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Alcohol consumption is a critical risk factor contributing to a verity of human diseases. The incidence of alcohol use disorder increases across adolescence in recent years. Accumulating line of evidence suggests that alcohol-induced changes of DNA cytosine methylation (5-methyl-2′-deoxycytidine, 5mC) in genomes play an important role in the development of diseases. However, systemic investigation of the effects of adolescent alcohol exposure on DNA and RNA modifications is still lacked. Especially, there hasn't been any report to study the effects of alcohol exposure on RNA modifications. Similar to DNA modifications, RNA modifications recently have been identified to function as new regulators in modulating numbers of biological processes. In the current study, we systematically investigated the effects of alcohol exposure on both DNA and RNA modifications in peripheral blood of adolescent rats by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. The developed LC-ESI-MS/MS method enabled the sensitive and accurate determination of 2 DNA modifications and 12 RNA modifications. As for the alcohol exposure experiments, the adolescent rats were intraperitoneally injected with ethanol with an interval of one day for a total 14 days. The quantification results by LC-ESI-MS/MS analysis showed that adolescent alcohol exposure could alter both DNA and RNA modifications in peripheral blood. Specifically, we observed an overall decreased trend of RNA modifications. The discovery of the significant alteration of the levels of DNA and RNA modifications under alcohol exposure indicates that alcohol consumption may increase the risk of the incidence and development of diseases through dysregulating DNA and RNA modifications.

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.

Mammalian cell nuclei contain copper, and cancer cells are known to accumulate aberrantly high copper levels, yet the mechanisms underlying nuclear accumulation and copper's broader functional significance remain poorly understood. Here, by combining APEX2-based proximity labeling focused on the copper chaperone Atox1 with mass spectrometry we identified a previously unrecognized nuclear copper binding protein, Cysteine-rich protein 2 (CRIP2), that interacts with Atox1 in the nucleus. We show that Atox1 transfers copper to CRIP2, which induces a change in CRIP2's secondary structure that ultimately promotes its ubiquitin-mediated proteasomal degradation. Finally, we demonstrate that depletion of CRIP2-as well as copper-induced CRIP2 degradation-elevates ROS levels and activates autophagy in H1299 cells. Thus, our study establishes that CRIP2 as an autophagic suppressor protein and implicates CRIP2-mediated copper metabolism in the activation of autophagy in cancer cells.

CD1d-restricted natural killer T (NKT) cells are innate-like T lymphocytes with protective or pathogenic roles in the development of influenza pneumonia. Here, we show that lung-infiltrated and activated NKT cells are the major cellular source of LIGHT/TNFSF14, which determines the severity of pulmonary pneumonia by highly deteriorative influenza A virus (IAV) infection. Compared to wild-type mice, LIGHT−/− mice exhibit much lower morbidity and mortality to IAV, due to alleviated lung damage and reduced apoptosis of alveolar macrophages (AMs). LIGHT preferentially promotes cell death of lymphotoxin β receptors positive (LTβR+) AMs but not herpesvirus entry mediator positive (HVEM+) AMs. Therefore, these results suggest that NKT-derived LIGHT augments cell death of the tissue protective AMs in exacerbating lung pathology and susceptibility to fatal influenza infection. Suppression of LIGHT signaling might be a viable option in the treatment of influenza-associated acute respiratory distress syndrome.

Disseminated infection caused by Nocardia farcinica with primary nephrotic syndrome is exceedingly rare. A 66-year-old female visited the outpatient department due to fever and fatigue who had been diagnosed as membranous nephropathy and with a long-term prednisone and immunosuppressive therapy. After lung biopsy for many times, culture from space-occupying lesion of the right lung and species identification by mass spectrometry-based methods (MALDI-TOF) revealed Nocardia farcinica. By imaging examination, space-occupying lesions from the lungs, brain, abdominal cavity and kidney were found. After 2 weeks of meropenem intravenous and up to 6 months of trimethoprim-sulfamethoxazole (TMP-SMX) therapy, our patient has remained relapse-free at that time of writing. Disseminated infection caused by Nocardia farcinica is usually subacute with complex clinical manifestations. In addition, it can be easily confused with diseases such as tumor and mycobacterial infection, and lead to fatal consequences. Therefore, we hope that we can remind clinicians considering by discussing common features of disseminated Nocardia farcinica infection.

AIM: To evaluate the effects, advantages, disadvantages, and indications of infrabrow skin excision to correct upper eyelid dermatochalasis in middle-aged and elderly Chinese women. METHODS: Sixty eyelids in 30 patients were subjected to this surgical procedure from January to June 2018. All patients had upper eyelid dermatochalasis, and the functions of their levator palpebrae were all normal. The primary indications of the procedure were upper lid dermatochalasis with lateral hooding. All 30 patients underwent infrabrow skin excision at Shanxi Eye Hospital. The degree of skin relaxation before and after surgery was evaluated in all patients, and surgical outcomes and postoperative complications were also assessed. RESULTS: All patients were female, ranging from 40 to 64 (mean: 53.20±7.10) years old. Skin relaxation of the upper eyelid was improved in all 30 patients. One month after the operation, 52 lids (86.7%) showed good results and 8 lids (13.33%) showed fair results. The objective Strasser system was applied to evaluate surgical results at 1 and 6 months. All patients had scores between 0 and 1 point, indicating good results. Preoperative unsatisfactory position and shape of the eyebrows were improved, and crow's feet and frontal lines were reduced. All patients were satisfied with the results. No complications related to wound dehiscence, lagophthalmos, or hypertrophic scars were observed. CONCLUSION: Infrabrow skin excision is a simple, useful operation to reconstruct the upper eyelids in selected patients of Chinese ancestry. This procedure not only retains the advantages of classic blepharoplasty, but also alleviates many eyebrow problems at the same time, and maintains the original shape of the eyelid, minimizes scarring, and produces a smoother, more youthful appearance.

Although bromocriptine (BRC) as first-line drug is recommended for treating patients with prolactinoma, a minority of patients with prolactinoma are resistance to BRC. Moreover, our previous study showed the difference in drug sensitivity in BRC-treated rat prolactinoma cells, MMQ cells are more resistant to BRC, and GH3 cells are more sensitive to BRC. Curcumin (Cur) has been shown to inhibit proliferation of prolactinoma cell lines. The aim of this study is to further investigate whether Cur could enhance the growth-inhibitory effect of BRC resistance on prolactinoma cell lines and its possible mechanism. CCK-8 kit was used to test cell growth. Cell cycle analysis and apoptosis were performed by flow cytometry. Electron microscopy was used to test autophagosome. The mRNA expression profiles were analyzed using the Affymetrix Gene-Chip array. Western blot was used to test protein expression. Our data showed that Cur enhanced the growth-inhibitory effect of BRC on GH3 and MMQ cell proliferation. BRC and Cur both induced cell apoptosis, and Cur could significantly increase the apoptosis of BRC on pituitary adenoma cells through the ERK/EGR1 signaling pathway. Moreover, Cur could enhance the autophagic cell death (ACD) of BRC on tumor cells by inhibiting the AKT/GSK-3β signaling pathway. The same results were confirmed invivo study. Taken together, Cur sensitizes rat prolactinoma cells to BRC by activating the ERK/EGR1 and inhibiting the AKT/GSK-3β signaling pathway.

