Preparation and Application of Monoclonal Antibody Against Human von Willebrand Factor Propeptide / 中国实验血液学杂志

OBJECTIVE@#To develop monoclonal antibodies that can specifically recognize human von Willebrand factor (VWF) propeptide (VWFpp) in plasma, and establish a rapid and reliable method for the detection of VWFpp antigen in plasma by using the double-antibody sandwich ELISA with the obtained anti-VWFpp monoclonal antibody.@*METHODS@#The recombinant human VWFpp (D1 and D2 regions) protein expressed in eukaryotic cells was used as immunogen to immunize BALB/c mice with routine method, so as to obtain clones of fusion cells. After screening and identification, hybridoma cell lines secreting monoclonal antibodies against VWFpp were selected, and then double-antibody sandwich ELISA assay was used to construct VWFpp antigen detection kit for the determination of VWFpp in human plasma. The levels of VWFpp antigen in plasma of 12 leukemia patients who underwent bone marrow transplantation were dynamically detected.@*RESULTS@#Two hybridoma cell lines that can be subcultured continuously and secrete monoclonal antibodies against VWFpp were obtained and named SZ175 and SZ176 respectively. Identified by ELISA and Western blot, the antibodies could both specifically recognize VWFpp but couldn't recognize mature VWF (without propeptide). Based on the principle of double-antibody sandwich ELISA, monoclonal antibodies SZ175 and SZ176 were successfully made into a kit for detecting VWFpp antigen. The plasma VWFpp levels of leukemia patients before and after bone marrow transplantation were dynamically detected. The results showed that the plasma VWFpp levels of the patients after transplantation were significantly higher than those before transplantation.@*CONCLUSION@#Two monoclonal antibodies against VWFpp were successfully prepared, and a double-antibody sandwich ELISA detection kit for VWFpp antigen was constructed, which provides a powerful tool for further study on the biological function of VWFpp, the clinical diagnosis and classification of von Willebrand disease (VWD), and the prognostic monitoring of endothelial injury-related diseases.

Protective effects of three kinds of borneol on different brain regions in acute cerebral ischemia/reperfusion model rats / 中国中药杂志

This study compared the ameliorating effects of L-borneol, natural borneol, and synthetic borneol on the injury of different brain regions in the rat model of acute phase of cerebral ischemia/reperfusion(I/R) for the first time, which provides a reference for guiding the rational application of borneol in the early treatment of ischemic stroke and has important academic and application values. Healthy specific pathogen-free(SPF)-grade SD male rats were randomly assigned into 13 groups: a sham-operation group, a model group, a Tween model group, a positive drug(nimodipine) group, and high-, medium-, and low-dose(0.2, 0.1, and 0.05 g·kg~(-1), respectively) groups of L-borneol, natural borneol, and synthetic borneol according to body weight. After 3 days of pre-administration, the rat model of I/R was established by suture-occluded method and confirmed by laser speckle imaging. The corresponding agents in different groups were then administered for 1 day. The body temperature was monitored regularly before pre-administration, days 1, 2, and 3 of pre-administration, 2 h after model awakening, and 1 d after model establishment. Neurological function was evaluated based on Zea-Longa score and modified neurological severity score(mNSS) 2 h and next day after awakening. The rats were anesthetized 30 min after the last administration, and blood was collected from the abdominal aorta. Enzyme-linked immunoassay assay(ELISA) was employed to determine the serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-4, and transforming growth factor-beta1(TGF-β1). The brain tissues were stained with triphenyltetrazolium chloride(TTC) for the calculation of cerebral infarction rate, and hematoxylin-eosin(HE) staining was used for observing and semi-quantitatively evaluating the pathological damage in different brain regions. Immunohistochemistry was employed to detect the expression of ionized calcium binding adapter molecule 1(IBA1) in microglia. q-PCR was carried out to determine the mRNA levels of iNOS and arginase 1(Arg1), markers of polarization phenotype M1 and M2 in microglia. Compared with the sham-operation group, the model group and the Tween model group showed significantly elevated body temperature, Zea-Longa score, mNSS, and cerebral infarction rate, severely damaged cortex, hippocampus, and striatum, increased serum levels of IL-6 and TNF-α, and decreased serum levels of IL-4 and TGF-β1. The three borneol products had a tendency to reduce the body temperature of rats 1 day after modeling. Synthetic borneol at the doses of 0.2 and 0.05 g·kg~(-1), as well as L-borneol of 0.1 g·kg~(-1), significantly reduced Zea-Longa score and mNSS. The three borneol products at the dose of 0.2 g·kg~(-1) significantly reduced the cerebral infarction rate. L-borneol at the doses of 0.2 and 0.1 g·kg~(-1) and natural borneol at the dose of 0.1 g·kg~(-1) significantly reduced the pathological damage of the cortex. L-borneol and natural borneol at the dose of 0.1 g·kg~(-1) attenuated the pathological damage of hippocampus, and 0.2 g·kg~(-1) L-borneol attenuated the damage of striatum. The 0.2 g·kg~(-1) L-borneol and the three doses of natural borneol and synthetic borneol significantly reduced the serum level of TNF-α, and the 0.1 g·kg~(-1) synthetic borneol reduced the level of IL-6. L-borneol and synthetic borneol at the dose of 0.2 g·kg~(-1) significantly inhibited the activation of cortical microglia, and 0.2 g·kg~(-1) L-borneol up-regulated the expression of Arg1 and down-regulated the expression level of iNOS. In conclusion, the three borneol products may alleviate inflammation to ameliorate the pathological damage of brain regions of rats in the acute phase of I/R by inhibiting the activation of microglia and promoting the polarization of microglia from M1 type to M2 type. The protective effect on brain followed a trend of L-borneol > synthetic borneol > natural borneol. We suggest L-borneol the first choice for the treatment of I/R in the acute phase.

