Objective To compare the mid- and long-term clinical results of mitral valve plasty (MVP) and mitral valve replacement (MVR) in the treatment of functional mitral regurgitation (FMR). Methods Patients with FMR who underwent surgical treatment in the Department of Cardiovascular Surgery of the General Hospital of Northern Theater Command from 2012 to 2021 were collected. The patients who underwent MVP were divided into a MVP group, and those who underwent MVR into a MVR group. The clinical data and mid-term follow-up efficacy of two groups were compared. Results Finally 236 patients were included. There were 100 patients in the MVP group, including 53 males and 47 females, with an average age of (61.80±8.03) years. There were 136 patients in the MVR group, including 72 males and 64 females, with an average age of (61.29±8.97) years. There was no statistical difference in baseline data between the two groups (P＞0.05). There was no statistical difference between the two groups in the extracorporeal circulation time, aortic occlusion time, postoperative hospital and ICU stay, intraoperative blood loss, or hospitalization death (P＞0.05), but the time of mechanical ventilation in the MVP group was significantly shorter than that in the MVR group (P=0.022). The total follow-up rate was 100.0%, the longest follow-up was 10 years, and the average follow-up time was (3.60±2.55) years. There were statistical differences in the left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac function between the two groups compared with those before surgery (P<0.05). The postoperative left ventricular ejection fraction in the MVP group was statistically higher than that before surgery (P=0.002), but there was no statistical difference in the MVR group before and after surgery (P=0.658). The left atrial diameter in the MVP group was reduced compared with the MVR group (P=0.026). The recurrence rate of mitral regurgitation in the MVP group was higher than that in the MVR group, and the difference was statistically significant (10.0% vs. 1.5%, P=0.003). There were 14 deaths in the MVP group and 19 in the MVR group. The cumulative survival rate (P=0.605) and cardiovascular events-free survival rate (P=0.875) were not statistically significant between the two groups by Kaplan-Meier survival analysis. Conclusion The safety, and mid- and long-term clinical efficacy of MVP in the treatment of FMR patients are better than MVR, and the left atrial and left ventricular diameters are statistically reduced, and cardiac function is statistically improved. However, the surgeon needs to be well aware of the indications for the MVP procedure to reduce the rate of mitral regurgitation recurrence.

To investigate the effect of Ginkgo biloba extract (GBE) on lipids accumulation and the progression of atherosclerosis(AS), ApoE-/- mice fed with HFD were injected i.g. with two different doses of GBE (GBE-L 50 mg/(kg·d) or GBE-H 150 mg/(kg·d)) for 9 weeks. The core targets and potential mechanisms of GBE therapy for AS were investigated using network pharmacological target prediction. Subsequently, oxidized low-density lipoprotein (ox-LDL)-induced THP-1 was used to investigate the effect of GBE on foam cell formation through oil red staining and Dil-oxLDL fluorescent staining. The mRNA alterations in cholesterol uptake and efflux receptors were detected by real-time quantitative PCR. Finally, the impact of GBE on the expression of PPARγ as the core target was assessed through Western blot and immunofluorescence. It was found that GBE improved serum lipid profile, reduced necrotic cores and lipid deposition in aortic root plaques, and decreased the level of inflammatory factors in serum of ApoE-/- mice. Moreover, GBE treatment reduced the level of intracellular lipid accumulation and inhibited cholesterol uptake and efflux to alleviate foam cell formation. GBE activated PPARγ to enhance ABCA1/ABCG1-induced cholesterol efflux in THP-1. These results suggest that GBE can suppress lipid accumulation and alleviate foam cell formation by activating PPARγ pathway.

