Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Yes-associated protein (YAP), the key transcriptional co-factor and downstream effector of the Hippo pathway, has emerged as one of the primary regulators of neural as well as glial cells. It has been detected in various glial cell types, including Schwann cells and olfactory ensheathing cells in the peripheral nervous system, as well as radial glial cells, ependymal cells, Bergmann glia, retinal Müller cells, astrocytes, oligodendrocytes, and microglia in the central nervous system. With the development of neuroscience, understanding the functions of YAP in the physiological or pathological processes of glia is advancing. In this review, we aim to summarize the roles and underlying mechanisms of YAP in glia and glia-related neurological diseases in an integrated perspective.
Humans ; Animals ; Neuroglia/metabolism* ; Signal Transduction/physiology* ; YAP-Signaling Proteins ; Nerve Regeneration/physiology* ; Nervous System Diseases/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism*

Soil cadmium (Cd) pollution is one of the major environmental problems globally. Ophiopogon japonicus, a multifunctional plant extensively used in traditional Chinese medicine, has demonstrated potential in environmental remediation. This study investigated the Cd accumulation pattern of O. japonicus under cadmium stress and identified the heavy metal ATPase (HMA) family members in this plant. Our results demonstrated that O. japonicus exhibited a Cd enrichment factor (EF) of 2.75, demonstrating strong potential for soil Cd pollution remediation. Nine heavy metal ATPase (HMA) members of P1B-ATPases were successfully identified from the transcriptome data of O. japonicus, with OjHMA1-OjHMA6 classified as the Zn/Co/Cd/Pb-ATPases and OjHMA7-OjHMA9 as the Cu/Ag-ATPases. The expression levels of OjHMA1, OjHMA2, OjHMA3, and OjHMA7 were significantly up-regulated under Cd stress, highlighting their crucial roles in cadmium ion absorption and transport. The topological analysis revealed that these proteins possessed characteristic transmembrane (TM) segments of the family, along with functional A, P, and N domains involved in regulating ion absorption and release. Metal ion-binding sites (M4, M5, and M6) existed on the TM segments. Based on the number of transmembrane domains and the residues at metal ion-binding sites, the plant HMA family members were categorized into three subgroups: P1B-1 ATPases, P1B-2 ATPases, and P1B-4 ATPases. Specifically, the P1B-1 ATPase subgroup included the motifs TM4(CPC), TM5(YN[X]₄P), and TM6(M[XX]SS); the P1B-2 ATPase subgroup featured the motifs TM4(CPC), TM5(K), and TM6(DKTGT); the P1B-4 ATPase subgroup contained the motifs TM4(SPC) and TM6(HE[X]GT), all of which were critical for protein functions. Molecular docking results revealed the importance of conserved sequences such as CPC/SPC, DKTGT, and HE[X]GT in metal ion coordination and stabilization. These findings provide potential molecular targets for enhancing Cd uptake and tolerance of O. japonicus by genetic engineering and lay a theoretical foundation for developing new cultivars with high Cd accumulation capacity.
