The biological age model for evaluating the degree of aging in centenarians.

BACKGROUND: Biological age (BA) has been used to assess individuals' aging conditions. However, few studies have evaluated BA models' applicability in centenarians. METHODS: Important organ function examinations were performed in 1798 cases of the longevity population (80∼115 years old) in Hainan, China. Eighty indicators were selected that responded to nutritional status, cardiovascular function, liver and kidney function, bone metabolic function, endocrine system, hematological system, and immune system. BA models were constructed using multiple linear regression (MLR), principal component analysis (PCA), Klemera and Doubal method (KDM), random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and light gradient boosting machine (lightGBM) methods. A tenfold crossover validated the efficacy of models. RESULTS: A total of 1398 participants were enrolled, of whom centenarians accounted for 49.21%. Seven aging markers were obtained, including estimated glomerular filtration rate, albumin, pulse pressure, calf circumference, body surface area, fructosamine, and complement 4. Eight BA models were successfully constructed, namely MLR, PCA, KDM1, KDM2, RF, SVM, XGBoost and lightGBM, which had the worst R2 of 0.45 and the best R2 of 0.92. The best R2 for cross-validation was KDM2 (0.89), followed by PCA (0.62). CONCLUSION: In this study, we successfully applied eight methods, including traditional methods and machine learning, to construct models of biological age, and the performance varied among the models.

Compression Degree of Trigeminal Nerve and Type of Conflicting Vessels Determine Short- and Long-Term Complete Pain Relief in Adult Patients with Primary Trigeminal Neuralgia After Microvascular Decompression: A Three-Year Retrospective Study of 200 Adult Patients with Primary Trigeminal Neuralgia.

Objective: In this study, we aimed to explore the demographic and clinical factors that could determine short- and long-term complete pain relief (CPR) in adult patients with primary trigeminal neuralgia (PTN) after microvascular decompression (MVD) to guide clinical practice. Methods: This single-center retrospective study included adult patients with PTN who underwent MVD as their initial neurosurgical procedure in the Department of Neurosurgery at the Second Affiliated Hospital of Harbin Medical University from January 2017 to December 2019 and completed a 3-year post-surgery follow-up. Demographic and clinical information was obtained from medical records. Pain relief of adult patients with PTN at various time points after sufficient decompression of trigeminal nerve (TN) during MVD was determined and classified by the patient's subjective response and medications use. Pain relief of local patients was evaluated by outpatient follow-up at various time points, whereas that of local cases who could not return to outpatient or non-local cases was assessed through telephone or WeChat. Results: In univariate analysis, compression degree of TN and type of conflicting vessels constantly showed significant differences between the two groups at 3 months, 6 months, 1 year, 2 years, and 3 years after MVD. Compression degree of TN and type of conflicting vessels at various time points after MVD were always the related factors to CPR in logistic regression analysis, with the former having the greatest impact. The areas under the receiver operating characteristic (ROC) curve of CPR at various time points after MVD were 0.937, 0.874, 0.879, 0.864, and 0.869, respectively. Conclusion: In summary, compression degree of TN and type of conflicting vessels can determine short- and long-term CPR in adult patients with PTN after MVD.

Metagenomic next-generation sequencing and proteomics analysis in pediatric viral encephalitis and meningitis.

Introduction: Early and accurate identification of pathogens is essential for improved outcomes in patients with viral encephalitis (VE) and/or viral meningitis (VM). Methods: In our research, Metagenomic next-generation sequencing (mNGS) which can identify viral pathogens unbiasedly was performed on RNA and DNA to identify potential pathogens in cerebrospinal fluid (CSF) samples from 50 pediatric patients with suspected VEs and/or VMs. Then we performed proteomics analysis on the 14 HEV-positive CSF samples and another 12 CSF samples from health controls (HCs). A supervised partial least squaresdiscriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) model was performed using proteomics data. Results: Ten viruses in 48% patients were identified and the most common pathogen was human enterovirus (HEV) Echo18. 11 proteins overlapping between the top 20 DEPs in terms of P value and FC and the top 20 proteins in PLS-DA VIP lists were acquired. Discussion: Our result showed mNGS has certain advantages on pathogens identification in VE and VM and our research established a foundation to identify diagnosis biomarker candidates of HEV-positive meningitis based on MS-based proteomics analysis, which could also contribute toward investigating the HEV-specific host response patterns.

