Enantioselective synthesis of chiral α,α-dialkyl indoles and related azoles by cobalt-catalyzed hydroalkylation and regioselectivity switch.

General, catalytic and enantioselective construction of chiral α,α-dialkyl indoles represents an important yet challenging objective to be developed. Herein we describe a cobalt catalyzed enantioselective anti-Markovnikov alkene hydroalkylation via the remote stereocontrol for the synthesis of α,α-dialkyl indoles and other N-heterocycles. This asymmetric C(sp3)-C(sp3) coupling features high flexibility in introducing a diverse set of alkyl groups at the α-position of chiral N-heterocycles. The utility of this methodology has been demonstrated by late-stage functionalization of drug molecules, asymmetric synthesis of bioactive molecules, natural products and functional materials, and identification of a class of molecules exhibiting anti-apoptosis activities in UVB-irradiated HaCaT cells. Ligands play a vital role in controlling the reaction regioselectivity. Changing the ligand from bi-dentate L6 to tridentate L12 enables CoH-catalyzed Markovnikov hydroalkylation. Mechanistic studies disclose that the anti-Markovnikov hydroalkylation involves a migratory insertion process while the Markovnikov hydroalkylation involves a MHAT process.

Plant water source effects on plant-soil feedback for primary succession of terrestrial ecosystems in a glacier region in China.

Despite the extensive research conducted on plant-soil-water interactions, the understanding of the role of plant water sources in different plant successional stages remains limited. In this study, we employed a combination of water isotopes (δ2H and δ18O) and leaf δ13C to investigate water use patterns and leaf water use efficiency (WUE) during the growing season (May to September 2021) in Hailuogou glacier forefronts in China. Our findings revealed that surface soil water and soil nutrient gradually increased during primary succession. Dominant plant species exhibited a preference for upper soil water uptake during the peak leaf out period (June to August), while they relied more on lower soil water sources during the post-leaf out period (May) or senescence (September to October). Furthermore, plants in late successional stages showed higher rates of water uptake from uppermost soil layers. Notably, there was a significant positive correlation between the percentage of water uptake by plants and available soil water content in middle and late stages. Additionally, our results indicated a gradual decrease in WUE with progression through succession, with shallow soil moisture utilization negatively impacting overall WUE across all succession stages. Path analysis further highlighted that surface soil moisture (0- 20 cm) and middle layer nutrient availability (20- 50 cm) played crucial roles in determining WUE. Overall, this research emphasizes the critical influence of water source selection on plant succession dynamics while elucidating underlying mechanisms linking succession with plant water consumption.

Kinematic and Joint Compliance Modeling Method to Improve Position Accuracy of a Robotic Vision System.

In the field of robotic automation, achieving high position accuracy in robotic vision systems (RVSs) is a pivotal challenge that directly impacts the efficiency and effectiveness of industrial applications. This study introduces a comprehensive modeling approach that integrates kinematic and joint compliance factors to significantly enhance the position accuracy of a system. In the first place, we develop a unified kinematic model that effectively reduces the complexity and error accumulation associated with the calibration of robotic systems. At the heart of our approach is the formulation of a joint compliance model that meticulously accounts for the intricacies of the joint connector, the external load, and the self-weight of robotic links. By employing a novel 3D rotary laser sensor for precise error measurement and model calibration, our method offers a streamlined and efficient solution for the accurate integration of vision systems into robotic operations. The efficacy of our proposed models is validated through experiments conducted on a FANUC LR Mate 200iD robot, showcasing notable improvements in the position accuracy of robotic vision system. Our findings contribute a framework for the calibration and error compensation of RVS, holding significant potential for advancements in automated tasks requiring high precision.

The acetylation of MDH1 and IDH1 is associated with energy metabolism in acute liver failure.

The liver is the main organ associated with metabolism. In our previous studies, we identified that the metabolic enzymes malate dehydrogenase 1 (MDH1) and isocitrate dehydrogenase 1 (IDH1) were differentially expressed in ALF. The aim of this study was to explore the changes in the acetylation of MDH1 and IDH1 and the therapeutic effect of histone deacetylase (HDAC) inhibitor in acute liver failure (ALF). Decreased levels of many metabolites were observed in ALF patients. MDH1 and IDH1 were decreased in the livers of ALF patients. The HDAC inhibitor ACY1215 improved the expression of MDH1 and IDH1 after treatment with MDH1-siRNA and IDH1-siRNA. Transfection with mutant plasmids and adeno-associated viruses, identified MDH1 K118 acetylation and IDH1 K93 acetylation as two important sites that regulate metabolism in vitro and in vivo.

