Search

Aggarwal J, Lustrino J, Stephens J, Morgenstern D, Tang WY. Clinicoecon Outcomes Res. 2020;12:389–397. Tables 1– 4 on pages 391-394, the reference citations listed in the Data Source columns are incorrect. The correct Tables 1– 4 are shown below. Page 397, references 41 and 42 are missing from the reference list. These references are shown below. 41. Jelacic S, Craddick K, Nair BG, et al. Relative Costs of Anesthesiologist Prepared, Hospital Pharmacy Prepared and Outsourced Anesthesia Drugs. Journal of Clinical Anesthesia. 2017;36:178-183. 42. van der Linden P, Douchamps J, Schmitt C, Forget D. Ready-to-Use Injection Preparations versus Conventional Reconstituted Admixtures: Economic Evaluation in a Real- Life Setting. PharmacoEconomics. 2002;20(8):529-536. Read the original article

Kashyap B Patel,1 Luiz H Arantes Jr,2 Wing Yu Tang,3 Selwyn Fung4 1Carolina Blood and Cancer Care, Rock Hill, SC, USA; 2Biosimilars Global Medical Affairs, Pfizer Essential Health, Pfizer Inc. New York, NY, USA; 3Health Economics and Outcomes Research, Pfizer Health & Impact, Pfizer Essential Health, Pfizer Inc. New York, NY, USA; 4Pfizer Essential Health Research & Development, Pfizer Inc. New York, NY, USA Abstract: Biopharmaceuticals (biologics) represent one of the fastest growing sectors of cancer treatment. They are recommended for treating underlying cancer and as supportive care for management of treatment side effects. Given the high costs of cancer care and the need to balance health care provision and associated budgets, patient access and value are the subject of discussion and debate in the USA and globally. As the costs of biologics are high, biosimilars offer the potential of greater choice and value, increased patient access to treatment, and the potential for improved outcomes. Value-based care aims to improve the quality of care, while containing costs. The Centers for Medicare & Medicaid Services (CMS) has developed value-based care programs as alternatives to fee-for-service reimbursement, including in oncology, that reward health care providers with incentive payments for improving the quality of care they provide. It is anticipated that CMS payments in oncology care will be increasingly tied to measured performance. This review provides an overview of value-based care models in oncology with a focus on CMS programs and discusses the contribution of biosimilars to CMS value-based care objectives. Biosimilars may provide an important tool for providers participating in value-based care initiatives, resulting in cost savings and efficiencies in the delivery of high-value care through expanded use of biologic treatment and supportive care agents during episodes of cancer care. Keywords: biologics, biosimilars, oncology, patient access, value-based care, supportive care

Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions primarily affecting the gastrointestinal tract. Previous studies established the role of the NF-κB signaling pathway in the development of IBDs, suggesting that anti-inflammatory therapies might offer a viable treatment strategy. Tanshinone IIA and salviadione, both derived from Salviae Miltiorrhizae Radix et Rhizoma, possess anti-inflammatory and anti-oxidative activities. A series of new compounds were synthesized by hybridizing salviadione with tanshinone. Among these compounds, 15a showed beneficial effects in LPS-induced acute lung injury and diabetes-induced renal injury mouse models. The current study explored the therapeutic efficacy of 15a using both acute and chronic colitis models and elucidated the underlying mechanisms. DSS-induced colitis models were established in mice, where acute colitis was treated with compound 15a (5 or 10 mg·kg -1 ·d -1 ) for 8 days, while chronic colitis mice received compound 15a (5 or 10 mg·kg -1 ·d -1 , i.g.) during 2.5% DSS administration. The 15a treatment significantly alleviated DSS-induced pathological and inflammatory damages in both acute and chronic colitis mouse models. In mouse intestinal epithelial cell line MODE-K, pretreatment with compound 15a (5 or 10 μM) significantly suppressed LPS + L18-MDP-induced inflammatory responses. The receptor-interacting serine/threonine kinase 2 (RIPK2) was identified as a direct binding target of compound 15a using microarrays and recombinant human proteins. Moreover, 15a could directly bind to and inhibit the phosphorylation of RIPK2, leading to the suppression of the NF-κB and MAPK signaling pathways. Furthermore, LEU153 and VAL32 were identified within the KD domain of RIPK2 as critical amino residues for the binding of 15a. Briefly, the current findings demonstrate that compound 15a holds promise as a therapeutic agent for managing acute and chronic colitis., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Xianglian pill (XLP) is a traditional Chinese medicine (TCM) that is widely used to treat ulcerative colitis (UC). However, its mechanism of action in UC is unclear., Purpose: This study aimed to investigate the mechanism of action of XLP in treating UC and role of M1 macrophage polarization in this process., Study Design: In vivo experiments were performed using UC mice while in vitro experiments were conducted using RAW264.7 cells., Methods: Mice were administered 3 % dextran sulfate to induce UC model and then treated with XLP. Changes in histopathology and pro-inflammatory cytokines were evaluated. The levels of M1 macrophages in mesenteric lymph nodes were detected by flow cytometry. Colon metabolite levels were analyzed using an energy metabolomic assay. To assess itaconate's impact, both in vivo (mice) and in vitro (RAW264.7 cells) models were employed. Immunofluorescence staining was used to measure the expression levels of TNF-α, IL-6, and iNOS, while qRT-PCR was utilized to quantify the mRNA levels of TET2, STAT1, and Nfkbiz., Results: XLP alleviated ulcerative damage and reduced TNF-α and IL-6 levels in colon, and also downregulated the levels of M1 macrophages and modulated the state of energy metabolism. Specifically, XLP significantly increased ITA level in colonic tissue and this increase was significantly associated with decreased levels of M1 macrophages and alleviation of UC following XLP treatment. Moreover, ITA directly suppressed the polarization of macrophage from M0 to M1 phenotype, accompanied by the decrease of TNF-α, IL-6, and iNOS levels. Further, ITA decreased inflammatory responses in M1 macrophage by inhibiting the TET2/STAT1 and TET2/NF-κB signaling pathways., Conclusion: XLP can treat UC by suppressing M1 macrophage polarization via increasing the level of energy metabolite ITA., Competing Interests: Declaration of competing interest The authors have no relevant interests to disclose. The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

