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1.
Acta Pharmaceutica Sinica ; (12): 64-75, 2022.
Article in Chinese | WPRIM | ID: wpr-913168

ABSTRACT

As a basic amino acid, histidine has a pKa close to the acidity of the tumor microenvironment, thus the charge and solubility of histidine are able to vary as the pH changes. Under a neutral environment, histidine is not charged and exhibits hydrophobic properties, while it can be protonated and becomes hydrophilic when exposed to mildly acidic pH, such as tumor microenvironment. Therefore, histidine is widely used in the design of drug delivery systems to target the mildly acidic pH of tumor microenvironment. This article reviews the recent progresses of histidine-based tumor-targeting drug delivery systems, and summarizes the principles on promoting internalization and tuning drug release by taking advantage of histidine. Finally, we point out the common issues on histidine application and illustrate its future prospects.

2.
Acta Pharmaceutica Sinica ; (12): 343-352, 2022.
Article in Chinese | WPRIM | ID: wpr-922910

ABSTRACT

Colorectal cancer (CRC) is a common malignancy burdening people globally, with increasing morbidity and mortality nowadays, due to the alternation in the diet type and lifestyle in modern society. Berberine, a type of benzylisoquinoline alkaloid, is widely present in numerous medicinal plants, particularly including Coptidis Rhizoma. Mounting evidence reveals that berberine possesses an array of pharmacological effects, such as anti-inflammation, anti-bacterium, anti-cancer, anti-diabetes mellitus and so on. In particular, berberine exhibits substantial inhibition on various types of cancers including CRC. Hereby, we sought to systematically review the suppressive effect of berberine on CRC through the diminishment of the proliferation and metastasis, induction of apoptosis, arrest of cell cycle, regulation of inflammatory reaction, the reverse of chemotherapeutic resistance and restoration of gut microbiota in CRC, so as to shed light on the in-depth mechanisms underlying the treatment of CRC with berberine in the clinical setting.

3.
Article in English | WPRIM | ID: wpr-915083

ABSTRACT

Objective@#Cytoreductive surgery followed by adjuvant chemotherapy is a standard frontline treatment for epithelial ovarian cancer (EOC). We aimed to develop an ovarian cancer risk score (OVRS) based on the expression of 10 ovarian-cancer-related genes to predict the chemoresistance, and outcomes of EOC patients. @*Methods@#We designed a case-control study with total 149 EOC women including 75 chemosensitives and 74 chemoresistants. Gene expression was measured using the quantitative real-time polymerase chain reaction. We tested for correlation between the OVRS and chemosensitivity or chemoresistance, disease-free survival (DFS), and overall survival (OS), and validated the OVRS by analyzing patients from the TCGA database. @*Results@#The chemosensitive group had lower OVRS than the chemoresistant group (5 vs.15, p≤0.001, Mann-Whitney U test). Patients with disease relapse (13 vs. 5, p60 months) of patients with OVRS ≥10 were significantly shorter than those of patients with OVRS <9). The high OVRS group also had significantly shorter median OS than the low OVRS group in 255 patients in the TCGA database (39 vs. 49 months, p=0.046). @*Conclusions@#Specific genes panel can be clinically applied in predicting the chemoresistance and outcome, and decision-making of epithelial ovarian cancer.

4.
Article in Chinese | WPRIM | ID: wpr-911447

ABSTRACT

A retrospective analysis of 7 patients of multiple myeloma (MM) with initial manifestation of bleeding and coagulation abnormalities were performed. Clinical manifestations, laboratory and imaging examinations were collected. The activity of coagulation factors was measured before the treatment. Single factor X deficiency was seen in one patient. Two cases had factor Ⅶ deficiency, while four other patients had multiple factor deficiency. The time from onset of symptoms to diagnosis ranged from 2 to 10 months. After anti-MM treatment started and plasma or coagulation factors were transfused, the prolonged coagulation time returned to normal from 28-84 days. Most of these patients presented large, deep and multiple sites of hematoma, which caused concerns of bone marrow puncture and may direct to other differential diagnoses. This is helpful to improve physicians′ understanding of the special clinical characteristics in MM patients.

