ABSTRACT
RNA therapeutics inhibit the expression of specific proteins/RNAs by targeting complementary sequences of corresponding genes, or synthesize proteins encoded by the desired genes to treat genetic diseases. RNA-based therapeutics are categorized as oligonucleotide drugs (antisense oligonucleotides, small interfering RNA, RNA aptamers), and mRNA drugs. The antisense oligonucleotides and small interfering RNA for treatment of genetic diseases have been approved by the FDA in the United State, while RNA aptamers and mRNA drugs are still in clinical trials. Chemical modifications are applied to RNA drugs, such as pseudouridine modification of mRNA, to reduce immunogenicity and improve the efficacy. The secure and effective delivery systems like lipid-based nanoparticles, extracellular vesicles, and virus-like particles are under development to address stability, specificity, and safety issues of RNA drugs. This article provides an overview of the specific molecular mechanisms of 11 RNA drugs currently used for treating genetic diseases, and discusses the research progress of chemical modifications and delivery systems of RNA drugs.
ABSTRACT
RNA therapeutics inhibit the expression of specific proteins/RNAs by targeting complementary sequences of corresponding genes or encode proteins for the synthesis desired genes to treat genetic diseases. RNA-based therapeutics are categorized as oligonucleotide drugs (antisense oligonucleotides, small interfering RNA, RNA aptamers), and mRNA drugs. The antisense oligonucleotides and small interfering RNA for treatment of genetic diseases have been approved by the FDA in the United States, while RNA aptamers and mRNA drugs are still in clinical trials. Chemical modifications can be applied to RNA drugs, such as pseudouridine modification of mRNA, to reduce immunogenicity and improve the efficacy. The secure and effective delivery systems such as lipid-based nanoparticles, extracellular vesicles, and virus-like particles are under development to address stability, specificity, and safety issues of RNA drugs. This article provides an overview of the specific molecular mechanisms of eleven RNA drugs currently used for treating genetic diseases, and discusses the research progress of chemical modifications and delivery systems of RNA drugs.
Subject(s)
Aptamers, Nucleotide , RNA, Small Interfering/therapeutic use , RNA, Messenger , Oligonucleotides, Antisense/therapeutic useABSTRACT
Objective:To investigate the efficacy of intermittent pneumatic compression (IPC) combined with drugs in the prevention of lower extremity deep venous thrombosis (DVT) after joint replacement and its risk factors.Methods:A total of 80 patients receiving joint replacement surgery in Jinhua People's Hospital from January 2019 to December 2020 were included in this study. They were randomly divided into observation and control groups, with 40 patients in each group. To prevent lower extremity deep venous thrombosis, the control group was given low molecular weight heparin, and the observation group was given IPC in addition to DVT. The incidence of DVT post-surgery and coagulation function pre- and post-surgery were compared between the two groups. The incidence of adverse reactions was recorded in each group. In addition, 40 patients who developed DVT after joint replacement surgery from January 2019 to December 2020 (DVT group) and 40 patients who did not develop DVT (no DVT group) were included. The factors influencing the occurrence of DVT were analyzed by binary logistic regression.Results:The incidence of DVT in the observation group was significantly lower than that in the control group (5.00% vs. 20.00%, χ2 = 4.11, P < 0.05). At 7 days after surgery, prothrombin time, activated partial thromboplastin time, fibrinogen in the observation group were (11.73 ± 0.51) seconds, (27.05 ± 1.17) seconds, (3.89 ± 0.52) g/L, respectively, which were significantly lower than (12.03 ± 0.43) seconds, (27.65 ± 1.30) seconds, and (4.18 ± 0.59) g/L in the control group ( t = 2.84, 2.33, 2.17, all P < 0.05). There was no significant difference in the incidence of adverse reactions between observation and control groups (5.00% vs. 2.50%, χ2 = 0.00, P > 0.05). There were significant differences in age, body mass index, history of hypertension, and operative time between patients with DVT and those without DVT ( χ2 = 4.11, 5.16, 4.71, 8.65, all P < 0.05). Logistic regression analysis showed that age ( OR = 1.57, 95% CI = 1.239 - 2.014), body mass index ( OR = 6.71, 95% CI = 1.298 - 34.794), history of hypertension ( OR = 3.23, 95% CI = 1.980 - 5.296), operative time ( OR = 6.29, 95% CI = 2.058 - 19.225) were independent risk factors for DVT after joint replacement surgery (all P < 0.05). Conclusion:There are many factors that influence the occurrence of DVT after joint replacement surgery. Intermittent pneumatic compression combined with drugs for prevention of lower extremity DVT is safe and effective.
