The present study employed UPLC-MS/MS to analyze and identify compounds in the raw powder of Tongluo Shenggu capsules. An HPLC method for the determination of vitexin content was established. The analysis of this drug was performed on a 30 ℃ thermostatic Acquity UPLC® BEH C18 (2.1 mm×100 mm,1.7 μm) column, with the mobile phase comprising 0.2% formic acid-methanol flowing at 0.3 mL /min in a gradient elution manner. Mass spectrometry was detected by ESI sources in both positive and negative ion modes for qualitative identification of chemical constituents. 12 flavonoid and 3 stilbenes compounds in the raw powder of Tongluo Shenggu capsules were successfully identified. Additionally, an HPLC method for the determination of vitexin content was established using a XBridge C18 column (4.6 mm × 250 mm, 5 µm) with a mobile phase of 0.05% glacial acetic acid in methanol for gradient elution, at a column temperature of 30 °C, a flow rate of 1.0 mL/min, and an injection volume of 20 μL. The method demonstrated good linearity in the concentration range of 10 µg/mL to 40 µg/mL (R=1.000) with an average recovery rate of 96.7%. The establishment of these methods provides a scientific basis for the quality control and development of the raw powder of Tongluo Shenggu capsules.

In recent years, China has been facing the dual challenges of declining fertility rates and births, with male reproductive health issues, especially the decline in semen quality, identified as a pivotal contributor to this phenomenon. Meanwhile, accumulating evidence indicates that air pollutants, an increasingly severe environmental problem, can damage semen quality not only directly through their biological toxicity but also indirectly by disrupting the composition of microbial communities in the gut and semen, thereby dysregulating immune function, endocrine homeostasis, and oxidative stress responses. The gut microbiota and semen microbiota, as important components of the human microecosystem, play crucial roles in maintaining reproductive health. This article comprehensively reviewed the research progress on the potential effects of air pollutants (particulate matter and gaseous pollutants), gut microbiota, and semen microbiota on semen quality. Specifically, it elucidated the mechanisms of interaction between these factors and explored how they affect male fertility.

Normal heart function depends on complex regulation by the brain, and abnormalities in the brain‒heart axis affect various diseases, such as myocardial infarction and anxiety disorders. However, systematic tracking of the brain regions associated with the input and output of the heart is lacking. In this study, we injected retrograde transsynaptic pseudorabies virus (PRV) and anterograde transsynaptic herpes simplex virus (HSV) into the left ventricular wall of mice to identify the whole-brain regions associated with the input to and output from the heart. We successfully detected PRV and HSV expression in at least 170 brain subregions in both male and female mice. Sex differences were discovered mainly in the hypothalamus and medulla, with male mice exhibiting greater correlation and hierarchical clustering than female mice, indicating reduced similarity and increased modularity of virus expression patterns in male mice. Further graph theory and multiple linear regression analysis of different injection timelines revealed that hub regions of PRV had highly similar clusters, with different brain levels, suggesting a top-down, hierarchically transmitted neural control pattern of the heart. Hub regions of HSV had scattered clusters, with brain regions gathered in the cortex and brainstem, suggesting a bottom-up, leapfrog, multipoint neural sensing pattern of the heart. Both patterns contain many hub brain regions that have been previously overlooked in brain‒heart axis studies. These results provide brain targets for future research and will lead to deeper insight into the brain mechanisms involved in specific heart conditions.
Animals ; Male ; Female ; Heart/physiology* ; Mice ; Herpesvirus 1, Suid ; Brain/physiology* ; Mice, Inbred C57BL ; Brain Mapping ; Efferent Pathways/physiology* ; Afferent Pathways/physiology* ; Simplexvirus ; Sex Characteristics

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Stromal interaction molecule 1 (STIM1) is a key component mediating store-operated calcium entry (SOCE), which controls the opening and closing of plasma membrane Ca 2+ channels by sensing the Ca 2+ content of endoplasmic reticulum luminal stores, and thus affects the processes of cell adhesion, migration, gene expression and proliferation. Studies have shown that STIM1 is abnormally expressed in a variety of cells such as neurons, endothelial cells and platelets during ischemic stroke (IS) development; it plays an important role in the pathological processes regulating hypertension, promoting thrombosis, activating cellular autophagy, mediating apoptosis and promoting neuroinflammation. This review summarizes the research progress of STIM1 in the development and prognostic assessment of IS, and seeks to provide theoretical references for potential therapeutic targets for IS.

