Baryon Electric Charge Correlation as a Magnetometer of QCD.

The correlation between net baryon number and electric charge, χ_{11}^{BQ}, can serve as a magnetometer of QCD. This is demonstrated by lattice QCD computations using the highly improved staggered quarks with physical pion mass of M_{π}=135 MeV on N_{τ}=8 and 12 lattices. We find that χ_{11}^{BQ} along the transition line starts to increase rapidly with magnetic field strength eB≳2M_{π}^{2} and by a factor 2 at eB≃8M_{π}^{2}. Furthermore, the ratio of electric charge chemical potential to baryon chemical potential, µ_{Q}/µ_{B}, shows significant dependence on the magnetic field strength and varies from the ratio of electric charge to baryon number in the colliding nuclei in heavy ion collisions. These results can provide baselines for effective theory and model studies, and both χ_{11}^{BQ} and µ_{Q}/µ_{B} could be useful probes for the detection of magnetic fields in relativistic heavy ion collision experiments as compared with corresponding results from the hadron resonance gas model.

Cracking the Code: Enhancing Molecular Tools for Progress in Nanobiotechnology.

Nature continually refines its processes for optimal efficiency, especially within biological systems. This article explores the collaborative efforts of researchers worldwide, aiming to mimic nature's efficiency by developing smarter and more effective nanoscale technologies and biomaterials. Recent advancements highlight progress and prospects in leveraging engineered nucleic acids and proteins for specific tasks, drawing inspiration from natural functions. The focus is developing improved methods for characterizing, understanding, and reprogramming these materials to perform user-defined functions, including personalized therapeutics, targeted drug delivery approaches, engineered scaffolds, and reconfigurable nanodevices. Contributions from academia, government agencies, biotech, and medical settings offer diverse perspectives, promising a comprehensive approach to broad nanobiotechnology objectives. Encompassing topics from mRNA vaccine design to programmable protein-based nanocomputing agents, this work provides insightful perspectives on the trajectory of nanobiotechnology toward a future of enhanced biomimicry and technological innovation.

Requirement analysis for an AI-based AR assistance system for surgical tools in the operating room: stakeholder requirements and technical perspectives.

PURPOSE: We aim to investigate the integration of augmented reality (AR) within the context of increasingly complex surgical procedures and instrument handling toward the transition to smart operating rooms (OR). In contrast to cumbersome paper-based surgical instrument manuals still used in the OR, we wish to provide surgical staff with an AR head-mounted display that provides in-situ visualization and guidance throughout the assembly process of surgical instruments. Our requirement analysis supports the development and provides guidelines for its transfer into surgical practice. METHODS: A three-phase user-centered design approach was applied with online interviews, an observational study, and a workshop with two focus groups with scrub nurses, circulating nurses, surgeons, manufacturers, clinic IT staff, and members of the sterilization department. The requirement analysis was based on key criteria for usability. The data were analyzed via structured content analysis. RESULTS: We identified twelve main problems with the current use of paper manuals. Major issues included sterile users' inability to directly handle non-sterile manuals, missing details, and excessive text information, potentially delaying procedure performance. Major requirements for AR-driven guidance fall into the categories of design, practicability, control, and integration into the current workflow. Additionally, further recommendations for technical development could be obtained. CONCLUSION: In conclusion, our insights have outlined a comprehensive spectrum of requirements that are essential for the successful implementation of an AI- and AR-driven guidance for assembling surgical instruments. The consistently appreciative evaluation by stakeholders underscores the profound potential of AR and AI technology as valuable assistance and guidance.

[A transcriptomic analysis of correlation between mitochondrial function and energy metabolism remodeling in mice with myocardial fibrosis following myocardial infarction].

