Depression is a common psychiatric disorder characterized by persistent low mood or mental disorders. Current treatments primarily focus on regulating neurotransmitter levels， but their effectiveness is limited. The mechanisms underlying its onset are complex， and there is no unified consensus. Abnormal signaling pathway transmission plays a crucial role in the development of depression， involving multiple pathways， including Toll-like receptor 4/nucleotide-binding oligomerization domain-like receptor protein 3 （TLR4/NLRP3）， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， mitogen-activated protein kinase/extracellular signal-regulated kinase （MAPK/ERK）， brain-derived neurotrophic factor/tyrosine kinase receptor B （BDNF/TrkB）， cyclic AMP/protein kinase A/cAMP response element-binding protein （cAMP/PKA/CREB）， and others. Traditional Chinese medicine（TCM） is based on a holistic approach and the principle of treatment based on the differentiation of syndromes， regulating the balance of multiple systems and organ functions from a macroscopic perspective. This approach has shown unique advantages in the treatment of depression. TCM attributes the onset of depression to dysfunction of the organ systems， involving liver Qi stagnation， heart spirit deficiency， kidney essence depletion， and spleen dysfunction. TCM compound treatments focus on soothing the liver， strengthening the spleen， calming the heart， and replenishing essence， with formulas such as Xiaoyaosan， Zishui Qinggan Yin， and Chahu Jia Guizhi Longgu Muli Tang. The active components of Chinese herbs mainly aim to tonify and regulate Qi， such as salidroside， ginsenoside Rb₁， astragaloside， and muscone. External TCM treatments， primarily acupuncture， aim to open the orifices and invigorate the spirit. Acupoints such as Baihui， Shenting， and Yintang are commonly used. Additionally， massage and moxibustion therapy can intervene in depression by regulating signaling pathways. This article reviews the core role of signaling pathways in the development of depression and the mechanism of TCM regulation of signaling pathways to intervene in depression， aiming to discover new therapeutic approaches that can improve the symptoms of depressed patients.

Objective : To investigate the role of enhancer of zeste homolog 2(EZH2)-trimethylated lysine 27 of histone H3(H3K27me3) axis in the dedifferentiation of thyroid cancer and its clinical value as a potential target for the treatment of anaplastic thyroid cancer(ATC). Methods : Immunohistochemical SP method was used to detect the expression of EZH2, H3K27me3, paired box gene 8(PAX8), thyroglobulin(TG) and thyroid transcription factor 1(TTF1) in ATC and papillary thyroid carcinoma(PTC) and their adjacent tissues. The relationship between EZH2 and thyroid differentiation markers(PAX8, TTF1, TG) was further analyzed by gene expression omnibus(GEO) database. ATC cell lines 8305C and BHT-101 were culturedin vitro. Real-time reverse transcription PCR(RT-qPCR) was used to detect the expression of thyroid differentiation markers(TTF1, PAX8) mRNA in ATC cell lines treated with EZH2 inhibitor(GSK126), and evaluate the potential therapeutic effect of GSK126in vitro. The effects of GSK126 and BRAF inhibitor vemurafenib on the proliferation of ATC cell lines were observed by cell proliferation assay. Results : The expression of EZH2 in ATC tissues was significantly higher than that in papillary thyroid carcinoma and adjacent tissues(P<0.05). The expression of H3K37me3 in ATC tissues was significantly lower than that in PTC tissues(P<0.05). EZH2 was negatively correlated with PAX8 and TG expression levels, but not with TTF1 expression level.In vitroexperiments, GSK126 could reverse the expression of thyroid differentiation markers PAX8 and TTF1 in ATC cell lines. GSK126 combined with BRAF inhibitor vemurafenib could significantly inhibit the growth of ATC cell lines. Conclusion The EZH2-H3K27me3 axis plays an important role in regulating thyroid specific markers, and the inhibition of EZH2 by small molecular compounds is a promising target for ATC treatment in the future.

