Objective To investigate the relationship between serum phosphorus variability and mortality in maintenance hemodialysis (MHD) patients. Methods A total of 502 MHD cases from Renji hospital hemodialysis center were registered in Shanghai Registry Network from January 2007 to April 2015. They were recruited with general information, laboratory results and outcomes. According to their median of coefficient of variation (CV) of blood phosphorus, the patients were divided into high variation group (CV≥0.226 mmol/L) and low variation group (CV<0.226 mmol/L). The relationship of serum phosphorus CV with all?cause mortality and cardiovascular disease mortality was assessed respectively. Results The average age was (63.9±14.6) years, the median dialysis age was 82.0 (43.0, 139.0) months, 118 patients (23.5%) died for all cause and 64 patients (12.7%) died for cardiovascular disease. Compared with patients in low phosphorus variation group, patients had a higher all?cause mortality in high phosphorus variation group (27.7% vs 19.3%, P=0.028). Higher cardiovascular disease mortality was observed in high variation group as well, but this difference was no statistical significant (15.4% vs 10.0%, P=0.082). COX regression analysis showed that >60 years of age (HR=2.762, 95%CI 1.707?4.468, P<0.001), low hemoglobin (HR=0.466, 95%CI 0.317?0.686, P<0.001), low albumin (HR=0.555, 95%CI 0.366?0.840, P=0.005), high CV of phosphorus (HR=1.479, 95%CI 1.023 ? 2.139, P=0.037) were independent risk factors for all ? cause mortality. Moreover, >60 years of age (HR=2.666, 95%CI 1.469?4.837, P=0.001), low hemoglobin (HR=0.480, 95%CI 0.238?0.801, P=0.005), and high CV of phosphorus (HR=1.655, 95%CI 1.003?2.729, P=0.049) were independent risk factors for cardiovascular disease mortality. There was no significant statistical difference between patients phosphorus on target and patients phosphorus below target in all?cause disease mortality (P=0.065) and cardiovascular disease mortality (P=0.425). High variation group whose phosphorus on target had higher all?cause mortality and cardiovascular disease mortality than those in low variation group (29.2% vs 16.9%, P=0.047; 15.0% vs 6.0%, P=0.033). Kaplan?Meier method showed that patients with high phosphorus variation had higher all?cause (P=0.023) and cardiovascular disease mortality (P=0.047) than patients with low phosphorus variation. Conclusions The high CV of phosphorus is independently correlated with all?cause and cardiovascular disease mortality. Patients with standard ? reaching phosphorus in the low variation group have a lower mortality. A serum phosphorus level sustainably reaching the standard may improve the survival in MHD patients.

This article summarized the experience of Professor Xiong Jibai,a national TCM master,in treating pulmonary nodules based on the theory of"body fluids and blood stasis mixing"in Huang Di Nei Jing.Professor Xiong Jibai believes that the basic pathogenesis of pulmonary nodules is that"body fluids and blood stasis mixing"accumulate in lung collaterals,and the fundamental pathological factor is phlegm and blood stasis.Xiong's treatment is based on dissipating phlegm and activating qi,activating blood circulation and resolving masses,paying attention to syndrome differentiation and treatment,examining syndromes and seeking causes,flexibly selecting prescriptions and treating both symptoms and root causes;attaching importance to maintaining healthy qi,preventing both illness and change,and preventing recovery after illness.Clinical medical records were attached to prove the clinical thinking and medication characteristics.