OBJECTIVE: To investigate the changes of mitochondrial respiratory function during myocardial fibrosis in mice with myocardial infarction (MI) and its correlation with the increase of glycolytic flux. METHODS: Forty C57BL/6N mice were randomized into two equal groups to receive sham operation or ligation of the left anterior descending coronary artery to induce acute MI. At 28 days after the operation, 5 mice from each group were euthanized and left ventricular tissue samples were collected for transcriptomic sequencing. FPKM method was used to calculate gene expression levels to identify the differentially expressed genes (DEGs) in MI mice, which were analyzed using GO and KEGG databases to determine the pathways affecting the disease process. Heat maps were drawn to show the differential expressions of the pathways and the related genes in the enrichment analysis. In primary cultures of neonatal mouse cardiac fibroblasts (CFs), the changes in mitochondrial respiration and glycolysis levels in response to treatment with the pro-fibrotic agonist TGF-ß1 were analyzed using Seahorse experiment. RESULTS: The mouse models of MI showed significantly increased diastolic and systolic left ventricular diameter (P < 0.05) and decreased left ventricular ejection fraction (P < 0.0001). A total of 124 up-regulated and 106 down-regulated DEGs were identified in the myocardial tissues of MI mice, and GO and KEGG enrichment analysis showed that these DEGs were significantly enriched in fatty acid metabolism, organelles and other metabolic pathways and in the mitochondria. Heat maps revealed fatty acid beta oxidation, mitochondrial dysfunction and increased glycolysis levels in MI mice. In the primary culture of CFs, treatment with TGF-ß1 significantly reduced the basal and maximum respiratory levels and increased the basal and maximum glycolysis levels (P < 0.0001). CONCLUSION: During myocardial fibrosis, energy metabolism remodeling occurs in the CFs, manifested by lowered mitochondrial function and increased energy generation through glycolysis.

[Low-dose CT reconstruction based on high-dimensional partial differential equation projection recovery].

OBJECTIVE: We propose a low-dose CT reconstruction method using partial differential equation (PDE) denoising under high-dimensional constraints. METHODS: The projection data were mapped into a high-dimensional space to construct a high-dimensional representation of the data, which were updated by moving the points in the high-dimensional space. The data were denoised using partial differential equations and the CT image was reconstructed using the FBP algorithm. RESULTS: Compared with those by FBP, PWLS-QM and TGV-WLS methods, the relative root mean square error of the Shepp-Logan image reconstructed by the proposed method were reduced by 68.87%, 50.15% and 27.36%, the structural similarity values were increased by 23.50%, 8.83% and 1.62%, and the feature similarity values were increased by 17.30%, 2.71% and 2.82%, respectively. For clinical image reconstruction, the proposed method, as compared with FBP, PWLS-QM and TGV-WLS methods, resulted in reduction of the relative root mean square error by 42.09%, 31.04% and 21.93%, increased the structural similarity values by 18.33%, 13.45% and 4.63%, and increased the feature similarity values by 3.13%, 1.46% and 1.10%, respectively. CONCLUSION: The new method can effectively reduce the streak artifacts and noises while maintaining the spatial resolution in reconstructed low-dose CT images.

Spot size measurement of a deuterium-tritium dense plasma focus using neutron radiography.

Neutron radiography is a technique uniquely suited to applications in nuclear diagnostics, non-destructive testing, and subcritical experiments. The spatial resolution of neutron radiographs is degraded by optical blur in the imaging system and the neutron source size, where the ideal source is point-like to optimize the point-spread function. A potential neutron source for radiography is the dense plasma focus (DPF), a coaxial Z-pinch that produces thermonuclear and beam-target neutrons. To assess if the source size is suitable for radiography, a neutron imaging system was used to measure the source size of the 4 MA Sodium DPF at the Nevada National Security Site operating with deuterium-tritium gas-fill. The source size was measured using the edge-spread function of tungsten objects, each having a rolled (convex) edge. The spot size was found to be 7-12 mm full-width at half-max (FWHM) assuming a Gaussian source, though comparison is presented for Lorentzian and Bennett distributions. The average FWHM was found to be 8.6 ± 1.2 mm vertically and 10.8 ± 1.2 mm horizontally with respect to the image plane, averaging over varied edges and alignments. The results were sensitive to source alignment and edge metrology, which introduced notable uncertainties. These results are consistent with separate experimental measurements as well as magnetohydrodynamics simulations of this DPF, which suggest that neutron production can originate from pinches ∼5-7 mm off-axis. These results suggest that the DPF should be used for radiography at low magnification (M < 1) where spot size does not dominate spatial blur.