In Situ Loading of Ni3ZnC0.7 Nanoparticles with Carbon Nanotubes to 3D Melamine Sponge Derived Hollow Carbon Skeleton toward Superior Microwave Absorption and Thermal Resistance.

The simple and low-cost construction of a 3D network structure is an ideal way to prepare high-performance electromagnetic wave (EMW) absorption materials. Herein, a series of carbon skeleton/carbon nanotubes/Ni3ZnC0.7 composites (CS/CNTs/Ni3ZnC0.7) are successfully prepared by in situ growth of Ni3ZnC0.7 and CNTs on 3D melamine sponge carbon. With the increase of precursor, Ni3ZnC0.7 nanoparticles nucleate and catalyze the generation of CNTs on the surface of the carbon skeleton. The minimum reflection loss (RL) value of the S60min composite (loading time of 60 min) reaches -86.6 dB at 1.6 mm and effective absorption bandwidth (EAB, RL≤-10 dB) is up to 9.3 GHz (8.7-18 GHz). The 3D network sponge carbon with layered micro/nanostructure and hollow skeleton promotes multiple reflection and absorption mechanisms of incident EMW. The N-doping and defects can be equivalent to an electric dipole, providing dipole polarization to increase dielectric relaxation. The uniform Ni3ZnC0.7 nanoparticles and CNTs play a key role in dissipating electromagnetic energy, blocking heat transfer, and enhancing the mechanical properties of the skeleton. Fortunately, the composite displays a quite low thermal conductivity of 0.09075 W m·K-1 and good flexibility, which can provide insulation and quickly recover to its original state after being stressed.

Simultaneous electrocoagulation and E-peroxone coupled with ultrafiltration membrane for shale gas produced water treatment.

Membrane fouling caused by the organics-coated particles was the main obstacle for the highly efficient shale gas produced water (SGPW) treatment and recycling. In this study, a novel hybrid electrocoagulation (EC) and E-peroxone process coupled with UF (ECP-UF) process was proposed to examine the efficacy and elucidate the mechanism for UF fouling mitigation in assisting SGPW reuse. Compared to the TMP (transmembrane pressure) increase of -15 kPa in the EC-UF process, TMP in ECP-UF system marginally increased to -1.4 kPa for 3 filtration cycles under the current density of 15 mA/cm2. Both the total fouling index and hydraulically irreversible fouling index of the ECP-UF process were significantly lower than those of EC-UF process. According to the extended Derjaguin-Landau-Verwey-Overbeek theory, the potential barriers was the highest for ECP-UF processes due to the substantial increase of the acid-base interaction energy in ECP-UF process, which was well consistent with the TMP and SEM results. Turbidity and TOC of ECP-UF process were 63.6% and 45.8% lower than those of EC-UF process, respectively. According to the MW distribution, the variations of compounds and their relative contents were probably due to the oxidation and decomposing products of the macromolecular organics. The number of aromatic compound decreased, while the number of open-chain compounds (i.e., alkenes, alkanes and alcohols) increased in the permeate of ECP-UF process. Notably, the substantial decrease in the relative abundance of di-phthalate compounds was attributed to the high reactivity of these compounds with ·OH. Mechanism study indicated that ECP could realize the simultaneous coagulation, H2O2 generation and activation by O3, facilitating the enhancement of ·OH and Alb production and therefore beneficial for the improved water quality and UF fouling mitigation. Therefore, the ECP-UF process emerges as a high-efficient and space-saving approach, yielding a synergistic effect in mitigating UF fouling for SGPW recycling.

20-hydroxyecdysone suppresses bladder cancer progression via inhibiting USP21: A mechanism associated with deubiquitination and degradation of p65.

