OBJECTIVE To investigate the protective effect and mechanism of saikosaponin C （SSC） on acute liver injury （ALI） in mice induced by carbon tetrachloride （CCl4） based on serum metabolomics. METHODS Forty mice were divided into blank group （water）， model group （water）， positive control drug group （Biphenyl diester drop pills， 150 mg/kg）， and SSC low- and high-dose groups （2.5， 10 mg/kg） using the random number table method， with 8 mice in each group. They were given water/ relevant drugs， once a day， for 7 consecutive days. One hour after the last administration， all mice were intraperitoneally injected with 0.2% CCl4 olive oil to induce ALI model， except for the blank group. After 17 hours of the modeling， the liver index of mice was calculated. The levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， lactate dehydrogenase （LDH）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β in serum of mice were detected. The histopathological changes of liver tissue were observed. Meanwhile， the serum metabolomics of mice were analyzed by liquid chromatography-mass spectrometry. RESULTS Compared with the blank group， the levels of liver index， ALT， AST， LDH， TNF-α， IL-6， and IL-1β in the model group were significantly increased （P＜0.01）. Hepatocytes were edema， vacuolar degeneration， more necrosis， and a large number of inflammatory cells were infiltrated. Compared with the model group， liver index and serum index levels of mice were significantly decreased （P＜0.05 or P＜0.01）， accompanied by marked improvement in histopathological damage to the liver tissue. The metabolomics results showed that compared with the model group， there were 63 up-regulated and 256 down-regulated differential metabolites in the serum of mice in the SSC high-dose group， including prostaglandin B2， 20-hydroxy-leukotriene B4， 5- hydroxy-L-tryptophan， 7α -hydroxycholesterol， etc.； these metabolites were primarily involved in metabolic pathways such as arachidonic acid metabolism， 5-hydroxytryptamine synapse， primary bile acid biosynthesis. CONCLUSIONS SSC exerts a protective effect against CCl4-induced ALI by down-regulating the level of key metabolites such as prostaglandin B2 and 20-hydroxy-leukotriene B4， and then ruducing metabolic pathways such as arachidonic acid metabolism， 5- hydroxytryptamine synapse， and primary bile acid biosynthesis.

[Objective] To analyze the loss rate of platelet donors and evaluate the strategies for establishing a platelet donor bank. [Methods] A total of 1 443 donors who joined the HLA and HPA gene donor bank for platelets in Henan Province from 2018 to 2020 were included in this study. Data on the total number of apheresis platelet donations, annual donation frequency, age at enrollment, donation habits (including the number of platelets donated per session and whether they had previously donated whole blood), and enrollment location were collected from the platelet donor information management system. Donor loss was determined based on the date of their last donation. The loss rates of different groups under various conditions were compared to assess the enrollment strategies. [Results] By the time the platelet bank was officially operational in 2022, 421 donors had been lost, resulting in an loss rate of 29% (421/1 443). By the end of 2023, the overall cumulative loss rate reached 52% (746/1 443). The loss rate was lower than the overall level in groups meeting any of the following conditions: total apheresis platelet donations exceeding 50, annual donation frequency of 10 or more, age at enrollment of 40 years or older, donation of more than a single therapeutic dose per session, or a history of whole blood donation two or more times. Additionally, loss rates varied across different enrollment locations, with higher enrollment numbers generally associated with higher loss rates. [Conclusion] Through a comprehensive analysis of donor loss, our center has adjusted its strategies for establishing the donor pool. These findings also provide valuable insights for other blood collection and supply institutions in building platelet donor banks.

Objective To explore and analyze the related factors of kinesiophobia in elderly patients with coronary heart disease (CHD) during cardiac rehabilitation exercise period, and to evaluate the effect of cognitive behavior therapy on improving kinesiophobia and promoting rehabilitation. Methods A total of 352 elderly patients with CHD admitted to the hospital were included from October 2023 to October 2024. Tampa Scale for Kinesiophobia-11 (TSK-11) was adopted to evaluate the kinesiophobia status. Patients with kinesiophobia were randomly grouped. Routine intervention (routine group, n=82) and cognitive behavior intervention (study group, n=82) were implemented respectively. The intervention effects were observed in both groups. Results Among the 352 patients, 46.59 % (164/352 ) of elderly patients with coronary heart disease had different degrees of kinesiophobia. The proportions of female, divorced/widowed, revascularization and family relationship disharmony and scores of Patient Health Questionnaire (PHQ9) and Generalized Anxiety Disorder Scale (GAD7) in patients with kinesiophobia were higher than those in patients without kinesiophobia (P<0.05) while the scores of General Self-Efficacy Scale (GSES) and Social Support Rating Scale (SSRS) were lower compared with those in patients without kinesiophobia (P<0.05). Logistic regression analysis found that female, divorced/widowed, family relationship disharmony, revascularization and scores of PHQ9, TSK-11, GAD7, GSES and SSRS were related to kinesiophobia (P<0.05). After intervention, the scores of TSK-11, PHQ9 and GAD7 in the study group were lower while the scores of GSES and SSRS, 6 min walking test distance, and cardiopulmonary exercise test peak oxygen uptake and anaerobic threshold were higher compared to the routine group (P<0.05). Conclusion The kinesiophobia in elderly patients with CHD during cardiac rehabilitation is related to gender, revascularization and psychosocial factors. Clinically, cognitive behavior intervention should be provided according to the situation and guided to carry out rehabilitation exercise regularly so as to promote improvement of cardiopulmonary function.