Causality between type 2 diabetes mellitus and age-related macular degeneration: a Mendelian randomization study / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the causality between type 2 diabetes mellitus(T2DM)and age-related macular degeneration(ARMD)based on two-sample Mendelian randomization(MR).METHODS: T2DM and ARMD samples were extracted from the FinnGen database. Inverse variance weighted(IVW)was used as the main analysis method, MR-Egger and weighted median(WM)as supplementary methods to analyze the potential relationship between them. In addition, Cochran Q test and MR-Egger intercept were also used to analyze the sensitivity, and the P-value was used as the index of research results.RESULTS: IVW showed that T2DM was associated with the incidence of exudative ARMD(OR=1.14, 95%CI 1.01～1.28, P=0.021), but it was not significantly associated with the incidence of atrophic ARMD(OR=0.96, 95%CI 0.86～1.07, P=0.554). The results of sensitivity analysis confirmed that there was no heterogeneity and pleiotropy in this study, and the results were reliable.CONCLUSION: There is a causal relationship between T2DM and exudative ARMD. Considering the high rate of blindness caused by ARMD, it is of great significance to recognize and control the risk factors of ARMD to reduce its prevalence rate and early diagnosis and treatment.

Sensitizing effect of d-borneol on cisplatin-resistant NSCLC based on transcriptomics and its mechanism / 中国药理学通报

Aim To explore the key targets of d-borneol combined with eisplatin for sensitization of cisplatin-resistant NCSLC cells by RNA-Seq and verify its mechanism. Methods Cisplatin-resistant human large cell lung cancer cells (H460/CDDP) were inoculated into the right armpit of male BALB/c nude mice (4 weeks old) to construct a xenograft tumor model. Then they were randomly divided into control group, vehicle group, eisplatin group, and combination group (d-borneol + eisplatin) with 6 nude mice and treated for 14 d. After last administration of 24 h, the tumor tissue was taken for RNA-Seq. And then real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were used to verify the expression of cell cycle-related molecules. Results RNA-seq analysis showed that there were significant differences in gene expression between the eisplatin group and combined group, and they were significantly enriched in cell cycle. RT-PCR and IHC results showed that d-borneol combined with eisplatin could significantly inhibit the expressions of cyclins (cyclin A2, cyclin D3) and cyclin-dependent kinases (CDK2, CDK6) and promote the expression of its upstream molecular cyclin-dependent kinase inhibitor CD-KI (P21, P27) (P<0. 05, P<0.01). Conclusions d-Borneol increases the sensitivity of eisplatin by increasing the expression of P21 and P27 and inhibiting the expression of cyclinA2/D3 and CDK2/6 to induce cell cycle arrest and inhibit the malignant proliferation of H460/CDDP cells, thereby achieving the effect of anti-drug sensitization.