Objective To investigate the mechanism of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair in the treatment of hypertension based on the network pharmacology method and animal experiment verification.Methods(1)TCMSP,BATMAN and TCMIP databases were used to screen the active components and targets of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair.The hypertension-related targets were obtained by searching the Drugbank,Genecard,TTD and Disgenet databases.The intersection(common target)of the active component target and the target related to hypertension disease was taken,and the obtained intersection target was the potential target of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair for the treatment of hypertension.The active ingredients and their targets of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair were imported into Cytoscape 3.9.1 software to construct a'Chinese medicines-active ingredients-targets'network and screen key active ingredients.The protein-protein interaction(PPI)network of potential targets was constructed to screen potential core targets.The Metascape platform was used to analyze the GO function and KEGG pathway enrichment of potential targets.The key active components and potential core targets were selected for molecular docking verification.(2)Thirty male spontaneously hypertensive rats(SHR)were randomly divided into model group,western medicine group(Candesartan Cilexetil,0.72 mg·kg-1)and low-,medium-and high-dose groups of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma(2.25,4.50,9.00 g·kg-1).Another male WKY rats were selected as blank group,with 6 rats in each group,once a day for 8 weeks.The systolic blood pressure of rat tail artery was detected before administration and 2,4,6 and 8 weeks after drug intervention.The pathological changes of thoracic aorta were observed by HE staining.The protein expression levels of GRP78,CHOP and Caspase-12 in aorta abdominalis were detected by Western Blot.Results(1)A total of 83 active components of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma were obtained,and 158 potential targets(intersection targets)for the treatment of hypertension were screened out.Five key active ingredients:p-hydroxybenzoic acid,4-hydroxybenzylamine,tanshinone I,tanshinone,γ-sitosterol;6 potential core targets:IL6,TNF,CASP3,JUN,PTGS2,IL1B;GO functional enrichment analysis obtained 1 826 biological process items,89 cell component items,and 199 molecular function items.KEGG pathway enrichment analysis obtained 186 pathways,mainly involving neuroactive ligand-receptor interaction,calcium signaling pathway,inflammatory response(such as TNF and MAPK signaling pathway),vascular protection(such as HIF-1 and cAMP signaling pathway),oxidative stress(such as PI3K-Akt signaling pathway)and other signaling pathways.Tanshinone I and tanshinone had strong binding force to 6 potential core targets,and γ-sitosterol had strong binding force to IL6,CASP3,JUN,PTGS2 and IL1B.(2)Compared with the blank group,the systolic blood pressure of the model group was significantly increased(P＜0.01).The thoracic aortic endothelial injury was obvious,the endothelial cell morphology was abnormal,swelling and exfoliated cells could be seen,the intima of the tissue was disordered,the intima structure was incomplete,and the intima was thickened.The protein expressions of GRP78,CHOP and Caspase-12 in abdominal aorta were significantly increased(P＜0.01).Compared with the model group,the systolic blood pressure of the rats in the administration group was significantly decreased(P＜0.01);the injury of thoracic aorta was alleviated,and the morphology,intima structure and thickness of endothelial cells were improved to varying degrees.The protein expressions of GRP78,CHOP and Caspase-12 in abdominal aorta were significantly decreased(P＜0.01).Conclusion Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair may act on core targets such as IL6,TNF,CASP3,JUN,PTGS2,and IL1B through key active components such as p-hydroxybenzoic acid,tanshinone,and γ-sitosterol,and regulate key signaling pathways such as TNF signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway,and PERK signaling pathway to improve vascular endothelial dysfunction,inhibit endoplasmic reticulum stress,and lower blood pressure.

Background and Objectives: Mesenchymal stromal cells (MSCs)-based treatment for degeneration of intervertebral disc (IVD) has been proposed recently. We here addressed whether MSC secreted factors can rejuvenate nucleus pulposus- derived stem/progenitor cells from degenerated disc (D-NPSCs) in vitro. Methods: and Results: We analyzed the expression of MSCs and NP cell specific surface markers, pluripotency related genes, multilineage potential and cell proliferative capacity of D-NPSCs upon incubation with the conditioned medium which was collected from the umbilical cord derived MSCs (UCMSCs). Our results indicated that the conditioned medium restore the stemness of D-NPSCs by up-regulating the expression level of CD29 and CD105, pluripotency related genes OCT4 and Nanog, and NP progenitor marker Tie2. The increased stemness was accompanied by promoted cell proliferative capacity and improved osteogenic and chondrogenic differentiation potential. Conclusions Our findings suggested that the UCMSCs derived conditioned medium might be used to rejuvenate the degenerated NP stem/progenitor cells.

AIM:To explore the effect of tomatidine(TA)on lipopolysaccharide(LPS)-induced nerve cell in-jury and the underlying mechanism.METHODS:The neuroinflammation model was induced by treating SH-SY5Y cells with LPS.These cells were divided into control(CON),LPS,and LPS+TA groups.The LPS group was treated with 5 μg/mL LPS for 24 h to establish an inflammatory model.The LPS+TA group was first treated with 5 μmol/L tomatidine for 24 h and then co-cultured with 5 μg/mL LPS for 24 h.Cell viability was detected using the CCK-8 assay.RT-qPCR was used to detect the mRNA expression of inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β).The protein expression of transcription factor EB(TFEB),p-TFEB,P62,and microtubule-associated protein 1 light chain 3(LC3)expression was detected through Western blot.TFEB localization and cleaved caspase-3 expression were detected through immunofluorescence.The cell apoptosis rate was detected through flow cytometry.RESULTS:(1)Compared with the CON group,the LPS group exhibited significant increases in IL-1β and TNF-α mRNA levels(P＜0.05),the cell apoptosis rate,and the p-TFEB level(P＜0.01).By contrast,P62,LC3-Ⅱ/LC3-Ⅰ,and TFEB protein ex-pression levels decreased significantly(P＜0.05),and TFEB was mainly localized in the cytoplasm.(2)Compared with the LPS group,tomatidine treatment significantly decreased the p-TFEB protein expression level(P＜0.01),increased the TFEB protein expression level(P＜0.01),and promoted the TFEB protein to migrate into the nucleus.After treatment of tomatidine,the LC3-Ⅱ/LC3-Ⅰ protein expression level significantly increased(P＜0.05),and the cell apoptosis rate signifi-cantly decreased(P＜0.01).In addition,the TNF-α mRNA level significantly decreased after tomatidine treatment(P＜0.01).CONCLUSION:Tomatidine improves autophagy dysfunction,inflammatory reaction,and cell apoptosis induced by LPS via activating the transcription factor EB.

