Anxiety and depression in nasopharyngeal carcinoma patients and network analysis to identify central symptoms: A cross-sectional study from a high-incidence area.

PURPOSE: To determine the prevalence of anxiety and depression in patients with nasopharyngeal carcinoma (NPC) and to identify central symptoms and bridge symptoms among psychiatric disorders. METHODS: This cross-sectional study recruited patients with NPC in Guangzhou, China from May 2022, to October 2022. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used for screening anxiety and depression, respectively. Network analysis was conducted to evaluate the centrality and connectivity of the symptoms of anxiety, depression, quality of life (QoL) and insomnia. RESULTS: A total of 2806 respondents with complete GAD-7 and PHQ-9 scores out of 3828 were enrolled. The incidence of anxiety in the whole population was 26.5% (depression, 28.5%; either anxiety or depression, 34.8%). Anxiety was highest at caner diagnosis (34.2%), while depression reached a peak at late-stage radiotherapy (48.5%). Both moderate and severe anxiety and depression were exacerbated during radiotherapy. Coexisting anxiety and depression occurred in 58.3% of those with either anxiety or depression. The generated network showed that anxiety and depression symptoms were closely connected; insomnia was strongly connected with QoL. "Sad mood", "Lack of energy", and "Trouble relaxing" were the most important items in the network. Insomnia was the most significant bridge item that connected symptom groups. CONCLUSION: Patients with NPC are facing alarming disturbances of psychiatric disorders; tailored strategies should be implemented for high-risk patients. Besides, central symptoms (sad mood, lack of energy, and trouble relaxing) and bridge symptoms (insomnia) may be potential interventional targets in future clinical practice.

Antifreezing, Antidrying, and Conductive Hydrogels for Electronic Skin Applications at Ultralow Temperatures.

Although conductive hydrogel-based flexible electronic devices have superb flexibility and high conductivities, they tend to malfunction in dry or frigid areas. Herein, an ultralow-temperature tolerant, antidrying, and conductive composite hydrogel is designed for electronic skin applications on the basis of the synergy of double-cross-linked polymer networks, Hofmeister effect, and electrostatic interaction and fabricated by in situ free radical polymerization of 2-acrylamido-2-methyl-1-propanesulfonic acid and acrylic acid in the presence of poly(vinyl alcohol) and conductive MXene sheets, followed by impregnation with LiCl. Thanks to the synergy of LiCl and the charged polar terminal groups of the synthesized polymers, the composite hydrogel can not only bear an ultralow temperature of -80 °C without freezing but also maintain its original mass. Meanwhile, the resultant hydrogel possesses satisfactory self-regeneration ability benefiting from the moisturizing effect of LiCl. The conductive network of MXene sheets greatly improves the ionic conductivity of the hydrogel at low temperatures, exhibiting an ionic conductivity of 1.4 S m-1 at -80 °C. Furthermore, the electronic skin assembled by the multifunctional hydrogel is efficient in monitoring human motions at -80 °C. The antifreezing and antidrying features along with favorable ionic conductivity, high tensile strength, and outstanding flexibility make the composite hydrogel promising for applications in frigid and dry regions.

Chinese organic rice transition spatial econometrics empirical analysis.

Based on the integrated model of Super-SBM model, spatial Durbin model (SDM) and Grey neural network model, this paper analyzes the panel data of various provinces in China from multiple angles and dimensions. It was found that there were significant differences in eco-efficiency between organic rice production and conventional rice production. The response of organic rice to climate change, the spatial distribution of ecological and economic benefits and the impact on carbon emission were analyzed. The results showed that organic rice planting not only had higher economic benefits, but also showed a rising trend of ecological benefits and a positive feedback effect. This finding highlights the importance of organic rice farming in reducing carbon emissions. Organic rice farming effectively reduces greenhouse gas emissions, especially carbon dioxide and methane, by improving soil management and reducing the use of fertilizers and pesticides. This has important implications for mitigating climate change and promoting soil health and biodiversity. With the acceleration of urbanization, the increase of organic rice planting area shows the trend of organic rice gradually replacing traditional rice cultivation, further highlighting the potential of organic agriculture in emission reduction, environmental protection and sustainable agricultural production. To this end, it is recommended that the Government implement a diversified support strategy to encourage technological innovation, provide guidance and training, and raise public awareness and demand for organic products. At the same time, private sector participation is stimulated to support the development of organic rice cultivation through a public-private partnership model. Through these measures, further promote organic rice cultivation, achieve the dual goals of economic benefits and environmental benefits, and effectively promote the realization of double carbon emission reduction targets.

