Based on the theory of "sweet-flavored medicinals retaining and restoring body fluid"， this paper proposed that the core pathogenesis of hypercoagulable state in malignant tumors is qi deficiency and fluid consumption， blood stasis and vessels stagnation， which evolves dynamically according to the pattern "qi deficiency → fluid consumption → blood stasis". Accordingly， a staged treatment system is established with the general principle of "fortifying the middle jiao， restoring fluid and activating blood circulation". In the initial stage， invigorating the spleen and boosting qi to generate body fluid， targeting the onset of middle jiao deficiency and body fluid consumption； in the middle stage， nourishing yin and unblocking collaterals to facilitate body fluid circulation， addressing the disorder of body fluid transportation and collateral injury caused by internal dryness； in the late stage， consolidating yin and resolving blood stasis to retain body fluid， resolving yin impairment， fluid exhaustion， and binding of stasis and toxin. By regulating body fluid metabolism to improve the hypercoagulable state， this system is intended to provide insights for the prevention and treatment of hypercoagulable state in malignant tumors with traditional Chinese medicine.

Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease （DKD）， and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group， and forty db/db mice were randomly divided into a model group， low-， medium-， and high-dose Danggui Shaoyaosan groups （8.39， 16.77， 33.54 g·kg^-1）， and an irbesartan group （0.025 g·kg^-1）. All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention， 24-h urine samples were collected using metabolic cages， after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein （GSP）， serum creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， and triglycerides （TG）. The urinary albumin-to-creatinine ratio （UACR） was measured. Renal pathological changes were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and monocyte chemoattractant protein-1 （MCP-1） levels. Immunofluorescence （IF） was performed to detect F4/80 expression in renal tissue， and immunohistochemistry （IHC） was used to assess CD206 expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA expression of TNF-α， IL-10， inducible nitric oxide synthase （iNOS）， and arginase-1 （Arg-1）. Western blot analysis was used to detect the protein expression of iNOS， Arg-1， CD86， and CD206 in renal tissue. ResultsCompared with the normal group， the model group showed increased levels of GSP， UACR， SCr， BUN， TC， and TG， elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1， and decreased IL-10 levels （P<0.01）. Pathological examination revealed glomerular hypertrophy， mesangial cell proliferation with marked mesangial expansion， inflammatory cell infiltration， vacuolar degeneration of renal tubular epithelial cells， prominent glycogen deposition， and increased collagen fiber deposition. In addition， relative F4/80 fluorescence intensity was enhanced， CD206 expression in the glomeruli and renal interstitium was reduced， and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased， iNOS and CD86 protein expression was increased， and Arg-1 and CD206 protein expression was decreased （P<0.05， P<0.01）. Compared with the model group， the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP， UACR， SCr， BUN， TC， and TG， reduced serum TNF-α and MCP-1 levels， and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced， CD206 expression in the glomeruli and renal interstitium was increased， and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased， iNOS and CD86 protein expression was reduced， and Arg-1 and CD206 protein expression was increased （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization， promoting M2 anti-inflammatory macrophage polarization， reducing inflammatory responses， delaying the progression of renal fibrosis， improving renal pathological injury， and thereby exerting renal protective effects.

