Drug-drug interaction between diltiazem and tacrolimus in relation to CYP3A5 genotype status in Chinese pediatric patients with nephrotic range proteinuria: a retrospective study.

Background: Tacrolimus is widely used to treat pediatric nephrotic range proteinuria (NRP). Diltiazem, a CYP3A4/5 inhibitor, is often administered with tacrolimus, affecting its pharmacokinetic profile. The impact of this combination on tacrolimus exposure, particularly in CYP3A5*3 genetic polymorphism, remains unclear in pediatric NRP patients. This study aimed to evaluate the effects of diltiazem on tacrolimus pharmacokinetics, focusing on the CYP3A5*3 polymorphism. Methods: We conducted a retrospective clinical study involving pediatric NRP patients, divided into two groups: those receiving tacrolimus with diltiazem and those receiving tacrolimus alone. Propensity score matching (PSM) was used to balance the baseline characteristics between the groups. We compared daily dose-adjusted trough concentrations (C0/D) of tacrolimus in both the original and PSM cohorts. The influence of diltiazem on tacrolimus C0/D, stratified by CYP3A5*3 genetic polymorphism, was assessed in a self-controlled case series study. Results: Before PSM, the tacrolimus C0/D in patients taking diltiazem was significantly higher compared to those with tacrolimus alone (75.84 vs. 56.86 ng/mL per mg/kg, P = 0.034). This finding persisted after PSM (75.84 vs. 46.93 ng/mL per mg/kg, P= 0.028). In the self-controlled case study, tacrolimus C0/D elevated about twofold (75.84 vs. 34.76 ng/mL per mg/kg, P < 0.001) after diltiazem administration. CYP3A5 expressers (CYP3A5*1/*1 and *1/*3) and CYP3A5 non-expressers (CYP3A5*3/*3) experienced a 1.8-fold and 1.3-fold increase in tacrolimus C0/D when combined with diltiazem, respectively. Conclusion: Diltiazem significantly increased tacrolimus C0/D, with CYP3A5*3 expressers showing higher elevations than non-expressers among pediatric NRP patients. These findings highlight the importance of personalized tacrolimus therapy based on CYP3A5*3 genotypes in pediatric patients taking diltiazem.

Synapse Neurotransmitter Channel-Inspired AlOx Memristor with "V" Type Oxygen Vacancy Distribution.

Memristor possesses great potential and advantages in neuromorphic computing, while consistency and power consumption issues have been hindering its commercialization. Low cost and accuracy are the advantages of human brain, so memristors can be used to construct brain-like synaptic devices to solve these problems. In this work, a five-layer AlOx device with a V-shaped oxygen distribution is used to simulate biological synapses. The device simulates synapse structurally. Further, under electrical stimulation, O2- moves to the Ti electrode and oxygen vacancy (Vo) moves to the Pt electrode, thus forming a conductive filament (CF), which simulates the Ca2+ flow and releases neurotransmitters to the postsynaptic membrane, thus realizing the transmission of information. By controlling applied voltage, the regulation of Ca2+ gated pathway is realized to control the Ca2+ internal flow and achieve different degrees of information transmission. Long-term Potentiation (LTP)/Long-term Depression (LTD), Spike Timing Dependent Plasticity (STDP), these basic synaptic performances can be simulated. The AlOx device realizes low power consumption (56.7 pJ/392 fJ), high switching speed (25 ns/60 ns), and by adjusting the window value, the nonlinearity is improved (0.133/0.084), a high recognition accuracy (98.18%) is obtained in neuromorphic simulation. It shows a great prospect in multi-value storage and neuromorphic computing.

Semi-supervised multi-modal medical image segmentation with unified translation.