Discovery of palmatine derivatives as potent neuroprotective agents.

Alzheimer's disease is a neurodegenerative disorder characterized by the presence of neurodegenerative lesions and cognitive impairment. In this study, a series of novel palmatine derivatives were designed and synthesized through the introduction of a heteroatom using carbodiimide-mediated condensation. The synthesized compounds were then screened for toxicity and potency, leading to the identification of compound 2q, which exhibited low toxicity and high potency. Our findings demonstrated that compound 2q displayed significant neuroprotective activity in vitro, emerging as a promising candidate for Alzheimer's disease treatment.

Fufang Luohanguo Qingfei granules reduces influenza virus susceptibility via MAVS-dependent type I interferon antiviral signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. AIM OF THE STUDY: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. MATERIALS AND METHODS: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs-/-) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. RESULTS: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-ß transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. CONCLUSION: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-ß antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.

Automated identification of protein expression intensity and classification of protein cellular locations in mouse brain regions from immunofluorescence images.

Knowledge of protein expression in mammalian brains at regional and cellular levels can facilitate understanding of protein functions and associated diseases. As the mouse brain is a typical mammalian brain considering cell type and structure, several studies have been conducted to analyze protein expression in mouse brains. However, labeling protein expression using biotechnology is costly and time-consuming. Therefore, automated models that can accurately recognize protein expression are needed. Here, we constructed machine learning models to automatically annotate the protein expression intensity and cellular location in different mouse brain regions from immunofluorescence images. The brain regions and sub-regions were segmented through learning image features using an autoencoder and then performing K-means clustering and registration to align with the anatomical references. The protein expression intensities for those segmented structures were computed on the basis of the statistics of the image pixels, and patch-based weakly supervised methods and multi-instance learning were used to classify the cellular locations. Results demonstrated that the models achieved high accuracy in the expression intensity estimation, and the F1 score of the cellular location prediction was 74.5%. This work established an automated pipeline for analyzing mouse brain images and provided a foundation for further study of protein expression and functions.

Three-Dimensional Porous Si@SiOx/Ag/CN Anode Derived from Deposition Silicon Waste toward High-Performance Li-Ion Batteries.

The application of photovoltaic (PV) solid waste to the field of lithium-ion batteries is deemed to be an effective solution for waste disposal, which can not only solve the problem of environmental pollution but also avoid the loss of secondary resources. Herein, based on the volatile deposited waste produced by electron beam refining polysilicon, a simple and environmentally friendly method was designed to synthesize P-Si@SiOx/Ag/CN as an anode material for lithium-ion batteries. Remarkably, the presence of silver and the formation of a carbon-nitrogen network can enhance the electrical conductivity of the composite and boost the transport efficiency of lithium ions. Furthermore, the porous Si@SiOx structure is generated by silver-assisted chemical etching (Ag-ACE), and the carbon-nitrogen grid architecture is formed after lyophilization with NaCl as a template, which can jointly provide sufficient buffer space for the volume change of silicon during lithiation/delithiation. Benefitting from these advantages, the P-Si@SiOx/Ag/CN anode exhibits outstanding cycling performance with 759 mA h g-1 over 300 cycles at 0.5 A g-1. Meanwhile, the lithium-ion batteries employing the P-Si@SiOx/Ag/CN anodes present a superior rate capability of 950 mA h g-1 at 2 A g-1 and retain a high reversible specific capacity of 956 mA h g-1 at 1 A g-1 after 50 cycles. This work opens up a new economic strategy for the fabrication of high-performance silicon anodes and affords a promising avenue for the recycling of PV silicon waste.