Cadmium/metabolism* ; Adenosine Triphosphatases/metabolism* ; Ophiopogon/drug effects* ; Soil Pollutants/toxicity* ; Plant Proteins/metabolism* ; Stress, Physiological ; Multigene Family ; Gene Expression Regulation, Plant

Objective To investigate the protective effect and mechanism of tanshinone ⅡA on D-galactosamine(D-GalN)-induced acute liver failure in rats.Methods SD rats were randomly di-vided into control group,model group(intraperitoneal injection of 1.1 g/kg D-GalN),low-dose group(intraperitoneal injection of 1.1 g/kg D-GalN+daily gavage of 25 mg/kg tanshinone ⅡA),and High-dose group(intraperitoneal injection of 1.1 g/kg D-GalN+daily gavage of 50 mg/kg tan-shinone ⅡA).Liver function indicators[aspartate aminotransferase(AST),alanine aminotransferase(ALT),and γ-glutamyltransferase(γ-GT)]were measured using a Hitachi7600-210 biochemical an-alyzer,and serum total bilirubin(TBIL)and direct bilirubin(DBIL)levels were determined.The mitotic index(MI)and proliferating cell nuclear antigen(PCNA)positivity in liver tissues were examined.Enzyme-linked immunosorbent assay(ELISA)was used to detect plasma levels of tumor necrosis factor(TNF-α),interleukin(IL)-1β,IL-10,and IL-6 in rats from each group.Kits were employed to measure superoxide dismutase(SOD),glutathione(GSH),and malondialdehyde(MDA)contents in liver tissues of rats from each group.The TUNEL method was adopted to detect hepatocyte apoptosis rates in liver tissues,and immunoblotting was used to assess the expression of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2)and extracellular signal-regu-lated kinase 1/2(ERK1/2)proteins in liver tissues.Results Compared with the control group,the model group exhibited increased p-ERK1/2 protein expression(P＜0.05).Compared with the model group,both the low-dose and high-dose groups showed decreased p-ERK1/2 protein expres-sion(P＜0.05).The model group had an increased hepatocyte apoptosis index compared with the control group(P＜0.05).Both the low-dose and high-dose groups demonstrated decreased hepato-cyte apoptosis indices compared with the model group(P＜0.05).Compared with the control group,the model group had increased MDA levels and decreased SOD and GSH levels(P＜0.05).Both the low-dose and high-dose groups exhibited decreased MDA levels and increased SOD and GSH levels compared with the model group(P＜0.05).The model group showed increased levels of TNF-α,IL-1β,IL-10,and IL-6 compared with the control group(P＜0.05).Both the low-dose and high-dose groups had decreased levels of TNF-α,IL-1 β,IL-10,and IL-6 compared with the model group(P＜0.05).Compared with the control group,the model group had decreased MI and PCNA positivity rates(P＜0.05).Both the low-dose and high-dose groups exhibited increased MI and PCNA positivity rates compared with the model group(P＜0.05).The model group had in-creased AST,ALT,γ-GT,TBIL and DBIL values compared with the control group(P＜0.05).Both the low-dose and high-dose groups showed decreased AST,ALT,γ-GT,TBIL and DBIL val-ues compared with the model group(P＜0.05).Conclusion Tanshinone ⅡA may alleviate D-GalN-induced acute liver failure in rats through the ERK1/2 signaling pathway.

OBJECTIVE: To observe the effects of Xingnao Kaiqiao acupuncture technique (for regaining consciousness and opening orifice) on methylation of N6-methyladenosine (m6A), and key methyltransferases and demethylases, so as to clarify the mechanism of acupuncture on cerebral ischemia-reperfusion injury (CIRI). METHODS: Of 68 male Sprague-Dawley rats of SPF grade, 15 rats were randomly selected as a sham-operation group, and the remaining rats were subjected to the model of middle cerebral artery occlusion using the suture ligation. CIRI was induced by ischemia for 2 h followed by reperfusion. Rats that failed to modeling or died were excluded. The rest 45 rats were randomly divided into three groups, i.e. model group, acupuncture group, and non-point acupuncture group, with 15 rats in each group. The rats in the