Objective To study the effect of Mycobacterium tuberculosis (Mtb) Pro-Pro-Glu-59 (PPE59) protein on the biological function of Mycobacterium smegmatis (Ms) and the regulation of host cell immune response. Methods PPE59 gene fragment was obtained by PCR amplification, cloned into pALACE, constructed into recombinant pALACE-PPE59 vector, and electro-transformed into Ms. Western blot was applied to analyse PPE59 expression and subcellular localization. The survival of Ms_Vec and Ms_PPE59 under low acid (pH=3 and pH=5) conditions and active surface pressure sodium dodecyl sulfate (SDS) conditions and their intracellular survival in macrophages were analyzed. ELISA was used to detect the cytokine (IL-1β, IL-6, IL-12, TNF-α and IL-10) expression levels of Ms_Vec and Ms_PPE59 infected macrophages. Results PPE59 protein localized to the cell wall of Ms can enhance the acid-resistance and anti-SDS effect of Ms, which is conducive to the survival of Ms in macrophages. PPE59 significantly decreased the secretion levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-12 and TNF-α), and promoted the secretion levels of anti-inflammatory cytokine (IL-10). Conclusion PPE59 enhances the survival ability of Ms under low acid and SDS pressure and promotes its intracellular survival by regulating the cytokine secretion levels.
Mycobacterium smegmatis/metabolism* ; Macrophages/metabolism* ; Cytokines/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Bacterial Proteins/metabolism* ; Animals ; Mice ; Antigens, Bacterial/metabolism*

Aconitum (Ranunculaceae) has a long-standing history in traditional Chinese medicine (TCM), where it has been widely used to treat conditions such as rheumatoid arthritis (RA), myocardial infarction, and heart failure. However, the potency of Aconitum alkaloids, the primary active components of Aconitum, also confers substantial toxicity. Therefore, assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety. Metabolomics, a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways, provides a comprehensive view of the metabolic state across multiple systems in vivo. This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity, identifying potential sensitive biomarkers, and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM. This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing, aiming to identify more viable methods for characterizing toxic medicinal plants.
Aconitum/metabolism* ; Metabolomics/methods* ; Alkaloids/metabolism* ; Humans ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective To analyze the differences in static balance plantar pressure characteristics between female adolescent idiopathic scoliosis(AIS)patients with moderate Lenke 3CN and healthy adolescents of the same age,and provide a scientific basis for scoliosis screening,assessment,treatment,and prognosis evaluation.Methods A total of 30 female patients with moderate Lenke 3CN AIS as the AIS group and 30 healthy female adolescents of the same age as the control group were selected,respectively.The plantar pressure data of the subjects were collected,and the characteristics of equilibrium plantar pressure distributions in two groups were comparatively analyzed.Results Regarding the plantar pressure characteristics,the average pressure(P<0.05)and hindfoot pressure(P<0.05)of the left and right foot in the AIS group were significantly greater than those of the control group,the forefoot pressure was significantly lower than that of the control group(P<0.05),and the symmetry index(SI)of both feet was significantly greater than that of the control group(P<0.05).The plantar pressure of the left foot in the AIS group was significantly larger than that of the control group in the medial mid-foot area and 1st toe area(P<0.05),and significantly smaller than that of the control group in the 1st,2nd,3rd,4th and 5th metatarsal areas(P<0.05);the plantar pressure of the right foot in the AIS group was significantly greater than that of the control group in the medial heel area and the1st toe area(P<0.05),and significantly smaller than that of the control group in the lateral mid-foot area,the 3rd,4th,5th metatarsal area and 3rd,4th,5th toe area(P<0.05);and the plantar pressure in the right foot of the AIS group was significantly smaller than that of the control group in the medial heel area and 1st toe area(P<0.05).The plantar pressures at lateral midfoot area,the 3rd,4th,5th metatarsal area and the 3rd,4th,5th toe area of the right foot were significantly larger than those of the control group(P<0.05).Regarding the center of pressure(COP),the length of the COP trajectory,the ellipse area of the 95%confidence interval,the maximum distance of COP left-right movement(COP-X),and the maximum distance of COP anterior-posterior movement(COP-Y)of the AIS group were significantly larger than those of the control group(P<0.05).Conclusions There are significant differences in static balance plantar pressure characteristics between female AIS patients with moderate Lenke 3CN and healthy female adolescents of the same age,with foot pressure favoring the side of the lateral convexity,poorer symmetry and stability of the feet,and weaker balance control.