Noninvasive identificational diagnosis of diabetic nephropathy and non-diabetic renal disease based on clinical characteristics of Traditional Chinese Medicine symptom pattern and conventional medicine.

OBJECTIVE: To study the clinical characteristics relating to differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD). METHODS: The subjects were patients with type 2 diabetes mellitus (T2DM) complicated with chronic kidney disease (CKD). Western medical history data and Traditional Chinese Medicine (TCM) symptom pattern were collected, and logistic regression was used to analyze. RESULTS: Blood deficiency pattern [odds ratio () = 2.269, 0.017] and stagnation pattern ( = 1.999, 0.041) are independently related to DN. CONCLUSIONS: TCM factors blood deficiency pattern and stagnation pattern are relating to differential diagnosis of DN and NDRD.

Matrine suppresses NLRP3 inflammasome activation via regulating PTPN2/JNK/SREBP2 pathway in sepsis.

BACKGROUND: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Abnormal activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome plays a vital role in the pathogenesis of sepsis. Matrine is proved to show good anti-inflammatory properties, whereas its effect and the underlying molecular machinery on sepsis remains unclear. PURPOSE: The aim of this study is to evaluate the effect and mechanism of Matrine on sepsis. STUDY DESIGN: THP-1 cells and J774A.1 cells were stimulated by lipopolysaccharide (LPS) with nigericin or adenosine triphosphate (ATP) to establish an in vitro model. Cecal ligation and puncture (CLP)-induced sepsis mouse model was used. Matrine was given by gavage. METHODS: To investigate the NLRP3 inflammasome activation, phorbol myristate acetate (PMA)-induced THP-1 cells were first primed with LPS and then stimulated by matrine, followed by treatment with nigericin or ATP. The concentration of interleukin 1ß (IL-1ß) and interleukin 18 (IL-18) in the cell culture supernatant was detected. The mechanism was explored by cell death assay, immunoblots and immunofluorescence in vitro. C57BL/6 mice were intragastrically administered with matrine for 5 days before CLP. The therapeutic effect of matrine was evaluated by symptoms, pathological analysis, ELISA and RT-qPCR. RESULTS: Our results revealed that matrine inhibited IL-1ß and IL-18 secretion, suppressed caspase-1 activation, reduced cell death, and blocked ASC speck formation upon NLRP3 inflammasome activation. Furthermore, matrine restrains NLRP3 inflammasome activation as well as pyroptosis through regulating the protein tyrosine phosphatase non-receptor type 2 (PTPN2)/JNK/SREBP2 signaling. Matrine also prominently improved the symptoms and pathological changes with reduced levels of TNF-α, IL-1ß, and IL-6 in the lung tissues and serum in a dose-dependent manner. CONCLUSION: Matrine effectively alleviates the symptoms of CLP-induced sepsis in mice, restrains NLRP3 inflammasome activation by regulating PTPN2/JNK/SREBP2 signaling pathway, and may become a promising therapeutic agent for sepsis treatment.

Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine / 中国结合医学杂志

OBJECTIVE@#To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine.@*METHODS@#Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients.@*RESULTS@#Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD.@*CONCLUSIONS@#Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

Traditional Chinese Medicine Intervention in Membranous Nephropathy Based on Podocyte Injury： A Review / 中国实验方剂学杂志

Membranous nephropathy， an autoimmune kidney disease with glomerular podocyte injury as the core mechanism， is a common pathological type of adult nephrotic syndrome and has become the main cause of end-stage renal disease in China. Podocytes are terminally differentiated cells that play an important role in maintaining the structural and functional stability of glomeruli and are molecular barriers for protein filtration. Glomerular filtration membrane injury induced by podocyte injury is an important cause of massive proteinuria. Persistent or aggravated proteinuria may prolong the course of membranous nephropathy. It is believed that podocyte destruction in membranous nephropathy is mainly related to oxidative stress， autophagy dysregulation， abnormal expression of podocyte marker proteins， chronic inflammation， epithelial-mesenchymal cell transdifferentiation， and so on. At present， western medicine mostly uses immunosuppressants and hormones for treatment according to its pathological stage， but there are certain adverse reactions. Traditional Chinese medicine （TCM） has made some achievements in the prevention and treatment of membranous nephropathy. In recent years， studies have found that many Chinese medicines can affect the occurrence and development of membranous nephropathy in different links by acting on multiple targets in the human body， with manifest advantages. This paper overviewed the podocyte injury mechanism in membranous nephropathy and summarized the treatment of membranous nephropathy with Chinese medicine monomers， compounds， and Chinese patent medicines in intervening related target pathways， aiming to provide a basis for the clinical treatment， basic research， and targeted drug development of TCM against membranous nephropathy.

