ObjectiveTo establish an in vitro culture model of rat corpora cavernous smooth muscle cells （CCSMCs） using a modified tissue block adherence method. MethodsCorpus cavernosum smooth muscle tissue was digested with collagenase type I and subsequently cultured using an adherent method. Cells were purified via differential adhesion and identified through immunofluorescence and Western blotting. ResultsCCSMCs began to emerge from the tissue block after 3 days， increased significantly by day 7， and converged by day 12. Post-passage， CCSMCs exhibited strong proliferation and a “peak-to-valley” phenomenon. After purification， the cells tested positive for α-smooth muscle actin （α-SMA）， confirming the successful establishment of the in vitro culture model. ConclusionThe modified tissue block adherence method is a cost-effective and efficient way to obtain high-purity CCSMCs.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objective To investigate the safety, economic benefits and psychological effects of day breast conserving surgery for breast cancer. Methods The demographic data and clinical data of breast cancer patients undergoing day (day surgery group) and ward (ward surgery group) breast conserving surgeries in West China Hospital of Sichuan University from March 2020 to June 2021 were retrospectively collected; the demographic data, clinical data, medical and related transportation costs, and preoperative and postoperative BREAST-Q scores of breast cancer patients undergoing day (day surgery group) and ward (ward surgery group) breast conserving surgery in West China Hospital of Sichuan University from June 2021 to June 2022 were prospectively collected. The safety, economic benefit, and psychological satisfaction of day surgery was analyzed. Results A total of 42 women with breast cancer were included in the retrospective study and 39 women with breast cancer were included in the prospective study. In both prospective and retrospective studies, the mean age of patients in both groups were <50 years. There were only statistical differences between the two groups in the aspects of hypertension (P=0.022), neoadjuvant chemotherapy (P=0.037) and postoperative pathological estrogen receptor (P=0.033) in the prospective study. In postoperative complications, there were no statistical differences in the surgical-related complications or anesthesia-related complications between the two groups in either the prospective study or the retrospective study (P>0.05). In terms of the overall cost, we found that the day surgery group was more economical than the ward surgery group in the prospective study (P=0.002). There were no statistical differences in postoperative psychosocical well-being, sexual well-being, satisfaction with breasts or chest condition between the two groups (P>0.05). Conclusion It is safe and reliable to carry out breast conserving surgery in day surgery center under strict management standards, which can save medical costs and will not cause great psychological burden to patients.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Traditionally, platelets, which are anucleate cell fragments derived from blood cells, have been primarily associated with their pivotal functions in hemostasis and thrombosis. However, recent research has elucidated their significant role in immune regulation, highlighting their expression of various immune receptors, involvement in numerous immune-related signaling pathways, and activation of diverse effector functions. This paper elaborates on the fundamental biological characteristics and immune functions of platelets, the involvement of activated platelets in immune regulation, and their prospective applications in clinical therapy. Furthermore, the paper discusses future directions in platelet immune research, as well as the prospects and developmental trends in immunotherapy, aiming to furnish a thorough reference for the investigation and clinical utilization of platelets within the domain of immune regulation.

Nanometal materials have been extensively studied due to their non-toxic,stable,and efficient biological properties.Among them,nano-zinc oxide(ZnO-NPs),which exhibits good biocompatibility,is considered a promising antibacterial material for medical applications due to its broad-spectrum antibacterial effects and photocatalytic activity.The antibacterial mechanism of ZnO-NPs is not yet fully understood,but two widely recognized modes have been proposed:one is a non-contact mechanism dominated by reactive oxygen species(ROS)generated by ZnO-NPs and the release of Zn2+,and the other is a direct contact antibacterial mechanism involving the interaction between ZnO-NPs and bacterial cell wall components.These two distinct antibacterial mechanisms are attributed to the physicochemical properties of ZnO-NPs.As a wide-bandgap semiconductor,the antibacterial efficacy of ZnO-NPs is influenced not only by light exposure but also by factors such as particle size,concentration,morphology,as well as the type and structure of the target bacteria.Therefore,understanding the precise mechanisms is crucial for elucidating the antibacterial functions of ZnO-NPs against bacteria and fungi.This review summarizes the latest research progress on the antibacterial mechanisms of ZnO-NPs and their influencing factors,and provides an overview of the factors affecting the antibacterial performance of ZnO-NPs,offering a basis for a deeper understanding and application of ZnO-NPs in antibacterial therapy.

Objective To heterologously express and purify the small ubiquitin-like modifier(SUMO)tag fused organo-phosphorus hydrolase mutant H257Y/L303T(YT),namely SUMO-YT,and evaluate its hydrolytic capacity against ethyl paraoxon and soman.Methods The SUMO tag encoding gene was constructed at the N-terminus of the YT encoding gene with a linker sequence via enzyme digestion and ligation before SUMO-YT was expressed in Escherichia coli.SUMO-YT and YT were purified through ammonium sulfate precipitation and affinity chromatography to obtain high-purity target proteins.The activity and kinetic parameters of the recombinant enzymes were examined using ethyl paraoxon and soman as substrates.Results The system for expression and purification of recombinant enzymes was established,yielding SUMO-YT and YT,and the former exhibited more significantly enhanced hydrolytic efficiency than the latter,with catalytic rates 11-fold higher for paraoxon and 4.4-fold higher for soman.At 37 ℃ and pH 7.2,SUMO-YT reduced the inhibition rate of acetylcholinesterase(AChE)by soman from 100％to 45.7％within 3 minutes,whereas YT reduced it to no more than 80％.Conclusion The high-activity recombinant SUMO-YT is prepared.SUMO tag fusion can significantly enhance the hydrolytic capacity of YT against ethyl paraoxon and soman.

