A Review of the Extent of Pain Catastrophizing in Patients Who Have Undergone Total Knee Replacement.

OBJECTIVES: This study aimed to analyze the current status and influencing factors of pain catastrophizing in patients undergoing total knee replacement (TKR) and to provide a basis and reference for the clinical improvement of pain catastrophizing in these patients. DESIGN: This study was designed in accordance with PRISMA guidelines. DATA SOURCES: PubMed, the Web of Science, the Elton B. Stephens Company, the Cochrane Library, Embase, Chinese National Knowledge Infrastructure, the WanFang, Weipu and Chinese Biomedical Literature Databases. REVIEW/ANALYSIS METHODS: A scoping review was performed using PubMed, the Web of Science, the Elton B. Stephens Company, the Cochrane Library, Embase, Chinese National Knowledge Infrastructure, the WanFang, Weipu, and Chinese Biomedical Literature Databases, and after literature screening and data extraction, the results were summarized. RESULTS: A total of 23 articles were included in the study. Pain catastrophizing is mostly assessed using the Pain Catastrophizing Scale and the Coping Strategies Questionnaire. The level of pain catastrophizing is an independent predictor of pain in patients undergoing TKR and is influenced by demographic, psychological, co-morbid, and prognostic factors. Pain catastrophizing interventions mainly consist of surgery, physiotherapy, medication, and psychological therapy. CONCLUSIONS: Pain catastrophizing involves multiple factors, and it is necessary to explore the predictors affecting pain catastrophizing, improve the systematic evaluation of pain catastrophizing and adopt the appropriate intervention methods.

Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease: Mechanism, clinical evidence, and prospect.

The population of non-alcoholic fatty liver disease (NAFLD) patients along with relevant advanced liver disease is projected to continue growing, because currently no medications are approved for treatment. Fecal microbiota transplantation (FMT) is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease. There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment, however, existing findings diverge on its effects. Herein, we briefly summarized the mechanism of FMT for NAFLD treatment, reviewed randomized controlled trials for evaluating its efficacy in NAFLD, and proposed the prospect of future trials on FMT.

Observation of an isothermal glass transition in metallic glasses.

Glass transition, commonly manifested upon cooling a liquid, is continuous and cooling rate dependent. For decades, the thermodynamic basis in liquid-glass transition has been at the center of debate. Here, long-time isothermal annealing was conducted via molecular dynamics simulations for metallic glasses to explore the connection of physical aging in supercooled liquid and glassy states. An anomalous two-step aging is observed in various metallic glasses, exhibiting features of supercooled liquid dynamics in the first step and glassy dynamics in the second step, respectively. Furthermore, the transition potential energy is independent of initial states, proving that it is intrinsic for a metallic glass at a given temperature. We propose that the observed dynamic transition from supercooled liquid dynamics to glassy dynamics could be glass transition manifested isothermally. On this basis, glass transition is no longer cooling rate dependent, but is shown as a clear phase boundary in the temperature-energy phase diagram. Hence, a modified out-of-equilibrium phase diagram is proposed, providing new insights into the nature of glass transition.

The impact of enhanced recovery after surgery on inflammatory indicators and prognosis related to complex appendicitis in children.

