Garcinol, a benzenetriol compound extracted from Garcinia cambogia, has antitumor activity, however, its antitumor mechanism remains unclear. The aim of this study was to investigate the role and mechanism of garcinol as a novel potential proteasome inhibitor. We applied the drug affinity responsive target stability (DARTS) method coupled to mass spectrometry to determine the binding protein of garcinol; the proteasome activity assay was used to determine the effect of garcinol on its hydrolase activity; immunofluorescence and proximity ligation assay (PLA) were used to detect the effects of garcinol on ubiquitin and RPN6; and flow cytometry were used to determine the effects of garcinol on cell apoptosis; and the anti-cancer effect was studied in organoid models. The results showed that RPN6 was a direct binding protein of garcinol; garcinol inhibited the hydrolase activity of proteasome, and induced the accumulation and aggregation of ubiquitin protein, and its proteasomal inhibitory effect was dependent on RPN6; further studies showed that garcinol induced oligomerization of RPN6 and formation of granules in the nucleus; finally, it was verified that garcinol induced apoptosis of tumor cells, and inhibited the growth of organoids of Apc^min/+ small intestine mice. These results suggest that garcinol is a potential proteasome inhibitor, which inhibits proteasome activity by directly targeting RPN6 on proteasome 19S, which in turn induces cell apoptosis and inhibits tumor growth.

Overdenture as a treatment modality for both partially and fully edentulous patients is costeffective and less expensive.The purpose of the present study was to examine the newly fabricated attachments by comparing them with conventional O-ring attachment in vitro in terms of retention force and cyclic aging resistance.A total of 150 samples were prepared and divided into five groups according to the materials used (O-ring attachment,Deflex M10 XR,Deflex Classic SR,Deflex Acrilato FD,and flexible acrylic resin).The retention force of different attachments was measured by a mini dental implant after three subsequent aging (0,63,and 126) cycles in the circumstances similar to the oral environment.The gap space between the head of the implant and the inner surface of the attachments was detected.Two-way analysis of variance (ANOVA) analysis with multiple comparisons test was applied for statistical analysis.The results showed that Deflex M10 XR had the highest retention force and the lowest gap space after cyclic aging;in addition,by comparing the relative force reduction,the lowest values were obtained in the O-ring attachment and the highest values in the flexible acrylic resin attachment.The retention force measured after cyclic aging for the Deflex M10 XR attachment was greatly improved when compared with the O-ring attachment and other types of attachment materials;in addition,the Deflex M10 XR attachment exhibited the minimum gap space between the inner surface and the mini dental implant head.In conclusion,Deflex M10 XR has the ability to withstand weathering conditions and retains its durable and retentive properties after aging when compared with other attachments.

Salvianolic acid A (Sal A) is one of the most effective compounds isolated from the root of Salvia miltiorrhiza. Up to now, several studies regarding the pharmacokinetic profiles of Sal A have been reported, however there is no such study reported in monkeys, the species which is more similar to human. The aim of this study is to develop a LC-MS method for the determination of Sal A in monkey plasma and apply it to the pharmacokinetic studies of monkeys. After single intravenous administration of Sal A, the plasma concentration-time curves were observed and the main pharmacokinetic parameters were calculated. The plasma concentration at 2 min (C2 (min)) values were (28.343 ± 6.426), (45.679 ± 12.301) and (113.293 ± 24.360) mg x L(-1) for Rhesus monkeys treated with Sal A at 2.5, 5 and 10 mg x kg(-1). The area under the concentration-time curve (AUC(0-∞)) values were (3.316 ± 0.871), (5.754 ± 2.150) and (13.761 ± 2.825) μg x L(-1) x h, respectively. Furthermore, this method was improved and applied to the simultaneous determination of Sal A, Sal B and Sal C, which provided useful information for preclinical studies and clinical trials of Sal A, Sal B and Sal C.
Administration, Intravenous ; Animals ; Caffeic Acids ; pharmacokinetics ; Chromatography, Liquid ; Drugs, Chinese Herbal ; pharmacokinetics ; Lactates ; pharmacokinetics ; Macaca mulatta ; Mass Spectrometry ; Plant Roots ; chemistry ; Salvia miltiorrhiza ; chemistry

