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Tao Zhang,1 Zhu-Bin Pan,1 Wen-Jia Tong,2 Yu-Liang Zhou,1 Yuan Cheng,1 Dan-Qun Jin,2 Shi-Qin Qi,1 Zhen-Qiang Zhang1 1Department of General Surgery, Anhui Provincial Children’s Hospital, Children’s Hospital of Fudan University Anhui Hospital, Children’s Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of China; 2Department of Pediatric Intensive Care Unit, Anhui Provincial Children’s Hospital, Children’s Hospital of Fudan University Anhui Hospital, Children’s Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of ChinaCorrespondence: Zhu-Bin Pan, Department of General Surgery, Anhui Provincial Children’s Hospital, Children’s Hospital of Fudan University Anhui Hospital, Children’s Hospital of Anhui Medical University, No. 39 of Wang Jiang Dong Street, Bao He District, Hefei, 230000, People’s Republic of China, Tel +86 13349207050, Fax +86 551 62237461, Email panzhubinpzb5@126.comBackground: Paraneoplastic syndromes often cause endocrine, neurological, cutaneous, and hematologic pathologies, and cases with digestive symptoms as prominent cases are rare.Case Description: A 1-year-old child admitted to the emergency department with severe abdominal distension was later diagnosed with sacrococcygeal yolk cystoma with ulcerative colitis. After symptomatic management, surgical removal of the tumor, and JEB chemotherapy, the symptoms of ulcerative colitis disappeared completely. After 7 years of follow-up, the child grew and developed well, and there was no recurrence of tumor and ulcerative colitis.Conclusion: Yolk sac tumor with ulcerative colitis is a rare paraneoplastic syndrome with complex clinical manifestations.Keywords: children, paraneoplastic syndrome, toxic megacolon, ulcerative colitis, yolk sac tumor

Hao Zhang,1,* Ping Zhou,1,* Yi Jiang,1 Liu Li,1 Fei Ju,2 Quan Cheng,1 You Lang Zhou,2 Yuan Zhou1 1Department of Pain, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, People’s Republic of China; 2Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan Zhou; You Lang Zhou, Tel +86 0513 85052222 ; +86 0513 85052488, Email nina_shine@126.com; zhouyoulang@ntu.edu.cnIntroduction: Esketamine, one of the few non-opioid potent analgesics, has demonstrated efficacy in the treatment of various chronic pain, particularly neuropathic pain. However, its potential clinical applications are confined due to its short half-life and severe side effects including delirium, hallucinations, and other psychiatric symptoms. Here, we reported a nanosized drug delivery system for sustained-release esketamine based on polylactic-co-glycolic acid (PLGA) nanoparticles and hyaluronic acid (HA) hydrogel.Results: In this study, esketamine in the delivery system was continuously released in vitro for at least 21 days, and spinal nerve root administration of the delivery system successfully attenuated (spinal nerve ligation) SNL-induced pain hypersensitivity for at least 14 days. Notably, the excitability of neurons in murine dorsal root ganglion (DRG) was inhibited and the activation of astrocytes in the spinal cord was additionally reduced after administration. Finally, there was no obvious pathophysiological change in the nerves at the administration site after treatment at 14 days.Conclusion: These results indicate that the sustained-release esketamine based on the nanoparticle-hydrogel delivery system can safely produce a lasting analgesic effect on SNL mice, and its mechanism might be related to modulating the activation of astrocytes in the spinal cord and inhibiting the excitability of neurons in DRG.Keywords: esketamine, nanoparticles, hyaluronic acid hydrogel, neuropathic pain

An Wen,1,2 Er-Ling Leng,3 Wen-Feng Cao,1,2 Zheng-bing Xiang,1,2 Wei Rao,1,2 Wen Cai,1,2 Yong-Liang Zhou,1,2 Fan Hu,1,2 Ling-feng Wu,1,2 Ping Zhang,1,2 Shi-Min Liu1,2 1Department of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 2Institution of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 3Department of Pediatrics, Jiangxi provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of ChinaCorrespondence: Shi-Min Liu, Department of Neurology, Jiangxi provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), No. 92 Aiguo Road, Nanchang, 330006, People’s Republic of China, Tel +791-8772-1401, Email aifeng420@163.comObjective: Central nervous system (CNS) infection has a high incidence and mortality worldwide. Tuberculous meningitis (TBM) accounts for approximately 5– 6% of all extrapulmonary tuberculosis (TB), and is considered an extremely lethal form of CNS TB, which has become an important threat to human health. Anemia is a common symptom of TB, and its prevalence is generally higher in patients with TBM than in other meningitis patients and healthy individuals. Anemia can increase a person’s susceptibility to common infectious diseases, including TB, by compromising the immune system. Information regarding anemia during the hospitalization of TBM is still scarce in China. This study aimed to describe in detail the prevalence of anemia in patients with TBM in Southern China and its association with the clinical forms of TB, as well as other characteristics of these patients.Methods: We conducted a retrospective analysis of patients diagnosed with TBM at two tertiary hospitals in southern China. The demographic characteristics, clinical characteristics, and laboratory results of 114 patients with TBM were collected. Multivariate logistic regression analysis was performed to explore the risk factors for anemia in patients with TBM.Results: Electronic medical record data of adult patients diagnosed with TBM from January 2004 to December 2019 were reviewed. Among 134 patients with TBM, 20 were excluded and 114 were analyzed, of whom 33 had anemic, the prevalence rate of anemia was 28.9%. Among patients with anemia, 51.5% had hypochromic microcytic anemia, 33.3% had normochromic normocytic anemia, and 15.2% had macrocytic anemia. Fever duration, TBM grade III and ESR were found to be independent predictors of anemia.Conclusion: Anemia was highly prevalent in patients with TBM, mainly hypochromic microcytic anemia. Besides, Fever duration, TBM grade III and ESR are predictors of anemia in patients with TBM.Keywords: tuberculosis, tuberculous meningitis, anemia, risk factors, prediction