Objective: To explore the application effect of enhanced recovery after surgery (ERAS) perioperative plan in the treatment of complex appendicitis in children, and further enrich the implementation plan of ERAS in the field of pediatric surgery. Method: This study selected 122 children who underwent laparoscopic complex appendectomy at Inner Mongolia Maternal and Child Health Hospital and Baotou Fourth Hospital from August 2018 to July 2022, and randomly divided them into a traditional surgery group (TS) and an enhanced recovery surgery group (ERAS). The changes of white blood cell (WBC), hypersensitive C-reactive protein (CRP), pro Calcitonin (PCT) and interleukin 6 (IL-6) before and after surgery were compared. The degree of pain, recovery time of intestinal function, length of hospital stay, hospital costs, postoperative complications and parental satisfaction were compared between the two groups. Result: The WBC and CRP levels in the ERAS group at 6 h after surgery, as well as the IL-6 levels on the 3rd day after surgery, were lower than those in the TS group. Meanwhile, the analgesic effect of ERAS group at 3 h and 6 h after surgery was better than that of TS group. And the ERAS group had a shorter postoperative first exhaust time, fewer overall hospital stays, and lower hospitalization costs. In addition, the ERAS group had high parental satisfaction during hospitalization. There was no statistically significant difference in postoperative complications between the two groups of children. Conclusion: ERAS can promote postoperative recovery of children, reduce surgical stress, save family medical expenses, alleviate the pain of children, and improve parental satisfaction. It is a safe and effective method for treating complex appendicitis in children.

Low glucose metabolite 3-phosphoglycerate switches PHGDH from serine synthesis to p53 activation to control cell fate.

Glycolytic intermediary metabolites such as fructose-1,6-bisphosphate can serve as signals, controlling metabolic states beyond energy metabolism. However, whether glycolytic metabolites also play a role in controlling cell fate remains unexplored. Here, we find that low levels of glycolytic metabolite 3-phosphoglycerate (3-PGA) can switch phosphoglycerate dehydrogenase (PHGDH) from cataplerosis serine synthesis to pro-apoptotic activation of p53. PHGDH is a p53-binding protein, and when unoccupied by 3-PGA interacts with the scaffold protein AXIN in complex with the kinase HIPK2, both of which are also p53-binding proteins. This leads to the formation of a multivalent p53-binding complex that allows HIPK2 to specifically phosphorylate p53-Ser46 and thereby promote apoptosis. Furthermore, we show that PHGDH mutants (R135W and V261M) that are constitutively bound to 3-PGA abolish p53 activation even under low glucose conditions, while the mutants (T57A and T78A) unable to bind 3-PGA cause constitutive p53 activation and apoptosis in hepatocellular carcinoma (HCC) cells, even in the presence of high glucose. In vivo, PHGDH-T57A induces apoptosis and inhibits the growth of diethylnitrosamine-induced mouse HCC, whereas PHGDH-R135W prevents apoptosis and promotes HCC growth, and knockout of Trp53 abolishes these effects above. Importantly, caloric restriction that lowers whole-body glucose levels can impede HCC growth dependent on PHGDH. Together, these results unveil a mechanism by which glucose availability autonomously controls p53 activity, providing a new paradigm of cell fate control by metabolic substrate availability.

Investigation on risk factors of chronic diseases among community residents: A study based on health management systems supported by Mobile phones.

AIM: To explore the physical and mental health status of community residents and to identify the risk factors of chronic diseases. DESIGN: A cross-sectional, descriptive correlational study was conducted. METHODS: A total of 579 participants were recruited from 15 communities in Tianjin. The demographic information sheet, 7-item Generalized Anxiety Disorder scale (GAD-7) and Patient Health Questionnaire (PHQ-9) were used. Data collection was undertaken based on the health management system on mobile phones from April to May 2019. RESULTS: Eighty-four participants of the total number of surveyed were with chronic disease. The incidence of depression and anxiety in participants was 44.2% and 41.3%. Logistic regression analysis showed that age (OR = 4.905, 95%CI: 2.619-9.187), religious belief (OR = 0.445, 95%CI: 1.510-11.181) and working condition (OR = 0.161, 95%CI: 0.299-0.664) entered the regression equation. Old age is a risk factor for chronic diseases. No religious belief and working condition are protective factors for chronic diseases.

Genotype and clinical phenotype analysis of a Family with Kennedy disease.