ABSTRACT
OBJECTIVE：To explore the role of pharmacists i n developi ng the outpatient and emergency prescription pre-audit with the help of rational drug use software. METHODS ：With the help of rational drug use software ，outpatient and emergency prescription pre-aduit was conducted during Jan.-Apr. 2020；the intervention effects of irrational prescriptions were analyzed. The prescriptions from Sept. to Dec. in 2019 were included in the control group （only for post review ），and the prescriptions from Jan. to Apr. in 2020 were included in the intervention group （pre-audit and post review ）；the unreasonable prescriptions were compared before and after the intervention. The prescriptions intercepted by the software system from Nov. to Dec. in 2019 were further selected as the interception control group ，and the prescriptions intercepted from Jan. to Feb. in 2020 were selected as the interception intervention group ；the interception situation of prescriptions before and after the intervention was compared ，and the influence of pre-audit on physicians ’prescription behavior was evaluated. In addition ，108 992 prescriptions in Apr. 2020 were selected for post review using the traditional model （i.e. complete manual audit ）and the information model （i.e. software-assisted manual audit ）respectively；the effects of two models were compared. RESULTS ：From Jan. to Apr. in 2020，a total of 2 393 prescriptions were pre-audited by pharmacists ，among which 1 387 prescriptions were reasonable （57.96％）and 1 006 prescriptions were unreasonable and intervened （42.04％）. After pharmacist intervention ，983 prescriptions were modified by doctors ，and the success rate of intervention was 97.71％ . Compared with control group ，unreasonable rate of outpatient and emergency prescriptions，that of each type of prescriptions were all decreased significantly （P＜0.001）. Compared with interception control group（1 402 pieces），the number of intercepted prescriptions （721 pieces）was significantly reduced in interception intervention group （P＜0.001）. Compared with traditional model ， the number of prescriptions requiring manual post review and E-mail：xss306@126.com “false positive ” prescriptions were decreased significantly # under information model ， and the number of discovered unreasonable prescriptions were increased significantly （P＜ 0.001）. CONCLUSIONS ：With the help of rational drug use software ，prescription pre-audit by pharmacists can significantly improve reasonable rate of outpatient and emergency prescriptions. The work intensity of pharmacists in post review of prescriptions can be reduced and the accuracy of prescription review can be improved in the information mode.
ABSTRACT
OBJECTIVE：To summarize and analyze t he clinical characteristics of acarbose-induced skin ADR ，and to provide reference for its therapy. METHODS ：Clinical pharmacists participated in the treatment of a patient with acarbose-induced skin ADR. The patient developed erythema multiforme several days after oral administration of Acarbose tablets （100 mg/d）. After consultation by dermatology and clinical pharmacy ，considering that the adverse reaction was related to acarbose ，clinical pharmacists suggested to stop the drug. Based on the above cases ，clinical pharmacists searched Wanfang database ，CNKI， PubMed，Embase and other databases to collect case reports of skin ADR caused by acarbose ，summarize its general situation （gender，age，usage and dosage ，etc.），latency，ADR（diagnosis and manifestation ），intervention and outcome ，etc. RESULTS ： The doctor adopted the pharmacist s’advice，stopped the use of acarbose ，and gave symptomatic treatment as Methylprednisolone sodium succinate for injection 40 mg（intravenous injection ，qd）+Medloratadine tablets 8.8 mg（oral administration ，qd）+Calamine lotion（for external use ）. The patient improved and was discharged after 10 days. A total of 12 literatures involving 12 patients were retrieved. Among the 13 patients included in the analysis （including the above clinical case and 12 literature cases ），there were 8 males and 5 females，and 8 patients of them aged 50 and over；the dosage of acarb ose in most patients was within the requirements of the drug instructions. The primary diseases of 12 patients were diabetes mellitus. The latency of skin ADR in 11 patients was within 6 days of administration. Among the 13 patients，the ADR were diagnosed as rash in 4 cases，pustulosis in 3 cases， erythema multiforme in 2 cases， urticaria in 2 cases， maculopapular rash in 1 case and lip swelling in 1 case. The ADR of 1 patient improved after drug withdrawal ，and 12 patients also improved after drug withdrawal and symptomatic treatment such as glucocorticoid or antihistamine. Acarbose was re-used in 2 patients after the improvement of first skin ADR ，and skin ADR occurred again ，and the ADR were improved after drug withdrawal and symptomatic treatment. CONCLUSIONS ：Skin ADR are acarbose-induced rare ADR ，mostly within 6 days of medication ，and are more likely to occur in middle-aged and older men. When the patients suffer from ADR ，the drug should be stopped in time and given glucocorticoids or antihistamines for symptomatic treatment. Clinical pharmacists should do a good job in drug publicity and education ，remind patients to closely monitor relevant indicators and ensure drug safety.