AIM: To prepare a nanodrug MMC-ATS-@PLGA using polylactic acid hydroxyacetic acid copolymer(PLGA)as a carrier and mitomycin C(MMC)loaded on PLGA, and to analyse the biological safety and treatment effect of this nanodrug on inhibiting the proliferation of filtering bleb scarring after glaucoma surgery in vivo.METHODS: The thin-film dispersion hydration ultrasonic method was used to prepare the MMC-ATS-@PLGA, and its physical and chemical properties were detected. The effect of MMC-ATS@PLGA on rabbit corneas was analysed through corneal fluorescence staining and HE staining, and tear film rupture time(BUT), Schirmer test and intraocular pressure data were collected to analyse ocular surface biosafety. A slit lamp was used to observe and calculate the filtration bubble size, and the tissue morphological changes were analysed by conjunctival HE staining. In addition, immunohistochemistry and Elisa were used to compare the anti-inflammatory effects of Flumiolone Eye Drops(FML), MMC, and MMC-ATS-@PLGA nanoparticles on inhibiting the formation of filtering bleb scarring after glaucoma surgery from multiple perspectives via comparative proteomic analysis.RESULTS: The average particle size and zeta potential of MMC-ATS-@PLGA were 128.78±2.54 nm and 36.49±4.25 mV, respectively, with an encapsulation efficiency and a drug loading rate of(78.49±2.75)% and(30.86±1.84)%, respectively. At 33°C(the ocular surface temperature), the cumulative release rate of the MMC-ATS-@PLGA nanoparticles reached(76.58±2.68)% after 600 min. Moreover, corneal fluorescence staining, HE, BUT, Schirmer, and intraocular pressure results showed that MMC-ATS-@PLGA had good biocompatibility with the ocular surface of rabbits. At 3 wk after surgery, the area of filtering blebs in the MMC-ATS-@PLGA group was significantly larger than that in the FML group and MMC group, and the filtering blebs in the control group had basically disappeared. Pathological tissue analysis of the conjunctiva in the filtering blebs area of the eyes of the rabbits revealed that compared with that in the normal group, the morphology of the collagen fibres in the MMC-ATS-@PLGA group was relatively regular, the fibres were arranged neatly, and the tissue morphology was similar to that of the normal group. Immunohistochemistry and Elisa confirmed that compared with those in the normal group, the expression levels of α-SMA, CTGF, and type Ⅲ collagen fibre antibodies were significantly increased in the control group. After FML, MMC, or MMC-ATS-@PLGA treatment for 3 wk, the expression of inflammatory factors gradually decreased. Among the groups, the MMC-ATS-@PLGA group showed the most significant decrease(P<0.05).CONCLUSION: This study successfully synthesized a nanomedicine(MMC-ATS-@PLGA)that inhibits scar proliferation after glaucoma filtration surgery. The drug had stable physicochemical properties, good biocompatibility, and better anti-inflammatory effects by inhibiting the expression of α-SMA, CTGF, and type Ⅲ collagen fibres, which can prevent the formation of scarring in the filtering blebs area, thereby improving the success rate of glaucoma filtering surgery.

Objective:To compare the imaging quality and metabolic quantitative parameters of pulmonary nodules between Q. Flex whole information five-dimensional (5D) and conventional three-dimensional (3D) PET/CT imaging for clinical evaluation.Methods:Fifty-four patients (30 males, 24 females, age: 60(42, 75) years; 78 solid pulmonary nodules (maximum diameter≤3 cm) with abnormal uptake of 18F-FDG) from Tianjin Cancer Hospital Airport Hospital between June 2022 and August 2022 were enrolled in this retrospective study. All patients underwent 5D scanning and 3D, 5D reconstruction. Image quality scores, signal-to-noise ratio (SNR), SUV max, SUV mean and metabolic tumor volume (MTV) of pulmonary nodules of 5D group and 3D group were evaluated and compared with χ2 test and Wilcoxon signed rank test. Correlation of quantitative parameters between 2 groups were analyzed by using Spearman rank correlation analysis. Results:Thirty-five of 78(45%) pulmonary nodules with image quality score≥4 were found in 5D group, which were more than those in 3D group (22/78(28%); χ2=4.67, P=0.031). Meanwhile, SNR, SUV max, SUV mean, and MTV were significantly positively correlated between the 2 groups ( rs values: 0.86, 0.86, 0.85, and 0.95, all P<0.001). SNR, SUV max and SUV mean of pulmonary nodules in 5D group were significantly higher than those in 3D group, which were 37.46(18.42, 62.00) vs 32.72(16.97, 54.76) ( z=-4.07, P<0.001), 9.71(5.48, 13.82) vs 8.96(4.82, 12.63) ( z=-3.05, P<0.001) and 6.30(3.39, 8.94) vs 5.61(2.99, 7.63)( z=-4.07, P<0.001) respectively. MTV of pulmonary nodules in 5D group was significantly lower than that in 3D group, which was 1.72(0.66, 2.74) cm 3vs 1.98(1.06, 4.63) cm 3 ( z=-7.13, P<0.001). Quantitative parameters of lower lung field and nodules with maximum diameters of >10 mm and ≤20 mm based on 5D scanning changed most significantly compared with those based on 3D scanning ( z values: from -5.23 to -2.48, all P<0.05). Conclusion:Q. Flex 5D PET significantly improves the quantitative accuracy of SUV and MTV of pulmonary nodules, and the improvement of image quality is substantial without increasing the radiation dose, which has clinical practical value.