Traumatic heterotopic ossification (HO) is the abnormal formation of bone in soft tissues as a consequence of injury. However, the pathological mechanisms leading to traumatic HO remain unknown. Here, we report that aberrant expression of IL‐17 promotes traumatic HO formation by activating β‐catenin signalling in mouse model. We found that elevated IL‐17 and β‐catenin levels are correlated with a high degree of HO formation in specimens from patients and HO animals. We also show that IL‐17 initiates and promotes HO progression in mice. Local injection of an IL‐17 neutralizing antibody attenuates ectopic bone formation in a traumatic mouse model. IL‐17 enhances the osteoblastic differentiation of mesenchymal stem cells (MSCs) by activating β‐catenin signalling. Moreover, inhibition of IL‐17R or β‐catenin signalling by neutralizing antibodies or drugs prevents the osteogenic differentiation of isolated MSCs and decreases HO formation in mouse models. Together, our study identifies a novel role for active IL‐17 as the inducer and promoter of ectopic bone formation and suggests that IL‐17 inhibition might be a potential therapeutic target in traumatic HO.

Assessing the downstaging effects of neoadjuvant chemotherapy (NACT) in patients with locally advanced nasopharyngeal carcinoma (LANPC) and predicting response to treatment remain challenging. The present study aimed to evaluate the long-term prognosis of downstaging after NACT in patients with LANPC and to investigate the prognostic value of post-NACT tumor downstaging on treatment outcomes in the era of concurrent chemoradiotherapy (CCRT). This retrospective study included 226 patients with stage III (n = 188) and IVA (n = 38) NPC admitted to Haikou People’s Hospital between 1 October 2009 and 1 October 2012. The patients were grouped as downstaging or no after NACT. Overall survival (OS), locoregional failure-free survival (LFFS), and distant failure-free survival (DFFS) were analyzed. Among 226 patients, 196 (86.7%) were in the downstaging group and 30 (13.3%) were in the non-downstaging group. The longest follow-up was 76 months, and the median was 45 months. The 3-year OS rates of the downstaging group and non-downstaging group were 91.0% (95% CI 0.89–0.93) and 69.5% (95% CI 0.66–0.72) (P = 0.005). The 5-year OS rates were 81.6% (95% CI 0.78–0.86) and 53.3% (95% CI 0.49–0.61) (P = 0.001). N downstaging (3-year OS, HR 0.491, 95% CI 0.221–0.881, P = 0.022; 5-year OS, HR = 0.597, 95% CI 0.378–0.878, P = 0.021) was independently associated with OS. In the treatment of LANPC, the patients with downstaging after NACT have a better prognosis than those without downstaging. This study suggests that NACT can improve the prognosis for patients with LANPC if there is downstaging.

Background This study sought to explore the clinical effects of vancomycin-loaded calcium phosphate cement (CPC) in the treatment of chronic osteomyelitis. Methods Ninety-eight patients with chronic osteomyelitis, who were treated at our Department from December 1st, 2014 to December 1st, 2015, were randomly allocated into the research group or the control group. Each group comprised 49 patients. Patients in the research group (Group A) received a 1-stage treatment of vancomycin-loaded CPC after debridement, while those in the control group (Group B) received an irrigation and drainage device that administered irrigated antibiotics. The treatment effects, recurrence rates, and safety outcomes of the two groups were observed. Results Patients in the two groups were followed up with for a period of 12 months. The control group without recurrence in one case. There was some systemic adverse postoperative effects and safety issues. The X-ray film showed that CPC filling is good and part of the degradation of osteogenesis. Some patients in the research group the CPC particles were absorbed, the bone defect area was healed, after One-year postoperatively. Further, the cure rate was high. Conclusions One-stage vancomycin-loaded CPC implantation osteomyelitis lesions fill the die cavity, enable patients to continue to fight infection, induce bone defect osteogenesis, reduce the recurrence of chronic osteomyelitis, and are an effective method for treating chronic osteomyelitis. Trial registration Chinese Clinical Trial Registry website (ChiCTR2100044724).

Oral submucous fibrosis (OSMF) is a kind of chronic, insidious disease, and it is categorized into potentially malignant disorders (PMD), which poses a global and regional problem to public health. It is considered to be a multifactorial disease, such as due to areca nut chewing, trace element disorders, and genetic susceptibility. However, there is still no unanimous conclusion on its pathogenesis, diagnosis, and treatment strategies. Hence, this article provides a comprehensive review and prospect of OSMF research, providing scholars and clinicians with a better perspective and new ideas for the research and treatment of OSMF.

BACKGROUND: The outbreak of COVID-19 poses a major and urgent threat to global public health. CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. This study aimed to retrospectively analyze abnormal lung changes following initial computed tomography (CT) among patients with coronavirus disease 2019 (COVID-19) in Yunnan, and to evaluate the effectiveness of a chest CT-based model for the diagnosis of COVID-19. METHODS: One hundred and nine patients with COVID-19 pneumonia confirmed with the positive new coronavirus nucleic acid antibody who exhibited abnormal findings on initial CT were retrospectively analyzed. Thereafter, changes in the number, distribution, shape, and density of the lesions were observed. Further, the epidemiological, clinical, and CT imaging findings (+/-) were correlated. Following univariate and multivariate logistic regression analysis, receiver operating characteristic (ROC) curves were generated for significant factors, and models were established to evaluate the diagnostic ability of CT for COVID-19. RESULTS: Our results showed significant differences between patients with COVID-19 in epidemiological history (first, second, and third generation), clinical type (moderate, severe, and critical), and abnormal CT imaging characteristics (+/-) (P

Objective By observing the 3D anatomy of normal adult cervical facet joints, using the picture archiving and communication system to measure its 3D parameters and discussing its clinical significance, the aim of this study was to provide a reliable morphological basis for the design and manufacture of lower cervical facet joint interface distractors. Methods We selected 200 patients who underwent cervical spine 3D spiral computed tomography (CT) examination in the imaging department of our hospital from September 2019 to May 2020 and whose spiral CT images showed no cervical spinal canal stenosis, cervical disc herniation, obvious bone hyperplasia, or infection. The anterior and posterior diameters of the facet joints on both sides of the cervical spine, the space between the joints, and the left and right diameters were measured on the sagittal, cross-sectional and coronal planes after reconstruction with 3D spiral CT. Results The anterior and posterior diameters of the facet joints of the cervical spine, the space between the joints, and the left and right diameters all increased from top to bottom along the cervical spine. The 3D parameters of the C2-3~C6-7 segments were significantly different between the male and female groups. Conclusion The anteroposterior diameter, joint space interval, and left and right diameter of cervical facet joints are different in each segment and between the sexes. The lower cervical facet joint interface fusion device designed according to the measurement results can fully meet the needs of most patients.

Previous studies have reported the association between branched-chain amino acid trasaminase1 (BCAT1) and IDH1 wild-type gliomas. Nonetheless, as a promising target for treatment of primary glioblastoma, comprehensive reports on BCAT1 in gliomas are still lacking. In the present study, we accessed glioma patient cohorts and tissue microarray to evaluate the expression pattern of BCAT1 for determining its prognostic value and its relationship with IDH1 mutation status. Furthermore, we explored the potential regulatory mechanism of BCAT1 in gliomas by comparing the BCAT1 mRNA expression pattern with selected tumor biological signatures. The results showed that BCAT1 is highly expressed in GBM versus lower grade gliomas and could represent the poor survival of IDH1 wild-type gliomas. Moreover, BCAT1 is an independent prognostic factor for glioma patients, high BCAT1 expression is related to unfavorable clinical parameters including older age, IDH wildtype, no 1p/19q codeletion, ATRX wildtype and MGMT unmethylated. Additionally, BCAT1 correlated with apoptosis, hypoxia and angiogenesis processes in gliomas and high expression of BCAT1 revealed higher glycolysis level and increased immunosuppressive status in tumor progression. We concluded that BCAT1 is a strong prognostic factor for glioma patients and involved in the malignant progression of IDH1 wild-type gliomas.