5.
Article in Chinese | WPRIM | ID: wpr-910019

ABSTRACT

Objective:To analyze the effect of systematic exercise with a self-designed foot-ankle exerciser on postoperative ankle function in patients with tibial pilon fracture.Methods:A retrospective study was conducted of the 84 patients with tibial pilon fracture who had been treated by open reduction and internal fixation at Nanhua Hospital Affiliated to Nanhua University from May 2018 to January 2020. According to the difference in rehabilitation, they were divided into a control group ( n=42) which were subjected to staged functional rehabilitation after operation and an observation group ( n=42) which was subjected to systematic exercise with a self-designed foot-ankle exerciser. In the control group there was 26 males and 16 females with an age of (36.6±4.8) years (from 20 to 55 years); in the observational group there were 27 males and 15 females with an age of (36.4±4.5) years (from 21 to 57 years). The 2 groups were compared in terms of postoperative recovery, ankle functional recovery, postoperative quality of life, and rate of complications. Results:The 2 groups were comparable due to the insignificant differences in their preoperative general data ( P>0.05). The time for first ambulation [(3.7±0.3) weeks], time for fracture union [(9.1±0.8) weeks], and time for full-weight bearing [(6.5±0.9) weeks] in the observational group were all significantly shorter than those in the control group [(4.1±0.5) weeks, (10.9±1.2) weeks and (7.2±1.1) weeks] ( P<0.05). The good to excellent rate of ankle functional recovery was 92.9% (39/42) for the observational group, significantly higher than that for the control group (73.8%, 31/42) ( P<0.05). The scores for postoperative quality of life in the observational group were significantly higher than those in the control group in dimensions of material, psychology, society and body ( P<0.05). The rate of total postoperative complications in the observational group was 2.4% (1/42), significantly lower than that in the control group (10.9%, 8/42) ( P<0.05). Conclusions:For patients with tibial pilon fracture undergoing the same surgical procedures, systematic exercise with our self-designed foot-ankle exerciser can promote functional recovery of the ankle joint, improve postoperative quality of life, and reduce incidence of postoperative complications.

6.
Article in Chinese | WPRIM | ID: wpr-909620

ABSTRACT

Many drug candidates identified from natural products are poorly water-soluble. The surfactants used to disperse the hydrophobic anticancer drugs in water may cause a serious of acute hypersensitivity reactions. Nanotech?nology provides an alternative strategy for delivery of anticancer drugs. Drugs can be encapsulated or attached to the nanomaterials such as lipids, polymers and solid-core nanoparticles. In the present study, porous inorganic nanoparti?cles have been utilized for delivery of water-insoluble anticancer drugs. The synthesized nanoparticles were functional?ized with different organic polymers. The porous nanoparticles were readily internalized by human glioblastoma U-87 MG cells, and didn't display cytotoxicity. The internalized nanoparticles were mainly localized in endosomes/lysosomes in cells. With the hydrophobic curcumin and carfilzomib as model drugs, intracellular delivery of hydrophobic anticancer drugs by the porous inorganic nanoparticles was studied. The porous nanoparticle-based encapsulation of hydrophobic drug provides the aqueous dispersion of the drugs. In endosomes/lysosomes mimicking buffers with a pH of 4.5-5.5, pH-dependent drug release was observed from drug loaded nanoparticles. The intracellular drug content and cytotoxicity were significantly higher for drug loaded nanoparticles than free drug. These results suggested porous inorganic nanoparticles might be a promising intracellular carrier for hydrophobic anticancer drugs.

7.
Article in Chinese | WPRIM | ID: wpr-909619

ABSTRACT

OBJECTIVE To investigate the pharmacological effect of ursolic acid (UA) on colitis-associated colorec?tal cancer (CAC) and its underlying mechanism based on the Wnt signaling pathway. METHODS The CAC model in mice was established by azoxymethane (AOM) combined and dextran sulfate sodium salt (DSS), accompanied by treat?ment with various dosages of UA and concomitant appraisal of body weight, stool and physical state of the mice. After the sacrifice of the mice, the tumor and length of the colorectum were measured, followed by retrieval of the liver, spleen, thymus and tumor tissue for downstream assays. The levels of inflammatory factors interleukin-6 (IL-6), IL-1βand C-reactive protein (CRP) in the tumor and serum were examined by enzyme-linked immunosorbent assay (ELISA). The pathological changes of colorectal tissues were observed by HE staining. The levels in tumors of Wnt/β-catenin sig?naling pathway-related proteins Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry (IHC). The mRNA expressions of Wnt4, GSK-3β,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, Bax, caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR (RT-qPCR). The protein levels of Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, phospho-β-catenin, phospho-GSK-3β, Bcl-2 and Bax in tumors were probed by analyzed by Western blotting (WB). Also, RNA-seq was employed to assess the gut microbiota in the mice. RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC, evidenced by improved physical state, body weight, survival rate, colorectal length, the mass of liver, thy?mus, spleen, and decreased CAC load and colorectal mass. UA attenuated the levels of IL-6, IL-1β and CRP in the mouse serum and colorectal tumor in a dose-dependent manner. HE staining showed that UA lessened carcinogenesis in the colorectum, with lower infiltration of lymphocytes, versus the control. IHC indicated that UA mitigated the expres?sion of Wnt4,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and promoted the GSK-3βexpression, compared with the control. Furthermore, UA diminished the mRNA expressions of Wnt4, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and heightened the mRNA levels of GSK-3β, caspase-3, capase-9 and Bax in CAC. The results of mRNA expressions were verified by WB analysis, which revealed that UA impeded the protein expression of Wnt4,β-catenin, c-Myc, cyclin D1, Bcl-2, TCF4, LEF1, and elevated the protein levels of GSK-3βand Bax, phospho-β-catenin in mouse CAC. In addi?tion, UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC. CONCLU?SION Ursolic acid may protect against CAC, potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.