Objective To discuss the clinical safety,feasibility and efficacy of transcatheter arterial infusion chemotherapy(TAI)combined with lipiodol chemoembolization in the treatment of advanced colorectal cancer(CRC).Methods The clinical data of 37 patients with advanced CRC,who received TAI combined with lipiodol chemoembolization at the First Affiliated Hospital of Zhengzhou University of China between June 2016 and December 2022,were retrospectively analyzed.The clinical efficacy was evaluated,the progression-free survival(PFS)and the serious complications were recorded.Results A total of 55 times of TAI combined with lipiodol chemoembolization procedures were successfully accomplished in the 37 patients.The mean used amount of lipiodol emulsion was 2.9 mL(0.8-10 mL).No serious complications such as bleeding and intestinal perforation occurred.The median follow-up time was 24 months(range of 3-48 months).The postoperative one-month,3-month,6-month and 12-month objective remission rates(ORR)were 67.6%(25/37),67.6%(25/37),64.9%(24/37)and 56.8%(21/37)respectively,and the postoperative one-month,3-month,6-month and 12-month disease control rates(DCR)were 91.9%(34/37),91.9%(34/37),89.2%(33/37)and 81.1%(30/37)respectively.The median PFS was 16 months(range of 2-47 months).As of the last follow-up,22 patients survived and 15 patients died of terminal stage of tumor.Conclusion Preliminary results of this study indicate that TAI combined with lipiodol chemoembolization is clinically safe and effective for advanced CRC,and it provide a new therapeutic method for patients with advanced CRC.

Objective To investigate the effects of different culture conditions(RPMI-1640,DMEM and DMEM/F12 medium)on the passage of MPM cells isolated from the tissues of Malignant pleural mesothelioma(MPM),and to study the effects of CDKN2B on the proliferation,invasion and apoptosis of MPM cells.Methods MPM cells were isolated from MPM tissues and cultured in RPMI-1640,DMEM and DMEM/F12 medium,respectively.Cell proliferation was examined by CCK-8,and the nuclei and chromosomes were observed by Wright-Giemsa staining.Fluorescence intensities of Calretinin,CD141,CK5,EMA and WT-1 were conducted by immunofluorescence assay.The mRNA and protein expression of CDKN2B were detected by RT-qPCR and Western blot,respectively.Transwell was used to detect cell invasion and flow cytometry was used to detect cell apoptosis.Results The established MPM cells showed good viability when passaged to the 10th generation in RPMI-1640,DMEM and DMEM/F12 cultures,and the MPM markers Calretinin,CD141,CK5,EMA and WT-1 were all expressed in the cells.The viability of MPM cells in RPMI-1640 culture medium was relatively stable.CDKN2B was downregulated in MPM cells(P<0.05),and overexpression of CDKN2B significantly suppressed the proliferation(P<0.05),invasion(P<0.05)and epithelial interstitial transformation of MPM cells(P<0.01),and promoted the apoptosis(P<0.01).Conclusion The established MPM cells were stably passaged in RPMI-1640 culture medium,and CDKN2B may be a potential target for the diagnosis and treatment of MPM.

Objective To investigate the relationship between the ratio of soluble hemoglobin scavenger receptor 163 protein(sCD163)/soluble tumor necrosis factor-like weak inducer of apoptosis(sTWEAK)in plasma and prognosis in patients with spontaneous acute cerebral hemorrhage(ACH).Methods From August 2020 to August 2022,90 patients with ACH admitted to the Department of Neurosurgery,Harison International Peace Hospital,Hengshui City were regarded as the research group.According to the Glasgow outcome scale,patients with ACH were separated into the poor prognosis group(n=38)and the good prognosis group(n=52).Another 45 healthy examinee who underwent physical examination were used as the control group.Enzyme linked immunosorbent assay(ELISA)was applied to detect plasma sCD163 and sTWEAK levels,and the sCD163/sTWEAK ratio was calculated.Pearson method was applied to analyze the correlation between plasma sCD163,sTWEAK levels,sCD163/sTWEAK ratio and clinical data.Logistic regression was applied to analyze influencing factors of poor prognosis in patients with ACH.Receiver operating characteristic(ROC)was applied to analyze the predictive value of sCD163/sTWEAK ratio for poor prognosis of patients with ACH.Results The plasma levels of sCD163,sTWEAK and sCD163/sTWEAK ratio were obviously higher in the research group than those in the control group(P＜0.05).The plasma levels of sCD163,sTWEAK and sCD163/sTWEAK ratio were obviously lower in the good prognosis group than those in the poor prognosis group(P＜0.05).Hematoma volume,National Institutes of Health Stroke Scale(NIHSS)scores,hypertension and subtentorial hemorrhage were lower in the good prognosis group than those in the poor prognosis group,and low density lipoprotein cholesterol(LDL-C)was higher in the good prognosis group than that in the poor prognosis group(P＜0.05).Correlation analysis showed that plasma sCD163,and sTWEAK levels and the sCD163/sTWEAK ratio were positively correlated with bleeding site,hematoma volume,NIHSS score,white blood cell count,platelet count and neutrophil/lymphocyte ratio(NLR)(P＜0.05).Results of Logistic regression analysis showed that sCD163,sTWEAK,sCD163/sTWEAK ratio,hematoma volume,bleeding site and NIHSS score were influencing factors for poor prognosis in patients with ACH(P＜0.05).Results of receiver operating characteristic showed that the AUC of sCD163/sTWEAK ratio in evaluating poor prognosis of patients with ACH was 0.850,and the sensitivity and specificity were 86.84%and 69.23%.Conclusion The sCD163/sTWEAK ratio has a high level in the plasma of patients with ACH,which is associated with poor prognosis and has important value in predicting the prognosis of patients with ACH.

