ObjectiveThis study aimed to elucidate the specific molecular mechanism by which PAGE5 promotes breast cancer cell invasion and hepatic metastasis through regulating the PI3K/AKT signaling pathway and its downstream effector， matrix metalloproteinase 1 （MMP1）. MethodsBioinformatics analysis using the TCGA database was performed to evaluate PAGE5 expression in metastatic breast cancer tissues. The effects of PAGE5 on the proliferation， migration， and invasion capabilities of breast cancer cells were analyzed using CCK-8， EdU， Transwell， and wound healing assays. A splenic injection hepatic metastasis model in NOD-SCID mice was employed to validate the impact of PAGE5 on breast cancer liver metastasis. Transcriptome sequencing and KEGG enrichment analysis were conducted to identify potential signaling pathways regulated by PAGE5. Western blot was used to detect AKT phosphorylation levels. Quantitative real-time polymerase chain reaction （qPCR） was applied to screen and validate downstream target molecules of PAGE5. ResultsBioinformatic analysis revealed that PAGE5 expression was significantly upregulated in distant metastasis of breast cancer. Both in vitro and in vivo experiments confirmed that PAGE5 overexpression markedly enhanced the migration and invasion abilities of breast cancer cells and promoted the formation of liver metastatic lesions， whereas PAGE5 knockdown suppressed breast cancer liver metastasis （P＜0.000 1）. Transcriptome sequencing and KEGG enrichment analysis indicated that PAGE5 significantly activated the PI3K-AKT signaling pathway （P=0.028 5）. Western blot confirmed that PAGE5 upregulated p-AKT levels， which could be reversed by MK2206. The qPCR results confirmed that MMP1 is a key downstream effector of PAGE5， and its expression can be inhibited by MK2206 （P＜0.000 1）. ConclusionsThis study preliminarily demonstrates that PAGE5 can activate the PI3K/AKT signaling pathway and mediate the invasion and liver metastasis of breast cancer through MMP1.

ObjectiveThis study aimed to elucidate the specific molecular mechanism by which PAGE5 promotes breast cancer cell invasion and hepatic metastasis through regulating the PI3K/AKT signaling pathway and its downstream effector， matrix metalloproteinase 1 （MMP1）. MethodsBioinformatics analysis using the TCGA database was performed to evaluate PAGE5 expression in metastatic breast cancer tissues. The effects of PAGE5 on the proliferation， migration， and invasion capabilities of breast cancer cells were analyzed using CCK-8， EdU， Transwell， and wound healing assays. A splenic injection hepatic metastasis model in NOD-SCID mice was employed to validate the impact of PAGE5 on breast cancer liver metastasis. Transcriptome sequencing and KEGG enrichment analysis were conducted to identify potential signaling pathways regulated by PAGE5. Western blot was used to detect AKT phosphorylation levels. Quantitative real-time polymerase chain reaction （qPCR） was applied to screen and validate downstream target molecules of PAGE5. ResultsBioinformatic analysis revealed that PAGE5 expression was significantly upregulated in distant metastasis of breast cancer. Both in vitro and in vivo experiments confirmed that PAGE5 overexpression markedly enhanced the migration and invasion abilities of breast cancer cells and promoted the formation of liver metastatic lesions， whereas PAGE5 knockdown suppressed breast cancer liver metastasis （P＜0.000 1）. Transcriptome sequencing and KEGG enrichment analysis indicated that PAGE5 significantly activated the PI3K-AKT signaling pathway （P=0.028 5）. Western blot confirmed that PAGE5 upregulated p-AKT levels， which could be reversed by MK2206. The qPCR results confirmed that MMP1 is a key downstream effector of PAGE5， and its expression can be inhibited by MK2206 （P＜0.000 1）. ConclusionsThis study preliminarily demonstrates that PAGE5 can activate the PI3K/AKT signaling pathway and mediate the invasion and liver metastasis of breast cancer through MMP1.