8.
Article in Chinese | WPRIM | ID: wpr-909613

ABSTRACT

OBJECTIVE To investigate the effect of scutellarin on the apoptosis of human colorectal cancer cells via the Hippo signaling pathway in vitro. METHODS MTT colorimetric method was used to detect the influence of scutellar?in on the survival rate of HCT116 cells. And the effect of scutellarin at various concentrations on cell morphology was observed by microscopy. Cell scratch experiment was used to detect the influence of scutellarin on the migration of HCT116 cells. Hoechst33342/PI double staining method was used to detect the effect of scutellarin on the apoptosis of HCT116 cells. Western blotting method was used to assess the action of scutellarin on the expressions of Hippo signal?ing pathway-related proteins Mst1, Lats1, YAP1, p-YAP(Ser127), TAZ, and its downstream effector proteins c-Myc and cyclin D1, as well as apoptosis-related proteins Bcl-2 and Bax in HCT116 cells. RESULTS Scutellarin significantly affected the morphology of HCT116 cells and reduced the survival rate of HCT116 cells. Hoechst33342/PI double stain?ing showed that scutellarin effectively induced the apoptosis of HCT116 cells. Western blotting analysis showed that the expression levels of Hippo signaling pathway-related proteins Mst1, Lats1, YAP1, TAZ and its downstream effector pro?teins c-Myc, cyclin D1 were down-regulated in a concentration-dependent manner by scutellarin, and the expression of p-YAP (ser127) was up-regulated. Moreover, scutellarin substantially lessened the expression level of apoptosis-related protein Bcl-2, and promoted the protein level of Bax. CONCLUSION Scutellarin may inhibit the proliferation and migra?tion of HCT116 cells, while induce its apoptosis, potentially by activation of Hippo signaling pathway.

9.
Article in Chinese | WPRIM | ID: wpr-909607

ABSTRACT

OBJECTIVE To investigate the inhibition and mechanism of berberine on human colorectal cancer HCT116 cells through canonical Hedgehog signaling pathway. METHODS The effect of berberine on cell morphology was observed by microscopy. MTT colorimetric assay, cell scratch experiment, colony formation assay and Hoechest/PI staining were utilized to detect the activities of berberine on cell viability, cell migration and cell apoptosis. Flow cytome?try was applied to examine the cell apoptosis. The effects of berberine on caspase-3 and caspase-9 were detected by caspase activity detection kit. The expressions of Hedgehog signaling pathway-related proteins SHH, GLI1, PTCH1, SMO, SUFU, apoptosis-related proteins Bax and Bcl-2 as well as cell cycle-related proteins cyclin D1 were detected by Western blotting. Additionally, quantitative real time RT-PCR was employed to assess the mRNA expression levels of Hedgehog signaling pathway-related genes SHH, GLI1, PTCH1, SMO, SUFU, apoptosis-related genes Bax and Bcl-2 as well as cell cycle-related genes cyclin D1. RESULTS Berberine sharply altered the morphology of human colorectal cancer HCT116 cells, demonstrated by that migration ability of HCT116 cells was reduced significantly and the nuclei were densely stained. Berberine could induce apoptosis in a dose-dependent manner. The activities of caspase-3 and caspase-9 were increased prominently. The expression levels of Hedgehog signaling pathway-related protein SUFU and apoptosis-related protein Bax were augmented substantially. The expression levels of Hedgehog signaling pathway-related proteins SHH, GLI1, PTCH1, SMO, apoptosis-related protein Bcl-2 as well as cell cycle-related genes cyclin D1 were markedly lessened. Besides, the mRNA expression levels of Hedgehog signaling pathway-related gene SUFU and apoptosis-related gene Bax were augmented substantially. The mRNA expression levels of Hedgehog signaling path?way-related genes SHH, GLI1, PTCH1, SMO, apoptosis-related gene Bcl-2 as well as cell cycle-related gene cyclin D1 were markedly lessened. CONCLUSION Berberine, which is the main component of coptidis rhizoma, can remarkably restrain the growth and proliferation, promote apoptosis of human colorectal cancer cells HCT116, and the underlying mechanism may be involved in suppressing the activity of the Hedgehog signaling pathway.

