OBJECTIVE To study the pharmacokinetic characteristics of antidepressant active components from Jiaotai pills in healthy subjects. METHODS Eight healthy subjects （3 males and 5 females） were recruited and given a single oral dose of 8.55 g of Jiaotai pills. Venous blood samples were collected before administration （0 h） and at intervals from 0.25 to 36.0 hours post- administration. After treating the plasma samples with protein precipitation， the blood concentrations of the antidepressant active ingredients （coptisine， berberine， magnoflorine， and palmatine） in Jiaotai pills were determined using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. DAS 2.0 software was employed to calculate the pharmacokinetic parameters of healthy subjects [half-life （t1/2）， peak concentration （cmax）， time to peak concentration （tmax）， area under the concentration-time curve （AUC）， and mean residence time （MRT）] using a non-compartmental model. RESULTS After healthy subjects took Jiaotai pills， the drug-time curve of the four antidepressant active ingredients conforms to a two-compartment model and tmax values were similar， with all reaching peak blood concentrations within 2.00 to 4.00 hours post-administration. However， the t1/2 and MRT of coptisine and berberine were significantly longer than that of magnoflorine and palmatine. There were also significant differences in the AUC and cmax among the four antidepressant active ingredients， with magnoflorine exhibiting markedly higher AUC0-t and cmax compared to the other three components. CONCLUSIONS In this study，LC-MS/MS is used to analyze the pharmacokinetic characteristics of the antidepressant active ingredients from Jiaotai pills in healthy subjects， can provide valuable references for the clinical application of Jiaotai pills.

ObjectiveTo investigate the effects of Hei Xiaoyaosan on neuroinflammation in APP/PS1 mice and decipher the mechanism based on the C-X3-C chemokine ligand 1 （CX3CL1）-CX3CL1 receptor 1 （CX3CR1） signaling axis. MethodsSixty 16-week-old male APP/PS1 mice were selected and acclimatized for one week， and they were then randomly allocated into a model group， a CX3CL1 group （bilateral hippocampal injection of CX3CL1 at 0.5 g·L^-1）， and high-， medium-， and low-dose （22.10， 11.05， and 5.53 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 12 mice in each group. Twelve age-matched male C57BL/6J mice served as the blank group （bilateral hippocampal injection of an equal volume of PBS）. The high-， medium-， and low-dose Hei Xiaoyaosan groups received corresponding drugs via gavage， while the blank group received an equal volume of normal saline， with an intervention period of 90 days. Morris water maze was used to assess learning and memory abilities. Nissl staining was performed to observe the pathological changes in neurons of the hippocampal CA1 region. Immunohistochemistry was adopted to detect amyloid-β_1-42 （Aβ_1-42） deposition in the hippocampal CA1 region. The immunofluorescence assay was employed to detect the expression of M1 and M2 microglial markers， including cluster of differentiation 86 （CD86）/ionized calcium-binding adapter molecule 1 （Iba-1） and arginase-1 （Arg1）/Iba1. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-8 （IL-8） and interleukin-13 （IL-13） in the hippocampal tissue. Western blot was employed to determine the protein levels of CX3CL1， CX3CR1， CREB-binding protein （CBP）， cyclic AMP response element-binding protein （CREB）， phosphorylated （p）-CREB， and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group exhibited prolonged escape latency on day 5 and a reduced swimming distance in the target quadrant （P<0.01）， disarrangement of hippocampal neurons， with a reduced number of cells and uneven Nissl body staining， increased CD86/Iba1 expression， decreased Arg1/Iba1 expression （P<0.01）， enhanced Aβ expression （P<0.01）， an elevated IL-8 level and a declined IL-13 level （P<0.01）， and downregulated protein levels of CX3CL1， CX3CR1， CBP， p-CREB， and BDNF （P<0.01）. Compared with the model group， all treatment groups showed shortened escape latency on day 5 and an increased swimming distance in the target quadrant （P<0.05， P<0.01）， regular arrangement of neurons with an increased number and increased Nissl bodies， reduced CD86/Iba1 expression， increased Arg1/Iba1 and decreased Aβ expression （P<0.01）， and a declined IL-8 level and an elevated IL-13 level （P<0.05， P<0.01）. In the CX3CL1 group and the high- and medium-dose Hei Xiaoyaosan groups， the relative expression levels of CX3CL1， CX3CR1， CBP， and p-CREB were upregulated （P<0.01）. In the low-dose Hei Xiaoyaosan group， the relative expression levels of CX3CL1， CX3CR1， CBP， p-CREB/CREB， and BDNF were upregulated （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan can improve learning and cognitive abilities in APP/PS1 mice. Specifically， it may regulate the CX3CL1/CX3CR1 signaling axis to activate the CREB/BDNF signaling pathway for the subsequent release of BDNF， modulation of microglial polarization， reduction of inflammatory cytokine levels， and attenuation of Aβ deposition.