B cells play a critical role in the adaptive recognition of foreign antigens through diverse receptor generation. While targeted immune sequencing methods are commonly used to profile B cell receptors (BCRs), they have limitations in cost and tissue availability. Analyzing B cell receptor profiling from non-targeted transcriptomics data is a promising alternative, but a systematic pipeline integrating tools for accurate immune repertoire extraction is lacking. Here, we present bcRflow, a Nextflow pipeline designed to characterize BCR repertoires from non-targeted transcriptomics data, with functional modules for alignment, processing, and visualization. bcRflow is a comprehensive, reproducible, and scalable pipeline that can run on high-performance computing clusters, cloud-based computing resources like Amazon Web Services (AWS), the Open OnDemand framework, or even local desktops. bcRflow utilizes institutional configurations provided by nf-core to ensure maximum portability and accessibility. To demonstrate the functionality of the bcRflow pipeline, we analyzed a public dataset of bulk transcriptomic samples from COVID-19 patients and healthy controls. We have shown that bcRflow streamlines the analysis of BCR repertoires from non-targeted transcriptomics data, providing valuable insights into the B cell immune response for biological and clinical research. bcRflow is available at https://github.com/Bioinformatics-Core-at-Childrens/bcRflow., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Obeticholic acid (OCA), a semisynthetic bile acid derivative, was approved for its therapeutic use in primary biliary cirrhosis. OCA has a enterohepatic circulation and host-gut microbiota metabolic interaction, which produce various metabolites. Such metabolites, especially structural isomers of OCA, together with the need to achieve idea lower limit of quantitation (LLOQ) with minimum matrix interference, bring about significant difficulties to the bioanalysis of OCA. Herein, by applying a combination of solid-phase extraction (SPE) and ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), we introduced an approach for the bioanalysis of OCA along with its two major metabolites-glyco-OCA (GOA) and tauro-OCA (TOA) in human plasma, the full validation results of which showed excellent performance. The quantitative range is 0.2506 ∼ 100.2 ng/mL for OCA, 0.2500 ∼ 100.0 ng/mL for GOA, as well as 0.1250 ∼ 50.00 ng/mL for TOA, respectively. This method was successfully applied to the pharmacokinetic studies in healthy subjects following administration of OCA tablets., 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 tkt (transketolase) gene is one of the seven gene fragments used in the multilocus sequence typing (MLST) system for Streptococcus agalactiae . We discovered that the tkt_134 allele is derived from a homologous gene (which we designate tktX ) that is not present in all S. agalactiae ; all known strains that contain a match to the tkt_134 allele also contain a gene sequence that is much closer in sequence identity to the other non-tkt_134 alleles (i.e., the canonical tkt gene) in the database. Based on these data, the tkt_134 allele has been removed from the MLST database as of September 2021, and all sequence types containing tkt_134 have also been removed.IMPORTANCEMultilocus sequence typing (MLST) databases are a common good and remain important for research, medical, and epidemiological purposes. This remains true even in the context of widespread whole-genome sequencing. We discovered a contaminating allele of the tkt gene in the S. agalactiae MLST database that led to unstable, ambiguous, or erroneous MLST assignment. The allele has since been removed from the public database based on the results presented in this manuscript., Competing Interests: The authors declare no conflict of interest.

Few studies have focused on the risk factors for necrotizing enterocolitis (NEC) in small for gestational age (SGA) infants. The aim of this study was to identify the risk factors for NEC in SGA newborns. This study included consecutive SGA neonates admitted to a tertiary hospital in Jiangxi Province, China from Jan 2008 to Dec 2022. Patients with NEC (Bell's stage ≥ II) were assigned to the NEC group. Gestational age- and birth weight-matched non-NEC infants born during the same period at the same hospital were assigned to the control group. The risk factors associated with NEC were analyzed with univariate and logistic regression models. During the study period, 2,912 SGA infants were enrolled, 150 (5.15%) of whom developed NEC. In total, 143 patients and 143 controls were included in the NEC and control groups, respectively. Logistic regression analysis revealed that sepsis (OR 2.399, 95% CI 1.271-4.527, P = 0.007) and anemia (OR 2.214, 95% CI 1.166-4.204, P = 0.015) might increase the incidence of NEC in SGA infants and that prophylactic administration of probiotics (OR 0.492, 95% CI 0.303-0.799, P = 0.004) was a protective factor against NEC. Therefore, sepsis, anemia and a lack of probiotic use are independent risk factors for NEC in SGA infants., (© 2024. The Author(s).)

The progression of atherosclerosis (AS), the pathological foundation of coronary artery disease (CAD), is featured by massive lipid deposition in the vessel wall. LncRNAs are implicated in lipid disorder and AS, whereas the specific role of lncRNA DANCR in atherogenesis remains unknown. Here, we demonstrated that DANCR promotes macrophage lipid accumulation by regulating the expression of membrane cholesterol transport proteins. qPCR showed that compared to control groups, CAD patients and atherosclerotic mice had higher DANCR levels. Treating human THP-1 macrophages and mouse RAW264.7 macrophages with ox-LDL significantly upregulated the expression levels of DANCR. Oil Red O staining showed that the silence of DANCR robustly reduced, while overexpression of DANCR significantly increased the numbers and size of lipid droplets in ox-LDL-treated THP-1 macrophages. In contrast, the opposite phenomena were observed in DANCR overexpressing cells. The expression of ABCA1, ABCG1, SR-BI, and NBD-cholesterol efflux was increased obviously by DANCR inhibition and decreased by DANCR overexpression, respectively. Furthermore, transfection with DANCR siRNA induced a robust decrease in the levels of CD36, SR-A, and Dil-ox-LDL uptake, while DANCR overexpression amplified the expression of CD36, SR-A and the uptake of Dil-ox-LDL in lipid-laden macrophages. Lastly, we found that the effects of DANCR on macrophage lipid accumulation and the expression of membrane cholesterol transport proteins were not likely related to miR-33a. The present study unraveled the adverse role of DANCR in foam cell formation and its relationship with cholesterol transport proteins. However, the competing endogenous RNA network underlying these phenomena warrants further exploration.

