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Abstract Background A comprehensive understanding of the genetic basis of rare diseases and their regulatory mechanisms is essential for human molecular genetics. However, the genetic mutant spectrum of pathogenic genes within the Chinese population remains underrepresented. Here, we reported previously unreported functional ABHD12 variants in two Chinese families and explored the correlation between genetic polymorphisms and phenotypes linked to PHARC syndrome. Methods Participants with biallelic pathogenic ABHD12 variants were recruited from the Chinese Deafness Genetics Cohort. These participants underwent whole-genome sequencing. Subsequently, a comprehensive literature review was conducted. Results Two Han Chinese families were identified, one with a compound heterozygous variant and the other with a novel homozygous variant in ABHD12. Among 65 PHARC patients, including 62 from the literature and 3 from this study, approximately 90% (57 out of 63) exhibited hearing loss, 82% (50 out of 61) had cataracts, 82% (46 out of 56) presented with retinitis pigmentosa, 79% (42 out of 53) experienced polyneuropathy, and 63% (36 out of 57) displayed ataxia. Seventeen different patterns were observed in the five main phenotypes of PHARC syndrome. A total of 33 pathogenic variants were identified in the ABHD12. Compared with other genotypes, individuals with biallelic truncating variants showed a higher incidence of polyneuropathy (p = 0.006), but no statistically significant differences were observed in the incidence of hearing loss, ataxia, retinitis pigmentosa and cataracts. Conclusions The diagnosis of PHARC syndrome is challenging because of its genetic heterogeneity. Therefore, exploring novel variants and establishing genotype-phenotype correlations can significantly enhance gene diagnosis and genetic counseling for this complex disease.

IntroductionWaardenburg syndrome (WS) is a genetic disorder characterized by hearing loss, hypopigmentation, and distinct facial features. Despite > 60% molecular diagnosis rate for WS patients, pathogenic variants within coding regions are predominant, with few non-coding copy number variations (CNVs) reported.MethodsIn this study, we performed whole genome sequencing (WGS) on 59 undiagnosed WS patients and analyzed the CNVs within the promoter and enhancer regions of the SOX10 gene.ResultsWe identified five novel pathogenic deletions ranging from 448 bp to 70 kb upstream of SOX10. Two deletions were in the enhancer region, while three were in the promoter and 5'UTR region. These CNVs manifested as WS type II in eight patients from five unrelated families, demonstrating phenotypic heterogeneity. Furthermore, analysis of CNV1 within the enhancer region suggested a potential mechanism involving Alu-mediated non-allelic homologous recombination (NAHR).ConclusionOur findings extend the mutation spectrum of the SOX10 gene and elucidate the pathogenic role of CNVs in cis-regulatory elements, particularly variations in enhancer and promoter regions, thereby enhancing clinical gene detection and interpretation of non-coding regions.

Abstract Signal transmission in the brain relies on voltage-gated ion channels, which exhibit the electrical behaviour of memristors, resistors with memory. State-of-the-art technologies currently employ semiconductor-based neuromorphic approaches, which have already demonstrated their efficacy in machine learning systems. However, these approaches still cannot match performance achieved by biological neurons in terms of energy efficiency and size. In this study, we utilise molecular dynamics simulations, continuum models, and electrophysiological experiments to propose and realise a bioinspired hydrophobically gated memristive nanopore. Our findings indicate that hydrophobic gating enables memory through an electrowetting mechanism, and we establish simple design rules accordingly. Through the engineering of a biological nanopore, we successfully replicate the characteristic hysteresis cycles of a memristor and construct a synaptic device capable of learning and forgetting. This advancement offers a promising pathway for the realization of nanoscale, cost- and energy-effective, and adaptable bioinspired memristors.

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory disease characterized by familial and acquired forms. Here, we present the case of a 26-year-old male patient with relapsed/refractory peripheral T-cell lymphoma and concurrent HLH. Whole-exon sequencing revealed germline mutations associated with HLH, including those in critical genes such as CD27 and UNC13D and other germline heterozygous variants ( NOTCH2, NOTCH3, IL2RA, TYK2, AGL, CFD , and F13A1 ). CD107a analyses consistently demonstrated impaired degranulation of cytotoxic T-lymphocytes and natural killer (NK) cells. Examination of the patient’s family pedigree revealed that his father and mother harbored UNC13D and CD27 mutations, respectively; his brother carried the same CD27 heterozygous mutation. However, none of them manifested the disease. Despite the missense mutation of CD27 (c.779C>T; p.Pro260Leu) lacking previous documentation in databases, comprehensive analysis suggested non-pathogenic mutations in the CD27 variant, indicating minimal impact on T- and NK-cell functions. These results ultimately supported the option of hematopoietic stem cell transplantation (HSCT) as a successful curative therapeutic approach. As of this report, the patient has remained free of lymphoma and quiescent HLH 15.2 months post-HSCT. This study underscores the efficacy of genetic tests in identifying significant mutations and confirming their etiologies, providing an early basis for treatment decisions and the selection of suitable transplant donors.

