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Abstract Background Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor. Objective To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris. Methods This was a randomized, controlled, assessor-blind, phase III study conducted in patients with moderate facial acne vulgaris. Results A total of 1617 patients were enrolled. At week 12, patients in the adapalene–clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (− 66.85%), compared with adapalene alone (− 50.82%) or clindamycin gel alone (− 57.61%). The difference in the least square means of the adapalene–clindamycin gel group and adapalene group, or clindamycin gel group was − 16.08% (95% CI − 19.95% to − 12.21%) and − 9.38% (95% CI − 13.25% to − 5.51%;), respectively. At week 12, 19.28% of participants who received adapalene–clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95% CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95% CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups. Conclusion Adapalene 0.1%–clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris. Trial Registration ClinicalTrials.gov identifier NCT03615768.

Abstract Background Bosma arhinia microphthalmia syndrome (BAMS; MIM603457) is a rare genetic disorder, predominantly autosomal dominant. It is a multi-system developmental disorder characterized by severe hypoplasia of the nose and eyes, and reproductive system defects. BAMS is extremely rare in the world and no cases have been reported in Chinese population so far. Pathogenic variants in the SMCHD1 gene (MIM614982) cause BAMS, while the underlying molecular mechanisms requires further investigation. Case presentation In this study, a Chinese girl who has suffered from congenital absence of nose and microphthalmia was enrolled and subsequently submitted to a comprehensive clinical and genetic evaluation. Whole-exome sequencing (WES) was employed to identify the genetic entity of thisgirl. A heterozygous pathogenic variant, NM_015295, c.1025G > C; p. (Trp342Ser) of SMCHD1 was identified. By performing very detailed physical and genetic examinations, the patient was diagnosed as BAMS. Conclusion This report is the first description of a variant in SMCHD1 in a Chinese patient affected with BAMS.Our study not only furnished valuable genetic data for counseling of BAMS, but also confirmed the diagnosis of BAMS, which may help the management and prognosis for this patient.

Abstract Gasdermin E (GSDME) has recently been identified as a critical executioner to mediate pyroptosis. While epidermal keratinocytes can initiate GSDME-mediated pyroptosis, the role of keratinocyte GSDME in psoriatic dermatitis remains poorly characterized. Through analysis of GEO datasets, we found elevated GSDME levels in psoriatic lesional skin. Additionally, GSDME levels correlated with both psoriasis severity and response to biologics treatments. Single-cell RNA sequencing (scRNA-seq) from a GEO dataset revealed GSDME upregulation in keratinocytes of psoriasis patients. In the imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model, both full-length and cleaved forms of caspase-3 and GSDME were elevated in the epidermis. Abnormal proliferation and differentiation of keratinocytes and dermatitis were attenuated in Gsdme -/- mice and keratinocyte-specific Gsdme conditional knockout mice after IMQ stimulation. Exposure of keratinocytes to mixed cytokines (M5), mimicking psoriatic conditions, led to GSDME cleavage. Moreover, the interaction between GSDME-FL and p65 or c-jun was significantly increased after M5 stimulation. GSDME knockdown inhibited nuclear translocation of p65 and c-jun and decreased upregulation of psoriatic inflammatory mediators such as IL1β, CCL20, CXCL1, CXCL8, S100A8, and S100A9 in M5-challenged keratinocytes. In conclusion, GSDME in keratinocytes contributes to the pathogenesis and progression of psoriasis, potentially in a pyroptosis-independent manner by interacting and promoting translocation of p65 and c-jun. These findings suggest that keratinocyte GSDME could serve as a potential therapeutic target for psoriasis treatment.

Abstract Objective The associations between plasma vitamin B12 level and anemia under different dietary patterns in elderly Chinese people are poorly understood. We aimed to examine the associations between plasma vitamin B12 levels and anemia under different dietary patterns in adults aged 65 years and older in nine longevity areas in China. Methods A total of 2405 older adults completed a food frequency questionnaire at the same time as a face-to-face interview. The dietary diversity score (DDS) was assessed based on the food frequency questionnaire, with the low DDS group referring to participants with a DDS score ≤ 4 points. Vitamin B12 levels were divided into two groups of high (>295 pg/mL) and low (≤ 295 pg/mL) with the median used as the cut-off point. Sub-analyses were also performed on older adults divided into tertiles of vitamin B12 levels: low ( 375 pg/mL) to study the association of these levels with anemia. Results Six hundred ninety-five (28.89%) of these people were diagnosed with anemia and had a mean age of 89.3 years. Higher vitamin B12 levels were associated with a decreased risk of anemia (multi-adjusted OR, 0.59, [95% CI, 0.45 ~ 0.77] P

Abstract Background Polycystic ovarian syndrome (PCOS) is a common endocrine and metabolic disease in women. Hyperandrogenaemia (HA) and insulin resistance (IR) are the basic pathophysiological characteristics of PCOS. The aetiology of PCOS has not been fully identified and is generally believed to be related to the combined effects of genetic, metabolic, internal, and external factors. Current studies have not screened for PCOS susceptibility genes in a large population. Here, we aimed to study the effect of TGF-β1 methylation on the clinical PCOS phenotype. Methods In this study, three generations of family members with PCOS with IR as the main characteristic were selected as research subjects. Through whole exome sequencing and bioinformatic analysis, TGF-β1 was screened as the PCOS susceptibility gene in this family. The epigenetic DNA methylation level of TGF-β1 in peripheral blood was detected by heavy sulfite sequencing in patients with PCOS clinically characterised by IR, and the correlation between the DNA methylation level of the TGF-β1 gene and IR was analysed. We explored whether the degree of methylation of this gene affects IR and whether it participates in the occurrence and development of PCOS. Results The results of this study suggest that the hypomethylation of the CpG4 and CpG7 sites in the TGF-β1 gene promoter may be involved in the pathogenesis of PCOS IR by affecting the expression of the TGF-β1 gene. Conclusions This study provides new insights into the aetiology and pathogenesis of PCOS.

Parkinson's disease can affect not only motor functions but also cognitive abilities, leading to cognitive impairment. One common issue in Parkinson's disease with cognitive dysfunction is the difficulty in executive functioning. Executive functions help us plan, organize, and control our actions based on our goals. The brain area responsible for executive functions is called the prefrontal cortex. It acts as the command center for the brain, especially when it comes to regulating executive functions. The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine. However, little is known about how dopamine affects the cognitive functions of patients with Parkinson's disease. In this article, the authors review the latest research on this topic. They start by looking at how the dopaminergic system, is altered in Parkinson's disease with executive dysfunction. Then, they explore how these changes in dopamine impact the synaptic structure, electrical activity, and connection components of the prefrontal cortex. The authors also summarize the relationship between Parkinson's disease and dopamine-related cognitive issues. This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson's disease.

Abstract In the study of brain functional connectivity networks, it is assumed that a network is built from a data window in which activity is stationary. However, brain activity is non-stationary over sufficiently large time periods. Addressing the analysis electroencephalograph (EEG) data, we propose a data segmentation method based on functional connectivity network structure. The goal of segmentation is to ensure that within a window of analysis, there is similar network structure. We designed an intuitive and flexible graph distance measure to quantify the difference in network structure between two analysis windows. This measure is modular: a variety of node importance indices can be plugged into it. We use a reference window versus sliding window comparison approach to detect changes, as indicated by outliers in the distribution of graph distance values. Performance of our segmentation method was tested in simulated EEG data and real EEG data from a drone piloting experiment (using correlation or phase-locking value as the functional connectivity strength metric). We compared our method under various node importance measures and against matrix-based dissimilarity metrics that use singular value decomposition on the connectivity matrix. The results show the graph distance approach worked better than matrix-based approaches; graph distance based on partial node centrality was most sensitive to network structural changes, especially when connectivity matrix values change little. The proposed method provides EEG data segmentation tailored for detecting changes in terms of functional connectivity networks. Our study provides a new perspective on EEG segmentation, one that is based on functional connectivity network structure differences.

