Search

Zhu-Quan Su,* Wan-Yuan Rao,* Xiao-Yi Pan, Jia-Xin Tang, Ming-Yue Fan, Xiao-Bo Chen, Shi-Yue Li State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shi-Yue Li; Xiao-Bo Chen, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, 510120, People’s Republic of China, Tel +86 20 8306 2896, Email lishiyue@188.com; xiaobo-win@163.comAbstract: Disseminated infection caused by Streptococcus constellatus was seldom occurred. We reported a case of Streptococcus constellatus infection, presenting as multiple pulmonary cavities, thoracic wall abscess and vertebral destruction. The 37-year-old male had recurrent fever, chest wall swelling and pain, and lower limb numbness, he had weak physical condition and previously suffered from poorly controlled diabetes and severe periodontal disease for 3 years. Definite diagnosis of Streptococcus constellatus infection was made by metagenomic next‑generation sequencing (mNGS) in abscess drainage fluid. Systemic antibiotics and thoracic wall drainage were given, and the pulmonary cavity and the thoracic intermuscular abscess were significantly decreased. Few to no study reported the disseminated infection (pulmonary cavities, thoracic wall abscess and vertebral destruction) caused by Streptococcus constellatus. This case report highlighted the importance of mNGS for accurate diagnosis, as well as the timely drainage and antibiotics for effective treatment of Streptococcus constellatus infection.Keywords: Streptococcus constellatus, pulmonary cavity, thoracic wall abscess, vertebral destruction, metagenomic next‑generation sequencing

Jian Tang,1 Hong Yuan,2 Yun Long Wu,1 Shui Fu,3 Xiao Yong Pan4 1Department of Intensive Care, First People’s Hospital of Linping District, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Cardiology, First People’s Hospital of Linping District, Hangzhou, Zhejiang Province, People’s Republic of China; 3Clinical Laboratory Department, First People’s Hospital of Linping District, Hangzhou, Zhejiang Province, People’s Republic of China; 4Clinical Laboratory Department, The People’s Hospital of Cangnan Zhejiang, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xiao Yong Pan, Clinical Laboratory Department, The People’s Hospital of Cangnan Zhejiang, Wenzhou, Zhejiang Province, People’s Republic of China, Email pxy01234567892023@163.comObjective: To explore the serial measurement of heparin-binding protein and D-dimer in the prediction of 28-day mortality and efficacy evaluation of critically-ill patients with sepsis.Methods: We recruited a total of 51 patients with sepsis in the ICU of our hospital. They were divided into a survival group or a death group according to their prognosis 28 days after treatment. The HBP and D-dimer levels in these patients were determined on the 1st (24h), 3rd, and 5th days. Besides, the sequential organ failure assessment (SOFA) score of these patients was recorded at admission. The patients in both groups were subjected to comparison regarding HBP and D-dimer levels and SOFA scores within 24h of admission. Additionally, a correlation between the levels of HBP and D-dimer and the SOFA score was statistically measured, while the predictive effectiveness of these factors for the prognosis of patients with sepsis was also determined. Moreover, the dynamic changes in HBP and D-dimer during the treatment of both groups were analyzed.Results: The HBP and D-dimer levels and the SOFA scores in the survival group were considerably lower than those in the death group, and the differences were statistically significant (P< 0.05). Additionally, the levels of HBP and D-dimer in sepsis patients were positively correlated with the SOFA score (P< 0.05). The area under the curve (AUC) of HBP, D-dimer, and their combination in predicting the prognosis of patients with sepsis was 0.824, 0.771, and 0.830, respectively. Besides, the sensitivity and specificity of their combination in predicting the prognosis of patients with sepsis were 68.42% and 92.31%, respectively. The HBP and D-dimer levels presented a downward trend in the survival group during treatment, while they exhibited an upward trend in the death group.Conclusion: HBP and D-dimer realize high predictive effectiveness for the prognosis of patients with sepsis, while the combined use of these two factors achieves superior effectiveness. Thus, they can be applied to the prediction of 28-day mortality and efficacy evaluation of sepsis patients.Keywords: sepsis, heparin-binding protein, HBP, D-dimer, sequential organ failure assessment score, SOFA, prognosis

Hong-Peng Chen,1,2,* Xiao-Yan Wang,1,* Xiao-Yan Pan,1 Wang-Wang Hu,1 Shu-Ting Cai,1 Kiran Joshi,3 Lie-Hua Deng,1,2 Daqing Ma3 1Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 2Zhanjiang Key Laboratory of Organ Injury and Protection and Translational Medicine, Zhanjiang, Guangdong, People’s Republic of China; 3Division of Anesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK*These authors contributed equally to this workCorrespondence: Lie-Hua Deng; Daqing MaDepartment of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, ChinaEmail glinson@126.com; d.ma@imperial.ac.ukIntroduction: Because of its high morbidity and mortality, sepsis remains the leading cause of death in the ICU. Microparticles (MP) have been largely studied as potential diagnostic or prognostic markers in various diseases including sepsis.Objective: The biological and clinical relevance of neutrophil-derived microparticles (NDMPs) within the MP population remains unclear. The objective of this study was to elucidate the relationship between plasma NDMPs and the prognosis of patients with sepsis and/or septic shock.Methods: The study was designed as an observational, noninterventional clinical study. The cohort for this study included 40 sepsis and 40 septic shock patients together with 10 healthy controls admitted to the Intensive Care Unit (ICU) and the Health Surveillance Center in the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China, from January to November 2018, respectively. The degree of critical disease for sepsis and septic shock was evaluated, with data analyses conducted from 2018 to 2019.Results: On days 1, 3 and 5 post-admission a series of data including plasma NDMP levels, patient demographics, TNF-α levels, IL-6 levels, sTREM-1 levels, and the sepsis severity score measurements were collected. A survival curve was plotted against levels of plasma NDMPs. Levels of NDMPs were observed to be higher in the septic shock patients than in the sepsis patients on days 1, 3, and 5 post-ICU admission (p < 0.05). NDMP levels were significantly increased in sepsis and septic shock patients with a parallel increase in pro-inflammatory mediators and sepsis severity score (p < 0.05) as well as mortality.Conclusion: Our data suggest that NDMPs may be a biomarker of sepsis severity and mortality although its implications on sepsis prognosis warrant further study.Keywords: sepsis, septic shock, cell-derived microparticles, biomarker, prognosis

Yun Shan Chen,*,1 Fen Liu,*,1 Yi Hong Luo,1 Yue Fan,1 Fang Gui Xu,1 Pin Li,1 Bei Zhou,1 Xiu Yu Pan,1 Chi Chiu Wang,2–4 Long Cui1,41Department of Obstetrics and Gynaecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, People’s Republic of China; 2Reproduction and Development Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong; 3School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong; 4Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong*These authors contributed equally to this workBackground: The role of endothelin receptor type B (EDNRB) isoform 3 involved in Temozolomide (TMZ)-induced melanoma cell death has not yet been elucidated.Methods: The subcellular localization of EDNRB isoform 3 was determined by confocal and immunoblotting assays. Silencing EDNRB isoform 3 was performed by CRISPR/Cas9. Apoptosis was assessed by annexin V/propium iodide staining and caspases 3/7/9 activity. Mitochondrial membrane potential, reactive oxygen species and mitochondrial Ca2+ were measured by flow cytometry. Apoptosis protein array was applied.Results: Confocal and immunoblot analyses indicate mitochondrial localization of EDNRB isoform 3 and the first N-terminal (1–22) amino acids are sufficient for its mitochondrial targeting. EDNRB isoform 3 depleted A375 cells significantly confers chemoresistance with mitochondrial depolarization, reduced reactive oxygen species, enhanced mitochondrial Ca2+ uptake and decreased caspase 9 activation. Additionally, apoptosis array shows that lack of EDNRB isoform 3 has relatively lower expression of phosphorylation of p53 at S392 and a slightly higher expression of Paraoxonase 2.Conclusion: Our findings raise the possibility of targeting EDNRB isoform 3 as a new therapeutic strategy in combination with TMZ for melanoma treatment.Keywords: melanoma, Temozolomide, mitochondrial targeting sequence, apoptosis, reactive oxygen species

Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by the infectious bursal disease virus (IBDV). Despite significant efforts, the lack of knowledge about host proteins that counteract IBDV replication has hindered progress in preventing and controlling IBD in chickens. This study identifies the mitochondria-associated protein vaccinia virus-related kinase 2 (VRK2) as an inhibitor of IBDV. Overexpression of VRK2 significantly reduced IBDV proliferation in DF-1 cells and chicken embryo fibroblasts (CEFs). Conversely, the absence of VRK2 resulted in higher viral loads in these cells. Additionally, we found that VRK2 interacts with voltage-dependent anion channel 2 (VDAC2) and Receptor for Activated C Kinase 1 (RACK1). Mechanistic studies revealed that VRK2 inhibits IBDV-induced apoptosis by targeting RACK1 phosphorylation, leading to reduced viral growth. This study enhances our understanding of VRK2's role in host anti-apoptotic mechanisms and offers novel insights into IBDV pathogenesis and vaccine development., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024. Published by Elsevier B.V.)

