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Introduction: Tobacco smoke is known to be the main cause of lung, head and neck tumors. Recently, evidence for an increasing breast cancer risk associated with tobacco smoke exposure has been emerging. We and other groups have shown that nicotine, as a non-conventional carcinogen, has the potential to facilitate cancer genesis and progression. However, the underlying mechanisms by which the smoke affects the breast, rather than the lung, remain unclear. Here, we examine possible downstream signaling pathways of the nicotinic acetylcholine receptor (nAChR) and their role in breast cancer promotion.Methods: Using human benign MCF10A and malignant MDA-MB-231 breast cells and specific inhibitors of possible downstream kinases, we identified nAChR effectors that were activated by treatment with nicotine. We further tested the effects of these effector pathways on the regulation of E2F1 activation, cell cycle progression and on Bcl-2 expression and long-term cell survival.Results: In this study, we demonstrated a novel signaling mechanism by which nicotine exposure activated Src to sensitize epidermal growth factor receptor (EGFR)-mediated pathways for breast cancer cell growth promotion. After the ligation of nAChR with nicotine, EGFR was shown to be activated and then internalized in both MCF10A and MDA-MB-231 breast cancer cells. Subsequently, Src, Akt and ERK1/2 were phosphorylated at different time points following nicotine treatment. We further demonstrated that through Src, the ligation of nicotine with nAChR stimulated the EGFR/ERK1/2 pathway for the activation of E2F1 and further cell progression. Our data also showed that Akt functioned directly downstream of Src and was responsible for the increase of Bcl-2 expression and long-term cell survival.Conclusions: Our study reveals the existence of a potential, regulatory network governed by the interaction of nicotine and nAChR that integrates the conventional, mitogenic Src and EGFR signals for breast cancer development. [ABSTRACT FROM AUTHOR]

Background: Despite the urgent need for improved outcomes in patients with metastatic Ewing sarcoma (EWS) and rhabdomyosarcoma (RMS), it is unknown how to best approach metastatic site radiation therapy for these patients and whether such treatment provides a significant oncologic benefit that outweighs the toxicities., Methods: We gathered a panel of pediatric radiation oncologists from academic hospitals to identify and discuss current controversies regarding the role of radiation in the management of metastatic EWS and RMS. The panel reviewed existing clinical data and ongoing trials to address five key questions: 1) the role of whole lung irradiation (WLI) in treating lung metastases 2) number of metastatic sites warranting radiotherapy and the radicality of such an approach; 3) radiation techniques, including stereotactic body radiation therapy (SBRT); 4) the timing of metastatic-site radiation therapy; and 5) the utility of metastatic site radiation therapy for relapsed metastatic disease., Results: After a review of existing data, consensus recommendations were developed to support the decision-making process in metastatic-site irradiation with the goal of improving long-term disease control. Patients with pulmonary metastases should receive WLI. In patients with limited (<8 sites) metastatic disease, a comprehensive approach should be taken to treat all sites of metastatic disease diagnosed at presentation. SBRT should be considered as a preferred treatment technique. The timing of metastatic-site treatment should coincide with the end of systemic therapy. However, if there is a dosimetric advantage or improved compliance, concurrent treatment with the primary site may be preferred., Conclusions: A consensus guideline was established to address several critical questions regarding the role of radiation in the treatment of metastatic EWS and RMS. The study highlights the existing controversies, provides a structured approach, and underscores the need for future studies to further evaluate the therapeutic ratio of metastatic-site directed therapy., Competing Interests: Declaration of competing interest LYL reports travel support from GT Medical Technologies. JB reports leadership role in PTCOG-NA. No other conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Despite bone metastases being present in 5% of patients at diagnosis, there are limited studies examining these outcomes. We sought to define the prognostic factors, clinical courses, and outcomes of children treated on Children's Oncology Group (COG) clinical trials with RMS metastatic to bone at diagnosis., Methods: We performed a retrospective analysis of patients diagnosed with bone metastatic RMS enrolled on COG RMS clinical trials (D9802, D9803, ARST0431, or ARST08P1) between 1997 and 2013., Results: RMS metastatic to bone was identified in 154 patients at a median age of 14.9 years at diagnosis. Fifty-eight percent of patients were male, 90% had metastases at additional sites, 74% had alveolar histology, and extremity was the most common primary site (31%). Eighty-six percent of patients (n = 133) received radiation therapy. The 3- and 5-year event-free survival (EFS) was 15.4% and 14.5%, respectively. The 3- and 5-year overall survival (OS) was 30.4% and 18.0%, respectively. We identified alveolar histology, FOXO1 fusion presence, unfavorable primary location, higher Oberlin score, and lack of radiation as poor prognostic characteristics for both EFS and OS in univariate analysis. Lack of radiation was not significant when excluding patients with events prior to 20 weeks., Conclusions: This study is the largest analysis of patients with bone metastatic RMS, and defines the poor overall outcomes and negative prognostic factors for these patients. They may be eligible for therapy deintensification for improved quality of life or pursuit of novel treatments/approaches, which are desperately needed., (© 2024 Wiley Periodicals LLC.)

Purpose: Patients with rhabdomyosarcoma with metastatic disease have a poor prognosis despite therapy intensification. The aim of this study was to investigate the efficacy of whole lung irradiation (WLI) in patients with rhabdomyosarcoma and lung metastases., Methods: Patients with rhabdomyosarcoma with lung metastases enrolled on four Children's Oncology Group protocols (D9802, D9803, ARST08P1, ARST0431) were retrospectively reviewed. Event-free survival (EFS) and overall survival (OS) were compared between patients who received and did not receive WLI., Results: In 143 patients with rhabdomyosarcoma with lung metastases, 65 patients (45.5%) received WLI and 78 patients (54.5%) did not receive WLI despite protocol requirements. The 5-year EFS was 38.3% (95% CI, 24.8 to 51.8) in patients who received WLI and 25.2% (95% CI, 13.8 to 36.6) in patients who did not receive WLI ( P = .0496). The 5-year OS was 45.5% (95% CI, 31.8 to 59.3) in patients who received WLI and 32.4% (95% CI, 20.4 to 44.4) in patients who did not receive WLI ( P = .08). In exploratory subgroup analyses, the benefit of WLI on EFS and OS was significant in patients 10 years and older. Other clinical factors associated with EFS on univariable analysis included age, histology FOXO1 fusion status, number of metastatic sites, location of metastatic sites, and Oberlin Score., Conclusion: WLI is associated with improved EFS in patients with rhabdomyosarcoma with lung metastases. These results highlight the potential importance of WLI and need for more stringent protocol compliance for administering WLI.

Background: Central obesity was considered as a risk factor for falls among the older population. Waist circumference (WC), lipid accumulation product (LAP), visceral adiposity index (VAI), and the Chinese visceral adiposity index (CVAI) are considered as surrogate markers for abdominal fat deposition in increasing studies. Nevertheless, the longitudinal relationship between these indices and falls among the older population remains indistinct. This study aimed to explore the association between abdominal obesity indices and falls among older community-dwellers., Methods: Our study included 3501 individuals aged ≥ 65 years from the Guangzhou Falls and Health Status Tracking Cohort at baseline in 2021 and then prospectively followed up in 2022. The outcome of interest was the occurrence of falls. The Kaplan-Meier curves and multivariable Cox regression analysis were used to explore the associations between abdominal obesity indices and falls. Moreover, the restricted cubic spline analysis (RCS) was conducted to test the non-linear relationships between abdominal obesity indices and hazards of falls incident., Results: After a median follow-up period of 551 days, a total of 1022 participants experienced falls. The cumulative incidence rate of falls was observed to be higher among individuals with central obesity and those falling within the fourth quartile (Q4) of LAP, VAI, and CVAI. Participants with central obesity and those in Q4 of LAP, VAI, and CVAI were associated with higher risk of falls, with hazard ratios (HRs) of 1.422 (HR 95%CI: 1.255-1.611), 1.346 (1.176-1.541), 1.270 (1.108-1.457), 1.322 (1.154-1.514), respectively. Each 1-SD increment in WC, LAP, VAI, and CVAI was a significant increased risk of falls among participants. Subgroup analysis further revealed these results were basically stable and appeared to be significantly stronger among those females, aged 65-69 years, and with body mass index (BMI) ≥ 28 kg/m 2 . Additionally, RCS curves showed an overall upward trend in the risk of falls as the abdominal indices increased., Conclusions: Abdominal obesity indices, as WC, LAP, VAI, and CVAI were significantly associated with falls among older community-dwellers. Reduction of abdominal obesity indices might be suggested as the strategy of falls prevention., (© 2024. The Author(s).)

