This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). After modeling, rats in the four groups were treated with double distilled water, SGDF suspension, and ROS suspension, respectively, by gavage every day. At the end of the 6 th week of drug administration, all the rats were sacrificed for collecting urine, blood, and kidney tissue, followed by the examination of rat general conditions, urine and blood biochemical indicators, glomerulosclerosis-related indicators, podocyte pyroptosis markers, insulin resistance(IR)-related indicators, and key molecules in the insulin receptor substrate(IRS) 1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt) signaling pathway. The results showed that SGDF and ROS improved the general conditions, some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG). Besides, they ameliorated the expression characteristics and levels of podocyte pyroptosis markers, alleviated IR, and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees. In conclusion, similar to ROS, SGDF relieves DKD by targeting multiple targets in vivo. Specifically, it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR. This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.
Animals ; Diabetes Mellitus ; Diabetic Nephropathies/drug therapy* ; Drugs, Chinese Herbal ; Insulin Resistance ; Podocytes ; Pyroptosis ; Rats

ObjectiveTo assess the diagnostic efficiency of different diffusion models （DTI， DKI and NODDI） in grading glioma and predicting IDH-1 mutation status， and to further build logistic regression prediction models. MethodsTotally 66 patients （22 females； mean age： 47.8） with pathologically proved gliomas were retrospectively included. All cases underwent bipolar spin echo diffusion examination. Parameters of DKI （MK； Ka； Kr）， DTI （MD and FA） and NODDI （intracellular volume fraction： icvf， orientation dispersion index： odi） were derived. ROIs were manually drawn and corresponding average values were calculated. Logistic regression was performed to build a predictive model. ROC curve was obtained， and Hosmer-lemeshow test was carried out to test the goodness of fit. ResultsDKI， DTI and NODDI parameters were significantly different between HGGs and LGGs （P < 0.01）. And among all diffusion parameters， a further logistic regression model for grading glioma only included age and MK， which showed the highest diagnostic value ［AUC=0.88， AUC 95%CI （0.79， 0.96）］. Hosmer-lemeshow Test present excellent of goodness of fit. With IDH-1 mutation status， NODDI showed no significant value for distinction， whereas DKI and DTI can significantly differentiate IDH-1 mutated and non-mutated glioma （P < 0.05）. Further logistic regression only selected Kr （P <0.01） in the model， which demonstrated the highest diagnostic value ［AUC=0.72， AUC 95%CI （0.59， 0.85）］. ConclusionsDKI is superior to DTI and NODDI in grading gliomas and identifying IDH-1 mutation status. The model of MK value and age variables present the best discriminatory capacity for grading glioma and Kr value may serve as a potential predictive index for identify IDH-1 mutation.

OBJECTIVE: To evaluate the value of capsule endoscopy in children with small intestinal diseases with hematochezia as the chief complaint. METHODS: A retrospective analysis was performed on the clinical data and capsule endoscopy findings of 93 children with hematochezia who were admitted to Children's Hospital of Fudan University from May 2015 to January 2019 and underwent capsule endoscopy. According to the capsule endoscopy findings of the jejunum and the ileum, they were divided into a positive lesion group with 39 patients and a negative lesion group with 54 patients. Related clinical data and the features of lesion on capsule endoscopy were analyzed for the two groups. RESULTS: There were no significant differences in age, sex, duration of capsule endoscopy, gastric transit time, and small intestinal transit time between the positive lesion and negative lesion groups (P>0.05). The positive lesion group had a significantly lower level of hemoglobin than the negative lesion group (P<0.05). Hemoglobin level was negatively correlated with the rate of positive lesions on capsule endoscopy (r=-0.342, P=0.001). Among the 39 patients with positive lesions on capsule endoscopy, the detection of Meckel's diverticulum was the highest (41%), followed by inflammatory bowel disease (21%). CONCLUSIONS Capsule endoscopy has a certain value in detecting small intestinal diseases, especially diseases in the jejunum and the ileum, in children with lower gastrointestinal hemorrhage.
Capsule Endoscopy ; Child ; Gastrointestinal Hemorrhage ; Humans ; Intestinal Diseases ; Jejunum ; Meckel Diverticulum ; Retrospective Studies