Osmanthus fragrans is widely used in gardening, but the short flowering period of O. fragrans affects its ornamental and economic value. ERF, as a plant ethylene response factor, is an important link in the regulation of plant senescence. In this study, we conducted a comprehensive analysis of the functional role of OfERF1-3 within the petals of O. fragrans. Specifically, the OfERF1-3 gene was cloned and subjected to rigorous sequence analysis. Subsequently, to evaluate its expression patterns and effects, gene overexpression experiments were carried out on both Nicotiana tabacum and O. fragrans. The results showed that OfERF1-3-overexpressing tobacco plants exhibited longer petal opening times compared with those of wild plants. Measurements of physiological parameters also showed that the flowers of overexpressed tobacco plants contained lower levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) than those of the wild type. There was a lower expression of senescence marker genes in overexpressed tobacco and O. fragrans. A yeast two-hybrid assay showed that OfERF1-3 interacted with OfSKIP14 in a manner related to the regulation of ABA. In summary, OfERF1-3 can play a delaying role in the petal senescence process in O. fragrans, and it interacts with OfSKIP14 to indirectly affect petal senescence by regulating the ABA pathway.

Abstract Gasdermin D (GSDMD)-mediated pyroptosis has a significant pro-inflammation characteristic due to dramatic secretion of pro-inflammatory substances. However, its role remains unclear in psoriasis as one chronic inflammatory skin disorder with high prevalence. We found that N-terminal GSDMD (N-GSDMD) was aberrantly expressed in epidermis of skin lesion in psoriasis patients and imiquimod-induced psoriasis-like dermatitis (IIPLD) mice. In epidermis of IIPLD mice and M5 (simulating psoriatic inflammatory challenge)-treated keratinocytes cultured in vitro, cleavage products of caspase-1, GSDMD and IL-1β were increased. M5-stimulated keratinocyte presented typical pyroptosis morphology accompanied with PI-staining. Gsdmd −/− keratinocytes could not present pyroptosis morphology while stimulated with M5. Electroporation of recombinant N-GSDMD could make the pyroptosis morphology reappear. In Gsdmd −/− mice or keratinocyte-specific Gsdmd conditional knockout mice, we observed the alleviation of psoriatic inflammation and epidermal aberrant expression of Ki-67 and differentiation markers (loricrin and keratin 5) after imiquimod stimulation. Transplanting skin tissue from control mice to Gsdmd −/− mice can evoke the response to imiquimod stimulation in the background of Gsdmd −/− mice (not limited in transplanting area). In M5-stimulated keratinocytes, disulfiram or GSDMD siRNA transfection can inhibit pyroptosis and eliminate disproportionate increases of Ki-67 and PI. We further validated that topically application of disulfiram (pyroptosis inhibitor) also alleviated IIPLD in mice. These findings indicate a novel mechanism that GSDMD-mediated keratinocyte pyroptosis facilitates hyperproliferation and aberrant differentiation induced by immune microenvironment in psoriatic skin inflammation, which contributes to pathogenesis of psoriasis. Our study provides an innovative insight that targeting pyroptosis can be considered as a therapeutic strategy against psoriasis.

Ethylene-Responsive Factor (ERF) is a key element found in the middle and lower reaches of the ethylene signal transduction pathway. It is widely distributed in plants and plays important roles in plant growth and development, hormone signal transduction, and various stress processes. Although there is research on AP/ERF family members, research on AP2/ERF in Osmanthus fragrans is lacking. Thus, in this work, AP2/ERF in O. fragrans was extensively and comprehensively analyzed. A total of 298 genes encoding OfAP2/ERF proteins with complete AP2/ERF domains were identified. Based on the number of AP2/ERF domains and the similarity among amino acid sequences between AP2/ERF proteins from A. thaliana and O. fragrans, the 298 putative OfAP2/ERF proteins were divided into four different families, including AP2 (45), ERF (247), RAV (5), and SOLOIST (1). In addition, the exon–intron structure characteristics of these putative OfAP2/ERF genes and the conserved protein motifs of their encoded OfAP2/ERF proteins were analyzed, and the results were found to be consistent with those of the population classification. A tissue-specific analysis showed the spatiotemporal expression of OfAP2/ERF in the stems and leaves of O. fragrans at different developmental stages. Specifically, 21 genes were not expressed in any tissue, while high levels of expression were found for 25 OfAP2/ERF genes in several tissues, 60 genes in the roots, 34 genes in the stems, 37 genes in young leaves, 34 genes in old leaves, 32 genes in the early flowering stage, 18 genes in the full flowering stage, and 37 genes in the late flowering stage. Quantitative RT-PCR experiments showed that OfERF110a and OfERF110b had the highest expression levels at the full-bloom stage (S4), and this gradually decreased with the senescence of petals. The expression of OfERF119c decreased first and then increased, while the expression levels of OfERF4c and OfERF5a increased constantly. This indicated that these genes may play roles in flower senescence and the ethylene response. In the subsequent subcellular localization experiments, we found that ERF1-4 was localized in the nucleus, indicating that it was expressed in the nucleus. In yeast self-activation experiments, we found that OfERF112, OfERF228, and OfERF23 had self-activation activity. Overall, these results suggest that OfERFs may have the function of regulating petal senescence in O. fragrans.

Hydrothermal carbonization is an innovation technology to realize the resource utilization of biomass. It has the advantages of directly treating wet biomass, low reaction temperature, short reaction time and obvious reduction effect. For its well-developed pore structure, rich oxygen-containing functional group, large specific surface area and high heating value, the hydrochar has been widely applied in the fields of environment, energy, electrochemistry and catalysis. Reaction conditions and reaction processes of hydrothermal carbonization technology were briefly described. Conventional modification methods such as the physical activation and chemical activation of hydrochar were also introduced. In particular, the effects of new modification methods, including non-thermal plasma, anaerobic fermentation, magnetization, solid-state microwave, polyethyleneimine and heteroatom doping, on the structure and surface functional groups of hydrochar were emphatically analyzed. The application progresses of hydrochar as adsorbents for heavy metal, organic matter and CO2, soil amendment, solid fuel, electrode material and catalysts were also reviewed. As adsorbents, hydrochar can remove 82%−99% of heavy metal elements (Cr, Cu, Zn, etc.) from wastewater and adsorb 1.2−8.3 mmol/g of CO2. As soil amendments, adding hydrochar can reduce the amount of nitrogen fertilizer. As solid fuels, the heating value of hydrochar produced from lignocellulose is as high as 30 MJ/kg. This value is close to the heating value of bituminous coal. As electrode materials, by improving the pore size distribution and increasing the number of oxygen- and nitrogen-containing functional groups, the electrochemical performance of hydrochar can be greatly improved, and the specific capacitance of hydrochar can reach more than 300 F/g. In the field of catalysis, hydrochar can serve as a catalyst or as a catalyst support for active components. Finally, it is pointed out that the future research should focus on the composite modification, the recycling and utilization of hydrochar, and its toxic mechanism to plants and soil microorganisms. Its combustion performance, specific capacitance, energy density and stability should be further improved to realize the commercial application of hydrochar.

Summary: Although the composition and assembly of stress granules (SGs) are well understood, the molecular mechanisms underlying SG disassembly remain unclear. Here, we identify that heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) is associated with SGs and that its absence specifically enhances the disassembly of arsenite-induced SGs depending on the ubiquitination-proteasome system but not the autophagy pathway. hnRNPA2B1 interacts with many core SG proteins, including G3BP1, G3BP2, USP10, and Caprin-1; USP10 can deubiquitinate G3BP1; and hnRNPA2B1 depletion attenuates the G3BP1-USP10/Caprin-1 interaction but elevates the G3BP1 ubiquitination level under arsenite treatment. Moreover, the disease-causing mutation FUSR521C also disassembles faster from SGs in HNRNPA2B1 mutant cells. Furthermore, knockout of hnRNPA2B1 in mice leads to Sertoli cell-only syndrome (SCOS), causing complete male infertility. Consistent with this, arsenite-induced SGs disassemble faster in Hnrnpa2b1 knockout (KO) mouse Sertoli cells as well. These findings reveal the essential roles of hnRNPA2B1 in regulating SG disassembly and male mouse fertility.

