Objective To identify flavonoid glycosides with quorum sensing inhibitory activity from Epimedium brevicornum and evaluate their bioactivity. Methods The minimum inhibitory concentrations （MICs） of five major flavonoid glycosides （baohuoside, icariin, epimedin A/B/C） and the extract of E. brevicornum were firstly determined. Subsequently, the inhibitory effects on the production of purple pigments in Chromobacterium violaceum CV026 were measured. Additionally, the biofilm formation and chitin quantification of Pseudomonas aeruginosa PAO1 were assessed. Results The extract of E. brevicornum and its primary components exhibited significant quorum sensing inhibitory activity. Particularly, icariin and epimedin C demonstrated superior inhibitory activity. Conclusion E. brevicornum demonstrates the ability to inhibit the quorum sensing system of Chromobacterium violaceum CV026 and Pseudomonas aeruginosa PAO1. Furthermore, icariin and epimedin C （100 μg/ml） show promise for development into novel drugs for quorum sensing inhibitor.

Objective:To explore the relationship between hemoglobin variability (Hb-var) and risk of all-cause death and cardiovascular death in patients with peritoneal dialysis (PD), and to provide basis for reducing the risk of death in PD patients.Methods:It was a multicenter retrospective cohort study. The clinical data of regular PD patients from Nanfang Hospital of Southern Medical University, Shunde Hospital of Southern Medical University, Foshan First People's Hospital and Ganzhou People's Hospital from July 1, 2008 to December 31, 2019 were collected. Hb-var was calculated based on hemoglobin at baseline before PD and in the first year after PD. The patients were divided into low Hb-var group, moderate Hb-var group and high Hb-var group according to the tertiles of first year Hb-var, and the differences of baseline clinical data among three groups were compared. Follow-up endpoints included death, transfer to hemodialysis, transfer to kidney transplantation, transfer to other centers, loss of follow-up, or on December 31, 2021. Cox regression analysis model was used to analyze the association of the first-year Hb-var with all-cause death and cardiovascular death. Fine-Gray competitive risk regression model was used to evaluate the impact of competitive events on mortality risk.Results:A total of 1 562 patients with PD were included in the study, aged (47.6±13.8) years old, with 821 males (52.6%) and baseline hemoglobin of 81 (69, 94) g/L. Hb-var in the first year of PD was 26.6 (16.7, 40.3) g/L. There were statistically significant differences in age, body mass index, serum albumin, hemoglobin, serum creatinine, serum calcium, serum phosphorus, intact parathyroid hormone and the proportion of renin-angiotensin system inhibitors among low Hb-var group (<20.0 g/L), moderate Hb-var group (20.0-35.5 g/L) and high Hb-var group (≥35.5 g/L, all P<0.05). The follow-up time was 33 (19, 51) months, and 208 patients (13.3%) died, among which 111 patients (53.4%) died of cardiovascular death. Multivariate Cox regression analysis showed that the higher Hb-var in the first year, the lower the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.018) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) in PD patients. Compared with low Hb-var group, the risk of all-cause death ( HR=0.56, 95% CI 0.37-0.82, P=0.003) and cardiovascular death ( HR=0.54, 95% CI 0.31-0.95, P=0.032) was lowest in the high Hb-var group. The competitive risk regression model analysis showed that Hb-var in the first year was still negatively correlated with the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.039). Conclusion:High Hb-var in the first year is associated with low risk of all-cause death and cardiovascular death in PD patients with severe anemia at baseline.

