Objective To study the effect of TMB 8 on cerebral blood flow(CBF) of focal cerebral ischemia in the rats.Methods CBF in the middle cerebral artery occlusion after the middle cerebral artery occlusion was measured by a Laser Doppler Flowmeter. TMB 8 was administered 30 min before occlusion and 20 min after occlusion respectively.Results CBF was reduced quickly. TMB 8 0.5,1,2 mg/kg was administered 30 min before occlusion of the middle cerebral artery.The dosage inhibited the reduction of CBF,20 min after occlusion, CBF was increased by TMB 8 1 mg/kg significantly.Conclusion TMB 8 could prevent and treat the reduction of CBF in focal cerebral ischemia of MCAO in the rats,and improved the supply of blood in ischemic area.

Abstract Socioeconomic status is an important factor affecting all-cause mortality. Income, education and occupation alone or in combination have been employed as a measure of socioeconomic status; however, the study results vary in measures. Material mechanism, lifestyle mechanism, psychological mechanism and community neighborhood mechanism have been accepted as the main intermediate mechanisms for the impact of socioeconomic status on all-cause mortality; however, the contribution of these mechanisms remains controversial. Based on the international and national publications pertaining to the association between socioeconomic status and all-cause mortality from 2012 to 2021, this review summarizes the relationship between socioeconomic status and all-cause mortality in different metrics and the intermediate mechanism of the impact of socioeconomic status on all-cause mortality, so as to provide insights for further studies.

OBJECTIVE To evaluate the long-term toxicity of fully human anti-human tumor necrosis factor-α monoclonal antibody(anti-hTNF-α FHMA)for injection in cynomolgus monkeys. METHODS Forty cynomolgus monkeys were randomly divided into 5 groups (4 males and 4 females in each group):negative control group,adalimumab 10 mg·kg-1 group,anti-hTNF-αFHMA 2,10 and 50 mg·kg-1 groups. Cynomolgus monkeys in each group were injected sc once a week for 5 consecutive times, followed by 4 weeks of recovery. During the test,general clinical observation,body mass,body temperature,electrocardiogram(ECG),hematology,coagulation function,blood biochemistry,urine, ophthalmology,immune index,and pathological changes in organs and tissues were observed. At the same time,plasma drug concentrations were detected and the toxicokinetics parameters were analyzed. RESULTS No significant toxicological changes related to drugs were observed in general clinical observation,body mass,body temperature,ECG,ophthalmic examination,blood cell counts,coagu?lation function,blood biochemistry,urine analysis,lymphocyte subsets,cytokines,serum immuno?globulin,serum complement. Neutralizing anti-drug antibody(ADA)could be detected in adalimumab group and anti-hTNF-αFHMA groups. Anti-hTNF-αFHMA showed linear dynamic characteristics in cyno?molgus monkeys. At the same dose(10 mg·kg-1),anti-hTNF-αFHMA had similar immunogenicity and kinetics characteristics to adalimumab. CONCLUSION The level of anti-hTNF-α FHMA at which no adverse effect was observed was 50 mg · kg-1,which is equivalent to 75 times clinical dosage of quasi (0.67 mg·kg-1),which suggests that anti-hTNF-αFHMA be safe in clinical use.

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.

Objective To detect the transcription factors of copper ion (Cu,2+) metabolism and oxidative stress by Candida albicans knocked down different transcription factors.Methods Spot assay, growth curve were used.Results The sensitivity to Cu,2+ in Cup2Δ/Δ was increasing and the growth of Cup2Δ/Δ was inhibited in 5 mmol /L Cu,2+ medium.The results showed that Cup2Δ/Δ also increased the sensitivity to H2O2, interestingly, Cu,2+and H2O2 played a synergistic antifungal effect.The tolerance of Cup2Δ/Δ and SN250 to H2O2 induced oxidative stress was increased after BCS chelating Cu,2+.In the fluconazole, miconazole and ketoconazole susceptibility experiments, Cup2Δ/Δ did not show susceptibility to azole drugs.Conclusion Knockout transcription factor Cup2, which could increase the sensitivity to Cu,2+ and H2O2in Candida albicans.Transcription factor Cup2 might be involved in the regulation and control of Candida albicansmetabolism on Cu,2+ and oxidative stress induced by H2O2, but not involved in the regulation and control of drug resistance to azole drugs.

