[Association between obstructive sleep apnea and vascular injury in hypertensive patients].

Objective: To investigate the relationship between obstructive sleep apnea (OSA), apnea hypopnea index (AHI) and vascular injury in hypertensive patients. Methods: This cross-sectional study enrolled patients admitted to the Hypertension Department of TEDA International Cardiovascular Hospital from April 2020 to April 2023, who finished portable sleep monitoring. Sleep monitoring indicators, flow-mediated vasodilation (FMD), carotid artery ultrasound, carotid intima-media thickness, cervical and femoral pulse wave conduction velocity (cfPWV), brachial and ankle pulse wave conduction velocity (baPWV) were analyzed. OSA was classified into mild (5 times/h≤AHI<15 times/h), moderate (15≤AHI<30 times/h), and severe (AHI≥30 times/h) based on AHI levels. FMD<6.0% was defined as vascular endothelial injury, and cfPWV>10 m/s and/or baPWV>18 m/s was defined as arterial stiffness. Multivariate logistic regression analysis was used to explore the correlation between AHI, OSA severity and vascular injury, and subgroup analysis was performed in young (age≤45 years) and middle-to-old patients (age>45 years). Sensitivity analysis was performed by excluding patients with diabetes, cerebrovascular disease and coronary heart disease. The correlation between AHI and vascular injury index was analyzed by restricted cubic spline. Results: A total of 555 adult hypertensive patients were included, the mean age was (39.7±9.2) years, 422 were males (76.0%), and the prevalence of OSA was 66.7% (370/555). Multivariate logistic regression analysis showed that moderate OSA (OR=2.83, P=0.019) and severe OSA (OR=3.40, P=0.016) were positively correlated with vascular endothelial injury after adjusting for age, sex, body mass index and mean arterial pressure. Subgroup analysis showed that log AHI (OR=1.99, P=0.035), moderate OSA (OR=4.83, P=0.010) and severe OSA (OR=4.64, P=0.015) were associated with vascular endothelial injury in young hypertensive patients. The results of sensitivity analysis were similar to the above results. The results of restricted cubic spline analysis showed that AHI was correlated with FMD (P=0.022), and the slope of the curve was the largest when AHI was between 0 and 10 times/h. There was no correlation between log AHI and OSA severity and carotid intima-media thickening and arterial stiffness (all P<0.05). Conclusions: OSA is associated with vascular endothelial injury in hypertensive patients, especially in young patients.

[Exploration of the connection between severe perioperative complications and preoperative basic diseases of surgical patients with non-small cell lung cancer].

Objective: To explore the connection between severe perioperative complications and preoperative basic diseases of surgical patients with non-small cell lung cancer (NSCLC). Methods: We retrospectively analyzed the data of surgical patients with NSCLC from January 1, 2016 to December 31, 2018 in Cancer Hospital, Chinese Academy of Medical Sciences (CAMS). The single factor analysis and logistic multivariate regression analysis were conducted to explicate the correlation of the risk factors especially preoperative basic diseases with severe perioperative complications. Results: A total of 12, 650 cases meeting our inclusion and exclusion criteria were included, of whom 5, 409 (42.76%) cases had various preoperative basic diseases and 140 (1.11%)cases occurred severe perioperative complications. Pulmonary and intrathoracic complications and circulatory system complications dominantly accounted for the severe perioperative complications, with incidence of 0.64% and 0.25%, respectively. The gender, age, tumor differentiation, surgical method, surgical approach, and preoperative basic diseases were significantly associated with the occurrence of severe perioperative complications in surgical patients with NSCLC according to the single factor analysis outcomes (P<0.05). Patients with pulmonary disease (P=0.02), heart disease (P=0.03) and diabetes (P=0.02) were more likely to occur severe complications according to the multivariate analysis outcomes. Conclusions: The forms of severe perioperative complications of surgical patients with NSCLC are various. Patients with pulmonary disease, heart disease and diabetes are likely to occur severe complications, besides patients with male sex, elder age, poorly differentiated tumor, and undergoing open thoracotomy. We should take more effective measures to avoid severe complications when deal with these patients.

[Risk factors associated with prolonged postoperative length of stay of patients with gastric cancer].

