A new variant of the colistin resistance gene MCR-1 with co-resistance to ß-lactam antibiotics reveals a potential novel antimicrobial peptide.

The emerging and global spread of a novel plasmid-mediated colistin resistance gene, mcr-1, threatens human health. Expression of the MCR-1 protein affects bacterial fitness and this cost correlates with lipid A perturbation. However, the exact molecular mechanism remains unclear. Here, we identified the MCR-1 M6 variant carrying two-point mutations that conferred co-resistance to ß-lactam antibiotics. Compared to wild-type (WT) MCR-1, this variant caused severe disturbance in lipid A, resulting in up-regulation of L, D-transpeptidases (LDTs) pathway, which explains co-resistance to ß-lactams. Moreover, we show that a lipid A loading pocket is localized at the linker domain of MCR-1 where these 2 mutations are located. This pocket governs colistin resistance and bacterial membrane permeability, and the mutated pocket in M6 enhances the binding affinity towards lipid A. Based on this new information, we also designed synthetic peptides derived from M6 that exhibit broad-spectrum antimicrobial activity, exposing a potential vulnerability that could be exploited for future antimicrobial drug design.

Glutamine metabolic competition drives immunosuppressive reprogramming of intratumour GPR109A+ myeloid cells to promote liver cancer progression.

OBJECTIVE: The metabolic characteristics of liver cancer drive considerable hurdles to immune cells function and cancer immunotherapy. However, how metabolic reprograming in the tumour microenvironment impairs the antitumour immune response remains unclear. DESIGN: Human samples and multiple murine models were employed to evaluate the correlation between GPR109A and liver cancer progression. GPR109A knockout mice, immune cells depletion and primary cell coculture models were used to determine the regulation of GPR109A on tumour microenvironment and identify the underlying mechanism responsible for the formation of intratumour GPR109A+myeloid cells. RESULTS: We demonstrate that glutamine shortage in liver cancer tumour microenvironment drives an immunosuppressive GPR109A+myeloid cells infiltration, leading to the evasion of immune surveillance. Blockade of GPR109A decreases G-MDSCs and M2-like TAMs abundance to trigger the antitumour responses of CD8+ T cells and further improves the immunotherapy efficacy against liver cancer. Mechanistically, tumour cells and tumour-infiltrated myeloid cells compete for glutamine uptake via the transporter SLC1A5 to control antitumour immunity, which disrupts the endoplasmic reticulum (ER) homoeostasis and induces unfolded protein response of myeloid cells to promote GPR109A expression through IRE1α/XBP1 pathway. The restriction of glutamine uptake in liver cancer cells, as well as the blockade of IRE1α/XBP1 signalling or glutamine supplementation, can eliminate the immunosuppressive effects of GPR109A+ myeloid cells and slow down tumour progression. CONCLUSION: Our findings identify the immunometabolic crosstalk between liver cancer cells and myeloid cells facilitates tumour progression via a glutamine metabolism/ER stress/GPR109A axis, suggesting that GPR109A can be exploited as an immunometabolic checkpoint and putative target for cancer treatment.

[Correlation between ecological factors and effective component content, flower, and leaf traits of Epimedium pubescens].

No systematic research has been reported on the correlation between different ecological factors and the effective component content, flower, and leaf traits of Epimedium pubescens. In this study, 21 kinds of E. pubescens in different regions were investigated, and the content of two effective components of icariin(I) and Epimedin C(C), as well as six leaf traits and 12 flower traits were determined. The correlation between 11 ecological factors and the above traits in different regions for five consecutive years was explored. The results showed that no significant correlation was observed between the ecological factors and the total content of two effective components(I+C) of E. pubescens. Latitude and temperature(including annual average temperature, annual average minimum temperature, and soil temperature of each soil layer) were significantly positively and negatively correlated with the ratio of the content of the two effective components(C/I)(P<0.01), respectively. There was a significant correlation between ecological factors and flower traits, and the annual average soil temperature of each soil layer, annual average temperature, and annual average minimum temperature were significantly correlated with most flower traits in multiple years(P<0.01). However, a weak correlation between ecological factors and leaf traits was detected. A significant positive correlation of the annual average soil temperature of each soil layer and annual average humidity(P<0.01) with the width of nutrient leaf in only a few years was detected. Therefore, it was concluded that the total content of effective components of E. pubescens was determined by genetics, with a slight influence of ecological factors. The annual average temperature, annual average minimum temperature, and soil temperature of each soil layer were the ecological factors that had the most significant impact on flower traits, which showed significant differences in different regions, and similar results were not found in leaf traits. Overall, this study systematically conducted a correlation analysis between ecological factors and the effective components, as well as flower and leaf traits, providing guidance for the quality improvement, introduction, and domestication of E. pubescens.

