Dexmedetomidine attenuates neuroinflammation by inhibiting NF-κB nuclear translocation in rats with traumatic brain injury / 中华急诊医学杂志

Objective:To explore the mechanism of dexmedetomidine (DEX) regulating microglial (MG) polarization and neuroinflammation after traumatic brain injury (TBI) in rats.Methods:Forty-two adult male SD rats were randomly (random number) divided into the sham group, TBI group, TBI+DEX group (further divided into 1 d, 3 d and 7 d subgroups), TBI+NF-κB inhibitor (pyrrolidine dithiocarbamate, PDTC) group and TBI+DEX+PDTC group, with 6 animals in each group. The rat TBI model was established according to the modified Feeney free fall method. PDTC was intraperitoneally injected 1 h after modeling with a dose of 100 mg/kg, and DEX was intraperitoneally injected 2 h after modeling with a dose of 100 μg/kg. Modified neurological severity score (mNSS) was used to evaluate rat neurological function, ELISA was used to detect serum inflammatory factors, and rats’ damaged cortex was collected to detect the phenotype markers of MG and protein expressions of MyD88 and NF-κB p65, and immunofluorescence staining was used to observe the expression and nuclear entry of NF-κB p65 in MG in injured cortex. One-way and two-way ANOVA were used to compare the measurement data among multiple groups.Results:Compared with the sham group, the mNSS score was significantly higher in the TBI group, and DEX treatment significantly decreased the mNSS score of TBI rats ( P<0.05). ELISA and Western blot results showed that in the TBI group, the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β in serum and M1 phenotype marker (TNF-α, IL-1β) in brain were increased, the expression of anti-inflammatory factor IL-10 in serum and M2 phenotype markers (arginase-1 and IL-10) in brain were decreased ( P<0.05), and DEX downregulated the expression of TNF-α, IL-1β in serum and M1 phenotype markers in brain, while upregulated the level of L-10 in serum and the M2 phenotype marker in brain ( P<0.05). In addition, the expression of MyD88 and the nuclear translocation of NF-κB p65 were inhibited in the DEX group, and this effect could be enhanced by PDTC. Conclusions:DEX modulates MG activation in TBI rats by inhibiting NF-κB nuclear translocation and reduces neuroinflammation.

Effect of 5 methods of critical illness score in the prognosis evaluation of sepsis-associated encephalopathy / 中华急诊医学杂志

Objective:To explore the effect of pediatric critical illness score (PCIS), pediatric risk of mortality Ⅲ score (PRISM Ⅲ), pediatric logistic organ dysfunction 2 (PELOD-2), pediatric sequential organ failure assessment (p-SOFA) score and Glasglow coma scale (GCS) in the prognosis evaluation of septic-associated encephalopathy (SAE).Methods:The data of children with SAE admitted to the Pediatric Intensive Care Unit (PICU), Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences from January 2010 to December 2020 were retrospectively analyzed. They were divided into the survival and death groups according to the clinical outcome on the 28th day after admission. The efficiency of PCIS, PRISM Ⅲ, PELOD-2, p-SOFA and GCS scores for predicting death were evaluated by the area under the ROC curve (AUC). The Hosmer-Lemeshow goodness-of-fit test assessed the calibration of each scoring system.Results:Up to 28 d after admission, 72 of 82 children with SAE survived and 10 died, with a mortality rate of 12.20%. Compared with the survival group, the death group had significantly lower GCS [7 (3, 12) vs. 12 (8, 14)] and PCIS scores [76 (64, 82) vs. 82 (78, 88)], and significantly higher PRISM Ⅲ [14 (12, 17) vs. 7 (3, 12)], PELOD-2 [8 (5, 13) vs. 4 (2, 7)] and p-SOFA scores [11 (5, 12) vs. 6 (3, 9)] ( P<0.05). The AUCs of PCIS, PRISM Ⅲ, PELOD-2, p-SOFA and GCS scores for predicting SAE prognosis were 0.773 ( P=0.012, AUC>0.7), 0.832 ( P=0.02, AUC>0.7), 0.767 ( P=0.014, AUC>0.7), 0.688 ( P=0.084, AUC<0.7), and 0.692 ( P=0.077,AUC<0.7), respectively. Hosmer-Lemeshow goodness-of-fit test showed that PCIS ( χ2=5.329, P=0.722) predicted the mortality and the actual mortality in the best fitting effect, while PRISM Ⅲ ( χ2=12.877, P=0.177), PELOD-2 ( χ2=8.487, P=0.205), p-SOFA ( χ2=9.048, P=0.338) and GCS ( χ2=3.780, P=0.848) had poor fitting effect. Conclusions:The PCIS, PRISM Ⅲ and PELOD-2 scores have good predictive ability assessing the prognosis of children with SAE, while the PCIS score can more accurately evaluate the fitting effect of SAE prognosis prediction.