Abstract Sphingolipids are ubiquitous components of membranes and function as bioactive lipid signaling molecules. Here, through genetic screening and lipidomics analyses, we find that the endoplasmic reticulum (ER) calcium channel Csg2 integrates sphingolipid metabolism with autophagy by regulating ER calcium homeostasis in the yeast Saccharomyces cerevisiae. Csg2 functions as a calcium release channel and maintains calcium homeostasis in the ER, which enables normal functioning of the essential sphingolipid synthase Aur1. Under starvation conditions, deletion of Csg2 causes increases in calcium levels in the ER and then disturbs Aur1 stability, leading to accumulation of the bioactive sphingolipid phytosphingosine, which specifically and completely blocks autophagy and induces loss of starvation resistance in cells. Our findings indicate that calcium homeostasis in the ER mediated by the channel Csg2 translates sphingolipid metabolism into autophagy regulation, further supporting the role of the ER as a signaling hub for calcium homeostasis, sphingolipid metabolism and autophagy.

In this paper, exact periodic wave solutions for the perturbed Boussinesq equation with power law nonlinearity are obtained for different nonlinear strengths n. When n=1, the periodic traveling wave solutions can be found by the definition of the Jacobian elliptic function. When n≥1, we construct a transformation to solve for the power law nonlinearity, and the periodic traveling wave solutions can be obtained by applying the extended trial equation method. In addition, we consider the limiting case where the periodicity of the periodic traveling wave solutions vanishes, and we obtain the soliton solution for n=1. Numerical simulations show the periodicity of the solution for the perturbed Boussinesq equation.

The use of alternative raw materials such as agricultural biomass and recycled wood waste and by-products in particleboard production is a viable approach to respond to the increased global demand for wood-based materials, and it is a key circular economy principle as well. Wood chips are the second most costly element after resin in particleboard production, where both elements accounting for more than 50% of the overall production cost. Therefore, a significant cost reduction could be achieved by replacing wood chips with lignocellulosic agricultural wastes. Agricultural biomass exists in abundant post-harvest and post-production processes and can be served as an ideal alternative for particleboard manufacturing. This study aimed to review and evaluate the current state-of-the-art particleboard production using a wide variety of environmentally-friendly agricultural biomass, recycled wood waste, and by-products. In this review, the agricultural biomass used for particleboard production was classified into seven different groups based on the part of the plant which they are extracted from, i.e. straw, stalk, bagasse, seed/fruit, leaf, grass, and palms. Particleboards' properties of these raw materials were also compared in terms of their mechanical parameters. The last part of this review concluded the challenges and future potential of using agricultural biomass and recycled wood waste.

BackgroundProphylactic medication in clinical detoxification programs for the treatment of medication overuse headache is still debated. Gastrodin, a main bioactive constituent of Rhizoma Gastrodiae, has been applied clinically to treat primary headache for more than 30 years in China due to its potential analgesic and anti-migraine mechanisms. However, clinical evidence supporting its routing use in MOH is insufficient. The present study aims to investigate the efficacy and tolerability of oral gastrodin in medication overuse headache.MethodsA multicenter, randomized, double-blind, parallel, placebo-controlled trial will be performed. A target sample size of 186 patients who fulfill the International Classification of Headache Disorders 3rd version (ICHD-3) criteria for MOH will be recruited and screened during a baseline screening period of 28 days before being randomly assigned to either the gastrodin or placebo group at a ratio of 1:1. Enrolled patients will be assessed for each 4 weeks during the 12-weeks double-blind phase and followed up at week 24. The primary endpoint is mean change in monthly headache day frequency. Secondary endpoints will be the proportion of remitted MOH, change in headache pain intensity, headache impact test (HIT-6) score, 50% responder rate, treatment failure, monthly acute medication intake days, and Short Form 36-Item Health Survey (SF-36) score. Tolerability will be assessed by drop-out rates though safety monitoring during treatment.DiscussionThe findings of the present study may help to provide new evidence on gastrodin as a prophylaxis treatment with both efficacy and high tolerability for the treatment of MOH.Clinical trail registrationChinese Clinical Trail Registry (ChiCTR2200063719), Protocol Version 1.1, May, 09, 2022.

Magnesium is an essential element to sustain all forms of life. Total intracellular magnesium content is determined by the balance of magnesium influx and efflux. CorA is a divalent selective channel in the metal ion transport superfamily and is the major Mg2+ uptake pathway in prokaryotes and eukaryotic mitochondria. Previous studies have demonstrated that CorA showed distinct magnesium bound closed conformation and Mg2+-free states. In addition, CorA is regulated by cytoplasmic magnesium ions and its gating mechanism has been investigated by electron paramagnetic resonance technique and molecular dynamic simulations. Here, we report a study of the putative CorA-type channel Bpss1228 from Burkholderia pseudomallei, which has been shown to be significantly associated with pseudomallei infection. We expressed and purified the Bpss1228 in full-length. Subsequently, electrophysiological experiments further investigated the electrical characteristics of Bpss1228 and revealed that it was a strictly cation-selective channel. We also proved that Bpss1228 not only possessed magnesium-mediated regulatory property a remarkable ability to be modulated by magnesium ions. Finally, we observed the three-step gating behavior of Bpss1228 on planar lipid bilayer, and further proposed a synergistic gating mechanism by which CorA family channels control intracellular magnesium homeostasis.