An Wen,1,2 Wen-Feng Cao,1,2 Shi-Min Liu,1,2 Yong-Liang Zhou,1,2 Zheng-Bing Xiang,1,2 Fan Hu,1,2 Ling-Feng Wu,1,2 Wen Cai,1,2 Er-Ling Leng3 1Department of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 2Institution of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 3Department of Pediatrics, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of ChinaCorrespondence: Er-Ling Leng, Department of Pediatrics, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), No.92 Aiguo Road, Nanchang, 330006, People’s Republic of China, Tel +86791-8772-1401, Email wenan666@sina.comObjective: Tuberculous meningitis (TBM) is a common form of central nervous system (CNS) tuberculosis (TB). Cranial nerve palsy is a serious complication of TBM. Literature regarding this subject is still limited in China. This study evaluated the incidence of cranial nerve palsy in patients with TBM in South China, its association with the clinical forms of TB, and other patient characteristics.Methods: A retrospective chart review of patients with a diagnosis of TBM between January 2004 and December 2019 was conducted, and the demographic characteristics, clinical characteristics, and laboratory results of 114 patients were collected and followed up for 3 months. A multivariate logistic regression analysis model was used to explore the risk factors of cranial nerve palsy in patients with TBM.Results: A total of 114 patients were enrolled in this study. Cranial nerve palsy was observed in approximately 38 (33.3%) of TBM patients. Among them, 13 (28.3%) had optic nerve palsy, 24 (52.2%) had oculomotor nerve palsy, 5 (10.9%) had abducens nerve palsy, 2 (4.3%) had auditory nerve palsy, 1 (2.2%) had glossopharyngeal nerve palsy, and 1 (2.2%) had vagus nerve palsy. Using logistic regression analysis, focal neurological deficit, extracranial TB and cerebrospinal fluid (CSF) total white cell count (WCC) were shown to be risk factors for cranial nerve palsy.Conclusion: The prevalence rate of cranial nerve palsy was 33.3% in patients with TBM. Focal neurological deficits, extracranial TB and CSF total WCC are important predictors of cranial nerve palsy in patients with TBM.Keywords: tuberculous meningitis, tuberculosis, cranial nerve palsy, risk factors, prediction

Li F, Wang F, Zhu C, Wei Q, Zhang T, Zhou YL. Int J Nanomedicine. 2018;13:2295–2307. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the integrity of the data and an investigation found overlap in images from Figure 4. Specifically, The image used in Figure 4D, 48 hours, Scramble has regions of overlap with Figure 4D, 48 hours, miR-221 inhibitor. The authors responded to our queries and provided data associated with the reported study. However, despite the authors’ assistance, a satisfactory explanation for how the images came to be duplicated could not be provided, and the validity of the published work could not be verified. The decision was made to retract the article and the authors were notified of this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Feng Li,1,* Feiran Wang,2,* Changlai Zhu,3 Qun Wei,1 Tianyi Zhang,1 You Lang Zhou4 1Department of Gastroenterology, 2Department of General Surgery, Affiliated Hospital of Nantong University, 3Key Laboratory of Neuroregeneration, Nantong University, 4The Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China *These authors contributed equally to this work Background: MicroRNA-221(miR-221) is frequently dysregulated in cancer. The purpose of this study was to explore whether miR-221 can be used as a potential diagnostic marker or therapeutic target for hepatocellular carcinoma (HCC). Methods: In this study, we investigated whether miR-221 expression was associated with clinicopathological characteristics and prognosis in HCC patients, and we developed a nanoparticle-based miRNA delivery system and detected its therapeutic efficacy in vitro and in vivo. Results: We found that miR-221 was upregulated in HCC tissues, cell lines and blood of HCC patients. Upregulated miR-221 was associated with clinical TNM stage and tumor capsular infiltration, and showed poor prognosis, suggesting that its suppression could serve as an effective approach for hepatocellular carcinoma therapy. Treatment of HCC cells with nanoparticle/miR-221 inhibitor complexes suppressed their growth, colony formation ability, migration and invasion. In vivo, the growth of the tumors treated by the nanoparticle/miR-221 inhibitor complexes were significantly less than those treated by the nanoparticle/miRNA scramble complexes. In addition, circulating miR-221 may act as a potential tumor biomarker for early diagnosis of HCC, and combined serum miR-221 and AFP detection gave a better performance than individual detection in early diagnosis of HCC. Conclusion: These findings suggest that a nanoparticle-based miRNA delivery system could potentially serve as a safe and effective treatment and miR-221 could also be a potential diagnostic marker for HCC. Keywords: hepatocellular carcinoma, nanoparticle, miR-221, biomarker, therapeutic target

Li F, Wang F, Zhu C, Wei Q, Zhang T, Zhou YL. Int J Nanomedicine. 2018;13:2295–2307. The authors have advised Figure 2B on page 2301 is incorrect. Due to an error at the time of figure assembly B1 and B2 were duplicated. The correct Figure 2 is shown below. The authors apologize for this error and advise it does not affect the results of the paper. Read the original article

Ye Jin,1,4 Jingyuan Wen,2 Sanjay Garg,3 Da Liu,1 Yulin Zhou,1 Lirong Teng,1,* Weiyu Zhang,4,*1College of Life Science, Jilin University, Jilin, People’s Republic of China; 2School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; 3School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia; 4School of Pharmacy, Changchun University of Chinese Medicine, Jilin, People’s Republic of China *These authors contributed equally to this workBackground: The aim of this study was to develop an optimal niosomal system to deliver Ginkgo biloba extract (GbE) with improved oral bioavailability and to replace the conventional GbE tablets.Methods: In this study, the film dispersion-homogenization method was used to prepare GbE niosomes. The resulting GbE niosome suspension was freeze-dried or spray-dried to improve the stability of the niosomes. GbE-loaded niosomes were formulated and characterized in terms of their morphology, particle size, zeta potential, entrapment efficiency, and angle of repose, and differential scanning calorimetry analysis was performed. In vitro release and in vivo distribution studies were also carried out.Results: The particle size of the optimal delivery system prepared with Tween 80, Span 80, and cholesterol was about 141 nm. There was a significant difference (P < 0.05) in drug entrapment efficiency between the spray-drying method (about 77.5%) and the freeze-drying method (about 50.1%). The stability study revealed no significant change in drug entrapment efficiency for the GbE niosomes at 4°C and 25°C after 3 months. The in vitro release study suggested that GbE niosomes can prolong the release of flavonoid glycosides in phosphate-buffered solution (pH 6.8) for up to 48 hours. The in vivo distribution study showed that the flavonoid glycoside content in the heart, lung, kidney, brain, and blood of rats treated with the GbE niosome carrier system was greater than in the rats treated with the oral GbE tablet (P < 0.01). No flavonoid glycosides were detected in the brain tissue of rats given the oral GbE tablets, but they were detected in the brain tissue of rats given the GbE niosomes.Conclusion: Niosomes are a promising oral system for delivery of GbE to the brain.Keywords: Ginkgo biloba extract, flavonoid glycosides, niosomes, oral delivery, in vivo distribution

