ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

BACKGROUND:How to improve the expansion of cells,reduce cell loss,increase homing rate and reduce apoptosis is the main problem in the preclinical research of human umbilical cord mesenchymal stem cells.Ginsenoside Rg1 can promote the proliferation and differentiation of mesenchymal stem cells in different microenvironments in vitro or in vivo,which may be a candidate drug to improve the efficiency of human umbilical cord mesenchymal stem cell transplantation.OBJECTIVE:To investigate the effect of human umbilical cord mesenchymal stem cells co-culture combined with ginsenoside Rg1 on pentobarbital sodium induced heart failure cell model.METHODS:H9C2 cells were divided into five groups:Control group,pentobarbital sodium group,human umbilical cord mesenchymal stem cell group,ginsenoside Rg1 group,and human umbilical cord mesenchymal stem cell+ginsenoside Rg1 group.H9C2 cells in the control group were cultured in normal DMEM for 24 hours.H9C2 cells in the other groups were cultured in DMEM containing 0.8％pentobarbital sodium for 7 minutes to establish a heart failure cell model.After modeling,above models were treated with human umbilical cord mesenchymal stem cells,ginsenoside Rg1,or their combination.CCK-8 assay and EdU staining were used to detect cell proliferation.TUNEL assay was used to detect cell apoptosis.Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities were detected according to kit instructions.The mRNA levels of tumor necrosis factor α,interleukin 1β,and interleukin 6 in the supernatant were determined by ELISA.The mRNA levels of tumor necrosis factor α,interleukin 1β,interleukin 6,Bax,and Bcl2 in the cells were determined by RT-qPCR.The protein levels of Bax,Bcl2,Toll-like receptor 4,p65,and p-p65 were determined by western blot assay.RESULTS AND CONCLUSION:(1)Compared with the pentobarbital sodium group,H9C2 cell viability and EdU positive rate were increased;TUNEL positive rate and Bax mRNA and protein expression were decreased,and Bcl-2 mRNA and protein expression were increased;Na+-K+-ATPase activity decreased;Ca2+-Mg2+-ATPase activity increased;tumor necrosis factor α,interleukin-1β,and interleukin-6 levels decreased in H9C2 cell supernatant,and tumor necrosis factor α,interleukin-1β,and interleukin-6 mRNA expression decreased in H9C2 cells;the expression of toll-like receptor 4 and P-P65 protein decreased with significant difference in human umbilical cord mesenchymal stem cell group,ginsenoside Rg1 group and human umbilical cord mesenchymal stem cell+ginsenoside Rg1 group(P＜0.05).(2)Compared with human umbilical cord mesenchymal stem cell group and ginsenoside Rg1 group,the above indexes in human umbilical cord mesenchymal stem cells+ginsenoside Rg1 group were further improved(P＜0.05).The results showed that human umbilical cord mesenchymal stem cells combined with ginsenoside Rg1 promoted the viability of heart failure cells induced by pentobarbital sodium and inhibited inflammation mediated by the Toll-like receptor 4/nuclear factor κB pathway.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.

