Search

The relationship between Roussouly type and Modic changes (MC) is unknown. The aim of our study was to investigate the influence of Roussouly type on the characteristics of MC in patients with lumbar degenerative disc disease.This cross-sectional observational study from Huashan Hospital included 270 patients with lumbar degenerative disc disease. Subjects were divided into 4 groups according to the Roussouly classification. Prevalence, subtype, and distribution characteristics of MC from L1-L2 upper end plate to L5-S1 lower end plate were compared between 4 Roussouly types.Of 270 patients, 65 (24.1%) were Roussouly type I, 115 (42.6%) were Roussouly type II, 55 (20.4%) were Roussouly type III, and 35 (13.0%) were Roussouly type IV. MC were present in 45.9% (n = 270) of patients, 12.7% (n = 2700) of end plates, and 11.8% (n = 1350) of intervertebral discs. The prevalence rate of MC by subtype and intervertebral disc among the 4 Roussouly types was statistically different (P0.05), and the prevalence rate of MC by intervertebral disc in Roussouly type I was statistically higher than the other 3 Roussouly types. In Roussouly types I and IV, the prevalence rate of MC at L4-L5 level showed no significant differences compared with those at upper lumbar levels, while in Roussouly types II and III, the prevalence rate of MC at L4-L5 level was significantly higher than those at upper lumbar levels.Roussouly types can influence prevalence, subtype, and distribution characteristics of MC in patients with lumbar degenerative disc disease.

Rezvilutamide, a novel androgen-receptor inhibitor with low blood-brain barrier penetration, has shown potent antitumour activity against metastatic castration-resistant prostate cancer. In this study, we aimed to evaluate the efficacy and safety of rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy (ADT) for high-volume, metastatic, hormone-sensitive prostate cancer.CHART is a randomised, open-label, phase 3 study done at 72 hospitals in China, Poland, Czech Republic, and Bulgaria. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had high-volume metastatic, hormone-sensitive prostate cancer. Previous chemotherapy or other localised treatment for prostate cancer were not allowed. Patients were randomly assigned (1:1) to receive ADT plus either rezvilutamide (240 mg) or bicalutamide (50 mg) orally once daily. Randomisation was done via an interactive response technology system (block size of four) and stratified according to ECOG performance status and presence of visceral metastasis (excluding lymph nodes). Herein, we present the results of the preplanned interim analyses for the two co-primary endpoints of radiographic progression-free survival assessed by a blinded independent review committee and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study medication. This study is ongoing, but is closed to recruitment. This trial is registered with ClinicalTrials.gov, NCT03520478.Between June 28, 2018, and Aug 6, 2020, 792 patients were screened and 654 patients were randomly assigned to receive rezvilutamide plus ADT (n=326) or bicalutamide plus ADT (n=328). At the preplanned interim analysis for radiographic progression-free survival (data cutoff May 16, 2021), the median follow-up duration was 21·2 months (IQR 16·6-25·8). Rezvilutamide significantly improved radiographic progression-free survival compared with bicalutamide (median radiographic progression-free survival not reached [95% CI not reached-not reached] vs 25·1 months [95% CI 15·7-not reached]; hazard ratio [HR] 0·44 [95% CI 0·33-0·58]; plt;0·0001). At the preplanned interim analysis for overall survival (data cutoff Feb 28, 2022), the median follow-up duration was 29·3 months (IQR 21·0-33·3). Rezvilutamide significantly improved overall survival compared with bicalutamide (HR 0·58 [95% CI 0·44-0·77]; p=0·0001; median overall survival was not reached [95% CI not reached-not reached] vs not reached [36·2-not reached]). The most common grade 3 or worse adverse events of any cause in the safety population were hypertension (26 [8%] of 323 patients in the rezvilutamide group vs 24 [7%] of 324 patients in the bicalutamide group), hypertriglyceridaemia (24 [7%] vs seven [2%]), increased weight (20 [6%] vs 12 [4%]), anaemia (12 [4%] vs 16 [5%]), and hypokalaemia (11 [3%] vs four [1%]). Serious adverse events were reported in 90 (28%) of 323 patients in the rezvilutamide group and 69 (21%) of 324 patients in the bicalutamide group. No treatment-related deaths occurred in patients in the rezvilutamide group; one treatment-related death of unknown specific cause (lt;1%) occurred in the bicalutamide group.In the two interim analyses, rezvilutamide plus ADT significantly improved radiographic progression-free survival and overall survival compared with bicalutamide plus ADT in patients with high-volume, metastatic, hormone-sensitive prostate cancer, with a tolerable safety profile.Jiangsu Hengrui Pharmaceuticals.

To evaluate the clinical efficacy and practicality of anterior trans-intervertebral space decompression and fusion (ATIDF) by comparing radiological and clinical outcomes between ATIDF and traditional anterior cervical corpectomy and fusion (ACCF) in cervical spondylosis patients with severe disc space narrowing.Seventy-one cervical spondylosis patients with severe disc space narrowing underwent anterior cervical spine surgery were included in this retrospective study. Thirty-seven patients underwent ATIDF and 34 patients underwent ACCF. The neck disability index (NDI), Japan Orthopaedic Association (JOA) score and the Hirabayashi improvement rate were used to evaluate patient neurological status. Cervical sagittal alignment (C2-C7 Cobb angle), surgical segment sagittal alignment (Cobb angle of surgical segment) and disc space height were also compared between the two groups.There were 39 males and 32 females; mean age was 63.72 ± 6.36 years (range, 39-81 years). Mean follow-up was 22.4 months (range, 6-45 months). All patients achieved an adequate neurological improvement. There were no significant differences in NDI, JOA scores and Hirabayashi improvement rate between the two groups. The change of C2-7 Cobb angle and surgical segment Cobb angle were both greater in the ATIDF group. The average intervertebral height ratio of the patients in the ATIDF group increased significantly after surgery (0.38 ± 0.17 before surgery to 1.13 ± 0.32 after surgery, P 0.01). The overall complication rate was lower in the ATIDF group than the ACCF group (35.14% and 44.12%). At 6 months follow-up, three patients in the ACCF group presented with subsidence of the titanium mesh cage.ATIDF is an effective technique for treating cervical spondylosis with severe disc space narrowing; it can achieve adequate decompression and improve sagittal alignment while avoiding and reducing the implant-related complications inherent to traditional ACCF.

Aging is characterized by a progressive deterioration of physiological integrity, leading to impaired functional ability and ultimately increased susceptibility to death. It is a major risk factor for chronic human diseases, including cardiovascular disease, diabetes, neurological degeneration, and cancer. Therefore, the growing emphasis on "healthy aging" raises a series of important questions in life and social sciences. In recent years, there has been unprecedented progress in aging research, particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes. In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases, we review the descriptive, conceptual, and interventive aspects of the landscape of aging composed of a number of layers at the cellular, tissue, organ, organ system, and organismal levels.

In December 2019, the novel coronavirus disease (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection broke. With the gradual deepening understanding of SARS-CoV-2 and COVID-19, researchers and clinicians noticed that this disease is closely related to the nervous system and has complex effects on the central nervous system (CNS) and peripheral nervous system (PNS). In this review, we summarize the effects and mechanisms of SARS-CoV-2 on the nervous system, including the pathways of invasion, direct and indirect effects, and associated neuropsychiatric diseases, to deepen our knowledge and understanding of the relationship between COVID-19 and the nervous system.

