OBJECTIVE To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）. METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （P＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail：stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down- regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （P＜0.05）. CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.

This paper summarizes the experience of professor LIU Shangyi in differentiating and treating rectal carcinoma from the perspective of "treating ulcers as tumors". It is believed that the manifestations of rectal cancer， such as anal itching， cauliflower-like or ulcerative tumors， and bloody stools， are similar to external skin itching， skin ulceration， swelling， and skin bleeding. Therefore， the treatment principles of sores and ulcers department can be applied to treat tumors. Following the diagnostic and treatment approach of dermatology regarding the clinical typical symptoms， for anal itching， the main treatment is to dispel wind and remove dampness， clear heat to relieve itching， using "skin medicinals" such as Difuzi （Fructus Kochiae） and Baixianpi （Cortex Dictamni）， as well as wind medicinals such as Shengma （Rhizoma Cimicifugae） and Fangfeng （Radix Saposhnikoviae）. For constipation， the method of clearing heat and resolving toxins， unblocking the bowels and discharging heat can be used， commonly using Baitouweng （Radix Pulsatillae）， Donglingcao （Herba Rabdosiae Rubescentis） and Dahuang （Radix et Rhizoma Rhei）. In terms of mucosal ulcers， it is critical to differentiate between yin and yang； the treatment of yang ulcers should focus on clearing heat and resolving toxins， commonly using modified Xianfang Huoming Beverage （仙方活命饮）； for yin ulcers， emphasis should be placed on removing dampness and resolving phlegm， commonly with modified Yiyi Fuzi Baijiang Powder （薏苡附子败酱散）. For bloody stool， differentiation is made between deficiency and excess， with the use of Diyu （Radix Sanguisorbae） and Huaihua （Flos Sophorae） for excess syndrome to cool and stop blee-ding， and both herbs dry-fried until charred combined with liver-tonifying medicinals for deficiency syndrome

BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

This paper explores the immune-inflammatory regulatory mechanism of colorectal cancer cachexia and corresponding traditional Chinese medicine （TCM） intervention strategies based on the TCM theory of reinforcing healthy qi and dispelling pathogenen. It is proposed that depletion of healthy qi is the root cause of colorectal cancer cachexia， while cancer toxins exuberance is the symptomatic manifestation of the disease， and failure of the spleen and stomach is the core pathogenesis. In terms of treatment， a TCM treatment system is constructed based on the principles of reinforcing healthy qi to consolidate the foundation and regulate immunity， and dispelling pathogen to remove toxins and alleviate inflammation. The system clarifies the healty qi-reinforcing method as fortifying spleen and boosting qi to enhance immune function， and nourishing blood and enriching yin to consolidate yin essence and healthy qi. It also emphasizes the pathogen-dispelling method as clearing heat and removing toxins to regulate the secretion of inflammatory cytokines， and promoting blood circulation and resolving stasis to improve the immune microenvironment and microcirculation. This therapeutic approach may provide valuable insights for TCM interventions in colo-rectal cancer cachexia.

BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

Based on the theory of traditional Chinese medicine （TCM） chronomedicine， this paper explores the pathogenesis and treatment strategies of colorectal cancer mediated by circadian rhythm disorders. It is believed that the imbalance of yin and yang is isomorphic to the disorder of biological clock genes， which is the root cause of the disease. The disharmony of ying and wei （营卫） corresponds to the imbalance of immunity and metabolism， which is the pivot of the disease. The disorder of qi movement is related to the imbalance of intestinal barrier， which is the manifestation of the disease. Accordingly， relevant strategies are proposed， including chronochemotherapy regimen that aligns with biological rhythms to enhance efficacy and reduce toxicity， acupuncture based on the ebb and flow of midnight and midday which selects acupoints along meridians to harmonize qi and blood， and a timed medication strategy that matches the disease mechanism by administering drugs at optimal times. These strategies aim to deepen the understanding of the pathogenesis of colorectal cancer mediated by circadian rhythm disorders from the perspective of TCM chronomedicine， thereby providing new ideas for clinical practice.

