ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine （TCM） in clinical practice， but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad， which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix， the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison， use of poison， anti-poison， and detoxification'' were employed to mine the relevant toxicity records， usage and dosage， processing compatibility， and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included， suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity， and the adverse reactions may be related to long-term use， excessive use， and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling， steaming with black beans， and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria， Psoraleae Fructus， and Cistanches Herba. ConclusionReasonable dosage， standard processing， correct compatibility， and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically， the toxicity classification of TCM should be strengthened， and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved， and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.

ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine （TCM） in clinical practice， but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad， which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix， the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison， use of poison， anti-poison， and detoxification'' were employed to mine the relevant toxicity records， usage and dosage， processing compatibility， and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included， suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity， and the adverse reactions may be related to long-term use， excessive use， and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling， steaming with black beans， and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria， Psoraleae Fructus， and Cistanches Herba. ConclusionReasonable dosage， standard processing， correct compatibility， and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically， the toxicity classification of TCM should be strengthened， and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved， and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

ObjectiveTo explore the mechanism by which modified Shaofu Zhuyutang inhibits angiogenesis in endometriosis via the vascular endothelial growth factor （VEGF）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/endothelial nitric oxide synthase （eNOS）-nitric oxide （NO） signaling pathway. MethodsEighty-four female SD rats were randomly assigned into blank， sham operation， model， positive control （gestrinone， 0.25 mg·kg^-1）， high-， medium-， and low-dose （30， 15， 7.5 g·kg^-1， respectively） traditional Chinese medicine （TCM， modified Shaofu Zhuyutang） groups. A rat model of endometriosis was established by the autotransplantation method. After successful modeling， rats in the drug intervention groups were administrated with corresponding agents by gavage， and those in the blank， sham operation， and model groups received an equal volume of distilled water. After 28 days of gavage， rats were administrated with oxytocin， and the number and latency period of writhing responses were observed. Serum samples from each group， ectopic lesions from modeling groups， and uteri from blank and sham operation groups were collected. Hematoxylin-eosin staining was used to observe the pathological morphology of endometriotic lesions. Immunohistochemistry was employed to observe the expression of angiogenesis-specific markers cluster of differentiation 34 antigen （CD34） and friend leukemia virus integration-1 （FLI-1）. Enzyme-linked immunosorbent assay and the nitrate reductase method were employed to determine the serum levels of VEGF and NO， respectively. Western blot was employed to measure the protein levels of VEGF， PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， eNOS， and phosphorylated eNOS （p-eNOS）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to determine the mRNA levels of VEGF， PI3K， Akt， and eNOS. ResultsThe blank group and the sham operation group had no significant changes in the number and latency period of writhing responses， serum VEGF and NO levels， protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS， and mRNA levels of VEGF， PI3K， Akt， and eNOS. The model group showed an increase in the number and a reduction in the latency period of writhing responses， enlargement of ectopic endometrial tissue in the abdominal wall， with stromal hyperplasia， glandular dilation， and increased vasculature. In addition， the modeling led to increased positive expression of CD34 and FLI-1， elevated serum VEGF and NO levels， and up-regulated protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS and mRNA levels of VEGF， PI3K， Akt， and eNOS （P<0.01）. Compared with the model group， the gestrinone and high-， medium-， and low-dose TCM groups showed a significant reduction in the number of writhing responses， a significant prolongation of the latency period， reduced ectopic endometrial tissue in the abdominal wall， alleviated pathological damage， and reduced positive expression of CD34 and FLI-1. The gestrinone group and the high- and medium-dose TCM groups showed lowered serum VEGF and NO levels as well as down-regulated protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS and mRNA levels of VEGF， PI3K， Akt， and eNOS. Moreover， the low-dose TCM group showed reductions in the serum VEGF level， the protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS， and the mRNA levels of VEGF and eNOS （P<0.05， P<0.01）. ConclusionModified SShaofu Zhuyutang can inhibit angiogenesis in endometriosis by antagonizing the abnormal activation of the VEGF/PI3K/Akt/eNOS-NO signaling pathway， thereby preventing the occurrence， development， and deterioration of endometriosis.