BACKGROUND: The volar locking plate technique with an L-shaped incision of the PQ muscle through the classic volar Henry approach is a popular method for treating distal radius fractures. Recently we revised and improved this traditional technique by performing mini-invasive surgery. OBJECTIVE: The purpose of this study was to evaluate the clinical effects after fixation of distal radius fracture with volar locking palmar plates while preserving the pronator quadratus through minimally invasive approach. METHODS: From May 2014 to March 2017, 58 patients (38 males and 21 females) with an age range of 22–72 years (mean age 44.6 years) and with distal radius fractures underwent open reduction and internal fixation with volar locking palmar plates. The patients were classified as 23A-2 through 23C-2 according to the Orthopedic Trauma Association fracture classification system. All surgeries were completed by one trained team. The group that received volar locking palmar plates of distal radius performed with the traditional method through Henry approach involved 33 patients (21 males and 12 females) and the group that received PQ through minimally invasive approach group involved 25 patients (16 males and 9 females). We compared the two groups for wrist pain, forearm range of motion, grip strength, preoperative complications and wrist functional recovery score. RESULTS: The minimum follow-up for the whole cohort was one year. The differences between the two groups were significant in terms of wrist pain, forearm range of motion, grip strength and wrist function at 1, 2, 6 weeks postoperatively, but insignificant at 3 and 12 months postoperatively. In the minimally invasive group a case of limited extension of the forefinger 3 months postoperatively was found. No significant differences were found for preoperative complications and radiographs postoperatively. CONCLUSION: Fixation with volar locking palmar plates through minimally invasive approach is a satisfactory and optional method in the treatment of distal radius fractures. This technique yields better early wrist function, shortens rehabilitation time and gets high psychological satisfaction.

To determine the compositions of Forsythia suspensa leaves tea (FSLT) and its safety, the chemical compounds were analysed with some methods, and the toxicity was evaluated in Kunming mice and Wistar rats. The results showed that FSLT contained rich flavonoid, lignans, triperpene acids, amino acids, and mineral elements. In the acute toxicity study, none of the mice died, and no obvious poisoning symptoms were observed after 14 days in mice at the dose of 15 mg/g·body weight (bw) FSLT; in the sub-chronic toxicity, no abnormal or dead rat was found at the dose of 1, 3, and 10 mg/g·bw during 90 days feeding administration; there was no significant difference in bw and food consumption; no significant differences were found in each hematology and serum biochemistry parameter and organ/body weight ratio comparing with the control experimental group. The results revealed that the FSLT has low or no toxicity via oral administration. Therefore, FSLT is very suitable and safe to be used as a new resource food.

Diets of overloaded purine-rich foods for a long time are one of the important reasons to cause renal lesions. Eucommia ulmoides is one of the traditional Chinese medicine herbs, which has been used to recover functions of the kidney. However, its mechanism remains unclear. The aim of this study was to explore the effects and protective mechanism of Eucommia ulmoides extract on renal injury caused by long-term high purine diets in rats. SD rats underwent an intragastric adenine (200 mg kg-1 d-1) administration for 9 weeks and were treated for 15 weeks. The results demonstrated that Eucommia ulmoides extract significantly reduced serum Cre and BUN levels in rats. H&E and Masson's trichrome stains showed notable lowering of the infiltration of inflammatory cells, the formation of fibrous tissues and collagen fibers, and improvement in the pathological morphology of kidneys. It also suppressed the protein and mRNA expressions of TGF-β1 and α-SMA and enhanced E-cadherin expression. Meanwhile, Eucommia ulmoides extract prominently inhibited the mRNA expression of Col I, Col III, Col IV, TIMP-1, and TIMP-2 and promoted expressions of MMP-1, MMP-2 and MMP-9. Through our study, it is the first time to prove that Eucommia ulmoides extract could ameliorate renal interstitial fibrosis and may involve in the regulation of the extracellular matrix (ECM) degradation enzyme (MMPs/TIMPs) system, promotion of the expression of E-cadherin, and suppression of expressions of TGF-β1 and α-SMA. The results provide a significant implication for the utilization of Eunomia Ulmoides extract as functional foods to enhance renal functions and improve renal injury caused by high purine diets.

Menstruation occurs in few species and involves a cyclic process of proliferation, breakdown and regeneration under the control of ovarian hormones. Knowledge of normal endometrial physiology, as it pertains to the regulation of menstruation, is essential to understand disorders of menstruation. Accumulating evidence indicates that autophagy in the endometrium, under the regulation of ovarian hormones, can result in the infiltration of immune cells, which plays an indispensable role in the endometrium shedding, tissue repair and prevention of infections during menstruation. In addition, abnormal autophagy levels, together with resulting dysregulated immune system function, are associated with the pathogenesis and progression of endometriosis. Considering its potential value of autophagy as a target for the treatment of menstrual-related and endometrium-related disorders, we review the activity and function of autophagy during menstrual cycles. The role of the estrogen/progesterone-autophagy-immunity axis in endometriosis are also discussed.

Ligamentum flavum hypertrophy (LFH) is an important cause of spinal canal stenosis and posterior longitudinal ligament ossification. Although a number of studies have focused on the mechanisms responsible for LFH, the cellular mechanisms remain poorly understood. The aim of the present study was to investigate the roles of differentially expressed genes (DEGs) in LFH, elucidate the mechanisms responsible for LFH and provide a potential therapeutic target for further studies. The GSE113212 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The microarray data were analyzed and DEGs were obtained. Bioinformatics methods, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and protein-protein interaction (PPI) network analyses were used to obtain the key genes and signaling pathways. In addition, cells derived from hypertrophied ligamentum flavum were cultured, and the key genes and signaling pathways in ligamentum cells were identified through in vitro cell biology and molecular biology experiments. A total of 2,123 genes were screened as DEGs. Among these DEGs, 1,384 genes were upregulated and 739 genes were downregulated. The KEGG pathway analysis revealed that the DEGs were mainly enriched in the PI3K/AKT signaling pathway, and the PPI network analysis screened A disintegrin and metalloproteinase 10 (ADAM10) as a key gene. In vitro experimental verification revealed that ADAM10 promoted the proliferation of ligamentum flavum cells and led to the hypertrophy of the ligamentum by activating the PI3K/AKT pathway. On the whole, the in vitro experimental results suggested that ADAM10 promoted the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway, which may represent a pathogenic mechanism of LFH. The findings of the present study may provide a basis and direction for further studies on the cellular mechanisms of LFH and present a potential novel therapeutic target and clinical approach.

Hepatocellular carcinoma (HCC) is the most common type in the sub-classification of liver cancer. Circular RNAs (circRNAs) play a fundamental role in tumor occurrence and progression. This research aimed to investigate the role and molecular basis of circRNA homeodomain-interacting protein kinase 3 (circ_HIPK3) in HCC. Circ_HIPK3 and DLX2 levels were enhanced, and miR-582-3p level was reduced in HCC tissues and cells. Silencing of circ_HIPK3 impeded proliferation, migration and invasion and expedited apoptosis in HCC cells. Furthermore, circ_HIPK3 modulated HCC progression via sponging miR-582-3p, and miR-582-3p suppressed HCC progression via targeting DLX2. Moreover, circ_HIPK3 knockdown inhibited tumor growth in vivo. Circ_HIPK3 facilitated HCC progression by mediating miR-582-3p/DLX2 pathway, suggesting a new potential biomarker for HCC treatment.