The two major challenges to deep-learning-based medical image segmentation are multi-modality and a lack of expert annotations. Existing semi-supervised segmentation models can mitigate the problem of insufficient annotations by utilizing a small amount of labeled data. However, most of these models are limited to single-modal data and cannot exploit the complementary information from multi-modal medical images. A few semi-supervised multi-modal models have been proposed recently, but they have rigid structures and require additional training steps for each modality. In this work, we propose a novel flexible method, semi-supervised multi-modal medical image segmentation with unified translation (SMSUT), and a unique semi-supervised procedure that can leverage multi-modal information to improve the semi-supervised segmentation performance. Our architecture capitalizes on unified translation to extract complementary information from multi-modal data which compels the network to focus on the disparities and salient features among each modality. Furthermore, we impose constraints on the model at both pixel and feature levels, to cope with the lack of annotation information and the diverse representations within semi-supervised multi-modal data. We introduce a novel training procedure tailored for semi-supervised multi-modal medical image analysis, by integrating the concept of conditional translation. Our method has a remarkable ability for seamless adaptation to varying numbers of distinct modalities in the training data. Experiments show that our model exceeds the semi-supervised segmentation counterparts in the public datasets which proves our network's high-performance capabilities and the transferability of our proposed method. The code of our method will be openly available at https://github.com/Sue1347/SMSUT-MedicalImgSegmentation.

Enhancing output current in degradable flexible piezoelectric nanogenerators through internal electrode construction.

Conventional piezoelectric nanogenerators (PNGs) face challenges in terms of degradation and reusability, which have negative environmental implications. On the other hand, biocompatible and degradable piezoelectric materials often exhibit lower piezoelectric response. In this study, potassium sodium niobate (KNN) powder and the biodegradable polymer poly(ε-caprolactone) (PCL) were used to fabricate piezoelectric composite films through solution casting. By constructing staggered electrodes, the total polarized charges quantity is increased, achieving a larger current output. The three-unit PNG (3-PNG) based on the composite film with 15 wt% KNN powder, reaches a maximum output current of 0.85 µA, which exhibits higher charging efficiency compared to 1-PNG. Moreover, the prepared 3-PNG can effectively harvest mechanical energy from human activities and maintain a stable output after 10,000 cycles of bending and releasing. The film exhibits complete degradation when exposed to acidic, neutral, and alkaline solutions. This research provides a promising option for environmentally friendly piezoelectric materials selected and output performance enhanced through optimized structural designs, making them more suitable for practical applications.

The absolute number of small and diminutive adenomas with high-grade dysplasia is substantially higher compared with large adenomas: a retrospective pooled study.

Introduction: The risk that a large polyp (≥10 mm) evolves into high-grade dysplasia (HGD) is relatively high compared with that of a small/diminutive polyp (<10 mm). Recently, the detection of small and diminutive polyps has been substantially improved with the advancement of endoscopy. However, further research is needed on the role of the incidence of HGD caused by the co-occurrence of small and diminutive polyps in the progression of HGD. In this study, we aim to investigate whether and how the small and diminutive polyps correlate with the incidence of HGD in the population. Methods: The pooled data were deeply analyzed from four published randomized controlled trials (RCTs) regarding colon polyp detection. All polyps detected were examined and confirmed by pathologists. The primary outcome was the composition ratio of the HGD polyps in each polyp size category. Results: Among a total of 3,179 patients with 2,730 polyps identified, there were 83 HGD polyps confirmed, and 68 patients had at least one polyp with HGD. The risk of development of HGD was lower for a single small and diminutive polyp than for one large polyp (2.18% vs. 22.22%, P < 0.0001). On the contrary, the composition ratio for HGD from small and diminutive polyps was significantly higher than that from the large ones (68.67% vs. 31.33%, P < 0.0001). The combined number of HGD presented a trend negatively correlated to size. Conclusions: Our data demonstrated that the absolute number of HGD significantly derives more from small and diminutive polyps than from the large ones, and the collective number of small and diminutive polyps per patient is indicative of his/her HGD exposure. These findings positively provide novel perspectives on the management of polyps and may further optimize the prevention of colorectal cancer. Systematic Review Registration: http://www.chictr.org.cn, identifier ChiCTR1900025235, ChiCTR1800017675, ChiCTR1800018058, and ChiCTR1900023086.

Preferences for Physical Examination Service in Community Health Service Center in China: A Discrete Choice Experiment.

