Research progress on natural cannabinoid receptor type 2( CB2R)regulators and their effects on bone metabolism / 中国中药杂志

Cannabinoid receptor type 2( CB2 R),a member of the G protein-coupled receptor( GPCR) superfamily,has a variety of biological activities,such as regulating pain response,resisting inflammation and fibrosis,and mediating bone metabolism. Some CB2 R regulators exhibit a good regulatory effect on bone metabolism. Cannabinoids in Cannabis sativa can cause psychoactive effects despite various pharmacological actions they exerted by targeting CB2 R. Therefore,it is of great significance to discover CB2 R regulators in non-Cannabis plants for finding new lead compounds without psychoactive effects and elucidating the action mechanism of plant drugs. The present study clarifies the discovery,structure,and physiological functions of CB2 R,especially its regulatory effects on bone metabolism,summarized CB2 R regulators extracted from non-Cannabis plants,and systematically analyzes the regulatory effects of CB2 R regulators on bone metabolism in animals,osteoblasts,and osteoclasts,to provide a scientific basis for the discovery of new CB2 R regulators and the development of anti-osteoporotic drugs.

Effects of hemodialysis and hemoperfusion combination treatment on maintenance hemodialysis patients / 上海交通大学学报（医学版）

Objective:To investigate the effects of hemodialysis (HD) and hemoperfusion (HP) combination treatment on maintenance hemodialysis (MHD) patients. Methods:A total of 80 MHD patients in Chongming Branch of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from July 2017 to July 2018 were randomly divided into two groups, i.e., HD+HP group (n=40) and HD group (n=40). The patients were followed up every 3 months for 1 year. The changes of laboratory indexes, dialysis adequacy indicators and quality of life scores of Kidney Disease Quality of Life-Short Form (KDQOL-SF) were compared between the two groups, and the prognosis, causes of death and adverse events were recorded. Results:At the end of one-year treatment, levels of parathyroid hormone (PTH), β2-microglobulin (β2-MG), high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and left ventricular mass index (LVMI) were significantly lower in HD+HP group than those in HD group (P0.05). The overall mortality rates of HD+HP group and HD group were 12.5% and 32.5%, respectively. No significant adverse events were observed during the follow-up. Conclusion:The effects of HD combined with HP on clearing middle and large molecular toxins, reducing microinflammation status, and improving renal anemia and left ventricular hypertrophy are better than those of only HD. There may be potential advantages of HD and HP combination in improving quality of life in MHD patients as well.

Isolation and identification of endophytic fungi producing harpagoside and harpagide from Scrophularia ningpoensis / 中国中药杂志

The endophytic fungi from root,main stem,branch and leaf of Scrophularia ningpoensis were isolated from Zhejiang,whether these strains could yield harpagide or harpagoside were tested by HPLC and LC-MS. According to the morphological characteristic and the similarity of the nucleotide sequence of internal transcribed spacer( ITS) between r DNAs,the strains producing harpagide or harpagoside were identified. The results showed that 210 strains were isolated from the samples,which were classified into 9 orders,13 families and 17 genera by morphological study. Harpagide was detected in endogenous fungi ZJ17 and harpagoside was detected in endogenous fungi ZJ25 by HPLC coupled with LC-MS. ZJ17 was identified as Alternaria alternate and ZJ25 was identified as A.gaisen by its morphology and authenticated by ITS( ITS4 and ITS5 regions and the intervening 5. 8 S rDNA region).

Effects of plasma containing invigorating blood and dissipating masses Chinese medicine compound on proliferation of rabbit RPE cell by PDGF intervention / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To invesitigate the effect of invigorating blood and dissipating masses traditional Chinese medicine compound drug-containing plasma on the proliferation of rabbit retinal pigment epithelium(RPE)cells treated with platelet derived growth factor(PDGF). <p>METHODS: Primary cells of RPE cells were obtained by enzymatic digestion, and the primitive culture and subculture of RPE cells were proceeded; prepared blood plasma-contained traditional Chinese medicine compound drug-containing plasma; the fourth genertation rabbit RPE cells were selected as the experimental cells by PDGF of low, medium and high doses(5μg/L, 10μg/L, 20μg/L)for 48h. Suitable concentration was detected and selected in cells experiment by using CCK-8 method. Establishing rabbit model of RPE cell proliferation treated with PDGF. The experimental groups were blank control group(DMEM), normal plasma group, PDGF(10 μg/L)group, PDGF(10 μg/L)+ AG1296(10 μmol/L)group, PDGF(10 μg/L)+ 10% drug-containing plasma, PDGF(10 μg/L)+ 20% drug-containing plasma. Respectively, transwell method was used to determine the migration of rabbit RPE cells after 24h intervention in each group; CCK-8 was used to determine the cell viability OD value of rabbit RPE cells after 48h of intervention in each group.<p>RESULTS: The plasma containing 10% and 20% concentration of invigorating blood and dissipating masses traditional Chinese medicine compound drug can effectively inhibit cell viability and cell migration of RPE cells treated with PDGF. <p>CONCLUSION: We found the certain concentration of invigorating blood and dissipating masses traditional Chinese medicine compound drug can effectively inhibit cell viability and cell migration of RPE cells treated with PDGF, which may be an effective treatment for proliferative vitreoretinopathy and provide a new way to study the mechanism of proliferative vitreoretinopathy.