Objectives: To investigate whether PET–CT or PET–MRI is more appropriate for imaging prostate cancer, in terms of primary tumor detection, local staging and recurrence, as well as lymph nodes and distant metastases. Methods: A systematic literature search was conducted on Embase, PubMed/MEDLINE, and the Cochrane Library database. Studies evaluating the diagnostic performance of PET–CT vs PET–MRI in prostate cancer patients were emphasized. Results: We reviewed 57 original research articles during the period 2016–2021: 14 articles regarding the radiotracer PSMA; 18 articles regarding the primary tumor detection, local tumor staging, managing local recurrence; 17 articles for managing lymph node metastases; and eight articles for managing bone and other distant metastases. PSMA PET could be complementary to mpMRI for primary prostate cancer localization and is particularly valuable for PI-RADS three lesions. PET–MRI is better than PET–CT in local tumor staging due to its specific benefit in predicting extracapsular extension in MRI-occult prostate cancer patients. PET–MRI is likely superior as compared with PET–CT in detecting local recurrence, and has slightly higher detection rates than PET–CT in lymph node recurrence. PET–CT and PET–MRI seem to have equivalent performance in detecting distant bony or visceral metastases. Conclusion: In conclusion, PET–MRI is suitable for local and regional disease, either primary staging or restaging, whereas PET–CT is valuable for managing distant bony or visceral metastasis. Advances in knowledge: We reviewed the emerging applications of PET–MRI and PET–CT in clinical aspects. Readers will gain an objective overview on the strength and shortfalls of PET–MRI or PET–CT in the management of prostate cancer.

Background Supraventricular tachycardia (SVT) with coronary sinus (CS) ostial atresia (CSA) or coronary sinus stenosis (CSS) causes difficulty in electrophysiological procedures, but its characteristics are poorly understood. Objective Study the anatomical and clinical features of SVT patients with CSA/CSS. Methods Of 6128 patients with SVT undergoing electrophysiological procedures, consecutive patients with CSA/CSS were enrolled, and the baseline characteristics, imaging materials, intraoperative data, and follow-up outcomes were analyzed. Results Thirteen patients, seven with CSA and six with CSS, underwent the electrophysiological procedure. Decapolar catheters were placed into the proximal CS in three cases, while the rest were placed at the free wall of the right atrium. Fourteen arrhythmias were confirmed: four atrioventricular nodal reentrant tachycardias, five left-sided accessory pathways, three paroxysmal atrial fibrillations, and two atrial flutters (AFLs). In addition to three patients who underwent only an electrophysiological study, the acute ablation success rate was 100% in 10 cases, with no procedure-related complications. After a median follow-up period of 59.6 months, only one case of atypical AFL recurred. For those cases (seven CSA and two CSS) with a total of 10 anomalous types of CS drainage, three types were classified: from the CS to the persistent left superior vena cava (n = 3), from an unroofed CS (n = 3), and from the CS to the small cardiac vein (n = 3) or Thebesian vein (n = 1). Conclusion Patients with CSA/CSS may develop different kinds of SVT. Electrophysiological procedures for such patients are feasible and effective. An individualized mapping strategy based on the three types of CS drainage will be helpful.

Background Gold nanoparticles with high biocompatibility and immunomodulatory properties have potential applications in the development of new diagnostic and therapeutic strategies for nanomedicine. Nanoparticles targeting macrophages can manipulate or control immunological diseases. This study assessed the activity of dendrimer-encapsulated gold nanodots (AuNDs) with three surface modifications [ie, outfacing groups with primary amine (AuNDs-NH2), hydroxyl (AuNDs-OH), and quaternary ammonium ions (AuNDs-CH3)] regulated macrophage function and antioxidant response through Nrf2-dependent pathway. Methods AuNDs were prepared and characterized. Intracellular distribution of AuNDs in human macrophages was observed through confocal microscopy. The activity of AuNDs was evaluated using macrophage functions and antioxidant response in the human macrophage cell line THP-1. Results AuNDs-NH2 and AuNDs-CH3, but not AuNDs-OH, drove the obvious Nrf2-antioxidant response element pathway in THP-1 cells. Of the three, AuNDs-NH2 considerably increased mRNA levels and antioxidant activities of heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1 in THP-1 cells. IL-6 mRNA and protein expression was mediated through Nrf2 activation in AuNDs-NH2-treated macrophages. Furthermore, Nrf2 activation by AuNDs-NH2 increased the phagocytic ability of THP-1 macrophages. Conclusion AuNDs-NH2 had immunomodulatory activities in macrophages. The findings of the present work suggested that AuNDs have potential effects against chronic inflammatory diseases via the Nrf2 pathway.

Objectives This study explored the factors influencing health behaviours during the coronavirus disease 2019 (COVID-19) outbreak in China. The impact of perceived stress and positive perception of interventions on health behaviours in China were assessed using the extended information-motivation-behaviour skills (IMB) model. Study design Cross-sectional survey. Methods The Questionstar online survey tool was used to construct a structured questionnaire based on the IMB model. Between 14 and 22 February 2020, during the peak of COVID-19 epidemic in China, 2449 participants were recruited by snowball sampling on WeChat and Tencent QQ social media platforms in China. Data were collected through an online questionnaire, and structural equation modelling was performed to evaluate the extended IMB model. Results Health behaviours were assessed using a scoring system (total score range: 8–40); the average health behaviour score in this study was 34.62 ± 4.44. The term ‘health risk stress’ refers to the impact that perceived stress has on health, and this was experienced by 39.9% of participants. Only 35.9% of participants answered all seven questions on COVID-19 information correctly. The final model showed that information, motivation, behavioural skills, heath risk stress and positive perception of interventions had significant direct effects on health behaviours. Health behaviours were positively associated with the positive perception of interventions but negatively associated with health risk stress. Behavioural skills had the greatest impact on health behaviours. Conclusions In the face of public health emergencies, the extended IMB model has been used as a theoretical framework to construct more effective interventions. The government should pay attention to publicity and guidance, strengthen positive interactions with the public and disclose relevant information in a timely manner to gain trust and to maintain the positive public perception of the interventions. In terms of health education, the government should focus on behavioural skills, promptly rectify ineffective prevention information and raise awareness about the disease to relieve stress and anxiety in the population., Highlights • Information, motivation, behavioural skills and positive perception of interventions were positive factors on health behaviours. • Health risk stress (i.e. the impact that perceived stress has on health) was negative factor on health behaviours. • Behavioural skills were the most important factor influencing health behaviour. • Of all residents, 39.9% of residents experienced health risk stress.

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related flaviviruses, ZIKV circulates in the population that has been JEV vaccinated in Southeast Asian countries. This alerts that a pre-existing immunity to JEV would impact ZIKV infection and/or pathogenesis. Herein we showed that the pre-existing immunity to JEV SA14-14-2 vaccination provided an ample protection against non-lethal or lethal dose of ZIKV infection in mice. This was in sharp contrast to the passive immunization of JEV antibodies, which failed to affect ZIKV infection or pathogenesis in mice, albeit these antibodies exhibited cross-reactivity and antibody dependent enhancement (ADE) of ZIKV infection in vitro. Furthermore, we determined that JEV vaccine-elicited CD8+ T cells were required to mediate the heterotypic protection of ZIKV infection, which cross-reacted to ZIKV E and NS5 antigens (E294-302 and NS52839-2848). Adoptive transfer of these CD8+ T cells could partially protect the mice from ZIKV challenge. Therefore, although short of epidemiological evidence, these results suggested that cross-reactive CD8+ T cells activated by JEV vaccination could protect potential ZIKV infection in human populations.

In the current study, a new Cu(II)-based metal-organic framework (MOF) formulated as {[Cu3(L)6(H2O)]·(H2O)4}n (1) (L = 4-(tetrazol-5-yl)phenyl-4,2′:6′,4″-terpyridine), has been synthesized by a sol...