Bladder cancer is one of the most common malignancies of the urinary tract and a prevalent cancer worldwide, still requiring efficient therapeutic agents and approaches. 20-Hydroxyecdysone (20-HE), a steroid hormone, can be found in insects and few plants and mediate numerous biological events to control the progression of varying diseases; however, its impacts on bladder cancer remain unclear. In the study, we found that 20-HE treatments effectively inhibited the viability and proliferation of bladder cancer cells and induced apoptosis by activating Caspase-3. The migratory and invasive potential of bladder cancer cells was markedly repressed by 20-HE in a dose-dependent manner. The inhibitory effects of 20-HE on bladder cancer were confirmed in an established xenograft mouse model, as indicated by the markedly reduced tumor growth rates and limited lung and lymph node metastasis. High-throughput RNA sequencing was performed to explore dysregulated genes in bladder cancer cells after 20-HE treatment. We identified ubiquitin-specific protease 21 (USP21) as a key deubiquitinating enzyme for bladder cancer progression and a positive correlation between USP21 and nuclear factor-κB (NF-κB)/p65 in patients. Furthermore, 20-HE treatments markedly reduced USP21 expression, NF-κB/p65 mRNA, stability and phosphorylated NF-κB/p65 expression levels in bladder cancer cells, which were validated in animal tumor tissues. Mechanistic studies showed that USP21 directly interacted with and stabilized p65 by deubiquitinating its K48-linked polyubiquitination in bladder cancer cells, which could be abolished by 20-HE treatment, contributing to p65 degradation. Finally, we found that USP21 overexpression could not only facilitate the proliferation, migration, and invasion of bladder cancer cells, but also significantly eliminated the suppressive effects of 20-HE on bladder cancer. Notably, 20-HE could still perform its anti-tumor role in bladder cancer when USP21 was knocked down with decreased NF-κB/p65 expression and activation, revealing that USP21 suppression might not be the only way for 20-HE during bladder cancer treatment. Collectively, all our results clearly demonstrated that 20-HE may function as a promising therapeutic strategy for bladder cancer treatment mainly through reducing USP21/p65 signaling expression.

SSTU: Swin-Spectral Transformer U-Net for hyperspectral whole slide image reconstruction.

Whole Slide Imaging and Hyperspectral Microscopic Imaging provide great quality data with high spatial and spectral resolution for histopathology. Existing Hyperspectral Whole Slide Imaging systems combine the advantages of the techniques above, thus providing rich information for pathological diagnosis. However, it cannot avoid the problems of slow acquisition speed and mass data storage demand. Inspired by the spectral reconstruction task in computer vision and remote sensing, the Swin-Spectral Transformer U-Net (SSTU) has been developed to reconstruct Hyperspectral Whole Slide images (HWSis) from multiple Hyperspectral Microscopic images (HMis) of small Field of View and Whole Slide images (WSis). The Swin-Spectral Transformer (SST) module in SSTU takes full advantage of Transformer in extracting global attention. Firstly, Swin Transformer is exploited in space domain, which overcomes the high computation cost in Vision Transformer structures, while it maintains the spatial features extracted from WSis. Furthermore, Spectral Transformer is exploited to collect the long-range spectral features in HMis. Combined with the multi-scale encoder-bottleneck-decoder structure of U-Net, SSTU network is formed by sequential and symmetric residual connections of SSTs, which reconstructs a selected area of HWSi from coarse to fine. Qualitative and quantitative experiments prove the performance of SSTU in HWSi reconstruction task superior to other state-of-the-art spectral reconstruction methods.

Multi-segment osteotomy with interlocking intramedullary nail fixation in the treatment of lower limb deformity in older children with hypophosphatemic rickets.

