (TVR). A total of 101 860 INR measurements were recorded, with the mean value of 1.8±0.5, and 64.8% (66 005/101 860) of them were within the range of 1.5-2.5. The rates of anticoagulation-related complications of the patients with INR of 1.5-2.5 (0.65/100 Pty) were lower than those of other INR value patients (INR<1.5: 1.31/100 Pty, RR =2.01, 95% CI : 1.59-2.51, P <0.001; INR>2.5: 2.34/100 Pty, RR =3.60, 95% CI : 2.84-4.52, P <0.001). The rates of anticoagulation-related complications of AVR and MVR patients without risk factors and with INR of 1.5-2.0 were lower than those of other INR value patients (AVR: 0.15/100 Pty vs 0.38/100 Pty, RR =2.57, 95% CI : 1.02-7.28, P =0.029; MVR: 0.23/100 Pty vs 0.56/100 Pty, RR =2.42, 95% CI : 1.39-4.38, P <0.001), and the rate of anticoagulation-related complications of DVR patients with INR of 2.0-2.5 was lower than those of other INR value patients (0.32/100 Pty vs 0.62/100 Pty, RR =1.94, 95% CI : 1.03-3.79, P =0.029). Conclusions: A target INR range of 1.5-2.5 is recommended for Chinese patients after mechanical heart valve replacement. The optimal INR value for isolated AVR or MVR patients without risk factors was 1.5-2.0, while the optimal INR value for isolated AVR or MVR patients with risk factors and all the TVR or DVR patients was 2.0-2.5.

Purpose: Prolactinomas are one of the most common pituitary neuroendocrine tumors (PitNETs), accounting for approximately 50% of all pituitary tumors. Dopamine agonists are the main treatment for prolactinoma, but a small number of patients are still resistant to pharmacotherapy. Recent discoveries have revealed that ferroptosis is involved in regulating tumor drug resistance. However, the role of ferroptosis in prolactinoma has not been reported. In this study, we aimed to explore the mechanism of a circRNA in ferroptosis in prolactinoma., Methods: The expression of circOMA1 in prolactinoma tissues was examined by quantitative reverse transcription PCR (qRT-PCR). The biological function of circOMA1 was evaluated in vitro and in vivo. To explore the role of ferroptosis in prolactinoma, we used qRT-PCR and western blotting. Glutamate-cysteine ligase, modifier subunit (GCLM) was predicted to be a direct target gene of miR-145-5p by bioinformatics analysis, which was confirmed by luciferase reporter assays., Results: circOMA1 was overexpressed in drug-resistant prolactinoma tissues compared with sensitive prolactinoma samples. We further found that circOMA1 promoted MMQ cells growth in vivo and in vitro. In addition, GCLM was directly targeted by miR-145-5p and indirectly regulated by circOMA1. Importantly, circOMA1 induced ferroptosis resistance through the increased expression of Nrf2, GPX4, and xCT, and circOMA1 attenuated CAB-induced ferroptosis in MMQ cells in vivo and in vitro., Conclusion: The present study demonstrates that circOMA1 attenuates CAB efficacy through ferroptosis resistance and may be a new therapeutic target for the individualized treatment of DA-resistant prolactinoma patients., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

This study aims to analyze the clinical characteristics and genetic variations of two cases with developmental delay and lactic acidosis in a family, and to explore the relationship between genetic variations and clinical features. A retrospective analysis was conducted on the clinical characteristics of two siblings with developmental delay and lactic acidosis who were treated at the Neonatal Department of Children's Hospital of Chongqing Medical University in May 2019 and December 2021, respectively. Whole-exome sequencing was used to detect genetic variations in the affected children. Homology modeling of the BCS1L protein was performed to analyze the structural and functional changes of the protein. The correlation between genetic variations and clinical phenotypes was analyzed. The results showed that the main clinical features of the two affected children in this family were manifestations of mitochondrial respiratory chain complex Ⅲ deficiency, including prematurity, developmental delay, respiratory failure, lactic acidosis, cholestasis, liver dysfunction, renal tubular lesions, coagulation dysfunction, anemia, hypoglycemia, hypotonia, and early death. Whole-exome sequencing revealed a novel deletion mutation c.486&#95;488delGGA (p.E163del) and a novel missense mutation c.992C>T (p.T331I) in the BCS1L gene. Structural analysis of the homology modeling showed that the compound heterozygous mutation had a significant impact on protein function. In conclusion, the novel mutation site c.992C>T (p.T331I) in the BCS1L gene is a "likely pathogenic" mutation, and the compound heterozygous mutation is closely related to the phenotype of mitochondrial respiratory chain complex Ⅲ deficiency.

Objective: Evidence for the mucolytic and expectorant efficacy of intravenous (IV) N-acetylcysteine (NAC) is limited. This study aimed to evaluate in a large, multicenter, randomized, controlled, subject, and rater-blinded study whether IV NAC is superior to placebo and non-inferior to ambroxol in improving sputum viscosity and expectoration difficulty., Patients and Methods: A total of 333 hospitalized subjects from 28 centers in China with respiratory disease (such as acute bronchitis, chronic bronchitis and exacerbations, emphysema, mucoviscidosis, and bronchiectasis) and abnormal mucus secretion were randomly allocated in a 1:1:1 ratio to receive NAC 600 mg, ambroxol hydrochloride 30 mg, or placebo as an IV infusion twice daily for 7 days. Mucolytic and expectorant efficacy was assessed by ordinal categorical 4-point scales and analyzed by stratified and modified Mann-Whitney U statistics., Results: NAC showed consistent and statistically significant superiority to placebo and non-inferiority to ambroxol in change from baseline to day 7 in both sputum viscosity scores [mean (SD) difference 0.24 (0.763), p<0.001 vs. placebo] and expectoration difficulty score [mean (SD) difference 0.29 (0.783), p=0.002 vs. placebo]. Safety findings confirm the good tolerability profile of IV NAC reported from previous small studies, and no new safety concerns were identified., Conclusions: This is the first large, robust study of the efficacy of IV NAC in respiratory diseases with abnormal mucus secretion. It provides new evidence for IV NAC administration in this indication in clinical situations where the IV route is preferred.