Objectives: To observe the effects of acupoint injection on the expression of p38 mitogen-activated protein kinase (MAPK), phosphorylated (p)-p38 MAPK, mucin 5 subtype AC (MUC5AC) in the nasal mucosa, and serum inflammatory factors of rats with allergic rhinitis, so as to explore the mechanism of acupoint injection in improving inflammatory reactions in the nasal mucosa of rats with allergic rhinitis., Methods: SD rats were randomly divided into the normal group, model group, acupoint injection group, and non-acupoint group, with 7 rats in each group. The allergic rhinitis rat model was established using ovalbumin sensitization. Intervention was performed by injecting dexamethasone and 1% lidocaine mixture (0.05 mL) into the bilateral "Yingxiang"(LI20) and "Yintang"(GV24 + ) acupoints, with injection at non-acupoints for non-acupoint group as the control, once every 3 days for a total of 4 times. Allergic symptoms in the rat nose were evaluated using a cumulative scoring method；histopathological changes in the nasal mucosa were observed after HE staining；serum histamine (HA), interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-α) contents were detected using ELISA；real-time fluorescent quantitative PCR was used to detect the expression of MUC5AC mRNA in the nasal mucosa；Western blot was used to detect the expression of p38 MAPK, p-p38 MAPK, and MUC5AC protein in the nasal mucosa., Results: Compared with the normal group, nasal allergic symptom score, serum HA, IL-6, IL-8, and TNF-α contents, nasal mucosal p38 MAPK, p-p38 MAPK proteins expression, MUC5AC mRNA and protein expression were significantly increased( P <0.01) in the model group. Compared with the model group and non-acupoint group, nasal allergic symptom score, serum HA, IL-6, IL-8, and TNF-α contents, nasal mucosal p38 MAPK and p-p38 MAPK proteins expression, MUC5AC mRNA and protein expression were significantly reduced ( P <0.01, P <0.05) in the acupoint injection group., Conclusions: Acupoint injection can reduce nasal allergic symptom, and MUC5AC secretion in rats with allergic rhinitis, alleviate nasal mucosal inflammatory reactions, and its mechanism of action may be related to the inhibition of p38 MAPK phosphorylation, thereby reducing the release of inflammatory factors.