Objective: Malformations of the lower limbs caused by hypophosphatemic rickets in older children are mostly complex, occurring on multiple planes without a single apex and showing arcuate bending of the diaphysis combined with torsion deformity, and are difficult to correct. This study retrospectively investigated the effect of and indicators for multi-segment osteotomy with interlocking intramedullary nail fixation in the treatment of bony deformity caused by hypophosphatemic rickets. Methods: The clinical data of 21 hypophosphatemic rickets patients seen between August 2007 and March 2022 were collected. The age range of the patients at the first surgery was 11 years and 1 month old to 15 years and 3 months old, with an average age of 12 years and 8 months. There were 6 males and 15 females. All patients had abnormal alignment of their lower limbs, with 32 limbs having varus deformity and 10 limbs having valgus deformity. Results: A total of 67 surgeries were performed across the 21 patients, including 24 cases of femoral osteotomy with antegrade intramedullary nail fixation, 6 cases of femoral osteotomy with retrograde intramedullary nail fixation, and 20 cases of tibial osteotomy with interlocking intramedullary nail fixation. A total of 34 limbs eventually underwent interlocking intramedullary nail fixation, 9 with genu valgum and 25 with genu varus. All 21 patients were followed up for a period of 14∼96 months, with an average of 42.6 months. The ends of the osteotomies achieved bony union in 4-9 months (average 6.8 months), after which normal weight-bearing walking could be resumed. No infection, vascular or neurological complications, or nonunion occurred. During postoperative follow-up, the alignment the lower limbs passed through zone 1 in 13 limbs, zone 2 in 12 limbs, and zone 3 in 5 limbs. The overall rate of an excellent effect was 83.3%. Conclusion: For lower limb deformity caused by hypophosphatemic rickets in older children, multi-segment osteotomy and strong fixation with interlocking intramedullary nails can achieve good correction outcomes.

Follow-up Value of Hip Medial Ultrasound in Infants and Children With Developmental Dysplasia of the Hip Treated With Reduction and Spica Casting.

OBJECTIVE: Closed or open reduction and spica casting are common treatments for children aged 6 to 18 months, as well as infants aged 0 to 6 months whose harness treatment for developmental dysplasia of the hip (DDH) was unsuccessful. The study aimed to quantify the distance between the femoral head and the acetabulum after closed or open reduction and evaluate the dynamic docking progression of the femoral head using serial hip medical ultrasound. METHODS: We retrospectively reviewed the medical records and hip medial ultrasound images of a consecutive series of patients with DDH who underwent spica casting after reduction and compared images obtained immediately after reduction and at follow-up. The first cast (stage I) was maintained for 2 to 3 months and scheduled for outpatient repeat ultrasound in 4 to 8 weeks. Then the second cast was placed (stage II), lasting for another 2 to 3 months. The triradiate cartilage-femoral head distance (TFD) was measured in the acetabulum coronal mid-sectional plane. The Wilcoxon signed-rank test was used to compare the TFD values. RESULTS: This study included 49 patients. All patients underwent hip medial ultrasound 0 to 3 days after stage I (time 1) and 4 to 8 weeks (time 2) postoperatively, with 24 patients reviewed again 0 to 7 days after stage II. The TFD values in time 1 and time 2 were 6.0 (5.0, 9.0) mm and 5.0 (3.6, 7.0) mm, respectively. There was a statistically significant difference between times 1 and 2 regarding TFD values in 49 close-reduction hips (6.0 vs 5.0 mm, P < 0.001). Similar findings were also observed in 13 open-reduction hips (6.0 vs 5.0 mm, P = 0.023). CONCLUSIONS: Hip medial ultrasonography during the period of cast immobilization after reduction in children with DDH can objectively and quantitatively show the dynamic change of the distance between the femoral head and the acetabulum, and can be used to assess reduction of the hip and progression of femoral head docking. LEVEL OF EVIDENCE: Level II-prognostic study.

Molecular identification and functional characterization of an environmental stress responsive glutaredoxin gene ROXY1 in Quercus glauca.

Quercus glauca is a valuable natural resource with both economic and ecological values. It is one of the dominant forest tree species widely distributed in Southern China. As a perennial broadleaf plant, Q. glauca inevitably encounters numerous stresses from environment. Glutaredoxins (GRXs) are a kind of small oxidoreductases that play an important role in response to oxidative stress. CC-type GRXs also known as ROXYs are specific to land plants. In this study, we isolated a CC-type GRX gene, QgROXY1, from Q. glauca. Expression of QgROXY1 is induced by a variety of environmental stimuli. QgROXY1 protein localizes to both cytoplasm and nucleus; whereas the nucleus localized QgROXY1 could physically interact with the basic region/leucine zipper motif (bZIP) transcription factor AtTGA2 from Arabidopsis thaliana. Transgenic A. thaliana ectopically expressing QgROXY1 is hypersensitive to exogenously applied salicylic acid. Induction of plant defense gene is significantly impaired in QgROXY1 transgenic plants that results in enhanced susceptibility to infection of Botrytis cinerea pathogen, indicating the evolutionary conserved function among ROXY homologs in weedy and woody plants. This is the first described function for the ROXYs in tree plants. Through this case study, we demonstrated the feasibility and efficacy of molecular technology applied to characterization of gene function in tree species.