In Xinjiang, previous reports of cystic echinococcosis (CE) in livestock have focused on West and Middle Tianshan Mountains. In contrast, there is an absence of research on CE in the East Tianshan Mountains. To determine the epidemiology and genetic diversity of Echinococcus granulosus sensu stricto (s.s.) in domestic animals in the East Tianshan Mountains, Xinjiang, China, the livers and lungs of 1773 domestic animals were examined, between January 2023 and March 2023, and 40 cysts were collected. Polymerase chain reaction was used for the molecular diagnosis of the cysts. Statistical results showed that the overall prevalence of echinococcosis in sheep was 6.92% (114/1646), which was significantly higher than that in cattle (1.57%, 2/127). A total of 40 cyst isolates were obtained, including 38 from sheep and 2 from cattle. Genomic DNA was extracted, and the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene was amplified by PCR to obtain the target 850 bp fragment. The results revealed that all the isolates had the G1 genotype, with similarities ranging from 98.88-100%. Haplotype network analysis revealed 32 haplotypes of the cox1 gene, among which Hap&#95;7 was the main haplotype. Furthermore, haplotype diversity (Hd = 0.313 ± 0.093) and nucleotide diversity (π = 0.00173 ± 0.00079) were lower in the East Tianshan Mountains than in other regions, indicating that the populations are genetically less differentiated. Tajima's D and Fu's Fs tests were negative (p ≤ 0.01), indicating an expansion of the population in the East Tianshan Mountains of Xinjiang, similar to the results previously reported for Xinjiang. The low fixation index (Fst) ranged from negative values (Gansu Province) to 0.30346 (Mongolia), indicating that the genetic differentiation between the East Tianshan Mountains and Gansu, and Tibet, Xinjiang was relatively low, with frequent gene flow. In this survey, two 'new' haplotypes were identified in the East Tianshan livestock. In addition, two different haplotypes of liver and lung infections were found in one cattle. This survey provides information on the epidemiology and genetic diversity of E. granulosus s.s. in the East Tianshan Mountains of Xinjiang, China., Competing Interests: Declarations. Ethics statement: Not applicable. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In situ gelling eye drops of tacrolimus (FK506 Gel) were developed to address the formulation challenge of tacrolimus for anterior ocular inflammatory diseases. Both in silico and in vitro investigations were conducted to screen a suitable cyclodextrin species to increase the drug solubility. Guanosine was employed as the gelator and combined with inclusion complexes of tacrolimus in the presence of borate anions to obtain FK506 Gel, which gelated when came into contact with cations in tear fluid and led to the formation of a nanofibrous hydrogel. The versatility of our design to improve the solubility and ocular retention of the hydrophobic drug was demonstrated in vivo with coumarin 6 as a model drug. A mouse dry eye model was used to evaluate the therapeutic effects of FK506 Gel, which, in combination with the biocompatibility study, suggested that FK506 Gel served as a superior treatment for anterior ocular inflammatory diseases.

Background: The clinical interpretation of patient-reported outcome measures (PROMs) after anterior cruciate ligament (ACL) reconstruction (ACLR) can be challenging. This study aimed to establish the clinical relevance of PROMs by determining maximal outcome improvement (MOI) thresholds at mid-term follow-up after primary ACLR., Methods: A total of 343 patients who underwent primary single-bundle ACLR using hamstring tendon autograft at our institute were included. Patients were queried with a 2-option anchor question regarding satisfaction with their current knee symptom state. The MOI of a PROM was calculated for each patient as the percentage of improvement normalized by the maximal possible improvement. The MOI threshold for each PROM was determined as the optimal cutoff value for predicting patient satisfaction based on receiver operating characteristic curve analysis. Multivariable logistic regression analyses were performed to identify predictors of achieving these thresholds. Subgroup analyses that stratified the time from injury to surgery within the cohort were performed, and MOI thresholds were recalculated within each of these subgroups. The PROMs evaluated in this study were the modified Lysholm Knee Score and the International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC) score., Results: The calculated MOI threshold was 35.1% for the Lysholm score and 46.7% for the IKDC score. A longer time from injury to surgery reduced the odds of achieving the MOI threshold for the Lysholm score (odds ratio [OR] per time bracket = 0.7114, p < 0.0001) and IKDC score (OR = 0.8038, p = 0.0003). Male sex was associated with higher odds of achieving the MOI threshold for the IKDC score (OR = 1.9645, p = 0.0143). For patients with chronicity of ≤6 months, the MOI threshold was 35.1% for the Lysholm score and 57.9% for the IKDC score, and for patients with chronicity of >6 months, the thresholds were 24.5% and 27.1%, respectively., Conclusions: The calculated MOI thresholds for the Lysholm and IKDC scores at mid-term follow-up after primary ACLR were 35.1% and 46.7%, respectively. Greater chronicity of the ACL injury was associated with lower odds of achieving the MOI thresholds for the PROMs at mid-term follow-up., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: This study was supported by the Clinical Cohort Project Program of Peking University Third Hospital (BYSYDL2021014, BYSYDL2023018). The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I270)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

The present work reveals a new metal-catalyzed synthetic reaction involving 1,2,3-benzotriazinones with carbonyl sulfoxonium ylide and iodonium ylide, resulting in divergent products. Within this catalytic system, 3-phenylbenzo[ d ][1,2,3]triazin-4(3 H )-one derivatives undergo C-H alkylation processes facilitated by a Cp*Rh(III) catalyst when combined with a carbonyl sulfoxonium ylide. On the other hand, when iodonium ylide substrates are used, they undergo an alkenylation reaction facilitated by a Cp*Ir(III) catalyst. In addition, hydrazone products are produced by synthesizing iodonium ylide substrates with the use of a copper catalyst. These transformations demonstrate mild reaction conditions, a wide range of substrates, and excellent compatibility with various functional groups. The strategy and tactics utilized have been effectively implemented on a significant scale.

Background: The ability of socially assistive robots (SARs) to treat dementia and Alzheimer's disease has been verified. Currently, to increase the range of their application, there is an increasing amount of interest in using SARs to relieve pain and negative emotions among children in routine medical settings. However, there is little consensus regarding the use of these robots., Objective: This study aimed to evaluate the effect of SARs on pain and negative affectivity among children undergoing invasive needle-based procedures., Design: This study was a systematic review and meta-analysis of randomized controlled trials that was conducted in accordance with the Cochrane Handbook guidelines., Methods: The PubMed, CINAHL, Web of Science, Cochrane Library, Embase, CNKI, and WanFang databases were searched from inception to January 2024 to identify relevant randomized controlled trials (RCTs). We used the Cochrane Risk of Bias tool 2.0 (RoB2.0) to assess the risk of bias among the included studies, and we used RevMan 5.4 software to conduct the meta-analysis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to assess the quality of the evidence., Results: Ten RCTs involving 815 pediatric subjects were selected for this review and reported outcomes related to pain and emotions during IV placement, port needle insertion, flu vaccination, blood sampling, and dental treatment. Children undergoing needle-related procedures with SARs reported less anxiety (SMD= -0.36; 95% CI= -0.64, -0.09) and fewer distressed avoidance behaviors (SMD= -0.67; 95% CI= -1.04, -0.30) than did those receiving typical care. There were nonsignificant differences between these groups in terms of in pain (SMD = -0.02; 95% CI = - 0.81, 0.78) and fear (SMD = 0.38; 95% CI= -0.06, 0.82). The results of exploratory subgroup analyses revealed no statistically significant differences based on the intervention type of robots or anesthetic use., Conclusions: The use of SARs is a promising intervention method for alleviating anxiety and distress among children undergoing needle-related procedures. However, additional high-quality randomized controlled trials are needed to further validate these conclusions., Trial Registration: The protocol of this study has been registered in the database PROSPERO (registration ID: CRD42023413279)., (© 2024. The Author(s).)