Electrical stimulation of the right median nerve can aid coma arousal after traumatic brain injury (TBI). This study aimed to confirm the efficacy further and explore possible mechanisms of right median nerve electrical stimulation (RMNS). Five comatose patients after severe TBI from May to September 2020 in the Tianjin Medical University General Hospital received RMNS for 2 weeks besides standard management. After the 2-week treatment, the mean Glasgow Coma Scale (GCS) and neurophysiological examination were used. We then investigated the alterations in microRNA (miRNA) expression in cerebrospinal fluid (CSF) by high-throughput whole transcriptome sequencing, analyzed the data by Gene Ontology (GO) and pathway analysis, and constructed the miRNA-target gene network. Patient awareness and brain function showed a more rapid increase after treatment. We also found 38 differently expressed miRNAs, 34 of which were upregulated and 4 downregulated. GO analysis showed a relation of these differentially expressed miRNAs with neuronal growth, repair, and neural signal transmission. The most highly correlated pathways were primarily associated with the tumor necrosis factor (TNF) signaling pathway and dopaminergic synapse. The application of RMNS effectively promoted early awakening in comatose patients with severe TBI. Moreover, differentially expressed miRNAs might reduce neuronal apoptosis and increase dopamine levels by regulating target gene expression, thus participating in the specific biological process after arousal therapy. Our study provided novel targets for further research on the molecular mechanisms of RMNS arousal treatment and a new way to treat neurotraumatic diseases.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported significantly improved failure-free survival using gemcitabine plus cisplatin induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized trial, patients were assigned to be treated with concurrent chemoradiotherapy alone (standard therapy, n = 238) or gemcitabine and cisplatin induction chemotherapy before concurrent chemoradiotherapy (n = 242). With a median follow-up of 69.8 months, the induction chemotherapy group had a significantly higher 5-year OS (87.9% v 78.8%, hazard ratio, 0.51 [95% CI 0.34 to 0.78]; P = .001) and a comparable risk of late toxicities (≥ grade 3, 11.3% v 11.4%). Notably, the depth of the tumor response to induction chemotherapy correlated significantly and positively with survival (complete response v partial response v stable/progressive disease, 5-year OS, 100% v 88.4% v 61.5%, P = .005). Besides, patients with a low pretreatment cell-free Epstein-Barr virus DNA load (< 4,000 copies/mL) might not benefit from induction chemotherapy (5-year OS, 90.6% v 91.4%, P = .77). In conclusion, induction chemotherapy before concurrent chemoradiotherapy improved OS significantly in patients with locally advanced nasopharyngeal carcinoma, without increasing the risk of late toxicities. Tumor response to induction chemotherapy and pretreatment cell-free Epstein-Barr virus DNA might be useful to guide individualized treatment.

The increasing burden of non-alcoholic fatty liver disease (NAFLD) worldwide imposes an emerging public health issue. We perform the current study to estimate the global prevalence, incidence, disease progression, and clinical outcomes of NAFLD.A systematic search was conducted in Medline, Embase, Web of Science, Google Scholar, and Cochrane CENTRAL that screened articles in English language published from January 2000 to December 2021. NAFLD prevalence, incidence, rate of disease progression, and outcomes were calculated with the DerSimonian-Laird random effects model with arcsine transformation.Our search identified 59,156 records, of which 578 studies fulfilled our inclusion criteria. The overall prevalence of NAFLD was 29.38% (95% confidence interval [CI] 28.09-30.69) regardless of the diagnostic techniques. Looking at the group in which the diagnosis was made by ultrasound exclusively, the pooled prevalence was 30.49% (95% CI 29.55-31.43). NAFLD has become more prevalent during the year 2011-2021 (31.63%, 95% CI 30.23-33.04) compared with year 2000-2010 (27.94%, 95% CI 26.23-29.69). The pooled estimation of non-alcoholic steatohepatitis prevalence was 8.26% (95% CI 1.13-21.01), 46.49% (95% CI 35.93-57.20), and 46.72% (95% CI 37.57-55.98) in general population, NAFLD patients, and severe/morbidly obese patients, respectively. Based on a total of 110,142 newly developed NAFLD patients, the pooled incident rate was estimated as 46.24 cases per 1000 person-years (95% CI 43.21-49.30). In patients with NAFLD, the incident rate of hepatocellular carcinoma was 1.46 (95% CI 0.90-2.03) cases per 1000 person-years. The overall pooled estimate of NAFLD related mortality was 23.91 (95% CI 13.55-37.18) death per 1000 person-years.The prevalence of NAFLD is increasing globally. It is contributing to poor clinical outcomes including hepatocellular carcinoma and death. Rising awareness and urgent actions are warranted to control the NAFLD pandemic across the globe.PROSPERO, No. CRD42020171104.

Ticagrelor provides more rapid, potent, and consistent anti-platelet efficacy than clopidogrel. This randomized trial aimed to evaluate the anti-inflammation effects of ticagrelor versus clopidogrel on thrombus aspirated from the ST-elevation myocardial infarction (STEMI) patients.A total of 98 patients with STEMI and intended percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (600-mg loading dose) or ticagrelor (180-mg loading dose), of whom 55 with large thrombus burden underwent thrombus aspiration during PCI. Thrombus specimens were successfully aspirated from 49 patients. Finally, 24 patients in the clopidogrel group and 23 in the ticagrelor group completed the study. Inflammatory cells within thrombi were assessed by hematoxylin-eosin and immunohistochemistry stainings.Compared with the clopidogrel group, the number of total inflammatory cells per mmIn patients with undergoing PCI for STEMI, the loading dose ticagrelor regimen was associated with a reduction in inflammatory cell infiltration within thrombus compared with the loading dose clopidogrel regimen.

Smile analysis in horizontally angled views is indispensable for esthetic assessment and could reveal teeth-to-lip disharmony, which might escape discovery in the frontal and profile views. However, evidence is lacking on where the anterior teeth should be positioned for esthetics in angled smiles.Based on 3-dimensional facial image processing and geometric analysis, the lip edges were projected to the horizontal plane, and the horizontal teeth-to-lip relation was simplified and represented by the distances from dental landmarks to lower bow-shaped curves (LBSC), with the distance from facial-axis (FA) point of the canine to LBSC (FA-tangent line [TL] distance) identified as the key parameter. Using photographic modification and esthetic assessment, the effect of FA-TL distances on the attractiveness of 45° angled smiles was tested, with esthetic ranges identified. A simplified method was developed to obtain the estimative LBSC and FA-TL distances using 2-dimensional photographs and geometric analysis to facilitate clinical application.The FA-TL distance remarkably affected the esthetics of 45° angled smiles. Smiles were attractive when the FA-TL distance ranged from -1.0 to 1.5 mm perceived by orthodontists and from -1.5 to 1.5 mm perceived by laypersons. The 2-dimensional photograph-derived estimative FA-TL distance was not significantly different from that obtained in a 3-dimensional image, validating the simplified method.The LBSC could serve as a reference frame to determine the lateral limit of the maxillary anterior arch for the esthetics of 45° angled smiles. The FA-TL distance, which represented the spatial relation of the maxillary canine with the lower lip, was an esthetically essential parameter. For females aged 20-30 years, the FA point of the maxillary canines should be positioned no more than 1.5 mm labial or lingual to the LBSC.

