AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

Objective To explore the targeted regulatory relationship of miR-330-5p on OY-TES-1 in glioblastoma and the effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma.Methods Bioinformatics analysis was performed to analyze the expression level of miR-330-5p in patients with glioblastoma and its influence on prognosis and survival of patients.The glioblastoma cells U251 were divided into miR-330-5p minics group,minics-NC group,and miR-330-5p+OY-TES-1 overexpression group(miR-330-5p minics+pcDNA3.1-OY-TES-1).The effect of miR-330-5p on the activity of OY-TES-1 3'UTR region was detected by double luciferase reporter gene experiment.The expression of OY-TES-1 mRNA was detected by qRT-PCR.The effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma cells was detected by Transwell migration assay.Results The expression of miR-330-5p in glioblastoma tissue was significantly lower than those in non-tumor brain tissue and low-grade glioma tissue(P<0.05).The survival time of glioblastoma patients with high expression of miR-330-5p was significantly longer than that of patients with low expression of miR-330-5p(P<0.05).After overexpression of miR-330-5p,the activity of OY-TES-1 3'UTR region was decreased(P<0.05).Compared with minics-NC group,the expression levels of OY-TES-1 mRNA of U251 and U87MG cells in miR-330-5p minics group were significantly decreased(P<0.01).Compared with minics-NC group,the numbers of migrating cells in miR-330-5p minics group and miR-330-5p+OY-TES-1 overexpression group were significantly decreased(P<0.05).Compared with miR-330-5p minics group,the number of migrating cells in miR-330-5p+OY-TES-1 overexpression group was significantly increased(P<0.01).Conclusion MiR-330-5p targets OY-TES-1 to inhibit the migration of glioblastoma.

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

Objective To explore the targeted regulatory relationship of miR-330-5p on OY-TES-1 in glioblastoma and the effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma.Methods Bioinformatics analysis was performed to analyze the expression level of miR-330-5p in patients with glioblastoma and its influence on prognosis and survival of patients.The glioblastoma cells U251 were divided into miR-330-5p minics group,minics-NC group,and miR-330-5p+OY-TES-1 overexpression group(miR-330-5p minics+pcDNA3.1-OY-TES-1).The effect of miR-330-5p on the activity of OY-TES-1 3'UTR region was detected by double luciferase reporter gene experiment.The expression of OY-TES-1 mRNA was detected by qRT-PCR.The effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma cells was detected by Transwell migration assay.Results The expression of miR-330-5p in glioblastoma tissue was significantly lower than those in non-tumor brain tissue and low-grade glioma tissue(P<0.05).The survival time of glioblastoma patients with high expression of miR-330-5p was significantly longer than that of patients with low expression of miR-330-5p(P<0.05).After overexpression of miR-330-5p,the activity of OY-TES-1 3'UTR region was decreased(P<0.05).Compared with minics-NC group,the expression levels of OY-TES-1 mRNA of U251 and U87MG cells in miR-330-5p minics group were significantly decreased(P<0.01).Compared with minics-NC group,the numbers of migrating cells in miR-330-5p minics group and miR-330-5p+OY-TES-1 overexpression group were significantly decreased(P<0.05).Compared with miR-330-5p minics group,the number of migrating cells in miR-330-5p+OY-TES-1 overexpression group was significantly increased(P<0.01).Conclusion MiR-330-5p targets OY-TES-1 to inhibit the migration of glioblastoma.

