OBJECTIVE To assess the cost-effectiveness of durvalumab combined with chemotherapy as a first-line treatment for advanced biliary tract cancer from the perspective of the Chinese healthcare system. METHODS Using data from the TOPAZ-1 clinical trial， a three-state Markov model comprising progression-free survival （PFS）， progressive disease （PD） and death was developed， with a cycle length of 21 days and a 10-year time horizon. Patients in the observation group received durvalumab in combination with gemcitabine and cisplatin， whereas those in the control group received placebo plus the same chemotherapy regimen. The evaluation indexes were quality-adjusted life year （QALY） and the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） threshold was set at three times the 2024 Chinese per capita gross domestic product （GDP） （287 247 yuan/QALY）. The sensitivity analyses， along with scenario analyses， were performed. RESULTS In the base-case analysis， the ICER of observation group compared to control group was 1 166 344.46 yuan/QALY， far exceeding the WTP threshold， indicating that the regimen was not cost-effective. One-way sensitivity analysis identified the PD state utility， discount rate， cost of durvalumab， and PFS state utility as the main drivers of ICER variation. Probabilistic sensitivity analysis showed that， at the above WTP threshold， the probability of the acceeptance of this regimen was 0， further supporting the robustness of the base-case findings. In the scenario analysis， inclusion of a patient assistance program reduced the ICER to 235 885.16 yuan/ QALY， below the above WTP threshold， suggesting cost-effectiveness under this assistance program. However， when applying a regional WTP threshold set at three times the per capita GDP （158 475 yuan/QALY） of Gansu Province （the province with the lowest GDP in China in 2024）， the ICER remained above the threshold， indicating that the regimen was not cost-effective at the regional level. CONCLUSIONS At current pricing， durvalumab plus chemotherapy as a first-line treatment for advanced biliary tract cancer is not cost-effective in China. Although the introduction of a patient assistance program can substantially reduce the ICER and achieve cost-effectiveness at a WTP threshold set at three times the 2024 per capita GDP of China， due to limited affordability in low-income areas， the program remains not cost-effective.

On August 2-4,2023,the"Third Summit Forum on'Building a Community of Shared Future for Doctors and Patients'"was jointly organized by institutions such as the Chinese Medical Ethics,the Hospital Humanities Management and Talent Training Special Committee of the China Population and Culture Promotion Association,Center for Ethical Studies of Renmin University of China,the Newspaper for China's Physicians,the China Health Law Society,the China Anti-Cancer Association,and the China Association For Ethical Studies in Harbin.The conference arranged a sub-forum for the"Seminar on the Construction of Chinese Medical Humanities",with domestic medical humanities scholars attending the conference.After heated discussions at the seminar,the Scholars'Consensus on the Construction and Development of Chinese Medical Humanities was formed.It was proposed that in the new era,it is urgent to build the medical humanities discipline,as well as lead the academic integration and development of medical humanities under the core socialist values.At the same time,for the construction of the medical humanities discipline,it is necessary to optimize the organizational mechanism,prosper and develop the overall framework of the medical humanities discipline,accelerate the construction of a professional teaching team for the medical humanities discipline,promote the establishment of a new carrier medical humanities education and teaching in cultivating morality and nurturing talents,as well as focus on solving problems related to the cultivation of medical humanities graduate students.

AIM To explore the effects of Zishui Qinggan Decoction on the mouse model of depression induced by chronic restraint stress(CRS)via ERK/GSK3β/CREB/BDNF signaling pathway.METHODS Except for those of the blank group,the mice of other groups were induced into depression models by CRS,and divided into the model group,the fluoxetine hydrochloride group(10 mg/kg)and the low,medium and high dose Zishui Qinggan Decoction groups(8.835,17.670 and 35.340 g/kg)for the corresponding drug intervention and simultanous CRS treatment.The mice had their sugar water preference experiment and behavior experiment on the 7th and 14th day after administration;the observation of the hippocampal morphological changes by HE staining,the detection of the superoxide dismutase(SOD)activity and malondialdehyde(MDA)level in serum by kits,the detection of levels of serum 5-hydroxytryptamine(5-HT),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)by ELISA,the detection of the hippocampal mRNA expressions of BDNF,TNF-α and IL-1β by RT-qPCR method,and the detection of the hippocampal protein expressions of ERK1/2,p-ERK1/2,GSK3β,p-GSK3β,CREB and BDNF by Western blot method 14 days after administration.RESULTS Compared with the model group,after 14 days of administration,both fluoxetine hydrochloride group and medium-dose Zishui Qinggan Decoction group displayed increased preference rate of sugar water(P<0.01),shortened immobility time of tail suspension and forced swimming(P<0.01),improved hippocampal damage of nerve cells,decreased levels of serum MDA,TNF-α and IL-1β(P<0.05,P<0.01),increased SOD activity and 5-HT level(P<0.05,P<0.01),decreased hippocampal mRNA expressions of TNF-α and IL-1β(P<0.01),and decreased expressions of BDNF mRNA and p-ERK1/2,p-GSK3β,CREB and BDNF proteins(P<0.05,P<0.01).CONCLUSION Zishui Qinggan Decoction can improve the depression-like behaviors in mice exposed to CRS,and its mechanism may be related to the regulation of hippocampal ERK/GSK3β/CREB/BDNF signaling pathway.

A liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was developed for determination of three kinds of β-agonists(Clenbuterol(CL),Ractopamine(RAC)and Salbutamol(SAL))residues in animal liver samples.The liver sample homogenates were extracted with organic solvent,followed by clean-up using the automatic magnetic solid-phase extraction(MSPE),and then analyzed using LC-MS/MS.The results showed that the magnetic mixed-mode cation exchange adsorbent(M-MCX)exhibited 34%higher adsorption capacity than the conventional mixed-mode cation exchange(MCX)column.Furthermore,the clean-up was conducted by using an automatic MSPE device,and 8 samples could be simultaneously treated within 30 min.The limits of detection(LOD)were 0.01-0.1 μg/kg,the average recoveries ranged from 88.2%to 110.5%,and the relative standard deviations(RSDs)were in range of 2.9%-10.3%at three spiked levels for the three kinds of β-agonists.Compared with the traditional SPE technique,the present method had many advantages such as simple operation,rapidity and high efficiency,which was suitable for high-throughput and automatic detection of residues in routine analysis.

OBJECTIVE To investigate the effects of Tongxie yaofang （TXYF） on the symptoms of rats with irritable bowel syndrome with diarrhea （IBS-D） by regulating colonic tryptophan hydroxylase 1 （TPH1）， serotonin transporter （SERT） and intestinal flora. METHODS Forty-two SD rats were randomly divided into control group （7 rats） and modeling group （35 rats）. In modeling group， rat model of IBS-D was established by intragastrical administration of 0.45 g/L senna leaf solution [10 mL/（kg·d）] combined with chronic unpredictable stimulation. Thirty-five successfully modeled rats were randomly divided into model group， pinaverium bromide group [15 mg/（kg·d）] and TXYF low-dose， medium-dose and high-dose groups [3.75、7.5、15 g/（kg·d）， calculated by crude drug]， with 7 rats in each group. Each administration group was orally administered the corresponding drug， once a day， for 10 consecutive days. The general condition and weight changes of each group of rats were compared before modeling， after modeling and before administration， after the last drug intervention； the diarrhea index and visceral sensitivity were detected， and pathological changes of colon tissue were observed after modeling and before administration， after the last drug intervention. The level and expression of 5-hydroxytryptamine （5-HT）， protein and mRNA expressions of TPH1 and SERT were determined in colon tissue. The diversity and structural changes of fecal intestinal flora of rats were analyzed. RESULTS There was no significant change in colon histopathology in each group. Compared with model group， the general condition of rats in each medication group improved. The daily body weight gain of rats was significantly increased， while diarrhea index， visceral sensitivity， the expressions of 5-HT and TPH1 in colon tissue were significantly decreased； SERT expression of colon tissue was significantly increased in TXYF medium-dose and high-dose groups （P＜0.05 or P＜0.01）. The diarrhea index， colon TPH1 protein expression and colon 5-HT protein positive rate in the TXYF low-dose group decreased while the mRNA expression of SERT increased significantly （P＜0.05）. There was a dose- dependent trend in the effect of TXYF. Compared with model group， Chao1 index and Shannon index of the rats in TXYF high- dose group were significantly decreased （P＜0.05 or P＜0.01）， the beneficial bacteria such as Firmicutes and Lactobacillus increased significantly， while the pathogenic bacteria such as Proteobacteria， Escherichia-Shigella and Rikenellaceae_RC9_gut_ group decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS TXYF can decrease the level of 5-HT and improve intestinal flora disorder by inhibiting the expression of TPH1 and up-regulating the expression of SERT in colon tissue， thus promoting the symptoms of IBS-D rats.