Objectives: The aim of this superiority trial was to investigate the clinical outcomes of arthrocentesis as an early treatment supported by use of an occlusal splint vs use of an occlusal splint only in the management of temporomandibular joint (TMJ) arthralgia., Methods: Ninety-five adults presenting with TMJ arthralgia were recruited into the study and randomised into 2 groups: Group 1 received arthrocentesis as an early treatment supported by use of an occlusal splint, whereas group 2 received treatment with an occlusal splint only. Seventy-four patients (group 1: n = 37; group 2: n = 37) completed the 1-year follow-up schedule and were included in the final analysis. Reduction of pain intensity measured by a numeric rating scale and increase in mouth opening distance (unassisted maximal, assisted maximal, and pain-free) was seen in both treatment groups., Results: In group 1, pain intensity significantly decreased at 6 weeks and all subsequent time points compared with group 2. In terms of mouth opening distance, a significant improvement was observed in both groups during the course of treatment, but statistical significance was not seen between the 2 treatment groups., Conclusions: Early arthrocentesis supported by use of an occlusal splint is superior to use of an occlusal splint alone in the treatment of TMJ arthralgia. Arthrocentesis with occlusal splint support could be discussed as first-line treatment for arthralgia of the TMJ, which may co-occur with various painful and nonpainful conditions of TMJ disorders., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Several studies have demonstrated that older adults with type 2 diabetes mellitus (T2DM) have a higher risk of falls compared to those without T2DM, which may lead to disability and a lower quality of life. While, limited prospective studies have quantified the associations in southern China. We conducted a longitudinal cohort study to quantify the associations between T2DM and falls and investigate the risk factors of falls among community-dwelling elderly people in Guangzhou, China., Methods: The population-based study included 8800 residents aged 65 and over in 11 counties of Guangzhou at baseline in 2020 and then prospectively followed up through 2022. Of 6169 participants had complete follow-up and were included in the present study. A fall event was identified by self-reported. The Cox regression was applied to quantify the associations between T2DM and falls, and hazard ratios (HRs) were calculated to the factors associated with falls among participants., Results: The median follow-up time for participants was 2.42 years. During the follow-up period, the incidence of falls among all participants was 21.96%. After adjusting for covariates in Cox regression models, T2DM remained a significant risk factor for falls, with HR of 1.781 (95% CI: 1.600-1.983) in the unadjusted covariates model and 1.757 (1.577-1.957) in the adjusted covariates model. Female (1.286, 1.136-1.457), older age (≥ 80: 1.448, 1.214-1.729), single marital status (1.239, 1.039-1.477), lower education level (primary school and below: 1.619, 1.004-1.361), hypertension (1.149, 1.026-1.286) and stroke (1.619, 1.176-2.228) were associated with a higher risk of falls, whereas everyday physical exercise (0.793, 0.686-0.918) was associated with a lower risk of falls., Conclusion: Falls are common, with risks between T2DM and falls quantified and several factors investigated in the longitudinal cohort study among community-dwelling elderly people in Guangzhou, China. Targeted action on the risk factors may reduce the burden of falls in elderly people with T2DM in the future., (© 2024. The Author(s).)

Postharvest rot caused by various fungal pathogens is a damaging disease affecting kiwifruit production and quality, resulting in significant annual economic losses. This study focused on isolating the strain P3-1W, identified as Diaporthe eres , as the causal agent of 'Hongyang' postharvest rot disease in China. The investigation highlighted cell wall degrading enzymes (CWDEs) as crucial pathogenic factors. Specially, the enzymatic activities of cellulase, β-galactosidase, polygalacturonase, and pectin methylesterases peaked significantly on the second day after infection of D. eres P3-1W. To gain a comprehensive understanding of these CWDEs, the genome of this strain was sequenced using PacBio and Illumina sequencing technologies. The analysis revealed that the genome of D. eres P3-1W spans 58,489,835 bp, with an N50 of 5,939,879 bp and a GC content of 50.7%. A total of 15,407 total protein-coding genes (PCGs) were predicted and functionally annotated. Notably, 857 carbohydrate-active enzymes (CAZymes) were identified in D. eres P3-1W, with 521 CWDEs consisting of 374 glycoside hydrolases (GHs), 108 carbohydrate esterase (CEs) and 91 polysaccharide lyases (PLs). Additionally, 221 auxiliary activities (AAs), 91 glycosyltransferases (GTs), and 108 carbohydrate binding modules (CBMs) were detected. These findings offer valuable insights into the CAZymes of D. eres P3-1W., Competing Interests: The authors declare that they have no competing interests., (© 2024 Ling et al.)