Objective To investigate the influence of different cell structures on the static and dynamic mechanical performance of porous titanium alloy scaffolds,and to provide a theoretical mechanical basis for the application of scaffolds in the repair of mandibular bone defects.Methods Porous titanium alloy scaffolds with diamond,cubic,and cross-sectional cubic cell structures were manufactured using three-dimensional printing technology.Uniaxial compression tests and ratcheting fatigue with compression load tests were conducted to analyze the static and dynamic mechanical performances of scaffolds with different cell structures.Results The elastic moduli of the diamond cell,cross-sectional cubic cell,and cubic cell scaffolds were 1.17,0.566,and 0.322 GPa,respectively,and the yield strengths were 71.8,65.1,and 31.8 MPa,respectively.After reaching the stable stage,the ratcheting strains of the cross-sectional cubic,diamond,and cubic cell scaffolds were 3.3%,4.0%,and 4.5%,respectively.The ratcheting strain increased with increasing average stress,stress amplitude,and peak holding time,and decreased with increasing loading rate.Conclusions The evaluation results of the static mechanical performance showed that the diamond cell scaffold was the best,followed by the cross-sectional cubic cell scaffold and the cubic cell scaffold.The evaluation results of the dynamic mechanical performance showed that the cross-sectional cubic cell scaffold performed the best,followed by the diamond cell scaffold,whereas the cubic cell scaffold performed the worst.The fatigue performance of the scaffold is affected by the loading conditions.These results provide new insights for scaffold construction for the repair of mandibular bone defects and provide an experimental basis for further clinical applications of this scaffold technology.

Objective:To evaluate the short-term clinical outcomes of meniscus reconstruction using autologous peroneus longus tendon grafts.Methods:A retrospective analysis was conducted on 20 patients (12 males, 8 females) with a mean age of 37.8±5.7 years (range, 31-47 years) and a mean body mass index (BMI) of 26.3±5.8 kg/m 2 (range, 20.1-31.3 kg/m 2) who underwent meniscal reconstruction with autologous peroneus longus tendon in Affiliated Xinhua Hospital of Dalian University from June 2020 to June 2022. A control group of 20 patients (15 males, 5 females), with a mean age of 39.1±6.2 years (range, 32-47 years) and a mean BMI of 25.6±5.4 kg/m 2 (range, 20.2-32.7 kg/m 2), underwent partial meniscectomy during the same period. Clinical outcomes were assessed using the International Knee Documentation Committee (IKDC) score, Lysholm score, visual analogue scale (VAS) for pain, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 3, 6, 12, and 24 months postoperatively. The morphology and signal intensity of grafts, Recht grading for cartilage damage, and the need for secondary arthroscopy were also evaluated. Results:The mean follow-up duration was 24.3±4.3 months for the tendon graft group and 24.2±3.6 months for the partial meniscectomy group. At 3 and 6 months postoperatively, the partial meniscectomy group demonstrated superior knee function scores compared to the tendon graft group ( P<0.05). Similarly, VAS were lower in the partial meniscectomy group at 3 months postoperatively ( P<0.05), although no significant difference was found at 6 months ( P>0.05). By 12 months postoperatively, differences in pain and function between the two groups were no longer statistically significant ( P>0.05). At 24 months, the tendon graft group exhibited significantly better outcomes in terms of the Lysholm score (84.31±12.20 vs. 72.67±14.18), IKDC score (82.21±10.55 vs. 74.09±11.68), VAS score (2.10±1.74 vs. 3.80±1.81), and KOOS score (85.37±13.14 vs.75.14±17.94) compared to the partial meniscectomy group ( P<0.05). Regarding graft healing, 19 patients in the tendon graft group demonstrated a grade 3 graft-residual meniscus complex at 24 months, significantly improved from 5 patients at 3 months postoperatively. Furthermore, no grafts showed a grade 3 signal intensity at 3 months, while 19 patients showed such improvements by 24 months. MRI at the 24-month follow-up revealed cartilage damage in 7 patients in the tendon graft group and 20 patients in the partial meniscectomy group, with severe cartilage damage (Recht grade>II) observed in 1 patient in the tendon graft group and 7 patients in the partial meniscectomy group. All 20 patients in the tendon graft group achieved minimal clinically significant differences by 24 months, and 4 of them underwent secondary arthroscopy, which revealed vascularization between the graft and residual meniscal tissue. Conclusion:The use of the peroneus longus tendon for meniscal reconstruction reduces knee pain, enhances knee function, and effectively fills the tibiofemoral joint space while protecting the articular cartilage through graft remodeling.