Prediction of Antibiotic Resistance Evolution by Growth Measurement of All Proximal Mutants of Beta-Lactamase.

The antibiotic resistance crisis continues to threaten human health. Better predictions of the evolution of antibiotic resistance genes could contribute to the design of more sustainable treatment strategies. However, comprehensive prediction of antibiotic resistance gene evolution via laboratory approaches remains challenging. By combining site-specific integration and high-throughput sequencing, we quantified relative growth under the respective selection of cefotaxime or ceftazidime selection in ∼23,000 Escherichia coli MG1655 strains that each carried a unique, single-copy variant of the extended-spectrum ß-lactamase gene blaCTX-M-14 at the chromosomal att HK022 site. Significant synergistic pleiotropy was observed within four subgenic regions, suggesting key regions for the evolution of resistance to both antibiotics. Moreover, we propose PEARP and PEARR, two deep-learning models with strong clinical correlations, for the prospective and retrospective prediction of blaCTX-M-14 evolution, respectively. Single to quintuple mutations of blaCTX-M-14 predicted to confer resistance by PEARP were significantly enriched among the clinical isolates harboring blaCTX-M-14 variants, and the PEARR scores matched the minimal inhibitory concentrations obtained for the 31 intermediates in all hypothetical trajectories. Altogether, we conclude that the measurement of local fitness landscape enables prediction of the evolutionary trajectories of antibiotic resistance genes, which could be useful for a broad range of clinical applications, from resistance prediction to designing novel treatment strategies.

Association of underweight and obesity with adverse postoperative renal outcomes in infants and young children undergoing congenital heart surgery.

Postoperative acute kidney injury (AKI) is a prevalent condition and associated with increased morbidity and mortality following cardiac surgery. This study aimed to investigate the association of underweight and obesity with adverse postoperative renal outcomes in infants and young children undergoing congenital heart surgery. This retrospective cohort study included patients aged from 1 month to 5 years who underwent congenital heart surgery with cardiopulmonary bypass at the Second Xiangya Hospital of Central South University from January 2016 to March 2022. On the basis of the percentile of body mass index (BMI) for age and sex, eligible participants were divided into three nutritional groups: normal bodyweight, underweight (BMI P5), and obesity (BMI P95). Primary outcomes included postoperative AKI and major adverse kidney events within 30 days (MAKE30). Multivariable logistic regression was performed to determine the association of underweight and obesity with postoperative outcomes. The same analyses were reproduced for classifying patients using weight-for-height instead of BMI. A total of 2,079 eligible patients were included in the analysis, including 1,341 (65%) patients in the normal bodyweight group, 683 (33%) patients in the underweight group, and 55 (2.6%) patients in the obesity group. Postoperative AKI (16% vs. 26% vs. 38%; P < 0.001) and MAKE30 (2.5% vs. 6.4% vs. 9.1%; P < 0.001) were more likely to occur in the underweight and obesity groups. After adjusting for potential confounders, underweight (OR1.39; 95% CI 1.08-1.79; P = 0.008) and obesity (OR 3.85; 95% CI 1.97-7.50; P < 0.001) were found to be associated with an increased risk of postoperative AKI. In addition, both underweight (OR 1.89; 95% CI 1.14-3.14; P = 0.014) and obesity (OR 3.14; 95% CI 1.08-9.09; P = 0.035) were independently associated with MAKE30. Similar results were also found when weight-for-height was used instead of BMI.    Conclusion: In infants and young children undergoing congenital heart surgery, underweight and obesity are independently associated with postoperative AKI and MAKE30. These results may help assess prognosis in underweight and obese patients, and will guide future quality improvement efforts. What is Known: • Postoperative acute kidney injury (AKI) is prevalent and associated with increased morbidity and mortality following pediatric cardiac surgery. • Major adverse kidney events within 30 days (MAKE30) have been recommended as a patient-centered endpoint for evaluating AKI clinical trajectories. A growing concern arises for underweight and obesity in children with congenital heart disease. What is New: • Prevalence of underweight and obesity among infants and young children undergoing congenital heart surgery was 33% and 2.6%, respectively. • Both underweight and obesity were independently associated with postoperative AKI and MAKE30 following congenital heart surgery.

