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Oxidative stress plays a critical role in the pathogenesis of low back pain. Higher serum levels of lutein and zeaxanthin are associated with reduced susceptibility to this disease due to their potent antioxidant properties. Our study aimed to assess the correlation between serum lutein and zeaxanthin levels and low back pain. This is a cross-sectional study based on publicly available data from the National Health and Nutrition Examination Survey. The National Health and Nutrition Examination Survey employs a complex, multistage probability sampling design in order to select a nationally representative sample. In our study, information was gathered from individuals who were 20 years old or older who took part in the National Health and Nutrition Examination Survey from 2001 through 2004. Detailed information was collected on low back pain, serum lutein and zeaxanthin levels, and various other crucial factors. Multivariable logistic regression and restricted cubic spline regression analyses were performed in order to investigate the relationship between serum lutein and zeaxanthin levels and the occurrence of low back pain. In our study 7,026 participants were included, of whom 38.21% (2,685 of 7,026) had low back pain. There was a nonlinear relationship (P < 0.001) between serum lutein and zeaxanthin levels and low back pain, depicted as a U-shaped curve in the restricted cubic spline. The occurrence rate for individuals with serum lutein and zeaxanthin levels below 25.3 nmol/dL was 0.975 (95% CI, 0.960-0.990; P < 0.001). In comparison, the occurrence rate for individuals with serum lutein and zeaxanthin levels exceeding 25.3 nmol/dL was 1.006 (95% CI, 1.000-1.013; P = 0.043). This is a cross-sectional study; therefore causality cannot be established. A nonlinear association between serum lutein and zeaxanthin levels and the risk of low back pain was observed in US adults. The ideal serum lutein and zeaxanthin level that corresponds to the lowest risk of low back pain is approximately 25.3 nmol/dL.

Ion channel drugs have been increasing used for chronic pain management with progress in the development of selective calcium channel modulators. Although ion channel drugs have been proven safe and effective in clinical practice, uncertainty remains regarding its use to treat chronic pain. To standardize the clinical practice of ion channel drug for the treatment of chronic pain, the National Health Commission Capacity Building and Continuing Education Center for Pain Diagnosis and Treatment Special Ability Training Project established an expert group to form an expert consensus on the use of ion channel drugs for the treatment of chronic pain after repeated discussions on existing medical evidence combined with the well clinical experience of experts. The consensus provided information on the mechanism of action of ion channel drugs and their recommendations, caution use, contraindications, and precautions for their use in special populations to support doctors in their clinical decision-making.

Background Previous studies have indicated that sarcopenia is associated with poor post‐operative outcomes in liver cancer patients, but the studies are limited by confounding from mixed diseases, retrospective data, and non‐standardized measurement methods. At present, there is no research with both muscle mass and strength as predictors for hepatocellular carcinoma (HCC) outcomes. We studied the impact of sarcopenia on post‐operative outcomes in HCC patients in a cohort study designed according to the European Working Group on Sarcopenia in Older People standards. Methods A total of 781 consecutive patients admitted to our centre were registered from May 2020 to August 2021. All participants submitted questionnaires and underwent handgrip strength, chair stand test, physical performance, and computed tomographic evaluation. Then, they were divided into three groups according to muscle mass and strength: Group A (reduced muscle mass and strength), Group B (reduced muscle strength or reduced muscle mass), and Group C (normal muscle mass and strength). The baseline data and post‐operative outcomes were compared and analysed. The primary outcome variable in this study was the presence of a major post‐operative complication, and the secondary outcome was the 90‐day re‐admission rate. Results A total of 155 patients [median age, 60.00 (IQR, 51.00–66.00) years; 20 females (12.90%)] were included after strict exclusion. The mean (SD) BMI was 23.37 ± 0.23 kg/m2. The mean (SD) SMI of all participants was 47.05 ± 0.79 cm2/m2, and the mean (SD) handgrip strength was 32.84 ± 0.69 kg. Among them, 77 (49.68%) patients underwent laparoscopic hepatectomy, and 73 (47.10%) patients received major hepatectomy. Regarding the post‐operative results, Group A had a higher rate of major complications [40.91% (9 of 22) vs. 11.94% (8 of 67) in Group B and 6.06 (4 of 66) in Group C; P = 0.001], higher rate of blood transfusion (77.27% vs. 46.27% in Group B and 42.42% in Group C; P = 0.015), higher hospitalization expenses (P = 0.001), and longer hospital stay (P < 0.001). There was no difference in 90‐day re‐admission rates among the three groups. Sarcopenia (hazard ratio, 10.735; 95% CI, 2.547–45.244; P = 0.001) and open surgery (hazard ratio, 4.528; 95% CI, 1.425–14.387; P = 0.010) were independent risk factors associated with major complications. Conclusions Sarcopenia is associated with adverse outcomes after liver resection for HCC. It should be evaluated upon admission to classify high‐risk patients and reduce the risk of major complications.

