Objective To explore the effect of LIMK1 on the progression of cervical cancer(CC).Methods HeLa and C-33A human cervical cancer cells overexpressing LIMK1 were established and injected subcutaneously into nude mice.The tumor volume was measured and expression of NOX2,NOX4,p-Src,p-RUNX3,RUNX3,and MMP-9 proteins in tumor cells was detected by Western blot assays.LIMK1-overexpressing HeLa and C-33A cells were cultured in 5％O2 with antioxidants.The protein expression of LIMK1,NOX4,p-Src,p-RUNX3,RUNX3 and MMP-9 in the cells was detected by Western blot assays.Cell migration was assessed by a scratch assay.Transwell assays were used to assess cell migration and invasion.A monoclonal proliferation assay was used to assess cell proliferation.Results The tumor volume in nude mice injected with LIMK1-overexpressing HeLa cells was increased significantly,and NOX2,NOX4,p-Src,p-RUNX3 and MMP-9 protein levels were increased,while RUNX3 protein expression was decreased.In LIMK1-overexpressing HeLa and C-33A cells,the protein expression of LIMK1,NOX4,p-Src,p-RUNX3,and MMP-9 was increased,RUNX3 protein expression was decreased,and cell migration,invasion,and proliferation were increased.However,after adding antioxidants,the expression levels of NOX4,p-Src,p-RUNX3,RUNX3 and MMP-9 proteins,and cell migration,invasion,and proliferation were not different from those of control cells.Conclusions LIMK1 promotes the progression of cervical cancer by enhancing the ROS/Src pathway,thereby promoting the migration,invasion,and proliferation of cervical cancer cells.

Objective:To explore the clinical effectiveness of functional magnetic stimulation (FMS) of the sacral nerve root in the treatment of diabetic neurogenic bladder (DNB).Methods:A total of 134 DNB patients were divided into an observation group and a control group, each of 67. Both groups were given conventional drug therapy and bladder function training, while the observation group was additionally provided with sacral nerve root FMS for 4 weeks. The urine and urine flow dynamics of both groups were tested before and after the experiment.Results:After treatment the average daily volume of single urination had increased significantly in both groups and the average daily urinations and incidence of incontinence had decreased significantly. The observation group′s average single urination volume was then significantly greater than that of the control group. The observation group′s average daily urinations (8.87±1.42) and incontinence incidents (3.04±1.93) were then significantly fewer than the control group′s. After the treatment the detrusor pressure at maximum flow, bladder sense initial volition and residual urine volume of both groups had decreased significantly compared with before the treatment, while their average maximum flow rates had increased significantly. But the observation group′s averages were in all cases significantly better than those of the control group. The treatment′s total effectiveness rate among the observation group (88%) was significantly better than among the control group (72%).Conclusions:Supplementing routine bladder function training with FMS applied to the root of the sacral nerve can further promote the regaining of bladder function among DNB patients, improve their urinary flow dynamics and improve their quality of life. Such combination therapy is worthy of clinical promotion and application.

Objective To investigate the clinical significance and serum changes of asprosin(ASP)levels in patients with essential hypertension and early renal damage.Methods According to urinary albumin/creatinine ratio(UACR),160 patients with essential hypertension were divided into the simple hypertension group(78 cases)and the early renal damage group(82 cases).Another 60 healthy subjects were selected as the control group.The differences of serum ASP,interleukin-6(IL-6)and UACR levels were compared between groups.The correlation between ASP and blood pressure,IL-6 and UACR was analyzed.Logistic regression analysis was used to analyze the factors influencing early renal damage in essential hypertension.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of each index for early renal injury.Results The serum levels of ASP,IL-6 and UACR were higher in the early renal damage group than those in the control group and the simple hypertension group(all P＜0.05).The serum levels of ASP and IL-6 showed an increasing trend with the increase of blood pressure.ASP was positively correlated with systolic blood pressure(SBP),diastolic blood pressure(DBP)and IL-6 levels in patients with essential hypertension(all P＜0.05).Serum ASP was positively correlated with SBP,UACR and IL-6 levels in essential hypertension patients(P＜0.05),and serum ASP was positively correlated with UACR and IL-6 levels in the early renal damage group(P＜0.05).Logistic regression analysis showed that higher levels of SBP,ASP and IL-6 were independent risk factors for early renal damage.ROC curve showed that ASP had the largest area under the curve(AUC)of 0.972(95%CI:0.950-0.993).The AUC of combined detection of ASP+IL-6+SBP was 0.986(95%CI:0.972-0.999).Conclusion The increased serum ASP level in patients with early renal damage in essential hypertension is a good predictor of early renal damage.The combined detection of ASP+IL-6+SBP is better than single detection.