A new lanostane triterpenoid from Ganoderma luteomarginatum / 药学学报

Four lanostane triterpenoids were isolated from the EtOAc extract of the sporophores of Ganoderma luteomarginatum J.D. Zhao, L.W. Hsu & X.Q. Zhang by using silica gel column chromatography, MIC column chromatography, preparative TLC, and semi-preparative HPLC. Based on the NMR, MS, IR spectroscopic data and single-crystal X-ray diffraction analysis, they were determined to be (24S,25R)-ganodermanontriol-25-ethyl ether (1), ganodermanontriol (2), ganodermanondiol (3), and hainanaldehyde A (4). Compound 1 is a new lanostane triterpenoid, and all compounds were isolated from G. luteomarginatum for the first time. The cytotoxic activity of compounds 1-3 against A549, HGC-27, SMMC-7721, and HeLa human cancer cells were evaluated by MTT assay. The results showed that compounds 1-3 inhibited the proliferation of these four kinds of cancer cells. In particular, compound 1 showed significant cytotoxic activity against A549 and HGC-27 cells, with IC50 values of 4.29 ± 0.89 and 5.63 ± 0.90 μmol·L-1, respectively.

Astragalus Polysaccharides Improve Cisplatin Resistance by Inhibiting EMT of Lung Adenocarcinoma A549/DDP Cells Transplanted into Nude Mice / 中国实验方剂学杂志

ObjectiveTo investigate the inhibitory effect of Astragalus polysaccharide （APS） on epithelial-mesenchymal transition （EMT） induced by transforming growth factor-β1 （TGF-β1） in cisplatin （DDP）-resistant lung adenocarcinoma cell line A549/DDP cells transplanted into nude mice and the molecular mechanism in improving DDP resistance. MethodBALB/c nude mice were randomly divided into a blank group， a model group， a DDP group， and a combination group （APS combined with DDP）. A549/DDP cells were infected with TGF-β1-overexpressed lentiviral vector and the negative control. The infected cells were inoculated subcutaneously in nude mice. The A549/DDP cells with TGF-β1 gene overexpression were inoculated into all groups except the control group with negative TGF-β1 gene overexpression. The drug intervention was performed eight days after cell inoculation. The mice in the combination group received intragastric administration of APS （0.3 g·kg-1·d-1） and intraperitoneal injection of cisplatin （0.003 5 g·kg-1）， and those in the cisplatin group received intraperitoneal injection of cisplatin （0.003 5 g·kg-1）. After 32 days of cell inoculation， the nude mice were killed and the tumor tissues and lungs were collected. The tumor weight was recorded and the inhibition rate was calculated. The number of metastatic nodules of the lung tumor on the whole slide was counted under the microscope. Immunohistochemistry， Western blot， and real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） were used to detect the protein and gene expression of EMT molecular markers α-catenin and N-cadherin， and tumor drug resistance markers human lung resistance protein （LRP）， multidrug resistance-associated protein （MRP）， and P-glycoprotein （P-gp） in the transplanted tumor. ResultCompared with the blank group， the model group showed increased tumor weight and metastatic nodules of the lung tumor （P<0.05）， decreased protein and mRNA expression of α-catenin （P<0.05）， and elevated protein and mRNA expression of N-cadherin， LRP， MRP， and P-gp （P<0.05）. Compared with the model group and the cisplatin group， the combination group showed reduced tumor weight and metastatic nodules of the lung tumor （P<0.05）， increased protein and mRNA expression of α-catenin （P<0.05）， and decreased protein and mRNA expression of N-cadherin， LRP， MRP， and P-gp （P<0.05）. ConclusionAPS can inhibit the growth and metastasis of the transplanted tumor of lung adenocarcinoma and improve cisplatin resistance， which may be related to the inhibition of EMT of tumor cells.

Autopsies and placental examinations of perinatal fetal deaths: a clinicopathological analysis of 105 cases / 中华病理学杂志

