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Background: Immune-related long noncoding RNAs (lncRNAs) play an important role in the development of cancer. This study aimed to identify immune-related lncRNAs in thyroid cancer (THCA) and develop a prognostic model for THCA. Method: We downloaded immune-related gene sets from the Gene Set Enrichment Analysis (GSEA) website and obtained THCA gene expression and clinical data from The Cancer Genome Atlas (TCGA) database. Immune-related lncRNAs were then obtained by performing correlation analysis on the expression of lncRNAs and immune-related genes. A prognostic model for THCA immune-related lncRNAs was developed through univariate Cox regression and multiple Cox regression analyses. We confirmed the results in clinical samples using quantitative real-time PCR. Results: A total of 26 immune-related lncRNAs in THCA were obtained. Then we constructed a prognosis model composed of seven lncRNAs (LINC01614, AC017074.1, LINC01184, LINC00667, ACVR2B-AS1, AC090673.1, and LINC00900). Our model can be used as an independent prognostic factor. Principal component analysis displayed that the lncRNAs in the model can distinguish between high and low-risk groups. Clinical correlation analysis showed that the expression levels of AC090673.1 (P Conclusion: We identified and experimentally validated seven immune-related lncRNAs that can serve as potential biomarkers for THCA prognosis.

Objectives Hepatocellular carcinoma (HCC) is difficult to diagnose early and progresses rapidly, making it one of the most deadly malignancies worldwide. This study aimed to evaluate whether salivary glycopattern changes combined with machine learning algorithms could help in the accurate diagnosis of HCC. Methods Firstly, we detected the alteration of salivary glycopatterns by lectin microarrays in 118 saliva samples. Subsequently, we constructed diagnostic models for hepatic cirrhosis (HC) and HCC using three machine learning algorithms: Least Absolute Shrinkage and Selector Operation, Support Vector Machine (SVM), and Random Forest (RF). Finally, the performance of the diagnostic models was assessed in an independent validation cohort of 85 saliva samples by a series of evaluation metrics, including area under the receiver operator curve (AUC), accuracy, specificity, and sensitivity. Results We identified alterations in the expression levels of salivary glycopatterns in patients with HC and HCC. The results revealed that the glycopatterns recognized by 22 lectins showed significant differences in the saliva of HC and HCC patients and healthy volunteers. In addition, after Boruta feature selection, the best predictive performance was obtained with the RF algorithm for the construction of models for HC and HCC. The AUCs of the RF-HC model and RF-HCC model in the validation cohort were 0.857 (95% confidence interval [CI]: 0.780–0.935) and 0.886 (95% CI: 0.814–0.957), respectively. Conclusions Detecting alterations in salivary protein glycopatterns with lectin microarrays combined with machine learning algorithms could be an effective strategy for diagnosing HCC in the future.

To investigate pregnancy outcomes and the effects of pregnancy on kidney function in patients with stage 3-5 chronic kidney disease (CKD).This was a retrospective study. The clinical data of women with pregnancies complicated by stage 3-5 CKD who delivered in the Peking University First Hospital from January 1st, 2013, to December 31st, 2020, were analyzed.Fifty-three patients with 54 pregnancies were studied. The mean levels of serum creatinine and eGFR in the first trimester were 138.4 ± 76.7 μmol/l and 44.9 ± 13.5 ml/min/1.73 mThe pregnancy outcomes of patients with stage 3a CKD and proteinuria1 g/24 h are acceptable. Pregnancy accelerates renal function deterioration more significantly among patients with stage 3-5 CKD and urinary protein concentrations above 1 g/24 h.

To date, only two whip spider species have been recorded in China. We describe a new species, Sarax sinensis sp. nov., from Fujian, China. This species is morphologically similar to S. ioanniticus (Kritscher, 1959), S. israelensis (Miranda et al., 2016), and S. seychellarum (Kraepelin, 1898), but can be distinguished by the combination of the following characters: 35 segments in leg I tarsus, eight teeth on cheliceral claw, and four dorsal and ventral spines respectively on pedipalp femur. To examine the evolutionary history of S. sinensis sp. nov., we sequenced 12S, 16S, and COI gene regions of our specimens and inferred its phylogenetic position. The inferred phylogenetic trees placed the new species within Sarax, with its closest relative being distributed across the western Asia. The type specimens are deposited in the Museum of Biology, East China Normal University (ECNU).

Esophageal squamous cell carcinoma (ESCC) is a common digestive cancer with high mortality rate due to late diagnosis and drug resistance. It is important to identify new molecular target and develop new anticancer strategy. ML323 is a novel USP1 inhibitor and exhibits anticancer activity against several cancers. Herein, we investigated whether ML323 has some cytotoxity effect on ESCC cells and explored the underlying mechanisms. Results revealed that ML323 impeded esophageal cancer cell viability and colony formation. Meanwhile, ML323 blocked cells at G0/G1 phase concomitant with the reduced protein level of c-Myc, cyclin D1, CDK4 and CDK6. ML323 treatment also triggered DNA damage and active p53. Then, ML323 induced apoptosis by p53-Noxa. Additionally, it stimulated protective autophagy. Co-treatment with CQ or BafA1, two classical autophagy inhibitors, enhanced the cytotoxity of ML323. These findings suggested that USP1 inhibitor (ML323) could be used as a viable anti-ESCC approach.

Microbiota in the oral cavity plays an important role in maintaining human health. Our previous studies have revealed significant alterations of salivary glycopatterns in gastric cancer (GC) patients, but it is unclear whether these altered salivary glycopatterns can cause the dysbiosis of oral microbiota. In this study, the oral microbiome of healthy volunteers (HVs) and GC patients were detected. The neoglycoproteins were then synthesized according to the altered glycopatterns in GC patients and used to explore the effects of specific salivary glycopattern against oral microbiota. The results showed that five species were significantly increased (p 0.05) while two species were significantly decreased (p 0.01) in the saliva of GC patients compared with that of HVs. And the fucose-neoglycoproteins (30-100 μg/mL) could reduce the adhesion and toxicity of Aggregatibacter segnis (A. segnis) to oral cells (HOEC and CAL-27), change the glycan structures of lipopolysaccharide on the surface of A. segnis, and enhance the capacity of A. segnis to trigger innate immune responses. This study revealed that the changes of salivary protein glycopatterns in GC patients might contribute to the dysbiosis of oral microbiota, and had important implications in developing new carbohydrate drugs to maintain a balanced microbiota in the oral.