Objective:To investigate the efficacy and safety of anlotinib combined with GP (gemcitabine+cisplatin) regimen in the treatment of advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy.Methods:A retrospective cohort study was conducted. Fifty two patients with advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy in Affiliated Jiangyin Hospital of Nantong University from January 2019 to June 2022 were selected. According to follow-up treatment methods, they were divided into the treatment group of anlotinib combined with GP regimen (observation group) and the treatment group of GP regimen alone (control group), with 26 cases in each group. The short-term efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1 after 2 cycles of treatment, and the adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events 4.0 after each treatment cycle. Kaplan-Meier method was used for analysis of progression-free survival (PFS) and overall survival (OS), and log-rank test was performed for inter group comparison. The scores of various dimensions of SF-36 quality of life scale before and after treatment were compared.Results:All 52 enrolled patients were able to evaluate the therapeutic effect. The objective response rate (ORR) of the observation group was 38.5% (10/26), and the disease control rate (DCR) was 84.6% (22/26). The ORR of the control group was 19.2% (5/26), and the DCR was 57.7% (15/26). The ORR and DCR of the observation group were higher than those in the control group, and the differences were statistically significant ( χ2 values were 10.82 and 7.18, respectively, both P < 0.05). The PFS [median PFS time, 5.4 months (95% CI: 5.0-5.8 months) vs. 3.9 months (95% CI: 3.6-4.2 months)] and OS [median OS time, 14.0 months (95% CI: 12.1-17.8 months) vs. 9.2 months (95% CI: 7.9-11.3 months)] of the observation group were better than those of the control group, and the differences were statistically significant (both P < 0.05). Compared with the control group, the incidence of hypertension [57.7% (15/26) vs. 3.8% (1/26)] and hand-foot syndrome [23.1% (6/26) vs. 0 (0/26)] in the observation group was higher (both P < 0.05), while there was no statistically significant difference in the incidence of nausea and vomiting, neutropenia, thrombocytopenia, anemia, bleeding, hyperbilirubinemia, fatigue, oral mucositis, and alopecia between the two groups (all P > 0.05). The scores of each dimension of the SF-36 quality of life scale in both groups of patients after treatment were higher than those before treatment (all P < 0.05), and the scores of each dimension in the observation group were higher than those in the control group after treatment (all P < 0.05). Conclusions:Anlotinib combined with GP regimen is effective in the treatment of advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy, this regimen will not significantly increase the adverse reactions of chemotherapy and can improve the prognosis and the quality of life of patients.

Schizophrenia,a severe mental illness characterized by high disability and chronicity,imposes a heavy disease burden on society and patients in China.Community-based management plays a crucial role in the long-term and comprehensive management of patients with schizophrenia.Through years of exploration,community-based management models—primarily focused on case management,assertive community treatment(ACT),and crisis intervention—have proven beneficial to the overall recovery of patients.However,notable differences exist in the implementation of these models between domestic and international practices.Given this context,we systematically analyze domestic and international research to examine the characteristics of different management models and the causes of the differences.Based on this analysis,we propose targeted recommendations for improving community-based management of schizophrenia in China.Regarding case management,a tiered approach should be adopted according to regional economic conditions and resource availability to optimize the efficiency of resource allocation.For ACT,we suggest developing a family-centered integrated intervention framework adapted to China's specific context.Finally,regarding crisis intervention,a collaborative family-community-police response mechanism should be established,complemented by enhanced professional training and streamlined referral procedures.We advocate enhancing resource allocation and theoretical research,along with broader involvement of all sectors of society,to jointly optimize the community-based management model for schizophrenia in China.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

OBJECTIVE: To explore the feasibility of using biomechanical indicators as supplementary evaluation to the Musculoskeletal Tumor Society Scoring System (MSTS) for amputee patients. METHODS: Twenty-four patients who underwent hemipelvectomy between September 2018 and January 2025 were enrolled. There were 15 males and 9 females with an average age of 61.4 years (range, 45-76 years). Participants performed gait tests at self-selected speeds using three assistive devices (prosthesis, single crutch, and double crutches). Motion data were analyzed using a customized OpenSim model. Biomechanical indicators of the intact limb exhibiting common characteristics were screened through correlation and sensitivity analyses. Test-retest reliability [interclass correlation coefficient (ICC)] of selected parameters was assessed to evaluate their potential as MSTS score supplements. RESULTS: All biomechanical indicators showed significant positive correlations with MSTS scores across assistive devices ( P<0.05). Seven indicators demonstrated |Pearson correlation coefficients|>0.8, including walking speed, maximum hip angle, maximum hip moment, peak hip flexion moment, peak hip extension moment, hip flexion impulse, and hip extension impulse. Among these, maximum hip moment, hip flexion impulse, and hip extension impulse exhibited significant between-group differences in adjacent MSTS levels ( P<0.05), indicating high sensitivity, along with excellent test-retest reliability (ICC>0.74, P<0.01). CONCLUSION Biomechanical indicators statistically qualify as potential supplements to MSTS scoring. Maximum hip moment, hip flexion impulse, and hip extension impulse demonstrate particularly high sensitivity to MSTS score variations.
Humans ; Male ; Middle Aged ; Female ; Aged ; Biomechanical Phenomena ; Amputees/rehabilitation* ; Feasibility Studies ; Artificial Limbs ; Reproducibility of Results ; Amputation, Surgical ; Crutches ; Gait