Activated fibroblasts and M2-polarized macrophages may contribute to the progression of pulmonary fibrosis by forming a positive feedback loop. This study was aimed to investigate whether fibroblasts and macrophages form this loop by secreting SDF-1 and TGF-β and the impacts of neotuberostemonine (NTS) and tuberostemonine (TS). Mice were intratracheally injected with 3 U·kg^-1 bleomycin and orally administered with 30 mg·kg^-1 NTS or TS. Primary pulmonary fibroblasts (PFBs) and MH-S cells (alveolar macrophages) were used in vitro. The animal experiments showed that NTS and TS improved fibrosis related indicators, inhibited fibroblast activation and macrophage M2 polarization, and reduced the levels of TGF-β and SDF-1 in alveolar lavage fluid. Cell experiments showed that TGF-β1 may activated fibroblasts into myofibroblasts secreting SDF-1 by activating the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways. It was also found for the first time that SDF-1 was able to directly polarize macrophages into M2 phenotype secreting TGF-β through the same pathways as mentioned above. Moreover, the results of the cell coculture confirmed that fibroblasts and macrophages actually developed a feedback loop to promote fibrosis, and the secretion of TGF-β and SDF-1 was crucial for maintaining this loop. NTS and TS may disturb this loop through inhibiting both the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways to improve pulmonary fibrosis. NTS and TS are stereoisomeric alkaloids with pyrrole[1,2-a]azapine skeleton, and their effect on improving pulmonary fibrosis may be largely attributed to their parent nucleus. Moreover, this study found that inhibition of both the AKT and ERK pathways is essential for maximizing the improvement of pulmonary fibrosis.
Animals ; Mice ; Pulmonary Fibrosis/metabolism* ; Transforming Growth Factor beta/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; MAP Kinase Signaling System ; Alkaloids/pharmacology* ; Fibroblasts ; Macrophages/metabolism*

Objective:To explore the relationship between metabolic acidosis and cardiac valve calcification in maintenance hemodialysis (MHD) patients in the Pearl River Delta Region.Methods:Patients on MHD greater than 3 months who were treated in 10 blood purification centers in the Pearl River Delta Region from July 1 to September 30, 2019 were selected for this multicenter cross-sectional study. Based on a Doppler ultrasound, MHD patients were further divided into non-valve calcification group and valve calcification group. The demographics data, frequency of dialysis, blood pressure, single pool Kt/V(spKt/V), dialysis medications and laboratory data were collected and compared. Spearman correlation analysis was used to analyze the correlation between serum carbon dioxide combining power (CO 2CP) and cardiac valve calcification. Multivariate logistic regression model was used to analyze the influencing factors of cardiac valve calcification. Results:A total of 664 MHD patients were included in this study, with age of (57.0±14.2) years old and dialysis age of 43.0 (22.3, 71.7) months, including 395 males (59.5%) and 269 females (40.5%). Among them, there were 119 patients (17.9%) with diabetes and 186 patients (28.0%) with dialysis 2 times per week. There were 329 patients (49.5%) in the valve calcification group, and 335 patients (50.5%) in the non-valve calcification group. Compared to those in non-valve calcification group, valve calcification group had longer duration of dialysis, higher proportion of patients with dialysis 2 times per week, higher levels of diastolic blood pressure, fasting blood glucose, intact parathyroid hormone and ferritin, higher proportion of patients with blood CO 2CP<19 mmol/L (median CO 2CP), higher proportion of patients on usage of calcium channel blocker, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, α-receptor blocker, β-receptor blocker, calcitriol and lanthanum carbonate (all P<0.05), while the levels of spKt/V, hemoglobin, serum CO 2CP, corrected calcium, blood phosphorus, blood alkaline phosphatase, albumin, total cholesterol, triacylglycerol, low-density lipoprotein, high-density lipoprotein, transferrin saturation, and the proportion of patients on usage of sevelamer and cinacalcet were lower (all P<0.05). Spearman analysis showed significant negative correlation between serum CO 2CP and valve calcification ( rs=-0.697, P<0.001). Multivariate logistic regression analysis showed that dialysis performed twice a week ( OR=2.789, 95% CI 1.232-6.305, P=0.014), blood total cholesterol ( OR=1.449, 95% CI 1.014-2.071, P=0.042), CO 2CP<19 mmol/L ( OR=22.412, 95% CI 10.640-47.210, P<0.001) were the influencing factor of valve calcification in MHD patients. Conclusions:MHD patients with cardiac valve calcification have significant acid loading. Metabolic acidosis is an independent influencing factor for cardiac valve calcification in MHD patients.