Objective: Physical examination services play a crucial role in the early detection of diseases, improving the effectiveness of treatment. However, the current physical examination services provided by community health service centers are limited. The objective of this study was to investigate the aspects of physical examination services that are most valued by residents. Methods: Identify and develop attributes and levels through literature research and expert group interviews. A discrete choice experiment was designed. The main effects design gives rise to 16 choice sets. The 16 choice sets were grouped into 2 blocks, and respondents were randomly assigned to one of the blocks. In each choice set, respondents were asked to choose from two alternatives with an opt-out option. In 2023, the discrete choice experiment was administered in several community health service centers within a China population sample. A mixed logit and a latent class analysis were conducted. Results: Participants (n = 399) preferred to receive health advice service. The services provided by the basic team with clinical experts are preferred over those provided solely by the basic team. The results indicated a preference for a participant to be serviced by face-to-face or telephone compared with WeChat. Low cost is also preferred. As participants grow older, their preference for face-to-face or telephone-based services increased. As participants' service demand increase, participants more preferred to receive interpretation of physical examination report and follow-up of important abnormal results, participants more preferred to be serviced by basic team with clinical experts or basic team with health manager etc. Conclusion: We should improve the construction of the service team, optimize the service mode, expand the scope of examination services, reduce the cost of examination services, and meet the needs of residents for physical examination services. More attention should be paid to the needs of elderly and rural residents.

A Meta-Analysis of the Prevalence of Children Goiter in High Water Iodine Areas of China.

Although there are now a large number of studies confirming that high iodine levels can cause goiter, there is controversy and a lack of quantitative data. A systematic search of PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and China Biomedical Database for literature on high iodine and goiter in children was performed with a time limit from January 2013 to October 2023. After screening the literature based on the inclusion criteria, extracting the literature data, and evaluating the risk of bias of the included studies, a single-arm meta-analysis was performed using R 4.0.4 software. Twenty-three studies with a total of 50,980 subjects were included. Meta-analysis showed that the prevalence of goiter among children in water-borne iodine-excess areas was 6.0% [95% CI (4.3%, 7.6%)], and subgroup analyses showed that the prevalence of goiter in children with water iodine 100.1-150 µg/L, 150.1-300 µg/L, and > 300 µg/L was 7.5% [95% CI (0.0%, 15.8%)], 5.5% [95% CI (3.1%, 8.0%)], and 10.2% [95% CI (6.7%, 13.6%)], respectively, and the difference was statistically significant (P < 0.01); The prevalence of goiter among children in the northern China (5.8% [95% CI (4.1%, 7.5%)]) was higher than that in the southern China (3.5% [95% CI (1.0%, 6.0%)]) (P < 0.01); the prevalence of goiter in children with urinary iodine levels 100-199 µg/L, 200-299 µg/L, and ≥ 300 µg/L was 2.4% [95% CI (1.9%, 2.9%)], 3.3% [95% CI (1.9%, 4.8%)], and 7.3% [95% CI (4.4%, 9.9%)], respectively, the difference was statistically significant (P < 0.01); the prevalence of goiter in children aged 8, 9, 10, 11, and 12 years old was 5.1% [95% CI (3.9%, 6.4%)], 8.0% [95% CI (4.0%, 11.9%)], 6.2% [95% CI (3.9%, 8.5%)], 5.5% [95% CI (0.0%, 13.2%)], and 5.4% [95% CI (0.0%, 15.1%)], and when age ≥ 9 years, the relationship between goiter prevalence and age showed a trend toward decreasing with age, but the relationship between different age was no statistical difference in the prevalence of goiter between ages. urinary iodine. The prevalence of goiter in children was higher in areas with high water iodine; the prevalence of goiter in children in the north was significantly higher than that in the south; the prevalence of goiter in children tends to increase with increased urinary iodine levels.

Integrative analysis of renal microRNA and mRNA to identify hub genes and pivotal pathways associated with cyclosporine-induced acute kidney injury in mice.