acupuncture group were treated with acupuncture at bilateral "Neiguan" (PC6) and "Shuigou" (GV26). In the non-point acupuncture group, acupuncture was delivered at three non-points, located 3 mm below the bilateral midaxillary line and 3 mm lateral to the tip of the coccyx. One intervention was operated in these two acupuncture groups and the needles were retained for 30 min. Before modeling start and 2 h after ischemia, a laser speckle flowmeter was used to monitor the cerebral blood perfusion. In 2 h of ischemia and 24 h of reperfusion, the neurological behavioral score was evaluated. The volume of rat cerebral infarction was determined by triphenyltetrazolium chloride (TTC) staining, and the level of m6A methylation in ischemic cortical area was detected by Dot blot, and the protein and mRNA expression of the demethylase i.e. fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and key methyltransferases, i.e. methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and Wilms' tumor 1-associated protein (WTAP) in ischemic cortical area were detected by Western blot and real-time PCR. RESULTS: Cerebral blood perfusion decreased by>70% after 2 h ischemia. Compared with the sham-operation group, the neurobehavioral score and the percentage of cerebral infarction volume increased in the model group (P<0.01); the level of m6A methylation in the ischemic cortical area increased (P<0.01), the protein and mRNA expression of FTO decreased (P<0.01), and that of ALKBH5, METTL3, and METTL14 increased (P<0.01, P<0.05) in the model group. When compared with the model group and the non-point acupuncture group, the acupuncture group showed a decrease in the neurobehavioral score and the percentage of cerebral infarction volume (P<0.01), the level of m6A methylation in the ischemic cortical area was reduced (P<0.01, P<0.05), and the protein and mRNA expression of FTO was elevated (P<0.01). CONCLUSION Xingnao Kaiqiao acupuncture technique presents its protective effect on the brain in the rats with CIRI, which is related to up-regulating the expression of FTO and modulating m6A methylation.
Animals ; Rats, Sprague-Dawley ; Male ; Acupuncture Therapy ; Reperfusion Injury/genetics* ; Rats ; Brain Ischemia/genetics* ; Humans ; Adenosine/metabolism* ; Methylation ; Acupuncture Points ; Cerebral Cortex/metabolism*

Medical imaging technology plays a crucial role in clinical diagnosis and treatment. Image compression technology provides robust technical support for the storage and transmission of massive medical imaging data, serving as an effective safeguard for hospital data backup and telemedicine. The technology holds broad application prospects in the medical field, enabling the processing of various imaging modalities, multidimensional imaging, and medical video imaging. This study elaborates on general image and video compression algorithms, the application of compression algorithms in the medical field, and the performance metrics of medical image compression, thereby providing critical technical support for enhancing clinical diagnostic efficiency and data management security.

Objective:To investigate the effect of transurethral green laser prostate enucleation (GreenLEP) in the treatment of benign prostate hyperplasia (BPH) with detrusor underactivity (DU).Methods:The clinical data of 157 BPH patients treated with GreenLEP at Zhejiang Provincial People's Hospital from June 2019 to June 2020 were retrospectively analysed. The average age of the patients was (73.2±7.9) years old, with disease duration of 4(2, 8) years. Prior to surgery, all patients underwent comprehensive urodynamic studies and prostate ultrasonography (or enhanced MRI). Preoperative prostate volume was 42.1(34.2, 59.4) ml, international prostate symptom score (IPSS) was (27.9±3.4), quality of life (QOL) score was (5.1±0.8), preoperative residual urine volume (PVR) was 40.0(20.0, 80.0) ml, and preoperative maximum urinary flow rate (Q max) was 4.0(2.0, 7.0) ml/s. Patients were