10.
Article in Chinese | WPRIM | ID: wpr-909606

ABSTRACT

Oleanolic acid (OA) is a pentacyclic triterpenoid chemical component that exists in natural plants with a molecular formula of C30H48O3 and a molecular weight at 456.71 g·mol-1. OA is widespread in traditional Chinese herbal medicine (Ligustri Lucidi Fructus, Achyranthis Bidentate Radix, Red Sage) and berries (blueberries, grapes). In recent years, because of the extensive pharmacological effects of OA, its advantages in disease treatment have become increasingly prominent and gradually attracted the attention of pharmaceutical researchers. OA has effective therapeutic effects on a series of chronic diseases such as inflammation, cancer, diabetes, and cardiovascular diseases through mul?tiple signaling pathways and various targets. Especially in cancers, such as colorectal cancer, liver cancer, gastric cancer, lung cancer, breast cancer and other malignancies, OA presents substantial efficacy. However, its poor aqueous solubility, needy bioavailability, and unsatisfactory pharmacological activity excessively restrict its clinical application. More impor?tantly, the improper utilization of OA can cause adverse reactions, toxic effects and even damage to organs in some spe?cific situations. With the discovery of various pharmacological effects, the complex action mechanisms of OA, the contin?uous progress in structural modification of OA, as well as the synthesis of OA derivatives, its application is expand?ing gradually. Among numerous studies, there is a clear indication that OA and its derivatives, if fully developed, may provide an alternative and cheaper treatment for a variety of chronic diseases. However, the specific molecular mecha?nisms of OA and its derivatives as an alternative therapy and supplementary therapy for cancer, diabetes, cardiovascular disease and other chronic diseases remain to be clarified. Therefore, it is necessary to further study the pharmacokinet?ics, pharmacological activity, specific targets and related mechanisms of OA to lay a solid foundation for drug devel?opment and the application of OA in clinical settings.

11.
Article in Chinese | WPRIM | ID: wpr-909601

ABSTRACT

Pulsatilla chinensis is a widely used traditional Chinese herb, which contains 56 types of chemical constit?uents, mainly including triterpenoid saponins, organic acids, coumarins and lignans. The largest portion of the ingredi?ents in Pulsatilla chinensis is the family of triterpenoid saponins, in which anemoside B4 is the major effective compound and indexing component. The main components of Pulsatilla chinensis can metabolize into a vast array of active prod?ucts in vivo, which play vital roles in its biological activity. Mounting evidence reveals that Pulsatilla chinensis exerts a wide range of therapeutic activities, such as anti-cancer, immunoregulation, anti-inflammation and anti-schistosome, with fewer adverse reactions, via various signaling pathways and multiple targets. It was documented that the active ingre?dient of Pulsatilla chinensis can lessen the drug resistance and synergize the effects of other natural products includ?ing paclitaxel, as well as ameliorate the clinical efficacy of chemical drugs, such as adriamycin. However, Pulsatilla chi?nensis was also reported to be possibly the main cause of hemolysis and chronic liver injury. The efforts should be made to deeply investigate the pharmacological actions and underlying mechanisms of Pulsatilla chinensis, with a focus on the anti-cancer efficacy, and develop new drugs based on the components of Pulsatilla chinensis for future utilization in the clinical setting.

12.
Article in Chinese | WPRIM | ID: wpr-909590

ABSTRACT

OBJECTIVE To identify the inhibitory effect of ursolic acid on the colorectal cancer HCT116 cells in vitro and in vivo, and to explore the underlying mechanism. METHODS The smoothened (SMO) gene-silenced human colorectal cancer HCT116hSMO- cell line was established by transfection with the lentivirus carrying SMO shRNA. The cytotoxic effect of ursolic acid on HCT116hSMO-cells was determined by MTT assay. The effect of ursolic acid on the migration of HCT116hSMO- cells was studied by wound healing assay. The effect of ursolic acid on apoptosis of HCT116hSMO-cells was explored by Hoechst33342/PI double staining and flow cytometry. The effects of ursolic acid on the expressions of apoptotic marker gene Bcl-2, Bax, caspase-3 and caspase-9 were measured by real-time quantitative RT-PCR (RT-qPCR) and Western blotting (WB) analysis. RT-qPCR and WB were used to examine the relationship between GLI1, c-Myc expression and PI3K/Akt pathway to further investigate the mechanism of GLI1 activation in HCT116hSMO- cells. The effects of ursolic acid on the expressions of GLI1, p-Akt, Akt, c-Myc, SHH and SUFU of nonca?nonical Hedgehog pathway were evaluated by RT-qPCR and WB assays. Xenograft nude mouse model bearing HCT116hSMO- cells was established and intraperitoneally treated with ursolic acid to investigate the effect on tumor growth in vivo. The body weight and tumor size of mice were assessed regularly every 2 d. The effect of ursolic acid on the apoptosis of tumor tissue was determined by TUNEL assay. The expressions of Bcl-2, Bax, GLI1, p-Akt, Akt, c-Myc, SHH, SUFU mRNA and proteins were measured by RT-qPCR and WB. The levels of Bcl-2, Bax, GLI1, p-Akt, c-Myc and SHH proteins in tumor tissues were also evaluated by immunohistochemistry. RESULTS Ursolic acid significantly inhibited the growth and migration of HCT116hSMO-cells in vitro, compared with the control (P<0.05). Meanwhile, ursolic acid also induced apoptosis of HCT116hSMO- cells in vitro (P<0.05). Furthermore, SC79 (Akt activator) enhanced the expressions of p-Akt, GLI1 and c-Myc, which could be abolished by ursolic acid, and the effect was equal to Akt inhibitor LY294002. The expressions of Bcl-2, GLI1, p-Akt, c-Myc, SHH mRNA and proteins were reduced by ursolic acid, while the levels of Bax and SUFU were increased. Ursolic acid could inhibit the growth and induce the apoptosis of colorectal cancer xeno?graft in vivo. Similarly, lower levels of Bcl-2, GLI1, p-Akt, c-Myc and SHH, and higher expression of Bax and SUFU were noted in ursolic acid-treated mice. CONCLUSION Ursolic acid can inhibit the growth and induce apoptosis of HCT116hSMO- cells both in vitro and in vivo. And the mechanism is related to the suppression of PI3K/Akt-mediated noncanonical Hedgehog signaling pathway.