Abstract Background Patients with polycystic ovary syndrome (PCOS) exhibit a chronic inflammatory state, which is often accompanied by immune, endocrine, and metabolic disorders. Clarification of the pathogenesis of PCOS and exploration of specific biomarkers from the perspective of immunology by evaluating the local infiltration of immune cells in the follicular microenvironment may provide critical insights into disease pathogenesis. Methods In this study, we evaluated immune cell subsets and gene expression in patients with PCOS using data from the Gene Expression Omnibus database and single-sample gene set enrichment analysis. Results In total, 325 differentially expressed genes were identified, among which TMEM54 and PLCG2 (area under the curve = 0.922) were identified as PCOS biomarkers. Immune cell infiltration analysis showed that central memory CD4+ T cells, central memory CD8+ T cells, effector memory CD4+ T cells, γδ T cells, and type 17 T helper cells may affect the occurrence of PCOS. In addition, PLCG2 was highly correlated with γδ T cells and central memory CD4+ T cells. Conclusions Overall, TMEM54 and PLCG2 were identified as potential PCOS biomarkers by bioinformatics analysis. These findings established a basis for further exploration of the immunological mechanisms of PCOS and the identification of therapeutic targets.

Abstract To increase the imaging resolution and detection capability, the field strength of static magnetic fields (SMFs) in magnetic resonance imaging (MRI) has significantly increased in the past few decades. However, research on the side effects of high magnetic field is still very inadequate and the effects of SMF above 1 T (Tesla) on B cells have never been reported. Here, we show that 33.0 T ultra‐high SMF exposure causes immunosuppression and disrupts B cell differentiation and signaling. 33.0 T SMF treatment resulted in disturbance of B cell peripheral differentiation and antibody secretion and reduced the expression of IgM on B cell membrane, and these might be intensity dependent. In addition, mice exposed to 33.0 T SMF showed inhibition on early activation of B cells, including B cell spreading, B cell receptor clustering and signalosome recruitment, and depression of both positive and negative molecules in the proximal BCR signaling, as well as impaired actin reorganization. Sequencing and gene enrichment analysis showed that SMF stimulation also affects splenic B cells' transcriptome and metabolic pathways. Therefore, in the clinical application of MRI, we should consider the influence of SMF on the immune system and choose the optimal intensity for treatment.

Abstract. Background:. The heavy metals cadmium (Cd) and mercury (Hg) are known to be widespread environmental contaminants and high occupational exposure adversely affects the risk of chronic kidney disease (CKD). However, evidence from epidemiological studies linking low Cd and Hg exposure (or non-industrial) to the risk of progression to CKD are conflicting. This study aimed to explore the association of low Cd and Hg exposure with the risk of CKD in Chinese adults aged ≥80 years. Methods:. The participants were recruited for the Healthy Aging and Biomarkers Cohort Study in 2017, an ongoing perspective survey conducted in longevity areas in China initially involving 3016 older adults. We used logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals of CKD setting Cd and Hg as categorical variables. Logistic regression with restricted cubic spline was used to characterize a dose-response relationships between Cd or Hg concentrations and the risk of CKD in the study population. Results:. The ORs for the risk of CKD comparing the fourth to the first quartile of blood Cd, blood Hg, urine Cd, and urine Hg were 1.77, 1.57, 2.03, and 1.50, respectively. Restricted cubic spline models showed that blood Cd and urine Hg were significantly linearly correlated with the risk of CKD, while blood Hg and urine Cd were non-linearly correlated with the risk of CKD with a steeper slope at concentrations

Abstract Keratinocyte necroptosis (with proinflammatory characteristic) is required for epidermal damage in contact hypersensitivity (CHS). In DNCB-induced CHS mice model, we observed the aggravated keratinocyte death and increased phosphorylation level of MLKL, RIPK3 and RIPK1. However, CHS skin lesion did not present in keratinocyte-specific Mlkl knockout mice. We validated that MLKL-mediated keratinocyte necroptosis is required for epidermal damage in response to immune microenvironment in CHS. Moreover, MLKL-mediated necroptosis deficiency or inhibition resulted in blocking recruitment and activation of inflammatory cells in CHS via reducing HMGB1 release in keratinocytes. This study suggests that MLKL-mediated keratinocyte necroptosis functions as a self-amplified actor in inflammatory responses and could be considered as an effective therapeutic target. It proposes an innovative prospective that inhibiting keratinocyte necroptosis can prevent the development of epidermal damage in CHS.

Abstract Gasdermin E (GSDME)-mediated pyroptosis is induced in keratinocytes of UVB-challenged skin. The role of GSDME in UVB-caused skin damage remains unknown. To explore the role of GSDME in UVB-induced skin inflammation. We compared differences in skin appearance, histological features, keratinocyte death modalities, infiltration of immune cells, and levels of some inflammatory cytokines between Gsdme −/− mice and wild type (WT) mice after UVB exposure. We explored whether keratinocytes contribute to GSDME deficiency-caused aggravation of UVB-induced skin inflammation in GSDME knockdown keratinocyte cultured in vitro and keratinocyte-specific Gsdme conditional knockout mice. We used anti-Ly6G antibody to deplete neutrophils and explore their role in UVB-caused skin damage. Skin damage and neutrophils infiltration were aggravated in UVB-challenged Gsdme −/− mice, compared with UVB-challenged WT mice. Apoptosis and necroptosis, which were initiated together with GSDME-mediated pyroptosis in UVB-challenged WT mice, were not enhanced in UVB-challenged Gsdme −/− mice. Neutrophils activation indicators and its recruiting cytokines were increased in skin tissue of UVB-challenged Gsdme −/− mice. However, GSDME knockdown did not lead to the further increase of mRNA and secretion of TNF-α and IL-6 in UVB-challenged keratinocytes. Skin damage was not aggravated in UVB-challenged Gsdme cKO mice. Neutrophils depletion alleviated UVB-caused skin damage in WT mice and Gsdme −/− mice, and eliminated its aggravation in Gsdme −/− mice. This study demonstrates that GSDME plays a restrictive role in UVB-induced skin damage through inhibiting excessive recruitment and activation of neutrophils in the immune microenvironment in UVB-caused skin inflammation. However, keratinocytes might not contribute to this restrictive function.

Summary: Metabolism plays a crucial role in B cell differentiation and function. GSDMA3 is related to mitochondrial metabolism and is involved in immune responses. Here, we used Gsdma3 KO mice to examine the effect of GSDMA3 on B cells. The results demonstrated that GSDMA3 deficiency reprogrammed B cell metabolism, evidenced by upregulating PI3K-Akt-mTOR signaling, along with elevated ROS reproduction and reduced maximal oxygen consumption rate in mitochondria. Moreover, the BCR signaling in the KO B cells was impaired. The reduced BCR signaling was associated with decreased BCR clustering, caused by inhibited activation of WASP. However, GSDMA3 deficiency had no effects on B cell development and functions in humoral immunity, which might be associated with the compensation of upregulated GSDMA2 expression and the fine balance between PI3K signaling and BCR signals interaction. Our observations reveal a previously unknown influence of GSDMA3 on B cells under physiological and immunized states.