BACKGROUND:In recent years,there have been many novel tympanic membrane repair materials,including patches and 3D-printed scaffolds.However,the tympanic membrane repaired by these materials is different from the natural tympanic membrane in terms of thickness and internal structure. OBJECTIVE:To explore the efficacy of bone marrow mesenchymal stem cells-loaded high-porosity polycaprolactone/collagen nanofiber membrane scaffolds in repairing chronic tympanic membrane perforation. METHODS:Polycaprolactone,polycaprolactone-collagen,and high-porosity polycaprolactone-collagen nanofiber membranes were prepared by electrospinning technology,and the surface morphology,porosity and cell compatibility of the scaffolds were characterized.The tympanic membrane perforation model of 50 male SD rats was established by puncturing the posterior lower part of both eardrums with a sterile 23-measure needle combined with mitomycin C and hydrocortisone.After 12 weeks of modeling,the rats were divided into five groups by the random number table method.The blank control group did not receive any treatment.In the other four groups,polycaprolactone nanofiber membrane(polycaprolactone group),polycaprolactone-collagen nanofiber membrane(polycaprolactone-collagen group),high-porosity polycaprolactone-collagen nanofiber membrane(high-porosity polycaprolactone-collagen group)and high-porosity polycaprolactone-collagen nanofiber membrane containing bone marrow mesenchymal stem cells(high-porosity polycaprolactone-collagen group)were implanted at the perforation of the tympanic membrane,respectively.Each group consisted of 10 animals.The healing of the tympanic membrane was examined by otoendoscopy after 1,2,3 and 4 weeks of stent implantation.Hematoxylin-eosin staining,Masson staining,and Ki-67 immunohistochemical staining were performed on the tympanic membrane after 4 weeks of implantation. RESULTS AND CONCLUSION:(1)Scaffold characterization:Scanning electron microscopy showed that compared with other nanofiber membranes,the high-porosity polycaprolactone-collagen nanofiber membranes had more orderly nanofiber structure,larger surface pore size,and higher porosity(P<0.001).Live/dead staining showed that bone marrow mesenchymal stem cells adhered well on the three scaffolds,and the number of living cells on the high-porosity polycaprolactone-collagen nanofiber membrane was more than that on the other two scaffolds.Almarin staining showed that the proliferation rate of bone marrow mesenchymal stem cells on the high-porosity polycaprolactone-collagen nanofiber membrane was higher than that of the other two fiber membranes.(2)Animal experiments:Except for the blank control group,the tympanic membrane of the other four groups healed gradually with the extension of the time of fibrous membrane implantation,among which the healing speed of the cell-loaded high-porosity polycaprolactone-collagen group was the fastest.Hematoxylin-eosin staining,Masson staining,and Ki-67 immunohistochemical staining showed that the tympanic membrane of rats in the cell-carrying high-porosity polycaprolactone-collagen group was moderate in thickness and a three-layer structure with uniform collagen fiber layers,similar to the normal tympanic membrane,and the repair quality of tympanic membrane was better than that of other fiber membrane groups.(3)The results showed that the high-porosity polycaprolactone-collagen nanofiber membrane containing bone marrow mesenchymal stem cells could not only rapidly repair the perforation of the tympanic membrane,but also the newly healed tympanic membrane was similar to normal tympanic membrane in structure and thickness.