[Incidence of common gene mutations in early-onset colorectal cancer and the association with cancer survival: a meta-analysis].

Objective: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally; however, the molecular characteristics and prognosis of sporadic EOCRC are unclear. In this systematic review and meta-analysis, we aimed to investigate the incidence of gene mutations and their association with cancer survival in sporadic EOCRC, focusing on six common gene mutations (TP53, BRAF, KRAS, NRAS, PTEN, and APC). Methods: Ovid Embase and Ovid Medline electronic databases were searched for studies involving patients with sporadic EOCRC (i.e., diagnosed with colorectal cancer before the age of 50 years and with no evidence of hereditary syndromes predisposing to colorectal cancer). The included articles were evaluated using quality assessment tools. Meta-analysis was performed using random-effects and fixed-effects models. Cochran's Q statistic and the I2 index were used to assess heterogeneity. The incidence of the six common gene mutations listed above in sporadic EOCRC and their association with cancer survival were evaluated. Results: (1) Incidence of specific gene mutations in sporadic EOCRC. A total of 34 articles were included in this meta-analysis. The incidence of APC gene mutation was 36% (from 13 articles, 95%CI: 19%-55%, P=0.043); of KRAS gene mutation 30% (from 26 articles, 95%CI: 24%-35%, P=0.190); of BRAF gene mutation 7% (from 18 articles, 95%CI: 5%-11%, P=0.422); of NRAS gene mutation 4% (from five articles, 95%CI: 3%-5%, P=0.586); of PTEN gene mutation 6% (from six articles, 95%CI: 4%-10%, P=0.968); and of TP53 gene mutation 59% (from 13 articles, 95%CI: 49%-68%, P=0.164). (2) Association between gene mutations and survival in sporadic EOCRC. A total of six articles were included in this meta-analysis. Compared with wild-type BRAF, mutant BRAF was significantly associated with increased overall mortality risk in patients with EOCRC (pooled HR=2.85, 95%CI: 1.45-5.60, P=0.002). Subgroup analysis showed that the incidence of BRAF gene mutation was higher in Eastern than in Western countries, whereas the incidence of TP53, KRAS, NRAS, and APC gene mutations was lower. There was no significant difference in the incidence of PTEN gene mutation between different regions. Conclusion: Compared with colorectal cancer occurring in the general population, the incidence of APC and KRAS mutations is lower in EOCRC, whereas the incidence of TP53 mutation remains consistent. BRAF mutation is associated with increased overall mortality risk in patients with EOCRC.

[Diagnostics and treatment challenges and research progress in early-onset gastric cancer].

The incidence of gastric cancer has decreased, while the occurrence of early-onset gastric cancer has increased. There is no consensus on the definition of early-onset gastric cancer currently. The characteristics of tumor staging and differentiation, coupled with the lack of targeted comprehensive treatment, present a significant clinical challenge in managing early-onset gastric cancer. Relevant studies have analyzed the genetic characteristics of early-onset gastric cancer and have preliminarily revealed its relationship with Helicobacter pylori infection and molecular subtypes. These findings have the potential to contribute to the prevention and personalized treatment of early-onset gastric cancer. In the future, larger-scale evidence-based data are needed to establish diagnostic criteria, elucidate the mechanisms, and develop targeted diagnostic and therapeutic strategies of early-onset gastric cancer.

[Correlation study between brain damage and anxiety, depression, and cognitive impairment in patients with moderate to severe obstructive sleep apnea hypopnea syndrome using diffusional kurtosis imaging].