Some epidemiological studies support a relationship between nickel exposure and diabetes in the general population. To address this, we tested the association of nickel exposure with diabetes in 10,890 adults aged ≥ 18 years old from the China National Human Biomonitoring study conducted in 2017–2018. Urinary nickel concentrations and fasting blood glucose (FBG) were measured, and lifestyle and demographic data were collected. Weighted logistic and linear regressions were used to estimate the associations of urinary nickel levels with diabetes prevalence and FBG. Restricted cubic splines (RCS) were used to test for the dose-response relationship. The odd ratio (95% confidence interval [CI]) of diabetes for the highest versus lowest quartiles of urinary nickel concentrations was 1.74 (1.28, 2.36) in the multivariate model (p trend =0.001). Each one-unit increase in log-transformed urinary nickel concentrations was associated with a 0.36 (0.17, 0.55) mmol/L elevation in FBG. The RCS curves showed a monotonically increasing dose-response relationship of urinary nickel with diabetes as well as FBG levels, and then tended to flatten after about 4.75 μg/L of nickel exposure. The nickel-diabetes association was stronger in individuals with lower than those with higher rice consumption (OR: 2.39 vs. 1.72). Our study supports a positive association between nickel exposure and diabetes prevalence in Chinese adults, especially in individuals with lower rice consumption. Further large-scale prospective studies are needed to validate our findings.

Abstract Aims/Introduction To explore the relationship between heart rate‐corrected QT (QTc) interval and diabetic peripheral neuropathy (DPN), and whether QTc interval has diagnostic utility for DPN beyond nerve conduction velocity. Materials and Methods A total of 965 patients with diabetes, including 473 patients with DPN and 492 patients without DPN, underwent standard 12‐lead electrocardiography and detailed assessments of peripheral neuropathy. Results Patients with DPN had longer QTc intervals than those without. Among participants, from the first to fourth quartile of QTc interval, the proportion of patients with DPN appreciably increased and the nerve conduction velocity obviously decreased (P for trend

Abstract Osmanthus fragrans is an important evergreen species with both medicinal and ornamental value in China. Given the low efficiency of callus proliferation and the difficulty of adventitious bud differentiation, tissue culture and regeneration systems have not been successfully established for this species. To understand the mechanism of callus proliferation, transcriptome sequencing and endogenous hormone content determination were performed from the initial growth stages to the early stages of senescence on O. fragrans calli. In total, 47,340 genes were identified by transcriptome sequencing, including 1798 previously unidentified genes specifically involved in callus development. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed genes (DEGs) was significantly enriched in plant hormone signal transduction pathways. Furthermore, our results from the orthogonal projections to latent structures discrimination analysis (OPLS-DA) of six typical hormones in five development stages of O. fragrans calli showed jasmonic acid (JA) could play important role in the initial stages of calli growth, whereas JA and auxin (IAA) were dominant in the early stages of calli senescence. Based on the weighted gene co-expression network analysis, OfSRC2, OfPP2CD5 and OfARR1, OfPYL3, OfEIL3b were selected as hub genes from the modules with the significant relevance to JA and IAA respectively. The gene regulation network and quantitative real-time PCR implied that during the initial stages of callus growth, the transcription factors (TFs) OfERF4 and OfMYC2a could down-regulate the expression of hub genes OfSRC2 and OfPP2CD5, resulting in decreased JA content and rapid callus growth; during the late stage of callus growth, the TFs OfERF4, OfMYC2a and OfTGA21c, OfHSFA1 could positively regulate the expression of hub genes OfSRC2, OfPP2CD5 and OfARR1, OfPYL3, OfEIL3b, respectively, leading to increased JA and IAA contents and inducing the senescence of O. fragrans calli. Hopefully, our results could provide new insights into the molecular mechanism of the proliferation of O. fragrans calli.

Background: The associations of legacy per- and polyfluoroalkyl substances (PFAS) with lipid metabolism are controversial, and there is little information about the impact of emerging PFAS (6:2 Cl-PFESA) on lipid metabolism in China. Objectives: We aimed to explore the associations of legacy and emerging PFAS with lipid profiles and dyslipidemia in Chinese adults. Methods: We included 10,855 Chinese participants aged 18 years and above in the China National Human Biomonitoring. The associations of 8 PFAS with 5 lipid profiles and 4 dyslipidemia were investigated using weighted multiple linear regression or weighted logistic regression, and the dose–response associations were investigated using restricted cubic spline model. Results: Among the 8 PFAS, the concentration of PFOS was the highest, with a geometric mean of 5.15 ng/mL, followed by PFOA and 6:2 Cl-PFESA, which were 4.26 and 1.63 ng/mL, respectively. Legacy (PFOA, PFOS, PFUnDA) or emerging (6:2 Cl-PFESA) PFAS were associated with lipid profiles (TC, LDL-C, HDL-C, non HDL-C) and dyslipidemia (high LDL-C, high TC, low HDL-C), and their effects on TC were most obvious. TC concentration increased by 0.595 mmol/L in the highest quartile (Q4) of PFOS when compared with the lowest quartile (Q1), (95 % CI:0.396, 0.794). Restricted cubic spline models showed that PFAS are nonlinearly associated with TC, non HDL-C, LDL-C and HDL-C, and that the lipid concentrations tend to be stable when PFOS and PFOA were > 20 ng/mL well as when the 6:2 Cl-PFESA level was > 10 ng/mL. The positive associations between PFAS mixtures and lipid profiles were also significant. Conclusions: Single and mixed exposure to PFAS were positively associated with lipid profiles, and China's unique legacy PFAS substitutes (6:2 Cl-PFESA) contributed less to lipid profiles than legacy PFAS. In the future, cohort studies will be needed to confirm our findings.

Abstract. Rosacea is a chronic inflammatory skin disease that primarily affects the centrofacial areas and mainly manifests as recurrent flushing and erythema. In recent years, there has been progress in the understanding of the diagnosis and treatment of rosacea. Therefore, a group of dermatological experts updated the guidelines based on the 2016 expert consensus statement on rosacea diagnosis and treatment in China. These new guidelines propose diagnostic criteria for rosacea at different sites to further standardize the diagnosis and treatment of rosacea in China.

Abstract. Objective:. Blocking mechanistic target of rapamycin (mTOR) activation with mTOR inhibitors has promising therapeutic potential for keloids. However, the precise mechanism of mTOR inhibitors remains unclear. This study was aimed to investigate the role of autophagy machinery in the anti-keloid effects of mTOR inhibitors. Methods:. We first validated the biological effects induced by the mTOR inhibitors rapamycin (100 nmol/L) and KU-0063794 (5 μmol/L) on the proliferation, apoptosis, migration, and collagen synthesis of keloid fibroblasts (KFs) derived from Han Chinese persons through a Cell Counting Kit-8 assay, 5-Bromo-2’-deoxyuridine incorporation, Annexin V/propidium iodide staining, migration, and western blotting. To explore whether autophagy machinery is involved in the anti-keloid effects of mTOR inhibitors, we first blocked the autophagy activation induced by rapamycin and KU-0063794 with a pharmacological autophagy inhibitor (wortmannin) or by silencing the key autophagy gene (ATG5), and we then re-evaluated these biological effects on KFs. Results:. Blocking mTOR activation with either rapamycin or KU-0063794 completely inhibited proliferation, migration, and collagen synthesis of primary KFs but did not affect apoptosis. Incubating KFs with the autophagy inhibitor wortmannin or performing ATG5 silencing abrogated the subsequent activation of autophagic activity induced by rapamycin (rapamycin + E-64d + pepstatin vs. rapamycin + wortmannin + E-64d + pepstatin: 1.88 ± 0.38 vs. 1.02 ± 0.35, F = 6.86, P = 0.013), (non-sense control + rapamycin vs. ATG5 small interfering RNA + rapamycin: 1.46 ± 0.18 vs. 0.75 ± 0.20, respectively; F = 7.68, P = 0.01) or KU-0063794 (KU-0063794 + E-64d + pepstatin vs. KU-0063794 + wortmannin + E-64d + pepstatin: 1.65 ± 0.35 vs. 0.76 ± 0.17, F = 10.01, P = 0.004), (NC + KU-0063794 vs. ATG5 small interfering RNA + KU-0063794: 1.59 ± 0.50 vs. 0.77 ± 0.09, F = 5.93, P = 0.02) as evidenced by decreased accumulation of LC3-II. However, blockage of autophagy induction in mTOR inhibitor-treated KFs with both methods did not disturb their anti-keloid effects, such as inhibition of cell viability, cell migration, and collagen synthesis (P > 0.05 each). Conclusion:. Blocking mTOR activation with the mTOR inhibitors rapamycin and KU-0063794 showed anti-keloid effects in KFs. Restoration of autophagy inhibition by mTOR inhibitors does not contribute to their anti-keloid effects.

