The COVID-19 outbreak has drawn attention to viral infectious diseases once again, and the development of antiviral drugs for both known and potentially emerging viruses is of great significance. In recent years, peptides and protein drugs are becoming a hot spot in the field of antiviral drug research and development. Phage display technology, as a powerful tool for screening peptides and protein drugs, has been increasingly concerned in the academic and industrial fields. The present review introduced the basic principle of phage display technology, summarized phage display libraries often used in antiviral drug discovery and their applications, discussed the challenges and future direction of antiviral drug research and development based on phage display technology.

BACKGROUNDBladder recurrent disease is still a challenge in the treatment of upper tract urothelial carcinoma (UTUC). This controlled study aims to investigate the efficacy of early clipping of the distal ureter prior to nephroureterectomy (NU) to prevent bladder recurrence after UTUC.

METHODSPatients with clinical diagnosis of UTUC were subjected to open trans-peritoneal NU and were randomly divided into two groups. One group received modified NU: clipping the distal ureter prior to NU; while the other group underwent traditional standard NU. Subsequent bladder recurrence was the primary endpoint.

RESULTSFrom January 2007 to December 2009, 85 eligible cases were enrolled in this study. Modified NU and standard NU were performed on 42 and 43 patients, respectively. Operation time ((215.73 ± 21.26) minutes vs. (220.19 ± 15.35) minutes), blood loss ((105.15 ± 11.32) ml vs. (110.12 ± 9.07) ml), transfusion event (11.20% vs. 9.78%), and the in-patient time (10.0 days vs 9.5 days) were not significant between the two groups. After a median follow-up of 28 months (5 - 60), six (14.3%) cases who received modified NU had bladder recurrence, which was significantly lower compared with 15 (34.9%) patients from the group that underwent standard NU (P = 0.026). In univariate and multivariate analysis, tumor grade (HR 4.33, 95%CI 2.66 - 6.30, P = 0.01) and operation type (HR 2.35, 95%CI 1.53 - 3.48, P = 0.041) were independent risk factors for subsequent bladder recurrence after UTUC.

CONCLUSIONSClipping the distal ureter at the beginning of NU significantly reduces bladder recurrence after UTUC. It is reasonable to conclude that clipping the distal portion of ureter trans-peritoneal is an effective surgical procedure for the treatment of UTUC.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Nephrectomy ; methods ; Ureter ; surgery ; Urinary Bladder Neoplasms ; surgery

Objective To observe effects of Heyutai Fuzhu Jiangtang Tablets combined with metformin in insulin resistance (IR); To discuss its mechanism of action. Methods 6–7 week old male ZDF (fa/fa) rats were randomly divided into model group,metformin group,Heyutai Fuzhu Jiangtang Tablets group(Jiangtang Tablets group),and metformin combined with Heyutai Fuzhu Jiangtang Tablets group.ZDF(fa/+)rats were chosen as normal group.Each medication group was given relevant medicine for gavage for 6 weeks. Body weight, FBG, TG, TC, FFA, FINS, HOMA-IR, OGTT and HE staining were tested. HE staining was used to observe the pathological changes of skeletal muscle. RT-PCR and Western blot were used to detect skeletal muscle corresponding gene and protein expression. Results Compared with Jiangtang Tablets group and metformin group, TC, FFA, FBG, and HOMA-IR in metformin combined with Heyutai Fuzhu Jiangtang Tablets group decreased significantly (P<0.05, P<0.01). Blood glucose level and AUC significantly decreased at each time point in OGTT. HE staining of skeletal muscle fibers arranged in order; nucleus increased and internal movement was not significant, without obvious infiltration of inflammatory cells. Expressions of skeletal muscle InsR, Akt, and Glut4 mRNA expression increased (P<0.05, P<0.01). Expressions of skeletal muscle p-InsR, p-Akt, and Glut4 protein expression increased (P<0.05, P<0.01). Conclusion Heyutai Fuzhu Jiangtang Tablets combined with metformin can improve IR in type 2 diabetic rats, and the effect is better than single-application.