Objective: To explore the brain white matter damage in patients with moderate to severe obstructive sleep apnea hypopnea syndrome(OSAHS) using diffusional kurtosis imaging(DKI), and to analyze its relationship with anxiety, depression and cognitive impairment in patients. Methods: This was a retrospective case-control study. Fifty confirmed cases (47 males and 3 females) of moderate to severe OSAHS diagnosed by polysomnography(PSG) from November 2017 to December 2022 were selected as OSAHS group(age range from 22 to 65 years old, with median age of 40 years old), and 32 healthy controls(27 males and 5 females) of non-OSAHS diagnosed by PSG were selected as control group(age range from 19 to 56 years old, with median age of 34 years old). DKI scanning, Beck Anxiety Inventory(BAI), Beck Depression Inventory-Ⅱ(BDI-Ⅱ), and Montreal cognitive assessment(MoCA) scores were performed in all subjects. Differences in kurtosis fractional anisotropy(KFA) of various brain regions were compared between the two groups to identify differential brain regions. Correlations were analyzed between KFA reduction and anxiety, depression, and cognitive impairment in OSAHS patients. To study the correlation between brain injury and anxiety, depressive mood, and cognitive dysfunction, statistical methods such as non-parametric tests for two independent samples, chi-square tests, and partial correlation analysis, were used to analyze the evaluation indicators of the two groups. Results: The KFA values in right external capsule, left anterior corona radiata, right anterior corona radiata, left posterior corona radiata, right posterior corona radiata, left superior corona radiata, right superior corona radiata, left superior longitudinal fasciculus, right superior longitudinal fasciculus, genu of corpus callosum, splenium of corpus callosum, body of corpus callosum, posterior cingulate gyrus of moderate to severe OSAHS group were all lower than those in the control group(t=-2.247, -3.028, -3.955, -4.871, -2.632, -2.594, -2.121, -2.167, -3.129, -2.015, -2.317, -2.313, -2.152,P<0.05). For the moderate to severe OSAHS group, the correlation between AHI and KFA values of right posterior corona radiata, right superior corona radiata, left anterior corona radiata, left posterior corona radiata, left superior corona radiata, left superior longitudinal fasciculus, genu of corpus callosum, body of corpus callosum, splenium of corpus callosum were all negative(r=-0.378, -0.307, -0.337, -0.343, -0.341, -0.613, -0.390, -0.384, -0.396, P<0.05). The correlation between LSO2 and KFA values of right anterior corona radiata, right posterior corona radiata, right superior corona radiata, right superior longitudinal fasciculus, left anterior corona radiata, left posterior corona radiata, left superior corona radiata, left superior longitudinal fasciculus, genu of corpus callosum, body of corpus callosum, splenium of corpus callosum, posterior cingulate gyrus were all positive(r=0.330, 0.338, 0.425, 0.312, 0.433, 0.358, 0.410, 0.459, 0.473, 0.659, 0.489, 0.356, P<0.05). The correlation between BAI scores and KFA values of right external capsule, right anterior corona radiata, left posterior corona radiata, left superior corona radiata, body of corpus callosum, splenium of corpus callosum were all negative(r=-0.306, -0.372, -0.296, -0.346, -0.318, -0.386, P<0.05). The correlation between BDI-Ⅱ scores and KFA values of right superior corona radiata, right superior longitudinal fasciculus, left anterior corona radiata, genu of corpus callosum, body of corpus callosum, splenium of corpus callosum were all negative(r=-0.334, -0.289, -0.309, -0.310, -0.503, -0.469, P<0.05). The correlation between MoCA scores and KFA values of right posterior corona radiata, right superior longitudinal fasciculus, left anterior corona radiata, left superior corona radiata, left superior longitudinal fasciculus, genu of corpus callosum, body of corpus callosum, splenium of corpus callosum were all positive(r=0.368, 0.431, 0.324, 0.410, 0.469, 0.384, 0.369, 0.309, P<0.05). Conclusions: With the aggravation of OSAHS, the damage to some brain regions becomes more pronounced in moderate to severe OSAHS patients. These damage brain functional areas are closely related to the anxiety, depression, and cognitive impairment of patients.