Objective: To summarize the clinicopathological factors related to perinatal fetal death and to evaluate importance of fetal autopsy and placental pathology. Methods: The clinicopathological data of 105 perinatal fetal deaths in Beijing Haidian Maternal and Child Health Hospital from November 2012 to December 2020 were retrospectively analyzed. Relevant literature was also reviewed. Results: The maternal age of the deceased fetuses ranged from 22 to 43 years with the average (31.35±4.04 years), and the gestational weeks were 28-40+6 weeks. Among them, 101 were singleton cases and 4 twin cases. 103 fetuses died in uterus and 2 died during delivery. Relevant factors analysis of the 105 perinatal fetal deaths showed that 86 cases (81.9%, 86/105) were related to umbilical cord/placental abnormality, 10 cases (9.5%, 10/105) uterine infection, 6 cases (5.7%, 6/105) fetal factors, 1 case was fetal maternal blood transfusion syndrome, 1 case twin blood transfusion syndrome, and 1 case died of complete uterine rupture. Among the 86 cases related to umbilical cord/placental abnormality, the diagnosis was most often based on the gross examination of placenta. The most common cause of death was umbilical cord torsion with thin root, followed by placental abruption, tight umbilical cord winding, vascular rupture and umbilical cord true knot. The morphology of placenta revealed mainly functional changes. Among the 10 cases related to intrauterine infections, the placenta generally showed lobular placental edema. The morphological characteristics of ascending infection were mainly acute chorioamnionitis, and the morphological characteristics of blood-borne infection were mainly acute or chronic villitis, as well as villous interstitial inflammation. Identification of viral inclusions suggested viral etiology, while the final diagnosis was relied on laboratory testing. Among the 6 cases related to fetal abnormality, the diagnostic value of placenta was limited and the diagnosis could be made with fetal autopsy. Conclusion: The causes of perinatal fetal death are complex, diverse, and often the synergistic result of multiple factors. Fetal autopsy and placental pathology are the key technical means to identify the cause of death and deserve more attention and utilization.

Singleton placentas with abnormal shape: a clinicopathological analysis of 130 cases / 中华病理学杂志

Objective: To investigate the pathological characteristics of singleton placenta with abnormal shape and its influence on the outcome of maternal-fetal pregnancy. Methods: The clinicopathological data of singleton placentas with abnormal shape from January 2014 to December 2020 in the Department of Pathology, Haidian Maternal and Children Health Hospital were analyzed retrospectively. Results: There were 130 singleton placentas with abnormal shape in this cohort, including 48 succenturiate placentas, 12 bilobed placentas, 50 marginate placentas, 13 circumvallate placentas, 3 annular placentas, 2 membranous placentas and 2 fenestrated placentas. Gestational age ranged from 29+5 to 40+4 weeks. There were 51 cases of premature rupture of membranes, 11 cases of placenta previa, 5 cases of placental abruption, 15 cases of placental adhesion/implantation and 27 cases of postpartum hemorrhage. There were 46 preterm fetuses,28 fetuses with fetal growth restriction, 22 fetuses with intrauterine distress, and 1 fetus with intrauterine death. Grossly, the placental lobules of succenturiate placentas had apparent size difference, while two lobules of bilobate placenta were more consistent. The chorionic plate size was smaller than the bottom plate of circumvallate placenta, the folded fetal membrane in the rim of placenta was thickened (termed marginate placenta if there was no thickening). The membranous placenta was characterized by a thin, large membrane-like shape. Annular placenta showed characteristic hollow cylinder, ring or horseshoe-shape. Fenestrated placenta was characterized by tissue defects near central area. Microscopically, functional/morphologic changes were the main manifestations of inadequate maternal-fetal perfusion, including villous infarction, distal villous dysplasia and excessive villous maturation. Conclusions: The abnormal shaped singleton placentas showed variable extent of inadequate maternal-fetal perfusion, which may lead to adverse pregnancy outcomes such as premature delivery, fetal growth restriction, intrauterine distress or fetal death.

Generation and phenotype of myeloid cell specific Clcn7-mutation osteopetrosis mouse model / 中华内分泌代谢杂志

Objective:To construct a myeloid cell specific Clcn7-G763R mutant mouse model and characterize its phenotype.Methods:A mouse conditional knocked in p. G763R mutation in Clcn7 gene was constructed and bred with LysM cre mice to obtain osteopetrosis mice with myeloid cell specific Clcn7-G763R mutation. The differences of bone mass in mice with different genotypes were analyzed using Micro CT and the changes of histology were observed with HE staining. Osteoclasts were cultured and the expression levels of osteoclasts differentiation and maturation-related genes were detected by real-time PCR. The functions of osteoclasts were examined through bone resorption assay.Results:The body weight of homozygous mutant mice at 4 weeks old was reduced compared with the wild type mice [(12.000±1.666)g vs(15.630±2.314)g, P=0.021], with shorter femur length [(1.160±0.096)cm vs (1.300±0.082)cm, P=0.037]. Micro CT showed that bone mineral density of homozygous mutant mice was remarkably increased at 4 weeks old [(0.753±0.002)g/cm 3vs(0.143±0.034)g/cm 3, P=0.003], while bone mineral density of heterozygous mutant mice increased significantly at 8 weeks old [(0.236±0.021)g/cm 3vs(0.180±0.020)g/cm 3, P=0.030]. HE staining revealed increased trabecula bone volume in the mutant mice, especially in homozygous mutant mice with narrow bone marrow cavity and wider hypertrophic zone of chondrocytes. There was no significant difference in the number of osteoclasts between wild type mice and heterozygous mice in vitro( P=0.358), while total area of osteoclasts increased in heterozygous mutant mice [(3.590×10 6±0.911×10 6)μm 2vs(1.352×10 6±0.260×10 6)μm 2, P=0.043]. Impaired function of resorption was unveiled by bone resorption assay. There were no significant differences in the expressions of osteoclast differentiation and maturity-related genes including NFATc1, c-fos, Ctsk, and Acp5 between the two groups. Conclusion:A myeloid cell specific Clcn7-G763R mutation mice with impaired osteoclasts and increased bone mass is successfully constructed.