In recent decades, haploidentical stem cell transplantation (haplo-SCT) to treat severe aplastic anemia (SAA) has achieved remarkable progress. However, long-term results are still lacking. We conducted a multicenter prospective study involving SAA patients who underwent haplo-SCT as salvage therapy. Long-term outcomes were assessed, mainly focusing on survival and quality of life (QoL). Longitudinal QoL was prospectively evaluated during pretransplantation and at 3 and 5 years posttransplantation using the SF-36 scale in adults and the PedsQL 4.0 scale in children. A total of 287 SAA patients were enrolled, and the median follow-up was 4.56 years (range, 3.01-9.05 years) among surviving patients. During the long-term follow-up, 268 of 275 evaluable patients (97.5%) obtained sustained full donor chimerism, and 93.4% had complete hematopoietic recovery. The estimated overall survival and failure-free survival for the whole cohort at 9 years were 85.4% ± 2.1% and 84.0% ± 2.2%, respectively. Age (≥18 years) and a poorer performance status (ECOG 1) were identified as risk factors for survival outcomes. For QoL recovery after haplo-SCT, we found that QoL progressively improved from pretransplantation to the 3-year and 5-year time points with statistical significance. The occurrence of chronic graft versus host disease was a risk factor predicting poorer QoL scores in both the child and adult cohorts. At the last follow-up, 74.0% of children and 72.9% of adults returned to normal school or work. These inspiring long-term outcomes suggest that salvage transplantation with haploidentical donors can be routine practice for SAA patients without human leukocyte antigen (HLA)-matched donors.

Integrative analysis of genome-wide association studies (GWASs) and gene expression studies in the form of a transcriptome-wide association study (TWAS) has the potential to better elucidate the molecular mechanisms underlying disease etiology. Here we present a method, METRO, that can leverage gene expression data collected from multiple genetic ancestries to enhance TWASs. METRO incorporates expression prediction models constructed in different genetic ancestries through a likelihood-based inference framework, producing calibrated p values with substantially improved TWAS power. We illustrate the benefits of METRO in both simulations and applications to seven complex traits and diseases obtained from four GWASs. These GWASs include two of primarily European ancestry (n = 188,577 and 339,226) and two of primarily African ancestry (n = 42,752 and 23,827). In the real data applications, we leverage gene expression data measured on 1,032 African Americans and 801 European Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study to identify a substantially larger number of gene-trait associations as compared to existing TWAS approaches. The benefits of METRO are most prominent in applications to GWASs of African ancestry where the sample size is much smaller than GWASs of European ancestry and where a more powerful TWAS method is crucial. Among the identified associations are high-density lipoprotein-associated genes including PLTP and PPARG that are critical for maintaining lipid homeostasis and the type II diabetes-associated gene MAPT that supports microtubule-associated protein tau as a key component underlying impaired insulin secretion.

Nasopharyngeal carcinoma (NPC) is a malignant tumor that usually occurs in people from Southeast Asia and Southern China. NPC is prone to migration and invasion, leading to poor prognosis. A large number of circular RNAs (circRNAs) exacerbate the process of metastasis in NPC; however, their underlying mechanisms remain unclear. We found that the circular RNA circCCNB1, encoded by the oncogene CCNB1, was downregulated in NPC biopsies and cell lines. In vitro assays show that circCCNB1 inhibits NPC cell migration and invasion. Moreover, circCCNB1 induces a protein, nuclear factor 90 (NF90), to bind and prolong the half-life of tight junction protein 1 (TJP1) mRNA. Upregulation of TJP1 enhances tight junctions between cancer cells and inhibits NPC cell migration and invasion. This study reveals a novel biological function of circCCNB1 in the migration and invasion of NPC by enhancing the tight junctions of cancer cells by binding to NF90 proteins and TJP1 mRNA, and may provide a potential therapeutic target for NPC.

Background Apolipoprotein E ε4 (APOE ε4) was shown to be a risk factor for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. When coupled with sleep disturbance, APOE ε4 posed additional risks to cognitive impairment. But the literature on the association between sleep disturbance and the APOE ε4 status of persons who are cognitively impaired has not yet been systematically examined. Objectives To explore and synthesize the relationship between sleep disturbance and APOE ε4 status of adults with MCI and AD. Methods An integrative review was guided by Whittemore and Knafl’s methodology. Systematic searches identified studies with multiple sources published before May 20, 2021. A matrix and narrative synthesis was employed to organize and synthesize the findings. Joanna Briggs Institute (JBI) Critical Appraisal tools (2020) were used to evaluate the quality of the selected studies. Results A total of 7 studies were included. APOE ε4 was associated with poor sleep quality in terms of the deterioration of nighttime total sleep time, 24-hour total sleep time, rapid eye movement, sleep efficiency, sleep latency, and wake after sleep onset in a population with MCI or AD. The interacted and adjusted relationship between sleep disturbance and APOE ε4 on the progression of cognitive decline was inconsistent. Conclusions There is evidence to support an association between sleep disturbance and APOE ε4 in individuals with cognitive impairment, but a further examination of the relationship between sleep parameters and APOE ε4 is warranted, especially as the causal or dose–response relationship remains unclear.

This study aimed to describe different patterns of self-management behaviors among clients with schizophrenia in China. Two hundred twenty-eight clients with schizophrenia living in eight communities of Beijing were investigated using the Self-Management Instrument for Persons with Schizophrenia and a Demographic and Clinical Characteristics Questionnaire. Cluster analysis was performed to categorize the data. Four distinct self-management behavior patterns and variables of clients associated with non-adherent self-management were identified. The self-management behaviors and demographic characteristics were similar in each pattern but different among patterns. These findings could guide the development of more personalized and cost-effective self-management interventions for different patterns of clients in the future.

Hydrogen therapy, an emerging therapeutic strategy, has recently attracted much attention in anticancer medicine. Evidence suggests that hydrogen (Hsub2/sub) can selectively reduce intratumoral overexpressed hydroxyl radicals (•OH) to break the redox homeostasis and thereby lead to redox stress and cell damage. However, the inability to achieve stable hydrogen storage and efficient hydrogen delivery hinders the development of hydrogen therapy. Furthermore, oxygen (Osub2/sub) deficiency in the tumor microenvironment (TME) and the electron-hole separation inefficiency in photosensitizers have severely limited the efficacy of photodynamic therapy (PDT). Herein, a smart PdH@MnOsub2/sub/Ce6@HA (PHMCH) yolk-shell nanoplatform is designed to surmount these challenges. PdH tetrahedrons combine stable hydrogen storage and high photothermal conversion efficiency of palladium (Pd) nanomaterials with near-infrared-controlled hydrogen release. Subsequently, the narrow bandgap semiconductor manganese dioxide (MnOsub2/sub) and the photosensitizer chlorin e6 (Ce6) are introduced into the PHMCH nanoplatform. Upon irradiation, the staggered energy band edges in heterogeneous materials composed of MnOsub2/suband Ce6 can efficiently facilitate electron-hole separation for increasing singlet oxygen (sup1/supOsub2/sub). Moreover, MnOsub2/subnanoshells generate Osub2/subin TME for ameliorating hypoxia and further improving Osub2/sub-dependent PDT. Finally, the hyaluronic acid-modified PHMCH nanoplatform shows negligible cytotoxicity and selectively targets CD44-overexpressing melanoma cells. The synergistic antitumor performance of the Hsub2/sub-mediated gas therapy combined with photothermal and enhanced PDT can explore more possibilities for the design of gas-mediated cancer therapy.