Proteomic profiling of cerebrospinal fluid in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder of the central nervous system. METHODS: Extracted proteins from 34 cerebrospinal fluid (CSF) samples [patients with MOGAD (MOG group, n = 12); healthy controls (HC group, n = 12); patients with MOG seronegative and metagenomics next-generation sequencing-negative inflammatory neurological diseases (IND group, n = 10)] were processed and subjected to label-free quantitative proteomics. Supervised partial least squares-discriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) models were also performed based on proteomics data. Functional analysis of differentially expressed proteins (DEPs) was performed using Gene Ontology, InterPro, and Kyoto Encyclopedia Genes and Genomes. An enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with MOGAD. RESULTS: Four hundred and twenty-nine DEPs (149 upregulated and 280 downregulated proteins) were identified in the MOG group compared to the HC group according to the P value and fold change (FC). Using the O-PLS-DA model, 872 differentially abundant proteins were identified with variable importance projection (VIP) scores > 1. Five proteins (gamma-glutamyl hydrolase, cathepsin F, interalpha-trypsin inhibitor heavy chain 5, latent transforming growth factor beta-binding protein 4 and leukocyte-associated immunoglobulin-like receptor 1) overlapping between the top 30 DEPs with top-ranked P value and FC and top 30 proteins in PLS-DA VIP lists were acquired. Functional analysis revealed that the dysregulated proteins in the MOG group were primarily involved in complement and coagulation cascades, cell adhesion, axon guidance, and glycosphingolipid biosynthesis compared to the HC group. CONCLUSION: The proteomic alterations in CSF samples from children with MOGAD identified in the current study might provide opportunities for developing novel biomarker candidates.

Getting tougher in the ultracold.

Certain alloys show exceptional toughness in a liquid helium environment.

Study on the single-mode condition for x-cut LNOI rib waveguides based on leakage losses.

Lithium niobate-on-insulator (LNOI) has recently emerged as a promising material platform for high-density and advanced photonics integrated circuits (PICs). And single-mode waveguides (SMW) are the most basic building blocks for structuring various PICs. In this paper, single-mode conditions (SMCs) for shallowly etched LNOI rib waveguides in x-cut LNOI wafer are investigated with the finite element method (FEM) in consideration of the lateral leakage and the magic width for the first time, to our best knowledge. Our results indicate that due to the lateral leakage and the magic width these shallowly etched x-cut LNOI rib waveguides have unique and complex SMCs. Our method and results provide a guidance in designing low-loss LNOI SMW and high-performance PICs.

Research status on efficacy enhancement and toxicity reduction of Chinese medicine in treatment of malignant tumors: a review of projects supported by National Natural Science Foundation of China / 中国中药杂志

Through a retrospective analysis of the projects supported by the National Natural Science Foundation of China in the past ten years in the field of Chinese medicine for the treatment of malignant tumors, this article systematically summarized the main research contents and hotspots of Chinese medicine in efficacy enhancement and toxicity reduction. The efficacy enhancement of Chinese medicine mainly included the mitigation of molecule-targeted drug resistance, multidrug resistance, and chemotherapy resistance, synergistic efficacy enhancement, and radiotherapy sensitization. The toxicity reduction is mainly reflected in the alleviation of the side effects of radiotherapy and chemotherapy. In addition, Chinese medicine has advantages in reducing serious adverse reactions of malignant tumors, providing more options for the adjuvant treatment of tumors.

Circular RNA PVT1 Promotes Proliferation and Represses Apoptosis of Colorectal Cancer Cells / 中国生物化学与分子生物学报