Effects of early life PM2.5 exposure on prefrontal cortex of offspring male rats / 中国应用生理学杂志

Objective: To investigate the effects of PM2.5 exposure at different stages of early life on the prefrontal cortex of offspring rats. Methods: Twelve pregnant SD rats were randomly divided into four groups: Control group (CG), Maternal pregnancy exposure group (MG), Early postnatal exposure group (EP) and Perinatal period exposure group (PP), 3 rats in each group. The pregnant and offspring rats were exposed to clean air or 8-fold concentrated PM2.5. MG was exposed from gestational day (GD) 1 to GD21. EP was exposed from postnatal day (PND) 1 to PND21, and PP was exposed from GD1 to PND21. After exposure, the prefrontal cortex of 6 offspring rats in each group was analyzed. HE staining was used to observe the pathological damage in the prefrontal cortex. ELISA was employed to detect neuroinflammatory factors, and HPLC/MSC was applied to determine neurotransmitter content. Western blot and colorimetry were applied for detecting astrocyte markers and oxidative stress markers, respectively. Results: Compared with MG and CG, the pathological changes of prefrontal cortex in PP and EP were more obvious. Compared with MG and CG, the neuroinflammatory factors (IL-1, IL-6, TNF-α) in PP and EP were increased significantly (P＜0.01), the level of MT were decreased significantly (P＜0.05), and the level of oxytocin (OT) showed a downward trend; the level of neurotransmitter ACh was also increased significantly (P＜0.01). Compared with MG and CG, the GFAP level of PP and EP showed an upward trend, the level of oxidative stress index SOD in PP and EP was decreased significantly (P＜0.01), and the level of ROS was increased significantly (P＜0.01). Compared with the offspring rats of CG and MG, the CAT level of PP was decreased significantly (P＜0.01, P＜0.05). Compared with the offspring rats of CG, the CAT level of EP was decreased significantly (P＜0.05). There was no significant difference in IL-1, IL-6, TNF-α, MT, OT, ACh, GFAP, SOD, ROS and CAT levels between PP and EP, or MG and CG. Conclusion: PM2.5 exposure in early life has adverse effects on the prefrontal cortex of offspring male rats, and early birth exposure may be more sensitive.

Low-frequency pulsed electromagnetic fields promote osteoblast mineralization and maturation of rats through the PC2/sAC/PKA/CREB signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore whether the effect of low-frequency pulsed electromagnetic fields (PEMFs) in promoting osteoblast mineralization and maturation is related to the primary cilia, polycystin2 (PC2) and sAC/PKA/CREB signaling pathway.@*METHODS@#We detected the expression levels of PC2, sAC, PKA, CREB and their phosphorylated proteins in primary rat calvarial osteoblasts exposed to 50 Hz 0.6 mT PEMFs for 0, 5, 15, 30, 60, 90, and 120 min. We blocked PC2 function with amiloride hydrochloride and detected the changes in the activity of sAC/PKA/CREB signal pathway and the mineralization and maturation of the osteoblasts. These examinations were repeated in the osteoblasts after specific knockdown of PC2 via RNA interference and were the co-localization of PC2, sAC, PKA, CREB and their phosphorylated proteins with the primary cilia were using immunofluorescence staining. The expressions of PC2 and the signaling proteins of sAC/PKA/CREB pathway were detected after inhibition of primary ciliation by RNA interference.@*RESULTS@#The expression levels of PC2, sAC, p-PKA and p- CREB were significantly increased in the osteoblasts after exposure to PEMFs for different time lengths (P < 0.01). Blocking PC2 function or PC2 knockdown in the osteoblasts resulted in failure of sAC/PKA/CREB signaling pathway activation and arrest of osteoblast mineralization and maturation. PC2, sAC, p-PKA and p-CREB were localized to the entire primary cilia or its roots, but PKA and CREB were not detected in the primary cilia. After interference of the primary cilia, PEMFs exposure no longer caused increase of PC2 expression and failed to activate the sAC/PKA/CREB signaling pathway or promote osteoblast mineralization and maturation.@*CONCLUSION@#PC2, located on the surface of the primary cilia of osteoblasts, can perceive and transmit the physical signals from PEMFs and promote the mineralization and maturation of osteoblasts by activating the PC2/ sAC/PKA/CREB signaling pathway.

