ObjectiveTo investigate the contamination status of ochratoxin A (OTA) in commercially available food products in Shanghai, and to assess OTA exposure levels and the associated non-carcinogenic and carcinogenic risks among pregnant women by integrating dietary consumption data of this population. MethodsThe levels of OTA contamination in 1 520 food samples collected in Shanghai from 2022 to 2023 were determined using liquid chromatography-tandem mass spectrometry. An exposure assessment model was developed based on the dietary consumption levels of pregnant women from the 2016‒2017 Shanghai Pregnant Women Dietary Monitoring Survey to calculate the estimated daily intake (EDI) of OTA, the margin of exposure for non-carcinogenic toxicity (MOE₁), and the margin of exposure for carcinogenic toxicity (MOE₂). An MOE₁ greater than 200 and an MOE₂ greater than 10 000 indicate that the non-carcinogenic toxicity and carcinogenic toxicity resulting from exposure are negligible, respectively. For samples with OTA contamination levels below the limit of detection (LOD), which accounted for more than 80% of the samples, the OTA levels were assigned values of 0 and LOD, respectively, for subsequent calculations. ResultsThe detection rates of OTA in cereals, nuts, dried fruits, and alcohol samples collected in 2022 were 2.03%, 0, 0, and 0, respectively. The OTA detection rates in cereals, nuts, dried fruits, beans, and alcohol samples collected in 2023 were 2.50%, 0.39%, 2.47%, 1.67%, and 13.33%, respectively. For pregnant women in Shanghai in 2022, simulation results indicated that when assigning a value of 0 and the LOD, theP₅₀ values of EDI for dietary OTA exposure were 0.05 and 0.72 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.25 and 2.40 ng·(kg·d)^-1, respectively. For pregnant women in Shanghai in 2023, the P₅₀ values of EDI for dietary OTA exposure were 0.04 and 1.00 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.23 and 2.67 ng·(kg·d)^-1, respectively, both substantially below the tolerable daily intake (TDI) for OTA [17 ng·(kg·d)^-1]. The EDI for dietary OTA exposure in 100.0% of Shanghai pregnant women was lower than the TDI, indicating an overall low level of dietary OTA exposure among this population. For 100.0% of pregnant women, the MOE₁ for dietary OTA exposure exceeded 200. When assigned a value of 0, the MOE₂ for 100.0% of pregnant women in both 2022 and 2023 exceeded10 000. When assigned the LOD value, 72.3% and 81.8% of pregnant women in 2022 and 2023, respectively, had an MOE₂ exceeding 10 000. ConclusionFrom 2022 to 2023, samples of cereals, nuts, dried fruits, beans, and alcohol sold in Shanghai exhibited varying degrees of OTA contamination. The overall EDI of OTA exposure among pregnant women in Shanghai remained at a low level. The non-carcinogenic and carcinogenic risks associated with OTA exposure were generally low and at controllable levels.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

This review analyzes the application status and pros-pect of big data and artificial intelligence technology in the field of pharmacology in recent years.Big data and artificial intelli-gence technology is the inevitable result of the information age,which not only promotes the development of biomedicine,but al-so opens up new ways for the development of pharmacology.Mo-reover,artificial intelligence(AI)is a multifaceted and evolving field applied to pharmaceutical R&D,health management,and new drug R&D.Consequently,this review discusses the applica-tion of artificial intelligence in pharmacology at different stages,discusses the existing shortcomings,and finally makes an out-look.

As the first defense of respiratory system,airway epi-thelial cells(AECs)play an important role in separating the re-spiratory internal and external environment.They are essential for the natural immune function.Small airway lesions are an im-portant early pathology of chronic obstructive pulmonary disease(COPD),when AECs are exposed to harmful particles or gases for a long time,the epithelial barrier is damaged,and the signa-ling pathways which involved in differentiation,repair,and in-flammatory are disordered,resulting in epithelial cell cycle stag-nation and accelerated aging.A number of studies have sugges-ted that AECs of COPD patients express high levels of aging markers,suggesting that senescence of AECs is closely related to COPD.This review discusses the potential mechanisms of AECs senescence in COPD,the impact of AECs senescence on the de-velopment and severity of the disease,and highlights potential targets for modulating cellular senescence in airway epithelium as a therapeutic approach in COPD.