[Corrigendum] Anti­osteoporotic effects of tetramethylpyrazine via promoting osteogenic differentiation and inhibiting osteoclast formation.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 2A on p. 8311, portraying the results of immunostaining experiments for osterix, the 'GIOP' and 'GIOP+TMP (20)' data panels contained overlapping data, such that these images were derived from apparently the same original source, where they were intended to show the results from differently performed experiments. Moreover, in Fig. 3A on p. 8312 showing the results from ALP staining and Alizarin Red S staining experiments, two pairs of apparently overlapping data panels were identified in the Dex 106 M / TMP 50 µM, 100 µM and 200 µM data panels. After having re­examined their original data, the authors have realized that the data featured in Figs. 2A and 3A were assembled incorrectly in these figures. Revised versions of Fig. 2 and 3, now containing replacement data for the experiments shown in Figs. 2A and 3A, are shown on the next page. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 16: 8307­8314, 2017; DOI: 10.3892/mmr.2017.7610].

Scutellaria baicalensis: a promising natural source of antiviral compounds for the treatment of viral diseases.

Viruses, the smallest microorganisms, continue to present an escalating threat to human health, being the leading cause of mortality worldwide. Over the decades, although significant progress has been made in the development of therapies and vaccines against viral diseases, the need for effective antiviral interventions remains urgent. This urgency stems from the lack of effective vaccines, the severe side effects associated with current drugs, and the emergence of drug-resistant viral strains. Natural plants, particularly traditionally-used herbs, are often considered an excellent source of medicinal drugs with potent antiviral efficacy, as well as a substantial safety profile. Scutellaria baicalensis, a traditional Chinese medicine, has garnered considerable attention due to its extensive investigation across diverse therapeutic areas and its demonstrated efficacy in both preclinical and clinical trials. In this review, we mainly focused on the potential antiviral activities of ingredients in Scutellaria baicalensis, shedding light on their underlying mechanisms of action and therapeutic applications in the treatment of viral infections.

Combination of metabolomics and network pharmacology analysis to decipher the mechanisms of total flavonoids of Litchi seed against prostate cancer.

OBJECTIVES: To explore the underlying mechanism of total flavonoids of Litchi seed (TFLS) in treating prostate cancer (PCa). METHODS: Cell Counting Kit-8 (CCK-8), EdU incorporation assay, trypan blue dye assay and colony formation assay were employed to evaluate the effect of TFLS on PCa in vitro. The xenograft mouse model was established to explore the anti-tumour effect of TFLS in vivo. Alterations in the metabolic profiles of the PC3 cells and mouse serum were obtained by untargeted metabolomics. Combination with metabolomics analysis and network pharmacology strategies, the potential targets were predicted and further validated by RT-qPCR. KEY FINDINGS: TFLS attenuated PCa progression both in vitro and in vivo. Metabolomics results yielded from cells and serum indicated that the anti-cancer effect of TFLS was correlated with synergistic modulation of five common metabolic pathways including glycerophospholipid metabolism, arginine and proline metabolism, glycine, serine and threonine metabolism, tryptophan metabolism and steroid biosynthesis. Using in silico prediction and RT-qPCR analysis, we further revealed that TFLS exerted anti-PCa activities via regulating the expressions of nine genes, including MAOA, ACHE, ALDH2, AMD1, ARG1, PLA2G10, PLA2G1B, FDFT1 and SQLE. CONCLUSIONS: TFLS suppressed tumour proliferation in PCa, which may be associated with regulating lipid and amino acid metabolisms.

Integrating metabonomics and metagenomics sequencing to study the anti-liver fibrosis effects of palmatine in Corydalis saxicola Bunting.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis saxicola Bunting (CS), a traditional Chinese folk medicine, has been effectively used for treating liver disease in Zhuang nationality in South China. However, the main anti-liver fibrosis ingredients in CS are incompletely understood. AIM OF THE STUDY: To elucidate the main anti-liver fibrosis ingredients in CS and its underlying mechanism. MATERIAL AND METHODS: Firstly, spectrum-effect relationship (SER) strategy was applied to identify the major ingredients against liver fibrosis in CS. Subsequently, 1H NMR metabonomics and metagenomics sequencing techniques were used to clarify the intervention of palmatine (PAL) on liver fibrosis. Furthermore, the expression of tight junction proteins and the levels of liver inflammation factors were examined, the effect of PAL on microbiota was verified by FMT. RESULTS: The SER model revealed that PAL was the most important active ingredient in CS. 1H NMR fecal metabonomics showed that PAL could reserve the abnormal levels of gut microbial-mediated metabolites of liver fibrosis, such as isoleucine, taurine, butyrate, propionate, lactate, glucose, which mainly involved in amino acid metabolism, intestinal flora metabolism and energy metabolism. Metagenomics sequencing found that PAL could callback the abundance of s__Lactobacillus_murinus, s__Lactobacillus_reuteri, s__Lactobacillus_johnsonii, s__Lactobacillus_acidophilus and s__Faecalibaculum_rodentium to varying degree. Furthermore, the intestinal barrier function and the levels of hepatic inflammation factors were significantly ameliorated by PAL. FMT demonstrated that the therapeutic efficiency of PAL was closely associated with gut microbiota. CONCLUSION: The effects of CS on liver fibrosis were attributed in part to PAL by alleviating metabolic disorders and rebalancing gut microbiota. The SER strategy may be a useful method for the discovery of active constituents in natural plants.