OBJECTIVE To investigate the effect and mechanism of Panax notoginseng saponins （PNS） on wound healing after anal fistula surgery in rats by regulating the hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF）/ vascular endothelial growth factor receptor-2 （VEGFR2） signaling pathway. METHODS SD rats were selected to establish a postoperative rat model of anal fistula by infecting wound with Escherichia coli. The model rats were randomly grouped into model group， PNS low-dose and high-dose groups （15， 30 mg/cm2）， high-dose of PNS+2-methoxyestradiol （2ME2） group （PNS 30 mg/cm2+HIF-1α inhibitor 2ME2 4 mg/kg）， with 10 rats in each group. Another 10 normal rats were selected for back hair removal treatment as the control group. Each drug group was injected with the corresponding drug solution intramuscularly or （and） intraperitoneally， once a day， for 3 weeks. After the last administration， the wound healing rate （excluding the control group）， microvascular density （MVD）， the expression of collagen Ⅰ and fibronectin （FN） in the wound tissue were detected in each group； the levels of angiogenic factors [VEGF， E-mail：842710813@qq.com angiopoietin-Ⅰ （Ang-Ⅰ）， Ang-Ⅱ] in serum， the levels of inflammatory factors [interleukin-6 （IL-6） and IL-2] in serum binggui7183@163.com and wound tissue as well as the expressions of the related proteins of HIF-1α/VEGF/VEGFR2 signaling pathway in the wound tissue of rats were also detected in each group. RESULTS The MVD， the expression of collagen Ⅰ and FN in the wound tissue， and the levels of IL-6 and IL-2 in serum and wound tissue of rats increased significantly in the model group， compared to the control group （P＜0.05）， while the serum levels of VEGF， Ang- Ⅰ and Ang-Ⅱ decreased significantly （P＜0.05）. The wound healing rate， the MVD in wound tissue， the serum levels of VEGF， Ang-Ⅰ and Ang-Ⅱ， the expressions of collagen Ⅰ and FN in the wound tissue， and protein expressions of HIF-1α， VEGF and VEGFR2 in the PNS low-dose and high-dose groups increased significantly， compared to the model group （P＜0.05）， while the levels of IL-6 and IL-2 in serum and wound tissue decreased significantly （P＜0.05）； the high-dose PNS had a stronger effect （P＜ 0.05）. 2ME2 could weaken the effect of PNS on above indicators of rats after anal fistula surgery （P＜0.05）. CONCLUSIONS PNS can promote the production of angiogenic factors and inhibit the production of pro-inflammatory factors， thereby promoting wound healing in rats after anal fistula surgery. The above effects are related to the activation of HIF-1α/VEGF/VEGFR2 signaling pathway.

More than 300 million people worldwide suffer from asthma, and the incidence is increasing year by year. As one of the most common chronic diseases, asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity. With the in-depth study of physiological and pathological mechanisms, therapeutic small molecule and hormone drugs have been introduced to control and treat most patients, but about 5% - 10% of patients still suffer from various subtypes of difficult to control and treat asthma, that is, severe asthma. In the past decade, with the rapid development of bio-pharmaceutical research, protein and antibody have become the key drugs for the treatment of severe asthma with high efficacy, high specificity and high safety. However, biological drugs are usually administered by injection, they cannot be noninvasive and directly delivered into the lung to quickly absorb and take effect. Therefore, there is an urgent need for the introduction of inhaled biologics with quick effectiveness, convenience, economy and safety in clinical. The review summarizes the existing small molecule, hormone and biological therapy drugs, and summarizes the development of inhalable biological agents of asthma, and analyzes the future prospects of the inhalable biological drugs, which is designed to deepen the perception of the direction of the inhalable biological drugs research, and update the information of the field, in order to provide reference for the development of more inhalable biologics.