The clinical success of dental implants can be improved by achieving optimum implant properties,such as their biomechanical and surface characteristics.Nano-structured coatings can play an important role in improving the implant surface.The purpose of the present study was to determine the most appropriate conditions for electrophoretic deposition (EPD) of nano-zirconia coatings on Ti-6Al-7Nb substrates and to evaluate the structural and biomechanical characteristics of these deposited coatings on the dental implants.EPD was used with different applied voltages and time periods to obtain a uniform layer of nano-zirconia on Ti-6Al-7Nb samples.The coated samples were weighed and the thickness of the product layer was measured.Surface analysis was performed by using optical microscopical examination,scanning electron microscope and X-ray diffraction phase analysis.For in vivo examination,48 screw-designed implants (24 uncoated and 24 nano-zirconia coated) were implanted in both tibiae of 12 white New Zealand rabbits and evaluated biomechanically after 4-and 12-week healing intervals.Results revealed that the use of different conditions for EPD affected the final coating film properties.Increasing the applied voltage and coating time period increased the deposited nano-zirconia film thickness and weight.By selecting the appropriate coating conditions,and analyzing scanning electron microscopical examination and XRD patterns,this technique could produce a thin and continuous nano-zirconia layer with a uniform thickness of the Ti-6Al-7Nb samples.Mechanically,the nano-zirconia-coated implants showed a highly statistically significant difference in removal torque values,while histologically these coated implants enhanced and promoted osseointegration after 4 and 12 weeks of healing,compared with the uncoated ones.In conclusion,EPD is an effective technique for providing a high quality nano-zirconia coating film on dental implant surfaces.Moreover,the osseointegration of these coated dental implants is improved compared with that of uncoated ones.

The SRY gene from buffalo (Bubalus bubalis) genome was amplified by the polymerase chain reaction ( PCR) with primers based on the sequence of Hostein SRY gene. The amplified fragment was 2005 bp include 5UTR ( 1 - 504bp) and 3'UTR(1196 - 2005bp). And the amplified fragment was cloned and sequenced. Sequence analysis showed that the coding region of SRY gene (505 - 1195bp) from buffalo was highly homologous with those of other bovine counterpart genes (96% homology) , especially in the HMG box region (99%homology). It was found that there were only signal on male buffalo genome on Southern blot,which indicate SRY gene are highly conservative on evolves.

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory dermatosis with a variety of clinical manifestations and difficult to cure. Currently, many AD drug candidates have entered the research and development pipeline. In order to provide technical specifications for the clinical development of AD drugs, the Center for Drug Evaluation of National Medical Products Administration released the "Technical Guidelines for Clinical Trials of Drugs for AD Treatment" (Draft for Comments) in November 2022. Non-clinical pharmacodynamics evaluation is an important research before the drug enters clinical trials. Oxazolone (OXA)- and 2,4-dinitro-fluorobenzene (DNFB)-induced models are the most popular classical hapten-induced AD murine models, but variations of modeling are existing in the methods from different studies, including sensitization sites, haptens' dosages, the period of challenges, and the skin lesions severity evaluation as well. In this study, the investigation of OXA- and DNFB-induced AD murine models with various conditions of modeling was performed to compare the characteristics of hapten-induced AD murine models in the pathological process and severity according to the appearance of AD patients, and the guidance of pharmacodynamics evaluation of AD-therapeutic drugs in clinical trials as well, which may provide a proposal for AD treatment drug candidates in the non-clinical pharmacodynamics evaluation. All animal experiments were approved by the Animal Care & Welfare Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (approval No.: 00007782 and 00007784).

