Objective:To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate.Methods:Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups.Results:A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. ① There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE Ⅱ: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [μmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. ② Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). ③ Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. ④ Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. Conclusions:CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.

The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients' outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol-miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.

PiggyBac is a transposable DNA element originally discovered in the cabbage looper moth (Trichoplusia ni). The T. ni piggyBac transposon can introduce exogenous fragments into a genome, constructing a transgenic organism. Nevertheless, the comprehensive analysis of endogenous piggyBac-like elements (PLEs) is important before using piggyBac, because they may influence the genetic stability of transgenic lines. Herein, we conducted a genome-wide analysis of PLEs in the brown planthopper (BPH) Nilaparvata lugens (Stål) (Hemiptera: Delphacidae), and identified a total of 28 PLE sequences. All N. lugens piggyBac-like elements (NlPLEs) were present as multiple copies in the genome of BPH. Among the identified NlPLEs, NlPLE25 had the highest copy number and it was distributed on five chromosomes. The full length of NlPLE25 consisted of terminal inverted repeats and sub-terminal inverted repeats at both terminals, as well as a single open reading frame transposase encoding 546 amino acids. Furthermore, NlPLE25 transposase caused precise excision and transposition in cultured insect cells and also restored the original TTAA target sequence after excision. A cross-recognition between the NlPLE25 transposon and the piggyBac transposon was also revealed in this study. These findings provide useful information for the construction of transgenic insect lines.
Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; DNA Transposable Elements/genetics* ; Hemiptera/genetics* ; Transposases/genetics*

Objective:To provide evidence for optimizing the screening strategy for gastric cancer (GC), we evaluated the risk of incident GC for individuals with different precancerous gastric lesions in a prospective cohort study.Methods:Based on the National Upper Gastrointestinal Cancer Early Detection Program launched in Linqu, Shandong, a high-risk area of gastric cancer in China, we included a total of 14 087 subjects diagnosed with different gastric lesions stages by endoscopic screening from 2012 to 2018. Study subjects were prospectively followed up until December 31, 2019. The incidence of GC during the follow-up was ascertained by repeated endoscopic examinations, cancer, death registry reports, and active follow-up of study subjects and was confirmed by reviewing medical records extracted from the hospital information management system. The Poisson regression model was applied to calculate the relative risk ( RR) and 95% CI for GC occurrence among subjects with different gastric lesions. Results:Among 14 087 subjects with different gastric lesions as determined by their first endoscopic examination in 2012-2018, 7 608 (54.00%) had a global diagnosis of superficial gastritis (SG), 2 848 (20.22%) had chronic atrophic gastritis (CAG), 3 103 (22.03%) had intestinal metaplasia (IM), and 520 (3.69%) had low-grade intestinal neoplasia (LGIN). During the follow-up, 109 subjects were diagnosed with GC, including 63 with high-grade intestinal neoplasia (HGIN) and 46 with invasive GC. Compared to subjects having normal gastric mucosa or SG, those with CAG ( RR=3.85, 95% CI: 2.04-7.28), IM ( RR=5.18, 95% CI: 2.79-9.60), and LGIN ( RR=19.08, 95% CI: 9.97-36.53) had significantly increased risk of progression to GC. Individuals with these gastric lesions had an elevated risk of developing HGIN and invasive GC. For subjects with LGIN, the RR was 22.96 (95% CI: 9.71-54.27) for developing HGIN and 14.64 (95% CI: 5.37-39.93) for developing invasive GC. Subgroup analyses found that all age group subjects with LGIN diagnosed during the initial endoscopic examination had a significantly increased risk of developing the GC. Conclusions:Our large-scale prospective study on a high-risk area of GC showed that most residents aged 40-69 years had gastric lesions of different stages. Subjects with more advanced gastric lesions had a significantly increased risk of progression to GC.

Objective:To explore the effect of repetitive high-frequency magnetic stimulation (H-F rTMS) of the dorsolateral part of the prefrontal cortex (DLPFC) combined with smoking-related cues on nicotine addicts′ cigarette craving, the concentration of exhaled CO and sleep quality.Methods:Sixty nicotine addicts were randomly divided into groups A, B and C, each of 20. All were given H-F rTMS five times a week for two weeks, while those in groups A and B watched smoking and non-smoking pictures for ten minutes, respectively. Before and after the intervention, all of the subjects self-reported their cigarette cravings using a visual analogue scale. Exhaled CO (CO ppm) was measured and the Pittsburgh sleep quality index (PSQI) was evaluated. Results:After the intervention the average craving score, CO ppm and PSQI score had improved significantly in all three groups. The average craving score and CO ppm of group A were both significantly better than in the other two groups. Conclusions:rTMS can significantly improve cigarette craving, CO ppm and sleep quality of cigarette adicts. Viewing smoking-related pictures as an addition to rTMS can even better the effects of rTMS.