Objective: High PM concentration is the main feature of increasing haze in developing states, but information on its microbial composition remains very limited. This study aimed to determine the composition of microbiota in PM in Guangzhou, a city located in the tropics in China. Methods: In Guangzhou, from March 5 to 10 , 2016, PM was collected in middle volume air samplers for 23 h daily. The 16S rDNA V4 region of the PM sample extracted DNA was investigated using high-throughput sequence. Results: Among the Guangzhou samples, , , , , and were the dominant microbiota accounting for more than 90% of the total microbiota, and was the dominant gram-negative bacteria, accounting for 21.30%-23.57%. We examined the difference in bacterial distribution of PM between Beijing and Guangzhou at the genus level; was found in both studies, but was only detected in Guangzhou. Conclusion In conclusion, the diversity and specificity of microbial components in Guangzhou PM were studied, which may provide a basis for future pathogenicity research in the tropics.
Air Microbiology ; Air Pollutants ; analysis ; Bacteria ; classification ; isolation & purification ; China ; Cities ; Environmental Monitoring ; Microbiota ; Particle Size ; Particulate Matter ; analysis ; RNA, Bacterial ; analysis ; RNA, Ribosomal, 16S ; analysis

In order to investigate the protective effect of tanshinone ⅡA sulfonate on the sciatic nerve activty in rats after cryopreservation as well as the nerve regeneration and functional recovery after allograft and its possible mechanism, Sprague-Dawley (SD) rats were divded into four groups at different doses of tanshinone ⅡA sulfonate (A 0 mg·L⁻¹, B 80 mg·L⁻¹, C 160 mg·L⁻¹, D 480 mg·L⁻¹) cryopreserved at -80 °C for 24 weeks. Fresh control group nerve segments were harvested without cryopreservation. The ultrastructure and the viable cells of the nerve segments after cryopreservation were observed by electron microscopy, calcein-AM/propidium iodide staining, respectively. The expression of Bax and Bcl-2 was detected by Western blot. After cryopreservation, the nerve segments were cultured in vitro for one week, the mRNA and protein level of NGF and GDNF were detected by PCR and Western blot respectively. In addition, the above four cryopreserved groups transplanted to the Wistar rats by allografting (A', B', C', D'). At 16-week postoperation, muscle compound action potential latency and nerve conduction velocity were examined by electrophysiological. The number and the thickness of myelinated nerve fibers were analyzed by toluidine blue staining. The ultrastructure of the sciatic nerve by electron microscopy was observed. According to the results, after the cryopreserved for 24 weeks, compared with groups A and B, the nerve demyelination and vacuolation were weak, and the more viable cells, the decreased Bax and increased Bcl-2, the increased NGF and GDNF in group C and D. At 16-week poseoperation, the results demonstrated that the more larger and thickly regenerated myelinated axons, the shorter latency of muscle compound action potentials and higher nerve conduction velocity in groups C' and D' compared with groups A' and B'. According to these results, tanshinone ⅡA sulfonate exerted a significant protective effect on the viability of the nerves during cryopreservation at -80 °C and promoted nerve regeneration and functional recovery after transplantation especially in middle- and high-dose of tanshinone ⅡA sulfonate.