The complex etiological factors associated with metabolic dysfunction-associated fatty liver disease (MAFLD), including perturbed iron homeostasis, and the unclear nature by which they contribute to disease progression have resulted in a limited number of effective therapeutic interventions. Here, we report that patients with metabolic dysfunction-associated steatohepatitis (MASH), a pathological subtype of MAFLD, exhibit excess hepatic iron and that it has a strong positive correlation with disease progression. FerroTerminator1 (FOT1) effectively reverses liver injury across multiple MASH models without notable toxic side effects compared with clinically approved iron chelators. Mechanistically, our multi-omics analyses reveal that FOT1 concurrently inhibits hepatic iron accumulation and c-Myc-Acsl4-triggered ferroptosis in various MASH models. Furthermore, MAFLD cohort studies suggest that serum ferritin levels might serve as a predictive biomarker for FOT1-based therapy in MASH. These findings provide compelling evidence to support FOT1 as a promising novel therapeutic option for all stages of MAFLD and for future clinical trials., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study is to investigate the role of PMMA-induced biofilm in nerve regeneration compared with silicone-induced biofilm involved in the mechanism., Methods: PMMA or silicon rods were placed next to the sciatic nerve to induce a biological membrane which was assayed by PCR, Western blot, immunohistochemistry, immunofluorescence and proteomics. A 10 mm sciatic nerve gaps were repaired with the autologous nerve wrapped in an induced biological membrane. The repair effects were observed through general observation, functional evaluation of nerve regeneration, ultrasound examination, neural electrophysiology, the wet weight ratio of bilateral pretibial muscle and histological evaluation. Cell proliferation and migration of Schwann cells co-cultured with EGF-treated fibroblasts combined with siRNA were investigated., Results: The results indicated that expression of GDNF, NGF and VEGF along with neovascularization was similar in the silicone and PMMA group and as the highest at 6 weeks after operation. Nerve injury repair mediated by toluidine blue and S100β/NF200 expression, the sensory and motor function evaluation, ultrasound, target organ muscle wet-weight ratio, percentage of collagen fiber, electromyography and histochemical staining were not different between the two groups and better than blank group. EGF-treated fibroblasts promoted proliferation and migration may be Tnc expression dependently., Conclusion: Our study suggested that PMMA similar to silicon induced biofilm may promote autogenous nerve transplantation to repair nerve defects through EGF/Tnc/FN1 to increase Schwann cells proliferation and migration., Competing Interests: 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., (© 2024 Published by Elsevier Ltd.)

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m 6 A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism., (© 2024 Wiley‐VCH GmbH.)

Objectives: This study aims to investigate the feasibility and safety of combined anesthesia with spontaneous breathing in the operation of intertrochanteric fracture of femur in the elderly., Patients and Methods: Between January 2020 and January 2023, a total of 141 elderly patients (45 males, 96 females; mean age: 72.5±6.8 years; range, 65 to 87 years) who underwent proximal femoral nail anti-rotation (PFNA) surgery for intertrochanteric fracture of femur were included in this single-blind, prospective, randomized-controlled study. The patients were randomly divided into three groups. Group A (experimental group) was a general anesthesia with laryngeal mask airway (LMA) group preserving spontaneous breathing, Group B (control group 1) was a general anesthesia with LMA group for mechanical ventilation, and Group C (control group 2) was a tracheal intubation anesthesia group for mechanical ventilation. The differences of related indexes among the three groups were compared., Results: The mean onset time of anesthesia (6.23±1.45 vs. 12.78±2.78 vs. 13.73±2.43 min), postoperative recovery time of consciousness (8.13±0.83 vs. 11.34±0.89 vs. 12.45±0.86 min), and postoperative complete awakening time (10.45±2.34 vs. 18.87±2.56 vs. 19.62±2.93 min) were significantly shorter in Group A than in Groups B and C (p<0.05). The duration of analgesic effect was longer in Group A than in Groups B and C (p<0.05). After anesthesia, the Ramsay Sedation Scale and Visual Analog Scale (VAS) scores were significantly lower in Group A than the other groups (p<0.05). The mean Mini-Mental State Examination (MMS) scores were significantly higher in Group A than in Groups B and C (p<0.05). Hemodynamic parameters showed that blood pressure, heart rate, cardiac output, and cardiac index (CI) levels were significantly higher in Group A than the other groups (p<0.05)., Conclusion: Our study results indicate that combined anesthesia preserving spontaneous breathing is safe and feasible in the operation of intertrochanteric fracture of femur in the elderly, with faster anesthesia recovery than the mechanical ventilation group.

Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation ( P =0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation ( P =0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation ( P =0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.

Aim: To explore the effects of hepatocyte growth factor (HGF) on retinal pigment epithelium (RPE) cell behaviors., Methods: The human adult retinal pigment epithelial cell line-19 (ARPE-19) were treated by HGF or mesenchymal-epithelial transition factor (MET) inhibitor SU11274 in vitro . Cell viability was detected by a Cell Counting Kit-8 assay. Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay, respectively. The expression levels of MET, phosphorylated MET, protein kinase B (AKT), and phosphorylated AKT proteins were determined by Western blot assay. The MET and phosphorylated MET proteins were also determined by immunofluorescence assay., Results: HGF increased ARPE-19 cells' viability, proliferation and migration, and induced an increase of phosphorylated MET and phosphorylated AKT proteins. SU11274 significantly reduced cell viability, proliferation, and migration and decreased the expression of MET and AKT proteins. SU11274 suppressed HGF-induced increase of viability, proliferation, and migration in ARPE-19 cells. Additionally, SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins., Conclusion: HGF enhances cellular viability, proliferation, and migration in RPE cells through the MET/AKT signaling pathway, whereas this enhancement is suppressed by the MET inhibitor SU11274. HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival., Competing Interests: Conflicts of Interest: Zhou SR, None; Zhu YS, None; Yuan WT, None; Pan XY, None; Wang T, None; Chen XD, None., (International Journal of Ophthalmology Press.)

Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity., (© 2024. The Author(s).)

Pycnoporus sanguineus is a fungus of the phylum Basidiomycota that has many applications in traditional medicine, modern pharmaceuticals, and agricultural industries. Light plays an essential role in the metabolism, growth, and development of fungi. This study evaluated the mycelial growth and antioxidant and anti-inflammatory activities in P. sanguineus fermentation broth (PFB) cultured under different wavelengths of LED irradiation or in the dark. Compared to the dark cultures, the dry weight of mycelia in red- and yellow-light cultures decreased by 37 and 35% and the yields of pigments increased by 30.92 ± 2.18 mg and 31.75 ± 3.06 mg, respectively. Compared with the dark culture, the DPPH free radical scavenging ability, ABTS + free radical scavenging capacity, and reducing power of yellow-light cultures increased significantly, and their total phenolic content peaked at 180.0 ± 8.34 μg/mL. However, the reducing power in blue-light cultures was significantly reduced, though the total phenol content did not vary with that of dark cultures. In LPS- and IFN-γ-stimulated RAW 264.7 cells, nitrite release was significantly reduced in the red and yellow light-irradiated PFB compared with the dark culture. In the dark, yellow-, and green-light cultures, TNF-α production in the inflamed RAW 264.7 cells was inhibited by 62, 46, and 14%, respectively. With red-, blue-, and white-light irradiation, TNF-α production was significantly enhanced. Based on these results, we propose that by adjusting the wavelength of the light source during culture, one can effectively modulate the growth, development, and metabolism of P. sanguineus., (© 2024. The Author(s), under exclusive licence to the European Photochemistry Association, European Society for Photobiology.)