ABSTRACT
Hippo signaling pathway is highly conservative in evolution. MST1/2, LATS1/2, and the effector protein YAP/TAZ are the core members of this signaling pathway in mammalian cells. There have been many studies on YAP/TAZ and its downstream, however, the upstream regulatory factors of the Hippo signaling pathway remain unclear, and become one of the hot research directions of this pathway at present. In addition, Hippo signaling pathway can cross-talk with other signaling pathways such as Wnt and Notch signaling pathways, and plays an important role in controlling organ size, maintaining tissue homeostasis, and promoting tissue repair and regeneration. Abnormal Hippo signaling pathway may lead to the occurrence of a variety of tumors, especially gastrointestinal cancers such as liver cancer, colorectal cancer and gastric cancer. The abnormal expression of its members in gastrointestinal cancers is related to cancer cell proliferation, apoptosis, invasion and migration. Hippo signaling pathway is vital for liver repair and regeneration. Its inactivation will lead to the occurrence of primary liver cancer. The mechanism of YAP in liver cancer mainly depends on TEAD-mediated gene transcription. Hippo signaling pathway is also important for maintaining intestinal homeostasis, and its imbalance can lead to the occurrence and recurrence of colorectal cancer. In primary and metastatic gastric cancer, the expression of YAP/TAZ is significantly up-regulated, but the specific molecular mechanism is unclear. This article summarizes the recent progress on Hippo signaling pathway and its upstream regulatory factors, its roles in the development of gastrointestinal cancers and related molecular mechanisms; and also discusses the future research directions of Hippo signaling pathway.
Subject(s)
Humans , Apoptosis , Physiology , Cell Proliferation , Physiology , Gastrointestinal Neoplasms , Signal TransductionABSTRACT
Objective To explore the value of three dimensional sampling perfection with application optimized contrasts using different flip angle evolutions (3D-SPACE)magnetic resonance for postoperative follow-up of intracranial artery stent. Methods The clinical and imaging data of 19 patients with intracranial atherosclerotic stenosis after stent implantation were collected retrospectively from April 2017 to April 2018 in the Department of Neurology, First Affiliated Hospital of Zhengzhou University. 3D-SPACE sequence magnetic resonance examination was performed within 3 days after digital substraction angiography (DSA). Double-blind readings of DSA and MRI images were performed by two physicians, and the degree of lumen stenosis in the stent was measured by the WASID study method. The intra-group correlation coefficient was used to evaluate the consistency of the DSA and 3D-SPACE sequence measurements between the two physicians.The sensitivity, specificity, positive predictive value, and negative predictive value of 3D-SPACE sequence measurement results were evaluated using DSA as the gold standard. Paired sample t test was used to compare the difference in the degree of stenosis between the 3D-SPACE sequence and the DSA. Results Good inter-observer agreement was noted between the two physicians. The ICC value of DSA was 0.903 (P<0.01), and the ICC value of the 3D-SPACE sequence was 0.875 (P<0.01). With DSA as the gold standard, the sensitivity, specificity, positive predictive value and negative predictive value of the 3D-SPACE sequence in the diagnosis of stent stenosis were 100.0％, 80.0％, 81.8％, and 100.0％, respectively. The average stenosis degree in the stent measured by DSA was (51.7 ±19.2)％, and the 3D-SPACE sequence was (55.5 ± 18.9)％. The difference was not statistically significant (t=1.675, P=0.111). Conclusions 3D-SPACE sequence magnetic resonance imaging can be used as a non-invasive imaging method for follow-up after intracranial stenting.
ABSTRACT
Objective To investigate the relationship between spina bifida occulta in lumbasacral portion and functional defe-cation abnormality among middle-aged and elderly people.Methods The cross-sectional and cluster random sampling survey meth-od was adopted to select the residents aged 45-90 years old in 7 communities of Zhengzhou City as the respondents.All respond-ents underwent the physical examination and lumbosacral digital radiography(DR)examination in the physical examination center of the First Affiliated Hospital of Zhengzhou University,and filled the related questionnaire about defecation abnormality.The rela-tionship between SBO and functional defecation abnormality among middle-aged and elderly people was studied by diagnosing and analyzing the functional constipation(FC)and functional incontinence(FC).Results The effective sample amounts were 1 057 ca-ses,including 497 males and 560 females,167 cases of SBO(86 males and 81 females).The morbidity rate of functional defecation abnormality was 26.02%(275/1 057),23.34%(116/497)in males and 28.39%(159/560)in females.Among 275 cases of functional defecation abnormality,there were 72 cases of complicating SBO.The Logistic regression analysis results showed that age,SOB,physical activity status,diet and living habits,education level and psychological factors were the risk factors for functional defecation abnormality (P<0.05),while there was no relationship between between past-history of stroke and functional defecation abnormality(P>0.05).Con-clusion SBO may be one of risk factors for functional defecation abnormality among middle-aged and elderly people.