Circular RNAs (circRNAs) are a novel class of long-chain non-coding RNAs. Preceding evidence has showed that circRNAs participate in the development and progression of various tumors. In the present study, we investigated the expression of circRNAs in 5 paired colorectal cancer (CRC) tissues and adjacent normal tissues with circRNA high-throughput sequencing. Totally 477 differentially expressed circRNAs were identified between CRC tissues and non-cancerous matched tissues, which included 252 significantly overexpressed circRNAs and 225 downregulated circRNAs. CircRNA plasmacytoma variant translocation 1 (circPVT1), the most up-regulated expression circRNA, was further confirmed by qRT-PCR in 150 colorectal cancer tissues and matched normal mucosae. Our data revealed that circPVT1 showed a significant up-regulation trend in CRC tissues compared with matched normal mucosae. Similarly, compared with normal colorectal mucosa cells, the expression of circPVT1 in colorectal cancer cell lines was significantly up-regulated (P<0. 05). Functionally, silence with siRNA or overexpression of circPVT1 in colorectal cancer cells was applied to determine the biological functions of circPVT1, including cell proliferation, apoptosis, and cell cycle, etc. The results show that circPVT1 expression significantly attenuated apoptosis, induced replication and promoted proliferation of colorectal cancer cells in vitro. In summary, our findings indicate that circPVT1 plays an oncogenic role in CRC and might be a potential novel target for CRC therapy.

Clinical characteristics and influencing factors for mortality of patients with intra-abdominal candidiasis: a multicenter retrospective study / 中华消化外科杂志

Objective:To investigate the clinical characteristics and influencing factors of mortality in patients with intra-abdominal candidiasis (IAC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 203 IAC patients who were admitted to 7 medical centers from June 2018 to June 2020 were collected, including 54 cases in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, 31 cases in Fujian Medical University Union Hospital, 25 cases in Beijing Hospital, 25 cases in the First Affiliated Hospital of Xi'an Jiaotong University, 24 cases in China-Japan Friendship Hospital, 22 cases in General Hospital of Eastern Theater Command of Chinese PLA and 22 cases in Chongqing University Cancer Hospital. There were 130 males and 73 females, aged (64±15)years. Observation indicators: (1) candida infection and treatment of IAC patients; (2) analysis of influencing factors for mortality of IAC patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analyses were performed by Logistic regression model. Results:(1) Candida infection and treatment of IAC patients: 134 cases of candida albicans were cultured in the initial abdominal drainage fluid or intraoperative abdominal specimens of 203 patients, and 49 cases were treated with fluconazole. Of 69 cases infected with non candida albicans, 13 cases were treated with fluconazole. The resistance rate of candida albicans to fluconazole was 5.91%(12/203). Of 203 patients, there were 68 cases with infections shock, 53 cases with renal failure, 84 cases with respiratory failure and 63 cases with multiple organ failure, respectively. There were 148 of 203 patients admitted to intensive care unit for 9 days(range, 3-20 days), and the total hospital stay was 28 days(range, 17-50 days). Of 203 patients, 86 cases were cured and discharged, 50 cases were improved and transferred to local hospitals, 32 cases gave up treatment and discharged automatically, 19 cases died, 16 cases had no follow-up data. The mortality was 25.12%(51/203). (2) Analysis of influencing factors for mortality of IAC patients. Results of univariate analysis showed that acute physiology and chronic health evaluation score, sequential organ failure assessment score, the Cr, bilirubin, albumin, procalcitonin, and PLT on the first day of candida positive culture, of the lowest value in a week and the highest in a week, heart disease, diabetes, infections shock, renal failure, respiratory failure, multiple organ failure, anti-fungal therapy were the related factors for mortality of IAC patients ( t=-2.322, Z=-2.550, -2.262, -4.361, t=2.085, Z=-3.734, -5.226, -2.394, -5.542, t=3.462, Z=-4.957, -5.632, 3.670, -5.805, t=3.966, Z=-3.734, -5.727, χ2=4.071, 4.638, 27.353, 18.818, 13.199, 26.251, 13.388, P<0.05). Multivariate analysis showed that the bilirubin, procalcitonin on the first day of candida positive culture and infections shock were independent risk factors for mortality of IAC patients ( odds ratio=1.021, 1.022, 6.864, 95% confidence interval as 1.010-1.033, 1.001-1.044, 1.858-25.353, P<0.05). Conclusions:The common fungus of IAC was candida albicans, and fluconazole can be used as the initial empirical treatment. The prognosis of patients with abdominal candidiasis is poor. Bilirubin, procalcitonin on the first day of candida positive culture and infections shock are indepen-dent risk factors for mortality of IAC patients.

Epidemiological and clinical characteristics of COVID-19 patients in Hengyang, Hunan Province, China.