The efficacy of 5-aminolevulinic acid photodynamic therapy for pediatric vulvar lichen sclerosus.

BACKGROUND: Prepubertal girls are one of the vulnerable populations of vulvar lichen sclerosus (VLS), which results in a decreased quality of life and increases risk of vulvar cancer. But the therapeutic effects of traditional topical remedies are unsatisfactory in some pediatric patients. 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for refractory VLS patients, but no study has been conducted in child patients. METHODS: The patients included in this study underwent three sessions of ALA-PDT at 2-week intervals. All patients were evaluated for objective clinical appearances and subjective symptoms quantitatively. Statistical analysis comparing parameters at baseline and after three-time ALA-PDT was performed. RESULTS: A total of seven VLS girl patients were included in this study. Both primary objective appearances (lesion size and depigmentation) and subjective symptoms (itching and burning pain) were improved remarkably after the third treatment. Besides, adverse effects, mainly as pain and post-treatment edema, were mild and could be tolerated. CONCLUSIONS: ALA-PDT is an effective and safe therapeutic option for VLS girl patients. Compared with adult patients, the symptoms resolved more quickly in child patients.

Removal of sulfonamide antibiotics by non-free radical dominated peroxymonosulfate oxidation catalyzed by cobalt-doped sulfur-containing biochar from sludge.

The reuse of activated sludge as a solid waste is severely underutilized due to the limitations of traditional treatment and disposal methods. Given that, the sulfur-containing activated sludge catalyst doped with cobalt (SK-Co(1.0)) was successfully prepared by one-step pyrolysis and calcinated at 850 â„ƒ. The generation of CoSx was successfully characterized by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), indicating that the sulfur inside the sludge was the anchoring site for the externally doped cobalt. Cobalt (Ⅱ) (Co2+), as the main adsorption site for peroxymonosulfate(PMS), formed a complex (SK-Co(1.0)-PMS* ) and created the conditions for the generation of surface radicals. The SK-Co(1.0)/PMS system showed high degradation efficiency and apparent rate constants for Sulfamethoxazole (SMX) (91.56% and 0.187 min-1) and Sulfadiazine (SDZ) (90.73% and 0.047 min-1) within 10 min and 30 min, respectively. Three sites of generation of 1O2, which played a dominant role in the degradation of SMX and SDZ in the SK-Co(1.0)/PMS system, were summarized as：sulfur vacancies (SVs), the Co3+/Co2+ cycles promoted by sulfur(S) species, oxygen-containing functional groups (C-O). The degradation mechanisms and pathways had been thoroughly investigated using DFT calculations. In view of this, a new idea for the resource utilization of activated sludge solid waste was provided and a new strategy for wastewater remediation was proposed.

IDH1/MDH1 deacetylation promotes acute liver failure by regulating NETosis.

BACKGROUND: Acute liver failure (ALF) is a life-threatening disease, but its pathogenesis is not fully understood. NETosis is a novel mode of cell death. Although the formation of neutrophil extracellular traps (NETs) has been found in various liver diseases, the specific mechanism by which NETosis regulates the development of ALF is unclear. In this article, we explore the role and mechanism of NETosis in the pathogenesis of ALF. METHODS: Clinically, we evaluated NETs-related markers in the liver and peripheral neutrophils of patients with ALF. In in vitro experiments, HL-60 cells were first induced to differentiate into neutrophil-like cells (dHL-60 cells) with dimethyl sulfoxide (DMSO). NETs were formed by inducing dHL-60 cells with PMA. In in vivo experiments, the ALF model in mice was established with LPS/D-gal, and the release of NETs was detected by immunofluorescence staining and western blotting. Finally, the acetylation levels of IDH1 and MDH1 were detected in dHL-60 cells and liver samples by immunoprecipitation. RESULTS: Clinically, increased release of NETs in liver tissue was observed in patients with ALF, and NETs formation was detected in neutrophils from patients with liver failure. In dHL-60 cells, mutations at IDH1-K93 and MDH1-K118 deacetylate IDH1 and MDH1, which promotes the formation of NETs. In a mouse model of ALF, deacetylation of IDH1 and MDH1 resulted in NETosis and promoted the progression of acute liver failure. CONCLUSIONS: Deacetylation of IDH1 and MDH1 reduces their activity and promotes the formation of NETs. This change aggravates the progression of acute liver failure.