Depressive symptoms have a significant impact on the quality-of-life among the oldest old (aged ≥ 80 years) in the population. Current research on the association of blood mercury with depressive symptoms has mainly targeted the general population. However, it is unclear whether this association is present in the oldest old. We used data from the Healthy Aging and Biomarker Cohort Study carried out in 2017–2018, with 1154 participants aged ≥ 80 years eligible for analysis. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to detect blood mercury (Hg) levels, while the CES-D10 depression scale was used to assess depressive symptoms. The association between blood mercury levels and depressive symptoms was investigated using log-binomial and Poisson regression models. We also used restricted cubic splines (RCS) to assess the linear or nonlinear association of blood mercury with depressive symptoms scores. The 1154 participants ranged in age from 80 to 120 years, while the geometric mean of blood mercury concentration was 1.01 μg/L. After adjustment for covariates, log-binomial and Poisson regression analyses revealed a statistically significant, positive association of blood mercury with depressive symptoms. In comparison to the first tertile, the adjusted relative risks of blood mercury and the presence of depressive symptoms in the second and third tertiles were 1.55 (1.20–1.99) and 1.45 (1.11–1.90), respectively. The RCS model showed a linear association between blood mercury level and depressive symptoms scores. In conclusion, among the oldest old, we demonstrated that blood mercury levels were positively associated with depressive symptoms. Further surveys, especially cohort studies and clinical trials are needed to confirm these results.

Miniaturized four-dimensional (4D) micro/nanorobots denote a forerunning technique associated with interdisciplinary applications, such as in embeddable labs-on-chip, metamaterials, tissue engineering, cell manipulation, and tiny robotics. With emerging smart interactive materials, static micro/nanoscale architectures have upgraded to the fourth dimension, evincing time-dependent shape/property mutation. Molecular-level 4D robotics promises complex sensing, self-adaption, transformation, and responsiveness to stimuli for highly valued functionalities. To precisely control 4D behaviors, current-laser-induced photochemical additive manufacturing, such as digital light projection, stereolithography, and two-photon polymerization, is pursuing high-freeform shape-reconfigurable capacities and high-resolution spatiotemporal programming strategies, which challenge multi-field sciences while offering new opportunities. Herein, this review summarizes the recent development of micro/nano 4D laser photochemical manufacturing, incorporating active materials and shape-programming strategies to provide an envisioning of these miniaturized 4D micro/nanorobots. A comparison with other chemical/physical fabricated micro/nanorobots further explains the advantages and potential usage of laser-synthesized micro/nanorobots.

Acer fabri is a widely distributed ornamental tree with colorful leaves and high ornamental value. Its young leaves change from red to red and green until turning fully green. To understand the mechanism of leaf color change, transcriptome sequencing and pigment content determination were performed in three stages during the leaf color change of A. fabri. In total, 53,550 genes, including 838 transcription factors (TFs), were identified by transcriptome sequencing. In addition, the results of orthogonal partial least squares-discriminant analysis (OPLS-DA) of three pigments in the three stages of leaf color development suggested that carotenoids played a major role in the process of leaf color change from red to red-green, whereas anthocyanins played an important role in the process of leaf color change from red to green. Based on weighted gene co-expression network analysis (WGCNA), Af0034384 (HSFB2A), Af0051627 (NMT1), and Af0052541 (THY-1) were selected as hub genes from characteristic modules with significant correlation between carotenoids and anthocyanins. The results of gene network regulation maps and real-time fluorescence quantitative PCR (qRT-PCR) showed that Af0010511 (NAC100) upregulated the expression of Af0034384 (HSFB2A), leading to an increase in carotenoid content and the gradual greening of leaves during the transition from red to green. However, during the transition from red to green leaves, Af0033232 (NAC83) and Af0049421 (WRKY24) downregulated the expression of Af0051627 (NMT1) and Af0052541 (THY-1), respectively, leading to a decrease in anthocyanin content and the complete greening of leaves. These results could provide new ideas for studying the molecular mechanism of leaf color change in A. fabri and other species.

A pioneer in laser material processing and super-resolution microsphere lens imaging, Prof. Lin Li’s achievements not only lead to advancing the scientific fields but also applications in our daily life.

Abstract. Objective:. The plant polyphenol resveratrol (3,4′,5-trihydroxystilbene) (RSV) has been proposed for use because of its protective effect on ultraviolet (UV)-induced skin disorders. In UVB-induced skin damage, cell autophagy and apoptosis have been approved to prevent the damage and to contribute to the cytoprotective role of RSV; however, the detailed mechanism remains unknown. So, we conducted this study to investigate the cytoprotective effects of RSV on UVB-irradiated human epidermal keratinocytes (HEKs) and its undergoing mechanisms. Methods:. Secretion of thirty-six inflammatory cytokines of HEKs induced by 50 mJ/cm2 UVB at 0, 12, 24, and 48 hours were detected by a human cytokine assay and the interleukin (IL)-8 protein level in the culture media were determined by ELISA. Next, HEKs were treated with or without 100 μmol/L RSV in the presence or absence of 50 mJ/cm2 UVB, and activator protein 1 and NF-κB-related proteins were measured by Western blot. Furthermore, cells exposed to UVB radiation were treated with apoptosis activators procaspase-activating compound 1 (PAC-1), apoptosis activator 2 (AA2) or RSV to investigate the effect of RSV on the percentage of apoptotic cells by flow cytometry. Then cells were treated with autophagy inhibitors LY294002, 3-methyladenine (3-MA) or RSV in the presence of UVB and chloroquine (CQ) to investigate the effect of RSV on autophagy through detecting microtubule-associated protein 1 light chain 3 (LC3) expression by western blot. Finally, the effect of LY294002, 3-MA, ATG5 siRNA, PAC-1, and AA2 on RSV-mediated reduction of IL-8 expression was determined by ELISA assay. Results:. RSV treatment decreased the secretion of IL-8 (UVB vs. UVB + RSV: [1454.05 pg/mL ± 52.95 pg/mL] vs. [553.68 pg/mL ± 206.03 pg/mL], P 0.05), whereas neither PAC-1 nor AA2 exerted similar effects. Conclusion:. RSV may regulate autophagic flux to inhibit IL-8 expression in UVB-challenged keratinocytes.

Abstract. Acne inversa/hidradenitis suppurativa is a chronic, recurrent, inflammatory skin disease that affects the pilosebaceous units, causinfollicular occlusion. The etiology and pathogenesis of acne inversa/hidradenitis suppurativa involves internal and external factors such as genetic susceptibility, inflammation and immunity, microorganisms, obesity, and smoking. acne inversa/hidradenitis suppurativa is difficult to treat, and the current aim of treatment is to control the frequency and duration of disease flares and improve the quality of life. Treatment protocols for acne inversa/hidradenitis suppurativa should be selected based on the disease severity grade. Medical treatments include antibiotics, retinoids, biologics, immunosuppressive agents, and antiandrogen agents. Adjuvant treatments include surgery and laser/light therapies. This consensus aims to further standardize the diagnosis and treatment procedures of acne inversa/hidradenitis suppurativa in China to facilitate its diagnosis and treatment.