RNA modification, such as N1-methyladenosine (m1A), affects the secondary structure of RNA and its ability to recognize specific reader proteins. Methods for detecting site-specific m1A are in demand. We report here a ligation-assisted differentiation approach for quantitative detection of m1A in mRNA with single-base resolution. The methyl group in m1A disrupts the Watson-Crick base pairing with uridine, resulting in a lower ligation efficiency of certain ligases and lower amounts of ligation products. Detection of the ligation products using quantitative real-time PCR provided site-specific evaluation of m1A. We first screened appropriate ligase and found that T3 DNA ligase offered the best discrimination between m1A and adenosine. We successfully detected and quantified m1A at position 1674 of bromodomain containing 2 (BRD2) mRNA from HEK293T cells. In lung carcinoma tissues, the level of m1A at position 1674 of BRD2 mRNA was significantly decreased compared to the tumor-adjacent normal tissues, suggesting that site-specific m1A may be involved in carcinogenesis.

Dopamine agonist (DA) is the first choice for the treatment of prolactinomas, and drug resistance is unavoidable during treatment due to the heterogeneity of tumors. The two prolactinoma cell lines (GH3 cells and MMQ cells) were found to have different sensitivity and responding modes to the cabergoline (CAB) and bromocriptine (BRC). In this research, we disclosed the capability of ACT001, a derivative of parthenolide analogs, to activate AMPK by increasing the intracellular reactive oxygen species (ROS) level and AMP/ATP ratio to reverse DA resistance through dual pathways in prolactinoma cells. The results indicated that ACT001 could reverse the CAB resistance in GH3 cells by inhibiting the mTOR signaling pathway, inducing cell death through autophagy, and reverse the BRC resistance in MMQ cells by activating the EGR1 signaling pathway, inducing cell death through apoptosis. Our results suggested that ACT001 is a promising therapeutic compound for treating DA-resistant prolactinomas.

Backgrounds: The ability of circulating tumor cells (CTCs) to identify lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) holds great promise for improving pathological diagnosis and selecting treatment in non-small cell lung cancer (NSCLC). In addition, previous studies have shown that DNA methylation exhibits cell and tissue specificity. Thus, we aimed to explore the methylation status of CTCs in LUAD and LUSC and identify the potential biomarkers. Methods: we first analyzed Infinium 450K methylation profiles obtained from The Cancer Genome Atlas and Gene Expression Omnibus and further identified the results by performing whole-genome sequencing of CTCs in tumor and matched normal lung tissues and white blood cells from 6 NSCLC patients. Results: the bioinformatic analysis revealed that an NSCLC-specific DNA methylation marker panel which could accurately distinguish between LUAD and LUSC with high diagnostic accuracy. The whole-genome sequencing of CTCs in NSCLC patients also showed 100% accuracy for distinguishing between LUAD and LUSC based on CTC methylation profiles. To investigate the function of CTCs, we further analyzed similar and different methylation profiles between CTCs and their primary tumors and found very high similarities between CTCs and their primary tumor tissues, indicating that these cells inherit information from primary tumors. CTCs also showed some characteristics that were different from those of the primary tumor tissues, suggesting that CTCs evolve some unique characteristics after migrating from the primary tumor; these characteristics may be one of the reasons for the ability of tumor cells to evade immune surveillance.Conclusion: thus, our study provides insight into the potential use of CTCs in pathological classification of NSCLC patients as well as CTC primary tumor inheritance and CTC evolution influence metastasis and immune escape.

Background Better protection can be provided during neurosurgery due to the establishment of somatosensory-evoked potential (SEP) and motor-evoked potential (MEP) monitoring technologies. However, some studies have showed that inhaled halogenated anesthetics have a significant impact on neurophysiological monitoring. Methods A total of 40 consecutive patients undergoing neurosurgery were randomly assigned to two groups receiving inhaled anesthetics, either desflurane or sevoflurane. Multiples levels (concentrations of 0.3, 0.6 and 0.9) of anesthetics were administered at minimum alveolar concentration (MAC), and then the latencies and amplitudes of SEPs and MEPs were recorded. Results SEP and MEP signals were well preserved in patients who underwent neurosurgery under general anesthesia supplemented with desflurane or sevoflurane at concentrations of 0.3, 0.6 and 0.9 MAC. In each desflurane or sevoflurane group, the amplitudes of SEPs and MEPs decreased and the latencies of SEPs were prolonged significantly as the MAC increased (P P P Conclusions SEPs and MEPs were inhibited in a dose-dependent manner by both desflurane and sevoflurane. At the same MAC concentration, desflurane appeared to have a stronger inhibitory effect than sevoflurane. All patients studied had normal neurological examination findings, hence, these results may not be applicable to patients with preexisting deficits. Trial registration The study registered on the Chinese Clinical Trial Registry (www.chictr.org.cn), Clinical Trials identifier ChiCTR2100045504 (18/04/2021).

Purpose: To investigate the factors influencing refracture after percutaneous kyphoplasty and to develop and validate a prognostic model.Method: We retrospectively collected clinical data in 392 patients with osteoporotic vertebral compression fractures who underwent percutaneous kyphoplasty at the Affiliated Hospital of Xuzhou Medical University from 1 January 2018 to 1 January 2020.Predictors significantly associated with refracture after PKP were selected based on last absolute shrinkage and selection operator regression. Then a prognostic model were developed and internal validated using enhanced Bootstrap validation.Results: Among the 392 patients who included in this study, there were 19 refracture after percutaneous kyphoplasty(4.8%). Four factors were selected by least absolute shrinkage and selection operator regression for significant association with refracture after percutaneous kyphoplasty, including body mass index, bone mineral density, unilateral puncture, and bone cement leakage. After enhance Bootstrap validation, the bias-corrected curve of the model fitted well with the apparent curve, with the area under ROC curve of 0.931 and 95% CI of (0.789,0.936).Conclusion: The prognostic model developed based on four clinical profiles: body mass index, bone mineral density, unilateral puncture, and bone cement leakage can be used to identify those at most risk of refracture after percutaneous kyphoplasty.

MVI has significant clinical value for treatment selection and prognosis evaluation in hepatocellular carcinoma (HCC). We aimed to construct a model based on MVI-Related Genes (MVIRGs) for risk assessment and prognosis prediction in patients with HCC. This study utilized various statistical analysis methods for prognostic model construction and validation in the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts, respectively. In addition, immunohistochemistry and qRT-PCR were used to analyze and identify the value of the model in our cohort. After the analyses, 153 differentially expressed MVIRGs were identified, and three key genes were selected to construct a prognostic model. The high-risk group showed significantly lower overall survival (OS), and this trend was observed in all subgroups: different age groups, genders, stages, and grades. Risk score was a risk factor independent of age, gender, stage, and grade. Moreover, the ICGC cohort validated the prognostic value of the model corresponding to the TCGA. In our cohort, qRT-PCR and immunohistochemistry showed that all three genes had higher expression levels in HCC samples than in normal controls. High expression levels of genes and high-risk scores showed significantly lower recurrence-free survival (RFS) and OS, especially in MVI-positive HCC samples. Therefore, the prognostic model constructed by three MVIRGs can reliably predict the RFS and OS of patients with HCC and is valuable for guiding clinical treatment selection and prognostic assessment of HCC.

