Objective To explore the improvements of high-fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improve ments. Methods SD rats were randomly assigned into three groups, including the normal control group (n = 10), the infection and normal diet group (n = 12) and the infection and high-fat diet group (n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high-fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high-fat diet. All rats were sacrificed 28 weeks post-infection, and serum samples and lung specimens were collected. Following hematoxylin-eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi-quantitative scoring. Serum interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real-time PCR (qPCR) and Western blotting assays. Results Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post-infection with P. proliferus in rats in the infection and high-fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high-fat diet group. The semi-quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high-fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL-1β [(151.586 ± 20.492)] pg/mL and TNF-α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL-1β: (103.226 ± 3.366) pg/mL; TNF-α: (144.807 ± 1.348) pg/mL] and the infection and high-fat diet group [IL-1β: (110.131 ± 12.946) pg/mL; TNF-α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high-fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05). Conclusion High-fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.

Objective: To assess the effectiveness of online and offline myopia prevention and control health education interventions using wearable behavior monitoring tools for non myopic elementary school students,so as to provide evidence based medical support for public health practices. Methods: From May to June in 2021, two schools were selected within the same county in Jiangsu Province. School 1 conducted online and offline parental health education ( n =111), while school 2 exclusively conducted offline health education activities, representing the traditional intervention group ( n =122). Students from both schools underwent monitoring through wearable behavior tracking tools, with feedback reports provided (eye distance, eye duration, ambient light, and outdoor exposure time). Both schools relied on activities to carry out health education interventions, and organized the distribution of promotional materials and display boards. The intervention group also established WeChat groups to conduct online "Healthy Parents Action" (answering and providing feedback on health knowledge related to myopia prevention and control, myopia prevention and control, science popularization, etc. raised by parents). Evaluation criteria included myopia rates, post dilation refractive error, and axial length, with a tracking period of two years (from 2021 to 2023). Additionally, the study collected refractive parameters from non myopic students who did not participate in wearable tool monitoring in the 12 classes across the two schools. Results: The baseline results indicated that there were no significant differences between the two groups in terms of refractive parameters and wearable tool monitoring results (including screen time, viewing distance, outdoor exposure time, and homework light exposure)( t/Z/χ 2=1.94,1.17,0.58,0.40,0.80,0.69,0.32, P >0.05). After a two-year follow up, in the first and second year, the myopia rate of the online Healthy Parents Action group (11.4%, 29.7%) were lower than that of the traditional group (26.2%, 50.9%), and the degree of refractive change in the intervention group [0.63(0.38,1.19)D] was lower than that of the traditional group [0.91(0.40,1.50)D], and all the differences were statistically significant( χ 2/ Z =4.93，10.37，2.29， P <0.05). However, there were no significant differences ( P >0.05) in axial length changes between the two groups over the twoyear intervention period. Nevertheless, in the second year, the axial length change in the traditional group [0.35(0.20,0.65)mm] was lower than that in the natural observation group [0.55(0.30,0.75)mm], and this difference was statistically significant ( Z =1.92, P <0.05). Conclusions Online and offline myopia prevention and control health education can effectively reduce myopia rates. The intervention mode combining wearable behavior monitoring tools with online health education may have better effects, but further large sample and multi center studies are needed to provide additional evidence and confirmation.

Objective To analyze the hepatitis B virus infection with extreme reduction of cholinesterase(CHE)not caused by liver synthesis dysfunction,and to explore its clinical significance.Methods The clinical data of 2 rare cases hospitalized in the 3rd people's hospital of Kunming in July 2021 and February 2022,including liver function,coagulation function,hepatitis B markers,hepatitis B virus volume,and whole exon sequencing,were collected and analyzed,and literature was reviewed.Results CHE was extremely reduced in 2 patients with HBV infection,liver synthesis function was good,and whole exon sequencing showed the presence of butyrylcholinesterase(BCHE)gene mutation.Conclusion The extremely low CHE in this case is not due to liver function disorder.Exon sequencing detected mutations in the BCHE gene in two patients.Screening for BCHE mutations may be necessary in patients with extremely low cholinesterase levels not due to liver dysfunction.

Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.
Anilides/pharmacology* ; Animals ; Carcinoma, Hepatocellular/drug therapy* ; Cell Line, Tumor ; Cell Proliferation ; Endothelial Cells/metabolism* ; Humans ; Liver Neoplasms/drug therapy* ; Pyridines/pharmacology* ; Sirolimus/pharmacology* ; Xenograft Model Antitumor Assays

Objective: This study aimed to find out the myopia rate and related ocular biological parameters of grade 1-3 students in Peixian, Xuzhou City, and to establish a cohort observation population, so as to provide baseline reference for control strategies for myopia and reduce the myopia rate. Methods: A total of 1 952 students from two nine year schools in Peixian were selected by stratified cluster sampling in June 2020. Visual examination was administered by trained personnel using uniformly equipped instruments, including uncorrected visual acuity, diopter, intraocular pressure, axial length. Results: The overall myopia rate of students from grade one to grade three in two schools in Peixian was 21.77%, and the myopia rate of girls (23.81%) was significantly higher than that of boys (20.16%). With the growth of age and grade, the myopia rate increased continuously, and the difference was statistically significant ( χ 2=134.10, 144.30, P <0.05). The myopia rate of 6-year-old group was 8.87 %. The axial length of the left and right eyes of the myopic group was significantly higher than that of the non myopic group ( t = 411.95, 366.85, P <0.01), the intraocular pressure and mean corneal curvature of the left eye of the myopic group were higher than those of the nonmyopic group ( t =5.91, 10.22 , P <0.05). Conclusion The baseline survey results show that the myopia rate of grade 1-3 in Peixian of Xuzhou City is low, but myopia has occurred in the 6-year-old group. With the growth of age and grade, the myopia rate continues to rise. So it is urgent to explore effective and feasible myopia prevention and control measures.

Objective:To analyze the effects of proton pump inhibitors(PPIs)on the prevention of stress ulcers(SU)in elderly patients with acute respiratory distress syndrome(ARDS), and to analyze related factors for the risk of short-term death.Methods:This study was a multicenter retrospective cohort study.Two hundred elderly ARDS patients diagnosed and treated at Peking University International Hospital, Anzhen Hospital and Ezhou Central Hospital from November 2017 to December 2019 were continuously included.These patients were treated with PPIs(omeprazole, pantoprazole, rabeprazole, lansoprazole and esomeprazole)within 48 hours after ICU admission to prevent SU and were considered as the PPI group.According to the propensity score matching method, 200 elderly ARDS patients admitted to the hospitals with similar ages, medical history and sequential organ failure assessment(SOFA)scores who did not use PPIs were selected as the control group.All patients were followed up for 30 days.Kaplan-Meier survival analysis and the log-rank test were used to compare the 30-day mortality risk between the two groups.Cox regression analysis was used to analyze the relevant factors affecting the 30-day mortality.The 30-day mortality risk and the incidence of clinically significant gastrointestinal bleeding were evaluated among patients using different PPIs.Results:The average time of PPI use was 8.4±4.4 d in the PPI group.In the control group, 38.0% of patients were treated with H 2 receptor antagonists, and the average time of use was 8.1±5.2 days.There was no significant difference in the 30-day all-cause mortality risk between the two groups(20.5% or 41 cases vs.23.5% or 47 cases, P>0.05). The incidences of clinically significant upper gastrointestinal tract bleeding(2.5% or 5 cases vs.7.0% or 14, P<0.05), gastrointestinal bleeding(5.5% or 11 cases vs.12.5% or 25 cases, P<0.05)and hospital-acquired pneumonia(9.0% or 18 vs.4.0% or 8 cases, P<0.05)had significant differences between the PPI group and the control group.Multivariate Cox regression analysis showed that age>70 years( HR=1.845, 95% CI: 1.131-3.010, P<0.05), arterial oxygen partial pressure <78.0 mmHg(1 mmHg=0.133 kPa, HR=2.143, 95% CI: 1.317-3.487, P<0.01), SOFA score>14( HR=3.603, 95% CI: 1.741-7.456, P<0.01)and blood lactic acid>3.8 mmol/L( HR=2.725, 95% CI: 1.437-5.167, P<0.01)were related factors for the 30-day mortality.Compared with the control group, there was no significant difference in 30-day mortality between the five subgroups taking different PPIs including omeprazole, pantoprazole, rabeprazole, lansoprazole and esomeprazole( P>0.05), and the incidence of clinically significant gastrointestinal bleeding was significantly reduced( P<0.05), but there was no significant difference between the five PPIs subgroups( P>0.05). Conclusions:Although PPIs have no effect on short-term death in elderly ARDS patients, it can increase the risk of hospital acquired pneumonia while reducing the occurrence of gastrointestinal bleeding.With PPI use, advanced age, low arterial oxygen partial pressure, high SOFA score and high blood lactate are risk factors for the 30-day mortality.

