Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

Objective To predict the potential suitable distribution areas of Sophora japonica cv.jinhuai in China;To provide a references for resource development and expanded cultivation of Sophora japonica cv.jinhuai.Methods Totally 85 pieces of information on the distribution of sample sites were collected and combined data on 72 environmental factors,and the dominant environmental factors affecting the suitability distribution of Sophora japonica cv.jinhuai were analyzed using the maximum entropy(MaxEnt)model and geographic information system software ArcGIS.Results The five dominant environmental factors influencing the suitability distribution of Sophora japonica cv.jinhuai were dry month precipitation,May light radiation,November precipitation,September mean temperature,and October light radiation.The potentially suitable distribution area of Sophora japonica cv.jinhuai in China was mainly concentrated in the transition zone between south-central Hunan Province and northeast Guangxi Zhuang Autonomous Region.Conclusion The results of this study can provide references for the selection of the cultivation areas of Sophora japonica cv.jinhuai and protection of wild reso of Sophora japonica cv.jinhuai.

Cultivating salt-alkali tolerant rice varieties is one of the important ways to meet the increasing food demand of growing global population. In this study, twenty-one rice germplasms with different salt-alkali tolerance were treated with six salt-alkali concentrations at germination and seedling stages. The germination potential, germination rate, shoot length, root length, root number, fresh weight of shoot and seedlings were measured. The average value of salt damage rate was used to evaluate the salt-alkali tolerance. As the salt-alkali concentration increases, the inhibition on seed germination and growth became more obvious. Upon treatment with 1% NaCl plus 0.25% NaHCO₃, the salt damage rate of germination rate has the largest variation, ranging from 0% to 89.80%. The salt damage rate of each trait shows a similar trend at all concentrations. Four germplasm resources with strong salt-alkali tolerance (Dajiugu, Nippobare, Mowanggu and 02428) and 7 sensitive germplasms were screened. The salt-tolerant gene sequence of 4 salt-alkali tolerant varieties and 3 sensitive germplasms were analyzed. OSHAL3 and OsRR22 were identical among the 7 germplasms, but SKC1 and DST showed clear variations between the salt-alkali tolerant and sensitive germplasms. Besides the salt-alkali tolerant germplasm resources, this study can also serve as a reference for mining of genes involved in salt-alkali tolerance and breeding of salt-alkali tolerant rice varieties.
Alkalies ; Germination ; Oryza/genetics* ; Plant Breeding ; Seedlings/genetics*

Objective:To investigate the clinical significance of inflammatory factors in bacterial infection children with glucose-6-phosphate dehydrogenase (G6PD) deficiency in PICU.Methods:A prospective cohort study was carried out from June 2014 to December 2017. 77 bacterial infection children with pediatric critical illness score less than 80 who were admitted to the PICU, were recruit in the study.The patient diagnosed as other basic diseases,with history of high-dose glucocorticoid use, discharged or died within 24 hours were excluded.The recruited patients were divided into G6PD deficiency group (observation group with 36 cases) and non-G6PD deficiency group (control group with 41 cases) according to the presence or absence of G6PD deficiency.Blood samples were taken at admission, 12 hand 24 h after hospitalization to detect the concentrations of tumor necrosis factor (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10) andC-reactive protein (CRP). T test, χ2 test and Fisher exact test were used to analyze the changes of the above inflammatory factors, complications, prognosis, PICU stay time and hospitalization costs. Results:The levels of inflammatory factors in the observation group were significantly higher than those in the control group at admission, 12 and 24 hours after hospitalization, the differences were statistically significant (all P< 0.05). There was no statistically significant difference in thechangerate of inflammatory factors between the two groups during treatment; The PICU stay time of observation group was longer [(7.98 ± 6.55) vs (5.01 ± 6.21)] and the hospitalization cost (yuan) was higher [(36 634.09 ± 11 876.67) vs (31 571.42 ± 10 245.80)], P<0.05; Compared to the control group, the incidence ofsevere sepsis, septic shock, MODS increased significantly, and the curative rate decreasedsignificantly in observation group( P<0.05). Conclusions:G6PD-deficient children with bacterial infections had serious inflammatory reactions with poor prognosis and higher hospitalization costs and were susceptible to the occurrence of severe sepsis, septic shock and MODS.

Objective:To explore the serum levels of inflammatory cytokines and prognosis in severe acute infection children with glucose-6-phosphate dehydrogenase(G6PD) deficiency.Methods:A total number of 160 children with severe acute infections admitted to PICU of Guangxi Zhuang Autonomous Region Maternal and Child Health Hospital from June 2014 to December 2017 were selected as subjects in this study, including 80 children with G6PD deficiency(observation group) and 80 children without G6PD deficiency(control group). The changes of TNF-α, IL-6, IL-10 and CRP were dynamically monitored at 0-hour, 12-hour and 24-hour after admision, and the occurrences of sepsis, multiple organ dysfunction syndrome(MODS) were prospectively analyzed.Results:The levels of serum cytokines and CRP in the observation group were significantly higher than those in the control group at admission[TNF-α: (65.57±19.09) pg/ml vs.(46.53±20.34) pg/ml; IL-6: (98.90±29.02) pg/ml vs.(89.89±25.54) pg/ml; IL-10: (87.66±21.84) pg/ml vs.(76.34±19.01) pg/ml; CRP: (60.18±22.24) mg/L vs.(41.43±19.51) mg/L, respectively], and the differences between two groups were statistically significant( P<0.05). The levels of cytokines and CRP in the observation group were higher than those in the control group at 12 h and 24 h after treatment( P<0.01). Compared with the control group, the incidences of sepsis(82.50% vs 67.50%) and MODS(73.75% vs 58.75%) in the observation group increased, and the recovery rate(81.25% vs 92.50%) decreased, with statistical significance between two groups( P<0.05). Conclusion:Children with G6PD deficiency need to be paid more attention to inflammation, sepsis, MODS and the difficulty of treatment when they are infected.The potential mechanism may be related to oxidative stress.