Effects of rosin diglucoside on bone metabolism in young rats / 中国药理学通报

Aim To research the effect of PDG on bone metabolism in young rats. Methods The experimental rats were randomly divided into contro group, PDG-25 group and PDG-50 group. PDG-25 group and PDG-50 group were given PDG at the dose of 25 mg·kg

Panax japonicus and chikusetsusaponins: A review of diverse biological activities and pharmacology mechanism / 中草药·英文版

Panax japonicus, which in the Tujia dialect is known as “Baisan Qi” and “Zhujieshen”, is a classic “qi” drug of Tujia ethnomedicine and it has unique effects on disease caused by “qi” stagnation and blood stasis. This paper serves as the basis of further scientific research and development of Panax japonicus. The pharmacology effects of molecular pharmacology were discussed and summarized. P. japonicus plays an important role on several diseases, such as rheumatic arthritis, cancer, cardiovascular agents, and this review provides new insights into P. japonicus as promising agents to substitute ginseng and notoginseng.

Short-term outcomes of single incision plus one port laparoscopic surgery for colorectal cancer / 中华胃肠外科杂志

Objective: Although single port laparoscopic surgery has achieved good clinical results, many surgeons are discouraged by the difficulties of operation, conflict of instruments, lack of antagonistic traction, and straight-line perspective. Therefore, some surgeons have proposed a single incision plus one hole laparoscopic surgery (SILS+1) surgical method. This study explored the safety and feasibility of SILS+1 for radical resection of colorectal cancer. Methods: A descriptive cohort study was carried out. The clinical data, including the operation, pathology and recovery situation, of 178 patients with colorectal cancer undergoing SILS+1 at Department of General Surgery, Nanfang Hospital, Southern Medical University from March 2018 to January 2019 were prospectively collected and retrospectively analyzed. Clavien-Dindo criteria was used for postoperative complication evaluation and visual analog scale was used for pain standard. Follow-up studies were conducted through outpatient service or telephone and the follow-up period was up to May 2019. Results: A total of 178 patients with colorectal cancer underwent SILS+1, including 111 male patients (62.4%) with an average age of 59 years. Eleven (6.2%) patients received added 1-3 operation ports during operation, and 1 patient was converted to open surgery due to ileocolic artery hemorrhage. The operative time was (135.2±42.3) minutes. The intraoperative blood loss was (34.6±35.5) ml. The number of harvested lymph nodes was 33.1±17.6. The distal margin was (4.7±17.8) cm. The proximal margin was (10.2±5.3) cm. Operation-related complications were observed in 16 patients (9.0%) within 30 days after the operation, of whom 6 had Clavien-Dindo III complications (3.4%). The postoperative pain scores were lower than 3. The average postoperative hospital stay was (5.6±2.6) days. Three patients (1.7%) returned to hospital within 30 days after operation due to intestinal obstruction and infection around stoma. The cosmetic evaluation of all the patients was basically satisfied. Conclusion: SILS+1 is safe and feasible in the treatment of colorectal cancer, and can reduce the postoperative pain.

Resting-state fMRI study of hippocampus in patients with Crohn′s disease / 中华全科医师杂志

Fifteen patients with Crohn′s disease (CD) in remission diagnosed at Shanghai Jing′an District Central Hospital from February 2018 to June 2019, and 26 matched healthy subjects were recruited. All participants underwent resting-state functional magnetic resonance imaging (fMRI) scans of hippocampus. The amplitude of low-frequency fluctuations (ALFF) was calculated to determine differences in the brain. Left hippocampus was selected as seeds for functional connectivity (FC) analysis, and the results were compared between two groups. The relationship between disease duration and ALFF/FC values in abnormal regions were analyzed with Pearson correlation. Compared with the controls, the ALFF of the left hippocampus (voxel size 32) of CD patients decreased [family-wise error correstion(FWE correction), cluster level P<0.05], and the ALFF of the left medial superior frontal gyrus (voxel size 126), left supplementary motor area (voxel size 126) and left anterior cingulate gyrus increased (voxel size 37) (FWE corrected, cluster level P<0.05). Using the left hippocampus as the seed point for the whole brain functional connectivity analysis, CD patients showed increased FC strength with the left superior temporal gyrus, left medial superior frontal gyrus, left inferior frontal gyrus (opercular part), and right supplementary motor area(FEW corrected, cluster level P<0.05). Correlation analysis did not show a significantly differences between ALFF/FC value of altered brain areas and the disease duration. It suggests that there are changes in spontaneous activities and functional connectivity in the left hippocampus in patients with CD.

