BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95％ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P＜0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P＜0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P＜0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P＜0.001),and their expression levels decreased after treatment(all P＜0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P＜0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P＜0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P＜0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.

BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95％ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P＜0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P＜0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P＜0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P＜0.001),and their expression levels decreased after treatment(all P＜0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P＜0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P＜0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P＜0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.

ObjectiveTo investigate the effects of Chaihu and Longgu Mulitang （CLMT） on hippocampal neural damage in the mouse model of depression via the extracellular signal-regulated protein kinase （ERK）/cAMP-response element-binding protein （CREB） signaling pathway. MethodsSeventy-eight male C57BL/6 mice were randomly allocated into normal control， model， low/medium/high-dose （2.89， 5.78， and 11.56 g·kg^-1， respectively） CLMT， and paroxetine （10 mg·kg^-1） groups. A depression model was established by chronic unpredictable mild stress （CUMS） combined with social isolation. Behavioral tests were carried out to evaluate depressive-like behaviors. Hematoxylin-eosin staining and Nissl staining were performed to assess hippocampal morphology and neuronal damage. Immunofluorescence was employed to detect glial fibrillary acidic protein （GFAP） and ionized calcium-binding adapter molecule 1 （Iba1）. Real-time PCR was employed to measure the mRNA levels of ERK and CREB. Western blot was employed to determine the expression of ERK/CREB pathway proteins and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. Molecular Operating Environment （MOE） software was used for molecular docking to evaluate the interactions between CLMT components and target proteins. ResultsCompared with the normal control group， the model group showed decreased sucrose preference （P0.01）， increased tail-suspension immobility time （P0.01）， decreased activity in the central region of the open field test （P0.01）， and decreased activity in the middle and open-arm region of the elevated plus maze test （P0.01）. The hippocampal area in the model group showed wrinkled cells and a reduction in the number of cells， neurons with reduced sizes and Nissl bodies， enhanced fluorescence intensity of GFAP and Iba1 （P0.01）， and down-regulated expression of phosphorylated （p）-ERK， p-CREB， and BDNF （P0.05， P0.01） and mRNA levels of ERK and CREB （P0.01）. Compared with the model group， the CLMT group showed increased body weight （P0.05， P0.01）， restored cell morphology， with only a small number of ruptured cells， normal neuronal structure and morphology with obvious nuclei and abundant Nissl bodies， weakened fluorescence intensity of GFAP and Iba1 （P0.05， P0.01）， up-regulated mRNA levels of ERK and CREB （P0.05， P0.01） and protein levels of phosphorylated （p）-ERK， p-CREB， and BDNF in the hippocampal tissue （P0.05， P0.01）. The results of molecular docking indicated that nine active ingredients in CLMT had good binding affinity with ERK and CREB. ConclusionCLMT may ameliorate the hippocampal nerve injury in the mouse model of depression by regulating the ERK/CREB pathway.

Due to genetic abnormalities,hypoxic injury or surgical trauma,some children with congenital heart disease have neurodevelopmental disorders,mainly manifested as generalized hypotonia and exercise developmental delay.Infants have strong neuroplasticity.Early exercise rehabilitation is helpful to improve their exercise function and neurodevelopment and promote their rehabilitation.This paper reviews the assessment,implementation methods and effect evaluation of early exercise rehabilitation in infants with congenital heart disease,and puts forward hindering factors and nursing countermeasures,in order to provide references for clinical nursing practice.

Objective:To investigate the clinical features and prognostic factors of newly-treated elderly acute myeloid leukemia (AML) patients with intermediate-risk karyotype.Methods:A retrospective case series study was conducted. A total of 87 newly-treated elderly AML patients with intermediate-risk karyotype in the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2013 to December 2023 were selected. The clinical characteristics were summarized. The Kaplan-Meier method was used for survival analysis and Cox proportional hazards model was used to make univariate and multivariate analyses of prognostic factors.Results:The median age [ M ( Q1, Q3)] of 87 patients was 69 (60, 87) years. The patients with normal karyotype and abnormal karyotype accounted for 77.1% (67/87), 22.9% (20/87), respectively. A total of 74 patients (85.1%) had 1 or more gene mutations, of which FLT3-ITD, NPM1 mutation, CEBPA mutation and WT1 high expression accounted for 29.9% (26/87), 26.4% (23/87), 19.5% (17/87), and 65.5% (57/87), respectively; additionally, 44.7% (39/87) of patients had 2 or more gene mutations. The objective response rate of patients after induction therapy was 47.7% (41/87), while the relapse rate was 73.2% (30/41). The median progression-free survival (PFS) time was 7.8 months, and the median overall survival (OS) time was 12.1 months. Univariate analysis result revealed that age, FLT3-ITD, hypomethylating agents, and minimal residual disease complete remission (MDR-CR) were factors influencing the OS of newly-treated elderly AML patients with intermediate-risk karyotype (all P < 0.05). Multivariate analysis indicated that MDR-CR was an independent risk factor for OS (yes vs. no: HR = 0.27, 95% CI: 0.14-0.51, P < 0.001). Conclusions:Newly-treated elderly AML patients with intermediate-risk karyotype have a high relapse rate and poor prognosis, and MDR-CR is identified as an independent influencing factor for the prognosis of these patients.