Globally, lung cancer remains the most commonly diagnosed cancer and the leading cause of cancer-related mortality. Lung adenocarcinoma (LUAD) is a common subtype of lung cancer and carries a poor prognosis. Treatment outcomes biomarkers in LUAD are critical, and there is currently a paucity of data; therefore, there is a need for novel biomarkers and newer therapeutic targets.Bayesian analysis was used to obtain the whole-genome t value of LUAD. Gene set enrichment analysis (GSEA) was conducted to obtain the normalized enrichment scores (NES) of the whole genome, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed using the Gene Set Analysis Toolkit. Herein, we investigated the PPP1R14D expression level at the protein level in LUAD and the impact of PPP1R14D knockdown on the proliferation and apoptosis of LUAD cells in vitro.A total of 483 LUAD samples and 59 normal control samples were included, and 904 differentially expressed genes (DEGs) and 504 LUAD-related genes reported in the literature were obtained. The DEGs showed that PPP1R14D was the most significantly up-regulated gene. Western blot of 30 cases of LUAD tissue and adjacent normal tissue also found that PPP1R14D was significantly highly expressed in cancer tissues. Lentivirus-mediated shRNA strategy effectively inhibited PPP1R14D expression in human LUAD cells DMS53, while PPP1R14D knockdown induced apoptosis and cell proliferation in DMS53 cells.Abnormally up-regulated PPP1R14D promotes the survival and proliferation of tumor cells in human LUAD and may serve as a therapeutic and diagnostic target for LUAD.

Polymeric carriers for RNA therapy offer potential advantages in terms of low immunogenicity, promoting modifiability and accelerating intracellular transport. However, balancing high transfection efficacy with low toxicity remains challenging with polymer-based vehicles; indeed, polyethyleneimine (PEI) remains the "gold standard" polymer for this purpose despite its significant toxicity limitations. Herein, we demonstrate the potential of polyvinylamine (PVAm), a commodity high-charge cationic polymer used in the papermaking industry and has similar structure with PEI, as an alternative carrier for RNA delivery. High levels of transfection of normal, tumor, and stem cells with a variety of RNA cargoes including small interfering RNA (siRNA), microRNA (miRNA), and recombinant RNA can be achieved in vitro under the proper complex conditions. While, both the anti-tumor effect achieved in a xenograft osteosarcoma model and lipid-lowering activity observed in a hyperlipidemia mice indicate the potential for highly effective in vivo activity. Of note, both the transfection efficiency and the cytotoxicity of PVAm compare more favorably with those of PEI, with PVAm offering the additional advantages of simpler purification and significantly lower cost. In addition, the mechanism for the difference in transfection efficiency between PVAm and PEI is explored by molecular docking as well as analyzing the process of association and dissociation between polymers (PVAm and PEI) and nucleic acids. Our research provides a novel, non-toxic, and cost-effective carrier candidate for next generation RNA therapy, and elucidates the potential mechanism of PVAm for its efficient delivery of RNA.

PurposeA disconnect often exists between those with the expertise to manage and analyze complex, multi-source data sets, and the clinical, social services, advocacy, and public health professionals who can pose the most relevant questions and best apply the answers. We describe development and implementation of a cancer informatics infrastructure aimed at broadening the usability of community cancer data to inform cancer control research and practice; and we share lessons learned. MethodsWe built a multi-level database known as The Ohio Cancer Assessment and Surveillance Engine (OH-CASE) to link data from Ohio’s cancer registry with community data from the U.S. Census and other sources. Space- and place-based characteristics were assigned to individuals according to residential address. Stakeholder input informed development of an interface for generating queries based on geographic, demographic, and disease inputs and for outputting results aggregated at the state, county, municipality, or zip code levels. ResultsOH-CASE contains 723,410 patient records for Ohioans diagnosed with cancer from 1/1/2006 – 12/31/2017 across 88 counties containing 1215 municipalities and 1197 zip codes. Stakeholder feedback from cancer center community outreach teams, advocacy organizations, public health, and researchers suggests a broad range of uses of such multi-level data resources accessible via a user interface. ConclusionOH-CASE represents a prototype of a transportable model for curating and synthesizing data to understand cancer burden across communities. Beyond supporting collaborative research, this infrastructure can serve the clinical, social services, public health, and advocacy communities by enabling targeting of outreach, funding, and interventions to narrow cancer disparities.

This study intended to compare the prevalence of hypertension in adolescents aged 15-17 years in China according to different criteria defined by various guidelines. We included 28 715 adolescents aged 15-17 years from the China Hypertension Survey study (CHS) 2012-2015, and the 2017 American Association of Pediatrics (AAP) Clinical Practice Guideline and 2018 Chinese guidelines for children and adults were used to define hypertension. The prevalence of hypertension among Chinese adolescents aged 15-17 years was 24.4% according to the 2018 Chinese guidelines for children; the corresponding values were 18.6% according to the 2017 AAP Guidelines, and 3.5% according to 2018 Chinese guidelines for adults. The age-specific prevalence of hypertension in the age of 15, 16, and 17 years in the same population was 26.2%, 24.4%, and 23.3% according to 2018 Chinese guidelines for children; 18.8%, 17.9%, and 19.2% as per the 2017 AAP Guidelines; 3.4%, 3.4%, and 3.6% as per the 2018 Chinese guidelines for adults. A highest prevalence of hypertension was observed according to 2018 Chinese guidelines for children than the other two guidelines. Compared with the 2018 Chinese guidelines for children, a higher 95

Background The aim of the study was to investigate and summarize the effectiveness and safety of CT-guided microcoil localization before video-assisted thoracic surgery (VATS) for the removal of ground-glass opacity (GGO). Methods A total of 147 patients with GGO who were treated at our hospital between January 2019 and February 2021 were retrospectively analyzed. They were divided into two groups according to the final position at the end of the microcoil: intracavity (n = 78) and extracavity (n = 69), which were compared based on puncture complications and influence of the coil end position on VATS. Results The proportions of supine and prone positions in the intracavity group were significantly higher than those in the extracavity group (82.1% vs. 66.7%, P 0.05). The time of VATS and the rate of conversion to thoracotomy in the intracavity group were significantly lower than those in the extracavity group (103.4 ± 21.0 min vs. 112.2 ± 17.3 min, 0% vs. 5.8%, P Conclusion CT-guided placement of the microcoil is a practical, simple, and convenient localization method before VATS, with a high success rate and few complications. Furthermore, it is a better alternative method to place the end of the coil in the pleural cavity because of the lower complication rate, shorter VATS time, and lower rate of thoracotomy conversion.

Objective In observational studies, testosterone has been reported to be associated with some types of cancers. However, the direction and magnitude of the causal association between testosterone and different types of cancer remain unclear. This Mendelian randomization study assessed the causal associations of total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in men. Methods We performed two-sample Mendelian randomization using publicly available GWAS summary statistics to investigate the genetically causal association between testosterone and the risk of 22 kinds of cancers in men. Causal estimates were calculated by the inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the casualty. Results Genetically predicted BT level were significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.17 95% confidence interval (CI): 1.09–1.26, P = 2.51E−05] in the MR analysis with the IVW method. TT was found to be the suggestive protective factor against stomach cancer (OR = 0.66, 95% CI: 0.48–0.93, P = 0.0116) as well as pancreatic cancer (OR = 0.59, 95% CI: 0.36–0.96, P = 0.0346). A suggestive association was found between TT and the occurrence of small intestine cancer (OR = 1.0004, 95% CI: 1.0001–1.0007, P = 0.0116). However, testosterone had no significant association with other cancers. Conclusion This study investigated the role of testosterone in the development of prostate cancer, stomach cancer, pancreatic cancer, and small intestine cancer but found no strong association with the other cancers in men.