This study aimed to investigate the potential mechanism and the compatibility significance of Tanyu Tongzhi Formula in treating atherosclerosis(AS) in mice based on the transforming growth factor-β(TGF-β)/Smad2/3 signaling pathway. Eight C57BL/6J mice were as assigned to a normal control group and fed a regular diet, while 35 ApoE~(-/-) mice of the same strain were fed a high-fat diet for 8 weeks to establish an AS model. The model mice were randomly divided into a model group, a Tanyu Tongzhi group(18.2 mg·kg~(-1)), a Huatan(phlegm-resolving) group(10.4 mg·kg~(-1)), and a Quyu(blood stasis-resolving) group(7.8 mg·kg~(-1)), with 8 mice in each group. Except for the normal group, all other groups continued to be fed a high-fat diet for 8 weeks to maintain the AS model, and then the mice were treated by gavage for 8 weeks. Plasma levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), interleukin-1β(IL-1β), and interleukin-18(IL-18) were measured using enzyme-linked immunosorbent assay(ELISA). Hematoxylin and eosin(HE) staining, oil red O staining, and Russell-Movat pentachrome staining were performed to observe the pathological changes in the aortic tissue. The proportions of aortic plaque area, lipid-stained area, collagen fibers, and elastic fibers were calculated. Immunofluorescence was used to detect the protein expression levels of matrix metalloproteinase 2(MMP2) and tissue inhibitor of metalloproteinases 2(TIMP2). Western blot was used to detect the protein expression levels of TGF-β1, TGF-β2, Smad2/3, and Smad7 in aortic tissue. Real-time fluorescence quantitative PCR(RT-qPCR) was used to measure the mRNA expression levels of TGF-β receptor(TGF-βR), TGF-β1, Smad2/3, Smad7, intercellular adhesion molecule-1(ICAM-1), and vascular cell adhesion molecule-1(VCAM-1) in aortic tissue. The results showed that compared with the normal control group, the model group had increased plasma TC and LDL-C, significantly decreased HDL-C, and significantly elevated plasma IL-1β and IL-18 levels. The model group also exhibited an increased proportion of aortic plaque area, lipid-stained area, and collagen fiber area, along with significantly upregulated MMP2 and downregulated TIMP2 expression in the aortic arch. Additionally, the expression levels of TGF-βR, TGF-β1, and p-Smad2/3 proteins and mRNA in the aortic tissue were significantly elevated, while Smad7 expression was decreased. Compared with the model group, the Tanyu Tongzhi group showed significantly reduced plasma TC and LDL-C levels, significantly increased HDL-C levels, and significantly decreased plasma IL-1β and IL-18 levels. The Tanyu Tongzhi group also exhibited a significant reduction in aortic plaque size and severity, a significant downregulation of MMP2 expression in the aortic arch, and significantly decreased ICAM-1 and VCAM-1 mRNA expression levels. Moreover, the Tanyu Tongzhi group demonstrated significantly reduced expression levels of TGF-β1 and p-Smad2/3 proteins and mRNA in the aortic tissue, and an increased expression level of Smad7 protein to varying degrees. Compared with the Tanyu Tongzhi group, the Quyu group had significantly higher LDL-C levels and elevated plasma IL-1β and IL-18 levels. The Huatan group showed upregulated MMP2 expression and downregulated TIMP2 expression in the aortic arch. In conclusion, Tanyu Tongzhi Formula, which is composed based on the pathogenesis of phlegm and blood stasis, maintains vascular homeostasis by primarily regulating lipid metabolism and controlling inflammatory factors through the Huatan group, and maintaining vascular wall permeability, inhibiting plaque development, and stabilizing plaques through the Quyu group. The mechanism of action may involve inhibiting TGF-β1 expression in the aorta, reducing Smad2/3 phosphorylation, and simultaneously increasing Smad7 expression.
Animals ; Atherosclerosis/metabolism* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Male ; Transforming Growth Factor beta/genetics* ; Humans ; Homeostasis/drug effects* ; Aorta/metabolism* ; Smad2 Protein/genetics* ; Smad3 Protein/genetics*

Objective:To analyze the blood flow parameters of the cavernous arteries of ED patients after injection of vasoac-tive drugs,and to explore the differences in blood flow of the cavernous arteries in different erectile states.Methods:Retrospectively analyzed the penile cavernous arterial blood flow parameters of 2568 adult male ED patients after injection of the vasoactive drug(al-prostadil).The patients were divided into three groups:maintaining erection group with EHS(erection hardness score)≥3 and sus-tained erection time≥20 minutes(967 cases),nonpersistent erection group with EHS ≥3 and sustained erection time＜5 minutes(788 cases),and incomplete erection group with EHS＜3(813 cases).Compared the parameters of age,EHS,duration of erection,cavernous artery peak systolic velocity(PSV),end diastolic velocity(EDV)and resistance index(RI)among the three groups re-spectively.The maintaining erection group was divided into the youth group(757 cases)which aged less than 40 years old and the middle-aged and elderly group(210 cases)with 40 years old or over.The parameters of PSV,EDV and RI between the two groups were compared.The incomplete erection group were divided into the good blood supply group(407 cases)with the bilateral PSV 35cm/s and the insufficient blood supply group(252 cases)with the bilateral PSV＜35cm/s.The parameters of age,EHS,EDV and RI between the two groups were compared.Results:The age,PSV,EDV and RI of the three groups were significantly different(P＜0.01).In the maintaining erection group,the PSV of the young group was significantly higher than that of the middle-aged and eld-erly group(P＜0.05),but there was no statistically significant difference in EDV and RI(P＞0.05).In the incomplete erection group,the EHS,PSV,EDV,and RI of the good blood supply group were significantly higher than those of the insufficient blood supply group(P＜0.05),while the age was significantly lower than that of the latter(P＜0.01).Conclusion:The injection of vasoactive drugs combined with color Doppler ultrasound can directly reflect the blood supply of the cavernous arteries of the penis.The better the erection state,the better the blood supply of cavernous arteries.The middle-aged and elderly people are more likely to have cavernous arteries problem of insufficient blood supply than the young people.