Coaxial Bright and Dark Field Optical Coherence Tomography.

To improve the signal collection efficiency of Optical Coherence Tomography (OCT) for biomedical applications. A novel coaxial optical design was implemented, utilizing a wavefront-division beam splitter in the sample arm with a 45-degree rod mirror. This design allowed for the simultaneous collection of bright and dark field signals. The bright field signal was detected within its circular aperture in a manner similar to standard OCT, while the dark field signal passed through an annular-shaped aperture and was collected by the same spectrometer via a fiber array. This new configuration improved the signal collection efficiency by ∼3 dB for typical biological tissues. Dark-field OCT images were found to provide higher resolution, contrast and distinct information compared to standard bright-field OCT. By compounding bright and dark field images, speckle noise was suppressed by ∼ √2 . These advantages were validated using Teflon phantoms, chicken breast ex vivo, and human skin in vivo. This new OCT configuration significantly enhances signal collection efficiency and image quality, offering great potential for improving OCT technology with better depth, contrast, resolution, speckles, and signal-to-noise ratio. We believe that the bright and dark field signals will enable more comprehensive tissue characterization with the angled scattered light. This advancement will greatly promote the OCT technology in various clinical and biomedical research applications.

Animal models of heart failure with preserved ejection fraction (HFpEF): from metabolic pathobiology to drug discovery.

Heart failure (HF) with preserved ejection fraction (HFpEF) is currently a preeminent challenge for cardiovascular medicine. It has a poor prognosis, increasing mortality, and is escalating in prevalence worldwide. Despite accounting for over 50% of all HF patients, the mechanistic underpinnings driving HFpEF are poorly understood, thus impeding the discovery and development of mechanism-based therapies. HFpEF is a disease syndrome driven by diverse comorbidities, including hypertension, diabetes and obesity, pulmonary hypertension, aging, and atrial fibrillation. There is a lack of high-fidelity animal models that faithfully recapitulate the HFpEF phenotype, owing primarily to the disease heterogeneity, which has hampered our understanding of the complex pathophysiology of HFpEF. This review provides an updated overview of the currently available animal models of HFpEF and discusses their characteristics from the perspective of energy metabolism. Interventional strategies for efficiently utilizing energy substrates in preclinical HFpEF models are also discussed.

Cadmium levels and soil pH drive structure and function differentiation of endophytic bacterial communities in Sedum plumbizincicola: A field study.

Sedum plumbizincicola is a promising hyperaccumulator for heavy metal phytoremediation. It grows in heavy metal polluted soil and stores specific endophyte resources with heavy metal tolerance or growth promotion characteristics. In this study, the endophyte communities of S. plumbizincicola, growing naturally in the field (two former mining locations and one natural location) were investigated, and their structure and function were comparatively studied. The bioaccumulation and translocation characteristics of cadmium (Cd) and selenium (Se) in S. plumbizincicola were also evaluated. The results showed that the heavy metal pollution reduced the richness and diversity of endophyte communities. Soil pH and Cd concentration could be the key factors affecting the composition of the endophyte community. Co-occurrence network analysis identified that 22 keystone taxa belonging to Actinobacteriota, Firmicutes, Myxococcota and Proteobacteria were positively correlated with Cd bioaccumulation and translocation. The predicted endophyte metabolic pathways were enriched in physiological metabolism, immune system, and genetic Information processing. These findings may help to understand how endophytes assist host plants to enhance their adaptability to harsh environments, and provide a basis for further exploration of plant-endophyte interactions and improvement in phytoremediation efficiency.

Lichen sclerosus associated with Turner syndrome treated with photodynamic therapy: A case report.