Poly (vinyl alcohol) (PVA) hydrogels are considered promising artificial articular cartilage. However, the weak attachment between PVA hydrogels and subchondral bone limit its application in the biomedical field. In this article, we present a new method to improve the mineralization of PVA hydrogels, and fabricate PVA hydrogels with continuously graded hydroxyapatite coating. The surface of the hydrogels was modified by dopamine self-polymerization and alendronate conjugation subsequently. Based on these, we used simulated body fluids to mineralize the hydrogels to mimic calcified cartilage zone. The modified surface of the PVA hydrogels showed excellent mineralization ability with continuously graded hydroxyapatite (HA). As the main component of human bones, HA can be chemically bonded body tissue on the interface, showing great biological activity. With the content of HA increasing, the cell adhesion ability of the hydrogels was enhanced, which helped the hydrogels integrate tightly with subchondral bone. These results demonstrate that the modified hydrogels could be promising substitutes for articular cartilage.

The optimal cutoff point for evaluating the prognosis of localized renal cell carcinoma (LRCC) remains unclear. This study aimed to verify the efficacy of tumor diameter in the 2010 American Joint Committee on Cancer (AJCC) TNM staging system and contribute to the modification of TNM staging on the prognosis of this disease. A total of 3748 patients with LRCC were enrolled and grouped according to the 2010 AJCC TNM staging system. COX analysis was used to stratify the prognosis. The optimal cutoff point of the tumor diameter in the T1 and T2 prognosis was explored. There were 3330 (88.9%) patients in stage T1 and 418 (11.1%) in stage T2. The cancer-specific mortality rate was 2.7% (100/3748). The mean follow-up was 49.8 months. A tumor diameter of 7 cm can determine the prognosis of patients at stages T1 and T2; however, 4.5 cm and 11 cm as the cutoff points for T1 and T2 sub-classification of patients with LRCC might show better recognition ability than 4 cm and 10 cm, respectively. The 2010 AJCC TNM stage can predict the prognosis of LRCC in stages T1 and T2. In addition, a tumor diameter of 4.5 cm and 11 cm might be the optimal cutoff points for the sub-classification of stages T1 and T2.

Background The correlation between modified bladder outlet obstruction index (MBOOI) and surgical efficacy still remains unknown. The purpose of the study was to investigate the clinical value of the MBOOI and its use in predicting surgical efficacy in men receiving transurethral resection of the prostate (TURP). Methods A total of 403 patients with benign prostate hyperplasia (BPH) were included in this study. The International Prostate Symptom Score (IPSS), quality of life (QoL) index, transrectal ultrasonography, and pressure flow study were conducted for all patients. The bladder outlet obstruction index (BOOI) (PdetQmax–2Qmax) and MBOOI (Pves–2Qmax) were calculated. All patients underwent TURP, and surgical efficacy was accessed by the improvements in IPSS, QoL, and Qmax 6 months after surgery. The association between surgical efficacy and baseline factors was statistically analyzed. Results A comparison of effective and ineffective groups based on the overall efficacy showed that significant differences were observed in PSA, Pves, PdetQmax, Pabd, BOOI, MBOOI, TZV, TZI, IPSS-t, IPSS-v, IPSS-s, Qmax, and PVR at baseline (p max, and the overall efficacy. Additionally, the ROC analysis further verified that MBOOI was more optimal than BOOI, TZV and TZI in predicting the surgical efficacy. Conclusion Although both MBOOI and BOOI can predict the clinical symptoms and surgical efficacy of BPH patients to a certain extent, however, compared to BOOI, MBOOI may be a more useful factor that can be used to predict the surgical efficacy of TURP. Trial registration retrospectively registered.

Background Transmission of malignancy is a notable problem that cannot always be absolutely predicted at the time of transplantation. In particular, donor-derived transmission of synovial sarcoma in solid-organ transplantation is a rare but catastrophic event. Case presentation We are the first to report three cases of synovial sarcoma transmitted from a single multi-organ donor in China. The donor died of respiratory failure caused by an intrathoracic tumor, which was diagnosed as benign at the time of donation. All three recipients developed synovial sarcoma 3–13 months after transplantation; all three cases were confirmed to be donor transmitted. The liver transplant recipient died of tumor metastasis after partial-allograft hepatectomy. The two renal-transplant recipients survived after comprehensive therapy, including allograft nephrectomy, withdrawal of immunosuppressants and targeted therapy with anlotinib. Conclusions This report highlights the importance of detailed donor assessment, close follow-up and timely treatment of unexpected donor-transmitted malignancy. Although pathology is the most important evidence for the exclusion of donors for malignant potential, it should be combined with tumor type, tumor size and speed of growth. Organs from donors with malignant potential should be discarded. Allograft nephrectomy should be considered after confirmation of renal-allograft synovial sarcoma. Anlotinib for synovial sarcoma seems to be effective and well tolerated during long-term follow-up.

Purpose To develop an end-to-end deep learning solution for quickly reconstructing radial simultaneous multi-slice (SMS) myocardial perfusion datasets with comparable quality to the pixel tracking spatiotemporal constrained reconstruction (PT-STCR) method. Methods Dynamic contrast enhanced (DCE) radial SMS myocardial perfusion data were obtained from 20 subjects who were scanned at rest and/or stress with or without ECG gating using a saturation recovery radial CAIPI turboFLASH sequence. Input to the networks consisted of complex coil combined images reconstructed using the inverse Fourier transform of undersampled radial SMS k-space data. Ground truth images were reconstructed using the PT-STCR pipeline. The performance of the residual booster 3D U-Net was tested by comparing it to state-of-the-art network architectures including MoDL, CRNN-MRI, and other U-Net variants. Results Results demonstrate significant improvements in speed requiring approximately 8 seconds to reconstruct one radial SMS dataset which is approximately 200 times faster than the PT-STCR method. Images reconstructed with the residual booster 3D U-Net retain quality of ground truth PT-STCR images (0.963 SSIM/40.238 PSNR/0.147 NRMSE). The residual booster 3D U-Net has superior performance compared to existing network architectures in terms of image quality, temporal dynamics, and reconstruction time. Conclusion Residual and booster learning combined with the 3D U-Net architecture was shown to be an effective network for reconstructing high-quality images from undersampled radial SMS datasets while bypassing the reconstruction time of the PT-STCR method.

Background We have recently showed that atorvastatin (ATO) combined with low dose of dexamethasone (DEX) was more efficacious in treating patients with chronic subdural haematoma (CSDH) than ATO monotherapy. This study was designed to investigate the underlying mechanisms of the improved efficacy of this combined therapy. Methods Mass spectrometry was performed to quantitatively detect drugs in haematoma fluids and serum samples from CSDH patients and also in cultured macrophages after treatment with either ATO alone or in combination with DEX. The differentiation and apoptosis of macrophages were evaluated using flow cytometry. The expression of cytokines, chemokines and angiogenesis-related proteins was evaluated using proteome profile arrays, immunoblots and ELISA, respectively. Results ATO was detected in haematoma fluids and serum samples, whose levels were increased significantly in samples collected from patients treated with both ATO and DEX. ATO was also increased in cultured macrophages treated with ATO and DEX. The numbers of M1-polarized macrophages were higher than the M2 phenotype in the haematoma fluids of patients. Cultured macrophages treated with ATO and DEX had reduced numbers of M1-polarized macrophages, increased numbers of M2-polarized macrophages as compared to monotherapies, and decreased rate of apoptosis induced by high-dose DEX. DEX enhanced the anti-inflammatory and anti-angiogenic activity of ATO by suppressing VEGFA and other inflammatory angiogenic factors. Consistent with the finding, patients responded well to the drug treatments had lower serum levels of VEGFA. Conclusions We have shown for the first time that ATO given orally was detected in CSDH haematoma fluids. DEX enhances the anti-inflammatory and anti-angiogenic effects of ATO, primarily by increasing the presence of ATO in haematoma and macrophages and by regulating the functions of macrophages.

