3D-printed PCL framework assembling ECM-inspired multi-layer mineralized GO-Col-HAp microscaffold for in situ mandibular bone regeneration.

BACKGROUND: In recent years, natural bone extracellular matrix (ECM)-inspired materials have found widespread application as scaffolds for bone tissue engineering. However, the challenge of creating scaffolds that mimic natural bone ECM's mechanical strength and hierarchical nano-micro-macro structures remains. The purposes of this study were to introduce an innovative bone ECM-inspired scaffold that integrates a 3D-printed framework with hydroxyapatite (HAp) mineralized graphene oxide-collagen (GO-Col) microscaffolds and find its application in the repair of mandibular bone defects. METHODS: Initially, a 3D-printed polycaprolactone (PCL) scaffold was designed with cubic disks and square pores to mimic the macrostructure of bone ECM. Subsequently, we developed multi-layer mineralized GO-Col-HAp microscaffolds (MLM GCH) to simulate natural bone ECM's nano- and microstructural features. Systematic in vitro and in vivo experiments were introduced to evaluate the ECM-inspired structure of the scaffold and to explore its effect on cell proliferation and its ability to repair rat bone defects. RESULTS: The resultant MLM GCH/PCL composite scaffolds exhibited robust mechanical strength and ample assembly space. Moreover, the ECM-inspired MLM GCH microscaffolds displayed favorable attributes such as water absorption and retention and demonstrated promising cell adsorption, proliferation, and osteogenic differentiation in vitro. The MLM GCH/PCL composite scaffolds exhibited successful bone regeneration within mandibular bone defects in vivo. CONCLUSIONS: This study presents a well-conceived strategy for fabricating ECM-inspired scaffolds by integrating 3D-printed PCL frameworks with multilayer mineralized porous microscaffolds, enhancing cell proliferation, osteogenic differentiation, and bone regeneration. This construction approach holds the potential for extension to various other biomaterial types.

Factors Associated with Acute Pulmonary Embolism in Patients with Hypoxia After off-Pump Coronary Artery Bypass Grafting: A Case-Control Study.

Purpose: This study aims to explore the factors linked to the occurrence of acute pulmonary thromboembolism (PE) within a cohort of patients exhibiting hypoxic saturation (oxygen saturation levels falling below 93%), subsequent to undergoing off-pump coronary artery bypass grafting (OPCABG). Methods: A retrospective case-control study was conducted. A total of 296 patients met the inclusion and exclusion criteria, divided into PE group (100 cases) and non-PE group (196 cases) according to whether they had PE or not. The preoperative and postoperative information of patients were collected and statistically analyzed. Results: The results from a multivariate logistic regression analysis indicated the following factors were independently linked to PE following OPCABG: history of smoking (OR = 3.019, 95% CI, 1.437-6.634, P = 0.004), preoperative arterial oxygen partial pressure ≤78.9 mmHg (OR = 3.686, 95% CI, 1.708-8.220, P = 0.001), presence of postoperative lower extremity deep venous thrombosis (OR = 4.125, 95% CI, 1.886-9.310, P < 0.001), elevated postoperative D-dimer levels >6.76 mg/l (OR = 8.078, 95% CI, 3.749-18.217, P<0.001), postoperative NT-BNP levels (OR = 1.001, 95% CI: 1.000-1.001, P = 0.011), and elevated postoperative pulmonary arterial pressure >33.0 mmHg (OR = 10.743, 95% CI: 3.422-37.203, P < 0.001). The developed nomogram exhibited a high predictive accuracy with an area under the curve of 0.913 (95% CI: 0.878-0.948). Conclusion: When patients have a history of preoperative smoking, decreased preoperative arterial oxygen pressure, postoperative lower limb DVT, increased postoperative pulmonary artery pressure, and elevated postoperative D-Dimer and NT pro-BNP levels, it is recommended to take perioperative preventive measures, timely diagnostic evaluation, and if necessary, anticoagulant treatment. In addition, the results of this study may improve the diagnostic sensitivity of medical staff for postoperative PE in OPCABG, thereby increasing the detection rate and potentially reducing the need for excessive medical imaging procedures.

Dual cation-modified hierarchical nickel hydroxide nanosheet arrays as efficient and robust electrocatalysts for the urea oxidation reaction.