Purpose: Growth hormone-secreting pituitary adenomas (GH-PAs) with a low Knosp grade are typically associated with a good postoperative biochemical remission (BR) rate. However, a proportion of patients do not achieve remission. In this study, we aimed to investigate predictive factors of postoperative remission for lower Knosp GH-PAs., Methods: In this retrospective study, we enrolled 140 patients who were diagnosed with lower Knosp (0-2) GH-PAs and received trans-sphenoidal surgery between December 2016 and June 2021 from the largest pituitary tumor surgery center in southern China. The univariate, binary Logistic regression, and receiver operating characteristic curve (ROC) analyses were employed to determine independent predictors and cutoff values of remission. The postoperative outcome was defined as remission using the 2010 consensus criteria of acromegaly., Results: One hundred and thirty six patients (97.1%) achieved gross total resection. The postoperative long-term BR was 68.6%. Empty sella, tumor maximum diameter and postoperative GH levels were independent factors predicting remission. ROC revealed that postoperative 24 h GH ≤ 1.3 ng/mL and  ≤ 1.23 ng/mL were valuable predictors for 3-month and long-term remission respectively, and that postoperative 3-month GH ≤ 1.6 ng/mL and tumor maximum diameter  ≤ 17 mm were predictors for delayed remission., Conclusion: Early postoperative GH levels can be used as predictors of remission. However, BR was not associated with preoperative somatostatin analogs therapy or Knosp grade (0-2). For patients without residual tumor or recurrence and whose GH levels are slightly elevated within 1 year after surgery, adjuvant treatments may not be necessary., (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Objective: To investigate the knowledge, use and barriers when prescribing GLP-1RA and SGLT2i among cardiologists, endocrinologists and general practitioners, and explore the influencing factors that hinder the use of these medications. Methods: A questionnaire was conducted among physicians in the above departments in Peking University Third Hospital and health service institutions at all levels in its medical consortium. A total of 342 physicians were involved. Among them, 40.6% (139) were cardiologists, 28.9% (99) were endocrinologists and 30.4% (104) were general practitioners; 66.7% (270) came from Beijing while 33.3% (72) from other provinces. The survey included clinicians' knowledge and current use of GLP-1RA and SGLT2i, and the possible reasons that influenced the prescription of these medications. Medical therapies of physicians were investigated by simulating different clinical scenarios. The difference of measures among physicians in different departments was compared. Results: A total of 342 physicians were involved, with the average age of 40 (35, 46) years old and the average working time of 13 (7, 20) years. Among them, 40.6% (139) were male. 77.5% (265) physicians had comprehensive knowledge of SGLT2i and prescribed it, which was higher than that for GLP-1RA (70.5%, 241) ( P <0.001). 21.1% (72) physicians prescribed SGLT2i more than 20 times per month, which was higher than that for GLP-1RA (8.2%, 28) ( P <0.001). Endocrinologists had more knowledge and prescribed more GLP-1RA and SGLT2i compared with other physicians (both P values < 0.001). 38.1% (53) cardiologists, 22.2% (22) endocrinologists, and 30.8% (32) general practitioners believed patients needed an endocrinologist to evaluate and adjust GLP-1RA, which was the primary barrier for the use of medications ( P= 0.042). 27.4% (38) cardiologists, 14.1% (14) endocrinologists, and 30.8% (32) general practitioners believed patients needed an endocrinologist to evaluate and adjust SGLT2i, which was the primary barrier for the use of medications ( P= 0.018). 21.6% (30) cardiologists, 45.5% (45) endocrinologists, and 31.7% (33) general practitioners believed side effects of SGLT2i was the primary barrier for the use of medications ( P< 0.001). For patients with unqualified glycemic control and cardiovascular complications, 65.4% (75) cardiologists, 69.7% (69) endocrinologists, and 43.3% (45) general practitioners chose the above medications ( P <0.001). For patients with qualified glycemic control, combined with cardiovascular complications and diabetic organ damage, 35.3% (49) cardiologists, 52.5% (52) endocrinologists, and 25.0% (26) general practitioners chose the above medications ( P< 0.001). Conclusions: Physicians had more knowledge and prescription of SGLT2i than that of GLP-1RA. Endocrinologists had more knowledge and prescription of the above medications than other physicians. The side effect of medications was potential primary barrier for the use of the novel hypoglycemic agent with cardiovascular benefits. In clinical practice, most of physicians considered that high-risk patients with cardiovascular comorbidities need to be referred to cardiologist or endocrinologist to adjust clinical therapies.

Superconductivity in the cuprates is found to be intertwined with charge and spin density waves. Determining the interactions between the different types of order is crucial for understanding these important materials. Here, we elucidate the role of the charge density wave (CDW) in the prototypical cuprate La 1.885 Sr 0.115 CuO 4 , by studying the effects of large magnetic fields (H) up to 24 Tesla. At low temperatures (T), the observed CDW peaks reveal two distinct regions in the material: a majority phase with short-range CDW coexisting with superconductivity, and a minority phase with longer-range CDW coexisting with static spin density wave (SDW). With increasing magnetic field, the CDW first grows smoothly in a manner similar to the SDW. However, at high fields we discover a sudden increase in the CDW amplitude upon entering the vortex-liquid state. Our results signify strong coupling of the CDW to mobile superconducting vortices and link enhanced CDW amplitude with local superconducting pairing across the H - T phase diagram., (© 2023. The Author(s).)

Background: Failure of Alzheimer's disease and related diseases (ADRD) research studies to include and engage Black participants is a major issue, which limits the impact and generalizability of research findings. Little is known about participation of Black adults in online ADRD-related research registries., Objectives: As part of the Community Engaged Digital Alzheimer's Research (CEDAR) Study, this study aims to increase our understanding of facilitators and barriers of Black adults to participating in ADRD-related online registries, as well as to understand their preferences for communication channels., Design, Setting, Participants, Measurements: We invited all Black participants enrolled in the Brain Health Registry (BHR) to complete a cross-sectional online survey. The survey consisted of rating scales and open-text questions asking about their attitudes towards brain health research, reasons for joining and continuing to participate in BHR, difficulties with participating, and preferences for modes of contact and website usage., Results: Of all invited Black BHR participants (N=3,636), 198 (5.5%) completed the survey. The mean age was 58.4 (SD=11.3), mean years of education were 16.3 (SD=2.4), and 85.5% identified as female. Reported facilitators for joining and continuing to participate in BHR were personal interest (e.g., learning more about own brain health) and altruism (e.g., helping research). Among additional registry features which could encourage return, receiving feedback or scores about BHR tasks was rated the highest. Of those who found BHR participation difficult (21%), the most frequent reason was time burden. The most preferred way of receiving study information was via email. Participants reported that the websites that they used the most were YouTube and Facebook., Discussion: The results of our study can inform the development of culturally-responsive registry features and engagement efforts to improve inclusion and participation of Black adults in online ADRD research. Providing participants with feedback about their registry performance and reducing the number of registry tasks are among the recommended strategies., Competing Interests: Danqi Zhu, Dr. Heining Cham, Jessica Bride, Emily McLean, Xinyue Deng Anna Aaronson, Catherine Conti, Carole Cypress, Philip Griffin, Regene Ross, Terrance Duncan, Aaron Ulbricht, Derek Flenniken, Diana Truran, Juliet Fockler, Monica Camacho, Dr. R. Scott Mackin, Dr. Carl V. Hill, and Dr. Robert Turner have nothing to disclose. Dr. Ashford reports grants from NIA during the conduct of the study (F32 AG072730-02). Dr. Byrd reports grants from Genetech during the conduct of the study. Dr. Weiner reports grants from National Institutes of Health (NIH), grants from Department of Defense (DOD), grants from Patient-Centered Outcomes Research Institute (PCORI), grants from California Department of Public Health (CDPH), grants from University of Michigan, grants from Siemens, grants from Biogen, grants from Hillblom Foundation, grants from Alzheimer’s Association, grants from The State of California, grants from Johnson and Johnson, grants from Kevin and Connie Shanahan, grants from GE, grants from VUmc, grants from Australian Catholic University (HBI-BHR), grants from The Stroke Foundation, grants from Veterans Administration, personal fees from Acumen Pharmaceutical, personal fees from Cerecin, personal fees from Dolby Family Ventures, personal fees from Eli Lilly, personal fees from Merck Sharp and Dohme Corp., personal fees from National Institute on Aging (NIA), personal fees from Nestle/Nestec, personal fees from PCORI/PPRN, personal fees from Roche, personal fees from University of Southern California (USC), personal fees from NervGen, personal fees from Baird Equity Capital, personal fees from BioClinica, personal fees from Cytox, personal fees from Duke University, personal fees from Eisai, personal fees from FUJIFILM-Toyama Chemical (Japan), personal fees from Garfield Weston, personal fees from Genentech, personal fees from Guidepoint Global, personal fees from Indiana University, personal fees from Japanese Organization for Medical Device Development, Inc. (JOMDD), personal fees from Medscape, personal fees from Peerview Internal Medicine, personal fees from Roche, personal fees from T3D Therapeutics, personal fees from WebMD, personal fees from Vida Ventures, personal fees from The Buck Institute for Research on Aging, personal fees from China Association for Alzheimer’s Disease (CAAD), personal fees from Japan Society for Dementia Research, personal fees from Korean Dementia Society, outside the submitted work; and I hold stocks or options with Alzheon Inc., Alzeca, and Anven. Dr. Rivera Mindt reports grants from NIH/NIA Pending # 1R01AG079285-01 , during the conduct of the study; grants from U19AG078109-01; R01AG066471; R56AG075744; R13AG071313-01; and R01AG065110 - 01A1; SC3GM141996; Genentech Health Equity Innovations 2020 Fund G-89294, outside the submitted work. Dr. Nosheny reports grants from NIH, grants from Genentech, Inc., grants from California Department of Public Health during the conduct of the study.