Objective: To investigate the efficacy of pars plana vitrectomy (PPV) without intraocular tamponade in the treatment of high myopic eyes with myopic foveoschisis (MF) accompanied by foveal detachment (FD). Methods: A retrospective case series study was conducted. The medical records of patients diagnosed with unilateral MF accompanied by FD at the Eye & ENT Hospital of Fudan University between May 2018 and December 2021 were collected. All patients underwent 23-gauge PPV with posterior vitreous cortex clearance, and no intraocular tamponade was applied. The cases were divided into groups based on whether the internal limiting membrane was peeled during surgery or retained. Follow-up was conducted for at least 12 months. The main outcome measures included postoperative best-corrected visual acuity (BCVA, converted to logarithm of the minimum angle of resolution), central foveal thickness (CFT), MF resolution, and complications. Statistical analyses were performed using t -tests, chi-square tests, Fisher's exact tests, and univariate and multivariate linear regression. Results: A total of 40 patients (40 eyes) with MF and FD were included in the study, with 30.0% being male and 70.0% female. The mean age was (56.9±11.7) years, and the axial length of the eyes was (29.1±1.9) mm. At 12 months postoperatively, BCVA improved from baseline 1.15±0.58 to 0.73±0.39 ( t =6.11, P <0.001), and CFT decreased from baseline (610.1±207.2) μm to (155.9±104.1) μm ( t =13.47, P <0.001). Complete resolution of MF with foveal reattachment was observed in 80.0% of eyes, with a median time of 6 (5, 8) months. There was no significant difference in BCVA and CFT between the internal limiting membrane peeled group and retained group [0.68±0.39 vs. 0.79±0.40, t =0.85, P =0.403; (148.3±63.8) vs. (164.3±137.2)um, t =0.48, P =0.634]. One eye experienced macular hole and another eye developed retinal detachment postoperatively. Correlation analysis showed a positive correlation between BCVA at 12 months postoperatively and baseline BCVA ( β =0.433, P <0.001). Conclusions: Pars plana vitrectomy without intraocular tamponade is effective in treating MF accompanied by FD. The choice between internal limiting membrane peeling and retention does not significantly affect visual prognosis.

Chronic obstructive pulmonary disease (COPD) remains a major public health challenge that contributes greatly to mortality and morbidity worldwide. Although it has long been recognized that the epithelium is altered in COPD, there has been little focus on targeting it to modify the disease course. Therefore, mechanisms that disrupt epithelial cell function in patients with COPD are poorly understood. In this study, we sought to determine whether epigenetic reprogramming of the cell-cell adhesion molecule E-cadherin, encoded by the CDH1 gene, disrupts epithelial integrity. By reducing these epigenetic marks, we can restore epithelial integrity and rescue alveolar airspace destruction. We used differentiated normal and COPD-derived primary human airway epithelial cells, genetically manipulated mouse tracheal epithelial cells, and mouse and human precision-cut lung slices to assess the effects of epigenetic reprogramming. We show that the loss of CDH1 in COPD is due to increased DNA methylation site at the CDH1 enhancer D through the downregulation of the ten-eleven translocase methylcytosine dioxygenase (TET) enzyme TET1 . Increased DNA methylation at the enhancer D region decreases the enrichment of RNA polymerase II binding. Remarkably, treatment of human precision-cut slices derived from patients with COPD with the DNA demethylation agent 5-aza-2'-deoxycytidine decreased cell damage and reduced air space enlargement in the diseased tissue. Here, we present a novel mechanism that targets epigenetic modifications to reverse the tissue remodeling in human COPD lungs and serves as a proof of concept for developing a disease-modifying target.

The carotid bodies (CBs) have been implicated in glucose abnormalities in obesity via elevation of activity of the sympathetic nervous system. Obesity-induced hypertension is mediated by insulin receptor (INSR) signaling and by leptin, which binds to the leptin receptor (LEPR b ) in CB and activates transient receptor potential channel subfamily M member 7 (TRPM7). We hypothesize that in mice with diet-induced obesity, hyperglycemia, glucose intolerance, and insulin resistance will be attenuated by the CB denervation (carotid sinus nerve dissection, CSND) and by knockdown of Lepr b , Trpm7, and Insr gene expression in CB. In series of experiments in 75 male diet-induced obese (DIO) mice, we performed either CSND (vs. sham) surgeries or shRNA-induced suppression of Lepr b , Trpm7 , or Insr gene expression in CB, followed by blood pressure telemetry, intraperitoneal glucose tolerance and insulin tolerance tests, and measurements of fasting plasma insulin, leptin, corticosterone, glucagon and free fatty acids (FFAs) levels, hepatic expression of gluconeogenesis enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G-6-Pase) mRNA and liver glycogen levels. CSND decreased blood pressure, fasting blood glucose levels and improved glucose tolerance without any effect on insulin resistance. CSND did not affect any hormone levels and gluconeogenesis enzymes, but increased liver glycogen level. Genetic knockdown of CB Lepr b , Trpm7, and Insr had no effect on glucose metabolism. We conclude that CB contributes to hyperglycemia of obesity, probably by modulation of the glycogen-glucose equilibrium. Diabetogenic effects of obesity on CB in mice do not occur via activation of CB Lepr b , Trpm7, and Insr . NEW & NOTEWORTHY This paper provides first evidence that carotid body denervation abolishes hypertension and improves fasting blood glucose levels and glucose tolerance in mice with diet-induced obesity. Furthermore, we have shown that this phenomenon is associated with increased liver glycogen content, whereas insulin sensitivity and enzymes of gluconeogenesis were not affected.

Background: Elemene, an active anticancer extract derived from Curcuma wenyujin, has well-documented anticarcinogenic properties. Nevertheless, the role of elemene in prostate cancer (PCa) and its underlying molecular mechanism remain elusive., Purpose: This study focuses on investigating the anti-PCa effects of elemene and its underlying mechanisms., Methods: Cell-based assays, including CCK-8, scratch, colony formation, cell cycle, and apoptosis experiments, to comprehensively assess the impact of elemene on PCa cells (LNCaP and PC3) in vitro. Additionally, we used a xenograft model with PC3 cells in nude mice to evaluate elemene in vivo efficacy. Targeted metabolomics analysis via HILIC-MS/MS was performed to investigate elemene potential target pathways, validated through molecular biology experiments, including western blotting and gene manipulation studies., Results: In this study, we discovered that elemene has remarkable anti-PCa activity in both in vitro and in vivo settings, comparable to clinical chemotherapeutic drugs but with fewer side effects. Using our established targeted metabolomics approach, we demonstrated that β-elemene, elemene's primary component, effectively inhibits glycolysis in PCa cells by downregulating 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) expression. Furthermore, we found that β-elemene accomplishes this downregulation by upregulating p53 and FZR1. Knockdown and overexpression experiments conclusively confirmed the pivotal role of PFKFB3 in mediating β-elemene's anti-PCa activity., Conclusion: This finding presents compelling evidence that elemene exerts its anti-PCa effect by suppressing glycolysis through the downregulation of PFKFB3. This study not only improves our understanding of elemene in PCa treatment but also provides valuable insights for developing more effective and safer therapies for PCa., 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 GmbH. All rights reserved.)