The apurinic/apyrimidinic (AP) site is an important intermediate in the DNA base excision repair (BER) pathway, having the potential of being a biomarker for DNA damage. AP sites could lead to the stalling of polymerases, the misincorporation of bases and DNA strand breaks, which might affect physiological function of cells. However, the abundance of AP sites in genomic DNA is very low (less than 2 AP sites/10 6  nts), which requires a sensitive and accurate method to meet its detection requirements. Here, we described an ultrasensitive quantification method based on a hydrazine-s-triazine reagent (i-Pr 2 N) labeling for AP sites combining with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The limit of detection reached an ultralow level (40 amol), realizing the most sensitive MS-based quantification for the AP site. To guarantee the accuracy of the quantitative results, the labeling reaction was carried out directly on DNA strands instead of labeling after DNA enzymatic digestion to reduce artifacts that might be produced during the enzymatic process of DNA strands. And selective detection was realized by MS to avoid introducing the false-positive signals from other aldehyde species, which could also react with i-Pr 2 N. Genomic DNA samples from different mammalian cell lines were successfully analyzed using this method. There were 0.4-0.8 AP sites per 10 6 nucleotides, and the values would increase 16.1 and 2.75 times when cells were treated with genotoxic substances methyl methanesulfonate and 5-fluorouracil, respectively. This method has good potential in the analysis of a small number of cell samples and clinical samples, is expected to be useful for evaluating the damage level of DNA bases, the genotoxicity of compounds and the drug resistance of cancer cells, and provides a new tool for cell function research and clinical precise treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The tumor suppressor gene BRCA1 associated protein-1 (BAP1) is frequently mutated in renal cell carcinoma (RCC). BAP1 loss-of-function mutations are associated with poor survival outcomes. However, personalized therapy for BAP1-mutated RCC is currently not available. Previously, we found that BAP1 loss renders RCC cells more sensitive to bromodomain and extra-terminal (BET) inhibitors, as demonstrated in both cell culture and xenografted nude mice models. Here, we demonstrate that BAP1 loss in murine RCC cells enhances sensitivity to BET inhibitors in ectopic and orthotopic allograft models. While BAP1 deletion suppresses RCC cell survival in vitro , it does not impede tumor growth in immunocompetent murine models. Thus, the effect of BAP1 loss on the interactions between tumor cells and host microenvironment plays a predominant role in RCC growth, highlighting the importance of utilizing immunocompetent animal models to assess the efficacy of potential anticancer therapies. Mechanistically, BAP1 deletion compromises DNA repair capacity, rendering RCC cells more vulnerable to DNA damage induced by BET inhibitors. Our results indicate that BET inhibitors show promise as targeted therapy for BAP1-deficient RCC., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Adhesion seriously affects the recovery of tendon gliding function. Our group previously found that inhibition of TGF-β1, which is closely related to adhesion formation, effectively attenuated adhesions but did not eliminate them, suggesting that there may be other mechanisms involved in adhesion formation. In this study, we considered that uncontrolled and excessively proliferating fibroblasts undergo immune escape, which aggravates the deposition of extracellular matrix during the adhesion formation. We found that the expression of the immune checkpoint PD-L1 was significantly elevated after injury and may be involved in adhesion formation. Therefore, we intended to silence both TGF-β1 and PD-L1 to improve the immune advantage in the microenvironment after flexor tendon injury to further reduce adhesion. We constructed the nanoparticle/TGF-β1 or/and PD-L1 siRNAs complexes and verified their high biocompatibility and high transfection efficiency. We found that CD8 + T cells had a greater killing effect on the excessively proliferating cells that were transfected with nanoparticle/TGF-β1 or/and PD-L1 siRNAs. The hydrogel-nanoparticle/TGF-β1 or/and PD-L1 siRNAs system could effectively improve the gliding function of the tendons without weakening the mechanical properties in injured rat FDL tendon and chicken FDP tendon models. In addition, the potential of CD8 + T cells to encircle the adhesion cells on the tendon surface was observed, which resulted in increased levels of cell apoptosis. Thus, our study confirmed that combined knockdown of TGF-β1 and PD-L1 could activate immunodominance after flexor tendon repair and provided a potential treatment to limit adhesion formation and improve gliding function. STATEMENT OF SIGNIFICANCE: Adhesion seriously affects the recovery of tendon gliding function. TGF-β1 is related to adhesion formation as it regulates the production of extracellular matrix. We found that excessively proliferated fibroblasts might undergo immune escape, which aggravated the deposition of extracellular matrix. Therefore, we constructed a hydrogel-nanoparticle/TGF-β1 and PD-L1 siRNAs system for silencing TGF-β1 and PD-L1 to improve the immune advantage in the microenvironment after tendon injury. This system could improve the gliding function of tendons without weakening the mechanical property and increase the killing effect of CD8 + T cells. Combined knockdown of TGF-β1 and PD-L1 could activate immunodominance after tendon repair and provide a potential treatment to limit adhesion formation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the prevalence, resistance and risk factors of community-onset urinary tract infections (COUTIs) caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) for providing a basis for the selection of clinical therapeutic agents., Design: A retrospective case-control study., Setting: The Affiliated Dazu Hospital of Chongqing Medical University (also known as The People's Hospital of Dazu Chongqing), a 1000-bed tertiary hospital in China., Data and Participants: This study encompassed adult patients diagnosed with community-acquired urinary tract infections (UTIs) caused by E. coli between May 2017 and December 2022 with exclusion criteria including incomplete clinical data, disagreement to participate in the study, hospitalisation duration exceeding 48 hours prior to confirmation of diagnosis and prior history of urinary tract infection caused by E. coli ., Outcome Measures: The risk factors for COUTIs caused by ESBL-EC were evaluated using a case-control design, defining patients who were diagnosed with UTIs and had an ESBL-positive urine culture as the case group and patients who were diagnosed with UTIs and had an ESBL-negative urine culture as the control group. Perform drug susceptibility testing and resistance analysis on isolated ESBL-EC., Results: In total, 394 cases of COUTIs caused by E. coli were included; 192 cases were ESBL-positive with a detection rate of 48.7% (192/394). Parenchymal tumour, history of urolithiasis stone fragmentation, history of urological surgery, hospitalisation within 6 months, indwelling catheter outside the hospital and antibiotic use (mainly third-generation cephalosporins) were the factors significantly associated with COUTIs caused by ESBL-EC (p<0.05) through logistic regression for univariate analysis. Multivariate analysis revealed that a history of urolithiasis stone fragmentation (OR=2.450; 95% CI: 1.342 to 4.473; p=0.004), urological surgery (OR=3.102; 95% CI: 1.534 to 6.270; p=0.002), indwelling catheter outside hospital (OR=2.059; 95% CI: 1.025 to 4.133; p=0.042), hospitalisation within 6 months (OR=2.127; 95% CI: 1.207 to 3.748; p=0.009) and use of third-generation cephalosporins (OR=1.903; 95% CI: 1.069 to 3.389; p=0.029) were the independent risk factors for COUTIs caused by ESBL-EC. The results of the drug susceptibility testing revealed that ESBL-EC exhibited the highest resistance rates to ampicillin, ceftriaxone and cefixime, all at 100%. Mezlocillin followed with a resistance rate of 98.7%. On the other hand, ESBL-EC strains displayed the highest sensitivity to carbapenem antibiotics (imipenem, meropenem, ertapenem) and amikacin, all at 100%. Sensitivity rates were also high for cefotetan at 96.6%, piperacillin/tazobactam at 95.3% and nitrofurantoin at 87.9%., Conclusions: Our results revealed high ESBL-EC detection rates. COUTIs caused by ESBL-EC are more likely to occur in patients with parenchymal tumour, a history of urolithiasis stone fragmentation, a history of urological surgery, hospitalisation within 6 months, indwelling catheter outside the hospital and use of third-generation cephalosporins. These patients were highly resistant to penicillins, cephalosporins and quinolones., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD. Methods: This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality. Results: A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC =0. 698,95% CI :0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC =0.596, 95% CI : 0.523-0.669) and DPG ( AUC =0.526, 95% CI : 0.452-0.601) (all P <0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P <0.05), while DPG did not showed significance ( P >0.05). Multivariate Cox regression analysis showed that age, PVR and log 2 N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P <0.05). Conclusion: Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Rationale: Cerebral infarction is a common ischemic cerebrovascular disease, associated with high rates of morbidity, disability, and recurrence, that can seriously affect patient physical and mental health, as well as quality of life. Carotid artery stenosis is an independent risk factor of cerebral infarction. Following rapid developments in interventional technology and materials science, carotid artery stenting has arisen an important treatment option for carotid artery stenosis. However, surgery is associated with complications, such as postoperative hyperperfusion syndrome, which poses a serious threat to the life and health of patients. Staged angioplasty (SAP), that is, one-time revascularization of the carotid artery stenting, is divided into 2 stages. This method reduces the occurrence of hyperperfusion syndrome after stenting by increasing the ipsilateral cerebral blood flow in stages and gradually increasing the cerebral perfusion pressure., Patient Concerns: Herein, we present 2 cases of elderly patients with severe carotid artery stenosis who underwent SAP to prevent hyperperfusion syndrome., Diagnoses: The final diagnosis was based on cervical vascular color Doppler ultrasonography, cervical vascular magnetic resonance angiography, and cerebral vascular digital subtraction angiography., Intervention: Both patients with severe carotid artery stenosis underwent a staged intravascular intervention., Outcomes: Both patients were followed up for 1 year, with neither developing any new cerebral infarction or recurrent stent restenosis., Lessons: When treating SAP, it is crucial to consider that patients with unstable carotid plaques may not be suitable for staging. Additionally, during phase II carotid stenting, it is important to assess any changes in the arterial morphology and select the appropriate device accordingly., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Current metagenomic tools can fail to identify highly divergent RNA viruses. We developed a deep learning algorithm, termed LucaProt, to discover highly divergent RNA-dependent RNA polymerase (RdRP) sequences in 10,487 metatranscriptomes generated from diverse global ecosystems. LucaProt integrates both sequence and predicted structural information, enabling the accurate detection of RdRP sequences. Using this approach, we identified 161,979 potential RNA virus species and 180 RNA virus supergroups, including many previously poorly studied groups, as well as RNA virus genomes of exceptional length (up to 47,250 nucleotides) and genomic complexity. A subset of these novel RNA viruses was confirmed by RT-PCR and RNA/DNA sequencing. Newly discovered RNA viruses were present in diverse environments, including air, hot springs, and hydrothermal vents, with virus diversity and abundance varying substantially among ecosystems. This study advances virus discovery, highlights the scale of the virosphere, and provides computational tools to better document the global RNA virome., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Protease-activated receptors (PARs) are a unique group within the G protein-coupled receptor superfamily, orchestrating cellular responses to extracellular proteases via enzymatic cleavage, which triggers intracellular signaling pathways. Protease-activated receptor 1 (PAR1) is a key member of this family and is recognized as a critical pharmacological target for managing thrombotic disorders. In this study, we present cryo-electron microscopy structures of PAR1 in its activated state, induced by its natural tethered agonist (TA), in complex with two distinct downstream proteins, the G q and G i heterotrimers, respectively. The TA peptide is positioned within a surface pocket, prompting PAR1 activation through notable conformational shifts. Contrary to the typical receptor activation that involves the outward movement of transmembrane helix 6 (TM6), PAR1 activation is characterized by the simultaneous downward shift of TM6 and TM7, coupled with the rotation of a group of aromatic residues. This results in the displacement of an intracellular anion, creating space for downstream G protein binding. Our findings delineate the TA recognition pattern and highlight a distinct role of the second extracellular loop in forming β-sheets with TA within the PAR family, a feature not observed in other TA-activated receptors. Moreover, the nuanced differences in the interactions between intracellular loops 2/3 and the Gα subunit of different G proteins are crucial for determining the specificity of G protein coupling. These insights contribute to our understanding of the ligand binding and activation mechanisms of PARs, illuminating the basis for PAR1's versatility in G protein coupling., (© 2024. The Author(s).)