Seroreactivity and immunogenicity of Tp0965, a hypothetical membrane protein of Treponema pallidum / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Treponema pallidum (T. pallidum) subsp. pallidum is the causative agent of syphilis. Analysis of recombinant antigens of T. pallidum led to the identification of potential candidate antigens for vaccine development and syphilis serodiagnosis. Tp0965 was predicted to be a membrane fusion protein and was found to be reactive with infected human sera in previous studies, but the results were controversial. In this research, the antigenicity and immunoreactivity of recombinant protein Tp0965 were assessed.</p><p><b>METHODS</b>T. pallidum subsp. pallidum (Nichols strain) was propagated and isolated and the genomic DNA was extracted. The Tp0965 gene was amplified by polymerase chain reaction (PCR). Then the recombinant protein Tp0965 was expressed in Escherichia coli and purified by nickel-nitrilotriacetic acid (Ni-NTA) purification system. The reactivities of protein Tp0965 were examined by immunoblot analysis and indirect enzyme-linked immunosorbent assay. The antisera against protein Tp0965 were obtained by immune rabbits and the immunogenicity of antisera were detected by indirect enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>Recombinant protein Tp0965 was expressed successfully in vitro. Immunoblot assay showed that the recombinant protein Tp0965 could be recognized by human syphilitic sera of all stages. Indirect enzyme-linked immunosorbent assay showed there were only 4 of 74 human syphilitic sera that failed to show reactivity to recombinant antigen Tp0965, and lack of reactivity of Tp0965 to all 28 uninfected sera. A low titer of antiserum against Tp0965 in immune rabbits could be detected after the third time of immunization.</p><p><b>CONCLUSIONS</b>The recombinant antigen Tp0965 shows excellent sensitivity for the reactivity with sera from syphilitic individuals at all stages. The results also demonstrate a potential application for the serodiagnosis of syphilis.</p>

Suppurative arthritis caused by Gemella morbillorum in a patient with rheumatoid arthritis of the knee / 南方医科大学学报

Rheumatoid arthritis of the knee is a common disease, but suppurative arthritis caused by Gemella morbillorum in the same joint is rare. We report a case of suppurative arthritis caused by Gemella morbillorum in a patient with rheumatoid arthritis. Because the infection symptoms was not typical, the diagnosis was delayed, and the delayed diagnosis and therapy led to a poor outcome of the patient.

Effects of extract of Buddleja officinalis eye drops on androgen receptors of lacrimal gland cells of castrated rats with dry eye / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of the extract of Buddleja officinalis eye drops (EBOED) on basic tears secretory volume, tear film stability, and expressions of androgen receptors (AR) in castrated rats with dry eye, and to investigate the mechanism of EBOED on dry eye caused by decreased anti-androgen levels.</p><p><b>METHODS</b>Forty-five male Wistar rats were randomly divided into the blank group, the model group, and the treatment group (treated by EBOED), respectively. Rats in each group were further divided into three sub-groups (fed for one month, two months, and three months, respectively). There were totally nine groups, with five in each. The dry eye model was established with orchiectomy of rats in the model group and the treatment group. EBOED was given to rats in the treatment group for one successive month. Schirmer I test (SIT) and breakup time of tear film (BUT) were determined in all experimental rats. Expressions of AR was analyzed by flow cytometer.</p><p><b>RESULTS</b>Ths SIT value, BUT, and AR positive rate in the model group at the 1st, 2nd, 3rd month were lower than those in the blank group of the same time points (P < 0.01). There was statistical difference in SIT value, BUT, and AR positive rate between the model group and the treatment group at the three time points (P < 0.01). Take the three-month subgroup as an example, the SIT value in the treatment group was (12.667 +/- 5.221) mm, obviously higher than that in the model group (2.676 +/- 1.987) mm. The BUT in the treatment group was (11.758 +/- 4.415) s, obviously longer than that of the model group (4.667 +/- 2.108) s. The AR positive rate in the treatment group was 49.33% +/- 3.44%, obviously higher than that of the model group (33.32% +/- 7.12%, all P < 0.01).</p><p><b>CONCLUSIONS</b>The main components of EBOED was the flavonoids which could significantly inhibit the occurrence of dry eye in rats with decreased androgen levels. Its mechanism might possibly be similar to androgen.</p>