Objective To investigate the therapeutic mechanism of Tujia medicine Toddalia asiatica alcohol extract(TAAE)for synovial pannus formation in rats with college-induced arthritis(CIA).Methods Sixty male SD rats were randomized into normal control group,CIA model group,TGT group,3 TAAE treatment groups at low,medium and high doses(n=10).Except for those in the normal control group,all the rats were subjected to CIA modeling using a secondary immunization method and treatment with saline,TGT or TAAE by gavage once daily for 35 days.The severity of arthritis was assessed using arthritis index(AI)score,and knee joint synovium pathologies were examined with HE staining.Serum levels of TNF-α,IL-6,and IL-1β were detected with ELISA;the protein expressions of PI3K,Akt,p-PI3K,p-Akt,VEGF,endostatin,HIF-1α,MMP1,MMP3,and MMP9 in knee joint synovial tissues were determined using Western blotting,and the mRNA expressions of TNF-α,IL-6,IL-1β,VEGF,HIF-1α,PI3K,and Akt were detected with RT-PCR.Results Treatment of CIA rat models with TAAE and TGT significantly alleviated paw swelling,lowered AI scores,and reduced knee joint pathology,neoangiogenesis,and serum levels of inflammatory factors.TAAE treatment obviously increased endostatin protein expression,downregulated p-PI3K,p-Akt,MMP1,MMP3,MMP9,VEGF,and HIF-1α proteins,and reduced TNF-α,IL-6,IL-1β,PI3K,Akt,VEGF,and HIF-1α mRNA levels in the synovial tissues,and these changes were comparable between high-dose TAAE group and TGT group.Conclusion TAAE can improve joint symptoms and inhibit synovial pannus formation in CIA rats by regulating the expressions of HIF-1α,VEGF,endostatin,MMP1,MMP3,and MMP9 via the PI3K/Akt signalling pathway.

【Objective】 To explore the relationship between polygenic risk score (PRS) and the sustainability of childhood obesity intervention, in order to provide scientific basis for future sustainable and personalized childhood obesity intervention based on genetic background. 【Methods】 A total of 148 children with overweight/obesity at baseline were selected as study subjects from a cluster randomized controlled trial (September 2018 to April 2021) regarding the effect of a childhood obesity intervention in Beijing, China. Saliva was collected to detect the whole genome sequencing. Four PRSs were built: weighted and unweighted PRS69, weighted and unweighted PRS67. The interactions between PRS and study arms on the sustainability of intervention effect (the changes in obesity-related indicators between the end of the intervention and the last follow-up) were analyzed. 【Results】 There were interactions between PRS and study arms on the rebound degree of waist circumference adjusted for body mass index (BMI), waist-to-hip ratio adjusted for BMI, and systolic blood pressure after the intervention. Compared with the control group, children in the intervention group carried each additional unit (standard deviation) of weighted PRS69, the waist circumference adjusted for BMI rebounded more by 0.34 (95%CI: 0.05 - 0.63, P=0.020), and waist-to-hip ratio adjusted for BMI rebounded more by 0.29 (95%CI: 0.03 - 0.56, P=0.031) at the last follow-up survey. When children in the intervention group carried each additional unit (standard deviation) of weighted PRS67 and unweighted PRS67, systolic blood pressure at the last follow-up survey rebounded more by 3.58 (95%CI:0.50 - 6.66, P=0.023) and 3.75 (95%CI: 0.78 - 6.71, P=0.014), respectively. 【Conclusions】 The higher PRS (the more risk alleles) children with overweight/obesity carried, their waist circumference, waist-to-hip ratio and systolic blood pressure are more likely to rebound after the intervention. Findings from this study suggest that future studies should focus more on these high-risk children after the intervention to prevent and control obesity rebound.