Aims: The recommended dosage of pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) for Western chemotherapy patients is 6 mg per cycle. However, for Eastern Asians, the optimal dose remains unknown., Methods: This open-label, randomized, non-inferiority trial (NCT05283616) enrolled Chinese female breast cancer patients receiving adjuvant chemotherapy. Participants were randomized to receive either 3 or 6 mg of PEG-rhG-CSF per cycle, stratified by body weight (BW; ≤60 kg vs. >60 kg). The primary endpoint was timely absolute neutrophil count (ANC) recovery before the second cycle of chemotherapy., Results: A total of 122 patients were randomized and 116 were included for efficacy analyses. The timely ANC recovery rate in the 3 mg arm was 89.8%, compared to 93.0% in the 6 mg arm (one-sided 95% confidence interval [CI] lower limit for difference: -11.7%), meeting the prespecified non-inferiority margin of 15%. The rate was 93.3% with PEG-rhG-CSF 3 mg and 96.6% with 6 mg in patients with BW ≤ 60 kg, and 86.2% and 89.3%, respectively, in those with BW > 60 kg. Although the incidence of severe neutropenia was similar across arms, the occurrence of excessively high ANC and white blood cell counts was higher in the 6 mg arm. No grade ≥3 adverse events related to PEG-rhG-CSF occurred., Conclusion: Three milligrams of PEG-rhG-CSF per cycle provided non-inferior neutrophil protection and attenuated neutrophil overshoot compared to 6 mg doses. This low-dose regimen could be a new supportive care option for Chinese breast cancer patients receiving anthracycline-based adjuvant chemotherapy., (© 2024 British Pharmacological Society.)

Objective: Facial paralysis (FP), which resulted from head and neck cancer resection, significantly impacts patients' quality of life. Traditional assessments rely on subjective evaluations and electromyography, whereas functional magnetic resonance imaging offers a noninvasive alternative for enhanced rehabilitation. Acupuncture has shown promise in promoting cerebral cortex reorganization, yet the precise relationship between acupuncture-induced structural and functional changes remains unclear, necessitating further investigation into therapeutic mechanisms., Methods: Fifty-five patients afflicted with FP underwent evaluations using voxel-mirrored homotopic connectivity (VMHC) and tract-based spatial statistics and were divided into the acupuncture intervention group (n = 35) and pseudo intervention group (n = 20). Comparative analyses of metrics pre and postintervention were conducted to delineate therapy-induced modifications in acupuncture intervention. The postacupuncture effect between groups to verify the necessity of accurate positioning for the rehabilitation of FP., Results: Patients with FP showed deficits in VMHC in regions of the postcentral, precentral, and parietal areas. Corpus callosum and internal capsule showed significantly increased fractional anisotropy of the white matter skeleton in tract-based spatial statistics after treatment. Comparison postintervention results between groups exhibited deficits in VMHC and increased fractional anisotropy in regions of the corpus callosum in the acupuncture intervention group., Conclusions: Early acupuncture intervention may suppress cortical hyperactivation and restore interhemispheric inhibition across the corpus callosum to inhibit maladaptive structural plasticity. Precise acupoint localization is crucial for effective therapy, highlighting the potential of postacupuncture cortical space data for refining therapeutic strategies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Chronic neutrophil leukemia (CNL) is a rare and life-threatening disease. Cases of CNL combined with lymphoma are rare. Here, we report a case of CNL with T-acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) in a 28-year-old male. After a regimen of ruxolitinib, VICLP (Vincristine, Idarubicin, Cyclophosphamide, Prednisone, Peg-asparaginase) regimen, high-dose cytarabine, and methotrexate regimens, the patient's bone marrow condition partially resolved. However, when the disease relapsed four months later, despite attempts with selinexor, venetoclax, and CAG(aclarubicin hydrochloride, Algocytidine, Granulocyte Stimulating Factor) chemotherapy, the leukocytes and peripheral blood primitive cells reduced, but the bone marrow did not achieve remission. This pathogenesis may be related to microenvironmental immune escape under prolonged inflammatory stimulation and gene disruption affecting protein function due to colony-stimulating factor 3 receptor gene (CSF3R) mutations. For this type of disease, early intervention may delay disease progression., (© 2024. The Author(s).)