Objective:To observe the preliminary clinical application value of the handheld non-mydriatic visual electrophysiological diagnostic system RETeval in screening for diabetic retinopathy (DR).Methods:Retrospective clinical study. Fifty-eight patients with type 2 diabetes mellitus and 16 normal subjects who were admitted to Wuhan General Hospital of the PLA from November 2017 to May 2018 were enrolled in this study. All patients had not received any ophthalmologic treatment. All patients were examined by the default "DR assessment protocol" model of the RETeval device, and the "DR score" were measured by the system. The FFA results were used as the gold standard, and the DR was graded according to the international DR grading standard established in 2002. Patients were divided into vision threatening DR (VTDR) positive group and VTDR (?) group, DR (+) group and DR (?) group. Two independent sample t tests was used to compare the implicit time, amplitude, and pupil area ratio between eyes of different groups. Spearman correlation analysis was used to analyze the relationship between "DR score" and DR severity. The receiver operating characteristic area under the curve (AUC) assesses the sensitivity and specificity of RETeval in detecting DR and VTDR. The threshold of sensitivity and specificity was determined by using the maximum Youden index as a standard. Results:The AUC of DR was 0.936, the sensitivity was 81%, the specificity was 92%; the AUC of VTDR was 0.976, the sensitivity was 96% and the specificity was 70%. Compared with DR (?) group, the implicit time of DR (+) group was delayed and the amplitude and pupil area were decreased ( t=-13.43, 5.49, 6.09; P=0.000, 0.000, 0.000). Compared with VTDR (?) group, the implicit time of VTDR (+) group was delayed and the amplitude and pupil area were decreased ( t=-11.05, 7.46, 5.73; P=0.000, 0.000, 0.000). The "DR score" was significantly correlated with the severity of DR ( r=0.89, P<0.05). Conclusions:The "DR score" measured by the RETeval instrument has a high degree of specificity and sensitivity in the diagnosis of DR and VTDR. It is highly correlated with the severity of DR.

In recent years, the overall incidence of gastric cancer has been decreasing worldwide, while the incidence of the esophagogastric junction tumor is increasing year by year. With the progress of the diagnostic technology of upper gastrointestinal tumors and the gradual popularization of early cancer screening, the detection rate of early esophagogastric junction tumor keeps increasing. Therefore, in recent years, the clinical application of gastric function preserving surgery is gradually increasing. As an important part of the surgical treatment strategy of esophagogastric junction tumors, proximal gastrectomy has attracted more and more attention with the confirmation of oncological safety. Compared with total gastrectomy, patients after proximal gastrectomy have better nutritional status and quality of life. However, the high incidence of reflux esophagitis after traditional proximal gastrectomy has seriously affected the quality of life of patients, and also hindered the application of proximal gastrectomy in esophagogastric junction tumors. How to reduce the occurrence of reflux esophagitis after proximal gastrectomy by optimizing the method of digestive tract reconstruction has been a big challenge in clinical practice. This article reviews the current methods of anti-reflux surgery for proximal gastrectomy for esophagogastric junction tumors, aiming to provide a reference for choosing a reasonable anti-reflux surgery.

In recent years, the overall incidence of gastric cancer has been decreasing worldwide, while the incidence of the esophagogastric junction tumor is increasing year by year. With the progress of the diagnostic technology of upper gastrointestinal tumors and the gradual popularization of early cancer screening, the detection rate of early esophagogastric junction tumor keeps increasing. Therefore, in recent years, the clinical application of gastric function preserving surgery is gradually increasing. As an important part of the surgical treatment strategy of esophagogastric junction tumors, proximal gastrectomy has attracted more and more attention with the confirmation of oncological safety. Compared with total gastrectomy, patients after proximal gastrectomy have better nutritional status and quality of life. However, the high incidence of reflux esophagitis after traditional proximal gastrectomy has seriously affected the quality of life of patients, and also hindered the application of proximal gastrectomy in esophagogastric junction tumors. How to reduce the occurrence of reflux esophagitis after proximal gastrectomy by optimizing the method of digestive tract reconstruction has been a big challenge in clinical practice. This article reviews the current methods of anti-reflux surgery for proximal gastrectomy for esophagogastric junction tumors, aiming to provide a reference for choosing a reasonable anti-reflux surgery.