Objective:To evaluate the classification of petroclival meningiomas(PCM), proposed selection of microsurgical approach and therapeutic outcomes.Methods:Retrospectively analyzed clinical data of 179 cases of PCM from Department of Neurosurgery, Xiangya Hospital, Central South University between January 2011 and November 2020. There were 28 males and 151 females with an age of(49.9±10.2) years(range: 22 to 75 years) and the tumor size of(44.8±10.3)mm(range: 15 to 80 mm). The mean duration of symptom ( M( Q R)) was 18.0(40.6)months(range:1 week to 320 months) and the mean preoperative Karnofsky performance scale(KPS) was 78.6±13.3(range: 40 to 100). The PCM were classified into 5 types according to the difference in the origin of dural attachment, involvement of adjacent structures and growth patterns through preoperative MRI. The surgical approaches were selected based on the proposed classification, and the clinical characteristics, surgical record, and follow-up data of each type were reviewed. Results:The PCM were divided into clivus type(CV, 4 cases), petroclival type(PC, 60 cases), petroclivosphenoidal type(PC-S, 62 cases), sphenopetroclival type with 2 subtypes(S-PC, 50 cases) and central skull base type(CSB, 3 cases). All of 176 cases were obtained microsurgical treatment except CSB type. The gross total resection reached in 124 cases(70.5%) with 112 cases of retrosigmoid approach(RSA), 27 cases of subtemporal transtentorial transpetrosal approach, 13 cases of pretemporal trancavernous anterior transpetrosal approach(PTCA), 12 cases of extended pterional transtentorial approach(EPTA) and presigmoid combined supra-infratentorial approach, respectively. The RSA could be adopted in both of CV type and PC type and most of PC-S type(71.0%). S-PC subtype Ⅰ and subtype Ⅱ were mainly underwent EPTA(40.8%) and PTCA(52.2%), respectively. Seventy-two cases(40.9%) gained new neurological dysfunctions mainly with the cranial nerve paralysis. The postoperative morbidity and complications were recovered or improved with conservative and positive symptomatic and supportive treatment. There was no intraoperative and postoperative death case. One hundred and sixty four cases(93.2%) of operative patients were followed with the duration of 24(48)months(range:3 to 108 months). Tumor recurrence and progress were identified in 14 cases(10.4%) and 14 cases(28.6%), respectively. Compared with postoperative neurological status, 89 patients(54.3%) had improved and 38 patients(23.2%) were still suffering various degrees of neurological dysfunctions during the follow-up. The recent KPS was 84.2±11.4(range: 50 to 100) without statistical difference from preoperative KPS ( t=-1.356, P=0.125). As for each type, there were statistically significant differences in brain stem edema (χ 2=3.482, P=0.038), gross total resection (χ 2=9.127, P=0.001), surgical duration( F=8.954, P=0.013), postoperative length of stay( F=3.652, P=0.025), postoperative complications (χ 2=1.550, P=0.024), postoperative KPS( F=2.856, P=0.042) and tumor recurrence/progress (χ 2=4.824, P=0.013). Conclusion:The precise and comprehensive classification of PCM and specific individual treatment strategy are benefit to evaluate the diverse clinical prognosis, choose optimal surgical approaches, elevate gross total resection, diminish neurological dysfunctions and restraint tumor recurrence, so as to improve the quality of life for patients.