Ideological and political education within the curriculum of higher institutions of traditional Chinese medicine （TCM） not only bears the important responsibility of promoting China's outstanding traditional culture but also serves as a vital domain for upholding integrity and innovation in medical education. These institutions must profoundly comprehend the contemporary significance of curriculum-based ideological and political education， clarify its core role in talent cultivation， leverage the distinctive advantages of TCM culture， and promote the organic integration of ideological education and professional training. By reviewing the current situation and development trends of ideological and political education in the curriculum of higher TCM institutions， this paper has analyzed the challenges in teaching design， teachers' ideological and political literacy and competence， and the integration of ideological content with specialized courses， and has proposed implementation strategies such as using TCM culture as a guiding force， strengthening teachers' teaching capacity in ideological and political education， developing distinctive educational resources， and improving evaluation and incentive mechanisms. These strategies aim to effectively enhance the impact of ideological and political education in the new era， fostering well-rounded TCM talents with both moral integrity and professional competence.

Objective To analyze the disease burden of early-onset colorectal cancer (EOCRC) at the global, regional, and national levels from 1990 to 2021, and to predict the disease burden trend from 2022 to 2026. Methods Based on the Global Burden of Disease (GBD) database, the incidence, mortality, and disability-adjusted life year (DALY) rate of EOCRC across 204 countries and regions from 1990 to 2021 were obtained. The time trends of these indicators were assessed by calculating the estimated annual percentage change (EAPC), and the contributions of ten risk factors to the EOCRC burden were analyzed. The autoregressive integrated moving average (ARIMA) model was used to predict the disease burden from 2022 to 2026. Results From 1990 to 2021, the number of new global EOCRC cases increased from 107 310 to 211 890, with the incidence rising from 3.96 to 5.37 per 100 000 people. In 2021, global EOCRC incidence, mortality, and DALY rate increased with age; males had higher rates than females in terms of incidence, mortality, and DALY rate in all age groups. In 2021, East Asia had the highest number of new cases, deaths, and DALY. From 1990 to 2021, the global EAPC for incidence rate was 0.96%, and death rate was –0.38%. ARIMA model indicated that from 2022 to 2026, the global incidence of EOCRC would continue to rise, while mortality and DALY rate would be expected to decline. Conclusions The disease burden of EOCRC has significantly increased globally from 1990 to 2021, with notable regional, age, and sex differences. By 2026, the mortality and DALY rate of EOCRC will decline, while the incidence is expected to further increase, highlighting the urgency of taking active measures to address the growing trend of EOCRC.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective:To establish HPLC fingerprint and methods for determining the contents of four iridoid glycosides of Gentiana rigescens; To evaluate the quality of Gentiana rigescens from different origins; To improve the quality control level of Gentiana rigescens medicinal materials.Methods:Using 15 batches of Gentiana rigescens from the main production areas and authentic production areas as raw materials, the common mode of HPLC fingerprints of Gentiana rigescens was established, and the chemical components of the common peaks were identified. Referring to the common mode of fingerprints, similarity analysis was conducted on the fingerprints of Gentiana rigescens from different origins. Using chemometric methods, cluster analysis (HCA), principal component analysis (HCA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed on 15 batches of Gentiana rigescens, with the common peak area of fingerprint as the variable. The contents of four types of iridoid glycosides in Gentiana rigescens were determined. Combined with the fingerprints and the content results of four types of iridoid glycosides, the quality of Gentiana rigescens from different origins was evaluated.Results:The fingerprints of Gentiana rigescens contained 9 common peaks, with 4 identified iridoid glycosides. The similarity of the fingerprints of 15 batches of Gentiana rigescens ranged from 0.962 to 0.999. HCA and PCA divided the 15 batches of Gentiana rigescens into two categories. OPLS-DA analyzed 3 significantly different components, namely gentiopicroside, peak 7, and loganic acid. The content determination results showed that the average contents of loganic acid, swertiamarin, and gentiopicroside in Gentiana rigescens from Dali Bai Autonomous Prefecture and Yunnan Province were the highest, and the total amount of four iridoid glycosides was also significantly higher than that from other regions, indicating that the overall quality of Gentiana rigescens from Dali Bai Autonomous Prefecture and Yunnan Province was relatively good.Conclusion:This method is simple, fast, accurate, and can provide reference for improving the quality standards of Gentiana rigescens.