Background: Although Black/African American older adults bear significant inequities in prevalence, incidence, and outcomes of Alzheimer's disease and related dementias, they are profoundly under-included in Alzheimer's Disease research. Community-Engaged Research (e.g., equitable community/science partnerships) is an evidence-based approach for improving engagement of underrepresented populations into Alzheimer's Disease research, but has lacked scalability to the national level. As internet use among older adults from underrepresented populations continues to grow, internet-based research shows promise as a feasible, valid approach to engagement and longitudinal assessment. The Community Engaged Digital Alzheimer's Research (CEDAR) study utilizes a community-engaged research approach to increase the engagement and research participation of Black/African American adults in the Brain Health Registry (BHR) and Alzheimer Disease clinical research., Objectives: To describe the methods and evaluate the feasibility of the CEDAR culturally-informed digital platform within BHR., Design: All Black/African American participants in BHR were invited to enroll in CEDAR and to consider serving on a newly convened Community-Scientific Partnership Board to guide the study. The community board guided the development a culturally-informed cadre of engagement materials and strategies to increase research participation. Engagement strategies included incentives for study task completion, culturally-informed communications (e.g., landing page, emails and social media), resources about brain health, and video and written testimonials by CEDAR participants., Setting: BHR, an Internet-based registry and cohort., Participants: BHR participants self-identifying as Black/African American were invited to enroll. All participants who signed an online informed consent document were enrolled., Measurements: We report the number of participants invited, enrolled, completed tasks, and volunteered to join the community board. We compared the demographics, cognitive profile, and baseline BHR task completion rates between CEDAR participants and all those invited to join the study., Results: Of 3738 invited, 349 (9.34%) enrolled in CEDAR. 134 (37% of CEDAR participants) volunteered to join the community board, of which 19 were selected for the community board. Compared to those invited, the CEDAR cohort had a higher percentage of female participants (84.5%) and a lower percentage of participants who identify as belonging to more than one ethnocultural group (21.8%). Compared to those did not enroll in CEDAR, those enrolled in CEDAR had a higher percentage of participants completing all BHR tasks (22%) and a higher percentage of participants completing at least one cognitive test (76%). Those enrolled in CEDAR also had a higher percentage of participants having an enrolled study partner (18%)., Conclusions: A culturally-informed Community-Engaged Research approach, including a remotely-convened community board, to engagement of Black/African American participants in an online research registry is feasible. This approach can be adapted for use in various clinical studies and other settings. Future studies will evaluate the effectiveness of the engagement strategies., Competing Interests: Danqi Zhu, Dr. Heining Cham, Anna Aaronson, Catherine Conti, Xinyue Deng, Jennefer Sorce, Carole Cypress, Philip Griffin, Derek Flenniken, Monica Camacho, Juliet Fockler, Diana Truran, Dr. R. Scott Mackin, Dr. Carl V. Hill and Dr. Robert Turner have nothing to disclose. Dr. Rivera Mindt reports grants from NIH/NIA Pending # 1R01AG079285-01, during the conduct of the study; grants from U19AG078109-01; R01AG066471; R56AG075744; R13AG071313-01; R01AG065110 - 01A1; SC3GM141996; Genentech Health Equity Innovations 2020 Fund G-89294, outside the submitted work. Dr. Ashford reports grants from NIA during the conduct of the study (F32 AG072730-02). Roxanne Alaniz reports personal fees from eVAL, personal fees from ADNI4, personal fees from SALUD, personal fees from US Pointer, personal fees from Active6, outside the submitted work. Roxanne Alaniz reports personal fees from eVAL, personal fees from ADNI4, personal fees from SALUD, personal fees from US Pointer, personal fees from Active6, outside the submitted work. Dr. Byrd reports grants from Genetech during the conduct of the study. Dr. Weiner reports grants from National Institutes of Health (NIH), grants from Department of Defense (DOD), grants from Patient-Centered Outcomes Research Institute (PCORI), grants from California Department of Public Health (CDPH), grants from University of Michigan, grants from Siemens, grants from Biogen, grants from Hillblom Foundation, grants from Alzheimer’s Association, grants from The State of California, grants from Johnson & Johnson, grants from Kevin and Connie Shanahan, grants from GE, grants from VUmc, grants from Australian Catholic University (HBI- BHR), grants from The Stroke Foundation, grants from Veterans Administration, personal fees from Acumen Pharmaceutical, personal fees from Cerecin, personal fees from Dolby Family Ventures, personal fees from Eli Lilly, personal fees from Merck Sharp & Dohme Corp., personal fees from National Institute on Aging (NIA), personal fees from Nestle/Nestec, personal fees from PCORI/PPRN, personal fees from Roche, personal fees from University of Southern California (USC), personal fees from NervGen, personal fees from Baird Equity Capital, personal fees from BioClinica, personal fees from Cytox, personal fees from Duke University, personal fees from Eisai, personal fees from FUJIFILM-Toyama Chemical (Japan), personal fees from Garfield Weston, personal fees from Genentech, personal fees from Guidepoint Global, personal fees from Indiana University, personal fees from Japanese Organization for Medical Device Development, Inc. (JOMDD), personal fees from Medscape, personal fees from Peerview Internal Medicine, personal fees from Roche, personal fees from T3D Therapeutics, personal fees from WebMD, personal fees from Vida Ventures, personal fees from The Buck Institute for Research on Aging, personal fees from China Association for Alzheimer’s Disease (CAAD), personal fees from Japan Society for Dementia Research, personal fees from Korean Dementia Society, outside the submitted work; and I hold stocks or options with Alzheon Inc., Alzeca, and Anven. Dr. Nosheny reports grants from NIH, grants from Genentech, Inc., grants from California Department of Public Health during the conduct of the study.