Objective:To evaluate the classification of petroclival meningiomas(PCM), proposed selection of microsurgical approach and therapeutic outcomes.Methods:Retrospectively analyzed clinical data of 179 cases of PCM from Department of Neurosurgery, Xiangya Hospital, Central South University between January 2011 and November 2020. There were 28 males and 151 females with an age of(49.9±10.2) years(range: 22 to 75 years) and the tumor size of(44.8±10.3)mm(range: 15 to 80 mm). The mean duration of symptom ( M( Q R)) was 18.0(40.6)months(range:1 week to 320 months) and the mean preoperative Karnofsky performance scale(KPS) was 78.6±13.3(range: 40 to 100). The PCM were classified into 5 types according to the difference in the origin of dural attachment, involvement of adjacent structures and growth patterns through preoperative MRI. The surgical approaches were selected based on the proposed classification, and the clinical characteristics, surgical record, and follow-up data of each type were reviewed. Results:The PCM were divided into clivus type(CV, 4 cases), petroclival type(PC, 60 cases), petroclivosphenoidal type(PC-S, 62 cases), sphenopetroclival type with 2 subtypes(S-PC, 50 cases) and central skull base type(CSB, 3 cases). All of 176 cases were obtained microsurgical treatment except CSB type. The gross total resection reached in 124 cases(70.5%) with 112 cases of retrosigmoid approach(RSA), 27 cases of subtemporal transtentorial transpetrosal approach, 13 cases of pretemporal trancavernous anterior transpetrosal approach(PTCA), 12 cases of extended pterional transtentorial approach(EPTA) and presigmoid combined supra-infratentorial approach, respectively. The RSA could be adopted in both of CV type and PC type and most of PC-S type(71.0%). S-PC subtype Ⅰ and subtype Ⅱ were mainly underwent EPTA(40.8%) and PTCA(52.2%), respectively. Seventy-two cases(40.9%) gained new neurological dysfunctions mainly with the cranial nerve paralysis. The postoperative morbidity and complications were recovered or improved with conservative and positive symptomatic and supportive treatment. There was no intraoperative and postoperative death case. One hundred and sixty four cases(93.2%) of operative patients were followed with the duration of 24(48)months(range:3 to 108 months). Tumor recurrence and progress were identified in 14 cases(10.4%) and 14 cases(28.6%), respectively. Compared with postoperative neurological status, 89 patients(54.3%) had improved and 38 patients(23.2%) were still suffering various degrees of neurological dysfunctions during the follow-up. The recent KPS was 84.2±11.4(range: 50 to 100) without statistical difference from preoperative KPS ( t=-1.356, P=0.125). As for each type, there were statistically significant differences in brain stem edema (χ 2=3.482, P=0.038), gross total resection (χ 2=9.127, P=0.001), surgical duration( F=8.954, P=0.013), postoperative length of stay( F=3.652, P=0.025), postoperative complications (χ 2=1.550, P=0.024), postoperative KPS( F=2.856, P=0.042) and tumor recurrence/progress (χ 2=4.824, P=0.013). Conclusion:The precise and comprehensive classification of PCM and specific individual treatment strategy are benefit to evaluate the diverse clinical prognosis, choose optimal surgical approaches, elevate gross total resection, diminish neurological dysfunctions and restraint tumor recurrence, so as to improve the quality of life for patients.