BACKGROUND:Astrocytes play an important role in the pathology of central nervous system diseases.The phenotypic and functional changes in astrocytes suggest that it may be an effective therapeutic target for central nervous system diseases.Our previous studies have confirmed that astragaloside can inhibit the lipopolysaccharide-induced astrocyte inflammatory response.Whether astragaloside can regulate the phenotype and function of astrocytes through Notch-1 and its downstream signaling pathway remains unclear. OBJECTIVE:To explore the effect of astragaloside on astrocyte activation and inflammatory response induced by inflammation and its possible mechanism. METHODS:Cerebral cortex astrocytes derived from neonatal C57BL/6 mouse were cultured in vitro.CCK-8 assay was used to determine the optimum concentration of astragaloside and Notch active inhibitor DAPT.The astrocytes were divided into five groups:PBS group,lipopolysaccharide group,lipopolysaccharide + astragaloside group,lipopolysaccharide + DAPT group and lipopolysaccharide + DAPT + astragaloside group.The secretion level of inflammatory factors was detected by ELISA,and the level of nitric oxide was detected by Griess method.The astrocytes and splenic mononuclear cells were co-cultured in Transwell chamber to observe the migration of CD4T cells.The expression of astrocyte activation marker GFAP,A1 marker C3 and A2 marker S100A10 as well as Notch 1 and Jag-1 was detected by immunofluorescence staining.The expressions of CFB,C3,S100A10,PTX3,Notch-1,Jag-1,and Hes were detected by western blot assay. RESULTS AND CONCLUSION:(1)According to the results of CCK8 assay,the final concentration of astragaloside was selected as 25 μmol/L and the final concentration of DAPT was 50 μmol/L for follow-up experiments.(2)Compared with PBS group,interleukin-6,interleukin-12 and nitric oxide secretion levels in the lipopolysaccharide group were significantly increased(P<0.05,P<0.05,P<0.01).Compared with the lipopolysaccharide group,interleukin-6(all P<0.05),interleukin-12(P>0.05,P<0.05,P<0.05)and nitric oxide(P<0.05,P<0.01,P<0.01)secretion significantly reduced in the lipopolysaccharide + astragaloside group,lipopolysaccharide +DAPT group,lipopolysaccharide + DAPT + astragaloside group.(3)Compared with the PBS group,the expression of GFAP that is the marker of activated astrocytes and the migration of CD4 T cells were significantly increased in the lipopolysaccharide group(P<0.01).Compared with the lipopolysaccharide group,astrocyte activation was significantly inhibited and CD4 T cell migration was significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group(P<0.05,P<0.05,P<0.01).(4)Compared with the PBS group,the expressions of A1 markers C3 and CFB in the lipopolysaccharide group were increased(P<0.01,P<0.05),and the expressions of A2 markers S100A10 and PTX3 were decreased(P<0.01,P<0.05).Compared with the lipopolysaccharide group,C3(all P<0.01)and CFB(both P<0.05)were significantly reduced and S100A10(all P<0.01)and PTX3(P<0.05,P<0.05 and P>0.05)were increased in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(5)Compared with the PBS group,the expressions of Jag-1,Notch-1 and Hes in the lipopolysaccharide group were significantly increased(all P<0.01).Compared with the lipopolysaccharide group,the expressions of Jag-1(all P<0.01),Notch-1(all P<0.01)and Hes(P<0.05,P<0.01 and P<0.01)were significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(6)The results indicate that astragaloside can promote the transformation of astrocytes from A1 to A2 by regulating Notch-1 signaling pathway,reduce the secretion of inflammatory factors and the migration of CD4 T cells,and thus inhibit astrocyte activation and inflammatory response.