Objective:To investigate the effects of target-oriented liquid therapy on the treatment outcomes of skin grafting in patients with severe burns.Methods:A total of 60 patients with severe burns (total burn area over 20%, and deep second-degree burn area ≥ 10%) who were scheduled for skin graft surgery at the Marine Police Corps Hospital of Chinese People's Armed Police Force from January 2019 to January 2022 were included in this cohort study. The patients were randomly divided into a control group (conventional fluid therapy) and an observation group (target-oriented fluid therapy) using a random number table method, with 30 patients in each group.The levels of lactate (Lac) and high-sensitivity cardiac troponin I (cTnI) were compared between the two groups. The usage of colloid and crystalloid fluids, urine output, length of hospital stay, and the incidence of complications were compared between the two groups.Results:At the end of the surgery, the levels of Lac and cTnI in the observation group were (1.13 ± 0.22) mmol/L and (0.95 ± 0.25) μg/L, respectively, both of which were significantly lower than those in the control group [(1.52 ± 0.34) mmol/L, (1.10 ± 0.31) μg/L; t = 5.24, 0.83, P < 0.001, P = 0.044]. The differences in Lac and cTnI levels in the observation group were (0.53 ± 0.36) and (0.13 ± 0.07), respectively, which were significantly greater than those in the control group [(0.23 ± 0.16), (0.02 ± 0.01), t = -4.17 and -3.45, P < 0.001, P = 0.001]. The volumes of colloid and crystalloid fluids and the length of hospital stay in the observation group were (960.25 ± 153.32) mL, (1 680.52 ± 253.08) mL, and (51.36 ± 17.25) days, respectively. These values were significantly lower or shorter than those in the control group [(1 459.73 ± 203.41) mL, (2 401.89 ± 301.23) mL, (81.05 ± 25.08) days, t = 10.74, 10.04, 5.34,all P < 0.001]. The incidences of postoperative infection, pneumonia, and arrhythmia in the observation group were 33.33% (10/30), 16.67% (5/30), and 16.67% (5/30), respectively, which were significantly lower than those in the control group [63.33% (19/30), 46.67% (14/30), 30.00% (15/30); χ2 = 5.41, 6.24, 7.50, P = 0.020, P = 0.013, P = 0.006]. However, there was no statistically significant difference in acute lung injury, heart failure, and myocardial injury between the two groups ( χ2 = 1.36, 1.92, 0.29; P = 0.243, 0.166, 0.592). Conclusions:Compared with traditional fluid replacement therapy, target-oriented fluid therapy has a more significant therapeutic effect on patients with severe burns. It not only reduces fluid usage and the length of hospital stay but also decreases the incidence of infection, pneumonia, and arrhythmia in these patients.

AIM To study the chemical constituents from the branches and leaves of Michelia yunnanensis Franch.ex Finet & Gagnep.and their anti-inflammatory activities.METHODS The methanol extract was isolated and purified by silica gel,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Twenty compounds were isolated and identified as dihydrodehydrodiconifenyl alcohol(1),8-hydroxypinoresinol(2),lariciresinol(3),isolariciresinol(4),(7S,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-aldehyde(5),thero-2,3-bis-(4-hydroxy-3-methoxypheyl)-3-methoxy-propanol(6),evofolin B(7),(E)-p-coumaryl alcohol γ-O-methyl ether(8),ω-hydroxypropioguaiacone(9),sinapaldehyde(10),isoscopoletin(11),6-hydroxy-5,7-dimethoxycoumarin(12),2α,3α-dihydroxy-2-methylbutyrolactone(13),6-hydroxy-3(1-hydroxy-1-methylethyl)-6-methyl-2-cyclohexen-1-one(14),benzofuran-2-carboxaldehyde(15),3,4-dihydroxy-5-methoxybenzaldehyde(16),3,5-dimethoxy-4-hydroxybenzaldehyde(17),3,4-dihydroxybenzaldehyde(18),3,4-dihydroxybenzoic methyl ester(19),vanillic acid(20).The inhibition rate of compound 1 on NO was 45.39％±0.32％.CONCLUSION Compounds 1-16,18-20 are first isolated from this plant.Compound 1 has anti-inflammatory activity.

Aim To investigate the effect of ACSL4 on the malignant biological behavior of esophageal cancer cells and gefitinib resistance by regulating FASN,and to explore the related mechanism.Methods Thirty-five fresh esophageal cancer tissues and adjacent nor-mal tissues,and 30 esophageal cancer tissues with ge-fitinib resistance were collected.The expressions of ACSL4 and FASN were detected by qRT-PCR and im-munohistochemistry.The expression levels of ACSL4 and FASN in human normal esophageal cells HET-1 A,esophageal cancer cell lines ECA109,EC9706,TE-1 and TE-1/GR were detected by qRT-PCR.Cells in each group were constructed by liposome transfection technique,and the drug resistance and proliferation a-bility of cells were detected by cloning and CCK-8 as-say,cell apoptosis was detected by flow cytometry,cell invasion ability was detected by Transwell,and EMT pathway protein expression was detected by Western blot.Results Compared with adjacent normal tis-sues,the expression of ACSL4 and FASN genes in cancer tissues increased,and there was a positive corre-lation.The expression of ACSL4 significantly increased in ECA109,EC9706 and TE-1 cells compared with HET-1 A cells.With the increase of gefitinib concen-tration,the expression of ACSL4 in TE-1 cells gradually increased,and the expression of ACSL4 in TE-1/GR cells was higher than that of TE-1.Compared with the control group and the si-NC group,the cell proliferation and invasion ability of si-ACSL4 group decreased,the number of apoptosis increased,the expression of E-Cadherin increased,and the expression of N-Cadherin,Vimentin and β-catenin decreased.The response ex-periment showed that compared with the si-ACSL4 group and the si-ACSL4+oe-NC group,the cells in the si-ACSL4+oe-FASN group increased drug resistance,increased proliferation and invasion ability,decreased apoptosis number and decreased expression of E-Cad-herin.The expressions of N-Cadherin,Vimentin and β-catenin increased.Conclusions By down-regulating the expression of FASN,ACSL4 reverses the resistance of esophageal cancer TE-1/GR cells to gefitinib and in-hibits the proliferation,invasion and accelerates apopto-sis of TE-1/GR cells,which may be related to the regu-lation of EMT signaling pathway.