Background: Multimorbidity, individuals suffering from two or more chronic diseases, has become a major health challenge worldwide, especially in populous and prosperous cities, where studies of this phenomenon in China are limited. We examined the prevalence, trends, patterns, and associated factors of multimorbidity from 2009 to 2018 among community-dwelling adults in Guangzhou, China., Methods: We conducted serial cross-sectional surveys for chronic diseases in Guangzhou, China, in 2009, 2013, and 2018. General and stratified prevalence were standardized using demographic data. Multivariable logistic regression and hierarchical cluster analysis were applied to identify associated factors and to assess the correlations and patterns of multimorbidity, respectively., Results: This study included 23,284 adults aged 18 and over in 2009, 18,551 in 2013, and 15,727 in 2018. The standardized prevalence of multimorbidity increased substantially, with 12.69% (95% CI: 10.45-15.33) in 2009, 25.44% (95% CI: 23.47-27.52) in 2013, and 35.13% (95% CI:32.64-37.70) in 2018 (P for trend <0.001). The highest bi- and triple-conditions of multimorbidity were dyslipidemia (DP) and overweight or obesity (OO) (12.54%, 95% CI: 11.68-13.46), and DP, OO, and Hypertension (HT) (3.99%, 95% CI: 3.47-4.58) in 2018. From 2009 to 2018, (1) The majority of multimorbidity patterns showed a high prevalence; (2) The percentage of participants with only one chronic condition was found lower, while the percentage with multiple conditions was higher., Conclusions: The prevalence of chronic disease multimorbidity in Guangzhou China, has increased substantially among adults. Effective policies targeting multimorbidity are urgently needed, especially for the health management of primary medical institutions., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: In patients undergoing spine surgery for renal cell carcinoma (RCC), we sought to: (1) describe patterns of postoperative targeted systemic therapy and radiotherapy (RT), (2) compare perioperative outcomes among those treated with targeted systemic therapy to those without, and (3) evaluate the impact of targeted systemic therapy and/or RT on overall survival (OS) and local recurrence (LR)., Methods: A single-institution, retrospective cohort study of patients undergoing spine surgery for metastatic RCC from 2010 to 2021 was undertaken. Treatment groups were RT alone, targeted systemic therapy alone, dual therapy consisting of RT and targeted systemic therapy, and neither therapy. Multivariable Cox regression controlled for age, race, sex, insurance, and preoperative targeted systemic therapy., Results: Forty-nine patients underwent spine surgery for RCC. Postoperatively, 4 patients (8%) received RT alone, 19 (38.8%) targeted systemic therapy alone, 12 (24.5%) dual therapy, and 13 (28.6%) neither. All groups were similar in demographics, preoperative Karnofsky Performance Score ( P = 0.372), tumor size ( P = 0.413), readmissions ( P = 0.884), complications ( P = 0.272), Karnofsky Performance Score ( P = 0.466), and Modified McCormick Scale ( P = 0.980) at last follow-up. Higher 1-year survival was found in dual therapy (83.3%) compared with other therapies. OS was significantly longer in patients with dual therapy compared with other therapies (log-rank; P = 0.010). Multivariate Cox regression (HR = 0.08, 95% CI = 0.02-0.31, P < 0.001) showed longer OS in dual therapy compared with other therapies. Seven patients (14.3%) experienced LR, and a similar time to LR was found between groups (log-rank; P = 0.190)., Conclusion: In patients undergoing metastatic spine surgery for RCC, postoperative dual therapy demonstrated significantly higher 1-year survival and OS compared with other therapies., Clinical Relevance: Multidisciplinary management of metastatic RCC is necessary to ensure timely implementation of targeted systemic therapy and RT to improve outcomes., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Objective: In patients undergoing metastatic spine surgery, we sought to 1) report time to postoperative radiation therapy (RT), 2) describe the predictive factors of time to postoperative RT, and 3) determine if earlier postoperative RT is associated with improved local recurrence (LR) and overall survival (OS)., Methods: A single-center retrospective cohort study was undertaken of all patients undergoing spine surgery for extradural metastatic disease and receiving RT within 3 months postoperatively between January 2010 and January 2021. Time to postoperative RT was dichotomized at <1 month versus 1-3 months. The primary outcomes were LR, OS, and 1-year survival. Secondary outcomes were wound complication, Karnofsky Performance Status, and modified McCormick Scale (MMS) score. Regression analyses controlled for age, body mass index, tumor size, preoperative RT, preoperative/postoperative chemotherapy, and type of RT., Results: Of 76 patients undergoing spinal metastasis surgery and receiving postoperative RT within 3 months, 34 (44.7%) received RT within 1 month and 42 (55.2%) within 1-3 months. Patients with larger tumor size (β = -3.58; 95% confidence interval [CI], -6.59 to -0.57; P = 0.021) or new neurologic deficits (β = -16.21; 95% CI, -32.21 to -0.210; P = 0.047) had a shorter time to RT. No significant association was found between time to RT and LR or OS on multivariable logistic/Cox regression. However, patients who received RT between 1 and 3 months had a lower odds of 1-year survival compared with those receiving RT within 1 month (odds ratio, 0.18; 95% CI, 0.04-0.74; P = 0.022). Receiving RT within 1 month versus 1-3 months was not associated with wound complications (7.1% vs. 2.9%; P = 0.556) (odds ratio, 4.40; 95% CI, 0.40-118.0; P = 0.266) or Karnofsky Performance Status/modified McCormick Scale score., Conclusions: Spine surgeons, oncologists, and radiation oncologists should make every effort to start RT within 1 month to improve 1-year survival after metastatic spine tumor surgery., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Obtaining timely postoperative radiotherapy (RT) following separation surgery is critical to avoid local recurrence of disease yet can be a challenge due to scheduling conflicts, insurance denials, and travel arrangements. In patients undergoing metastatic spine surgery for spinal cord compression, the authors sought to: 1) report the rate of postoperative RT, 2) describe reasons for patients not receiving postoperative RT, and 3) investigate factors that may predict whether a patient receives postoperative RT., Methods: A single-center retrospective case series was undertaken of all patients who underwent metastatic spine surgery for extradural disease between January 2010 and January 2021. Inclusion criteria were patients with intermediate or radioresistant tumors with evidence of spinal cord compression who underwent surgery. The primary outcome was the occurrence of RT within 3 months following surgery. Multivariable logistic regression analysis was performed controlling for age, BMI, race, total number of decompressed levels, tumor size, other organ metastasis, and preoperative RT or chemotherapy to predict patients receiving postoperative RT., Results: Of 239 patients undergoing spine surgery for metastatic disease, 113 (47.3%) received postoperative RT while 126 (52.7%) did not. In the postoperative RT group, 24 (21.2%) received stereotactic body radiation therapy while 89 (78.8%) received conventional external-beam radiation therapy. The most common reasons for patients not receiving postoperative RT included death or transfer to hospice (31.0%), RT not being recommended by radiation oncology (30.2%), and loss to follow-up (23.8%). On critical review with the radiation oncology department, the authors estimated that 101 of 126 (80.2%) patients who did not receive postoperative RT were potential candidates for postoperative RT. Patients who received postoperative RT had more documented inpatient (48.7% vs 32.5%, p < 0.001) and outpatient (100.0% vs 65.1%, p < 0.001) radiation oncology consultations than those who did not. Additionally, patients who received postoperative RT had a higher rate of postoperative chemotherapy (53.1% vs 25.4%, p < 0.001), while patients who did not receive postoperative RT had a higher rate of preoperative RT (7.1% vs 31.0%, p < 0.001). Multivariable analysis confirmed that patients who received preoperative RT had lower odds of undergoing postoperative RT (OR 0.14, 95% CI 0.06-0.34; p < 0.001), and patients who underwent postoperative chemotherapy had higher odds of undergoing postoperative RT (OR 3.83, 95% CI 2.05-7.17; p < 0.001)., Conclusions: In the current study reflecting real-world care of patients with metastatic spine disease after undergoing separation surgery, 47% of patients did not receive postoperative RT, and 80% of those patients were potential candidates for postoperative RT. Radiation oncology consultation and postoperative chemotherapy were significantly associated with receiving postoperative RT, whereas preoperative RT was significantly associated with not receiving postoperative RT. The lack of timely postoperative RT highlights a potential gap in metastatic spine tumor care and underscores the necessity for prompt radiation oncology consultation and effective planning.

Background: Sheep and goats have undergone domestication and improvement to produce similar phenotypes, which have been greatly impacted by structural variants (SVs). Here, we report a high-quality chromosome-level reference genome of Asiatic mouflon, and implement a comprehensive analysis of SVs in 897 genomes of worldwide wild and domestic populations of sheep and goats to reveal genetic signatures underlying convergent evolution., Results: We characterize the SV landscapes in terms of genetic diversity, chromosomal distribution and their links with genes, QTLs and transposable elements, and examine their impacts on regulatory elements. We identify several novel SVs and annotate corresponding genes (e.g., BMPR1B, BMPR2, RALYL, COL21A1, and LRP1B) associated with important production traits such as fertility, meat and milk production, and wool/hair fineness. We detect signatures of selection involving the parallel evolution of orthologous SV-associated genes during domestication, local environmental adaptation, and improvement. In particular, we find that fecundity traits experienced convergent selection targeting the gene BMPR1B, with the DEL00067921 deletion explaining ~10.4% of the phenotypic variation observed in goats., Conclusions: Our results provide new insights into the convergent evolution of SVs and serve as a rich resource for the future improvement of sheep, goats, and related livestock., (© 2024. The Author(s).)

Purpose: In patients with Wilms tumor with lung metastases, a cardiac-sparing intensity modulated radiation therapy (CS-IMRT) technique is increasingly being adopted for whole lung irradiation. However, the standard technique for flank and whole abdomen radiation remains 2-dimensional anterioposterior (AP), and overlap at the junction between the whole lung CS-IMRT and abdominal AP fields can result in overdose to normal organs. Here, we compared the dosimetry of patients who received whole lung irradiation and flank or abdominal radiation therapy with CS-IMRT with AP abdominal field (IMRT-AP) versus CS-IMRT with IMRT abdominal field (combined IMRT)., Methods and Materials: We retrospectively reviewed the radiation plans of 2 patients with Wilms tumor who received CS-IMRT and flank or whole abdomen irradiation with a combined IMRT approach. Comparison IMRT-AP plans were generated with equivalent target coverage of 95% receiving the prescribed dose. Maximum doses to normal organs were compared at the junctional overlap., Results: Overlap at the junction between CS-IMRT and abdominal fields resulted in a significantly lower dose with combined IMRT plans compared with IMRT-AP plan. Differences in maximum doses (in cGy) to normal organs between combined IMRT versus IMRT-AP plans were most significant in the vertebral body (patient 1 = 1277 vs 2065; patient 2 = 1334 vs 2287), lungs (patient 1 = 1298 vs 2081; patient 2 = 1234 vs 1820), spinal cord (patient 1 = 1235 vs 1975; patient 2 = 1345 vs 2253), stomach (patient 1 = 1264 vs 1977; patient 2 = 1118 vs 2062), and liver (patient 1 = 1297 vs 1889; patient 2 = 1334 vs 2237)., Conclusions: The combined IMRT approach for Wilms patients who require whole lung and abdomen irradiation can provide more uniform dose distribution in the junction area and significantly lower doses to normal organs at the junctional overlap., Competing Interests: LYL reports travel reimbursement from GT Medical Technologies, unrelated to this study. The other 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 The Authors.)

