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

The ethical dilemma in scientific research exists at all stages of the scientific research activities among medical graduate students,mainly involving conflicts of interest,clinical trials,animal experiments,and the relationship between teachers and students.If medical graduate students are in the ethical dilemma in scientific research for a long time,their research activities will be greatly affected.By discussing the connotation,evaluation tools,current situation,influencing factors,and improvement measures of ethical dilemmas in scientific research,this paper proposed some suggestions,such as comprehensively investigating the influencing factors of ethical dilemmas in scientific research,and formulating targeted improvement measures,with a view to helping medical graduate students identify and get rid of ethical dilemmas in scientific research,and promote the stability of research activities.

Objective:To investigate the effects of Porphyromonas gingivalis derived outer membrane vesicles (Pg OMV) on osteoclast differentiation of macrophages and its underlying mechanisms. Methods:The morphology and the size distribution of Pg OMV were analyzed by transmission electron microscopy and nanoparticle tracing analysis, respectively. The osteoclast precursors were treated with 1, 3 and 10 mg/L Pg OMV (1, 3 and 10 mg/L OMV treatment group) or phosphate buffer solution (PBS)(control group). The formation of osteoclasts was analyzed by tartrate-resistant acid phosphase (TRAP) staining and F-actin staining and real-time quantitative PCR (RT-qPCR) were used to detect the expression of Fos and matrix metallopeptidase 9 (MMP9). Polymyxin B (PMB) was used to block lipopolysaccharide (LPS) and then Pg OMV was used to treat osteoclast precursor (PMB-OMV treatment group), and OMV treatment group was used as control. TRAP and F-actin staining were used to observe the formation of osteoclasts and actin rings. The effect of Pg OMV on the expression of Toll-like receptor (TLR) 2 and TLR4 in preosteoclasts was detected by Western blotting. The osteoclast precursors were pretreated with 10, 50, 100 and 200 μmol/L C29, an inhibitor of TLR2, and then treated with Pg OMV(OMV+10, 50, 100 and 200 μmol/L C29 treatment group) and OMV treatment group without C29 pretreatment was control. TRAP and F-actin staining were used to observe the formation of osteoclasts and actin rings. The osteoclast precursor cells were treated with OMV (OMV treatment group) and OMV incubated with PMB (PMB-OMV treatment group) and the expression of TLR2 in osteoclast precursor was detected by Western blotting.Results:Pg OMV showed classical vesicular structures, and the average particle size of Pg OMV were 179.2 nm. A large number of actin rings were observed in the 3 and 10 mg/L OMV treatment groups. The percentages of TRAP-positive osteoclast area in 3 mg/L OMV treatment group [(22.6±2.1)%] and 10 mg/L OMV treatment group [(32.0±2.3)%] were significantly increased compared with control group [(4.9±0.5)%] ( P<0.001). Compared with the control group (1.000±0.029), the mRNA relative expression of Fos in 3 mg/L OMV treatment group (1.491±0.114) and 10 mg/L OMV treatment group (1.726±0.254) was significantly increased ( P=0.013, P=0.001). Compared with the control group (1.007±0.148), the mRNA relative expression of MMP9 in the group of 10 mg/L OMV (2.232±0.097) was significantly increased ( P<0.001). Actin ring formation was less in PMB-OMV treatment groups than in OMV treatment groups. The proportion of TRAP-positive osteoclasts area [(14.8±3.8)%] in PMB-OMV treatment group was significantly lower than OMV treatment group [(31.5±6.7) %] ( P=0.004). The relative expression of TLR2 in OMV treatment group (1.359±0.134) was significantly higher than that in the control group (1.000±0.000) ( t=4.62, P=0.044). Compared with the OMV treatment group [(29.4±1.7)%], 50, 100 and 200 μmol/L C29 significantly decreased the formation of osteoclasts [(24.0±1.7)%, (18.5±2.1)%, (9.1±1.3) %] ( P=0.026, P<0.001, P<0.001). TLR2 protein expression in PMB-OMV group (0.780±0.046) was significantly lower than that in OMV group (1.000±0.000)( t=8.32, P=0.001). Conclusions:Pg OMV can promote osteoclast differentiation by carrying LPS, TLR2 plays an important role in Pg OMV mediated osteoclast differentiation.

The accurate assessment of burn injuries is complex and difficult. The emergence of some new skin imaging techniques, such as hyperspectral imaging, unilateral magnetic resonance imaging, laser Doppler perfusion imaging, etc., has made great progress in research on burn injury assessment. With the continuous progress of imaging technology and medical imaging, medical imaging technologies such as digital radiography, computed tomography, magnetic resonance imaging, and ultrasonography, and so on, have played an important role in burn injury assessment. However, there are still relatively few research reports on burn injury imaging, which may be due to the fact that the imaging techniques and diagnostic experience used for burn injury assessment are not yet fully popular in some medical institutions, and the imaging manifestations related to burns are complex and lack of specificity. This article mainly reviews the application research progress of various imaging techniques in the assessment of burn injury in recent years, aiming to explore the application value of various imaging techniques in burn injury assessment.

Objective:To investigate the clinical efficacy of over-the-top reconstruction combined with the modified Lemaire technique in the treatment of anterior cruciate ligament (ACL) injuries with pivot-shift positive.Methods:From March 2020 to October 2021, a total of 46 patients with ACL injury and pivot-shift test grade II or above were admitted to Xinhua Hospital Affiliated to Dalian University. There were 28 males and 18 females, aged 28.0±10.5 years (range, 15-45 years). All cases were unilateral, including 17 cases of left knee and 29 cases of right knee. The pivot-shift test showed that 30 cases were grade II and 16 cases were grade III, and the cause of injury was sports injury. The semitendinosus muscle and gracilis muscle were harvested, and the ACL was reconstructed with the over-the-top combined modified Lemaire technique. The International Knee Documentation Committee (IKDC) score, Lysholm score and KT-2000 side-to-side difference before and after operation were compared.Results:All patients successfully completed the operation and were followed up for 26.6±2.3 months (range, 24-28 months). The Lysholm scores of the patients at 3 months and 24 months after operation were 73.6±4.3 and 91.6±2.8, which were higher than those before operation (58.5±4.6), and the difference was statistically significant ( F=18.351, P<0.001). The IKDC scores of patients at 3 months and 24 months after operation were 59.0±2.0 and 91.8±3.2, respectively, which were higher than those before operation 50.3±2.8, and the difference was statistically significant ( F=17.290, P<0.001). The side-to-side difference of KT-2000 was 1.7±0.8 mm and 1.5±0.4 mm at 3 and 24 months after operation, respectively, which was lower than that before operation (5.9±1.1 mm), and the difference was statistically significant ( F=14.192, P<0.001). At 24 months after operation, 3 patients had pivot shift test grade I and 4 patients had Lachman test grade I, but they complained of good knee stability and did not receive further treatment. At the last follow-up, there were no complications such as incision and intra-articular infection, deep vein thrombosis, knee stiffness, quadriceps musculus ossificans myositis, and reconstruction ligament rupture. All patients returned to sports with an average time of 15.7±2.6 months (range, 12-24 months). Conclusion:Over-the-top reconstruction combined with the modified Lemaire technique for the treatment of ACL injury with positive pivot shift test effectively improves knee function and promotes the patient's return to sports, with a low incidence of surgical complications.

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.