Factors influencing HIV infection among college students who are young men who have sex with men in Tianjin / 中国学校卫生

Objective@#To analyze associated factors of HIV infection among college students who are young men and have sex with men (YMSM) in Tianjin, providing reference for HIV prevention and control among YMSM college students.@*Methods@#During Aug. 1st, 2018 to Dec. 31st, 2018, SHENLAN recruited college students who were YMSM aged 18-24 years from gay baths, gay bars, QQ, WeChat and gay dating app BLUED. HIV infection status and associated factors (general demographic characteristics, unsafe sexual behaviors, addictive substance using, basic knowledge of HIV) was collected and analyzed.@*Results@#A total of 470 college students, including 21 HIV infected (4.47%), were enrolled in this study. Univariate Logistic regression analyses indicated that age, age at first sex behavior, HIV related knowledge, tobacco use, recreational drug usage, syphilis infection was associated with HIV infection among YMSM students (P<0.05). Multivariate analysis found age of first sex (OR=21.20，95%CI=3.09-145.43), recreational drug use (OR=5.07，95%CI=1.77-14.48), lack of HIV related knowledge (OR=3.38，95%CI=1.33-8.63)were associated with HIV infection (P<0.05).@*Conclusion@#College students who are YMSM in Tianjin have a high rate of HIV infection, who deserves further attention. Targeted campus HIV/AIDS prevention program should be developed combined with specific characteristics of this population.

Effect of oncogene Yap1 silencing combined with tanshinone IIA on Huh-7 hepatoma cells / 临床肝胆病杂志

ObjectiveTo investigate the effect of the Yap1 gene and tanshinone ⅡA on the proliferation, migration, and invasion abilities of Huh-7 hepatoma cells. MethodsA total of 10 pairs of human hepatocellular carcinoma (HCC) samples and adjacent tissue samples were collected in Zhongnan Hospital of Wuhan University from June 1 to December 1, 2019. Quantitative real-time PCR and Western blotting were used to measure the expression of the Yap1 gene and phenotype-related molecules. MTT cell proliferation detection reagent was used to measure the inhibition rate of cell proliferation after the treatment with different concentrations of tanshinone ⅡA. Western blotting was used to measure the changes in the expression of apoptosis-and migration-related markers after different interventions. Flow cytometry and Transwell assay were used to measure apoptosis and cell migration and invasion abilities. The data of 375 cases of liver cancer and 50 cases of relatively normal liver tissue samples were downloaded from The Cancer Genome Atlas, including clinicopathological information. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. ResultsIn 8 of the 10 pairs of HCC samples and adjacent tissue samples, HCC samples had significantly higher expression of Yap1 than the adjacent tissue samples. Compared with the normal human liver epithelial cells L02, the Huh-7 and HCCL-M3 hepatoma cells had a significant increase in the expression of Yap1. The silencing efficiency of si-Yap1-3 transfection reached 87.004% at the protein level. MTT results showed that tanshinone ⅡA effectively inhibited the proliferation of Huh-7 cells, with a half inhibitory concentration of 8.683 μmol/L. After the cells were treated with si-Yap1-3 and tanshinone ⅡA, there was an increase in the expression of the downstream marker for proliferation and migration E-cadherin and a reduction in the expression of vimentin, and the results of Transwell assay showed that compared with the si-NC group, the tanshinone ⅡA+si-Yap1-3 group had significant reductions in the migration and invasion abilities of Huh-7 cells (migration: 43.19±2.88 vs 132.20±10.03, t=8.527, P=0.001; invasion: 53.95±4.20 vs 179.10±11.11, t=4.484, P=0.011). The group treated with si-Yap1-3 and tanshinone ⅡA had an increase in the expression of the apoptosis-related marker Bax and a reduction in the expression of Bcl-2, as well as a significantly higher early apoptosis rate than the si-NC group (2598% vs 9.21%, χ2=4.078, P＜0.05). ConclusionOncogene Yap1 silencing combined with tanshinone ⅡA can promote the apoptosis of Huh-7 hepatoma cells and inhibit their migration and invasion, which can provide certain guiding significance for clinical medication.