Background and Aims:Perihilar cholangiocarcinoma(pCCA)is associated with poor prognosis.Radical resection remains the mainstay of treatment;however,high recurrence rates and limited overall survival(OS)after surgery.Metabolic syndrome(MetS)has been linked to unfavorable outcomes in various malignancies,but its impact on postoperative outcomes in pCCA is unclear.This study aimed to evaluate the influence of MetS on perioperative and long-term outcomes in patients undergoing radical resection for pCCA.Methods:A retrospective analysis was conducted on 223 patients who underwent radical resection for pCCA at the First Affiliated Hospital of Army Medical University between January 2018 and December 2023.Patients were categorized into a MetS group(n=50)and a non-MetS group(n=173)according to diagnostic criteria.Perioperative complications,overall survival(OS),and recurrence-free survival(RFS)were compared between groups.Prognostic factors were identified using multivariate analysis.Results:No significant differences were observed between the two groups regarding median hospital stay,overall complications,or severe complications(all P＞0.05).The 1-,3-,and 5-year OS rates in the MetS group were 62.3％,22.3％,and 0,respectively,compared with 78.2％,39.5％,and 22.0％in the non-MetS group.Corresponding RFS rates were 46.2％,16.9％,and 0 in the MetS group vs.63.8％,29.6％,and 18.8％in the non-MetS group.Median OS and RFS were significantly shorter in the MetS group than in the non-MetS group(15.0 vs.27.0 months;12.0 vs.21.0 months;P=0.021 and P=0.037,respectively).Multivariate analysis identified MetS and major vascular invasion as independent predictors of OS,while MetS,jaundice,R0 resection,and major vascular invasion were independent predictors of RFS(all P＜0.05).Conclusion:MetS is significantly associated with worse long-term survival and higher recurrence risk after radical resection for pCCA.Incorporating MetS into preoperative assessment and postoperative management strategies may help improve patient outcomes.

Objective:To explore the causal relationship between 1 400 blood metabolites and hyperthyroidism or hypothyroidism by using Mendelian randomization(MR) approach.Methods:This study employed a bi-directional Mendelian randomization analysis and sourced data of blood metabolites related to hyperthyroidism and hypothyroidism from the genome-wide association study(GWAS) database. R software and TwoSampleMR software package were used for analysis. The inverse variance weighting method(IVW) was used as the main method, and MR-Egger regression, weighted median method, simple mode and weighted mode were used as supplementary methods to analyze the causal relationship between blood metabolites and hyperthyroidism and hypothyroidism. The false-positive rate was corrected by false discovery rate(FDR, FDR<0.2) to control for false positives; Meta-analysis of different sample pools was performed for overall assessment. Results:The analysis found three blood metabolites significantly linked to hypothyroidism: pregnenediol disulfate(IVW: OR=1.068, 95% CI 1.032-1.106, P<0.001), 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE(IVW: OR=0.891, 95% CI 0.840-0.944, P<0.001), and linoleic-arachidonic glycerin(IVW: OR =0.923, 95% CI 0.885-0.963, P<0.001). Glutamine was also noted(IVW: OR=0.998, 95% CI 0.997-0.999, P<0.001). Reverse MR showed no significant correlation between hyperthyroidism and the four metabolites(IVW: P>0.05). Validation from FinnGen Biospecimen Library and UKB Biospecimen Library confirmed these findings. Conclusions:Among 1 400 blood metabolites, pregnenediol disulfate showed a positive correlation with hypothyroidism. In contrast, 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE and linoleic-arachidonic glycerin exhibited negative correlations with hypothyroidism, while glutamine showed a negative correlation with hyperthyroidism. This study offers insights into the pathogenesis, early screening, and treatment of hyperthyroidism and hypothyroidism.

Objective:To explore the position and length of anchor placement during the repair of anterior talofibular ligament (ATFL) in adolescents with unclosed epiphyseal plates by measuring the relevant data in three-dimensional CT.Methods:A total of 100 three-dimensional CT images of adolescent patients with unclosed epiphyseal plates were collected from the database of the Radiology Center of Renhe Hospital Affiliated to China Three Gorges University from January 1, 2017 to January 1, 2024. There were 69 males and 31 females, aged 12.38±0.90 years (range, 11-14 years), 47 on the left side and 53 on the right side, with a height of 155.72±5.84 cm (range, 145-175 cm), a weight of 48.02±5.93 kg (range, 40-72 kg), and a body mass index (BMI) of 19.77±1.61 kg/m 2 (range, 17.69-24.91 kg/m 2). The built-in measurement tool of the picture archiving and communication system (PACS) was used to measure the angle (α) between the direction of the nail placement and the longitudinal axis of the fibula, the distance between the nail placement point and the posterior edge of the fibula ( d), and the height from the nail placement point to the level of the fibula tip ( h) to evaluate the position and length of the anchor placement. Results:In adolescent patients, α was 47.50°±3.28° (range, 40.00°-56.00°), d was 17.12±1.80 mm (range, 11.70-21.90 mm), and h was 5.21±1.17 mm (range, 3.40-7.90 mm). The α, d and h of male patients were 47.48°±3.13° (range, 42.00°-56.00°), 17.49±1.54 mm (range, 14.45-21.90 mm) and 5.25±1.07 mm (range, 3.70-7.90 mm), respectively. Those of female patients were 47.55°±3.66° (range, 40.00°-53.00°), 16.30±2.07 mm (range, 11.65-20.30 mm) and 5.07±1.56 mm (range, 3.40-7.00 mm), respectively. There was a significant difference in d between male and female patients ( t=3.193, P=0.002), but there was no significant difference in α and h ( t=0.098, P=0.922; t=0.296, P=0.770). Conclusions:The safe range of anchor placement during ATFL anatomical repair in adolescents with unclosed epiphyseal plates is about 3.40-7.90 mm above the tip of fibula and 56°-90° with the longitudinal axis of fibula. Male patients with unclosed epiphyseal plates should choose anchors with a length of 14 mm and shorter, while females should choose anchors with a length of 10.8 mm.

