AIM:To elucidate the pharmacody-namic and network pharmacological mechanisms of total flavonoids of Carthamus tinctorius L.,to ex-plore their key targets and related pathways,and to clarify their mechanism of action against hepatic fibrosis.METHODS:The total flavonoids of Cartha-mus tinctorius L.were determined by LC-MS/MS and analysed for their compositions;the active in-gredients were screened by TCMSP database,SWISS ADME database and literature search;the targets related to total flavonoids of Carthamus tinctorius L.were screened by Swiss Target Predic-tion database;and the targets related to hepatic fi-brosis were screened by GeneCards database;the anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained by taking the intersection of Venny.2.1.0;the protein interac-tions were analysed by STRING database;the visu-alization analysis was carried out by Cytoscape soft-ware;the GO function and KEGG pathway analysis was carried out by Metascape platform;and molec-ular docking was verified by using AutoDock soft-ware for the core targets and active ingredients.The mechanism of anti-hepatic fibrosis of total fla-vonoids of Carthamus tinctorius L.was verified by animal model and in vitro cell experiments.RE-SULTS:A total of 41 flavonoid components were identified in Carthamus tinctorius L.Through the network pharmacological analysis,149 anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained,including 23 core tar-gets.The GO enrichment analyses involved a total of three aspects,namely,biological process(BP),cellular component(CC),and molecular function(MF).KEGG enrichment results showed that PI3K/Akt and MAPK are pathways involved in the devel-opment of hepatic fibrosis.Molecular docking veri-fied that the active ingredients Quercetin,Acacetin and Glabridin were tightly bound to Akt1 and HI-FIA,respectively.In animal model experiments,it was observed by HE and Masson staining that fibro-plasia was reduced,collagen deposition was re-duced,inflammatory cell infiltration was reduced,and fibrotic liver tissues were improved in total fla-vonoids of Carthamus tinctorius L.administration group.In isolated cell experiments:Western blot-ting results suggested that total flavonoids of Car-thamus tinctorius L.could decrease the hepatic fi-brosis marker factor α-SMA,Collagen1(P＜0.01)and PI3K,Akt protein expression(P＜0.01).CONCLU-SION:Total flavonoids of Carthamus tinctorius L.ex-erted anti-hepatic fibrosis effects through multi-components,multi-targets and multi-pathways,and their mechanism of action may be achieved by regulating the PI3K/Akt signalling pathway.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective To investigate the effect of closed-chain exercise training on hemiplegic shoulder pain and shoulder joint sta-bility in stroke patients,and to explore the relationship between hemiplegic shoulder pain and shoulder joint sta-bility.Methods A total of 52 stroke patients with hemiplegic shoulder pain in Jiangsu Province Hospital from October,2020 to January,2023 were selected,and were randomly divided into control group(n=26)and experimental group(n=26).Both groups received conventional rehabilitation therapy,while the experimental group additionally under-went closed-chain exercise training for shoulder joint.Pain severity and motor function were assessed using Visu-al Analog Scale(VAS)and Fugl-Meyer Assessment-Upper Extremities(FMA-UE)before and after intervention.Musculoskeletal ultrasound was used to measure acromion-greater tuberosity distance(AGT),acromion-lesser tu-berosity distance(ALT),acromiohumeral distance(AHD)and supraspinatus thickness(SST)to evaluate shoulder joint stability.Correlation analysis was conducted on the improvements in shoulder pain and shoulder joint stabil-ity in the experimental group.Results Two cases in the control group and two in the experimental group dropped down.Both groups showed signifi-cant improvements in VAS and FMA-UE scores after intervention(|t|>5.214,P<0.001),and the scores im-proved more in the experimental group than in the control group(|t|>2.087,P<0.05).The experimental group also showed significant improvements in AGT,ALT,AHD and SST(|t|>4.187,P<0.001),with AGT,ALT and AHD being superior to those in the control group(|t|>2.155,P<0.05).The difference of VAS score in the exper-imental group was correlated with the difference of FMA-UE,AGT and ALT after intervention(r>0.434,P<0.05).Conclusion Closed-chain shoulder exercise training can significantly improve shoulder joint stability while alleviating shoulder pain,and effectively enhancing upper limb function in stroke patients with hemiplegic shoulder pain.Hemiplegic shoulder pain is correlated with shoulder joint stability.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