Chemotherapy-induced nausea and vomiting (CINV) is a troublesome side-effect of chemotherapy in pediatric patients undergoing osteosarcoma treatment. In this context, the role of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists needs to be explored.To evaluate the superiority of single-dose palonosetron over granisetron in pediatric patients undergoing highly emetogenic chemotherapy (HEC) for osteosarcoma.In this double-blind, randomized study, pediatric patients were assessed in terms of acute nausea and vomiting following HEC for osteosarcoma. These children were assigned to group 1 (palonosetron) and group 2 (granisetron) without any other antiemetic prophylaxis. The primary outcome variable was the children's segment with a complete response (CR) during the acute phase of the 1st on-study chemotherapy cycle. The risk factors associated with the emesis were analyzed. The patients were followed up for the first 24 h after chemotherapy.A total number of 200 children were evaluated in terms of the response, and other factors that might alter the response were assessed in the 2 groups. These 200 children underwent 604 blocks of chemotherapy. Complete responses were documented in 83% and 72% of children receiving palonosetron and granisetron, respectively, during the acute phase. Only dexamethasone, used as a rescue medication, was found to be a significant risk factor that predisposed to the response (p0.05).Single-dose palonosetron is an effective alternative to granisetron for preventing CINV in children receiving HEC for osteosarcoma.

Aim: To evaluate the correlation of long noncoding RNAs (lncRNAs) expression in circulating exosomes and the cancerous and noncancerous tissues in patients with non-small-cell lung carcinoma. Methods: The relative expression of the four lncRNAs including LUADT1, MALAT1, NEAT1 and MIAT between tumor tissue, adjacent noncancerous tissues and circulating exosomes were evaluated by quantitative reverse transcription PCR. Results & conclusion: The relative expression of the lncRNAs, including LUADT1, MALAT1 and NEAT1, was upregulated and MIAT was downregulated in tumor tissue compared with noncancerous tissue samples. The expression of lncRNAs in circulating exosomes was not significantly different from cancerous tissue. Our results indicate that the studied exosomal lncRNAs have a good potential to be further evaluated as prognostic/diagnostic biomarkers in patients with non-small-cell lung cancer.

Several monoclonal antibodies targeting the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway have been used successfully in anticancer immunotherapy. Inherent limitations of antibody-based therapies remain, however, and alternative small-molecule inhibitors that can block the PD-1/PD-L1 axis are urgent needed. Herein, we report the discovery of compound

RNA molecules with repeat expansion sequences can phase separate into gel-like condensate, and this process may lead to neurodegenerative diseases. Here we report that in the presence of Mg2+ion, RNA molecules containing 20×CAG repeats coacervate into filled droplets or hollowed condensate. Using hyperspectral stimulated Raman spectroscopy, we show that RNA coacervation is accompanied by the stacking and clustering of nucleobases, while forfeiting the canonical base-paired structure. At an increasing RNA/Mg2+ratio, the RNA droplets first expand in sizes, and then shrink and adopt hollow vesicle-like structures. Significantly, for both large and vesicle-like droplets, the nucleobase-clustered structure is more prominent at the rim than at the center, accounting for the rigidification of RNA droplets. Thus, our finding has broad implications for the general aging processes of RNA-containing membrane-less organelles.

Objective Stroke survivors are usually unable to perform activities of daily living (ADL) independently due to loss of hand functions. Soft pneumatic gloves provide a promising assistance approach for stroke survivors to conduct ADL tasks. However, few studies have explored effective control strategies for the 'human-soft robot' integrated system due to challenges in the nonlinearities of soft robots and uncertainties of human intentions. Therefore, this work aims to develop control approaches for the system to improve stroke survivors hand functions. Methods Firstly, a soft pneumatic glove was utilized to aid with stroke-impaired hands. Secondly, a probabilistic model-based learning control approach was proposed to overcome the challenges. Then a task-oriented intention-driven training modality was designed. Finally, the control performance was evaluated on three able-bodied subjects and three stroke survivors who attended 20-session rehabilitation training. Results The proposed approach could enable the soft pneumatic glove to provide adaptive assistance for all participants to accomplish different tasks. The tracking error and muscle co-contraction index showed decreasing trends while the hand gesture index showed an increasing tendency over training sessions. All stroke survivors showed improved hand functions and better muscle coordination after training. Conclusion This work developed a learning-based soft robotic glove training system and demonstrated its potential in post-stroke hand rehabilitation. Significance This work promotes the application of soft robotic training systems in stroke rehabilitation.

Dysregulated energy metabolism has recently been recognized as an emerging hallmark of cancer. Tumor cells, which are characterized by abnormal glycolysis, exhibit a lower extracellular pH (6.5–7.0) than normal tissues (7.2–7.4), providing a promising target for tumor-specific imaging and therapy. However, most pH-sensitive materials are unable to distinguish such a subtle pH difference owing to their wide and continuous pH-responsive range. In this study, we developed an efficient strategy for the fabrication of a tumor metabolic acidity-activatable calcium phosphate (CaP) fluorescent probe (termed MACaP9). Unlike traditional CaP-based biomedical nanomaterials, which only work within more acidic organelles, such as endosomes and lysosomes (pH 4.0–6.0), MACaP9 could not only specifically respond to the tumor extra-cellular pH but also rapidly convert pH variations into a distinct fluorescence signal to visually distinguish tumor from normal tissues. The superior sensitivity and specificity of MACaP9 enabled high-contrast visualization of a broad range of tumors, as well as small tumor lesions.

Cryopreservation of single seminiferous tubule is significant for fertility preservation, especially for male patients with cryptorchidism, Y-chromosome deletion and orchitis. However, there are few studies on cryopreservation of single seminiferous tubule. This study proposes several improved strategies for cryopreservation of single seminiferous tubule in mice. First, single seminiferous tubule was cryopreserved with modified slow freezing and vitrification methods. The results showed that the apoptosis negative rates of spermatogenic cells in single seminiferous tubule with modified slow freezing method were significantly higher than vitrification with plastic slide. Then, plastic slide and two metal vitrification carriers with high thermal conductivity, copper mesh and aluminum foil, were used to vitrify single seminiferous tubule. The metal carriers could improve the outcome of vitrification than plastic slide. The apoptosis negative rates of spermatogenic cells in the aluminum foil group was significantly higher than that in the copper mesh group. Finally, single seminiferous tubule was perfused with CPAs by micro-injection technique and vitrified. The results of cryo-microscopy experiments showed that the ice crystals formed inside the injected seminiferous tubule was reduced during the cooling process, the apoptosis negative rate of spermatocytes, spermatids and Sertoli cells were significantly higher than that of the non-injection group, indicating that the injection technique can effectively improve the effect of vitrification. This study has potential clinical value for in-vitro culture of spermatogonial stem cells and autologous testicular tissue grafting in patients with azoospermia.