BACKGROUND: In December 2019, an ongoing outbreak of coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China. The characteristics of COVID-19 patients treated in local hospitals in Wuhan are not fully representative of patients outside Wuhan. Therefore, it is highly essential to analyze the epidemiological and clinical characteristics of COVID-19 in areas outside Wuhan or Hubei Province. To date, a limited number of studies have concentrated on the epidemiological and clinical characteristics of COVID-19 patients with different genders, clinical classification, and with or without basic diseases. AIM: To study the epidemiological and clinical characteristics of COVID-19 patients in Hengyang (China) and provide a reliable reference for the prevention and control of COVID-19. METHODS: From January 16 to March 2, 2020, a total of 48 confirmed cases of COVID-19 were reported in Hengyang, and those cases were included in this study. The diagnostic criteria, clinical classification, and discharge standard related to COVID-19 were in line with the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) released by National Health Commission and National Administration of Traditional Chinese Medicine. The presence of SARS-CoV-2 in pharyngeal swab specimens was detected by quantitative reverse transcription polymerase chain reaction. All the data were imported into the excel worksheet and statistically analyzed by using SPSS 25.0 software. RESULTS: A total of 48 cases of COVID-19 were collected, of which 1 was mild, 38 were moderate, and 9 were severe. It was unveiled that there were 31 (64.6%) male patients and 17 (35.4%) female patients, with a female-to-male ratio of 1.82:1. The range of age of patients with COVID-19 was dominantly 30-49 years old [25 (52.1%) of 48], followed by those aged over 60 years old [11 (22.9%)]. Besides, 29.2% (14 of 48) of patients had basic diseases, and 57.2% (8 of 14) of patients with basic diseases were aged over 60 years old. The occupations of 48 COVID-19 patients were mainly farmers working in agricultural production [15 (31.5%) of 48], rural migrant workers from Hengyang to Wuhan [15 (31.5%)], and service workers operating in the service sector [8 (16.7%)]. The mean latent period was 6.86 ± 3.57 d, and the median was 7 [interquartile range (IQR): 4-9] d. The mean time from onset of symptoms to the first physician visit was 3.38 ± 2.98 (95%CI: 2.58-9.18) d, with a median of 2 (IQR: 1-5) d, and the mean time from hospital admission to confirmed diagnosis was 2.29 ± 2.11 (95%CI: 1.18-6.42) d, with a median of 2 (IQR: 1-3) d. The main symptoms were fever [43 (89.6%) of 48], cough and expectoration [41 (85.4%)], fatigue [22 (45.8%)], and chills [22 (45.8%)]. Other symptoms included poor appetite [13 (27.1%)], sore throat [9 (18.8%)], dyspnea [9 (18.8%)], diarrhea [7 (14.6%)], dizziness [5 (10.4%)], headache [5 (10.4%)], muscle pain [5 (10.4%)], nausea and vomiting [4 (8.3%)], hemoptysis [4 (8.3%)], and runny nose [1 (2.1%)]. The numbers of peripheral blood leukocytes, lymphocytes, and eosinophils were significantly reduced in the majority of the patients. The levels of C-reactive protein, fibrinogen, blood glucose, lactate dehydrogenase, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GT), myoglobin (MB), and creatine kinase (CK) were increased in 64.6%, 44.7%, 43.2%, 37.0%, 29.5%, 22.9%,20.8%, 21.6%, 13.6%, and 12.8% of patients, respectively. The incidence of ALT elevation in male patients was remarkably higher than that in females (P < 0.01), while the incidences of AST, CK, and blood glucose elevations in severe patients were remarkably higher than those in moderate patients (P < 0.05, respectively). Except for the mild patients, chest computed tomography showed characteristic pulmonary lesions. All the patients received antiviral drugs, 38 (79.2%) accepted traditional Chinese medicine, and 2 (4.2%) received treatment of human umbilical-cord mesenchymal stem cells. On March 2, 2020, 48 patients with COVID-19 were all cured and discharged. CONCLUSION: Based on our results, patients with COVID-19 often have multiple organ dysfunction or damage. The incidences of ALT elevation in males, and AST, CK, and blood glucose elevations in severe patients are remarkably higher.

A child with household transmitted COVID-19.