This paper was aimed to investigate the effects of emodin on oxidative stress and inflammatory response in rats with acute spinal cord injury（SCI）, and to explore the protective mechanism of emodin on neurons after SCI. Rat SCI models were established using a modified Allen's method. One hundred and ninety five Sprague-Dawley rats were randomly divded into sham (group A), model (group B), emodin group of 20 mg·kg⁻¹(group C), emodin group of 40 mg·kg⁻¹(group D), emodin group of 80 mg·kg⁻¹(group E). Functional recovery was evaluated using the Basso-Beattie-Bresnahan (BBB) scale and inclined plate test on the 3rd, 7th, 14th and 28th day. On the 7th day after SCI, neuron nylon body was observed with toluidine blue staining. The changes of myelinated nerve fibers were observed by transmission electron microscope. Nrf2, HO-1, NQO1, GFAP, NF-κB protein were detected by Western blot. The content of TNF-α, IL-1β, IL-6 were detected by ELISA. Immunofluorescence staining was performed to observe the expression of the GFAP, NG2 and ED-1. The BBB and inclined plate scores of group C, D and E were higher than group B on the 7th, 14th, 28th day,the difference was statistically significant (<0.05). On the 7th day, Nylon Body of group B and C started to fuse,the fusion of group D and E were significantly alleviated than group B and C. Transmission electron microscope showed that the changes of demyelination were obvious in group B and C, group D and E were significantly improved than group B and C. Western blot showed that Nrf2, HO-1, GFAP, NF-κB protein expression,group C, D, E compared with group B, NQO1 protein expression, group D, E compared with group B, the difference was statistically significant (<0.05). ELISA showed that the content of TNF-α, IL-6,group C, D, E compared with group B,the content of IL-1β,group D, E compared with group B, the difference was statistically significant (<0.05)；Immunofluorescence showed that the expressions of GFAP and NG2 in group C, D and E were higher than that in group B, and the group D and E were more obvious. The expression of ED-1 in group C, D, E were decreased significantly compared with group B. Emodin has protective effect on neurons after SCI. The mechanism may connect with activting Nrf2-ARE pathway, reducing the expression of NF-κB, ED-1, TNF-α, IL-1β, IL-6, and promoting the expression of GFAP and NG2.

Objective To investigate the effect of emodin on spinal cord edema induced by acute spinal cord injury (SCI) and its mechanism. Methods A total of 180 healthy female Sprague-Dawley rats were randomly divided into sham group(group A),model group(group B),and low-dose group(group C),middle-dose group(group D)and high-dose group(group E)of emodin,with 36 cases in each group.The SCI model was established with the modified Allen's method.Function-al recovery was evaluated with Basso-Beattie-Bresnahan(BBB)score and inclined plate test three days,seven days,14 days and 28 days after modeling.Three days after modeling,the pathological changes of the spinal cord were observed by HE staining; the water content of spinal cord was detected by dry-wet weight method, the blood-spinal cord barrier(BSCB)permeability was detected by Evans blue(EB)staining,and the expression of aquaporin-4 (AQP-4) and matrix metalloproteinase-2 (MMP-2) mRNA and protein were detected by RT-PCR and Western blotting respectively.Results The BBB score and inclined plate scores were better in groups C,D and E than in group B(P<0.05)seven days, 14 days and 28 days after modeling, especially in group E (P<0.05). Three days after modeling, HE staining showed that there was a large hemorrhage in the section of group B,the nerve cells were swollen and damaged, and a large number of inflammatory cells were infiltrated,the tissue gap was widened and the edema was severe. The above pathological changes were better in groups C,D and E than in group B,especially in group E.The spi-nal cord water content was higher in group B than in group A(P<0.05),and was lower in groups D and E than in groups B and C(P<0.05).EB content was higher in group B than in group A(P<0.05),and was lower in groups C, D and E than in group B (P<0.05). The expression of AQP-4, MMP-2 mRNA and protein were lower in groups C,D and E than in group B(P<0.05),especially in group E(P<0.05). Conclusion Emodin can alleviate spinal cord edema,and improve hind limb movement function after SCI,which could be related with the down-regulation of AQP-4 and MMP-2 expression,and the reduction of the permeability of BSCB.