13.
Article in Chinese | WPRIM | ID: wpr-909589

ABSTRACT

OBJECTIVE Interleukin (IL)-1β, one of the principal inflammatory cytokines mainly secreted by mono?cytes and macrophages, is produced by cleavage of the inactive pro-IL-1βprecursor by caspase-1 via the NLRP3 inflam?masome complex. The fruits of Garcinia cambogia (Clusiaceae) are widely developed as health products for anti-obese purpose. 14-deoxygarcinol (DOG) is a polyisoprenylated benzophenone from the fruits of G. cambogia, which showed potent anti-inflammatory effect in our previous study. The objective of this study was to explore the anti-inflammatory mechanism of DOG and its roles in alleviating adipose tissue inflammation and insulin resistance. METHODS The anti-inflammatory effect of DOG was evaluated on LPS plus nigericin-induced THP-1 macrophages. The expression of NLRP3 inflammasome complex proteins was analyzed by Western blotting, immunofluorescence staining and co-immu?noprecipitation. The pro-inflammatory cytokines levels were determined by ELISA kits. RESULTS DOG increased the expression of Sirtuin 2 (SIRT2) deacetylase and enhanced its deacetylating activity to suppress the NLRP3 inflamma?some activation and IL-1βsecretion in THP-1 macrophages. Moreover, DOG attenuated macrophage conditioned medium-induced inflammatory responses in adipocytes and blocked THP-1 macrophages migration towards 3T3-L1 adipocytes. CONCLUSION DOG attenuated the inflammatory crosstalk between macrophages and adipocytes through SIRT2-mediated NLRP3 inflammasome inhibition, which might be used for the treatment of adipose tissue inflammation-related metabolic disorders.

14.
Article in Chinese | WPRIM | ID: wpr-909587

ABSTRACT

OBJECTIVE To investigate the therapeutic effect of scutellarin on colitis-associated cancer (CAC) and its underlying mechanism based on Wnt/β-catenin signaling pathway. METHODS The mouse model of CAC was estab?lished by azomethane oxide (AOM) and sodium dextran sulfate (DSS), followed by scutellarin treatment, with recording the body weight, diarrhea and hematochezia. After sacrificing the mice, the colorectal length and colorectal tumor were assessed. The levels of pro-inflammatory factors TNF-α and IL-6 in mice's sera were measured by the enzyme-linked immunosorbent assay (ELISA). The colorectal lesions were appraised by hematoxylin and eosin (H&E) staining. Theβ-catenin level in CAC tissues was probed by immunofluorescent analysis. The apoptosis-related genes Bax and Bcl-2, and Wnt signaling pathway-related genes β-catenin, GSK-3β, TCF4, c-Myc and cyclin D1 were detected by real-time quantitative RT-PCR (RT-qPCR). Finally, Western blotting analysis (WB) was employed to examine the expressions of the apoptosis and Wnt signaling pathway-related proteins. RESULTS Scutellarin significantly improved AOM/DSS-caused weight loss, colorectal length shortening, and tumor growth in mice (P<0.01). Meanwhile, colorectal lesions could be substantially alleviated by scutellarin. ELISA results showed that the levels of pro-inflammatory factors TNF-αand IL-6 were drastically lessened (P<0.01). Scutellarin also sharply inhibited the nuclear translocation of β-catenin, as evidenced by the reduction in the nuclear level ofβ-catenin protein. In addition, scutellarin attenuated the mRNA expres?sion of Wnt signaling pathway-relatedβ-catenin, TCF4, c-Myc and cyclin D1, whereas it heightened GSK-3βmRNA level. These results were consolidated by WB analysis, which indicated that scutellarin could mitigate the protein levels of phospho-GSK-3β,β-catenin, TCF4, c-Myc and cyclin D1, with the increase in GSK-3β protein in CAC tissue. Moreover, scutellarin could induce the apoptosis of CAC, demonstrated by enhanced expression of Bax and diminished expression of Bcl-2 in both mRNA and protein levels. CONCLUSION Scutellarin may ameliorate colitis-associated colorectal cancer by weakening Wnt/β-catenin signaling cascade.

