OBJECTIVE To evaluate the therapeutic effects and safety of everolimus combined with letrozole and conventional chemotherapy for metastatic or recurrent endometrial carcinoma （EC）. METHODS The clinical and follow-up data of 156 patients with metastatic or recurrent EC admitted to Nanyang Central Hospital from January 2020 to January 2024 were analyzed retrospectively. They were divided into a control group （77 cases） and an observation group （79 cases） according to different therapeutic regimens. The control group received paclitaxel+carboplatin/cisplatin regimen， and concurrently took Letrozole tablets at a dose of 2.5 mg orally once daily； the observation group took Everolimus tablets 10 mg orally， once a day， in addition to the treatment regimen given to the control group. Each treatment cycle lasted 21 days， and both groups of patients underwent continuous treatment for 6 to 8 cycles. The short-term efficacy indicators （objective response rate and disease control rate）， the levels of serum tumor markers [carbohydrate antigen 125， human epididymis protein 4， vascular endothelial growth factor and matrix metalloproteinase-9] and medium- to long-term efficacy indicators [progression-free survival （PFS） and overall survival （OS）] were compared between the two groups. Additionally， the occurrence of toxic and side effects in both groups of patients was recorded. RESULTS The objective response rate （53.16%）， disease control rate （89.87%）， median PFS （6.47 months） and median OS （10.79 months） of the observation group were significantly higher or longer than those （22.08%， 68.83%， 4.63 months， 8.84 months） of the control group （P＜0.05）. Compared with before treatment， the levels of serum tumor markers in both groups decreased significantly after 6 cycles of treatment； the above indexes of the observation group were significantly lower than those of the control group （P＜0.05）. The proportion of patients with stomatitis in the observation group was significantly higher than that of the control group （P＜0.05）， and there was no statistically significant difference in the proportions of patients experiencing other toxic and side effects， such as leukopenia， between the two groups （P＞0.05）. CONCLUSIONS The everolimus combined with letrozole and conventional chemotherapy can effectively improve the short-term efficacy and prolong the survival period in patients with metastatic or recurrent EC， but attention should be paid to the occurrence of toxic and side effects， especially stomatitis.

Pancreatic cancer is a highly malignant solid tumor of the digestive system with extremely poor treatment prognosis. Although its incidence rate is low， its mortality rate is extremely high. In recent years， the number of diagnosed cases worldwide has continued to rise， making pancreatic cancer the sixth leading cause of cancer-related deaths globally. Currently， clinical treatment primarily relies on operation and chemotherapy to suppress tumors. However， these approaches face challenges such as suboptimal efficacy， high postoperative recurrence rates， and severe adverse reactions. Therefore， identifying safe and effective treatment modalities remains a pressing challenge for the medical community. In recent years， research on traditional Chinese medicine （TCM） interventions for pancreatic cancer has increased significantly. Multiple studies have shown that single-herb TCM， TCM formulas， and their derived single compounds can regulate the levels of tumor cell signaling pathways through multiple action targets. They inhibit the development and progression of pancreatic cancer by inhibiting cancer cell proliferation， promoting cell apoptosis， inhibiting tumor angiogenesis， reducing cancer cell invasion and migration capabilities， regulating the cell cycle， and modulating the tumor microenvironment. Additionally， TCM has the advantages of significantly enhancing the anticancer efficacy of chemotherapy drugs and causing fewer adverse reactions. However， the specific action mechanisms by which TCM intervenes in pancreatic cancer remain unclear. Further extensive research is still needed to validate the role of regulating classical signaling pathways such as phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Wnt/β-catenin， nuclear transcription factor-κB （NF-κB）， notch， and hedgehog in the treatment of pancreatic cancer. Therefore， this paper reviewed Chinese and international studies on TCM intervention in pancreatic cancer through relevant signaling pathways in recent years， summarized the potential action mechanisms of TCM in the treatment of pancreatic cancer， and provided references for related research in the future.