Abstract Interface between neuron cells and biomaterials is the key to real-time sensing, transmitting and manipulating of neuron activities, which are the long-term pursue of scientists and gain intense research focus recently. It is of great interest to develop a sensor with exquisite sensitivity and excellent selectivity for real-time monitoring neurotransmitters transport through single live cell. Sensing techniques including electrode-based methods, optogenetics, and nanowire cell penetration systems have been developed to monitor the neuron activities. However, their biocompatibilities remain a challenge. Protein nanopores with membrane compatibility and lumen tunability provide real-time, single-molecule sensitivities for biosensing of DNA, RNA, peptides and small molecules. In this study, an engineered protein nanopore MspA (Mycobacterium smegmatis porin A) through site-directed mutation with histidine selectively bind with Cu2+ in its internal lumen. Chelation of neurotransmitters such as L-glutamate (L-Glu), dopamine (DA) and norepinephrine (NE) with the Cu2+ creates specific current signals, showing different transient current blockade and dwell time in single channel electrophysiological recording. Furthermore, the functionalized M2MspA-N91H nanopores have been embedded in live HEK293T cell membrane for real-time, in situ monitoring of extracellular L-glutamate translocating through the nanopore. This biomimetic neurotransmitter nanopore has provided a new platform for future development of neuron sensors, drug carrier and artificial synapse.

Abstract The general condition, clinical and pathological characteristics, and treatment regimens of patients prenatally and postnatally diagnosed with congenital choledochal malformation (CM) were analyzed in order to investigate the clinical significance of early diagnosis, treatment, and intervention in CM. We retrospectively analyzed 33 children who were admitted to the Children’s Hospital of Soochow University between 1 March 2010 and 31 May 2019, and their diagnosis of CM was confirmed by radiological, surgical and pathological findings. All the patients were under 36 months of age. The patients were divided into prenatally diagnosed and postnatally diagnosed groups. There were 16 and 17 CM patients in the prenatally and postnatally diagnosed groups, respectively, with a preponderance of females in both groups. Compared with the prenatally diagnosed group, the postnatally diagnosed group had a higher incidence of abdominal pain and vomiting (p

Abstract Background Chondromyxoid fibroma-like osteosarcoma (CMF-OS) is an exceedingly rare subtype of low-grade central osteosarcoma (LGCO), accounting for up to 10% of cases and making it difficult to diagnose. CMF-OS is frequently misdiagnosed on a radiological examination and biopsy, even after the initial operation. Its treatment is a controversial issue due to its low-grade classification and actual high-grade behavior. Case presentation We retrospectively reviewed the medical charts of more than 2000 osteosarcoma patients between 2008 and 2019; 11 patients with CMF-OS were identified, of which six patients were treated by our institution with complete clinical characteristics, including treatment and prognosis, radiological and pathological features were reviewed. Three males and three females with a median age of 46 (range 22–56) years were pathologically proven to have CMF-OS. The radiological presentation of CMF-OS is variable, thus radiological misdiagnoses are common. However, one must not ignore a malignant radiologic appearance. The most distinctive pathological feature conferring the diagnosis of CMF-OS is the presence of osteoid production directly by the tumor cells under a chondromyxoid fibroma (CMF)-like background. Differential diagnoses based on comprehensive data from CMF, LGCO, chondrosarcoma (CHS), conventional osteosarcoma (COS), etc., are needed. All patients were treated with an operation and chemotherapy, and one patient received additional radiotherapy. Nevertheless, recurrence and metastasis are common in CMF-OS patients. Relatively invasive biological behavior of CMF-OS is against the low-grade classification of this disease. Conclusions It is important to recognize CMF-OS and distinguish it from CMF, CHS, COS and other LGCOs. CMF-OS has a relatively poor prognosis despite its low-grade classification.

Abstract Gene heterogeneity leads to the differences in cellular behaviors in a wide range, such as tumor drug‐resistant mutation, epithelial‐mesenchymal transition, and migration, posing significant challenges to the development of biomedicine. Traditional gene analysis methods, such as polymerase chain reaction, employ a mass of cells as the gene source, resulting in that the gene properties from a specific single cell are hidden in massive gene information. Recent decades have seen the emerging single‐cell gene analysis techniques with their unprecedented opportunities to study gene heterogeneity with high precision and high throughput. In this review, we summarized the state‐of‐the‐art techniques for single‐cell sequencing and on‐chip gene analysis systems. The principles of each technique are introduced in detail, with the focus on the application scenarios in gene heterogeneity research. Looking forward, we also introduced the challenges in current technologies and point out the future direction for facilitating the technical improvement and clinical applications of single‐cell gene analysis techniques.

