Comparative pharmacokinetic study on phenolic acids and flavonoids in normal and microcirculation dysfunction rats plasma by UPLC-TQ/MS/MS after oral administration of Salvia miltiorrhiza stem-leaf extracts.

According to the Standard of Chinese Medicinal Materials of Shaanxi Province (2015 edition), Salvia miltiorrhiza caulis et folium is the dried stems and leaves of Salvia miltiorrhiza, which could activate blood and dispell blood stasis, clear the mind and remove annoyance. In this study, the dynamic absorption changes of phenolic acids (FS) and phenolic acids-flavonoids (FT) in rats after oral administration were studied by UPLC-TQ/MS/MS, to elucidate the pharmacokinetics of seven major bioactive components of the stem-leaf of Salvia miltiorrhiza in vivo. The results showed that the pharmacokinetic parameters of FS and FT were significantly different in normal rats and model rats. Compared with the control group, after injecting 10 % polymer dextran 500 into the tail vein to establish a model of microcirculation disturbance, the Cmax of caffeic acid decreased. The Cmax of rosmarinic acid and lithospermic acid increased. Danshensu showed a decrease in CLz/F, accompanied by an increase in both AUC0-t and AUC0-∞. The AUC0-t of lithospermic acid was also increased. These results indicated that microcirculation disturbance could decrease the absorption of caffeic acid while increasing the absorption of danshensu, rosmarinic acid and lithospermic acid. After oral administration of FT, the Cmax of danshensu and the AUC0-t of caffeic acid were increased significantly, suggesting that the presence of flavonoids may promote the absorption and exposure of phenolic acids in vivo. This study provides a reference for the elucidation of the in vivo substances and the mechanisms of action of FS and FT from the stem-leaf of Salvia miltiorrhiza.

Large Tunable Spin-to-Charge Conversion in Ni80Fe20/Molybdenum Disulfide by Cu Insertion.

Spin-to-charge conversion at the interface between magnetic materials and transition metal dichalcogenides has drawn great interest in the research efforts to develop fast and ultralow power consumption devices for spintronic applications. Here, we report room temperature observations of spin-to-charge conversion arising from the interface of Ni80Fe20 (Py) and molybdenum disulfide (MoS2). This phenomenon can be characterized by the inverse Edelstein effect length (λIEE), which is enhanced with decreasing MoS2 thicknesses, demonstrating the dominant role of spin-orbital coupling (SOC) in MoS2. The spin-to-charge conversion can be significantly improved by inserting a Cu interlayer between Py and MoS2, suggesting that the Cu interlayer can prevent magnetic proximity effect from the Py layer and protect the SOC on the MoS2 surface from exchange interactions with Py. Furthermore, the Cu-MoS2 interface can enhance the spin current and improve electronic transport. Our results suggest that tailoring the interface of magnetic heterostructures provides an alternative strategy for the development of spintronic devices to achieve higher spin-to-charge conversion efficiencies.

Xianlian Jiedu Decoction alleviates colorectal cancer by regulating metabolic profiles, intestinal microbiota and metabolites.

BACKGROUND: Xianlian Jiedu Decoction (XLJDD) has been used for the treatment of colorectal cancer (CRC) for several decades because of the prominent efficacy of the prescription. Despite the clear clinical efficacy of XLJDD, the anti-CRC mechanism of action is still unclear. PURPOSE: The inhibitory effect and mechanism of XLJDD on CRC were investigated in the azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mice. METHODS: The AOM/DSS-induced mice model was adopted to evaluate the efficacy after administering the different doses of XLJDD. The therapeutic effects of XLJDD in treating AOM/DSS-induced CRC were investigated through histopathology, immunofluorescence and ELISA analysis methods. In addition, metabolomics profile and 16S rRNA analysis were used to explore the effective mechanisms of XLJDD on CRC. RESULTS: The results stated that the XLJDD reduced the number of tumor growth on the inner wall of the colon and the colorectal weight/length ratio, and suppressed the disease activity index (DAI) score, meanwhile XLJDD also increased body weight, colorectal length, and overall survival rate. The treatment of XLJDD also exhibited the ability to lower the level of inflammatory cytokines in serum and reduce the expression levels of ß-catenin, COX-2, and iNOS protein in colorectal tissue. The findings suggested that XLJDD has anti-inflammatory properties and may provide relief for those suffering from inflammation-related conditions. Mechanistically, XLJDD improved gut microbiota dysbiosis and associated metabolic levels of short chain fatty acids (SCFAs), sphingolipid, and glycerophospholipid. This was achieved by reducing the abundance of Turicibacter, Clostridium_sensu_stricto_1, and the levels of sphinganine, LPCs, and PCs. Additionally, XLJDD increased the abundance of Enterorhabdus and Alistipes probiotics, as well as the content of butyric acid and isovaleric acid. CONCLUSION: The data presented in this article demonstrated that XLJDD can effectively inhibit the occurrence of colon inner wall tumors by reducing the level of inflammation and alleviating intestinal microbial flora imbalance and metabolic disorders. It provides a scientific basis for clinical prevention and treatment of CRC.

