BACKGROUND:Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration,and ultrasound guidance can increase the precision of needle-knife release;however,the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified. OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. METHODS:Twenty-four New Zealand rabbits were randomized into control(n=6)and model(n=18)groups.A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine.After successful modeling,the model rabbits were subdivided into a control group,a model group,an ultrasonic needle-knife group,and a sham needle-knife group according to a random number table method,with six animals in each group.The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1,once every week,for a total of four times.The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group,but the ligamentum flavum was not released.At 30 days after the intervention,MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment.Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment.Immunohistochemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment.RT-PCR and western blot were used to detect the expression of integrin α5 and β1,p38,and nuclear factor κB in the L7/S1 segment. RESULTS AND CONCLUSION:MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color,and the gray value of the nucleus pulposus was significantly lower than that of the control group(P<0.01).The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group,and the gray value of the nucleus pulposus was higher than that of the model group(P<0.01).Results from hematoxylin-eosin staining showed that in the model group,the shape of the nucleus pulposus was irregular,the number of nucleus pulposus cells was reduced,the extracellular matrix was compressed,the fibrous ring was ruptured,the structure and boundary of the end plate were unclear,and the chondrocytes were arranged disorderly.Compared with the model group,the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus,an improvement in the rupture of the fibrous ring,and more regular arrangement of cartilage endplate cells.Results from immunohistochemical staining showed an increase in positive expression of type I collagen(P<0.01)and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group(P<0.01).RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group(P<0.01);the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group(P<0.01).To conclude,ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits,which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression.

Objective To explore the medication rules and mechanism of Xin'an physicians in the treatment of diabetes mellitus.Methods The prescriptions for the treatment of diabetes mellitus in Xin'an medical writings were collected.The core drug prescriptions were obtained by using IBM SPSS Modeler 18.0 for dispensing association rules as well as complex network analysis,and the cluster analysis of high-frequency traditional Chinese medicines was carried out by using IBM SPSS Statistics 25.0.The active ingredients and targets of the core drugs were extracted from the BATMAN-TCM database.The GeneCards database was used to search for diabetes gene targets,and after obtaining the intersecting targets,the STRING online platform was imported to construct the protein interactions network,and screened the core genes by using the Cytoscape 3.9.1 software,and imported into the DAVID database for GO function and KEGG pathway enrichment analysis.Results A total of 135 valid prescriptions were included,involving 184 flavors of traditional Chinese medicines,with cold and mild properties.Sweet,bitter and pungent flavors,and the main attributes of lung,spleen,kidney,stomach and heart meridians.The association rules mined 14 pairs of commonly used medicine pairs.Cluster analysis clustered the top 20 traditional Chinese medicines into five cluster groups.Complex network visualization analysis formed a core prescription consisting of honey-fried licorice root,ginseng,rhizoma anemarrhenae,ophiopogon japonicus,poria cocos.The core prescription drugs were screened for 164 effective active ingredients,1,498 action targets,1,995 diabetes gene targets,404 intersecting targets,10 core targets were extracted,and a total of 1,363 items covering BP were obtained from GO functional enrichment analysis,129 items involving CC,264 items containing MF,and 206 items of KEGG signaling pathway.Conclusion The prescriptions and medicines used by Xin'an doctors in the treatment of diabetes mellitus reflect the academic idea of"treating both the symptoms and the root cause"as well as the therapeutic thought of"using cold and warmth,supplementing with sweetness and warmth,opening up and lowering with bitterness,cultivating the earth and generating gold,and consolidating the root and cultivating the elements",which provide references for the treatment of diabetes mellitus in today's clinics.

Diabetes mellitus （DM） is a metabolic disease caused by absolute or relative insulin deficiency and reduced insulin sensitivity in peripheral cells， posing a serious threat to global health. Chronic complications arising in the later stages of DM can lead to the decline or even loss of function in multiple organs， including the eyes， heart， liver， kidneys， nerves， and feet， making them the primary cause of mortality in DM patients. Although modern medicine has made some progress in the treatment of these complications， challenges such as high costs and adverse drug reactions remain. Thus， identifying highly effective drugs with minimal adverse effects has become a top priority. Astragalus membranaceus is a shining gem in the treasure trove of Chinese medicine. Numerous studies have shown that its primary active component， astragaloside Ⅳ， possesses various biological activities， including anti-inflammatory， antioxidant， and antiviral effects， as well as benefits for cardiac and cerebral function， nerve conduction， and myocardial protection. Meanwhile， the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a crucial role in regulating oxidative stress， inflammatory responses， apoptosis， and autophagy. Extensive research has highlighted the significant role of this pathway in various DM complications， leading to widespread studies on its interaction with astragaloside Ⅳ. This review summarizes research findings on how astragaloside Ⅳ alleviates pancreatic cytotoxicity in DM patients by modulating the PI3K/Akt pathway. Additionally， it highlights its protective effects on basic cardiac function， inhibition of retinal cell damage， improvement of cerebral nerve dysfunction， reduction of chronic kidney and liver damage， and mitigation of neurovascular toxicity in the lower limbs. These insights provide a valuable reference for the clinical application of A. membranaceus and its active monomer， astragaloside Ⅳ， in the treatment of DM and its complications.