The rational modification of electronic structures to create catalytically active sites has been proved to be a promising strategy to efficiently facilitate the urea oxidation reaction (UOR). Herein, a well-defined nanosheet arrays catalyst of Ni(OH)2 doped with dual cations of Co and Mn on Ni foam (NF) (Co/Mn-Ni(OH)2) is synthesized through a simple hydrothermal process. Benefiting from the advantages of unique structures and modified binding strengths, it is found experimentally that the obtained Co/Mn-Ni(OH)2 catalyst only requires a potential of 1.38 V to deliver a current density of 100 mA cm-2 and exhibits a small Tafel slope of 35 mV dec-1, outperforming single-component-incorporated Ni(OH)2. Moreover, the catalyst has shown excellent stability for 25 h at a current density of 50 mA cm-2. Additionally, first-principles calculations demonstrate that the co-incorporation of Co and Mn remarkably lowers the adsorption barrier of CO(NH2)2* on the catalyst surface, and accelerates the dissociation of the CO(NH2)2* intermediate into CO* and NH* intermediates, which synergistically improve the UOR reaction kinetics. This work provides a generic paradigm for designing advanced and effective catalysts toward the UOR.

A phase I dose-finding trial of hyperthermic intraperitoneal docetaxel combined with cisplatin in patients with advanced-stage ovarian cancer.

OBJECTIVE: To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m²) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. METHODS: In this phase I trial, a time-to-event Bayesian optimal interval design was used. Docetaxel was given at a starting dose of 60 mg/m² and was increased in 5 mg/m² increments until the MTD was determined or the maximum dose level of 75 mg/m² was reached. The dose-limiting toxicity (DLT) rate was set at 25%, with a total sample size of 30 patients. HIPEC was delivered immediately following debulking surgery at a target temperature of 43°C for 90 minutes. RESULTS: From August 2022 to November 2022, 30 patients were enrolled. Among the patients who received a dose of docetaxel ≤65 mg/m², no DLT was reported. DLTs were observed in one patient who received 70 mg/m² docetaxel (grade 3 anaemia) and in three patients who received 75 mg/m² docetaxel (one case of grade 3 anaemia, one case of grade 3 hepatic impairment and one case of grade 4 thrombocytopenia). Patients treated with docetaxel 75 mg/m² in combination with cisplatin 75 mg/m² had an estimated DLT rate of 25%, which was the closest to the target DLT rate and was therefore chosen as the MTD. CONCLUSION: Docetaxel, in combination with a fixed dose of cisplatin (75 mg/m²), can be used safely at intraperitoneal doses of 75 mg/m² in ovarian cancer patients who received HIPEC (43°C, 90 minutes) following debulking surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05410483.

Determining the maximum tolerated dose of paclitaxel combined with fixed dose of cisplatin for hyperthermic intraperitoneal chemotherapy in ovarian cancer: A multicenter phase I trial.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of paclitaxel combined with a fixed dose of cisplatin (75 mg/m2) delivered via hyperthermic intraperitoneal chemotherapy (HIPEC) to patients with ovarian cancer. METHODS: This multicenter Phase I trial employed a Bayesian Optimal Interval (BOIN) design. The MTD was determined to have a target dose-limiting toxicity (DLT) rate of 25%. The starting dose was 175 mg/m2. The Data and Safety Monitoring Board made decisions regarding dose escalation or de-escalation in increments of 25 mg/m2 for subsequent patient cohorts, up to a maximum sample size of 30 or 12 patients treated at a given dose. RESULTS: Twenty-one patients participated in this study. Among the three evaluable patients who received 150 mg/m2 paclitaxel, no DLTs were observed. Among the 12 evaluable patients who received 175 mg/m2 paclitaxel, two reported DLTs: one had grade 4 neutropenia and one had grade 4 anemia, neutropenia, and leukopenia. Four of the six evaluable patients who received 200 mg/m2 paclitaxel reported DLTs: one patient had grade 4 diarrhea, one had grade 3 kidney injury, and two had grade 4 anemia. The isotonic estimate of the DLT rate in the 175 mg/m2 dose group was 0.17 (95% confidence interval, 0.02-0.42), and this dose was selected as the MTD. CONCLUSION: Paclitaxel, when combined with a fixed dose of cisplatin (75 mg/m2), can be safely administered intraperitoneally at a dose of 175 mg/m2 in patients with ovarian cancer who received HIPEC (43 °C, 90 min) following cytoreductive surgery.