Ascertaining sensitive exposure biomarkers of various metal(loid)s to embryo implantation.

Close relationships exist between metal(loid)s exposure and embryo implantation failure (EIF) from animal and epidemiological studies. However, there are still inconsistent results and lacking of sensitive metal(loid) exposure biomarkers associated with EIF risk. We aimed to ascertain sensitive metal(loid) biomarkers to EIF and provide potential biological explanations. Candidate metal(loid) biomarkers were measured in the female hair (FH), female serum (FS), and follicular fluid (FF) with various exposure time periods. An analytical framework was established by integrating epidemiological association results, comprehensive literature searching, and knowledge-based adverse outcome pathway (AOP) networks. The sensitive biomarkers of metal(loid)s along with potential biological pathways to EIF were identified in this framework. Among the concerned 272 candidates, 45 metal(loid)s biomarkers across six time periods and three biomatrix were initially identified by single-metal(loid) analyses. Two biomarkers with counterfactual results according to literature summary results were excluded, and a total of five biomarkers were further determined from 43 remained candidates in mixture models. Finally, four sensitive metal(loid) biomarkers were eventually assessed by overlapping AOP networks information, including Se and Co in FH, and Fe and Zn in FS. AOP networks also identified key GO pathways and proteins involved in regulation of oxygen species biosynthetic, cell proliferation, and inflammatory response. Partial dependence results revealed Fe in FS and Co in FH at their low levels might be potential sensitive exposure levels for EIF. Our study provided a typical framework to screen the crucial metal(loid) biomarkers and ascertain that Se and Co in FH, and Fe and Zn in FS played an important role in embryo implantation.

Predicting brain age using partition modeling strategy and atlas-based attentional enhancement in the Chinese population.

As a biomarker of human brain health during development, brain age is estimated based on subtle differences in brain structure from those under typical developmental. Magnetic resonance imaging (MRI) is a routine diagnostic method in neuroimaging. Brain age prediction based on MRI has been widely studied. However, few studies based on Chinese population have been reported. This study aimed to construct a brain age predictive model for the Chinese population across its lifespan. We developed a partition prediction method based on transfer learning and atlas attention enhancement. The participants were separated into four age groups, and a deep learning model was trained for each group to identify the brain regions most critical for brain age prediction. The Atlas attention-enhancement method was also used to help the models focus only on critical brain regions. The proposed method was validated using 354 participants from domestic datasets. For prediction performance in the testing sets, the mean absolute error was 2.218 ± 1.801 years, and the Pearson correlation coefficient (r) was 0.969, exceeding previous results for wide-range brain age prediction. In conclusion, the proposed method could provide brain age estimation to assist in assessing the status of brain health.

Exploration of the Healthy Donor Effect Among 0.6 Million Blood Donors in China: Longitudinal Study.