CEMIP-mediated hyaluronan metabolism facilitates SCLC metastasis by activating TLR2/c-Src/ERK1/2 axis.

Small-cell lung cancer (SCLC) is a highly metastatic and recalcitrant malignancy. Metastasis is the major cause of death in patients with SCLC but its mechanism remains poorly understood. An imbalance of hyaluronan catabolism in the extracellular matrix accelerates malignant progression in solid cancers due to the accumulation of low-molecular-weight HA. We previously found that CEMIP, a novel hyaluronidase, may act as a metastatic trigger in SCLC. In the present study, we found that both CEMIP and HA levels were higher in SCLC tissues than in paracancerous tissues from patient specimens and in vivo orthotopic models. Additionally, high expression of CEMIP was associated with lymphatic metastasis in patients with SCLC, and in vitro results showed that CEMIP expression was elevated in SCLC cells relative to human bronchial epithelial cells. Mechanistically, CEMIP facilitates the breakdown of HA and accumulation of LMW-HA. LMW-HA activates its receptor TLR2, and subsequently recruits c-Src to activate ERK1/2 signalling, thereby promoting F-actin rearrangement as well as migration and invasion of SCLC cells. In addition, the in vivo results verified that depletion of CEMIP attenuated HA levels and the expressions of TLR2, c-Src, and phosphorylation of ERK1/2, as well as liver and brain metastasis in SCLC xenografts. Furthermore, the application of the actin filament inhibitor latrunculin A significantly inhibited the liver and brain metastasis of SCLC in vivo. Collectively, our findings reveal the critical role of CEMIP-mediated HA degradation in SCLC metastasis and suggest its translational potential as an attractive target and a novel strategy for SCLC therapy.

Adaptive and Adjustable MXene/Reduced Graphene Oxide Hybrid Aerogel Composites Integrated with Phase-Change Material and Thermochromic Coating for Synchronous Visible/Infrared Camouflages.

Although single-function camouflage under infrared/visible bands has made great advances, it is still difficult for camouflage materials to cope with the synergy detection spanning both visible and infrared spectra and adapt to complex and variable scenarios. Herein, a trilayer composite integrating thermal insulation, heat absorption, solar/electro-thermal conversions, and thermochromism is fabricated for visible and infrared dual camouflages by combining anisotropic MXene/reduced graphene oxide hybrid aerogel with the n-octadecane phase change material in its bottom and a thermochromic coating on its upper surface. Benefiting from the synergetic heat-transfer suppression derived from the thermal insulation of the porous aerogel layer and the heat absorption of the n-octadecane phase-change layer, the composite can serve as a cloak to hide the target signatures from the infrared images of its ambient surroundings during the day in the jungle and at night in all scenes and can assist the target in escaping visual surveillance by virtue of its green appearance. For desert scenarios, the composite can spontaneously increase its surface temperature via its solar-thermal energy conversion, merging infrared images of the targets into the high-temperature surroundings; meanwhile, it can vary the surface color from the original green to yellow, enabling the target to visually disappear from ambient sands and hills. This work provides a promising strategy for designing adaptive and adjustable integrated camouflage materials to counter multiband surveillance in complicated environments.

CEMIP promotes small cell lung cancer proliferation by activation of glutamine metabolism via FBXW7/c-Myc-dependent axis.