Objective:To analyze the level of interleukin-36(IL-36) family cytokines in peripheral blood, and explore the regulatory role of recombinant human IL-36α in monocyte function in patients with diabetic kidney disease(DKD).Methods:A total of 41 type 2 diabetes mellitus(T2DM) patients, 36 DKD patients, and 20 controls were consecutively enrolled. Plasma and peripheral blood mononuclear cells(PBMCs) were isolated. Enzyme-linked immunosorbent assay(ELISA) was used to measure plasma levels of IL-36α, IL-36β, IL-36γ, and IL-36 receptor antagonist(IL-36Ra). PBMCs were sorted, and real-time quantitative PCR was performed to detect the mRNA expression of IL-36 receptor subunits in monocytes. Monocytes were stimulated with recombinant IL-36α, and levels of cytotoxic molecules and cytokines in the culture supernatant were measured. Flow cytometry was used to assess the expressions of programmed death receptor-1(PD-1) and cytotoxic T-lymphocyte-associated protein 4(CTLA-4). Co-culture of monocytes with Vero cells was performed to evaluate monocyte cytotoxicity.Results:Plasma levels of IL-36α and IL-36β in the T2DM and DKD groups were significantly higher than those in the control group. The DKD group also showed higher plasma levels of IL-36α compared to the T2DM group( P<0.05). There were no significant differences in IL-36γ and IL-36Ra levels among the three groups( P>0.05). The mRNA expression of IL-36 receptor subunits in monocytes was comparable among the three groups( P>0.05). The DKD group had higher level of tumor necrosis factor-alpha(TNF-α) compared to the control and T2DM groups( P<0.05). The levels of PD-1 and CTLA-4 were lower in the DKD group than those in the control and T2DM groups( P<0.05). The proportion of monocyte-induced Vero cell death was significantly higher in the DKD group compared to the control and T2DM groups( P<0.05). After stimulation with recombinant human IL-36α, monocytes from DKD patients showed a significant increase in the secretion of granzyme B and TNF-α( P<0.05), as well as an increased proportion of monocyte-induced Vero cell death( P=0.024). Conclusion:In DKD patients, elevated IL-36α and granzyme B levels in monocytes enhance monocyte function.

Objective : To study the effect and mechanism of action of Silibinin on the differentiation of 3T3-F442A preadipocytes in murine． Methods : The effects of 0－400 μmol / L Silibinin on the proliferation of 3T3-F442A adi- pocytes at 24，48 and 72 h were detected by 3-(4，5-dimethylthiazol-2) -2，5-diphenyltetrazolium bromide ( MTT) assay，and the effects of Silibinin on the adipogenesis of 3T3-F442A adipocytes were visualized by Oil Red O stai- ning ; RT-qPCR , Western blot and ELISA assays were used to detect the effects of Silibinin on 3T3-F442A adipo- cyte differentiation-associated transcription factor CCAAT / enhancer binding protein ( C / EBP) α , C / EBP β , per- oxisome proliferator-activated receptor γ cular endothelial growth factor (VEGF) -α and VEGF receptor 2 (VEGFR-2) ，matrix metalloproteinase (MMP) -2 and MMP-9，mitogen-activated protein kinase (MEK) and phosphorylated MEK (p-MEK) ，and extracellular regu- lated protein kinase (ERK) and phosphorylated ERK (p-ERK) expression. (PPARγ) ，adipocyte protein 2 (aP2) ，adipose generation-associated vas Results : MTT assay showed that the cell proliferation rate of 3T3-F442A preadipocytes decreased after 100，200，and 400 μmol /L Silibinin treatment compared with the control group (P＜0. 001) ; Oil Red O staining assay showed that the accumulation of red lipid droplets of the cells in the 160 μmol /L Silibinin assay group significantly decreased ; RT-qPCR assay showed that mRNA expression of C/EBPα , C/EBPβ , PPARγ , aP2，VEGF-α , VEGFR-2，MMP-2，and MMP-9 was down-reg- ulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin compared with the control group (P＜0. 001) ; Western blot assay showed that protein expression of C /EBPα , C /EBPβ , PPARγ and aP2 was down-regulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin (P＜0. 001) ，and the phosphorylation level of p-MEK/ MEK and p-ERK/ ERK proteins was down-regulated compared with the control group (P ＜0. 001) ; ELISA assay showed that the protein concentrations of MMP-2 and MMP-9 in the cell supernatant were down-regulated (P < 0. 001) in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin． Conclusion Silibinin inhibited 3T3-F442A adipocyte differentiation and adipogenesis through inhibition of the MEK/ ERK pathway and matrix metalloproteinase activity.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.