Objective:To evaluate and compare the foveal microvascular morphology and central foveal thickness (CFT) after laser retinal photocoagulation and intravitreal injection of anti-vascular endothelial growth factor (VEGF) in patients with retinopathy of prematurity (ROP), and to explore the factors affecting the prognosis of vision.Methods:A cohort study was conducted.Forty children (40 eyes) aged 4-6 years, who had been treated in Peking University People's Hospital for type 1 ROP from January 2019 to December 2020, were enrolled.Optical coherence tomography angiography (OCTA), best corrected visual acuity (BCVA) and refractive status of the patients were examined.The patients were divided into laser retinal photocoagulation group and anti-VEGF group according to they received a single laser retinal photocoagulation therapy or a single intravitreal injection of anti-VEGF drugs (conbercept or ranibizumab 0.25 mg/0.025 mL) after birth.Twenty age-matched full-term healthy children (20 eyes) were enrolled as the normal control group.The FAZ area, superficial and deep foveal vessel density (VD) and CFT of the affected eyes were measured by OCTA at 4-6 years after treatment to investigate the influence of gestational age, birth weight, morphological characteristics of foveal microvessels and CFT on the prognosis of BCVA.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Peking University People's Hospital (No.2017PHB179-01). Written informed consent was obtained from the guardians prior to any medical examination.Results:There were statistically significant differences in FAZ area, superficial foveal VD and deep foveal VD among the three groups ( F=12.321, 8.436, 5.497; all at P<0.05). The FAZ area was smaller, and the superficial and deep foveal VD of the laser photocoagulation group and the anti-VEGF group were greater than those in the normal control group, and the difference was statistically significant (all at P<0.05). The CFT of the laser photocoagulation group was (267.6±11.8)μm, greater than (259.5±12.9)μm of the anti-VEGF group and (242.4±12.3)μm of normal control group, and the CFT value of the anti-VEGF group was greater than that of the normal control group, and the differences were statistically significant (all at P<0.05). There was a strong negative correlation between the superficial foveal VD and FAZ area ( r=-0.713, P<0.05), a moderate negative correlation between the deep foveal VD and FAZ area ( r=-0.565, P<0.05), and a moderate positive correlation between gestational age and FAZ area ( r=0.485, P<0.05). Pearson correlation analysis results showed that gestational age, FAZ, superficial foveal VD, deep foveal VD, CFT were all correlated with BCVA (all at P<0.05). The effects of gestational age and FAZ on BCVA were both statistically significant ( R2=0.615, both at P<0.05). Conclusions:The morphology of microvessels in macular fovea and the prognosis of BCVA in the affected eye is similar at 4-6 years after laser retinal photocoagulation and intravitreal injection of anti-VEGF drugs for type 1 ROP.The CFT of the affected eye after anti-VEGF drug therapy is better than those after laser retinal photocoagulation.Gestational age and FAZ are the influencing factors of visual acuity after treatment in children with type 1 ROP.