BACKGROUND:After the treatment of femoral shaft fracture with the intramedullary nail,the third fracture open reduction indications are controversial.Some scholars believe that limited open reduction can achieve anatomical reduction,conducive to fracture healing;but some scholars believe that no open reduction of the third fracture still has a high fracture healing rate. OBJECTIVE:To investigate the effect of the circumference and displacement of the third fragment on fracture healing after intramedullary nailing of femoral shaft fractures with the third fragment. METHODS:A retrospective cohort study was conducted to analyze the clinical data of 142 patients suffered a femoral shaft fracture with a third fragment admitted to the Affiliated Lianyungang Hospital of Xuzhou Medical University from February 2016 to December 2021.The fracture were classified into three types according to the circumference of the third fracture with reference to the diaphyseal circumference at the fracture site:type 1 in 71 cases,type 2 in 52 cases,and type 3 in 19 cases.Referring to the diaphyseal diameter,the fractures were classified into three degrees according to the degree of the third fragment displacement:degree I in 95 cases,degree II in 31 cases,and degree III in 16 cases.All patients were treated with femoral interlocking intramedullary nails,and no intervention was performed for the displaced third fragment during the operation.Postoperative follow-up was performed to compare the fracture healing rate,healing time,and the modified Radiographic Union Scale for Tibia at month 9 after surgery in each group.The effect of third fracture fragment circumference and degree of displacement on fracture healing was assessed. RESULTS AND CONCLUSION:(1)All 142 patients were followed up for at least 12 months,with a mean of(14.7±4.1)months,and the overall healing rate was 73.4%.(2)When the third fragment was displaced by degree I,the healing rate,healing time,and modified Radiographic Union Scale for Tibia score at month 9 were not statistically significant among the three sub-groups of circumference classification.(3)When the third fragments were displaced by degree II or III,the healing rate and healing time were not statistically significant among the three subgroups of circumference classification;the modified Radiographic Union Scale for Tibia score at month 9 in the type 1 group was higher than that in the type 2 and 3 groups(P = 0.017).(4)Logistic regression analysis showed that a greater third fragment displacement and circumference were associated with lower fracture healing rates(P<0.05).(5)These findings indicate that in the treatment of femoral shaft fractures with third fragment by intramedullary nails,when the fracture fragment is displaced to degree I,the circumference size has little effect on fracture healing,and no intervention is required during surgery.When the third fragment is displaced to degree II or III and the circumference of which is type 1,a higher modified Radiographic Union Scale for Tibia score can still be obtained with no intervention of the third fragment.However,when the circumference is of type 2 or type 3,it significantly affects the fracture healing.Consequently,intraoperative intervention to reduce the distance of displacement of the fragment is required to lower the incidence of nonunion.The displacement of the third fracture fragments has a greater impact on fracture healing than their circumference.

OBJECTIVE To study the repair effect of ephedrine on lipopolysaccharide （LPS）-induced microglia function injury and its mechanism. METHODS Human microglia cells （HMC3） were used as research objects to investigate the effects of different concentrations of ephedrine （75， 150， 300， 600 μg/mL） on the viability and apoptosis of HMC3 cells. HMC3 cells were divided into control group （without drug intervention）， LPS group （1 μg/mL）， ephedrine group （1 μg/mL LPS+300 μg/mL ephedrine）， BAY11-7082 group [1 μg/mL LPS+5 μmol/L nuclear factor-κB （NF-κB） pathway inhibitor BAY11-7082]， inhibitor group （1 μg/mL LPS+300 μg/mL ephedrine+5 μmol/L BAY11-7082） and activator group （1 μg/mL LPS+300 μg/mL ephedrine+1 μmol/L NF-κB pathway activator Prostratin）. After 24 hours of drug treatment， cell migration， the levels of soluble interleukin-6（sIL-6）， interleukin-10（IL-10）， superoxide dismutase（SOD）and malondialdehyde（MDA）， and the expressions of NF-κB pathway-related proteins were all detected. RESULTS The viability of HMC3 cells could be increased significantly by 300 μg/mL ephedrine， while the apoptotic rate was decreased significantly （P＜0.05）. Compared with the control group， the number of migrating cells was increased significantly in the LPS group； the levels of sIL-6 and MDA， the phosphorylation of NF-κB protein were increased significantly， while the levels of IL-10 and SOD were decreased significantly （P＜0.05）. Compared with the LPS group， the above indexes were reversed significantly in the ephedrine group and BAY11-7082 group （P＜0.05）. Compared with the ephedrine group， the number of migrating cells was decreased significantly in the inhibitor group； the levels of sIL-6 and MDA， the phosphorylation of NF-κB protein were decreased significantly， while the levels of IL-10 and SOD were increased significantly （P＜0.05）. The above indexes were reversed significantly in the activator group （P＜0.05）can repair cell injury by inhibiting LPS induced apoptosis， migration， inflammation and oxidant stress of HMC3 cells， the mechanism of which may be associated with inhibiting the activity of the NF-κB signaling pathway.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.