Small cell lung cancer (SCLC) is the most malignant lung cancer with rapid growth and early metastasis, but still lacks effective targeted therapies to improve the prognosis. Here, we demonstrated that a novel oncogenic protein, cell migration inducing hyaluronic binding protein (CEMIP), was robustly overexpressed in SCLC tissues than that in noncancerous tissues and high expression of CEMIP predicted poor outcomes in clinical specimens and in large sample size cohorts from public databases (GEPIA 2 and CPTAC). Liquid chromatography mass spectrometry (LC-MS) and in vitro/in vivo functional assays indicated that CEMIP contributed to the proliferation by increasing glutamine consumption and their metabolites (glutamate and glutathione) levels in SCLC cells. Moreover, the addition of a GLS1 inhibitor CB-839 dramatically reduced CEMIP-induced SCLC cell proliferation. Mechanistically, beyond as a scaffold protein, CEMIP facilitates glutamine-dependent cell proliferation through inhibiting c-Myc ubiquitination and increasing c-Myc stabilization and nuclear accumulation via hindering the interaction between FBXW7 (a E3 ubiquitin ligase) and its target substrate c-Myc. Taken together, our findings reveal a novel oncogenic role of CEMIP in sustaining SCLC growth via FBXW7/c-Myc-dependent axis, and provide new evidence that inhibition of CEMIP might be a potential therapeutic strategy for the treatment of SCLC.

Total flavonoids of Litchi seed attenuate stem cell-like properties in breast cancer by regulating Notch3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer has been the most commonly-diagnosed cancer worldwide, and the treatment and prognosis of which are often limited by breast cancer stem cells (BCSCs). Litchi seeds have shown good anti-cancer activity in various cancers including prostate cancer, lung cancer and breast cancer. However, the activity and underlying mechanism of Litchi seeds against BCSCs remain unknown. AIM OF THE STUDY: To investigate the activity and mechanism of total flavonoids of litchi seed (TFLS) against BCSCs in vitro and in vivo. MATERIALS AND METHODS: Two orthotopic xenograft mouse models were established using HCC1806 cells pretreated or untreated with TFLS to determine whether TFLS could target BCSCs in vivo. Mammosphere formation and flow cytometry assays were employed to evaluate the effect of TFLS on BCSCs in vitro. The underlying mechanism was investigated using RT-qPCR, Western blot, immunohistochemistry and immunofluorescence experiments. RESULTS: TFLS could significantly inhibit the viability of HCC1806, MCF-7 and HCC1937 cells in vitro and suppress the growth of HCC1806 cells in vivo. TFLS attenuated stem cell-like properties of breast cancer through reducing the percentage of CD44+CD24-/low cells, inhibiting the mammospheres formation and down-regulating the mRNA and protein levels of cancer stem cells related markers (Oct4, Nanog, Sox2) in MCF-7 and HCC1806 cells. Meanwhile, TFLS suppressed the tumor-initiating ability of BCSCs via reducing the percentage of CD44+CD24-/low cells in tumor and lowering tumor incidence rate in orthotopic xenograft mice. In addition, TFLS treatments restricted the expression and nuclear translocation of Notch3, subsequently down-regulated Hes1 and Runx2 expressions. CONCLUSIONS: TFLS could suppress the growth of breast cancer and eliminate breast cancer stem cells by inhibiting the Notch3 signaling pathway.

Chlorogenic Acid Inhibits Epithelial-Mesenchymal Transition and Invasion of Breast Cancer by Down-Regulating LRP6.