Chronic spinal cord injury (CSCI) results from progressive compression of the spinal cord over time. A variety of factors cause CSCI, and its exact pathogenesis is unknown. Cyclin-dependent kinase 1 (CDK1) is closely related to the apoptosis pathway, but no CSCI-related studies on CDK1 have been conducted. In this study, the role of CDK1 in CSCI was explored in a rat model. The CSCI model was established by screw compression using the cervical anterior approach for twelve weeks. The neurological function of the rats was evaluated using the neurological severity scores (NSS) and motor evoked potentials (MEPs). Pathological changes in spinal cord tissue were observed by hematoxylin-eosin (HE) staining, and Nissl staining was performed to assess the survival of motor neurons in the anterior horn of the spinal cord. Changes in autophagy and apoptosis in anterior horn of spinal cord tissue were detected using transmission electron microscopy and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively. The expression levels of glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor (IBA) and choline acetyltransferase (CHAT) in the anterior horn were determined using immunohistochemistry assays to investigate astrocytes, microglia and motor neurons, respectively, in the anterior horn. Western blot assays were used to detect the expression levels of CDK1, Bcl-2, Bax, Caspase 3, LC3 and Beclin1. Changes in the expression of CDK1, LC3 and Beclin1 were also observed using immunohistochemistry. The results indicated that CSCI resulted in neuronal injury and a decrease in the NSS. In the CSCI model group, anterior horn astrocytes and microglia were activated, and motor neurons were decreased. Neuronal apoptosis was promoted, and the number of autophagic vacuoles was elevated. Rats treated with the CDK1 shRNA-expressing lentivirus exhibited better NSS, more surviving motor neurons, and fewer apoptotic neurons than the model rats. The occurrence of autophagy and the expression of proapoptotic and autophagy-related proteins were lower in the CDK1 shRNA group than the model group. In conclusion, CDK1 downregulation suppressed the activation of anterior horn astrocytes and microglia, promoted motor neuron repair, and inhibited neurons apoptosis and autophagy to promote the recovery of motor function after spinal cord injury.

Dysmenorrhea is one of the most common diseases in women. Dysmenorrhea is divided into primary dysmenorrhea (PD) and secondary dysmenorrhea (SD) . The prevalence of dysmenorrhea is high. However, there is no unified treatment for dysmenorrhea at home and abroad. In this paper, the relevant literatures of acupuncture and moxibustion for dysmenorrhea in China and Europe in recent years are systematically sorted, analyzed, concluded and summarized. The purpose of this paper is to explore the differences in classification, acupoint selection, treatment methods and needle retention time between China and Europe in the treatment of dysmenorrhea by acupuncture.

Purpose Heterogeneity assessment has been applied in medical imaging analysis. We aim to evaluate first-order and texture analysis (TA) metrics in 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging for classification of metastatic and benign bone lesions in patients with cervical cancer.Materials and Methods: 18F-FDG PET studies for cervical cancer patients performed on a specific PET/CT system from 2016 to 2018 were retrieved. Bone lesions extracted from studies in 2016-2017 were used as the training dataset and those in 2018 as the validation dataset. Metastatic bone lesions were identified in each dataset, with an equal number of benign bone lesions selected. Cuboid volume of interest (VOI) consisting of 3 by 3 by 5 reconstructed voxels was defined for first-order metrics and cubic VOI consisting of smaller voxels with trilinear interpolation of standardized uptake value (SUV) was adopted for TA metrics. First-order metrics included maximum SUV (SUVmax) of lesion and mean, standard deviation (SUVsd), skewness and kurtosis of voxel SUV in VOI. A total of 4464 TA metrics based on 62 texture features were evaluated. Logistic regression was used for classification with area under the receiver operating characteristic curve (AUC) as the performance measure.Results: From the training and validation datasets, 98 and 42 metastatic bone lesions were identified respectively. SUVsd achieves a better performance than SUVmax in both training (AUC .798 vs .732, P < .001) and validation (AUC .786 vs .684, P < .001) datasets. Top-performing TA metrics achieved significantly better performance in the training dataset but failed to retain this advantage in the validation dataset.Conclusion: This study identified a simple first-order measure of heterogeneity, SUVsd, to be superior to SUVmax in the classification of metastatic and benign bone lesions. The effect of multiple hypothesis testing can result in false-positive findings in TA with multiple features and parameters and careful validation is needed.

Debilitating mutation in RNA viruses can be repaired via different mechanisms, while triggering factors of mutation repair were poorly understood. In this study, multiple levels of triggering factors of mutation repair was identified based on genetic damage of tRNA-like structure (TLS) in cucumber mosaic virus (CMV). TLS mutation in different RNAs of CMV distinctively impacted the pathogenicity and mutation repair. Relative quantity defect of RNA2 or quality defect of RNA3 resulting from TLS mutation was correlated with high rate of mutation repair, and TLS mutation of RNA1 failed to be repaired. However, TLS mutation of RNA1 can be repaired in the mixed inoculation with RNA2 having pre-termination mutation of 2b or at the low dose of original inoculation, especially around dilution end-point. Taken together, TLS mutation resulting into quality or quantity defect of viral genome or TLS mutation at low dose around dilution end-point was inclined to be repaired. In addition, different levels of mutation repair of TLS necessarily required the cell-to-cell movement, which implied the positive effect of cell-to-cell bottleneck on evolution of low-fitness virus, a phenomenon opposite to the Muller ratchet. This study provided important revelations on virus evolution and application of viral mild vaccine.Author summaryDue to the low-fidelity of replicase, debilitating RNA viruses can be repaired through different mechanisms, which implied the resilience of RNA viruses. In this study, we identified multiple levels of triggered factors and occurrence occasion of mutation repair using the divided genome of CMV, which contained conserved cis-element tRNA-like structure (TLS) at the 3’end. TLS mutation of different RNA in CMV presented different rate of mutation repair from 0-80%. TLS mutation resulting into genomic quality or quantity defect or at low dose around dilution end-point was inclined to be repaired. However, all above types of mutation repair necessarily required cell-to-cell movement, which presented the positive effect of cell-to-cell bottleneck on virus evolution and increased fitness of low-fitness RNA viruses. It is an opposite phenomenon to the Muller ratchet, in which bottleneck always decreased the fitness of viruses. Except to identify the triggering factors of mutation repair in RNA viruses, this study also provided important revelations on creation and application of mild vaccine based on RNA viruses.

Although bromocriptine (BRC) as first-line drugs are recommended for treating patients with prolactinoma, a minority of patients with prolactinoma resistance to BRC. Moreover, our previous study showed that the difference in drug sensitivity in BRC- treated rat prolactinoma cells, MMQ cells are more resistant to BRC, and GH3 cells are more sensitive to BRC. Curcumin (Cur) has been shown to inhibit proliferation of prolactinoma cell lines. The aim of this study is to further investigate whether Cur could enhance the growth-inhibitory effect of BRC resistance on prolactinoma cell lines and its possible mechanism. CCK-8 kit was used to test cell growth. Cell-cycle analysis and apoptosis was performed by flow cytometry. Electron microscopy was used to test autophagosome. The mRNA expression profiles were analysed using the Affymetrix Gene-Chip array. Western blotting was used to test protein expression. Our data showed that Cur enhanced the growth-inhibitory effect of BRC on GH3 and MMQ cell proliferation. BRC and Cur both induced cell apoptosis, and Cur could significantly increase the apoptosis of BRC on pituitary adenoma cells through the ERK/EGR1 signaling pathway. Moreover, Cur could enhance the autophagic cell death (ACD) of BRC on tumor cell by inhibiting the AKT/GSK3β signaling pathway. The same results were confirmed in vivo study. Taken together, Cur sensitizes rat pituitary adenoma cell to BRC by activating the ERK/EGR1 and inhibiting AKT/GSK3β signaling pathway.

