OBJECTIVE To optimize the extraction process of organic acids from Angelica sinensis using deep eutectic solvents （DESs）， and conduct characterization， antioxidant activity evaluation， and extraction mechanism analysis. METHODS The conductor-like screening model for realistic solvation with segment activity coefficients （COSMO-SAC） was employed to screen the types of DESs. With total organic acid content as the response value， single-factor experiments and Box-Behnken response-surface methodology were used to optimize the extraction conditions. Using A. sinensis decoction pieces and/or A. sinensis methanol extract as references， scanning electron microscope and Fourier transform infrared spectrometer （FTIR） were applied to characterize the products. Additionally， the 1，1-diphenyl-2-picrylhydrazyl （DPPH） and 2，2′-azino-bis（3-ethylbenzothiazoline-6- sulfonic acid） （ABTS） free radical scavenging capacities were determined. Density functional theory （DFT） was used to analyze the extraction mechanism of ferulic acid and chlorogenic acid by the DESs. RESULTS & CONCLUSIONS The optimal DESs was choline chloride-propanediol. The optimal extraction conditions for organic acids from A. sinensis were as follows： choline chloride- propanediol molar ratio of 1∶1， DESs water content of 70%， solid-liquid ratio of 1∶10， heating temperature of 57 ℃， and heating and stirring time of 8 min. In three validation experiments， the total organic acid content was 2.92 mg/g， yielding a relative error of 0.34% compared to the predicted value （2.91 mg/g）. Compared with A. sinensis decoction pieces and methanol extracts， the agglomerated structure of the DESs extract powder almost disappeared， showing the presence of lamellar structures similar to those of the intestinal wall. Compared with the methanol extract， the DES extract exhibited higher FTIR characteristic peak intensity and peak area integration， as well as stronger scavenging capacities against DPPH and ABTS free radicals. The extraction of organic acids from A. sinensis by DESs is the result of the combined effects of polarity matching， hydrogen bonding， and structural adaptation.

The prevalence rate of nonalcoholic fatty liver disease(NAFLD)reaches up to 30%around the world,and the disease has a serious impact on human health and constitutes a public health burden.Due to difficulties in the diagnosis and monitoring of NAFLD,it is important to identify potential drug targets and biomarkers,and multi-omics techniques hold great promise in the search for early diagnostic markers,therapeutic targets,and outcome and prognostic assessment of NAFLD.This article reviews the research advances in multi-omics techniques in the field of NAFLD in recent years,in order to provide a richer theoretical basis and new strategies for the prevention and treatment of NAFLD.

Objective To investigate associations between three-dimensional(3D)morphology of cervical vertebrae and skeletal mat-uration by cone-beam computed tomography(CBCT)and establish corresponding regression models for quantitatively evaluating cervical vertebral maturation(CVM).Methods The analyzed sample consisted of 358 CBCT images(175 male,183 female),of which 277 images were randomly selected as the model development group and 81 as the performance test group.Twenty-one 3D morphological pa-rameters were defined and measured,incorporating all parts of the cervical vertebrae,including the cervical vertebral bodies,transverse processes,spinous processes,pedicles,lamina,and articular processes.The cervical vertebral maturation index(CVMI)was determined by experienced orthodontists as reference standard.Spearman's rank correlation coefficient and multivariable stepwise regression analysis were used to identify the associations and build regression models.The performance test group was employed to ex-amine each model's reliability.Paired-samples Wilcoxon signed-rank test compared the CVMI of the model prediction with the reference standard.Results Three-dimensional morphological changes in various parts of the cervical vertebrae correlated with CVMI(P＜0.05).Six 3D morphometric parameters were each recognized for male and female models,three of which were identical.The adjusted R2 was 0.899 for males and 0.902 for females,with corresponding accuracies of 85.0%and 85.4%,respectively.These models showed no difference as compared with the reference standard(P＞0.05).Con-clusion New associations were found between 3D morphology of cer-vical vertebrae and skeletal maturation.The 3D-driven morphometric CVM assessment method and corresponding regression models exhibited good credibility and high consistency with experts.