To investigate the clinical phenotype-genotype correlations of a family with Kennedy disease (KD) and improve our understanding of the disease. KD was confirmed after clinical phenotypic analyses, laboratory tests, polymerase chain reaction assays for cytosine-adenine-guanine (CAG) repeats, and neuro-electrophysiological tests. The disease was assessed using the KD1234 scale and the spinal and bulbar muscular atrophy functional rating scale. The average age of disease onset was 30.8 ± 2.85 years. Clinically diagnosed members had 48 CAG repeats (≥35 is abnormal) in the androgen receptor gene. The patients exhibited gynecomastia and testicular dysfunction. The lesions mainly involved the medulla oblongata and spinal cord. Progesterone and serum creatine kinase levels were significantly high. Electromyography showed chronic neurogenic damage and abnormal sensory and motor conduction in family members who did not participate in sports, exercise, or physical hobbies. Our study showed that this family had a stable inheritance of CAG repeats, and the genotype was consistent with the clinical phenotype. Gynecomastia was the first symptom, with progressive androgen resistance resulting in testicular atrophy, infertility, and sexual dysfunction. Changes in serum creatine kinase may indicate the progression or relief of symptoms, and rehabilitation may delay the progression of muscle atrophy.

Relationships among social support, coping style, self-stigma, and quality of life in patients with diabetic foot ulcer: A multicentre, cross-sectional study.

Patients with diabetic foot ulcer have a significantly lower quality of life. Quality of life could be connected to other psychological or social processes. The purpose of this study was to examine the relationships between social support, decision regret, self-stigma, and quality of life in patients with diabetic foot ulcers. The sample of the study consisted of 229 diabetic foot ulcer patients. Data were collected from September 2019 to March 2020. The demographic and clinical information, the Stigma Scale for Chronic Illness, Medical Coping Scale, Social Support Scale, and Quality of Life scale were used to assess the quality life for diabetic foot ulcer. Pearson correlation coefficient and structural equation modelling were used for data analysis. The quality of life was negatively correlated with self-stigma, positively correlated with social support, giving up coping, and not significantly correlated with confrontation coping and avoidance coping. Self-stigma has significant indirect effects on quality of life through social support and coping style. Further clinical intervention strategies for decreasing self-stigma as well as strengthening social support and positive coping styles are needed to inform diabetic foot ulcer patients, thus improving their quality of life.

Distinct relaxation mechanism at room temperature in metallic glass.

How glasses relax at room temperature is still a great challenge for both experimental and simulation studies due to the extremely long relaxation time-scale. Here, by employing a modified molecular dynamics simulation technique, we extend the quantitative measurement of relaxation process of metallic glasses to room temperature. Both energy relaxation and dynamics, at low temperatures, follow a stretched exponential decay with a characteristic stretching exponent ß = 3/7, which is distinct from that of supercooled liquid. Such aging dynamics originates from the release of energy, an intrinsic nature of out-of-equilibrium system, and manifests itself as the elimination of defects through localized atomic strains. This finding is also supported by long-time stress-relaxation experiments of various metallic glasses, confirming its validity and universality. Here, we show that the distinct relaxation mechanism can be regarded as a direct indicator of glass transition from a dynamic perspective.

Adebrelimab (SHR-1316) in Combination With Chemotherapy as Perioperative Treatment in Patients With Resectable Stage II to III NSCLCs: An Open-Label, Multicenter, Phase 1b Trial.

