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.

ObjectiveThis study aims to investigate the therapeutic effects of Wenyang Xiaoyin Prescription （Linggui Zhugan Tang combined with Tingli Dazao Xiefei Tang） on a doxorubicin-induced mouse model of chronic heart failure （CHF）. The multi-targeting action mechanism of the therapy is revealed， based on the arginine vasopressin （AVP）-vasopressin V₂ receptor （V2R）-aquaporin 2 （AQP2） signaling pathway and nuclear transcription factor -κB （NF-κB） pathway mediated by the liver X receptor （LXR） in the heart， brain， and kidney tissue. MethodsCHF mouse models were established by using intraperitoneal injection of doxorubicin and subsequently divided into a blank control group， a model control group， Wenyang Xiaoyin Prescription groups （Linggui Zhugan decoction combined with Tingli Dazao Xiefei decoction） with various doses， a captopril group， and a combination group receiving both Wenyang Xiaoyin prescription （as before） and captopril. Cardiac function was assessed by using color Doppler echocardiography， while the levels of brain natriuretic peptide （BNP）， AVP， and the renin-angiotensin-aldosterone system （RAAS） in the serum were measured via enzyme-linked immunosorbent assay （ELISA）. Pathological changes and ventricular remodeling in ventricular tissues were evaluated through hematoxylin and eosin （HE） and Masson staining， and myocardial cell apoptosis of mice was assessed by using TdT-mediated dUTP Nick-End Labeling （TUNEL） staining. Western blot and real-time polymerase chain reaction （Real-time PCR） were employed to detect the protein and RNA expression levels of LXRα， nuclear factor kappa-light-chain-enhancer of activated B cells （NF-κB）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS） in the cardiac tissue， LXRβ， AVP in the hypothalamus， and LXRβ， V2R， and AQP2 in the kidneys. Furthermore， immunohistochemistry was used to quantify AQP2-positive collecting ducts in renal tissues. ResultsThe Wenyang Xiaoyin prescription significantly enhanced cardiac function indicators in CHF mice， reducing levels of BNP， AVP， and RAAS in the serum. It also mitigated myocardial cell damage and fibrosis change. The Wenyang Xiaoyin prescription inhibited the expressions of NF-κB and its downstream targets TNF-α and iNOS and improved myocardial inflammatory response， cell apoptosis， and ventricular remodeling by upregulating the expression of LXRα in cardiac tissues. Concurrently， the Wenyang Xiaoyin prescription elevated LXRβ expression in the kidneys and hypothalamus while downregulating the expression levels of AVP， V2R， and AQP2， as well as water permeability in the collecting ducts， thereby alleviating cardiac load. ConclusionThe intervention of Wenyang Xiaoyin prescription demonstrates a significant therapeutic effect on CHF， and its role involves the multi-target effect mechanism of the AVP/V2R/AQP2 and NF-κB pathways mediated by the nuclear receptor LXR in the heart， brain， and kidney tissue.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

The pathogenesis of painful diabetic peripheral neuropathy(PDPN)is very complicated and tricky treat,which seriously affects the physical and mental health of patients.TCM has certain advantages in treating PDPN,but lacks theoretical guidance centered on pathogenesis.The dynamic evolution of the pathogenesis of PDPN fits the theory of"deficient-qi induced stagnation".PDPN is mainly characterized by pain,with prolonged pain entering the collaterals.This article discussed the pathogenesis of PDPN from the theory of"deficient-qi induced stagnation"based on collateral disease.Among them,the"deficient qi"is mainly responsible for the deficiency of qi,blood,yin and yang,and the collaterals are not be nourished;"stagnation"includes the pathological state of qi stagnation,phlegm and stasis caused by the abnormal movement of qi,blood and body fluid,and the obstruction of collaterals."Deficient qi"and"stagnation"interact with each other to promote the progress of PDPN.The article concluded that the key point of treatment is to regulate the deficiency qi(tonify deficiency)and remove stagnation and clear collaterals(smooth the stagnation),which could provide a new diagnosis and treatment idea and theoretical basis for the clinical differentiation and treatment of PDPN.