ABSTRACT
Objective To analyze the epidemiological characteristics of fatty liver complicating gallbladder diseases among the people undergoing healthy physical examination and to investigate its onset risk factors.Methods A total of 7 364 subjects undergoing abdominal color Doppler ultrasonography in the physical examination center of this hospital from June 2011 to June 2015 were selected as the study subjects and divided into 4 groups according to the examination results,fatty liver complicating gallbladder disease group,simple fatty liver group,simple gallbladder diseases group and non-fatty liver and non-gallbladder disease group.The Logistic regression model was used to analyze the influence of related factors on the patients with fatty liver complicating gallbladder diseases.Results The prevalence rate of gallbladder diseases in the patients with fatty liver ia significantly higher than that in the patients without fatty liver(P＜0.05).The multivariate Logistic regression model statistical analysis results showed that often skip breakfast,greasy food,eating more meat,eating much sweet food,dirking more tea,gender(female),age and LDL-C were the independent risk factors for fatty liver complicating gallbladder diseases(P＜0.05).Conclusion The unhealthy living habits were the independent risk factors for fatty liver complicating gallbladder diseases.
ABSTRACT
Objective To study the effect of Shaoyao Gancao Grain on serum prolactin level in female schizophrenia patients with high prolactin induced by risperidone.Methods 100 patients were randomly divided into the control group 50 cases,which were given risperidone. The study group 50 cases,which were given Shaoyao Gancao Grain on the basis of the control group. The two groups were treated for 12 weeks. Positive And Negative Syndrome Scale,serum prolactin and Estrogen level were measured by immunohistochemistry before and after 12 weeks of treatenmt.Results After 12 weeks of treatenmt,serum prolactin levels were decreased in the study group than control group (46.28 ± 14.06 ng/mlvs. 117.89 ± 22.11 ng/ml;t=10.242,P0.05). ConclusionsShaoyao-Gancao grain can decrease serum prolactin level in female schizophrenia patients with high prolactin induced by risperidone,does not affect estrogen levels.
ABSTRACT
Breast cancer is a heterogeneous disease.Its invasion and metastasis,recurrence and part of the chemotherapy drug tolerance are currentlv difficulties of treatment.Breast cancer stem cells have the ability of selfrenewal,proliferation and differentiation potential,which may correlate closely with breast cancer recurrence,treatment failure.This assay aims to briefly analyse markers and significance of breast cancer stem cells,and the relationship between the treatment of breast cancer and breast cancer stem cells.
ABSTRACT
The uptake of oral administered drugs primarily occurs in the small intestine,which also has the capability to metabolize drugs.Both phase Ⅰ and phase Ⅱ metabolic enzymes were expressed in the intestinal mucosa,and cytochromes P450(CYP450s) are the principle enzymes attributed to the biotransformation of drugs.CYP3A and CYP2C are the most abundant subfamilies,accounting for approximately 80% and 16% of total CYP450s in the intestine.Compared to the liver,the expression and activity of CYP450 enzymes in the intestine was susceptible to inducers or inhibitors,leading to drug-drug interaction.This article reviews the expression of CYP enzymes in small intestine and the role of the gut wall in CYP-mediated xenobiotic metabolism.Possible drug-drug interactions due to induction or inhibition of CYP enzymes in the small intestine are also addressed.
ABSTRACT
To produce recombinant Maxadilan using gene engineering technology, the gene of recombinant Maxadilan which expressed in protocaryon were designed and synthesized according to the amino acid sequences of Maxadilan. The recombinant plasmid pKYB-MAX was constructed and transformed into host bacteria Escherichia coli strain ER2566. After the MAX-intein-CBD fusion protein was purified by chintin-affinity chromatography, the self-cleavage activity of the intein was induced by beta-mercaptoethanol and the recombinant Maxadilan was released from the chitin-bound intein tag. The molecular weight of peptides was determined by the laser flight mass spectrometry and the results was conformity with the theoretical value. The biological activity analysis showed that recombinant Maxadilan significantly enhanced the concentration of serum glucose.