Osteoporosis can be caused by a multitude of factors and is defined by a decrease in bone density and mass caused by the destruction of bone microstructure, resulting in increased bone brittleness. Thus, it is a systemic bone disease in which patients are prone to fracture. The role of ferroptosis in the pathogenesis of osteoporosis has become a topic of growing interest. In this review, we discuss the cell morphology, basic mechanisms of ferroptosis, the relationship between ferroptosis and osteoclasts and osteoblasts, as well as the relationship between ferroptosis and diabetic osteoporosis, steroid-induced osteoporosis, and postmenopausal osteoporosis. Emerging biomedical research has provided new insights into the roles of ferroptosis and osteoporosis, such as in cellular function, signaling pathways, drug inhibition, and gene silencing. The pathophysiology and mechanism of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and immune regulation. Studies using animal models of osteoporosis in vivo and cell models in vitro will help clarify the relationship between ferroptosis and osteoporosis and provide research ideas for the elucidation of new mechanisms and development of new technologies and new drugs for the treatment of osteoporosis in the future.

The interaction of inhibitory receptors with self–MHC class I (MHC-I) molecules is responsible for NK cell education. The intensity of DNAM-1 expression correlates with NK cell education. However, whether DNAM-1 expression directly influences the functional competence of NK cells via the KIR/MHC-I interaction remains unclear. Based on allogeneic haploidentical hematopoietic stem cell transplantation, we investigated the intensity of DNAM-1 expression on reconstituted NK cells via the interaction of KIR with both donor HLA and recipient HLA at days 30, 90, and 180 after hematopoietic stem cell transplantation. The reconstituted NK cells educated by donor and recipient HLA molecules showed the highest DNAM-1 expression, whereas DNAM-1 expression on educated NK cells with only recipient HLA molecules was higher than that on educated NK cells with only donor HLA molecules, indicating that NK cells with donor or recipient HLA molecules regulate DNAM-1 expression and thereby affect NK cell education. Additionally, the effects of recipient cells on NK cell education were greater than those of donor cells. However, only when the DNAM-1, NKP30, and NKG2D receptors were blocked simultaneously was the function of educated and uneducated NK cells similar. Therefore, activating receptors may collaborate with DNAM-1 to induce educated NK cell hyperresponsiveness. Our data, based on in vitro and in vivo studies, demonstrate that the functional competence of NK cells via the KIR/MHC-I interaction correlates with DNAM-1 expression in human NK cells.

Chemotherapy is a conventional cancer treatment in clinical settings. Although numerous nano drug delivery systems have been developed, the chemotherapeutic effect is greatly limited by abnormal tumor mechanics in solid tumors. Tumor stiffening and accumulated solid stress compress blood vessels and inhibit drug delivery to tumor cells, becoming critical challenges for chemotherapy. By loading doxorubicin (DOX), tissue plasminogen activator (tPA), and fibrin targeting peptide CREKA (Cys-Arg-Glu-Lys-Ala) within pH responsive amphiphilic block polymers, pyridyldithio-hydroxyethyl starch-Schiff base-polylactic acid (PA-HES-pH-PLA), we report a smart nanomedicine, DOX@CREKA/tPA-HES-pH-PLA (DOX@CREKA/tPA-HP), which exhibits a potent antitumor efficacy. In triple-negative breast cancer (TNBC) 4T1 tumors, DOX@CREKA/tPA-HP precisely targeted and effectively decomposed fibrin matrix. By measuring Young's Modulus of tumor slices and quantifying tumor openings, we demonstrated that DOX@CREKA/tPA-HP remarkably reduced tumor stiffness and solid stress. Consequently, the alleviated tumor mechanics decompressed tumor blood vessels, promoted drug delivery, and led to amplified antitumor effect. Our work reveals that decomposing fibrin is a significant means for modulating tumor mechanics, and DOX@CREKA/tPA-HP is a promising smart nanomedicine for treating TNBC.

Multifunctional phototherapy nanoagents for imaging-guided synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) are highly desirable in the field of solid tumor therapy. Nevertheless, the tumor microenvironment (TME) inherently associated with hypoxia significantly hampers the photodynamic effect of these multifunctional nanoagents. Herein, Pd nanocubes coated with an ultrathin Pt shell were prepared and further conjugated with fluorescein labeled and thiol functionalized polyethylene glycol (FITC-PEG-SH) (denoted as Pd@Pt-PEG). The deposition of a Pt shell on Pd nanocubes not only enhances the photothermal performance, exhibiting excellent hyperthermia outcomes and impressive photothermal (PT) imaging quality, but also leads to the formation of singlet oxygen (1O2) induced by plasmonic excitation. In the meantime, the catalytic activity of the Pt layer is enhanced by electronic coupling and the plasmonic effect, which induces the decomposition of endogenous overexpressed hydrogen peroxide (H2O2) in tumors to generate O2 for conquering TME and augmenting 1O2 generation for efficacious tumor cell apoptosis. The modification of FITC-PEG-SH improves the biocompatibility and provides outstanding fluorescence (FL) imaging properties. Upon NIR laser irradiation, Pd@Pt-PEG allows in situ O2 generation and dual-mode imaging-guided synergistic PTT/PDT that effectively kills hypoxic tumor cells, which makes it a promising nanotherapeutic agent for enhanced tumor therapy.

Background A Chinese surgical robot, Micro Hand S, was introduced for clinical use as a novel robotic platform. This study aimed to comprehensively compare the early experience of the Micro Hand S robot-assisted total mesorectal excision (TME) with conventional approaches. Methods Between May 2017 and April 2018, 99 consecutive patients who underwent open, laparoscopic and Micro Hand S robot-assisted TME (O-/L-/RTME) for rectal cancer were included. Clinical and pathological outcomes were retrospectively analyzed. Surgical success as the primary endpoint was defined as the absence of (i) conversion, (ii) incomplete TME, (iii) involved circumferential and distal resection margins (CRM/DRM), (iv) severe complications. Results The rate of surgical success was similar (89.7 vs. 86.4 vs. 84.6%, p = 0.851) in the three groups and the respective incidences were as follows: conversion (not applicable, 4.5 vs. 2.3%, p = 1.000), incomplete TME (6.9 vs. 6.8 vs. 3.8%, p = 0.980), involved CRM/DRM (0 vs. 2.3 vs. 3.8%, p = 0.592), severe complications (3.4 vs. 4.5 vs. 7.7%, p = 0.844). Compared with open and laparoscopic surgery, the robotic surgery was associated with longer operative time, less blood loss, earlier first flatus time and liquid intake time, and shorter length of hospital stay (p Conclusions The Micro Hand S assisted TME is safe and feasible, showing comparable outcomes than conventional approaches, with superiority in blood loss, recovery of bowel function, length of hospital stay, but with increased operative time.