15.
Article in Chinese | WPRIM | ID: wpr-908888

ABSTRACT

Objective:To evaluate the effect of combined teaching of optical laryngoscope and general laryngoscope on anesthesia undergraduate practice.Methods:A total of 40 anesthesia undergraduate students were randomly divided into group A (using the optical laryngocope only in the first month and the general laryngoscope only in the second month, n=20), and group B (using the general laryngocope only in the first month and the optical laryngoscope only in the second month, n=20). The teaching effect was evaluated through the first month and the second month of tracheal intubation assessment and questionnaire survey results. SPSS 23.0 was used for t test and chi-square test. Results:In the first month, the success rate was 90% in group A and 60% in group B, which showed that the success rate of group B was lower, with significant differences ( P < 0.05). The time for tracheal intubation in group A was (61.8±5.0) s, and that in the group B was (83.0±4.9) s, showing that the time of group B was longer, with significant differences ( P < 0.05). The complications in group A was 5%, and that in group B was 14%, showing that the group B had more cases of implications, with significant differences ( P < 0.05). In the second month, there was no significant difference in the one-time success rate, the time for tracheal intubation, and complications between the two groups ( P > 0.05). There was no significant difference in one-time success rate and complications between groups. Both groups showed that the time for general laryngoscope intubation was longer, with significant differences ( P < 0.05). All of the students believed that applying optical laryngoscope teaching was beneficial and could enhance the interest of learning, and the combination of the two methods was better. Conclusion:Using the optical laryngoscope first and then the general laryngoscope teaching is more beneficial for students to master the two methods of tracheal intubation, improve the success rate, reduce complications, and cultivates their self-confidence.

16.
Article in Chinese | WPRIM | ID: wpr-908551

ABSTRACT

Objective:To compare the therapeutic effect between regular spherical corneal refractive therapy (CRT) and dual axis CRT on myopia with corneal astigmatism.Methods:A non-randomized controlled study was conducted.Aged 8 to 14 years old, forty-eight patients (48 eyes) wearing CRT orthokeratology enrolled from May, 2018 to December, 2018 in First Affiliated Hospital of Army Medical University were divided into dual axis CRT group (24 eyes) and spherical CRT group (24 eyes) according to their guardians' willingness.After 1-year follow-up, the visual acuity, eccentricity distance in treatment area, annual axial growth and the corneal punctate staining incidence of the two groups were compared.The study followed the Declaration of Helsinki, and was approved by an Ethics Committee of First Affiliated Hospital of Army Medical University (No.KY201975). Written informed consent was obtained from guardians prior to any examination.Results:The uncorrected visual acuity of the dual axis CRT group was better than that of the spherical CRT group at one week and one month after correction, and the differences were statistically significant (both at P<0.05), and there was no significant difference in uncorrected visual acuity between the two groups at other time points (all at P>0.05). The deviations of optical center in the spherical CRT group at each observation time points were significantly larger than that in the dual axis group (all at P<0.05), and the deviation was not obviously changed with time in both groups and there was no significant difference in deviation change between the two groups ( Ftime=2.301, P=0.074). The eccentricity was mainly in horizontal direction in spherical CRT group.The median annual axial growth was 0.12 (0.10, 0.45)mm in the dual axis CRT group and 0.14 (0.10, 0.46)mm in the spherical CRT group, with no significant difference between the two groups ( Z=0.248, P=0.804). There was 4.2%(1/24) of the patients having grade Ⅲ-Ⅳ corneal punctate staining in the dual axis CRT group, and 25.0%(6/24) in the regular spherical CRT group, showing significant difference between the two groups ( χ2=4.180, P=0.049). Conclusions:For the treatment of myopia with astigmatism, dual axis CRT shows better centricity and safety than spherical CRT.

