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 explore and evaluate the economy of pembrolizumab combined chemotherapy in the first-line treatment of advanced malignant pleural mesothelioma from the perspective of China's healthcare system,and to provide pharmacoeconomic evidence and reference for clinical medication and related health decisions.Methods A partition survival model was constructed based on the IND227 study data,with 21 d as the model period and simulated to 99％of patients died.The model output index was the quality-adjusted life year(QALY).The cost-utility analysis was used to evaluate the economics of combination chemotherapy for advanced malignant pleural mesothelioma by chemotherapy alone.Further,the robustness of the basic analysis results was proved by univariate sensitivity analysis and probabilistic sensitivity analysis.Results The results of basic analysis showed that compared with chemotherapy alone,the incremental cost-utility ratio(ICUR)of pembrolizumab combined with chemotherapy was 1 447 296.58 yuan/QALY,which was greater than 3 times China's per capita GDP(268 074 yuan/QALY)in 2023 as the willingness-to-pay(WTP)threshold,which was not economical.In the case of receiving charity drug donations,the ICUR was 102 236.18 yuan/QALY,which was below the WTP threshold.The results of univariate sensitivity analysis showed that the cost of pembrolizumab,utility discount rate and supportive therapy in the chemotherapy group had more significant effects on the results.The results of the probability sensitivity analysis showed that the basic analysis results showed good robustness.Conclusion At a WTP threshold of 3 times China's per capita GDP in 2023,pembrolizumab combined with chemotherapy is not cost-effective for treating advanced malignant pleural mesothelioma.However,if the patient receives charity donations,combination of pembrolizumab and chemotherapy is more cost-utility.

Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.
Child ; Child, Preschool ; Consensus ; Dental Caries/prevention & control* ; Dental Caries Susceptibility ; Humans ; Oral Health

Objective:To evaluate the reading speed and related factors of normally-sighted middle-aged and elderly people, and compare with those assessed in age-related macular degeneration (AMD) patients.Methods:Prospective case control study. Participants aged 45 to 85 years old with junior high school or above education and BCVA no less than 0.6 from the community around the First Hospital of Tsinghua University were recruited. People with ocular and nervous system diseases were excluded. AMD patients without other ocular and nervous system diseases, with the BCVA of their better eye above 0.05, were recruited from the Low Vision Clinic of the First Hospital of Tsinghua University. The best corrected vision, contrast sensitivity, and reading acuity were tested. Reading speed was evaluated with IReST Chinese version. Single factor correlation analysis was used to assess different factors which may be related with the reading speed, then multiple linear regression analysis was conducted further.Results:From January to April, 2016, 53 volunteers aged 60.7±8.8 years old participated in the survey including 17 males and 36 females. Their median of best vision acuity both distance and near was 1.0, and their average reading speed was 244±55 characters/min. The average reading speed of younger participants in the middle-aged group (45-59 years old) was statistically faster ( P<0.05) than the elderly group (≥60 years old), which was 267±53 and 227±51 characters/min separately. The reading speed was correlated with age ( r=-0.476, P=0.000), gender ( t=-2.291, P=0.031), educational level ( t=2.656, P=0.011), reading habits ( t=7.346, P=0.000), best corrected distance vision ( r=-0.293, P=0.033), best corrected near vision ( r=-0.460, P=0.001), and reading acuity ( r=-0.558, P=0.000) by single factor correlation analysis. Further analysis with multiple linear regression showed that reading acuity, gender, education level, and reading habits were significantly correlated with reading speed ( β=-283.312, 28.303, -37.700, -45.505; P=0.000, 0.022, 0.019, 0.023). Totally 22 AMD patients aged 77.4±8.2 (59-90) years old joined the study from September 2016 to August 2018, including 16 males and 6 females. The median reading speed was 118 characters/min. Compared with the normally-sighted elderly, there were more males in AMD patients ( χ 2=3.981, P=0.046). They were older ( t=-4.285, P=0.000), with significant poorer visual acuity ( t=-6.176, P=0.000) and lower reading speed ( t=-5.719, P=0.000). Significant correlation was found between reading speed and best binocular distance or near vision, reading acuity and contrast sensitivity ( r=-0.771, -0.805, -0.776, 0.511; P=0.000, 0.000, 0.000, 0.015), no statistic relationship was found between reading speed and age( r=0.021, P=0.926) or gender( Z=-0.382, P=0.703) in AMD patients. Conclusions:The reading speed of normally- sighted people declined with age. Reading acuity may be a better predictive factor than distance vision for reading function. Compared with normally-sighted group, the reading acuity and reading speed of AMD patients was significantly lower. The main factor affecting their reading speed was the severity of their visual impairment.