Objective: To investigate the value of next-generation sequencing (NGS) technology in the prognosis monitoring and treatment guidance for molecular minimal residual disease (MRD) in acute myeloid leukemia (AML) patients with complete remission (CR). Methods: The clinical data of 68 AML (non-acute promyelocytic leukemia) patients who received gene mutation spectrum by using NGS technology at initial diagnosis and in CR phase in Tangdu Hospital of Air Force Military Medical University from January 2016 to July 2018 were retrospectively analyzed. The recurrence and survival of both molecular MRD positive group and negative group were analyzed and compared, and the value of NGS technology and multiparameter flow cytometry (MFC) were also analyzed in MRD monitoring. Results: There were 39 males (57.4%) and 29 females (42.6%) in 68 patients, and the median age was 52 years old (8-82 years old). Molecular MRD positive group included 38 patients, while negative group included 30 patients. Residual mutation gene type in CR phase was most frequently detected in epigenetic regulator gene mutations, such as ASXL1, TET2, DNMT3A and IDH1/IDH2. Statistical analysis showed that the 2-year cumulative recurrence rate (CIR) in the molecular MRD positive group was higher than that in the molecular MRD negative group (86.8% vs. 51.3%; χ² = 9.249, P = 0.002); the 2-year relapse-free survival (RFS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (13.2% vs. 48.7%; χ² = 9.249, P = 0.002); the 2-year overall survival (OS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (58.0% vs. 100%; χ² = 4.122, P = 0.042). Up to follow-up date, 3 patients with molecular MRD positive and 1 patient with molecular MRD negative who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) were still in disease-free survival. The results of monitoring MRD showed high consistency (76.7%, 33/43) in NGS and MFC. Compared with the other groups, the patients with both positive NGS and MFC had a higher relapse rate, and the difference was statistically significantly (P < 0.05). Conclusions Molecular MRD of AML patients is detected by using NGS technology, which could be used to predict the relapse and survival, suggesting that molecular MRD may guide post-remission treatment regimens and the determination of allo-HSCT indications.

Objective To observe the effect ofconbercept combined with 577 nm subthreshold micropulse laser photocoagulation on diabetic macular edema (DME).Methods A prospective randomized controlled clinical study.From June 2016 to June 2017,68 eyes of 68 patients with DME diagnosed in Central Theater Command General Hospital were enrolled in the study.The patients were randomly assigned to two different treatment groups:36 eyes (36 patients) in the conbercept combined with 577 nm subthreshold micropulse lase group (combined treatment group) and 32 eyes (32 patients) in conbercept group (drug treatment group).All patients received three initial intravitreous injection of conbercept and re-treatment was performed according to the criteria which has been disigned before.BCVA was measured by ETDRS charts.The central macular thickness (CMT),total macular volume (TMV) were measured by Topcon 3D-OCT 2000.The BCVA,CMT and TMV in the combined treatment group and the drug treatment group were 57.9 ± 12.4 letters,427.8± 129.4 μm,10.14± 1.50 mm3 and 59.0± 16.0 letters,441.0 ±135.7 μm,10.43 ±2.10 mm3,respectively.There was no significant difference (t=0.321,0.410,0.641;P=0.749,0.683,0.524).The follow-up period was more than 12 months.The changes of BCVA,CMT and TMV were compared between the two groups.Comparison ofBCVA,CMT,TMV before and after treatment in and between groups using repeated measures analysis of variance.Results The average annual injection times was 5.8 ± 1.9 in the combined treatment group and 8.5± 2.4 in the drug treatment group.The difference was statistically significant (t=5.12,P=0.000).The BCVA in the 3rd,6th,9th and 12th month were 64.9± 11.1,65.6± 10.5,67.0± 10.8,66.6± 10.7 letters and 65.7± 15.8,66.9 ± 15.7,66.4 ± 13.0,67.3 ± 16.4 letters,respectively,and there were significant differences compared with BCVA before treatment (F=34.234,10.137;P=0.000,0.000).The CMT were 335.2± 105.9,352.6± 106.6,336.2± 120.8,305.9±97.0 μm and 323.9±92.8,325.5±90.2,327.6± 108.2,312.2± 106.8 μm,respectively.The TMV were 9.20± 1.08,9.26± 1.20,9.20± 1.63,9.05± 1.18 mm3 and 9.19± 1.21,9.35± 1.69,9.09± 1.20,8.92± 1.10 mm3,respectively.Compared with the CMT (F=12.152,12.917;P=0.000,0.000) and TMV (F=11.198,11.008;P=0.000,0.000) before treatment,the differences were statistically significant.Conclusion Conbercept combined with 577 nm subthreshold micropulse laser and conbercept can effectively reduce CMT,TMV and improve BCVA in patients with DME,but combination therapy can reduce the injection times of conbercept.