BACKGROUND: The World Health Organization emphasizes the importance of completely voluntary blood donation to maintain safe and sustainable blood supplies. However, the benefits of blood donation for donors, such as reducing the risk of disease, remain a topic of debate due to the existence of the healthy donor effect (HDE). This effect arises because of inherent health differences between blood donors and the general population, and it is also considered a methodological issue. OBJECTIVE: This study aims to generate a more detailed health profile of blood donors from a donor cohort study to mitigate and quantify the HDE and properly interpret the association between blood donation and disease outcomes among blood donors. METHODS: A retrospective cohort study was conducted between January 2012 and December 2018 among donors before their first donation. One-to-one propensity score matching was conducted through a random selection of individuals without any history of blood donation, as reported from their electronic health records. We conducted a Poisson regression between blood donors and non-blood donors before the first donation to estimate the adjusted incidence rate ratio (AIRR) of selected blood donation-related diseases, as defined by 13 categories of International Classification of Diseases, Tenth Revision (ICD-10) codes. RESULTS: Of the 0.6 million blood donors, 15,115 had an inpatient record before their first donation, whereas 17,356 non-blood donors had an inpatient record. For the comparison between blood donors and the matched non-blood donors, the HDE (the disease incidence rate ratio between non-blood donors and blood donors) was an AIRR of 1.152 (95% CI 1.127-1.178; P<.001). Among disease categories not recommended for blood donation in China, the strongest HDE was observed in the ICD-10 D50-D89 codes, which pertain to diseases of the blood and blood-forming organs as well as certain disorders involving the immune mechanism (AIRR 3.225, 95% CI 2.402-4.330; P<.001). After age stratification, we found that people who had their first blood donation between 46-55 years old had the strongest HDE (AIRR 1.816, 95% CI 1.707-1.932; P<.001). Both male and female donors had significant HDE (AIRR 1.082, 95% CI 1.05-1.116; P=.003; and AIRR 1.236, 95% CI 1.196-1.277; P<.001, respectively) compared with matched non-blood donors. CONCLUSIONS: : Our research findings suggest that the HDE is present among blood donors, particularly among female donors and those who first donated blood between the ages of 46 and 55 years. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200055983; https://www.chictr.org.cn/showproj.html?proj=51760.

Integrated Network Analysis of Symptom Clusters Across Monkeypox Epidemics From 1970 to 2023: Systematic Review and Meta-Analysis.

BACKGROUND: The worldwide spread of monkeypox (mpox) has witnessed a significant increase, particularly in nonendemic countries. OBJECTIVE: We aimed to investigate the changing clinical symptoms associated with mpox from 1970 to 2023 and explore their interrelations. METHODS: In this systematic review and meta-analysis, 3 electronic databases were searched for English peer-reviewed studies conducted from January 1970 to April 2023 that reported any symptoms among confirmed mpox cases. We categorized the mpox epidemics into 3 periods: 1970-2002 (period 1, within the African region), 2003-2021(period 2, epidemics outside Africa), and 2022-2023 (period 3, worldwide outbreak). Following PRISMA guidelines, a meta-analysis was performed to estimate the pooled prevalence for each symptom. The correlation among symptoms was analyzed and visualized using network analysis. RESULTS: The meta-analysis included 61 studies that reported 21 symptoms in 720 patients from period 1, 39 symptoms in 1756 patients from period 2, and 37 symptoms in 12,277 patients from period 3. The most common symptom among patients from all 3 periods was rash (period 1: 92.6%, 95% CI 78.2%-100%; period 2: 100%, 95% CI 99.9%-100%; and period 3: 94.8%, 95% CI 90.9%-98.8%), followed by lymphadenopathy (period 1: 59.8%, 95% CI 50.3%-69.2%; period 2: 74.1%, 95% CI 64.2%-84.1%; and period 3: 61.1%, 95% CI 54.2%-68.1%). Fever (99%, 95% CI 97%-100%), enlarged lymph nodes (80.5%, 95% CI 75.4%-85.0%), and headache (69.1%, 95% CI 4%-100%) were the main symptoms in period 1, with a significant decrease in period 3: 37.9%, 31.2%, and 28.7%, respectively. Chills/rigors (73.3%, 95% CI 60.9%-85.7%), fatigue (68.2%, 95% CI 51.6%-84.8%), and dysphagia/swallowing difficulty (61.2%, 95% CI 10.5%-100%) emerged as primary new symptoms in period 2 and decreased significantly in period 3. Most other symptoms remained unchanged or decreased in period 3 compared to the former 2 periods. Nausea/vomiting had the highest degree of correlation (with 13 symptoms) and was highly positively correlated with lymphadenopathy (r=0.908) and conjunctivitis (r=0.900) in period 2. In contrast, rash and headache were 2 symptoms with the highest degree of correlation (with 21 and 21 symptoms, respectively) in period 3 and were highly positively correlated with fever (r=0.918 and 0.789, respectively). CONCLUSIONS: The manifestation of symptoms in patients with mpox has become more diverse, leading to an increase in their correlation. Although the prevalence of rash remains steady, other symptoms have decreased. It is necessary to surveil the evolving nature of mpox and the consequential changes in clinical characteristics. Epidemic countries may shift their focus on the potential association among symptoms and the high synergy risk. TRIAL REGISTRATION: PROSPERO Registration: CRD42023403282; http://tinyurl.com/yruuas5n.

