Objective To investigate the function of glymphatic system in patients with mild traumatic brain injury via diffusion tensor imaging analysis along the perivascular space(DTI-ALPS)index and its relationship with clinical features.Methods The clinical and imaging data from 163 patients with mild traumatic brain injury were retrospectively collected,including 31 cases with MRI-negative findings and 132 cases with MRI-positive findings.In addition,29 healthy individuals underwent physical examinations were included as a control group.The differences in DTI-ALPS index and clinical features between mild traumatic brain injury and control group,as well as among subgroups of traumatic brain injury were analyzed.Results The DTI-ALPS index in patients with mild traumatic brain injury were significantly higher than those in control group(P＜0.05).Subgroup analysis showed that DTI-ALPS index of traumatic brain injury patients with MRI-negative findings and MRI-positive findings were all significantly higher than those of control group(P=0.023 and 0.004,respectively).Compared to control group,DTI-ALPS index in mild traumatic brain injury patients gradually increased with the progression of injury,and the difference was statistically significant(P=0.008).Conclusion Patients with mild traumatic brain injury exhibit increased functional activity of glymphatic system,as indicated by increased DTI-ALPS index,which further increase with the progression of injury.

Objective To study the effect of intra-aortic balloon pump(IABP)in the therapy of ST-segment-elevation myocardial infarction(STEMI)patients complicated with ventricular septal rupture(VSR).Methods A retrospective analysis was performed on 35 STEMI patients complicated with VSR.Those patients were admitted in Yan'an Hospital Affiliated to Kunming Medical University from January 2019 to June 2023.Patients were divided into the combine-treated group(20 cases)and the drug-treated group(15 cases)according to the therapeutic strategies.The combine-treated group received IABP implantation and drug therapy,and the drug-treated group only received drug therapy.The clinical characteristics,hemodynamic and cardiac function improvement and mortality were evaluated.Hemodynamic and cardiac function improvement were compared between the two groups.Results There were no statistically significant differences in age,male proportion and size of VSR between the two groups(P>0.05).In the combine-treated group,the average heart rate,the average arterial blood pressure,central venous pressure,the LVEF value of cardiac ultrasound,pleural effusion,B-Line of lung,the level of B-type natriuretic peptide(BNP),the level of serum creatinine and the level of serum lactic acid were improved at 72 h after IABP use(all P<0.05).All these indicators got worse in the drug-treated group.The mortality rate of the combine-treated group was markedly lower than that of the drug-treated group(P<0.05).The mortality rate of patients who received IABP implantation within 72 h after VSR was lower than that of patients who received IABP implantation beyond 72 h after VSR.Conclusion For patients with AMI complicated with VSR,implantation of IABP can significantly improve hemodynamics,cardiac function and reduce mortality.