INTRODUCTION: This study evaluated adebrelimab (a programmed death-ligand 1 antibody) plus nab-paclitaxel and carboplatin as perioperative treatment for resectable NSCLC. METHODS: Eligible patients had resectable stage II to III NSCLCs without driver gene. Patients received neoadjuvant treatment with three cycles of intravenous adebrelimab (20 mg/kg on day 1), nab-paclitaxel (100 mg/m2 on days 1, 8, and 15), and carboplatin (area under the curve 5 mg/mL per min on day 1), of each 21-day cycle before surgical resection, and followed by 16 cycles of adebrelimab (20 mg/kg on day 1 in 3 wk) adjuvant treatment. The primary end point was major pathologic response (MPR) per blinded independent pathologic review. RESULTS: A total of 37 patients were enrolled and received planned neoadjuvant therapy. There were 34 patients (91.9%) who underwent surgery. As of data cutoff on January 25, 2022, 19 of the 37 patients (51.4%, 95% confidence interval [CI]: 35.9-66.6) achieved MPR per blinded independent pathologic review and 11 patients (29.7%, 95% CI: 17.5-45.8) achieved pathologic complete response. Furthermore, 26 patients (70.3%, 95% CI: 54.2-82.5) had an objective response per Response Evaluation Criteria in Solid Tumors version 1.1. The 12-month event-free survival rate was 77.8% (95% CI: 54.1-90.3). In addition, 29 patients (78.4%) had grade greater than or equal to three treatment-related adverse events (AEs) and nine (24.3%) had treatment-related serious AEs. No treatment-related deaths occurred. Grade greater than or equal to three surgery-related AEs within 30 or 90 days after surgery were both reported in five patients (14.7%). CONCLUSIONS: Adebrelimab plus nab-paclitaxel and carboplatin as perioperative therapy led to a substantial proportion of MPR and high resectability, with manageable toxicities. On the basis of the phase 1b results, phase 3 trial was initiated.

The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK.

The activity of 5'-adenosine monophosphate-activated protein kinase (AMPK) is inversely correlated with the cellular availability of glucose. When glucose levels are low, the glycolytic enzyme aldolase is not bound to fructose-1,6-bisphosphate (FBP) and, instead, signals to activate lysosomal AMPK. Here, we show that blocking FBP binding to aldolase with the small molecule aldometanib selectively activates the lysosomal pool of AMPK and has beneficial metabolic effects in rodents. We identify aldometanib in a screen for aldolase inhibitors and show that it prevents FBP from binding to v-ATPase-associated aldolase and activates lysosomal AMPK, thereby mimicking a cellular state of glucose starvation. In male mice, aldometanib elicits an insulin-independent glucose-lowering effect, without causing hypoglycaemia. Aldometanib also alleviates fatty liver and nonalcoholic steatohepatitis in obese male rodents. Moreover, aldometanib extends lifespan and healthspan in both Caenorhabditis elegans and mice. Taken together, aldometanib mimics and adopts the lysosomal AMPK activation pathway associated with glucose starvation to exert physiological roles, and might have potential as a therapeutic for metabolic disorders in humans.

Attribute Analytics Performance Metrics from the MAM Consortium Interlaboratory Study.

The multi-attribute method (MAM) was conceived as a single assay to potentially replace multiple single-attribute assays that have long been used in process development and quality control (QC) for protein therapeutics. MAM is rooted in traditional peptide mapping methods; it leverages mass spectrometry (MS) detection for confident identification and quantitation of many types of protein attributes that may be targeted for monitoring. While MAM has been widely explored across the industry, it has yet to gain a strong foothold within QC laboratories as a replacement method for established orthogonal platforms. Members of the MAM consortium recently undertook an interlaboratory study to evaluate the industry-wide status of MAM. Here we present the results of this study as they pertain to the targeted attribute analytics component of MAM, including investigation into the sources of variability between laboratories and comparison of MAM data to orthogonal methods. These results are made available with an eye toward aiding the community in further optimizing the method to enable its more frequent use in the QC environment.

[Latest Research Findings on the Role of Non-Tumor Cells in Glioma Microenvironment].

As the tumor cell-centered treatment strategies cannot curb the malignant progression of glioblastoma effectively, the therapeutic effect of glioblastoma is still not satisfactory. In addition to glioma cells, glioma microenvironment (GME) comprises massive numbers of non-tumor cells and soluble cytokines. The non-tumor cells include endothelial cells, pericytes, microglia/macrophages, mesenchymal cells, astrocytes, neurons, etc. These non-tumor cell components, together with glioma cells, form one organism which regulates the progression of glioma. Considerable progress has been been in research on GME, which will be conducive to the development of non-tumor cell targeted therapies and and improvements in the prognosis of glioma patients. Herein, we summarized the interaction of glioma cells with endothelial cells, pericytes, microglia/macrophages, astrocytes, neurons and mesenchymal cells, a topic that has been extensively researched, as well as the corresponding translational studies. We also discussed the potential challenges and opportunities of developing glioma treatments based on tumor microenvironment.