Frasier syndrome (FS) is a rare inherited disorder characterized by gonadal dysgenesis and progressive nephropathy, resulting from mutations in the intron 9 splice donor site of the Wilms tumor 1 (WT1) gene. It is associated with male gonadal dysgenesis (female external genitalia with a 46 XY karyotype), and a high risk of gonadoblastoma during adolescence. Patients with FS present early in childhood with proteinuria that progressively worsens with a high likelihood of end-stage renal disease (ESRD). Herein, we report a 15-year-old female (karyotype 46, XY) patient characterized by delayed puberty and steroid-resistant nephrotic syndrome, in whom whole genome sequencing showed a mutation in intron 9 of the WT1 gene, c.1447 + 4 C>T. This is the first case of FS with delayed puberty as the first complaint with no previous renal symptoms. We consider delayed puberty as an important manifestation of FS and summarize the diagnostic process of delayed puberty in the female phenotype. For clinicians, delayed puberty is a common disorder in pediatrics but requires vigilance for some rare causes. Etiological screening and chromosome karyotype analysis are important for the early diagnosis of FS in patients with delayed puberty.

Plasmodium falciparum, the deadliest causal agent of malaria, caused more than half of the 229 million malaria cases worldwide in 2019. The emergence and spreading of frontline drug-resistant Plasmodium strains are challenging to overcome in the battle against malaria and raise urgent demands for novel antimalarial agents. The P. falciparum formate-nitrite transporter (PfFNT) is a potential drug target due to its housekeeping role in lactate efflux during the intraerythrocytic stage. Targeting PfFNT, MMV007839 was identified as a lead compound that kills parasites at submicromolar concentrations. Here, we present 2 cryogenic-electron microscopy (cryo-EM) structures of PfFNT, one with the protein in its apo form and one with it in complex with MMV007839, both at 2.3 Å resolution. Benefiting from the high-resolution structures, our study provides the molecular basis for both the lactate transport of PfFNT and the inhibition mechanism of MMV007839, which facilitates further antimalarial drug design.

Active translocation of DNA through nanopores usually needs enzyme assistance. Here authors present a nanopore derived from helicase E1 of bovine papillomavirus (BPV) which acts as a conductive pore embedded in lipid membrane to allow the translocation of ssDNA and unwinding of dsDNA.

Precisely controlled lymphocyte migration is critically required for immune surveillance and successful immune responses. Lymphocyte migration is strictly regulated by chemokines and chemokine receptors. Here we show that protein geranylgeranylation, a form of post-translational protein lipid modification, is required for chemokine receptor-proximal signaling. Mature thymocytes deficient for protein geranylgeranylation are impaired for thymus egress. Circulating mature T cells lacking protein geranylgeranylation fail to home to secondary lymphoid organs or to transmigrate in response to chemokines in vitro. Mechanistically, protein geranylgeranylation modifies the γ-subunits of the heterotrimeric small GTPases that are essential for chemokine receptor signaling. In addition, protein geranylgeranylation also promotes the differentiation of IL-17-producing T helper cells while inhibiting the differentiation of Foxp3+ regulatory T cells. Finally, mice with T cell lineage-specific deficiency of protein geranylgeranylation are resistant to experimental autoimmune encephalomyelitis induction. This study elucidated a critical role of protein geranylgeranylation in regulating T lymphocyte migration and function.

Background: It was difficult to distinguish the cartilage thinning of an entire knee joint and to track the evolution of cartilage morphology alongside ages in the general population, which was of great significance for studying osteoarthritis until big imaging data and artificial intelligence are fused. The purposes of our study are (1) to explore the cartilage thickness in anatomical regions of the knee joint among a large collection of healthy knees, and (2) to investigate the relationship between the thinning pattern of the cartilages and the increasing ages.Methods: In this retrospective study, 2,481 healthy knees (subjects ranging from 15 to 64 years old, mean age: 35 ± 10 years) were recruited. With magnetic resonance images of knees acquired on a 3-T superconducting scanner, we automatically and precisely segmented the cartilage via deep learning and calculated the cartilage thickness in 14 anatomical regions. The thickness readings were compared using ANOVA by considering the factors of age, sex, and side. We further tracked the relationship between the thinning pattern of the cartilage thickness and the increasing ages by regression analysis.Results: The cartilage thickness was always thicker in the femur than corresponding regions in the tibia (p < 0.05). Regression analysis suggested cartilage thinning alongside ages in all regions (p < 0.05) except for medial and lateral anterior tibia in both females and males (p > 0.05). The thinning speed of men was faster than women in medial anterior and lateral anterior femur, yet slower in the medial patella (p < 0.05).Conclusion: We established the calculation method of cartilage thickness using big data and deep learning. We demonstrated that cartilage thickness differed across individual regions in the knee joint. Cartilage thinning alongside ages was identified, and the thinning pattern was consistent in the tibia while inconsistent in patellar and femoral between sexes. These findings provide a potential reference to detect cartilage anomaly.