Epithelial-mesenchymal transition (EMT) is a crucial biologic process for breast cancer metastasis, and inhibition of EMT could be an effective approach to suppress metastatic potential of mammary cancer. High expression of low-density lipoprotein receptor-related protein 6 (LRP6) is usually observed in breast carcinoma and predicts poor prognosis. In the present study, we investigated whether chlorogenic acid (CA) can inhibit the EMT of breast cancer cells and underlying molecular mechanism. We found that CA treatment transformed MCF-7 cell morphology from spindle shape (mesenchymal phenotype) to spherical shape (epithelial phenotype). CA clearly increased epithelial biomarkers' expression (E-cadherin and ZO-1) but decreased mesenchymal proteins' expression (ZEB1, N-cadherin, vimentin, snail, and slug). In addition, CA attenuated MMP-2 and MMP-9 activities and inhibited cell migration and invasion. CA downregulated the expression of LRP6 in MCF-7 cells. Knockdown LRP6 with siRNA repressed cell mobility and invasion, wheras overexpression of LRP6 promoted EMT and antagonized the EMT inhibitory effect of CA on MCF-7 cells. Furthermore, CA directly interacted with Wnt/ß-catenin signaling coreceptor LRP6 and reduced LRP6, p-LRP6, and ß-catenin expression levels in MCF-7 cells. In vivo study revealed that CA notably reduced tumor volume and tumor weight. CA decreased the expression of LRP6, N-cadherin, ZEB1, vimentin, MMP2, MMP9, and increased the expression of E-cadherin and ZO-1. In conclusion, CA inhibited EMT and invasion of breast cancer by targeting LRP6. SIGNIFICANCE STATEMENT: CA, the familiar polyphenol compound in traditional Chinese medicine, repressed EMT and weakened cellular mobility and invasion in MCF-7 cells. The mechanism studies demonstrated that CA could inhibit EMT and invasion of MCF-7 cells via targeting LRP6. Additionally, CA restrained tumor growth and xenograft tumor EMT in vivo. The EMT inhibitory property of CA warrants further studies of CA as a drug candidate for the therapy of metastatic breast carcinoma.

Comparison of the Clinical Efficacy of Two Reduction Methods for the Treatment of Irreducible Unilateral Subaxial Cervical Facet Joint Dislocation.

OBJECTIVE: To compare the clinical efficacy of the minimally invasive technique and the open method in the treatment of irreducible unilateral subaxial cervical facet joint dislocation (SCFD). METHODS: From March 2015 to September 2018, 62 patients with unilateral SCFD were studied. The cases were divided into 2 groups based on different surgery strategies. Thirty-one patients were enrolled in the minimally invasive surgery (MIS) group, and 31 patients were enrolled in the open surgery group. The duration of prone position operation, blood loss, and total hospitalization costs were recorded. The clinical effects were evaluated using visual analogue scale scores, the Oswestry Disability Index, and Japanese Orthopedic Association scores at each follow-up. In addition, the segmental Cobb angle and intervertebral height were recorded and compared. RESULTS: The amount of intraoperative blood loss, prone position operation duration, and total hospital costs in the MIS group were significantly lower than in the open surgery group. The visual analogue scale, Oswestry Disability Index, and Japanese Orthopedic Association scores of the 2 groups significantly improved after the operation. A satisfactory fusion rate was obtained in both groups, and the segmental Cobb angle and intervertebral height scores in both groups improved significantly. CONCLUSIONS: Minimally invasive reduction had equal clinical efficacy to posterior open surgery. However, MIS was less invasive and had lower costs. Therefore, it is a potential option in the treatment of SCFD.

Automated classification of protein expression levels in immunohistochemistry images to improve the detection of cancer biomarkers.

BACKGROUND: The expression changes of some proteins are associated with cancer progression, and can be used as biomarkers in cancer diagnosis. Automated systems have been frequently applied in the large-scale detection of protein biomarkers and have provided a valuable complement for wet-laboratory experiments. For example, our previous work used an immunohistochemical image-based machine learning classifier of protein subcellular locations to screen biomarker proteins that change locations in colon cancer tissues. The tool could recognize the location of biomarkers but did not consider the effect of protein expression level changes on the screening process. RESULTS: In this study, we built an automated classification model that recognizes protein expression levels in immunohistochemical images, and used the protein expression levels in combination with subcellular locations to screen cancer biomarkers. To minimize the effect of non-informative sections on the immunohistochemical images, we employed the representative image patches as input and applied a Wasserstein distance method to determine the number of patches. For the patches and the whole images, we compared the ability of color features, characteristic curve features, and deep convolutional neural network features to distinguish different levels of protein expression and employed deep learning and conventional classification models. Experimental results showed that the best classifier can achieve an accuracy of 73.72% and an F1-score of 0.6343. In the screening of protein biomarkers, the detection accuracy improved from 63.64 to 95.45% upon the incorporation of the protein expression changes. CONCLUSIONS: Machine learning can distinguish different protein expression levels and speed up their annotation in the future. Combining information on the expression patterns and subcellular locations of protein can improve the accuracy of automatic cancer biomarker screening. This work could be useful in discovering new cancer biomarkers for clinical diagnosis and research.

Optimizing estradiol level for gonadotrophin-releasing hormone antagonist initiation among patients with simple tubal factor infertility.