Gray and white matter abnormalities in children with type 2 and 3 SMA: A morphological assessment.

This study investigated the changes in brain gray and white matter structure in SMA patients and their correlation with the severity of the disease. A total of 43 SMA patients (including 22 type II and 21 type III SMA patients) and 37 healthy controls were evaluated by MRI. The gray matter volume, gray matter thickness, gray matter surface area, and white matter volume of designated brain regions automatically segmented by FreeSurfer, were compared. We evaluate clinical characteristics of SMA and study the correlation between clinical characteristics and structural changes. SMA showed significant bilateral cortical superficial area loss in the frontal, parietal, and temporal lobes and global white matter volume decreases. Moreover, these patients were also found with an increased mean thickness of entire brain and right gray matter. An increased right postcentral gyrus superficial area, right central sulcus volume, and white matter volume of the right postcentral were associated with higher HFMSE scores. CONCLUSION: Type 2 and 3 children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. The lack of SMN protein possibly interacted with cerebellar structural changes in somatosensory areas. WHAT IS KNOWN: • MRI has found brain changes in SMA patients, however, there is no unified conclusion and lack of correlation with clinical degree in children SMA with type 2-3. WHAT IS NEW: • Type II and II children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. Cerebellar structural changes in somatosensory areas may attribute to the lack of SMN protein.

Predictive value of peripheral blood biomarkers in patients with non-small-cell lung cancer responding to anti-PD-1-based treatment.

BACKGROUND: The introduction of the anti-PD-1 antibody has greatly improved the clinical outcomes of patients with non-small cell lung cancer (NSCLC). In this study, we retrospectively analyzed the efficacy of PD-1 antibody-based therapy in patients with locally advanced inoperable or metastatic NSCLC and reported an association between peripheral blood biomarkers and clinical response in these patients. METHODS: This single-center study included medical record data of patients with NSCLC treated with the PD-1 antibody as a first-line or subsequent line of treatment, either as monotherapy or in combination with chemotherapy. The patients were enrolled from 2020 to 2022. We dynamically evaluated multiple Th1 and Th2 cytokines in the blood serum and analyzed the phenotype of T cells from the peripheral blood to explore the correlation between cytokine levels, T cell phenotypes, and clinical response. RESULTS: A total of 88 patients with stage IIIA-IV NSCLC were enrolled, out of which 60 (68.18%) achieved a partial response (PR), 13 (14.77%) had stable disease (SD), and 15 (17.05%) experienced disease progression (PD). The disease control rate was 82.95%. Our results suggested a significant reduction (P = 0.002, P < 0.005) in lymphocyte absolute counts after treatment in patients with PD. Higher levels of IFN-γ (P = 0.023, P < 0.05), TNF-α (P = 0.00098, P < 0.005), IL-4 (P = 0.0031, P < 0.005), IL-5 (P = 0.0015, P < 0.005), and IL-10 (P = 0.036, P < 0.05) were detected in the peripheral blood before treatment in the PR group compared to the PD group. Moreover, patients with high levels of IL-5, IL-13, IL-4, IL-6, IFN-γ, and TNF-α (> 10 ng/mL) had superior progression-free survival compared to those with low levels (< 10 ng/mL). Furthermore, PD-1 expression on CD8+ T cells was higher in patients who showed a PR than in those who did not show a response (SD + PD; P = 0.042, P < 0.05). CONCLUSIONS: The findings of this study imply that the decrease in absolute blood lymphocyte counts after treatment is correlated with disease progression. Serum cytokine levels may predict the effectiveness and survival rates of anti-PD-1 blockade therapy in patients with NSCLC. In addition, PD-1 expression on CD8+ T cells was positively associated with better clinical response. Our findings highlight the potential of peripheral blood biomarkers to predict the effectiveness of PD-1-targeted treatments in patients with NSCLC. Larger prospective studies are warranted to further clarify the value of these biomarkers.