BACKGROUND: Although people of all ages are susceptible to the novel coronavirus infection, which is presently named "Coronavirus Disease 2019" (COVID-19), there has been relatively few cases reported among children. Therefore, it is necessary to understand the clinical characteristics of COVID-19 in children and the differences from adults. CASE PRESENTATION: We report one pediatric case of COVID-19. A 14-month-old boy was admitted to the hospital with a symptom of fever, and was diagnosed with a mild form of COVID-19. The child's mother and grandmother also tested positive for SARS-CoV-2 RNA. However, the lymphocyte counts were normal. The chest computed tomography (CT) revealed scattered ground glass opacities in the right lower lobe close to the pleura and resorption after the treatment. The patient continued to test positive for SARS-CoV-2 RNA in the nasopharyngeal swabs and stool at 17 days after the disappearance of symptoms. CONCLUSION: The present pediatric case of COVID-19 was acquired through household transmission, and the symptoms were mild. Lymphocyte counts did not significantly decrease. The RNA of SARS-CoV-2 in stool and nasopharyngeal swabs remained positive for an extended period of time after the disappearance of symptoms. This suggests that attention should be given to the potential contagiousness of pediatric COVID-19 cases after clinical recovery.

Insulin-Like Growth Factor-1 Down-Regulates the Phosphorylation of FXYD1 and Rescues Behavioral Deficits in a Mouse Model of Rett Syndrome.

Rett syndrome (RTT) is a neurodevelopmental disease in children that is mainly caused by mutations in the MeCP2 gene, which codes for a transcriptional regulator. The expression of insulin-like growth factor-1 (IGF-1) is reduced in RTT patients and animal models, and IGF-1 treatment is a promising therapeutic strategy for RTT. However, the mechanism underlying the effects of IGF-1 remains to be further explored. FXYD1 is an auxiliary subunit of Na, K-ATPase. Overexpression of FXYD1 is involved in the pathogenesis of RTT. However, whether IGF-1 exerts its effect through normalizing FXYD1 is completely unknown. To this end, we evaluated the effect of IGF-1 on FXYD1 expression and posttranslational modification in a mouse model of RTT (MeCP2308) using both in vitro and in vivo experiments. The results show that FXYD1 mRNA and phosphorylated protein (p-FXYD1) were significantly elevated in the frontal cortex in RTT mice, compared to wild type. In RTT mice, IGF-1 treatment significantly reduced levels of FXYD1 mRNA and p-FXYD1, in parallel with improvements in behavior, motor coordination, and cognitive function. For mechanistic insight into the effect of IGF-1 on p-FXYD1, we found the decreased phosphorylated forms of PI3K-AKT-mTOR signaling pathway components in the frontal cortex of RTT mice and the normalizing effect of IGF-1 on the phosphorylated forms of these components. Interestingly, blocking the PI3K/AKT pathway by PI3K inhibitor could abolish the effect of IGF-1 on p-FXYD1 level, in addition to the effect of IGF-1 on the phosphorylation of other components in the PI3K/AKT pathway. Thus, our study has provided new insights into the mechanism of IGF-1 treatment for RTT, which appears to involve FXYD1.

Prevalence of radiographic parameters on CT associated with femoroacetabular impingement in a Chinese asymptomatic population.

BACKGROUND: Imaging evaluation of femoroacetabular impingement (FAI) plays a major role in early diagnosis and treatment, preventing irreversible degenerative changes in hip joints. PURPOSE: To investigate the anatomical parameters associated with FAI in a Chinese asymptomatic population by computed tomography (CT) and to evaluate the prevalence of the radiographic features of cam and pincer types in Chinese patients. MATERIAL AND METHODS: We reviewed the CT images of 470 hips in 235 Chinese patients who underwent abdominal and pelvic CT scans for reasons unrelated to hip symptoms at our hospital between February and October 2017. The following measurements were made on each hip joint: acetabular version angle (AV); anterior acetabular sector angle (AASA); posterior acetabular sector angle (PASA); the lateral center edge angle (LCE); the alpha angle (AA); and femoral head-neck offset (FHNO). RESULTS: Significant differences in all parameters were seen between men and women. Young men and elderly women showed more retroversion in our study. LCE, AA, and FHNO were all larger in men than women. The data showed 25% of female joints and 34.5% of male joints had at least one predisposing factor for FAI using measurement parameters by CT images in Chinese asymptomatic patients, and the prevalence of pincer lesion (19.1%) was larger than cam lesion (9.1%). CONCLUSION: Morphological features associated with FAI are also present in Chinese asymptomatic patients. The threshold values for abnormal parameters should be reconsidered based on gender, age, and other factors in order to improve the accuracy of diagnosis.