ObjectiveTo explore the effects of Wumeiwan on liver metastasis and lung metastasis of colorectal cancer and its potential mechanism. MethodsFirstly， mice were randomized into control， low-dose （20 g·kg^-1） Wumeiwan， high-dose （40 g·kg^-1） Wumeiwan， and paclitaxel （10 mg·kg^-1） groups. Secondly， liver metastasis and lung metastasis models of colorectal cancer were established in mice. After 4 weeks of intervention， the body weight of each mouse was recorded， and the lung weight， liver weight， and survival time of mice with metastatic colorectal cancer were determined. Hematoxylin-eosin （HE） staining was employed to detect the effects of Wumeiwan on liver metastasis and lung metastasis. Real-time PCR was employed to determine the mRNA levels of M1 and M2 macrophage markers in the liver tissue. Finally， the content of M1 macrophage markers CD80 and CD86 in the liver tissue was measured by flow cytometry. ResultsCompared with the control group， Wumeiwan and paclitaxel reduced the body weight （P<0.01） and liver weight （P<0.01） and prolonged the survival of the mouse model of liver metastasis of colorectal cancer （P<0.01）. In the mouse model of lung metastasis of colorectal cancer， Wumeiwan and paclitaxel also reduced the body weight （P<0.01） and lung weight （P<0.01） and extended the survival time （P<0.01）. Histopathological results showed that compared with the control group， Wumeiwan inhibited the liver and lung metastases of colorectal cancer. Real-time PCR results showed that compared with the control group， Wumeiwan upregulated the mRNA levels of M1 macrophage markers IL-1β， IL-6， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and prostaglandin-endoperoxide synthase 2 （PTGS2） in the liver and lung tissue of mice with liver metastasis and lung metastasis of colorectal cancer （P<0.01）. Meanwhile， Wumeiwan downregulated the mRNA levels of M2 macrophage markers Arg1， CD163， and CD206 （P<0.01）. Meanwhile， the flow cytometry results showed that compared with the control group， Wumeiwan increased the content of CD86 and CD80 （P<0.01）. In addition， immunohistochemical results showed that Wumeiwan promoted the expression of CD86 and inhibited the expression of CD206 in the liver and lung tissue of mice with liver metastasis and lung metastasis. ConclusionWumeiwan can inhibit the liver metastasis and lung metastasis of colorectal cancer by promoting the M1 polarization of macrophages in the liver and lung of the model mice.

ObjectiveTo evaluate the clinical efficacy and safety of Jingmaiyan granules （composed of Lonicerae Japonicae Flos， Sedi Herba， Paeoniae Radix Rubra， Moutan Cortex， Rhei Radix et Rhizoma Praeparata， and Glycyrrhizae Radix et Rhizoma） combined with external application of Jinhuang Ointment in treating acute-stage blood heat stasis type superficial thrombophlebitis （ST） of lower extremities， and to explore their effects on hemorheology and serum inflammatory factors. MethodsA randomized， double-blind， placebo-controlled clinical trial was conducted. A total of 124 patients with lower extremity ST were randomized into two groups（62 cases in each group）. The control group received external application of Jinhuang ointment and oral placebo treatment， while the observation group received external application of Jinhuang ointment and oral Jingmaiyan granules. Both groups were treated for 2 weeks. The clinical symptom scores， therapeutic efficacy of traditional Chinese medicine （TCM） syndrome， pain visual analog scale （VAS） scores， hemorheological indices ［including whole blood high-shear， medium-shear， and low-shear viscosity， as well as plasma viscosity （PV）］， and inflammatory factors ［C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）］ were compared before and after treatment. ResultsAfter 2 weeks of treatment， the total effective rate in the observation group （98.3%， 60/62） was significantly higher than that in the control group （83.8%， 52/62）， with a statistically significant difference （Z=3.512 1， P<0.05）. Compared with pre-treatment scores， the scores for skin color， skin temperature， swelling， pain， and cord or nodules were significantly reduced in both groups （P<0.05）， with more pronounced improvement in the observation group （P<0.05）. Additionally， compared with pre-treatment levels， the whole blood viscosity （low-， medium-， and high-shear） significantly improved in both groups after treatment （P<0.05）， with more marked improvement in the observation group （P<0.05）. Furthermore， the plasma viscosity， CRP， IL-6， and TNF-α levels were significantly reduced in both groups after treatment （P<0.05）， with more pronounced improvement observed in the observation group （P<0.05）. ConclusionThe combination of external application of Jinhuang ointment and oral Jingmaiyan granules effectively improves clinical symptoms， hemorheological abnormalities， and inflammatory responses in patients with acute stage blood heat stasis type ST of lower extremities. The treatment is safe and holds clinical promotion value.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

Recently， Asian Pacific Association for the Study of the Liver published the recommendations for the diagnosis and management of non-cirrhotic portal fibrosis （NCPF）/idiopathic portal hypertension （IPH）. The guidelines mainly elaborate on the definition， diagnosis， histological features， natural history， and management of NCPF/IPH， in order to strengthen the understanding of NCPF/IPH-related issues and establish a global consensus. This article makes an excerpt of the key statements in the guidelines.