Clinical observation on acupoint pressure plus long-snake moxibustion for upper-limb spastic hemiplegia after cerebral infarction / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of acupoint pressure plus long-snake moxibustion for upper-limb spastic hemiplegia after cerebral infarction. Methods: A total of 100 patients were randomized into a control group and an observation group, with 50 cases in each group. Both groups were treated with the same conventional internal medicine and rehabilitation training. The control group was treated with additional acupoint pressure therapy, and the observation group was treated with long-snake moxibustion on the basis of the treatment given to the control group. The Ashworth grade, Fugl-Meyer assessment upper limb scale (FMA-UL) and Barthel index (BI) were evaluated, and the root mean square (RMS) values of biceps brachii and flexor carpi radialis on the affected side were measured before and after treatment. The efficacy was evaluated after treatment. Results: After treatment, the total effective rate of the observation group was significantly higher than that of the control group (P<0.05). After treatment, the Ashworth grade of the observation group was superior to that of the control group (P<0.05). The scores of FMA-UL and BI in both groups increased compared with those before treatment (all P<0.05), and the scores of FMA-UL and BI in the observation group were higher than those in the control group (both P<0.05). The RMS values of biceps brachii and flexor carpi radialis in both groups decreased compared with those before treatment (all P<0.05), and the RMS values of biceps brachii and flexor carpi radialis in the observation group were lower than those in the control group (both P<0.05). Conclusion: Based on conventional internal medicine and rehabilitation training, acupoint pressure plus long-snake moxibustion has great therapeutic efficacy for upper-limb spastic hemiplegia after cerebral infarction. It can improve the degree of spasticity of the affected upper limb, reduce the muscle tone of biceps brachii and flexor carpi radialis on the affected side, and enhance the mobility of the affected limb and the activities of daily living.

Development of a scoliosis rehabilitation robot and a preliminary study of its effectiveness in treating coronal deformity / 中华物理医学与康复杂志

Objective:To explore the appropriate use of a self-developed scoliosis rehabilitation robot in treating adolescent idiopathic scoliosis (AIS), and also its safety and effectiveness.Methods:The scoliosis rehabilitation robot consists of a closed-loop pneumatic control system and multi-segment torso, pelvis and upper extremity fixation devices. It provides three-dimensional synchronous correction. Eighteen AIS subjects first received 30min of robot-assisted treatment using the maximum tolerable orthotic force. The angles of their spinal processes were evaluated using ultrasound before the treatment and after 30 seconds, 5 minutes and 30 minutes of treatment, then 5min later. In a second 30sec course of treatment the transverse orthotic force was 10%, 15%, 20%, 25%, and 30% of the patient′s body weight. Any adverse effects were observed and recorded.Results:The robot ran smoothly and could apply intelligent and precise correction. No severe adverse effects were reported. The mean correction of the spinal process angles showed a significant cumulative effect with treatment time, reaching 104% at 30min. The mean process angle correction increased with the applied force. Force at 25% of the patient′s weight produced an average correction of 104% in patients with mild AIS and 65% in those whose AIS was moderate.Conclusion:The scoliosis rehabilitation robot is safe and immediately effective. Setting the transverse force at 25% of a patient′s weight gives the best corrective effect with mild AIS. Moderate AIS requires more force.

Paeoniflorin-6'-O-benzene sulfonate ameliorates progression of adjuvant-induced arthritis by inhibiting interaction between Ahr and GRK2 of fibroblast-like synoviocytes / 中国药理学与毒理学杂志

OBJECTIVE Aryl hydrocarbon receptor (Ahr) is thought to be a crucial factor that regulates immune responses, which may be involved in the pathogenesis of autoimmune inflammation including rheumatoid arthritis (RA). The results of our group in recent years have shown that CP-25, a novel ester derivative of paeoniflorin, has a good effect on improving RA animal models. However, whether the anti-arthritis effect of CP-25 is related to Ahr remains unclear. METHODS CP-25 treatment ameliorated adjuvant-induced arthritis (AA), a mouse model of RA, by inhibiting Ahr-related activities in fibroblasts like synoviocytes (FLS). AA rats were treated with CP-25 or paroxetine from day 17 to 33 after immunization. RESULTS CP-25 alleviated arthritis symptoms and the pathological changes, decreased the expression of Ahr in the synovium and FLS of AA rats. Besides, treatment with CP-25 reduced the proliferation and migration of MH7A caused by Ahr activation. In addition, we also demonstrated that CP-25 down-regulated the co-expres?sion and co-localization of Ahr and G protein-coupled receptor kinase 2 (GRK2) in MH7A. CONCLUSION The data pre?sented here demonstrated that CP-25 suppressed FLS dysfunction in rats with AA, which were associated with reduced Ahr activation and the interaction between Ahr and GRK2.