Objective:To investigate the efficacy and safety of anlotinib combined with GP (gemcitabine+cisplatin) regimen in the treatment of advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy.Methods:A retrospective cohort study was conducted. Fifty two patients with advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy in Affiliated Jiangyin Hospital of Nantong University from January 2019 to June 2022 were selected. According to follow-up treatment methods, they were divided into the treatment group of anlotinib combined with GP regimen (observation group) and the treatment group of GP regimen alone (control group), with 26 cases in each group. The short-term efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1 after 2 cycles of treatment, and the adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events 4.0 after each treatment cycle. Kaplan-Meier method was used for analysis of progression-free survival (PFS) and overall survival (OS), and log-rank test was performed for inter group comparison. The scores of various dimensions of SF-36 quality of life scale before and after treatment were compared.Results:All 52 enrolled patients were able to evaluate the therapeutic effect. The objective response rate (ORR) of the observation group was 38.5% (10/26), and the disease control rate (DCR) was 84.6% (22/26). The ORR of the control group was 19.2% (5/26), and the DCR was 57.7% (15/26). The ORR and DCR of the observation group were higher than those in the control group, and the differences were statistically significant ( χ2 values were 10.82 and 7.18, respectively, both P < 0.05). The PFS [median PFS time, 5.4 months (95% CI: 5.0-5.8 months) vs. 3.9 months (95% CI: 3.6-4.2 months)] and OS [median OS time, 14.0 months (95% CI: 12.1-17.8 months) vs. 9.2 months (95% CI: 7.9-11.3 months)] of the observation group were better than those of the control group, and the differences were statistically significant (both P < 0.05). Compared with the control group, the incidence of hypertension [57.7% (15/26) vs. 3.8% (1/26)] and hand-foot syndrome [23.1% (6/26) vs. 0 (0/26)] in the observation group was higher (both P < 0.05), while there was no statistically significant difference in the incidence of nausea and vomiting, neutropenia, thrombocytopenia, anemia, bleeding, hyperbilirubinemia, fatigue, oral mucositis, and alopecia between the two groups (all P > 0.05). The scores of each dimension of the SF-36 quality of life scale in both groups of patients after treatment were higher than those before treatment (all P < 0.05), and the scores of each dimension in the observation group were higher than those in the control group after treatment (all P < 0.05). Conclusions:Anlotinib combined with GP regimen is effective in the treatment of advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy, this regimen will not significantly increase the adverse reactions of chemotherapy and can improve the prognosis and the quality of life of patients.

BACKGROUND:Intervertebral disc degeneration is clinically considered to be the main cause of low back pain,but due to the unclear pathogenesis of intervertebral disc degeneration,there is still a lack of effective means to delay the progression of the disease.Single-cell RNA sequencing technology can amplify and sequence mRNA at the single-cell level,reveal the gene expression intensity of a single cell,discover different cell subsets in tissues according to the heterogeneity of cells,study the pathogenesis of intervertebral disc degeneration at the molecular level,and provide a new theoretical basis for its early diagnosis and treatment. OBJECTIVE:To introduce the basic principles of single-cell RNA sequencing technology and review the research progress of single-cell RNA sequencing technology in intervertebral disc degeneration in recent years. METHODS:A computer was used to search PubMed,Web of Science,CNKI and WanFang databases for the literature published from 2012 to 2022.Key words were"single-cell RNA sequencing,intervertebral disc degeneration,sequencing Technology"in Chinese and English.Duplicate,poor-quality and irrelevant articles were excluded;a total of 70 articles were eventually included. RESULTS AND CONCLUSION:(1)We identified new cell subsets such as homeostatic chondrocytes,hypertrophy chondrocyte-like nucleus pulposus cells and fibrous nucleus pulposus cells,identified the marker genes and transcription factors of these cell subsets,and described the functions,differentiation paths and cell fate of these cell subsets during the development and progression of intervertebral disc degeneration,and proposed the concept of progenitor nucleus pulposus cells.A cell subpopulation with progenitor nucleus pulposus cells properties was identified and its effectiveness in treating intervertebral disc degeneration was verified in mice.(2)Fibro chondrocyte-like annulus fibrosus cells and annulus fibrosus stem cells with both cartilage and fiber properties were identified,and a new type of composite hydrogel was prepared by combining fibrous cartilage inducers silk fibroin and hyaluronic acid in vitro.Experiments in mice demonstrated that this hydrogel could repair both annulus fibrosus tissue and cartilage matrix,and was remarkably effective in the treatment of intervertebral disc degeneration.(3)Regulatory chondrocytes were found in endplate cartilage.Two distinct fates in the progression of intervertebral disc degeneration were analyzed and the differential genes in the two fates were identified.Intercellular communication analysis indicated that regulatory chondrocytes interact with endothelial cells to promote angiogenesis.(4)Immune cells such as macrophages,T cells,myeloid progenitor cells and neutrophils were identified in the degenerated intervertebral disc tissues,demonstrating the existence of immune response during intervertebral disc degeneration.It was found that apolipoprotein induced the polarization of macrophages M1 and M2 subtypes,and this polarization process affected the activity of progenitor nucleus pulposus cells by amplifying the inflammatory response through the MIF signaling pathway.