Epilepsy and major depressive disorder are the two of the most common central nervous system (CNS) diseases. Clinicians and patients call for new antidepressants, antiseizure medicines, and in particular drugs for depression and epilepsy comorbidities. In this work, a dozen new triazole-quinolinones were designed, synthesized, and investigated as CNS active agents. All compounds reduced the immobility time significantly during the forced swim test (FST) in mice at the dosage of 50 mg/kg. Compounds 3f–3j gave superior performance over fluoxetine in the FST with more reductions of the immobility time. Compound 3g also reduced immobility time significantly in a tail suspension test (TST) at the dosage of 50 mg/kg, though its anti-immobility activity was inferior to that of fluoxetine. An open field test was carried out and it eliminated the false-positive possibility of 3g in the FST and TST, which complementarily supported the antidepressant activity of 3g. We also found that almost all compounds except 3k exhibited antiseizure activity in the maximal electroshock seizure (MES) model at 100 or 300 mg/kg. Compounds 3c, 3f, and 3g displayed the ED50 of 63.4, 78.9, and 84.9 mg/kg, and TD50 of 264.1, 253.5, and 439.9 mg/kg, respectively. ELISA assays proved that the mechanism for the antiseizure and antidepressant activities of compound 3g was via affecting the concentration of GABA in mice brain. The molecular docking study showed a good interaction between 3g and the amino acid residue of the GABAA receptor. Excellent drug-like properties and pharmacokinetic properties of compound 3a–l were also predicted by Discovery Studio. These findings provided a new skeleton to develop agents for the treatment of epilepsy and depression comorbidities.

In this study, fourteen celastrol derivatives (1-14) were synthesised by esterification of celastrol at the 29th position. The in vitro anticancer activity of them was determined by the MTT assay. All the synthetic compounds showed significant antiproliferative activity against six cancer cells, with IC 50 of the submicron molar level. The most promising compound (2) blocked the cell cycle in the G2 phase and inhibited the expression of VEGF and MMP-9 in gastric cancer cell line MGC-803. In flow cytometry analysis, compound 2 induced cancer cell apoptosis in a dose-dependent manner. In the mouse tumour xenograft model, compound 2 showed significant anti-tumour activity in vivo at the dosage of 2.5 mg/kg and 1 mg/kg, with a higher inhibition rate than 5-FU (10 mg/kg). What's more, the anticancer mechanism involved in the inhibition of VEGF and the toxicity evaluation of compound 2 were also investigated.

A challenge of chronic diseases that remains to be solved is how to liberate patients and medical resources from the burdens of long-term monitoring and periodic visits. Precise management based on artificial intelligence (AI) holds great promise; however, a clinical application that fully integrates prediction and telehealth computing has not been achieved, and further efforts are required to validate its real-world benefits. Taking congenital cataract as a representative, we used Bayesian and deep-learning algorithms to create CC-Guardian, an AI agent that incorporates individualized prediction and scheduling, and intelligent telehealth follow-up computing. Our agent exhibits high sensitivity and specificity in both internal and multi-resource validation. We integrate our agent with a web-based smartphone app and prototype a prediction-telehealth cloud platform to support our intelligent follow-up system. We then conduct a retrospective self-controlled test validating that our system not only accurately detects and addresses complications at earlier stages, but also reduces the socioeconomic burdens compared to conventional methods. This study represents a pioneering step in applying AI to achieve real medical benefits and demonstrates a novel strategy for the effective management of chronic diseases.