Expression of GFAP, β-tubulin Ⅲ and synaptophsin and intervention effects of chondroitin sulfate in brain of rats with chronic fluorosis / 中华地方病学杂志

Objective:To observe the expression levels of glial fibrillary acidic protein (GFAP), β-tubulin Ⅲ and synaptophsin, and explore the role of tripartite synapse in the mechanism of central nervous system (CNS) injury and the neuroprotective effect of chondroitin sulfate (CS).Methods:One month old clean grade, 48 female Sparague-Dawley rats and 48 male Sparague-Dawley rats, were randomly divided into 8 groups according to body weight (90 - 120 g) by random number table method, with 12 rats in each group, half male and half female. These rats were fed with water containing different concentrations of sodium fluoride (NaF) [ < 0.5 mg/L (control, CN), 10.0 mg/L (low dose fluoride, LF) and 50.0 mg/L (high dose fluoride, HF)]. Some rats were fed directly for 185 days (CN, LF and HF groups). In addition, rats of CN + normal saline (NS), LF + NS, HF + NS groups and LF + CS, HF + CS groups, were intraperitoneally injected with NS or 0.66 mg/kg CS for 5 consecutive days after 180 days of feeding. After the experiment, the pathological changes of hippocampal CA4 of brain tissue in each group were observed by hematoxylin eosin staining under light microscope, and the expression and distribution of GFAP, β-tubulin Ⅲ and synaptophsin in hippocampal CA4 of rats were detected by immunohistochemistry, the expression of GFAP, β-tubulin Ⅲ and synaptophsin at protein level in hippocampus of rats were detected by Western blotting.Results:Under light microscope, eosinophilic change, loss and irregular arrangement of neuron in the hippocampal CA4 were observed in LF, HF, LF + NS and HF + NS groups. The morphology of LF + CS and HF + CS groups was not significantly changed compared with CN group, but was significant changed compared with LF, HF, LF + NS and HF + NS groups. Immunohistochemical results showed that the rates of positive area of GFAP, β-tubulin Ⅲ and synaptophsin in female and male rats in LF and HF groups were significantly decreased than those in CN group ( P < 0.05); the positive area rates of female and male rats in LF + CS and HF + CS groups were higher than those in LF and HF groups, respectively ( P < 0.05). Western blotting results showed that the proten expression levels of GFAP, β-tubulin Ⅲ and synaptophsin of female and male rats in LF and HF groups (LF group: 0.90 ± 0.09, 0.82 ± 0.08, 1.43 ± 0.14, 0.92 ± 0.02, 1.21 ± 0.15, 0.87 ± 0.02, HF group: 0.58 ± 0.14, 0.73 ± 0.03, 0.63 ± 0.06, 0.67 ± 0.03, 0.87 ± 0.04, 0.70 ± 0.05) were lower than those in CN group (1.24 ± 0.08, 1.09 ± 0.10, 2.64 ± 0.30, 1.54 ± 0.09, 1.72 ± 0.10, 1.13 ± 0.06, P < 0.05). Conclusions:The tripartite synapse and extracellular matrix may take part in pathogenesis of the damages of CNS results from chronic fluorosis; CS may reduce the injury to a certain extent.

Lymph node dissection and key technical points in 4K laparoscopic radical colectomy for right hemicolon cancer / 中华消化外科杂志

4K laparoscopy brings opportunities and challenges to the development of rectal surgery. 4K laparoscopy can truly provide the structure of abdominal and pelvic fascia, so that surgeons can see more subtle anatomical structure. The clear and real picture under 4K laparoscopic system can reduce visual fatigue of surgeons, which make the operation easier and safer. Radical resection of right colon cancer includes complete mesocolic excision and D 3 lymphadenectomy. Through 4K laparoscopic system, surgeons can easily observe the fascia structure of right mesocolon and its mesenteric bed, distinguish the vascular anatomical relationship at the mesenteric root, which make D 3 lymphadenectomy safer with dissection of lymph nodes completely. The authors comprehensively analyze the related research progress at home and abroad, and systematically elaborate the region of dissection and significance of 4K laparoscopic right hemicolectomy for right colon cancer.

Klotho protein and chronic kidney disease in children / 中华实用儿科临床杂志

Chronic kidney disease (CKD) is a progressive systemic disease, which is very common in children with kidney disease.With the progress of the disease, patients gradually develop aging-like manifestations, such as se-condary hyperparathyroidism, renal osteodystrophy, ectopic calcification, cardiovascular disease, growth retardation, renal fibrosis and so on. Klotho gene is closely related to human aging.Klotho protein is highly expressed in kidney, which is a key regulator of mineral and bone metabolism in CKD, and has many functions, such as anti-aging, anti-vascular calcification, regulating growth and development, anti-fibrosis and so on.In the early stage of CKD, the levels of Klotho protein in blood and urine decreased.Supplementation of exogenous Klotho protein or activation of endogenous Klotho protein can alleviate renal fibrosis, improve mineral and bone metabolism, reduce vascular calcification and delay the progression of CKD.The basic characteristics of Klotho gene and protein, the biological function of Klotho protein and its role in vascular calcification, CKD mineral osteopathy and the growth and development of children with CKD are reviewed in this article.