Background and purpose:Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases(LM)from solid tumors.A previous phase Ⅰ study demonstrated the safety and potential efficacy of intrathecal anti-programmed death receptor 1(anti-PD-1)for LM from melanoma.The synergistic efficacy of systemic chemotherapy combined with anti-PD-1 has been widely known.This study aimed to evaluate the safety and feasibility of intrathecal chemotherapy(pemetrexed)and anti-PD-1(toripalimab)for LM patients from solid tumors.Methods:The subjects were patients with LM from solid tumors who were treated at Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City.A 3+3 dose de-escalation strategy was implemented to determine the recommended dose with an initial dose of PD-1 inhibitor(toripalimab)40 mg and pemetrexed 15 mg.Pemetrexed was administered twice weekly for the initial 2 weeks of induction therapy,once weekly for the subsequent 4 weeks of consolidation therapy,and once monthly during maintenance therapy.PD-1 inhibitor was initiated at the 4th administration of pemetrexed,administered every 2 weeks for 6 weeks;subsequently,responders continued monthly maintenance therapy alongside pemetrexed.The primary objective was to assess safety based on adverse events and the recommended dose.All participants were observed to investigate the clinical response rate(CRR),disease control rate(DCR)and overall survival(OS).This study was approved by the ethics committee of Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City(ethics number:2024-KY-029-01).Results:Seven patients(male:3,female:4,median age:57 years)were enrolled between June and September 2024,including non-small cell lung cancer(6)and breast cancer(1).All patients presented with positive cerebrospinal fluid(CSF)cytology.Six patients presented LM-related neurological dysfunction.Five patients showed LM-related neuroimaging findings.Six patients completed the induction and consolidation therapy,and subsequently received maintenance therapy.One patient,due to bacterial meningitis,did not complete the final administration of toripalimab during consolidation therapy,and maintenance therapy was administered after infection control.Adverse events rate was 100%(7/7),including myelosuppression(100.00%,n=7),elevation of hepatic aminotransferases(42.86%,n=3),fatigue(28.57%,n=2)and hypothyroidism(14.29%,n=1).Three(42.86%)patients had grade 3 adverse events(myelosuppression).The immune-related adverse event(irAE)rate was 14.29%,manifested as hypothyroidism(Grade 2).No dose-limiting toxicity(DLT)was observed.Thus,no de-escalation was applied.The recommended dose was determined to be PD-1 inhibitor 40 mg in combination with pemetrexed 15 mg.Three patients showed improved neurological dysfunction,1 with CSF cytological response,and 2 with neuroimaging improvement.CRR was 57.14%(4/7)by response assessment in neuro-oncology(RANO)proposal criteria.DCR was 100%(7/7).Three patients exhibited abscopal effects with regression of brain metastasis lesions,primary lung lesion and mediastinal lymph nodes,respectively.As of April 10,2025,1 patient died.The median follow-up time was 7.7(5.9-9.3)months.The median OS was not reached with a 6-month OS rate of 85.71%.Conclusion:The combination therapy of intrathecal pemetrexed and a PD-1 inhibitor was well-tolerated and feasible,while also exhibiting potential clinical efficacy in treating LM from solid tumors including non-small cell lung cancer.