The protein-coding ability of circular RNAs (circRNAs) has recently been a hot topic, but the expression and roles of protein-coding circRNAs in triple-negative breast cancer (TNBC) remain uncertain. By intersecting circRNA sequencing data from clinical samples and cell lines, we identified a circRNA, termed circ-EIF6, which predicted a poorer prognosis and correlated with clinicopathological characteristics in a cohort of TNBC patients. Functionally, we showed that circ-EIF6 promoted the proliferation and metastasis of TNBC cells in vitro and in vivo. Mechanistically, we found that circ-EIF6 contains a 675-nucleotide (nt) open reading frame (ORF) and that the -150-bp sequence from ATG functioned as an internal ribosome entry site (IRES), which is required for translation initiation in 5' cap-independent coding RNAs. circ-EIF6 encodes a novel peptide, termed EIF6-224 amino acid (aa), which is responsible for the oncogenic effects of circ-EIF6. The endogenous expression of EIF6-224aa was further examined in TNBC cells and tissues by specific antibody. Moreover, EIF6-224aa directly interacted with MYH9, an oncogene in breast cancer, and decreased MYH9 degradation by inhibiting the ubiquitin-proteasome pathway and subsequently activating the Wnt/beta-catenin pathway. Our study provided novel insights into the roles of protein-coding circRNAs and supported circ-EIF6/EIF6-224aa as a novel promising prognostic and therapeutic target for tailored therapy in TNBC patients.

Excessive cadmium ions in water bodies pose a severe challenge to ecology and human health, and the development of cadmium metal ion sensors is imperative. Here, we showed a dual-signal sensor based on colorimetry and fluorescence that was self-assembled from FeOOH nanosheets and TMPyP4. This nanocomposite enabled quick, selective cadmium ion detection. The Soret band at 442 nm in the UV absorption spectrum represented the coordination of cadmium ions with FeOOH@TMPyP4, and the absorbance increased linearly with increasing cadmium ion concentration (

A multifunctional magnetic cationic MOF composite (Fe3O4@ILI-01@Ti4+) was successfully prepared for the synchronous enrichment of phosphopeptides/glycopeptides.

Conventionally, Rho guanine nucleotide exchange factors (GEFs) are known activators of Rho guanosine triphosphatases (GTPases) that promote tumorigenesis. However, the role of Rho GEFs in non-small cell lung cancer (NSCLC) remains largely unknown. Through the screening of 81 Rho GEFs for their expression profiles and correlations with survival, four of them were identified with strong significance for predicting the prognosis of NSCLC patients. The four Rho GEFs, namely ABR, PREX1, DOCK2 and DOCK4, were downregulated in NSCLC tissues compared to normal tissues. The downregulation of ABR, PREX1, DOCK2 and DOCK4, which can be attributfed to promoter methylation, is correlated with poor prognosis. The underexpression of the four key Rho GEFs might be related to the upregulation of MYC signaling and DNA repair pathways, leading to carcinogenesis and poor prognosis. Moreover, overexpression of ABR was shown to have a tumor-suppressive effect in PC9 and H1703 cells. In conclusion, the data reveal the unprecedented role of ABR as tumor suppressor in NSCLC. The previously unnoticed functions of Rho GEFs in NSCLC will inspire researchers to investigate the distinct roles of Rho GEFs in cancers, in order to provide critical strategies in clinical practice.

BACKGROUND Glottic entrance stenosis is an important cause of difficult airway intubation and may be potentially associated with scoliosis. This retrospective study from a single center in China aimed to investigate the parameters and risk factors associated with glottic entrance stenosis by evaluating 154 patients with scoliosis who underwent posterior surgical correction, internal fixation, and fusion. MATERIAL AND METHODS A total of 161 patients diagnosed with scoliosis from 2018 to 2020 were included and grouped by classification, and 7 of them were excluded from the risk factor analysis. All patients underwent posterior surgical correction, internal fixation, and fusion. Basic data, scoliosis-related information, and radiological image were collected. Sagittal and transverse diameter and cross-section area were measured. A new definition of glottic entrance stenosis was proposed based on the traditional formula for prediction of tracheal tuba diameter. RESULTS The percentage of transverse stenosis in these patients was 35.4%, and the incidence of sagittal stenosis and area stenosis were 9.9% and 12.4% respectively, while 37.9% of scoliosis patients also have at least 1 type of glottic entrance stenosis. Longer course of disease is a proven risk factor for sagittal stenosis (P=0.037). Smaller lumbar lordosis indicates higher risk of transverse stenosis (P=0.024). Wedged vertebrae are a risk factor for area stenosis (P=0.024). CONCLUSIONS This study comprehensively measured glottic entrance parameters in patients with scoliosis, proposed a new definition of glottic entrance stenosis, and found that longer course of disease, smaller lumbar lordosis, and wedged vertebrae were risk factors for sagittal stenosis, transverse stenosis, and area stenosis, respectively.

At present, acute myeloid leukemia (AML) is mainly treated with combination medication, high-dose, and early intensification. The treatment has achieved good results, but the long-term treatment effect is still not satisfactory. Studies have shown that the different levels of cytokine expression in AML patients can help AML risk stratification, search for treatment directions and predict the prognosis. It has been confirmed that the expression of IL-1β, IL-6, TNF-α, and TGF-β1 are increased in AML patients, and they all indicate a poor prognosis. However, IL-8, IFN-γ, and CCL5 have great research value in chemotherapy resistance and improvement of treatment effect. This article reviews the research progress of cytokine biomarkers in the prognosis of AML patients.细胞因子在急性髓系白血病预后中的研究进展.目前急性髓系白血病（AML）的治疗以联合用药、大剂量、早期强化为主，且取得了较好的治疗效果，但是远期治疗效果仍令人不满意。研究表明，AML患者细胞因子的不同程度表达有助于AML危险分层、寻找治疗方向以及预测AML患者预后。目前已证实IL-1β、IL-6、TNF-α、TGF-β1在AML患者中高表达，且均提示不良预后，而IL-8、IFN-γ、CCL5在化疗耐药性及改善治疗效果方面具有较大的研究价值。本文就细胞因子类生物标志在AML患者预后中的研究进展作一综述.

Haploidentical allogeneic haematopoietic stem cell transplantation (haplo-HSCT) is a significant alternative treatment for severe aplastic anaemia (SAA). To improve this process by modifying the risk stratification system, we conducted a retrospective study using our database. 432 SAA patients who received haplo-HSCT between 2006 and 2020 were enrolled. These patients were divided into a training (n = 288) and a validation (n = 144) subset randomly. In the training cohort, longer time from diagnosis to transplantation, poorer Eastern Cooperative Oncology Group (ECOG) status and higher haematopoietic cell transplantation-specific comorbidity index (HCT-CI) score were independent risk factors for worse treatment-related mortality (TRM) in the final multivariable model. The haplo-HSCT scoring system was developed by these three parameters. Three-year TRM after haplo-HSCT were 6% [95% confidence interval (CI), 1-21%], 21% (95% CI, 7-40%), and 47% (95% CI, 20-70%) for the low-, intermediate-, and high-risk group, respectively (P < 0·0001). In the validation cohort, the haplo-HSCT scoring system also separated patients into three risk groups with increasing risk of TRM: intermediate-risk [hazard ratio (HR) 2·45, 95% CI, 0·92-6·53] and high-risk (HR 11·74, 95% CI, 3·07-44·89) compared with the low-risk group (P = 0·001). In conclusion, the haplo-HSCT scoring system could effectively predict TRM after transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used in the treatment of hematological diseases. It is well known that allogeneic grafts play a key role in predicting transplantation prognosis. Hematopoietic stem cells (HSCs) are a functional part of grafts and are capable of reconstructing hematopoiesis and immunity, but purified HSCs have not been identified or isolated to date. In clinical practice, allogeneic grafts have been optimized to improve transplantation outcomes. The optimized grafts are considered to engraft successfully, reconstruct immunity rapidly, and exert a graft-vs-leukemia (GVL) effect without causing severe graft-vs-host disease (GvHD). In the last several decades, considerable efforts have been made in searching for optimized grafts based on different graft manipulation approaches and different graft sources. Currently, there is no uniform standard for optimized grafts in allogeneic transplantation. In the future, sorting out the cellular elements responsible for the effects of allo-HSCT might be a research direction for further optimization of grafts. In this review, we propose the concept of optimized grafts and summarize the recent advances made in the process of optimizing grafts.