Objective: To investigate the value of decreased carbohydrate antigen 19-9(CA19-9) kinetics in predicting short-term outcomes and determining prognosis among advanced biliary or pancreatic cancer patients receiving first-or second-line therapy in the real world. Methods : Eighty-nine patients were retrospectively collected with advanced biliary or pancreatic cancer, especially on the CA19-9 dynamics and decline rates at different time points. This study evaluated the association of CA19-9 changes with clinicopathological features, short-term response to antitumor therapy, and survival outcomes. Results : The enrolled patients recorded baseline CA19-9 levels ranging from 1.20 to 65 706.40 U/ml, with a median of 303.11 U/ml. There was no statistical correlation between baseline CA19-9 levels and gender, age, body mass index, primary tumor site, hepatic metastases, pulmonary metastases, lymph node metastases, peritoneal metastases, performance status, treatment lines, and combinations of drug types. Baseline CA19-9 levels were not associated with systemic immunoinflammatory index, prognostic nutritional index, and total bilirubin. A 25% or 50% decrease in CA19-9 after 2-3 therapy courses indicated short-term efficacy in reaching tumor objective remission or disease control. Both combinations of multiple drug types and a 25% decline in CA19-9 after one course of treatment were independent prognostic factors that affected the longer progression-free survival of patients receiving first or second line of treatment. Conclusion Decreased CA19-9 kinetics has specific values in predicting the efficacy and prognosis of advanced biliary or pancreatic cancer.

A solid-phase extraction-ultra-performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS)method was established for simultaneous determination of 10 kinds of neonicotinoid pesticide residues in aquaculture water.Based on the chemical properties of neonicotinoid pesticides and the matrix characteristics of aquaculture water,suitable temporary storage methods for water samples and appropriate solid-phase extraction columns were selected,and the extraction conditions(including elution solvents and sample loading volumes)were optimized.The method employed acetonitrile and 5 mmol/L ammonium acetate solution(containing 0.1%formic acid)as the mobile phase and an Oasis HLB solid-phase extraction column combined with PSA as a dispersive sorbent for sample purification.The method exhibited good linearity in detection of neonicotinoid in concentration range of 0.2-50 ng/mL(R2>0.99797),with a detection limit of 0.5 ng/L and a quantification limit of 1 ng/L,which were significantly lower than the maximum acceptable method detection limits(9-500 ng/L)for neonicotinoid insecticides in water published by the European Commission.In pond water,rice-fish water,and seawater,the average recoveries of the 10 target analytes were 74.6%-114.1%,with relative standard deviations ranging from 0.3%to 9.6%.Using this method,actual sample tests were conducted on the Pearl River water,Zhaoqing pond water,and Qingyuan rice-fish aquaculture water.The total concentration of five neonicotinoid pesticides in the Pearl River water ranged from 154.8 to 246.6 ng/L,the total concentration of four neonicotinoid pesticides in the Zhaoqing pond water was 95.0-176.1 ng/L,and the total concentration of three neonicotinoid pesticides in the Qingyuan rice-fish aquaculture water was 2.3-11.7 ng/L.This method was simple in operation,highly sensitive,and had strong resistance to interference.It was suitable for detection of trace neonicotinoid pesticides in aquaculture water and could provide technical support for construction of a green aquaculture environment and resolution of international trade disputes.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.