Objective To investigate the effects of 3-methyladenine(3-MA)on mouse mesangial cell line MES-13 cultured in high glucose,and on the kidney of streptozotocin(STZ)-induced mouse model of diabetes and the po-tential mechanism.Methods MES-13 cells were divided into low glucose control group(LG),hyper osmotic pres-sure control group(HOP),high glucose group(HG),3-methyladenine+high glucose group(HG+3-MA)and chloroquine+high glucose group(HG+CQ).The groups were respectively incubated with low glucose DMEM,30 mmol/L mannitol hypertonic control medium,30 mmol/L high glucose medium,5 mmol/L 3-MA+30 mmol/L high glucose medium and 10 mmol/L CQ+30 mmol/L high glucose medium for 24 hours.CCK-8 assay and Western blot were performed.In vivo experiment:Male C57BL/6J mice were induced diabetes for model development by in-tra-peritoneal injection of STZ 60 mg/kg for five consecutive days.After two weeks of injection,the blood glucose was measured.Animals with blood glucose level higher than 16.7 mmol/L(250 mg/dL)were randomly divided in-to diabetes control group(DM),3-MA intervention group(DM+3-MA)and CQ intervention group(DM+CQ),then were fed under the same conditions as normal control group(NC)mice.The DM+3-MA group was given 10 mg/kg of 3-MA aqueous solution by gavage every day,the DM+CQ group was given 50 mg/kg of CQ by intrap-eritoneal injection every three days,the NC group and DM group were given the same amount of normal saline and killed after 6 weeks.The kidneys were stripped for kidney/body weight ratio determination,periodic acid-schiff staining(PAS),MASSON staining microscopy and Western blot.Results In vitro experiment:Compared to the LG group,the cell viability,PCNA expression,ratio of phosphorylated Akt to total Akt(p-Akt/Akt)and ratio of phosphorylated rpS6 to total rpS6(p-rpS6/rpS6)were significantly increased in the HG group(P＜0.05).Com-pared with HG group,the cell viability,PCNA and p-Akt/Akt ratio of HG+3-MA group and HG+CQ group were significantly decreased and p-rpS6/rpS6 ratio of HG+3-MA group was significantly decreased(P＜0.01).In vivo experiment:Compared to NC group,the kidney/body weight ratio,glomerular volume,renal tubular injury index,PCNA,fibronectin,COL1A1,p-Akt/Akt,p-rpS6/rpS6 in DM group were all significantly up-regulated(P＜0.05).Compared with DM group,the kidney/body weight ratio,glomerular volume,renal tubular injury in-dex,PCNA,fibronectin,COL1A1,p-Akt/Akt,p-rpS6/rpS6 of DM+3-MA group mice were all significantly de-creased(P＜0.05).Conclusions 3-MA can improve glomerular mesangial cell proliferation and renal ECM deposi-tion in early diabetes nephropathy(DN).The improvement of 3-MA in early DN may be related to the inhibition of Akt/rpS6 signaling pathway.

Objective To analyze the application value of 3D Slicer software in endoscopic transsphenoidal surgery for pituitary adenoma resection.Methods A retrospective analysis was made on the clinical data of 36 patients with pituitary adenomas treated with 3D Slicer-assisted endoscopic transsphenoidal surgery(3D Slicer group)in the Department of Neurosurgery,The Second Affiliated Hospital of Xi'an Jiaotong University,from January 2024 to December 2024.Preoperatively,multimodal images were fused and reconstructed using 3D Slicer software to systematically evaluate bony anatomical structures such as sphenoid sinus ostia,intrasphenoidal septa,and sellar floor structures,design the size of pedicled nasoseptal flaps,and clarify the positional relationships between pituitary adenomas and surrounding vital structures including the internal carotid artery,pituitary gland,and optic chiasm,so as to provide real-time guidance for intraoperative procedures.Meanwhile,45 patients with pituitary adenomas treated with neuronavigation-assisted endoscopic transsphenoidal surgery from January 2023 to December 2023 were included as the control group(neuronavigation group).The surgical outcomes and postoperative complications were compared between the two groups.Results Compared with the neuronavigation group,the 3D Slicer group demonstrated higher identification rates of the optic nerve groove and carotid artery impression(94.4％vs.77.8％),shorter operative time[(2.9±0.6)h vs.(3.5±0.9)h],less intraoperative bleeding[(159.7±70.5)mL vs.(237.8±96.0)mL],and a lower incidence of postoperative olfactory dysfunction(8.3％vs.26.7％),with statistically significant differences(P＜0.05).However,there were no statistically significant differences between the two groups in the identification rate of the sphenoid sinus ostium(100.0％vs.97.8％),gross total resection rate(75.0％vs.64.4％),and the incidence of other postoperative complications,including cerebrospinal fluid leakage(0.0％vs.6.7％),intracranial infection(2.8％vs.11.1％),transient diabetes insipidus(30.6％vs.22.2％),and hypopituitarism(38.9％vs.37.8％,P＞0.05).Conclusion 3D Slicer software helps improve the mastery of anatomical basics in endoscopic transsphenoidal approach among junior and primary physicians,enhancing the clinical efficacy and safety of pituitary adenoma resection,and thus is worthy of clinical promotion.