In situ fabrication of a 3D self-supported porous Ni-Mo-Cu catalyst for an efficient hydrogen evolution reaction.

It is still a challenge to develop very effective and stable non-noble catalysts for the hydrogen evolution reaction (HER). Here, a self-supported porous Ni-Mo-Cu coating is prepared by the dynamic hydrogen bubble template (DHBT) method. This three-dimensional (3D) porous Ni-Mo-Cu coating can offer a large surface area, which helps expose more active sites and promote the transmission of electrons and materials. To achieve this, the 3D porous Ni-Mo-Cu coating catalyst requires a low overpotential value of 70 mV at 10 mA cm-2 in 1 M KOH and stable catalytic properties at a high current density of 500 mA cm-2 for more than 10 h with no obvious evidence of degradation. DFT calculations show the source of the excellent catalytic performance of the 3D porous Ni-Mo-Cu catalyst in alkaline media, including the kinetic energy and adsorption energy. This work provides significant insight into the design of efficient 3D porous materials.

Image classification of hyperspectral remote sensing using semi-supervised learning algorithm.

Hyperspectral images contain abundant spectral and spatial information of the surface of the earth, but there are more difficulties in processing, analyzing, and sample-labeling these hyperspectral images. In this paper, local binary pattern (LBP), sparse representation and mixed logistic regression model are introduced to propose a sample labeling method based on neighborhood information and priority classifier discrimination. A new hyperspectral remote sensing image classification method based on texture features and semi-supervised learning is implemented. The LBP is employed to extract features of spatial texture information from remote sensing images and enrich the feature information of samples. The multivariate logistic regression model is used to select the unlabeled samples with the largest amount of information, and the unlabeled samples with neighborhood information and priority classifier discrimination are selected to obtain the pseudo-labeled samples after learning. By making full use of the advantages of sparse representation and mixed logistic regression model, a new classification method based on semi-supervised learning is proposed to effectively achieve accurate classification of hyperspectral images. The data of Indian Pines, Salinas scene and Pavia University are selected to verify the validity of the proposed method. The experiment results have demonstrated that the proposed classification method is able to gain a higher classification accuracy, a stronger timeliness, and the generalization ability.

Postoperative subacute static progressive stretch does not increase the risk of distal lower limb venous thromboembolism.

PURPOSE: Static progressive stretch (SPS) can be applied to treat chronic joint stiffness. However, the impacts of subacute application of SPS to the distal lower limbs, where deep vein thrombosis (DVT) is common, on venous thromboembolism remain unclear. This study aims to explore the risk of venous thromboembolism events following subacute application of SPS. METHODS: A retrospective cohort study was conducted on patients diagnosed with DVT following a lower extremity orthopedic surgery before being transferred to the rehabilitation ward from May 2017 to May 2022. Patients with unilateral lower limb comminuted para-articular fractures, transferred to rehabilitation ward for further treatment within 3 weeks after operation, followed up more than 12 weeks since initial manual physiotherapy, and diagnosed DVT by ultrasound before rehabilitation course were included in the study. Patients with polytrauma, without evidence of previous peripheral vascular disease or incompetence, had medication for thrombosis treatment or prophylaxis before the operation, detected with paralysis due to nervous system impairment, infected after operation during the regime, or with acute progression of DVT were excluded. The included patients were randomized to the standard physiotherapy and the SPS integrated groups for observation. Associated DVT and pulmonary embolism data were collected during the physiotherapy course to compare the groups. SSPS 28.0 and GraphPad Prism 9 were used for data processing. A p < 0.05 was set significant difference. RESULTS: In total of 154 patients with DVT participating in this study, 75 of them were treated with additional SPS for postoperative rehabilitation. The participants in the SPS group showed improved range of motion (12.3° ± 6.7°). However, in the SPS group, there was no difference in thrombosis volume between the start and termination (p = 0.106, p = 0.787, respectively), although difference was seen intra-therapy (p < 0.001). Contingency analysis revealed the pulmonary embolism incidence (OR = 0.703) in the SPS group compared to the mean physiotherapy. CONCLUSION: The SPS technique is a safe and reliable option to prevent potential joint stiffness without aggravating the risk of distal DVT for postoperative patients suffering from relevant trauma.