Here, we report a case of a patient with symptoms of Cushing syndrome, who is diagnosed with primary generalized glucocorticoid hypersensitivity in the end. The patient's relevant laboratory tests and imaging examinations are described. Mifepristone, a glucocorticoid receptor antagonist, was prescribed and its therapeutic effect on the patient's electrolyte level, lipid metabolism, and bone metabolism was observed during the treatment. The endocrine assessment indicated normal pituitary-adrenal axis regulation function but reduced Cortisol secretion. Quantitative reverse transcription-polymerase chain reaction indicated reduced mRNA level of mineralocorticoid receptor gene. Pituitary magnetic resonance imaging showed normal pituitary anatomy, while adrenal computed tomography scan showed bilateral adrenal atrophy and increased content of visceral and abdominal subcutaneous fat. Moreover, chromosome examination revealed a normal 46, XY chromosome. In this case, mifepristone was administered to treat primary generalized glucocorticoid hypersensitivity. To the best of our knowledge, there are a few reports on mifepristone-treated primary generalized glucocorticoid hypersensitivity. In the one-year follow-up visits, the evaluated results of electrolyte level, lipid metabolism, and bone metabolism indicated that the patient's symptoms resulting from Cortisol hypersensitivity were relieved progressively. Keywords: primary generalized glucocorticoid hypersensitivity, mifepristone, glucocorticoid receptor, electrolyte, lipid metabolism, bone metabolism

The purpose of this study was to analyze the effects of bufalin on the gene expression of K562 cells and on the expression of BMI-1 pathway constituents in K562 cell apoptosis. K562 cells were treated with bufalin, and the inhibition rate and apoptosis were detected by an MTT assay, flow cytometry and a microarray assay. BMI-1, p16INK4a and p14ARF were examined by quantitative polymerase chain reaction (qPCR). Bufalin induced significant changes in the gene expression of the K562 cells; 4296 genes were differentially expressed, 2185 were upregulated and 2111 were downregulated. The most upregulated genes were associated with transcription regulation, while the most downregulated genes were associated with the non-coding RNA metabolic processes and DNA repair. qPCR analysis demonstrated that BMI-1 was overexpressed in the K562 cells. Bufalin is able to downregulate BMI-1 expression levels in K562 cells prematurely and cause an increase in the expression levels of p16INK4a and p14ARF. Moreover, bufalin downregulated BCR/ABL expression levels in a time-dependent manner, and the expression of BCR/ABL was not associated with the upregulation or downregulation of BMI-1 expression. Bufalin may induce K562 cell apoptosis by downregulating BMI-1 expression levels and accordingly upregulating the expression levels of p16INK4a and p14ARF. Bufalin may also induce K562 cell apoptosis via downregulating BCR/ABL expression levels, and this pathway may be independent of the BMI-1 pathway.

Understanding the molecular and cellular mechanisms that underlie complex traits in pigs is crucial for enhancing their genetic improvement program and unleashing their substantial potentials in human biomedicine research. Here, we conducted a meta-GWAS analysis for 232 complex traits with 28.3 million imputed whole-genome sequence variants in 70,328 individuals from 14 pig breeds. We identified a total of 6,878 genomic regions associated with 139 complex traits. By integrating with the Pig Genotype-Tissue Expression (PigGTEx) resource, we systemically explored the biological context and regulatory circuits through which these trait-associated variants act and finally prioritized 16,664 variant-gene-tissue-trait circuits. For instance, rs344053754 regulates the expression of UGT2B31 in the liver by affecting the activity of regulatory elements and ultimately influences litter weight at weaning. Furthermore, we investigated the conservation of genetic and regulatory mechanisms underlying 136 human traits and 232 pig traits. Overall, our multi-breed meta-GWAS in pigs provides invaluable resources and novel insights for understanding the regulatory and evolutionary mechanisms of complex traits in both pigs and humans.

Apolygus lucorum (Meyer-Dür.) and Erythroneura apicalis (Nawa) are important pests that affect the quality and the yield of grapevine and cause huge economic losses. This paper focuses on the selection of effective botanical pesticides to control A. lucorum and E. apicalis. This experiment explores the effect of several botanical pesticides for A. lucorum and E. apicalis, including the 0.5% veratrine, the 0.6% Oxygen * Lactone agent, the 5% natural pyrethrin, the composite neem pesticide, the rotenone and the composite nicotine. The 0.5% veratrine shows a stable control efficacy, which is higher than 60% in Chengdu, while the composite nicotine shows the highest efficacy against A. lucorum, which is above 70%. In Yinchuan, the 0.5% veratrine shows the highest efficacy, against the first generation adults and the second generation larvae of E. apicalis, while the 5% natural pyrethrin shows 100% control efficacy against E. apicalis in Nanjiang. The 0.5% veratrine and the composite neem could be used as effective pesticides to control A. lucorum and the 5% natural pyrethrin can be used to control E. apicalis. They could be widely used in the production of pollution-free grapes.