17.
Acta Pharmaceutica Sinica ; (12): 3353-3361, 2021.
Article in Chinese | WPRIM | ID: wpr-906835

ABSTRACT

italic>Aconitum pendulum is a Tibetan medicine that is rich in bioactive compounds such as aconitine-type C19-diterpenoid alkaloids. To investigate the key enzymes in the aconitine biosynthesis pathway, roots, leaves and flowers of Aconitum pendulum were subjected to a high-throughput transcriptomic sequencing analysis by Illumina HiSeqTM2000. Trinity de novo assembly yielded 47 264 unigenes with an average length of 1 140 bp and N50 of 1 678 bp, of which 30 231 unigenes (63.96%) were annotated. In the KEGG database, 542 unigenes were implicated in 17 secondary metabolic pathways; the analysis showed that 44 genes encoded 20 key enzymes in the diterpene skeleton of aconitine biosynthesis and 12 BAHD acyltransferase genes were related to the acetylation modification, with differential expression among three organs. For example, ApTPS8 was the only committed enzyme in the upstream aconitine biosynthetic pathway. The high expression level of ApTPS8 in root indicated that it is the main tissue for the production of precursors of diterpene alkaloids. Consistent with the accumulation of aconitine, we propose that ApBAHD1/2/8 is involved in the biosynthesis of 2-hydroxyaconitine, dehydrated 14-benzoylaconitine, 8-O-methyl-14-benzoylaconine, benzoyldeoxyaconitine and benzoylaconitine, and ApBAHD10 is involved in the biosynthesis of acontine, lucidusculine, 14-O-acetylneoline and 14-O-acetylvirescenin. Comparative transcriptome analysis of A. pendulum and A. carmichaeli indicates significant gene loss in the family of diterpene synthases and acyltransferases in A. pendulum, which is in accordance with the significantly fewer type and quantity of aconitine compounds in this species. Therefore, A. pendulum has proved to be an ideal material for the study of the aconitine biosynthesis pathway. This work provides basic scientific data for further study of aconitine biosynthesis, the discussion of molecular mechanisms of toxicity, and the synthesis of genuine medicinal materials.

18.
China Pharmacy ; (12): 3024-3030, 2021.
Article in Chinese | WPRIM | ID: wpr-906785

ABSTRACT

OBJECTIVE:To prov ide referen ce for clinical safe and rational use of belimumab by mining the risk signals of adverse drug event (ADE). METHODS :ADE reports related to belimumab were collected from FDA adverse event reporting system(FAERS)from the first quarter of 2015 to the first quarter of 2021. The reporting odds ratio (ROR)method and the Medicines and Healthcare Products Regulatory Agency (MHRA)method were adopted to mine the ADE risk signals related to belimumab,setting the threshold as the number of reports >3 and the lower limit of 95% CI >1(ROR method )and the proportional reporting ratio (PRR)>2,and χ2 >4(MHRA method ). ADEs were counted and classified by using the preferred system organ class (SOC)and preferred term (PT)of Medical Dictionary for Regulatory Activities (MedDRA). RESULTS & CONCLUSIONS:A total of 3 529 ADE reports with belimumab as the primary suspicious drug were screened ,in which female patients(90.31%)were much more than male patients (6.15%);age distribution was concentrated in 18-59 years old (41.80%). There were 1 234 cases(34.97%)of severe ADE reports ,mainly involving hospital or prolonged hospital stay. Most of the reporters were consumers or other non-medical professionals (81.84%). North America reported the most (70.39%)and the main reporting country was the United States (2 029 reports). A total of 180 PTs were mined from 3 529 reports,in addition to PTs associated with primary disease (systemic lupus erythematosus ,pain,arthralgia,pyrexia,weight decreased ,swelling,oropharyngeal pain , etc.),PTs related to medication error (product dose omission ,inappropriate schedule of product administration ,underdose, product availability issue ,etc.)and PTs related to infection (influenza,urinary tract infection ,infection,sinusitis,etc.)were reported in a large number of cases. Twenty-six SOCs were involved ,the top 10 SOC in ADE reports were all kinds of injuries , poisoning and surgical complications (2 225 reports),infections and infectious diseases (1 247 reports),general disorders and administration site conditions (1 196 reports),musculoskeletal and connective tissue disorders (1 195 reports),surgical and medical procedures(515 reports),etc. PTs in SOC in the first place (all kinds of injuries ,poisoning and surgical complications )of ADE reports were all related to medication error ;herpes zoster ,kidney infection and cellulitis in SOC in the second place (infections and infectious diseases )of ADE reports were not included in the drug instruction of belimumab ;most PTs in SOCs such as various nervous system diseases ,immune system diseases ,mental diseases ,benign,malignant and unknown tumors (including cystic and polypoid)which were taken attention in clinic were not included in the drug instruction of belimumab. It is suggested to avoid medication errors as far as possible in clinical use of belimumab ,and to guard against adverse reactions such as herpes zoster , kidney infection ,cellulitis and various nervous system diseases ,immune system diseases and mental diseases. In addition ,the patients with malignant tumor or related history should use belizumab carefully.