Objective To observe the clinical effect of Peiyuan Yangxin(cultivating vital essence and nourishing heart)acupuncture and moxibustion method combined with Gubu Pills in the treatment of type 2 diabetes mellitus complicated with osteoporosis(T2DOP).Methods A total of 70 patients with T2DOP were randomly divided into treatment group and control group,with 35 cases in each group.The control group was treated with conventional hypoglycemic and calcium supplementation.On the basis of the control group,the treatment group was treated with Peiyuan Yangxin acupuncture and moxibustion method combined with Gubu Pills for eight weeks.After two months of treatment,the clinical efficacy of the two groups was evaluated,and the changes of serum osteocalcin(OC),total type 1 collagen amino acid extension peptide(PINP),β-collagen special sequence(β-CTX),inorganic phosphorus(P)and glycosylated hemoglobin(HbA1c)were observed before and after treatment.The changes of pain Visual Analogue Scale(VAS),Hamilton anxiety scale(HAMA)and diabetes specific quality of life scale(DSQL)scores were compared before and after treatment between the two groups.The safety and adverse reactions of the two groups were evaluated,and the recurrence rate and rehospitalization rate of the two groups were counted.Results(1)After treatment,the serum OC,PINP,β-CTX and P levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving serum OC,PINP,β-CTX and P levels,with a statistically significant difference(P＜0.05).(2)After treatment,the HbA1c level of patients in both groups was significantly improved(P＜0.05),and the treatment group was significantly superior to the control group in improving HbA1c level,with statistically significant differences(P＜0.05).(3)After treatment,the VAS,HAMA and DSQL scores of patients in the two groups were significantly improved(P＜0.05),and the treatment group was significantly superior to the control group in improving VAS,HAMA and DSQL scores,with statistically significant differences(P＜0.05).(4)The total effective rate was 88.57％(31/35)in the treatment group and 68.57％(24/35)in the control group.The efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(5)The recurrence in the treatment group was significantly less than that in the control group,and the difference was statistically significant(P＜0.05).(6)There were no statistically significant differences of the incidence of adverse reactions between the two groups of patients(P＞0.05).Conclusion Peiyuan Yangxin acupuncture and moxibustion method combined with Gubu Pills in the treatment of T2DOP can significantly reduce the pain and anxiety symptoms of patients,improve the biochemical indexes of bone metabolism,thereby improving the quality of life of patients,increasing the effective rate of treatment,and reducing the recurrence rate and the rate of rehospitalization in the short term.

As one of the most important laboratory tools for the research of quantum chemistry and astrochemistry, a microwave spectrometer can make accurate measurement of molecular spectra arising from rotational transitions. Fourier transform microwave (FTMW) spectrometers, in many cases, require down-conversion mixing plans by using mixers to bring the molecular signal down for A/D sampling, and multiple signal averaging to improve the signal/noise ratio as well. Two detection schemes, homodyne and heterodyne detection modes,were proposed in this project along with two data processing plans, averaging in the time domain and averaging in the frequency domain,to develop efficient,sensitive and accurate detection solutions for molecular rotational spectroscopy. With 0. 5% OCS gas in argon as standard sample, verification experiment was conducted with frequency difference between LO and cavity resonance at 200 MHz and 0.4 MHz. The experimental results indicate that, the heterodyne detection method can provide better sensitivity than the homodyne scheme, but with increased cost for more devices, while the time-domain averaging can obtain much better signal-to-noise ratio than frequency-domain averaging,but with stronger data processing capacity and more time required.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

Objective:To analyze the contractile properties of the lumbar erector spinae in patients with chronic nonspecific low back pain (CNLBP), and to explore their correlation with pain and dysfunction. Methods:From January to June, 2020, 24 patients with CNLBP in the outpatient and the ward of geriatric rehabilitation medicine department and 26 asymptomatic volunteers were included. Their contractile properties of the lumbar erector spinae were measured with tensiomyography, including maximum radial muscle displacement (Dm), contraction time (Tc), delay time (Td), sustain time (Ts), half-time relaxation (Tr) and lateral symmetry (LS). The contraction velocity (V_C) was calculated. Potential associations of tensiomyography parameters to Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were assessed using correlation analysis. Results:No significant differences were found in Td, Ts, Tc, Tr and LS between two groups (P > 0.05). Dm and Vc were significantly lower in both sides of CNLBP group than in the control group (t > 2.058, P < 0.01). Dm or Vc were not correlated with VAS and ODI (P > 0.05). Conclusion:Erector spinae are stiff and fatiguable in patients with CNLBP, however, they are not associated with pain and dysfunction. Tensiomyography could be used for accurate diagnosis and treatment of CNLBP.