Objective:To explore the strategy of prostate biopsy in patients with prostate specific antigen(PSA)gray zone based on prostate imaging reporting and data system (PI-RADS).Methods:The clinical data of 427 patients who underwent transperineal prostate biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2022 were retrospectively analyzed. The median age was 66 (61, 72) years old. The median PSA was 6.62 (5.46, 8.19) ng/ml. The median PSA density (PSAD) was 0.15 (0.11, 0.21) ng/ml 2. The median prostate volume (PV) was 43.68 (31.12, 56.82) ml. PSA velocity (PSAV) data were available in 65 patients with negative MRI examination(PI-RADS <3), and the median PSAV was 1.40 (0.69, 2.89) ng/(ml· year). Among the patients with positive MRI(PI-RADS≥3), there were 174 patients with only 1 lesion and 83 patients with ≥2 lesions. A total of 170 patients with negative MRI underwent systematic biopsy, and 257 patients with positive MRI underwent systematic combined targeted biopsy. The PI-RADS score, regions of interest(ROI), PSAD, f/tPSA and PSAV were analyzed to explore the biopsy strategy for patients with PSA gray area based on bpMRI imaging. Results:Of the 427 patients included in the study, 194 were positive and 233 were negative. Among the patients with positive biopsy pathology, 140 cases were clinically significant prostate cancer (CsPCa). Among the MRI-negative patients, there were 33 cases with PSAV ≥1.4 ng/(ml·year), and 10 cases of prostate cancer and 6 cases of CsPCa were detected by systematic biopsy.In 32 cases with PSAV <1.4 ng/(ml·year), 3 cases of prostate cancer and 0 case of CsPCa were detected by systematic biopsy. The sensitivity of systematic biopsy for the diagnosis of prostate cancer and CsPCa in patients with PSAV≥1.4 ng/(ml·year) were 76.9% (10/13) and 100.0% (6/6) respectively, the specificity were 55.8% (29/52) and 54.2% (32/59) respectively, the negative predictive value were 90.6% (29/32) and 100.0% (32/32) respectively, and the positive predictive value were 30.3% (10/33) and 18.2% (6/33) respectively. In MRI-positive patients with PI-RADS 3, the prostate cancer detection rates of targeted biopsy combined with systematic biopsy, systematic biopsy and targeted biopsy were 41.7% (45/108), 32.4% (35/108) and 35.2% (38/108), respectively ( P=0.349). The detection rates of CsPCa were 27.8% (30/108), 21.3% (23/108) and 25.0% (27/108), respectively ( P=0.541). In patients with PI-RADS 4-5 and PSAD > 0.15 ng/ml 2, the detection rates of CsPCa in targeted biopsy combined with systematic biopsy, systematic biopsy and targeted biopsy were 67.8% (61/90), 58.9% (53/90) and 67.8% (61/90), respectively ( P=0.354). Conclusions:For MRI-negative patients, all CsPCa could be detected by perineal systematic biopsy when PSAV ≥1.4 ng/(ml·year), and active observation could be performed when PSAV <1.4 ng/(ml·year). For MRI-positive patients, targeted combined systemic biopsy was required when PI-RADS score was 3, and targeted biopsy only could be performed when PI-RADS score ≥4 and PSAD >0.15 ng/ml 2, otherwise targeted combined systemic biopsy was required.