Introduction: Perivascular epithelioid cell tumors (PEComas) are a family of mesenchymal tumors that rarely arise as a primary bone tumor. Material and methods: We report a case of primary malignant bone PEComa. A literature review via PubMed, Embase and Web of Science databases with the keyword “PEComa” and “bone” was performed. Results: We reported a 33-year-old female with primary malignant bone PEComa in right distal humerus. The patient received an inhibitor of the mammalian target of rapamycin (mTOR) protein based on negative molecular investigation result of transcription factor E3 (TFE3) rearrangement, and additional therapies including palliative radiotherapy, anti-angiogenics and immunotherapy when the disease progression was detected. The patient was alive with the disease twenty-three months postoperatively. A total of nineteen related literature cases were retrieved and reviewed. Taking current case into account, ten males and ten females with median age of 24 years (range, 3–93 years) were identified, who were most frequently affected in tibia. The median follow-up duration of 24 months (range, 3–96 months). One patient died due to this disease, and six patients showed metastases. Three patients experienced recurrence, and two of them experienced twice and three times, respectively. Conclusion: To our knowledge, this is the first case of primary malignant bone PEComa arising in humerus. Clinicopathological and radiological correlation is mandatory to the correct diagnosis and to determine its malignancy. More studies are required to understand the role of molecular test and imaging in selecting suitable treatment and mechanisms of treatment resistance.

Abstract Background Biotinidase deficiency (OMIM 253260) is an autosomal recessively inherited disorder affecting about 1/60,000 people worldwide. The absence or deficiency of biotinidase impairs free biotin recycling and affects biotin‐dependent carboxylase functions. Methods A Chinese patient with spontaneous recurrent epilepsy, an eczema‐like rash, hair loss, hypotonia, and hearing loss began at three months of age. Her biotinidase activity was 1.0 nmol/ml/min, 9.5% of the mean control activity, which confirmed profound biotinidase deficiency. Results Compound heterozygous for c.250‐1G > C and c.878dupT variants in the BTD gene were identified in this patient. These two variants were novel and absent in the population matched controls and any databases. Conclusions This study expanded the mutation spectrum of alterations of the BTD gene. Our patient also emphasized the critical role of biotinidase activity measurement combined with mutation analysis in early diagnosis of biotinidase deficiency.

Sensitive detection of SARS-CoV-2 is of great importance for inhibiting the current pandemic of COVID-19. Here, we report a simple yet efficient platform integrating a portable and low-cost custom-made detector and a novel microwell array biochip for rapid and accurate detection of SARS-CoV-2. The instrument exhibits expedited amplification speed that enables colorimetric read-out within 25 minutes. A polymeric chip with a laser-engraved microwell array was developed to process the reaction between the primers and the respiratory swab RNA extracts, based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP). To achieve clinically acceptable performance, we synthesized a group of six primers to identify the conserved regions of the ORF1ab gene of SARS-CoV-2. Clinical trials were conducted with 87 PCR-positive and 43 PCR-negative patient samples. The platform demonstrated both high sensitivity (95.40%) and high specificity (95.35%), showing potentials for rapid and user-friendly diagnosis of COVID-19 among many other infectious pathogens.

Multiple sclerosis (MS) is a complex, progressive neuroinflammatory disease associated with autoimmunity. Currently, effective therapeutic strategy was poorly found in MS. Experimental autoimmune encephalomyelitis (EAE) is widely used to study the pathogenesis of MS. Cumulative research have shown that bone marrow mesenchymal stem Cells (BMSCs) transplantation could treat EAE animal models, but the mechanism was divergent. Here, we systematically evaluated whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes to alleviate the symptoms of EAE mice. We used Immunofluorescence staining to detect MAP-2, GFAP, and MBP to evaluate whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes. The effect of BMSCs transplantation on inflammatory infiltration and demyelination in EAE mice were detected by Hematoxylin-Eosin (H&E) and Luxol Fast Blue (LFB) staining, respectively. Inflammatory factors expression was detected by ELISA and RT-qPCR, respectively. Our results showed that BMSCs could be induced to differentiate into neuron cells, astrocytes and oligodendrocyte in vivo and in vitro, and BMSCs transplanted in EAE mice were easier to differentiate than normal mice. Moreover, transplanted BMSCs reduced neurological function scores and disease incidence of EAE mice. BMSCs transplantation alleviated the inflammation and demyelination of EAE mice. Finally, we found that BMSCs transplantation down-regulated the levels of pro-inflammatory factors TNF-α, IL-1β and IFN-γ, and up-regulated the levels of anti-inflammatory factors IL-10 and TGF-β. In conclusion, this study found that BMSCs could alleviate the inflammatory response and demyelination in EAE mice, which may be achieved by the differentiation of BMSCs into neurons, astrocytes and oligodendrocytes in EAE mice.