ObjectiveTo observe the effects of the Fuyuan Tongluo prescription （composed of Astragali Radix， Carthami Flos， Spatholobi Caulis， Liquidambaris Fructus， Lycopodii Herba， Centellae Herba， etc.） in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans， and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group （n₁=44） received dual antiplatelet therapy with aspirin and clopidogrel. The observation group （n₂=44） was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate， symptom scores， ankle-brachial index （ABI）， coagulation function， and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate， after 36 weeks of treatment， the observation group had a significantly better primary patency rate than the control group （χ²=4.14，P<0.05）. After 24 weeks of treatment， there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison： Based on symptom quantification scores， and using the Nimodipine method as a reference， the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment （χ²=2.24，P<0.05）. ABI levels： The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment （P<0.05）. Coagulation function indicators： After 24 and 36 weeks of treatment， D-dimer and fibrinogen levels in both groups were lower than before treatment （P<0.05）. Inflammatory markers： After 24 and 36 weeks of treatment， CRP levels in the observation group were lower than those in the control group （P<0.05）. There were no significant differences in white blood cell （WBC） and erythrocyte sedimentation rate （ESR） levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms， demonstrating clinical application value.

To systematically review randomized controlled trials （RCTs） of traditional Chinese medicine （TCM） intervention in ulcerative colitis （UC）， and analyze the characteristics of these studies and their outcome indicators， thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed， and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included， with a sample size of 44 853 participants. The largest sample size was 218 cases， and the smallest was 28 cases， with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types， the top three were large intestine dampness-heat syndrome （31.05%）， spleen and kidney yang deficiency syndrome （12.47%）， and spleen deficiency with dampness syndrome （9.17%）. The interventions， ranked by frequency of use， included internal Chinese medicine compounds/preparations （64.5%）， Chinese medicine compounds/preparations with retained enema （18.2%）， internal Chinese medicine compounds/preparations + external TCM treatment （5.95%）， and external TCM treatment alone （4.86%）. The treatment duration was mainly 4-8 weeks （64.86%）， with 61 studies （10.99%） reporting follow-up time. A total of 157 outcome indicators were used， with a frequency of 3 460 occurrences， classified into six domains： TCM syndromes and symptoms （346 occurrences， 10%）， symptoms/signs （541 occurrences， 15.64%）， physical and chemical examinations （2 119 occurrences， 61.24%）， quality of life （107 occurrences， 3.09%）， long-term prognosis （61 occurrences， 1.76%）， and safety events （284 occurrences， 8.21%）. The analysis reveals several limitations in the outcome indicators of TCM intervention in UC， including the lack of a basis for sample size calculation， non-standardized TCM syndrome classification， absence of trial design and registration， inadequate blinding and allocation concealment， adherence issues with interventions， imbalanced selection of surrogate and endpoint indicators， inconsistency in the timing of outcome measurements， design issues that require standardization， and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification， clear efficacy evaluation indicators， key endpoint indicators， and reasonable measurement time points. Long-term prognostic impacts， comprehensive assessments of patients' quality of life， and consideration of economic benefits should be emphasized， providing a basis for the clinical practice of TCM in the treatment of UC.

ObjectiveTo observe the effects of the Fuyuan Tongluo prescription （composed of Astragali Radix， Carthami Flos， Spatholobi Caulis， Liquidambaris Fructus， Lycopodii Herba， Centellae Herba， etc.） in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans， and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group （n₁=44） received dual antiplatelet therapy with aspirin and clopidogrel. The observation group （n₂=44） was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate， symptom scores， ankle-brachial index （ABI）， coagulation function， and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate， after 36 weeks of treatment， the observation group had a significantly better primary patency rate than the control group （χ²=4.14，P<0.05）. After 24 weeks of treatment， there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison： Based on symptom quantification scores， and using the Nimodipine method as a reference， the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment （χ²=2.24，P<0.05）. ABI levels： The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment （P<0.05）. Coagulation function indicators： After 24 and 36 weeks of treatment， D-dimer and fibrinogen levels in both groups were lower than before treatment （P<0.05）. Inflammatory markers： After 24 and 36 weeks of treatment， CRP levels in the observation group were lower than those in the control group （P<0.05）. There were no significant differences in white blood cell （WBC） and erythrocyte sedimentation rate （ESR） levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms， demonstrating clinical application value.

To systematically review randomized controlled trials （RCTs） of traditional Chinese medicine （TCM） intervention in ulcerative colitis （UC）， and analyze the characteristics of these studies and their outcome indicators， thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed， and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included， with a sample size of 44 853 participants. The largest sample size was 218 cases， and the smallest was 28 cases， with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types， the top three were large intestine dampness-heat syndrome （31.05%）， spleen and kidney yang deficiency syndrome （12.47%）， and spleen deficiency with dampness syndrome （9.17%）. The interventions， ranked by frequency of use， included internal Chinese medicine compounds/preparations （64.5%）， Chinese medicine compounds/preparations with retained enema （18.2%）， internal Chinese medicine compounds/preparations + external TCM treatment （5.95%）， and external TCM treatment alone （4.86%）. The treatment duration was mainly 4-8 weeks （64.86%）， with 61 studies （10.99%） reporting follow-up time. A total of 157 outcome indicators were used， with a frequency of 3 460 occurrences， classified into six domains： TCM syndromes and symptoms （346 occurrences， 10%）， symptoms/signs （541 occurrences， 15.64%）， physical and chemical examinations （2 119 occurrences， 61.24%）， quality of life （107 occurrences， 3.09%）， long-term prognosis （61 occurrences， 1.76%）， and safety events （284 occurrences， 8.21%）. The analysis reveals several limitations in the outcome indicators of TCM intervention in UC， including the lack of a basis for sample size calculation， non-standardized TCM syndrome classification， absence of trial design and registration， inadequate blinding and allocation concealment， adherence issues with interventions， imbalanced selection of surrogate and endpoint indicators， inconsistency in the timing of outcome measurements， design issues that require standardization， and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification， clear efficacy evaluation indicators， key endpoint indicators， and reasonable measurement time points. Long-term prognostic impacts， comprehensive assessments of patients' quality of life， and consideration of economic benefits should be emphasized， providing a basis for the clinical practice of TCM in the treatment of UC.