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This study was conducted to investigate the effects of glutamine (Gln) on blood biochemistry and activity of serum enzymes in broilers challenged with Salmonella enteritidis. 240 one-day-old Arbor Acres broilers were distributed into four groups treated in a completely randomized design for 21 days. The groups included a noninfection control (CON); infected with S. enteritidis (SCC); infected +0.5% Gln (Gln 1), and infected +1.0% Gln (Gln 2). The plasma total protein, albumin, and globulin concentration, AST, LDH and CK activity in SCC group were lower than the CON overall except the albumin at 14, 21 d, and CK at 14 d. SCC group had lower RBC at 7 d; lower MCHC at 14 d; higher MCHC, and MCH at 7 d, or 21 d; higher WBC at d 7, 14, and 21; higher γ-GGT activity at d 14, and 21than the CON group. Gln group had higher plasma total protein, albumin, and globulin concentration, AST, LDH and CK activity than those in SCC overall except the albumin at 14, 21 d, and CK at 14 d. Gln group had higher RBC at 7 d; higher MCHC at 14 d; lower MCHC, and MCH at 7 d, or 21 d; lower WBC at d 7, 14, and 21, and lower γ-GGT activity at d 14, and 21 than the SCC group. These results suggest that Gln could effective improve the physiological responses and maintain the normal health status of S. enteritidis infection of broilers.

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.