Objective: This study aims to systematically evaluate the efficacy of probiotics in treating minimum hepatic encephalopathy (MHE)., Methods: A systematic search was conducted across three major databases: PubMed, China National Knowledge Infrastructure and Wanfang. The search period spanned from the inception of each database to 9 March 2023. The objective was to identify all randomised controlled trials (RCTs) examining the efficacy of probiotic preparations in treating MHE. The search terms included 'probiotics' along with other clinically relevant terms to comprehensively capture all pertinent studies., Results: A total of 18 RCTs were included. The meta-analysis showed that probiotic treatment outperformed control groups in reducing blood ammonia levels (standard mean difference [MD] = -2.68, 95% confidence interval [CI]: -3.90 to -1.46, p < .0001), improving the remission rate of MHE (risk ratio [RR] = 2.79, 95% CI: 1.23-6.35, p = .01) and lowering alanine aminotransferase levels (MD = -11.10, 95% CI: -16.17 to -6.03, p < .0001). It also significantly reduced the Model for End-Stage Liver Disease scores (MD = -2.55, 95% CI: -3.56 to -1.54, p < .00001) and the incidence of MHE (RR = .18, 95% CI: .09-.34, p < .00001)., Conclusion: Our study demonstrates that probiotics effectively improve blood ammonia levels, liver function and cognitive function in patients with MHE. They significantly enhance the remission rate of MHE and effectively reduce its incidence, providing solid new evidence for treating MHE with probiotics., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background: The prevalence of heatstroke is rising due to global warming, making it a serious but preventable condition, highlighting the urgent need for effective dissemination of relevant health education to the general public. Advances in technology have made accessing health information more convenient and rapid. In recent years, short videos have become a primary medium for delivering health education, with TikTok gaining considerable popularity among the general public. However, the quality of heatstroke-related health education content on TikTok deserves closer scrutiny., Objective: This study aimed to evaluate the quality and content of heatstroke-related videos available on TikTok., Methods: The present study analyzed the top 100 heatstroke-related short videos on TikTok, focusing on their characteristics, quality, and the content they conveyed. The quality of these videos was assessed using the DISCERN instrument. In addition, the completeness of the videos was assessed by examining six key aspects: disease definition, clinical manifestations, risk factors, assessment, management, and outcomes., Results: The study included a total of 90 videos. The results showed that news organizations and healthcare professionals were the primary contributors to these videos, with those from news organizations receiving the most attention. In contrast, those from healthcare professionals received comparatively less engagement. Overall, the quality of the information was found to be moderately low, with the highest quality videos posted by non-profit organizations, followed by those posted by healthcare professionals. The majority of videos uploaded described the disease definition, clinical presentation, risk factors, assessment, management, and outcomes of heatstroke., Conclusion: The quality of information provided in heatstroke-related short videos on TikTok is generally inadequate and requires significant improvement. In addition, such content should be subject to government review to ensure its accuracy and reliability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qiu and Zhou.)

The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA-coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child-Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro-inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver-related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Incorporating ultralow loading of nanoparticles into polymers has realized increases in dielectric constant and breakdown strength for excellent energy storage. However, there are still a series of tough issues to be dealt with, such as organic solvent uses, which face enormous challenges in scalable preparation. Here, a new strategy of dual in situ synthesis is proposed, namely polymerization of polyethylene terephthalate (PET) synchronizes with growth of calcium borate nanoparticles, making polyester nanocomposites from monomers directly. Importantly, this route is free of organic solvents and surface modification of nanoparticles, which is readily accessible to scalable synthesis of polyester nanocomposites. Meanwhile, uniform dispersion of as ultralow as 0.1 wt% nanoparticles and intense bonding at interfaces have been observed. Furthermore, the PET-based nanocomposite displays obvious increases in both dielectric constant and breakdown strength as compared to the neat PET. Its maximum discharged energy density reaches 15 J cm -3 at 690 MV m -1 and power density attains 218 MW cm -3 under 150 Ω resistance at 300 MV m -1 , which is far superior to the current dielectric polymers that can be produced at large scales. This work presents a scalable, safe, low-cost, and environment-friendly route toward polymer nanocomposites with superior capacitive performance., (© 2024 Wiley‐VCH GmbH.)

Background: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children., Methods: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world's first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for "macrolide-resistant", "Mycoplasma pneumoniae", "MP", "M. pneumoniae", "pneumonia", "MRMP", "lower respiratory tract infection", "Mycoplasma pneumoniae infection", "children", and "pediatric"., Results: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics., Conclusions: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains., (© 2024. The Author(s).)