Background: Carbohydrate antigen 72-4 (CA72-4) is generally recognized as a tumor marker of digestive system. However, elevated serum CA72-4 level is also evident in many benign diseases and healthy subjects, and its sensitivity in diagnosing malignant tumor is quite poor. Aims: To reassess the value of CA72-4 in tumor screening and diagnosis. Methods: Three cohorts were established in this study. Inpatients who underwent a serum CA72-4 measurement and had a definite final diagnosis were included into Cohort 1 (retrospective study). Inpatients with elevated serum CA72-4 level who had not been diagnosed as malignant tumor before admission were included into Cohort 2 (retrospective study). Individuals who underwent a serum CA72-4 measurement and willing to take a follow-up for at least 2 years were included into Cohort 3 (prospective study). Malignancies had been preliminarily excluded in all individuals in Cohort 3 before enrollment. Results: Among the 2 173 patients recruited in Cohort 1, the prevalence of positive serum CA72-4 was significantly higher in patients with malignancies than those without (16.4% vs. 7.4%, P<0.05). The sensitivity and specificity of CA72-4 for diagnosis of malignant tumor were 36.5% and 76.2%, respectively, at the cut-off value (2.955 U/mL) identified by ROC curve analysis. Among the 1 807 patients recruited in Cohort 2, most of the participants (76.5%) did not have malignancies. Serum CA72-4 level was associated with the histological classification, tumor differentiation and TNM staging of malignancies (P<0.05). Among the 376 individuals who underwent a follow-up for no less than 2 years in Cohort 3, elevated serum CA72-4 level did not increase the risk of malignant tumor (OR=1.268, 95% CI: 0.283-5.687). Conclusions: CA72-4 is not a sensitive marker for tumor screening, its value as an item in physical examination should be re-evaluated. In patients who had positive serum CA72-4 and malignant tumor was ruled out in initial examination, the necessity of long-term follow-up of serum CA72-4 needs to be discussed.

Objective To investigate the expression and role of the Sonic Hedgehog (Shh) signaling pathway in intestinal mucosal barrier injury in rats with severe acute pancreatitis (SAP). Methods A total of 48 Sprague-Dawley rats were divided into sham-operation group (Sham group), SAP model group (SAP group), SAP+Shh signaling pathway-specific agonist purmorphamine group (PUR+SAP group), and SAP+Shh signaling pathway-specific antagonist cyclopamine group (CYC+SAP group) using a random number table, with 12 rats in each group, and each group was further divided into 12-hour and 24-hour subgroups, with 6 rats in each subgroup. Rats were given retrograde injection of 5% sodium taurocholate into the pancreatic and bile ducts to establish a model of SAP, and rats in the intervention groups were given intraperitoneal injection of 0.69 mg/kg purmorphamine and 0.69 mg/kg cyclopamine before modeling. Related samples were collected at 12 and 24 hours after modeling. HE staining was used to observe the pathological changes of the pancreas and the ileum; ELISA was used to measure the serum levels of amylase, lipase, diamine oxidase (DAO), and endotoxin-core antibody (EndoCAb); the TUNEL method was used to observe the apoptosis of intestinal epithelial cells; Western blot was used to measure the expression levels of Shh, Ptch1, and Gli1 in ileal tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. Results Compared with the Sham group, the SAP group had significant increases in the pathological scores of pancreatic and ileum tissue, the serum levels of lipase, amylase, DAO, and EndoCAb, the apoptosis of intestinal epithelial cells, and the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Compared with the SAP group, the PUR+SAP group had significantly alleviated pathological injury and dysfunction of the pancreas and intestine, a significant reduction in the apoptosis of intestinal epithelial cells, and significant increases in the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Compared with the SAP group, the CYC+SAP group had significant aggravation of the pathological injury and dysfunction of the pancreas and intestine, a significant increase in the apoptosis of intestinal epithelial cells, and significant reductions in the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Conclusion The Shh signaling pathway may be involved in intestinal mucosal barrier injury in SAP and exerts a protective effect.

