MD-UNet: a medical image segmentation network based on mixed depthwise convolution.

In the process of cancer diagnosis and treatment, accurate extraction of the lesion area helps the doctor to judge the condition. Currently, medical image segmentation algorithms based on UNet have been verified to be able to play an important role in clinical diagnosis. However, these methods still have the following drawbacks in extracting the region of interest (ROI): (1) ignoring the intra-class variability of medical images. (2) Failure to obtain effective feature redundancy. To address these problems, a U-shaped medical image segmentation network based on a Mixed depthwise convolution residual module (MDRM), called MD-UNet, is proposed in this paper. In MD-UNet, the MDRM built with a Mixed depthwise convolution attention block (MDAB) captures both local and global dependencies in the image to mitigate the effects of intra-class differences. MDAB captures valid redundant features and further captures global features of the input data. At the same time, the lightweight MDAB senses changes in the receptive field and generates multiple feature mappings. Compared with UNeXt on the ISIC2018 dataset, the MD-UNet segmentation accuracy Dice and IoU are improved by 1.33% and 1.91%, respectively. The code is available at https://github.com/Cloud-Liu/MD-UNet .

Inherited disease-linked arginine76/75 mutants in Cx50 and Cx45 showed impaired homotypic and heterotypic gap junction function, but not Cx43.

Connexins form intercellular communication channels, known as gap junctions (GJs), in many tissues/organs. Mutations in connexin genes are found to be linked to various inherited diseases, but the mechanisms are not fully clear. The Arg76 (R76) in Cx50 is fully conserved across the entire connexin family and is a hotspot for five connexin-linked inherited diseases, including Cx50 and Cx46-linked congenital cataract, Cx43-linked oculodentodigital dysplasia, and Cx45-linked cardiac arrhythmias. To better understand the molecular and cellular mechanism of dysfunction caused by R76/75 mutations, we examined the functional status and properties of GJs containing R76 mutations in Cx50 (R76H/C), Cx43 (R76H/S/C), and Cx45 (R75H) with an emphasis on heterotypic GJs in connexin-deficient model cells. All tested mutants showed an impairment of homotypic GJ function reflected by a decreased coupling% and conductance, except for Cx43 R76H/S. These connexin mutants also showed impaired GJ function when paired with a docking-compatible connexin, such as Cx50/Cx46 or Cx45/Cx43, except for all mutants on Cx43 which formed functional heterotypic GJs with Cx45. Localization studies on fluorescent protein tagged connexin mutants revealed that Cx45 R75H and Cx43 R76C showed impaired localization. Our homology structure models indicated that mutations of R76/75 in these GJs led to a loss of intra- and/or inter-connexin non-covalent interactions (salt bridges) at the sidechain of this residue, which could contribute to the observed GJ impairments underlying diseases. It is interesting that unlike those disease-linked variants in Cx50 and Cx45, Cx43 can tolerate some variations at R76.

[Effect of knee arthroscopy on subsequent total knee arthroplasty: Meta-analysis].

OBJECTIVE: To evaluate effect of knee arthroscopy on prognosis of subsequent total knee arthroplasty (total knee arthroplasty, TKA) by Meta-analysis. METHODS: Databases including PubMed, Embase, Cochrane Library, CNKI, Wanfang and other databases were searched by computer from establishing to October 2020 to collect literatures on effect of knee arthroscopy on prognosis of subsequent TKA. Quality evaluation and data extraction were carried out according to inclusion, exclusion criteria and literature screening. Newcastle-Ottawa Scale (NOS) was used to evaluate literature quality of non-randomized controlled studies. RevMan 5.3 software was applied to Meta-analysis on revision rate, reoperation rate, postoperative stiffness rate, periprosthetic infection rate, postoperative venous thrombosis venous thromboembolism(VTE) rate and postoperative knee flexion range of motion after TKA. RESULTS: Eight literatures were finally included with totally sample size of 182 815 patients. Among them, 6 998 patients were in knee arthroscopy group and 175 817 patients were in knee arthroscopy group. Meta-analysis results showed that there were statistical differences in revision rate after TKA[OR=1.66, 95%CI(1.37, 2.00), P<0.000 01], re-operation rate[OR=2.31, 95%CI(1.59, 3.36), P<0.000 1], postoperative stiffness rate[OR=1.78, 95%CI(1.02, 3.11), P=0.04] and infection rate around prosthesis[OR=1.40, 95%CI(1.19, 1.66), P<0.000 1]. While there were no difference in VTE rate[OR=1.06, 95%CI(0.83, 1.35), P=0.64], postoperative knee flexion range of motion[MD=-1.21, 95%CI(-3.07, 0.65), P=0.20]. CONCLUSION: Knee arthroscopy has a negative impact on subsequent TKA surgery. Previous arthroscopic increased risk of stiffness, periprosthetic joint infection, revision and reoperation after TKA, but there was no significant difference in postoperative knee flexion range of motion and incidence of VTE.