[Predictive Value of Peripheral Blood Biomarkers in the Treatment of 
Lung Cancer Patients with Anti PD-1 Immunotherapy].

BACKGROUND: The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses. METHODS: We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed. RESULTS: All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline. CONCLUSIONS: Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.

Epitaxial Growth and Characterization of Nanoscale Magnetic Topological Insulators: Cr-Doped (Bi0.4Sb0.6)2Te3.

The exploration initiated by the discovery of the topological insulator (BixSb1-x)2Te3 has extended to unlock the potential of quantum anomalous Hall effects (QAHEs), marking a revolutionary era for topological quantum devices, low-power electronics, and spintronic applications. In this study, we present the epitaxial growth of Cr-doped (Bi0.4Sb0.6)2Te3 (Cr:BST) thin films via molecular beam epitaxy, incorporating various Cr doping concentrations with varying Cr/Sb ratios (0.025, 0.05, 0.075, and 0.1). High-quality crystalline of the Cr:BST thin films deposited on a c-plane sapphire substrate has been rigorously confirmed through reflection high-energy electron diffraction (RHEED), X-ray diffraction (XRD), and high-resolution transmission electron microscopy (HRTEM) analyses. The existence of a Cr dopant has been identified with a reduction in the lattice parameter of BST from 30.53 ± 0.05 to 30.06 ± 0.04 Å confirmed by X-ray diffraction, and the valence state of Cr verified by X-ray photoemission (XPS) at binding energies of ~573.1 and ~583.5 eV. Additionally, the influence of Cr doping on lattice vibration was qualitatively examined by Raman spectroscopy, revealing a blue shift in peaks with increased Cr concentration. Surface characteristics, crucial for the functionality of topological insulators, were explored via Atomic Force Microscopy (AFM), illustrating a sevenfold reduction in surface roughness as the Cr concentration increased from 0 to 0.1. The ferromagnetic properties of Cr:BST were examined by a superconducting quantum interference device (SQUID) with a magnetic field applied in out-of-plane and in-plane directions. The Cr:BST samples exhibited a Curie temperature (Tc) above 50 K, accompanied by increased magnetization and coercivity with increasing Cr doping levels. The introduction of the Cr dopant induces a transition from n-type ((Bi0.4Sb0.6)2Te3) to p-type (Cr:(Bi0.4Sb0.6)2Te3) carriers, demonstrating a remarkable suppression of carrier density up to one order of magnitude, concurrently enhancing carrier mobility up to a factor of 5. This pivotal outcome is poised to significantly influence the development of QAHE studies and spintronic applications.

Altered neurovascular coupling in the children with attention-deficit/hyperactivity disorder: a comprehensive fMRI analysis.

The coupling between resting-state cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) signals reflects the mechanism of neurovascular coupling (NVC), which have not been illustrated in attention-deficit/hyperactivity disorder (ADHD). Fifty ADHD and 42 age- and gender-matched typically developing controls (TDs) were enrolled. The NVC imaging metrics were investigated by exploring the Pearson correlation coefficients between CBF and BOLD-derived quantitative maps (ALFF, fALFF, DCP maps). Three types of NVC metrics (CBF-ALFF, CBF-fALFF, CBF-DCP coupling) were compared between ADHD and TDs group, and the inner association between altered NVC metrics and clinical variables in ADHD group was further analyzed. Compared to TDs, ADHD showed significantly reduced whole-brain CBF-ALFF coupling (P < 0.001). Among regional level (all PFDR < 0.05), ADHD showed significantly lower CBF-ALFF coupling in bilateral thalamus, default-mode network (DMN) involving left anterior cingulate (ACG.L) and right parahippocampal gyrus (PHG.R), execution control network (ECN) involving right middle orbital frontal gyrus (ORBmid.R) and right inferior frontal triangular gyrus (IFGtriang.R), and increased CBF-ALFF coupling in attention network (AN)-related left superior temporal gyrus (STG.L) and somatosensory network (SSN))-related left rolandic operculum (ROL.L). Furthermore, increased CBF-fALFF coupling was found in the visual network (VN)-related left cuneus and negatively correlated with the concentration index of ADHD (R = - 0.299, PFDR = 0.035). Abnormal regional NVC metrics were at widespread neural networks in ADHD, mainly involved in DMN, ECN, SSN, AN, VN and bilateral thalamus. Notably, this study reinforced the insights into the neural basis and pathophysiological mechanism underlying ADHD.

Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS). METHODS: Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson's correlation was used to analyze the correlation with clinical symptoms. RESULTS: The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r = - 0.323, p < 0.05). CONCLUSIONS: Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD. CLINICAL RELEVANCE STATEMENT: Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder. KEY POINTS: • Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children. • The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder. • The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.

Salvianolic acid B and tanshinone IIA synergistically improve early diabetic nephropathy through regulating PI3K/Akt/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes, which lacks effective treatment. Salviae Miltiorrhizae Radix Et Rhizoma is one of the key compatible traditional Chinese medicine in the prescription for the treatment of DN. Salvianolic acid B and tanshinone IIA are two monomer active components with high content and clear structure in Salvia miltiorrhiza, which can effectively improve early (DN), respectively. AIM OF THE STUDY: To evaluate the compatible effect of salvianolic acid B and tanshinone IIA on early DN rats and elucidate the mechanism. METHODS: Early DN rats were induced by streptozotocin combined with high glucose and high fat diet, and intervened by salvianolic acid B, tanshinone IIA and their combinations. The pathological sections of kidney, liver and biochemical indexes were analyzed. Network pharmacology method was used to predict the possible mechanism. The mechanisms were elucidated by metabolomics, Elisa, and Western blot. RESULTS: Given our analysis, salvianolic acid B and tanshinone IIA can synergistically regulate 24 h UTP, Urea and Scr and improve kidney damage in early DN rats. The metabolic abnormalities of early DN rats were improved by regulating the biosynthesis of saturated fatty acids, glycerol phospholipid metabolism, steroid biosynthesis, alanine, and arachidonic acid. Salvianolic acid B combined with tanshinone IIA at a mass ratio of 13.4:1 can significantly reduce kidney inflammation, up-regulate p-PI3K/PI3K and p-Akt/Akt and down-regulate p-NF-κB/NF-κB, which better than the single-used group and can be reversed by PI3K inhibitor LY294002. CONCLUSION: Salvianolic acid B and tanshinone IIA can synergistically improve glucose and lipid disorders, liver and kidney damage, and resist kidney inflammation in early DN rats, and the mechanism may be related to regulating PI3K/Akt/NF-κB signaling pathway.

Exploring multimorbidity profiles in middle-aged inpatients: a network-based comparative study of China and the United Kingdom.

BACKGROUND: Multimorbidity is better prevented in younger ages than in older ages. This study aims to identify the differences in comorbidity patterns in middle-aged inpatients from China and the United Kingdom (UK). METHODS: We utilized 184,133 and 180,497 baseline hospitalization records in middle-aged populations (40-59 years) from Shaanxi, China, and UK Biobank. Logistic regression was used to calculate odds ratios and P values for 43,110 unique comorbidity patterns in Chinese inpatients and 21,026 unique comorbidity patterns in UK inpatients. We included the statistically significant (P values adjusted by Bonferroni correction) and common comorbidity patterns (the pattern with prevalence > 1/10,000 in each dataset) and employed network analysis to construct multimorbidity networks and compare feature differences in multimorbidity networks for Chinese and UK inpatients, respectively. We defined hub diseases as diseases having the top 10 highest number of unique comorbidity patterns in the multimorbidity network. RESULTS: We reported that 57.12% of Chinese inpatients had multimorbidity, substantially higher than 30.39% of UK inpatients. The complete multimorbidity network for Chinese inpatients consisted of 1367 comorbidities of 341 diseases and was 2.93 × more complex than that of 467 comorbidities of 215 diseases in the UK. In males, the complexity of the multimorbidity network in China was 2.69 × more than their UK counterparts, while the ratio was 2.63 × in females. Comorbidities associated with hub diseases represented 68.26% of comorbidity frequencies in the complete multimorbidity network in Chinese inpatients and 55.61% in UK inpatients. Essential hypertension, dyslipidemia, type 2 diabetes mellitus, and gastritis and duodenitis were the hub diseases in both populations. The Chinese inpatients consistently demonstrated a higher frequency of comorbidities related to circulatory and endocrine/nutritional/metabolic diseases. In the UK, aside from these comorbidities, comorbidities related to digestive and genitourinary diseases were also prevalent, particularly the latter among female inpatients. CONCLUSIONS: Chinese inpatients exhibit higher multimorbidity prevalence and more complex networks compared to their UK counterparts. Multimorbidity with circulatory and endocrine/nutritional/metabolic diseases among both Chinese and UK inpatients necessitates tailored surveillance, prevention, and intervention approaches. Targeted interventions for digestive and genitourinary diseases are warranted for the UK.