Objective: To explore the medication compliance for secondary prevention drugs and long-term prognosis of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) between hospitals in different regions of China. Methods: The Optimal Antiplatelet Therapy for Chinese Patients with Coronary Artery Disease (OPT-CAD) study was a prospective, multi-center and registered study. Patients diagnosed as ACS and underwent PCI in OPT-CAD study were selected. Taking the Yangtze River as the dividing line between the south and the north of China, these patients were divided into two groups according to the hospitals where the patients visited, namely the southerns region group (n=1 958) and the northerns region group (n=5 091). In order to reduce selection bias and potential confounding factors, the patients in the two groups were matched by the tendency score, and the patients in the two groups were matched by the 1: 1 nearest match method according to the tendency score. The main endpoint of this study was the major adverse cardiovascular and cerebrovascular events (MACCE) occurring within 5 years after discharge, namely the composite endpoint of cardiac death, myocardial infarction, and/or ischemic stroke. Secondary endpoints were all-cause death, cardiac death, myocardial infarction, ischemic stroke, and type 2, 3, and 5 bleeding events defined by the Academic Research Consortium on Hemorrhage (BARC) within 5 years. The secondary preventive drugs was recorded, including antiplatelet drugs, statins, beta blockers, angiotensin converting enzyme inhibitors/angiotensinⅡreceptor blockers (ACEI/ARB), etc. Before and after the matching, the secondary preventive medication and the incidence of clinical events of the two groups were compared. Results: A total of 7 049 ACS patients, including 1 958 patients in the southern region group and 5 091 patients in the northern region group were enrolled in this study. There were 5 319 males (37.9%), and the aged was (60.7±6.7) years. After propensity score matching, there were 1 324 cases in each group. Before matching, in the northern region group, the proportion of smoking, hypertension and diabetes, previous history (myocardial infarction, PCI and stroke) and family history of coronary heart disease were higher (all P<0.05). The proportion of complex lesions, diffuse lesions, small vessel lesions and thrombotic lesions in the northern region group was higher than that in the southern region group (all P<0.05). Sixty months after discharge, the antiplatelet patterns were quite different between patients in the northern and southern region group (P<0.001). The proportion of clopidogrel monotherapy in the southern region group was higher than that in the northern region group (9.8% (130/1324) vs. 1.1% (14/1324)), while the proportion of aspirin monotherapy in the northern region group was higher than that in the southern region group (67.4% (893/1324) vs. 46.5% (616/1324)). As for the use of other secondary prophylactic drugs, the proportion of patients in southern region group receiving beta blockers (24.5% (325/1324) vs. 16.8% (222/1324), P<0.001) and ACEI/ARB (19.4% (257/1324) vs. 10.0% (133/1324), P<0.001) was higher than that in northern region group. After matching, the incidence of MACCE (8.4%(111/1 324) vs.6.2% (82/1 324), P=0.030) and BARC 2, 3 and 5 bleeding (6.0% (80/1 324) vs. 4.0% (53/1 324), P=0.020) was higher in patients in northern region group. Conclusions: ACS patients who undergo PCI in northern area hospital is at higher prevalence of comorbidities and complicated coronary artery lesions compared to patients in the southern area hospital, and the drug compliance is worse than that in southern area, and the prognosis is also relatively poor.
Acute Coronary Syndrome/drug therapy* ; Aged ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; China ; Humans ; Male ; Medication Adherence ; Middle Aged ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; Prospective Studies ; Secondary Prevention ; Treatment Outcome

Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.

Neobavaisoflavone is one of flavonoids of traditional Chinese medicine Psoralea corylifolial. It has numerous biological properties such as antibacterial, anti-inflammatory, anti-cancer, and anti-osteoporosis effects. This paper aimed to investigate the absorption mechanism of neobavaisoflavone in Caco-2 cell monolayer model. The analyte and osalmide were separated on Thermo Syncronis C18 column with methanol-0.1% formic acid solution (90∶10) as the mobile phase, at a flow rate of 0.2 mL•min⁻¹. The concentration of neobavaisoflavone was determined in eletrospray ionization(ESI) positive ion mode with osalmide as an the internal standard. The effects of time, concentration, P-gp inhibitor verapamil, MRP-2 inhibitor MK-571 and BCRP inhibitor Ko143 on the absorption of neobavaisoflavone were investigated. According to the results, neobavaisoflavone showed a good linearity within the concentration of 10-2 000 μg•L⁻¹, and the results of its specificity, matrix effect, extraction recovery, precision, accuracy and stability all met the requirements. In the Caco-2 cell monolayer model, the transport volume of neobavaisoflavone was correlated positively with the time and concentration. The ER values of 15, 30, 50 μmol•L⁻¹ neobavaisoflavone were 1.64, 1.94,0.99, respectively. As compared with the control group, all of verapamil hyduochloride, MK-571 and Ko143 could promote the transportation of neobavaisoflavone, and the effect was more obvious in verapamil hyduochloride and Ko143. The absorption of neobavaisoflavone may be mainly of active transport in Caco-2 cell monolayer model, and also involve passive transport. Excretion mechanism of intestinal transport protein may be also involved.