Change of renin-angiotensin system in cultured mesangial cells by serum from nephrectomized rats feeding with low protein diet and α-keto acid supplement / 中华肾脏病杂志

Objective To observe the changes of renin-angiotensin system (RAS) in cultured mesangial cells by serum from 3/4 nephrectomized rats feeding with low protein diet and α-keto acid. Methods Thirty male SD rats received 3/4 nephrectomy (Nx) were placed on 18%normal protein diet (NPD,n=10),6% low protein diet(LPD,n=10) or 5% low protein plus 1%α-keto acid diet (LK,n=10) flor 12 weeks.Ten male SD sham-operated rats fed with 18% normal protein diet were used as control (sham group).In addition,mesangial cells were cultured in sera (10%) collected from above animals treated with or without losartan (0.02 mmol/L)for 48 hours.ELISA was applied to detect the level of Ang II,TGF-β1 and fibronectin (FN) in cell medium.Westem blotting was used to determine the protein level of ATI receptor (AT1R)and real-time PCR was used to detect the mRNA level of AT1R,TGF-β1 and FN. Results (1) Nutritional indices including body weight,total protein and albumin had no significant difference in each group. (2) Serum creatinine and 24 h pruteinuria were significantly inceased in nephrectomized groups compared to sham group(P<0.05,respectively).24 h proteinuria was greatly lower in LK group than that in NPD and LPD groups(P<0.05,respectively).(3)LK greatly decteased the level of Ang II[NPD(12.70±0.12)mg/g protein;sham(8.04±0.62)mg/g protein]in supernatant as well as the protein and mRNA expression of AT1R in cultured mesangial cells (P<0.05).(4)NPD serum directly induced higher secretion[FN:sham(20.58±0.46)g/g protein,NPD (39.84±0.06)g/g protein;TGF-β1:sham(10.12±O.56)mg/g protein,NPD(83.85±3.58)mg/g protein] and mRNA expression of FN and TGF-β1 compared with sham group (P<0.05).LPD decreased these increment (P<0.05) and LK showed stronger inhibitory effect (P<0.05). (5)Losartan application sharply reduced FN and TGF-β1 production both in supematant and in mRNA expression in NPD serum treated cells (P<0.05,respectively). Conclusion Low protein diet with α-keto acids supplement directly inhibits the RAS in mesangial cells which may contribute to its beneficial effect on the kidney.

Effects of low protein diet with α-keto acid supplement on kidney sclerosis and renin-angiotensin system in renal ablation rats / 中华肾脏病杂志

Objective To observe the influence of low protein diet with α-keto acid on kidney sclerosis and renin-angiotensin system in renal ablation rats. Methods Chronic renal failure rat model was established by renal ablation in 30 male SD rats,then the animals were randomly assigned to the following diet groups:normal protein group (NPD:18%casein protein),low protein group (LPD:6%casein protein) and supplemented low protein group (LK:5%casein protein+1%α-keto acids).Ten male SD sham-operated rats received 18%casein protein as control.All the rats were killed at the end of the 12th week.Pathologic changes were assessed by PAS staining.Ang II in homogenate and plasma were measured by radioimmunoassay and ELISA respectively.Immunohistochemistry and Western blotting were used to detect the protein expression of TGF-β1,renin and AT1R.Real-time PCR was used to detect the gene expression of renin and ATla,the main subtype of AT1 receptor. Results Body weight,total protein and serum albumin had not significant difference among the four groups(all P>0.05).Serum creatinine and proteinuria of nephrectomized rats were significantly higher compared to the control group (all P<0.05).Proteinuria of the LK group was lower than that of NPD and LPD groups (all P<0.05).Pathological results indicated fibrosis indices were significantly improved after LPD and LK intervention.Expressions of renin,Ang II and AT1R in LK group were significantly lower than those in NPD group (all P<0.05). Conclusions Low protein diet with α-keto acids supplement therapy exhibits renal protective effects of reducing urine protein excretion and improving renal fibrosis,which might be related to the attenuation of local renin-angiotensin system in activity nephrectomized rats.

Compound erythromycin sustained release preparation and its in vitro release / 药学学报

Using the weight-average molecular weight 50 000 polylactic acid (PLA) as a carrier, and a certain proportion of erythromycin (EM) and prednisone acetate (PNA) to mixed prepare the compound erythromycin sustained release preparation (sustained-release tablets). Using ultraviolet spectrophotometry and high performance liquid chromatography (HPLC) to detect separately the release amount of EM and PNA in vitro medium. The sustained-release tablets release for about 21 days, the average content of EM is 99.7 mg/table, RSD = 0.82%; and the average content of PNA is 10.03 mg/table, RSD = 0.93%. Within 21 days, the cumulative releases of EM and PNA are 86.1% and 78.3%, respectively. The drug release is steady and slow after 5 days, the burst release phenomenon in early stage is more significant. The results showed that the sustained-release tablet preparation method is feasible, the release performance is good and the clinical efficacy is significant.