In this paper, a kind of tightly coupled array (TCA) with time-domain beam scan is developed for the radiation of high-power ultrawideband (UWB) electromagnetic pulses, and the peak-power pattern is proposed to characterize the directivity. First, the active voltage standing wave ratio (AVSWR) bandwidth of the TCA is optimized, which is the precondition for the beam scan. It indicates that the lower-cutoff frequency (LCF) is inversely proportional to the total length of the whole array; an increase in the distance between the array and the ground plane could remarkably reduce the LCF; and an increase in the element number can also decrease the LCF because of the increase in length, but more elements would make the center elements difficult to match in the low-frequency range, so there is a limitation on the number of elements for a certain LCF. Based on these results, a six-element linear array is designed. Then, the definition of the peak-power pattern is proposed to characterize the directivity of the UWB pulsed antenna. Finally, the optimized six-element array is developed, and the measured working band is 276 MHz-6.4 GHz (AVSWR < 3). The effective potential gain is 1.76, and it improves by 51.7% with a reduction in the aperture area by 68.4% compared with the previous TCA, which means that the aperture efficiency is remarkably improved. The half-power beam width of the developed TCA with the scan angle of 0° is 45°. The time-domain beam scan could be performed with time-delay feeding lines, and the maximum scan angle is over ±30° in the E-plane. The developed TCA can be applied for the generation of high-power electromagnetic environments for the study of intentional electromagnetic interference., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: 30-day readmission after hip fracture surgery in the elderly is common and costly. A predictive tool to identify high-risk patients could significantly improve outcomes. This study aims to develop and validate a risk nomogram for 30-day readmission after hip fracture surgery in geriatric patients., Patients and Methods: We retrospectively analyzed 1,249 geriatric hip fracture patients (≥60 years) undergoing surgery at Dandong Central Hospital from October 2011 to October 2023. Using a 7:3 ratio, patients were randomly divided into training (n=877) and validation (n=372) sets. Independent risk factors for 30-day readmission were identified using LASSO regression and logistic regression in the training set. A nomogram was constructed using the identified predictors. Finally, the C-index, ROC curve, calibration curve, and decision curve analysis were used to validate the model in the training and validation sets respectively., Results: The nomogram was developed based on the 8 predictors of age, prior stroke, chronic liver disease, treatment, uric acid (UA), total protein (TP), albumin (ALB), and pneumonia that were found to be independently associated with 30-day readmission. The nomogram showed good discrimination with a C-index of 0.88 in the training set and 0.84 in the validation set. Calibration curves exhibited good agreement between predicted and observed outcomes. Decision curve analysis demonstrated clinical utility., Conclusions: We developed and validated a nomogram incorporating eight clinical variables to accurately predict the individualized risk of 30-day readmission after hip fracture surgery in elderly patients. The model demonstrated favorable discrimination, calibration, and clinical utility. It can help to identify high-risk patients needing additional interventions to prevent avoidable hospital readmissions.

Owing to the ubiquity of the hydroxyl group, reductive deoxygenation of alcohols has become an active research area. The classic Barton-McCombie reaction suffers from a tedious two-step procedure. New efficient methods have been developed, but they have some limitations, such as a narrow substrate scope and the use of moisture-sensitive Lewis acids. In this work, we describe the Ph 3 P/ICH 2 CH 2 I-promoted reductive deoxygenation of alcohols with NaBH 4 . The process is applicable to benzyl, allyl and propargyl alcohols, and also to primary and secondary alcohols, demonstrating a wide substrate scope and a good level of functional group tolerance. This protocol features convenient operation and low cost of all reagents.

Objective: This study aims to develop and validate a risk nomogram for urinary tract infections (UTIs) in geriatric patients with hip fractures., Patients and Methods: A total of 900 geriatric patients who underwent hip fracture surgery at Dandong Central Hospital between June 2017 and June 2023 were systematically collected. The cohort was randomly divided into a training set (70%, n=632) and a validation set (30%, n=268) for model development and validation, respectively. Univariate and multivariate logistic regression analyses were conducted to identify the independent risk factors associated with UTIs. Based on the results of the multivariate analysis, a UTI nomogram prediction model was developed and evaluated in the training and validation sets using the C-index, ROC curve, calibration curve, and decision curve analysis to assess discrimination, calibration, and clinical utility, respectively., Results: Out of the 900 participants, 24.6% were diagnosed with UTIs. The nomogram was developed based on 9 predictors that were found to be independently associated with UTI. The area under the curve (AUC) for predicting UTI in geriatric patients with hip fractures was 0.829 in the training set and 0.803 in the validation set. Following internal verification, the modified C-index remained at 0.829. Furthermore, the nomogram's calibration plot and decision curve analysis demonstrated good performance in both the training and validation sets., Conclusions: The established and validated nomogram provides a reliable and convenient tool for predicting UTI risk in geriatric patients with hip fractures. This model facilitates the early identification of high-risk patients and offers guidance for implementing targeted preventive interventions.

Objective: This study aimed to develop and validate a risk nomogram for preoperative proximal and distal deep vein thrombosis (DVT) in geriatric patients with hip fractures., Patients and Methods: The 970 collected geriatric hip fracture patients were randomly divided into a training set (70%, n=682) and a validation set (30%, n=288). Multivariate logistic regression analyses were used to optimize the predictive risk variables for proximal and distal preoperative lower extremity DVT in the training set, respectively, and the selected variables were finally incorporated to establish preoperative DVT nomogram prediction models. Receiver operating characteristic curves (ROC), calibration plots, and decision curve analysis (DCA) were performed to validate the nomograms in the training and validation sets, respectively., Results: Among the 970 patients, 125 (12.88%) were diagnosed with preoperative DVT. The area under the curve (AUC) for predicting preoperative proximal DVT was 0.888 in the training and 0.792 in the validation sets. The AUC for predicting preoperative distal DVT was 0.907 in the training and 0.790 in the validation sets. The calibration plots and decision curve analysis for preoperative proximal DVT performed well in the training set and slightly worse in the validation set. The calibration plots and decision curve analysis for preoperative distal DVT performed well in both the training and validation sets., Conclusions: To construct nomograms for predicting the risk of proximal and distal preoperative lower extremity DVT in geriatric hip fracture patients. For patients at high risk, as assessed by this model, clinicians should intervene and treat them promptly before surgery.