Objective: To investigate the risk factors of prolonged postoperative length of stay (LOS) in patients with gastric cancer. Methods: A retrospective study was performed on 2033 patients who underwent curative surgery in Department of Pancreatic-gastric, Cancer Hospital, Chinese Academy of Medical Sciences. Eightieth percentile of postoperative hospital stay for all patients was taken as the cutoff, the patients were divided into the normal group (1 532 patients) and the extended group (501 patients). Logistic regression model was used to determine the risk factors related to prolonged postoperative LOS in gastric cancer. Results: A total of 417 cases with postoperative complications were recruited in extended group. The five highest complications accounting for prolonged LOS were: abdominal infection in 69 cases (13.77%), pleural effusion in 60 cases (11.98%), anastomotic leakage in 43 cases (8.58%), poor wound healing in 34 cases (6.79%), and bleeding in 25 cases (4.99%). Logistic regression analysis showed that age (OR=1.348, P=0.013), surgical procedure (OR=2.712, P<0.001), extent of resection (OR=2.035, P<0.001), degree of incision healing(OR=4.867, P<0.001), and perioperative blood transfusion (OR=1.711, P<0.001) were independent risk factors for prolonged postoperative LOS. Conclusions: The most common complication associated with prolonged postoperative LOS for gastric cancer patients is abdominal infection. Age, surgical procedure, extent of resection, degree of incision healing, and perioperative blood transfusion are the independent risk factors for prolonged postoperative LOS.

[Comprehensive analysis of unplanned reoperations in colorectal cancer surgery].

Objective: To investigate the causes and impacts of unplanned reoperations (UO) in patients underwent colorectal cancer surgery, and its effect on the length of hospital stays and hospitalization fees of these patients. Methods: we retrospectively analyzed the data of colorectal tumor patients underwent resection and UO from January 2014 to November 2017 in Cancer Hospital, Chinese Academy of Medical Sciences (CAMS). Student t tests, ANOVA analysis and chi-square test were used to compare the paired data and data of multiple groups, respectively. Results: There were 5 923 cases who underwent colorectal cancer surgery from 2014 to 2017. Among them, 75 cases further accepted UO, the incidence rate of UO was 1.27%. Among the 75 patients of UO, 60 were male and 15 were female, 21 patients underwent colonic operation and 54 patients underwent rectal operation. The average length of hospital stays were 25.8 days and the average hospitalization fees were 110 647.04 yuan. The gender construction, surgical site, average length of hospital stays and hospitalization fees of UO were significantly different from those of operative colorectal tumor patients during this period (all P<0.01). There were 40 patients underwent anastomotic fistula, 11 patients underwent stoma complications and 10 patients underwent bowel obstruction, respectively, which accounts for the three most common causes of UO after colorectal cancer surgery, and the total incidence was 81.3%. The interval of reoperation and the first operation significantly impacted the average length of hospital stays of UO patients (P=0.003), while marginally affected the hospitalization fees (P=0.847). Conclusions: UO are more possible to occur to the male patients who undergo rectal operation. The length of hospital stays and hospitalization fees of UO are significantly increased when compare to those of operative colorectal cancer patients. The time of reoperation significantly impacts the length of hospital stays but has little effect on the hospitalization fees of UO patients.

[Effects of enhancing the expression of aryl hydrocarbon receptor in post-traumatic mice macrophages on the inflammatory cytokine level and bactericidal ability].