[Development and Evaluation of Prognostic Nomogram Model for Adult Ventricle Glioma Patients].

Objective: To explore the prognostic factors of adult ventricle glioma (AVG) and to construct and evaluate a survival-related prognostic nomogram model, which could provide further reference for the clinical management of AVG patients. Methods: The patients covered in the study were selected from the Surveillance Epidemiology and End Results (SEER) database (1973-2016). They all had definite histological diagnosis of AVG. They were assigned randomly to the training cohort and the validation cohort by random number table at a 2/1 ratio. Survival analysis was performed by Kaplan-Meier analysis. Cox regression analysis was employed to determine the independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Then, integrating the basic characteristics of patients, the survival-related nomogram predictive model for OS and CSS in the training cohort was constructed, respectively. After that, internal cross validation and external validation of the model were carried out with the training cohort and the validation cohort in succession. The authenticity and reliability of the nomogram model were evaluated by calculating the concordance index (C-index). Calibration plots were constructed to assess the agreement between the predicted values and the observed values in the training cohort and the validation cohort. Results: A total of 369 AVG patients, including 218 males and 151 females, were included. The median age of the patients was 53. According to the WHO classification of gliomas, 66 (17.9%) patients had grade Ⅱ gliomas, 73 (19.8%) had grade Ⅲ gliomas, and 230 (62.3%) had grade Ⅳ gliomas. Regarding the extent of resection (EOR), 59 (16.0%) had gross total resection (GTR) and 145 (39.3%) had subtotal resection (STR) or partial resection (PR). Of all the patients, 167 (45.3%) received postoperative radiotherapy and 143 (38.8%) received postoperative chemotherapy. Patients were randomized into the training cohort ( n=246) and the validation cohort ( n=123), and there was no significant difference ( P>0.05) in the basic clinical characteristics between the training cohort and the validation cohort. In the training cohort, Cox regression analysis revealed that the independent prognostic factors for OS and CSS included age≥65, grades Ⅲ and Ⅳ according to the WHO classification of gliomas, and not receiving radiotherapy. Furthermore, 5 variables, including age, gender, WHO grades, surgery, and radiotherapy, were used to construct the nomogram model for predicting 6-month, 1-year, and 2-year OS and CSS. The results of internal cross validation in the training cohort showed that the C-indexes of OS and CSS were 0.758 and 0.765, respectively. The external validation results of the validation cohort showed that the C-indexes of OS and CSS were 0.733 and 0.719, respectively. Calibration plots for 6-month, 1-year, and 2-year OS in the training cohort showed relatively good agreement, while in the validation cohort the agreement was relatively low. The 6-month, 1-year, and 2-year CSS calibration plots had results similar to the calibration plots of OS. Conclusion: This nomogram predictive model of OS and CSS showed moderately reliable predictive performance, providing helpful reference information for clinicians to make quick and simple assessment of the survival probability of AVG patients.

Evaluation of CD98 light chain-LAT1 as a potential marker of cancer stem-like cells in glioblastoma.