Genomic analysis of 9 infants with hypermethioninemia by whole-exome sequencing among in Henan, China.

BACKGROUND: Hypermethioninemia is an inborn error of metabolism with elevated plasma methionine (Met) caused by methionine adenosyltransferase deficiency. Methionine adenosyltransferase (MAT) I/III deficiency is the most common cause of hypermethioninemia. Except for increased blood Met, most patients have no symptoms, but a small number have nervous system complications, including cognitive impairment and mental retardation. OBJECTIVE: To investigate the gene variation of patients with hypermethioninemia in newborns in Henan province. METHODS: 9 cases of hypermethioninemia were screened for amino acids profile and acyl carnitine by tandem mass spectrometric (MS/MS) among 245 054 newborns. We performed whole-exome sequencing on 9 families of infants with hypermethioninemia. We identified mutated genes under different models of inheritance and further assessed these mutations through Sanger sequencing and association analysis. RESULTS: The incidence of neonatal hypermethioninemia was 1:27 228 in Henan province. A total of ten mutations in the MAT1A gene in the 9 patients were identified, including nine reported mutations (c.1070C > T, c.895C > T, c.100 T > A, c.315C > A, c.529C > T, c.623A > C, c.407G > T, c.1066C > T, 867G > T) and one novel mutations (c.772G > C). c.772G > C was detected in 2 families and is the most common variant. 7 infants (7/9) with hypermethioninemia were genetically autosomal dominant, and 2 infants (2/9) with hypermethioninemia were genetically autosomal recessive. CONCLUSION: Our findings expand the mutational spectrum of hypermethioninemia, with the description of one new mutation. They improve the understanding of the genetic background and clinical manifestation of MAT1A in Chinese patients.

Association of fish oil containing lipid emulsions with retinopathy of prematurity: a retrospective observational study.

BACKGROUND: Retinopathy of prematurity (ROP) remains a leading cause of childhood blindness worldwide. This study aimed to investigate whether supplementation of n-3 polyunsaturated fatty acids (n-3 PUFAs) in parenteral nutrition may have beneficial effects on ROP in preterm infants. METHODS: A total of 89 preterm infants, admitted to Neonatal Intensive Care Unit (NICU) in Anhui Provincial Children's Hospital from September 2017 to August 2020, were recruited in the study. Based on the medical documents, the subjects were categorised into two groups: administration of the fish oil emulsion (n=43) containing soy oil, medium-chain-triglycerides (MCT), olive oil and fish oil (6g/dL, 6g/dL, 5g/dL and 3g/dL respectively), and the soy oil emulsion (n=46) containing 10g/dL of soy oil and MCT each. At 4 weeks of hospitalization, ROP was screened and diagnosed. Fatty acids in erythrocytes were determined using gas chromatography. RESULTS: The averaged birth weight and gestational age were 1594±296 g and 31.9±2.3 wk, 1596±263 g and 31.6±2.3 wk respectively for preterm infants in the fish oil group and soy oil group. After 4 to 6 weeks of hospitalization, among all the preterm infants, 52 developed ROP (all stages) indicating an incidence of ROP at 58.43%. Although the incidence of ROP with any stages showed no differences between the two groups, the severe ROP incidence in the group with fish oil emulsions (2.33%) was significantly lower than that in the group with soy oil emulsions (23.91%) (P<0.05). After 14 days of nutrition support, the preterm infants administered fish oil emulsions had an increase in erythrocyte DHA content, with a reduction in ratio of arachidonic acid (AA) to DHA and an increase of n-3 index. CONCLUSION: Supplementation of n-3 PUFAs through parenteral fish oil containing lipid emulsions resulted in an increase in erythrocyte DHA, and this might have beneficial effects on prevention of severe ROP in preterm infants.

Hyperthermia inhibits growth of nasopharyngeal carcinoma through degradation of c-Myc.