ObjectiveTo observe the effects of Tongmai Kaiqiao pills on AMP-activated protein kinase （AMPK）/peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α） signaling pathway and mitochondrial biogenesis in hippocampal tissue of rats with vascular cognitive impairment （VCI） and to investigate the potential mechanism of Tongmai Kaiqiao pills in improving cognitive impairment in rats with VCI. MethodsTwelve of 72 male SD rats were selected as the sham operation group， and the remaining rats were modelled using the modified 2VO method. The rats that were successfully modelled were divided into the model group， the high-dose group of Tongmai Kaiqiao pills （27.6 g·kg^-1）， the low-dose group of Tongmai Kaiqiao pills （13.8 g·kg^-1）， the combination group （27.6 g·kg^-1 Tongmai Kaiqiao pills + 25 mg·kg^-1 dorsomorphin）， and the donepezil hydrochloride group （0.45 g·kg^-1） according to the random number table method. After four weeks of continuous intraperitoneal injection of the corresponding drugs， the Morris water maze test was used to test the learning and memory ability of rats. Hematoxylin-eosin （HE） staining and Nissl staining were used to detect pathological changes in the hippocampus of the rats. The content of mitochondrial adenosine triphosphate （ATP） in the brain hippocampus was detected by colorimetry， and reactive oxygen species （ROS） level was detected in rat mitochondria by MitoSOX Red assay. Mitochondrial DNA copy number was detected by real-time fluorescent quantitative PCR （Real-time PCR）. Pathological changes in mitochondria were observed by transmission electron microscopy （TEM）， and AMPK， PGC-1α， phosphorylated AMP-activated protein kinase （p-AMPK）， nuclear respiratory factor 1 （Nrf1）， and mitochondrial transcription factor A （TFAM） protein expression in the hippocampus of the rats were detected by Western blot. ResultsCompared with those in the sham operation group， rats in the model group had a reduced number of platform crossings （P<0.01）， significantly prolonged evasion latency （P<0.01）， disorganized neuronal arrangement in the hippocampal region， widened gaps， and blurred nucleus membrane and nucleolus boundaries. The emergence of necrotic cells was visible. The color of the nissl bodies was light， and the number was reduced with severe loss. Mitochondria were atrophied， and cristae were lost. Severe damage was observed. The content of ROS was increased， and the level of ATP was decreased. mtDNA copy number decreased significantly （P<0.01）， and the protein expression of p-AMPK， PGC-1α， Nrf1， and TFAM decreased （P<0.05， P<0.01）. Compared with those in the model group， rats in the high-dose group of Tongmai Kaiqiao pills and donepezil hydrochloride group showed a shorter time to find the platform （P<0.01）， increased number of platform crossings （P<0.01）， restored mitochondrial morphology and structure of the hippocampal neurons， alleviated neuronal death， increased number of nissl bodies， weaken degree of injury， lower content of ROS， and significantly increased levels of ATP and number of copies of mtDNA （P<0.05， P<0.01）. In addition， there was increased protein expression of p-AMPK， PGC-1α， Nrf1， and TFAM （P<0.05， P<0.01）. Compared with the model group， the evasion latency was shortened in the low-dose group of Tongmai Kaiqiao pills （P<0.01）， and the number of platform crossings was increased， but the difference was not statistically significant. The mitochondria were swollen and deformed， and the cristae became shorter and partially disappeared. The degree of damage did not improve significantly， and the number of nissl bodies was increased but not statistically significant. The ROS content decreased （P<0.01）， but there was no significant difference in ATP level and mtDNA copy number. The protein expression of PGC-1α was increased （P<0.05）， but there was no significant difference in the protein expression of p-AMPK， Nrf1， and TFAM， and the results were not statistically significant. Compared with the donepezil hydrochloride group， there was no significant change in the results of each assay in the high-dose group of Tongmai Kaiqiao pills， and the difference was not statistically significant. Compared with the high-dose group of Tongmai Kaiqiao pills， rats in the combination group had a significantly lower number of platform crossings （P<0.01）， a significantly longer evasion latency （P<0.01）， a reduced number of neuronal cells， disorganized tissue structure， swollen and blurred cell outlines， a significant reduction in the number of nissl bodies. Moreover， there was an increase in the content of ROS， a decrease in the level of ATP and the number of mtDNA copies （P<0.01）， and a decrease in the expression of p-AMPK， PGC-1α， Nrf1， and TFAM （P<0.05）. ConclusionTongmai Kaiqiao pills is able to improve cognitive function in rats by activating the AMPK/PGC-1α signaling pathway， promoting mitochondrial biogenesis， and attenuating pathological damage to neurons in the hippocampal region， thereby demonstrating its therapeutic potential.

