Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocytes. However, it remains unclear about the pathogenesis of this carcinoma, which may be related to multiple factors. Currently, CCA is mainly treated by surgery, chemotherapy, and radiotherapy. Among them, surgery is the only potentially curative option for CCA. Nevertheless, the high malignancy and asymptomatic nature of CCA may lead to poor treatment outcomes. It has been demonstrated that Chinese medicine (CM) plays a significant role in various antitumor applications. Meanwhile, CM exhibits fewer side effects and high availability. Moreover, the in vitro application of CM monomers has been explored in many domestic and foreign studies. This article mainly reviews the signaling pathways and molecular mechanisms of CM monomers in the treatment of CCA in recent years. These findings are expected to provide new insights into the treatment of CCA.
Cholangiocarcinoma/drug therapy* ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Bile Duct Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Animals ; Signal Transduction/drug effects*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) method was established for the simultaneous determination of 498 farm chemical residues in Atractylodis Macrocephalae Rhizoma. Furthermore, the established method was used to determine the residues in 30 batches of Atractylodis Macrocephalae Rhizoma samples from different habitats. The samples were extracted with acetonitrile containing 1% glacial acetic acid, and the extract was purified by dispersive solid-phase extraction with sorbents of magnesium sulfate, primary secondary amine(PSA), C_(18), silica gel, and graphitized carbon black(GCB). The prepared samples were then analyzed by HPLC-MS/MS, and the internal standard method was used to quantify the residues. The experimental results showed that the 498 farm chemicals presented good linear relationship within the range of 5-400 ng·mL~(-1), with correction coefficients greater than 0.990. Within the linear ranges, the recovery of 495 farm chemicals(except daimuron, chinomethionat, and emamectin benzoate) at three spiked levels(0.05, 0.10, and 0.20 mg·kg~(-1)) was in the range of 61.18%-132.1%, with the RSD of 0.24%-15%. A total of 16 farm chemicals were detected in 30 batches of samples. Among them, difenoconazole and tebuconazole showed higher detection rates, and the detection rate of difenoconazole was 76.7%. The residues of 4 batches of samples exceeded the limits of quantitation of 33 banned farm chemicals stipulated in the Chinese Pharmacopoeia. The theoretical maximum residue limits of the farm chemicals except banned farm cheimicals were used as the judgment standard of safety risks, under which the detected residues of clothianidin, difenoconazole, and pirimiphos-methyl exceeded the theoretical maximum residue limits. The new method established in this paper is simple and reliable, and it can thus be used for qualitative and quantitative analyses of farm chemical residues in Atractylodis Macrocephalae Rhizoma.
Tandem Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Atractylodes/chemistry* ; Rhizome/chemistry* ; Drugs, Chinese Herbal/analysis* ; Pesticide Residues/analysis* ; Liquid Chromatography-Mass Spectrometry

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Background and Aims:Papillary thyroid carcinoma(PTC)is the most common endocrine malignancy,yet the molecular mechanisms underlying its invasion and metastasis remain unclear.This study aimed to investigate the role of the transcription factor ETV4 in PTC and its regulatory relationship with cadherin-3(CDHP/CDH3).Methods:Expression levels of ETV4 and CDHP were analyzed using TCGA and GTEx databases,and further validated in normal thyroid cells and multiple PTC cell lines by qRT-PCR and Western blot analysis.ETV4-knockdown models were established using siRNA,and changes in CDHP expression and cellular behaviors were assessed by qRT-PCR,Western blot,CCK-8,wound healing,and Transwell assays.Results:Bioinformatics analysis revealed significantly higher expression of ETV4 and CDHP in PTC tissues compared to normal thyroid tissues(P<0.001).Correlation analysis demonstrated a strong positive association between ETV4 and CDHP expression(R2>0.5,P<0.01).In vitro assays confirmed that both ETV4 and CDHP were upregulated in all tested PTC cell lines at the mRNA and protein levels(all P<0.05).Knockdown of ETV4 led to marked reduction of CDHP expression(P<0.05),accompanied by decreased cell proliferation,migration,and invasion as demonstrated by CCK-8,wound healing,and Transwell assays(all P<0.05).Conclusion:ETV4 may transcriptionally upregulates CDHP to promote proliferation,migration,and invasion of PTC cells.The ETV4/CDHP axis may serve as a novel biomarker and potential therapeutic target in PTC.

Objective:To develop an exercise rehabilitation program based on the Temporal Self-regulation Theory and evaluate its effectiveness in elderly patients with hip fractures.Methods:A total of 84 elderly patients with hip fractures admitted to the Department of Trauma Orthopedics at the First Affiliated Hospital of University of South China from May to August 2024 were enrolled using convenience sampling. Participants were randomly assigned to an experimental group ( n=42) and a control group ( n=42) using a random number table. The control group received routine exercise rehabilitation, while the experimental group received an exercise rehabilitation program constructed based on the Temporal Self-regulation Theory. The program included components such as establishing a unified concept of "exercise-rehabilitation", enhancing time-limited efficacy, achieving behavioral advantages, and improving self-regulation of active movement. Both groups received interventions for 12 weeks. Functional exercise adherence, activities of daily living, and hip joint function were assessed using the Orthopedic Exercise Adherence Scale, Modified Barthel Index, and Harris Hip Score at four time points: before intervention, on the day of discharge, and at 4 and 12 weeks postoperatively. Results:During the study, two patients from each group dropped out. Results of the generalized estimating equations showed group effects, time effects, and interaction effects in adherence scores with statistically significant differences ( P<0.01). On the day of discharge, and at 4 and 12 weeks postoperatively, the adherence scores in the experimental group were significantly higher than those in the control group, and the differences were statistically significant ( P<0.05). Repeated measures ANOVA indicated that group effects, time effects, and interaction effects were also statistically significant in scores for daily living ability and hip joint function ( P<0.05). The experimental group scored higher than the control group at each time point with statistically significant differences ( P<0.05) . Conclusions:The exercise rehabilitation program based on the Temporal Self-regulation Theory is scientifically sound and practical. It can effectively improve functional exercise adherence, enhance daily living ability, and promote postoperative recovery of hip joint function in elderly patients with hip fractures.