Objective To evaluate the effects of nitrous oxide inhalation on conscious sedation of patients during colonoscopy and analyze its risk factors. Methods From October 2016 to July 2017, a total of 154 patients undergoing colonoscopy were included in the study. The comfort level was rated using Modified Gloucester Comfort Scale ( MGCS). Factors affecting comfort level were analyzed by univariate analysis and multivariate Logistic regression, and then a comfort stratification predicting model was created. Results All 154 patients finished colonoscopy. The mean time of ideal anesthesia state was 195. 15 s. Among the 154 cases, 115 ( 74. 7%) were identified as comfort ( grade of MGCS from 1 to 3) and 39 (25. 3%) were rated as discomfort ( grade of MGCS from 4 to 5). Multivariate regression indicated that age ≥60 years ( P＝0. 000, OR＝1. 074, 95%CI: 1. 036-1. 114) and mild anxiety ( P＝0. 018, OR＝3. 338, 95%CI: 1. 227-9. 079) were associated with comfort level during colonoscopy.The established model with the age (X1) and mild anxiety (X2) was P＝eY/(1+eY), Y＝－3. 812+0. 071X1+1. 205X2(no anxiety was assigned 1, mild anxiety was assigned 2), and the area under the receiver operating characteristics curve was 0. 746 (95%CI: 0. 661-0. 830), which showed moderate predictive power of the final model. The model reached the highest predictive accuracy when the Yoden Index was 0. 838 with sensitivity of 50. 4% and specificity of 89. 7% for predicting comfort level of patients in conscious sedation status induced by nitrous oxide inhalation during colonoscopy. Conclusion Nitrous oxide can ease pain during colonoscopy, especially for patients over 60 years old and with anxiety. We can use it as an option according to actual circumstance in practice.

Objective To establish a coupled model combining the rat brain nuclei microelectrode recordings and the behavioristics for rehabilitation experiment. Methods The modified indwelling tube connection fixed device was put inside the rats' back, and the microprobes were implanted into related neural nucleus. A signal connection was made between self-administration system and electrophysiological data acquisition system. The rat was addicted after training by self-administration system. The related cerebral nucleus electrophysiological sig-nals were recorded in different states of addiction. Results and Conclusion The modified indwelling tube connection fixed device has a bet-ter quality for reducing the phenomenon of leak. The signal was well in the combination of two different systems. The signals for the rat's ac-tion and neural electrical were recorded in the same time.

BACKGROUND:Acellular matrix and annulus fibrosus-derived stem cells are both derived from the annulus tissue, and their tissue engineering complexes may have better biocompatibility. OBJECTIVE:To culture rabbit annulus fibrosus-derived stem cells on the porcine decellularized annulus fibrosus matrix, and to observe the growth of annulus fibrosus-derived stem cells on the decellularized matrix scaffold. METHODS:Decellularized annulus fibrosus matrix from porcine was prepared and detected by scanning electron microscopy, DAPI staining and Fourier transform infrared spectroscopy analysis. After isolation and culture, annulus fibrosus-derived stem cells were seeded onto the decellularized annulus fibrosus matrix. cellgrowth on the scaffolds was observed by cytoskeleton staining, inverted immunofluorescence microscopy and scanning electron microscopy to draw cellgrowth curve. RESULTS AND CONCLUSION:The prepared decellularized annulus fibrosus matrix was white and translucence liquid. The result of Fourier transform infrared spectroscopy indicated that the main component of the decellularized annulus fibrosus matrix was col agen. DAPI staining and scanning electron microscopy results showed no cells resident. The cytoskeleton staining displayed that annulus fibrosus-derived stem cells grew wel on the scaffolds at 1, 3, 7 days. These findings indicated that annulus fibrosus-derived stem cells have a good biocompatibility with the decellularized annulus fibrosus matrix in vitro.

Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M (1)H-nuclear magnetic resonance ((1)H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R(2)=0.812, Q(2)=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that (1)H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.
Animals ; Antirheumatic Agents ; administration & dosage ; Arthritis ; chemically induced ; drug therapy ; urine ; Biomarkers ; urine ; Collagen Type II ; Dose-Response Relationship, Drug ; Immunosuppressive Agents ; administration & dosage ; Magnetic Resonance Spectroscopy ; methods ; Male ; Metabolome ; Methotrexate ; administration & dosage ; Proteome ; analysis ; Protons ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Treatment Outcome