Enolase 1 (ENO1) is a moonlighting protein, function as a glycolysis enzyme, a plasminogen receptor and a DNA binding protein. ENO1 play an important role in the process of cancer development. The transcription, translation, post-translational modifying activities and the immunoregulatory role of ENO1 at the cancer development is receiving increasing attention. Some function model studies have shown that ENO1 is a potential target for cancer treatment. In this review, we provide a comprehensive overview of the characterization, function, related transduction cascades of ENO1 and its roles in the pathophysiology of cancers, which is a consequence of ENO1 signaling dysregulation. And the development of novels anticancer agents that targets ENO1 may provide a more attractive option for the treatment of cancers. The data of sarcoma and functional cancer models indicates that ENO1 may become a new potential target for anticancer therapy.

Bromodomain and extraterminal (BET) proteins including BRD4 play important roles in oncogenesis and immune inflammation. Here we demonstrate that cancer cells with loss of the retinoblastoma (RB) tumor suppressor became resistant to small molecule bromodomain inhibitors of BET proteins. We find that RB binds to bromodomain-1 (BD1) of BRD4, but binding is impeded by CDK4/6-mediated RB phosphorylation at serine-249/threonine-252 (S249/T252). ChIP-seq analysis shows RB knockdown increases BRD4 occupancy at genomic loci of genes enriched in cancer-related pathways including the GPCR-GNBIL-CREB axis. S249/T252-phosphorylated RB positively correlates with GNBIL protein level in prostate cancer patient samples. BET inhibitor resistance in RB-deficient cells is abolished by co-administration of CREB inhibitor. Our study identifies RB protein as a bona fide intrinsic inhibitor of BRD4 and demonstrates that RB inactivation confers resistance to small molecule BET inhibitors, thereby revealing a regulatory hub that converges RB upstream signaling onto BRD4 functions in diseases such as cancer.

Atherosclerotic cardiovascular disease is a major cause of human disability and mortality. Our previous study demonstrated the safety and efficacy of sonodynamic therapy (SDT) on atherosclerotic plaques. However, traditional single-element therapeutic transducer has single acoustic field, and positioning therapeutic and imaging transducers in the same position is difficult during ultrasound imaging-guided SDT. Continuously changing the position of transducers to intervene lesions in different positions is required, increasing the difficulty of treatment. Thus, an SDT device with precise theranostics is required. Therefore, we designed and fabricated a "concentric ultrasound transducer for theranostics" (CUST-T), comprising a central 8-MHz linear array transducer for ultrasound imaging, and a peripheral 1-MHz hollow two-dimensional (2-D) planar array transducer for generating phased-array focused ultrasound (PAFUS). The CUST-T exhibited high imaging resolution at a distance of up to 20 mm from the transducer and could generate a personalized complex PAFUS acoustic field to match various lesions. In vitro biomedical results showed that PAFUS-SDT induced RAW264.7-derived foam cell apoptosis leading to a targeting field apoptotic rate 4.36-6.24 times that of the nontargeting field and the significant apoptotic region was consistent with the PAFUS acoustic field. In vivo, PAFUS-SDT guided by ultrasound imaging significantly increased the lumen area ( ) and collagen level ( ), whereas the wall thickness ( ) and lipid content ( ) of rabbit femoral artery were reduced. In conclusion, CUST-T provided image guidance sufficient for accurate SDT for atherosclerotic plaques in peripheral arteries and could be applied in clinical practice.

A circadian rhythm is an internalized timing system that synchronizes the cellular, behavioral, and physiological processes of organisms to the Earth’s rotation. Because all physiological activities occur at a specific time, circadian rhythm disturbances can lead to various pathological disorders and diseases. Growing evidence has shown that the circadian clock is tightly connected to male fertility, and circadian perturbations contribute to infertility. The night shiftwork, insufficient sleep, and poor sleep quality are common causes of circadian disturbances, and many studies have reported that they impair sperm quality and increase the risk of male infertility. However, research on the impacts of light, body temperature, and circadian/circannual rhythms is relatively lacking, although some correlations have been demonstrated. Moreover, as the index of sperm quality was diverse and study designs were non-uniform, the conclusions were temporarily inconsistent and underlying mechanisms remain unclear. A better understanding of whether and how circadian disturbances regulate male fertility will be meaningful, as more scientific work schedules and rational lifestyles might help improve infertility.

Bladder cancer (BLCA) is a common malignancy of the urinary system. The gut microbiome produces various metabolites that play functional roles in tumorigenesis and tumor progression. However, the integrative analysis of the gut microbiome and metabolome in BLCA has still been lacking. Thus, the aim of this study was to identify microbial and functional characteristics and metabolites in BLCA in a Chinese population. Metagenomics, targeted metabolomics, bioinformatics, and integrative analysis were used in fecal samples of BLCA patients and healthy individuals. We found gut microbiomes were significantly dysregulated in BLCA patients, including Bifidobacterium, Lactobacillus, Streptococcus, Blautia, and Eubacterium. We also found 11Z-eicosenoic acid, 3-methoxytyrosine, abrine, aniline-2-sulfonate, arachidic acid, conjugated linoleic acids, elaidic acid, glycylleucine, glycylproline, leucyl-glycine, linoelaidic acid, linoleic acid, nicotinamide hypoxanthine dinucleotide, oleic acid, petroselinic acid, and ricinoleic acid to be significantly decreased, while cholesterol sulfate was significantly increased in BLCA patients. Integration of metagenomics and metabolomics revealed interactions between gut microbiota and metabolites and the host. We identified the alterations of gut microbiomes and metabolites in BLCA in a Chinese population. Moreover, we preliminarily revealed the associations between specific gut microbiomes and metabolites. These findings determined potential causative links among gut dysbiosis, dysregulated metabolites, and BLCA.

Background There were relatively few studies about the incidence and risk factors for bloodstream infection (BSI) in patients with severe acute respiratory distress syndrome (ARDS) supported by veno–venous extracorporeal membrane oxygenation (VV–ECMO). Methods Patients who were diagnosed with severe ARDS and received VV–ECMO treatment in the medical intensive care unit of China–Japan Friendship Hospital from August 2013 to March 2019 were retrospectively studied. The pathogens isolated from blood culture (BC) were identified and analyzed for drug sensitivity. The risk factors for BSI were analyzed by logistic regression. Results A total of 105 patients were included in this single–center retrospective cohort study. Among them, 23 patients (22%) had BSIs. 19 cases were identified as primary BSI; while the other 4 cases were as secondary BSI. A total of 23 pathogenic strains were isolated from BCs, including gram–negative (G–) bacilli in 21 (91%) cases, gram–positive (G+) cocci in 1 case, fungus in 1 case, and multidrug–resistant (MDR) organisms in 8 cases. Compared with patients without BSI, patients with BSI had a higher Murray score (odds ratio = 6.29, P = 0.01) and more blood transfusion (odds ratio = 1.27, P = 0.03) during ECMO. Conclusions The incidence of BSI in patients with severe ARDS supported by VV–ECMO was 22%. G– bacilli was the main pathogen, and most of them were MDR–G– bacilli (MDR–GNB). Higher Murray score and more blood transfusion may be the independent risk factors for BSI.

