[Efficacy of different regimens and prognostic factors in patients with first relapsed multiple myeloma treated after front-line bortezomib, cyclophosphamide, and dexamethasone].

Objective: To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD). Methods: A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses. Results: A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) (χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months (χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS (χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group (χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy (HR=0.11, 95%CI 0.05-0.27), achievement of efficacy of partial response or better (HR=0.47, 95%CI 0.34-0.66), and non-aggressive relapse (HR=0.25, 95%CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion: In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

[Analysis of the efficacy and influencing factors of sodium channel blockers in the treatment of focal epilepsy in infants under 6 months of age].

Objective: To analyze the efficacy and safety of the sodium channel blockers (SCB) antiseizure medication in the treatment of focal epilepsy in infants under 6 months of age. Methods: This was a case series study. Infants with focal epilepsy with onset within 6 months of age and treated with SCB attending the Department of Neurology of Beijing Children's Hospital from June 2016 to April 2022 were collected. The clinical data, auxiliary examinations, SCB application, efficacy, adverse reactions, and prognosis were analyzed retrospectively. Patients were grouped according to type of seizure and epileptic syndrome, age of onset and etiology. Chi square test and Fisher exact test were used to analyze the differences between groups statistically. Results: A total of 118 infants were enrolled, 65 males and 53 females, with an age of epilepsy onset of 56 (4, 114) days. Developmental and epileptic encephalopathy was diagnosed in 60 infants, 39 had self-limited neonatal and (or) infantile epilepsy, and 19 had non-syndromic focal epilepsy. Application of SCB: 106 used oxcarbazepine, 2 used lacosamide, 9 switched from oxcarbazepine to lacosamide or a combination of 2 SCB, and 1 used oxcarbazepine, lacosamide, and lamotrigine successively; oxcarbazepine was the first choice in 46 cases. The age at which SCB was applied was 103 (53, 144) days. The children were followed up for 6 months to 6 years. SCB was effective in 89 cases (75.4%), including 70 cases (59.3%) who achieved seizure freedom. The seizure-free rate was higher in the focal epilepsy only group than in the group with other seizure types (64.4% (65/101) vs. 4/17, χ²=9.99, P<0.05). The responder and seizure-free rates were all higher in the group with the onset age of >3-6 months than the group >1-3 months (84.4% (38/45) vs. 62.5% (20/32), 73.3% (33/45) vs. 46.9% (15/32), χ²=4.85 and 5.58, both P<0.05). With the exception of variants in the PRRT2 gene, those with variants in sodium or potassium channels had higher responder and seizure-free rates than those with variants in other genes(86.2% (25/29) vs. 45.5% (10/22), 62.1% (18/29) vs. 22.7% (5/22), χ²=9.65 and 7.82,both P<0.05). The most common adverse event was transient hyponatremia, which happened in 66 cases (55.9%). There were 9 cases of rash, which subsided in 6 cases after discontinuing oxcarbazepine and switching to lacosamide, and 7 cases of electrocardiogram abnormalities, which improved after withdrawing oxcarbazepine and changing to lacosamide in 1 case. Conclusion: SCB are effective and tolerable in the treatment of focal epilepsy in infants under 6 months of age, with better efficacy in patients with genetic variants of the sodium or potassium channel, focal seizures only, and seizure onset >3-6 months of age.

Topological edge solitons and their stability in a nonlinear Su-Schrieffer-Heeger model.

We study continuations of topological edge states in the Su-Schrieffer-Heeger model with on-site cubic (Kerr) nonlinearity, which is a 1D nonlinear photonic topological insulator (TI). Based on the topology of the underlying spatial dynamical system, we establish the existence of nonlinear edge states (edge solitons) for all positive energies in the topological band gap. We discover that these edge solitons are stable at any energy when the ratio between the weak and strong couplings is below a critical value. Above the critical coupling ratio, there are energy intervals where the edge solitons experience an oscillatory instability. Though our paper focuses on a photonic system, we also discuss the broader relevance of our methods and results to 1D nonlinear mechanical TIs.

[Pathogen distribution and antimicrobial resistance among lower respiratory tract infections in patients with hematological malignancies].