ObjectiveTo explore the mechanism by which modified Shaofu Zhuyutang inhibits angiogenesis in endometriosis via the vascular endothelial growth factor （VEGF）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/endothelial nitric oxide synthase （eNOS）-nitric oxide （NO） signaling pathway. MethodsEighty-four female SD rats were randomly assigned into blank， sham operation， model， positive control （gestrinone， 0.25 mg·kg^-1）， high-， medium-， and low-dose （30， 15， 7.5 g·kg^-1， respectively） traditional Chinese medicine （TCM， modified Shaofu Zhuyutang） groups. A rat model of endometriosis was established by the autotransplantation method. After successful modeling， rats in the drug intervention groups were administrated with corresponding agents by gavage， and those in the blank， sham operation， and model groups received an equal volume of distilled water. After 28 days of gavage， rats were administrated with oxytocin， and the number and latency period of writhing responses were observed. Serum samples from each group， ectopic lesions from modeling groups， and uteri from blank and sham operation groups were collected. Hematoxylin-eosin staining was used to observe the pathological morphology of endometriotic lesions. Immunohistochemistry was employed to observe the expression of angiogenesis-specific markers cluster of differentiation 34 antigen （CD34） and friend leukemia virus integration-1 （FLI-1）. Enzyme-linked immunosorbent assay and the nitrate reductase method were employed to determine the serum levels of VEGF and NO， respectively. Western blot was employed to measure the protein levels of VEGF， PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， eNOS， and phosphorylated eNOS （p-eNOS）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to determine the mRNA levels of VEGF， PI3K， Akt， and eNOS. ResultsThe blank group and the sham operation group had no significant changes in the number and latency period of writhing responses， serum VEGF and NO levels， protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS， and mRNA levels of VEGF， PI3K， Akt， and eNOS. The model group showed an increase in the number and a reduction in the latency period of writhing responses， enlargement of ectopic endometrial tissue in the abdominal wall， with stromal hyperplasia， glandular dilation， and increased vasculature. In addition， the modeling led to increased positive expression of CD34 and FLI-1， elevated serum VEGF and NO levels， and up-regulated protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS and mRNA levels of VEGF， PI3K， Akt， and eNOS （P<0.01）. Compared with the model group， the gestrinone and high-， medium-， and low-dose TCM groups showed a significant reduction in the number of writhing responses， a significant prolongation of the latency period， reduced ectopic endometrial tissue in the abdominal wall， alleviated pathological damage， and reduced positive expression of CD34 and FLI-1. The gestrinone group and the high- and medium-dose TCM groups showed lowered serum VEGF and NO levels as well as down-regulated protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS and mRNA levels of VEGF， PI3K， Akt， and eNOS. Moreover， the low-dose TCM group showed reductions in the serum VEGF level， the protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS， and the mRNA levels of VEGF and eNOS （P<0.05， P<0.01）. ConclusionModified SShaofu Zhuyutang can inhibit angiogenesis in endometriosis by antagonizing the abnormal activation of the VEGF/PI3K/Akt/eNOS-NO signaling pathway， thereby preventing the occurrence， development， and deterioration of endometriosis.

[Objective] To compare the diagnostic accuracy of three imaging modalities, inlducing CT urography (CTU), contrast-enhanced MRI (CE-MRI), and contrast-enhanced ultrasound (CEUS) in the qualitative diagnosis of renal space-occupying lesions. [Methods] A retrospective analysis was performed on 542 patients with renal lesions confirmed by surgical pathology in our hospital during Jan.2019 and May 2024.The diagnostic results of CTU, CE-MRI and CEUS were compared and analyzed based on the patients' clinical and pathological data. [Results] The diagnostic accuracy rate of CTU, CE-MRI and CEUS were 84.50%, 83.14% and 86.14%, respectively.For the 161 patients who underwent all three examinations, CEUS was significantly more accurate than CTU (84.16% vs. 77.02%, P=0.018), while there was no significant difference between CTU or CEUS and CE-MRI (79.81%) (P>0.05). Further analysis found that for lesions ≤4 cm, the accuracy of the three examinations was as follows: CEUS=CTU 79.55%, CE-MRI 76.14%, with no significant difference (P>0.05). However, for lesions >4 cm, CEUS ranked the first, followed by CE-MRI and CTU (89.73% vs. 84.25% vs. 73.97%), and CEUS and CE-MRI were better than CTU (P<0.05). Additionally, for the diagnosis of clear cell renal carcinoma and benign renal space-occupying lesions, there was no statistically significant difference among the three imaging modalities (P>0.05), while for the qualitative diagnosis of non-clear cell renal carcinoma, CEUS ranked the first, followed by CE-MRI and CTU (83.87% vs. 74.19% vs. 56.45%), and CE-MRI and CEUS were better than CTU (P<0.05). [Conclusion] All of them have important diagnostic value, and the appropriate selection should be based on patients' specifc conditions.CEUS and CE-MRI are more accurate in the qualitative diagnosis of renal space-occupying lesions than CTU, especially for large lesions and non-clear cell carcinoma.