Hepatic protective effects of Shenling Baizhu powder, a herbal compound, against inflammatory damage via TLR4/NLRP3 signalling pathway in rats with nonalcoholic fatty liver disease / 中西医结合学报

OBJECTIVE@#High-fat diet (HFD) and inflammation are two key contributors to nonalcoholic fatty liver disease (NAFLD). Shenling Baizhu powder (SLBZP), a classical herbal compound, has been successfully used to alleviate NAFLD. However, its specific mechanisms are not fully understood. In this study, we assessed the anti-NAFLD effect of SLBZP in vivo.@*METHODS@#Rats were fed an HFD with or without SLBZP or with probiotics. At the end of week 16, an echo magnetic resonance imaging (EchoMRI) body composition analyser was used to quantitatively analyse body composition; a micro-computed tomography (micro-CT) imaging system was used to evaluate whole body and liver fat; and the Moor full-field laser perfusion imager 2 was used to assess liver microcirculation, after which, all rats were sacrificed. Then, biochemical indicators in the blood and the ultrastructure of rat livers were evaluated. Protein expression related to the liver Toll-like receptor 4 (TLR4)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) signalling pathway was assessed using Western blot analysis. Further, high-throughput screening of 29 related inflammatory factors in liver tissue was performed using a cytokine array.@*RESULTS@#SLBZP supplementation reduced body weight, serum free fatty acid, and insulin resistance index (P < 0.05). It also ameliorated liver microcirculation and ultrastructural abnormalities. EchoMRI and micro-CT quantitative analyses showed that treatment with SLBZP reduced fat mass and visceral fat (P < 0.05 and P < 0.01, respectively). In addition, SLBZP decreased the expression of lipopolysaccharide (LPS)-activated TLR4/NLRP3 signalling pathway-related proteins and altered the expression levels of some inflammatory cytokines in liver tissues.@*CONCLUSION@#SLBZP can inhibit NLRP3 inflammasome activation and interleukin-1β release by suppressing LPS-induced TLR4 expression in rats with HFD-induced NAFLD. Thus, SLBZP may be beneficial for the prevention and treatment of inflammatory damage and associated diseases.

Anti-inflammatory Effect of Gentiopicroside in Adjuvant-induced Arthritis Rats / 中国实验方剂学杂志

Objective::To study the therapeutic and inflammatory effects of gentiopicroside(GPS) on adjuvant-induced arthritis (AA) rats. Method::The 36 male SD rats were randomly divided into six groups, namely the model group, GPS groups (low, medium and high dose), and the methotrexate (MTX) group, with six rats in each group. AA rats were induced through intradermal injection with 0.1 mL complete Freund's adjuvant (CFA) into the right hind paw, except the normal group. After modeling, rats in each group were treated with drugs for 7 days, once a day. The doses were 30, 60, 120 mg·kg-1 in the GPS groups, and 0.2 mg·kg-1 in the MTX group. The normal group and the model group were intragastrically treated with the same volume of normal saline. During the experiment, the paw thickness and paw volume of rats were recorded everyday by the digital vernier calipers and the toe volume measuring instrument. On the seventh day, X-ray and histopathological examination of the ankle joints were performed by the small animal living imaging instrument and hematoxylin eosin stain. Blood samples were collected from the abdominal aorta at the end of the experiment to determine the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in serum by enzyme-linked immunosorbent assay(ELISA) kits. The mRNA levels of IL-6 and TNF-α in synovial tissues were determined by Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR). Result::Compared with the normal group, the results of each index in the model group were significantly different (P<0.01). Compared with the model group, the results of paw volume and paw thickness decreased significantly (P<0.01), TNF-α level decreased significantly (P<0.01), and IL-6 and TNF-α mRNA levels decreased significantly (P<0.05, P<0.01) in drug treated groups. The results of X-ray and histopathological examinations indicated that GPS had a protective effect on the ankle joints of AA rats. Conclusion::GPS has the therapeutic effect on AA rats by inhibiting levels of proinflammatory cytokines in serum and relevant mRNA levels in synovial tissues.