Objective:To explore the functional connections of the whole brain and the two hemispheres in patients with obsessive-compulsive disorder (OCD).Methods:Twenty-six patients with obsessive-compulsive disorder(patients group) and thirty-seven healthy controls matched in gender, age and education(control group) were enrolled.All the participants accepted the resting-state functional magnetic resonance (rs-fMRI) scan.Based on DPABI and REST software, degree centrality (DC) and voxel - mirrored homotopic connectivity (VMHC) approaches were used to explore the pattern of functional connection in OCD.Results:Compared with the control group, the DC values in the right posterior cerebellar lobe(MNI: x, y, z=45, -87, -12), left precentral gyrus(MNI: x, y, z=-54, 9, 39), left inferior parietal lobule(MNI: x, y, z=-48, -51, 42), right anterior cingulate cortex(MNI: x, y, z=3, 18, 48) were significantly higher( t values were 5.75, 5.26, 5.28 and 5.16, respectively), and the DC values in the left inferior frontal gyrus(MNI: x, y, z=-36, 9, 30) were significantly lower( t value was -6.65) in patients group.The VMHC values in bilateral posterior cerebellar lobe(MNI: x, y, z=±51, -69, -33), bilateral inferior parietal lobule(MNI: x, y, z=±48, -51, 54), bilateral anterior cingulate cortex(MNI: x, y, z=±3, 21, 45)in patients group were significantly higher that those in control group( t values were 5.19, 5.19, 5.02, 5.02, 5.15 and 5.15, respectively). The DC and VMHC values in patients group were not significantly correlated with clinical symptoms(-0.23< r<0.19, P>0.05). Conclusion:OCD patients have abnormal connections between key brain network nodes and relevant brain regions, and functional connections have increased among multiple cerebral hemispheres.

Objective To investigate the clinical treatment strategy of large and giant pituitary adenomas invading the cavernous sinus.Methods One hundred and nine patients with large and giant pituitary adenomas invading the cavernous sinus,admitted to our hospital from January 2010 to December 2018,were chosen in our study.Four patients with prolactin-type pituitary adenomas received oral treatment with bromocriptine;the remaining 105 patients received surgical treatment,and choices of surgical approach were based on classification of pituitary adenomas.The clinical data and efficacies of these patients accepted different treatment approach were retrospectively analyzed.Results Of the 105 patients with pituitary adenomas,63 (60％) were of type Ⅰ,15 (14.3％) were of type Ⅱ,18 (17.1％)were of type Ⅲ,and 9 (8.6％) were of type Ⅳ.Single extended transsphenoidal approach was used in 75 patients,transcranial approach was used in 26 patients,and combined extended transsphenoidal and transcranial approach was used in 4 patients.Gross total tumor resection was achieved in 86 patients,subtotal resection in 17 patients,and partial resection in two patients.Ten patients had new cranial nerve palsy after surgery,including 7 with oculomotor nerve palsy and three with abductor nerve palsy;two patients with preoperative neurological paralysis were aggravated,and both of them were oculomotor nerves;transient insipidus was noted in 19 patients and electrolyte disorder was noted in 23 patients;no permanent insipidus,cerebrospinal fluid leakage or intracranial infection,and no new or aggravated visual field vision disorder were noted.Conclusion Reasonable clinical treatment strategies and appropriate microsurgical approaches can achieve good therapeutic effect in patients with large and giant pituitary adenomas invading the cavernous sinus.