Objective To investigate the effect of cold-inducible RNA binding protein(CIRP)on the viability of cryopreserved sciat-ic nerve and nerve regeneration after allograft. Methods Sciatic nerve segments of 15 mm from male Sprague-Dawley rats were placed in DMEM solution and pretreat-ed with 4 ℃, 15 ℃ and 32 ℃ for 24 hours (group A, group B and group C, respectively). Fresh nerve group (group D)without pretreatment was set up.The mRNA and protein level of CIRP was detected by RT-PCR and Western blotting,respectively.The above nerves were cryopreserved in liquid nitrogen for four weeks.The via-ble cells of the nerve segments after cryopreservation were observed by calcein-AM/propidium iodide staining. The expression of Bax and Bcl-2 was detected by Western blotting.After cryopreservation,the nerve segments were cultured in vitro for one week, the protein level of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor(GDNF)was detected by Western blotting.In addition,the above four cryopreserved groups were transplanted to the Wistar rats by allografting(groups A',B',C'and D').Fresh nerve allograft group(E')and isograft group(F')were set up.At four-week post operation,the expression of CD4of the nerve and plasma level of interleukin(IL)-6 and interferon(IFN)-γ were detected by immunohistochemistry and ELISA,respectively.At 20-week postoperation, the muscle compound action potential (CMAP) and motor nerve conduction velocity (MNCV) were examined by electrophysiological examination. The number and the thickness of myelinated nerve fibers were analyzed by toluidine blue staining. The ultrastructure of the sciatic nerve was observed by electron microscopy. Results The mRNA and protein of CIRP were significantly higher in group C than in groups A and B(P<0.05).After 4 weeks of cryopreservation,compared with groups A,B and D,the viable cells increased,the expression of Bax decreased and the expression of Bcl-2 increased in group C (P<0.05). The expression of NGF and GDNF in-creased in group C than in groups A and B(P<0.05).At four-week postoperation,the expression of CD4and plas-ma concentration of IL-6 and IFN-γ significantly decreased in group C'than in group E'(P<0.05),however,no significant difference was found in group C'compared with groups D'and F'(P>0.05).At 20-week postopera-tion, CMAP, MNCV, the number of axon, and thickness of myelin sheath were significantly better in group C' than in groups A',B',D'and E'(P<0.05).Compared with groups A',B',D'and E',the myelinated nerve fibers were more, the fiber thickness was more uniform, the fiber distribution was wider, and the myelin sheath was thicker in groups C'and F'. Conclusion CIRP was induced at 32℃in the sciatic nerve,which exerted a significant protective effect on the viability of the nerves during cryopreservation,and promoted nerve regeneration and functional recovery after transplanta-tion.

The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP). We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality (CSM) in patients with ≥15% CRMP4 methylation were 6.81 (95% CI: 2.34-19.80) and 12.83 (95% CI: 2.16-26.10), respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels ≥15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ≥6 and CRMP4 methylation levels ≥15% were independent predictors of these outcomes (uni- and multi-variable Cox regression analyses). The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ≥15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.
Aged ; Androgen Antagonists/therapeutic use* ; Biomarkers, Tumor/blood* ; Female ; Hormone Replacement Therapy ; Humans ; Male ; Methylation ; Middle Aged ; Muscle Proteins/metabolism* ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Progression-Free Survival ; Prostatectomy ; Prostatic Neoplasms/metabolism* ; Retrospective Studies ; Risk Assessment ; Treatment Outcome

Chemical constituents in extract of Scrophulariae Radix and their metabolites in rat plasma after oral administration were identified by HPLC-LTQ-Orbitrap. Samples were separated by a Venusil MP C₁₈ column using a binary gradient elution. The information on the total ion chromatogram, the extraction chromatogram and the mass spectrogram in a negative mode were synthetically analyzed by comparing the retention time, MS and MS/MS spectra with literature data and some of reference standards to conduct a qualitative study on constituents of Radix Scrophulariae extract in vivo and in vitro. Totally 37 compounds from Scrophularia ningpoensis extract were detected including 12 iridoid glycosides, 20 phenylpropanoids and 5 unknown compounds. In vivo, harpagide, harpagoside and angoroside C were confirmed to enter into the blood in prototype forms. Besides, another 2 prototype compounds and 2 metabolites were detected in rat plasma after oral administration of S. ningpoensis extract. The results are beneficial for the determination of bioactive substances of S. ningpoensis and significant for further studies on S. ningpoensis.