Objective: The aim of this study is to investigate the optimal estradiol (E2) level on the day of gonadotropin-releasing hormone antagonist (GnRH-ant) initiation to maximize the clinical pregnancy rate (CPR) after fresh embryo transfer among patients with simple tubal factor infertility. Methods: A retrospective cohort study was conducted in the Reproductive Medicine Center, the Second Hospital of Hebei Medical University. A total of 1,493 IVF-ET cycles of patients diagnosed with single tubal factor infertility from August 2016 to August 2021 were included and equally allocated into five distinct groups according to the quintile serum E2 levels on the day of GnRH-ant initiation. The five groups had similar baseline data except for antral follicle count. Results: The serum E 2 level on GnRH-ant initiation day was determined as an independent predictor of clinical pregnancy after adjusting for confounding factors such as age, infertility duration, body mass index, cycle number, antral follicle count, and the number of transferred embryos. Through smooth curve fitting, we found that, with the increase of serum E2 levels on the day of GnRH-ant initiation, CPR showed a trend of slight increase and then slight decrease. The maximal CPR was achieved when the serum E2 level on GnRH-ant initiation day was 498 pg/ml. When E2 was less than 498 pg/ml, the odds ratio (OR) of clinical pregnancy was 1.05 (95% CI: 1.00, 1.11, P = 0.0583). When E2 was greater than 498 pg/ml, the OR of clinical pregnancy was 0.97 (95% CI: 0.95, 0.98, P = 0.0003). Furthermore, CPR remained high when E2 was 436.8-658.6 pg/ml but declined significantly by more than 40% when E2 was ≥ 894.4 pg/ml (P < 0.05). Conclusions: The serum E2 level should be considered as an adjuvant parameter for GnRH-ant initiation. The best E2 value was 498 pg/ml, and GnRH-ant administration could be recommended to initiate when serum E2 was 436.8-658.6 pg/ml. If GnRH-ant was initiated when serum E2 was above 894.4 pg/ml, then the CPR after fresh embryo transfer may decline dramatically, and thus, cancellation of fresh embryo transfer and earlier initiation of GnRH-ant in future cycles should be considered.

Nitidine chloride induces caspase 3/GSDME-dependent pyroptosis by inhibting PI3K/Akt pathway in lung cancer.

BACKGROUND: As the increasing mortality and incidence of lung cancer (LC), there is an urgent need to discover novel treatment agent. In this study, we aimed to investigate the anti-LC effects of nitidine chloride (NC), a small molecular compound extracted from Chinese herbal medicine, while detailing its underlying mechanisms. METHODS: Cell viability was detected by MTT assays and five cell death inhibitors, including ferrostatin-1 (Fer-1), Z-VAD-FMK, necrostatin-1 (Nec-1), disulfiram (DSF) and IM-54 were used to explore the type of cell death induced by NC. The microscopic features of NC-induced pyroptosis were assessed by transmission electron microscopy (TEM) and the pyroptotic-related proteins such as caspase and gasdermin family, were examined by western blot. Network pharmacology was employed to predict the potential mechanisms of NC in lung cancer treatment. CETSA and DARTs were used to determine the activity of NC binding to targeted protein. Xenograft mice model was established to further investigate the inhibitory effect and mechanism of NC against LC. RESULTS: The pyroptosis inhibitor (DSF) and apoptosis inhibitor (Z-VAD-FMK) but not IM-54, necrostatin-1, or Ferrostatin-1 rescued NC-induced cell death. Morphologically, H1688 and A549 cells treated with NC showed notably pyroptotic features, such as cell swelling and large bubbles emerging from the plasma membrane. Gasdermin E (GSDME) rather than GSDMC or GSDMD was cleaved in NC-treated H1688 and A549 cells with an increased cleavage of caspase 3. Combined with network pharmacology and molecule docking, PI3K/Akt signaling axis was predicted and was further verified by CETSA and DARTs assay. In addition, the activation of PI3K is able to rescue the pyroptosis induced by NC in vitro. In xenograft model of LC, NC significantly hindered the transduction of PI3K-AKT pathway, inducing pyroptosis of tumor. CONCLUSION: Our data indicated that NC is a potential therapeutic agent for the treatment of LC via triggering GSDME-dependent pyroptosis.