Purpose: To determine the advantages of next-generation metagenomic sequencing (mNGS) technology in the diagnosis and treatment of infectious keratitis (IK)., Methods: A total of 287 patients with IK admitted to the Department of Ophthalmology of Nanjing First Hospital between August 2018 and December 2022 were analyzed retrospectively, and the pathogenic causes, etiological characteristics, detection, treatment methods, and efficacy were summarized., Results: Trauma and foreign matter were the most common causes of IK (144 patients, 50.2%). Of the 287 patients, 228 (79.4%) were diagnosed with a specific etiology, including 110 (48.2%) fungal infections, 44 (19.3%) viral infections, 42 (18.4%) mixed infections, and 30 (13.2%) bacterial infections. Filamentous fungi represented by Fusarium and Aspergillus were the most common, followed by bacteria such as Pseudomonas aeruginosa , Streptococcus pneumoniae , viruses (Herpes Simplex Virus/Varicella-Zoster Virus), and parasites. The positivity rates of secretion culture, corneal laser confocal microscopy (CM), mNGS, and pathological sections were 47.3% (133/281), 45.3% (111/245), 83.9% (104/124), and 19.3% (40/207), respectively. The positivity rate of mNGS for bacteria and viruses was higher than that of the other methods, and the positivity rate for fungi was the same as that for CM. As a result, 214 cases (74.6%) were cured, 51 cases (17.8%) improved, 8 cases (2.8%) did not heal, ocular content enucleation was performed in 14 cases (4.9%), and the overall efficacy rate was 92.3%., Conclusion: Trauma and foreign matter are the main causes of IK. The mNGS technology is an efficient and comprehensive detection method for viruses and bacteria, especially for mixed infections., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Xin-Yu Pan et al.)

An Fe-catalyzed visible-light induced condensation of alkylbenzenes with anthranilamides has been developed. Upon irradiation, the trivalent iron complex could generate chlorine radicals, which successfully abstracted the hydrogen of benzylic C-H bonds to form benzyl radicals. And these benzyl radicals were converted into oxygenated products under air conditions, which subsequently reacted with anthranilamides for the synthesis of quinazolinones.

A visible-light-induced chemodivergent synthesis of tetracyclic quinazolinones and 3-iminoisoindoliones has been developed. This chemodivergent reaction afforded two kinds of different products by substrate control. A detailed investigation of the reaction mechanism revealed that this consecutive photoinduced electron transfer (ConPET) cascade cyclization involved a radical process, and the aryl radical was the crucial intermediate. This method employed 4-DPAIPN as a photocatalyst and i -Pr 2 NEt as a sacrificial electron donor leading to metal-free conditions.

Background: Reduced graft failure rates have been reported after anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex (ALC) augmentation. However, the preoperative diagnosis of concomitant ALC injury remains a clinical challenge., Purpose: To identify the altered rotational tibiofemoral position on magnetic resonance imaging (MRI) in ACL-injured patients with concomitant ALC injury., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Based on the evaluation of ALC abnormalities on MRI scans by experienced surgeons, 123 patients with nonchronic (<3 months) ACL injury confirmed by arthroscopy were included. The patients were divided into 2 groups-an ALC-injured group (n = 57) and an ALC-intact group (n = 66). The altered rotational tibiofemoral position was evaluated and compared by quantitatively measuring internal rotational tibial subluxation (IRTS) and axial internal tibial rotation (ITR a ) on MRI. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were performed to identify the factors associated with concomitant MRI-determined ALC injury., Results: The ALC-injured group showed significantly increased IRTS ( P < .001), ITR a ( P < .001), lateral anterior tibial subluxation (ATS) ( P < .001), and global ATS (GATS) ( P = .002) compared with the ALC-intact group, while no significant difference in medial ATS ( P = .810) was observed. A strong positive correlation was identified between IRTS and ITR a ( r P = 0.809; P < .001). Multivariate analyses revealed that IRTS ( P < .001) and GATS ( P = .016) were associated factors for the presence of concomitant MRI-determined ALC injury. IRTS (area under the curve [AUC] = 0.734) was more strongly associated with the outcome than GATS (AUC = 0.658) in ROC analyses, suggesting a more significant internal rotational subluxation than anterior subluxation of the tibia. An IRTS threshold of 3.1 mm demonstrated a specificity of 84.2% for indicating the presence of concomitant MRI-determined ALC injury., Conclusion: The presence of concomitant MRI-determined ALC injury in ACL-injured patients was associated with a significant increase in IRTS and ITR a compared with those with intact ALC, indicating that these MRI measurements of the altered rotational tibiofemoral position could serve as potential quantifiable indicators for identifying concomitant ALC injury in clinical practice., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Research support was received from the National Natural Science Foundation of China grant (82072403) and the Clinical Cohort Project Program of Peking University Third Hospital (BYSYDL2021014). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Objective: The aim of this study was to construct a multicompartment synchronous rotating bioreactor (MCSRB) for batch-production of homogenized adipose-derived stem cell (ADSC) microspheres and treat neurogenic erectile dysfunction (ED)., Methods: Firstly, an MCSRB was constructed using a centrifugal device and hinged trays. Secondly, influence factors (density, rotational speed) on the formation of ADSC-spheroids were explored. Finally, a neurogenic ED model was established to verify the effectiveness and safety of ADSC-spheroids for ED treatment., Results: An MCSRB promoted ADSCs to gather microspheres, most of which were 90-130 μm in diameter. Supernatant from three-dimensional culture led to a significant increase in cytokine expression in ADSCs and migration rate in human umbilical vein endothelial cells (HUVECs) compared to control groups. The erectile function and pathological changes of the penis were improved in the ADSC-spheroids treatment group compared to the traditional ADSCs treatment group (p < 0.01)., Conclusion: Efficient, batch, controlled and homogenized production of ADSC stem cell microspheres, and effective improvement of erectile dysfunction in neurogenic rats can be achieved using the MCSRB device., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Scraping therapy is widely used in treating stage I and II essential hypertension in China. However, there has been no systematic evaluation of the efficacy of scraping therapy on blood pressure and sleep quality in stage I and II essential hypertension., Search Strategy: Seven electronic databases (PubMed, Scopus, Cochrane Library, Web of Science, EBSCO, China National Knowledge Infrastructure and Wanfang Data electronic databases) were searched from inception to December 2022. Based on the principle of combining subject words with text words, the search strategy was constructed around search terms for "scraping therapy," "scraping," "Guasha," "Gua sha," "hypertension," and "high blood pressure" during the database searches., Inclusion Criteria: Randomized controlled trials (RCTs) were included if they recruited patients with stage I and II essential hypertension and included a scraping therapy intervention. The intervention group received antihypertensive drugs and scraping therapy, while the control group only took antihypertensive drugs., Data Extraction and Analysis: Review Manager 5.4.0 and STATA 15.1 were used to enter all the relevant outcome variables to conduct the meta-analysis. The quality of the selected RCTs was assessed using the PEDro scale. The sensitivity analysis was carried out by iteratively excluding individual studies and repeating the analysis to determine the stability of the findings and identify any studies with greater influence on the outcome. Subgroup analysis was performed to find the source of heterogeneity. Funnel plots were used to evaluate the publication bias of included studies., Results: Nine RCTs including 765 participants were selected. Meta-analysis showed that scraping therapy combined with medication had an advantage over the use of medication alone in lowering systolic blood pressure (mean difference [MD] = -5.09, 95% confidence interval [CI] = -6.50 to -3.67, P < 0.001) and diastolic blood pressure (MD = -2.66, 95% CI = -3.17 to -2.14, P < 0.001). Subgroup analysis showed that scraping therapy improved sleep quality in middle-aged patients with hypertension, but the efficacy was better in elderly patients (MD = -7.91, 95% CI = -8.65 to -7.16, P < 0.001) than in middle-aged patients (MD = -2.67, 95% CI = -4.12 to -1.21, P = 0.0003)., Conclusion: The available evidence indicates that scraping therapy has significant effects on patients with stage I and II hypertension, and it improves sleep quality for elderly patients with hypertension better than for middle-aged ones. Scraping therapy can be an adjunctive treatment for stage I and II essential hypertension. However, further high-quality studies are needed to verify its effectiveness and the best therapeutic strategies. Please cite this article as: Zhu, Z, Wang J, Pan, X. Efficacy of scraping therapy on blood pressure and sleep quality in stage I and II essential hypertension: A systematic review and meta-analysis. J Integr Med. 2024; 22(1): 12-21., 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 © 2023 Shanghai Changhai Hospital. Published by ELSEVIER B.V. Published by Elsevier B.V. All rights reserved.)