Abstract Background CCR2 is involved in maintaining immune homeostasis and regulating immune function. This study aims to elucidate the mechanism by which CCR2 regulates B‐cell signalling. Methods In Ccr2‐knockout mice, the development and differentiation of B cells, BCR proximal signals, actin movement and B‐cell immune response were determined. Besides, the level of CCR2 in PBMC of SLE patients was analysed by bioinformatics. Results CCR2 deficiency reduces the proportion and number of follicular B cells, upregulates BCR proximal signalling and enhances the oxidative phosphorylation of B cells. Meanwhile, increased actin filaments aggregation and its associated early‐activation events of B cells are also induced by CCR2 deficiency. The MST1/mTORC1/STAT1 axis in B cells is responsible for the regulation of actin remodelling, metabolic activities and transcriptional signalling, specific MST1, mTORC1 or STAT1 inhibitor can rescue the upregulated BCR signalling. Glomerular IgG deposition is obvious in CCR2‐deficient mice, accompanied by increased anti‐dsDNA IgG level. Additionally, the CCR2 expression in peripheral B cells of SLE patients is decreased than that of healthy controls. Conclusions CCR2 can utilise MST1/mTORC1/STAT1 axis to regulate BCR signalling. The interaction between CCR2 and BCR may contribute to exploring the mechanism of autoimmune diseases.

Abstract Background Discordance between traditional cytogenetic and molecular cytogenetic tests is rare but not uncommon. The explanation of discordance between two genetic methods is difficult but especially important for genetic counseling, particularly for prenatal genetic diagnosis. Case presentation Two unrelated fetuses were diagnosed with cardiac defects by prenatal ultrasound examination, and invasive cordocentesis was performed to obtain cord blood samples for prenatal genetic diagnosis. For both fetuses, chromosomal microarray analysis (CMA) detected a novel approximately 27-Mb mosaic duplication with a high copy number of approximately six to seven copies on chromosome 8q24.1q24.3 that was not identified by karyotyping. To exclude artificial errors and validate laboratory detection results, multiple procedures including copy number variation sequencing, fluorescence in situ hybridization, and short tandem repeat and single-nucleotide polymorphism genotype comparison were performed, confirming the discordant results between CMA and karyotyping. The potential causes of discordance between CMA and karyotyping using fetal blood lymphocytes are discussed; we suggest that extrachromosomal DNA or cell-free DNA fragmentation originating from certain tumor tissues with 8q24.1q24.3 duplication might deserve further investigation. Conclusions This study may be helpful for prenatal evaluation and genetic counseling for subsequent patients with similar mosaic 8q24.1q24.3 duplications. Additionally, more cases and further research are needed to understand whether mosaic 8q24.1q24.3 duplication is associated with certain genetic disorders and to investigate the causes of discordance between molecular and morphological methods.

Abstract Background The surgical indications for liver hemangioma remain unclear. Methods Data from 152 patients with hepatic hemangioma who underwent hepatectomy between 2004 and 2019 were retrospectively reviewed. We analyzed characteristics including tumor size, surgical parameters, and variables associated with Kasabach–Merritt syndrome and compared the outcomes of laparoscopic and open hepatectomy. Here, we describe surgical techniques for giant hepatic hemangioma and report on two meaningful cases. Results Most (63.8%) patients with hepatic hemangioma were asymptomatic. Most (86.4%) tumors from patients with Kasabach–Merritt syndrome were larger than 15 cm. Enucleation (30.9%), sectionectomy (28.9%), hemihepatectomy (25.7%), and the removal of more than half of the liver (14.5%) were performed through open (87.5%) and laparoscopic (12.5%) approaches. Laparoscopic hepatectomy is associated with an operative time, estimated blood loss, and major morbidity and mortality rate similar to those of open hepatectomy, but a shorter length of stay. 3D image reconstruction is an alternative for diagnosis and surgical planning for partial hepatectomy. Conclusion The main indication for surgery is giant (> 10 cm) liver hemangioma, with or without symptoms. Laparoscopic hepatectomy was an effective option for hepatic hemangioma treatment. For extremely giant hemangiomas, 3D image reconstruction was indispensable. Hepatectomy should be performed by experienced hepatic surgeons.

Abstract. Atopic dermatitis (AD) is a common disease clinically characterized by chronic recurrent eczematous lesions, dry skin, and pruritus. AD can negatively impact patients’ quality of life. The prevalence of AD in China has been increasing during the past few decades. Based on the most recent advances in the treatment of AD, we updated the 2014 version of the Guidelines for Diagnosis and Treatment of Atopic Dermatitis in China regarding the definition, epidemiology, pathogenesis, clinical classification, diagnosis, prevention, and treatment of AD.

Long-term overall survival (OS) after liver resection for non-cirrhotic hepatocellular carcinoma (NCHCC) has been reported recently. The aim of this study was to review outcomes systematically and analyze risk factors for survival after surgical resection for HCC without cirrhosis. A literature search was performed of the PubMed and Embase databases for papers published between January 1995 and October 2012, which focused on hepatic resection for HCC without underlying cirrhosis. Cochrane systematic review methodology was used for this review. Outcomes were OS, operative mortality and disease-free survival (DFS). Pooled hazard ratios (HR) were calculated using the random effects model for parameters considered as potential prognostic factors. Totally, 26 retrospective case series were eligible for inclusion. The 1-, 3- and 5-year OS rate after surgical resection of NCHCC ranged from 62% to 100%, 46.3%–78.0%, and 30%–64%, respectively. The corresponding DFS rates ranged from 48.7% to 84%, 31.0%–66.0%, and 24.0%–58.0%, respectively. Five variables were related to poor survival: multiple tumors (HR 1.68, 95%CI 1.25–2.11); larger tumor size (HR 2.66, 95%CI 1.69–3.63); non-clear resection margin (R0 resection) (HR 3.52, 95%CI 1.63–5.42); poor tumor stage (HR 2.61, 95%CI 1.64–3.58); and invasion of the lymphatic vessels (HR 4.85, 95%CI 2.67–7.02). In sum, hepatic resection provides excellent OS rates for patients with NCHCC, and results have tended to improve recently. Risk factors for poor prognosis comprise multiple tumors, lager tumor size, non-R0 resection and invasion of the lymphatic vessels.

Abstract. Allergic contact dermatitis is a common clinical allergic disease. The patch test is the gold standard for finding and clarifying contact allergens. With the deepening understanding of the epidemiology, pathogenesis, and clinical manifestations of contact dermatitis, as well as the increased requirements for the standardized application of patch tests, the relevant consensus needs to be continuously updated. This consensus is updated on the basis of the version issued in 2015. In this revised version, it refines the selection of clinical indications, improves the judgment and interpretation of results, adds delayed detection and patient education, and so on, which aims to further standardize clinical applications and improve the value of patch test.

Abstract Objectives Both low vitamin D status and metabolic syndrome (MetS) are worldwide concerns, and low 25-hydroxyvitamin D [25(OH)D] levels are associated with MetS; however, related epidemiological evidence based on elderly Chinese individuals, especially those over 80 years of age, is limited. In the present study, we aimed to evaluate the association between serum 25(OH)D and MetS in elderly Chinese individuals. Method Serum 25(OH)D was measured in a cross-sectional sample of 2493 elderly people aged 65–112 years from eight areas of China in which the density of centenarians is exceptionally high. MetS was diagnosed according to blood pressure, lipid, and blood sugar levels; waist circumference; and body mass index (BMI). Adjusted multivariable logistic regression was used to analyze the associations between vitamin D and MetS based on different diagnostic criterias. Results A total of 890 (35.7%) of the recruited elderly individuals had insufficient levels of vitamin D, and 1029 participants (41.3%) were vitamin D deficient. High serum vitamin D concentrations were associated with a low prevalence of MetS according to the modified Adult Treatment Panel III (ATP III) criteria for adequate versus deficient vitamin D levels (OR: 0.63, 95% CI: 0.45, 0.88) and inadequate versus deficient vitamin D levels (OR: 0.70, 95% CI: 0.52, 0.92). Each 10 ng/ml increase in serum vitamin D was significantly associated with a decreased prevalence of MetS according to the modified ATP III criteria for people with normal waist circumference (WC) (OR: 0.55, 95% CI: 0.43,0.71). However, no significant statistical correlation was found among elderly people with a high WC. Additionally, in the analysis of the individual components, the ORs of adequate versus deficient vitamin D levels were 0.46 (95% CI: 0.30, 0.71) for elevated triglycerides and 0.64 (95% CI: 0.42, 0.97) for reduced high-density lipoprotein cholesterol (HDL-C) after adjustment for other components. Conclusions Vitamin D deficiency is very common among elderly Chinese individuals. Vitamin D deficiency may be a risk factor for MetS; however, the association was only statistically significant among elderly people with noncentral obesity. Further studies are needed to examine the causal direction of the association.