Background and purpose:Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases(LM)from solid tumors.A previous phase Ⅰ study demonstrated the safety and potential efficacy of intrathecal anti-programmed death receptor 1(anti-PD-1)for LM from melanoma.The synergistic efficacy of systemic chemotherapy combined with anti-PD-1 has been widely known.This study aimed to evaluate the safety and feasibility of intrathecal chemotherapy(pemetrexed)and anti-PD-1(toripalimab)for LM patients from solid tumors.Methods:The subjects were patients with LM from solid tumors who were treated at Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City.A 3+3 dose de-escalation strategy was implemented to determine the recommended dose with an initial dose of PD-1 inhibitor(toripalimab)40 mg and pemetrexed 15 mg.Pemetrexed was administered twice weekly for the initial 2 weeks of induction therapy,once weekly for the subsequent 4 weeks of consolidation therapy,and once monthly during maintenance therapy.PD-1 inhibitor was initiated at the 4th administration of pemetrexed,administered every 2 weeks for 6 weeks;subsequently,responders continued monthly maintenance therapy alongside pemetrexed.The primary objective was to assess safety based on adverse events and the recommended dose.All participants were observed to investigate the clinical response rate(CRR),disease control rate(DCR)and overall survival(OS).This study was approved by the ethics committee of Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City(ethics number:2024-KY-029-01).Results:Seven patients(male:3,female:4,median age:57 years)were enrolled between June and September 2024,including non-small cell lung cancer(6)and breast cancer(1).All patients presented with positive cerebrospinal fluid(CSF)cytology.Six patients presented LM-related neurological dysfunction.Five patients showed LM-related neuroimaging findings.Six patients completed the induction and consolidation therapy,and subsequently received maintenance therapy.One patient,due to bacterial meningitis,did not complete the final administration of toripalimab during consolidation therapy,and maintenance therapy was administered after infection control.Adverse events rate was 100%(7/7),including myelosuppression(100.00%,n=7),elevation of hepatic aminotransferases(42.86%,n=3),fatigue(28.57%,n=2)and hypothyroidism(14.29%,n=1).Three(42.86%)patients had grade 3 adverse events(myelosuppression).The immune-related adverse event(irAE)rate was 14.29%,manifested as hypothyroidism(Grade 2).No dose-limiting toxicity(DLT)was observed.Thus,no de-escalation was applied.The recommended dose was determined to be PD-1 inhibitor 40 mg in combination with pemetrexed 15 mg.Three patients showed improved neurological dysfunction,1 with CSF cytological response,and 2 with neuroimaging improvement.CRR was 57.14%(4/7)by response assessment in neuro-oncology(RANO)proposal criteria.DCR was 100%(7/7).Three patients exhibited abscopal effects with regression of brain metastasis lesions,primary lung lesion and mediastinal lymph nodes,respectively.As of April 10,2025,1 patient died.The median follow-up time was 7.7(5.9-9.3)months.The median OS was not reached with a 6-month OS rate of 85.71%.Conclusion:The combination therapy of intrathecal pemetrexed and a PD-1 inhibitor was well-tolerated and feasible,while also exhibiting potential clinical efficacy in treating LM from solid tumors including non-small cell lung cancer.

Due to genetic abnormalities,hypoxic injury or surgical trauma,some children with congenital heart disease have neurodevelopmental disorders,mainly manifested as generalized hypotonia and exercise developmental delay.Infants have strong neuroplasticity.Early exercise rehabilitation is helpful to improve their exercise function and neurodevelopment and promote their rehabilitation.This paper reviews the assessment,implementation methods and effect evaluation of early exercise rehabilitation in infants with congenital heart disease,and puts forward hindering factors and nursing countermeasures,in order to provide references for clinical nursing practice.

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Objective To systematically search,evaluate and summarize the best evidence for prevention and management of extravasation in peripheral intravenous infusion in NICU neonates,and provide a reference for clinical practice and standard formulation.Methods A comprehensive systematic search of websites and databases was conducted to explore literature on prevention and management of extravasation in NICU neonates,including clinical decisions,guidelines,expert consensuses,evidence summaries and systematic reviews.The search encompassed the entire period from database inception to July 2023.2 researchers independently evaluated the quality of the literature,extracted and integrated the evidence.Results The study included a total of 9 articles,comprising 1 clinical decision,3 guidelines,3 expert consensus documents,and 2 evidence summaries.Ultimately,25 pieces of evidence were synthesized,covering risk factors,catheter indwelling and maintenance,extravasation assessment and treatment,and team building,education and training.Conclusion The evidence provided practical and specific recommendations that can guide healthcare institutions in formulating strategies to prevent and treat extravasation during peripheral intravenous infusion in NICU neonates,while also offering evidence-based guidance for applying the evidence in clinical practice.