OBJECTIVE： To establish HPLC fingerprints of Nauclea officinalis extract syrup， and to determine the contents of 9 components. METHODS： HPLC method was adopted. The determination was performed on Diamonsil C18（2）column with mobile phase consisted of acetonitrile-0.1％ phosphoric acid solution （gradient elution） at the flow rate of 1.0 mL/min. The detection wavelength was set at 240 nm， and column temperature was 30 ℃. The sample size was 10 μL. Using strictosamide as reference， HPLC chromatograms of 20 batches of N. officinalis extract syrup were drawn. The similarity of HPLC chromatograms were evaluated by using TCM Fingerprint Similarity Evaluation System （2004A edition） to confirm common peaks. The contents of 9 components were determined by standard curves. RESULTS： There were 26 common peaks in 20 batches of HPLC chromatograms， and the similarity was higher than 0.98. Compared with mixed control， 9 chemical components were identified， such as 3，4-dihydroxybenzoic acid， neochlorogenic acid， loganic acid， chlorogenic acid， cryptochlorogenic acid， swertioside， pumiloside， strictosamide and vincosamide. The linear range of 9 components were 17.24-275.84， 7.56-120.96， 15.40-246.40， 7.84-125.44， 8.64-138.24， 7.96-127.36， 8.40-134.40， 48.56-776.96， 4.16-66.56 μg/mL（all r≥0. 999）， respectively. The limits of detection were 0.043 1， 0.126 0， 0.038 5， 0.130 7， 0.144 0， 0.066 3， 0.070 0， 0.012 1， 0.052 0 μg/mL， respectively. The limits of quantitation were 0.215 5， 0.189 0， 0.077 0， 0.196 0， 0.288 0， 0.132 7， 0.105 0， 0.097 6， 0.138 7 μg/mL， respectively. RSDs of precision， stability and reproducibility tests were all lower than 2.0％ （n＝6）. Average recoveries were 99.6％、106.3％、100.1％、102.0％、98.4％、100.0％、99.3％、100.6％ and 101.2％， and RSDs were 1.20％、0.24％、0.59％、1.00％、0.73％、1.30％、1.10％、1.80％、1.90％（n＝6）. CONCLUSIONS： Established HPLC fingerprints and quantitative determination method of N. officinalis extract syrup are accurate， specific and sensitive. It can provides reference for quality control of N. officinalis extract syrup.

Objective: To explore the clinical value of new rapid pathological diagnosis technology in the examination of cervical lesions in primary medical institution. Methods: In the Affiliated Hospital of Yangzhou University, 25 cases of cervical scraping and 22 cases of cervical biopsy were selected.Twenty-five cases of cervical scraping scraped two wipers during operation, the results were compared with conventional pathological techniques and new rapid pathological diagnosis techniques.Twenty-two cases of cervical biopsy used a new rapid pathological diagnosis technique to perform cytological diagnosis of biopsy tissue rolls in biopsy operation.According to the results of rapid pathological diagnosis, the biopsy operation plan was adjusted to analyze the clinical value of the new rapid pathological diagnosis technique in cervical lesions in primary medical institution. Results: The new rapid pathological diagnosis technology required less space and no pollution, and the diagnosis took about 2-3 min, which did not affect the normal inspection operation.Twenty-five cases of cervical scraping were produced with new rapid pathological diagnosis technique, and the quality of cervical scraping produced with conventional pathological technique was consistent, which could satisfy the needs of pathological cytological diagnosis; twenty-two cases of cervical biopsy under the vaginal device were assisted by this technology and it could increase the positive rate of the first biopsy. Conclusion Cervical scraping and cervical biopsy are still the main methods for cervical lesions examination in primary hospitals.The new rapid pathological diagnosis technology can provide the real-time pathological diagnosis of cervical scraping, improve the positive detection rate of the first biopsy of cervical biopsy, and the cost is low, suitable for promotion in primary medical institution.

Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.
Humans ; Pregnancy ; Female ; Lupus Erythematosus, Systemic/pathology* ; Signal Transduction ; N-Acetylneuraminic Acid/metabolism* ; Immunoglobulin G ; Dendritic Cells/pathology*