Abstract. Objective:. Genital chlamydial infection is a globally common sexually transmitted infection caused by Chlamydia trachomatis. This study aimed to describe the epidemiological characteristics of the disease reported in China in 2019. Methods:. Genital chlamydial infection cases were identified in 105 national sexually transmitted disease surveillance sites from the National Notifiable Infectious Disease Reporting System, which covers 31 provinces, autonomous regions, and municipalities in Chinese mainland. Data were collected and used to calculate the overall incidence, and the incidences per surveillance site, province, sex, and age group. Results:. In 2019, there were 50,874 new cases of genital chlamydial infection reported in China, corresponding to an incidence of 55.32 cases per 100,000 population, and comprising a 9.98% increase from 2018 (50.30 cases per 100,000 population). The highest incidences of genital chlamydial infection occurred in Zhejiang, Guangdong province, Guangxi autonomous region, and Hainan province (average 137.49–233.37 cases per 100,000 population). The incidence of genital chlamydial infection was much higher in females than males, with a female-to-male ratio of 3.09 (84.55 per 100,000 population vs 27.35 per 100,000 population). The highest incidence of genital chlamydial infection was reported in the 20–24-year age group (184.70 cases per 100,000 population), followed by the 25–29-year age group (180.79 cases per 100,000) and 30–34-year age group (151.53 cases per 100,000 population). The highest proportion (68.30%) of genital chlamydial infection was reported from general hospitals, followed by maternal and child health hospitals (25.59%). Conclusion:. The incidence rate of genital chlamydial infection in 2019 has an increase trend from 2018 and be a common sexually transmitted infection in China. The incidence is much higher in females than in males. Sexually active young adults are the highest risk population. There is substantial geographic diversity in incidence, with the highest incidence occurring in the southeast coastal areas with a developed economy. Epidemic of genital chlamydial infection in China should be concerned, and its surveillance needs to be improved.

Abstract. Biologic drugs have been increasingly used in the treatment of psoriasis and are especially favorable for severe, recalcitrant, and special-type cases. Therefore, appropriate, effective, and safe use of biologic drugs has drawn attention from dermatologists. For this purpose, Chinese experts majoring in psoriasis analyzed domestic and international research data, summarized current clinical experiences, investigated features of Chinese patients with psoriasis, and finally formulated the present consensus, which provides detailed guidances to clinicians in terms of the principles and methods of the application of biologics, the efficacy and safety profile, patient screening and monitoring, main adverse events and corresponding solutions, and precautions for special patient populations.

Abstract. Objective:. To describe the epidemiological characteristics of leprosy in China in 2018 and provide the essential evidences for leprosy control. Methods:. We collected data of leprosy cases nationwide from Leprosy Management Information System in China (LEPMIS) except Hong Kong, Macao, and Taiwan. And then we performed a descriptive and comparative analysis. Results:. A total of 521 new leprosy cases were detected nationwide in 2018, with a case detection rate of 0.037/100,000. The proportion of children under 15 years of age, multi-bacillary (MB) cases, and cases with WHO grade 2 disability (G2D) were 1.3%, 89.4%, and 19.0%, respectively. There were 2,479 registered cases of leprosy in China by the end of 2018, accounting for a prevalence rate of 0.178/100,000, with 43 replase cases. Southwest China separately accounted for 312/521 (59.9%) newly detected cases and 1180/2479 (47.6%) registered cases of leprosy in China. Conclusion:. China is a low endemic country for leprosy and the detection rate was much lower than the global average. Southwest China is still the key regions for leprosy control, including Yunnan, Guizhou, and Sichuan. In addition, leprosy in low endemic provinces also needs to be focused.

Cryotherapy is one of the most common treatments for warts; however, pain during treatment and relatively high recurrence rates limit its use. Local hyperthermia has also been used successfully in the treatment of plantar warts. The aim of this study was to compare the clinical effectiveness of local hyperthermia vs cryotherapy for the treatment of plantar warts. This multi- centre, open, 2-arm, non-randomized concurrent controlled trial included 1,027 patients, who received either cryotherapy or local hyperthermia treatment. Three months after treatment, local hyperthermia and cryotherapy achieved complete clearance rates of 50.9% and 54.3%, respectively. Recurrence rates were 0.8% and 12%, respectively. Pain scores during local hyperthermia were significantly lower than for cryotherapy. Both local hyperthermia and cryotherapy demonstrated similar efficacy for clearance of plantar warts; while local hyperthermia had a lower recurrence rate and lower pain sensation during treatment.

The study of mental workload has attracted much interest in neuroergonomics, a frontier field of research. However, there appears no consensus on how to measure mental workload effectively because the mental workload is not only regulated by task difficulty but also affected by individual skill level reflected as mental schema. In this study, we investigated the alterations in the functional brain network induced by a 10-day simulated piloting task with different difficulty levels. Topological features quantifying global and local information communication and network organization were analyzed. It was found that during different tests, the global efficiency did not change, but the gravity center of the local efficiency of the network moved from the frontal to the posterior area; the small-worldness of the functional brain network became stronger. These results demonstrate the reconfiguration of the brain network during the development of mental schema. Furthermore, for the first two tests, the global and local efficiency did not have a consistent change trend under different difficulty levels, but after forming the developed mental schema, both of them decreased with the increase in task difficulty, showing sensitivity to the increase in mental workload. Our results demonstrate brain network reconfiguration during the motor learning process and reveal the importance of the developed mental schema for the accurate assessment of mental workload. We concluded that the efficiency of the brain network was associated with mental workload with developed mental schema.

Background: Metals can be either toxic or essential to health, as they play different role in oxidative stress and metabolic homeostasis during the ageing process. Population-based biomonitoring have documented levels and ranges in concentrations among general population of 0–79 years of age. In people aged 80 and above, toxic metals and essential metals may have different risk profiles, and thus need to be better studied. Objective: Our aim is to investigate concentrations of toxic metals (arsenic, cadmium, lead and mercury) and essential metals (chromium, cobalt, molybdenum, manganese, nickel and selenium) and their role in diseases, nutritional status among younger elderly, octogenarians, nonagenarians and centenarians. Methods: A total of 932 younger elderly, 643 octogenarians, 540 nonagenarians, 386 centenarians were included from the cross-sectional Healthy Aging and Biomarkers Cohort Study in 2017–2018. Blood or urine biological substrates were collected from each participant to determine the concentrations of toxic metals and essential metals by inductively coupled plasma mass spectrometry. Random forest was constructed to rank the importance of toxic metals and essential metals in longevity. LASSO penalized regressions were performed to select the most significant metals associated with diseases and nutritional status, of which simultaneously included all metals and adjusted for the confounding factors. Results: Compared to women, we found higher biomarker concentrations in men for toxic metals (41.2 µg/L vs 34.4 µg/L for blood lead, 1.56 µg/L vs 1.19 µg/L for blood mercury) and lower concentration of essential metals (0.48 µg/L vs 0.58 µg/L for blood molybdenum, 10.0 µg/L vs 11.1 µg/L for blood manganese). These factors may contribute to gender difference observed in longevity, that women live longer than men. Blood lead and urine cadmium tended to increase with age (P