OBJECTIVE To provide reference for optimizing or formulating unified evaluation methods for evidence and recommendation in expert consensus on off-label use of drugs. METHODS Retrieved from CNKI， Wanfang data， VIP， CBM， PubMed and Web of Science， Chinese expert consensuses on off-label use of drugs involving evaluation methods for evidence and recommendations were collected from the inception to August 1， 2024. After screening the literature and extracting relevant data， descriptive statistical analysis was conducted. RESULTS & CONCLUSIONS Among the 32 articles included， 14 articles （43.8%） used Micromedex’s Thomson grading system， only 7 articles （21.9%） considered economic factors when forming recommendations， 10 articles （31.3%） reported the conflicts of interest； only 2 articles （6.3%） involved experts in the field of evidence-based medicine methodology. There were differences in the sources of evidence， factors considered in forming recommendations， and the grading standards for evidence and recommendations among different expert consensus evidence evaluation methods. There were also differences in evidence levels and recommendation strength of the same drug off-label use in different expert consensus. It is recommended that in future consensus-building processes， greater attention should be paid to potential conflicts of interest among participants， collaboration with methodological experts should be enhanced， and efforts should be expedited to establish unified standards for evaluating evidence and recommendation methodologies.

Parkinson’s disease （PD） is a common chronic neurodegenerative disease with movement disorders as the main clinical manifestation. The nuclear factor-erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway is closely associated with the occurrence and progression of PD. TCM flavonoid monomers （luteolin， rutin， etc.）， alkaloids （camptothecin， sinomenine， and alkaloids extracted from Uncaria rhynchophylla）， terpenes （tanshinone ⅡA， carvacrol， paeoniflorin）， phenols （ellagic acid， rosmarinic acid）， saponins （ginsenoside RK1）， and traditional Chinese medicine compounds （Wuzi yanzong pill and PD formula-2） can resist oxidative stress damage， inhibit inflammatory responses and abnormal aggregation of α-synuclein， and regulate neurotrophic factors by activating the Nrf2/HO-1 signaling pathway， thereby alleviating dopaminergic neuronal damage.

OBJECTIVE To optimize the forming process of Yindan huoxue tongyu granules， and evaluate the quality of the granules. METHODS Taking forming rate， angle of repose， moisture， moisture absorption rate and dissolution rate as indexes， single factor experiment combined with Plackett-Burman design was adopted to screen key process parameters； analytic hierarchy process combined with entropy weight method and Box-Behnken response surface method were used to optimize the molding process of Yindan huoxue tongyu granules， and the forming process was verified. The relative homogeneity index， bulk density， vibration density， Hausner ratio， angle of repose， moisture and hygroscopicity were used as secondary physical indexes to establish the physical fingerprints of 10 batches of Yindan huoxue tongyu granules to evaluate particle quality consistency. RESULTS The optimal molding process of Yindan huoxue tongyu granules was as follows： mannitol as the fixed excipient， the drug-assisted ratio was 1∶1（m/m） and the drying time was 1 h； 90% ethanol was used as wetting agent and the amount of it was 32%， the drying temperature was 70 ℃. The results of validation tests showed that the average comprehensive score was 97.45， which was close to the predicted value of 97.18. The similarities between the physical fingerprints of 10 batches of Yindan huoxue tongyu granules prepared by the optimal molding process and the reference physical fingerprint were all higher than 0.99. CONCLUSIONS The molding process is stable and feasible， and the quality of Yindan huoxue tongyu granules produced is stable and controllable.