Objective: To explore the effect of "one-stop" outpatient management on the therapeutic schedule and control rate of patients with metabolic disorders. Methods: A total of 332 patients who met the inclusion criteria were enrolled and treated regularly in the "one-stop" outpatient department of the Department of Cardiology of the Third Hospital of Peking University from November 1, 2020 to April 30, 2022. The general information, personal history, family history, drug treatment plan, blood pressure, height, weight, waist circumference, and hip circumference of patients were collected through the outpatient electronic medical record system, and patients were followed up through conducting "one-stop" comprehensive management. The baseline clinical characteristics were analyzed, and the changes of metabolic indexes, treatment conditions and control rate of patients with different metabolic disorders before and after the "one-stop" outpatient management were compared. Results: The time interval between the first visit and the last visit was 44 (26, 60) weeks in 332 patients, whose age was (57.2±13.2) years, including 219 males (66.0%). After the "one-stop" outpatient management, fasting blood glucose (FBG) [ 6.6 (5.6, 7.9) mmol/L vs 6.3 (5.6, 6.9) mmol/L], glycosylated hemoglobin A1c (HbA1c) [ (7.2±1.5) % vs (6.6±0.8) %], low density lipoprotein cholesterol (LDL-C) [ 2.70 (1.97, 3.55) mmol/L vs 2.04 (1.66, 2.63) mmol/L] and blood uric acid (UA) [ (383.7±107.1) μmol/L vs (341.2±90.6) μmol/L] all decreased significantly (all P values<0.05). The control rates of hypertension (19.8% vs 28.2%), diabetes (45.2% vs 66.5%), hyperlipidemia (54.9% vs 87.6%) and hyperuricemia (16.7% vs 49.0%) were significantly improved after the "one-stop" outpatient management (all P values<0.05). Conclusion: The "one-stop" outpatient management of cardiovascular department can significantly improve the metabolic condition and the control rate of patients with multiple metabolic disorders.

Objective: To evaluate the diagnostic value and application of 24 h multichannel intraluminal impedance-pH (24 h MII-pH) monitoring in children with gastroesophageal reflux disease (GERD). Methods: This is a cross-sectional study. From January 2013 to December, 2020, 417 patients who received 24 h MII-pH monitoring in Department of Gastroenterology of Children's Hospital Capital Institute of Pediatrics were included. According to results, these children were divided into the GERD and non-GERD groups. Furthermore, the 132 children with GERD who had gastroscopy were divided into the reflux esophagitis (RE) and non-erosive reflux disease (NE) groups to investigate the differences in their refluxes. Non-parametric Mann-Whitney U test or indepentent sample t test was used for comparisons between the groups. Results: Among the 417 children, 232 were males and 185 females, aged (7.3±3.9) years. The course of disease was 0.5 (0.1, 2.0) years. The main clinical symptoms included acid reflux (128 cases), vomiting (173 cases), abdominal pain (101 cases), and cough (76 cases). The 24 h MII-pH monitoring were positive in 243 children (58.3%, 243/417), which was higher than that by 24 h esophageal pH monitoring (43.6%, 182/417). The 24 h MII-pH monitoring results demonstrated significant differences in the episodes of acid reflux, weakly acidic reflux, non-acidic reflux, liquid reflux and mixed reflux between GERD and non-GERD groups (10 (4, 19) vs . 4 (1, 9) times/24 h, 14 (6, 32) vs . 7 (3, 13) times/24 h, 0 (0, 0) vs . 0 (0, 0) times/24 h, 19 (10, 34) vs . 8 (3, 14) times/24 h, and 6 (2, 12) vs . 3 (1, 5) times/24 h, Z =-6.96, -7.25, -5.62, -8.75, and -6.48, all P <0.05, respectively). Besides, the results also showed significant differences in Boix-Ochoa score, episodes of long reflux, course of long reflux, and episodes of weakly acidic reflux between the RE and NE groups (51.2 (21.4, 153.2) vs . 20.7 (12.1, 34.7), 5 (2, 10) vs . 1 (0, 4) times/24 h, 19 (7, 87) vs . 8 (3, 22) min, and 5 (2, 15) vs . 15 (6, 33) times/24 h, Z =-3.44, -3.41, -2.65, and -2.27, all P <0.05, respectively). Conclusion: 24 h MII-pH monitoring not only improves the detection rate of GERD in children, but also provides a possibility to early etiological diagnosis.

Objectives: To analyze the effects of Helicobacter pylori ( H. pylori) infection and eradication therapy on small intestinal bacterial overgrowth (SIBO). Methods: From September to December 2021, patients with abdominal symptoms who received 13 C urea breath test at the Department of Gastroenterology in Peking University First Hospital were enrolled. 13 C urea breath test was used to detect H. pylori infection and patients were divided into H. pylori positive and negative groups accordingly. Lactulose hydrogen methane breath test was performed to determine SIBO. H. pylori positive patients were treated with quadruple therapy including amoxicillin, metronidazole, rabeprazole and bismuth potassium citrate. 13 C urea breath test and lactulose hydrogen methane breath test were reexamined 6 weeks after the treatment. Results: A total of 102 patients (49 males and 53 females) were enrolled, with a mean age of (42.1±9.9) years. Among them, 49 patients were H. pylori negative and 53 were H. pylori positive. Moreover, 47 patients were SIBO positive and 55 were SIBO negative. There was no significant difference in age, sex, body mass index, abdominal symptoms and the diagnosis of chronic atrophic gastritis between H. pylori positive and negative patients at the enrollment (all P >0.05). The detection rate of SIBO in H. pylori infected patients was higher than that in uninfected patients, and the difference was statistically significant (60.4% vs 30.6%, P =0.003). Patients with SIBO had significantly more frequent abdominal distension (36.2% vs 10.9%, P =0.002) and constipation (27.7% vs 1.8%, P <0.001) than patients without SIBO. The rate of SIBO after H. pylori eradication treatment was significantly lower than that before treatment (20.8% vs 60.4%, P <0.001). The remission rate of SIBO after eradication therapy was 66.7% (20/30). Besides, patients had obvious improvement of constipation (6.0% vs 18.9%, P =0.008), and the incidence of other abdominal symptoms decreased to various degrees including diarrhea, abdominal pain, abdominal distention and poor appetite. Conclusion: H. pylori infection increases the risk of SIBO, and the quadruple regimen containing amoxicillin and metronidazole has a therapeutic effect for patients with H.pylori infection and concomitant SIBO.

As we approach the era of quantum advantage, when quantum computers (QCs) can outperform any classical computer on particular tasks, there remains the difficult challenge of how to validate their performance. While algorithmic success can be easily verified in some instances such as number factoring or oracular algorithms, these approaches only provide pass/fail information of executing specific tasks for a single QC. On the other hand, a comparison between different QCs preparing nominally the same arbitrary circuit provides an insight for generic validation: a quantum computation is only as valid as the agreement between the results produced on different QCs. Such an approach is also at the heart of evaluating metrological standards such as disparate atomic clocks. In this paper, we report a cross-platform QC comparison using randomized and correlated measurements that results in a wealth of information on the QC systems. We execute several quantum circuits on widely different physical QC platforms and analyze the cross-platform state fidelities., (© 2022. The Author(s).)