Objective To investigate the susceptibility and infection characteristics of dengue virus(DENV)in cells derived from diverse tissues of tree shrews and to provide a basis for expanding the repertoire of DENV-permissive cell models in this species.Methods DENV was inoculated at a multiplicity of infection(MOI)of 0.02 into tree shrew skin fibroblasts(TSFs),primary tree shrew renal epithelial cells(pTRECs),tree shrew aortic endothelial cells(TAECs),tree shrew aortic smooth muscle cells(TASMCs),tree shrew hepatocytes(THs),tree shrew corneal stromal cells(TCSCs),tree shrew brain microvascular endothelial cells(TBMECs),and tree shrew retinal microvascular endothelial cells(TRMECs).C6/36,Vero,A549,and BHK-21 cells(commonly used for DENV propagation)were used as positive controls.Over 6 days post-infection,cellular cytopathic effects were monitored at 12-hour intervals using an inverted microscope,viral RNA loads in cell lysates were quantified by real-time fluorescent quantitative PCR to generate proliferation curves,and viral titers were determined by plaque assay.Results Seven types of tree shrew cells,except TRMECs,were susceptible to DENV.Prolonged infection induced pronounced cytopathic effects,including cell rounding,detachment,necrosis,and lysis,across all susceptible cells.The viral RNA loads detected in lysates of pTRECs,TBMECs,TASMCs,TAECs and THs,approached those of positive controls(≥4×107 copies/μL).Infectious progeny viruses were produced by these five cell types,with three(TAECs,3.13×105 PFU/mL;THs,2.03×105 PFU/mL;pTRECs,1.58×105 PFU/mL)exhibiting titers comparable to C6/36(3.85×10 5 PFU/mL)and earlier viral harvests.Conclusion DENV exhibits broad susceptibility to tree shrew cells of multiple tissue origins,with proliferation rates surpassing those of conventional cell lines sourced from other species.TAECs,THs,and pTRECs are particularly suitable for large-scale DENV proliferation,suggesting their potential involvement in in vivo infection.

Objective To investigate the clinical characteristics of severe and critical influenza children and analyze the risk factors affecting the prognosis of children.Methods Clinical data from children diagnosed with severe and critical influenza who were hospitalized in the pediatric intensive care unit of Tongji hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2020 to December 2023 were retrospectively collected and analyzed.Results Among the 121 children,86 cases had severe influenza and 35 cases had critical influenza.There were 102 children in the good prognosis group and 19 children in the poor prognosis group.In all,93 cases(76.9％)were infected with influenza A,27 cases(22.3％)were in-fected with influenza B,and 1 case(0.8％)was infected with both influenza A and B.Sixty-seven cases(55.4％)were under 5 years old.The main clinical manifestations were fever,cough and convulsions.Seventy-five cases(62.0％)were complicated with pneumonia,65 cases(53.7％)were diagnosed with influenza-associated encephalopathy,and 22 cases(18.2％)developed multiple organ dysfunction syndrome.Fifty-five cases(45.5％)were infected with other pathogens,21 cases(17.4％)had bacterial infec-tion.The incidence of bacterial infection in children with critical influenza(31.4％)was higher than that in children with severe influenza(11.6％)(P＜0.05).Bacterial infection,neurological symptoms and elevated PCT were independent risk factors for poor prognosis(P＜0.05).Conclusion Children under 5 years old are more likely to develop severe and critical influen-za.Bacterial co-infection increases the risk of poor prognosis.Poor-prognostic severe or critical influenza is often accompanied by neurological manifestations and residual neurological sequelae.

With the prevalence of kidney disease continues to rise,it has become a serious global public health issue that significantly impacts patients'quality of life.The complex pathogenesis of kidney disea-ses presents challenges for its prevention and treatment.Research has shown that imbalances in metabolic homeostasis often affect kidney function,leading to renal damage.Peroxisome proliferator-activated re-ceptors(PPARs),as transcription factors activated by endogenous ligands,play a crucial role in regula-ting metabolic molecular networks,particularly in oxidative phosphorylation,lipid metabolism,and glu-cose metabolism.Activating PPARs can improve mitochondrial damage,promote tatty acid breakdown,and alleviate insulin resistance,thereby restoring renal metabolic function and mitigating kidney damage.Although various small-molecule drugs that activate PPARs have been developed,adverse reactions have been observed during clinical trials.Currently,there is still a lack of safe and effective treatment options for kidney diseases.A detailed analysis of the molecular mechanisms by which the PPAR family regulates renal cell energy metabolism,as well as the search for and development of new small-molecule drugs tar-geting PPARs and their regulated downstream metabolic pathways,is of significant importance for under-standing and treating kidney diseases.On the other hand,clarifying the metabolic changes during the progression of different kidney diseases and applying targeted PPAR-based drugs or strategies for their treatment is particularly important.Here we summarize how PPAR family members regulate target gene transcription and their roles in the remodeling of oxidative phosphorylation and lipid/glucose metabolism,as well as the impact of changes in PPAR expression or activity on acute and chronic kidney diseases and age-related kidney conditions.This knowledge may provide new insights and theoretical support for the prevention and treatment of kidney diseases.