Objective: To investigate the pathogen distribution and antimicrobial resistance among lower respiratory tract infections in patients with hematological malignancies. Methods: Sputum samples were collected from 967 patients with hematological malignancies and lower respiratory tract infections in Department of Hematology,the Second Hospital of Shanxi Medical University from January 2017 to July 2020. The pathogens and drug sensitivity reports were carried out by automatic bacterial identification instruments. WHONET 5.6 and SPSS 20.0 softwares were used for statistical analysis. Results: A total of 961 strains of pathogens were isolated, 516 (53.7%) pathogens were Gram-negative bacteria, mainly 118 strains of Klebsiella pneumonia (12.3%), 68 strains of Pseudomonas aeruginosa (7.1%), 67 strains of Acinetobacter baumannii (7.0%),52 strains of Stenotrophomonas maltophilia (5.4%), 43 strains of Escherichia coli (4.5%), and 42 strains of Enterbacter cloacae (4.4%). There were 171 (17.8%) strains of Gram-positive bacteria and 274 (28.5%) fungi. The drug resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem were 22.1%-31.3%. Stenotrophomonas maltophilia was sensitive to levofloxacin, compound sulfamethoxazole and minocycline. The antimicrobial resistance rates of these three enterobacteria to carbapenems, cefoperazone/sulbactam, piperacillin/tazobactam were low (<10%). The resistant Gram-positive bacteria to ticoplanin, vancomycin and linazolamide were not detected. Conclusion: The major pathogens related to lower respiratory tract infections in patients with hematological malignancies are gram-negative bacteria in our centre. Different pathogens appear different characteristics of antimicrobial resistance.

Pathogenic analysis of suspected COVID-19 patients in a SARS-CoV-2 non-epidemic area of China.

OBJECTIVE: The aim of this study is to find the distributions of pathogens in 164 suspected COVID-19 patients from the outpatient clinic of Shenjing Hospital of China Medical University from 24th January, 2020, to 29th February of 2020. PATIENTS AND METHODS: 164 COVID-19 suspected patients were from the Shengjing Hospital of China Medical University. Oropharyngeal swab specimens were acquired by respiratory doctors under standardized conditions. Specific nucleic acids of SARS-CoV-2, influenza A and B, respiratory syncytial virus A and B, adenovirus, parainfluenza virus, along with pneumonic mycoplasma were detected by real-time fluorescence PCR. Symptomatic, epidemiologic, laboratory and radiological data of the patients were obtained from the electronic medical record system of our hospital. RESULTS: Among the 164 patients, 3 were positive for SARS-CoV-2, 15 were positive for other respiratory viruses and 16 were positive for pneumonic mycoplasma. Of the positive patients above, 1 patient was co-infected with SARS-CoV-2 and adenovirus, and 1 was co-infected with influenza B and pneumonic mycoplasma. The 3 SARS-CoV-2 infected patients were clinically diagnosed as COVID-19 because they meet the diagnostic criteria listed in "Chinese Clinical Guidance for COVID-19 Pneumonia diagnosis and treatment", including epidemic history, symptom and pathogenic detection, as well as abnormalities of the laboratory and radiological data. However, the clinical characteristics of COVID-19 patients were non-specific compared to those of the patients infected with other respiratory viruses. CONCLUSIONS: The endemic common respiratory pathogens are more prevalent than SARS-CoV-2 in the SARS-CoV-2 non-epidemic areas of this research. Detection of the pathogen is the unique means for definite COVID-19 diagnosis.

[Clinical characteristics of patients with ankylosing spondylitis and inflammatory bowel disease].

Objective: To analyze the clinical characteristics of patients with ankylosing spondylitis (AS) with inflammation bowel disease (IBD). Methods: AS patients fulfilling the 1984 modified New York diagnostic criteria were recruited in Chinese AS Prospective Imaging Cohort (CASPIC) consecutively from April 2016 to June 2017 in Chinese People's Liberation Army General Hospital by using smart management system for spondyloarthritis (SpAMS). The diagnosis of IBD was confirmed by tissue pathology via ileocolonoscopy. Demographic, clinical and biochemical data were collected. Results: In total, 893 patients with AS were recruited with the mean age 30.8 years. The majority were men (739, 82.8%). There were 64 (7.2%) patients concomitant with IBD. The mean age [(34.5±7.5) years vs. (30.5±8.8) years, P<0.001] was older and the disease duration [(10.8±6.9) years vs. (8.1±5.9) years, P=0.001] was longer in patients with IBD than patients without. Compared with patients without IBD, patients with IBD had more frequent involvement of the cervical spine [(21.9% (14/64) vs. 10.5% (87/829), P=0.006) and thoracic spine [29.7% (19/64) vs. 12.3% (102/829), P<0.001]. Uveitis [28.1% (18/64) vs. 16.4% (136/829), P=0.017] and psoriasis [7.8% (5/64) vs. 2.3% (19/829), P=0.009] were also more common in patients concomitant with IBD. In addition, patients with IBD had significantly higher scores in BASDAI (3.3±2.1 vs. 2.4±1.8, P<0.001), BASFI [2.2 (1.0,3.3) vs. 1.1(0.2,2.4), P<0.001)] and ASAS HI (7.1±4.3 vs. 5.3±3.7, P= 0.001) than patients without IBD. Conclusions: Compared with patients without IBD, AS patients concomitant with IBD have more severe disease activity and organ dysfunction. Furthermore, the uveitis and psoriasis are more frequently accompanied in AS patients with IBD.