Objective:To evaluate the accuracy of an artificial intelligence (AI) model in measuring key angles on pelvic radiographs of the hip and assess its effectiveness in diagnosing developmental dysplasia of the hip (DDH) and borderline developmental dysplasia of the hip (BDDH).Methods:A retrospective analysis was conducted using anteroposterior pelvic X-ray films from 1,029 patients with suspected DDH. The data were collected from the Department of Radiology, Fourth Medical Center of the Chinese PLA General Hospital. Among the patients, 273 were male, and 756 were female, with an average age of 57.01 ± 18.16 years (range, 12-88 years). The dataset was randomly divided into a training set (720 cases), a test set (206 cases), and a validation set (103 cases). Two radiologists identified and marked key anatomical points of the hip joint to establish the training dataset, which was then used to develop a deep learning-based AI model capable of locating these key anatomical positions. Using the identified anatomical points, the AI model automatically measured and calculated the Sharp angle, center-edge (CE) angle, and T?nnis angle in the test dataset. The measurement results from the AI model were compared with those of the radiologists to evaluate the model's accuracy. The validation set was used to optimize model parameters, and the test dataset was used to evaluate the diagnostic performance of DDH. Receiver operating characteristic (ROC) curves were employed to assess the diagnostic efficacy of the AI model for DDH and BDDH.Results:The accuracy rates of the AI model in measuring the left Sharp angle, CE angle, and T?nnis angle for diagnosing DDH were 89.8%, 90.1%, and 86.8%, respectively. For the right side, the accuracy rates were 93.7%, 92.2%, and 80.5%, respectively. There were no statistically significant differences in the mean values of the Sharp, T?nnis, and CE angles between manual and AI measurements ( P>0.05). Pearson correlation tests and intraclass correlation coefficient (ICC) analyses revealed high consistency between AI and manual measurements of the Sharp angle, T?nnis angle, and CE angle, with r-values and ICC values exceeding 0.75. Additionally, the AI model performed measurements significantly faster (1.7±0.1 s) than radiologists (88.1±8.4 s and 90.3±7.4 s, P<0.001). The areas under the ROC curves (AUCs) for diagnosing DDH using the Sharp angle, CE angle, and T?nnis angle measured by the AI model were 0.883, 0.922, and 0.908 (left side) and 0.924, 0.871, and 0.922 (right side), respectively. For diagnosing BDDH, the AUCs of the left and right CE angles measured by the AI model were 0.787 and 0.676, respectively. Kappa test results indicated good agreement between the AI model and manual measurements as well as final clinical diagnoses. For the CE angle, the κ value of the AI model was 0.663, while κ values for the Sharp and T?nnis angles were all greater than 0.800. Conclusion:The convolutional neural network-based AI model effectively and automatically measures the Sharp, CE, and T?nnis angles and demonstrates high diagnostic efficacy for DDH and BDDH.

Objective To develop the volume adjustable vegetable facilities and meet the demands of research on the growing technique of vegetables.Methods Three series of adjustable volume vegetable facilities were developed with light and ventilation module,growth module,cultivation tray module and measurement module.Telescopic structure was adopted in the facilities and the performance testing and characteristics analyses were carried out.Results The facilities could be adjusted at the height range of 250-700 mm.Three kinds of LED lights and replaceable cultivation tray and matrix were installed in the facilities.The parameters including water content,electric conductivity and temperature in the matrix,CO2 concentration in the atmosphere of facilities were monitored.The test results showed that the performances and the indexes of facilities met the subsequent experimental demands.Conclusion Light weight,small volume,and adjustable volume vegetable facilities were developed.The production efficiency of lettuce(12 plants/0.12 m2)grown in the facilities was 49.7 g(FW)plant-1.The development of facilities laid the foundation of construction of on-orbit vegetable facility.

Objective To investigate whether norepinephrine (NE) regulates the oxidative stress in human endom-etrial epithelial cells (hEECs) by activating nuclear factor E2-related factor 2(Nrf2)/ heme oxygenase -1(HO-1) signal pathway.Methods Cultured hEECs were used.The expression of α and β adrenergic receptors was detec-ted by reverse transcription-polymerase chain reaction (RT-PCR).Cell counting kit-8(CCK-8) assay was applied to test the effect of NE on cell viability, then the cells were divided into Control group and NE treatment group, and the appropriate concentrations were chosen.The expression of tight junction proteins Occludin and zona occludens-1(ZO-1), apoptosis-related proteins apoptosis-related protein B-cell lymphoma-2 protein(Bcl-2) and Bcl-2 associ-ated X protein(Bax) , antioxidant proteins Nrf2 and HO-1 were examined by Western blot.The apoptosis was de-tected by flow cytometry.The malonaldehyde (MDA) and superoxide dismutase(SOD) in the cell culture medium were detected by enzyme-linked immunosorbent assays kit (ELISA).Results The mRNA expression of α1 a,α1 b,α2 a,α2 b,α2 c,β1, β3 was detected in the hEECs.After the NE treatment, no significant change in cell viability was observed in low concentration (5 μmol/L and 10 μmol/L) groups, while 15 μmol/L and 20μmol/L NE treatments for 6 h or 24 h promoted the cell viability significantly.The expression of ZO-1 and Occlu-din increased significantly in 15 μmol/L group after 24 h treatment, the expression of ZO-1 decreased in 6 h treat-ment group, significant down regulation was observed after 15 μmol/L NE application, the expression of Occludin increased in 6 h group.The cell apoptosis increased compared with the control group after NE stimulation, espe-cially a significantly increase in 6 h 15 μmol/L group was detected,while the fall in increased apoptosis was ob-served after 24 h treatment.The ration of Bcl-2/Bax>1.The expression of Nrf2 and HO-1 was elevated by NE.There was no obvious change in MDA level while significant elevation in SOD was detected in cell culture medium.Conclusion Nrf2/HO-1 signal is activated after application of NE to the hEECs, which may responsible for the upregulation of SOD, antioxidant and anti-apoptotic effect in the hEECs.