Introduction: Small cell osteosarcoma (SCOS) is a rare subtype of osteosarcoma, with limited studies mainly focusing on histological features. Our study aims to analyze our own patients and those reported in the literature to increase the recognition of this rare disease, to evaluate patient survival and to further determine potential prognostic factors. Material and methods: Twenty patients with SCOS were treated in our hospital between 2010 and 2019. Their follow-up data were collected retrospectively. A total of 336 literature cases from 58 manuscripts were retrieved by means of a PubMed search with the key word “small cell osteosarcoma”. Data pertaining to treatment and follow-up were extracted. We performed a pooled analysis for the survival of patients and the risk factors for local recurrence (LR), as well as metastatic disease (MD), in a total of 160 patients using the Kaplan-Meier method and Cox regression method. Results: We reported our experience in diagnosing and treating SCOS. In our cases, elevated alkaline phosphatase (P = 0.013) and lactate dehydrogenase (P = 0.001) significantly impaired overall survival. In the pooled analysis, SCOS was diagnosed at the median age of 17 years and affected both sexes almost equally. The median follow-up duration was 19.5 months. In the pooled analysis cases, the 5-year overall survival rate was 38.6%, and 36.4% of patients survived 10 years. However, an increasing trend was detected, indicating recent improvements in management. The surgical margin status (P = 0.024) and metastases (P = 0.008) significantly impaired overall survival, and the response to chemotherapy was related to disease-free survival (P = 0.012). LR and MD were significantly correlated (P = 0.002) and could be observed after 5 years of follow-up. LR was significantly dependent on response to chemotherapy (P = 0.020). The development of MD seemed to be affected by response to chemotherapy (P = 0.060). Correlations between imaging features and prognosis were not detected. Conclusions: This study suggested that positive margins, poor response to chemotherapy and MD are negative prognostic factors for SCOS, implied the potential role of laboratory examinations in the survival prediction and supported the need for prolonged or more intensive surveillance in patients with MD or LR. More well-documented literatures are encouraged to allow further confirmations.

This is a retrospective, single-center observational study to explore the predictors of chest drainage for neonatal pneumothorax. A total of 183 neonates (age ≤28 days) who presented to the Children's Hospital of Soochow University between January 1, 2015 and December 31, 2018 for pneumothorax or developed pneumothorax during a hospital stay were included. Demographic data, clinical presentation, and imaging characteristics of neonatal pneumothorax were collected and analyzed. We used univariate and multivariate logistic regression analyses to determine significant predictors of chest drainage of pneumothorax in neonates. Pneumothorax occurred within 24 h after birth in 131 (71.6%) cases, between 24 and 48 h after birth in 41 (22.4%) cases, and 48 h after birth in 11 (6.0%) cases. Univariate and multivariate logistic regression analyses revealed that lung collapse ≥1/3 on initial chest X-ray (OR 4.99, 95%CI 2.25-11.07), chest retractions (OR 8.12, 95%CI 2.88-22.89), cyanosis (OR 2.25, 95%CI 1.08-4.66), and frothing from mouth (OR 2.49, 95%CI 1.12-5.49) (P

The adsorption properties of Leucaena leucocephala biomass to clean malachite green contaminated water were investigated in this work. BET surface analysis showed a surface area of 0.5724 m²/g. Batch adsorption studies and isothermic studies determined that the best time and temperature for the adsorption process to become efficient were 60 min of contact time and 25 °C, respectively. The KF value of 0.3372 mg adsorbed per mg of adsorbent of the L. leucocephala biomass for malachite green was the highest at 50 °C. It was shown that the n values were n

The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is rapidly increasing worldwide in recent decades and poses a challenge for today’s clinical practice. Rapid detection of CRKP can avoid inappropriate antimicrobial therapy and save lives. Traditional detection methods for CRKP are extremely time-consuming; PCR and other sequencing methods are too expensive and technologically demanding, making it hard to meet the clinical demands. Nanopore assay has been used for screening biomarkers of diseases recently because of its high sensitivity, real-time detection, and low cost. In this study, we distinguished CRKP from carbapenem-sensitive K. pneumoniae (CSKP) by the detection of increasing amount of extracted 16S ribosomal RNA (16S rRNA) from bacterial culture with antibiotics imipenem, indicating the uninhibited growth of CRKP by the imipenem. Specific signals from single channel recording of 16S rRNA bound with probes by MspA nanopore allowed the ultra-sensitive and fast quantitative detection of 16S rRNA. We proved that only 4 h of CRKP culture time was needed for nanopore assay to distinguish the CRKP and CSKP. The time-cost of the assay is only about 5% of disk diffusion method while reaching the similar accuracy. This new method has the potential application in the fast screening of drug resistance in clinical microorganism samples.