BK virus (BKV) is one of the most common pathogens in post-transplantation infections. For kidney transplantation, BKV infection results in the impairment of allograft function and thus increases the risk of allograft loss. However, clinical evaluation of the prognosis of BKV-associated allograft impairment is difficult. In the present study, differential plasma proteins were screened using proteomic methods from ten patients with a transition from BKV-negative to BKV activation. We identified 12 differentially expressed proteins, and S100A8 and S100A9 were the top two upregulated proteins. Data from a cross-sectional study with 66 BKV-negative and 66 BKV-positive recipients of renal transplantation indicated that plasma S100A8/A9 was upregulated in BKV-infected recipients. Plasma S100A8/A9 positively correlated with the 1 month creatinine increase (ρ = 0.499,iP/i= 0.021) and negatively correlated with the 1 month estimated glomerular filtration rate change (ρ = -0.618,iP/i= 0.003) in recipients with BK viremia. Using least absolute shrinkage and selection operator regression models, we found that S100A8/A9 was an independent risk factor for the decrease in allograft function after BKV infection. In conclusion, S100A8/A9 is a potential host biomarker for the clinical evaluation of BKV-associated allograft function impairment in kidney transplantation.

To determine if contemporary 0.55 T MRI supports the use of contrast-optimal flip angles (FA) for simultaneous multi-slice (SMS) balanced SSFP (bSSFP) cardiac function assessment, which is impractical at conventional field strengths because of excessive SAR and/or banding artifacts.Blipped-CAIPI bSSFP was combined with spiral sampling for ventricular function assessment at 0.55 T. Cine movies with single band and SMS factors of 2 and 3 (SMS 2 and 3), and FA ranging from 60° to 160°, were acquired in seven healthy volunteers. Left ventricular blood and myocardial signal intensity (SI) normalized by background noise and blood-myocardium contrast were measured and compared across acquisition settings.Myocardial SI was slightly higher in single band than in SMS and decreased with an increasing FA. Blood SI increased as the FA increased for single band, and increment was small for FA ≥120°. Blood SI for SMS 2 and 3 increased with an increasing FA up to ∼100°. Blood-myocardium contrast increased with an increasing FA for single band, peaked at FA = 160° (systole: 28.43, diastole: 29.15), attributed mainly to reduced myocardial SI when FA ≥120°. For SMS 2, contrast peaked at 120° (systole: 21.43, diastole: 19.85). For SMS 3, contrast peaked at 120° in systole (16.62) and 100° in diastole (19.04).Contemporary 0.55 T MR scanners equipped with high-performance gradient systems allow the use of contrast-optimal FA for SMS accelerated bSSFP cine examinations without compromising image quality. The contrast-optimal FA was found to be 140° to 160° for single band and 100° to 120° for SMS 2 and 3.

Objective: Observational studies have shown the association between iron status and osteoarthritis (OA). However, due to difficulties of determining sequential temporality, their causal association is still elusive. Based on the summary data of genome-wide association studies (GWASs) of a large-scale population, this study explored the genetic causal association between iron status and OA. Methods: First, we took a series of quality control steps to select eligible instrumental SNPs which were strongly associated with exposure. The genetic causal association between iron status and OA was analyzed using the two-sample Mendelian randomization (MR). Inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods were used for analysis. The results were mainly based on IVW (random effects), followed by sensitivity analysis. IVW and MR-Egger were used for heterogeneity testing. MR-Egger was also used for pleiotropy testing. Leave-one-SNP-out analysis was used to identify single nucleotide polymorphisms (SNPs) with potential impact. Maximum likelihood, penalized weighted median, and IVW (fixed effects) were performed to further validate the reliability of results. Results: IVW results showed that transferrin saturation had a positive causal association with knee osteoarthritis (KOA), hip osteoarthritis (HOA) and KOA or HOA (p < 0.05, OR > 1), and there was a negative causal association between transferrin and HOA and KOA or HOA (p < 0.05, OR < 1). The results of heterogeneity test showed that our IVW analysis results were basically free of heterogeneity (p > 0.05). The results of the pleiotropy test showed that there was no pleiotropy in our IVW analysis (p > 0.05). The analysis results of maximum likelihood, penalized weighted median and IVW (fixed effects) were consistent with our IVW results. No genetic causal association was found between serum iron and ferritin and OA. Conclusions: This study provides evidence of the causal association between iron status and OA, which provides novel insights to the genetic research of OA.

Background Myofascial pain syndrome (MPS) is a condition with local and referred pain characterized by trigger points (taut bands within the muscle). Ischemic compression is a noninvasive manual therapy technique that has been employed for the treatment of MPS in past decades. However, little attention has been devoted to this topic. Objectives The present review was designed to explore the efficacy of ischemic compression for myofascial pain syndrome by performing a descriptive systematic review and a meta-analysis to estimate the effect of ischemic compression on MPS. Methods A systematic review and meta-analysis concerning randomized controlled trials (RCTs) with myofascial pain subjects who received ischemic compression versus placebo, sham, or usual interventions. Five databases (PubMed, The Cochrane Library, Embase, Web of Science, Ovid) were searched from the earliest data available to 2022.1.2. The standardized mean difference (SMD) and the 95% confidence interval (CI) were used for statistics. Version 2 of the Cochrane risk of tool 2 (RoB 2) was used to assess the quality of the included RCTs. Results Seventeen studies were included in the systematic review, and 15 studies were included in the meta-analysis. For the pressure pain threshold (PPT) index, 11 studies and 427 subjects demonstrated statistically significant differences compared with the control at posttreatment (SMD = 0.67, 95% CI [0.35, 0.98], P 2 = 59%). For visual analog scale (VAS) or numeric rating scale (NRS) indices, 7 studies and 251 subjects demonstrated that there was no significant difference between ischemic compression and controls posttreatment (SMD = − 0.22, 95% CI [− 0.53, 0.09], P = 0.16, I2 = 33%). Conclusion Ischemic compression, as a conservative and noninvasive therapy, only enhanced tolerance to pain in MPS subjects compared with inactive control. Furthermore, there was no evidence of benefit for self-reported pain. The number of currently included subjects was relatively small, so the conclusion may be changed by future studies. Big scale RCTs with more subjects will be critical in future.

Objective We focus on providing the first comprehensive national dataset on the incidence, injury aetiology and mortality of TSCI in China. Methods A multi-stage stratified cluster sampling method was used. We included TSCI cases from all hospitals in three regions, nine provinces and 27 cities in China via search of electronic medical records and retrospectively analysed the characteristics of TSCI in China from 2009 to 2018. We estimated the incidence of TSCI in the total population and subgroups. Results There were 5954 actual cases in 2009, corresponding to a total estimated TSCI incidence of 45.1 cases per million population (95% CI, 44.0–46.3). There were 10,074 actual cases in 2018, corresponding to a total estimated TSCI incidence of 66.5 cases per million population (95% CI, 65.2–67.8) (P P Conclusions The TSCI incidence increased significantly from 2009 to 2018. The incidence in the elderly populations was consistently high and continues to increase over time. The mortality of TSCI patients in hospitals is relatively low and continues to decrease each year, but elderly individuals remain at a high risk of hospital death.

Objective: The aim of this study is to validate the efficacy and reliability of two predictive models for postoperative fever after retrograde intrarenal surgery (RIRS) in pediatric patients Materi...

Aim This study aims to evaluate the feasibility and advantages of immediate urinary catheter removal compared with prolonged indwelling catheterization in lung cancer lobectomy. Design This study was designed as a prospective, single‐centre, randomized and open‐label clinical study. Methods People with lung cancer undergoing lobectomy/pneumonectomy were recruited and randomly allocated to two groups. One group had their urinary catheter removed immediately while the other group had it removed 48 hr after surgery. Results No significant difference in the incidence of postoperative urinary retention (POUR) was observed between the two groups. However, the incidence of postoperative catheter‐associated urinary tract infection (CAUTI) in the immediate removal group (6.7%) was lower than the control group (17.2%) (p = .030). Furthermore, the incidence of catheter‐associated emergence agitation (CAEA) in the control group (25.3%) was higher than the immediate removal group (8.9%) (p = .007). The average length of hospital stay of the immediate removal group [6.51(4–11) days] was shorter than the control group [7.20(5–12) days] (p = .002). Immediate removal of urinary catheter appeared to have fewer complications and shorter hospital stay than delayed removal.