[High-value utilization technology and approach of Chinese medicinal residues under background of "Dual Carbon"].

In recent years, the traditional Chinese medicine(TCM)industry has experienced rapid development, resulting in a significant amount of Chinese medicinal residues generated during the industrial manufacturing process. Currently, the main methods of handling Chinese medicinal residues include stacking, landfilling, and incineration, which lead to substantial resource waste and potential environmental pollution. With "carbon peak" and "carbon neutrality"( "Dual Carbon")becoming national strategic goals, the TCM industry is ushering in a new wave of "low-carbon" trends, and the high-value utilization of Chinese medicinal residues has become a breakthrough for implementing a low-carbon economy in the TCM sector. From the perspective of a low-carbon economy, this article reviewed literature in China and abroad to summarize the microbial transformation technology, enzymatic conversion technology, biomass pyrolysis, gasification, hydrothermal liquefaction, and other high-value utilization technologies for Chinese medicinal residues. It also overviewed the applications of Chinese medicinal residue in feed additives, organic fertilizers, edible mushroom cultivation substrates, preparation of activated carbon for wastewater treatment, and new energy batteries. Considering the current status of resource utilization of Chinese medicinal residues, feasible strategies and suggestions for resource development and utilization were proposed to improve the quality and efficiency of the Chinese medicinal resource industry chain and promote green development, thereby providing research ideas and theoretical basis for achieving carbon peak and carbon neutrality goals.

Comparison of three fundus inspection methods during phacoemulsification in diabetic white cataract.

AIM: To investigate whether Wild Field Imaging System (WFIS SW-8000), 25G endoilluminator, and intraoperative optical coherence tomography (iOCT) can perform real-time screening and diagnosing in patients with suspicious diabetic retinopathy (DR) during phacoemulsification, especially in cases of white cataract. METHODS: A cross-sectional study was carried out. A total of 204 dense diabetic cataractous eyes of 204 patients with suspected DR treated from April 2020 to March 2021 were included. Phacoemulsification combined with intraocular lens implantation was performed. Following the removal of the lens opacity, the 25G endo-illuminator, fundus photography, and iOCT were performed successively. Optical coherence tomography (OCT) and/or fundus fluorescein angiography (FFA) were used to verify the fundus findings postoperatively. Intraoperative and postoperative results were compared to verify the accuracy of intraoperative diagnosis in each group. RESULTS: Intraoperative and postoperative examinations revealed 58 and 62 eyes with DR, respectively (positive rate, 28.43% and 30.39%, respectively). During the phacoemulsification, WFIS SW-8000 detected 44 eyes with DR (the detection rate, 70.97%); 25G endo-illuminator found 56 eyes with DR (the detection rate, 90.32%); iOCT found 46 eyes with DR (the detection rate, 74.19%); and 58 eyes with DR were found by combining the three methods (the detection rate, 93.55%). There were statistically significant differences in the diagnostic sensitivity for DR among the methods (χ2=16.36, P=0.001). CONCLUSION: WFIS SW-8000, 25G endo-illuminator, iOCT, and especially their combination can be used to inspect the fundus and detect DR intraoperatively; they are helpful for the timely diagnosis and treatment of DR in patients with dense cataract.

[Measures for waste and by-product recycling and circular economy of whole industry chain of traditional Chinese medicine resources facing carbon peak and carbon neutrality (dual carbon) goals].