OBJECTIVE:To establish a method for the determination of brucine concentration in plasma of rats,and to compare the pharmacokinetic differences between brucine and its nanostructure lipid carrier (NLC) in rats. METHODS:Sixteen male SD rats were randomly divided into brucine NLC solution group and brucine solution group(using normal saline as solvent, and containing brucine 1.28 mg/mL),with 8 rats in each group. They were given relevant solution 10 mg/kg via tail vein. Blood sample 0.5 mL was collected from fundus venous plexus capillary before medication and 15,20,30,40,45,60,90,120,150, 180,210,240,480 min after medication. HPLC method was adopted. The determination was performed on Dikma C18column with mobile phase consisted of methanol-water containing acetic acid and triethylamine(30∶70,V/V)at the flow rate of 1 mL/min. The detection wavelength was set at 265 nm,and column temperature was 30 ℃. Sample size was 10 μ L. Pharmacokinetic parameters of rats in 2 groups were calculated by using DAS 2.0 software,and the difference of them were compared by F test. RESULTS:The linear range of brucine plasma concentration were 1.03-66.00 μg/mL(R2＝0.999 6);the limit of quantitation was 1.03 μg/mL,and lowest detection limit was 0.515 μg/mL. RSDs of intra-day and inter-day were lower than 5%;method recoveries were 84.90%-100.88%, extraction recoveries were 80.60%-91.98%(all RSDs were lower than 10%). Average plasma concentration-time curve of single administration of brucine NLC solution and brucine solution were all in line with two-compartment model after medication via tail vein. The pharmacokinetic parameters included t1/2αwere(0.24±0.11)and(0.06± 0.03)h;t1/2 βwere (2.90 ± 0.22) and (0.57 ± 0.32)h;AUC0-twere (88.00 ± 6.98) and (28.50 ± 5.87)μg·h/mL;AUC0-∞were (109.96±7.99)and(45.06±6.66)μg·h/mL. Compared with brucine solution group,t1/2 α,t1/2 β,AUC0-tand AUC0- ∞of brucine NLC solution group were increased significantly;while CL, k10and k12were decreased significantly, with statistical significance (P＜0.05 or P＜0.01). There was no statistical significance in k21between 2 groups (P＞0.05). CONCLUSIONS: Established HPLC method is simple, specific,sensitive,precise and highly recoverable. It can be used for the determination of plasma concentration and phamacokinetic study of brucine in rats. After brucine NLC is prepared,the pharmacokinetic parameters of brucine change significantly;retention time of brucine is significantly prolonged and the clearance rate decreases significantly.

Aim To investigate the effects of β1-ad-renergic receptor (β1-AR ) on rapid component of the delayed rectifier potassium current ( IKr ) in ventricular
myocytes of guinea pigs with chronic heart failure ( CHF) . Methods The CHF model of guinea pigs was established by descending thoracic aortic banding .
Whole-cell patch-clamp technique was used to record IKr in ventricular myocytes. The effects ofβ1-AR on IKr in CHF ventricular myocytes were detected and its mechanisms were studied by pretreatment with protein kinase A ( PKA ) inhibitor and calmodulin kinase II( CaMK II) inhibitor. Results In CHF ventricular myocytes, xamoterol, the selectiveβ1-AR agonist, de-creased IKr by (52±8)% and prolonged action poten-tial duration. These effects were completely abolished by pretreatment of myocytes with CGP20712A, a selec-tive β1-AR antagonist. íamoterol only decreased IKr
by (28±3)% by pretreatment of CHF myocytes with specific PKA inhibitor KT5720 . KN93 , an inhibitor of CaMKII, did not attenuate the inhibitory effect on CHF ventricular myocytes. Conclusion IKr is inhibi-ted by β1-AR activation in CHF ventricular myocytes. PKA, but not CaMKII signaling pathway is involved in, at least in part, the inhibitory effect ofβ1-AR acti-vation on IKr.

Objective To investigate the stress reaction of the medical staff who suffered workplace violence,and provide reference for nursing interventions.Methods 13 medical staff who suffered work-place violence were interviewed through semi-constitutional formula,the data were analyzed by phenomenological method of qualitative research.Results The psychological stress of medical staff mainly included 3 themes:complex emotions,eager to help; psychological adjustment required internal and external integration; different stress reaction affected the psychological state.Conclusions The medical staff suffer seriously from the workplace violence both on the physical and mental health,individuals should learn how to deal with it correctly,and the relevant departments should pay full attention to the humane care to victims of violence,guide them to view the stress correctly,and to take effective measures to prevent and control workplace violence.