Serum miR-133 as a novel biomarker for predicting treatment response and survival in acute myeloid leukemia.

OBJECTIVE: MiRNA-133 (miR-133) has been identified as a tumor suppressor in many types of human cancers. However, its clinical significance in acute myeloid leukemia (AML) is still unclear. The purpose of this study was to assess the correlation of miR-133 expression with clinical variables and prognosis in AML patients. PATIENTS AND METHODS: Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) was performed to analyze blood samples from 145 patients with AML and 70 healthy volunteers. RESULTS: Decreased miR-133 levels were observed in AML patients and closely associated with aggressive clinical parameters, such as white blood cells and poor Karyotype subgroups. In addition, receiver operator characteristic (ROC) analysis revealed that serum miR-133 could efficiently screen AML patients from normal controls with high sensitivity and specificity. More interestingly, serum miR-133 levels were remarkably elevated in the patients with favorable response after standard induction chemotherapy or achieving a complete remission. Furthermore, patients in the high serum miR-133 expression group had better overall survival and recurrence-free survival than those in the low serum miR-133 expression group. Meanwhile, multivariate analysis identified serum miR-133 as a significant independent predictor for survival. CONCLUSIONS: Low miR-133 expression was a common event and correlated with worse clinical outcome in AML, suggesting that serum miR-133 might serve as a promising indicator for the early detection and prognosis evaluation of AML.

Recognizing basal cell carcinoma on smartphone-captured digital histopathology images with a deep neural network.

BACKGROUND: Pioneering effort has been made to facilitate the recognition of pathology in malignancies based on whole-slide images (WSIs) through deep learning approaches. It remains unclear whether we can accurately detect and locate basal cell carcinoma (BCC) using smartphone-captured images. OBJECTIVES: To develop deep neural network frameworks for accurate BCC recognition and segmentation based on smartphone-captured microscopic ocular images (MOIs). METHODS: We collected a total of 8046 MOIs, 6610 of which had binary classification labels and the other 1436 had pixelwise annotations. Meanwhile, 128 WSIs were collected for comparison. Two deep learning frameworks were created. The 'cascade' framework had a classification model for identifying hard cases (images with low prediction confidence) and a segmentation model for further in-depth analysis of the hard cases. The 'segmentation' framework directly segmented and classified all images. Sensitivity, specificity and area under the curve (AUC) were used to evaluate the overall performance of BCC recognition. RESULTS: The MOI- and WSI-based models achieved comparable AUCs around 0·95. The 'cascade' framework achieved 0·93 sensitivity and 0·91 specificity. The 'segmentation' framework was more accurate but required more computational resources, achieving 0·97 sensitivity, 0·94 specificity and 0·987 AUC. The runtime of the 'segmentation' framework was 15·3 ± 3·9 s per image, whereas the 'cascade' framework took 4·1 ± 1·4 s. Additionally, the 'segmentation' framework achieved 0·863 mean intersection over union. CONCLUSIONS: Based on the accessible MOIs via smartphone photography, we developed two deep learning frameworks for recognizing BCC pathology with high sensitivity and specificity. This work opens a new avenue for automatic BCC diagnosis in different clinical scenarios. What's already known about this topic? The diagnosis of basal cell carcinoma (BCC) is labour intensive due to the large number of images to be examined, especially when consecutive slide reading is needed in Mohs surgery. Deep learning approaches have demonstrated promising results on pathological image-related diagnostic tasks. Previous studies have focused on whole-slide images (WSIs) and leveraged classification on image patches for detecting and localizing breast cancer metastases. What does this study add? Instead of WSIs, microscopic ocular images (MOIs) photographed from microscope eyepieces using smartphone cameras were used to develop neural network models for recognizing BCC automatically. The MOI- and WSI-based models achieved comparable areas under the curve around 0·95. Two deep learning frameworks for recognizing BCC pathology were developed with high sensitivity and specificity. Recognizing BCC through a smartphone could be considered a future clinical choice.

Regulatory effects of CCDC3 on proliferation, migration, invasion and EMT of human cervical cancer cells.