China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

The complexity of glucose time series is associated with short- and long-term mortality in critically ill adults: a multi-center, prospective, observational study.

BACKGROUND: The wealth of data taken from continuous glucose monitoring (CGM) remains to be fully used. We aimed to evaluate the relationship between a promising new CGM metric, complexity of glucose time series index (CGI), and mortality in critically ill patients. METHODS: A total of 293 patients admitted to mixed medical/surgical intensive care units from 5 medical centers in Shanghai were prospectively included between May 2020 and November 2021. CGI was assessed using intermittently scanned CGM, with a median monitoring period of 12.0 days. Outcome measures included short- and long-term mortality. RESULTS: During a median follow-up period of 1.7 years, a total of 139 (47.4%) deaths were identified, of which 73 (24.9%) occurred within the first 30 days after ICU admission, and 103 (35.2%) within 90 days. The multivariable-adjusted HRs for 30-day mortality across ascending tertiles of CGI were 1.00 (reference), 0.68 (95% CI 0.38-1.22) and 0.36 (95% CI 0.19-0.70), respectively. For per 1-SD increase in CGI, the risk of 30-day mortality was decreased by 51% (HR 0.49, 95% CI 0.35-0.69). Further adjustment for HbA1c, mean glucose during hospitalization and glucose variability partially attenuated these associations, although the link between CGI and 30-day mortality remained significant (per 1-SD increase: HR 0.57, 95% CI 0.40-0.83). Similar results were observed when 90-day mortality was considered as the outcome. Furthermore, CGI was also significantly and independently associated with long-term mortality (per 1-SD increase: HR 0.77, 95% CI 0.61-0.97). CONCLUSIONS: In critically ill patients, CGI is significantly associated with short- and long-term mortality.

ELABELA-APJ Axis Enhances Mesenchymal Stem Cell Proliferation and Migration via the METTL3/PI3K/AKT Pathway.

Mesenchymal stem cells (MSCs) possess a strong therapeutic potential in regenerative medicine. ELABELA (ELA) is a 32 amino acid peptide that binds to the apelin peptide jejunum receptor (APJ) to regulate cell proliferation and migration. The aim of this study was to investigate the function of ELA vis-a-vis the MSC proliferation and migration, and further explore the underlying mechanism. We demonstrated that the exogenous supplement of ELA boosts the proliferation and migration ability of MSCs, alongside improved in vitro cell viability. These capabilities were rendered moot upon APJ knockdown. In addition, ELA (5-20 µM) was shown to upregulate the expression of METTL3 in a concentrationdependent pattern, a capacity which was suppressed by APJ reduction, whereas the downregulation of METTL3 expression blocked the beneficial effects induced by ELA. ELA was also observed to upregulate the phosphorylation level of AKT. This ELA-induced activation of the PI3K/AKT pathway, however, is inhibited with knockdown of METTL3. Our data indicate that ELA could act as a promoter of MSC proliferation and migration in vitro through the APJ receptor, something which might be attributed to the activation of the METTL3/PI3K/AKT signaling pathway. Therefore, ELA is a candidate for optimizing MSC-based cell therapy, while METTL3 is a potential target for its promoting action on MSCs.

Associations of ambient temperature and total cloud cover during pregnancy with newborn vitamin D status.