stratified into DU and non-DU groups using a bladder contractility index (BCI) threshold of less than 100 to diagnose DU. The cohort comprised 76 individuals in the DU group and 81 in the non-DU group. At the three-month postoperative juncture, a follow-up assessment was conducted on the patients, focusing on the evolution of subjective metrics (IPSS, QOL) and objective parameters (PVR, Q max). This study defined successful treatment outcomes at the 3-month mark as achieving PVR<20 ml and Q max>10 ml/s. Cases not meeting these criteria were categorized as treatment failure. Based on treatment outcomes, receiver operator characteristic (ROC) curve were plotted to identify the optimal cutoff value of BCI for predicting treatment efficacy. Subsequently, DU patients were classified into mild and severe DU groups based on this optimal BCI threshold. The differences of subjective indicators (IPSS, QOL) and objective parameters (PVR, Q max) preoperatively among non-DU, mild DU, and severe DU groups, as well as changes in these indices three months postoperatively were analyzed. Results:All 157 surgeries were successfully completed, with a median hospital stay of 6(5, 8) days. At the 3-month postoperative follow-up, 78 patients were deemed treatment successes and 3 as failures in non-DU group, 64 were successful and 12 failed in DU group. Utilizing ROC curve analysis, the BCI was optimally set at 57.5. This stratification resulted in 56 cases classified as mild DU (57.5≤BCI<100) group and 20 cases as severe DU (BCI<57.5) group. A comparative analysis of the three patient cohorts, revealed no significant statistical variation in terms of age, disease duration, or prostate volume ( P>0.05). In the non-DU, mild DU, and severe DU groups, IPSS were (26.8±3.4), (28.6±3.0), and (30.6±2.4) respectively, QOL sores were (4.9±0.9), (5.2±0.7), and (5.7±0.5) respectively, PVR volumes were 50.0(20.0, 90.0), 20.0(10.0, 50.0), and 60.0(27.5, 165.0) ml respectively, Q max were 4.0(2.0, 7.0), 5.0(4.0, 6.0), and 0(0, 2.3) ml/s respectively. Preoperative IPSS and QOL were significantly lower in the non-DU group compared with mild and severe DU groups ( P<0.05). Mild DU group had lower preoperative IPSS and QOL than the severe DU group ( P<0.05). Preoperative PVR in the mild DU group was less than that in both non-DU and severe DU groups ( P<0.05), but there was no statistically significant difference in preoperative PVR between non-DU and severe DU groups ( P>0.05). Preoperative Q maxof non-DU and mild DU groups was significantly higher than that of severe DU group ( P<0.05), with no significant difference between non-DU and mild DU ( P>0.05). Three months after surgery, IPSS scores of non-DU group, mild DU group and severe DU group were (12.5±4.7), (14.9±3.6) and (18.8±4.1), respectively. QOL scores of the 3 groups improved to (1.1±0.4), (1.2±0.5) and (1.9±1.0), respectively. PVR was 0 in non-DU and mild DU, and 20.0 (19.5, 61.3) ml in severe DU. Q max of the 3 groups were improved to 22.0(18.0, 27.0), 17.0(14.0, 22.3), and 9.0(6.8, 13.0) ml/s, respectively. Significant improvements of subjective symptoms (IPSS, QOL) and objective parameters (PVR, Q max) were observed in non-DU and mild DU group compared with preoperative( P<0.05). Significant improvements of IPSS, QOL and Q max ( P<0.05) but not PVR ( P=0.14)were observed in severe DU group. Additionally, significant differences were noted in PVR and Q max changes among the three groups ( P<0.05), but not in IPSS and QOL changes ( P>0.05). The absolute value of PVR and Q max changes in the non-DU group were higher than those in the mild DU group and the severe DU group ( P<0.05). Additionally, the change of Q max in mild DU group was significantly higher than that in severe DU group ( P<0.05). Conclusions:BPH patients with different degrees of DU can benefit from GreenLEP surgery, but for BPH patients with severe DU (BCI < 57.5), the improvements in PVR and Q max are less than that in the non-DU group.