Objective To analyze the risk factors affecting postoperative incisional infection in Crohn's disease (CD) patients after bowel resection.Methods The retrospective case-control study was conducted.The clinicopathologieal data of 239 CD patients who underwent bowel resection in the Sixth Affiliated Hospital of Sun Yat-sen University between January 2007 and December 2016 were collected.All patients underwent bowel resection.Observation indicators:(1) surgical situations;(2) follow-up;(3) risk factors analysis affecting postoperative incisional infection;(4) clinical factors affecting preoperative anemia.The follow-up using outpatient examination or ward diagnosis was performed to detect incisional infection within 30 days postoperatively up to January 2017.The normality test was done by Shapiro-Wilk.Measurement data with normal distribution were represented as x-±s,and comparison between groups was evaluated with the t test.Measurement data with skewed distribution were described as M (range),and comparison between groups was analyzed using the Wilcoxon ranksum test.The univariate analysis and multivariate analysis were done using the Logistic regression model.The P＜ 0.05 in univariate analysis was incorporated into multivariate analysis for analysis in the forward wald.Results (1) Surgical situations:of 239 patients,11 underwent emergency surgery and 228 underwent elective surgery;65 and 174 underwent respectively laparoscopic surgery and open surgery;179 received digestive tract reconstruction and anastomosis and 81 received enterostomy (21 combined with anastomosis and enterostomy).Among 239 patients,137,113,101,58,54 and 11 were complicated respectively with fiber stenosis,intestinal fistula,obstruction of small intestine,abscess,cellulitis and enterobrosis (some patients combined with multiple signs).(2) Follow-up:239 patients were followed up at 30 days postoperatively.During the follow-up,48 with incisional infection were improved by symptomatic treatment.(3) Risk factors analysis affecting postoperative incisional infection:① Results of univariate analysis showed that illness behavior,sedimentation rate of RBC ＞ 20 mm/h,preoperative anemia,preoperative chronic intestinal fistula,open surgery,intraoperative fiber stenosis and intraoperative intestinal fistula were risk factors affecting occurrence of postoperative incisional infection [odds ratio (0R)=2.530,2.579,4.233,2.988,2.554,0.503,3.052,95％ confidence interval (CI):1.218-2.259,1.141-5.833,1.598-11.210,1.522-5.864,1.082-6.029,0.265-0.954,1.555-5.993,P＜0.05].② Results of multivariate analysis showed that preoperative anemia and intraoperative intestinal fistula were independent risk factors affecting occurrence of postoperative incisional infection (OR =3.881,2.837,95％ CI:1.449-10.396,1.429-5.634,P＜0.05).(4) Clinical factors affecting preoperative anemia:cases (male) with preoperative anemia,body mass index (BMI),cases with sedimentation rate of RBC ＞ 20 mm/h,platelet (PLT) ＞ 300x109/L,elevated C-reactive protein,albumin (Alb) ＜35 g/L were respectively 120,(17.4±2.9)kg/m2,130,75,139,65 in patients with preoperative anemia and 65,(18.3±2.9)kg/m2,36,12,39,10 in patients without preoperative anemia,with statistically significant differences (x2 =17.966,t =2.210,x2 =12.219,14.440,14.661,12.272,P＜0.05).Conclusion The preoperative anemia and intraoperative intestinal fistula are independent risk factors affecting occurrence of postoperative incisional infection,and preoperative anemia is associated with perioperative inflammatory conditions.

OBJECTIVETo explore the value of baseline serum alkaline phosphatase (ALP) for predicting 2-year fracture in patients with chronic kidney disease (CKD) on maintenance dialysis.

METHODSA total of 139 patients with CKD undergoing maintenance dialysis in our hospital were enrolled in this study. According to the median serum ALP level, the patients were divided into high ALP and low ALP groups. The demographic and clinical data of the patients including dialysis duration, serum calcium level, serum phosphorus level, and serum intact parathyroid hormone level were recorded, and their bone mineral density of the femur and the lumbar spine was measured using dual energy X-ray absorptiometry. The patients were followed up for 2 years and fracture events were recorded. The risk factors of fracture were analyzed using logistic regression analysis, and their predictive value for fracture was analyzed using receiver-operating characteristic (ROC) curve.

RESULTSThe mean baseline serum ALP level was 132.55±167.68 U/L in these patients, significantly higher than that in the normal population (=2.816, =0.006). Baseline serum ALP level was negatively correlated with the bone mineral density of the lumbar spine (=-0.203, =0.006) and the femur (=-0.196, =0.021). Fractures occurred in 21 (15.1%) of the patients during the 2-year follow-up, and the fracture rate was significantly higher in patients with high ALP levels. Logistic regression analysis identified serum ALP level as an independent risk factor of fracture (OR: 1.010, =0.001, 95%CI: 1.004-1.016). The areas under the ROC curve were 0.900 and 0.768 for serum ALP level and intact parathyroid hormone level in predicting 2-year fractures, respectively.

CONCLUSIONSSerum ALP may serve as a good indicator for predicting 2-year fractures in patients with CKD on maintenance dialysis.