Objective:To analyze the clinical effects of an anterior cruciate ligament (ACL) tunnel locator applied in the arthroscopic reduction and fixation of Schatzker type Ⅳ tibial plateau fracture plus posterolateral column collapse.Methods:A retrospective study was conducted to analyze the clinical data of 12 patients with Schatzker type IV tibial plateau fracture combined with posterolateral column collapse who had undergone arthroscopic reduction and fixation assisted by an ACL locator at Department of Orthopedics and Trauma Surgery, The Hospital Affiliated to Yunnan University from January 2020 to December 2022. There were 8 males and 4 females with an age of (44.5±6.4) years (set as an observation group). According to a 1∶1 ratio, another contemporary 12 patients of the same category were selected as a control group who had been treated by double-plate-screw fixation through internal and external double incisions. They were 7 males and 5 females with an age of (42.6±6.3) years. The operation time, incision length, intraoperative blood loss, postoperative hospital stay, and postoperative complications were recorded and compared between the 2 groups. At the same time, the Rasmussen radiological and functional scores at 1, 3, and 12 months after operation were recorded for intergroup and intragroup comparisons.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, showing the 2 groups were comparable ( P>0.05). All the 24 patients were followed up for (18.2±3.5) months after operation. In the observation group, the operation time [(96.3±6.3) min], incision length [(8.5±0.6) cm], and postoperative hospital stay [(8.1±1.3) d] were significantly shorter than those in the control group [(128.2±7.5) min, (15.9±0.8) cm, and (9.3±1.2) d], and the intraoperative blood loss [50.0 (41.5, 59.0) mL] was significantly less than that in the control group [135.0 (121.5, 147.5) mL] (all P<0.05). However, intergroup comparisons showed no statistically significant differences in Rasmussen radiographic scores or functional scores at 1 month, 3 months, or 12 months postoperatively between the 2 groups ( P>0.05). Additionally, no significant differences were observed in postoperative complications between the 2 groups ( P>0.05). Conclusions:In the arthroscopic reduction and fixation of Schatzker type Ⅳ tibial plateau fracture plus posterolateral column collapse, compared with the traditional double-plate-screw fixation through double incisions, assistance of an ACL tunnel locator leads to advantages of being more minimally invasive and more surgically efficient. However, the 2 techniques lead to comparable postoperative functional recovery.

Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

Objective To observe the effects of Jianpi Huatan Prescription on hepatic cholesterol synthesis in subclinical hypothyroidism(SCH)mice;To discuss its mechanism based on cAMP/CREB/HMGCR signaling pathway.Methods Totally 80 C57BL/6 male mice were randomly divided into control group(10 mice)and modeling group(70 mice),and the modeling group was given methimazole 0.08 mg/(kg·d)in drinking water for 16 weeks to establish a SCH mdoel.The model mice were randomly divided into model group,euthyrox group and Jianpi Huatan Prescription high-,medium-and low-dosage groups,with 10 mice in each group,and were given corresponding drugs for gavage for 6 weeks.HE staining and Oil red O staining were used to observe the morphology and lipid deposition of liver tissue,ELISA was used to detect serum contents of thyroid stimulating hormone(TSH),triiodothyronine(T3),thyroid hormone(T4),total cholesterol(TC),triglycerides(TG),and TC,cyclic adenosine monophosphate(cAMP)in liver tissue,Western blot was used to detect the expressions of protein kinase A(PKA),cyclic adenosine response element binding protein(CREB),p-CREB and 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR)in liver tissue.Results Compared with the control group,the liver tissue of mice in the model group showed fat vacuoles of different sizes and obvious lipid deposition;the contents of TSH,TC,TG in serum and TC,cAMP in liver tissue significantly increased(P＜0.05,P＜0.01);the protein expressions of PKA,p-CREB and HMGCR significantly increased(P＜0.01).Compared with the model group,lipid deposition in liver tissue and structure of liver cells was improved to varying degrees in euthyrox group and Jianpi Huatan Prescription high-and medium-dosage groups,and the contents of serum TSH,TC,TG,and liver tissue TC,cAMP decreased(P＜0.05,P＜0.01);the expressions of PKA,p-CREB and HMGCR protein in liver tissue increased significantly(P＜0.01).Conclusion Jianpi Huatan Prescription can significantly inhibit hepatic cholesterol synthesis in SCH mice,and improve hepatic fat vacuoles and lipid deposition,and its mechanism may be to reduce TSH levels in SCH mice by regulating the cAMP/CREB/HMGCR signaling pathway.