Background Macro-reentrant atrial tachycardias (MATs) are a common complication after cardiac valve surgery. The MAT types and the effectiveness of MAT ablation might differ after different valve surgery. Data comparing the electrophysiological characteristics and the ablation results of MAT post-tricuspid or mitral valve surgery are limited. Methods Forty-eight patients (29 males, age 56.1 ± 13.3 years) with MAT after valve surgery were assigned to tricuspid valve (TV) group (n = 18) and mitral valve (MV) group (n = 30). MATs were mapped and ablated guided by a three-dimensional navigation system. The one-year clinical effectiveness was compared in two groups. Results Nineteen MATs were documented in TV group, including 16 cavo-tricuspid isthmus (CTI)-dependent AFL and 3 other MATs at right atrial (RA) free wall, RA septum and left atrial (LA) roof. Thirty-nine MATs were identified in MV group, including15 CTI-dependent AFL, 8 RA free wall scar-related, 2 RA septum scar-related, 8 peri-mitral flutter, 3 LA roof-dependent, 2 LA anterior scar-related, and 1 right pulmonary vein-related MAT. Compared with TV group, MV group had significantly lower prevalence of CTI-dependent AFL (38.5% vs. 84.2%), higher prevalence of left atrial MAT (35.9 vs.5.3%) and higher proportion of patients with left atrial MAT (40 vs. 5.6%), P = 0.02, 0.01 and 0.01, respectively. The acute success rate of MAT ablation (100 vs. 93.3%) and the one-year freedom from atrial tachy-arrhythmias (72.2 vs. 76.5%) was comparable in TV and MV group. No predictor for recurrence was identified. Conclusion Although the types of MATs differed significantly in patients with prior TV or MV surgery, the acute and mid-term effectiveness of MAT ablation was comparable in two groups. Trial registration: This study was registered as a part of EARLY-MYO-AF clinical trial at the website ClinicalTrials. gov (NCT04512222).

Summary We propose a new concept that human somatic cells can be converted to become male germline stem cells by the defined factors. Here, we demonstrated that the overexpression of DAZL, DAZ2, and BOULE could directly reprogram human Sertoli cells into cells with the characteristics of human spermatogonial stem cells (SSCs), as shown by their similar transcriptomes and proteomics with human SSCs. Significantly, human SSCs derived from human Sertoli cells colonized and proliferated in vivo, and they could differentiate into spermatocytes and haploid spermatids in vitro. Human Sertoli cell-derived SSCs excluded Y chromosome microdeletions and assumed normal chromosomes. Collectively, human somatic cells could be converted directly to human SSCs with the self-renewal and differentiation potentials and high safety. This study is of unusual significance, because it provides an effective approach for reprogramming human somatic cells into male germ cells and offers invaluable male gametes for treating male infertility., Highlights • Human Sertoli cells can be converted into SSCs by overexpressing DAZ family genes • Human Sertoli cell-derived cells have phenotypic features with SSCs in vivo • Human Sertoli cell-derived SSCs differentiate into haploid spermatids in vitro • Human Sertoli cell-derived SSCs have normal chromosomes and no gene microdeletion, In this article, Zuping He and colleagues show that human Sertoli cells can be converted directly into human spermatogonial stem cells that are able to self-renew in vivo and differentiate into spermatocytes and haploid spermatids in vitro via the overexpression of three DAZ family genes.

Accurate diagnosis and precise and effective treatment are currently the two magic weapons for dealing with cancer. However, a single marker is often associated with multiple cellular events, which is not conducive to accurate diagnosis, and overly mild treatment methods often make the treatment effect unsatisfactory. In this paper, we construct a Au/Pd octopus nanoparticle-DNA nanomachine (Au/Pd ONP-DNA nanomachine) as a fully automatic diagnosis and treatment logic system. In this system, multiple DNA components are targeting detection units, Au/Pd ONPs act as carriers, and Au/Pd ONPs with an 808 nm laser is the treatment unit. In order to achieve the purpose of precise treatment, we will detect two secondary markers under the premise of detecting one major tumor marker. When all of the designated targets are detected (the logic system input is (1, 1, 1), and the output is (1, 1)), the 808 nm laser can be programmed to automatically radiate tumors and perform photothermal therapy and photodynamic therapy. In vivo and in vitro experiments show that this logic system not only can accurately identify tumor cells but also has considerable therapeutic effects.

Gastric cancer (GC) ranks the third among global cancer-related mortality, especially in East Asia. Angiogenesis plays an important role in promoting tumor progression, and clinical trials have demonstrated that anti-angiogenesis therapy is effective in GC management. Natriuretic peptide receptor A (NPRA) functions significantly in promoting GC development and progression. Whether NPRA can promote angiogenesis of GC remains unclear. Tumor samples collection and immunohistochemical experiment showed that the expression of NPRA was positively correlated with the expression of CD31 and vessel density. In vivo and in vitro analysis showed that NPRA could promote GC-associated angiogenesis and tumor metastasis. Results of Co-IP/MS showed that NPRA could prevent HIF-1α from being degraded by binding to HIF-1α. Protection of HIF-1α improved VEGF levels and thus promoted angiogenesis. In summary, NPRA protected HIF-1α from proteolysis by binding to HIF-1α, increased the expression of HIF-1α, and promoted GC angiogenesis. This study has discovered a new mechanism for NPRA to promote gastric cancer development and a new regulatory mechanism for HIF-1α.

Research question Is vitrification with microinjection of single seminiferous tubules an efficient cryopreservation approach for limited testicular tissue? Design Testicular tissue from 10 patients with normal spermatogenesis were assigned to a fresh control group or one of the following cryopreservation procedures: uncontrolled slow freezing (USF) using either 1.5 or 2.1 M DMSO combined with sucrose and vitrification with or without single seminiferous tubules microinjection. Results Single seminiferous tubules microinjected with cryoprotective agents (CPA) enhanced the penetration of CPA compared with CPA-treated testicular tissue fragments. Microinjection of seminiferous tubules (VLP) maintained tubule structural integrity and germ cell numbers, and reduced spermatogonial apoptosis after cryopreservation compared with vitrification without microinjection (apoptosis rate: VLP versus vitrification without microinjection, P = 0.047; VLP versus USF, P= 0.049). Freezing of single seminiferous tubules using 0.25-ml straws and traditional sperm freezing methods protected sperm retrieval and recovery rates, and the progressive motility index. Conclusions Vitrification of single seminiferous tubule with microinjection of low CPA concentration is an effective approach to testicular cryopreservation.