Numerical simulation and post processing of tumor microvasculature / 医用生物力学

Objective In order to provide a more realistic microvasculature model for the study on tumor hemodynamics and drug delivery, a simulated tumor microvascular network was developed by the technique of numerical simulation and post processing. Method We constructed a tumor microvascular model with host arteriole venule system, in which the variation in vascular branching and dimensions was taken into account. A sensitivity analysis was made for the parameters of the model to evaluate the adjustability of simulated results. The connectivity of the vascular network was tested to ensure the integrity of the network. The vascular network was smoothed afterwards to reduce flow resistance resulting from numerical networks. Results The simulated results are consistent with the characteristics of real tumor microvasculature, which show intact circulation, local adjustability, high network connectivity and smooth degree. Conclusions This study provid a numerical microvasculature model for the research on tumor hemodynamics, drug delivery and vascular targeted therapy.

Three dimensional numerical simulation of microcirculation and drug delivery in solid tumors / 医用生物力学

Objective To study the characteristics of micro environmental flow and the process of macromolecular drug delivery in solid tumor. Method3D models simulating tumor hemodynamics and drug delivery were developed. Microcirculation and concentration distribution of two macromolecular drugs in tumor were simulated. ResultsThe model successfully reflected abnormal tumor hemodynamics, which results in impeded drug delivery and uneven concentration distribution of the drug. The results also shows that the drug with lower molecular weight is more easy to spread in tumor and excrete with interstitial fluid flow. In contrast, the drug with higher molecular weight tends to accumulate and maintain an effective concentration in tumor for a longer period. ConclusionsThe results derive from this model can reflect physiological conditions, providing a reliable numerical model for the investigation of tumor micro environment, drug delivery and strategy of therapy.

Effect of Buddleia flavonoids drug-containing plasma on the expression of STAT1 phosphoprotein in lacrimal gland epithelial cells in vitro / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the effect of Buddleia flavonoids drug-containing plasma and androgen receptor(AR) blocker on the expression of STAT1 phosphoprotein.METHODS: In vitro lacrimal gland epithelial cells were cultivated with H2O2 to establish the dry eye apoptosis state. Blank plasma group, Buddleia officinalis plasma total flavonoids interfere with drug-containing group, and the intervention group of testosterone propionate were set. The expressions of STAT1 phosphoprotein of each group were observed by Western blot and AR blocker flutamide was used to explore the intended androgen effect of Buddleia flavonoids.RESULTS: After the intervention of drug-containing plasma, the expression of STAT1 Phosphoprotein in Buddleja officinalis drug-containing plasma intervention group(0.353±0.494) and testosterone propionate intervention group(0.502±0.036) were enhanced and the differences between the two groups were significant (P<0.01). After using the AR blocker in all groups, the expression of STAT1 phosphoprotein in each group (0.268±0.061,0.283±0.106,0.213±0.071) had no difference.CONCLUSION: Buddleja officinalis drug-containing plasma total flavonoids can promote the expression of STAT1 phosphorylation.

Effects of extract of Buddleja officinalis eye drops on androgen receptors of lacrimal gland cells of castrated rats with dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the effects of the extract of Buddleja officinalis eye drops in basic tears secretory volume, tear film stability, expression of androgen receptors(AR) in castrated rats with dry eye, and to investigate the therapeutic effects of extract of Buddleja officinalis on dry eye caused by gonadal hormones level imbalance. METHODS:A total of 45 Wistar masculinity rats were divided at random into 9 groups, including normal group(A1,A2 and A3), model group(B1,B2 and B3), therapy group with extract of Buddleja officinalis eye drops(C1,C2 and C3). The "1" stood for being fed for 1 month, and "2" for 2 months, and "3" for 3 months. The dry eye model was established with orchiectomy on group B,C. Group C was treated with Buddleja officinalis extract eye drops for one month. All rats were checked with Schirmer Ⅰ test (SⅠt) and tear film break-up time (BUT). Expression of AR was analyzed by flow cytometer(FCM). RESULTS:The SⅠt value of group C was significantly higher than that of group B (P<0.01) and the BUT value of group C was significantly longer than that of group B (P<0.01), which indicated the eye drop could significantly keep basic tears secretory volume and tear film stability. And the expression of AR of group C was much higher than that of group B,which showed that available composition of the eye drops maybe display androgen-like activity.CONCLUSION:The main components of extract of Buddleja officinalis is the flavonoids which could significantly inhibit happening of dry eye of rat after androgen level lowered. Its mechanism is like androgen's and it could display androgen-like activity to keep basic tears secretory volume and tear film stability.