Objective:To analyze the predictive factors associated with late-onset sepsis(LOS) in very low birth weight infants,and to develop a risk prediction score scale applicable to these infants three days postnatal.This will provide valuable insights for early diagnosis and timely intervention.Methods:Very low birth weight infants admitted to the Children's Hospital of Fudan University from January 1,2022,to June 30,2024,were selected as research subjects.These infants were categorized into two groups:the LOS group and the non-LOS group,based on whether they developed LOS.LASSO regression analysis,alongside univariate and multivariate regression analyses,was employed to identify predictive factors for LOS in this population.A Logistic model was constructed using the optimal combination of predictive variables,and a risk assessment scale was subsequently developed.The prediction performance of the model was evaluated using the Hosmer-Lemeshow chi-square test and the receiver operating characteristic curve.Results:A total of 444 cases of very low birth weight infants were included,of which 185 had LOS and 259 did not.After screening the variables,seven independent factors were included into the model:birth weight,gestational age,tracheal intubation,abnormal skin color,abdominal distension,elevated C-reactive protein levels,and right hand perfusion index.A predictive scoring scale was developed based on the regression coefficients of each variable,with corresponding risk scores assigned as follows:1,4,3,2,1,1,and 2; a score of ≥3.5 indicated high-risk groups.The Hosmer-Lemeshow test results demonstrated that χ2 = 7.602( P = 0.473).The area under the receiver operating characteristic curve was 0.792 ( P<0.001),with a sensitivity of 73.5% and specificity of 71.0%. Conclusion:The risk score scale developed in this study exhibits significant predictive capability,providing valuable insights for clinical medical personnel to assess the risk of LOS in very low birth weight infants during the early postnatal period.

Objective To explore the medication rules and mechanism of Xin'an physicians in the treatment of diabetes mellitus.Methods The prescriptions for the treatment of diabetes mellitus in Xin'an medical writings were collected.The core drug prescriptions were obtained by using IBM SPSS Modeler 18.0 for dispensing association rules as well as complex network analysis,and the cluster analysis of high-frequency traditional Chinese medicines was carried out by using IBM SPSS Statistics 25.0.The active ingredients and targets of the core drugs were extracted from the BATMAN-TCM database.The GeneCards database was used to search for diabetes gene targets,and after obtaining the intersecting targets,the STRING online platform was imported to construct the protein interactions network,and screened the core genes by using the Cytoscape 3.9.1 software,and imported into the DAVID database for GO function and KEGG pathway enrichment analysis.Results A total of 135 valid prescriptions were included,involving 184 flavors of traditional Chinese medicines,with cold and mild properties.Sweet,bitter and pungent flavors,and the main attributes of lung,spleen,kidney,stomach and heart meridians.The association rules mined 14 pairs of commonly used medicine pairs.Cluster analysis clustered the top 20 traditional Chinese medicines into five cluster groups.Complex network visualization analysis formed a core prescription consisting of honey-fried licorice root,ginseng,rhizoma anemarrhenae,ophiopogon japonicus,poria cocos.The core prescription drugs were screened for 164 effective active ingredients,1,498 action targets,1,995 diabetes gene targets,404 intersecting targets,10 core targets were extracted,and a total of 1,363 items covering BP were obtained from GO functional enrichment analysis,129 items involving CC,264 items containing MF,and 206 items of KEGG signaling pathway.Conclusion The prescriptions and medicines used by Xin'an doctors in the treatment of diabetes mellitus reflect the academic idea of"treating both the symptoms and the root cause"as well as the therapeutic thought of"using cold and warmth,supplementing with sweetness and warmth,opening up and lowering with bitterness,cultivating the earth and generating gold,and consolidating the root and cultivating the elements",which provide references for the treatment of diabetes mellitus in today's clinics.