Objective To explore the correlation between serum microRNA-29a-3p(miR-29a-3p),throm-bospondin 2(THBS2)and cardiopulmonary function in children with chronic pulmonary heart disease.Meth-ods A total of 136 children with chronic pulmonary heart disease treated in Shijiazhuang Hospital of Tradi-tional Chinese Medicine from July 2019 to September 2023 were selected as the study subjects.Based on their clinical signs,cardiopulmonary function,and symptoms,they were divided into a compensated group(74 ca-ses)and a decompensated group(62 cases).Real-time fluorescence quantitative PCR(RT-qPCR)method was applied to detect serum miR-29a-3p level,and enzyme-linked immunosorbent assay(ELISA)was applied to detect serum THBS2 level.Moreover,ultrasound diagnostic equipment was applied to detect cardiac function indicators such as left ventricular ejection fraction(LVEF)and cardiac output(CO).Creatine kinase isoenzyme(CK-MB)and troponin(cTnl)were detected by electroluminescence analysis.Pulmonary function indicators were detected by pulmonary artery systolic pressure(PASP),mean pulmonary artery pressure(MPAP)and pulmonary artery diastolic pressure(PADP).Pearson correlation was used to analyze the corre-lation between serum miR-29a-3p and THBS2 levels and cardiopulmonary function indexes in children with chronic pulmonary heart disease,and multivariate Logistic regression analysis was used to screen the influen-cing factors of the disease in children with chronic pulmonary heart disease.Receiver operating characteristic(ROC)curve was drawn to analyze the evaluation value of serum miR-29a-3p and THBS2 levels in children with chronic pulmonary heart disease.Results The THBS2,CK-MB,cTnI,PASP,MPAP,and PADP in the decompensated group were higher than those in the compensated group(P＜0.05),while miR-29a-3p,LVEF,and CO were lower than those in the compensated group(P＜0.05).Serum miR-29a-3p in children with chro-nic pulmonary heart disease was positively correlated with LVEF and CO(P＜0.05),but negatively correla-ted with CK-MB,cTnI,PASP,MPAP,and PADP(P＜0.05).THBS2 was negatively correlated with LVEF and CO(P＜0.05),but positively correlated with CK-MB,cTnI,PASP,MPAP,and PADP(P＜0.05).MiR-29a-3p was a protective factor for exacerbation of chronic pulmonary heart disease in children(P＜0.05),while THBS2 was an independent risk factor for exacerbation of chronic pulmonary heart disease in children(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of serum miR-29a-3p and THBS2 levels alone and in combination for evaluating the severity of chronic pulmonary heart disease in children were 0.827,0.817 and 0.915,respectively.Conclusion Serum miR-29a-3p and THBS2 levels are both factors affecting the disease of children with chronic pulmonary heart disease,and are closely related to the disease and cardiopulmonary function of children with chronic pulmonary heart disease.

The lingnan liver-soothing and spirit-regulating acupuncture and moxibustion technique,developed by Professor FU Wen-Bin,a renowned traditional Chinese medicine expert in Guangdong Province,represents an innovative achievement in acupuncture therapy for depression-related disorders.Drawing upon the rich legacy of master scholars,meticulous study of medical literature,and over three decades of continuous research and innovation,Professor FU has formulated this technique with profound influence and widespread application.By tracing the developmental trajectory of the Lingnan liver-soothing and spirit-regulating technique,this paper sheds light on its significant guiding principles and reference value for the development of other distinctive acupuncture techniques.Furthermore,it offers insights and inspiration for advancement in various fields of traditional Chinese medicine.

Objective To investigate the effect of microplastic(MPs)exposure on learning and memory in mice,and its mechanism by observing the protein expression of brain-derived neurotrophic factor(BDNF)/tyrosine receptor kinase B(TrkB)/N-methyl-D-aspartate receptor subtype 2B(NR2B)signaling pathway and neurogenesis.Methods Forty male C57BL/6 mice were randomly divided into control group(Ctrl)and microplastics exposure group(MPs).Mice in MPs group were treated with 0.3 mg/(kg·d)microplastics,administered by gavage at a volume of 200 μl for 30 consecutive days.Morris water maze test was used to evaluate the spatial learning and memory ability of mice.Western blotting was used to detect the protein levels of BDNF,TrkB and NR2B in hippocampus of mice.Immunofluorescent staining was used to observe the number of doublecortin(DCX)and neuronal nuclei antigen(NeuN)positive cells in the hippocampus of mice to evaluate hippocampal neurogenesis.Results Compared with the control group,the ability of learning and memory decreased significantly in MPs group mice(P＜0.01).The expression levels of BDNF,TrkB and NR2B in the hippocampus of MPs group mice were significantly lower than those of control group(P＜0.05).The number of DCX and NeuN positive cells in the hippocampus of MPs group was significantly lower than that of control group(P＜0.01).Conclusion MPs exposure induces learning and memory impairment which may be related to inhibiting BDNF/TrkB/NR2B signaling pathway and reducing hippocampal neurogenesis.