Cyclosporine (CsA) is an immunosuppressive agent that often causes acute kidney injury (AKI) in children. The specific mechanisms underlying CsA-induced AKI are currently unknown. This study used an integrated network analysis of microRNA (miRNA) and mRNA expression profiles, biochemical and pathological analyses to further investigate these potential mechanisms of CsA-induced AKI. Small RNA sequence analysis identified 25 differentially expressed miRNAs, RNA sequencing analysis identified 4,109 differentially expressed mRNAs. We obtained a total of 4,367 target genes from the 25 differentially expressed miRNAs based on three algorithms, including the Mirdb, Mirtarbase, and TargetScan. 971 target genes overlapped between the 4,367 target genes and 4,109 differentially expressed mRNAs were identified for further bioinformatics analysis. Finally, 30 hub genes and two main modules were recognized. Functional enrichment analysis of 30 hub genes indicated that inflammation and epithelial-mesenchymal transition (EMT) related genes were mainly concentrated together. Pathway analysis revealed that the PI3K-Akt signaling pathway plays an integral role in CsA-induced AKI. Network analysis identified 3 important miRNAs, mmu-miR-17b-5p, mmu-miR-19b-3p, and mmu-mir-423-5p that may further promote the development of inflammatory responses and EMT by mediating a complex network of factors. Our research provides a clearer understanding the molecular mechanism of this specific drug-induced AKI by CsA use, which is useful for discovering potential targets for gene therapies, and drug development in CsA-induced AKI.

Metanephric stromal tumor in an adult with PDGFRA mutation: a case report.

BACKGROUND: Metanephric stromal tumors (MST) are rare benign renal tumors that mainly occur in infants and children. Approximately 72% of MST in children have the B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation. To date, only five cases of adult MSTs have been reported and no clear genetic alterations have been found. CASE PRESENTATION: We report a case of MST in a 45-year-old woman who complained of left lower back pain for a week, accompanied by hypertension (150/79 mmHg). Magnetic resonance imaging (MRI) showed an abnormally enhanced nodule (1.1 cm in the middle of the left kidney), which was histopathologically consistent with an MST. The BRAF V600E mutation was not detected in tumor cells using PCR and next-generation sequencing (NGS). However, a platelet-derived growth factor receptor alpha (PDGFRA) mutation was detected in this case using NGS. The patient showed no recurrence or metastasis nine months after partial nephrectomy, and her blood pressure was consistently normal. CONCLUSION: This is the first report of alterations in PDGFRA in MSTs. This result advances our knowledge of genetic variations in adult MSTs, which may have different gene alterations from MSTs in children.

Bimetallic UiO-66-NH2(Zr-Hf) synergistic photocatalytic and piezoelectric effects for the degradation of rhodamine B.

A series of bimetallic UiO-66-NH2(Zr-Hf) metal-organic frameworks (MOFs) were prepared by a green hydrothermal method and tested for their photocatalytic and piezo-catalytic properties. Among them, UN(0.75Zr) (metal node: 0.75Zr : 0.25Hf) shows the most superior piezo-photocatalytic activity. The degradation rate for 40 mg L-1 rhodamine B (Rh B) could reach 96.78% within 30 min, which was ∼4.66 and ∼3.30 times higher than that of photocatalysis and piezo-catalysis, respectively. Moreover, the main reactive oxidizing substances (ROS), including vacancies (h+) and hydroxyl radicals (˙OH), were identified by free radical scavenging experiments. In addition, the intermediates generated during Rh B degradation were analyzed by HPLC-MS, while a reasonable degradation pathway was presented. Our work utilizes a green and environmentally friendly method to prepare bimetallic MOFs, providing a novel solution for the rapid degradation of highly concentrated dye wastewater.

Analysis of kidney proteomes to identify biological pathways associated with vancomycin-induced nephrotoxicity in mice by tandem mass tag-labeled quantitative and parallel reaction monitoring phosphoproteomics.

Vancomycin (VCM)-induced nephrotoxicity impedes its treatment applications. Thus, it is important to clarify the relevant mechanism. This study investigated phosphoprotein changes attributable to the VCM nephrotoxicity mechanisms. Biochemical, pathological and phosphoproteomic analyses based on C57BL/6 mice were performed to explore the mechanisms.VCM-treated mice showed increased levels of blood urea nitrogen and creatinine, and signs of acute tubular necrotic lesions. Phosphoproteomic profiling identified 3025 differentially phosphorylated phosphopeptides between the model and control group. Gene Ontology enrichment analysis demonstrated that Molecular Function "oxidoreductase activity" and Cellular Component "peroxisome" were markedly enriched. KEGG pathway analysis identified an enrichment in peroxisome pathway and PPAR (peroxisome proliferator-activated receptor) signaling pathways. Parallel reaction monitoring analysis revealed a significant downregulation of CAT, SOD-1, AGPS, DHRS4, and EHHADH at phosphorylation level by VCM. Notably, the phosphorylation of ACO, AMACR, and SCPX was downregulated by VCM, which are the fatty acid ß-oxidation-related proteins involved in PPAR signaling pathways. The phosphorylated PEX5 involved in peroxisome biogenesis was upregulated by VCM. Collectively, these findings indicated that VCM-induced nephrotoxicity is closely associated with peroxisome pathway and PPAR signaling pathways. The current study provides important insight into the mechanisms of VCM nephrotoxicity and will aid in the development of preventive and therapeutic strategies against this nephropathy.