OBJECTIVE: To investigate the effect and mechanism of Shuangshi Tonglin Capsules (SSTL) in the treatment of prostate fibrosis (PF). METHODS: Human prostate stromal cells (WPMY-1) were used for in vitro experiments to establish PF cell models induced with estradiol (E₂). The cell proliferation, migration and clonogenic capacity were determined by cell counting kit-8, scratch assay, and crystal violet staining, respectively. Sprague-Dawley rats were used for in vivo experiments. The changes in histomorphology and organ index of rat prostate by SSTL were determined. Pathologic changes and collagen deposition changes in rat prostate were observed by haematoxylin and eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay kits were used to determine changes in rat PF markers fibroblast growth factor-23 (FGF-23), E₂ and prostate specific antigen (PSA). Mechanistically, changes in oxidative stress indicators by SSTL were determined in WPMY-1 cells and PF rats. Then the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins as well as Nrf2 and TGF-β1 mRNA were further detected by Western blot or quantitative real-time polymerase chain reaction both in vivo and in vitro. RESULTS: In the efficacy study, SSTL significantly reduced the proliferation, migration, and clonogenic ability of cells, improved the morphology of the glandular tissue, significantly reduced the prostate index, reduced glandular fibrous tissue and collagen deposition, and resulted in a significant decrease in the levels of FGF-23, E₂ and PSA (P<0.01 or P<0.05). In the mechanistic study, SSTL ameliorated oxidative stress by significantly increasing superoxide dismutase and glutathione peroxidase levels and decreasing malondialdehyde level in WPMY-1 cells and rats (P<0.01 or P<0.05). SSTL significantly elevated the expressions of Nrf2, HO-1, NAD(P)H quinone oxidoreductase 1 (NQO-1), and Smad7 proteins in both cells and rats, and significantly decreased the expressions of TGF-β1, collagen I, α-smooth muscle actin and Smad4 proteins (P<0.01 or P<0.05). SSTL also elevated the content of Nrf2 mRNA and decreased the content of TGF-β1 mRNA in cells and rats (P<0.01 or P<0.05). The Nrf2 inhibitor ML385 was added in in vitro experiments to further validate the pathway relevance. CONCLUSION SSTL was effective in improving PF in vivo and in vitro, and its mechanism of action may function through the Nrf2/TGF-β1 signaling pathway.
Male ; NF-E2-Related Factor 2/metabolism* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Humans ; Fibrosis ; Prostate/drug effects* ; Cell Proliferation/drug effects* ; Capsules ; Cell Movement/drug effects* ; Oxidative Stress/drug effects* ; Rats

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Episodic memory, our ability to recall past experiences, is supported by structures in the medial temporal lobe (MTL) particularly the hippocampus, and its interactions with fronto-parietal brain regions. Understanding how these brain regions coordinate to encode, consolidate, and retrieve episodic memories remains a fundamental question in cognitive neuroscience. Non-invasive brain stimulation (NIBS) methods, especially transcranial magnetic stimulation (TMS), have advanced episodic memory research beyond traditional lesion studies and neuroimaging by enabling causal investigations through targeted magnetic stimulation to specific brain regions. This review begins by delineating the evolving understanding of episodic memory from both psychological and neurobiological perspectives and discusses the brain networks supporting episodic memory processes. Then, we review studies that employed TMS to modulate episodic memory, with the aim of identifying potential cortical regions that could be used as stimulation sites to modulate episodic memory networks. We conclude with the implications and prospects of using NIBS to understand episodic memory mechanisms.
Humans ; Memory, Episodic ; Transcranial Magnetic Stimulation/methods* ; Brain/physiology* ; Nerve Net/physiology* ; Mental Recall/physiology* ; Neural Pathways/physiology*