Hepatitis C virus (HCV), one of the major pathogens of viral hepatitis, causes significant hazards in humans. Interferon treatment in combination with ribavirin is used as the first line clinical treatment for HCV infection. However, good response to this treatment has only been observed in few patients and repeated recurrence has also been reported frequently. Therefore, new antiviral agents and therapies are in urgent demand. Here, we report a newly constructed Escherichia coli RNase P based M1GS ribozyme that can specifically and efficiently target the core gene of HCV. The guide sequence (GS) of this M1IGS was designed according to the sequence of the core coding region of HCV genome. The GS was then covalently linked to the 3' terminus of M1 RNA, the catalytic subunit of RNase P from Escherichia coli. The specification of this sequence-specific ribozyme, M1GS, was then examined using an in vitro cleavage assay. The cytotoxicity and its activity in inhibition of HCV gene expression and viral proliferation were further studied in vivo. Our results show that the reconstructed M1GS ribozyme displayed obvious catalytic activity in cleaving target mRNAs fragment in vitro. Notable reduction in the expression of HCV core protein and a 1 000-fold reduction in viral growth were also observed in cultured HCV infected Huh7.5.1 cells expressing the functional M1GS ribozyme. This study demonstrated a direct evidence for the antiviral activity of the customized M1GS-HCV/C141 ribozyme, and thus provided a promising new strategy for clinical treatment of HCV infection.
Antiviral Agents ; pharmacology ; Escherichia coli ; genetics ; Genetic Engineering ; Hepacivirus ; genetics ; physiology ; RNA, Catalytic ; genetics ; pharmacology ; RNA, Guide ; genetics ; Ribonuclease P ; genetics ; Viral Core Proteins ; genetics

Through the study on traditional Chinese medicine (TCM) data mining methods, the traditional mining model was revealed to have certain limitations. New ways and means should be searched in order to tap the potential, deep level and greater value of TCM knowledge. In view of the situation, advantages of strategy pattern thought for medicine data mining were discussed. And deep research was carried on. New ideas on TCM data mining based on strategy pattern was proposed.

Objective: To investigate the clinical efficacy of Tengmei decoction combined with leflunomide and methotrexate in the treatment of patients with rheumatoid arthritis. Methods: From February 2015 to February 2017, 72 patients with heat-tolerant rheumatoid arthritis were enrolled in Linhai Hospital of Traditional Chinese Medicine (TCM). They were randomly divided into treatment group and control groupaccording to the digitaltable, with 36 cases in each group.The control group was given leflunomide (20mg/time, 1 time/d) combined with methotrexate (15mg/time, 1 time/week). The treatment group was given Tengmei decoction on the basis of the control group.Both two groups were treated for 12 weeks.TCM symptom scores, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), platelet (PLT), joint disease activity (DAS) score, tender joint count (TJC) and swollen joint count(SJC)before and after treatment were compared between the two groups.The clinical efficacy and adverse reactions after treatment were observed. Results: The total effective rate of the treatment group was 88.89%, which was significantly higher than that of the control group (69.44%), the difference was statistically significant (χ²=4.126, P=0.042). After treatment, the TCM symptom scores (morning stiffness, joint swelling and joint pain etc.), DAS score, TJC and SJC levels in the two groups, were significantly decreased(t_{treatment group}=28.935, 26.430, 25.824, 6.889, 9.222, 5.437; t_{control group}=23.790, 21.704, 21.685, 3.312, 8.134, 2.379, all P<0.05), and those in the treatment group decreased more significantly (t=10.004, 5.488, 7.593, 3.511, 2.554, 3.764, all P<0.05). After treatment, the ESR, RF, CRP, PLT levels of the treatment group and ESR, RF, CRP levels of the control group were significantly decreased (t_{treatment group}=3.969, 2.821, 5.970, 2.791, t_{control group}=5.240, 2.246, 5.452, all P<0.05), and the ESR and CRP levels in the treatment group were significantly lower than those in the control group (t=2.394, 3.895, all P<0.05). Conclusion The efficacy of Tengmei decoction combined with leflunomide and methotrexate in the treatment of patients with heat-toxic phlegm-restricted rheumatoid arthritis is effective, which can effectively reduce inflammatory indicators and improve TCM symptom scores, and is safe and reliable.