[Research on ontology construction of acupuncture effect based on ISO/TS 16843-6: 2022].

In order to specify the information expression of acupuncture effect and realize the knowledge reuse and sharing, in view of animal experiments and clinical trials, the relevant knowledge of acupuncture effect is allocated. Using seven-step method and Protégé5.5.0 tool, the ontology of acupuncture effect is constructed on the base of ISO/TS 16843-6: 2022. A total of 199 classes are constructed, including 7 categories (acupuncture point, acupuncture therapy, needling method, biological process, genes and gene products, disorder, and anatomic structure), 12 object properties, 1 108 instances and 5 123 axioms. A semantic network with the characteristics of acupuncture and moxibustion is established and the structured expression for the knowledge of acupuncture effects is obtained, which lays the foundation for the innovation and development in the field of acupuncture and moxibustion.

Staged revascularization vs. culprit-only percutaneous coronary intervention for multivessel disease in elderly patients with ST-segment elevation myocardial infarction.

Backgroundand objective: Studies have highlighted the significant role of staged percutaneous coronary intervention (PCI) for a multivessel disease (MVD) among patients with ST-elevation myocardial infarction (STEMI). However, the relative benefit of staged vs. culprit-only PCI for MVD in elderly patients with STEMI remains undetermined. Thus, the present study compared the clinical outcomes of staged and culprit-only PCI in this cohort. Methods: From January 2014 to September 2019, 617 patients aged ≥65 years with STEMI and MVD who underwent primary PCI of the culprit vessels within 12 h of symptom onset were enrolled. They were then categorized into the staged and culprit-only PCI groups according to intervention strategy. Propensity score matching (PSM) was conducted to adjust for confounding factors between groups. The primary end point was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, cardiac death, recurrent myocardial infarction (MI), stroke, and ischemia-driven revascularization. Results: During a mean follow-up of 56 months, 209 patients experienced MACCE and 119 died. Staged revascularization was associated with a lower risk of MACCE, all-cause death, and cardiac death than culprit-only PCI in both overall patients and the PSM cohorts. In contrast, there was no significant difference in stroke or ischemia-driven revascularization. Moreover, on multivariate Cox regression analysis, staged PCI was a significant predictor of a lower incidence of MACCE and all-cause death. Conclusion: In elderly patients with STEMI and MVD, staged PCI is superior to culprit-only PCI.

Identification and functional characterization of BICD2 as a candidate disease gene in an consanguineous family with dilated cardiomyopathy.

BACKGROUND: Familial dilated cardiomyopathy (DCM) is a genetic cardiomyopathy that is associated with reduced left ventricle function or systolic function. Fifty-one DCM-causative genes have been reported, most of which are inherited in an autosomal dominant manner. However, recessive DCM-causative gene is rarely observed. METHODS: Whole-exome sequencing (WES) was performed in a consanguineous family with DCM to identify candidate variants. Sanger sequencing was utilized to confirm the variant. We then checked the DCM candidate gene in 210 sporadic DCM cases. We next explored BICD2 function in both embryonic and adult bicd2-knockout zebrafish models. In vivo cardiac function of bicd2-knockout fish was detected by echocardiography and RNA-seq. RESULTS: We identified an autosomal recessive and evolutionarily conserved missense variant, NM_001003800.1:c.2429G > A, in BICD2, which segregated with the disease phenotype in a consanguineous family with DCM. Furthermore, we confirmed the presence of BICD2 variants in 3 sporadic cases. Knockout of bicd2 resulted in partial embryonic lethality in homozygotes, suggesting a vital role for bicd2 in embryogenesis. Heart dilation and decreased ejection fraction, cardiac output and stroke volume were observed in bicd2-knockout zebrafish, suggesting a phenotype similar to human DCM. Furthermore, RNA-seq confirmed a larger transcriptome shift in in bicd2 homozygotes than in heterozygotes. Gene set enrichment analysis of bicd2-deficient fish showed the enrichment of altered gene expression in cardiac pathways and mitochondrial energy metabolism. CONCLUSIONS: Our study first shows that BICD2 is a novel candidate gene associated with familial DCM, and our findings will facilitate further insights into the molecular pathological mechanisms of DCM.