The role of hypoxia-regulated long non-coding RNA (lncRNA) in the development of head and neck squamous cell carcinoma (HNSCC) remains to be elucidated. In the current study, we initially screened hypoxia-regulated lncRNA in HNSCC cells by RNA-seq, before focusing on the rarely annotated lncRNA USP2 antisense RNA 1 (USP2-AS1). We determined that USP2-AS1 is a direct target of HIF1α and is remarkably elevated in HNSCC compared with matched normal tissues. Patients with a higher level of USP2-AS1 suffered a poor prognosis. Next, loss- and gain-of-function assays revealed that USP2-AS1 promoted cell proliferation and invasion in vitro and in vivo. Mechanically, RNA pulldown and LC–MS/MS demonstrated that the E3 ligase DDB1- and CUL4-associated factor 13 (DCAF13) is one of the binding partners to USP2-AS1 in HNSCC cells. In addition, we assumed that USP2-AS1 regulates the activity of DCAF13 by targeting its substrate ATR. Moreover, the knockdown of DCAF13 restored the elevated cell proliferation and growth levels achieved by USP2-AS1 overexpression. Altogether, we found that lncRNA USP2-AS1 functions as a HIF1α-regulated oncogenic lncRNA and promotes HNSCC cell proliferation and growth by interacting and modulating the activity of DCAF13.

The reason that immune checkpoint inhibitors have not been widely applied to pancreatic cancer treatment is probably because of low immunogenicity or dense stromal fibrosis. Recently, only pembrolizumab was recommended for DNA mismatch repair deficiency or high microsatellite instability by National Comprehensive Cancer Network guideline. Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of pancreatic cancer, with a poor overall survival rate, the value of immunotherapy for PDAC needs more research. Here, we report a 56-year-old man suffered from PDAC with liver metastasis after radical surgery. The next-generation sequencing result demonstrated that it had remarkably high tumor mutational burden (TMB) of 49.92 Muts/Mb and microsatellite stability. Sintilimab (anti-PD-1) monotherapy was continuously administrated after failure of combined chemotherapy in second line, achieving stable disease within 22 months and few immunotherapy-related adverse events. To our knowledge, this is the first time to report a good outcome achieving 22 months with progression-free survival after PDAC metastasis with monotherapy of sintilimab. TMB may serve as a potential efficacy-related predictor in PDAC patients with sintilimab and help physicians make optimum clinical strategy.

BACKGROUND Studies on the relationship between serum creatinine and the prognosis of prostate cancer have been very limited. The aim of this study was to investigate the role of serum creatinine in the prognostic risk stratification of patients with prostate cancer. MATERIAL AND METHODS We identified 1134 eligible patients from the "Prostate Cancer Data Set" in the National Clinical Medical Science Data Center. Patients with prostate cancer were divided high- and low-risk prognostic groups according to prostate-specific antigen levels and Gleason scores and were divided into 5 groups according to serum creatinine quintile: Q1 (70.1 umol/L), Q2 (70.1-76.8 umol/L), Q3 (76.8-83.4 umol/L), Q4 (83.4-92.1 umol/L), and Q5 (92.1 umol/L). Multivariate logistic regression and a multiple restricted cubic spline method were used to evaluate the relationship between serum creatinine level and the level of prostate cancer prognostic risk. RESULTS Of the 1134 patients with prostate cancer, 134 (11.8%) had a high-risk prognosis. Compared with the Q2 group (the reference group), the lowest serum creatinine levels in the Q1 group and the highest serum creatinine levels in groups Q5, Q3, and Q4 were associated with a high-risk prognosis, and this association remained significant after adjusting for confounders. The multiple restricted cubic spline regression model showed the relationship between serum creatinine level and high-risk prognosis was U-shaped. CONCLUSIONS Serum creatinine level was an independent predictor of high-risk prognosis. Controlling serum creatinine levels between 70.1 and 76.8 umol/L in patients with prostatic cancer may benefit the prognosis of patients with prostatic cancer.

State-of-art non-invasive diagnosis processes for bladder cancer (BLCA) harbour shortcomings such as low sensitivity and specificity, unable to distinguish between high- (HG) and low-grade (LG) tumours, as well as inability to differentiate muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). This study investigates a comprehensive characterization of the entire DNA methylation (DNAm) landscape of BLCA to determine the relevant biomarkers for the non-invasive diagnosis of BLCA.A total of 304 samples from 224 donors were enrolled in this multi-centre, prospective cohort study. BLCA-specific DNAm signature discovery was carried out with genome-wide bisulfite sequencing in 32 tumour tissues and 12 normal urine samples. A targeted sequencing assay for BLCA-specific DNAm signatures was developed to categorize tumour tissue against normal urine, or MIBC against NMIBC. Independent validation was performed with targeted sequencing of 259 urine samples in a double-blinded manner to determine the clinical diagnosis and prognosis value of DNAm-based classification models. Functions of genomic region harbouring BLCA-specific DNAm signature were validated with biological assays. Concordances of pathology to urine tumour DNA (circulating tumour DNA [ctDNA]) methylation, genomic mutations or other state-of-the-art diagnosis methods were measured.Genome-wide DNAm profile could accurately classify LG tumour from HG tumour (LG NMIBC vs. HG NMIBC: p = .038; LG NMIBC vs. HG MIBC, p = .00032; HG NMIBC vs. HG MIBC: p = .82; Student's t-test). Overall, the DNAm profile distinguishes MIBC from NMIBC and normal urine. Targeted-sequencing-based DNAm signature classifiers accurately classify LG NMIBC tissues from HG MIBC and could detect tumours in urine at a limit of detection of less than .5%. In tumour tissues, DNAm accurately classifies pathology, thus outperforming genomic mutation or RNA expression profiles. In the independent validation cohort, pre-surgery urine ctDNA methylation outperforms fluorescence in situ hybridization (FISH) assay to detect HG BLCA (n = 54) with 100% sensitivity (95% CI: 82.5%-100%) and LG BLCA (n = 26) with 62% sensitivity (95% CI: 51.3%-72.7%), both at 100% specificity (non-BLCA: n = 72; 95% CI: 84.1%-100%). Pre-surgery urine ctDNA methylation signature correlates with pathology and predicts recurrence and metastasis. Post-surgery urine ctDNA methylation (n = 61) accurately predicts recurrence-free survival within 180 days, with 100% accuracy.With the discovery of BLCA-specific DNAm signatures, targeted sequencing of ctDNA methylation outperforms FISH and DNA mutation to detect tumours, predict recurrence and make prognoses.

A wide sex disparity has been demonstrated in cancer incidence, tumor aggressiveness, prognosis, and treatment response of different types of cancer. The sex specificity of cancer appears to be a relevant issue in managing the disease, and studies investigating the role of sex and gender are becoming extremely urgent. Immunotherapy plays a leading role in cancer treatment, offering a new perspective on advanced malignancies. Gender has not been considered in standard cancer treatment, suggesting increasing the recognition of sex differences in cancer research and clinical management. This paper provides an overview of sex and gender disparities in cancer immunotherapy efficacy, anti-cancer immune response, predictive biomarkers, and so on. We focus on the molecular differences between male and female patients across a broad range of cancer types to arouse the attention and practice of clinicians and researchers in a sex perspective of new cancer treatment strategies.