Objective:To evaluate the long-term outcomes of posterior release, reduction, fixation, and fusion for irreducible atlantoaxial dislocation (AAD).Methods:Between January 2005 and June 2016, a total of 31 patients with irreducible AAD who had received posterior approach surgery were included. Among them, there were 13 males and 18 females, the average age was 39.1±13.5 years (range 9-72 years). The clinical data of the eligible individuals were collected and analyzed. Neck disability index (NDI) and Japanese Orthopaedic Association (JOA) scores were recorded to evaluate the recovery of neck and neurological functions. The atlantodental interval (ADI), clivus-canal angle (CCA), and cervico-medullary angle (CMA) were measured to evaluate the reduction of AAD. C 0-C 2 angle and C 2-C 7 angle were measured to evaluate the recovery of cervical alignment. For individuals with basilar invagination, the distances from the tip of odontoid process to Chamberlain line and Wackenheim line were measured to assess the reduction in the vertical direction. The duration of bony fusion and complications were also analyzed. Results:The mean follow-up period was 82.7±26.4 months (range 61-170 months). In terms of functional scores, the NDI dropped from 43.41%±11.60% before surgery to 12.19%±6.97% at the six months follow-up, and 9.45%±7.51% at the last follow-up ( F=89.56, P<0.001). The JOA increased from 9.48±2.41 points before surgery to 14.71±1.42 points at the six months follow-up, and 14.97±1.47 points at the last follow-up ( F=52.89, P<0.001). Regarding the horizontal and vertical dislocations, the ADI decreased from 9.16±2.32 mm before surgery to 1.39±1.04 mm at the six months follow-up, and 1.29±1.08 mm at the last follow-up ( F=189.61, P<0.001). The distance from the tip of odontoid process to Chamberlain line decreased from 11.15±4.35 mm before surgery to 2.03±2.83 mm at the six months follow-up, and 2.15±3.02 mm at the last follow-up ( F=37.58, P<0.001). The distance from the tip of odontoid process to Wackenheim line reduced from 6.81±2.57 mm before surgery to -2.23±1.58 mm at the six months follow-up, and -2.27±1.58 mm at the last follow-up ( F=122.16, P<0.001). For the amelioration of the compression on medulla and spinal cord, the CCA increased from 113.68°±12.67° before surgery to 143.39°±7.38° at the six months follow-up, and 142.39°±7.13° at the last follow-up ( F=67.13, P<0.001). The CMA increased from 115.71°±13.69° before operation to 145.58°±10.78° at the last follow-up ( F=41.44, P<0.001). Regarding the curvature of the cervical spine, the C 0-C 2 angle recovered from 1.94°±15.82° before surgery to 14.84°±6.45° at the last follow-up ( F=11.97, P<0.001), and the C 2-C 7 angle ameliorated from 27.26°±8.49° before operation to 19.26°±5.44° at the last follow-up ( F=11.13, P<0.001). Bony fusion was achieved in all cases, the fusion time was 9.71±2.55 months (range 5-15 months). A total of five complications occurred in the cases (two cerebrospinal fluid leakages, one deep infection, one transient neurologic deficit, and one dysphagia). They were all cured with corresponding treatments. In the last follow-up, none of the cases developed failure of internal fixation or re-dislocation. Conclusion:Posterior approach release, reduction, fixation and fusion technique is a safe and efficient surgical strategy with favorable long-term follow-up outcomes for irreducible AAD.

Objective:To explore the current situation of the demand for home care services for the elderly in communities in Jiangsu Province, and to analyze its influencing factors.Methods:From May to August 2020, convenience sampling was used to select 592 community elderly people in Jiangsu Province for a survey. The survey tools included the General Information Questionnaire and Home Care Service Demands Questionnaire.Results:A total of 588 valid questionnaires were recovered, with a valid recovery rate of 99.32%. The demands of the elderly in the community for home care services from high to low were medical care needs (87.07%) , life care needs (68.37%) , spiritual comfort needs (58.16%) , cultural and leisure needs (34.18%) , policy and regulation needs (31.63%) . Logistic regression analysis showed that age, gender, region, type of chronic disease, monthly income and payment method of medical expenses were the main influencing factors of the demand for home care services ( P<0.05) . Conclusions:The elderly in the community have real needs for home care services. It is recommended to establish a diversified, multi-path and layered service system for the needs of the elderly, and strive to improve the effectiveness and efficiency of home elderly care services.

Ambystoma mexicanum/immunology* ; Amputation ; Animals ; Biomarkers/metabolism* ; Blastomeres/immunology* ; Cell Lineage/immunology* ; Connective Tissue Cells/immunology* ; Epithelial Cells/immunology* ; Forelimb ; Gene Expression ; High-Throughput Nucleotide Sequencing ; Humans ; Immunity ; Peroxiredoxins/immunology* ; Regeneration/immunology* ; Regenerative Medicine/methods* ; Single-Cell Analysis/methods*