Objective To analyze the application value of 3D Slicer software in endoscopic transsphenoidal surgery for pituitary adenoma resection.Methods A retrospective analysis was made on the clinical data of 36 patients with pituitary adenomas treated with 3D Slicer-assisted endoscopic transsphenoidal surgery(3D Slicer group)in the Department of Neurosurgery,The Second Affiliated Hospital of Xi'an Jiaotong University,from January 2024 to December 2024.Preoperatively,multimodal images were fused and reconstructed using 3D Slicer software to systematically evaluate bony anatomical structures such as sphenoid sinus ostia,intrasphenoidal septa,and sellar floor structures,design the size of pedicled nasoseptal flaps,and clarify the positional relationships between pituitary adenomas and surrounding vital structures including the internal carotid artery,pituitary gland,and optic chiasm,so as to provide real-time guidance for intraoperative procedures.Meanwhile,45 patients with pituitary adenomas treated with neuronavigation-assisted endoscopic transsphenoidal surgery from January 2023 to December 2023 were included as the control group(neuronavigation group).The surgical outcomes and postoperative complications were compared between the two groups.Results Compared with the neuronavigation group,the 3D Slicer group demonstrated higher identification rates of the optic nerve groove and carotid artery impression(94.4％vs.77.8％),shorter operative time[(2.9±0.6)h vs.(3.5±0.9)h],less intraoperative bleeding[(159.7±70.5)mL vs.(237.8±96.0)mL],and a lower incidence of postoperative olfactory dysfunction(8.3％vs.26.7％),with statistically significant differences(P＜0.05).However,there were no statistically significant differences between the two groups in the identification rate of the sphenoid sinus ostium(100.0％vs.97.8％),gross total resection rate(75.0％vs.64.4％),and the incidence of other postoperative complications,including cerebrospinal fluid leakage(0.0％vs.6.7％),intracranial infection(2.8％vs.11.1％),transient diabetes insipidus(30.6％vs.22.2％),and hypopituitarism(38.9％vs.37.8％,P＞0.05).Conclusion 3D Slicer software helps improve the mastery of anatomical basics in endoscopic transsphenoidal approach among junior and primary physicians,enhancing the clinical efficacy and safety of pituitary adenoma resection,and thus is worthy of clinical promotion.

BACKGROUND:How to improve the expansion of cells,reduce cell loss,increase homing rate and reduce apoptosis is the main problem in the preclinical research of human umbilical cord mesenchymal stem cells.Ginsenoside Rg1 can promote the proliferation and differentiation of mesenchymal stem cells in different microenvironments in vitro or in vivo,which may be a candidate drug to improve the efficiency of human umbilical cord mesenchymal stem cell transplantation.OBJECTIVE:To investigate the effect of human umbilical cord mesenchymal stem cells co-culture combined with ginsenoside Rg1 on pentobarbital sodium induced heart failure cell model.METHODS:H9C2 cells were divided into five groups:Control group,pentobarbital sodium group,human umbilical cord mesenchymal stem cell group,ginsenoside Rg1 group,and human umbilical cord mesenchymal stem cell+ginsenoside Rg1 group.H9C2 cells in the control group were cultured in normal DMEM for 24 hours.H9C2 cells in the other groups were cultured in DMEM containing 0.8％pentobarbital sodium for 7 minutes to establish a heart failure cell model.After modeling,above models were treated with human umbilical cord mesenchymal stem cells,ginsenoside Rg1,or their combination.CCK-8 assay and EdU staining were used to detect cell proliferation.TUNEL assay was used to detect cell apoptosis.Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities were detected according to kit instructions.The mRNA levels of tumor necrosis factor α,interleukin 1β,and interleukin 6 in the supernatant were determined by ELISA.The mRNA levels of tumor necrosis factor α,interleukin 1β,interleukin 6,Bax,and Bcl2 in the cells were determined by RT-qPCR.The protein levels of Bax,Bcl2,Toll-like receptor 4,p65,and p-p65 were determined by western blot assay.RESULTS AND CONCLUSION:(1)Compared with the pentobarbital sodium group,H9C2 cell viability and EdU positive rate were increased;TUNEL positive rate and Bax mRNA and protein expression were decreased,and Bcl-2 mRNA and protein expression were increased;Na+-K+-ATPase activity decreased;Ca2+-Mg2+-ATPase activity increased;tumor necrosis factor α,interleukin-1β,and interleukin-6 levels decreased in H9C2 cell supernatant,and tumor necrosis factor α,interleukin-1β,and interleukin-6 mRNA expression decreased in H9C2 cells;the expression of toll-like receptor 4 and P-P65 protein decreased with significant difference in human umbilical cord mesenchymal stem cell group,ginsenoside Rg1 group and human umbilical cord mesenchymal stem cell+ginsenoside Rg1 group(P＜0.05).(2)Compared with human umbilical cord mesenchymal stem cell group and ginsenoside Rg1 group,the above indexes in human umbilical cord mesenchymal stem cells+ginsenoside Rg1 group were further improved(P＜0.05).The results showed that human umbilical cord mesenchymal stem cells combined with ginsenoside Rg1 promoted the viability of heart failure cells induced by pentobarbital sodium and inhibited inflammation mediated by the Toll-like receptor 4/nuclear factor κB pathway.

Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.