Mitigating the Negative Piezoelectricity in Organic/Inorganic Hybrid Materials for High-performance Piezoelectric Nanogenerators.

The conversion of ecofriendly waste energy into useable electrical energy is of significant interest for energy harvesting technologies. Piezoelectric nanogenerators based on organic/inorganic hybrid materials are a key promising technology for harvesting mechanical energy due to their high piezoelectric coefficient and good mechanical flexibility. However, the negative piezoelectric effect of the polymer component in composite devices severely undermines its overall piezoelectricity, compromising the output performance of PVDF-based piezoelectric hybrid nanogenerators. Here, to conquer this, we report a two-step poling schedule to orient the dipoles of organic and inorganic components in the same direction. The optimized nanogenerator delivers a combination of high piezoelectric coefficient, great output performance, and remarkable stability. The isotropic piezoelectricity in the composite device collaborates to output a maximum voltage of 110 V and a power density of 7.8 µW cm-2. This strategy is also applied to elevate the piezoelectricity of other organic/inorganic-hybrid-based nanogenerators, substantiating its universal applicability for composite piezoelectric nanogenerators. This study presents a feasible strategy for enhancing the effective output capability of composite nanogenerator technologies.

The CaMYB340 transcription factor induces chilling injury in post-harvest bell pepper by inhibiting fatty acid desaturation.

Bell pepper (Capsicum annuum L.) is a tradable and desirable crop; however, its perishable nature requires low-temperature handling. Paradoxically, cold causes chilling injury (CI) and post-harvest waste. Current knowledge about CI in pepper is limited. The mechanism of CI is multi-faceted; therefore, we focused on fatty acid (FA) desaturation. We identified an upstream nuclear transcription factor (TF), CaMYB340, belonging to the R2R3 MYB subfamily, that negatively regulates FA desaturation and CaCBF3 expression and whose gene and protein expression is induced by low temperature (4°C). Specifically, McrBC treatment and bisulfite sequencing PCR indicate that exposure to cold triggers DNA methylation on one of the CHH sites in the CaMYB340 promoter. This epigenetic event at least partly contributes to the upregulation of CaMYB340 transcript levels. Increased expression of CaMYB340 results in the formation of protein complexes with CabHLH93 and CaMYB1R1, which in turn downregulate the expression of downstream genes. For peppers held at low temperature, transient overexpression of CaMYB340 reduced unsaturated FA content and membrane fluidity, resulting in cold-induced poor peel texture. Transient CaMYB340 silencing increased FA desaturation and lowered electrolyte leakage, enhancing cold tolerance in CaMYB340 knockdown fruits. Overall, these results underscore the intricacy of transcriptional networks in plants and highlight the role of CaMYB340 in CI occurrence in pepper fruits.

Whether Social Participation Can Affect the Central Government Public Policy Response to the COVID-19 in China.

Objective: The coronavirus disease 2019 (COVID-19) outbreak has threatened the state's governance and public safety. This study investigates whether and how public participation can affect central government policy response to this pandemic in the context of China. Methods: This study constructs the theoretical framework based on theoretical analysis, and Social Network Analysis is used to analyze data on the public participation, New Media, and the central government response in this pandemic. Results: Findings show that the Chinese central government does not always adopt top-down elitist governance strategies in risk management. The central government will also adopt the bottom-up governance strategy triggered by public participation. In this process, New Media acts as a catalyst. Specifically, when faced with a public emergency and needs a policy response from the central government, public participation firstly creates "participation" with the authority of the media, forms public opinion, and then the prompt policy response from the central government. Conclusion: This study confirms that the central government will refer to public participation to decide the policy response. It also shows that the theory of government response applies to both the local government and the central government.