Asymmetric and zwitterionic Blatter diradicals.

Asymmetric diradical molecular systems with different resonance mechanisms are largely unexplored. Herein, two conjugated asymmetric diradicals with Blatter and phenoxyl moieties (pBP and mBP) have been synthesized and studied in depth. A complete set of spectroscopic, X-ray crystallographic and magnetic techniques, together with quantum chemical calculations, have been used. The para-isomer (pBP) bears diradical and zwitterionic resonant forms, the latter by a electron delocalization mechanism, which are synergistically integrated by a sequence of nitrogen, provided by the Blatter moiety imine and amine (of different acceptor nature). In the meta-isomer (mBP), the zwitterionic form promoted in pBP by the lone-pair electron of the amine nitrogen is not available, yet it possesses a pseudo-hyperconjugation effect where the N lone pair mediates in a bonding coupling in a counter homolytic bond scission mechanism. Both electronic effects converge to promote medium diradical characters and narrow singlet-triplet gaps to the two electronic isomers. All these aspects delineate the subtle balance that shapes the electronic structure of open-shell molecules, which is even more challenging in the case of asymmetric systems, such as those described here with asymmetric phenoxyl-Blatter diradicals.

Fas/FasL and Complement Activation are Associated with Chronic Active Epstein-Barr Virus Hepatitis.

Background and Aims: Chronic active Epstein-Barr virus hepatitis (CAEBVH) is a rare and highly lethal disease characterized by hepatitis and hepatomegaly. This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH. Methods: Ten patients with confirmed Epstein-Barr virus hepatitis infection were enrolled. The clinicopathological characteristics of these patients were summarized and analyzed. Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms. Lastly, immunohistochemical staining was employed to verify pathogenic mechanisms. Results: Clinical features observed in all Epstein-Barr virus hepatitis patients included fever (7/10), splenomegaly (10/10), hepatomegaly (9/10), abnormal liver function (8/10), and CD8+ T cell lymphopenia (6/7). Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver. Positive Epstein-Barr virus-encoded small RNA in-situ hybridization (EBER-ISH) of lymphocytes of liver tissues was noted. Whole exome sequencing indicated that cytotoxic T lymphocytes and the complement system were involved. The expression of CD8, Fas, FasL, and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls (p<0.05). Lastly, Complement 1q and complement 3d expression, were higher in CAEBVH patients relative to controls (p<0.05). Conclusions: CAEBVH patients developed fever, hepatosplenomegaly, and lymphadenopathy. Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity. Fas/FasL and complement activation were involved in CAEBVH patients.

Acceleration of melanocyte senescence by the proinflammatory cytokines IFNγ and TNFα impairs the repigmentation response of vitiligo patients to narrowband ultraviolet B (NBUVB) phototherapy.

Vitiligo is a chronic autoimmune disease characterized by the T helper 1 (Th1) cytokine-driven immune destruction of melanocytes (MCs). Although narrowband ultraviolet B (NBUVB) phototherapy has been proven to be an effective therapeutic option, the repigmentation response to that phototherapy varies greatly in different vitiligo patients. Here, we demonstrate that there is an increase of NBUVB-induced cellular senescence in vitiligo MCs exposed to Th1 cytokine interferon γ (IFNγ) and/or tumor necrosis factor α (TNFα) in lesional vitiligo skin from poor responders who had undergone NBUVB phototherapy. Supplementation with exogenous recombinant human stem cell factor (rhSCF) in the culture medium as well as the lentiviral vector-mediated overexpression of cKIT could prevent the MCs from the IFNγ/TNFα-accelerated cellular senescence. Mechanistic studies indicated that the reduced ratio of membrane-bound KIT (mKIT) to the soluble form of KIT (sKIT) is directly related to the cellular senescence of vitiligo MCs following exposure to IFNγ and TNFα. Furthermore, the matrix metalloprotease 9 (MMP9) inhibitor GM6001 attenuates the production of sKIT via the suppression of cKIT ectodomain shedding. Altogether, our study indicates that the presence of Th1 cytokines IFNγ and/or TNFα in the epidermal milieu might impair the repigmentation response of vitiligo patients to NBUVB phototherapy.

