OBJECTIVE To investigate the effects of N,N'-Dinitrosopiperazine (DNP) on the cell proliferation of nasal and nasopharyngeal epithelia and the expression levels of TRAF2 and p16 genes in TgN (p53mt-LMP1)/HT transgenic mice and the relationships between them.METHODS The epithelial proliferating characteristics of nasal cavity and nasopharynx in TgN (p53mt-LMP1)/HT cancerous lesion inducing group treated by DNP (TI),TgN (p53mt-LMP1)/HT controlling group (TC), C57BL/6J cancerous lesion inducing group (CI) treated by DNP and C57BL/6J controlling group (CC) were observed for pathological evaluation by HE staining,and the expression levels of TRAF2 and p16 genes in these tissue samples were determined by immunohistochemical methods.RESULTS The occurring rates of precancerous lesions in nasal and/or nasopharyngeal epithelia in TI,TC,CI and CC groups were 90%,10%,0 and 0,respectively (P

Objective:To evaluate the value of improved pulmonary ultrasonography in the follow-up assessment of lung damage in patients who recovered from corona virus disease 2019(COVID-19).Methods:Twenty-two patients who were cured of COVID-19 in Quanzhou First Hospital from January to May 2020 were randomly selected and divided into 7 mild cases, 12 moderate cases and 3 severe cases according to the first high-resolution CT (HRCT) at admission. Six months after recovery, modified lung ultrasonography and HRCT were used prospectively to assess the lung damage and evaluate the correlation and consistency between the two techniques.Results:①There were significant differences in lung damage between the mild group and the moderate group, severe group (all P<0.05), while there was no significant difference between the moderate group and severe group ( P>0.05). ②There was good consistency between the improved lung ultrasound examination and HRCT (Kappa=0.776, P<0.001). ③There was a positive correlation between the score of improved pulmonary ultrasound examination and HRCT Warrick score ( r=0.755, P<0.001). Conclusions:Improved pulmonary ultrasonography can be used as a priority in the evaluation of pulmonary damage follow-up in patients with COVID-19 recovery, reducing the use of CT, and providing favorable evidence for further clinical management.

Objective To analyze the protective effect of esmolol combined with early goal-directed therapy on myocardial function in patients with severe sepsis. Methods The clinical data of patients with severe sepsis who were treated in our hospital were retrospectively analyzed. According to the principles of randomization, balance and control, 30 cases receiving esmolol combined with early goal-directed therapy were selected as the observation group. The other 30 cases who were given early goal-directed therapy during the same period were selected as the control group. The effects of the two treatment regimens on the levels of hemodynamic indices, cTnT, BNP, TNF-a, IL-1β, Lac, central venous oxygen saturation(ScvO2) and other indices were compared, and 28-day survival rate was statistically analyzed. Results After treatment, Ea/Aa in the observation group was increased significantly, and HRwas decreased significantly. Only HRwas decreased significantly in the control group. There was no statistically significant difference within groups and between the two groups in other hemodynamic indices (P＞0. 05); the levels of cTnT, BNP, TNF-a, and IL-1β in both groups were significantly decreased and the observation group was lower than the control group. The differences within groups and between groups were statistically significant; the serum Lac was decreased and ScvO2 was increased in both groups. The serum Lac in the observation group was lower than that in the control group, and ScvO2 was higher than that in the control group. There were statistically significant differences within groups and between groups (P＜0. 05); the survival rate in the observation group was slightly higher than that in the control group, but the difference was not statistically significant(χ2=0. 480, P=0. 488). Conclusion Esmolol combined with early goal-directed therapy may benefit myocardial protection in patients with severe sepsis.

Pancreatic cancer is one of the common gastrointestinal malignancies,the incidence of which is increasing year by year and has become one of the most important public health problems worldwide.At present,tumor treatment has entered the era of immunotherapy,but the response of pancreatic cancer patients to immune checkpoint inhibitors is not ideal.In addition,there is a lack of effective and validated biomarkers to stratify patients who may benefit from immunotherapy.This review has summarized the current research advances of immunotherapeutic biomarkers in pancreatic cancer,hoping to help clinicians understand relevant biomarkers systematically and guide the precise treatment of pancreatic cancer.