Objective: To explore the effect of polyethylene glycol loxenatide (long-acting GLP-1R agonist) on the lipid, glucose levels, and weight in type 2 diabetes mellitus patients with obesity., Patients and Methods: A total of 40 obese patients with type 2 diabetes mellitus in our hospital from July 2019 to June 2020 were randomly divided into a control group and a study group. The study group was treated with metformin and polyethylene glycol loxenatide injection, while the control group was treated with metformin., Results: Before treatment, there was no significant difference in FPG (Fasting Blood Glucose) and PPG (Post Prandial Glycaemia) levels between the study group and the control group (p>0.05). After a treatment period, the FPG and PPG levels in the study group were significantly lower than those in the control group (p<0.05). With the longer treatment time, the patient's weight and BMI were lower (p<0.05). The weight and BMI of patients changed the least after one month of treatment, and the weight and BMI changed the most after more than seven months of treatment. After a period of treatment, the levels of FPG and PPG in the blood of male patients in the study group were significantly lower than those of female patients (p<0.05). After treatment, the TG level of the study group was significantly lower than that of the control group (p<0.05). In comparison, the HDL-C level was significantly higher than that of the control group (p<0.05)., Conclusions: Lipid and glucose levels of type 2 diabetes mellitus patients with obesity have decreased after 12 weeks of polyethylene glycol loxanatide use. The weight of type 2 diabetes mellitus patients with obesity has changed after using polyethylene glycol loxenatide for a period of treatment. Among them, there is a certain relationship between body weight and treatment time, gender, and original body weight, which is worthy of further research and promotion in clinical practice.

We use an x-ray free-electron laser to study the lattice dynamics following photoexcitation with ultrafast near-UV light (wavelength 266 nm, 50 fs pulse duration) of the incipient ferroelectric potassium tantalate, KTaO&#95;{3}. By probing the lattice dynamics corresponding to multiple Brillouin zones through the x-ray diffuse scattering with pulses from the Linac Coherent Light Source (LCLS) (wavelength 1.3 Å and <10  fs pulse duration), we observe changes in the diffuse intensity associated with a hardening of the transverse acoustic phonon branches along Γ to X and Γ to M. Using force constants from density functional theory, we fit the quasiequilibrium intensity and obtain the instantaneous lattice temperature and density of photoexcited charge carriers. The density functional theory calculations demonstrate that photoexcitation transfers charge from oxygen 2p derived π-bonding orbitals to Ta 5d derived antibonding orbitals, further suppressing the ferroelectric instability and increasing the stability of the cubic, paraelectric structure.

X-ray free-electron lasers (XFELs) deliver pulses of coherent X-rays on the femtosecond time scale, with potentially high repetition rates. While XFELs provide high peak intensities, both the intensity and the centroid of the beam fluctuate strongly on a pulse-to-pulse basis, motivating high-rate beam diagnostics that operate over a large dynamic range. The fast drift velocity, low X-ray absorption and high radiation tolerance properties of chemical vapour deposition diamonds make these crystals a promising candidate material for developing a fast (multi-GHz) pass-through diagnostic for the next generation of XFELs. A new approach to the design of a diamond sensor signal path is presented, along with associated characterization studies performed in the XPP endstation of the LINAC Coherent Light Source (LCLS) at SLAC. Qualitative charge collection profiles (collected charge versus time) are presented and compared with those from a commercially available detector. Quantitative results on the charge collection efficiency and signal collection times are presented over a range of approximately four orders of magnitude in the generated electron-hole plasma density., (open access.)

We report the observation of photo-induced plasmon-phonon coupled modes in the group IV-VI semiconductor PbTe using ultrafast x-ray diffuse scattering at the Linac Coherent Light Source. We measure the near-zone-center excited-state dispersion of the heavily screened longitudinal optical (LO) phonon branch as extracted from differential changes in x-ray diffuse scattering intensity following above bandgap photoexcitation. We suggest that upon photoexcitation, the LO phonon-plasmon coupled (LOPC) modes themselves become coupled to longitudinal acoustic modes that drive electron band shifts via acoustic deformation potentials and possibly to low-energy single-particle excitations within the plasma and that these couplings give rise to displacement-correlations that oscillate in time with a period given effectively by the heavily screened LOPC frequency., (© 2022 Author(s).)

Objective: To explore the efficacy and safety of stereotactic electroencephalography (SEEG)-guided conformal radiofrequency thermocoagulation for epilepsy caused by focal cortical dysplasia (FCD) in eloquent cortex. Methods: The data of epilepsy patients with conformal thermocoagulation in the Epilepsy Center of Guangdong Sanjiu Brain Hospital from September 2017 to August 2020 were retrospectively analyzed. SEEG electrodes were placed in patients with drug-refractory epilepsy caused by FCD in eloquent cortex with limited boundaries, which was confirmed by preoperative evaluation methods such as imaging and electroencephalography. When designing the electrode placement plan, related software was used to reconstruct the three-dimensional MRI image and lesion. SEEG electrode contacts should be designed to fully cover the lesion as much as possible. After the completion of SEEG monitoring and cortical electrical stimulation, the pre-thermocoagulation and permanent thermocoagulation modes were used in sequence. The mode of direct damage between adjacent contacts of a single electrode and cross-destruction between adjacent contacts of multiple electrodes was combined to ablate the lesions point by point. Results: A total of 22 patients were enrolled, ranging from 2 to 30 years old, with an average age of (15±9) years old. MRI showed that FCD lesions located at pre-central gyrus in 19 cases, at post-central gyrus in 3 cases, at left frontal lobe in 3 cases, at both pre-central and post-central gyrus in 1 case and at both pre-central and left frontal lobe in 2 cases. The length of the lesion was 1.2-4.0 cm, with an average length of (2.2±0.7) cm. Moreover, 7-12 SEEG electrodes were implanted, with an average of (9±2) electrodes. The number of electrodes passing through the lesion was 2-8, with an average of 5±2. The number of thermocoagulation target points was 6 to 83, with an average of 29±18, while the number of target points which proved to have function by cortical simulation was 0-21, with a median of 3.5. The number of direct thermocoagulation target points was 6 to 58, with an average of 23±13, while the number of cross thermocoagulation target points was 0 to 30, with a median of 3. The completion of the whole thermocoagulation was divided into 2 to 5 times. There were 11 cases (50%) who experienced immediate muscle strength decline, 1 case (4.5%) showed slower speech speed during thermocoagulation, 3 cases (13.6%) exhibited muscle strength decline after thermocoagulation, however, only 1 case (4.5%) had permanent hemiparalysis. There were 17 cases of Engel Ⅰ (77.3%), 3 cases of Engel Ⅱ (13.6%), and 2 case of Engel Ⅲ (9.1%), respectively, after follow-up for 6-42 months, with an average of (20±10) months. Conclusion: SEEG-guided conformal radiofrequency thermocoagulation is safe and effective for epilepsy caused by FCD in eloquent cortex with limited boundaries.