Machine Learning-Based Prediction of Acute Kidney Injury Following Pediatric Cardiac Surgery: Model Development and Validation Study.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major complication following pediatric cardiac surgery, which is associated with increased morbidity and mortality. The early prediction of CSA-AKI before and immediately after surgery could significantly improve the implementation of preventive and therapeutic strategies during the perioperative periods. However, there is limited clinical information on how to identify pediatric patients at high risk of CSA-AKI. OBJECTIVE: The study aims to develop and validate machine learning models to predict the development of CSA-AKI in the pediatric population. METHODS: This retrospective cohort study enrolled patients aged 1 month to 18 years who underwent cardiac surgery with cardiopulmonary bypass at 3 medical centers of Central South University in China. CSA-AKI was defined according to the 2012 Kidney Disease: Improving Global Outcomes criteria. Feature selection was applied separately to 2 data sets: the preoperative data set and the combined preoperative and intraoperative data set. Multiple machine learning algorithms were tested, including K-nearest neighbor, naive Bayes, support vector machines, random forest, extreme gradient boosting (XGBoost), and neural networks. The best performing model was identified in cross-validation by using the area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using the Shapley additive explanations (SHAP) method. RESULTS: A total of 3278 patients from one of the centers were used for model derivation, while 585 patients from another 2 centers served as the external validation cohort. CSA-AKI occurred in 564 (17.2%) patients in the derivation cohort and 51 (8.7%) patients in the external validation cohort. Among the considered machine learning models, the XGBoost models achieved the best predictive performance in cross-validation. The AUROC of the XGBoost model using only the preoperative variables was 0.890 (95% CI 0.876-0.906) in the derivation cohort and 0.857 (95% CI 0.800-0.903) in the external validation cohort. When the intraoperative variables were included, the AUROC increased to 0.912 (95% CI 0.899-0.924) and 0.889 (95% CI 0.844-0.920) in the 2 cohorts, respectively. The SHAP method revealed that baseline serum creatinine level, perfusion time, body length, operation time, and intraoperative blood loss were the top 5 predictors of CSA-AKI. CONCLUSIONS: The interpretable XGBoost models provide practical tools for the early prediction of CSA-AKI, which are valuable for risk stratification and perioperative management of pediatric patients undergoing cardiac surgery.

Minimally Invasive 980 nm Laser-Assisted Lipolysis and Skin Tightening on Lower Eyelids of Asian Patients.