Objective To investigate the susceptibility and infection characteristics of dengue virus(DENV)in cells derived from diverse tissues of tree shrews and to provide a basis for expanding the repertoire of DENV-permissive cell models in this species.Methods DENV was inoculated at a multiplicity of infection(MOI)of 0.02 into tree shrew skin fibroblasts(TSFs),primary tree shrew renal epithelial cells(pTRECs),tree shrew aortic endothelial cells(TAECs),tree shrew aortic smooth muscle cells(TASMCs),tree shrew hepatocytes(THs),tree shrew corneal stromal cells(TCSCs),tree shrew brain microvascular endothelial cells(TBMECs),and tree shrew retinal microvascular endothelial cells(TRMECs).C6/36,Vero,A549,and BHK-21 cells(commonly used for DENV propagation)were used as positive controls.Over 6 days post-infection,cellular cytopathic effects were monitored at 12-hour intervals using an inverted microscope,viral RNA loads in cell lysates were quantified by real-time fluorescent quantitative PCR to generate proliferation curves,and viral titers were determined by plaque assay.Results Seven types of tree shrew cells,except TRMECs,were susceptible to DENV.Prolonged infection induced pronounced cytopathic effects,including cell rounding,detachment,necrosis,and lysis,across all susceptible cells.The viral RNA loads detected in lysates of pTRECs,TBMECs,TASMCs,TAECs and THs,approached those of positive controls(≥4×107 copies/μL).Infectious progeny viruses were produced by these five cell types,with three(TAECs,3.13×105 PFU/mL;THs,2.03×105 PFU/mL;pTRECs,1.58×105 PFU/mL)exhibiting titers comparable to C6/36(3.85×10 5 PFU/mL)and earlier viral harvests.Conclusion DENV exhibits broad susceptibility to tree shrew cells of multiple tissue origins,with proliferation rates surpassing those of conventional cell lines sourced from other species.TAECs,THs,and pTRECs are particularly suitable for large-scale DENV proliferation,suggesting their potential involvement in in vivo infection.

Objective To investigate the clinical characteristics of severe and critical influenza children and analyze the risk factors affecting the prognosis of children.Methods Clinical data from children diagnosed with severe and critical influenza who were hospitalized in the pediatric intensive care unit of Tongji hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2020 to December 2023 were retrospectively collected and analyzed.Results Among the 121 children,86 cases had severe influenza and 35 cases had critical influenza.There were 102 children in the good prognosis group and 19 children in the poor prognosis group.In all,93 cases(76.9％)were infected with influenza A,27 cases(22.3％)were in-fected with influenza B,and 1 case(0.8％)was infected with both influenza A and B.Sixty-seven cases(55.4％)were under 5 years old.The main clinical manifestations were fever,cough and convulsions.Seventy-five cases(62.0％)were complicated with pneumonia,65 cases(53.7％)were diagnosed with influenza-associated encephalopathy,and 22 cases(18.2％)developed multiple organ dysfunction syndrome.Fifty-five cases(45.5％)were infected with other pathogens,21 cases(17.4％)had bacterial infec-tion.The incidence of bacterial infection in children with critical influenza(31.4％)was higher than that in children with severe influenza(11.6％)(P＜0.05).Bacterial infection,neurological symptoms and elevated PCT were independent risk factors for poor prognosis(P＜0.05).Conclusion Children under 5 years old are more likely to develop severe and critical influen-za.Bacterial co-infection increases the risk of poor prognosis.Poor-prognostic severe or critical influenza is often accompanied by neurological manifestations and residual neurological sequelae.