ObjectiveTo investigate the potential mechanism of Danggui Shaoyaosan （DSS） in ameliorating renal injury in db/db mice. MethodsThirty 8-week-old specific pathogen-free （SPF）-grade male db/db mice and six db/m mice were acclimated for one week. Urinary microalbumin and blood glucose levels were measured weekly in both db/db and db/m mice. Successful modeling was determined by significantly higher microalbuminuria in db/db mice compared to db/m mice and a fasting blood glucose ≥16.7 mmol·L^-1. The 30 db/db mice were randomly divided into five groups： the model group， the irbesartan （IBN） group， and three DSS dose groups （low-， medium-， and high-dose DSS groups， administered at 16.77， 33.54， 67.08 g·kg^-1·d^-1， respectively）. Additionally， the six db/m mice served as the normal control group. The IBN group received irbesartan at 0.025 g·kg^-1·d^-1 by gavage， while the three DSS groups received DSS at 16.77， 33.54， and 67.08 g·kg^-1·d^-1 by gavage， respectively. The normal and model groups were administered with an equivalent volume of normal saline by gavage. All interventions lasted for 8 consecutive weeks. After intervention， serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary total protein （UTP）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） were measured to evaluate the therapeutic efficacy of the treatments. Renal histopathological changes were observed with hematoxylin-eosin （HE） staining. Western blot was used to detect the protein expression of silencing information regulator 1 （SIRT1）， hypoxia-inducible factor-1α （HIF-1α）， very low-density lipoprotein receptor （VLDLr）， and cluster of differentiation 31 （CD31）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA levels of HIF-1α and VLDLr. Immunohistochemistry was used to observe the expression and distribution of HIF-1α and Caspase-3. ResultsCompared to the normal group， the model group showed significantly increased SCr， BUN， UTP， TG， and LDL-C. HE staining revealed glomerulosclerosis， mesangial matrix hyperplasia， capillary loop distortion and thickening， with extensive inflammatory cell infiltration. Protein expression of SIRT1 and CD31 significantly decreased （P<0.05）， while HIF-1α and VLDLr protein and mRNA levels increased （P<0.05）. Immunohistochemistry showed increased expression of HIF-1α and Caspase-3 （P<0.05）， indicating hypoxia and apoptosis in renal cells. In all treatment groups， SCr， BUN， TG， and LDL-C were significantly reduced compared to the model group （P<0.05）， and UTP was significantly improved in the medium-dose DSS group （P<0.05）. Renal tissue structure and morphology were improved， inflammatory cells were reduced， and no vascular hyaline degeneration was observed. SIRT1 and CD31 protein expression was elevated to varying degrees compared to the model group （P<0.05）， while HIF-1α and VLDLr protein and mRNA levels decreased （P<0.05）. Immunohistochemistry showed reduced expression of HIF-1α and Caspase-3 in all treatment groups （P<0.05）， with the most significant improvement observed in the IBN group and medium-dose DSS group （P<0.05）. ConclusionDSS can effectively ameliorate glomerulosclerosis and lipid deposition in db/db mice， and its mechanism may involve the SIRT1/HIF-1α/VLDLr signaling pathway.

ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 （TLR4/NF-κB p65/NLRP3） signaling pathway in the renal tissues of db/db mice with spontaneous diabetes， and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease （DKD）. MethodsThirty db/db mice were divided into five groups： A model group， Danggui Shaoyaosan low- （16.77 g·kg^-1·d^-1）， medium- （33.54 g·kg^-1·d^-1）， and high-dose （67.08 g·kg^-1·d^-1） intervention groups， as well as an irbesartan group （0.025 g·kg^-1·d^-1） by the random number table method， with 6 mice in each group. Additionally， 6 db/m mice were assigned to the normal group. After 8 weeks of intervention， the following parameters were determined by corresponding methods： body weight， fasting blood glucose （FBG）， 24-hour urinary protein （24 h-UTP）， and serum creatinine （SCr） levels， renal histopathological analysis by hematoxylin-eosin （HE） staining， Masson staining， and periodic acid-Schiff （PAS） staining， the protein and mRNA expression levels of TLR4， NF-κB p65， NLRP3， tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and interleukin-18 （IL-18） by Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR）， as well as TLR4， NF-κB p65， and NLRP3 protein expression in renal tissues by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group exhibited increased body weight， FBG， 24 h-UTP， and SCr levels （P<0.05）； disordered renal structure， thickened basement membrane， and interstitial inflammatory cell infiltration， elevated TLR4， NF-κB p65， NLRP3， TNF-α， IL-1β， IL-6， and IL-18 expression； as well as decreased IL-10 expression （P<0.05）. Compared with the model group， these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees （P<0.05）. ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.

ObjectiveTo investigate the therapeutic efficacy of Danggui Shaoyaosan （DSS） on renal injury in db/db mice and its impact on endoplasmic reticulum stress （ERS） in renal tissues. MethodsThirty 8-week-old male db/db mice and six db/m mice were acclimated for one week， after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease （DKD） model. The model mice were randomly divided into a model group， an irbesartan group， and three DSS treatment groups with different doses （16.77， 33.54， and 67.08 g·kg^-1·d^-1）. A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention， general conditions were observed. Serum cystatin C （Cys-C）， 24-hour urinary total protein （24 h-UTP）， 24-hour urinary microalbumin （24 h-UMA）， urinary creatinine （Ucr）， and urea nitrogen （UUN） were measured. Transmission electron microscopy （TEM） was used to observe glomerular basement membrane （GBM） and ultrastructural changes of the endoplasmic reticulum （ER） in glomerular endothelial cells. Western blot， real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78， CHOP， and related markers. ResultsCompared with the normal group， the mice in the model group showed curled posture， sluggish response， poor fur condition， increased levels of Cys-C， 24 h-UTP， 24 h-UMA， and UUN （P<0.05）， while Ucr decreased （P<0.05）. The GBM was significantly thickened， with podocyte and foot process fusion. The protein expressions of GRP78， CHOP， and ATF6 were significantly upregulated （P<0.05）， the mRNA levels of GRP78 and CHOP increased （P<0.05）， and immunohistochemistry showed an enhanced GRP78 signal （P<0.05）. After treatment， the mice exhibited improved behavior， normalized GBM and podocyte structure， improved ER morphology and markedly better biochemical indicators. Western blot， Real-time PCR， and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups （P<0.05）， suggesting alleviated ERS and improved renal function. ConclusionDSS can effectively ameliorate renal pathological damage in db/db mice， possibly by regulating ERS in glomerular endothelial cells， although the underlying signaling mechanisms require further investigation.