OBJECTIVE: The present study aimed to evaluate the effectiveness of minimally invasive 980 nm laser-assisted lipolysis and skin tightening in lower eyelid blepharoplasty of Asian patients. METHODS: Patients with mild and moderate degree of eyebags underwent 980 nm laser-assisted lipolysis via lower eyelid stab incision between December 2017 and December 2019. Evaluation criteria was reviewed by photographs taken preoperatively and 6 months postoperatively in accordance with guidelines of Global Aesthetic Improvement Scale, the patient's perspective from the questionnaire with the perception of reduction in eyebags size, the average perception of improvement in skin tightening, and the patient overall satisfaction, all with a score of 1 to 5 (5 being the most noticeable and very satisfied) and complications such as dyspigmentation, hematoma, prolonged edema, skin bump and thermal burn were documented as well. RESULTS: A total of 178 cases with 137 women and 41 men (age range from 23 to 50 years) were included. Total energy of 1200 J to 2000 J was delivered to both eyebags at 6 to 10 W. They were followed up for at least 6 months. A total of 166 patients (93.26%) revealed an improvement in Global Aesthetic Improvement Scale, with the 12 patients (6.74%) complaint no change 6 month postoperatively. Perception of improvement in eye bag protrusion scored 4.39 ± 0.59, improvement in skin tightening scored 4.42 ± 0.58 and the overall patient's satisfaction scored 4.59 ± 0.53. The patients' average recovered swelling from 4.35 ± 2.3 days. There were 5 patients (2.8%) with dyspigmentation, 3 patients (1.69%) with prolonged edema and 2 patients (1.12%) with skin bump and none of the patients had thermal burn. All of them resolve after 6 months of follow up. CONCLUSION: Patients with mild to moderate degree of eyebags who resist surgery are good candidates for laser-assisted lower eyelid blepharoplasty.

Application of CUBE-STIR MRI and high-frequency ultrasound in contralateral cervical 7 nerve transfer surgery.

OBJECTIVE: The objective of the study was to investigate the feasibility of CUBE-SITR MRI and high-frequency ultrasound for the structural imaging of the brachial plexus to exclude neoplastic brachial plexopathy or structural variation and measure the lengths of anterior and posterior divisions of the C7 nerve, providing guidelines for surgeons before contralateral cervical 7 nerve transfer. METHODS: A total of 30 patients with CNS and 20 with brachial plexus injury were enrolled in this retrospective study. All patients underwent brachial plexus CUBE-STIR MRI and high-frequency ultrasound, and the lengths of the anterior and posterior divisions of C7 nerve were measured before surgery. Precise length of anterior and posterior divisions of contralateral C7 nerve was measured during surgery. RESULTS: MRI-measured lengths of anterior and posterior divisions of C7 nerves were positively correlated with that measured during surgery (anterior division, r = 0.94, p < .01; posterior division, r = 0.92, p < .01). High agreement was found between MRI-measured and intra-surgery measured length of anterior and posterior divisions of C7 nerve by BLAD-ALTMAN analysis. Ultrasonography could feasibly image supraclavicular C7 nerve and recognize small variant branches derived from middle trunk of C7 nerve root, which could be dissected intra-operatively and confirmed by electromyography during the procedure of contralateral C7 nerve transfer. CONCLUSION: CUBE-STIR MRI had advantages for the imaging of the brachial plexus and measurement of the length of root-trunk-anterior/posterior divisions of C7 nerve. The clinical role of ultrasonography may be a simple way of evaluating general condition of C7 nerve and provide guidelines for contralateral C7 nerve transfer surgery.

Antibacterial oxygenated ergostane-type steroids produced by the marine sponge-derived fungus Aspergillus sp.

Two oxygenated ergostane-type steroids including one new compound, 3ß-hydroxy-5α,6ß-methoxyergosta-7,22-dien-15-one (1) along with a known analogue ergosta-6,22-dien-3ß,5α,8α-triol (2) were isolated from the crude extracts of the marine sponge-derived fungus Aspergillus sp. Their structures were elucidated on the basis of combined NMR and MS spectroscopic methods. Compound 1 was a marine ergostane-type steroid with two methoxy groups at C-5 and C-6, respectively. These oxygenated ergostane-type steroids were evaluated for their antibacterial activities against human or aquatic pathogens. Among them, compound 1 exhibited antibacterial activity against Staphylococcus aureus.

[Environmental pollutants and Alzheimer's disease].

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. The main hypotheses about the pathogenesis of AD include the hypothesis of ß-amyloid protein, the hypothesis of abnormal phosphorylation of Tau protein, and the hypothesis of neuroinflammation. In recent years, environmental pollutants have been considered as an important factor in causing neurological dysfunction. Common environmental pollutants include heavy metals, pesticides, polychlorinated biphenyls, microplastics, and air pollutants, all of which have been proven to have neurotoxicity. In this review, we not only discussed epidemiological and animal experimental studies that link environmental pollution with AD, but also summarized the mechanisms of action of relevant toxins, providing insights for studying the interrelationships between environmental pollutants and AD.