Light intensity, wavelength, and photoperiod have a combined effect on chicken incubation. This study was conducted to evaluate the effect of 12-h light, 12-h dark (12L:12D) photoperiod of white light (380-780 nm, WL), blue light (455/447.5-462.5 nm, BL), and green light (525/515-535 nm, GL) in chicken perceived light intensity during layer incubation on hatching performance, embryo development, eye structure, and melatonin concentration. Three batches of eggs from Jinghong No. 1 layer breeder were used in this experiment. Light stimulation had no effect on hatchability, and no consistent effect on embryo weight and newly hatched chick weight. However, the average hatching time of white light group and green light group was 7.3 h and 5.5 h later than that of the control group. Therefore, the holding period of chicks was significantly shortened (P = 0.001) in these 2 light groups. Light stimulation had a significant effect on the thickness of retinal layers (P < 0.05), retinal layers of white light group was thicker than that of the other 3 groups. Melatonin levels of chicks hatched in the green light and blue light were significantly higher than that of chicks hatched in the white light and darkness (P < 0.05). It indicated that the monochrome green and blue light promoted the expression of melatonin in chicken embryos. No significant diurnal rhythms were found at the level of plasma melatonin in 4 groups on d 21 using cosine analysis. It was concluded that green light has a positive effect on embryo development and melatonin secretion, while white light probably has positive effect on eye development. Furthermore, both green and white light stimulation resulted in late hatch for layer egg incubation. The obtained results are important in determining the light protocol for chicken incubation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Streptococcus agalactiae (group B Streptococcus) sequence type 283 bacteremia, found almost exclusively in Southeast Asia, is associated with consuming raw freshwater fish, but some patients deny consumption. We detected fecal carriage in 5/184 (2.7%) persons in northeast Thailand. Human carriers might contribute to transmission or be the original source of this sequence type.

Ethnopharmacological Relevance: The rhizome of Curcuma wenyujin Y.H. Chen & C. Ling, also known as Wen-E-Zhu, has been used for cancer treatment since ancient times, with roots dating back to the Song Dynasty. Elemene (EE), a sesquiterpene extract with potent anticancer properties, is extracted from Wen-E-Zhu, with β-elemene (BE) being its main active compound, along with trace amounts of β-caryophyllene (BC), γ-elemene and δ-elemene isomers. EE has demonstrated broad-spectrum anti-cancer effects and is commonly used in clinical treatments for various types of malignant cancers, including lung cancer. Studies have shown that EE can arrest the cell cycle, inhibit cancer cell proliferation, and induce apoptosis and autophagy. However, the exact mechanism of its anti-lung cancer activity remains unclear and requires further research and investigation., Aim of the Study: In this study, the possible mechanism of EE and its main active components, BE and BC, against lung adenocarcinoma was investigated by using A549 and PC9 cell lines., Materials and Methods: The subcutaneous tumor model of nude mice was constructed to evaluate the efficacy of EE in vivo, then the in vitro half-inhibitory concentration (IC 50 ) of EE and its main active components, BE and BC, on A549 and PC9 cells at different concentrations were determined by CCK-8. Flow cytometry was used to detect the apoptosis and cycle of A549 and PC9 cells treated with different concentrations of BE and BC for 24 h. Non-targeted metabolomics analysis was performed on A549 cells to explore potential target pathways, which were subsequently verified through kit detection and western blot analysis., Results: Injection of EE in A549 tumor-bearing mice effectively suppressed cancer growth in vivo. The IC 50 of EE and its main active components, BE and BC, was around 60 μg/mL. Flow cytometry analysis showed that BE and BC blocked the G 2 /M and S phases of lung adenocarcinoma cells and induced apoptosis, leading to a significant reduction in mitochondrial membrane potential (MMP). Results from non-targeted metabolomics analysis indicated that the glutathione metabolism pathway in A549 cells was altered after treatment with the active components. Kit detection revealed a decrease in glutathione (GSH) levels and an increase in the levels of oxidized glutathione (GSSG) and reactive oxygen (ROS). Supplementation of GSH reduced the inhibitory activity of the active components on lung cancer and also decreased the ROS content of cells. Analysis of glutathione synthesis-related proteins showed a decrease in the expression of glutaminase, cystine/glutamate reverse transporter (SLC7A11), and glutathione synthase (GS), while the expression of glutamate cysteine ligase modified subunit (GCLM) was increased. In the apoptosis-related pathway, Bax protein and cleaved caspase-9/caspase-9 ratio were up-regulated and Bcl-2 protein was down-regulated., Conclusions: EE, BE, and BC showed significant inhibitory effects on the growth of lung adenocarcinoma cells, and the mechanism of action was linked to the glutathione system. By down-regulating the expression of proteins related to GSH synthesis, EE and its main active components BE and BC disrupted the cellular redox system and thereby promoted cell apoptosis., 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.)

La 2 O 3 and CeO 2 , as main rare earth oxides, with unique physical and chemical properties have been widely used in catalyst and grinding industry. In this study, the effects of La 2 O 3 and CeO 2 on the anaerobic process were investigated. The biological methane production tests showed that 0-0.05 g/L La 2 O 3 and 0-0.05 g/L CeO 2 enhanced anaerobic methanogenesis process. The result showed maximum specific methanogenic rates of La 2 O 3 and CeO 2 were 56.26 mL/(h·gVSS) and 49.43 mL/(h·gVSS) and, compared with the control, increased 4% and 3%, respectively. La 2 O 3 significantly reduced the accumulation of volatile fatty acids (VFAs), whereas CeO 2 had no similar effect. Dissolution experiments demonstrated that the content of extracellular La in the anaerobic granular sludge reached 404 μg-La/g volatile suspended solid (VSS), which was 134 times higher than that of extracellular Ce (3 μg-Ce/gVSS). The content of intracellular La reached 206 μg-La/gVSS, which was 19 times higher than that of intracellular Ce (11 μg-Ce/gVSS). The different stimulation between La 3+ and Ce 3+ could be attributed to the different dissolution of La 2 O 3 and CeO 2 . The result of this work is helpful to optimize anaerobic processes and to develop novel additives. PRACTITIONER POINTS: Novel anaerobic additives were developed. La2O3 and CeO2 in 0-0.05 g/L enhanced organics degradation and methane production. The addition of La2O3 significantly reduced the accumulation of volatile fatty acids. The solubilization of La2O3 was stronger than CeO2. The promoting effects of low concentrations of La2O3 and CeO2 were derived from dissolved La and Ce., (© 2023 Water Environment Federation.)