Objective: Early diagnosis of Severity Mycoplasma Pneumoniae Pneumonia (SMPP) has been a worldwide concern in clinical practice. Two cytokines, soluble Triggering Receptor Expressed on Myeloid cells (sTREM-1) and Interferon-Inducible Protein-10 (IP-10), were proved to be implicated in bacterial infection diseases. However, the diagnostic value of sTREM-1 and IP-10 in MPP was poorly known. This study aimed to investigate the diagnostic value of sTREM-1 and IP-10 for SMPP., Methods: In this prospective study, the authors enrolled 44 children with MPP, along with their clinical information. Blood samples were collected, and cytokine levels of sTREM-1 and IP-10 were detected with ELISA assay., Results: Serum levels of sTREM-1 and IP-10 were positively correlated with the severity of MPP. In addition, sTREM-1 and IP-10 have significant potential in the diagnosis of SMPP with an Area Under Curve (AUC) of 0.8564 (p-value = 0.0001, 95% CI 0.7461 to 0.9668) and 0.8086 (p-value = 0.0002, 95% CI 0.6918 to 0.9254) respectively. Notably, the combined diagnostic value of sTREM-1 and IP-10 is up to 0.911 in children with SMPP (p-value < 0.001, 95% CI 0.830 to 0.993)., Conclusions: Serum cytokine levels of sTREM-1 and IP-10 have a great potential diagnostic value in children with SMPP., 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 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances. However, its contribution to the progression of liver damage remains unclear., Aim: To determine the role and mechanism of UGT1A1 in liver damage progression., Methods: We investigated the relationship between UGT1A1 expression and liver injury through clinical research. Additionally, the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study., Results: Patients with UGT1A1 gene mutations showed varying degrees of liver damage, while patients with acute-on-chronic liver failure (ACLF) exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis. This suggests that low UGT1A1 levels may be associated with the progression of liver damage. In mouse models of liver injury induced by carbon tetrachloride (CCl 4 ) and concanavalin A (ConA), the hepatic levels of UGT1A1 protein were found to be increased. In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression, the hepatic protein levels of UGT1A1 were decreased, which is consistent with the observations in patients with ACLF. UGT1A1 knockout exacerbated CCl 4 - and ConA-induced liver injury, hepatocyte apoptosis and necroptosis in mice, intensified hepatocyte endoplasmic reticulum (ER) stress and oxidative stress, and disrupted lipid metabolism., Conclusion: UGT1A1 is upregulated as a compensatory response during liver injury, and interference with this upregulation process may worsen liver injury. UGT1A1 reduces ER stress, oxidative stress, and lipid metabolism disorder, thereby mitigating hepatocyte apoptosis and necroptosis., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: Application of highly selective editing RF pulses provides a means of minimizing co-editing of contaminants in J-difference MRS (MEGA), but it causes reduction in editing yield. We examined the flip angles (FAs) of narrow-band editing pulses to maximize the lactate edited signal with minimal co-editing of threonine., Methods: The effect of editing-pulse FA on the editing performance was examined, with numerical and phantom analyses, for bandwidths of 17.6-300 Hz in MEGA-PRESS editing of lactate at 3T. The FA and envelope of 46 ms Gaussian editing pulses were tailored to maximize the lactate edited signal at 1.3 ppm and minimize co-editing of threonine. The optimized editing-pulse FA MEGA scheme was tested in brain tumor patients., Results: Simulation and phantom data indicated that the optimum FA of MEGA editing pulses is progressively larger than 180° as the editing-pulse bandwidth decreases. For 46 ms long 17.6 Hz bandwidth Gaussian pulses and other given sequence parameters, the lactate edited signal was maximum at the first and second editing-pulse FAs of 241° and 249°, respectively. The edit-on and difference-edited lactate peak areas of the optimized FA MEGA were greater by 43% and 25% compared to the 180°-FA MEGA, respectively. In-vivo data confirmed the simulation and phantom results. The lesions of the brain tumor patients showed elevated lactate and physiological levels of threonine., Conclusion: The lactate MEGA editing yield is significantly increased with editing-pulse FA much larger than 180° when the editing-pulse bandwidth is comparable to the lactate quartet frequency width., (© 2023 International Society for Magnetic Resonance in Medicine.)

Ethnopharmacological Relevance: The dried fruit of Schisandra chinensis (Turcz.) Baill (S. chinensis) is widely used in treating central nervous system disorders. Increasing evidence has suggested that alcohol-soluble extracts and lignans from S. chinensis could significantly ameliorate depression-like behaviors in animal models, while there was little research on the potential of alcohol-insoluble polysaccharides as a candidate in the treatment of depression., Aim of the Study: Our research was designed to explore both the physicochemical characteristics and antidepressant-like effects of an alcohol-insoluble polysaccharide-rich fraction named SCP from S. chinensis. Simultaneously, the underlying mechanisms were elucidated in the study., Materials and Methods: The physicochemical characteristics were accomplished by colorimetric assays, CE, HPGPC, and FT-IR. Behavioral despair testing accompanied by LAT were processed to promptly assess the antidepressant-like effects of SCP in mice. Then OBX-induced mice were established to explore the impacts of chronic co-treatments with SCP. Furthermore, effects of SCP on the HPA axis, oxidant/antioxidant system, neurotrophic and synaptic factors, and gut microbiota in OBX-induced mice were detected through ELISA and 16S rDNA (V3 + V4 regions) gene sequencing., Results: SCP is a polysaccharide-rich fraction mainly comprised of xylose, glucose, rhamnose, galactose, mannose, and galacturonic acid in ratios of 0.27, 5.09, 0.24, 1.00, 0.63, and 2.86, of which the MW distribution ranges from 681 to 3232 Da. Acute pre-treatment with SCP (200 mg/kg, i.g.) remarkably reduced mice's immobility in the FST without motor stimulation. Prolonged pre-treatments effectively enhanced the effects of SCP on the behavioral despair testing in mice. Chronic co-treatments with SCP (50, 200, and 800 mg/kg, i.g.) could ameliorate the slow increase of body weight and behavioral abnormality of OBX-induced mice in systemic behavioral testing. SCP (200 mg/kg) also successfully restored hyperactivity of the HPA axis, oxidative damage in the liver, neurotrophic disturbance and abnormal synaptic plasticity in the hippocampus, and dysregulation of gut microbiota in OBX-induced mice., Conclusion: SCP exerts noteworthy antidepressant-like impacts on behavioral despair mice and OBX-induced mice via multiple targets, indicating a potential therapeutic candidate in depression therapy., 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. Published by Elsevier B.V.)

Background: The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis. SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer., Aim: To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer., Methods: This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years (median age 65) between July 2006 and April 2007. Patients were followed up until death or the study ended (median follow-up duration of 28.5 mo). The samples were used to generate tissue microarrays (TMAs) for immunohistochemical (IHC) staining. The expressions of TGF-β1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1 in gastric cancer (GC) tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients. Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015. The relationship between TGF-β1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient. The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test. A survival curve was generated using the Kaplan-Meier survival analysis., Results: TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent non-cancerous tissue. The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site [pSMAD3C(S423/425): 51.0% and pSMAD3L(S204): 31.6%]. High expression of pSMAD3L(S204) was significantly correlated with larger tumors ( P = 0.038) and later N stages ( P = 0.035). Additionally, high expression of VEGFR-1 was closely correlated with tumor size ( P = 0.015) and pathological grading ( P = 0.013). High expression of both pSMAD3L(S204) and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival (OS). Multivariate analysis indicated that high expression of pSMAD3L(S204) and VEGFR-1 were independent risk factors for prognosis in GC patients. VEGFR-1 protein expression was correlated with TGF-β1 ( r = 0.220, P = 0.029), pSMAD3C(S423/425) ( r = 0.302, P = 0.002), and pSMAD3L(S204) ( r = 0.201, P = 0.047), respectively. Simultaneous overexpression of pSMAD3L(S204) and VEGFR-1 was associated with poor OS in gastric cancer patients., Conclusion: Co-upregulation of pSMAD3L(S204) and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis, and pSMAD3L(204) may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study established an HPLC fingerprint and multi-component content determination method for salt-fired Eucommiae Cortex, and evaluated the quality of salt-fired Eucommiae Cortex from different sources using fingerprint similarity evaluation, cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least square discriminate analysis(OPLS-DA). HPLC was launched on a Cosmosil 5C&#95;(18)-MS-Ⅱ column(4.6 mm×250 mm, 5 μm) by gradient elution with a mobile phase of methanol-0.2% phosphoric acid aqueous solution at a flow rate of 1.0 mL·min~(-1), detection wavelength of 238 nm, column temperature of 30 ℃, and an injection volume of 10 μL. The results of fingerprint similarity evaluation for 20 batches of salt-fired Eucommiae Cortex indicated that, except for batch S3 with a similarity of 0.893, the similarity of the other 19 batches was of ≥ 0.919, suggesting good similarity. Fourteen common peaks were calibrated and seven common peaks were identified including geniposidic acid. The mass fractions of geniposidic acid, chlorogenic acid, geniposide, genipin, pinoresinol diglucoside, liriodendrin, and pinoresinol-4-O-β-D-glucopyranoside were 0.062 0%-0.426 9%, 0.024 9%-0.116 5%, 0.009 5%-0.052 9%, 0.005 5%-0.034 8%, 0.115 9%-0.317 8%, 0.016 4%-0.108 8%, and 0.026 4%-0.039 8%, respectively. Using CA, PCA, and OPLS-DA, the 20 batches of salt-fired Eucommiae Cortex were classified into three categories. Additionally, through the analysis of variable importance in projection(VIP) under OPLS-DA, two differential quality markers, geniposidic acid and chlorogenic acid, were identified. The established HPLC fingerprint and multi-component content determination method is stable and reliable, providing a reference for quality control of salt-fired Eucommiae Cortex.