Background and Aims:Papillary thyroid carcinoma(PTC)is the most common endocrine malignancy,yet the molecular mechanisms underlying its invasion and metastasis remain unclear.This study aimed to investigate the role of the transcription factor ETV4 in PTC and its regulatory relationship with cadherin-3(CDHP/CDH3).Methods:Expression levels of ETV4 and CDHP were analyzed using TCGA and GTEx databases,and further validated in normal thyroid cells and multiple PTC cell lines by qRT-PCR and Western blot analysis.ETV4-knockdown models were established using siRNA,and changes in CDHP expression and cellular behaviors were assessed by qRT-PCR,Western blot,CCK-8,wound healing,and Transwell assays.Results:Bioinformatics analysis revealed significantly higher expression of ETV4 and CDHP in PTC tissues compared to normal thyroid tissues(P<0.001).Correlation analysis demonstrated a strong positive association between ETV4 and CDHP expression(R2>0.5,P<0.01).In vitro assays confirmed that both ETV4 and CDHP were upregulated in all tested PTC cell lines at the mRNA and protein levels(all P<0.05).Knockdown of ETV4 led to marked reduction of CDHP expression(P<0.05),accompanied by decreased cell proliferation,migration,and invasion as demonstrated by CCK-8,wound healing,and Transwell assays(all P<0.05).Conclusion:ETV4 may transcriptionally upregulates CDHP to promote proliferation,migration,and invasion of PTC cells.The ETV4/CDHP axis may serve as a novel biomarker and potential therapeutic target in PTC.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective:To develop an exercise rehabilitation program based on the Temporal Self-regulation Theory and evaluate its effectiveness in elderly patients with hip fractures.Methods:A total of 84 elderly patients with hip fractures admitted to the Department of Trauma Orthopedics at the First Affiliated Hospital of University of South China from May to August 2024 were enrolled using convenience sampling. Participants were randomly assigned to an experimental group ( n=42) and a control group ( n=42) using a random number table. The control group received routine exercise rehabilitation, while the experimental group received an exercise rehabilitation program constructed based on the Temporal Self-regulation Theory. The program included components such as establishing a unified concept of "exercise-rehabilitation", enhancing time-limited efficacy, achieving behavioral advantages, and improving self-regulation of active movement. Both groups received interventions for 12 weeks. Functional exercise adherence, activities of daily living, and hip joint function were assessed using the Orthopedic Exercise Adherence Scale, Modified Barthel Index, and Harris Hip Score at four time points: before intervention, on the day of discharge, and at 4 and 12 weeks postoperatively. Results:During the study, two patients from each group dropped out. Results of the generalized estimating equations showed group effects, time effects, and interaction effects in adherence scores with statistically significant differences ( P<0.01). On the day of discharge, and at 4 and 12 weeks postoperatively, the adherence scores in the experimental group were significantly higher than those in the control group, and the differences were statistically significant ( P<0.05). Repeated measures ANOVA indicated that group effects, time effects, and interaction effects were also statistically significant in scores for daily living ability and hip joint function ( P<0.05). The experimental group scored higher than the control group at each time point with statistically significant differences ( P<0.05) . Conclusions:The exercise rehabilitation program based on the Temporal Self-regulation Theory is scientifically sound and practical. It can effectively improve functional exercise adherence, enhance daily living ability, and promote postoperative recovery of hip joint function in elderly patients with hip fractures.

Objective To investigate the protective effect of butyrolphthalein on nerve injury in rats with acute cerebral infarction(ACI)by regulating Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB)pathway.Methods SD rats were randomly divided into model group and experimental-L,-M,-H groups;ACI models were established in vivo except sham operation group.The experimental-L,-M,-H groups were given 20,40,80 mg·kg-1 butylphthalide,qd,for 7 days;the sham operation group and the model group were given the same amount of 0.9％NaCl,for 7 days.Neural function score,bilateral sticker removal time,balance beam crossing score,cerebral water content and cerebral infarction volume of rats in each group were measured.The expression of axonal growth inhibitory factor A(Nogo-A)and serum inflammatory factor in hippocampus were detected by enzyme-linked immunosorbent assay(ELISA).The expression of TLR4/NF-κB pathway related proteins was detected by Western blot.Results The neural function scores of sham operation group,model group,and experimental-L,-M,-H groups were 0,3.55±0.52,2.55±0.52,1.82±0.60,0.91±0.30,respectively;the Nogo-A in hippocampus were(0.93±0.23),(6.32±0.53),(5.10±0.55),(3.54±0.57),(1.58±0.30)ng·L-1,respectively;serum Nogo-A were(0.49±0.12),(5.09±0.82),(3.83±0.54),(2.23±0.64),(1.13±0.25)ng·L-1,respectively;TLR4 protein expression were 0.44±0.05,1.23±0.14,0.93±0.07,0.75±0.06,0.55±0.07,respectively;the expressions of p-p65 NF-κB protein were 0.32±0.05,0.82±0.06,0.68±0.08,0.57±0.07,0.44±0.05,respectively.There were statistically significant differences between sham operation group and model group(all P＜0.05).There were significant differences in the above indexes between the model group and the experimental-L,-M,-H groups(P＜0.05).Conclusion Butylphthalein can play a neuroprotective role in ACI rats by regulating TLR4/NF-κB pathway to improve nerve function and reduce inflammatory damage.