OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

In response to the new requirements for course instruction outlined in the revised training program for medical imaging program, this study integrated medical imaging technology courses based on the principle of outcome-oriented education and by leveraging self-developed digital resources, with imaging methods as the entry point. The core elements of the course teaching were re-optimized and reorganized to transcend the temporal and spatial limitations of course delivery, enabling the rational application of diverse teaching methods. This approach facilitated the integration of knowledge across three specialized courses, namely medical imaging physics, medical imaging equipment, and medical imaging examination techniques, and achieved full-dimensional and whole-process teaching evaluation. While reducing the number of hours allocated to theoretical instruction, the teaching objectives were achieved with high quality, providing a reference for the integration of digital technologies into the teaching of medical imaging and related disciplines.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

In response to the new requirements for course instruction outlined in the revised training program for medical imaging program, this study integrated medical imaging technology courses based on the principle of outcome-oriented education and by leveraging self-developed digital resources, with imaging methods as the entry point. The core elements of the course teaching were re-optimized and reorganized to transcend the temporal and spatial limitations of course delivery, enabling the rational application of diverse teaching methods. This approach facilitated the integration of knowledge across three specialized courses, namely medical imaging physics, medical imaging equipment, and medical imaging examination techniques, and achieved full-dimensional and whole-process teaching evaluation. While reducing the number of hours allocated to theoretical instruction, the teaching objectives were achieved with high quality, providing a reference for the integration of digital technologies into the teaching of medical imaging and related disciplines.

This article reviews relevant literature on the prevention and treatment of cancer with hesperidin published in the past 10 years by searching electronic databases such as China National Knowledge Infrastructure（CNKI）， Wanfang， and PubMed， and summarizes the research progress on the anticancer mechanism of hesperidin. Hesperidin has a wide range of pharmacological effects， including anti-inflammatory， antioxidant， antibacterial， antiviral， anticancer， immune-regulatory， anti-radiation， neuroprotective and cardiovascular protective properties and so on. Its anticancer mechanisms mainly include inhibiting cancer cell proliferation， promoting apoptosis， reducing angiogenesis， inhibiting invasion and migration of cancer cells， regulating immunity and autophagy， and exerting antioxidant and anti-inflammatory effects. As a broad-spectrum anticancer drug， hesperidin manifests chemo-preventive and therapeutic effects across various cancers， contingent upon its multifaceted anticancer mechanisms. Furthermore， this article summarizes the synergistic effects of hesperidin in combination with cisplatin， doxorubicin， cyclophosphamide and paclitaxel. It elucidates that hesperidin can enhance the cytotoxicity of these anticancer drugs against cancer cells while mitigating drug resistance and adverse side effects. Nonetheless， the clinical use is somewhat constrained due to its poor water solubility and limited bioavailability. Therefore， this article also outlines the current strategies for enhancing hesperidin's bioavailability， including structural modification， combination with other chemical substances， and utilization of nano drug carriers.The discovery of derivatives of hesperidin not only preserves the anticancer efficacy of hesperidin, but also effectively overcomes the shortcomings of poor water solubility and low bioavailability of hesperidin, effectively predicting the good application prospects of hesperidin and its derivatives.

ObjectiveTo explore the possible mechanism of Bushen Huoxue Formula （补肾活血方， BHF） in the treatment of Parkinson's disease （PD） from the the perspective of intestinal flora. MethodsSeventy-two male C57/BL6J mice were randomly divided into blank group， model group， Madopar group and low-， medium- and high-dose BHF groups， with 12 mice in each group. The mice in the blank group were intraperitoneally injected with 10 ml/kg of normal saline， and those in the other groups were intraperitoneally injected with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） at a concentration of 3 mg/ml to induce PD mice model， both once a day for 7 consecutive days. After successful modeling， the low-， medium-， and high-dose BHF groups were given 7.5， 15， and 30 g/（kg·d） of BHF by gavage， respectively， while the Madopar group was given 112.5 mg/（kg ·d） of Domedopar tablets by gavage， and the blank group and the model group were given 15 ml/（kg·d） of distilled water， all once a day for 14 consecutive days. The rod climbing test， rotating rod test， grip strength test and weight-bearing swimming test were used to evaluate the behavioral indicators of mice. Western blotting was used to measure the protein expression levels of Toll-like receptor （TLR）/nuclear factor kappa B （NF-κB） pathway inflammatory factors in the mouse ileum， including Toll-like receptor 2 （TLR2）， Toll-like receptor 4 （TLR4）， NF-κB， tumor necrosis factor α （TNF-α）， interleukin 6 （IL-6）， and interleukin 17 （IL- 17）. 16S rRNA high-throughput sequencing was used to analyze changes in mouse intestinal flora. ResultsCompared to those in the blank group， the mice in the model group had longer bottoming time when climbing the pole， reduced grip strength， shortened rotary pole duration and swimming duration， and increased protein expression levels of TLR2， TLR4， NF-κB， TNF-α， and IL-6 in the ileal tissue （P＜0.01）. Compared to the model group， the Madopar group and the low-， medium- and high-dose BHF groups had shortened bottoming time of the climbing pole and increased grip strength； the Madopar group and the high-dose BHF group had prolonged rotary pole duration， and reduced protein expressions of TLR2， TLR4， NF-κB， TNF-α， IL-6， and IL-17 levels； and only the high-dose BHF group had prolonged swimming duration （P＜0.05 or P＜0.01）. Compared to those in the low-dose BHF group， the bottoming time of the climbing pole were shorter in the moderate- and high-dose groups （P＜0.05 or P＜0.01）， and the grip strength increased while the protein expression levels of TLR2， TLR4 and IL-17 decreased in the high-dose group （P＜0.05 or P＜0.01）. The intestinal flora results showed significant differences between the blank group and the model group in the Dominance index， Pielou_e index， Shannon index， and Simpson index （P＜0.05 or P＜0.01）. Compared to those of the model group， the Shannon index， Chao1 index， and Observed_otus index of the Madopar group， as well as the Chao1 index， Observed_otus index， Dominance index， Pielou_e index， Shannon index， and Simpson index of the high-dose BHF group all showed significantly statistical differences （P＜0.05 or P＜0.01）. At the phylum level， the relative abundance categories of bacterial phyla with statistically significant differences in each group included Proteobacteria， Bacteroidetes， and Firmicutes （P＜0.05 or P＜0.01）. At the genus level， the relative abundance categories of bacterial genera with statistically significant diffe-rences among each group included Muribaculaceae， Akkermansia， and Helicobacter pylori （P＜0.05 or P＜0.01）. ConclusionThe possible mechanism of BHF in treating PD may be to reconstruct the disordered intestinal flora structure and improve the inflammatory response.

Nuclear factor E2-related factor 2 (Nrf2) is a major regulator of redox homeostasis in cells, and Nrf2 signaling pathway has anti-inflammatory, anti-oxidative stress, and anti-fibrosis effects while plays an important role in wound healing and pathological scar formation and progression. This article reviewed the related research regarding the effect of oxidative stress and Nrf2 signaling pathway on pathological scars, furthermore, it investigated the relationship between Nrf2 signaling pathway, oxidative stress and pathological scars, providing a new perspective for the study of mechanism and clinical prevention and treatments of pathological scars.