OBJECTIVE: To elucidate the potential effects of Coiled coil domain-containing 3 (CCDC3) on proliferative, migratory, invasive potentials and epithelial-mesenchymal transition (EMT) of human cervical cancer cells. MATERIALS AND METHODS: Protein and mRNA levels of CCDC3 in C33 and HeLa cells were determined by quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Proliferative capacity and clonality of C33 and HeLa cells transfected with sh-CCDC3 were evaluated by cell counting kit-8 (CCK-8) and colony formation assay, respectively. Transwell assay and wound healing assay were conducted to determine the invasive and migratory potentials of cervical cancer cells with CCDC3 knockdown. Protein expressions of EMT-related genes in C33 and HeLa cells with CCDC3 knockdown were determined by Western blot. RESULTS: Transfection of sh-CCDC3 in C33 and HeLa cells markedly inhibited CCDC3 expression compared with those transfected with sh-EGFP. CCDC3 knockdown remarkably attenuated proliferative, migratory and invasive capacities. Moreover, CCDC3 knockdown inhibited protein levels of EMT-related genes in C33 and HeLa cells. CONCLUSIONS: Low expression of CCDC3 attenuated proliferative, migratory, invasive potentials and EMT of cervical cancer cells. Hence, CCDC3 may be utilized as a novel therapeutic target for cervical cancer.

[Comparison of clinical manifestations according to HLA-B(27) genotype in ankylosing spondylitis patients: real-world evidence from smart management system for spondyloarthritis].

Objective: The aim of this study was to set up a large, longitudinal and prospective database to compare the clinical manifestations in human leucocyte antigen (HLA)-B(27) positive and negative patients with ankylosing spondylitis(AS) based on real-world evidence in Chinese population. Methods: A total of 897 outpatients with confirmed AS were recruited consecutively by smart management system for spondyloarthritis (SMSP) from April 13, 2016 to June 6, 2017 in Chinese PLA General Hospital from 30 provinces and autonomous regions. 801 patients with HLA-B(27) data were included in the analysis. Demographic and clinical parameters including Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), ankylosing spondylitis disease activity score (ASDAS), arthritis, enthesitis, Bath ankylosing spondylitis metrology index (BASMI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were compared between HLA-B(27) positive and negative groups. Results: A total of 801 patients were included in the analysis with an average age of (30.7±8.8) years. There were 659 males and 142 females and HLA-B(27) was present in 88.0%(705/801). Males were significantly more in HLA-B(27) positive patients [83.3%(587/705) vs. 75.0%(72/96); P=0.047].The average age at disease onset was (22.3±7.6)years in HLA-B(27) positive patients and (24.4±8.7) years in HLA-B(2)7 negative ones (P=0.028).There was significant difference in diagnose delay between two groups [14.3(2.5,43.6)months in HLA-B(27) positive patients vs. 20.3(5.0,67.4) months in HLA-B(27) negative ones, P=0.041]. Anterior uveitis was found to be significantly more common in HLA-B(27) positive patients [18.9% (133/705)vs.7.3%(7/96),P=0.005], and knee involvement less common in HLA-B(27) positive patients [4.0%(27/682) vs.10.0%(9/90), P=0.010], conversely. CRP[6.5(3.0, 16.4)mg/L vs. 3.5(1.6, 12.3)mg/L] and ESR[11.0(4.0, 24.0)mm/1h vs. 7.0(3.0, 16.0)mm/1h] were significantly higher in HLA-B(27) positive patients(P=0.005,0.013, respectively).But no differences in BASDAI,ASDAS,BASFI and BASMI were obtained between two groups. Conclusions: HLA-B(27) positive patients had a higher proportion of males, a younger age of onset and a greater risk for occurrence of anterior uveitis, suggesting a poorer prognosis.

Effects of mulberry leaf polysaccharide on oxidative stress in pancreatic ß-cells of type 2 diabetic rats.