Objective:To analyze the correlation between drug-induced sleep endoscopy (DISE), results, polysomnography (PSG) indicators, and clinical parameters in patients with obstructive sleep apnea (OSA), and to establish and validate a predictive model for tongue base plane obstruction.Methods:This retrospective study analyzed 117 OSA patients diagnosed via PSG and treated at the Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, between October 2014 and March 2022. The cohort comprised of 114 males and 3 females, with an age range of 20 to 54 years (mean age 38.1±8.4 years). Data on DISE results, PSG results, and clinical indicators were collected for all 117 patients. Logistic regression analysis was performed to identify relevant indicators, and a predictive model for tongue base plane obstruction was constructed and internally validated using the R programming language.Results:Univariate logistic regression analysis identified four independent risk factors for predicting tongue root plane obstruction: tonsil grading, N2, N3, and rapid eye movement sleep(REM) stage [ OR:0.412(0.260~0.652),1.045(1.012~1.079),0.943(0.903~0.984),0.961(0.925~0.998), P <0.05]. Multivariate logistic regression analysis confirmed tonsil grading and N3 sleep stage (12.48±12.22%) as significant predictors. A nomogram model incorporating these factors demonstrated good predictive performance, with an area under curve(AUC) of 0.82 (95% CI: 0.548-1.000), an optimal cutoff of 0.519, a specificity of 80.0%, and a sensitivity of 86.7%. Internal validation of the model in the validation cohort yielded an AUC of 0.751 (95% CI: 0.625-0.876). Conclusions:Tongue base plane obstruction observed during DISE in OSA patients is associated with tonsil grading and N3 sleep stage duration. The predictive model developed for tongue base plane obstruction based on DISE demonstrates good efficacy, as evidenced by its internal validation.

ObjectiveTo investigate the attenuating effect of Dioscoreae Bulbiferae Rhizoma（DBR） processed with Phaseoli Radiati Semen（PRS） juice， and explore the attenuating mechanism based on ferroptosis of the main toxic target organ. MethodSixty male ICR mice were randomly divided into blank group， DBR group， water roasted DBR group（hereinafter referred to as water group）， PRS juice-roasted DBR group 1（DBR-PRS 10∶1， stuffy moistening for 40 min， stir-fried at 130 ℃ for 18 min， hereinafter referred to as group 1）， PRS juice-roasted DBR group 2（DBR-PRS 10∶1， stuffy moistening for 80 min， stir-fried at 100 ℃ for 14 min， hereinafter referred to as group 2）， PRS juice-roasted DBR group 3（DBR-PRS=20∶3， stuffy moistening for 40 min， stir-fried at 160 ℃ for 14 min， hereinafter referred to as group 3）. The raw and processed groups of DBR were gavaged with their corresponding 95% ethanol extract at a dose of 3 g·kg^-1·d^-1， while the blank group was gavaged with an equal volume of 0.5% sodium carboxymethyl cellulose， once a day for 14 consecutive days. Hematoxylin-eosin（HE） staining was used to observe the histopathological changes of mouse liver. Alanine aminotransferase（ALT） and aspartate aminotransferase（AST） levels in serum， as well as malondialdehyde（MDA）， ferrous ions（Fe²⁺）， reduced glutathione（GSH） and superoxide dismutase（SOD） levels in liver tissue were detected by the biochemical detection. Western blot was used to detect the expression of iron key proteins such as ferritin heavy chain 1（FTH1） and glutathione peroxidase 4（GPX4）. ResultHE staining results showed that the liver tissue structure of the blank group was clear， the morphology of hepatocytes was normal， the cytoplasms of hepatocytes in the DBR group and water group were loose and vacuolar， with obvious pathological damages， and the pathologic damages of mice in the group 1-3 were significantly improved. Compared with the blank group， the levels of ALT， AST， MDA and Fe²⁺ in mice from the DBR group were significantly increased（P<0.01）， while GSH and SOD levels were significantly reduced（P<0.01）， and the protein expression levels of FTH1 and GPX4 were significantly decreased（P<0.01）. Compared with the DBR group， the ALT， AST，MDA and Fe²⁺ levels of mice in the group 1-3 were significantly reduced（P<0.05， P<0.01）， the GSH and SOD levels and the protein expression levels of FTH1 and GPX4 were significantly increased（P<0.01）. Compared with the water group， the AST and MDA levels of mice in the group 1-3 were significantly reduced（P<0.05， P<0.01）， the SOD level significantly increased（P<0.05， P<0.01）， the FTH1 protein expression significantly increased（P<0.01）， and the serum ALT level of mice in the group 2-3 significantly reduce（P<0.01）， Fe²⁺ level significantly reduced（P<0.01）， GSH level significantly increased（P<0.05， P<0.01）， and GPX4 protein expression significantly increased（P<0.05， P<0.01）. Among the group 1-3， the group 3 had the best detoxification effect. ConclutionProcessing with PRS juice can reduce the liver injury induced by DBR， and the mechanism may be related to the inhibition of ferroptosis in the liver.