Background: Infection with Neisseria gonorrhoeae in adults usually leads to vaginitis and acute urethritis, and infection through the birth canal in newborns can lead to acute neonatal conjunctivitis. In view of certain factors such as a high missed detection rate of N.gonorrhoeae from staining microscopy method, the time-consuming nature and limited sensitivity of bacterial culture method, complicated and inability of absolute quantification from the ordinary PCR method., Methods: This study aims to establish a ddPCR system to detect N.gonorrhoeae in a absolute quantification, high specificity, high stability and accurate way. We selected the pgi1 gene as the target gene for the detection of N.gonorrhoeae., Results: The amplification efficiency was good in the ddPCR reaction, and the whole detection process could be completed in 94 min. It has a high sensitivity of up to 5.8 pg/μL. With a high specificity, no positive microdroplets were detected in 9 negative control pathogens in this experiment. In addition, ddPCR detection of N.gonorrhoeae has good repeatability, and the calculated CV is 4.2 %., Conclusions: DdPCR detection technology has the characteristics of absolute quantification, high stability, high specificity and high accuracy of N.gonorrhoeae. It can promote the accuracy of the detecting of N.gonorrhoeae, providing a more scientific basis for clinical diagnosis and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The transcription factor MAFB is part of the MAF family and is known to promote hepatocellular carcinoma (HCC) by upregulating cyclin D1. However, its role in HCC immunity and prognosis remains unclear. This study explores the biological function, prognostic significance, and immune impact of MAFB in HCC., Methods: Immunohistochemistry was used to analyze MAFB expression in HCC and adjacent non-tumor tissues. RT-qPCR and Western blotting measured MAFB levels in HCC cell lines. Specific siRNA was used to knockdown MAFB in HCCLM3 and MHCC97H cells, followed by assays to evaluate cell proliferation, migration, and colony formation. Data from the TCGA database and online tools TIMER and TISDB were used to assess the relationship between MAFB and immune responses. A prognostic model based on MAFB-related immune genes was established, and drug sensitivity analysis was performed., Results: MAFB was significantly overexpressed in HCC tissues. Knockdown of MAFB in HCC cell lines reduced their proliferation and migration abilities. The risk model based on MAFB-related immune genes effectively predicted patient prognosis, supported by ROC curves. Gene set enrichment analysis indicated that MAFB is involved in immune-related pathways. Several drugs were identified as potentially sensitive to MAFB expression levels., Conclusion: MAFB plays a significant role in HCC development and immune regulation. The prognostic model combining MAFB-related immune genes provides valuable insights for predicting patient outcomes and identifying potential therapeutic targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Ulcerative colitis (UC) is a chronic inflammatory bowel condition that is frequently related with Spleen-Kidney Yang Deficiency Syndrome (SKYD) in Chinese medicine. Fuzi Lizhong Pill (FLZP), a traditional medicine for SKYD, has been utilized in China for generations, although the exact mechanism by which it treats UC is unknown., Aim of the Study: The goal of this study is to further understand FLZP's therapeutic mechanism in SKYD-associated UC., Materials and Methods: To investigate the impact of FLZP on SKYD-associated UC, we used a comprehensive method that included serum metabolomics and gut microbiota profiling. The chemical composition of FLZP was determined using mass spectrometry. UC rats with SKYD were induced and treated with FLZP. Serum metabolomics and 16S rRNA microbial community analysis were used to evaluate FLZP's effects on endogenous metabolites and gut microbiota, respectively. Correlation analysis investigated the association between metabolites and intestinal flora. A metabolic pathway analysis was undertaken to discover putative FLZP action mechanisms., Results: FLZP contains 109 components, including liquiritin (584.8176 μg/g), benzoylaconine (16.3087 μg/g), benzoylhypaconine (31.9583), and hypaconitine (8.1160 μg/g). FLZP predominantly regulated seven metabolites and eight metabolic pathways involved in amino acid and nucleotide metabolism, with an emphasis on energy metabolism and gastrointestinal digestion. FLZP also influenced intestinal flora variety, increasing probiotic abundance while decreasing pathogenic bacteria prevalence. An integrated investigation identified associations between changes in certain gut flora and energy metabolism, specifically the tricarboxylic acid (TCA) cycle., Conclusions: FLZP successfully cures UC in SKYD rats by regulating amino acid and energy metabolism. Its positive effects may include altering microbiota composition and metabolite profiles in UC rats with SKYD. These findings shed light on FLZP's mode of action and its implications for UC management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Enhanced dielectric constant and high breakdown strength offers immense promise for excellent energy storage performance, which is of critical significance in modern electronics and power systems. However, polymer nanocomposites with traditional routes have to balance between dielectric constant and breakdown strength, hence hindering substantive increases in energy density. Herein, a sandwiched polymer nanocomposite film has been constructed to take full advantage of the individual component layers. BaTiO 3 nanoparticles are coated with a fluoropolymer to form core-shell structures and then introduced into a polymer as the top and the bottom layers of a sandwich film for enhancing polarization. Moreover, boron nitride nanosheets (BNNSs) in the middle layer of the sandwich film exert positive effects on the inhibition of current leakage for high breakdown resistance. The breakdown strength increases from 480 MV m -1 of the neat polymer to 580 MV m -1 of the sandwiched film. Additionally, the film exhibits a higher dielectric constant in comparison with the neat polymer. The sandwiched film displays a superior energy density (15.75 J cm -3 ), which is about 1.9 times that of the neat polymer. This work proposes a feasible route to achieve excellent energy storage of polymer dielectrics by synergistically introducing insulating fillers and additional dipoles in a sandwiched polymer nanocomposite film.

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546])., Competing Interests: Declaration of competing interest RPG is a consultant to Antengene Biotech LLC; Medical Director, FFF Enterprises Inc.; A speaker for Janssen Pharma and Hengrui Pharma; Board of Directors: Russian Foundation for Cancer Research Support and Scientific Advisory Board, StemRad Ltd., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Facial palsy, often resulting from trauma or iatrogenic treatments, leads to significant esthetic and functional impairment. Surgical interventions, such as masseteric-to-facial nerve transfer combined with static suspension, are frequently recommended to restore facial nerve function and symmetry., Methods: This study examines how Botulinum Toxin A (BoNT-A) treatment on the unaffected side affects facial symmetry and brain connectivity in patients with severe oral commissure droop from facial nerve damage. Patients were divided into two groups: one received BoNT-A injections on the unaffected side, and the other did not., Results: Our findings revealed that BoNT-A treatment not only improved facial symmetry but also induced significant modifications in brain functional network connectivity. These modifications extended beyond the sensorimotor network, involving high-level cognitive processes, and exhibited a significant correlation with the degree of facial asymmetry., Conclusions: These results provide valuable insights into the mechanisms underlying the positive effects of BoNT-A intervention on motor recovery and brain plasticity in facial palsy patients. Furthermore, the study emphasizes the importance of a multidisciplinary approach to facial palsy rehabilitation. Understanding these intricate interactions between facial symmetry restoration and brain network adaptations may pave the way for more effective treatments and improved quality of life for individuals dealing with facial palsy., (Copyright © 2024 by the American Society of Plastic Surgeons.)

The efficient and complete extraction of uranium from aqueous solutions is crucial for safeguarding human health from potential radiotoxicity and chemotoxicity. Herein, an ultrathin 2D metal-organic framework (MOF) nanosheet with cavity structures was elaborately constructed, based on a calix[4]arene ligand. The large molecular skeleton and cup-shaped feature of the calix[4]arene enabled the as-prepared MOFs with large layer separations, which can be readily delaminated into ultrathin single-layer (∼1.25 nm) nanosheets. The incorporation of permanent cavity structures to the MOF nanosheets can fully utilize their structural features of readily accessible adsorption groups and exposed surface area in uranium removal, reaching ultrafast adsorption kinetics; the functionalized cavity structure endowed MOF nanosheets with the ability to preconcentrate and extract uranium from aqueous solutions with ultrahigh efficiencies, even at extremely low concentrations. As a result, relatively high removal ratios (>95%) can be achieved for uranium within 5 min, even in the ultralow concentration range of 75-250 ppb, and the residual uranium was reduced to below 4.9 ppb. The MOF nanosheets also exhibited extremely high anti-interference ability, which could efficiently remove the low-level uranium (∼150 ppb) from various real samples. The characterizations and density functional theory calculations demonstrated that the synergistic effects of multiple interactions between the carboxylate groups and cage-like cavities with uranyl ions can be responsible for the efficient and selective uranium extraction.