Objective: To explore the expression pattern of aryl hydrocarbon receptor (AhR) in mice peritoneal macrophages (PMs) after major trauma and analyze the effects of enhanced AhR expression on the inflammatory cytokine level and bactericidal ability after trauma. Methods: The experimental study method was used. Forty 6-8-week-old male C57BL/6J mice (the same mouse age, sex, and strain below) were divided into control group, post trauma hour (PTH) 2 group, PTH 6 group, and PTH 12 group according to the random number table (the same grouping method below), with 10 mice in each group. Mice in the latter 3 groups were constructed as severe trauma model with fracture+blood loss, while mice in control group were left untreated. The primary PMs (the same cells below) were extracted from the mice in control group, PTH 2 group, PTH 6 group, and PTH 12 group when uninjured or at PTH 2, 6, and 12, respectively. Then the protein and mRNA expressions of AhR were detected by Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction, respectively, and the gene expressions of AhR signaling pathway related molecules were analyzed by transcriptome sequencing. Twenty mice were divided into control group and PTH 6 group, with 10 mice in each group, and the PMs were extracted. The level of ubiquitin of AhR was detected by immunoprecipitation. Twelve mice were divided into dimethyl sulfoxide (DMSO) alone group, PTH 6+DMSO group, MG-132 alone group, and PTH 6+MG-132 group, with 3 mice in each group. After the corresponding treatment, PMs were extracted, and the protein expression of AhR was detected by Western blotting. Twenty mice were constructed as PTH 6 model. Then, the PMs were extracted and divided into empty negative control adenovirus (Ad-NC) group and AhR overexpression adenovirus (Ad-AhR) group. The protein expression of AhR was detected by Western blotting at 36 h after some PMs were transfected with the corresponding adenovirus. The rest cells in Ad-NC group were divided into Ad-NC alone group and Ad-NC+endotoxin/lipopolysaccharide (LPS) group, and the rest cells in Ad-AhR group were divided into Ad-AhR alone group and Ad-AhR+LPS group. The expressions of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the cell supernatant were detected by enzyme-linked immunosorbent assay at 12 h after the corresponding treatment (n=6). Twenty mice were obtained to extract PMs. The cells were divided into control+Ad-NC group, PTH 6+Ad-NC group, control+Ad-AhR group, and PTH 6+Ad-AhR group, and the intracellular bacterial load was detected by plate spread method after the corresponding treatment (n=6). Data were statistically analyzed with one-way analysis of variance, least significant difference test, analysis of variance for factorial design, and independent sample t test. Results: Compared with 1.16±0.28 of control group, the protein expressions of AhR in PMs in PTH 2 group (0.59±0.14), PTH 6 group (0.72±0.16), and PTH 12 group (0.71±0.17) were all significantly decreased (P<0.05). The overall comparison of the difference of AhR mRNA expression in PMs among control group, PTH 2 group, PTH 6 group, and PTH 12 group showed no statistical significance (P>0.05). The AhR signaling pathway related molecules included AhR, AhR inhibitor, cytochrome P450 family member 1b1, cytochrome P450 family member 11a1, heat shock protein 90, aryl hydrocarbon receptor-interaction protein, and heat shock protein 70 interaction protein. The heat shock protein 90 expression of PMs in PTH 2 group was higher than that in control group, while the expressions of other molecules did not change significantly after trauma. Compared with that in control group, the level of ubiquitin of AhR in PMs in PTH 6 group was increased. Compared with that in DMSO alone group, the protein expression of AhR in PMs in PTH 6+DMSO group was decreased, while that in PMs in MG-132 alone group had no significant change. Compared with that in PTH 6+DMSO group, the protein expression of AhR in PMs in PTH 6+MG-132 group was up-regulated. At transfection hour 36, compared with that in Ad-NC group, the protein expression of AhR in PMs in Ad-AhR group was increased. At treatment hour 12, compared with those in Ad-NC+LPS group, the expressions of IL-6 and TNF-α in PM supernatant of Ad-AhR+LPS group were significantly decreased (with t values of 4.80 and 3.82, respectively, P<0.05). The number of intracellular bacteria of 1×106 PMs in control+Ad-NC group, PTH 6+Ad-NC group, control+Ad-AhR group, and PTH 6+Ad-AhR group was (3.0±1.8), (41.8±10.2), (1.8±1.2), and (24.2±6.3) colony forming unit, respectively. Compared with that in PTH 6+Ad-NC group, the number of intracellular bacteria of PMs in PTH 6+Ad-AhR group was significantly decreased (t=3.61, P<0.05). Conclusions: Ubiquitin degradation of AhR in PMs of mice after major trauma results in decreased protein expression of AhR. Increasing the expression of AhR in post-traumatic macrophages can reduce the expressions of LPS-induced inflammatory cytokines IL-6 and TNF-α, and improve the bactericidal ability of macrophages after trauma.

Pyroelectric effect mediated infrared photoresponse in Bi2Te3/Pb(Mg1/3Nb2/3)O3-PbTiO3 optothermal ferroelectric field-effect transistors.