Aim: To evaluate the association between perihaematomal radiomics features and haematoma expansion (HE)., Materials and Methods: Clinical and radiological data were collected retrospectively. The 1:1 propensity score matching (PSM) method was used to balance the difference of baseline characteristics between patients with and without HE. Radiomics features were extracted from the intra- and perihaematomal regions. Top HE-associated features were selected using the minimum redundancy, maximum relevancy algorithm. Support vector machine models were used to predict HE. Predictive performance of radiomics features from different regions was evaluated by receiver operating characteristic curve and confusion matrix-derived metrics., Results: A total of 1,062 patients were enrolled. After PSM analysis, the propensity score-matched cohort (PSM cohort) included 314 patients (HE: n=157; non-HE: n=157). The PSM cohort was distributed into the training (n=218) and the validation cohorts (n=96). The predictive performance of intra- and perihaematomal features were comparable in the training (area under the receiver operating characteristic curve [AUC], 0.751 versus 0.757; p=0.867) and the validation cohorts (AUC, 0.724 versus 0.671; p=0.454). By incorporating intra- and perihaematomal features, the combined model outperformed the single intrahaematomal model in the training cohort (AUC, 0.872 versus 0.751; p<0.001). Decision curve analysis (DCA) further confirmed the clinical usefulness of the combined model., Conclusion: Perihaematomal radiomics features can predict HE. The integration of intra- and perihaematomal signatures may provide additional benefit to the prediction of HE., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objective: DNA damage induced by ROS is considered one of the main causes of nucleus pulposus (NP) cells degeneration during the progression of intervertebral disc degeneration (IVDD). cGAS-STING pathway acts as DNA-sensing mechanism for monitoring DNA damage. Recent studies have proved that cGAS-STING contributes to the development of various diseases by inducing inflammation, senescence, and apoptosis. This work explored the role of STING, the main effector of cGAS-STING signaling pathway, in NP degeneration., Method: Immunohistochemistry was conducted to measure STING protein levels in the nucleus pulposus tissues from human and puncture-induced IVDD rat models. TBHP induces degeneration of nucleus pulposus cells in vitro. For in vivo experiments, lv-NC or lv-STING were injected into the central intervertebral disc space. The degeneration level of IVDD was assessed by MRI, X-ray, HE, and Safranin O staining., Results: We found that the expression of STING was upregulated in human and rat degenerated NP tissue as well as in TBHP-treated NP cells. Overexpression of STING promoted the degradation of extracellular matrix; it also promoted apoptosis and senescence of TBHP-treated and untreated NP cells. Knock-down of STING significantly reversed these effects. Mechanistically, STING activated IRF3, whereas blockage of IRF3 attenuated STING-induced apoptosis, senescence and ECM degradation. In vivo experiments revealed that STING knock-down alleviated puncture-induced IVDD development., Conclusion: STING promotes IVDD progress via IRF3, while suppression of STING may be a promising treatment for IVDD., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Hypoxia is a pivotal initiator of tumor angiogenesis and growth through the stabilization of hypoxia-inducible factors (HIFs). This study set out to examine the involvement of HIF-1α and HIF-2α in colon cancer and ascertained whether ORAI3 was involved in the pathway., Materials and Methods: Patients and murine models as well as human colorectal adenocarcinoma tumor (CW2) cells were included to examine the levels of ORAI1/3 and HIF-1/2α levels. Calcium imaging was utilized to ascertain the activity of calcium channel. Scratch assay was used to assess the migration capacity of the cells., Results: Tumors from murine colon cancer xenograft models and patients with colon cancer displayed high ORAI1/3 and HIF-1/2α levels. Hypoxia treatment, mimicking the tumor microenvironment in vitro, increased ORAI1/3 and HIF-1/2α expression as well as store-operated Ca2+ entry (SOCE). Of note is that HIF-1/2α silencing decreased SOCE, and HIF-1/2α overexpression facilitated SOCE. Furthermore, ORAI3 rather than ORAI1 expression was inhibited by HIF-1/2α silencing while increased by ML228. Luciferase assay also confirmed that ORAI3 was elevated in the presence of ML228, indicating the linkage between HIF-1/2α and ORAI3. Additionally, colony-forming potential and cell migration capacity were decreased in siHIF-1α and siHIF-2α as well as siORAI3 cells, and the facilitating effect of ML228 on cell migration and colony-forming potential was also decreased in siORAI3 CW-2 cells, which points out the importance of ORAI3 in HIF1/2α pathway., Conclusion: Our findings allow to conclude that both HIF-1α and HIF-2α facilitate ORAI3 expression, hence enhancing colon cancer progression.

Objective: To investigate the karyotypes and C bands of Triatoma rubrofasciata in China, so as to understand its chromosome number, morphology and C-band staining of T. rubrofasciata ., Methods: The testis specimens were sampled from male T. rubrofasciata collected from Shunde City, Guangdong Province, prepared into slides of metaphase chromosomes and subjected to Giemsa staining and C-band staining. The morphology of metaphase chromosomes and the location of heterochromatin were observed using microscopy, and the long arm and short arm of each chromosome and total chromosome length were recorded to analyze the karyotypes and C bands of T. rubrofasciata ., Results: The male T. rubrofasciata presented a chromosome number of 2 n = 25, including 22 autosomes and 3 sex chromosomes. The relative length of chromosomes ranged from 3.59% to 12.76%, the arm ratio was 1.06 to 1.24, and the centromere index was 44.76% to 48.47%. All chromosomes were metacentric chromosomes and the karyotype formula was 2 n = 22 metacentric + X 1 X 2 Y, and the C bands varied on different chromosomes. No heterochromatin was found in the X chromosome, and the overall staining appeared pale, while heterochromatin was detected in all regions of the Y chromosome, and the overall staining appeared dark. In addition, heterochromatin was present in both ends of the autosome., Conclusions: The male T. rubrofasciata presents a chromosome number of 2 n = 25 in China, and the karyotype formula is 2 n = 22 metacentric + X 1 X 2 Y. C-banding shows dark staining of the Y chromosome, pale staining of the X chromosome, and dark staining of both ends of the autosome. Our data may provide insights into the investigation on the origin, evolution and gene mapping of T. rubrofasciata in China.

The spin-phonon interaction in spin density wave (SDW) systems often determines the free energy landscape that drives the evolution of the system. When a passing energy flux, such as photoexcitation, drives a crystalline system far from equilibrium, the resulting lattice displacement generates transient vibrational states. Manipulating intermediate vibrational states in the vicinity of the critical point, where the SDW order parameter changes dramatically, would then allow dynamical control over functional properties. Here we combine double photoexcitation with an X-ray free-electron laser (XFEL) probe to control and detect the lifetime and magnitude of the intermediate vibrational state near the critical point of the SDW in chromium. We apply Landau theory to identify the mechanism of control as a repeated partial quench and sub picosecond recovery of the SDW. Our results showcase the capabilities to influence and monitor quantum states by combining multiple optical photoexcitations with an XFEL probe. They open new avenues for manipulating and researching the behaviour of photoexcited states in charge and spin order systems near the critical point.

Background: Necrotizing lymphadenitis is a rare disease. It is often misdiagnosed because of the lack of typical clinical manifestations. It is worth noting that necrotizing lymphadenitis may be a precursor lesion of systemic lupus erythematosus or tumours, so regular follow-up is needed to facilitate early diagnosis. Here, we report a case and conduct a literature analysis summarizing the clinical features of necrotizing lymphadenitis and its treatment and management practices., Case Presentation: A 16-year-old young woman presented with fever and lymphadenopathy as the main clinical manifestations, accompanied by a rash during fever that disappeared as the fever subsided. After completing imaging and laboratory examinations, we excluded other diseases such as infections, autoimmune diseases, and malignant tumours. Finally, we diagnosed the patient with necrotizing lymphadenitis based on the results of lymph node biopsy. The symptoms of the patient improved after glucocorticoid treatment, and she was followed up for half a year without recurrence of symptoms., Conclusion: In the clinic, young women with fever and lymphadenopathy as major symptoms should be screened for necrotizing lymphadenitis to facilitate early diagnosis and treatment. Although necrotizing lymphadenitis is self-limiting, its clinical manifestations are similar to those of many diseases. Therefore, it is easily misdiagnosed. An in-depth understanding of the disease is conducive to early diagnosis and treatment in the clinic, thereby reducing further damage to the body and reducing unnecessary evaluation and treatment.