【Objective】 To investigate the influence of matrine (MT) on the balance of T helper cell 17 (Th17)/regulatory T cells (Treg) in rats with inflammatory bowel disease by regulating interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3)/nuclear transcription factor-κB (NF-κB) pathway. 【Methods】 SD rats were grouped into control check group (CK group), model group, low-dose MT group (MT-L group, 50 mg/kg), medium-dose MT group (MT-M group, 100 mg/kg), high-dose MT group (MT-H group, 200 mg/kg), mesalazine group (MSLM group, 0.42 g/kg), and MT-H+rIL-6 (IL-6 activator) group (200 mg/kg+0.05 mg/kg) according to the random number table method, with 18 in each group. Except for the CK group, the rats in other groups all received with 5% trinitrobenzenesulfonic acid (20 mg/kg) buffer solution mixed with 50% ethanol at a ratio of 1∶1 and then enema to construct a rat model of inflammatory bowel disease. After the successful modeling, they were treated with drug administration once a day for 7 weeks. The body weight of rats was measured at 1, 3, 5, and 7 weeks of administration; the changes of colon length of rats in each group were compared; HE staining was used to detect the pathological damage of rat colon tissue; the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-17 and IL-10 in serum of rats were detected by ELISA; the proportions of Th17 and Treg cells in peripheral blood of rats were detected by flow cytometry; Western blottingt was performed to detect the protein expression of retinoic acid-related orphan receptor γt (RORγt), forkhead box protein P3 (Foxp3), IL-6, p-STAT3, and p-NF-κB p65 in rat colon tissue. 【Results】 Compared with the CK group, the colon tissue of the model group was severely damaged by pathology, and the body weight (at 3, 5, and 7 weeks), the level of IL-10, the proportion of Treg cell, and the expression of Foxp3 protein were decreased, the colon length shortened, the levels of TNF-α, IL-17, the proportions of Th17 cell, Th17/Treg ratio, and the protein expression of RORγt, IL-6, p-STAT3, and p-NF-κB p65 increased (P<0.05). Compared with the model group, the corresponding indicators of the MT-L group, MT-M group, MT-H group, and MSLM group had the opposite trends (P<0.05); rIL-6 attenuated the promoting effect of high-dose MT on Th17/Treg balance in inflammatory bowel disease rats. 【Conclusion】 MT may promote Th17/Treg balance in inflammatory bowel disease rats by inhibiting IL-6/STAT3/NF-κB signaling pathway.

Transcranial electric stimulation (TES) is a non-invasive, economical, and well-tolerated neuromodulation technique. However, traditional TES is a whole-brain stimulation with a small current, which cannot satisfy the need for effectively focused stimulation of deep brain areas in clinical treatment. With the deepening of the clinical application of TES, researchers have constantly investigated new methods for deeper, more intense, and more focused stimulation, especially multi-electrode stimulation represented by high-precision TES and temporal interference stimulation. This paper reviews the stimulation optimization schemes of TES in recent years and further analyzes the characteristics and limitations of existing stimulation methods, aiming to provide a reference for related clinical applications and guide the following research on TES. In addition, this paper proposes the viewpoint of the development direction of TES, especially the direction of optimizing TES for deep brain stimulation, aiming to provide new ideas for subsequent research and application.
Transcranial Direct Current Stimulation/methods* ; Deep Brain Stimulation ; Brain/physiology* ; Head ; Electric Stimulation/methods*

Objective:In order to explore the possibility of expanding the surgical indications of the ambulatory laparoscopic transcystic common bill duct exploration(LTCBDE).Methods:A retrospective case-control study analysis was performed on the clinical data of 585 patients who underwent laparoscopic transcystic common bill duct exploration in the Beijing Friendship Hospital Affiliated to Capital Medical University from January 2015 to December 2018, including 155 cases of the ambulatory LTCBDE (study group) and 430 cases of the overnight LTCBDE (control group). The propensity score was used to match the related variables, and 144 pairs were successfully matched. The two groups were compared in surgery-related indicators, such the preoperative tests, history of acute exacerbation in the last one month, history of upper abdominal surgery, concomitant diseases (high blood pressure, diabetes mellitus, coronary heart disease, cerebrovascular disease and respiratory diseases), american society of anesthesiology (ASA) score, intraoperative bleeding, operation time, total medical costs, unplanned readmission rate. Measurement data with normal distribution were expressed as mean±standard deviation( ± s), chi-square test was used for comparison between groups, and M( Q1, Q3) was used for measurement data with non-normal distribution. Fisher exact probability test and Wilcoxon rank-sum test were used for comparison between groups. Results:The indexes of aspartate aminotransferase (AST), alanine aminotransferase(ALT), total bilirubin, direct bilirubin (DBIL), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), ASA score, intraoperative bleeding and total medical costs of the study group were 21.8(18.0, 31.0) U/L, 21.5(15.0, 42.5) U/L, 14.2(11.2, 18.6) umol/L, 2.6(2.1, 3.5) μmol/L, 91.0(73.3, 118.5) U/L, 44.5(22.0, 109.8) U/L, 2.0(2.0, 2.0) grade, 7.5(5.0, 10.0) mL, 9 659.0(8 704.8, 10 640.2) yuan respectively, and the control group were 26.0(17.7, 45.3) U/L, 29.5(16.0, 85.5) U/L, 17.2(13.0, 27.5) μmol/L, 3.8(2.4, 8.7) μmol/L, 105.0(81.0, 156.0) U/L, 86.5(25.0, 224.8) U/L, 2.0(2.0, 2.0) grade, 10.0(6.3, 20.0) mL, 14 366.6(11 766.4, 16 764.4) yuan, which the differences between the two groups were statistically significant ( P<0.05). In two groups of the surgery-related indicators, such as the history of acute exacerbation in the last one month, history of upper abdominal surgery, hypertension are significant statistical differences ( P<0.05). Then there were no significant differences in diabetes, coronary heart diseases, cerebrovascular disease, respiratory diseases, surgical time and unplanned readmission rate. Conclusion:The concomitant diseases may not be the absolute contraindications of the ambulatory LTCBDE. More patients can be treated with ambulatory LTCBDE in experienced centers if relevant outpatient assay and examinations can be further improved, risks of surgery and anesthesia can be fully evaluated, and surgical contraindications can be clearly excluded.