19.
Article in Chinese | WPRIM | ID: wpr-906313

ABSTRACT

Objective:To explore the potential molecular mechanism of Nelumbinis Plumula alkaloids (NAPs) in the prevention and treatment of non-small cell lung cancer (NSCLC) based on network pharmacology and cell experiment. Method:The main active components of NAPs were obtained by searching Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM), and their main targets were predicted and analyzed by employing Swiss Target Prediction. The main target genes of NSCLC were retrieved from GeneCards, Online Mendelian Inheritance in Man (OMIM) and DrugBank databases. The resulting common targets were imported into STRING platform for constructing the protein-protein interaction (PPI) network, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis based on Database for Annotation, Visualization, and Integrated Discovery (DAVID). The NAPs-common target -pathway network was constructed by Cytoscape 3.7.1. After NSCLC cell line A549 was treated with isoliensinine, the cell morphology was observed under an inverted fluorescence microscope. The effect of isoliensinine on A549 vitality was detected by cell counting kit-8 (CCK-8) assay and the target protein changes were verified by Western blot. Result:The main active components for NAPs against NSCLC were lysicamine, liensinine, and isoliensinine. The phosphatidylinositol-3-kinase-protein kinase B (PI3K-AKT), RAS-related protein 1 (Rap1), epidermal growth factor family of receptor tyrosine kinases (ErbBs), and hypoxia inducible factor-1 (HIF-1) pathways were mainly involved for binding adenosine triphosphate (ATP) and regulating protein kinase activity. The main targets included protein kinase B-1 (AKT1), alpha catalytic subunit of phosphoinositol-3-kinase (PIK3CA), cyclin-dependent kinase 2 (CDK2), mitogen-activated protein kinase-1 (MAPK1), epidermal growth factor receptor (EGFR), adenosine triphosphate-binding cassette B1 (ABCB1), mammalian target of rapamycin (mTOR), tyrosine kinase (Src), Janus kinase 1 (JAK1), and G1-phase-specific gene cyclin-D<sub>1</sub> (CCND1). The <italic>in vitro</italic> cell experiment also revealed that isoliensinine down-regulated the expression of phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) in a concentration- and time-dependent manner and inhibited the growth of A549 cells. Conclusion:NAPs exert the preventive and therapeutic effects against NSCLC through multiple components, multiple targets, and multiple pathways, especially the PI3K-AKT pathway.

20.
Article in Chinese | WPRIM | ID: wpr-906312

ABSTRACT

To systematically evaluate the effect of traditional Chinese medicine(TCM) on the expression of inflammatory factors in peripheral blood of patients with coronary heart disease complicated with anxiety and depression,and explore its efficacy and safety in treatment of anxiety and depression. In this study,CNKI,VIP database,WanFang database,PubMed and Cochrane Library were searched to collect randomized controlled trials(RCTs) of TCM in the treatment of coronary heart disease complicated with anxiety and depression,and 2 researchers independently screened the literatures and extracted the data. The quality of the included literatures was evaluated with Cochrance bias risk evaluation tool and Meta analysis was conducted by Cochrane Revman 5.3 software. A total of 21 research articles were included,with a total sample size of 2 342 cases,1 175 cases in the treatment group and 1 167 cases in the control group. Meta analysis results showed that the treatment group reduced the hypersensitive C-reactive protein(hs-CRP)[standard mean difference(SMD)=-1.61,95% confidence interval(CI)(-2.14,-1.09),P<0.01],interleukin(IL)-8[mean difference(MD)=-5.03,95% CI(-8.37,-1.70),P=0.003],IL-17[MD=-33.27,95% CI(-40.15,-26.39),P<0.01],tumor necrosis factor(TNF)-α[SMD=-1.18,95% CI(-1.98,-0.38),P<0.01],and homocysteine(Hcy)[MD=-3.45,95% CI(-4.85,-2.04),P<0.01]. The treatment group was better than the control group in terms of relieving anxiety and depression,i.e. scores of Hamilton anxiety scale(HAMA) [SMD=-1.97,95% CI(-2.48,-1.46),P<0.01],Hamilton depression scale(HAMD) [SMD=-1.94,95% CI(-2.50,-1.38),P<0.01],and self-rating depression scale(SDS)[SMD=-0.72,95% CI(-0.90,-0.54),P<0.01],so in terms of ,with statistically significant difference. 4 articles mentioned that no obvious adverse reactions occurred,4 articles mentioned that the treatment group had drowsiness,dry mouth and bitter mouth,gastrointestinal reactions,but the incidence rates were significantly lower than those of the control group. The other 13 articles did not mention the occurrence of adverse reactions.

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