Metal-organic frameworks (MOFs), which are self-assemblies of metal ions and organic ligands, provide a tunable platform to search a new state of matter. A two-dimensional (2D) perfect kagome lattice, whose geometrical frustration is a key to realizing quantum spin liquids, has been formed in the π - d conjugated 2D MOF [Cu 3 (C 6 S 6 )] n (Cu-BHT). The recent discovery of its superconductivity with a critical temperature T c of 0.25 kelvin raises fundamental questions about the nature of electron pairing. Here, we show that Cu-BHT is a strongly correlated unconventional superconductor with extremely low superfluid density. A nonexponential temperature dependence of superfluid density is observed, indicating the possible presence of superconducting gap nodes. The magnitude of superfluid density is much smaller than those in conventional superconductors and follows the Uemura's relation of strongly correlated superconductors. These results imply that the unconventional superconductivity in Cu-BHT originates from electron correlations related to spin fluctuations of kagome lattice., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Objective: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association., Design: A pooled analysis of six cohort studies., Setting: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE)., Population: 18 555 women from the UK, USA and Australia., Methods: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects., Main Outcome Measures: Hot flushes and night sweats., Results: Frequency data showed that early menarche ≤11 years was associated with an increased risk of 'often' hot flushes (RRR 1.48, 95% CI 1.24-1.76) and night sweats (RRR 1.59, 95% CI 1.49-1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94-1.42) and 1.27 (95% CI 1.01-1.58) for 'severe' hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and 'often' VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of 'severe' VMS., Conclusions: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk., Tweetable Abstract: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche., (© 2020 Royal College of Obstetricians and Gynaecologists.)

We developed superconducting nanowire single-photon detectors based on tungsten silicide, which show saturated internal detection efficiency up to a wavelength of 10 μ m. These detectors are promising for applications in the mid-infrared requiring sub-nanosecond timing, ultra-high gain stability, low dark counts, and high efficiency, such as chemical sensing, LIDAR, dark matter searches, and exoplanet spectroscopy.

Finite-temperature phases of many-body quantum systems are fundamental to phenomena ranging from condensed-matter physics to cosmology, yet they are generally difficult to simulate. Using an ion trap quantum computer and protocols motivated by the quantum approximate optimization algorithm (QAOA), we generate nontrivial thermal quantum states of the transverse-field Ising model (TFIM) by preparing thermofield double states at a variety of temperatures. We also prepare the critical state of the TFIM at zero temperature using quantum-classical hybrid optimization. The entanglement structure of thermofield double and critical states plays a key role in the study of black holes, and our work simulates such nontrivial structures on a quantum computer. Moreover, we find that the variational quantum circuits exhibit noise thresholds above which the lowest-depth QAOA circuits provide the best results., Competing Interests: Competing interest statement: C.M. is the cofounder and chief scientist at IonQ, Inc., a company that manufactures quantum computers. No IonQ employees, equipment, or other assets were involved with any aspect of the planning, design, execution, analysis, or reporting of this research., (Copyright © 2020 the Author(s). Published by PNAS.)

Background: Folate metabolism plays an important role in DNA methylation and nucleic acid synthesis and thus may function as a regulatory factor in cancer development. Genome-wide association studies (GWASs) have identified some single-nucleotide polymorphisms (SNPs) associated with cutaneous melanoma-specific survival (CMSS), but no SNPs were found in genes involved in the folate metabolic pathway., Objectives: To examine associations between SNPs in folate metabolic pathway genes and CMSS., Methods: We comprehensively evaluated 2645 (422 genotyped and 2223 imputed) common SNPs in folate metabolic pathway genes from a published GWAS of 858 patients from The University of Texas MD Anderson Cancer Center and performed the validation in another GWAS of 409 patients from the Nurses' Health Study and Health Professionals Follow-up Study, in which 95/858 (11·1%) and 48/409 (11·7%) patients died of cutaneous melanoma, respectively., Results: We identified two independent SNPs (MTHFD1 rs1950902 G>A and ALPL rs10917006 C>T) to be associated with CMSS in both datasets, and their meta-analysis yielded an allelic hazards ratio of 1·75 (95% confidence interval 1·32-2·32, P = 9·96 × 10 -5 ) and 2·05 (1·39-3·01, P = 2·84 × 10 -4 ), respectively. The genotype-phenotype correlation analyses provided additional support for the biological plausibility of these two variants' roles in tumour progression, suggesting that variation in SNP-related mRNA expression levels is likely to be the mechanism underlying the observed associations with CMSS., Conclusions: Two possibly functional genetic variants, MTHFD1 rs1950902 and ALPL rs10917006, were likely to be independently or jointly associated with CMSS, which may add to personalized treatment in the future, once further validated. What is already known about this topic? Existing data show that survival rates vary among patients with melanoma with similar clinical characteristics; therefore, it is necessary to identify additional complementary biomarkers for melanoma-specific prognosis. A hypothesis-driven approach, by pooling the effects of single-nucleotide polymorphisms (SNPs) in a specific biological pathway as genetic risk scores, may provide a prognostic utility, and genetic variants of genes in folate metabolism have been reported to be associated with cancer risk. What does this study add? Two genetic variants in the folate metabolic pathway genes, MTHFD1 rs1950902 and ALPL rs10917006, are significantly associated with cutaneous melanoma-specific survival (CMSS). What is the translational message? The identification of genetic variants will make a risk-prediction model possible for CMSS. The SNPs in the folate metabolic pathway genes, once validated in larger studies, may be useful in the personalized management and treatment of patients with cutaneous melanoma., (© 2020 British Association of Dermatologists.)

Purpose: The aim was to examine changes in the bone-derived hormone lipocalin 2 (LCN2) levels in patients with active acromegaly and to investigate the potential roles of LCN2 and osteocalcin in glucose metabolism., Methods: We recruited 50 consecutive acromegalic patients. Of those, 39 patients with complete postoperative follow-up data were included. Thirty sex-, age-, and BMI-matched healthy individuals were recruited as normal controls. The pre- and postoperative serum LCN2 and osteocalcin levels were compared. The homeostasis model assessment insulin resistance (HOMA-IR) index and secretion [β-cell function (HOMA-β)] were calculated., Results: Compared with controls, acromegalic subjects had lower LCN2 levels (34.15 ± 9.95 vs 57.50 ± 29.75 ng/mL, P < 0.01) and higher osteocalcin levels (55.45 ± 34.02 vs 19.46 ± 6.69 ng/mL, P < 0.01). Acromegalic patients also had elevated HOMA-IR levels, and the HOMA-β and the area under the curve for insulin (AUC INS) levels were slightly but nonsignificantly increased. The serum levels of LCN2 significantly increased after surgery (37.03 ± 9.73 vs 45.15 ± 15.33 ng/mL, P < 0.05), and those of osteocalcin significantly decreased [43.51 (26.73-65.66) vs 24.79 (18.39-32.59) ng/mL, P < 0.01]. Total lean mass was the only positive predictor of LCN2, and elevated serum IGF-I was a positive predictor of osteocalcin. Low LCN2 and elevated serum osteocalcin levels were predictors of the AUC INS, and osteocalcin was a positive predictor of HOMA-β., Conclusion: The bone-derived hormones, osteocalcin and LCN2 changed significantly in active acromegaly, were altered after treatment and served as predictors of β-cell function in acromegaly. This study shows that the bone could be involved in regulating glucose metabolism in acromegaly.