OBJECTIVE To know about the perception and current status of drug risk management among pharmacists in Chinese medical institutions， providing insights and recommendations for enhancing the drug risk management system in medical institutions. METHODS A questionnaire survey was conducted across 28 provinces， cities， and autonomous regions； stratified radom sampling was employed to study the population of medical workers and pharmaceutical professionals in medical institutions nationwide. The survey included information on the survey population， the current status of drug risk management implementation in medical institutions， the cognition， definition and process of drug risk management related concepts， and the content and mode of drug risk management work in medical institutions. Finally， suggestions were collected from various medical institutions on the system construction of drug risk management. Descriptive statistical analysis was adopted to summarize the obtained data. RESULTS A total of 446 questionnaires were collected in this survey， including 420 valid questionnaires and 26 invalid questionnaires. The questionnaire collection rate was 100%，and the effective rate was 94.17%. 51.19% of the respondents No.2020YFC2009001）。 based their understanding of drug risk management on Management Measures for Adverse Drug Reaction Reports and Monitoring， while 87.38% recognized the need for drug risk management throughout the drug use process. 63.33% of the participants stated that their medical institutions had dedicated positions related to drug risk management， with the highest proportion （72.17%） was in third-grade class A medical institutions. 66.43% reported implementing risk management across all drug use stages. Suggestions for the development of drug risk management systems in medical institutions by the research participants focused on enhancing guiding documents， clarifying concepts， establishing information-sharing mechanisms. CONCLUSIONS The overall awareness of drug risk management in China’s medical institutions is high， with practices in place across various stages in multiple forms. However， there remains a need to strengthen institutional documents， management regulations， system development， and information-sharing mechanisms to improve collaborative governance， improve drug management levels， and ensure patient safety.

OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance （IR） in type 2 diabetes mellitus （T2DM） rats. METHODS T2DM rat model was established by intraperitoneal injection of 30 mg/kg streptozotocin combined with high-fat and high-sugar diet. The rats were randomly divided into normal control group， model group， Qingxue xiaozhi jiangtang formula low-dose and high-dose groups （6.525， 13.05 g/kg， calculated by raw material） and metformin group （positive control， 0.18 g/kg）， with 8 rats in each group. Administration groups were given relevant medicine intragastrically； normal control group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 6 weeks. Body mass and fasting blood glucose （FBG） were determined， and oral glucose tolerance test was conducted. Serum fasting insulin （FINS） level was measured to calculate the insulin resistance index （HOMA-IR） and insulin sensitivity index （ISI）. Additionally， the level of serum lipids， liver function， oxidative stress indicators and inflammatory factors were assessed. The phosphorylation levels of kinase R-like endoplasmic reticulum kinase （PERK） and forkhead box O1 （FOXO1） protein in liver tissue of rats were determined. RESULTS Compared with model group， the body weight， ISI， the levels of high-density lipoprotein cholesterol and superoxide dismutase were increased significantly in Qingxue xiaozhi jiangtang formula high-dose group and metformin group （P＜0.05）； FBG， blood glucose level at 120 minutes of glucose loading， area under the curve of glucose， FINS， HOMA-IR， low-density lipoprotein cholesterol， total cholesterol， triglyceride， alanine transaminase， aspartate transaminase， alkaline phosphatase， malondialdehyde， interleukin-6， tumor necrosis factor-α， and C-reactive protein levels were significantly reduced （P＜ Δ0.05）； the pathological damage of liver tissue had significantlyimproved， and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased （P＜0.05）. CONCLUSIONS Qingxue xiaozhi jiangtang formula can regulate glucose and lipid metabolism， inflammation factor and oxidative stress levels， and alleviate insulin resistance in T2DM rats. Its mechanism of action may be related to the inhibition of the PERK/FOXO1 signaling pathway.