Objective:To analyze the predictive factors associated with late-onset sepsis(LOS) in very low birth weight infants,and to develop a risk prediction score scale applicable to these infants three days postnatal.This will provide valuable insights for early diagnosis and timely intervention.Methods:Very low birth weight infants admitted to the Children's Hospital of Fudan University from January 1,2022,to June 30,2024,were selected as research subjects.These infants were categorized into two groups:the LOS group and the non-LOS group,based on whether they developed LOS.LASSO regression analysis,alongside univariate and multivariate regression analyses,was employed to identify predictive factors for LOS in this population.A Logistic model was constructed using the optimal combination of predictive variables,and a risk assessment scale was subsequently developed.The prediction performance of the model was evaluated using the Hosmer-Lemeshow chi-square test and the receiver operating characteristic curve.Results:A total of 444 cases of very low birth weight infants were included,of which 185 had LOS and 259 did not.After screening the variables,seven independent factors were included into the model:birth weight,gestational age,tracheal intubation,abnormal skin color,abdominal distension,elevated C-reactive protein levels,and right hand perfusion index.A predictive scoring scale was developed based on the regression coefficients of each variable,with corresponding risk scores assigned as follows:1,4,3,2,1,1,and 2; a score of ≥3.5 indicated high-risk groups.The Hosmer-Lemeshow test results demonstrated that χ2 = 7.602( P = 0.473).The area under the receiver operating characteristic curve was 0.792 ( P<0.001),with a sensitivity of 73.5% and specificity of 71.0%. Conclusion:The risk score scale developed in this study exhibits significant predictive capability,providing valuable insights for clinical medical personnel to assess the risk of LOS in very low birth weight infants during the early postnatal period.

BACKGROUND:Mangiferin is a biphenylpyridone compound extracted from mango leaves,bark and roots.Previous studies have shown that mangiferin can exert anti-systemic inflammatory effects through the activation of transcription factors such as NF-κB and JAK/STAT. OBJECTIVE:To investigate the effects and mechanisms of mangiferin on proliferation,migration and inflammatory factor release of rheumatoid arthritis fibroblast-like synovial cells(RA-FLS). METHODS:RA-FLS were divided into blank group,R848(TLR7/8 agonists)stimulated group,mangiferin low-,medium-,high-dose groups(2,4 and 8 μg/mL)and positive control group(Cu-CPT8,TLR8 pathway inhibitor).The cytotoxic effect of different mass concentrations of mangiferin was detected using cell counting kit-8 method and the final cellular dosing mass concentration was screened.The proliferation ability of RA-FLS was detected by cell clone formation assay,the migration ability of RA-FLS was detected by scratch assay and Transwell migration assay,and the expression of interleukin 1β,interleukin 6 and tumor necrosis factor α mRNA in RA-FLS was detected by qRT-PCR. RESULTS AND CONCLUSION:Compared with the blank group,the viability of RA-FLS was inhibited after treatment with mangiferin at 2-10 μg/mL,but there was no significant difference among groups(P>0.05),indicating that the toxic effect on RA-FLS was minimal.Compared with the R848-stimulated group,mangiferin decreased the number of cell clones,the scratch healing rate and the number of migrating cells in all dosing groups(P<0.01);and the expression of interleukin 1β,interleukin 6 and tumor necrosis factor α mRNA was also reduced in the mangostin medium-and high-dose groups(P<0.01).Compared with the R848-stimulated group,the number of cell clones,the scratch healing rate and the number of migrating cells as well as the expression levels of interleukin 6 and tumor necrosis factor α mRNA were significantly reduced in the positive control group(P<0.05,P<0.01).But there was no significant difference in the expression level of interleukin 1β.To conclude,mangiferin may exert its anti-rheumatoid arthritis effects through the TLR7/8 signaling pathway by inhibiting RA-FLS proliferation,migration,and inflammatory factor release.

Objective To develop a comprehensive family integrated care program for very low birth weight in-fants and to investigate the initial application effect of the program.Methods The family integrated care program for very low birth weight infants was developed using semi-structured interviews,a comprehensive literature review,and an expert consensus.A non-synchronous controlled trial was subsequently carried out.Between January and May 2023,35 participants accompanied by their parents for a minimum of 6 hours daily over a span of at least 3 days,were consecutively selected as an intervention group.Between January and May 2022,35 participants in the control group were treated with routine closed neonatal intensive care unit model.The application effect of the pro-gram on the clinical outcomes of very low birth weight infants was assessed,such as weight gain rate during hospi-talization,breastfeeding days,incidence of late-onset sepsis,incidence of extrauterine growth restriction at discharge,TIMP level at corrected gestational age of 37 weeks and hospitalization days.Results The authority coefficient of the 8 invited experts specializing in neonatal nursing and nursing management was 0.925.A comprehensive pro-gram was developed,consisting of 2 stages—preparation and implementation,and addressing 7 key themes:staff team formation and training,environmental support,assessment,parental training,family-integrated care implementation,peer support,and comprehensive communication.No shedding cases occurred during the application of the program.The outcomes indicated that the intervention group experienced a higher rate of weight gain and more days of breast-feeding compared to the control group,and the incidence of extrauterine growth retardation upon discharge was also lower,with statistically significant differences(all P＜0.05).However,there were no significant differences in other clinical outcomes(all P＞0.05).Conclusion The family integrated care program for very low birth weight infants de-veloped in this study is scientifically grounded,comprehensive,and practical.The implementation of this program can promote the weight gain and breastfeeding among very low birth weight infants,reduce the occurrence of extrauter-ine growth restriction upon discharge,and does not increase the incidence of late-onset sepsis.