Melatonin,an endocrine hormone synthesized by the pineal gland,plays an important role in the reproduction.The growth and development of follicles is the basis of female mammalian fertility.Follicles have a high concentration of melatonin.Melatonin receptors exist on ovarian granulosa cells,follicle cells,and oocytes.It regulates the growth and development of these cells and the maturation and atresia of follicles,affecting female fertility.This paper reviews the protective effects and regulatory mechanisms of melatonin on the development of ovarian follicles,granulosa cells,and oocytes and makes an outlook on the therapeutic potential of melatonin for ovarian injury,underpinning the clinical application of melatonin in the future.

Background: Erectile dysfunction (ED) and weakness of the penis are processes related to hemodynamic alteration. Low-intensity pulsed ultrasound (LIPUS), as a new mechanical modality for the treatment of ED, deserves to be explored in depth for the biomechanical mechanisms it exerts., Objective: The aim of this study was to explore the role of YAP/TAZ-mediated mechanotransduction in mechanical therapy for the treatment of neurogenic erectile dysfunction (NED)., Materials and Methods: Forty-two male SD rats (12 w old) were randomly divided into sham-operated (n = 14), bilateral cavernous nerve injury (BCNI, n = 14), and LIPUS-treated (n = 14) groups. Intracavernosal pressure/mean arterial pressure (ICP/MAP) was measured 14 and 28 days after treatment. Penile tissue specimens were collected for pathological examination, and the changes in YAP, TAZ, connective tissue growth factor (CTGF), CYR61, LATS1, and p38 mitogen-activated protein kinase expression levels were assessed by Western blot, real-time quantitative polymerase chain reaction (RT-qPCR) and immunological staining., Results: Compared with BCNI, LIPUS significantly improved ICP/MAP levels and enhanced histopathological changes. The penile expression levels of YAP, TAZ, CTGF, and CYR61 were significantly downregulated in the BCNI group (p < 0.01), and LIPUS upregulated the expression levels of these proteins (p < 0.05). The expression levels of p-LATS1 and LATS1 were not significantly different among the groups (p > 0.05). Interestingly, the expression level of p-p38/p38 significantly increased in BCNI rats (p < 0.05), which was reversed by LIPUS treatment (p < 0.05). However, the p38 inhibitor SB203580 did not change the expression of YAP/TAZ in rat primary smooth muscle cells or mouse MOVAS cells (p > 0.05)., Discussion and Conclusion: LIPUS can effectively improve penile erectile function in NED rats. The underlying mechanism may be related to the regulation of YAP/TAZ-mediated mechanotransduction. However, the upstream regulatory signal may differ from the classical Hippo pathway., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Objectives: To evaluate the diagnostic performance in identifying an anterior cruciate ligament (ACL) injury and the reliability between two measuring protocols of anterior tibial subluxation (ATS)., Materials and Methods: A total of 165 patients with ACL injury and 157 ACL-intact patients were included in this study. Two different measuring protocols of ATS were performed on sagittal MR images, including the modified protocol using the longitudinal tibial axis (axis protocol) and the established protocol using a line perpendicular to the tibial plateau (plateau protocol). Receiver-operating characteristic (ROC) curves were calculated to evaluate the diagnostic performance in identifying an ACL injury, and areas under the curves (AUCs) were compared between the two protocols. Intra- and interobserver reliability tests were performed to evaluate the reliability of the measurements., Results: Lateral ATS (P < 0.001) and medial ATS (P < 0.001) were increased in patients with ACL injury under both protocols. To identify an ACL injury, ATS measured under the axis protocol showed higher AUC values than the plateau protocol, including lateral ATS (AUC 0.828 vs. 0.688, P < 0.001), medial ATS (AUC 0.829 vs. 0.789, P = 0.013), and the combined indicator of lateral and medial ATS (AUC 0.885 vs. 0.810, P < 0.001). Reliability tests showed that both protocols were reliable., Conclusions: ATS measured under the modified protocol using the longitudinal tibial axis showed superior diagnostic performance in identifying an ACL injury compared to the established protocol, indicating that the modified protocol may better reflect the characteristics of an ACL-deficient knee., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Objective: To systematically evaluate the efficacy and safety of new systemic therapies (biological agents and JAK inhibitors) in moderate-to-severe elderly atopic dermatitis. Methods: The database of Embase, PubMed, Web of Science,Cochrane, the Global Resource of Eczema Trials database, ClinicalTrials. Gov, CNKI, Wanfang, VIP were used to search for literatures of randomized controlled trials (RCTs) and real-world studies of the treatment of moderate-to-severe AD with the new systemic therapies from January 2014 to February 2023. Two reviewers independently screened the literature, extracted the data and evaluated the risk of bias included in the study. Data were analyzed by Review Manager 5.3 software for meta-analysis and odds ratio ( OR ) and 95% confidence interval were used as the effect statistics. The heterogeneity and publication bias were assessed. Results: A total of five studies (523 elderly patients and 802 young patients) using dupilumab were included for meta-analysis. Dupilumab showed good efficacy in elderly AD, with 74.6%(390/523) of patients whose EASI reached 75, which there was no significant difference with young patients ( OR =0.79, 95% CI :0.58-1.07, P =0.122); the proportion of elderly patients with NRS improvement≥4 was 68.7%(244/355), and there was no significant difference with young patients ( OR =0.79, 95% CI :0.55-1.14, P =0.213). The most common adverse reactions were conjunctivitis, facial and neck erythema and injection site reactions, and there are no serious adverse events in both groups. The incidence of adverse events in elderly patients was 24.3%(65/267), which was not significantly different from that in young patients ( OR =1.07, 95% CI :0.65-1.77, P =0.789). There are few studies on other biological agents and JAK inhibitors in elderly AD patients. We only found 4 studies of elderly AD patients using JAK inhibitors (2 studies on abrocitinib and 2 studies on upadacitinib). The clinical efficacy of abrocitinib in the elderly was not significantly different from that in the young. The incidence of serious adverse events of abrocitinib and upadacitinib increased in the elderly and was dose-related. Conclusion: The efficacy and safety of dupilumab in elderly AD patients were similar to those in the young patients, and the JAK inhibitor needs to be further studied and verified.

Metal injection molding (MIM) is a near net-shape manufacturing process combining conventional plastic injection molding and powder metallurgy. Two kinds of injections molds for MIM were developed using conventional mold steel and aluminum (Al)-filled epoxy resins in this study. The characteristics of the mold made by rapid tooling technology (RTT) were evaluated and compared with that of the fabricated conventional machining method through the MIM process. It was found that the service life of the injection mold fabricated by Al-filled epoxy resin is about 1300 molding cycles with the average surface roughness of 158 nm. The mold service life of the injection mold fabricated by Al-filled epoxy resin is about 1.3% that of the conventional mold steel. The reduction in manufacturing cost of an injection mold made by Al-filled epoxy resin is about 30.4% compared with that of the fabricated conventional mold steel. The saving in manufacturing time of an injection mold made by RTT is about 30.3% compared with that of the fabricated conventional machining method.