Central visual function and inner retinal structure in primary open-angle glaucoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

To investigate associations between central visual function and inner retinal structure in primary open-angle glaucoma (POAG). This study enrolled 78 POAG patients and 58 healthy controls. POAG was classified into early glaucoma and moderate to advanced glaucoma. The following tests were performed on all participants: isolated-check visual evoked potential (icVEP) testing, 24-2 standard automated perimetry (SAP), and Cirrus optical coherence tomography (OCT) examinations. Signal-to-noise ratio (SNR) measures obtained from icVEP responses to isolated checks presented at four depths of modulation (DOMs; 8%, 14%, 22%, and 32%) were explored. Mean macular sensitivity (mMS) was assessed by calculating the mean sensitivities of central 12 SAP points. Ganglion cell layer+ inner plexiform layer thickness (GCL+IPLT) and peripapillary retinal nerve fiber layer thickness (pRNFLT) were measured by OCT scanning. For each group of subjects, linear relationships among the following measures were analyzed: SNR, mMS, GCL+IPLT, and pRNFLT. SNR, mMS, GCL+IPLT, and pRNFLT were all more significantly decreased in glaucoma than in controls (P<0.001). A significant positive association was found between SNR at 14% DOM and GCL+IPLT at the inferior sector in early glaucoma (r=0.465, P=0.004). In moderate to advanced glaucoma, significant correlations were found between SNR at 32% DOM and mean GCL+IPLT (r=0.364, P=0.023), superior GCL+IPLT (r=0.358, P=0.025), and mean pRNFLT (r=0.396, P=0.025). In addition, in moderate to advanced glaucoma, there were significant correlations between mMS and all relevant measures of retinal thickness (r=0.330-0.663, P< 0.010). In early glaucoma, significant correlations were found between mean mMS and minimum GCL+IPLT (r=0.373, P=0.023), and between inferior mMS and superior GCL+IPLT (r=0.470, P=0.003). Linear models provided a good explanation for the relationship between SNR and inner retinal thickness (IRT), whereas nonlinear models better explained the relationship between mMS and IRT. In early glaucoma, both SNR and mMS were related moderately and significantly to IRT, whereas in moderate to advanced glaucoma, mMS was more strongly correlated with IRT than SNR.

Effect of Compatibility of Alcohol Extract of Magnoliae Officinalis Cortex and Alcohol Extract of Polygalae Radix on Fecal Metabolites of Rats / 中国实验方剂学杂志

Objective:To investigate the effect of alcohol extract of Magnoliae Officinalis Cortex,alcohol extract of Polygalae Radix and their compatibility on fecal metabolites of rats,analyze its potential metabolic pathways,and provide experimental basis for exploring the possible mechanism of Magnoliae Officinalis Cortex relieving gastrointestinal motility disorders induced by Polygalae Radix. Method:Forty male SD rats were randomly divided into the normal group,alcohol extract of Magnoliae Officinalis Cortex group(3.50 g·kg-1),alcohol extract of Polygalae Radix group(1.75 g·kg-1) and compatibility group (3.5 g·kg-1 of alcohol extract of Magnoliae Officinalis Cortex+1.75 g·kg-1 of alcohol extract of Polygalae Radix).Fecal samples were collected within 24 h after continuous gavage for 3 days.The fecal metabolites in each group was detected by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS),mobile phase was acetonitrile-0.1%formic acid solution for gradient elution,data collection range was m/z 50-1 200 under positive and negative ion mode of electrospray ionization.The characteristic biomarkers and corresponding metabolic pathways were analyzed or screened by Progenesis QI v2.0,SIMCA-P 14.0,SPSS 20.0,MetaboAnalyst 4.0 and other softwares. Result:A total of 17 characteristic metabolic markers were screened out,including 5-formiminotetrahydrofolic acid,L-3-hydroxykynurenine,7,8-dihydropteroic acid,etc.The main related pathways included biosynthesis of unsaturated fatty acids,linoleic acid metabolism,vitamin B6 metabolism,etc. Conclusion:The mechanism of Magnoliae Officinalis Cortex relieving gastrointestinal motility disorders induced by Polygalae Radix may be related to purine metabolism,folate biosynthesis,tryptophan metabolism and primary bile acid biosynthesis.