Long noncoding RNAs (lncRNAs) play a crucial role in cancer aerobic glycolysis. However, glycolysis‐related lncRNAs are still underexplored in breast cancer. In this study, we identified the five most glycolysis‐related lncRNAs in breast cancer to construct a prognostic signature, which could distinguish between patients with unfavorable and favorable prognoses. To investigate the role of signature lncRNAs in breast cancer, we profiled their expression levels in breast cancer progression cell line model. Real‐time PCR revealed that the five lncRNAs could contribute to breast cancer initiation or progression. Furthermore, we observed that the levels of four lncRNAs expression had a significant trend of gradient upregulation with the addition of glycolysis inhibitor in breast cancer cells. Afterward, random forest and logistic regression were conducted to assess the model's performance in stratifying glycolysis status. Finally, a nomogram including the lncRNA signature and clinical features was developed, and its efficacy in predicting the survival time and clinical utility was evaluated using a calibration curve, concordance index, and decision curve analysis. In this study, gene set enrichment analysis showed that the mTOR pathway, a central pathway in tumor initiation and progression, was significantly enriched in the high‐risk group. In addition, gene set variation analysis was performed to validate our findings in two independent datasets. Subsequent weighted gene co‐expression network analysis, followed by enrichment analysis, indicated that downstream cell growth‐related signaling was strikingly activated in the high‐risk group, and may directly promote tumor progression and escalate mortality risk in patients with high‐risk scores. Overall, our findings may provide novel insight into lncRNA‐related metabolic regulation, and help to develop promising prognostic indicators and therapeutic targets for breast cancer patients., In conclusion, we identified five glycolysis‐related lncRNAs to construct a lncRNA signature on the basis of the glycolysis score, which could predict survival probability and glycolysis status. Moreover, hallmark gene sets associated with cell growth were significantly activated in the high‐risk breast cancer patient subgroup. Overall, the lncRNA signature could function as a robust prognostic indicator and help develop novel therapeutic strategies for breast cancer patients.

Objective The present study aimed to verify the feasibility and preliminary effects of nurse-led square dancing designed to improve older adults’ cognitive function and depressive symptoms who with MCI. Methods A quasi-experimental pilot study design was adopted for the present study. Screening for cognitive function was conducted among older adults (≥ 60 years old) living in two communities in Beijing who complained of memory loss. A total of 107 older patients with MCI and depressive symptoms were diagnosed after obtaining informed consent. Thirty-five patients selected from each community were included in the study as control and intervention groups, respectively. The two groups of patients received health education while the intervention group participated in a square dance intervention program led by nurses three times per week for 60 min per session over a period of three months. The Montreal Cognitive Assessment-Peking version (MoCA-P) and Geriatric Depression Scale (GDS-30) were used to assess the cognitive function and depressive symptoms of patients in the two groups at three time intervals; before intervention, at the end of the three-month intervention period, and over a three-month follow-up period after the end of intervention. Results Feasibility of the intervention was established with a high completion rate of 90%. Data collection for 63 out of 70 patients enrolled for the study was completed after six months. MoCA-P and GDS-30 scores of the intervention group were significantly different after the intervention when compared with the control group. A significant improvement in cognition was observed in the intervention group, and depressive symptoms decreased after intervention and follow-up when compared with the control group. During the intervention and follow-up phases, the MoCA-P score of the intervention group increased gradually with time. Furthermore, the MoCA-P and GDS-30 scores of the control group remained unchanged. Conclusion This study has revealed that square dance intervention exerts a positive impact on cognitive function and depressive symptoms among older patients suffering from MCI and depressive symptoms. The results of this study support the feasibility and preliminary effects of square dancing on relieving cognitive decline and depressive symptoms. Square dancing is a recommended type of intervention that can be applied to the local Chinese population because of its simplicity, convenience, and suitability for the older adults.

Aims To examine the distributed characteristics and explore the research themes of Doctor of Nursing Practice (DNP) dissertations during the past two decades. Design A descriptive statistical and visualization bibliometric analysis was conducted. Methods Doctor of Nursing Practice dissertations submitted between January 2005 and June 2021 were collected from the ProQuest Dissertations and Theses database. A descriptive statistical analysis was conducted to calculate the distribution of the DNP dissertations by granting institution and the published year of publications. The VOSviewer 1.6.13 was used to explore the bibliometric networks and research priorities of the DNP dissertations. Results A total of 4989 DNP dissertations from 90 universities were included in this study, all from the United States. The number of DNP dissertations showed an upward trend, with steady growth from 2005 to 2014 and rapid growth after 2015. The DNP studies focused on five areas: health care management in clinical nursing, advanced practice in nursing education and health education, public health problems, mental health care for adolescents and nurses and the older people care and long-term care. Conclusion Parallel to the numerical increase in DNP dissertations is a steady expansion in the range of research topics and scopes, which is aligned with specific specializations of the DNP. Many are interdisciplinary and employ techniques imported from the fields of public health, psychology and social sciences, resulting in nursing educators and practitioners continually broaden their subject perspectives. Impact Knowing where, when and why DNP research trends developed will help nursing educators to further develop DNP education and optimize DNP programs in the future, such as paying more attention to the nursing practice. Moreover, this study will inspire DNP students and researchers to expand their subject perspectives and broaden the research scope to solve nursing practice problems based on interdisciplinary theories and methods.

To investigate the therapeutic effect of artesunate (ART) on influenza A viral pneumonia.A total of 36 mice were evenly and randomly assigned to six groups, a normal control group (C group), a solvent control group (M group, 10% DMSO), a positive drug group (P group, oseltamivir, 1.25 mg/kg/day), ART high-dose group (ART-G group, 120 mg/kg/day), ART medium-dose group (ART-Z group, 60 mg/kg/day), and ART low-dose group (ART-D group, 30 mg/kg/day). Except for group C, which did not receive any influenza A virus intervention or intraperitoneal injection, mice in the five other groups were infected with influenza A virus through intranasal drip. Then, after 12 hours, mice in the five other groups received intraperitoneal injection of the assigned drugs and dosage once a day. The signs, body weight, and survival of the mice were observed over the course of treatment. After 7 days of treatment, the lung tissue of the mice was collected and weighed, and the lung index was calculated accordingly. HE staining was performed to observe the pathological changes in the lung tissue. The mRNA and protein expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB [p65]), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and IL-1β were examined with RT-qPCR and Western blot, respectively.Compared with those in C group, mice in the M group had worse physical signs and lower body mass and survival, increased lung index, severe pathological changes in lung tissue, and increased levels of TLR4, NF-κB (p65), TNF-α, IL-6 and IL-1β mRNA and protein expression in their lung tissue (ART has therapeutic effects on influenza A viral pneumonia, and the mechanisms are related to the inhibition of TLR4/p65 signaling pathway activation and anti-inflammation.