Objective To evaluate the influence of Chinese patent medicine Banlangen Granules and Ganmao Qingre Granules on war‐farin anticogulation effect during the process for treating acute upper respiratory tract infection in the postoperative patients with mechanical valve replacement in order to provide the theoretical reference for clinical medication .Methods The patient receiving mitral valve replace‐ment ,aortic valve replacement or double‐valve replacement and long term postoperative oral warfarin anticoagulation treatment were select‐ed ,moreover the symptoms of complicating acute upper respiratory tract infection occurred .The patients were divided into 2 groups ,30 cases in each group .The group A adopted oral Banlangen Granules ,while the group B was treated by oral Ganmao Qingre Granules .The treat‐ment course was 3 d .The International Normalized Ratio (INR) in the two groups was monitored before medication ,at 72 h after medication and at 72 h after drug withdrawal .Complicating bleeding or embolism reaction was observed .The INR values at various time points were compared between the two groups and the INR values in each group were compared among 3 time points .Results The INR values in the Banlangen Granules group had statistical differences between 72 h and other two time points ,and the INR values at the same time point had statistical difference compared with the Ganmao Qingre Granules group (P<0 .05);the INR value in the Banlangen Granules group had no statistical difference between before medication and at 72 h after medication(P>0 .05) .Thirty cases had no complication occurrence .The Ganmao Qingre Granules group had no statistical difference among various time points (P>0 .05) ,thirty cases had no complication occur‐rence .Conclusion The warfarin combined with Banlangen Granules causes the INR value increase ,while warfarin combined with Ganmao Qingre Granules has no impact on the INR value ,therefore which suggests that the combination use of warfarin and Banlangen Granules should be cautious in clinic .

Objective: To investigate the influencing factors for postoperative urinary retention in patients with spinal surgery. Methods: The clinical data of patients with spinal surgery were collected and divided into two groups according to the occurrence of urinary retention (urinary retention group and non occurring urinary retention group). The factors that may affect postoperative urinary retention were compared and multiple factor Logistic regression was used. Results: Among the 292 patients, 56 cases had postoperative urinary retention and the morbidity was 19.18%. Single factor analysis indicated that Univariate analysis showed that there was a statistically significant difference in anesthetic mode, time of indwelling catheter, time of lying in bed, clamping catheter and timing of removal of urinary catheter (χ²=5.035-22.747, P<0.05 or <0.01). Multivariate Logistic regression analysis showed that the risk factors for urinary retention were time of catheter more than 3 days and bed time is no less than 5 days, and the protective factors were clamping the catheter indwelling training, having a sense of urine and bladder filling. Conclusions During the period of indwelling catheter can be closed catheter training, grasp the time of indwelling catheter 1-2 d best catheter time. Urinary catheter should be removed when urine is filled and bladder is filled. At the same time, under the premise of ensuring safety, the patient's bed time should be shortened as far as 5 days, and the rate of urinary retention can be reduced.

OBJECTIVE: To compare the efficacy of metformin plus megestrol acetate (MA) with that of MA alone for treating endometrial atypical hyperplasia (EAH). METHODS: This pilot study included 16 EAH patients who met at least one metabolic syndrome (MS) criterion and received either adjunctive metformin plus MA (MET group) or MA monotherapy (MA group). Each patient in the MA group received 160 mg of MA daily, whereas patients in the MET group received the same dose of MA plus 0.5 g of metformin thrice daily. Treatment response was assessed by histological examination of dilation and curettage specimens obtained after 12 weeks of therapy. RESULTS: Each group had eight patients, and half of the patients in each group were diagnosed with MS. The complete response (CR) rate was 75% (6/8) in the MET group and 25% (2/8) in the MA group (p=0.105). Complications of MS did not affect the response rates in either group. In the MET group, 75% (3/4) of the patients had CR in the presence or absence of MS. In the MA group, 50% (2/4) of the patients with MS had CR, whereas no patient without MS had CR. No irreversible toxicities were observed. CONCLUSION: Metformin plus MA may be a potential alternative therapy for treating EAH, and the MS status of patients may have no effect on the efficacy of metformin plus MA therapy.
Adult ; Antineoplastic Agents, Hormonal/*therapeutic use ; Drug Therapy, Combination ; Endometrial Hyperplasia/complications/*drug therapy/metabolism ; Female ; Humans ; Hypoglycemic Agents/*therapeutic use ; Megestrol Acetate/*therapeutic use ; Metabolic Syndrome X/complications/metabolism ; Metformin/*therapeutic use ; Pilot Projects ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Single-Blind Method ; Treatment Outcome