Extracellular matrix stiffening is a quintessential feature of cartilage aging, a leading cause of knee osteoarthritis. Yet, the downstream molecular and cellular consequences of age-related biophysical alterations are poorly understood. Here, we show that epigenetic regulation of α-Klotho represents a novel mechanosensitive mechanism by which the aged extracellular matrix influences chondrocyte physiology. Using mass spectrometry proteomics followed by a series of genetic and pharmacological manipulations, we discovered that increased matrix stiffness drove Klotho promoter methylation, downregulated Klotho gene expression, and accelerated chondrocyte senescence in vitro. In contrast, exposing aged chondrocytes to a soft matrix restored a more youthful phenotype in vitro and enhanced cartilage integrity in vivo. Our findings demonstrate that age-related alterations in extracellular matrix biophysical properties initiate pathogenic mechanotransductive signaling that promotes Klotho promoter methylation and compromises cellular health. These findings are likely to have broad implications even beyond cartilage for the field of aging research., (© 2023. The Author(s).)

Sleep-disordered breathing (SDB) affects over 50% of obese individuals. Exaggerated hypoxic chemoreflex is a cardinal trait of SDB in obesity. We have shown that leptin acts in the carotid bodies (CB) to augment chemoreflex and that leptin activates the transient receptor potential melastatin 7 (TRPM7) channel. However, the effect of leptin-TRPM7 signalling in CB on breathing and SDB has not been characterized in diet-induced obesity (DIO). We hypothesized that leptin acts via TRPM7 in the CB to increase chemoreflex leading to SDB in obesity. DIO mice were implanted with EEG/EMG electrodes and transfected with Lepr b short hairpin RNA (shRNA) or Trpm7 shRNA vs. control shRNA in the CB area bilaterally. Mice underwent a full-polysomnography and metabolic studies at baseline and after transfection. Ventilatory responses to hypoxia and hypercapnia were assessed during wakefulness. Lepr b and Trpm7 were upregulated and their promoters were demethylated in the CB of DIO mice. Lepr b knockdown in the CB did not significantly affect ventilation. Trpm7 knockdown in the CB stimulated breathing during sleep in normoxia. These effects were not driven by changes in CB chemosensitivity or metabolism. Under sustained hypoxia, Trpm7 shRNA in the CB augmented ventilation during sleep, but decreased oxyhaemoglobin saturation. We conclude that the suppression of TRPM7 in the CB improved sleep-related hypoventilation and that the respiratory effects of CB TRPM7 channels in obesity are independent of leptin. TRPM7 signalling in the CB could be a therapeutic target for the treatment of obesity-related SDB. KEY POINTS: The leptin-TRPM7 axis in the carotid bodies may play an important role in the pathogenesis of sleep-disordered breathing. TRPM7 channels regulate breathing during sleep by acting peripherally in the carotid bodies. Suppression of TRPM7 signalling in the carotid bodies improves the obesity-induced hypoventilation in mice. Pharmacological blockade of TRPM7 channels in the carotid bodies could be a therapy for sleep-disordered breathing in obesity., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

Introduction: We examined information and communications technology (ICT) use in family services and its perceived benefits and barriers amid the COVID-19 pandemic in Hong Kong., Methods: We invited all family service social workers of 12 NGOs to complete an anonymous online questionnaire in May 2020 (Part A) and a management representative from each NGO to provide written feedback on ICT use in January 2021 (Part B)., Results: In Part A, of 255 respondents (response rate: 67.3%), perceived ICT use in conducting programmes, groups, casework and preventive family programmes showed net increases of 33.9-54.5%; perceived ICT use in different work processes showed net increases of 18.8-48.6%. The three most common perceived benefits were "providing another option to service users" (74.2%), "more convenient service" (60.2%) and "maintaining normal service" (59.7%). In Part B, 12 management representatives consistently reported positive impacts of ICT use on family services. They shared actionable strategies (e.g., ICT skill-related training) and concerns about data privacy and management., Conclusions: ICT use in family services markedly increased amid the COVID-19 pandemic in Hong Kong. It helped make the services more accessible especially when the pandemic restricted face-to-face services.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46}  cm^{2} (90% C.L.) at DM mass of 10  MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14  MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4  kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m&#95;{χ} larger than 80  MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m&#95;{χ} larger than 90  MeV/c^{2} with heavy mediators and m&#95;{χ} larger than 100  MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.

Global climate change is leading to shifts in abiotic conditions. Short-term temperature stresses induced by marine heatwaves (MHWs) can affect organisms both during and after the events. However, the recovery capacity of organisms is likely dependent on the magnitude of the initial stress event. Here, we experimentally assessed the effect of MHW magnitude on behavioural and physiological responses of a common marine gastropod, Lunella granulata, both during and after the MHW. Self-righting behaviours tended to become faster under moderate MHWs, whereas there was a trend toward these behaviours slowing under extreme MHWs. After a recovery period at ambient temperatures, individuals that experienced extreme MHWs showed persistent small, but not significant, negative effects. Survival and oxygen consumption rates were unaffected by MHW magnitude both during and after the event. While extreme MHWs may have negative behavioural consequences for tropical marine gastropods, their physiological responses may allow continued survival., (© 2022. The Author(s).)

Based on the panel data of thirty-one provinces in China from 2003 to 2020, we constructed an evaluation index system of urban-rural integration development level from the perspective of factor flow. The combined weighting model of GI and CRITIC were used to evaluate the regional urban-rural integration development. The coefficient of variation and panel fixed effect model was used to explore convergence, absolute convergence, and conditional convergence. The impact of capital, labor, and technology factor flow on the convergence of urban-rural integration development level was further investigated. In addition, the difference analysis in time scale and impulse response function analysis was performed to explore the regular pattern of factor flow on the convergence of urban-rural integration development. The main conclusions were as follows: first, the growth of urban-rural integration development had an absolute convergence trend and tended to conditional convergence faster. Second, the capital flow positively affected the convergence of urban-rural integration development, while labor and technology flow had a slowing effect on the convergence of urban-rural integration development at this stage. Third, the impact of factor flow on the convergence of urban-rural integration development was dissimilar during different phases. The convergence rate of urban-rural integration development after 2012 was drastically slower than before., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Li Qian et al.)