Objective:To investigate the long-term therapeutic effects and safety of renal denervation (RDN) on hypertensive patients with different cardiovascular risks, as well as its impact on adverse events, cardiovascular death and all-cause mortality.Methods:This was a single-center, single-arm, real-world retrospective study. Patients with refractory hypertension who underwent RDN at Tianjin First Central Hospital from July 6, 2011 to December 23, 2015 were enrolled and divided into either a high or intermediate-low risk group based on baseline cardiovascular risk. The treatment responsiveness of hypertensive patients with different cardiovascular stratification to RDN was assessed by comparing the results of office blood pressure, home blood pressure, and 24-h ambulatory blood pressure monitoring at 1, 5, and 11 years after RDN. Long-term safety of RDN was assessed by creatinine, and estimated glomerular filtration rate (eGFR) at 1 and 11 years after RDN. In addition, the total defined daily dose (DDD) of antihypertensive medications and the incidence of long-term adverse events, cardiovascular deaths, and all-cause deaths after RDN were followed up 11 years after RDN in person or by telephone.Results:A total of 62 patients with refractory hypertension, aged (50.2±15.0) years, of whom 35 (56.5%) were male, were included. There were 35 cases in high-risk group and 27 cases in low and medium risk group. The decrease in clinic systolic blood pressure (high risk vs. low-medium risk: (-38.0±15.1) mmHg vs. (-25.0±16.6) mmHg(1 mmHg=0.133kPa), P=0.002), home self-measured systolic blood pressure ((-28.4±12.7) mmHg vs. (-19.7±13.1) mmHg, P=0.011) and clinic systolic blood pressure 11 years after RDN ((-43.0±18.4) mmHg vs. (-27.8±17.9) mmHg, P=0.003) in the high-risk group was significantly higher than that in the low-medium risk group. The differences in heart rate and the decrease in total DDD number of antihypertensive drugs between the two groups were not statistically significant (all P>0.05). Creatinine and eGFR levels in the two groups at 1 and 11 years after RDN were not statistically significant when compared with the baseline values (all P>0.05). The cumulative cardiovascular mortality rate was 1.6% (1/62) and 8.1% (5/62), and the cumulative all-cause mortality rate was 3.2% (2/62) and 11.3% (7/62) at 5 and 11 years after RDN, respectively. The differences in the incidence rate of adverse events, cardiovascular mortality, and all-cause mortality rate between the two groups were not statistically significant (all P>0.05). Conclusions:RDN has long-term antihypertensive effect and good safety. Hypertensive patients who belong to the high-risk stratification of cardiovascular risk may respond better to RDN treatment.

Objective To establish the ultra-high performance liquid chromatography(UPLC)chromatographic fingerprint of Notopterygii Rhizoma et Radix;To determine the contents of ferulic acid,nodakenin,ammijin,notopterol,isoimperatorin and volatile oil of Notopterygii Rhizoma et Radix from different producing areas;To provide reference for quality evaluation of Notopterygii Rhizoma et Radix.Methods Waters BEH C18 chromatographic column(2.1 mm×150 mm,1.7 μm)was used,with mobile phase acetonitrile-0.02%formic acid aqueous solution gradient elution,flow rate 0.25 mL/min,column temperature 25℃,detection wavelength 330 nm,injection volume 2 μL.UPLC fingerprints of 25 batches of Notopterygii Rhizoma et Radix were established,and the similarity analysis and chemometrics analysis were carried out.The contents of ferulic acid,nodakenin,ammijin,notopterol and isoimperatorin were determined simultaneously,and the contents of volatile oil was determined by steam distillation method.Results Totally 23 common fingerprint peaks were calibrated,11 known components were identified.According to the results of the cluster analysis and principal component analysis,25 batches of Notopterygii Rhizoma et Radix samples were divided into 3 categories,and the 6 potential differential components were screened out by orthogonal partial least squares-discriminant analysis(OPLS-DA).The results showed that the contents of notopterol and volatile oil from Sichuan Province were higher than those from Gansu Province and Qinghai Province.Conclusion The method established in the study is accurate and reliable,which can provide scientific basis and reference for the quality evaluation and control of Notopterygii Rhizoma et Radix.