Background: It remains unsolved that whether blood uric acid (UA) is a neuroprotective or neurotoxic agent. This study aimed to evaluate the longitudinal association of blood UA with mild cognitive impairment (MCI) among older adults in China.Methods: A total of 3,103 older adults (aged 65+ years) free of MCI at baseline were included from the Healthy Aging and Biomarkers Cohort Study (HABCS). Blood UA level was determined by the uricase colorimetry assay and analyzed as both continuous and categorical (by quartile) variables. Global cognition was assessed using the Mini-Mental State Examination four times between 2008 and 2017, with a score below 24 being considered as MCI. Cox proportional hazards models were used to examine the associations.Results: During a 9-year follow-up, 486 (15.7%) participants developed MCI. After adjustment for all covariates, higher UA had a dose-response association with a lower risk of MCI (all Pfor trend < 0.05). Participants in the highest UA quartile group had a reduced risk [hazard ratio (HR), 0.73; 95% (CI): 0.55–0.96] of MCI, compared with those in the lowest quartile group. The associations were still robust even when considering death as a competing risk. Subgroup analyses revealed that these associations were statistically significant in younger older adults (65–79 years) and those without hyperuricemia. Similar significant associations were observed when treating UA as a continuous variable.Conclusions: High blood UA level is associated with reduced risks of MCI among Chinese older adults, highlighting the potential of managing UA in daily life for maintaining late-life cognition.

Research in metal matrix composites (MMCs) indicates that superior mechanical properties may be achieved by embedding reinforcement materials. However, the development of new composite powder for additive manufacturing requires an in-depth understanding of its key characteristics prior to its use in the fabrication process. This paper focuses on the low-energy ball milling (LEBM) of aluminium 2024 alloy (AA2024) reinforced with graphene nanoplatelets (GNPs). The main aim is to investigate the effect of the milling time (from 0.5 to 16 h) on the morphology and flowability of the powder. The study shows that, while short milling times (under 2 h) could not break the Van der WaRals forces between nanoparticles, GNPs were well separated and sufficiently covered the powder surface after 4 h of milling, thanks to the continuously applied impact energy. Longer milling time provides increasingly similar flowability results, confirmed by both the experimental work and discrete element model (DEM) simulations. Moreover, the ball milling process decreases the crystallite size of the milled powder by 24%, leading to a 3% higher microhardness. Lastly, the surface energy of the powder was determined as 1.4 mJ/m2 by DEM, using the angle of repose of the as-received powder from experimental work.

Identifying the mechanisms underlying unexplained recurrent spontaneous abortion (URSA) can help develop effective treatments. This study provides novel insights into the biological characteristics and related pathways of differentially expressed genes (DEGs) in URSA. Nineteen patients with URSA and three healthy fertile women with regular menstruation (control group) were recruited. RNA was extracted from the two groups to determine the differential expression of immunoregulatory gene sequences. Gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the biological functions and pathways of the identified DEGs. A protein-protein interaction (PPI) network was constructed using the STRING database. Furthermore, qRT-PCR and ELISA were performed to validate the differential expression of the hub genes. We also explored the regulatory mechanism of Th1/Th2 imbalance. A total of 99 DEGs were identified, comprising 94 upregulated and five downregulated genes. Through GO analysis, nine immune cell function-related clusters were selected, and genes with significant differential expression were primarily enriched in eight immune regulatory functions related to the KEGG signalling pathway. Subsequently, five hub genes (TLR2, CXCL8, IFNG, IL2RA, and ITGAX) were identified using Cytoscape software; qRT-PCR confirmed the differential expression among the hub genes, whereas ELISA revealed a significant difference in extracellular IFN-γ and IL-8 levels. The levels of Th1 (IFN-γ) and the Th1/Th2 ratio were higher in the peripheral blood of URSA patients than in control group patients. These findings suggest that the occurrence of URSA may be associated with the abnormal expression of some specific immunoregulatory genes involved in T-cell activation and differentiation. Among the identified DEGs, IFNG may play a key role in regulating maternal immune response. Although further validation is required, our data provide an important theoretical basis for elucidating the pathogenesis of recurrent spontaneous abortion.

Purpose: This study aims to identify genetic lesions in patients with congenital heart disease (CHD) with or without other phenotypes. In this study, over 400 patients were recruited and several novel variants in known causative genes were identified. A Chinese patient clinically diagnosed with HHS (patent ductus arteriosus, persistent left superior vena cava, and congenital absence of left arm radius) was included in the study cohort.Methods: Targeted, whole exome, and Sanger sequencing were performed to identify genetic lesions. The effects of the variant on ACTL6A RNA and protein were assessed using bioinformatics analysis.Results: At the start of the study, no mutations in known and candidate causative genes associated with CHD were identified. Seven years later, we noticed craniofacial deformities and identified a de novo heterozygous deletion variant in ACTL6A (NM_004301, c.478_478delT; p.F160Lfs*9). Intellectual disability and short stature were identified by a follow-up visit 10 years later. This variant leads to frameshift sequences and a premature termination codon and may affect the features of proteins. According to the nonsense-mediated mRNA decay theory, this variant may induce the decay of ACTL6A mRNA in patients.Conclusion: Our study reported the first ACTL6A variant in a Chinese individual, providing further evidence that ACTL6A is involved in heart and upper limb skeletal and intellectual development, thereby expanding the spectrum of ACTL6A variants. Thus, mutation analysis of the ACTL6A gene should be considered in patients with BAF-opathies or heart-hand syndromes due to potential misdiagnosis. Craniofacial dysmorphisms and intellectual disability are key to distinguishing these two diseases clinically, and attention to developmental delay/intellectual disability and craniofacial deformities will contribute to the diagnosis of BAF-opathies.

Charcot neuroarthropathy is a systemic disease with pathological changes in the musculoskeletal system, which leads to fractures, dislocations, and deformities involving multiple bones and joints, particularly those of the feet. While the common underlying cause of Charcot neuroarthropathy is diabetes mellitus, it is also associated with congenital insensitivity to pain (CIP). CIP is a rare disorder caused by loss-of-function mutations in SCN9A encoding Nav1.7. In this study, we report a patient with CIP from a consanguineous family susceptible to Charcot neuroarthropathy with a novel SCN9A mutation. This report involves the case of a middle-aged man who suffered from CIP, had repeated painless fractures, and developed bone and joint destruction. The physical and radiological examinations revealed that multiple joints were swollen and deformed, and soft-tissue trauma was evident. We identified a novel homozygous SCN9A mutation (p.Cys1339Arg) by whole-exome sequencing (WES), which was verified using Sanger sequencing. In addition, the wild-type (WT) and mutated p. Cys1339Arg were assessed in HEK293 cells expressing Nav1.7, and the results showed that p. Cys1339Arg almost abolished the Nav1.7 sodium current. In conclusion, Charcot neuroarthropathy associated with CIP demonstrated a wider spectrum of Charcot neuroarthropathy than was previously recognized or documented. In addition, this finding is conducive to understanding the critical amino acids for maintaining the function of Nav1.7, thus contributing to the development of Nav1.7-targeted analgesics.

Abstract. The SARS-CoV-2 infection has brought a great challenge in prevention and control of the national epidemic of coronavirus disease 2019 (COVID-19) in China. During the COVID-19 epidemic, properly carrying out pre-examination and triage for patients with skin lesions and fever has become a practical problem encountered in hospitals for skin diseases and dermatology clinics in general hospitals. Some of the carriers of the SARS-CoV-2 and patients with COVID-19 in the early stage may not present with any symptoms of COVID-19, while certain other skin diseases can also cause fever. Therefore, to properly deal with the patients presenting at dermatology clinics, the Chinese Society of Dermatology organized experts to formulate principles and procedures for the pre-examination and triage of patients at dermatology clinics during the COVID-19 epidemic.