Bioinformatics analysis of differentially expressed genes in diabetic foot ulcer and preliminary experimental verification.

Background: Molecular changes are closely related to the pathogenesis and healing process of diabetic foot ulcers (DFUs), and are crucial for the early prediction and intervention of DFU. Methods: Bioinformatics analysis was performed in this study to identify the key differentially expressed genes (DEGs) in DFU, analyze their functions and function modes, and conduct preliminary experimental verification to determine the potential pivotal genes in the pathogenesis of DFU. Two datasets, GSE68183 and GSE80178, were obtained from the Gene Expression Omnibus (GEO). DEGs were obtained using GEO2R. Six co-expressed DEGs (co-DEGs) were obtained by R language analysis. The co-DEGs were constructed by using STRING and Cytoscape 3.7.2 to construct a protein-protein interaction (PPI) network, and two hub genes, NHLRC3 and BNIP3, were identified. The BNIP3 gene was selected for further analysis. Co-DEGs were used for Gene Ontology (GO) function analysis using the WebGestalt database, and BNIP3-related biological processes focused on mitochondrial protein decomposition. GO function analysis of the BNIP3 gene and its interacting genes was carried out using the cluster profile package and org.hs.eg. db package of the R language and its biological process was enriched in the cell response to external stimuli and autophagy. Results: BNIP3 and its interacting genes were retrieved from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and KEGG pathway enrichment analysis was performed using the WebGestalt database. The results showed that BNIP3 was significantly correlated with mitochondrial autophagy and the FoxO signaling pathway. The miRDB and TargetScan databases were used to identify the relevant microRNAs (miRNAs) regulating the BNIP3 gene, and it was found that miRNA-182 may be involved in the targeted regulation of BNIP3. Western blot analysis was performed to determine the abnormal expression of BNIP3. Conclusions: Our study found that the BNIP3 gene may be a new biomarker and intervention target for DFU.

Postoperative subacute static progressive stretch does not increase the risk of distal lower limb venous thromboembolism / 中华创伤杂志(英文版)

PURPOSE@#Static progressive stretch (SPS) can be applied to treat chronic joint stiffness. However, the impacts of subacute application of SPS to the distal lower limbs, where deep vein thrombosis (DVT) is common, on venous thromboembolism remain unclear. This study aims to explore the risk of venous thromboembolism events following subacute application of SPS.@*METHODS@#A retrospective cohort study was conducted on patients diagnosed with DVT following a lower extremity orthopedic surgery before being transferred to the rehabilitation ward from May 2017 to May 2022. Patients with unilateral lower limb comminuted para-articular fractures, transferred to rehabilitation ward for further treatment within 3 weeks after operation, followed up more than 12 weeks since initial manual physiotherapy, and diagnosed DVT by ultrasound before rehabilitation course were included in the study. Patients with polytrauma, without evidence of previous peripheral vascular disease or incompetence, had medication for thrombosis treatment or prophylaxis before the operation, detected with paralysis due to nervous system impairment, infected after operation during the regime, or with acute progression of DVT were excluded. The included patients were randomized to the standard physiotherapy and the SPS integrated groups for observation. Associated DVT and pulmonary embolism data were collected during the physiotherapy course to compare the groups. SSPS 28.0 and GraphPad Prism 9 were used for data processing. A p < 0.05 was set significant difference.@*RESULTS@#In total of 154 patients with DVT participating in this study, 75 of them were treated with additional SPS for postoperative rehabilitation. The participants in the SPS group showed improved range of motion (12.3° ± 6.7°). However, in the SPS group, there was no difference in thrombosis volume between the start and termination (p = 0.106, p = 0.787, respectively), although difference was seen intra-therapy (p < 0.001). Contingency analysis revealed the pulmonary embolism incidence (OR = 0.703) in the SPS group compared to the mean physiotherapy.@*CONCLUSION@#The SPS technique is a safe and reliable option to prevent potential joint stiffness without aggravating the risk of distal DVT for postoperative patients suffering from relevant trauma.