OBJECTIVE: To describe our experience in the clinical manifestation and treatment of malignant tumors of the external and middle ear. METHOD: The study reviewed 39 patients between 1994-2011 in our hospital, including 15 pinna tumors, 18 external canal tumors and 6 middle ear tumors. 23 males and 16 females were enrolled in this study. The mean age of patients at the time of surgery was 59. Radiotherapy or radiotherapy and chemotherapy were the only possible treatment in 6 cases. Thirty-three patients were treated surgically, and 9 patients also received radiotherapy after surgery. RESULT: All of the patients had been followed up over 3 years, except for 1 case of external canal and 1 case of middle ear tumor. The 3-year survival of pinna, external canal and middle ear tumors were 86.7%, 82.4% and 60.0% respectively. At the last follow up, the pinna tumors showed that the survival rate was 100% in T1, T2 and Tx stage, and 0% in T4 stage; the external canal tumors showed that the survival rate was 90% in T1 stage, and 66.7% in T2, T3 stage; the middle ear tumors showed that the survival rate was 100% in T1 and T2 stage, 0% in T3 stage. CONCLUSION The T staging system is for an important prognostic factor, and it is important for an early diagnosis and radical surgery to achieve a better therapeutical result.
Ear Auricle ; pathology ; Ear Canal ; pathology ; Ear Neoplasms ; pathology ; Ear, Middle ; pathology ; Female ; Humans ; Male ; Neoplasm Staging ; Retrospective Studies ; Survival Rate

The direct acting substances of Cuscuta chinensis in vivo were preliminarily identified through the correlation analysis of "metabolites-effect identification" model. The ovariectomized female rats were i.g administered with 95% ethanol extract part, 40% ethanol elution part and n-butanol extract part of Cuscuta chinensis. The serum fingerprints of different parts and times of administration were established by UPLC/Q-TOF-MS. At the same time, serum estradiol (E₂), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were detected. Bivariate correlation analysis and grey correlation analysis were used to screen estrogenic components. The results showed that nine direct acting substances in vivo highly related to estrogen effect were found in the drug containing serum, which were hyperoside, astragalin, methyl quercetin glucuronide, quercetin-diglucuronide, quercetin, apigenin, isoquercitrin, kaempferol glucuronide and kaempferol. We can preliminarily screen out the direct acting substance of estrogen effect of Cuscuta chinensis in vivo based on the research idea of serum spectrum effect correlation. It provides a reliable basis for revealing the estrogeneffective substances of Cuscuta chinensis and confirming the quality markers. This experiment was approved by Harbin University of Commerce Ethics Committees (Approval No. HSDU2020-065).

Objective To study hemodynamics of cerebral blood flow in newborns with asphyxia.Method Bilateral cerebral electrical admittance plethysmogram(BCEAP) was used to explore characteristics of cerebral blood flow in 20 healthy newborns and 20 newborns with asphyxia respectively from first to fourth day after birth.Results Both the ratio of Hs to b-S(Hs/ b-S) and index of admittance differential loop(ADL) Ⅰ+Ⅱ decreased significantly in newborns with asphyxia compared to normal control from first to fourth day after birth(P

Objective To evaluate the advantages of TB-IGRA and protein chip to detect the Mycobacterium tuberculosis. Methods From October 2013 to March 2014,collected 78 cases of clinical diagnosis of tuberculosis and normal control’s pe-ripheral blood specimens,used TB-IGRA kits and Mycobacteriumtuberculosis IgG kit(protein chip)to detected respectively. The results were analyzed and compared.Results The sensitivity of protein chip and TB-IGRA in the detection of Mycobac-teriumtuberculosis were 34.5% and 89.7% respectively,which was statistically significant (χ2=26.95,P<0.05).The spe-cificity of protein chip and TB-IGRA were 90.0%,95.0% respectively,which were not statistically significant (χ2=1.64,P> 0.05).The positive rate of TB-IGRA and Protein chip in tuberculosis were 90.5% and 42.9%.The positive rate of TB-IGRA and Protein chipin extrapulmonary tuberculosis were 89.20% and 29.7% respectively.Conclusion Compared TB-IGRA and protein chip,either diagnose tuberculosis or extrapulmonary tuberculosis has highly positive rate and sensitivity, TB-IGRA can be widely used in the early screening of tuberculosis.