BACKGROUND: Hyperthermia is a widely used adjunct treatment for different cancers including nasopharyngeal carcinoma (NPC). The protooncogene c-Myc is up-regulated in NPC and its expression is associated with poor prognosis. OBJECTIVE: We hypothesized that c-Myc constitutes an important hyperthermia treatment target, and we investigated its contribution to hyperthermia responses in NPC. METHODS: The growth of the human NPC cell lines CNE1 and CNE2 was analyzed using CCK-8 and clonogenicity assays after 43 °C hyperthermia, knockdown or overexpression of c-Myc. Flow cytometry measurements assessed cell cycle parameters and apoptosis, while levels of c-Myc together with key transcriptional targets were determined using qPCR and Western blotting. Parallel experiments were undertaken using NPC xenografts in nude mice and lastly, global transcriptomic changes were determined using 'RNAseq'. RESULTS: Hyperthermia increased the ubiquitination and proteasomal destruction of c-Myc, causing a rapid decline in c-Myc protein levels in NPC cells. Similar to c-Myc knockdown, NPC cells treated with hyperthermia showed growth inhibition associated with the downregulation of c-Myc target genes. Moreover, low levels of c-Myc could be sustainably repressed in NPC cells through repeated hyperthermia treatments. Importantly, the key findings of growth inhibition and decreased c-Myc protein levels were reproduced in NPC tumor xenografts. Bioinformatic analyses showed that downregulation of c-Myc constituted a central node in the hyperthermia response of NPC cells. CONCLUSION: Our study reveals that hyperthermia can readily destabilize c-Myc levels in NPC cells and inhibit tumor growth. This proposes new strategies for implementing hyperthermia to target c-Myc-driven cancers to improve therapeutic efficacy.

Survival Effects of Radiotherapy on Patients Newly Diagnosed with Distant Metastatic Nasopharyngeal Carcinoma in Non-High-Incidence Areas.

PURPOSE: To analyze the effects of radiotherapy and its timing on the survival and safety of patients with newly diagnosed distant metastatic NPC in non-high-incidence areas. PATIENTS AND METHODS: We retrospectively analyzed 94 newly diagnosed NPC patients with distant metastatic admitted to our hospital from January 2011 to June 2018. They were divided into three groups: no radiotherapy group received chemotherapy alone, early radiotherapy group was combined with radiotherapy during 1 to 3 cycles of chemotherapy, and late radiotherapy group was combined with radiotherapy after 4-6 cycles of chemotherapy were effective. The efficacy and side effects of the three groups were compared, and the prognostic factors were analyzed. RESULTS: The 6-month, 1-year and 2-year PFS were 53.6%, 14.3% and 3.6% in no radiotherapy group, 71.0%, 38.7% and 19.4% in early radiotherapy group, 88.6%, 48.6% and 22.9% in late radiotherapy group; the radiotherapy groups were better than the no radiotherapy group, and the difference was statistically significant (P < 0.017). The 1-year, 2-year and 3-year OS were 75.0%, 32.1% and 0 in no radiotherapy group, 77.4%, 54.8% and 12.9% in early radiotherapy group, 85.7%, 71.4% and 31.4% in late radiotherapy group; the radiotherapy groups were better than the no radiotherapy group, and the differences were statistically significant (P < 0.017). There was no significant difference in OS and PFS between the two radiotherapy groups. Univariate and multivariate analysis showed that HBV (P = 0.031), number of metastases (P = 0.002), liver metastases (P = 0.038), radiotherapy (P < 0.001) and treatment response (P = 0.011) were related to OS. There was no significant difference in the incidence of adverse events (P > 0.017). CONCLUSION: Early and late combined radiotherapy had similar clinical efficacy and both prolonged PFS and OS for patients with newly diagnosed distant metastatic NPC in non-high-risk areas. If chemotherapy response is expected to be poor, radiotherapy can be received early.

Histone demethylase KDM4A plays an oncogenic role in nasopharyngeal carcinoma by promoting cell migration and invasion.