In order to study the comprehensive effects of different types of dehydrating agents on the dewatering and solidification of dredged sediments, this study took the dredged sediments of Taihu Lake as the research object and selected microorganisms, polymeric iron aluminum salts, organic polymers, organic-inorganic composites, and aluminum salt microorganisms. These five types of composite dehydrating agents were used to conduct a three-month solidification test on the dredged sediment by means of geotechnical pipe bag solidification. The results of the study showed that the dehydration efficiency of organic polymers and organic-inorganic composite chemicals was better. After one month, the water content of sediment dropped to 61.78% and 63.26%, respectively, which then dropped to 40.56% and 32.16% after three months. Compared with that of the unsolidified sludge, the total nitrogen of the bottom sludge after solidification by the organic-inorganic composite agent was reduced by 74.82%, reaching 591 mg·kg -1 , primarily due to the reduction in ammonia nitrogen. The solid sludge contained mainly aluminum-bound phosphorus, calcium-bound phosphorus, and iron-bound phosphorus. Among them, four groups (organic-inorganic composite) had the largest reduction in active phosphorus, with the lowest being 64.3 mg·kg -1 . In addition, organic polymer agents had the best curing effect on heavy metals, the comprehensive ecological risk index of heavy metals was reduced by 51.3%, and the leaching toxicity concentration was far below the standard threshold. This study showed that organic polymers and organic-inorganic composite medicaments have a better effect on the dehydration and solidification of bottom sludge and thus have good application prospects.

Atherosclerosis, the pathological basis of most cardiovascular disease, is characterized by plaque formation in the intima. Secondary lesions include intraplaque hemorrhage, plaque rupture, and local thrombosis. Vascular endothelial function impairment and smooth muscle cell migration lead to vascular dysfunction, which is conducive to the formation of macrophage-derived foam cells and aggravates inflammatory response and lipid accumulation that cause atherosclerosis. Histone deacetylase (HDAC) is an epigenetic modifying enzyme closely related to chromatin structure and gene transcriptional regulation. Emerging studies have demonstrated that the Class I member HDAC3 of the HDAC super family has cell-specific functions in atherosclerosis, including 1) maintenance of endothelial integrity and functions, 2) regulation of vascular smooth muscle cell proliferation and migration, 3) modulation of macrophage phenotype, and 4) influence on foam cell formation. Although several studies have shown that HDAC3 may be a promising therapeutic target, only a few HDAC3-selective inhibitors have been thoroughly researched and reported. Here, we specifically summarize the impact of HDAC3 and its inhibitors on vascular function, inflammation, lipid accumulation, and plaque stability in the development of atherosclerosis with the hopes of opening up new opportunities for the treatment of cardiovascular diseases., Competing Interests: Competing interests The authors declare that there are no disputes of interest., (Copyright: © 2022 Jiang et al.)

Background: Ultrasound-guided internal jugular vein (IJV) catheterization has become a standard procedure as it yields a higher success rate and fewer mechanical complications compared with an anatomical landmark technique. There are several common methods for ultrasound guidance IJV catheterization, such as short-axis out-of-plane, long-axis in-plane and oblique axis in-plane, but these technologies are still developing. It is important to further study the application of different ultrasound-guided IJV puncture techniques and find an effective and safe ultrasound-guided puncture technique., Methods: A China randomized, open-label, parallel, single center, positive-controlled, non-inferiority clinical trial will evaluate 190 adult patients undergoing elective surgery and need right jugular vein catheterization. Study participants randomized in a 1:1 ratio into control and experimental groups. The control group will take the oblique axis in-plane method for IJV catheterization. The experimental group will take the Modified combined short and long axis method. The primary endpoint of the trial is the rate of one-time successful guidewire insertion without posterior wall puncture (PWP). Secondary endpoints are the number of needle insertion attempts, the total success rate, the procedure time, and mechanical complications., Conclusion: This randomized controlled trial will evaluate the effectiveness and safety of Modified combined short and long axis method and oblique axis in-plane method for right IJV catheterization in adult patients., 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 © 2022 Tang, Wang, Nian, Tang, Tang, Xiao and Liu.)

A prediction model of the welding process of Ti-6Al-4V titanium alloy was established by using the finite element method, which was used to evaluate the phase composition, residual stress and deformation of the welded joints of Ti-6Al-4V sheets with different processes (including tungsten inert gas welding, TIG, and laser beam welding, LBW). The Ti-6Al-4V structures of TIG welding and LBW are widely used in marine engineering. In order to quantitatively study the effects of different welding processes (including TIG welding and LBW) on the microstructure evolution, macro residual stress and deformation of Ti6Al4V titanium alloy sheets during welding, a unified prediction model considering solid-state phase transformation was established based on the ABAQUS subroutine. In this paper, LBW and TIG welding experiments of 1.6 mm thick Ti-6Al-4V titanium alloy sheets were designed. The microstructure distribution of the welded joints observed in the experiment was consistent with the phase composition predicted by the model, and the hardness measurement experiment could also verify the phase composition and proportion. From the residual stress measured by experiment and the residual stress and deformation calculated by finite element simulation of LBW and TIG weldments, it is concluded that the effect of phase transformation on residual stress is mainly in the weld area, which has an effect on the distribution of tensile and compressive stress in the weld area. The overall deformation of the welded joint is mainly related to the welding process, and the phase transformation only affects the local volume change of the weld seam. Importantly, the phase composition and residual stress, which are scalar fields, calculated by the established model can be introduced into the numerical analysis of structural fracture failure as input influence factors.