The responses of material properties to multi-field stimulation are often exploited to construct new types of multi-functional devices. Here, we demonstrate electrical, optical and thermal modulation of the electronic properties of optothermal ferroelectric field-effect transistors (FeFETs) which are fabricated by growing Bi2Te3 films on (111)-oriented 0.71Pb(Mg1/3Nb2/3)O3-0.29PbTiO 3 (PMN-PT) ferroelectric single-crystal substrates. Using the electric field to switch the polarization direction of PMN-PT, the carrier density and resistance of Bi2Te3 films are in situ, reversibly, and nonvolatilely modulated via the ferroelectric field effect. Moreover, through infrared light illumination on the bottom of PMN-PT substrates, the resistance of Bi2Te3 films in two polarization states could be further modulated, which is ascribed to the decreased polarization intensity at higher temperature due to the pyroelectric effect. Taking advantage of these two effects, the Bi2Te3/PMN-PT optothermal FeFETs exhibit multiple responses to optical and electric field stimulation at room temperature. Our work provides a strategy to design optoelectronic devices with both photodetector and memory functionalities.

[Study on the hospitalization cost and its influencing factors of imported malaria patients in Guangxi Zhuang Autonomous Region and Yunnan Province].

OBJECTIVE: To analyze the hospitalization cost and its influencing factors of imported malaria patients in Guangxi Zhuang Autonomous Region and Yunnan Province, so as to provide insights into the evaluation of the economic burden due to imported malaria, and the guiding of malaria control and the rational allocation of medical resources. METHODS: The data pertaining to the hospitalization costs of imported malaria patients admitted to Shanglin County People's Hospital in Guangxi Zhuang Autonomous Region during the period from January 1 through December 31, 2019, and Tengchong Municipal People's Hospital in Yunnan Province from January 1, 2015 to December 31, 2019, were collected, and the epidemiological data of these imported malaria patients were extracted from the Information Management System for Parasitic Diseases Control and Prevention, China. The composition of the hospitalization expenses was analyzed using a descriptive method. In addition, the factors affecting the hospitalization expenses of imported malaria patients were identified using a univariate analysis and a recursive system model. RESULTS: A total of 206 imported malaria patients were included in this study, including 194 men (94.17%) and 12 women (5.83%). The mean length of hospital stay was 5.00 days per patient and the median hospitalization expenses were 2 813.07 Yuan per time, in which the expenses for laboratory examinations were the highest (45.31%, 1 274.62/2 813.07). Univariate analysis showed that hospital (z = 5.43, P < 0.01), type of malaria (χ2 = 34.86, P < 0.01) and type of payment (χ2 = 7.72, P < 0.05) were factors affecting the hospitalization expenses of imported malaria patients. Recursion system modeling revealed that the total effects on hospitalization expenses of imported malaria patients included length of hospital stay (0.78), selection of hospital (0.34), basic medical insurance for urban and rural residents (0.19), new rural cooperative medical care (0.17), Plasmodium falciparum malaria (0.15), gender (0.11) and P. vivax malaria (0.09). CONCLUSIONS: The hospitalization expenses of imported malaria patients are affected by multiple factors in Guangxi Zhuang Autonomous Region and Yunnan Province, in which the length of hospital stay is the most predominant influencing factor. A reduction in the length of hospital stay is effective to decrease the hospitalization expenses of imported malaria patients.

The development of MetAP-2 inhibitors in cancer treatment.

Methionine aminopeptidases (MetAPs), which remove methionine residue from newly synthesized polypeptide chains, are a class of metalloproteases ubiquitously distributed in both eukaryotes and prokaryotes. MetAP-2 inhibition can induce G1 cell cycle arrest, cytostasis in tumor cells in vitro and inhibition of tumor growth in vivo. The discovery of fumagillin with potent antiangiogenic and antiproliferative activities promoted the development of fumagillin analogues as a novel class of anticancer agents. Early drug discovery efforts have focused on analogs of fumagillin, which irreversibly inhibit MetAP-2 through covalent modification of an epoxide. Several fumagillin analogs, like CKD-732, TNP-470 and PPI-2458, were found to be potent selective inhibitors of MetAP-2 (proteolytic activity) and endothelial cell proliferation. Further, they have entered in clinical trials for the treatment of different types of tumors. Recently, attention has been paid to reversible human MetAP-2 inhibitors, such as bengamides, 2-hydroxy-3-aminoamides, anthranilic acid sulfonamides and triazole analogs, which have demonstrated their potential to inhibit angiogenesis and tumor growth in vivo as well. This review article mainly discussed the development of MetAP-2 inhibitors in cancer therapy and also summarized their structure-activity relationships.