To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

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.

OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

Hepatitis B virus （HBV） exclusively infects liver parenchymal cells and forms covalently closed circular DNA （cccDNA） within their nuclei. HBV cccDNA serves as the essential template for viral gene transcription， the sole source of progeny virus production， and the key driver of viral antigen expression， and it is the molecular basis for the persistence of HBV infection. Therefore， elimination and/or functional silencing of cccDNA is the key to eradicate chronic HBV infection. This article discusses the critical scientific issues that need to be solved during elimination of the harm of HBV infection from the perspectives of the synthesis， transcription， and clearance of cccDNA， as well as the impact of nonparenchymal cells on cccDNA， in order to provide a reference for eradicating HBV infection in the future.

Tetrodotoxin（TTX）is a potent neurotoxin known for its specific sodium channel blocking effects, widely used in biomedical research. While TTX has been identified in various marine organisms, its true origin remains unclear, and the specific biosynthetic pathways are yet to be elucidated. The reported sources of TTX and the progress in research on TTX biosynthesis were summarized, with a focus on potential microbial sources of TTX, which could provide scientific reference for the production and biosynthesis studies of TTX.

OBJECTIVE To investigate the effects and potential mechanism of Yiqi wenyang huwei decoction （YQWY） in improving airway inflammation and remodeling in rats with bronchial asthma （BA） based on the Toll-like receptor 4 （TLR4）/myeloid differentiation primary response protein 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Male SD rats were randomly divided into the normal group， the model group， the dexamethasone group （positive control， 0.5 mg/kg）， and YQWY low-， medium- and high-dose groups （5， 10， 20 g/kg， calculated by the crude drug）， with 8 rats in each group. Except for the normal group， rats in all other groups were sensitized twice with ovalbumin combined with aerosol challenge to establish a BA model. From day 14 to day 34 of the experiment， the rats in each group were administered the corresponding drug solution or normal saline intragastrically， once a day， 1 hour before aerosol challenge. At 24 hours after the final aerosol challenge， asthma symptom scores were assessed， serum levels of immunoglobulin E （IgE） were measured， and the levels of inflammatory cytokines （interleukin-4， interleukin-5， interleukin-13 and tumor necrosis factor-α） and the numbers of inflammatory cells （white blood cell， eosinophil， neutrophil， lymphocyte， monocyte and basophil） in bronchoalveolar lavage fluid were determined. Pathological changes in lung tissue were observed. The mRNA expressions of TLR4， MyD88 and NF-κB， as well as the protein expressions of TLR4， MyD88， NF-κB p65 and phosphorylated NF-κB p65 in lung tissue， were detected. RESULTS Compared with the model group， the pathological changes， such as inflammatory cell infiltration， abnormal deposition of collagen fibers， and goblet cell hyperplasia in the lung tissue of rats in each drug group， were alleviated to varying degrees. The asthma symptom scores （except for the YQWY low-dose group）， the levels of IgE and inflammatory cytokines （except for interleukin-5 in the YQWY medium-dose group）， the number of inflammatory cells （except for monocyte and basophil in the YQWY low-dose group）， the mRNA expression of TLR4， MyD88 and NF-κB， as well as the protein expressions of TLR4， MyD88， NF-κB p65 and phosphorylated NF-κB p65 （except for MyD88 and NF-κB p65 proteins in the YQWY low-dose group as detected by Western blo t） were all significantly reduced or down-regulated （ P ＜0.05 or P ＜0.01）. CONCLUSIONS YQWY can alleviate asthma-like manifestations in BA rats and improve their airway inflammation and remodeling； these effects may be related to the formula’s inhibition of the abnormal activation of the TLR4/MyD88/NF-κB signaling pathway.

Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Tumorigenesis， invasion， and metastasis occur in the context of a persistent inflammatory microenvironment， and a variety of inflammatory factors can lead to the development of various tumors. Guided by the thought of "preventive treatment of disease" in TCM and the concept of tertiary prevention in modern medicine， it is of great significance to effectively intervene in the inflammatory stage of the disease， interrupt disease progression， prevent the occurrence of malignant tumors， and reverse the process of "inflammation-to-cancer transformation". Sinisan， a commonly used prescription in the Treatise on Febrile Diseases， has been widely applied in the treatment of precancerous lesions of the digestive system， demonstrating considerable advantages. This article reviewed literature from the past 20 years， summarizing the application of Sinisan in precancerous lesions of the digestive system from three aspects： the exploration of its prescription-syndrome relationship， clinical application， and mechanistic study. It is found that basic syndrome indications of Sinisan include harmonizing the Earth element to promote spleen-stomach transportation and transformation， soothing the liver and nourishing the Wood element to restore the smooth flow of Qi， and regulating Yin and Yang to relieve stagnation within the system. In clinical application， Sinisan has shown significant efficacy in atrophic gastritis and precancerous conditions such as intestinal metaplasia， gastric ulcer， ulcerative colitis， esophagitis， and pancreatitis. Mechanistic studies have revealed that Sinisan can inhibit inflammatory factors and improve the inflammatory microenvironment， inhibit cell proliferation and regulate apoptosis， exhibit anti-angiogenic and antitumorigenic effects， modulate immune function， and exert antioxidant effects. These mechanisms can be achieved by regulating pathways such as nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， farnesoid X receptor （FXR）/Nrf2， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Takeda G protein-coupled receptor 5/cyclic adenosine monophosphate/protein kinase A （TGR5/cAMP/PKA）， interleukin-4/signal transducer and activator of transcription 6 （IL-4/STAT6）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， RhoA/Rho-associated protein kinase （RhoA/ROCK）， and transforming growth factor-β/Smad proteins （TGF-β/Smads）， confirming Sinisan's role in reversing the inflammation-to-cancer transformation. The current research status of Sinisan in precancerous lesions of the digestive system was thoroughly examined through the above three aspects， along with the identification of limitations and areas for improvement in current research. The aim is to provide a basis and support for future in-depth research on Sinisan， promote the development of new integrated treatment models combining TCM and Western medicine for precancerous lesions， and aid in the research and development of drugs related to precancerous lesions.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.