Purpose: To determine the efficacy of physical therapy interventions on quality of life (QoL) and pain severity in post-mastectomy pain syndrome (PMPS)., Methods: Multiple databases were searched from database inception to October 2020. Searches were limited to human studies published in either English or Chinese in peer-reviewed journals with full text available for randomized controlled trials conducted on females. Trials comparing the effectiveness of physical therapy interventions against control conditions on QoL and pain were included., Results: Eighteen trials were included in the review. The pooled analysis of the four exercise trials revealed a significant effect of the intervention on general [standardized mean difference [SMD]: 0.87 (95%CI: 0.36, 1.37); p = 0.001], physical [SMD: 0.34 (95%CI: 0.01, 0.66); p = 0.044], and mental health components [SMD: 0.27 (95%CI: 0.03, 0.51); p = 0.027] of QoL compared with the control condition. Meta-analyses of six exercise trials, two myofascial release trials, and two acupuncture trials revealed a significant improvement in pain severity in the treatment group than in the control group. However, meta-analyses of two studies revealed a non-significant effect of compression therapy compared to control on pain severity., Conclusion: Our meta-analyses found that exercise is beneficial for improving the QoL and pain severity of women with PMPS. Future studies are needed to determine the optimal parameters for exercise interventions designed to improve QoL and pain severity in women with PMPS. The effect of acupuncture, myofascial release, and compression therapy remains inconclusive, and future research is required to validate the effect of these interventions on PMPS., (© 2022. The Author(s).)

Chimeric antigen receptor T-cell immunotherapy (CAR-T) has shown remarkable efficacy in treating tumors of lymphopoietic origin. Herein, we demonstrate an effective CAR-T cell treatment for recurrent and malignant CD30-positive peripheral T-cell lymphomas (PTCL) has been demonstrated. The extracellular fragment gene sequences of CD30 were obtained from tumor tissues of PTCL patients and cloned into a plasmid vector to express the CD30 antigen. The CD30 targeting single-chain antibody fragment (scFv) was obtained from CD30-positive monoclonal hybridoma cells, which were obtained from CD30 antigen immunized mice. After a second-generation of CAR lentiviral construction, CD30 CAR T cells were produced and used to determine the cytotoxicity of this construct toward Karpas 299 cells. The results of CD30 CAR T-mediated cell lysis show that 9C11-2 CAR T cells could significantly promote the lysis of CD30-positive Karpas 299 cells in both LDH and real-time cell electronic sensing (RTCA) assays. In vivo data show that 9C11-2 CAR T cells effectively suppress the tumor growth in a Karpas 299 cell xenograft NCG mouse model. The CD30 CAR T cells exhibited an efficient cytotoxic effect after being co-cultured with the target cells and they also exhibited a significant tumor-inhibiting ability after being intravenously injected into PTCL xenograft tumors; these observations suggest that the new CD30 CAR-T cell may be a promising therapeutic candidate for cancer therapy., (© 2021. The Author(s).)

Introduction: In situ hybridization (ISH) plays an important role in the field of molecular diagnostics, especially in an anatomical pathology laboratory. ISH is a technique that can detect the targeted DNA or RNA sequences in tissue sections from frozen or fixed materials with labeled DNA or RNA probes. Radioactive and non-radioactive probes are the two major probes that can be used to label the targeted nucleic acids., Areas Covered: Two decades after the Human Genome Project, ISH has not only simply been applied to identify the chromosomal location of a human gene but has also been extensively applied to gene expressions studies and utilized for clinical diagnosis, especially for the determination of biomarkers for breast and ovarian cancers - human epidermal growth factor receptor 2. Duchenne muscular dystrophy, Cri-du-chat syndrome, Angelman syndrome, PraderWilli syndrome, cystic fibrosis, and trisomy are diseases that can also be detected by ISH. In this review, the basic principles, historical development, advantages and disadvantages, enhancement in reporting molecules and probes, advancement in detection methods, in situ PCR, clinical applications and novel applications of ISH will be discussed., Expert Opinion: With the advancement in ISH technologies and appropriate training, diagnosis can be improved in Anatomical Pathology.

Objectives: Acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. Our aim was to identify a novel miRNA that can predict prognosis of childhood ALL patients and explore its potential mechanism., Methods: The miRNA expression profiles of childhood ALL were analyzed using GEO database and HiSeq instruments. The expression of miR-155 was examined by RT-PCR in 42 ALL patients. To investigate the role of miR-155 in ALL, four ALL cell lines (CEM-C1, Jurkat, MOLT-3 and MOLT-4) were transfected with miR-155 mimics, miR-155 inhibitors or corresponding controls. Dual-luciferase reporter system was applied to confirm the miR-155 target ZNF238. Moreover, proliferation and apoptosis were evaluated by MTT and flow cytometry., Results: Dataset GSE56489 and GSE23024 demonstrated that miR-155 was up-regulated and ZNF238 was down-regulated at diagnosis status of ALL. High miR-155 expression was associated with poor outcome. Overexpressed miR-155 promoted ALL cell proliferation and inhibited apoptosis. Dual-luciferase reporter result showed that miR-155 directly regulated ZNF238. Silencing ZNF238 promoted cell proliferation in ALL cells., Discussion: Our research indicating that miR-155 might possess potential value as a biomarker for predicting the prognosis of individuals. However, the role of ZNF238 in childhood ALL remain unknown. In the present study, we found the possible role of ZNF238 as a new tumor suppressor in ALL, which might be necessary for the antiproliferative functions of normal cells to counteract ALL formation., Conclusion: Our results propose that miR-155 is in association with poor prognosis of childhood ALL. Furthermore, miR-155 could promote cell proliferation targeting ZNF238.

Group B Streptococcus (GBS; Streptococcus agalactiae ) is the most common cause of neonatal meningitis and a rising cause of sepsis in adults. Recently, it has also been shown to cause foodborne disease. As with many other bacteria, the polysaccharide capsule of GBS is antigenic, enabling its use for strain serotyping. Recent advances in DNA sequencing have made sequence-based typing attractive (as has been implemented for several other bacteria, including Escherichia coli , Klebsiella pneumoniae species complex, Streptococcus pyogenes , and others). For GBS, existing WGS-based serotyping systems do not provide complete coverage of all known GBS serotypes (specifically including subtypes of serotype III), and none are simultaneously compatible with the two most common data types, raw short reads and assembled sequences. Here, we create a serotyping database (GBS-SBG, GBS Serotyping by Genome Sequencing), with associated scripts and running instructions, that can be used to call all currently described GBS serotypes, including subtypes of serotype III, using both direct short-read- and assembly-based typing. We achieved higher concordance using GBS-SBG on a previously reported data set of 790 strains. We further validated GBS-SBG on a new set of 572 strains, achieving 99.8% concordance with PCR-based molecular serotyping using either short-read- or assembly-based typing. The GBS-SBG package is publicly available and will hopefully accelerate and simplify serotyping by sequencing for GBS.