Lithium Ferrocyanide Catholyte for High-Energy and Low-cost Aqueous Redox Flow Batteries.

Aqueous redox flow batteries (ARFBs) are a promising technology for grid-scale energy storage, however, their commercial success relies on redox-active materials (RAM) with high electron storage capacity and cost competitiveness. Herein, a redox-active material lithium ferrocyanide (Li4 [Fe(CN)6 ]) is designed. Li+ ions not only greatly boost the solubility of [Fe(CN)6 ]4- to 2.32 M at room temperature due to weak intermolecular interactions, but also improves the electrochemical performance of [Fe(CN)6 ]4-/3- . By coupling with Zn, ZIRFBs were built, and the capacity of the batteries was as high as 61.64 Ah L-1 (pH-neutral) and 56.28 Ah L-1 (alkaline) at a [Fe(CN)6 ]4- concentration of 2.30 M and 2.10 M. These represent unprecedentedly high [Fe(CN)6 ]4- concentrations and battery energy densities reported to date. Moreover, benefiting from the low cost of Li4 [Fe(CN)6 ], the overall chemical cost of alkaline ZIRFB is as low as $11 per kWh, which is one-twentieth that of the state-of-the-art VFB ($211.54 per kWh). This work breaks through the limitations of traditional electrolyte composition optimization and will strongly promote the development of economical [Fe(CN)6 ]4-/3- -based RFBs in the future.

[Recent research on inhaled nitric oxide in preterm infants with a gestational age of <34 weeks]. / 胎龄<34å‘¨æ—©äº§å„¿ä¸€æ°§åŒ–æ°®å¸å ¥çš„ç ”ç©¶è¿›å±•.

Nitric oxide is a messenger molecule for vasodilation of vascular smooth muscle cells, and inhaled nitric oxide (iNO) can dilate pulmonary blood vessels and reduce pulmonary vascular resistance, thereby reducing pulmonary artery pressure, but with no influence on systemic circulation pressure. Guidelines in China and overseas recommend the use of iNO in full-term infants and late preterm infants, and it has been proved that it has a marked effect on persistent pulmonary hypertension and hypoxic respiratory failure in such infants. However, recent studies have shown that there is an increase in the off-label use of iNO in preterm infants with a gestational age of <34 weeks. This article reviews the research progress on the efficacy, safety, timing, dose, and withdrawal mode of iNO and its combination with vasoactive drugs in the treatment of preterm infants with a gestational age of <34 weeks in China and overseas, so as to provide a reference for clinical application.

Comparative genomic analyses of Polymyxin-resistant Enterobacteriaceae strains from China.

BACKGROUND: Mobile colistin resistance like gene (mcr-like gene) is a new type of polymyxin resistance gene that can be horizontally transferred in the Enterobacteriaceae. This has brought great challenges to the treatment of multidrug-resistant Escherichia coli and K. pneumoniae. RESULTS: K. pneumoniae 16BU137 and E. coli 17MR471 were isolated from the bus and subway handrails in Guangzhou, China. K. pneumoniae 19PDR22 and KP20191015 were isolated from patients with urinary tract infection and severe pneumonia in Anhui, China. Sequence analysis indicated that the mcr-1.1 gene was present on the chromosome of E. coli 17MR471, and the gene was in the gene cassette containing pap2 and two copies of ISApl1.The mcr-1.1 was found in the putative IncX4 type plasmid p16BU137_mcr-1.1 of K. pneumoniae 16BU137, but ISApl1 was not found in its flanking sequence. Mcr-8 variants were found in the putative IncFIB/ IncFII plasmid pKP20191015_mcr-8 of K. pneumoniae KP20191015 and flanked by ISEcl1 and ISKpn26. CONCLUSION: This study provides timely information on Enterobacteriaceae bacteria carrying mcr-like genes, and provides a reference for studying the spread of mcr-1 in China and globally.

Carriage of distinct blaKPC-2 and blaOXA-48 plasmids in a single ST11 hypervirulent Klebsiella pneumoniae isolate in Egypt.