Effect of Recombinant Protein in the Spacer Domain on ADAMTS13 Activity / 中国实验血液学杂志

OBJECTIVE@#To obtain the recombinant protein of spacer domain in von Willebrand factor cleaving protease (ADAMTS13), and further study its biological function in ADAMTS13.@*METHODS@#The prokaryotic expression vector was constructed by using the template of plasmid with full-length ADAMTS13, and then transfected into E coli., following the induction of IPTG with the low temperature (30 ℃). The recombinant protein was purified with Ni-NTA agarose column by gradient imidazole. The purity and immune activity of purified products were identified with SDS-PAGE and Western blot respectively. By Adding the recombinant protein to the plasma of immune-mediated thrombotic thrombocytopenic purpura (iTTP) patients, the activity of ADAMTS13 was tested.@*RESULTS@#The prokaryotic expression vector was successfully constructed and the protein of spacer domain with the high purity was obtained. Western blot showed that the recombinant fragment could both react with monoclonal antibody against 6×His and polyclonal sheep IgG against ADAMTS13 (Gln34-Trp688). The protein formed a main lane at the position of 15 kDa with SDS-PAGE. It was demonstrated that the recombinant protein could efficiently elevate the ADAMTS13 activity in plasma of iTTP patients to reach normal level by functional experiment.@*CONCLUSION@#The recombinant protein has high purity and immune activity, which provides the experimental basis for further research on mechanism of iTTP involved in spacer domain.

Analysis of urinary iodine in pregnant women with thyroid disease in Shenzhen / 中华地方病学杂志

Objective@#To study the urinary iodine level of pregnant women with thyroid disease in Shenzhen, and to provide scientific basis for rational iodine supplementation.@*Methods@#A total of 170 pregnant women with thyroid diseases who visited Department of Endocrinology, Peking University Shenzhen Hospital from January 2017 to March 2019 were selected as the subjects, they were divided into hyperthyroidism group (84 cases) and non-hyperthyroidism group (86 cases) according to whether they had hyperthyroidism or not. Morning urine sample was collected under normal dietary conditions; urinary iodine was detected by peroxyacetic acid tetramethylbenzidine oxidation colorimetry. Urinary iodine < 150 μg/L was iodine deficiency and 150-249 μg/L was appropriate iodine.@*Results@#The median of urinary iodine of pregnant women with thyroid disease in Shenzhen was 143.9 μg/L, which was slightly lower than the lowest limit of the appropriate iodine level. The median of urinary iodine in hyperthyroidism group was 116.6 μg/L, which was at the iodine deficiency level; the median of urinary iodine in non-hyperthyroidism group was 181.6 μg/L, which was at the appropriate iodine level. There was significant difference in urinary iodine levels between hyperthyroidism group and non-hyperthyroidism group (Z =-2.261, P < 0.05).@*Conclusion@#The urinary iodine of pregnant women with hyperthyroidism in Shenzhen is slightly low.

Effects of Kuntai capsule on GnRH-a-induced perimenopause symptoms:a prospective randomized controlled study / 中国实用妇科与产科杂志

OBJECTIVE: To evaluate the effect of Kuntai capsule on the gonadotrophin releasing hormone agonist(GnRH-a)-induced perimenopaus symptoms and the sex hormone levels.METHODS: A total of 99 patients with uterine fibroids,adenomyosis or moderate to severe endometriosis who needed the treatment of GnRH-a at Sun Yat-sen Memorial Hospital of Sun Yat-sen University from June 2015 to March 2016 were collected and randomly divided into research group(Kuntai capsule)and control group(Tibolone). GnRH-a was injected once every 28 days and first injection of GnRH-a was administered on the 2 nd to 4 th day of menstrual period or retraction bleeding after surgery.Kuntai capsule or Tibolone was orally taken beginning from the first GnRH-a injection,and the co-administration of Caltrate D-600 and alfacalcidol was given in both groups.The Kupperman scores,sex hormone levels including folliclestimulating hormone(FSH)and estrogen(E_2),and adverse events were recorded.RESULTS: Kuntai capsule kept the perimenopause symptoms at mild level with the slow increase of Kupperman scores,whose effect was significantly superior to Tibolone(P<0.05)after 8 weeks of treatment,especially in paresthesia,nervousness,and formication.The FSH and E_2 levels in both Kuntai and Tibolone groups were obviously decreased when compared with the pre-treatment(P<0.05),and these hormone levels in Kuntai group were comparable to those in Tibolone group.No adverse events occurred in either group. CONCLUSION: In the short-term treatment of GnRH-a,Kuntai capsule exhibits significant alleviating effects on perimenopause symptoms caused by GnRH-a with high safety and few adverse reactions.