Background and Objectives: Spinal cord compression caused by spinal tumors is measured using the epidural spinal cord compression scale, also known as the Bilsky score. Whether Bilsky score predicts short-/long-term outcomes remains unknown. The objectives were to determine the correlation of Bilsky score 0-1 vs 2-3 with regards to (1) preoperative presentation, (2) perioperative variables, and (3) long-term outcomes., Methods: A single-center, retrospective evaluation of a cohort of patients undergoing metastatic spine surgery was performed between 01/2010 and 01/2021. Multivariable logistic/linear/Cox regression were performed controlling for age, body mass index, race, total decompressed levels, tumor size, other organ metastases, and postoperative radiotherapy/chemotherapy., Results: Of 343 patients with extradural spinal metastasis, 92 (26.8%) were Bilsky 0-1 and 251 (73.2%) were Bilsky 2-3. Preoperatively, patients with Bilsky 2-3 lesions were older ( P = .008), presented more with sensory deficits ( P = .029), and had worse preoperative Karnofsky Performance Scale (KPS) ( P = .002). Perioperatively, Bilsky 2-3 patients had more decompressed levels ( P = .005) and transpedicular decompression ( P < .001), with similar operative time ( P = .071) and blood loss ( P = .502). Although not statistically significant, patients with Bilsky 2-3 had more intraoperative neuromonitoring changes ( P = .412). Although rates of complications ( P = .442) and neurological deficit ( P = .852) were similar between groups, patients with Bilsky 2-3 lesions had a longer length of stay ( P = .007) and were discharged home less frequently ( P < .001). No difference was found in 90-day readmissions ( P = .607) and reoperation ( P = .510) Long-term: LR ( P =.100) and time to LR (log-rank; P =0.532) were not significantly different between Bilsky 0-1 and Bilsky 2-3 lesions. However, patients with Bilsky 2-3 lesions had worse postoperative KPS ( P < .001), worse modified McCormick scale score ( P = .003), shorter overall survival (OS) (log-rank; P < .001), and worse survival at 1 year ( P = .012). Bilsky 2-3 lesions were associated with shorter OS on multivariable Cox regression (hazard ratio = 1.78, 95% CI = 1.27-2.49, P < .001), with no significant impact on time to LR (hazard ratio = 0.73, 95% CI = 0.37-1.44, P = .359)., Conclusion: Bilsky 2-3 lesions were associated with longer length of stay, more nonhome discharge, worse postoperative KPS/modified McCormick scale score, shorter OS, and reduced survival at 1 year. Higher-grade Bilsky score lesions appear to be at a higher risk for worse outcomes. Efforts should be made to identify metastatic spine patients before they reach the point of severe spinal cord compression.., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Metastatic disease occurs in 16% of all RMS cases and has a poor prognosis. There are limited studies examining the outcomes specific to patients with RMS metastatic to bone marrow despite an incidence of 6% at diagnosis. Our study aims to document the outcomes, prognostic factors, and clinical courses of children presenting with RMS metastatic to bone marrow treated on Children's Oncology Group (COG) cooperative trials., Methods: We performed a retrospective analysis of the patients diagnosed with RMS metastatic to bone marrow between 1997 and 2013 enrolled on one of four COG RMS clinical trials of D9802, D9803, ARST0431, and ARST08P1., Results: We identified 179 cases with RMS metastatic to bone marrow. Patients had a median age of 14.8 years, 58% were male, predominantly alveolar histology (76%), extremity was the most common primary site (32%), and 87% had metastatic disease to additional sites; 83% (n = 149) received radiation as a treatment modality. The 3- and 5-year event-free survival was 9.4% and 8.2%, respectively. The 3- and 5-year overall survival was 26.1% and 12.6%, respectively. Age ≥10 years, alveolar histology, FOXO1 fusion presence, unfavorable primary location, higher Oberlin score, and lack of radiation were identified as poor prognostic/predictive characteristics., Conclusions: This study represents the largest analysis of RMS metastatic to bone marrow, defining the poor prognostic outcome for these patients. These patients may be eligible for therapy deintensification or early pursuit of novel treatments/approaches that are desperately needed., (© 2023 Wiley Periodicals LLC.)

The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen., (© 2023 Deng et al.; Published by Cold Spring Harbor Laboratory Press.)

Aim: Cardiac injury, reflected by the measured concentrations of chemicals released from injured cardiac muscle, is common in acute pancreatitis (AP). However, there is no adequate evidence assessing the impact of cardiac injury on AP-related outcomes. Creatine kinase-myocardial band (CK-MB) mainly exists in the myocardium. Therefore, we sought to evaluate the relationship between the increase in CK-MB and the adverse clinical outcomes of AP., Methods: This propensity score-matched study analyzed AP patients admitted to the Department of Gastroenterology in the First Affiliated Hospital of Nanchang University from June 2017 to July 2022. Propensity score matching and multivariate logistic regression analysis were used to explore the relationship between CK-MB elevation and AP outcome variables., Results: A total of 5,944 patients were screened for eligibility, of whom 4,802 were ultimately enrolled. Overall, 896 (18.66%) of AP patients had elevated (>24 U/ml) CK-MB levels, and 895 (99.89%) were paired with controls using propensity score matching. The propensity score-matched cohort analysis demonstrated that mortality (OR, 5.87; 95% CI, 3.89-8.84; P < 0.001), severe acute pancreatitis (SAP) (OR, 2.74; 95% CI, 2.23-3.35; P < 0.001), and infected necrotizing pancreatitis (INP) (OR, 3.40; 95% CI, 2.34-4.94; P < 0.001) were more frequent in the elevated CK-MB (>24 U/ml) group than in the normal CK-MB (≤ 24 U/ml) group. Using the multivariate logistic regression analysis, elevated CK-MB levels were independently associated with increased mortality (OR, 2.753, 95% CI, 2.095-3.617, P < 0.001), SAP incidence (OR, 2.223, CI, 1.870-2.643, P < 0.001), and INP incidence (OR, 1.913, 95% CI, 1.467-2.494, P < 0.001). CK-MB elevation was an independent risk factor for adverse clinical outcomes in AP patients., Conclusion: CK-MB elevation was significantly related to adverse outcomes in AP patients, which makes it a potentially useful laboratory parameter for predicting adverse clinical outcomes of AP., 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 © 2023 Jiang, Ding, Huang, Lei, Ke, Xiong, Luo, He, Xia, Lu and Zhu.)