OBJECTIVES: We aimed to estimate the effects of temperature and total cloud cover before birth on newborn vitamin D status. STUDY DESIGN: Prospective birth cohort. METHODS: This study included 2055 mother-newborn pairs in Wuhan, Hubei province, China. The data of temperature and total cloud cover from 30 days before birth were collected, and cord blood 25-hydroxyvitamin D [25(OH)D] were determined. Restricted cubic spline regression models, multiple linear regression models, and logistic regression models were applied to estimate the associations. RESULTS: A "J" shaped curve was observed between temperature and vitamin D status, and an inverse "J" shaped curve was observed between total cloud cover and vitamin D status. Compared to the fourth quartile (75-100th percentile, Q4) of average temperature (30 days before birth), the odds ratio (OR) for Q1 (0-25th percentile) associated with the vitamin D deficiency occurrence (<20 ng/mL) was 3.63 (95% CI, 1.54, 8.65). Compared to Q1 of the average total cloud cover (30 days before birth), the OR associated with the occurrence of vitamin D deficiency was 2.38 (95% CI, 1.63, 3.50) for the Q4. CONCLUSIONS: Low temperature and high cloud cover before delivery were significantly associated with an increased probability of vitamin D deficiency in newborns. The findings suggested that pregnancy women lacking sufficient sunlight exposure still need vitamin D supplement to overcome the potential vitamin D deficiency status.

Risk factors for gingival invagination: A retrospective study.

AIM: This study aimed to identify the risk factors for gingival invagination during orthodontic treatment after premolar extraction. MATERIALS AND METHODS: The medical records of 135 patients who had undergone interdental space closure after premolar extraction were collected, and cone beam computed tomography was performed to determine the presence of gingival invagination. The risk factors were examined using mixed-effects models and generalized propensity score weighting (GPSW) to develop a predictive model. RESULTS: Univariate analysis revealed that the extraction site, buccal bone thickness 4 mm apical to the cemento-enamel junction (MB1), mid-root buccal bone thickness (MB2) and vertical skeletal relationships were related to gingival invagination (p < .05). Furthermore, a subsequent multivariable mixed-effects model analysis indicated a significantly increased risk of gingival invagination at MB1 < 1 mm (p < .001; odds ratio [ORMB1≤0.5mm] = 29.304; 95% confidence interval [CI]: 8.986-93.807; OR0.5

Novel Measurement of the Neutron Magnetic Form Factor from A=3 Mirror Nuclei.

The electromagnetic form factors of the proton and neutron encode information on the spatial structure of their charge and magnetization distributions. While measurements of the proton are relatively straightforward, the lack of a free neutron target makes measurements of the neutron's electromagnetic structure more challenging and more sensitive to experimental or model-dependent uncertainties. Various experiments have attempted to extract the neutron form factors from scattering from the neutron in deuterium, with different techniques providing different, and sometimes large, systematic uncertainties. We present results from a novel measurement of the neutron magnetic form factor using quasielastic scattering from the mirror nuclei ^{3}H and ^{3}He, where the nuclear effects are larger than for deuterium but expected to largely cancel in the cross-section ratios. We extracted values of the neutron magnetic form factor for low-to-modest momentum transfer, 0.6

[Value of peripheral blood rare cell EGFR gene amplification detection in the evaluation of benign and malignant pulmonary nodules].