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.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

OBJECTIVE To predict and validate the potential mechanisms of Kaixinsan （KXS） in ameliorating neuroinflammation in Alzheimer’s disease （AD）. METHODS Network pharmacology was employed to identify core anti- inflammatory components and key inflammatory targets of KXS for AD. Gene ontology （GO） functional annotation， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment， and molecular docking were performed. Based on these findings， male SD rats were used to establish an AD model via chronic D-galactose induction. The effects of KXS on AD rats were evaluated， including quantitative behavioral score， learning and memory parameters （escape latency， platform crossings， platform quadrant distance and time）， organ indexes （heart， liver， spleen， thymus）， histopathological alterations in the hippocampus， and expressions of inflammation-related pathway proteins and their upstream/downstream regulators. RESULTS Core anti-inflammatory components of KXS for AD included gomisin B， panaxytriol， gomisin A， enhydrin， vulgarin and panaxydol， while key inflammatory targets involved nuclear factor-kappa B subunit 1（ NFKB1）， nuclear factor-κB p65（ NF-κB p65）， interleukin-1β（ IL- 1β）， IL-6， Toll-like receptor 4 （TLR4）， tumor necrosis factor， nucleotide-binding domain leucine-rich repeat and pyrin domain- containing receptor 3 （NLRP3） and caspase-1 （CASP1）. GO and KEGG pathway enrichment involved inflammatory response， phosphorylation and the NF-κB signaling pathway. Molecular docking confirmed strong binding affinities between core components and key targets. Animal experiments demonstrated that， compared to the model group， KXS significantly alleviated histopathological damage （e.g.， neuronal shrinkage， reduced Nissl bodies in hippocampal CA1， CA3， and DG regions）， increased organ indexes （except for liver index） and Nissl-stained positive cells， improved learning and memory performance， and reduced behavioral scores （at the 8 and 12 weeks of the experiment） and protein expression of NF- κB p65， phosphorylated NF- κB p65， TLR4， NLRP3， CASP1 and IL-1β. CONCLUSIONS KXS effectively mitigates neuroinflammation， reduces hippocampal neuronal injury， and enhances learning and memory ability in AD rats， potentially through suppressing the NF-κB signaling pathway and its upstream/ downstream regulators.

Objective: To compare the changes in the concentration of relevant growth factors released from platelet-rich plasma (PRP) stored at -80℃ by cryopreservation and at 4℃ by refrigerated lyophilization over 2 years, aiming to provide a theoretical basis for prolonging PRP storage duration. Methods: PRP (n=15) was separated using a blood cell separator and stored under -80℃ cryopreservation (F-PRP group) and 4℃ refrigerated freeze-drying conditions (FD-PRP group). The contents of growth factors (PDGF-AA, PDGF-BB, EGF, TGF-β1, and VEGF) in both groups were measured by ELISA at 1, 3, 6, 9, 12 and 24 months. Results: PDGF-AA and VEGF maintained good stability in both groups for up to 24 months. PDGF-BB and TGF-β1 showed high stability in the first 12 months but their stability decreased gradually from 12th to 24th months. EGF demonstrated good stability in the first 6 months, and its stability gradually decreased from the 9th to 24th months. Comparing the F-PRP and FD-PRP groups, the concentrations of the five growth factors in the FD-PRP group were either not statistically different or higher than those in the F-PRP group at all time points. Specifically, the concentrations of EGF were significantly higher in the FD-PRP group at all time points. Conclusion: Both -80℃ freezing and 4℃ freeze-drying enable long-term preservation of PRP. Freeze-drying imposes less stringent storage requirements and facilitates growth factor compared to frozen storage.