Objective:To investigate the prognostic value of aldosterone synthase (CYP11B2) immunohistochemical expression in adrenal specimens for surgical outcomes of primary aldosteronism (PA).Methods:The clinical data of 99 patients who underwent total unilateral adrenalectomy from June 2022 to January 2023 at Beijing Anzhen Hospital was retrospectively analysed. The clinical data of 99 patients who underwent unilateral total adrenalectomy at Beijing Anzhen Hospital from June 2022 to January 2023 were retrospectively analyzed.There were 59 patients in the PA group, age (53.02±10.56) years, body mass index (BMI) (26.28±4.33) kg/m 2, preoperative aldosterone 29.0(15.9, 61.5)ng/dl, plasma renin 1.3(0.6, 2.8)μIU/ml, aldosterone renin ratio (ARR) 19.3(9.1, 59.2) μg/μIU, preoperative potassium (3.60±0.69) mmol/L, and systolic blood pressure (156.54±21.39) mmHg (1 mmHg=0.133 kPa).There were 40 cases in the nonfunctioning adenoma (NFA) group, age (57.23±9.39) years, BMI (27.07±3.46) kg/m 2, preoperative aldosterone 9.0(7.2, 14.1) ng/dl, plasma renin 18.0(5.2, 47.6)μIU/ml, ARR 0.6(0.2, 1.4) μg/μIU, preoperative potassium (4.17±0.41) mmol/L, and systolic blood pressure (157.97±26.87) mmHg. The differences between the two groups were statistically significant for potassium ( P<0.01), aldosterone ( P=0.012), renin ( P<0.01), and ARR ( P<0.01).Surgical outcomes were assessed using the Consensus on the Outcome of Surgery for Primary Aldosteronism (PASO) (complete/partial/no success for clinical and biochemical outcomes). CYP11B2 expression was evaluated by immunohistochemistry using the 2022 World Health Organization's histopathology of primary aldosteronism (HISTALDO) criteria. The correlation between the expression of CYP11B2 and surgical outcomes was assessed. Results:The mean follow-up of 99 patients was (11.73±4.92) months. Of these, 36 out of 59 PA patients had positive CYP11B2 expression in their adrenal specimens, while 23 were negative; all 40 NFA patients were negative for CYP11B2. Among the 36 CYP11B2-positive PA patients, there were 19 cases of aldosterone-producing adenomas, 3 aldosterone-producing nodules, 4 aldosterone-producing micronodules, 8 multiple aldosterone-producing micronodules, and 2 aldosterone-producing diffuse hyperplasia. 36 cases of CYP11B2-positive PA patients had complete clinical success in 15 cases, partial success in 20 cases, and no success in 1 case, and complete biochemical success in 24 cases, partial success in 11 cases, and no success in 1 case; 23 CYP11B2-negative PA patients had complete clinical success in 4 cases, partial success in 15 cases, and no success in 4 cases, and complete biochemical success in 6 cases, partial success in 15 cases, and no success in 2 cases. Adrenal specimens from CYP11B2-positive PA patients had significantly better clinical ( P=0.038) and biochemical ( P=0.008) success rates than CYP11B2-negative PA patients. Patients with aldosterone-producing adenomas had complete clinical success in 8 cases, partial success in 11 cases, and no success in 0 cases, and biochemical success was completely achieved in 16 cases, partially achieved in 2 cases, and not successful in 1 case. They also had significantly higher clinical ( P=0.028) and biochemical ( P<0.01) success rates compared to CYP11B2-negative PA patients. Conclusions:Patients with PA who had immunohistochemical staining for CYP11B2 positivity and high expression in adrenal specimens had a better postoperative clinical and biochemical prognosis. Patients with aldosterone-producing adenomas had the greatest postoperative outcome of all pathological subtypes of PA.