Objective: To analyze the clinical characteristics and efficacy of drug treatment in children with inflammatory bowel disease (IBD) at different ages of onset. Methods: The clinical data of 87 children with IBD admitted to Department of Gastroenterology in Children's Hospital, Capital Institute of Pediatrics from January 2009 to December 2018 were collected. The patients were divided into four groups according to the age of onset: 0 -<2 years old group (36 cases), 2 -<6 years old group (10 cases), 6 -<10 years old group (12 cases) and 10 -<18 years old group (29 cases). The clinical manifestations, laboratory examination, endoscopic findings, pathologic and genetic changes, and treatment were compared among different age groups with chi-square test or Fisher's exact text. Results: (1) A total of 87 patients were diagnosed with IBD, including 50 Crohn's disease (CD) (57%), 25 ulcerative colitis (UC) (29%) and 12 unclassified inflammatory bowel disease (IBD-U) (14%). (2) Patients with fever accounted for 78% (28/36) and 8/10 in the 0 -<2 years old group and 2 -<6 years old group, respectively. Patients with abdominal pain and perianal diseases accounted for 6% (2/36) and 47% (17/36) in the 0 -<2 years old group, and their proportions were significantly different among the four groups (χ(2)=8.369, 40.317 and 13.130, all P< 0.05). (3) Leukocytosis, thrombocytosis and anemia were more common in the 0-<2 years old group, seen in 72% (26/36), 31% (11/36) and 81% (29/36), respectively. There were significant differences in the changes of complete blood count among the four groups (χ(2)=21.919, 8.095 and 11.520, all P< 0.05). (4) Colonic involvement accounted for 85% (17/20) in the 0 -<2 years old CD patients. While in the CD patients over 6 years old, 61% (14/23) had inflammation of ileum and colon, with a significant difference compared to that in patients under 6 years old (19% (5/27) , χ(2)=9.455, P= 0.003). Also, the location of bowel inflammation among the four groups were significantly different (χ(2)=21.120, P< 0.01). (5) Noncaseating granulomas were found in 15 (30%) CD patients, and crypt abscess was found in 11 (44%) UC patients. (6) Among the 24 patients whose genes were analyzed by high throughput sequencing, 12 had pathogenic single gene mutation. (7) There were 25 patients treated with total enteral nutrition. Among the 25 patients treated with thalidomide, 20 (80%) had clinical remission or partial remission. Among the 19 CD patients treated with infliximab (IFX), 14 had clinical remission at the 6(th) week of treatment, and the proportion of remission maintenance at the 30(th) week of treatment was 12/14. (8) The rate of clinical remission or partial remission was 64% (23/36) in the 0 -<2 years old group, 8/10 in the 2 -<6 years old group, 11/12 in the 6 -<10 years old group, and 83% (24/29) in the 10 -<18 years old group. Conclusions: The proportion of CD was higher than that of UC in this study. Infant onset inflammatory bowel disease was more likely to present with perianal lesions, and was usually associated with leukocytosis, thrombocytosis and anemia, and has high possibility of single gene mutation. IFX may be effective in treating CD.

Aims: Although comammox have been discovered in a variety of ecosystems, there are few studies in urban lakes. This paper attempted to confirm whether this ammonia-oxidizing microbe exists in urban lakes and to determine the factors influencing its existence., Methods and Results: This study investigated the diversity and abundance of comammox bacteria in sediments of a typical urban lake in China, and their ecological relationship with other ammonia-oxidizing micro-organisms. The phylogenetic analysis indicated that comammox clade A existed in the sediment of Lake Donghu, and the comammox bacteria co-existed with ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB) and anaerobic ammonia-oxidizing (anammox) bacteria in the sediment of this lake. The abundances of the ammonia monooxygenase subunit A (amoA) genes for comammox, AOA, AOB and anammox 16S rRNA were 2·43 × 10 8 , 1·07 × 10 8 , 3·24 × 10 7 and 3·21 × 10 11 copies per gram dry sediment respectively. Moreover, the amoA gene abundance of comammox was positively correlated with that of AOA and AOB. The redundancy analysis showed that the abundance of the comammox amoA gene was negatively correlated with the concentration of main indicators for nitrogen status in both the sediment and the water column, indicating that eutrophication may inhibit the growth of comammox bacteria., Conclusions: Comammox bacteria play an important ecological role in the nitrogen cycle of urban lake sediments., Significance and Impact of the Study: Our results indicated comammox bacteria were widespread in urban lakes and eutrophication may inhibit their growth., (© 2020 The Society for Applied Microbiology.)

Purpose: To describe an interesting not previously described morphokinetic finding., Methods: Retrospective case report of a couple undergoing controlled ovarian stimulation (COS) followed by in vitro fertilization and blastocyst transfer., Results: We identified a unique finding of blastulation of a fertilized human zygote after conventional in vitro fertilization. The fertilized zygote did not show any clear cytokinesis until approximately 107 h post insemination, when it started dividing into a blastocyst. By 113 h post insemination, inner cell mass and trophectoderm cells could be clearly distinguished and the blastocyst was completely hatched by 136 h post insemination., Conclusion: Time-lapse systems offer more detailed observations of embryonic development. Here, we report an atypical development of an embryo that was not described previously. We hope to become an insightful discussion among peers and incentive the publication of such findings in the future.

Objective: Glioma is one of the most common and invasive brain tumors worldwide. Long non-coding RNAs (LncRNAs) play an important role in the development of glioma. However, the regulatory mechanism of LncRNAs in glioma has not been fully elucidated. This study aimed to explore the interaction of lncRNA maternally expressed gene 3 (MEG3) and aberrant histone modification in glioma., Materials and Methods: The expression levels of MEG3 and miR-21-3p in glioma cells were measured by quantitative polymerase chain reaction (qPCR). EZH2 (enhancer of zeste homolog 2) and H3K27me3 expression in glioma cells were detected by Western Blot (WB). The binding site of the promoter of MEG3 by H3K27me3 was confirmed by ChIP-Real-time PCR. The direct target of MEG3 and miR-21-3p in glioma cells was measured by a luciferase reporter assay. Cell proliferation was detected by Cell Counting Kit-8 (CCK8), and cell invasion and migration were measured by Transwell assays., Results: EZH2 and miR-21-3p were upregulated and MEG3 was downregulated in glioma cells. Silencing of EZH2 inhibited cell proliferation, migration, and invasion in U87 and U251 cells. Meanwhile, the expression of H3K27me3 could be significantly inhibited by EZH2 interference. H3K27me3 protein can bind to MEG3 promoter directly. EZH2 inhibition and MEG3 down-expression in U87 cells reversed the effects of silencing of EZH2 on glioma cell growth and metastasis. However, EZH2 inhibition and MEG3 overexpression in U251 cells restricted cell proliferation, migration, and invasion. Furthermore, miR-21-3p was verified to interact with MEG3 by direct binding. Inhibition of MEG3 promoted U87 cell growth and metastasis, which was further strengthened following the co-transfection of si-MEG3 and miR-21-3p. Overexpressed MEG3 inhibited U251 cell growth and metastasis and a complete reversal of the results observed in the co-transfection of LV-MEG3 and miR-21-3p., Conclusions: EZH2 was highly expressed in glioma cells and EZH2-mediated H3K27me3 enrichment on the MEG3 promoter regulated the growth and metastasis of glioma cells by targeting miR-21-3p. It potentially provided a new therapeutic marker targeting glioma.