ObjectiveTo investigate the possible mechanism of Hewei Anshen Formula （和胃安神方） in the treatment of insomnia. MethodsSixty male SD rats were randomly divided into the normal group， the model group， the eszopiclone group and the low-， medium- and high-dose Hewei Anshen Formula groups. The insomnia model was constructed by intraperitoneal injection of p-chlorophenylalanine （PCPA） for 2 days in all groups except the normal group. After successful modelling， the eszopiclone group was given 0.33 mg/（kg·d） eszopiclone aqueous solution by gavage， the low-， medium- and high-dose Hewei Anshen Formula groups were given 10 ml/kg of Hewei Anshen Formula with a concentration of 1， 2 and 4 g/ml， respectively， and the rats in the normal group and the model group were given 10 ml/kg of saline by gavage， once a day for 7 consecutive days. The general condition of the rats was observed during the experiment， and the body mass of the rats was measured every day after medication administration. The following day after the last medication administration， pentobarbital sodium co-test was used to observe the sleep condition， and the sleep latency and sleep duration were recorded； immunohistochemistry and Western blot were used to detect the expression of hypothalamic clock rhythm regulating protein （CLOCK） and brain and muscle aromatic hydrocarbon receptor nuclear transporter-like protein 1 （BMAL1） in the rats. ResultsThe body mass of rats in the model group was lower than that of rats in the normal group at all time points （P＜0.01）； compared with the same time in the eszopiclone group， the body mass of rats in the low-dose Hewei Anshen Formula group was elevated on the 5th， 6th and 7th days of medication administration （P＜0.05）. Compared with the normal group， the sleep duration of rats in the model group was shortened （P＜0.01）； compared with the model group， the sleep duration of rats in each dosage group increased （P＜0.01）， and the difference between the high-dose Hewei Anshen Formula group and the eszopiclone group showed no statistically significant （P＞0.05）， while the sleep duration of the low- and medium-dose Hewei Anshen Formula groups were shorterned than the eszopiclone group （P＜0.01）. The difference in sleep latency showed no statistically significant among each group （P＞0.05）. The results of both immunohistochemistry and Western blotting showed that the expression of CLOCK and BMAL1 in the hypothalamus of rats in the model group was significantly reduced compared with that in the normal group （P＜0.01）； the expression of CLOCK and BMAL1 in the hypothalamus of rats in the low- and high-dose Hewei Anshen Formula groups increased than that in the model group （P＜0.05 or P＜0.01）. ConclusionHewei Anshen Formula can improve insomnia in model rats， and its mechanism of action may be related to the up-regulation of the expression of the hypothalamic biological clock genes CLOCK and BMAL1 protein.

Objective:To describe the characteristics, etiology and patterns of outpatients and inpatients patients with moderate or severe valvular heart disease (VHD).Methods:This is a cross-sectional study. Outpatients and inpatients with moderate or severe VHD who underwent transthoracic echocardiography for first examination from 1 st January 2001 to 1 st January 2020 in Southwest Hospital, Army Medical University were enrolled. Data were collected from medical records and big data platform of Southwest Hospital. Characteristics of age and gender, etiology and types of VHD were descriptively analysed. Results:A total of 68 354 patients with moderate or severe VHD were enrolled. The age was 63 (50, 72) years. And 35 706 (52.24%) patients were female. (1) Age characteristics: There was similar age trend between male and female patients with moderate or severe VHD. The number of patients increased firstly and then decreased and reached its peak in the age group of 65-69 years old. The peak age of mitral stenosis patients was 45-49 years, which was earlier than that of whole patients with moderate or severe VHD. The median age of patients with bicuspid aortic valve was 42 years. (2) Gender characteristics: The proportion of tricuspid regurgitation, pulmonary regurgitation, mitral regurgitation, mitral stenosis and valve surgery in female patients with moderate or severe VHD were higher than those in male patients. The proportion of aortic regurgitation, aortic stenosis and bicuspid aortic valve in male patients with moderate or severe VHD were significantly higher than those in female patients (all P<0.05). (3) Etiology: The proportion of rheumatic VHD was 13.07% (8 934/68 354), which was higher than that of degenerative VHD (0.67% (458/68 354)). (4) Types of VHD: Tricuspid regurgitation made contribution to the largest proportion with 60.72% (41 503/68 354), followed by mitral regurgitation, aortic regurgitation, mitral stenosis, pulmonary regurgitation and aortic stenosis. Conclusions:There are certain regional characteristics in the prevalence of moderate or severe VHD in southwest China, suggesting different attention should be paid on the whole process of refined management of moderate or severe VHD.