OBJECTIVE: Glioma stem cells (GSCs) are a minority population of glioma cells that regarded as the cause of tumor formation and recurrence. Identifying new molecular strategies targeting GSCs must be urgently developed to treat glioblastoma. In this study, one of CD98 light chain-L type amino acid transporter 1 (LAT1) was found as a potential GSC marker. LAT1 served as EAA transporter has been shown to be closely related with tumor invasion, metastasis, angiogenesis, and radiosensitivity. METHODS: LAT1+ and LAT1- glioma cells were sorted by flow cytometry. Cellular immunofluorescence, sphere-formation arrays, and in vitro limiting dilution experiments were used to identify cell stemness. Differentiated glioma stem cells were cultured, and the expressions of ß-tubulinIII, GFAP, and LAT1 were detected by Western blot. Nude mouse models were constructed to observe tumor formation and metastasis in nude mice. RESULTS: LAT1+ glioma cells were testified a small percentage of all cells and selected as the subsequent sorting marker. LAT1+ cells were separated from U87 and U251 cells could express high level of stem cell markers, and possessed GSC properties including self-renewal ability and multi-directional differentiation potential. But LAT1- cells did not have these characteristics. In addition, LAT1+ cells were able to generate tumors in vivo, tumor size of LAT1+ cells formed were much bigger than that of LAT1- cells. CONCLUSION: Our study, including molecular, cell, vitro and vivo experiments, has shown that LAT1+ cells possess GSC properties, and present for the first time that LAT1 can be used as a new marker for GSCs screening.

Effect of hypertensive disorders of pregnancy on peripheral venous blood cell count in preterm infants with a gestational age of 28-34 weeks. / å¦Šå¨ æœŸé«˜è¡€åŽ‹ç–¾ç— å¯¹èƒŽé¾„28~34周早产儿外周静脉血细胞计数的影响.

OBJECTIVES: To study the effect of hypertensive disorders of pregnancy on peripheral venous blood cell count in preterm infants with a gestational age of 28-34 weeks. METHODS: A total of 227 preterm infants with a gestational age of 28-34 weeks who were admitted to the Department of Pediatrics, the First Hospital Affiliated to Kunming Medical University, from January to December 2020, and whose mothers had hypertensive disorders of pregnancy were enrolled as the study group. A total of 227 preterm infants with a gestational age of 28-34 weeks who were admitted during the same period and whose mothers did not have hypertensive disorders of pregnancy were enrolled as the control group. According to maternal blood pressure during pregnancy, the study group was divided into three subgroups: gestational hypertension (n=75), mild preeclampsia (n=81), and severe preeclampsia (n=71). According to the birth weight of the preterm infants, the study group was divided into two subgroups: small for gestational age (SGA) (n=113) and appropriate for gestational age (AGA) (n=114). Peripheral blood cell count on day 1 after birth was compared between the study and control groups, as well as between the subgroups of the study group. RESULTS: Compared with the control group, the study group had significantly lower white blood cell count, absolute neutrophil count, and blood platelet count (P<0.05) and significantly higher incidence rates of leucopenia and neutropenia (P<0.05). The subgroup analysis showed that the mild preeclampsia and severe preeclampsia subgroups had significantly lower white blood cell count, absolute neutrophil count, and blood platelet count than the gestational hypertension subgroup (P<0.05), and that the SGA subgroup had significantly lower white blood cell count, absolute neutrophil count, and blood platelet count than the AGA subgroup (P<0.05). CONCLUSIONS: Hypertensive disorders of pregnancy can affect the peripheral venous blood cell count of preterm infants, which is more significant in infants with maternal preeclampsia and SGA infants.

Driver mutations in ADGRL3 are involved in the evolution of ependymoma.

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

Data-driven discovery of a universal indicator for metallic glass forming ability.

Despite the importance of glass forming ability as a major alloy characteristic, it is poorly understood and its quantification has been experimentally laborious and computationally challenging. Here, we uncover that the glass forming ability of an alloy is represented in its amorphous structure far away from equilibrium, which can be exposed by conventional X-ray diffraction. Specifically, we fabricated roughly 5,700 alloys from 12 alloy systems and characterized the full-width at half-maximum, Δq, of the first diffraction peak in the X-ray diffraction pattern. A strong correlation between high glass forming ability and a large Δq was found. This correlation indicates that a large dispersion of structural units comprising the amorphous structure is the universal indicator for high metallic glass formation. When paired with combinatorial synthesis, the correlation enhances throughput by up to 100 times compared to today's state-of-the-art combinatorial methods and will facilitate the discovery of bulk metallic glasses.