The critical role of protein disequilibrium in driving carcinogenesis has long been recognized. Though several inhibitors of heat shock protein (HSP) family members have entered clinical trials, none of them have been approved for clinical use as a result of inevitable toxicity, leading to the identification of safer therapeutic approaches sharing a similar efficacy relevant and urgent. Through delineating the role of HSP90 inhibitors in arresting cancer hallmarks, this paper identified HSP90 inhibition as an effective therapeutic strategy capable of concomitantly targeting multiple key transformed properties of cancers via modulating cellular proteostasis. Through interrogating intrinsic connections between proteostasis and redox homeostasis, this paper proposed cold atmospheric plasma (CAP) as a possible alternative of HSP90 inhibitors with little adverse effects. This paper extended the therapeutic spectrum of HSP90 inhibitors and CAP to inflammation-driven pathologies including autoimmune diseases, as inflammation is a manifestation of failed proteostasis. These insights may conceptually advance our understandings on the driving force of cancers that can be easily extended to other disorders originated from imbalanced proteostasis and abnormal inflammation. Tools proposed here for inhibiting HSP90 including CAP and its possible synergy with HSP90 inhibitors may shift the current treatment paradigm to a new avenue in oncology and other relevant fields.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Objective:To investigate the effect of "four-staff co-management" follow-up mode on risk factor control and medium-term prognosis improvement in patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:This was a intervention study. Patients with coronary heart disease who were admitted to the Xiamen Cardiovascular Hospital of Xiamen University from June 2021 to January 2022 and successfully discharged after PCI were included. According to the different types of follow-up after discharge, patients were divided into the traditional follow-up group and the "four-staff co-management" follow-up group. The "four-staff co-management" follow-up mode means that specialists, specialist managers in third-level A hospitals and general practitioners and health managers in basic hospitals were jointly responsible for post-discharge follow-up of PCI patients. Baseline clinical data were collected. The primary endpoints were the rate of compliance of coronary heart disease risk factor control at 12 months after surgery, the rate of secondary surgery, and the incidence of mid-term major adverse cardiovascular and cerebrovascular events (MACCE). Unplanned secondary PCI included symptom-driven secondary PCI and asymptomatic secondary PCI. MACCE includes myocardial infarction, hospitalization for heart failure, stroke, major bleeding, all-cause death, and composite endpoints including these events.Results:A total of 2 181 patients were enrolled, including 1 097 patients in the traditional follow-up group and 1 084 patients in the "four-staff co-management" follow-up group. At baseline, there were no statistically significant differences in gender, age, discharge diagnosis, co-existing diseases, echocardiographic indexes, and coronary artery lesions between the two groups (all P>0.05). There were no significant differences between the two groups in total PCI stent length, maximum internal diameter of stent, proportion of patients using drug balloon, proportion of patients with a planned second surgery during hospitalization, and discharge with drugs (all P>0.05). Twelve months after PCI, the reduction in HbA1c and low-density lipoprotein cholesterol was greater in the "four-staff co-management " follow-up group than that in the traditional follow-up group (all P<0.05), and the rate of reaching the standard for low-density lipoprotein cholesterol was higher than that in the traditional follow-up group ( P=0.001), but there was no statistical significance between the two groups for blood pressure and blood glucose (all P>0.05). During the follow-up period, the proportion of symptom-driven second operation patients was lower in the "four-staff co-management" follow-up group than that in the traditional follow-up group ( P<0.001), and there was no significant difference in the proportion of asymptomatic second operation patients between the two groups ( P=0.191). The proportion of hospitalized patients with heart failure in the "four-staff co-management" follow-up group was lower than that in the traditional follow-up group ( P=0.029), and there was no significant difference in the proportion of myocardial infarction, cerebral infarction, cerebral hemorrhage, massive hemorrhage, death and complex endpoint events between the two groups (all P>0.05). Conclusion:The "four-staff co-management" follow-up mode can effectively improve the control of risk factors and medium-term prognosis in patients with coronary heart disease after PCI.

Objective To investigate the function of glymphatic system in patients with mild traumatic brain injury via diffusion tensor imaging analysis along the perivascular space(DTI-ALPS)index and its relationship with clinical features.Methods The clinical and imaging data from 163 patients with mild traumatic brain injury were retrospectively collected,including 31 cases with MRI-negative findings and 132 cases with MRI-positive findings.In addition,29 healthy individuals underwent physical examinations were included as a control group.The differences in DTI-ALPS index and clinical features between mild traumatic brain injury and control group,as well as among subgroups of traumatic brain injury were analyzed.Results The DTI-ALPS index in patients with mild traumatic brain injury were significantly higher than those in control group(P＜0.05).Subgroup analysis showed that DTI-ALPS index of traumatic brain injury patients with MRI-negative findings and MRI-positive findings were all significantly higher than those of control group(P=0.023 and 0.004,respectively).Compared to control group,DTI-ALPS index in mild traumatic brain injury patients gradually increased with the progression of injury,and the difference was statistically significant(P=0.008).Conclusion Patients with mild traumatic brain injury exhibit increased functional activity of glymphatic system,as indicated by increased DTI-ALPS index,which further increase with the progression of injury.