Objective The oxidative damage of DNA can be caused by excessive levels of Reactive oxygen species(ROS).Monitoring of DNA oxidative damage enables effective evaluation of ROS damage effects.Although the detection of DNA damage effects based on microbial sensor allows quantitative analysis of oxidative damage,the ROS clearance mechanism existed in bacterial will affect the sensitive of detection.The work of this article is to knockout the key genes of ROS clearance mechanism and construct an antioxidant gene-knock-out microbial sensor.The microbial sensor can realize sensitive monitoring of DNA damage effects and then evaluates the damage effects of cells by ROS.Methods The antioxidant damage genes of bacterial ahpCF,katE and katG were knocked out by λ-Red homologous recombination and antioxidant gene-knockout microbial sensor was constructed.The nalidixic acid sodium salt and UV irradiation were used to characterize the performance for monitoring of DNA damage effects.Results The antioxidant gene-knockout microbial sensors ΔahpC,ΔahpCF/ΔkatEG and ΔahpCF/ΔkatE/ΔkatG were constructed successfully.The results showed that the microbial sensor ΔahpCF/ΔkatE/ΔkatGl had the highest sensitive of damage effects and the limit of detection for nalidixic acid sodium salt was 0.40 μmol/L.In addition,1.80 min of UV irradiation(254 nm)was sufficient to induce a significant fluorescent expression effect in the engineered bacteria.Conclusion In this article,antioxidant gene-knockout microbial sensors had been constructed to realize active and sensitive monitoring of DNA damage effects such as DNA damage reagents and UV irradiation.The sensors could provide an active,effective,and sensitive potential monitoring method for future evaluation of radiation effects in space.

Objective:The 97.5th percentile upper reference limit (97.5th URL) of N-terminal prob-type natriuretic peptide (NT-proBNP) is influenced by multiple factors and depends on the inclusion criteria of apparently healthy people. In this study, the reference upper limit of NT-proBNP was established on apparently healthy people in Beijing area with abnormal hs-cTn as the exclusion criterion.Methods:According to the latest expert consensus recommendation standards of natriuretic peptide in the detection and clinical application of heart failure published by the Clinical Application Group of Cardiac Bio-Markers of the International Union of Clinical Chemistry, 1 635 healthy people without abnormal appearance of routine indicators such as sex, age, glycated hemoglobin, estimated glomerular filtration rate and medical history were collected. After excluding participants with potential myocardial injury according to hs-cTnI and/or hs-cTnT concentration>99th URL, NT-proBNP 97.5th URL was established in healthy subjects aged 21-40 years ( n=205), 41-50 years ( n=535), 51-60 years ( n=556) and >60 years ( n=339) based on non-parametric statistics. Results:The level of NT-proBNP was positively correlated with age ( r=0.254, P<0.001). The levels of NT-proBNP were positively correlated with hs-cTnI, hs-cTnT in males ( r=0.377 and r=0.429, both P<0.001). The levels of NT-proBNP were also positively correlated with hs-cTnI, hs-cTnT in females ( r=0.132 and r=0.296, both P<0.001). When hs-cTn>99th URL was used as the criterion to exclude patients with potential myocardial injury, among apparently healthy people aged 21-40 years old, 41-50 years old, 51-60 years old and >60 years old, male NT-proBNP 97.5th URL was 81.9 (90% CI 60.0-588.8), 141.2 (90% CI 100.0-263.6), 272.0 (90% CI 193.0-494.0) and 547.9 (90% CI 311.2-738.6), respectively; For females, the rates were 227.5 (90% CI 81.9-360.8), 153.2 (90% CI 128.2-239.5), 300.6 (90% CI 211.0-376.4) and 395.8 (90% CI 242.3-543.5) ng/L, respectively. Conclusions:This study confirmed that hs-cTn>99th URL can be used as an apparent population screening criterion for natriuretic peptide reference interval studies, which is helpful to remove conventional means to include individuals with occult myocardial injury in apparently healthy patients, so as to establish a more rigorous healthy cohort and establishing solid normal NT-proBNP reference interval.

Yigongsan is derived from Xiaoer Yaozheng Zhijue written by QIAN Yi in the Northern Song dynasty， which is the No. 3 formula in the Catalogue of Ancient Famous Classical Formulas（The Second Batch of Pediatrics） released by the National Administration of Traditional Chinese Medicine（TCM） in September 2022， and it can be developed as a class 3.1 new TCM drug. By referring to ancient medical books and modern literature， this study conducted herbal textual research on Yigongsan from five aspects， including historical evolution， origin and processing， dosage conversion， usage and preparation methods， and functional application， then formed the key information table of this formula， in order to provide reference for the development of reference samples and preparations of Yigongsan. Based on the results of the study， it is recommended that Panax ginseng should be removed the basal part of stem（rhizoma）， Poria cocos should be removed the peel， Citrus reticulata should be cut into shreds and Glycyrrhiza uralensis should be used. According to 4.13 g/Qian（钱）， 1 g/slice for ginger， 3 g for each jujube and 300 mL/Zhan（盏）， the doses of Ginseng Radix， Poria， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma， Citri Reticulatae Pericarpium， Zingiberis Rhizoma Recens， Jujubae Fructus were 1.652， 1.652， 1.652， 1.652， 1.652， 5， 6 g， and the total amount was 19.26 g. The decocting method was to crush the medicinal materials into fine powder with 50-80 mesh， add 300 mL of water and decoct to 210 mL for each dose， then remove the dregs and take it warmly. This formula was recorded in ancient books as the main treatment for the cold-deficiency of spleen and stomach， and Qi stagnation in children with vomiting and diarrhea and lack of appetite. It has been flexibly applied by later generations of physicians， and is often used to treat anorexia， inflammation of the digestive tract， diarrhea and other diseases in children.