Objective: To understand the prevalence and associated factors of school bullying among primary and secondary school students in Haidian District, and to provide scientific basis for intervention plan. Methods: From September to October 2021, 1 906 primary and secondary school students in Haidian District were selected by stratified cluster random sampling for electronic questionnaire survey,an electronic questionnaire survey was conducted on students by using the questionnaire of the Student Health Status and Influencing Factors Questionnaire. Results: The prevalence of campus bullying among primary and secondary school students in Haidian District was 4.3%, of which primary school (7.6%) > junior middle school (4.1%) > vocational high school (2.5%) > senior high school (1.9%) ( χ 2=23.49, P ＜0.01), boys (5.5%) were more than girls (3.0%) ( χ 2=7.44, P ＜ 0.01 ), students from abnormal families (6.9%) were higher than students from normal families (3.9%) ( χ 2=4.24, P =0.04). Multivariate Logistic regression analysis showed that students in primary school had a higher risk of being bullied in school ( OR =2.13). Abnormal family ( OR = 1.07 ), smoking experience ( OR =2.28), experience of being beaten and scolded by parents( OR =2.49) and fighting behavior ( OR =1.84) were positively correlated with school bullying ( P <0.05). Conclusion Campus bullying is prevalent in primary and secondary schools in Haidian District, which warrents further attention of schools and education departments. Family school partnership and targeted prevention and intervention measures for key populations are expected.

Objective:To explore the diagnosis and treatment of hepatocellular adenoma.Methods:The clinical data of 23 hepatocellular adenoma patients admitted to the Affiliated Hospital of Qingdao University from May 2013 to May 2020 were retrospectively analyzed.Results:Fifteen patients were female, the age ranged from 21 to 60. The maximum tumor diameter was from 2.5 cm to 15 cm.Most patients (15/23) were asymptomatic. There were 20 cases (87%) with single lesion and 3 cases (13%) with multiple lesions. Contrast-enhanced CT and MRI showed enhancement in the arterial phase, and de-enhancement in the portal phase as well as in the delayed phase. All cases underwent tumor resection. Hepatocellular adenoma was confirmed by pathology with partial canceration in one case and intratumoral hemorrhage in two cases. Sixteen cases were misdiagnosed preoperatively, 20 were followed up with the median follow-up time of 36 months. Recurrence was not found.Conclusion:Hepatocellular adenoma is uncommon and often misdiagnosed. Preoperative diagnosis is dependent on MRI.Given the fact of high rate misdiagnosis and a tendency of canceration,resection is recommended.

Objective:To investigate whether coxsackievirus A 16 (CVA16) infection would affect the expression of N6-methyladenosine (m 6A) methylation-related proteins in human bronchial epithelial cells (16HBE), ICR suckling mice and SCRBA2 humanized mice and influence their subcellular localization. Methods:CVA16 was used to infect 16HBE cells at a multiplicity of infection (MOI) of 0.1 and mice at 10 7 CCID 50/ml. Changes in the expression of methyltransferases, demethylases and methylated reading proteins were analyzed by Western blot. Cellular localization of these proteins was observed using immunofluorescence. Results:The expression of m 6A methylation-related proteins was gradually reduced in CVA16-infected cells with time, but showed no obvious change in ICR suckling mice or SCRBA2 humanized mice. After infection, m 6A methylation-related proteins were redistributed in both the nucleus and cytoplasm and even degraded. Conclusions:CVA16 replication in host cells altered the expression and cellular localization of m 6A methylation-related proteins, which indicated that m 6A modification might be a new potential target for enterovirus therapy.

Objective:To provide epidemiological data and clinical evidence for cosmetic adverse reactions.Methods:A retrospective clinical analysis was carried out on a total 820 outpatients (23 males and 797 females) suspected to be with cosmetic adverse reactions from January 2014 - October 2017, and average age of these patients was 7~75 (32.66±8.09) years. Suspicious cosmetics patch tests were performed in some patients. Suspicious cosmetics patch tests were performed in 687 patients.Results:Among 820 patients with cosmetic adverse reactions, women accounted for 97.20% and men accounted for 2.80%. Age distribution was most common among young people aged 21-40 years, accounting for 71.34%. The highest level of education was higher education, accounting for 59.69%. Occupational distribution was most commonly concentrated in employees and unemployed persons, accounting for 28.54% and 18.66%, respectively. A history of cosmetics allergies accounted for 17.28%. Cosmetic contact dermatitis was the most common clinical type of cosmetic adverse reactions, accounting for 92.70%. A total of 1682 suspected pathogenic cosmetics were involved. The positive rate of the cosmetic original patch test was 42.39%. Among the cosmetics with a positive patch test, moisturizing, anti-wrinkle and whitening freckle cosmetics accounted for the highest proportion, 31.59%, 15.09%, and 12.68%, respectively.Conclusions:Cosmetic contact dermatitis is the most common type of cosmetic adverse reaction. Patch testing is helpful in identifying the contact allergens in cosmetic adverse reaction.