The clinical assessment of the risk of rupture and dissection of thoracic aortic aneurysm(TAA) is mainly dependent on the measurement of the maximum diameter and growth rate of the aneurysm itself. The use of aortic size alone may ignore the role of vascular heterogeneity in assessing the risk of catastrophic complications. Biomechanics could help predict the risk of TAA in a more sophisticated way. In this paper, we reviewed the latest advances in biomechanical assessment of risk characteristics of TAA.

OBJECTIVETo explore the efficacy and the mechanism of Bisacodyl in treating slow transit constipation model rats.

METHODSA total of 30 healthy rats were enrolled. Twenty rats received intragastric diphenoxylate to develop slow transit constipation (STC) model, and 10 untreated rats were set as blank control. STC rats were subdivided into two groups: STC Bisacodyl group (fed with Bisacodyl) and STC control group (common feed). Body weight, number and dry weight of faeces, and intestinal transit time were compared among 3 groups. Interstitial cells of Cajal(ICC) and c-Kit protein expression were measured by immunohistochemical staining. Restults Compared to blank control rats, at 100-day of receiving intragastric diphenoxylate, above 20 rats presented the decrease of body weight and feces number, the increase of dry weight of faeces, and the delay of intestinal transit time, indicating the successful establishment of STC rat model. One month after feeding, compared to STC control group, STC Bisacodyl grap had an increased feces number[(36.6±6.8) pill/day vs. (26.8±6.0) pill/day], decreased dry weight of feces [(150.6±10.5) mg/pill vs. (171.6±16.3) mg/pill] and shortened intestinal transit time [(416.9±50.6) minutes vs. (495.3±66.8) minutes], and the differences were statistically significant(all P<0.05). Dissolution of ICC basement membrane, damage of connection between ICC and surrounding cells, and atrophy of ICC nucleus structure were found in STC control rats. ICC (8.20±1.92 per field] and c-Kit expression (12.68%±2.59% ) in STC control rats were significantly lower than those in blank control rats(36.00±6.25 per field and 71.50 %±8.27%) (P=0.000). Compared to STC control group, the connection between ICC and surrounding cells enhanced obviously, ICC (18.80±3.70 per field) and c-Kit expression (45.91%±6.80%) were significantly higher in STC Bisacodyl group (all P=0.000).

CONCLUSIONBisacodyl treatment can relieve STC symptoms, which may be associated with increased ICC number and c-Kit protein expression.

Paeoniae Radix Rubra has the effects of clearing heat, cooling blood, dissipating blood stasis and pain relieving (in terms of Chinese medicine). Paeoniae Radix Rubra and its active ingredients have significant pharmacological effects in anti-tumor，protecting liver, nerve and heart. By reviewing the relevant literatures published in recent years, we found that the studies on Paeoniae Radix Rubra are mainly focused in the mechanism of action, drug development and clinical application. In this review, we summarize the research results of the pharmacological effects of Paeoniae Radix Rubra and its active ingredients in order to provide the reference for the future research and clinical application of Paeoniae Radix Rubra.

Objective To explore the in vitro fungistasis of nanometer silvers made by different methods on Candida al-bicans .Methods The minimal inhibitory concentrations (MICs) of Candida albicans strains stimulated to silver nanoparticles were determined by microdilution method .The combination effects of silver nanoparticles with fluconazole were determined by chess board check assay .Results The inhabitation effect of two kinds of silver nanoparticles were different on the growth of Candida albicans .Silver nanoparticles had a synergistic effect with fluconazole on Candida albicans .Conclusion The two kinds of silver nanoparticles had various antifungal activities in vitro and had a synergistic effect with fluconazole on Candida albicans .