Compelling evidence has indicated the vital role of lysine-specific demethylase 4 A (KDM4A), hypoxia-inducible factor-1α (HIF1α) and the mechanistic target of rapamycin (mTOR) signaling pathway in nasopharyngeal carcinoma (NPC). Therefore, we aimed to investigate whether KDM4A affects NPC progression by regulating the HIF1α/DDIT4/mTOR signaling pathway. First, NPC and adjacent tissue samples were collected, and KDM4A protein expression was examined by immunohistochemistry. Then, the interactions among KDM4A, HIF1α and DDIT4 were assessed. Gain- and loss-of-function approaches were used to alter KDM4A, HIF1α and DDIT4 expression in NPC cells. The mechanism of KDM4A in NPC was evaluated both in vivo and in vitro via RT-qPCR, Western blot analysis, MTT assay, Transwell assay, flow cytometry and tumor formation experiments. KDM4A, HIF1α, and DDIT4 were highly expressed in NPC tissues and cells. Mechanistically, KDM4A inhibited the enrichment of histone H3 lysine 9 trimethylation (H3K9me3) in the HIF1α promoter region and thus inhibited the methylation of HIF1α to promote HIF1α expression, thus upregulating DDIT4 and activating the mTOR signaling pathway. Overexpression of KDM4A, HIF1α, or DDIT4 or activation of the mTOR signaling pathway promoted SUNE1 cell proliferation, migration, and invasion but inhibited apoptosis. KDM4A silencing blocked the mTOR signaling pathway by inhibiting the HIF1α/DDIT4 axis to inhibit the growth of SUNE1 cells in vivo. Collectively, KDM4A silencing could inhibit NPC progression by blocking the activation of the HIF1α/DDIT4/mTOR signaling pathway by increasing H3K9me3, highlighting a promising therapeutic target for NPC.

Potential Value of Radiomics in the Identification of Stage T3 and T4a Esophagogastric Junction Adenocarcinoma Based on Contrast-Enhanced CT Images.

PURPOSE: This study was designed to evaluate the predictive performance of contrast-enhanced CT-based radiomic features for the personalized, differential diagnosis of esophagogastric junction (EGJ) adenocarcinoma at stages T3 and T4a. METHODS: Two hundred patients with T3 (n = 44) and T4a (n = 156) EGJ adenocarcinoma lesions were enrolled in this study. Traditional computed tomography (CT) features were obtained from contrast-enhanced CT images, and the traditional model was constructed using a multivariate logistic regression analysis. A radiomic model was established based on radiomic features from venous CT images, and the radiomic score (Radscore) of each patient was calculated. A combined nomogram diagnostic model was constructed based on Radscores and traditional features. The diagnostic performances of these three models (traditional model, radiomic model, and nomogram) were assessed with receiver operating characteristics curves. Sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and areas under the curve (AUC) of models were calculated, and the performances of the models were evaluated and compared. Finally, the clinical effectiveness of the three models was evaluated by conducting a decision curve analysis (DCA). RESULTS: An eleven-feature combined radiomic signature and two traditional CT features were constructed as the radiomic and traditional feature models, respectively. The Radscore was significantly different between patients with stage T3 and T4a EGJ adenocarcinoma. The combined nomogram performed the best and has potential clinical usefulness. CONCLUSIONS: The developed combined nomogram might be useful in differentiating T3 and T4a stages of EGJ adenocarcinoma and may facilitate the decision-making process for the treatment of T3 and T4a EGJ adenocarcinoma.

Variant analysis of HPD genes from two families showing elevated tyrosine upon newborn screening by tandem mass spectrometry (MS/MS).

Background Alterations in the structure and activity of 4-hydroxyphenylpyruvate dioxygenase (HPD) are causally related to two different metabolic disorders: recessively inherited tyrosinemia type III and dominantly inherited hawkinsinuria. The aim of this study was to provide a new perspective for the clinical understanding of the pathogenesis of tyrosinemia type III or hawkinsinuria. Case presentation A full-term newborn baby born after a safe pregnancy and childbirth with a birth weight of 3200 g and another full-term baby born after a safe pregnancy and childbirth with a birth weight of 2800 g are reported and analysed. DNA extraction, next-generation sequencing, bioinformatics analysis, Sanger sequencing and biochemical analysis were performed. One patient with a heterozygous HPD gene (NM_002150.2) c.460G > A mutation and one patient with a heterozygous HPD gene (NM_002150.2) c.248delG mutation showing elevated tyrosine levels upon newborn screening by tandem mass spectrometry (MS/MS) are reported. Conclusions The HPD gene may not be a strictly autosomal recessive pathogenic gene, which provides a new perspective for the clinical understanding of the pathogenesis of tyrosinemia type III or hawkinsinuria.

Efficacy of secondary closure technique after extraction of third molars: a meta-analysis.