Background: Lung cancer is a highly malignant disease, primarily due to its propensity for metastasis. AMP-activated protein kinase (AMPK), the principal downstream effector of Liver Kinase B1 (LKB1), orchestrates a broad spectrum of molecular targets, thereby constraining tumor invasion and metastasis. In parallel, the RNA-binding protein RBMS3 (RNA-binding motif, single-stranded-interacting protein 3) plays a pivotal role in the epithelial-mesenchymal transition (EMT), a pivotal process in tumorigenesis. Therefore, our research aims to clarify the important role of RBMS3 as a mediator in the LKB1/AMPK inhibition of tumor invasion and metastasis. Methods: We investigated the expression and correlation between RBMS3 and LKB1 in lung cancer tissues utilizing immunohistochemistry and TCGA-LUAD data, respectively. The relationship between RBMS3 and clinical pathological features and prognosis of lung cancer was also analyzed. The functions of RBMS3 in lung cancer cell proliferation, invasion, and migration were investigated in real-time in vitro . Additionally, we investigated the effects of AMPK agonists and inhibitors to explore the mediating role of RBMS3 in AMPK-induced inhibition of lung cancer invasion and migration. Results: The IHC and TCGA data both revealed low expression of RBMS3 in lung cancer. Moreover, we found that low expression of RBMS3 was positively associated with lung cancer's histological grade, clinical stage, and N stage. Additionally, low RBMS3 expression was associated with poor overall survival. Cox regression analysis revealed that RBMS3 was an independent prognostic factor for lung cancer patients. In vitro experiments verified that RBMS3 inhibited lung cancer cell proliferation, invasion, and migration. Furthermore, our findings suggested that RBMS3 played an essential role in mediating AMPK's inhibitory effect on lung cancer invasion and migration. Conclusion: Our study highlights a novel mechanism by which LKB1/AMPK pathway activation inhibits lung cancer invasion and metastasis by promoting RBMS3 expression, offering insights in developing innovative lung cancer therapies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To evaluate the immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine (PPV23) in elderly people aged ≥60 years. Methods: The elderly aged ≥60 years with 1 dose of PPV23 vaccination were selected as revaccination group and those without history of pneumococcal vaccine immunization were selected as the first vaccination group. One dose of PPV23 was administered to both groups, and the first blood samples were collected before vaccination while the second blood samples were collected on day 28-40 after vaccination. ELISA was used to detect the concentrations of anti-specific serotype Streptococcus pneumoniae podocyte polysaccharide immunoglobulin G, and the safety of the vaccination was evaluated after 30 days. Results: The geometric mean concentration (GMC) of antibody to 23 serotypes before the vaccination (0.73-13.73 μg/ml) was higher in revaccination group than in the first vaccination group (0.39-7.53 μg/ml), the GMC after the vaccination (1.42-31.65 μg/ml) was higher than that before the vaccination (0.73-13.73 μg/ml) in the revaccination group, and the GMC after the vaccination (1.62-43.76 μg/ml) was higher than that before the vaccination (0.39-7.53 μg/ml) in the first vaccination group; the geometric mean growth multiple in revaccination group (2.16-3.60) was lower than that in the first vaccination group (3.86-16.13); The mean 2-fold antibody growth rate was lower in revaccination group (53.68%, 95% CI : 52.30%-55.06%) than in the first vaccination group (93.16%, 95% CI : 92.18%- 94.15%), all differences were significant ( P <0.001). After the vaccination, 13 serotypes of GMC were higher in the first vaccination group than in revaccination group ( P <0.001), the differences were not significant for 10 serotypes of GMC ( P >0.05). The incidence of local adverse reaction was 19.20% and 13.27% in revaccination group and the first vaccination group, respectively ( P =0.174). Conclusions: The antibody level in ≥60 years people who received one dose of PPV23 after a 5-year interval was still higher than that in unvaccinated people. The antibody level decreased after 5 years of the first vaccination, and the antibody level could be rapidly increased by one more dose vaccination, but the overall immune response was lower than that of the first vaccination; revaccination with PPV23 has a good safety.

Introduction: Rhabdomyosarcoma (RMS) of the chest wall presents unique management challenges and local control considerations. The benefit of complete excision is uncertain and must be weighed against potential surgical morbidity. Our aim was to assess factors, including local control modality, associated with clinical outcomes in children with chest wall RMS., Methods: Forty-four children with RMS of the chest wall from low-, intermediate-, and high-risk Children's Oncology Group studies were reviewed. Predictors of local failure-free survival (FFS), event-free survival (EFS), and overall survival (OS) were assessed, including clinical characteristics and staging, primary tumor anatomic locations, and local control modalities. Survival was assessed by Kaplan-Meier analysis and the log-rank test., Results: Tumors were localized in 25 (57%) and metastatic in 19 (43%), and they involved the intercostal region (52%) or superficial muscle alone (36%). Clinical group was I (18%), II (14%), III (25%), and IV (43%), and ultimately 19 (43%) patients had surgical resection (upfront or delayed), including 10 R0 resections. Five-year local FFS, EFS, and OS were 72.1%, 49.3%, and 58.5%, respectively. Univariate factors associated with local FFS included age, International Rhabdomyosarcoma Study (IRS) group, extent of surgical excision, tumor size, superficial tumor location, and presence of regional or metastatic disease. Other than tumor size, the same factors were associated with EFS and OS., Conclusions: Chest wall RMS has variable presentation and outcome. Local control is a significant contributor to EFS and OS. Complete surgical excision, whether upfront or after induction chemotherapy, is usually only possible for smaller tumors confined to the superficial musculature but is associated with improved outcomes. While overall outcomes remain poor for patients with initially metastatic tumors, regardless of local control modality, complete excision may be beneficial for patients with localized tumors if it can be achieved without excess morbidity., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: To determine outcomes of children with rhabdomyosarcoma (RMS) with isolated lung metastases., Methods: Data were analyzed for 428 patients with metastatic RMS treated on COG protocols. Categorical variables were compared using Chi-square or Fisher's exact tests. Event-free survival (EFS) and overall survival (OS) were estimated using Kaplan-Meier method and compared using the log-rank test., Results: Compared with patients with other metastatic sites (n = 373), patients with lung-only metastases (n = 55) were more likely to be <10 years of age, have embryonal histology (embryonal rhabdomyosarcoma), have N0 disease, and less likely to have primary extremity tumors. Lung-only patients had significantly better survival outcomes than patients with all other sites of metastatic disease (p < .0001) with 5-year EFS of 48.1 versus 18.8% and 5-year OS of 64.1 versus 26.9%. Patients with lung-only metastases, and those with a single extrapulmonary site of metastasis, had better survival compared with patients with two or more sites of metastatic disease (p < .0001). In patients with ERMS and lung-only metastases, there was no significant difference in survival between patients ≥10 years and 1-9 years (5-year EFS: 58.3 vs. 68.2%, 5-year OS: 66.7 vs. 67.7%)., Conclusions: With aggressive treatment, patients with ERMS and lung-only metastatic disease have superior EFS and OS compared with patients with other sites of metastatic disease, even when older than 10 years of age. Consideration should be given to including patients ≥10 years with ERMS and lung-only metastases in the same group as those <10 years in future risk stratification algorithms., (© 2023 Wiley Periodicals LLC.)