The prevalence of selenium-cadmium （Se-Cd） symbiosis in soils of geologically high background areas directly affects the safe utilization of Se-rich land resources. To investigate the migration and accumulation characteristics and bio-effectiveness of Se-Cd in the soil-crop system in typical geological high background areas of Southwest China and to realize the safe use of natural Se-rich land resources in geological high background areas, we collected 84 samples of agricultural crops （maize） and their supporting root systems and analyzed the Se-Cd content and physicochemical properties. Se-Cd accumulation characteristics, influencing factors, and bio-effectiveness of the soil-crop system were evaluated using geostatistics, bioenrichment factors, and geographic detectors. The results showed that the Se-Cd content in the study area was significantly higher than the background value of the soil in the whole country and in Yunnan Province. Influenced by the geological background, secondary enrichment in the process of soil formation, and agricultural activities, the accumulation and enrichment characteristics of Se in the root soil varied from no enrichment to slightly enriched, and the occurrence form was dominated by the residue state. The accumulation index of soil Cd was mainly in the medium pollution level, and the occurrence form was mainly in the residual state and the combined state of iron and manganese. The Se-enrichment rate of crop seeds reached 98.8% （DB 50/T 524-2013 standard）, and the average value of bioconcentration factor was 5.8%. The exceeding rate of Cd content in crop seeds was only 1.19% （GB 2762-2022 standard）, and the average value of Cd bioconcentration factor was 2.11%, so the ecological risk of heavy metal Cd in crop seeds was relatively low. In the Se-Cd symbiosis area under geological background, the weak alkaline environment of the soil could effectively reduce the bioavailability of Cd in crop seeds, and the Se-rich soil could inhibit the uptake of Cd by the crops to a certain extent. Correlation analysis showed that the migration and accumulation of Se and Cd from soil to crop seeds in the soil-crop system were affected by the elemental accumulation pattern and the physical and chemical properties （pH） of the soil, and at the same time, there was a certain synergistic-antagonistic effect between Se and Cd in the soil-crop system. Correlation analysis showed that the migration and accumulation of Se and Cd from soil to crop seeds in the soil-crop system was influenced by the occurrence of elements, soil physicochemical properties （pH）, and other factors, and there was also a certain synergistic-antagonistic interaction between Se and Cd in the soil-crop system.

In order to place newly discovered fossil taxa (Palaeosymbius gen. nov. with P. groehni and P. mesozoicus spp. nov.) from the mid-Cretaceous amber from northern Myanmar, we investigated the relations of extant and extinct lineages of the coccinellid group of Coccinelloidea with emphasis on the family Anamorphidae. We assembled a taxonomic sampling of 34 taxa, including 15 genera and 19 species of Anamorphidae, the most comprehensive sampling of Anamorphidae at the generic level in a phylogenetic analysis. A morphological dataset of 47 characters was built as well as a molecular alignment of 7140 bp including fragments of eight genes (12S, 16S, 18S, 28S, COI, COII, H3 and CAD). Five anamorphid and one endomychid species were sequenced for the first time and added to the dataset. We performed parsimony-based analysis of the morphological dataset and Bayesian inference analysis of the combined matrix (morphological plus molecular data). Our results confirm that Palaeosymbius belongs to Anamorphidae and represents the oldest known member of this family so far. Among Anamorphidae, Symbiotes (with extant and known Eocene species) was recovered as the most probable closest relative of Palaeosymbius. Our morphological studies additionally revealed the presence of probable glandular openings in the anterolateral corners of the pronotal margins in Asymbius sp. and Anamorphus sp., representing the first report of secretory openings in the family Anamorphidae. Similar openings are found in other cucujiform beetles such as Cryptophagidae and Boganiidae with possible defensive purposes., (© 2024 Willi Hennig Society.)

Background: Lower eyelid suspension, a common therapeutic procedure for facial paralysis-induced eyelid retraction, faces challenges due to high recurrence in patients lacking facial muscle function and impedes wider adoption. This research aims to explore the potential effects of restoring orbicularis oculi muscle tension through facial nerve reanimation prior to lower eyelid suspension and to define the indications for lower eyelid suspension., Methods: The study encompassed 32 individuals with complete facial paralysis, segmented into group A (reanimation group) and group B (non-reanimation group), based on whether the orbicularis oculi muscle's tension was restored through facial nerve reconstruction prior to lower eyelid suspension. Subjective assessments of eyelid closure (the inter-eyelid gap upon gentle closure) and objective methods measures of scleral show (the distance from the pupil's center to the lower eyelid margin, MRD2) were used to provide a comprehensive analysis of long-term effectiveness., Results: The group A exhibited significantly greater long-term improvement in lagophthalmos and lower eyelid ectropion. The alterations in MRD2 measured 2.66 ± 0.27 mm in the group A versus 2.08 ± 0.53 mm in the group B, denoting a statistically significant variance (p < 0.001). Moreover, while the ratio of MRD2 preoperative 6 months postoperative revealed no significant difference between groups, a significant difference emerged in 12 months postoperative (group A: 1.02 ± 0.21; group B: 1.18 ± 0.24; p < 0.05), with the values in group A closer to 1, indicative of enhanced symmetry., Conclusions: Restoring the tension in the orbicularis oculi muscle through facial nerve reconstruction prior to palmaris longus tendon sling could effectively sustain long-term outcomes of lower eyelid retraction correction and reduce the recurrence rate., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Objective: To construct a predictive model to direct the dissection of the central lymph nodes in papillary thyroid cancer (PTC) with BRAF V600E mutation by identifying the risk variables for central lymph node metastases (CLNM)., Methods: Data from 466 PTC patients with BRAF V600E mutations underwent thyroid surgery was collected and analyzed retrospectively. For these patients, we conducted univariate and multivariate logistic regression analysis to find risk variables for CLNM. To construct a nomogram, the independent predictors were chosen. The calibration, discrimination, and clinical utility of the predictive model were assessed by training and validation data., Results: CLNM was present in 323/466 PTC patients with BRAF V600E mutations. By using univariate and multivariate logistic regression, we discovered that gender, age, tumor size, multifocality, and pathological subtype were all independent predictors of CLNM in PTC patients with BRAF V600E mutations. A predictive nomogram was created by combining these variables. In both training and validation groups, the nomogram demonstrated great calibration capacities. The training and validation groups' areas under the curve (AUC) were 0.772 (specificity 0.694, sensitivity 0.728, 95% CI: 0.7195-0.8247) and 0.731 (specificity 0.778, sensitivity 0.653, 95% CI: 0.6386-0.8232) respectively. According to the nomogram's decision curve analysis (DCA), the nomogram might be beneficial. As well, an online dynamic calculator was developed to make the application of this nomogram easier in the clinic., Conclusion: An online nomogram model based on the 5 predictors included gender, age, pathological subtype, multifocality, and tumor size was confirmed to predict CLNM and guide the central lymph nodes dissection in PTC patients with BRAF V600E mutations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)