Uncoupling melanogenesis from proliferation in epidermal melanocytes responding to stimulation with psoriasis-related proinflammatory cytokines.

BACKGROUND: Few studies have addressed the impact of the psoriasis-related proinflammatory cytokines on the proliferation and melanogenesis of melanocytes (MCs) in lesional psoriatic skin. OBJECTIVE: We investigated the effects of TNFα, IL17A, and IL8 on the proliferation and melanin synthesis of MCs. METHODS: Skin specimens were biopsied from patients with psoriasis vulgaris at the active stage, or from the tail skin of Dct-LacZ mice with imiquimod (IMQ)-induced psoriasiform dermatitis. Cultured keratinocytes (KCs), MCs, and human skin explants were used in this study. The numbers of MCs were measured via ß-galactosidase staining, EdU incorporation and HMB45 immunohistochemical staining. The expression of human ß-defensin 3 (hBD3) in KCs was silenced by siRNA, the conditioned medium (CM) from siRNA-transfected KCs was used to treat MCs, then followed by αMSH stimulation. The melanogenesis-related genes were examined by using qRT-PCR and western blotting. RESULTS: The increased number of MCs and decreased melanin content were highly relevant to the enhanced expression of IL8 and BD3 both in human psoriatic skin and in IMQ-treated mouse tail skin. IL8 expression in KCs and CXCR2 expression in MCs was significantly increased by IL17A and TNFα, the αMSH-induced upregulations of microphthalmia-associated transcription factor (MITF) and tyrosinase in MCs were abrogated by the CM from hBD3-unsilenced KCs, but not from hBD3-silenced KCs. CONCLUSION: Our results suggest the roles of IL8-CXCR2 activation in promoting MC proliferation and of BD3 upregulation in reducing melanogenesis. These findings have been implicated in the underlying mechanism that active psoriasis prefers hypopigmentation despite chronic inflammation.

Effects of neoadjuvant hyperthermic intraperitoneal chemotherapy on chemotherapy response score and recurrence in high-grade serous ovarian cancer patients with advanced disease: A multicentre retrospective cohort study.

OBJECTIVE: To investigate whether the combination of neoadjuvant hyperthermic intraperitoneal chemotherapy (NHIPEC) plus intravenous neoadjuvant chemotherapy (IV NACT) has superior efficacy to IV NACT alone. DESIGN: Retrospective cohort study. SETTING: Two tertiary referral university hospitals. POPULATION: Patients with ovarian cancer who received NACT-interval debulking surgery (IDS) between 2012 and 2020. METHODS: The tumour response to NACT was evaluated with the chemotherapy response score (CRS) system. Survival outcomes were compared. MAIN OUTCOME MEASURES: CRS 3, progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 127 patients were included, and 46 received NHIPEC plus IV NACT. The addition of NHIPEC was independently associated with an increased likelihood of CRS 3 (p = 0.033). Patients who received NHIPEC + IV NACT had significantly improved PFS compared with those who received IV NACT alone (median PFS: 22 versus 16 months, p < 0.001). The use of NHIPEC was identified as an independent predictor of PFS (p < 0.0001). OS did not differ significantly between treatment groups (p = 0.062), although a trend favouring NHIPEC was noted. Incidence of grade 3-4 adverse events and the surgical complexity score of IDS were similar between the two groups. CONCLUSIONS: Compared with IV NACT alone, the combination of NHIPEC and IV NACT resulted in improved tumour response and longer PFS. The addition of NHIPEC did not increase the risk of adverse effects or affect the complexity of IDS.

Analysis Of The Association Between Sh2B1 chr16.28884655 And Type 2 Diabetes.