Protein Z (PZ), a vitamin-K-dependent anticoagulant glycoprotein, is reported to be highly expressed in various malignant tissues and correlated with a poor prognosis in patients with lung cancer. This study aimed to investigate the pathological activity of PZ on lung cancer cell migration, invasion, and metastasis. PZ was assessed by Western blot in three non-small-cell lung cancer cell lines (A549, H1299, and H1975). Meanwhile,western blot was used to detect the expression of EMT pathway-related proteins (Slug, Vimentin, and N-cadherin) in the A549 cells knocked down with siRNA. The cellular proliferation, migration, and invasion were detected by Cell Counting Kit (CCK)-8, wound healing, and Transwell assays in the A549 cells. The results showed that PZ expression was higher in A549, H1299, and H1975 cells, according to Western blot. CCK-8, wound healing, and Transwell assays showed that knockdown of PZ significantly decreased cellular proliferation, migration, and invasion, as well as the protein levels of Slug, Vimentin, and N-cadherin in the A549 cells. In conclusion, the pro-metastasis activity of PZ may modulate the epithelial-mesenchymal transition pathway in lung cancer A549 cells., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter.)

Glucocorticoids (GCs) are the important stress hormones and widely prescribed as drugs. Although stress has been suggested as a promoter of tumor progression, the direct influence of GCs on metastasis of tumor is not fully understood. Metastasis is a major cause of death in pancreatic cancer patients. In the present study, we investigated the effect of GCs on progression of pancreatic cancer and elucidated the underlying mechanism. It was found that GCs significantly promote cell adhesion, migration, and invasion of pancreatic cancer cells in vitro and their lung metastasis in vivo. Further mechanistic studies showed that GCs notably up-regulate the expression of a trans-membrane glycoprotein, mucin 1 (MUC1) and increase the activation of AKT. Inhibiting MUC1 expression not only attenuates the activation of AKT, but also significantly reduces the promoting effects of GCs on cell adhesion, migration, invasion, and lung metastasis of pancreatic cancer cells. Moreover, GCs not only significantly up-regulate expression of Rho-associated kinase 1/2 (ROCK1/2) and matrix metalloproteinase 3 and 7 (MMP3/7), but also activate ROCK2, which are also involved in the pro-migratory and pro-invasive effects of GCs in pancreatic cancer cells. Taken together, our findings reveal that GCs promote metastasis of pancreatic cancer cells through complex mechanism. MUC1-PI3K/AKT pathway, ROCK1/2 and MMP3/7 are involved in the promoting effect of GCs on cell migration, invasion and metastasis in pancreatic cancer cells. These results suggest the importance of reducing stress and GCs administration in patients with pancreatic cancer to avoid an increased risk of cancer metastasis.

Objective: To analyze the concentrations of glyphosate and its metabolites in occupational exposed workers and their possible effects on human health, so as to provide a reference for improving the safe use of glyphosate and toxicity research. Methods: From April to December 2020, 247 workers directly exposed to glyphosate in 5 enterprises were selected as the contact group, and 237 workers who were not exposed to glyphosate and other pesticides in the same enterprise were selected as the control group. Questionnaire survey and occupational health examination were conducted on objects, and the concentrations of glyphosate and its metabolites in the air of workplaces and biological samples were detected. The correlation between the concentrations and the difference of health examination between the two groups were analyzed. Results: The urine glyphosate concentration (0.022-47.668 mg/L), the rate of exceeding the standard (60.32%, 149/247) and the urine aminomethyl phosphonic acid concentration (<0.010-1.624 mg/L) in the contact group were higher than those in the control group [urine glyphosate concentration (<0.020-4.482 mg/L), the rate of exceeding the standard (2.53%, 6/237) and the urine aminomethyl phosphonic acid concentration (<0.010-0.524 mg/L) ], respectively ( P <0.001). The exceeding standard rate of glyphosate concentration in the workplace was 33.67% (33/98). The concentration of glyphosate in the workplace was positively correlated with the concentrations of glyphosate and aminomethylphosphonic acid in urine ( r (s)=0.804, 0.238, P <0.001), and the concentration of glyphosate in urine was positively correlated with the concentration of aminomethylphosphonic acid in urine ( r (s)=0.549, P <0.001). The alanine aminotransferase (ALT), white cell ratio, creatinine, uric acid, the abnormal rates of ALT and total protein (TP) in the contact group were higher than those in the control group, and TP was lower than that in the control group, the differences were statistically different ( P <0.05). The abnormal rates of overall liver function, overall renal function, blood routine test, urine routine test, electrocardiogram, liver B ultrasound and blood lipid in the contact group were significantly higher than those in the control group ( P <0.05) . Conclusion: The concentration of glyphosate in the workplace is related to the concentrations of glyphosate and aminomethyl phosphonic acid in the urine of workers, and exposure to glyphosate may have some harmful effects on human health.

Over the past decade, iterative projection algorithms, an effective approach to recovering phases from a single intensity measurement, have found application in protein crystallography to directly surmount the `phase problem'. However, previous studies have always assumed that some prior knowledge constraints (i.e. a low-resolution envelope about the protein structure in the crystal cell or histogram matching requiring a similar density distribution to the target crystal) must be known for successful phase retrieval, thus hindering its widespread application. In this study, a novel phase-retrieval workflow is proposed that eliminates the need for a reference density distribution by utilizing low-resolution diffraction data in phasing algorithms. The approach involves randomly assigning one out of 12 possible phases at 30° intervals (or two for centric reflections) to produce an initial envelope, which is then refined through density modification after each run of phase retrieval. To evaluate the success of the phase-retrieval procedure, information entropy is introduced as a new metric. This approach was validated using ten protein structures with high solvent content, demonstrating its effectiveness and robustness.

Biochar can inhibit soil acidification by decreasing the H + input from nitrification and improving soil pH buffering capacity (pHBC). However, biochar is a complex material and the roles of its different components in inhibiting soil acidification induced by nitrification remain unclear. To address this knowledge gap, dissolved biochar fractions (DBC) and solid biochar particles (SBC) were separated and mixed thoroughly with an amended Ultisol. Following a urea addition, the soils were subjected to an incubation study. The results showed that both the DBC and SBC inhibited soil acidification by nitrification. The DBC inhibited soil acidification by decreasing the H + input from nitrification, while SBC enhanced the soil pHBC. The DBC from peanut straw biochar (PBC) and rice straw biochar (RBC) decreased the H + release by 16 % and 18 % at the end of incubation. The decrease in H + release was attributed to the inhibition of soil nitrification and net mineralization caused by the toxicity of the phenols in DBC to soil bacteria. The abundance of ammonia-oxidizing bacteria (AOB) and total bacteria decreased by >60 % in the treatments with DBC. The opposite effects were observed in the treatments with SBC. Soil pHBC increased by 7 % and 19 % after the application of solid RBC and PBC particles, respectively. The abundance of carboxyl on the surface of SBC was mainly responsible for the increase in soil pHBC. Generally, the mixed application of DBC and SBC was more effective at inhibiting soil acidification than their individual applications. The negative impacts of dissolved biochar components on soil microorganisms need to be closely monitored., 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 © 2023 Elsevier B.V. All rights reserved.)

Our previous study has shown that ATP action on P2X7R could be the second signal to induce the onset of gouty arthritis. However, the functional changes of P2X7R single nucleotide polymorphisms (SNPs) on the effects of ATP-P2X7R-IL-1β signaling pathway and uric acid remained unknown. We aimed to investigate the association between the functional change of P2X7R containing the Ala 348 to Thr polymorphisms (rs1718119) and the pathogenesis of gout. First, 270 gout patients and 70 hyperuricemic patients (without gout attack history in recent 5 years) were recruited for genotyping. In addition, the changes of ATP-induced pore formation were assessed in HEK-293T cells overexpressing different mutants in P2RX7, and the effects on P2X7R-NLRP3-IL-1β pathway activation were explored in P2RX7 overexpression THP-1 cells. The risk allele for gout was A at rs1718119, and the AA and AG genotypes exhibited a higher risk of gout. Furthermore, Ala 348 to Thr mutants increased P2X7-dependent ethidium + bromide uptake, upregulated IL-1β and NLRP3 levels as compared to the wild-type. We suggest that genetic polymorphisms of P2X7R containing the Ala 348 to Thr are associated with the increased risk of gout, showing an enhanced gain-of-function effect on the development of this disease., (© 2023. The Author(s).)