Objective To develop a comprehensive family integrated care program for very low birth weight in-fants and to investigate the initial application effect of the program.Methods The family integrated care program for very low birth weight infants was developed using semi-structured interviews,a comprehensive literature review,and an expert consensus.A non-synchronous controlled trial was subsequently carried out.Between January and May 2023,35 participants accompanied by their parents for a minimum of 6 hours daily over a span of at least 3 days,were consecutively selected as an intervention group.Between January and May 2022,35 participants in the control group were treated with routine closed neonatal intensive care unit model.The application effect of the pro-gram on the clinical outcomes of very low birth weight infants was assessed,such as weight gain rate during hospi-talization,breastfeeding days,incidence of late-onset sepsis,incidence of extrauterine growth restriction at discharge,TIMP level at corrected gestational age of 37 weeks and hospitalization days.Results The authority coefficient of the 8 invited experts specializing in neonatal nursing and nursing management was 0.925.A comprehensive pro-gram was developed,consisting of 2 stages—preparation and implementation,and addressing 7 key themes:staff team formation and training,environmental support,assessment,parental training,family-integrated care implementation,peer support,and comprehensive communication.No shedding cases occurred during the application of the program.The outcomes indicated that the intervention group experienced a higher rate of weight gain and more days of breast-feeding compared to the control group,and the incidence of extrauterine growth retardation upon discharge was also lower,with statistically significant differences(all P＜0.05).However,there were no significant differences in other clinical outcomes(all P＞0.05).Conclusion The family integrated care program for very low birth weight infants de-veloped in this study is scientifically grounded,comprehensive,and practical.The implementation of this program can promote the weight gain and breastfeeding among very low birth weight infants,reduce the occurrence of extrauter-ine growth restriction upon discharge,and does not increase the incidence of late-onset sepsis.

Objective:To analyze the changes of peripheral perfusion index (PPI) with late-onset sepsis (LOS) in very low birth weight infants during hospitalization.Methods:Very low birth weight infants admitted to the neonatal intensive care unit of Children′s Hospital of Fudan University from August 1, 2021 to August 31, 2022 were consecutively included.Infants with admission age ≥three days and unstable circulation, or positive blood culture within three days after birth were excluded.From the day of admission, the PPI values of the right hand and either foot of the infants were measured with Masimo SET Radical-7 everyday while whether LOS occurred during hospitalization was observed.The mean PPI curve of very and extremely low birth weight infants without LOS was plotted.For those with LOS confirmed by blood culture, the PPI change trajectory three days before and after the occurrence of LOS was drawn, and the change trend of PPI before the occurrence of LOS was analyzed by trend chi-square test.Non-parametric test was used to analyze the effect of LOS on pre- and post-ductal PPI values.Results:A total of 107 very low birth weight infants were included in the final analysis.Among them, there were 11 infants confirmed as LOS by blood culture, 37 infants diagnosed as clinical LOS, and 59 infants without LOS.Pre-and post-ductal PPI values of very low birth weight infants without LOS were 2.06±1.30 and 1.72±0.92, respectively; those with clinical LOS were 1.90±0.94 and 1.58±0.83, respectively; those with LOS confirmed by blood culture were 1.92±1.11 and 1.62±0.82, respectively.For infants with LOS confirmed by blood culture, the pre-and post-ductal PPI values showed a continuous downward trend during three days before the onset of disease, with the lowest PPI values on the first day before the diagnosis of blood culture.The downtrend of pre-ductal PPI was statistically significant ( χtrend2=5.57, P<0.05). Conclusion:The PPI value of very low birth weight infants show a downward trend when LOS occurs.It should be observed dynamically in clinical practice, which is helpful to suspect or identify LOS as early as possible.