Objective To investigate the predictive value of interleukin-33(IL-33),eosinophil chemotactic factor(Eotaxin),soluble scavenger receptor CD163(sCD163)for recurrent wheezing in children with bronchi-olitis.Methods A total of 120 children with bronchiolitis who were treated in Jiamusi Maternal and Child Health Hospital from August 2019 to October 2021 were enrolled in the study.The clinical data of the chil-dren were collected,including demographic factors,birth factors,atopic factors,length of hospital stay,time from symptom onset to visit,and respiratory distress assessment tool(RDAI)score.Respiratory syncytial vi-rus(RSV)and rhinovirus(RV)were detected.Blood samples were collected for detection.Blood test indica-tors included total immunoglobulin E(IgE),white blood cell count(WBC),IL-33,Eotaxin and sCD163.The discharged children were followed up for 1 year,and they were divided into non-recurrent group and recurrent group according to the number of wheezing episodes.The two groups were compared in terms of clinical data and blood test indicators.Logistic regression was used to analyze the risk factors for recurrent wheezing in children with bronchiolitis.Pearson correlation analysis was used to analyze the correlation between blood test indexes and RDAI score.The receiver operating characteristic(ROC)curve was drawn to analyze the value of IL-33,Eotaxin,and sCD163 levels alone and in combination in predicting recurrent wheezing in children with bronchiolitis.Results Compared with the non-recurrent group,the recurrent group had significantly higher RDAI score,higher proportion of patients with a history of eczema,a personal history of allergy,and a signifi-cantly higher RSV infection rate(P＜0.05).The recurrent group had significantly higher levels of IL-33,Eotaxin,and sCD163 than the non-recurrent group(P＜0.05).Pearson correlation analysis showed that the levels of IL-33,Eotaxin,and sCD163 in children with bronchiolitis were positively correlated with RDAI score(r=0.516,0.611,0.522,P＜0.05).Logistic regression analysis showed that RDAI score,history of eczema,personal history of allergy,RSV infection,increased IL-33 levels,increased Eotaxin levels,and increased sCD163 levels were risk factors for recurrent wheezing in children with bronchiolitis(OR＞1,P＜0.05).The ROC curve found that The area under the curve(AUC)of IL-33,Eotaxin,and sCD163 levels alone and in combination for predicting recurrent wheezing in children with bronchiolitis was 0.829(95％CI:0.757-0.901),0.858(95％CI:0.794-0.922),and 0.857(95％CI:0.789-0.925)and 0.954(95％CI:0.921-0.987).Conclusion Increased levels of IL-33,Eotaxin and sCD163 in children with bronchiolitis can increase the risk of recurrent wheezing,and the combined detection of the three can effectively predict the occurrence of recurrent wheezing.

Objective:To evaluate the efficacy and safety of stereotactic ablative radiotherapy (SABR) in patients with pulmonary oligometastases.Methods:Clinical data of patients with pulmonary metastases treated with SABR from 2011 to 2018 were retrospectively analyzed. The local control rate (LCR) and overall survival (OS) were calculated by Kaplan- Meier method. log-rank test was used for univariate analysis and Cox’s regression model for multivariate analysis. Results:A total of 214 lung metastases were detected in 159 patients, and the median follow-up time was 43 months. The 1-, 3-and 5-year LCR were 90.1%, 73.9% and 65.8%, respectively. The 1-, 3-and 5-year OS were 73.8%, 43.6% and 11.9%, respectively. Univariate analysis showed that biological effective dose (BED)≥100 Gy was significantly correlated with LCR ( P=0.033). Cox’s multivariate analysis showed that BED and primary tumor source were the independent prognostic factors of LCR ( P=0.023, P=0.043). No>grade 3 adverse events were observed in all patients during treatment. Conclusions:SABR is a safe and effective treatment of lung oligometastases. SABR should be actively aD ministered for pulmonary oligometastases, especially for those with lesions from lung cancer and the radiation dose should be selected as BED ≥100 Gy.

Objective To analyze the management and countermeasures of adverse nursing events in a municipal tertiary hospital in Guangxi Zhuang Autonomous Region.Methods The adverse nursing events in 2023 in a municipal tertiary hospital in Guangxi were retrospectively analyzed.Logistic regression analysis was utilized to identify the causes of these adverse events and propose suitable countermeasures.Results In 2023,a total of 121 adverse nursing events were recorded,with falls being the most prominent(42 cases,accounting for 34.71％),followed by drug extravasation,drug safety incidents and unplanned ex-tubation,accounting for 13.22％,9.92％,and 7.44％respectively.Logistic regression analysis revealed that factors such as age ≥70 years,coexisting diseases,Basel Index score ≤40,pain score ≥4,tube slip risk assessment ≥10,RASS sedation score ≥3,NGASR score ≥9,lost risk assessment score ≥ 7,GCS Coma Scale score ≤8,Stress Injury Assessment Scale score ≤10,and Morse score ≥45 were associated with the risk of adverse nursing events.In addition,inadequate awareness of nursing risks among nursing staff,ineffective patient health education methods,and non-compliance to nursing protocols were identified as primary causes of adverse nursing events.Conclusion Advanced age,combined with other diseases,and hospitali-zation scale assessment results are critical factors for adverse nursing events.Lack of nursing responsibility and risk awareness among nursing staff,inadequate system implementation,and irregular operations can increase the risk.Hospitals should optimize management systems and work processes,enhance nursing staff training,and develop targeted preventive measures for adverse nursing events to improve the quality of nursing management and reduce the risk of adverse nursing events.

Disulfiram (DSF) has been widely used in clinical treatment of alcoholism.To date,in vivo and in vitro experiments have demonstrated that DSF has strong anti-cancer activity and could improve patient's survival,and the underlying mechanism has been elaborated.In addition,it was reported that,during radiotherapy,DSF could protect normal tissue and cells meanwhile enhance the radiosensitivity of tumor cells by forming complexes with copper ions,suppressing cancer stem cells and inhibiting ubiquitin-proteasome system activity in cancer cells.This review summarizes the completed and ongoing clinical trials of disulfiram,and its anti-tumor mechanisms and advances in radiation biology.