Objective: To analyze the electroencephalogram (EEG) features of anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) and to study the clinical assessment value of the degree of EEG background slowing and the presence of δ brush., Methods: We enrolled 52 patients with anti-NMDARE and collected their clinical data, including age, sex, form of disease onset, status of tumor comorbidity, auxiliary examination findings (cerebrospinal fluid [CSF] anti-methyl-D-aspartate receptor antibody titers, magnetic resonance imaging [MRI] reports, and EEG results), treatment status, and follow-up after discharge. The degree of EEG background abnormality and the presence of δ brush in the EEG of patients with different clinical features were analyzed., Results: Among the 52 patients, 7 (14%) had normal EEG, and 45 (87%), abnormal EEG, including 25 (48%) with mild abnormalities, 11 (21%) with moderate abnormalities, and 9 (17%) with severe abnormalities. δ brush was seen in 6 (12%) patients. At the time of EEG, 32 (62%) patients were in the mild condition group and 20 (38%) patients were in the severe condition group. After 1 year of follow-up, there were 45 (86%) patients in the good prognosis group and 7 (14%) patients in the poor prognosis group. The exacerbation of EEG background abnormalities and the presence of δ brush were indications for an increase in the proportion of patients who were in severe condition, who needed ICU admission, and who had poor prognosis ( P <0.01). The worse the EEG background abnormalities, the higher the proportion of CSF antibody titers>1∶10 ( P =0.035), and the higher the proportion of patients initiating second-line immunotherapy ( P =0.008). The δ brush was seen a higher proportion in patients with comorbid tumors ( P =0.012). The probability of δ brush presence was higher in the first-time diagnosis cases than that in recurrent cases ( P =0.023)., Conclusions: The degree of EEG slowing and the presence of δ brush have shown consistent performance in assessing patients' condition and predicting prognosis. The slower the EEG, the more severe the disease, and the worse the prognosis. The presence of δ brush indicates severe disease and poor prognosis. EEG slowing is correlated with the immune status of patients with anti-NMDARE. The slower the EEG, the more severe the immune abnormalities. In clinical practice, patient EEG should be under dynamic monitoring in order to evaluate the effect of immunotherapy. If EEG slowing is not improved, enhanced immunotherapy should be considered as early as possible. The δ brush is seen at a higher proportion in patients with comorbid tumors. Therefore, active efforts should be made to screen for tumors when δ brush is present., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

The clinical benefits of diquafosol tetrasodium (DQS), a hydrophilic P2Y2 receptor agonist for dry eye, have been hindered by a demanding dosing regimen. Nevertheless, it is challenging to achieve sustained release of DQS with conventional drug delivery vehicles which are mainly designed for hydrophobic small molecule drugs. To address this, we developed an affinity hydrogel for DQS by taking advantage of borate-mediated dynamic covalent complexation between DQS and hydroxypropyl guar. The resultant formulation (3% DQS Gel) was characterized by sustained release, low corneal permeation, and extended ocular retention, which were desirable attributes for ocular surface drug delivery. Both in vitro and in vivo studies had been carried out to verify the biocompatibility of 3% DQS Gel. Using corneal fluorescein staining, the Schirmer's test, PAS staining, quantitative PCR and immunohistological analyses as outcome measures, the superior therapeutic effects of 3% DQS Gel over PBS, the hydrogel vehicle and free DQS were demonstrated in a mouse dry eye model. Our DQS delivery strategy reported herein is readily applicable to other hydrophilic small molecule drugs with cis-diol moieties, thus providing a general solution to improve clinical outcomes of numerous diseases., Competing Interests: Declaration of Competing Interest J.J.W, X.X.L, T.Z.W, and K.H.N have a pending patent application related to this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Preeclampsia (PE) is characterised by systemic vascular endothelium dysfunction. Circulating trophoblastic secretions contribute to endothelial dysfunction, resulting in PE; however, the underlying mechanisms remain unclear. Herein, we aimed to determine the potential correlation between the release of trophoblastic mitochondrial deoxyribonucleic acid (DNA) (mtDNA) and endothelium damage in PE., Materials and Methods: Umbilical cord sera and tissues from patients with PE were investigated for inflammasome activation. Following this, trophoblastic mitochondria were isolated from HTR-8/SVneo trophoblasts under 21 % oxygen (O 2 ) or hypoxic conditions (1 % O 2 for 48 h) for subsequent treatments. Primary human umbilical veinendothelial cells (HUVECs) were isolated from the human umbilical cord and then exposed to a vehicle (phosphate-buffered saline [PBS]), mtDNA, hypo-mtDNA, or hypo-mtDNA with INF39 (nucleotide oligomerisation domain-like receptor family pyrin domain containing 3 [NLRP3]-specific inhibitor) for 12 h before flow cytometry and immunoblotting. The effects of trophoblastic mtDNA on the endothelium were further analysed in vivo using enzyme-linked immunosorbent assay (ELISA) and vascular reactivity assay. The effects of mtDNA on vascular phenotypes were also tested on NLRP3 knockout mice., Results: Elevated interleukin (IL)-1β in PE sera was accompanied by NLRP3 inflammasome activation in cord tissues. In vitro and in vivo experiments revealed that the release of trophoblastic mtDNA could damage the endothelium via NLRP3 activation, resulting in the overexpression of NLRP3, caspase-1 p20, IL-1β p17, and gasdermin D (GSDMD); reduced endothelial nitric oxide synthase (eNOS) levels; and impaired vascular relaxation. Flow cytometric analysis confirmed that extensive cell death was induced by mtDNA, and simultaneously, a more pronounced pro-apoptotic effect was caused by hypoxia-treated trophoblastic mtDNA. The NLRP3 knockout or pharmacologic NLRP3 inhibition partially reversed tumour necrosis factor-α (TNF-α) and IL-1β levels and endothelium-dependent vasodilation in mice., Conclusion: These findings demonstrate that trophoblastic mtDNA induced NLRP3/caspase-1/IL-1β signalling activation, eNOS-related endothelial injury, and vasodilation dysfunction in PE., 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 © 2022 Elsevier B.V. All rights reserved.)

Dry eye disease (DED) is a widespread and frequently reported multifactorial ocular disease that not only causes ocular discomfort but also damages the cornea and conjunctiva. At present, topical administration is the most common treatment modality for DED. Due to the existence of multiple biological barriers, instilled drugs generally exhibit short action times and poor penetration on the ocular surface. To resolve these issues, several advanced drug delivery systems have been proposed. This review discusses new dosage forms of drugs for the treatment of DED in terms of their characteristics and advantages. Innovative formulations that are currently available in the market and under clinical investigation are elaborated. Meanwhile, their deficiencies are discussed. It is envisioned that the flourishing of advanced drug delivery systems will lead to improved management of DED in the near future.

Objective: To explore clinical effect of the first metatarsophalangeal joint fusion combined with lateral toe rotation Weil osteotomy in treating hallux valgus with severe metatarsal adduction., Methods: From March 2017 to August 2021, 37 patients ( 69 feet ) with severe plantar adductor hallux valgus were treated with the first metatarsophalangeal joint fusion combined with rotational Weil osteotomy were retrospectively analyzed, including 8 males(11 feet) and 29 females (58 feet), aged from 67 to 83 years old with an average of (70.03±2.87) years old;3 cases on the left side, 2 cases on the right side and 32 cases on both sides. Visual analogue scale(VAS) was used to evaluate degree of pain relief before operation, 6 weeks after operation and at the final follow-up. American Orthopaedic Foot and Ankle Surgery (AOFAS) forefoot score was used to evaluate function of the affected foot before operation and final follow-up. Hallux valgus angle(HVA) and intermetatarsal angle(IMA) were measured before operation and at the final follow-up., Results: Thirty-seven patients(69 feet) were followed up from 12 to 48 months with an average of(22.8±0.6) months. Bone healing was achieved at the first metatarsophalangeal joint from 7 to 10 weeks with an average of (8.00±1.21) weeks after operation, without delay and nonunion. HVA was increased from (44.30±2.84)° before operation to (15.20±2.13) °at the final follow-up, and had statistical difference( t =65.781, P <0.05);while no difference in IMA before and after operation( P >0.05). VAS was decreased from (6.73±1.48) points to (2.78±0.71) points at 6 months after operation( t =3.279, P <0.05), and had difference compared with the latest follow-up(1.16±1.12)( t =4.859, P <0.05). AOFAS forefoot score increased from (52.14±5.78) preoperatively to (86.70±4.86) at the fonal follow-up, and 25 feet got excellent results, 40 feet good and 4 feet fair., Conclusion: The first metatarsophalangeal joint fusion combined with lateral toe rotation Weil osteotomy in treating severe plantar adduction hallux valgus could significantly relieve pain and appearance of forefoot, stabilize the first sequence, and significantly improve walking function.