OBJECTIVE: To explore and discuss the effects and mechanisms of mulberry leaf polysaccharide (MLP) on oxidative stress in pancreatic ß-cells of type 2 diabetic rats. MATERIALS AND METHODS: The model of diabetic rats was established by inducing the Sprague-Dawley (SD) rats with high-sugar and high-fat diet for 6 weeks and then giving them streptozotocin (STZ) by single intraperitoneal injection. The mulberry leaf polysaccharide was administered via gavage daily for 8 weeks, and the tissue morphology was observed through electron microscopy. The levels of fasting blood glucose (FBG), free fatty acid (FFA), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were detected. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the pancreas were tested. The activities of mitochondrial cytochrome C oxidase (CCO) and succinate dehydrogenase (SDH) in the pancreatic cell were examined. RESULTS: Compared with the normal control group, the level of FBG increased (p < 0.01), the levels of FFA, TG, LDL-C, IL-6, and TNF-α were higher (p < 0.05), the content of MDA increased (p < 0.05) and the activity of SOD, CCO and SDH declined (p < 0.05) in the model group. In comparison with the model group, the level of FBG in the group intervened by mulberry leaf polysaccharide decreased [(23.9 ± 2.5) vs. (16.8 ± 2.1) mmol•L-1]; the levels of FFA, TG and LDL-C dropped from (1.18 ± 0.24), (2.95 ± 0.65) and (2.18 ± 0.46) mmol•L-1 to (0.65 ± 0.14), (2.20 ± 0.45) and (1.08 ± 0.42) mmol•L-1, respectively; the levels of IL-6 and TNF-α declined from (60.78 ± 5.02) ng•L-1 and (2.34 ± 0.42) µg•L-1 to (30.94 ± 3.02) ng•L-1 and (1.02 ± 0.12) µg•L-1, respectively; the content of MDA w as reduced from (1.38 ± 0.21) µmol•g-1 to (0.78 ± 0.12) µmol•g-1; the activities of SOD, CCO and SDH increased from (25.32 ± 3.58) KU•g-1, (15.00 ± 1.58) mmol•g-1 and (3.23 ± 0.32) KU•g-1 to (32.87 ± 2.62) KU•g-1, (18.30 ± 1.78) mmol•g-1 and (5.62 ± 0.38) KU•g-1, respectively; the electron microscopy results indicated that the intervention of mulberry leaf polysaccharide could improve the morphological structure of the pancreatic ß-cells. CONCLUSIONS: The mulberry leaf polysaccharide can lower down the levels of inflammatory mediators and free fatty acid in the diabetic rats, alleviate oxidative stress injury, improve the mitochondrial functions of islet cells and protect the pancreatic ß-cells.

[Dynamin-1-related infantile spasms: a case report and review of literature].

Objective: To analyze the clinical and gene mutation characteristics of dynamin-1 (DNM1)-related infantile spasms. Method: Clinical, laboratory and genetic data of one case of DNM1-related infantile spasms diagnosed by Xiangya Hospital in September 2015 were analyzed.Through taking "Dynamin-1" "DNM1" as key words to search at CNKI, Wanfang, PubMed and OMIM to date (April 2016), the clinical characteristics of 9 reported cases of DNM1-related epileptic encephalopathy in international literature with our case were reviewed. Result: The boy is the second child of healthy and nonconsanguineous parents.At 7 months, he started to have seizures with head dropping, and he was brought for the first time to our hospital at the age of 17 months.The patient presented with severe psychomotor retardation, epilepsy, muscular hypotonia, and electroencephalography showed hypsarhythmia.He received 28 days of adrenocorticotropic hormone (ACTH) therapy.After that, his seizures were improved with valproic acid and levetiracetam, and disappeared between 3 years and 5 months to 5 years and 5 months of age on treatment with valproic acid only.Exome-sequencing study (trios) identified novel heterozygous mutation c. 443A>G (p.Glu148Arg) in DNM1. Up to now, 9 cases of epileptic encephalopathy (infantile spasms or Lennox-Gastaut syndrome) associated with de novo DNM1 gene mutations have been reported. Conclusion: The main clinical features of DNM1 mutations include intractable seizures, intellectual disability, developmental delay, hypotonia, and developmental delay before the onset of seizures.

Composition formulas of binary eutectics.

The present paper addresses the long-standing composition puzzle of eutectic points by introducing a new structural tool for the description of short-range-order structural unit, the cluster-plus-glue-atom model. In this model, any structure is dissociated into a 1(st)-neighbor cluster and a few glue atoms between the clusters, expressed by a cluster formula [cluster]gluex. This model is applied here to establish the structural model for eutectic liquids, assuming that a eutectic liquid consist of two subunits issued from the relevant eutectic phases, each being expressed by the cluster formula for ideal metallic glasses, i.e., [cluster](glue atom)(1 or 3). A structural unit is then composed of two clusters from the relevant eutectic phases plus 2, 4, or 6 glue atoms. Such a dual cluster formulism is well validated in all boron-containing (except those located by the extreme phase diagram ends) and in some commonly-encountered binary eutectics, within accuracies below 1 at.%. The dual cluster formulas vary extensively and are rarely identical even for eutectics of close compositions. They are generally formed with two distinctly different cluster types, with special cluster matching rules such as cuboctahedron plus capped trigonal prism and rhombidodecahedron plus octahedral antiprism.