BACKGROUND: Carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) causes serious infections with significant morbidity and mortality. However, the epidemiology and transmission mechanisms of CR-hvKP and the corresponding carbapenem-resistant plasmids require further investigation. Herein, we have characterized an ST11 K. pneumoniae strain EBSI041 from the blood sample encoding both hypervirulence and carbapenem resistance phenotypes from a patient in Egypt. RESULTS: K. pneumoniae strain EBSI041 showed multidrug-resistance phenotypes, where it was highly resistant to almost all tested antibiotics including carbapenems. And hypervirulence phenotypes of EBSI041 was confirmed by the model of Galleria mellonella infection. Whole-genome sequencing analysis showed that the hybrid plasmid pEBSI041-1 carried a set of virulence factors rmpA, rmpA2, iucABCD and iutA, and six resistance genes aph(3')-VI, armA, msr(E), mph(E), qnrS, and sul2. Besides, blaOXA-48 and blaSHV-12 were harboured in a novel conjugative IncL-type plasmid pEBSI041-2. The blaKPC-2-carrying plasmid pEBSI041-3, a non-conjugative plasmid lacking the conjugative transfer genes, could be transferred with the help of pEBSI041-2, and the two plasmids could fuse into a new plasmid during co-transfer. Moreover, the emergence of the p16HN-263_KPC-like plasmids is likely due to the integration of pEBSI041-3 and pEBSI041-4 via IS26-mediated rearrangement. CONCLUSION: To the best of our knowledge, this is the first report on the complete genome sequence of KPC-2- and OXA-48-coproducing hypervirulent K. pneumoniae from Egypt. These results give new insights into the adaptation and evolution of K. pneumoniae during nosocomial infections.

UDP-glucose 6-dehydrogenase lessens sorafenib sensitivity via modulating unfolded protein response.

As the first-generation targeted therapy, sorafenib remains an effective single-drug treatment for advanced hepatocellular carcinoma (HCC). Unfortunately, the existence of resistance restricts the long-term benefit of patients. UDP-glucose 6-dehydrogenase (UGDH) is the key enzyme of glucuronic acid metabolism which was largely reported in mediating drug systemic elimination. In this study, we explore its critical role in regulating sorafenib sensitivity. Here we find sorafenib exposure could activate glucuronic acid metabolism, accompanied with the elevated expression of UGDH. Interference with the route by silencing UGDH could boost HCC cells sensitivity to sorafenib. Meanwhile, the analysis of HCC patients with sorafenib treatment displayed that low UGDH expression predicted superior prognosis. Further screening assay suggested that unfolded protein response (UPR) involves in UGDH silencing-mediated apoptosis. Xenograft model confirmed that combined UGDH intervention could significantly improve sorafenib efficacy. Our results reveal the impact of sorafenib exposure on glucuronic acid metabolism reprogramming and provide UGDH as a promising target to improve sorafenib efficacy.

Catalytic Enantioselective Steglich-Type Rearrangement of Enol Lactones: Asymmetric Synthesis of Spirocyclic 1,3-Diketones.

An example of asymmetric Steglich-type rearrangement of enol lactones is reported. This highly enantioselective acyl transfer reaction is catalyzed by chiral isothiourea at ambient temperature and provides a useful synthetic approach to access enantioenriched spirotricyclic ß,ß'-diketones from a broad range of indanone or tetralone-derived lactones. Preliminary mechanistic studies suggest the initial formation of an N-acylated iminium cation intermediate that induces a following facial selective condensation.

CircRNA hsa_circ_0014130 function as a miR-132-3p sponge for playing oncogenic roles in bladder cancer via upregulating KCNJ12 expression.