Study Design: Retrospective case-control study., Objective: In a cohort of patients undergoing metastatic spine surgery, we sought to: (1) identify risk factors associated with unplanned readmission, and (2) determine the impact of an unplanned readmission on long-term outcomes., Summary of Background Data: Factors affecting readmission after metastatic spine surgery remain relatively unexplored., Materials and Methods: A single-center, retrospective, case-control study was undertaken of patients undergoing spine surgery for extradural metastatic disease between 02/2010 and 01/2021. The primary outcome was 3-month unplanned readmission. Preoperative, perioperative, and tumor-specific variables were collected. Multivariable Cox regression was performed, controlling for tumor size, other organ metastasis, and preoperative/postoperative radiotherapy/chemotherapy., Results: A total of 357 patients underwent surgery for spinal metastases with a mean follow-up of 538.7±648.6 days. Unplanned readmission within 3 months of surgery occurred in 64/357 (21.9%) patients, 37 (57.8%) were medical, 27 (42.2%) surgical, and 21 (77.7%) were related to their spine surgery. No significant differences were found regarding demographics and preoperative variables, except for insurance, where most readmitted patients had private insurance compared with nonreadmitted patients ( P =0.021). No significant difference was found in preoperative radiotherapy/chemotherapy. Regarding perioperative exposure variables, readmitted patients had a higher rate of postoperative complications (68.8% vs. 24.2%, P <0.001) and worse postoperative Karnofsky Performance Score ( P =0.021) and Modified McCormick Scale ( P =0.015) at the time of first follow-up. On multivariate logistic regression, postoperative complications were associated with increased readmissions (odds ratio=1.38, 95% CI=1.25-1.52, P <0.001). Regarding the impact of unplanned readmission on long-term tumor control, unplanned readmission was associated with shorter time to local recurrence (log-rank; P =0.029) and reduced overall survival (OS) (log-rank; P <0.001). On multivariate Cox regression, other organ metastasis [hazard ratio (HR)=1.48, 95% CI=1.13-1.93, P =0.004] and 3-month readmission (HR=1.75, 95% CI=1.28-2.39, P <0.001) were associated with worsened OS, with no impact on LR. Postoperative chemotherapy was significantly associated with longer OS (HR=0.59, 95% CI=0.45-0.77, P <0.001)., Conclusions: Postoperative complications were associated with unplanned readmission following metastatic spine surgery. Furthermore, 3-month unplanned readmission was associated with a shorter time to local recurrence and decreased OS. These results help surgeons understand the drivers of readmissions and the impact of readmissions on patient outcomes., Level of Evidence: 3., Competing Interests: S.L.Z. reports being an unaffiliated neurotrauma consultant for the National Football League. B.F.S. is a consultant for Nuvasive and Carbofix and receives institutional research support from Nuvasive and Stryker Spine. A.M.A. receives an institutional research support from Stryker Spine. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Patients undergoing surgery for cervical spine metastases are at risk for unplanned readmission due to comorbidities and chemotherapy/radiation. Our objectives were to: 1) report the incidence of unplanned readmission, 2) identify risk factors associated with unplanned readmission, and 3) determine the impact of an unplanned readmission on long-term outcomes., Methods: A single-center, retrospective, case-control study was undertaken of patients undergoing cervical spine surgery for metastatic disease between 02/2010 and 01/2021. The primary outcome of interest was unplanned readmission within 6 months. Survival analysis was performed for overall survival (OS) and local recurrence (LR)., Results: A total of 61 patients underwent cervical spine surgery for metastatic disease with the following approaches: 11 (18.0%) anterior, 28 (45.9%) posterior, and 22 (36.1%) combined. Mean age was 60.9 ± 11.2 years and 38 (62.3%) were males. A total of 9/61 (14.8%) patients had an unplanned readmission, 3 for surgical reasons and 6 for medical reasons. No difference was found in demographics, preoperative Karnofsky Performance Scale (P = 0.992), motor strength (P = 0.477), or comorbidities (P = 0.213) between readmitted patients versus not. Readmitted patients had a higher rate of preoperative radiation (P = 0.009). No statistical differences were found in operative time (P = 0.893), estimated blood loss (P = 0.676), length of stay (P = 0.720), discharge disposition (P = 0.279), and operative approach (P = 0.450). Furthermore, no difference was found regarding complications (P = 0.463), postoperative Karnofsky Performance Scale (P = 0.535), and postoperative Modified McCormick Scale (P = 0.586). Lastly, unplanned readmissions were not associated with OS (log-rank; P = 0.094) or LR (log-rank; P = 0.110)., Conclusions: In patients undergoing cervical spine metastasis surgery, readmission occurred in 15% of patients, 33% for surgical reasons, and 67% for medical reasons. Preoperative radiotherapy was associated with an increased rate of unplanned readmissions, yet readmission had no association with OS or LR., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Many studies have shown mutual interaction between temporomandibular disorders (TMD) and psychological distress. However, evidence on the effectiveness of therapeutic interventions for TMD on psychological outcomes is scarce. This review aimed to summarise the best evidence on the association between interventions for TMD and psychological outcomes regarding symptoms of anxiety and depression. Electronic search was carried out in databases, including Pubmed, Web of Science, Medline, Cochrane Library, and Scopus. All eligible studies were included for narrative synthesis. Eligible randomised controlled trials (RCTs) were included for the meta-analysis. The overall effect size of interventions for TMD was analysed in standardised mean difference (SMD) in levels of anxiety and depression. Ten studies were included in the systematic review. Of these, nine were included in the narrative analysis and four were included in the meta-analysis. All included studies and the result of the narrative analysis showed a statistically significant beneficial effect of interventions for TMD on improving symptoms of anxiety and depression ( p < 0.0001); however, a statistically significant overall effect was not found in the meta-analyses. Current evidence is in favour of the interventions for TMD in improving symptoms of depression and anxiety. However, the effect is statistically uncertain and warrants future studies to enable the best synthesis of the evidence.

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali ( O ammon polii , 2 n = 56), a female Tibetan sheep ( O aries , 2 n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2 n = 54 than with 2 n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F 2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals., (© 2022 Li et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: Radiation after resection of an atypical lipomatous tumor (ALT) is controversial. This study evaluates local control and complications after the first resection of ALTs of the extremity with or without adjuvant radiation., Methods: A dual institution, retrospective review of patients treated from 1995 to 2020 with first-time resection of an ALT in the extremity was performed. In total, 102 patients underwent adjuvant radiation (XRT group) and 68 patients were treated with surgery alone (no-XRT group). The median follow-up time was 4.6 years (interquartile range (IQR) 2.0-7.3 years). The median radiation dose was 60 Gy (IQR 55-66 Gy). Univariable and multivariable analyses evaluated the association of patient, tumor, and treatment variables with recurrence and complications. Kaplan-Meier analysis evaluated local recurrence-free survival (LRFS) and time to complication., Results: The overall incidence of local recurrence was 1% (1/102) in the XRT group and 24% (16/68) in the no-XRT group ( p < 0.001). The median time-to-recurrence was 8.2 years (IQR 6.5-10.5 years). In the XRT and the no-XRT groups, 5-yr LRFS was 98% and 92% ( p =0.21) and 10-yr LRFS was 98% and 41% ( p < 0.001), respectively. The absence of radiation (HR = 23.63, 95% CI (3.09-180.48); p < 0.001) and R2 surgical resection margins (HR = 11.04, 95% CI (2.07-59.03); p < 0.001) incurred a 23-fold and 11-fold increased risk of local recurrence, respectively, while tumor size, depth, location, and neurovascular involvement were not found to be independent predictors of recurrence. The complication rate was 37% (38/102) in the XRT group and 10% (7/68) in the no-XRT group ( p < 0.001). Eight patients (8/102, 8%) required surgical management for complication in the XRT group compared with two patients (2/68, 3%) in the no-XRT group ( p =0.10). Higher radiation dose had a modest correlation with increased severity of complication ( ρ =0.24; p =0.02)., Conclusions: Adjuvant radiation after first-time resection of an ALT of the extremity was associated with a significantly reduced risk of local recurrence but a three-fold increase in complication rate. These data support a 10-year follow-up for these patients and inform a notable clinical trade-off if considering adjuvant radiation for this tumor with recurrent potential., Competing Interests: The authors declare no relevant or conflicting interest related to this work., (Copyright © 2022 Joshua M. Lawrenz et al.)

Aim: To investigate whether the subtle change of choroidal/retinal vessel densities and volumes in thyroid-associated ophthalmopathy (TAO) could be an early sign to detect dysthyroid optic neuropathy (DON)., Methods: This was a retrospective cross-sectional study, and a total of 98 eyes from 50 subjects were enrolled under certain criteria. Thirty-four eyes of normal controls and 64 eyes of TAO, including 39 eyes of DON and 25 eyes of TAO without DON, underwent optical coherence tomography angiography (OCTA) scanning. All the tested parameters of OCTA scanning including choroid radial peripapillary capillaries (RPC), retinal nerve fiber layer (RNFL), and macular ganglion cell complex (GCC) were compared among groups, and the correlation between OCTA parameters and visual function parameters was also investigated., Results: Whole choroidal RPC was significantly reduced in DON (48.24%±0.4978%) compared to normal (50.33%±0.3173%) and TAO without DON (49.16%±0.5463%; P =0.0041). The reduction of whole choroidal RPC was also correlated with visual field (VF) defect in DON ( r =0.5422, n =39). Although vision acuity and VF were improved in all the patients with DON after being treated with medical and surgical decompression, the reduction of RPC density were not reversed., Conclusion: There is a notable reduction in choroidal RPC in DON, which is correlated with VF defect. The reduction of RPC density could not be reversed immediately by medical and surgical decompression even when vision and VF were improved. These findings suggest that choroidal RPC could be a useful parameter to diagnose and monitor early stage of DON., (International Journal of Ophthalmology Press.)

Background: It is known that inflammatory bowel disease is the result of a defective immune system, and immunotherapy and biological therapy have gradually become important means to treat it. This paper focused on the bibliometric statistical analysis of the current research progress to summarize the research status of this field and analyze the research trends in recent years., Methods: Two visualization tools, CiteSpace and VOSviewer, were used to explore the data of journals, institutions, countries/regions, authors, references, and keywords for the literature included in the Web of Science Core Collection from January 1, 2002, to December 31, 2021., Results: A total of 312 papers were published in 120 journals by 603 institutions from 40 countries/regions, with 9463 co-cited references. The United States has the most publications with the highest total citations in the world. Inflammatory Bowel Diseases published the maximum number of papers, and Gastroenterology devoted the most co-citations to immunotherapy and biological therapy for IBD. In addition, we found that the studies before 2009 mostly focused on clinical trials while researchers have paid more attention to clinical management in therapy for IBD since 2009. Combination therapy and management of the treatment for the disease have become research hotspots., Conclusion: The focus of immunotherapy and biotherapy for IBD has shifted from clinical trials to the management of the risks and benefits of immunotherapy., (© 2022. The Author(s).)