The T cell co-stimulatory molecule OX40 and its cognate ligand OX40L have attracted broad research interest as a therapeutic target in T cell-mediated diseases. Accumulating preclinical evidence highlights the therapeutic efficacy of both agonist and blockade of the OX40-OX40L interaction. Despite this progress, many questions about the immuno-modulator roles of OX40 on T cell function remain unanswered. In this review we summarize the impact of the OX40-OX40L interaction on T cell subsets, including Th1, Th2, Th9, Th17, Th22, Treg, Tfh, and CD8 T cells, to gain a comprehensive understanding of anti-OX40 mAb-based therapies. The potential therapeutic application of the OX40-OX40L interaction in autoimmunity diseases and cancer immunotherapy are further discussed; OX40-OX40L blockade may ameliorate autoantigen-specific T cell responses and reduce immune activity in autoimmunity diseases. We also explore the rationale of targeting OX40-OX40L interactions in cancer immunotherapy. Ligation of OX40 with targeted agonist anti-OX40 mAbs conveys activating signals to T cells. When combined with other therapeutic treatments, such as anti-PD-1 or anti-CTLA-4 blockade, cytokines, chemotherapy, or radiotherapy, the anti-tumor activity of agonist anti-OX40 treatment will be further enhanced. These data collectively suggest great potential for OX40-mediated therapies.

Due to the critical correlation between inflammation and carcinogenesis, a therapeutic candidate with anti-inflammatory activity may find application in cancer therapy. Here, we report the therapeutic efficacy of celastrol as a promising candidate compound for treatment of pancreatic carcinoma naïve neutrophil membrane-coated poly(ethylene glycol) methyl ether--poly(lactic--glycolic acid) (PEG-PLGA) nanoparticles. Neutrophil membrane-coated nanoparticles (NNPs) are well demonstrated to overcome the blood pancreas barrier to achieve pancreas-specific drug delivery . Using tumor-bearing mice xenograft model, NNPs showed selective accumulations at the tumor site following systemic administration as compared to nanoparticles without neutrophil membrane coating. In both orthotopic and ectopic tumor models, celastrol-loaded NNPs demonstrated greatly enhanced tumor inhibition which significantly prolonged the survival of tumor bearing mice and minimizing liver metastases. Overall, these results suggest that celastrol-loaded NNPs represent a viable and effective treatment option for pancreatic carcinoma.

In recent years,based on low-dose computed tomography (CT) scan developed for physical examination,the number of synchronous multiple primary lung cancer (SMPLC) has gradually increased.The research showed the morbidity of SMPLC up to 0.2％-8％.The current diagnostic criteria of SMPLC is Martini-Melamed criteria.SMPLC:(1) Tumours should be located distantly and separately;(2) Histological types:Different histology;If same histology,they should be located at different segment,lobe or lung and originated from carcinoma insitu.No presence of carcinoma at shared lymphatic drainage.No extrapulmonary metastases at the diagnosis.MMPLC:(I) Different histology;(2) Disease free duration more than 2 years.Originated from carcinoma in situ location of second cancer at different lobe or lung.No presence of carcinoma at shared lymphatic drainage.No extrapulmonary metastases at the diagnosis.In 2013 Intemational association for lung cancer research (IASLC) amended and supplemented the Martini-Melamed criteria,by multidisciplinary classification of lung adenocarcinoma,epidermal growth factor receptor (EGFR),K-ras added for differential diagnosis.It also suggest that the gene mutation detection for each lesion of SMPLC is especially significant for therapeutic strategy.We herein report the case of a 60-yearold woman diagnosed with SMPLC of four adenocarcinoma and EGFR-mntated lesions,who received lung resection for each lesions.

A phospholipid-based injectable gel was developed for the sustained delivery of leuprolide acetate (LA). The gel system was prepared using biocompatible materials (SPME), including soya phosphatidyl choline (SPC), medium chain triglyceride (MCT) and ethanol. The system displayed a sol state with low viscosity in vitro and underwent in situ gelation in vivo after subcutaneous injection. An in vitro release study was performed using a dialysis setup with different release media containing different percentages of ethanol. The stability of LA in the SPME system was investigated under different temperatures and in the presence of various antioxidants. In vivo studies in male rats were performed to elucidate the pharmacokinetic profiles and pharmacodynamic efficacy. A sustained release of LA for 28 days was observed without obvious initial burst in vivo. The pharmacodynamic study showed that once-a-month injection of LA-loaded SPME (SPME-LA) led to comparable suppression effects on the serum testosterone level as observed in LA solution except for the onset time. These findings demonstrate excellent potential for this novel SPME system as a sustained release delivery system for LA.