Benign prostatic hyperplasia (BPH) is the most common and progressive urological disease in elderly men worldwide. Epidemiological studies have suggested that the speed of disease progression varies among individuals, while the pathophysiological mechanisms of accelerated clinical progression in some BPH patients remain to be elucidated. In this study, we defined patients with BPH as belonging to the accelerated progressive group (transurethral resection of the prostate [TURP] surgery at ≤50 years old), normal-speed progressive group (TURP surgery at ≥70 years old), or non-progressive group (age ≤50 years old without BPH-related surgery). We enrolled prostate specimens from the three groups of patients and compared these tissues to determine the histopathological characteristics and molecular mechanisms underlying BPH patients with accelerated progression. We found that the main histopathological characteristics of accelerated progressive BPH tissues were increased stromal components and prostatic fibrosis, which were accompanied by higher myofibroblast accumulation and collagen deposition. Mechanism dissection demonstrated that these accelerated progressive BPH tissues have higher expression of the CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis. Estrogen functions via GPER/Gαi signaling to modulate the EGFR/ERK and HIF-1α/TGF-β1 signaling to increase prostatic stromal cell proliferation and prostatic stromal fibrosis. The increased stromal components and prostatic fibrosis may accelerate the clinical progression of BPH. Targeting this newly identified CYP19/estrogen/GPER/Gαi signaling axis may facilitate the development of novel personalized therapeutics to better suppress the progression of BPH.

Autophagy maintains cellular homeostasis by degrading and recycling cytoplasmic components under stress conditions, which is identified to be involved in tumorigenesis and now has been recognized as novel target in cancer treatment. In present study, we gathered total autophagy‐related genes and established an autophagy‐related genes signature (ATGRS) through LASSO cox regression analysis in BLCA. Kaplan‐Meier survival and multivariate cox regression analyses both showed the ATGRS was a robust independent prognostic factor with high accuracy. Subsequently, integrated analyses indicated that ATGRS had a strong correlation with molecular subtypes, clinicopathological characteristics and somatic mutation alteration. Moreover, ATGRS was found to be positively correlated with the infiltration of immune cells in tumour microenvironment (TME) and immune checkpoint expression, indicating the potent role of autophagy by regulating the TME. In addition, ATGRS was proved to be efficient in predicting the clinical benefit of immune checkpoint inhibitors (ICIs) based immunotherapy and chemotherapy in BLCA. Furthermore, we observed abnormal expression levels of autophagy‐related genes and found the different behaviour of ATGRS in pancancer by LASSO cox regression analysis. Therefore, construction of ATGRS in BLCA could help us to interpret the underlying mechanism of autophagy and sheds a light on the clinical application for a combination of autophagy modification with targeted immunotherapy and chemotherapy in BLCA.

Through specific structural modification of a 4-phenylindoline precursor, new 4-arylindolines containing a thiazole moiety were developed and found to be promising modulators of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis. Compound A30 exhibited outstanding biochemical activity, with an IC50 of 11.2 nM in a homogeneous time-resolved fluorescence assay. In the cell-based assay, A30 significantly promoted IFN-γ secretion and rescued T-cell proliferation, which were inhibited by PD-1 activation. Furthermore, A30 showed favorable in vivo antitumor activity in a mouse 4T1 breast carcinoma model. Moreover, in mouse CT26 colon carcinoma models, A30 potently suppressed the growth of CT26/PD-L1 tumor but did not obviously affect the growth of CT26/vector tumor. The results of flow cytometry analysis indicated that A30 inhibited tumor growth by activating the immune microenvironment. We concluded that A30 is a new starting point for further development of PD-1/PD-L1 interaction inhibitors as antitumor agents.

Background The identification of NTRK fusions in tumours has become critically important due to the actionable events predictive of response to TRK inhibitor. It is not clear whether the NTRK breakpoint location is different for response to targeted therapy and NTRK fusions affects the efficacy of immunotherapy. Case presentation Here we reported a 60-year-old female diagnosed with advanced lung adenocarcinoma. NGS-based molecular profiling identified a novel NCOR2-NTRK1 fusion and high tumor mutational burden (TMB) (58.58 mutations/Mb) in this case. Additionally, program death-ligand 1 (PD-L1) expression was detected in 20–30% of the tumor cells by immunohistochemical (IHC) staining. The patient received treatment with anti-PD-1 immune checkpoint inhibitor of camrelizumab. After two cycles of treatment, the CT scan showed some tumor nodules were still enlarged, indicating disease progression. She was then changed to TRK inhibitor larotrectinib. One month later, the CT scan showed the volume of some lesions started to decrease, and no metastasis lesions were found. The patient then continued the administration of larotrectinib, and some lesion sizes were significantly reduced or even disappeared in the next few months. Currently, this patient is still alive. Conclusions Altogether, this report provided a new driver of lung adenocarcinoma expanded the mutational spectrum of NTRK1 fusion variants and suggested using larotrectinib as the targeted therapy is more effective than anti-PD-1 inhibitor in lung adenocarcinoma harboring with NTRK fusion, positive PD-L1 expression, and high TMB simultaneously.

Background: Neuron-specific enolase (NSE) is one of the biomarkers of neuroendocrine neoplasms (NEN). Its level of evidence is significantly lower than some other biomarkers. However, the ratio of NSE serum concentration (NSE ratio) before and after the treatment cycle may be a good tool for evaluating the therapeutic effect of metastatic neuroendocrine neoplasms of the liver (MNENOL). Methods: We collected clinical cases of NEN with liver metastases, calculating the ratio of NSE in each case before and after the treatment cycle, using thin-slice computed tomography or magnetic resonance imaging as a reference to evaluate the therapeutic effect. We analyzed the correlation between NSE ratio and NSE serum concentration and curative effect, and then compared the evaluation performance of the two. Results: We found that increase in the NSE ratio is a risk factor for the progression of MNENOL. Compared with NSE, NSE ratio has a greater advantage in evaluating the effect of MNENOL. NSE ratio is related to the curative effect of NEN, and the correlation is better than that of NSE. When judging whether NEN has new metastasis, the NSE ratio shows a similar effect to NSE, and there is no significant difference between the two. Conclusion: NSE ratio is more effective than NSE in evaluating the therapeutic effect of MNENOL, but it is not significantly different from NSE in terms of predicting new metastases.

Enterovirus 71 (EV71) infection is more likely to cause hand, foot and mouth disease (HFMD) in children, which can lead to neurogenic complications and higher mortality. As a commonly used clinical medicine, Reduning injection (RDN) helps to shorten the symptoms of patients with HFMD and facilitate the early recovery of children. However, the regulatory mechanism of RDN on the HFMD immune system disorder caused by EV71 remains to be discussed. This study collected detailed treatment data of 56 children with HFMD who entered the affiliated Children's Hospital of Nanjing Medical University during 2019. Retrospective analysis of clinical data showed that the symptoms of the RDN treatment group were improved compared with the untreated group. To explore its mechanism, the relevant detection indicators were detected by flow cytometry, enzyme-linked immunosorbent assay and real-time quantitative PCR. It was found that the number and function of innate immune (ILCs) and adaptive immunity (Th1, Th2 and secreted cytokines) were reduced, suggesting that RDN plays a role by regulating cellular immunity. The in vitro differentiation inhibition test further confirmed that RDN affected Th1 differentiation by inhibiting the expression of transcription factors on the basis of Th1 cell differentiation in vitro.