Objective To investigate the value of fasting plasma glucose (FPG) in 75 g oral glucose tolerance test (OGTT) on the diagnosis of gestational diabetes mellitus (GDM).Methods Data of 6516 pregnant women who accepted prenatal cares from Beijing Obstetrics and Gynecology Hospital,Capital Medical University between Jan.2010 and Dec.2010 were collected.All patients had normal FPG at first trimester,and accepted 75 g OGTT after abnormal 50 g glucose challenge test (≥7.8 mmol/L).According to the result of OGTT,they were divided into 12 groups,and Chisquare test was used to analyze the role of FPG of OGTT in GDM diagnosis.Results According to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria,15.0％ (980/ 6516) of this group of pregnant women was diagnosed with GDM by FPG (≥5.1 mmol/L) of OGTT in this study.Then,the rest 5536 pregnant women with normal FPG of OGTT were divided into 12 groups according to FPG level (FPG level interval 0.1 mmol/L).As FPG level rose,the incidence of GDM also rose (X2 =282.175,P =0.000).Similar results also appeared when the interval was 0.2 mmol/L and the FPG level was between 4.0 and 4.8 mmol/L (X2 =274.364,P=0.000).When FPG level was lower than 4.2 mmol/L(22.1％,1226/5536),the incidence of GDM diagnosed by OGTT was 3.6％ (44/1226).And when FPG level of OGTT was higher than 4.8 mmol/L,the incidence of GDM was 26.2％ (298/1138).Conclusions FPG screening is recommended between 24 and 28 gestational weeks before OGTT,and GDM low-risk women whose FPG ≤4.2 mmol/L do not need OGTT.

Nowadays, SUMO fusion system is important for recombinant protein production in Escherichia coli, yet a few aspects remain to be improved, including the efficacy for vector construction and protein solubility. In this study, we found the SUMO gene Smt3 (Sm) of Saccharomyces cerevisiae conferred an unexpected activity of constitutive prokaryotic promoter during its PCR cloning, and the gene coding regions of SUMOs in most species had a sigma70-dependent prokaryotic promoter embedded, through the prediction via the BPROM program developed by Softberry. By combining the characters of Sm promoter activity and the Stu I site (added at the 3'-terminal of Sm), and introducing a His-tag and a hyper-acidic solubility-enhancing tag, we further constructed a set of versatile vectors for gene cloning and expression on the basis of Sm'-LacZa fusion gene. Experimentally started from these vectors, several target genes were subcloned and expressed through blue-white screening and SDS-PAGE analysis. The results manifest a few of expectable advantages such as rapid vector construction, highly soluble protein expression and feasible co-expression of correlated proteins. Conclusively, our optimized SUMO fusion technology herein could confer a large potential in E. coli protein expression system, and the simultaneously established co-expression vector systems could also be very useful in studying the protein-protein interactions in vivo.
Amino Acid Sequence ; Base Sequence ; Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; genetics ; Lac Operon ; genetics ; Molecular Sequence Data ; Promoter Regions, Genetic ; genetics ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Saccharomyces cerevisiae Proteins ; biosynthesis ; genetics ; Small Ubiquitin-Related Modifier Proteins ; biosynthesis ; genetics ; Sumoylation

BACKGROUND:Mental material has shadow intervention effects on multi-slice helical CT (MDCT).Mental wall thickness and lumens inner diameter in stent structure can significantly affect longitudinal axis imaging quality of MDCT target vessel stent.However.there are few studies involved in this aspect.OBJECTIVE:To analyze the effect of various coronary stent materials and structures on patency images of target vessel by MDCT evaluation,and to provide clinical evidences for improving stent technique.DESIGN,TIME AND SETTING:The comparison observation was conducted at the Shenzhou Hospital,Shenyang Medical College.and Shengjing Hospital,China Medical University from January 2006 to December 2008.PARTICIPANTS:A total of 139 patients with coronary heart disease who were treated with stent implantation were divided into material and construct groups (227 stents were implanted).There were 92 stainless steel stents,135 nick-eltitanium alloy stents,85 thin mental wall stents (<140μm).142 thick mental wall stents (≥140μm).71 small diameter stents (<3 mm),and 156 big diameter stents (≥3mm).METHODS:During following up,patients were checked using 64-slice helical CT and routine coronary arteriongraphy to compare patency images of target vessels in the two groups.MAIN OUTCOME MEASURES:MDCT was scored by four-mark standard to evaluate sensitivity,specificity,accuracy,positive and negative predictive values of MDCT.RESULTS:A total of 227 stents were implanted into 139 patients.CT images of stainless steel stent group were poorer than nickel-titanium alloy group,and the indicators including image score,sensitivity,specificity,positive and negative predictive values of the stainless steel stent group were significantly less than nickel-titanium alloy group (P<0.05).CT images of thick-wall stent were poorer than thin-wall stent,while the indicators including image score,sensitivity,specificity,positive and negative predictive values of the thick-wall stent were significantly less than thin-wall stent (P<0.05).CT images of small-diameter stent were poorer than large-diameter stent,while the indicators including image score,sensitivity,specificity,positive and negative predictive values of the small-diameter stent were significantly less than large-diameter stent (P<0.05).CONCLUSION:Materials,wall thickness and diameter of coronary stent may influence images of target vessels via MDCT evaluation.