This study focuses on curative effects of teniposide combining with semustine on patients with neuroglioma and the influences on the expression of Twist and E-cadherin in tissue. Sixty-eight patients with neuroglioma taking operation in our hospital were divided into two groups randomly. Single radiotherapy was given to 34 patients in group A, and teniposide (VM-26) and semustine (Me-CCUN) were added to radiotherapy for 34 patients in group B. Then, curative effects, survival rate, living quality and adverse reaction rate after operation were compared between two groups. Moreover, the difference in positive expression rate of Twist and E-cadherin before and after treatment between two groups was analyzed by immunohistochemistry. Results: In group B, the effective rate of treatment was 88.2%, and the disease control rate was 70.6%, higher than 52.9% and 32.4% in group A with statistical significance (P 0.05). In addition, the difference in positive expression rate of Twist and E-cadherin between group A and group B has no statistical significance before treatment (P > 0.05). After treatment, however, the positive rate of Twist in group B is lower than that in group A, while the positive rate of E-cadherin is higher. Both differences have statistical significance (P

Adipose-derived stem cells have been shown to promote peripheral nerve regeneration through the paracrine secretion of neurotrophic factors. However, it is unclear whether these cells can promote myogenic differentiation in muscular dystrophy. Adipose-derived stem cells (6 × 10 6 ) were injected into the gastrocnemius muscle of mdx mice at various sites. Dystrophin expression was found in the muscle fibers. Phosphorylation levels of Akt, mammalian target of rapamycin (mTOR), eIF-4E binding protein 1 and S6 kinase 1 were increased, and the Akt/mTOR pathway was activated. Simultaneously, myogenin levels were increased, whereas cleaved caspase 3 and vimentin levels were decreased. Necrosis and fibrosis were reduced in the muscle fibers. These findings suggest that adipose-derived stem cells promote the regeneration and survival of muscle cells by inhibiting apoptosis and fibrosis, thereby alleviating muscle damage in muscular dystrophy.

Compared to carotid endarterectomy, carotid artery stenting (CAS) is reportedly associated with higher perioperative risks in elderly patients. To verify the long-term safety and efficacy of CAS with embolic protection in elderly patients, we retrospectively reviewed the medical records of patients with carotid stenosis treated between January 2003 and March 2010 at the Department of Neurology of a large university hospital in China. We included patients with symptomatic, moderate, or severe carotid stenosis of atherosclerotic etiology (other etiologies were excluded), with a disability score ≤ 3 on the modified Rankin Scale, and who received CAS instead of carotid endarterectomy. The clinical endpoints studied were stroke recurrence and all-cause death. The 84 patients included in this study (median follow-up, 8.08 years) were stratified according to age at surgery (

Objective The clinical manifestation and electron transfer flavoprotein dehydrogenase (ETFDH) gene mutation of riboflavin-responsive lipid storage myopathy were analyzed for early diagnosis and treatment.mutation of riboflavin-responsive lipid storage myopathy were analyzed for early diagnosis and treatment. Methods Clinical material, ETFDH gene mutation and the motor function before and after vitamin B2 treatment in 3 patients from 2 predigrees were collected from August 2012 to March 2013 in our hospital. Results Case 1 was 16-year-old female. The chief complaint was difficulty of breathing and expectorating for over 3 years. Clinical symptoms included progressive respiratory muscle and proximal limb muscle weakness and worsen by fever, cardiac involvement, myopathic electromyography (EMG) changes and deposition of lipid droplets in muscle fiber by oil red O staining. Case 2 and Case 3 were brothers, the chief complaint of whom was fatigue after exercise for more than 1 year and 1 month, respectively. Clinical symptoms included significantly weakness of lower limbs and neck muscles after exercise and myopathic EMG changes. All 3 patients from two predigrees presented ETFDH gene mutation [c.250G > A (Ala84Thr) homozygous mutations and c.250G > A (Ala84Thr) and c.524G > A (Arg175His) compound heterozygous mutations, respectively]. They all had a dramatic response to vitamin B2 treatment with muscle strength and motor function recovering to normal. The symptoms of Case 1 were completely disappeared with vitamin B2 treatment for over 10 months, including respiratory muscle and proximal limb muscle weakness, and the motor function of her limbs returned to normal, characterized by completing over 10 squat-stand in 1 min. Case 2 could walk and run as ordinary people, raise his head without difficulty and play basketball about 2 h without fatigue after vitamin B2 treatment for over 2 months. Case 3 could participate in any kind of strenuous exercise without fatigue after vitamin B2 treatment for over 2 months. Conclusions Riboflavin-responsive lipid storage myopathy is mainly characterized by proximal limb and trunk muscle weakness and intolerance of movement, however, rare cases with first symptom of respiratory muscle weakness should also be concerned. In addition, it is a treatable genetic disease. The patients could be cured or significantly improved with vitamin B2 monotherapy. So vitamin B2 exploratory treatment should be given when the patients are suspected of riboflavin-responsive lipid storage myopathy. doi: 10.3969/j.issn.1672-6731.2014.06.004