The modern categories of endogenous non-coding RNAs, namely circular RNAs (circRNAs), involved within the carcinogenesis and progression of various human cancers. The fundamental aim of the current investigation was the evaluation of the hsa_circ_0014130 expressions, their biological functions, and potential regulatory network in bladder cancer. The level of expression for hsa_circ_0014130 was evaluated by qRT-PCR, and its relationships to clinicopathological features and survival outcomes of cases experiencing cancer of the bladder were scrutinized. The impact of hsa_circ_0014130 expressions on biological attitudes of bladder cancer cells in vitro was investigated. The interactions between hsa_circ_0014130 and microRNA (miRNA) sponge, miRNA, and its direct targets were determined by RNA pull-down as well as luciferase reporter gene assay. The correlations of their expression were determined by Pearson's correlation analysis. Rescue experiments were carried out to identify the biological roles of the regulation network. The expressions of hsa_circ_0014130 were markedly ameliorated in bladder cancer samples and linked with aggressive characteristics and unfavorable survival. Ectopic expression of hsa_circ_0014130 clearly enhanced the differentiation, proliferative, migratory, invasive potential of the cell in bladder cancer, and the development of tumor xenograft in vivo, while malignant biological behaviors were inhibited by hsa_circ_0014130 knockdown. The expression of hsa_circ_0014130 was tied to miR-132-3p in a negative manner with the cells and tissues of bladder cancer. hsa_circ_0014130 function as a competitive endogenous RNA for miR-132-3p to play oncogenic roles in bladder cancer cells. On the other hand, KCNJ12 was a straightforward target of miR-132-3p at the downstream, and the expressions of KCNJ12 were inversely related to that of miR-132-3p. Furthermore, a significantly positive correlation was found between hsa_circ_0014130 and KCNJ12 mRNA expression. More importantly, the oncogenic impact of hsa_circ_0014130 on bladder cancer cells was partly suppressed by ectopic expression of miR-132-3p or KCNJ12 knockdown. The underlined data revealed that hsa_circ_0014130 exerted its biological roles by regulating miR-132-3p/KCNJ12 expression. Further research revealed hsa_circ_0014130/miR-132-3p/KCNJ12 axis has participated in the Epithelial-mesenchymal transition (EMT) progress and GSK3ß/AKT signaling pathway. hsa_circ_0014130 works as a sponge of miR-132-3p to advance the oncogenesis and metastasis of bladder cancer by regulation of the KCNJ12 expression. These achievements might ameliorate the comprehension of tumor pathogenesis and provide novel therapeutic targets for cancer of the bladder.

A Retrospective Study of the Safety and Efficacy of Endoscopic Radiofrequency Therapy Under Direct Vision in 59 Patients with Gastroesophageal Reflux Disease from 2 Centers in Beijing, China Using the Gastroesophageal Reflux Disease Questionnaire.

BACKGROUND This retrospective study from 2 centers in Beijing, China aimed to assess the safety and efficacy of endoscopic radiofrequency therapy under direct vision in 59 patients with gastroesophageal reflux disease (GERD) using the gastroesophageal reflux disease questionnaire (GerdQ). MATERIAL AND METHODS Fifty-nine GERD patients who underwent endoscopic radiofrequency treatment were included. Patients were divided into 2 groups: the endoscopic radiofrequency therapy under direct vision group and the non-direct vision radiofrequency therapy group. Indicators such as GerdQ score, lower esophageal sphincter (LES) pressure, DeMeester score, acid exposure time, and proton pump inhibitors (PPIs) use were collected before and after radiofrequency treatment. Postoperative complications were also recorded. The efficacy and safety of endoscopic radiofrequency therapy under direct vision were evaluated by comparing the indicators of patients in the 2 groups. RESULTS At 3 months after radiofrequency treatment, patients in the endoscopic radiofrequency therapy under direct vision group improved significantly in GerdQ score, decreased from 11.0 (10.0, 12.0) to 6.0 (6.0, 8.0), better than patients in the non-direct vision radiofrequency therapy group, and the better improvements remained at 12 months after the procedure (P<0.05). At 6 months after treatment, patients in the endoscopic radiofrequency therapy under direct vision group had significant improvements in LES pressure, which increased from 8.15 (3.18, 12.88) mmHg to 15.20 (10.25, 27.03) mmHg (P<0.05). There were no severe complications in our trial. CONCLUSIONS When compared with non-visualized endoscopic radiofrequency therapy, treatment under direct vision was safer and improved the GerdQ score and LES pressure at up to 12 months.