Analysis of urinary iodine in pregnant women with thyroid disease in Shenzhen / 中华地方病学杂志

Objective To study the urinary iodine level of pregnant women with thyroid disease in Shenzhen, and to provide scientific basis for rational iodine supplementation. Methods A total of 170 pregnant women with thyroid diseases who visited Department of Endocrinology, Peking University Shenzhen Hospital from January 2017 to March 2019 were selected as the subjects, they were divided into hyperthyroidism group (84 cases) and non-hyperthyroidism group (86 cases) according to whether they had hyperthyroidism or not. Morning urine sample was collected under normal dietary conditions; urinary iodine was detected by peroxyacetic acid tetramethylbenzidine oxidation colorimetry. Urinary iodine < 150 μg/L was iodine deficiency and 150 - 249 μg/L was appropriate iodine. Results The median of urinary iodine of pregnant women with thyroid disease in Shenzhen was 143.9 μg/L, which was slightly lower than the lowest limit of the appropriate iodine level. The median of urinary iodine in hyperthyroidism group was 116.6 μg/L, which was at the iodine deficiency level; the median of urinary iodine in non -hyperthyroidism group was 181.6 μg/L , which was at the appropriate iodine level. There was significant difference in urinary iodine levels between hyperthyroidism group and non-hyperthyroidism group (Z =- 2.261, P < 0.05). Conclusion The urinary iodine of pregnant women with hyperthyroidism in Shenzhen is slightly low.

Research progress of portable artificial kidney / 国际生物医学工程杂志

Chronic kidney diseases severely affects human health and quality of life.The end-stage renal disease (ESRD) patients require extensive blood purification treatments.Due to the limitations of methods,traditional dialysis treatments greatly limit the activity of the patients undergoing dialysis.Portable artificial kidneys can meet the diverse needs of these patients,and has become a new direction of research.There are two types of portable artificial kidneys,which are respectively based on hemodialysis and peritoneal dialysis,such as wearable artificial kidney (WAK) and bio-implantable artificial kidney (BAK).At present,preclinical experiments with artificial kidneys have achieved initial success,basically meeting treatment needs.Portable artificial kidneys are expected to achieve a mobile continuous dialysis treatment,reduce hospitalization and mortality in ESRD patients,save medical resources,improve the life quality of the patients,and make the patients return to normal lifestyles.The research status of WAK and BAK was reviewed,and their future developments were prospected.

Effect of vimentin on activation of NLRP3 inflammasome in the brain of mice with EV71 infection / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore whether vimentin (VIM) mediates the activation of inflammasome in mice with EV71 infection in the central nervous system.</p><p><b>METHODS</b>Forty VIM knockout mice (VIM, 3 to 5 days old) were randomly divided into control group and infection group. The infection group was intraperitoneally injected with EV71 (10 TCID), while the control group was injected with PBS (10 µL); another 40 wild-type mice (WT, 3 to 5 days old) were grouped in the same manner. The general conditions of mice were observed each day. Western blotting, ELISA, and RT-PCR were used to measure the levels of IL-1β and casepase-1 in the brain or cerebrospinal fluid. The pathological changes in the cerebella and brain were observed using immunohistochemistry.</p><p><b>RESULTS</b>Compared with the control group, the VIM mice infected with EV71 showed no significant changes in NLRP3, IL-1β or caspase-1 expression. The WT mice infected with EV71 showed obviously increased NLRP3, IL-1β, and caspase-1 expressions in the central nervous system. The neurons of infected VIM mice exhibited milder cell damage than the those in WT mice.</p><p><b>CONCLUSION</b>VIM mediates the activation of inflammasome and promotes brain inflammation and neuronal damage in mice with EV71 infection in the central nervous system.</p>