BackgroundSupraventricular tachycardia (SVT) occurs commonly and is strongly correlated with clinical deterioration in patients with pulmonary hypertension (PH). This study aimed to investigate the feasibility and long-term outcome of radiofrequency catheter ablation (RFCA) in PH patients with SVT.Materials and MethodsConsecutive PH patients with SVT who were scheduled to undergo electrophysiological study and RFCA between September 2010 and July 2019 were included. The acute results and long-term success of RFCA were assessed after the procedure.ResultsIn total, 71 PH patients with 76 episodes of SVT were analyzed. Cavotricuspid isthmus-dependent atrial flutter (n = 33, 43.5%) was the most common SVT type, followed by atrioventricular nodal reentrant tachycardia (n = 16, 21.1%). Of the 71 patients, 60 (84.5%) underwent successful electrophysiological study and were subsequently treated by RFCA. Among them, acute sinus rhythm was restored in 54 (90.0%) patients, and procedure-related complications were observed in 4 (6.7%) patients. Univariate logistic regression analysis showed that cavotricuspid isthmus-independent atrial flutter [odds ratio (OR) 25.00, 95% confidence interval (CI) 3.45–180.98, p = 0.001] and wider pulmonary artery diameter (OR 1.19, 95% CI 1.03–1.38; p = 0.016) were associated with RFCA failure. During a median follow-up of 36 (range, 3–108) months, 7 patients with atrial flutter experienced recurrence, yielding a 78.3% 3-year success rate for RFCA treatment.ConclusionThe findings suggest that RFCA of SVT in PH patients is feasible and has a good long-term success rate. Cavotricuspid isthmus-independent atrial flutter and a wider PAD could increase the risk for ablation failure.

Background: Post-stroke fatigue seriously affects the quality of life for stroke patients. There is no effective treatment at present. transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation which may have therapeutic effect on post-stroke fatigue. This study will explore about this. Method: A total of 60 patients with post-stroke fatigue were randomly divided into the control group and the treatment group with 30 patients each by minimization randomization. Both groups received basic treatment and conventional rehabilitation. In the treatment group, patients were treated with active tDCS, while in the control group, sham tDCS. Both active and sham tDCS were administered 6 times a week for 4 weeks. Before and after the trial, the Fatigue Severity Scale (FSS), Fugl-Meyer Assessment (FMA) and Modified Barthel Index (MBI) were evaluated and analyzed. And comparisons were made among groups. And there were an 8-week follow-up after the intervention. Result: Before the intervention, there were no significant differences in baseline data and assessment scores between the groups (P > 0.05). After 4 weeks of intervention, FSS scores in the treatment group were significantly lower than those in the control group (P = 0.012), and FMA and BMI scores were significantly higher than those in the control group (P 0.05). Discussion: TDCS is a safe treatment that can effectively reduce the degree of fatigue after stroke, improve the motor function and daily activity ability of patients after stroke, and the efficacy is better than only routine rehabilitation training. Trial registration number: Chinese Clinical Trial Registry, ChiCTR2000031120. Registered on March 22, 2020.

The present study aimed to investigate the mechanism of intervertebral disc degeneration (IVDD) and identify an efficient treatment for low back pain. Rabbit annulus fibrosus stem cells (AFSCs) were treated with metformin and lipopolysaccharide (LPS). The results indicated that LPS induced HMGB1 release from the nuclei of AFSCs and caused cell senescence in a concentration-dependent manner. The production of PGE2 and HMGB1 was increased in the medium of the LPS-treated AFSCs. Certain inflammation-associated genes (IL-β1, IL-6, COX-2 and TNF-α) and proteins (IL-β1, COX-2 and TNF-α) and specific catabolic genes (MMP-3 and MMP-13) exhibited increased expression in LPS-treated AFSCs. However, the expression levels of other anabolic genes, such as collagen I and collagen II were decreased in LPS-treated AFSCs. Following addition of metformin to LPS-containing medium, HMGB1 was retained in the nuclei of AFSCs and the production of PGE2 and HMGB1 was reduced. The expression levels of the catabolic genes and proteins were decreased and those of the anabolic genes were increased. The findings indicated that metformin exerted an anti-inflammatory effect by blocking the HMGB1 translocation and by inhibiting catabolic production and cell senescence in AFSCs. Therefore, metformin may be used as an efficient treatment for the disc degenerative disease.

Background: The exact morbidity of myocarditis is unknown, as the treatment is generally delayed in virtue of misdiagnosis or missed diagnosis. Aim: The aim of this study was to identify prognostic factors of left-ventricular remodeling on CMRI performed in patients with pathological proven myocarditis. Methods: Sixty-two cases with various presentations of myocarditis (39 cases with heart failure; 23 cases with arrhythmias) were selected. All patients, who underwent coronary angiography, endomyocardial biopsy, were divided into positive-remodeling and negative-remodelling groups to analyse LGE and cardiac cine parameters at presentation and subsequent to 3 months. Results: Comparison of two subgroups in CMRI is as follows: positive LGE (65.6% vs. 86.7%; p Conclusion: LGE-MRI is rewarding as an independent predictor in left-ventricular positive and negative remodelling of myocarditis.

Wang et al. identify Rab7 as a novel regulator of primary cilia disassembly. Their findings demonstrate that Rab7 localization to primary cilia is required for intraciliary F-actin polymerization, which is indispensable for the regulation of cilia ectocytosis and disassembly., The primary cilium is a sensory organelle that protrudes from the cell surface. Primary cilia undergo dynamic transitions between assembly and disassembly to exert their function in cell signaling. In this study, we identify the small GTPase Rab7 as a novel regulator of cilia disassembly. Depletion of Rab7 potently induced spontaneous ciliogenesis in proliferating cells and promoted cilia elongation during quiescence. Moreover, Rab7 performs an essential role in cilia disassembly; knockdown of Rab7 blocked serum-induced ciliary resorption, and active Rab7 was required for this process. Further, we demonstrate that Rab7 depletion significantly suppresses cilia tip excision, referred to as cilia ectocytosis, which has been identified as required for cilia disassembly. Mechanically, the failure of F-actin polymerization at the site of excision of cilia tips caused suppression of cilia ectocytosis on Rab7 depletion. Overall, our results suggest a novel function for Rab7 in regulating cilia ectocytosis and cilia disassembly via control of intraciliary F-actin polymerization.

In recent years, research on glioma immunotherapy have grown rapidly. However, the autoimmune‐like side effects that are caused by blocking immunological checkpoints hinder their clinical application in gliomas currently. Galectin‐9, a ligand for T‐cell immunoglobulin mucin 3, has shed a new light on the treatment of malignant glioma. However, the potential mechanism of Galectin‐9 is still under discussion. In this study, first, we methodically gathered 1,027 glioma patients with RNA‐seq and 986 patients with survival data to explore the role and mechanism of Galectin‐9 in gliomas. Second, we analyzed glioma samples from 50 patients in the Department of Neurosurgery, Tianjin Medical University General Hospital. Finally, we found that Galectin‐9 was strongly upregulated in glioblastoma multiforme compared with normal brain tissues and lower‐grade glioma. Patients with Galectin‐9 overexpression had a significantly shorter overall survival. Moreover, the tissue microarray data displayed that the expression of Galectin‐9 in the core of tumor is higher than that in the border and was correlated with the shorter survival in glioma patients. Galectin‐9 is more highly expressed in the mesenchymal subtype of glioblastoma multiforme than in the other subtypes. Simultaneously, Galectin‐9 was closely associated with the immune response and lymphocyte activation, especially T‐cell activation. To further determine the underlying role of Galectin‐9 in the immune response, we selected seven immune metagenes. Through cluster analysis and correlation analysis, we discovered that Galectin‐9 was highly correlated with immune checkpoint molecules and M2 tumor‐associated macrophages. In summary, Galectin‐9 serves as a potential therapeutic target to treat glioblastoma multiforme., In this study, we evaluated the expression status of Galecin‐9 and its associated biological processes and prognosis by analyzing RNA‐seq and clinical data from TCGA and CGGA databases, with the hope of obtaining a comprehensive understanding of Galectin‐9 and new findings in its use for the treatment of glioblastoma multiforme (GBM)