Objective To explore the validity and feasibility of the left transthoracic and esophageal hiatal approach for Siewert type Ⅱ adenocarcinoma of the esophagogastric junction under a single position.Methods The clinical data of 64 patients with Siewert type Ⅱ AEG(single position transthoracic approach group)treated with the left transthoracic and esophageal hiatal approach under a single position and 56 patients with the laparoscopic transesophageal slit approach(transabdominal approach group)in the Department of Thoracic Surgery,Huaihe Hospital of Henan University,from January 2017 to December 2018 were retrospectively analyzed.The clinical and pathological data,perioperative indicators(operation time,intraoperative blood loss,postoperative first ambulation time,postoperative first peristalsis time,postoperative drainage volume at 3 d,incidence of postoperative complications,postoperative hospital stay),postoperative complications(positive surgical margin,proximal esophageal resection margin,tumor diameter,total number of dissected lymph nodes,positive lymph node dissection rate,postoperative histopathology,and TNM staging of tumor pathology),and survival indicators(tumor recurrence and metastasis rate and survival at 1 month,3 months,6 months,1 year,3 years,5 years after surgery)were compared between the two groups.Kaplan-Meier method was used to analyze the postoperative survival rate of the two groups.Univariate analysis using χ2 test was employed to analyze factors influencing 5-year postoperative survival rate in Siewert type Ⅱ AEG patients.Results No significant difference was observed in clinical and pathological data,such as gender,age,American Society of Anesthesiologists(ASA)grade,tumor differentiation,pTNM stage,and tumor diameter between the two groups(P>0.05).No significant differences were noted in intraoperative blood loss,incidence of postoperative complications,and survival rates at 1 month,3 months,6 months,1 year,and 3 years after surgery between the two groups(P>0.05).The single position transthoracic approach group exhibited a higher postoperative drainage volume at 3 d compared to the transabdominal approach group(P<0.001),a shorter surgical time(P<0.001),a longer time to first mobilization,first intestinal peristalsis,and hospital stay after surgery(P<0.01),a longer proximal esophageal margin(P<0.001),a higher total number of lymph node dissections(P<0.001),and a higher positive lymph node dissection rate(P<0.05)than the transabdominal approach group.The 5-year recurrence-free survival rate of the single position transthoracic approach group was higher than that of the transabdominal approach group,with a statistically significant difference(P=0.013).The Kaplan-Meier survival curve showed no statistically significant difference in the 5-year overall survival rate between the two groups of patients after surgery(P=0.456).The results of univariate analysis indicated that there are significant relationships between tumor differentiation degree,pTNM stage,tumor diameter,and lymph node positivity rate with the 5-year postoperative survival rate in Siewert type Ⅱ AEG patients(P<0.05).Conclusion Siewert type Ⅱ AEG patients can be treated with the left transthoracic and esophageal hiatal approach under a single position,achieving the same effect as laparoscopic transesophageal slit approach,and it can be actively promoted as a complementary choice of operation in the clinic.

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

OBJECTIVE: This cross-sectional study assessed the methodological quality of systematic reviews (SRs) of Chinese herbal medicine (CHM) published in Chinese between Jan 2021 and Sep 2022. METHODS: Chinese language CHM SRs were identified through literature searches across 3 international and 4 Chinese databases. Methodological quality was appraised using A MeaSurement Tool to Assess systematic Reviews 2. Logistic regressions were used to explore associations between bibliographical characteristics and quality. RESULTS: Analyses of methodological quality found that among the 213 sampled SRs, 69.5% were of critically low quality, 30.5% were of low quality, and none achieved high or moderate quality. Common shortcomings included the failure to identify the studies excluded from the analysis, failure to disclose funding sources, and limited evaluation of the potential impact of bias on conclusions. Logistic regressions revealed that SRs led by corresponding authors affiliated with universities or academic institutions tended to be of lower quality than SRs led by authors affiliated with hospitals or clinical facilities. CONCLUSION Recent Chinese language CHM SRs exhibited limited methodological quality, making them unlikely to support the development of clinical practice guidelines. Urgent initiatives are needed to enhance training for researchers, peer-reviewers and editors involved in the preparation and publication of SRs. Adoption of Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines in Chinese language journals is crucial to improve the relevance of SRs for Chinese medicine development. Addressing deficiencies in methodology and reporting is essential for promoting evidence-based practices and informed clinical decisions in Chinese medicine. Please cite this article as: Jiang Y, Zhong CC, Wang BH, Xu SS, Ho FF, Kwong MH, Ho L, Zhou JHS, Lam KC, Liu JP, Zhang BT, Chung VCH. Methodological quality of systematic reviews on orally administered Chinese herbal medicine published in Chinese between 2021 and 2022: A cross-sectional study. J Integr Med. 2025; 23(5):492-501.
Cross-Sectional Studies ; Drugs, Chinese Herbal/administration & dosage* ; Systematic Reviews as Topic/standards* ; Humans ; China ; Administration, Oral ; Medicine, Chinese Traditional