Objective:To analyze the effects of low-molecular-weight heparin combined with insulin (LMWH+INS) and double filtration plasmapheresis (DFPP) on lipid profiles and clinical outcomes in patients with hypertriglyceridemic acute pancreatitis (HTG-AP) based on propensity score matching.Methods:The clinical data of 126 patients with HTG-AP from October 2022 to February 2024 in The Third Affiliated Hospital of Nanjing Medical University, Changzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing Traditional Chinese Medicine University and Changzhou First People's Hospital were retrospectively included. Patients were divided into LMWH+INS group ( n=87) and DFPP group ( n=39) according to the treatment. Propensity score matching was applied at a 1∶1 ratio. The repeated measures analysis of variance was conducted to assess dynamic changes of blood lipids within the 5 days of admission between the LMWH+INS and DFPP groups after matching. Clinical symptoms and outcomes were compared between the two matched groups following matching. Results:29 patients were included in both LMWH+INS group and DFPP group after propensity score matching. No statistically significant differences were observed in triglycerides (TG), acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score, or bedside index for the severity of acute pancreatitis (BISAP) between the two groups (all P value >0.05), indicating comparability. Repeated measures analysis of variance revealed that TG and TC levels in the DFPP group were significantly lower than those in the LMWH+INS group at 2-5 days after admission [TG 2 d: (5.26±2.59) mmol/L vs (10.79±3.81) mmol/L, 3 d: (3.35±1.01) mmol/L vs (7.72±3.64) mmol/L, 4 d: (3.45±0.77) mmol/L vs (6.57±3.17) mmol/L, 5 d: (3.73±1.26) mmol/L vs (5.61±3.07) mmol/L; TC 2 d: (4.83±2.29) mmol/L vs (8.2±2.82) mmol/L, 3 d: (4.23±2.17) mmol/L vs (7.71±2.68) mmol/L, 4 d: (4.28±1.59) mmol/L vs (7.55±2.41) mmol/L, 5 d: (4.1±1.21) mmol/L vs (7.84±2.6) mmol/L], with a more rapid decrease. LDL levels in the LMWH+INS and DFPP groups showed similar trends, with significant decreases at 2 day after admission [(5.41±3.24) mmol/L vs (2.96±1.47) mmol/L, (4.99±3.51) mmol/L vs (2.47±1.53) mmol/L]. The differences mentioned above are all statistically significant (all P value <0.001). No significant changes were observed in HDL levels in either LMWH+INS and DFPP groups at 2-5 days after admission. After matching, the DFPP group had a significantly longer time of resuming feeding [3(2, 3) days vs 4(3, 6) days] and higher hospital cost [12113.87 (9055.31, 14401.84) yuan vs 28025.34 (25388.11, 36335.48) yuan] compared with the LMWH+INS group, with statistically significant differences. Conclusions:DFPP could reduce TG and TC levels more rapidly and effectively than LMWH combined with INS, but does not show an advantage in improving clinical outcomes and reducing hospitalization costs.

Oral squamous cell carcinoma(OSCC)accounts for over 90％of oral malignancies,with more than 370 000 new cases and approximately 188 000 deaths annually worldwide.In China,there are roughly 65 000 new cases and 35 000 deaths each year,showing a significant upward trend compared with 2015 statistics.Despite continuous advancements in treatment modalities,the 5-year survival rate remains stagnant at 50％-60％,where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology.To address these critical challenges,this study established a standardized bioban-king protocol for OSCC patient-derived organoids(PDOs)(Patent:Method for constructing an oral squa-mous cell carcinoma organoid bank,ZL202311378598.3).Through groundbreaking optimization of cul-ture media,enzymatic digestion kinetics,and stepwise cryopreservation,we achieved a biobanking suc-cess rate exceeding 95％and pioneered synchronous cultivation of matched primary tumors,lymph node metastases,and adjacent normal mucosa from individual patients,preserving spatial heterogeneity and stromal interactions.Leveraging this platform,we developed high-throughput drug screening:Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate(ATP)-based viability as-says;We discovered resistance mechanisms:Identified sialylated cancer IgG(SIA-cIgG)-mediated cis-platin resistance(primary/secondary)through PTPN13 suppression,with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy.Besides,we elucidated metastatic drivers:CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming,activating epithelial-mesenchymal plasticity(EMP)and inducing partial epithelial-mesenchymal transi-tion(pEMT).This"holographic patient-mirroring"platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Techni-cal Guidelines(Technical guideline for establishing patient-derived oral squamous cell carcinoma or-ganoid banks,CHSA 2024-08).Future integration of immune-competent organoids,3D-bioprinted vas-culature,and multi-omics-AI systems will accelerate personalized oncology.These innovations will accelerate clinical translation of personalized therapeutic regimens,ultimately bridging the gap between bench research and bedside application.