The purpose of this study was to assess the influence of two suture methods on the postoperative complications of extraction of mandibular third molars (M3M). We searched the MEDLINE (PubMed), Cochrane Library, and Web of Science databases until 18 May 2018 for randomised controlled trials (RCT) that evaluated the influence of any suture techniques on postoperative complications after the removal of impacted M3M. Pain, facial swelling, and trismus were measured for both the early stage (2-3 days) and late stage (5-7 days) after extraction. We identified 655 records, of which five were assessed for eligibility. All trials included had a moderate risk of bias. The analysis showed that the patients whose wounds had been closed primarily had significantly more pain than those whose wounds were closed secondarily (a wedge of mucosa) during the early stage (standardised mean difference (SMD), -0.49; 95% CI -0.71 to -0.27; P<0.0001) and the late stage (SMD -0.36; 95% CI -0.54 to -0.19; P<0.0001) after the removal of impacted M3M. Patients whose wounds were closed secondarily had less swelling (mm) at the postoperative early stage (SMD -1.12; 95% CI -1.57 to -0.66; P<0.00001) and late stage (SMD -0.51; 95% CI -0.68 to -0.33; P<0.00001). There was more trismus in the primary closure group than in the secondary group during both stages. Our findings suggest that secondary closure causes less pain, facial swelling, and trismus in both early and late stages of surgical removal of impacted M3M, and therefore it improves the quality of life by reducing postoperative discomfort.

[Preparation and chromatographic performance of a silica-bonded (4-cyclopentadienyl benzoic acid-iron-toluene) hexafluorophosphoric acid stationary phase].

Based on the unique molecular structure of ferrocene and its potential as a new liquid chromatography separation medium, a new silica-bonded (4-cyclopentadienyl benzoic acid-iron-toluene) hexafluorophosphoric acid stationary phase was prepared. The structure of this new material was characterized by infrared spectroscopy, elemental analysis, thermogravimetric analysis et al. The chromatographic performance and retention mechanism of this new stationary phase were evaluated using different solute probes, including polycyclic aromatic hydrocarbons (PAHs), positional isomers of naphthylamine, positional isomers of nitro-aniline, nitroimidazoles, organic phosphorus et al. It could provide various action sites for different solutes in normal-phase chromatography such as π electron transfer, π-π electron interactions, dipole-dipole interactions, and electrostatic interactions with the substrates. And the possible separation mechanisms are discussed.

Cytokine responses and correlations thereof with clinical profiles in children with enterovirus 71 infections.

BACKGROUND: Severe complications associated with EV71 infections caused many infants death. However, the pathogenesis of EV71 infection in the severe cases remained poorly understood. METHODS: In this study we collected plasma and cerebrospinal fluid (CSF) specimens drawn in the acute and/or recovery phases from EV71-infected individuals, and plasma specimens from healthy children served as normal controls. We compared the levels of cytokines and chemokines determined by a Luminex-based cytokine bead array. RESULTS: The plasma levels of IL-1ß and IL-6 were significantly higher in severe and critical cases than in mild patients and normal controls. Higher plasma levels of IL-6, IL-10, and IL-8 were evident in critical than severe cases. The CSF levels of IL-6, IL-8, and IP-10 were higher, and that of RANTES lower (compared to plasma), in severe and critical patients. Significantly lower CSF levels of cytokines and chemokines were recorded in the recovery than the acute phase in severe and critical cases treated with intravenous immunoglobulin (IVIG) and glucocorticoids. Only the CSF levels of IL-6, IP-10, and IL-8 were significantly correlated with white blood cell counts, and absolute neutrophil and monocyte counts, in severe cases. Furthermore, the CSF levels of IL-6 were correlated with temperature in both cases. CONCLUSIONS: These data indicate that a major cytokine response and inflammation, in both plasma and the CNS, are features of disease caused by EV71 infection. Systemic inflammation caused by EV71 infection exacerbated the deterioration of the disease, and resulted in the disease progression to the critical illness stage.

[Molecular and epidemiological study of human adenovirus among infants with diarrhea in Nanjing].

OBJECTIVE: To study the prevalence, clinic features and epidemiologic characteristics of human adenovirus diarrhea in Nanjing. METHODS: 730 stool specimens were collected from children with diarrhea in Nanjing Children's Hospital of Nanjing Medical University from June 2009 to June 2011. Polymerase chain reaction (PCR) was employed to detect human adenovirus. The total positive PCR products were typed by nest-PCR or multiple PCR. RESULTS: 21 samples (21/730) were positive for human adenovirus of all 730 samples from June 2009 to June 2011 and enteric HAdV-41 is the predominant stain. CONCLUSION: Enteric HAdV-41 and non-enteric adenovirus were the major etiological agents of viral diarrhea among infants and children in Nanjing from 2009 to 2011. We should take the long-term systematic surveillance seriously.