Hexavalent chromium [Cr(VI)] compounds that are generated during industrial processes are widely recognized as highly toxic and carcinogenic. It has been reported that exposure to Cr(VI) can produce some chromium intermediates and reactive oxygen species (ROS), which causes DNA damages, genetic instability, and eventually leads to the elevated risk of various diseases including cancers. In recent years, it has been proposed that epigenetic-based mechanisms may involve in the toxic heavy metals-induced cytotoxicity and mutagenicity besides the genetic-based mechanisms. However, whether Cr(VI) could impose its cytotoxic effect through dysregulating the RNA epigenetic modifications remains poorly defined. We systematically investigated the effects of Cr(VI) exposure on 14 kinds of modifications in mRNA of HEK293T cells. We found that Cr(VI) exposure can induce an obvious decrease of inosine in mRNA. In addition, we observed that the expression level of the adenosine deaminase acting on RNA (ADAR1) was significantly decreased upon Cr(VI) exposure, which could be responsible for the induced decrease of inosine in mRNA by Cr(VI) exposure. Together, we demonstrated that Cr(VI) could interrupt A-to-I RNA editing in mRNA, which may eventually lead to the cytotoxicity and mutagenicity.

Purpose Evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) insertion on patients with schistosomiasis-induced liver fibrosis, and compare with that of patients with HBV-induced cirrhosis. Materials and Methods This was a retrospective study from November 2015 to December 2018 including 82 patients diagnosed with portal hypertension, one group of which is induced by schistosomiasis (n = 20), the other by hepatitis B virus (HBV) (n = 62). Both groups of subjects underwent TIPS placement for the management of portal hypertension complications. Results TIPS was inserted successfully in all patients (technical success 100%). After a median follow-up of 14 months following TIPS insertion, portal pressure gradient (PPG) value in both schistosomiasis-induced group and HBV-induced group underwent a significant decrease with no major difference between the two groups. There exists no significant difference demonstrated by Kaplan–Meier curves between two groups concerning cumulative rate of hepatic encephalopathy (HE) (log-rank p = 0.681), variceal rebleeding (log-rank p = 0.837) and survival (log-rank p = 0.429), and no statistically difference was found in terms of alleviation of portal vein thrombosis (PVT). In addition, splenectomy (HR 19, 95% CI 4–90, p

strongBACKGROUND/strongThe diagnosis of myocarditis is challenging, and the treatment is generally delayed due to misdiagnosis or missed diagnosis. Endomyocardial biopsy (EMB) is not a specific or sensitive method. A case-controlled observational study was conducted to evaluate early gadolinium enhancement (EGE) and left ventricular functional parameters on Artificial Intelligence in cine-MRI in patients with acute myocarditis.strongMATERIAL AND METHODS/strongWe selected 21 patients with pathologically proven acute myocarditis. We analyzed the EGE findings (total/serial number and location of positive-segments using the 17-segment model according to the American Heart Association) and clinical characteristics (symptoms, arrhythmias in ECG, coronary angiography, and EMB). All patients were divided into positive EGE and negative EGE groups to analyze left ventricular functional parameters (LVEF, FS, LVEDD, LVEDV, LVESV, LVMM, LVSV, CO, and CI) on Artificial Intelligence.strongRESULTS/strongWe enrolled 21 patients (11 males) with a mean age of 32.6±9.8 years (range, 16 to 51 years). Abnormalities on EGE were found in 2/3 of patients, involving 41 segments among multiple locations on the myocardium. The differences in LVEF (40.2±10.2%ivs./i51.3±3.6%), LVESV (69.0±16.1mlivs./i52.5±10.6ml) and LVSV (42.6±11.4ivs./i52.8±2.8 ml) on Artificial Intelligence was statistically significant between the positive EGE and negative EGE groups (p0.05).strongCONCLUSIONS/strongOur results suggest a significant role of EGE on the basis of Lake Louise criteria in evaluating patients with clinical suspicion of acute myocarditis. Parameters, including LVEF, LVESV, and LVSV, on Artificial Intelligence, may be useful independent predictors for capillary leakage and microcirculatory disturbance in myocarditis.

Background and Aim This study aims to evaluate and compare the survival and other portal hypertension‐related complications of patients with portal pressure gradient (PPG) ≥ 25 mmHg using transjugular intrahepatic portosystemic shunt (TIPS) as the first‐line and second‐line therapies in secondary prophylaxis of variceal hemorrhage. Methods Fifty patients diagnosed with liver cirrhosis were enrolled in this retrospective study, with 35 of whom received TIPS as the first‐line therapy in secondary prophylaxis of variceal hemorrhage and 15 of whom as second‐line treatment. We observed and analyzed the survival, occurrence of variceal rebleeding and hepatic encephalopathy (HE) of patients in the two groups during the follow up. Results The technical success rate was 100%. In a median follow‐up time of 12 (1–37) and 15 (2–27) months, respectively, significant statistical difference was observed between the first‐line group and the second‐line group concerning cumulative survival rate (94.3% vs 66.7%, log–rank P = 0.01). But that was not the case when it comes to the cumulative rate of variceal rebleeding (8.6% vs 26.7%, log–rank P = 0.164) and HE (22.9% vs 20.0%, log–rank P = 0.793). And multivariate analysis indicated that group assignment (hazard ratio = 8.250, 95% confidence interval = 1.383–49.213, P = 0.021) was the only predictor of survival. Interestingly, we found that spleen diameter (hazard ratio = 0.578, 95% confidence interval = 0.393–0.849, P = 0.005) could be regarded as independent predictor of the occurrence of HE. Conclusions For patients with PPG ≥ 25 mmHg who have recovered from an episode of acute esophageal variceal hemorrhage, utilizing TIPS as the first‐line therapy to prevent rebleeding is demonstrated effective in improving the survival and therefore should be recommended to a wider range of clinical practice.

Background:Breast cancer is one of the most common malignancies, and a threat to female health all over the world. However, the molecular mechanism of breast cancer has not been fully discovered yet.Objective:It is crucial to identify breast cancer-related genes, which could provide new biomarker for breast cancer diagnosis as well as potential treatment targets.Methods:Here we used the minimum redundancy-maximum relevance (mRMR) method to select significant genes, then mapped the transcripts of the genes on the Protein-Protein Interaction (PPI) network and traced the shortest path between each pair of two proteins.Results:As a result, we identified 24 breast cancer-related genes whose betweenness were over 700. The GO enrichment analysis indicated that the transcription and oxygen level are very important in breast cancer. And the pathway analysis indicated that most of these 24 genes are enriched in prostate cancer, endocrine resistance, and pathways in cancer.Conclusion:We hope these 24 genes might be useful for diagnosis, prognosis and treatment for breast cancer.

To propose a novel morphological classification method for notches, which may provide new evidence for notchplasty based on the three-dimensional (3D) features of notches and the risk of anterior cruciate ligament (ACL) injury. Three hundred individuals in total were included in our study, including 150 patients with ACL ruptures (75 males and 75 females) and 150 age- and gender-matched individuals without ACL ruptures. The notches were divided into four types according to the notch widths at the notch inlet, outlet, and ACL attachment based on the preoperative MRI, the notch volume was calculated, and the risk of ACL injury was compared. The surgical records were reviewed and whether these cases performed notchplasty were collected. The inlet-and-outlet stenosis notch type was associated with smaller notch volume (P = 0.007) and a higher risk of ACL injury (P