Objective:To analyze the effects of low-molecular-weight heparin combined with insulin (LMWH+INS) and double filtration plasmapheresis (DFPP) on lipid profiles and clinical outcomes in patients with hypertriglyceridemic acute pancreatitis (HTG-AP) based on propensity score matching.Methods:The clinical data of 126 patients with HTG-AP from October 2022 to February 2024 in The Third Affiliated Hospital of Nanjing Medical University, Changzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing Traditional Chinese Medicine University and Changzhou First People's Hospital were retrospectively included. Patients were divided into LMWH+INS group ( n=87) and DFPP group ( n=39) according to the treatment. Propensity score matching was applied at a 1∶1 ratio. The repeated measures analysis of variance was conducted to assess dynamic changes of blood lipids within the 5 days of admission between the LMWH+INS and DFPP groups after matching. Clinical symptoms and outcomes were compared between the two matched groups following matching. Results:29 patients were included in both LMWH+INS group and DFPP group after propensity score matching. No statistically significant differences were observed in triglycerides (TG), acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score, or bedside index for the severity of acute pancreatitis (BISAP) between the two groups (all P value >0.05), indicating comparability. Repeated measures analysis of variance revealed that TG and TC levels in the DFPP group were significantly lower than those in the LMWH+INS group at 2-5 days after admission [TG 2 d: (5.26±2.59) mmol/L vs (10.79±3.81) mmol/L, 3 d: (3.35±1.01) mmol/L vs (7.72±3.64) mmol/L, 4 d: (3.45±0.77) mmol/L vs (6.57±3.17) mmol/L, 5 d: (3.73±1.26) mmol/L vs (5.61±3.07) mmol/L; TC 2 d: (4.83±2.29) mmol/L vs (8.2±2.82) mmol/L, 3 d: (4.23±2.17) mmol/L vs (7.71±2.68) mmol/L, 4 d: (4.28±1.59) mmol/L vs (7.55±2.41) mmol/L, 5 d: (4.1±1.21) mmol/L vs (7.84±2.6) mmol/L], with a more rapid decrease. LDL levels in the LMWH+INS and DFPP groups showed similar trends, with significant decreases at 2 day after admission [(5.41±3.24) mmol/L vs (2.96±1.47) mmol/L, (4.99±3.51) mmol/L vs (2.47±1.53) mmol/L]. The differences mentioned above are all statistically significant (all P value <0.001). No significant changes were observed in HDL levels in either LMWH+INS and DFPP groups at 2-5 days after admission. After matching, the DFPP group had a significantly longer time of resuming feeding [3(2, 3) days vs 4(3, 6) days] and higher hospital cost [12113.87 (9055.31, 14401.84) yuan vs 28025.34 (25388.11, 36335.48) yuan] compared with the LMWH+INS group, with statistically significant differences. Conclusions:DFPP could reduce TG and TC levels more rapidly and effectively than LMWH combined with INS, but does not show an advantage in improving clinical outcomes and reducing hospitalization costs.

Objective:To investigate the effect of "four-staff co-management" follow-up mode on risk factor control and medium-term prognosis improvement in patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:This was a intervention study. Patients with coronary heart disease who were admitted to the Xiamen Cardiovascular Hospital of Xiamen University from June 2021 to January 2022 and successfully discharged after PCI were included. According to the different types of follow-up after discharge, patients were divided into the traditional follow-up group and the "four-staff co-management" follow-up group. The "four-staff co-management" follow-up mode means that specialists, specialist managers in third-level A hospitals and general practitioners and health managers in basic hospitals were jointly responsible for post-discharge follow-up of PCI patients. Baseline clinical data were collected. The primary endpoints were the rate of compliance of coronary heart disease risk factor control at 12 months after surgery, the rate of secondary surgery, and the incidence of mid-term major adverse cardiovascular and cerebrovascular events (MACCE). Unplanned secondary PCI included symptom-driven secondary PCI and asymptomatic secondary PCI. MACCE includes myocardial infarction, hospitalization for heart failure, stroke, major bleeding, all-cause death, and composite endpoints including these events.Results:A total of 2 181 patients were enrolled, including 1 097 patients in the traditional follow-up group and 1 084 patients in the "four-staff co-management" follow-up group. At baseline, there were no statistically significant differences in gender, age, discharge diagnosis, co-existing diseases, echocardiographic indexes, and coronary artery lesions between the two groups (all P>0.05). There were no significant differences between the two groups in total PCI stent length, maximum internal diameter of stent, proportion of patients using drug balloon, proportion of patients with a planned second surgery during hospitalization, and discharge with drugs (all P>0.05). Twelve months after PCI, the reduction in HbA1c and low-density lipoprotein cholesterol was greater in the "four-staff co-management " follow-up group than that in the traditional follow-up group (all P<0.05), and the rate of reaching the standard for low-density lipoprotein cholesterol was higher than that in the traditional follow-up group ( P=0.001), but there was no statistical significance between the two groups for blood pressure and blood glucose (all P>0.05). During the follow-up period, the proportion of symptom-driven second operation patients was lower in the "four-staff co-management" follow-up group than that in the traditional follow-up group ( P<0.001), and there was no significant difference in the proportion of asymptomatic second operation patients between the two groups ( P=0.191). The proportion of hospitalized patients with heart failure in the "four-staff co-management" follow-up group was lower than that in the traditional follow-up group ( P=0.029), and there was no significant difference in the proportion of myocardial infarction, cerebral infarction, cerebral hemorrhage, massive hemorrhage, death and complex endpoint events between the two groups (all P>0.05). Conclusion:The "four-staff co-management" follow-up mode can effectively improve the control of risk factors and medium-term prognosis in patients with coronary heart disease after PCI.