PURPOSE: To determine correlation between genetic susceptibility of type 2 diabetes mellitus (T2DM) and Src homology 2 B adapter protein 1 (SH2B1) gene polymorphism in a diabetic population.  Methods: A total of 111 T2DM patients (DM group) and 34 healthy controls (NC group) from Shanxi Provincial People's Hospital were included in this study. Exon 9 of the SH2B1 gene was detected using the Sanger sequencing method, and the relationship between SH2B1 gene polymorphism and diabetes was analyzed.  Results: Comparison of the data between the two groups showed that the values of TG, the updated HOMA of insulin resistance (HOMA2-IR), weight, body mass index, waist circumference, fasting blood glucose and fasting insulin levels of the DM group were higher than those of the NC group (P < 0.05). The HOMA2 insulin sensitivity (%S) of the DM group was lower than that of the NC group (P < 0.05). Sequencing analysis revealed that the following five single nucleotide polymorphisms in exon 9 of SH2B1 may be related to T2DM: rs181578610, rs550079240, chr16.28884655, chr16.28884659 and chr16.28884831. Among them, chr16.28884655 was found to be significantly related to diabetes; this site, located on the NM_015503 exon, was related to TG, LDL-C and waist circumference. CONCLUSION: The SH2B1 gene locus chr16.28884655 was found to be significantly related to genetic susceptibility to T2DM.

Association between subtypes of metabolic syndrome and prognosis in patients with stage I endometrioid adenocarcinoma: A retrospective cohort study.

Purpose: To investigate the association between subtypes of metabolic syndrome (MetS) and prognosis of patients with stage I endometrioid adenocarcinoma. Patients and methods: Patients with stage I endometrioid adenocarcinoma who received surgical treatment as primary therapy at the Department of Gynecology of the Sun Yat-sen Memorial Hospital between June 2015 and December 2019 were retrospectively enrolled. According to the diagnosis criteria of MetS, the patients were categorized as patients without MetS, patients with MetS but without raised fasting plasma glucose (FPG, including previously diagnosed diabetes), and patients with MetS and raised FPG. All the included patients were followed from the dates of surgery until death, June 2021, or loss to follow-up, whichever came first, and cancer recurrence (including metastasis) was studied as the main outcome. Cox regression was used to evaluate the associations between subtypes of MetS and the study outcome adjusting for potential confounding factors. Results: Among the included 387 patients with stage I endometrioid adenocarcinoma, 193 (49.9%) were without MetS, 65 (16.8%) were with FPG not involving MetS, and 129 (33.3%) were with raised FPG involved MetS. With a median follow-up of 1,253 days, the cumulative incidence of cancer recurrence was 8.76% (95% confidence interval (CI) 2.5%-14.62%), 28.31% (95% CI 2.33%-47.38%), and 7.54% (95% CI 1.54%-13.17%), respectively. After adjusting for age, menopause, histological grade, tumor size, lymph-vascular space invasion, deep myometrial invasion, and treatments, comorbid FPG not involving MetS is a stronger risk factor of cancer recurrence than comorbid raised FPG involving MetS (hazard ratio 2.82 (95% CI 1.10-7.24) versus 1.18 (95% CI 0.45-3.13)) when compared to patients without MetS. Conclusion: Comorbid MetS generally presents as a risk factor of poor prognosis in patients with stage I endometrioid adenocarcinoma after surgical treatment, but the magnitude of the association may vary between subtypes, in which FPG not involving MetS appears to be predominant.

Differential responses of the properties of soil humic acid and fulvic acid to nitrogen addition in the North China Plain.

Humus (HS) is an important component of soil organic matter. Humic acid (HA) and fulvic acid (FA) are two of the most important components of HS, as they substantially affect biogeochemical processes and the migration and transformation of pollutants in soil. Long-term nitrogen (N) addition can lead to changes in soil physical and chemical properties, affect the structural characteristics of soil HS (HA and FA), cause changes in the adsorption and migration of pollutants, and ultimately result in the continuous deterioration of the soil ecological environment. However, few studies have examined the effects of N addition on the structural characteristics of soil HS, including the responses of soil HA and FA to N addition. Here, we conducted a long-term positioning experiment with different levels of N addition (CK: 0 kg N ha-1 yr-1, LN: 100 kg N ha-1 yr-1, and HN: 300 kg N ha-1 yr-1) in typical farmland soils of the North China Plain to study the response of soil HA and FA to N addition. N addition altered the physical and chemical properties of soil (e.g., pH, SOC, TN, and enzyme activity), which affected the responses of the chemical structure, quality indexes, and composition distribution of soil HA and FA to N addition. Differences in the response to N addition between HA and FA were observed. The structural characteristics of FA were stronger in response to HN compared with those of soil HA. As the level of N added increased, soil FA degradation increased, the composition distribution changed, the aromatization degree and molecular weight decreased, and the molecular structure became simpler. The properties of soil HA did not significantly respond to N addition. Given increases in the global N input (N addition and N deposition), our results have implications for agricultural fertilization, soil management, and other activities.