Objective To analyze the epidemiological and clinical characteristics of scrub typhus in Liuyang People's Hospital Hunan Province for better diagnosis,treatment,prevention and control of scrub typhus.Methods A retrospective study was conducted on 159 confirmed cases of scrub typhus.The demographic data of patients,clinical manifestations of scrub typhus,laboratory tests,and chest CT findings,complications,treatment,and outcomes were analyzed.Results The 159 patients with scrub typhus included 142 males and 17 females.The average age of patients was(53.8±11.9)(18-82)years old.The peak incidence of scrub typhus was in the period from July to September(87.42％).The common clinical manifestations included fever(97.48％),headache(41.51％),and fatigue(23.90％).The most common signs were eschar(92.45％)on the lower limbs(25.16％),scrotum(15.72％),and buttocks(11.32％).Laboratory test results upon admission showed decreased platelet count(64.15％),elevated creatinine(38.36％),elevated AST(90.57％),ALT(80.50％),and LDH(90.57％).Pulmonary imaging study revealed pulmonary inflammation(22.64％),pleural effusion(13.21％),and pericardial effusion(6.29％).The common complications included liver impairment(69.81％)and decreased platelet count(50.94％),as well as other complications such as renal dysfunction,myocardial injury,sepsis,respiratory failure,and disseminated intravascular coagulation(DIC).Doxycycline-based therapies resulted in cure rate of 98.11％(156/159).Three patients died due to severe complications.Conclusions The peak incidence of scrub typhus was in the period from July to September in Hunan Province.Eschar is a key feature for clinical diagnosis.Scrub typhus can affect multiple organ systems,leading to various systemic complications.The cure rate is high with doxycycline treatment,but some patients may die from severe complications due to delayed medical treatment.

Objective To examine the effects of SSRO(sagittal split ramus osteotomy)for Class Ⅲ malocclusion treatment on pha-ryngeal airway space(PAS)and respiratory function during sleep.Methods The subjects were 18 patients in whom mandibular prog-nathism was corrected by sagittal split ramus osteotomy.Morphological changes were studied using cone beam computed tomography at 3 days before surgery and 6 months after surgery.3D models of the craniofacial and pharyngeal airway morphology were reconstructed with a 3D image analysis system(Mimics Innovation Suite).The anteroposterior dimension,lateral width,cross-sectional area of each subject's pharyngeal airway were measured before and after surgery.The three airway volumes and total PAS volume were measured be-fore and after surgery.Single polysomnography(PSG)monitoring was performed using the polysomnography system 3 days before and 6 months after orthognathic surgery,respectively,and the monitoring data were recorded.Statistical analysis of the data was performed using SPSS 25.0 software package.Results SP-AP and SP-CSA decreased after operation(P＜0.05).EP-AP was significantly de-creased(P＜0.01)and EP-CSA decreased(P＜0.05).The oropharynx volume and total PAS volume were significantly decreased,and the epiglottic volume decreased(P＜0.05).There were no significant changes in respiratory function during sleep.Conclusion SP-AP,SP-CSA,EP-AP,EP-CSA,the oropharynx volume,the epiglottic volume and total PAS volume were decreased significantly after surgery.There were no significant changes in respiratory function during sleep.

As the first defense of respiratory system,airway epi-thelial cells(AECs)play an important role in separating the re-spiratory internal and external environment.They are essential for the natural immune function.Small airway lesions are an im-portant early pathology of chronic obstructive pulmonary disease(COPD),when AECs are exposed to harmful particles or gases for a long time,the epithelial barrier is damaged,and the signa-ling pathways which involved in differentiation,repair,and in-flammatory are disordered,resulting in epithelial cell cycle stag-nation and accelerated aging.A number of studies have sugges-ted that AECs of COPD patients express high levels of aging markers,suggesting that senescence of AECs is closely related to COPD.This review discusses the potential mechanisms of AECs senescence in COPD,the impact of AECs senescence on the de-velopment and severity of the disease,and highlights potential targets for modulating cellular senescence in airway epithelium as a therapeutic approach in COPD.