Turner syndrome (TS) is a rare clinical condition associated with a completely or partially absence, or structural abnormality of an X chromosome, mainly representing as short stature and skeletal anomalies, female hypergonadotropic hypogonadism and infertility. Skin is frequently involved in TS, especially autoimmune diseases like vitiligo and lichen sclerosus (LS). Here, we present a 10-year-old Chinese girl with TS combined with both vulvar LS (VLS) and extragenital LS, who had been misdiagnosed as eczema and vitiligo for years. In order to control LS sufficiently and allay the parents' concerns of potential side effects of topical corticosteroids, she was prescribed with tacrolimus ointment on the extragenital lesions, and photodynamic therapy (PDT) for vulvar lesions. For PDT regimen, we used 5-aminolevulinic acid (ALA) as photosensitizer and 633 nm red light to irradiate the lesion area at 60 mW / cm2 for 30 min each time. After 6 times of treatment at 2-week intervals, a satisfactory remission of both pruritus and lesion severity was achieved. So far, the guideline on TS did not include LS as a common comorbidity to raise attention. However, accurate diagnosis and effective treatment are essential for LS to avoid the possibilities of developing labial atrophy, adhesion, or even vulvar cancer. Based on our research, PDT can significantly relieve subjective symptoms, objective lesion severity and histopathological changes of VLS with good tolerance, and therefore can also be a safe and effective therapeutic alternative in such comorbidity in TS patients.

A new strategy for the treatment of heavily pretreated metastatic breast cancer: A case report and review of the literature.

BACKGROUND: Breast cancer is one of the most common type of cancers worldwide and remains a critical health issue. Although there are numerous treatment options for advanced metastatic breast cancer, the results are not satisfactory, particularly for triple-negative breast cancer. New treatment modalities need to be explored. CASE PRESENTATION: We present the case of a breast cancer patient with multiple metastases who achieved a good response and tolerance to the combination treatment of utidelone plus capecitabine. After being treated with 10 cycles of combined treatment, the patient is now in a good general condition with a progression-free survival time of 10 months. CONCLUSION: To our knowledge, this is the first report of utidelone plus capecitabine successfully treating a patient with heavily pretreated metastatic breast cancer. This combined treatment offers a new option for patients with multi-drug resistant breast cancer.

Genetic variants of ERBB4 gene and risk of gestational diabetes mellitus: a susceptibility and diagnostic nomogram study.

Introduction: Gestational diabetes (GDM) is one of the common complications of female pregnancy, which seriously affects the health of mothers and their offspring. So far, the etiology has not been fully clarified. Methods: A case-control study was conducted to clarify the relationship between Erb-b2 receptor tyrosine kinase 4 (ERBB4) functional tag genetic variants (rs1595064, rs1595065, rs1595066 and rs6719645) and the risk of GDM. Associations between variants and GDM risk were evaluated with the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Subsequently, the false-positive reporting probability (FPRP), multi-factor dimension reduction (MDR) and bioinformatics analysis were adopted to confirm the significant associations. A nomogram model was constructed to predict the risk of GDM. Results: Association analysis demonstrated that rs1595066 TT genotype performed a protective effect on GDM risk among all subjects (TT vs. CC: adjusted OR = 0.60, 95% CI = 0.38 - 0.94, P = 0.026; TT vs. CC/CT: adjusted OR = 0.61, 95% CI = 0.40 - 0.95, P = 0.027). Meanwhile, stratified analysis showed that rs1595066 TT can also reduce the GDM risk in age > 30.09 years old, pre-pregnancy BMI > 22.23 Kg/m2, SBP ≤ 110.08 mmHg, etc subgroups. Interactions between rs1595066 and DBP (P interaction = 0.01), FPG (P interaction < 0.001) and HbA1c (P interaction < 0.001) were detected. The FPRP analysis confirmed that association between rs1595066 and GDM risk in subjects of FPG < 4.79 mmol/L (P = 0.199) is true. The MDR analysis showed that rs1595066 was the best single locus model while the 4-loci model was the best multiple factors model to predict GDM risk. Functional prediction revealed that rs1595066 may disturb the stability of miRNA-mRNA binding. The predictive nomogram model has a well consistence and acceptable discriminative ability with a diagnosed AUC of 0.813. Discussion: ERBB4 variants can change an individual's susceptibility to GDM via the interaction of gene-gene, gene-environment and changes in the regulatory effects of miRNAs on ERBB4 expression.