In condensed-matter systems, electrons are subjected to two different interactions under certain conditions. Even if both interactions are weak, it is difficult to perform perturbative calculations due to the complexity caused by the interplay of two interactions. When one or two interactions are strong, ordinary perturbation theory may become invalid. Here we consider undoped graphene as an example and provide a non-perturbative quantum-field-theoretic analysis of the interplay of electron-phonon interaction and Coulomb interaction. We treat these two interactions on an equal footing and derive the exact Dyson-Schwinger (DS) integral equation of the full Dirac-fermion propagator. This equation depends on several complicated correlation functions and thus is difficult to handle. Fortunately, we find that these correlation functions obey a number of exact identities, which allows us to prove that the DS equation of full fermion propagator is self-closed. After solving this self-closed equation, we obtain the renormalized fermion velocity and show that its energy (momentum) dependence of renormalized fermion velocity is dominantly determined by the electron-phonon (Coulomb) interaction. In particular, the renormalized velocity exhibits a logarithmic momentum dependence and a non-monotonic energy dependence., (© 2022 IOP Publishing Ltd.)

Although many studies have investigated functional molecules in extracellular vesicles (EVs), the exact number of ribonucleic acid molecules in a single-EV is unknown. Therefore, it is critical to explore the transcriptomic features and heterogeneity at the level of a single-EV. Here, using the 10x Genomics platform, the RNA cargos are profiled in single EVs derived from human K562 and mesenchymal stem cells. The key steps are labeling intact EVs using calcein-AM, detecting the EV concentration via flow cytometry, and using the CB2 algorithm with adaptive thresholds to effectively distinguish real EVs from background. The gene number in a single-EV varied from 6 to 148, with a mean of 52. Ribosomal genes, mitochondrial genes, and eukaryotic translation elongation factor 1 alpha has a high EV percentage in all EV samples. Hemoglobin genes are uniquely highly expressed in K562-EVs, and cytoskeleton genes are enriched in MSC-EVs. Ten or more clusters with different marker genes in each single-EV dataset demonstrated EV heterogeneity. Moreover, integrating EVs and their parental cells reveal both EVs and cells in each cluster, indicating different cell origins of various EVs. To the best of the author's knowledge, this study provides the first high-throughput transcriptome at the single-EV level and improves the understanding of EVs., (© 2022 Wiley-VCH GmbH.)

Purpose: Anatomic factors, such as posterior tibial slope (PTS) and anterior tibial subluxation (ATS) obtained by quantitative measurement, have been proposed as predictors for clinical outcomes of anterior cruciate ligament (ACL) reconstruction. However, the correlation between PTS and ATS is controversial, and the method for quantitative ATS measurement remains unsettled. This study aimed to identify the correlation between PTS and ATS in patients with injured and intact ACLs and compare the two ATS measuring protocols., Methods: This study included 128 ACL-injured and 176 ACL-intact patients with no concomitant ligament injuries. PTS and ATS were measured on sagittal MRI. ATS was measured using two measuring protocols, including the modified protocol using the longitudinal tibial axis (axis protocol) and the established protocol using a line perpendicular to the tibial plateau (plateau protocol). Correlation analyses between PTS and ATS and between PTS and the difference in the ATS value measured under the two protocols (ATS diff ) were performed. The difference between the two ATS measuring protocols was further analyzed by trigonometric analysis. Intra- and interobserver reliability tests were performed for the axis protocol., Results: Under the axis protocol, ATS was positively correlated with PTS in both the ACL-injured and ACL-intact groups (p < 0.001). Under the plateau protocol, no correlation was observed in the ACL-injured group. In the ACL-intact group, no correlation was observed for lateral ATS, and a negative correlation was observed for medial ATS (p = 0.001). ATS diff was positively correlated with PTS (p < 0.001), indicating that the two protocols varied greatly in those with a steep PTS. Trigonometric analysis showed that a steep PTS influenced the measurement of ATS under the plateau protocol but not the axis protocol. Intra- and interobserver reliability tests showed good-to-excellent strength of reliability for the ATS measurement under the axis protocol., Conclusion: ATS measured under the axis protocol was positively correlated with PTS, indicating that a steep PTS was associated with a worse anatomic tibiofemoral relationship. The axis protocol for ATS measurement is a promising method for clinical use since it is not influenced by PTS and reflects the global position of the tibia., Level of Evidence: III., (© 2022. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Papilio machaon was assigned as the type species for all butterflies by Linnaeus and P. bianor is a congener but exhibits a great difference in morphology (especially larva and adult color pattern) and larval host plants from P. machaon. Thus, they are the ideal models to investigate genetic mechanisms underlying morphology and plasticity between congeners. The reference genomes of both species were dissected in our previous studies, but little is known about their regulatory genome and the epigenetic regulation of gene expression throughout developmental stages. Here, we profiled the chromatin accessibility and gene expression of three developmental stages (the 4th instar larva [L4], the 5th instar larva [L5], and pupa [P]) using transposase accessible chromatin sequencing (ATAC-seq) and RNA-seq. Results showed that many accessible chromatin peaks were identified at three developmental stages (peak number, P. machaon: 44,977 [L4], 36,919 [L5], 47,147 [P]; P. bianor: 20,341 [L4], 44,668 [L5], 62,249 [P]). Moreover, the number of differentially accessible peaks and differentially expressed genes between larval stages of each butterfly species are significantly fewer than that between larval and pupal stages, suggesting a higher similarity within larvae and a significant difference between larvae and pupae. This study added the annotated information of chromatin accessibility genome-wide of the two papilionid species and will promote the investigation of gene regulation in butterfly evolution., (© 2022 Wiley Periodicals LLC.)

Background/purpose of the Study: Although low skeletal muscle mass is associated with non-alcoholic fatty liver disease (NAFLD), it is currently uncertain whether there are associations between weight-adjusted appendicular skeletal muscle (ASM%), severity of histological features of NAFLD, and the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism. Our aim was to test for a possible influence of the PNPLA3 rs738409 variant on the association between ASM% and severity of NAFLD histological features., Methods: We enrolled 401 Chinese male with biopsy-proven NAFLD. Using a bioelectrical-impedance body composition analyzer (BIA, Inbody 720, Japan Inc., Tokyo), we calculated the ASM% as the percentage of total appendicular skeletal muscle mass (ASM, kg)/total body mass (kg) × 100., Results: Compared to those with high ASM%, patients with low ASM% (≤ 30.6, i.e., the median value of distribution of the whole sample) had a greater severity of individual histological features of NAFLD. These patients also had a higher risk of severe steatosis and non-alcoholic steatohepatitis (NASH) (adjusted-odds ratio [OR] 2.34, 95% CI 1.39-3.93, and adjusted-OR 2.22, 95% CI 1.30-3.77) even after adjusting for age, body mass index, diabetes, and serum creatinine levels. Carriage of the G allele of PNPLA3 rs738409 plus low ASM% was associated with a higher risk of severe steatosis and presence of liver fibrosis (OR 3.02, 95% CI 1.46-6.26, p = 0.003 and OR 2.18, 95% CI 1.03-4.60, p = 0.041 respectively), and there was a non-significant but borderline increased risk of NASH (OR 2.00, 95% CI 0.98-4.06, p = 0.056)., Conclusions: Low ASM% and the presence of a G allele within PNPLA3 rs738409 is associated with more severe histological features of NAFLD., (© 2022. Asian Pacific Association for the Study of the Liver.)