Tubulointerstitial diseases is one of the common causes of renal dysfunction. Some rare pathological types are easy to be misdiagnosed and missedly diagnosed because of their low prevalence and relatively insufficient understanding, which affects the treatment and prognosis of patients. This study aims to explore clinical manifestations and pathological characteristics of several rare tubulointerstitial diseases, and therefore to improve their diagnosis and treatment.A total of 9 363 patients diagnosed by renal biopsy in the Department of Nephrology, Second Xiangya Hospital, Central South University from November 2011 to September 2021 were selected. Six cases of light chain cast nephropathy (LCCN), 2 cases of light chain proximal tubulopathy (LCPT), 1 case of LCCN with LCPT, 4 cases of genetic tubulointerstitial disease, and 6 cases of non-genetic related tubulointerstitial lesion were screened out, and their clinical manifestations and renal biopsy pathological results were collected, compared, and analyzed.Patients with LCCN presented with mild to moderate anemia, microscopic hematuria, and mild to moderate proteinuria. Compared with patients with LCPT, proteinuria and anemia were more prominent in patients with LCCN. Five patients with LCCN and 2 patients with LCPT had elevated serum free kappa light chain. Five patients with LCCN presented clinically with acute kidney injury (AKI). Two patients with LCPT and 1 patient with LCCN and LCPT showed CKD combined with AKI, and 1 LCPT patient presented with typical Fanconi syndrome (FS). Five patients with LCCN, 2 patients with LCPT, and 1 patient with LCCN and LCPT were diagnosed with multiple myeloma. Five patients with LCCN had kappa light chain restriction in tubules on immunofluorescence and a "fractured" protein casts with pale periodic acid-Schiff (PAS) staining on light microscopy. Immunohistochemical staining of 2 LCPT patients showed strongly positive kappa light chain staining in the proximal tubular epithelial cells. And monoclonal light chain crystals in crystalline LCPT and abnormal lysosomes and different morphological inclusion bodies in noncrystalline LCPT were observed under the electron microscope. Six patients with LCCN were mainly treated by chemotherapy. Renal function was deteriorated in 1 patient, was stable in 4 patients, and was improved in 1 patient. Two patients with LCPT improved their renal function after chemotherapy. Four patients with genetic tubulointerstitial disease were clinically presented as CKD, mostly mild proteinuria, with or without microscopic hematuria, and also presented with hyperuricemia, urine glucose under normal blood glucose, anemia, polycystic kidneys. Only 1 case had a clear family history, and the diagnosis was mainly based on renal pathological characteristics and genetic testing. Compared with patients with non-genetic related tubulointerstitial lesion, patients with genetic tubulointerstitial disease had an earlier age of onset, higher blood uric acid, lower Hb and estiated glomemlar fitration (eGFR), and less edema and hypertension. Renal pathology of genetic tubulointerstitial disease presented tubular atrophy and interstitial fibrosis, abnormal tubular dilation, glomerular capsuledilation, and glomerular capillary loop shrinkage. Glomerular dysplasia and varying degrees of glomerular sclerosis were observed. Genetic tubulointerstitial disease patients were mainly treated with enteral dialysis, hypouricemic and hypoglycemic treatment. Two genetic tubulointerstitial disease patients had significantly deteriorated renal function, and 2 patients had stable renal function.Patients with AKI or FS, who present serum immunofixation electrophoresis and/or serum free kappa light chain abnormalities, should be alert to LCCN or LCPT. Renal biopsy is a critical detection for diagnosis of LCCN and LCPT. Chemotherapy and stem cell transplantation could delay progression of renal function in patients with LCCN and LCPT. If the non-atrophic area of the renal interstitium presents glomerular capsule dilatation, glomerular capillary loop shrinkage, and abnormal tubular dilatation under the light microscopy, genetic tubulointerstitial disease might be considered, which should be traced to family history and can be diagnosed by genetic testing.

Spinal fractures are common intra-articular fractures. Osteoporosis is a common and frequent disease among the elderly with a poor prognosis and a high risk of spinal fractures. However, the underlying factors for spinal fractures in patients with osteoporosis are unclear. A total of 105 patients with osteoporosis were recruited. Clinical and followed-up information was recorded. And vitamin B12, vitamin B2, vitamin A, and vitamin B9 in the blood were tested. Pearson's chi-squared and spearman tests were performed to analyze the correlation between spinal fractures and relative parameters. Univariate and multivariate logistic regression, univariate and multivariate Cox proportional hazards regression analysis. There exists strong relation between the expression level of vitamin B12 and spinal fractures. Pearson's chi-square and Spearman correlation test showed a strong association between vitamin B12 and vitamin B9 and a spinal fracture. Univariate logistic regression analysis showed that vitamin B12 and vitamin B9 were significantly associated with a spinal fracture. Multivariate logistic regression analysis showed that vitamin B12 was associated considerably with a spinal fracture. In addition, Cox regression analysis showed that vitamin B12 expression was significantly associated with maintenance time from recovery to recurrence (MTRR) of spinal fractures in patients with osteoporosis. Enhanced vitamin B12 is significantly correlated with the poor prognosis of patients with osteoporosis and the increasing incidence of a spinal fracture. The higher the vitamin B12, the higher the risk of spinal fracture and the shorter the time to spinal fracture recurrence.

Background and methodsThe study evaluated prognostic factors associated with varicella-zoster virus (VZV) infection and mortality in children with acute lymphoblastic leukemia (ALL) using data from the multicenter Chinese Children’s Cancer Group ALL-2015 trial.ResultsIn total, 7,640 patients were recruited, and 138 cases of VZV infection were identified. The incidence of VZV infection was higher in patients aged ≥ 10 years (22.5%) and in patients with the E2A/PBX1 fusion gene (11.6%) compared to those aged P = 0.003) or with other fusion genes (4.9%, P = 0.001). Of the 10 deaths in children with ALL and VZV infection, 4 resulted from VZV complications. The differences between groups in the 5-year overall survival, event-free survival, cumulative recurrence, and death in remission were not statistically significant. The proportion of complex infection was higher in children with a history of exposure to someone with VZV infection (17.9% vs. 3.6%, P = 0.022).ConclusionVZV exposure was associated with an increased incidence of complex VZV infection and contributed to VZV-associated death in children with ALL.

Glycosphingolipids (GSLs) are widely distributed in the phospholipid bilayer of various cell membranes, which play an important role in maintaining cell membrane stability, and regulate various cellular processes including adhesion, proliferation, apoptosis and recognition, as well as participate in various cellular activities. In addition, GSLs are not only involved in the process of apoptosis, but also regulate multiple signals in tumorigenesis and tumor development. The tumor-associated GSLs are expected to be used as diagnostic markers and immunotherapeutic targets for malignant tumors. These findings have important implications for the study of apoptosis and provide the new direction of tumor therapy. This review summarized the latest research progress of GSLs-mediated apoptosis and its effect on the genesis, development and metastasis of tumor cells. Moreover, we discussed the metabolic pathway of GSLs-mediated apoptosis and its application in tumor therapy, as well as the development prospect of targeted therapy strategies based on GSLs.