OBJECTIVE To evaluate the quality of Yindan huoxue tongyu granules. METHODS Taking high performance liquid chromatography with ultraviolet and evaporative light scattering detection as method， the fingerprint of 15 batches of Yindan huoxue tongyu granules was established， and similarity evaluation was performed by Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition） to determine common peaks. The common peaks were identified by comparing with reference substance chromatograms and single decoction piece chromatograms. Network pharmacology was used to screen out core targets and pathways of identified components， construct a “component-target-pathway” network diagram， and predict the pharmacodynamic components of Yindan huoxue tongyu granules， and the content determination of these components was carried out by the same method. RESULTS HPLC fingerprints of 15 batches of Yindan huoxue tongyu granules were characterized with 40 common peaks， and 17 components including salvianolic acid B， astragaloside Ⅳ， notoginsenoside R1， and ginkgolide A were identified. Network pharmacology predicted that 17 components mainly acted on 97 core targets and 137 pathways to exert their pharmacological effect. Average contents of 13 bioactive components in 15 batches of samples were 0.126 8， 0.232 0， 0.073 8， 0.353 2， 3.620 2， 0.191 0， 0.333 3， 0.317 4， 0.785 0， 0.538 2， 0.460 0， 2.475 1 and 0.347 7 mg/g， including calycosin-7-O-β-D-glucoside， rosmarinic acid， formononetin， lithospermic acid， salvianolic acid B， ononin， ginsenoside Rb1， ginsenoside Rd， ginkgolide C， ginkgolide A， ginkgolide B， notoginsenoside R1， and astragaloside Ⅳ. CONCLUSIONS The established fingerprint of Yindan huoxue tongyu granules can reflect the overall characteristics of the preparation. The content determination method for its pharmacodynamic components， developed in combination with network pharmacology， is accurate， reliable， and exhibits good repeatability， making it suitable for evaluating the quality of Yindan huoxue tongyu granules.

OBJECTIVE To optimize the water extraction technology for Kaixin granules. METHODS UPLC-MS/MS method was established for the simultaneous determination of ginsenoside Rg1， ginsenoside Re， ginsenoside Rb1， tenuifolin， polygalaxanthone Ⅲ and 3， 6′-disinapoyl-sucrose. An orthogonal test was designed with extraction times， extraction duration， and the volume of added water as factors. Using the contents of the aforementioned six indicator components and the extract yield as evaluation indexes， analytic hierarchy process-entropy weight method was employed to determine the combined weights of each indicator. Subsequently， process optimization and validation were conducted by integrating grey relational analysis （GRA） and back propagation （BP） neural network. RESULTS The water extraction technology optimized by the orthogonal test and GRA was 10- fold water for the first decoction and 8-fold water for the subsequent two， extracting 3 times，extracting for 1 h each time； the average comprehensive score of the validation experiment was 91.10 （RSD＝0.31%， n＝3）. The water extraction technology optimized by BP neural network was extracting 3 times with 10-fold water added each time， extracting for 1.5 h each time； the average comprehensive score of the validation experiment was 95.89 （RSD＝0.73%， n＝3）. Considering practical production requirements， the optimal water extraction technology was extraction performed three times， with 10-fold water for the first decoction and 8-fold water for the subsequent two extractions， with an extraction time of 1 h each. CONCLUSIONS The optimized water extraction technology for Kaixin granules is stable and feasible.