ObjectiveTo investigate the association and translational mechanism between the hepatotoxicity of Xianling Gubao （XLGB） and its treatment of osteoporosis based on a zebrafish model. MethodsZebrafish were randomly selected four days after fertilization （4 dpf） and exposed to different concentrations of XLGB （0.7，0.35 mg·L^-1） for 96 h. At the endpoint of the exposure， the mortality rates of zebrafish in the treatment groups of different concentrations were counted， and the "dose-toxicity" curves were plotted. The 10% sublethal concentration （LC₁₀） was calculated. The liver area， acridine orange staining， and pathological tissue sections of transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP）］ were used as indicators to confirm the hepatic damage caused by the sublethal concentration of XLGB. By using the prednisolone （PNSL）-induced osteoporosis model of zebrafish， the anti-osteoporosis activity of XLGB was evaluated by using the area of skull stained by alizarin red and the cumulative optical density value as indicators. Then， the toxicity difference of XLGB on the liver of zebrafish in healthy and osteoporotic states was compared， and the mechanism of the translational action of the toxicity of XLGB was predicted based on network pharmacology and real-time polymerase chain reaction（Real-time PCR）. ResultsThe LC₁₀ of XLGB on zebrafish （8 dpf） was 0.7 mg·L^-1. Compared with the blank group， the sublethal concentration （LC₁₀=0.7 mg·L^-1， 1/2 LC₁₀=0.35 mg·L^-1） of XLGB induced an increase in the number of apoptosis of hepatocytes in a dose-dependent manner， and the tissue arrangement of the liver was disordered and loose. The vacuoles were obvious， and the fluorescence area of the liver was significantly reduced （P<0.01）. Compared with the blank group， the mineralized area and cumulative optical density value of zebrafish skull in the PNSL model group were significantly reduced （P<0.01）， and those in the 0.7，0.35 mg·L^-1 XLGB treatment group were significantly increased compared with the model group （P<0.01）. Most importantly， 0.7 mg·L^-1 XLGB had no significant effect on the liver of zebrafish in the osteoporosis disease model compared with the blank group. The results of network pharmacology and real-time PCR experiments showed that the toxic transformation of XLGB might be related to the differences in the expression levels of key targets， such as tumor protein 53 （TP53）， cysteine aspartic acid specific protease-3（Caspase-3）， interleukin（IL）-6， and alkaline phosphatase（ALP） in different organismal states. ConclusionUnder certain conditions， XLGB has hepatotoxicity in normal zebrafish， but under osteoporotic conditions， XLGB not only exerts significant anti-osteoporosis activity but also alleviates hepatotoxicity significantly， which provides a reference for the safe clinical use of XLGB and real evidence for the theories of traditional Chinese medicine of attacking poison with poison and of treating disease with corresponding drugs without damage to the body.

ObjectiveTo investigate the effects of jujuboside A （JuA） on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment （VCI） and explore the potential mechanisms by which JuA treats VCI. MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group （n=10）， a blank control group （n=10）， and a modeling group （n=30）. The rats in the modeling group underwent bilateral carotid artery ligation （2-VO） for the modeling of VCI. After stabilization， the VCI rats were randomized into model， JuA （20 mg·kg^-¹）， and donepezil （0.45 mg·kg^-¹） groups. After 4 weeks of gavage， the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β （GSK-3β）， cAMP response element-binding protein （CREB）， B cell lymphoma-2 （Bcl-2）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β， p-GSK-3β， p-CREB， Bcl-2， PI3K， p-PI3K， Akt， and p-Akt in the hippocampal tissue. ResultCompared with the sham operation group， the model group exhibited declines in the learning and memory abilities （P<0.01）， neuronal damage and decreased neurons in the hippocampal CA1 region （P<0.01）， up-regulation in the mRNA level of GSK-3β （P<0.01）， and down-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2， as well as the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.01）. In comparison to the model group， both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities （P<0.05， P<0.01）， with reduced neuronal damage and increased neurons （P<0.05， P<0.01）. In addition， the two groups showed down-regulation in the mRNA level of GSK-3β （P<0.01） and up-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2 and the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.05， P<0.01）. There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities， neuron count， and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors. ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway， reducing the apoptosis of hippocampal neurons， and alleviating the hippocampal neuronal damage.