A new Hermitian Mindlin plate wavelet element is proposed. The two-dimensional Hermitian cubic spline interpolation wavelet is substituted into finite element functions to construct frequency response function (FRF). It uses a system’s FRF and response spectrums to calculate load spectrums and then derives loads in the time domain via the inverse fast Fourier transform. By simulating different excitation cases, Hermitian cubic spline wavelets on the interval (HCSWI) finite elements are used to reverse load identification in the Mindlin plate. The singular value decomposition (SVD) method is adopted to solve the ill-posed inverse problem. Compared with ANSYS results, HCSWI Mindlin plate element can accurately identify the applied load. Numerical results show that the algorithm of HCSWI Mindlin plate element is effective. The accuracy of HCSWI can be verified by comparing the FRF of HCSWI and ANSYS elements with the experiment data. The experiment proves that the load identification of HCSWI Mindlin plate is effective and precise by using the FRF and response spectrums to calculate the loads.

Pancreaticobiliary maljunction (PBM) is associated with high risk of epithelial atypical growth and malignant transformation of the bile duct or gallbladder. However, overall changes in genetic expression have not been examined in children with PBM. Genome-wide expression was analyzed using peripheral blood samples from 10 children with PBM and 15 pediatric controls. Differentially expressed genes (DEGs) were identified using microarray. Bioinformatics analysis was conducted using Gene Ontology and KEGG analyses. The top 5 in the up-regulated genes in PBM were verified with qRT-PCR. Receiver operator characteristic curve analysis was conducted to evaluate the predictive accuracy of selected genes for PBM. The microarray experiments identified a total of 876 DEGs in PBM, among which 530 were up-regulated and the remaining 346 were down-regulated. Verification of the top 5 up-regulated genes (TYMS, MYBPC1, FUT1, XAGE2, and GREB1L) by qRT-PCR confirmed the up-regulation of MYBPC1 and FUT1. Receiver operating characteristic curve analysis suggested that FUT1 and MYBPC1 up-regulation could be used to predict PBM, with the area under the curve of 0.873 (95%CI=0.735−1.000) and 0.960 (95%CI=0.891−1.000), respectively. FUT1 and MYBPC1 were up-regulated in children with PBM, and could be used as potential biomarkers for PBM.

C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to infection and during chronic inflammatory disorders. Systemic inflammation is a major driver of cirrhosis progression from the compensated to the decompensated stage. Previous studies have shown that pentameric CRP (pCRP) to be a weak predictor of disease severity and prognosis in patients with decompensated hepatitis B cirrhosis, with it being only helpful for identifying patients with a higher short-term risk of death under certain conditions. Accumulating evidence indicates that pCRP dissociates to and acts primarily as the monomeric conformation (mCRP) at inflammatory loci, suggesting that mCRP may be a potentially superior disease marker with higher specificity and relevance to pathogenesis. However, it is unknown whether mCRP and anti-mCRP autoantibodies are associated with disease severity, or progression in decompensated hepatitis B cirrhosis. In this study, we evaluated the serum levels of mCRP and anti-mCRP autoantibodies in patients with decompensated cirrhosis of hepatitis B and their association with disease severity and theoretical prognosis. The results showed that patients with high mCRP and anti-mCRP autoantibody levels had more severe liver damage and that coagulation function was worse in patients with high anti-mCRP autoantibodies. Analysis of the correlation between pCRP, mCRP and anti-mCRP autoantibody levels with Model for End-Stage Liver Disease (MELD), Albumin-Bilirubin (ALBI), and Child–Turcotte–Pugh (CTP) prognostic scores showed that mCRP was the most strongly correlated with MELD score, followed by anti-mCRP autoantibodies; conversely, pCRP was not significantly correlated with prognostic score. Therefore, mCRP and anti-mCRP autoantibodies may be more advantageous clinical indicators than pCRP for evaluating the pathological state of decompensated hepatitis B cirrhosis. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by infiltration of the blood and bone marrow, exhibiting a low remission rate and high recurrence rate. Current research has demonstrated that class I HDAC inhibitors can downregulate anti-apoptotic proteins, leading to apoptosis of AML cells. In the present investigation, we conducted structural modifications of marine cytotoxin Santacruzamate A (SCA), a compound known for its inhibitory activity towards HDACs, resulting in the development of a novel series of potent class I HDACs hydrazide inhibitors. Representative hydrazide-based compound 25c exhibited concentration-dependent induction of apoptosis in AML cells as a single agent. Moreover, 25c exhibited a synergistic anti-AML effect when combined with Venetoclax, a clinical Bcl-2 inhibitor employed in AML therapy. This combination resulted in a more pronounced downregulation of anti-apoptotic proteins Mcl-1 and Bcl-xL, along with a significant upregulation of the pro-apoptotic protein cleaved-caspase3 and the DNA double-strand break biomarker γ-H2AX compared to monotherapy. These results highlighted the potential of 25c as a promising lead compound for AML treatment, particularly when used in combination with Venetoclax. [ABSTRACT FROM AUTHOR]