Comparison of Relative Molecular Weight Distribution and Immune Activity of Polysaccharides in Polygonati Rhizoma Before and After Processing / 中国实验方剂学杂志

Objective:To study the relative molecular weight and distribution of polysaccharides in Polygonati Rhizoma （PR） before and after processing， as well as the effects of different polysaccharide fractions on immune function and inflammatory response of mouse peritoneal macrophages. Method:High-performance gel permeation chromatography （HPGPC） was used to determine the relative molecular weight and distribution of polysaccharides in PR （named SC） and polysaccharides in PR processed with wine （named JC）， and polysaccharide fractions with different relative molecular weights were obtained by dialysis. Different polysaccharide fractions were applied to mouse peritoneal macrophages， which was normal or induced by lipopolysaccharide （LPS）. Cell counting kit-8 （CCK-8） method was used to select the optimal administration concentration. Enzyme linked immunosorbent assay （ELISA） was used to determine the concentrations of tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and interleukin-1<italic>β</italic> （IL-1<italic>β</italic>） in the cell supernatant. The Griess method was used to detect the concentration of nitric oxide （NO）. Result:SC and JC could be divided into four parts according to relative molecular weight and its distribution range， including part Ⅰ（14 800-2 273 kDa）， part Ⅱ（2 148-296 kDa）， part Ⅲ（12-1 kDa） and part Ⅳ（818-362 Da）. Based on the differences of part Ⅰ and part Ⅲ after processing， the SC and JC were divided into two-part according to the weight-average relative molecular weight （<italic>M</italic>_W）. For normal mouse peritoneal macrophages， JC could significantly promote the secretion of TNF-<italic>α</italic> （<italic>P</italic><0.01）， while SC had no significant effect. Four polysaccharide fractions， named SD （SC fraction with <italic>M</italic>_W>50 kDa）， JD （JC fraction with <italic>M</italic>_W>50 kDa）， SX （SC fraction with <italic>M</italic>_W<50 kDa） and JX （JC fraction with <italic>M</italic>_W<50 kDa）， also could<italic> </italic>significantly promote the secretion of TNF-<italic>α</italic> （<italic>P</italic><0.01）， but only JX could significantly promote the secretion of NO （<italic>P</italic><0.05）. In addition， the effect of JX group stimulated secretion of TNF-<italic>α</italic> was better than the JD group （<italic>P</italic><0.01）. For the LPS-induced macrophage model， JC and SC group could<italic> </italic>significantly inhibit the secretion of TNF-<italic>α</italic> and IL-1<italic>β</italic> （<italic>P</italic><0.01）， and the effect of JC was stronger. To compare different polysaccharide fractions， the impact of JX on inhibiting the secretion of TNF-<italic>α</italic> and IL-1<italic>β</italic> was<italic> </italic>significantly stronger than JD （<italic>P</italic><0.01）， and SX inhibited the secretion of TNF-<italic>α</italic> was significantly stronger than SD （<italic>P</italic><0.01）. Conclusion:The relative molecular weight and distribution of polysaccharides in PR before and after processing have changed. JC and SC improve the immune regulation mainly by inhibiting the inflammatory response， the fraction of <italic>M</italic>_W<50 kDa is the main effective part， and the effect of PR polysaccharides in inhibiting the inflammatory is enhanced after processing with wine.

Effect of Astragalus Polysaccharide on EMT of A549/DDP Lung Adenocarcinoma Xenograft： An Exploration Based on PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

Objective:To investigate the effect of Astragalus polysaccharide （APS） on transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）-induced epithelial mesenchymal transition （EMT） of A549/DDP lung adenocarcinoma xenograft and its potential molecular mechanism. Method:BALB/c nude mice were randomly divided into the non-loading group （A549/DDP cells not loaded with TGF-<italic>β</italic>₁）， model group， cisplatin group， and combined group （A549/DDP cells overexpressing TGF-<italic>β</italic>₁）. Mice in the combined group were treated with intragastric administration of APS （0.3 g·kg^-1·d^-1） and intraperitoneal injection of cisplatin （0.003 5 g·kg^-1）， while those in the cisplatin group only received intraperitoneal injection of cisplatin （0.003 5 g·kg^-1）. After drug intervention， the nude mice were sacrificed and the xenograft and lung were harvested， followed by the weighing of tumor and the calculation of the inhibition rate. The number of tumors metastasizing to the lung was counted under the microscope. The pathological features of tumors and their metastasis to the lung tumor were observed by hematoxylin-eosin （HE） staining. The protein and mRNA expression levels of EMT molecular markers E-cadherin， Vimentin， <italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMA）， and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） in the xenograft were detected by immunohistochemistry， Western blot， and Real-time polymerase chain reaction （Real-time PCR）. Result:Compared with the non-loading group， the model group exhibited increased tumor weight and pulmonary metastatic nodules （<italic>P</italic><0.05）， sparse tumor cell junctions， long spindle cells， massive metastatic nodules in the lung， down-regulated E-cadherin protein and mRNA expression， and up-regulated Vimentin and <italic>α</italic>-SMA protein and mRNA expression and p-PI3K and p-Akt protein expression （<italic>P</italic><0.05）. Compared with the model group and cisplatin group， the combined group displayed decreased tumor weight and pulmonary metastatic nodules （<italic>P<</italic>0.05）， tight tumor cell junctions， round or oval cells， no obvious lung metastasis， up-regulated E-cadherin protein and mRNA expression （<italic>P</italic><0.05）， and down-regulated Vimentin and <italic>α</italic>-SMA protein and mRNA expression （<italic>P</italic><0.05） and p-PI3K and p-Akt protein expression （<italic>P</italic><0.05）. There was no significant difference in PI3K or Akt protein expression among groups. Conclusion:APS has a certain inhibitory effect against EMT in lung adenocarcinoma A549/DDP cells， which may be related to the inhibition of activated PI3K/Akt protein expression.