Evaluation of the clinical sensitivity and specificity of the BD Max™ Enteric Bacterial Panel for molecular detection of pathogens for acute gastroenteritis in the Singaporean population.

PURPOSE: Acute gastroenteritis (AGE) is caused by a wide range of pathogens. Culture methods for the detection of bacterial pathogens is time consuming and labour intensive. This study compared a same-day-to-result commercial molecular method using BD Max™ Enteric Bacterial Panel against conventional culture and laboratory-developed PCR assays (LDTs), and characterised the epidemiology of bacterial AGE in Singapore. METHODOLOGY: PCRs for Campylobacter spp., Salmonella spp., Shigella spp./Enteroinvasive Escherichia coli (EIEC) and Shiga toxin-producing E. coli (STEC)/Shigella dysenteriae were performed on the BD Max™ platform. Concurrent routine bacterial culture ("reference standard") was performed for Campylobacter, Salmonella, Shigella, Vibrio and Aeromonas spp. In the event of a discrepancy, an "expanded reference standard" (bacterial culture with LDT) was used. RESULTS: There were 299 stool specimens in the study, with no bacterial pathogens detected in 190 samples (63.5%). The positive samples (n = 109,36.5%) were detected with Salmonella (n = 57,19.1%), Campylobacter (n = 28,9.4%), Vibrio parahaemolyticus (n = 6,2.0%), Shigella/EIEC (n = 6,2.0%), ETEC (n = 4,1.3%), STEC (n = 2,0.7%), Aeromonas (n = 2,0.7%), Plesiomonas shigelloides (n = 1,0.3%) and 3(1.0%) co-infections. Compared to the "expanded reference standard", conventional culture missed 38/112 (33.9%) pathogens. Conversely, testing by BD Max™ alone failed to detect 17 pathogens. BD Max™ reported seven (2.3%) false-positive results. CONCLUSIONS: BD Max™ increased the detection rate of bacterial AGE pathogens in the panel, but was limited by the absence of detection capability for Vibrio and Aeromonas spp.

sPmel17 Secreted by Ultraviolet B-Exposed Melanocytes Alters the Intercellular Adhesion of Keratinocytes.

Repigmentation of the skin in patients with vitiligo represents an intricate process in which the depigmented epidermis is replenished by functional melanocytes (MCs) that migrate from undamaged hair follicles and/or surrounding areas. We characterized whether MCs release a secreted form of Pmel17 (sPmel17) protein after exposure to UVB, thereby weakening the cell-cell adhesions of keratinocytes (KCs), which provides MCs the opportunity to migrate to areas devoid of MCs. At first, we examined the interactions of sPmel17 and FHL2 (four-and-a-half LIM domain protein 2) in KCs treated with the conditioned media (CM) from MCs exposed to UVB. The results showed that both the protein and mRNA levels of FHL2 were significantly upregulated in KCs treated with sPmel17-enriched CM from UVB-exposed MCs. We also found that there are physical interactions between sPmel17 and FHL2 as analyzed by reciprocal coimmunoprecipitation assays and double immunofluorescence staining. The CM from UVB-exposed MCs signaled KCs to remodel the actin cytoskeleton and reduce E-cadherin expression. However, the CM from UVB-exposed and Pmel17-silenced or from UVB-unexposed MCs failed to do this. To further determine the in situ distributions of sPmel17, FHL2, and E-cadherin, we examined the expression profiles of those proteins in the skin from healthy subjects and from depigmented or repigmented vitiligo using immunofluorescence and immunohistochemical staining. The results showed that the expression of sPmel17 was positively correlated with FHL2 but not to E-cadherin. The colocalization of FHL2 and sPmel17 was also observed in UVB-exposed mouse tail skin. Together, the upregulation of FHL2 in KCs requires stimulation by sPmel17 secreted from MCs and activation of the sPmel17-FHL2-E-cadherin axis offers a potential therapeutic target to expedite the repigmentation process in patients with vitiligo.