Pu-erh tea processed from the sun-dried green tea leaves can be divided into ancient tea (AT) and terrace tea (TT) according to the source of raw material. However, their similar appearance makes AT present low market identification, resulting in a disruption in the tea market rules of fair trade. Therefore, this study analyzed the classification by principal component analysis/hierarchical clustering analysis and conducted the discriminant model through stepwise Fisher discriminant analysis and decision tree analysis based on the contents of water extract, phenolic components, alkaloid, and amino acids, aiming to investigate whether phytochemicals coupled with chemometric analyses distinguish AT and TT. Results showed that there were good separations between AT and TT, which was caused by 16 components with significant (p < 0.05) differences. The discriminant model of AT and TT was established based on six discriminant variables including water extract, (+)-catechin, (−)-epicatechin, (−)-epigallocatechin, theacrine, and theanine. Among them, water extract comprised multiple soluble solids, representing the thickness of tea infusion. The model had good generalization capability with 100% of performance indexes according to scores of the training set and model set. In conclusion, phytochemicals coupled with chemometrics analyses are a good approach for the identification of different raw materials.

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Mitochondrial reactive oxygen species (ROS) damage and atrial remodeling serve as the crucial substrates for the genesis of atrial fibrillation (AF). Branched-chain amino acids (BCAAs) catabolic defect plays critical roles in multiple cardiovascular diseases. However, the alteration of atrial BCAA catabolism and its role in AF remain largely unknown. This study aimed to explore the role of BCAA catabolism in the pathogenesis of AF and to further evaluate the therapeutic effect of melatonin with a focus on protein kinase G (PKG)-cAMP response element binding protein (CREB)-Krüppel-like factor 15 (KLF15) signaling. We found that angiotensin II-treated atria exhibited significantly elevated BCAA level, reduced BCAA catabolic enzyme activity, increased AF vulnerability, aggravated atrial electrical and structural remodeling, and enhanced mitochondrial ROS damage. These deleterious effects were attenuated by melatonin co-administration while exacerbated by BCAA oral supplementation. Melatonin treatment ameliorated BCAA-induced atrial damage and reversed BCAA-induced down-regulation of atrial PKGIα expression, CREB phosphorylation as well as KLF15 expression. However, inhibition of PKG partly abolished melatonin-induced beneficial actions. In summary, these data demonstrated that atrial BCAA catabolic defect contributed to the pathogenesis of AF by aggravating tissue fibrosis and mitochondrial ROS damage. Melatonin treatment ameliorated Ang II-induced atrial structural as well as electrical remodeling by activating PKG-CREB-KLF15. The present study reveals additional mechanisms contributing to AF genesis and highlights the opportunity of a novel therapy for AF by targeting BCAA catabolism. Melatonin may serve as a potential therapeutic agent for AF intervention., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis is an autoimmune disease usually with severe multiple dysfunction syndrome, especially prominent acute renal failure. A 65-year-old woman was admitted with progressive dyspnoea for six months and fever, sputum with blood, pain of the lower extremities and intermittent claudication for two days, indicating multiple organ involvement (respiratory system, blood vessels). The renal involvement was relatively mild, presenting with microscopic haematuria. The chest computed tomography demonstrated multiple pulmonary embolisms. Ultrasound and computed tomography angiography for the lower extremity vessels showed venous and arterial thrombosis. Exclusion of other diseases that can cause multiple organ damage and thrombosis, the positive perinuclear ANCA and MPO-ANCA strongly support the diagnosis of MPO-ANAC-associated vasculitis. The patient's physical condition has been greatly improved by treatment with corticosteroids and anticoagulation.

Objective: To investigate the stigma and marital adjustment of the female patients undergoing artificial insemination with donor sperm (AID) and analyze their correlation., Methods: Using the convenience sampling method, we selected 208 infertile female patients undergoing AID from March to December 2020. We conducted a cross-sectional survey among the patients with General Information Questionnaire, Infertility Stigma Scale (ISS), and Dyadic Adjustment Scale (DAS)., Results: The total ISS score and DAS score of the patients were 54.19 ± 14.52 and 116.23 ± 15.30, respectively. Pearson analysis showed that the total and individual item ISS scores were negatively correlated with the DAS score (P < 0.01). Multivariate linear regression analysis manifested that stigma was an important factor influencing marriage adjustment (P < 0.01) and explained 34.1% of the total variations., Conclusions: Stigma is an important factor affecting marital adjustment in female patients undergoing AID and negatively correlated with marital adjustment: The lower the stigma, the better the marital adjustment. Adequate attention should be paid to the stigma of the infertile women undergoing AID and targeted measures should be developed for its intervention.

Heavy metal pollution in rice fields leads to huge losses in rice yield every year and is thus of increasing concern. Therefore, it is important to understand the changes in the microecology and physicochemical properties of paddy soil under different levels of cadmium pollution. The purpose of this study was to investigate the response of the photosynthetic bacterial community in paddy soil to different cadmium pollution levels using 16S sequencing technology. The results showed that pH, total cadmium, and available cadmium content decreased gradually with the increase in cadmium pollution. The soil α diversity was slightly different in the high cadmium (Cd), medium Cd, and low Cd groups; however, the enriched photosynthetic populations and photosynthetic bacterial communities were significantly different among these groups. The effective connections between photosynthetic bacterial species in the high Cd group were significantly greater than those in the medium and low Cd groups, the connections were closer, and the density was higher. Alkaline nitrogen, pH, available (P/K), total (N/P), organic matter, total cadmium, and available cadmium were important factors affecting the photosynthetic bacterial community and were significantly correlated with the photosynthetic bacterial community, explaining 59.90% of the variation in the photosynthetic bacterial community. Effective Cd content was significantly positively correlated with Methylorubrum populi , Methylorubrum extorquens , Methylobacterium sp. Leaf125, and Rhodopseudomonas sp. AAP120 ( R >0.05, P <0.05). This study will provide a theoretical basis for the microbial remediation of cadmium contamination in paddy fields. This study is important for understanding the effects of cadmium pollution on specific functional microbial populations in paddy soils.

Objective: To investigate the optimal time of monitoring minimal residual disease (MRD) for predicting survival and prognosis in children with T-cell acute lymphoblastic leukemia (T-ALL) after treated by CCLG-ALL2008 chemotherapy., Methods: 96 children with T-ALL receiving CCLG-ALL2008 chemotherapy treated in our hospital from January 2015 to January 2020 were retrospectively summarized. The follow-up time was 9.0-65.0 months, with a median of 43.5 months. Kaplan-Meier survival curve was used to detect the overall event-free survival (EFS) and overall survival (OS) of the patients. The clinical data, MRD levels after 15 d, 33 d and 90 d chemotherapy between EFS group and relapse group, as well as OS group and death group were compared by using univariate analysis. Multivariate Logistic regression analysis was used to screen the main risk factors affecting EFS and OS of the patients. The patients were divided into low, moderate and high-risk according to the MRD level after 15 d, 33 d and 90 d, the differences of EFS and OS between each groups were compared again., Results: By the end of follow-up, 50 patients recurred and other 46 patients non-recurred; 40 patients died and 56 patients survived, the EFS was (49.5±6.3)% and OS was (61.5±5.9)%. Univariate analysis showed that the initial WBC count in EFS group (n=46) was significantly lower than that in relapse group (n=50), and MRD levels after 33 d and 90 d were significantly less also (P<0.05). Prednisone response in OS group (n=56) was better than that in death group (n=40), and central nerve invasion rate was lower, MRD level after 33 and 90 d were lower (P<0.05). Logistic regression analysis showed that MRD level after 90 d was the main risk factor affecting EFS of the patients; prednisone reaction, central nerve invasion and MRD level after 90 d were the main risk factors affecting OS of the patients (P<0.05). There were no differences of EFS or OS between the groups according to the MRD levels after 15 and 33 d (P>0.05), however for 90 d, EFS and OS of the patients in high-risk group were significantly lower than those in medium-risk group, and those in medium-risk group were lower than those in low-risk group (P<0.05)., Conclusion: The MRD level after 90 days CCLG-ALL2008 chemotherapy may be the best time to predict the survival and prognosis in T-ALL children.