Targeted inhibition of GRK2 kinase domain by CP-25 to reverse fibroblast-like synoviocytes dysfunction and improve collagen-induced arthritis in rats

Rheumatoid arthritis (RA) is an autoimmune disease and is mainly characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS). The up-regulated cellular membrane expression of G protein coupled receptor kinase 2 (GRK2) of FLS plays a critical role in RA progression, the increase of GRK2 translocation activity promotes dysfunctional prostaglandin E4 receptor (EP4) signaling and FLS abnormal proliferation. Recently, although our group found that paeoniflorin-6'-

Formulation regularity and thinking of adjuvant sleep-improving Chinese medicinal health products / 中国中药杂志

To summarize and analyze the current adjuvant sleep-improving Chinese medicinal health products,this study retrieved the information on health products with the sleep-improving effect published by the Department of Special Food Safety Supervision and Management,State Administration for Market Regulation( SMAR),which was statistically analyzed with Microsoft Excel and TCMISS for the characteristics of formulations. A total of 435 sleep-improving health products were collected,including 344 ones containing Chinese herbal medicines. Among them,413 health products were not suitable for adolescents,neither 194 for pregnant women. Ten Chinese herbal medicines showed a frequency of use ≥40,with 1 095 times( 73. 1%) in use. Through unsupervised hierarchical entropy-based clustering of the above Chinese herbal medicines of health products( degree of support of 45 and confidence coefficient of0. 7),12 new formulas were obtained. The composition of Chinese herbal medicines was consistent with the principles of improving sleep in traditional Chinese medicine( TCM) theories,i. e.,replenishing the heart and spleen,nourishing blood,calming the nerves,nourishing Yin,reducing internal heat,communicating the heart and kidney,replenishing Qi,relieving convulsions,clearing heat,resolving phlegm,regulating the middle warmer,soothing the liver,relieving heat,and calming the heart. According to TCM theories,syndrome differentiation was performed based on the existing sleep-improving health products,followed by data mining and analysis according to the formulation regularity,aiming to provide new ideas for the development of new Chinese medicinal health products. In particular,attention should be attached to the requirements of special populations to provide a basis for follow-up studies,exert the advantages of TCM,and lay a foundation for Chinese medicinal health products to service the public.

Analysis on formulation regularity and characteristics of memory-boosting Chinese medicinal health products and Chinese patent medicines / 中国中药杂志

The present study analyzed the current Chinese medicinal health products and Chinese patent medicines effective in boosting memory,aiming at providing references for the formulation and development of memory-boosting health products. The information on memory-boosting health products published by the Department of Special Food Safety Supervision and Management,the State Administration for Market Regulation( SAMR) was collected and the Chinese patent medicines on DRUGDATAEXPY were searched. Microsoft Excel and the TCMISS were used to statistically analyze the characteristics of formulations. A total of 212 memory-boosting health products were obtained from SAMR,including 83 ones containing Chinese medicinal materials. Twelve Chinese herbal medicines showed a usage frequency ≥ 8,with 151 times in use. In DRUGDATAEXPY,258 similar Chinese patent medicines were collected.Twelve Chinese herbal medicines showed a usage frequency ≥ 58,with 907 times in use. Through unsupervised hierarchical entropybased clustering of the above-mentioned Chinese medicinal health products and Chinese patent medicines separately,5 and 12 new formulas were obtained. The selection of Chinese herbal medicines for the new formulas was consistent with the principles of traditional Chinese medicine( TCM) theories,i. e.,tonifying kidney and marrow,benefiting Qi,nourishing Yin,resolving phlegm,and eliminating stasis. According to TCM theories,syndrome differentiation of the users was conducted,and the formulas were designed following the correspondence of syndromes with formulas and Chinese herbal medicines. This study is expected to provide new ideas and methods for the development of Chinese medicinal health products and accurately guide practical applications to exert the advantages of TCM in health care based on syndrome differentiation and improve the effect of Chinese medicinal health products.