Four calcium signaling pathway-related genes were upregulated in microcystic adnexal carcinoma: transcriptome analysis and immunohistochemical validation.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a skin cancer with challenges in diagnosis and management. This study was aimed to detect molecular alterations of MAC and guide its pathologic diagnosis and treatment. METHODS: We performed transcriptome analysis on 5 MAC and 5 normal skin tissues, identified the differentially expressed genes, and verified them by immunohistochemistry. RESULTS: Three hundred four differentially expressed genes (DEGs) in MAC were identified by next-generation transcriptome sequencing, among which 225 genes were upregulated and 79 genes were downregulated. Four genes of the calcium signaling pathway, including calcium voltage-gated channel subunit alpha 1 S (CACNA1S), ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 (ATP2A1), ryanodine receptor 1 (RYR1), and myosin light chain kinase 3 (MYLK3), were upregulated and then been verified by immunohistochemistry. The expression of CACNA1S, ATP2A1, RYR1, and MYLK3 was upregulated in MAC compared with normal sweat glands and syringoma tumor cells and was generally negative in trichoepithelioma and infundibulocystic type basal cell carcinoma. CONCLUSIONS: The four genes of the calcium signaling pathway were upregulated in MAC at both RNA and protein levels. CACNA1S, ATP2A1, RYR1, and MYLK3 may be new diagnostic molecular markers and therapeutic targets for MAC.

Risk assessment and control of infectious disease prevention and control in elementary and secondary schools in Tianjin / 中国学校卫生

Objective@#To establish a risk assessment system for the prevention and control of infectious diseases in primary and secondary schools in Tianjin and reduce the risk of infectious disease prevention and control through risk assessment and control.@*Methods@#Based on the failure modes and effect analysis method, a quantitative risk assessment of infectious disease prevention and control in 45 primary and secondary schools in Tianjin was carried out. Risk based supervisory process was assessed, while control effect was evaluated for contined improvement in the prevention and control of infectious diseases in the primary and secondary schools.@*Results@#The top three risk aspects found in the infectious disease prevention and control system in primary and secondary schools in Tianjin included failure to provide sanitation professionals (82.22%) in accordance with regulations, no hand sanitizer or disinfectant (35.56%) in wash basins, and drinking water related products without approval (28.89%). The results of the risk assessment indicated that the three risk aspects with the highest risk priority number (RPN) included failure to provide health professionals( n = 144), no morning and afternoon inspection arrangement( n =126), and low quality of morning and afternoon inspections( n =126). After optimizing the supervision measures for the risk aspects with a detectable degree≥7 points, a quantitative risk assessment was carried out again, the RPN values of all risk points fell below 125, indicating reasonable control effect.@*Conclusion@#Based on the failure mode and effect analysis method, the establishment of a risk assessment system for the prevention and control of infectious diseases in primary and secondary schools and regular risk assessments can timely detect risk aspects in the infectious disease prevention and control, to promote effective prevention of infectious diseases in schools.

Evolution of the conductive filament system in HfO2-based memristors observed by direct atomic-scale imaging.

The resistive switching effect in memristors typically stems from the formation and rupture of localized conductive filament paths, and HfO2 has been accepted as one of the most promising resistive switching materials. However, the dynamic changes in the resistive switching process, including the composition and structure of conductive filaments, and especially the evolution of conductive filament surroundings, remain controversial in HfO2-based memristors. Here, the conductive filament system in the amorphous HfO2-based memristors with various top electrodes is revealed to be with a quasi-core-shell structure consisting of metallic hexagonal-Hf6O and its crystalline surroundings (monoclinic or tetragonal HfOx). The phase of the HfOx shell varies with the oxygen reservation capability of the top electrode. According to extensive high-resolution transmission electron microscopy observations and ab initio calculations, the phase transition of the conductive filament shell between monoclinic and tetragonal HfO2 is proposed to depend on the comprehensive effects of Joule heat from the conductive filament current and the concentration of oxygen vacancies. The quasi-core-shell conductive filament system with an intrinsic barrier, which prohibits conductive filament oxidation, ensures the extreme scalability of resistive switching memristors. This study renovates the understanding of the conductive filament evolution in HfO2-based memristors and provides potential inspirations to improve oxide memristors for nonvolatile storage-class memory applications.