It has become a common consensus that resource conservation and intensive recycling for improving resource utilization efficiency is an important way to achieve carbon peak and carbon neutrality(dual carbon). Traditonal Chinese medicine(TCM)resources as national strategic resources are the material basis and fundamental guarantee for the development of TCM industry and health services. However, the rapid growth of China's TCM industry and the continuous expansion and extension of the industrial chain have exposed the low efficiency of TCM resources. Resource waste and environmental pollution caused by the treatment and discharge of TCM waste have emerged as major problems faced by the development of the industry, which has aroused wide concern. Considering the dual carbon goals, this paper expounds the role and potential of TCM resource recycling and circular economy industry development. Taking the typical model of TCM resource recycling as the case of circular economy industry in reducing carbon source and increasing carbon sink, this paper puts forward the suggestions for the TCM circular economy industry serving the double carbon goals. The suggestions mainly include strengthening the policy and strategic leading role of the double carbon goals, building an objective evaluation system of low-carbon emission reduction in the whole industrial chain of TCM resources, building an industrial demonstration park for the recycling of TCM resources, and promoting the establishment of a circular economy system of the whole industrial chain of TCM resources. These measures are expected to guide the green transformation of TCM resource industry from linear economic model to circular economy model, provide support for improving the utilization efficiency and sustainable development of TCM resources, and facilitate the low-carbon and efficient development of TCM resource industry and the achievement of the double carbon goals.

Pathology of MRI and second-look ultrasound detected multifocal breast cancer.

INTRODUCTION: Targeted second-look ultrasound (US) is often performed following MRI of the breast to determine if an MRI-detected lesion is visible on US and thus amenable to US-guided biopsy. This study aimed to assess the pathology of lesions detected and biopsied on the second-look US. In particular, for multifocal cancers, whether the pathology of additional lesions detected by second-look US is different to the index lesion. METHODS: Multicentre single-institution retrospective study of 300 consecutive cases of second-look US biopsies from August 2017 to April 2022 was performed, with their histopathology and imaging characteristics recorded. For multifocal cancers, Wilcoxon Signed Ranks Tests were used to compare differences between the index and additional lesions in the histopathology category (i.e., high-risk benign, precursor or malignant) and BRE grade. RESULTS: 69 multifocal cancers were detected. For the purposes of this study, additional lesions were considered more invasive if they were of a higher histopathological category or BRE grade, or demonstrated lymphovascular invasion when the primary lesion did not. 15/69 additional lesions were not seen on the initial mammogram/tomography or ultrasound, seen on subsequent MRI and second look US, and were less invasive than the index lesion. 3/69 additional lesions were more invasive than their index lesions. Wilcoxon Signed Ranks test showed additional lesions were of either similar or lesser invasiveness compared to index lesions (z= -3.207, p = 0.001) in the histopathological category, and the same or lower BRE grade (z= -2.972, p = 0.003). CONCLUSION: In multifocal breast cancers, additional lesions detected on MRI and second-look US have the same or less invasive histopathology compared to the index lesion.

Recent advances in neoantigen vaccines for treating non-small cell lung cancer.

The breakthrough of programmed cell death protein 1 (PD-1) blockade therapy has changed the clinical treatment of non-small cell lung cancer (NSCLC) in the past few years. The success of PD-1 blockade therapy has been attributed to high tumor mutation burden and high immunogenicity of lung cancer cells. To further improve the efficacy of NSCLC immunotherapy and overcome the resistance of lung cancer cells to immune checkpoint blockade, new approaches that enhance the active immune response, such as neoantigen vaccines and cellular-based therapies, are urgently required. Neoantigens are considered ideal targets for cancer immunotherapy because of their high immunogenicity and specificity. In this mini review, we first discuss the current advances in neoantigen vaccines for treating cancers and then review the results of preclinical studies and early-phase human clinical trials of neoantigen-based therapies for NSCLC. Finally, we focus on the identification of neoantigens in patients with NSCLC and review the candidate mutations reported by recent studies and our investigations. The review concludes that, in addition to immune checkpoint blockade, approaches targeting neoantigens are promising for improving the efficacy of NSCLC immunotherapy.