Objective: To explore the value of detection of epidermal growth factor receptor (EGFR) gene amplification in peripheral blood rare cells in the assessment of benign and malignant pulmonary nodules. Methods: A total of 262 patients with pulmonary nodules were selected as the retrospectively study subjects from the Second Affiliated Hospital of Army Military Medical University and Peking Union Medical College Hospital from July 2022 to August 2023. There were 98 males and 164 females, with the age range from 16 to 79 (52.1±12.1) years. The EGFR gene amplification testing was performed on the rare cells enriched from patients' peripheral blood, and the clinical manifestations, CT imaging features, histopathological and/or pathological cytological confirmed results of patients were collected. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of the method of detection of EGFR gene amplification in peripheral blood rare cells, and its diagnostic efficacy was evaluated. Results: Among the 262 patients, 143 were malignant pulmonary nodules and 119 were benign pulmonary nodules. The differences between malignant pulmonary nodules and benign pulmonary nodules in nodule diameter and nodule density were statistically significant (both P<0.001), while the differences in age, gender and nodule number were not statistically significant (all P>0.05). The number [M (Q1, Q3)] of EGFR gene amplification positive rare cells in patients with malignant pulmonary nodule was 8 (6, 11), which was higher than that in patients with benign pulmonary nodule [2 (1, 4), P<0.001]. The ROC curve results showed that when the optimal cut-off value was 5 (that was, the number of EGFR gene amplification positive rare cells was>5), the area under the curve (AUC) of the detection of EGFR gene amplification in peripheral blood rare cells for discrimination of benign and malignant pulmonary lesions was 0.816 (95%CI: 0.761-0.870), with a sensitivity of 83.2%, a specificity of 80.7%, and an accuracy of 82.1%. Based on the analysis of the diameter of the nodules, the AUC for distinguishing between benign and malignant pulmonary nodules with diameter 5-9 mm and 10-30 mm was 0.797 (95%CI: 0.707-0.887) and 0.809 (95%CI: 0.669-0.949), respectively, with sensitivity, specificity and accuracy reached 75% or above. Based on the analysis of nodule density, the AUC for distinguishing between benign and malignant solid nodule and subsolid nodule was 0.845 (95%CI: 0.751-0.939) and 0.790 (95%CI: 0.701-0.880), respectively, with sensitivity, specificity and accuracy reached 75% or above. Based on the analysis of nodule number, the AUC for distinguishing between benign and malignant solitary pulmonary nodule and multiple pulmonary nodule was 0.830 (95%CI: 0.696-0.965) and 0.817 (95%CI: 0.758-0.877), respectively, with sensitivity, specificity and accuracy reached 80% or above. Conclusion: The detection of EGFR gene amplification in peripheral blood rare cells contributes to the evaluation of benign and malignant pulmonary nodules, and can be used in the auxiliary diagnosis of benign and malignant pulmonary nodules.

[Jisuikang formula promotes spinal cord injury repair in rats by activating the YAP/PKM2 signaling axis in astrocytes].

OBJECTIVE: To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. METHODS: Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. RESULTS: The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. CONCLUSION: Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.

[Arbutin ameliorates liver fibrosis in mice by inhibiting macrophage recruitment and regulating the Akt/NF-κB and Smad signaling pathways].

OBJECTIVE: To investigate the protective effect of arbutin against CCl4-induced hepatic fibrosis in mice and explore the underlying mechanisms. METHODS: Twenty-four C57BL/6 mice were randomly divided into control group, model group, and low- and high-dose arbutin treatment (25 and 50 mg/kg, respectively) groups. Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4, and arbutin was administered daily via gavage for 6 weeks. After the treatments, serum biochemical parameters of the mice were tested, and liver tissues were taken for HE staining, Sirius Red staining and immunohistochemical staining. RT-qPCR was used to detect the mRNA levels of α-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-a, and Western blotting was performed to detect α-SMA protein expression in the liver tissues. In the cell experiment, the effect of arbutin treatment for 24 h on THP-1 and RAW264.7 cell migration and recruitment was examined using Transwell migration assay and DAPI staining; The changes in protein levels of Akt, p65, Smad3, p-Akt, p-p65, p-Smad3 and α-SMA in arbutintreated LX-2 cells were detected with Western blotting. RESULTS: Arbutin treatment significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels, alleviated liver tissue damage and collagen deposition, and reduced macrophage infiltration and α-SMA protein expression in the liver of the mouse models (P < 0.05 or 0.001). Arbutin treatment also significantly reduced CCl4-induced elevation of a-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-a mRNA levels in mice (P < 0.05). In the cell experiment, arbutin treatment obviously inhibited migration and recruitment of THP-1 and RAW264.7 cells and lowered the phosphorylation levels of Akt, p65 and Smad3 and the protein expression level of α-SMA in LX-2 cells. CONCLUSION: Arbutin ameliorates liver inflammation and fibrosis in mice by inhibiting hepatic stellate cell activation via reducing macrophage recruitment and infiltration and suppressing activation of the Akt/NF-κB and Smad signaling pathways.