Prevalence of autism spectrum disorder diagnosis by birth weight, gestational age, and size for gestational age: a systematic review, meta-analysis, and meta-regression.

We aimed to comprehensively pool the prevalence of autism spectrum disorder (ASD) diagnosis by birth weight, gestational age, and size for gestational age. PubMed, EMBASE, Web of Science, Ovid PsycINFO, and Cochrane Library were searched up to December 22, 2021. We pooled data using the random-effects model and quantified heterogeneity using the I2 statistic. Of 66 643 records initially identified, 75 studies were included in the meta-analysis. The pooled prevalence estimates of ASD diagnosis are as follows: very-low-birth weight, 3.1% (912 ASD/66,445 individuals); low-birth weight, 2.3% (5672 ASD/593,927 individuals); normal-birth weight, 0.5% (17,361 ASD/2,378,933 individuals); high-birth weight, 0.6% (4505 ASD/430,699 individuals); very preterm, 2.8% (2113 ASD/128,513 individuals); preterm, 2.1% (19 672 ASD/1 725 244 individuals); term, 0.6% (113,261 ASD/15,297,259 individuals); postterm, 0.6% (9419 ASD/1,138,215 individuals); small-for-gestational-age, 1.9% (6314 ASD/796,550 individuals); appropriate-for-gestational-age, 0.7% (21,026 ASD/5,936,704 individuals); and large-for-gestational-age, 0.6% (2607 ASD/635,666 individuals). Compared with the reference prevalence (those in normal-birth weight, term, and appropriate-for-gestational-age individuals), the prevalence estimates of ASD diagnosis in very-low-birth weight, low-birth weight, very preterm, preterm, and small-for-gestational-age individuals increased significantly, while those in high-birth weight, postterm, and large-for-gestational-age individuals did not change significantly. There were geographical differences in the prevalence estimates. This meta-analysis provided reliable estimates of the prevalence of ASD diagnosis by birth weight, gestational age, and size for gestational age, and suggested that low-birth weight (especially very-low-birth weight), preterm (especially very preterm), and small-for-gestational-age births, rather than high-birth weight, postterm, and large-for-gestational-age births, were associated with increased risk of ASD diagnosis. However, in view of marked between-study heterogeneity in most conditions, unknown effects of certain important confounders associated with ASD due to limited information in original articles, and included studies from a relatively small number of countries, the findings of this study should be interpreted with caution.

Quality analysis of hawthorn leaves (the leaves of Crataegus pinnatifida Bge. var major N.E.Br) in different harvest time.

INTRODUCTION: Harvest time plays an important role on the quality of medicinal plants. The leaves of Crataegus pinnatifida Bge. var major N.E.Br (hawthorn leaves) could be harvested in summer and autumn according to the Pharmacopoeia of the People's Republic of China (Pharmacopoeia). However, little is known about the difference of the chemical constituents in hawthorn leaves with the harvest seasonal variations. OBJECTIVE: The chemical constituents of hawthorn leaves in different months were comprehensively analysed to determine the best harvest time. METHODS: Initially, the chemical information of the hawthorn leaves were obtained by ultra-high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). Subsequently, principal component analysis (PCA) was applied to compare the chemical compositions of hawthorn leaves harvested in different months. Then, an absolute quantitation method was established using high-performance liquid chromatography-charged aerosol detector (HPLC-CAD) to determine the contents of five compounds and clarify the changes of these components with the harvest seasonal variations. Meanwhile, a semi-quantitative method by integrating HPLC-CAD with inverse gradient compensation was also established and verified. RESULTS: Fifty-eight compounds were identified through UHPLC-Q-TOF-MS. PCA revealed that the harvest season of hawthorn leaves had a significant effect on the chemical compositions. The contents of five components were relatively high in autumn. Other four main components without reference standards were further analysed through the semi-quantitative method, which also showed a high content in autumn. CONCLUSIONS: This work emphasised the effect of harvest time on the chemical constituents of hawthorn leaves and autumn is recommended to ensure the quality.