Objective To explore the correlation between the pathogenesis of toxins damaging liver collateral and the incidence of type 2 diabetes mellitus(T2DM)based on the theory of five circuits and six qi.Methods A total of 986 patients with T2DM treated in the Department of Endocrinology and Metabolism at the Affiliated Hospital of Changchun University of Chinese Medicine from February 2019 to October 2023 were selected as the study subjects.The influences of circuit and qi indicators in the theory of five circuits and six qi on the constitutional characteristics of T2DM patients and the role of pathogenesis of toxins damaging liver collateral in the incidence of T2DM were investigated.Results(1)The five-circuit and six-qi analysis showed that the yearly circuit and sitian/zaiquan conditions had no significant effect on the constitutional characteristics of patients with T2DM(P＞0.05).However,dominant circuit,guest circuit,dominant qi and guest qi significantly influenced the constitutional characteristics of patients with T2DM(P＜0.05).For the distribution of circuit-qi indicators at birth among the 986 patients,dominant circuit was predominated by the terminal circuit of taiyang cold-water,guest circuit was characterized by deficient wood circuit or excessive water circuit,dominant qi was predominated by yangming dry-metal,and guest qi was characterized by taiyin damp-earth.(2)The correlation between the pathogenesis of toxins damaging liver collateral and the incidence of T2DM through comparative analysis revealed that the conveying and dispersing function of the liver plays a leading role in maintaining the body's yin-yang balance and ensuring free movement of qi,indicating that the critical role of toxins damaging liver collateral is the key to the incidence of diabetes.Conclusion Circuit-qi indicators have a certain influence on the constitutional characteristics of T2DM patients.The circuit-qi features at birth of the individuals prone to T2DM are as follows:dominant circuit predominated by the terminal circuit of taiyang cold-water,guest circuit characterized by deficient wood circuit or excessive water circuit,dominant qi being yangming dry-metal,and guest qi being taiyin damp-earth.Pathogenesis of toxins damaging liver collateral is closely related to the incidence of T2DM.Therefore,in treatment,the regulatory role of the liver should be emphasized,and liver-soothing herbs should be used based on syndrome differentiation,aiming for holistic treatment of the physique and the spirit and enhancing the therapeutic efficacy.The exploration will provide a new perspective and approach for the treatment of T2DM.

Objective To evaluate the gap between China's top-tier medical institutions and top-tier international medical institutions,and to provide references for the construction of first-class medical science discipline in China.Methods Using globally recognized rankings of medical institutions,we selected 24 top-tier international medical institutions and 11 top-tier Chinese medical institutions.Publicly available,general,and comparable data on indicators were collected to analyze the performance and gaps between top-tier international and Chinese medical institutions in human resources development,talent cultivation,scientific research,social services,and discipline construction.Results In the field of medicine,the largest gap between top-tier international and Chinese medical institutions was in high-level talent.Specifically,the average numbers of individuals who are Clarivate Analytics'Highly Cited Researchers,who are Nobel Prize laureates in Physiology or Medicine,and who serve on advisory boards or editorial boards of top medical journals,and who rank among the Top 2 000 Medicine Scientists were 1.00,0.09,0.45 and 4.00,respectively,among top-tier Chinese medical institutions,while those of the top-tier international medical institutions were 131.46,118.25,9.72,and 6.76 times,respectively,those of the Chinese medical institutions.The second largest gap was in social services and medical innovation.The average proportion of industrial collaboration papers and the number of clinical trials of China's top-tier medical institutions were 1.51％and 1 851,respectively,while those of international top-tier medical institutions were 3.62 and 1.87,times,respectively,those of top-tier Chinese medical institutions.However,the average number of(untranslated)patents held by top-tier international medical institutions was only 15％ of that of China's top-tier medical institutions.The third largest gap was in scientific research.The average number of papers published in New England Journal of Medicine,Journal of the American Medical Association,The Lancet,and British Medical Journal,the percentage of hot papers in papers included in Web of Science,the percentage of highly cited papers,the percentage of international collaboration papers,the total number of citations per paper,category normalized citation impact(CNCI),and the number of publications of top-tier Chinese medical institutions were 78,0.03％,1.39％,22.55％,19.61,1.26,30 706,while those of the top-tier international medical institutions were 6.96,2.66,2.57,2.15,1.83,1.58 and 1.54 times those of the Chinese medical institutions,respectively.However the average percentage of zero-citation papers of top-tier international medical institutions was only 71％of that of China's top-tier medical institutions.Furthermore,in discipline development,the average overall scores of the Times Higher Education(THE)and QS rankings for medicine-related disciplines of top-tier Chinese medical institutions were 72.84 and 69.30,respectively,while those of top-tier international medical institutions were 1.38 and 1.21 times those of the Chinese medical institutions.However,in terms of talent cultivation,the average number of students of China's top-tier medical institutions was 10724,which is roughly double that of international institutions.Conclusion Currently,China's top-tier medical institutions are still in a basic stage that emphasizes the quality of talent cultivation and medical services.There is considerable room for development and potential for catching up in multiple aspects,especially in high-level talent,medical research,and innovation.It is recommended that the construction experience of top-tier international medical institutions should be fully utilized to build China's first-class medical science discipline.

Objective:To explore the prognosis of patients with gastric cancer peritoneal metastasis (PM) receiving programmed cell death-1 (PD-1) antibody therapy, and investigate the biomarkers that affect the prognosis of anti-PD-1 therapy.Methods:This restrospecific study collected the clinic-pathological data of 56 patients with peritoneal metastasis of gastric cancer who received first-line treatment in the Nanjing Drum Town Hospital from March 2020 to September 2023, among which 41 had received anti-PD-1 immunotherapy and 15 hadn't. The relationship between overall survival (OS) and anti-PD-1 immunotherapy was evaluated by Kaplan-Meier analysis. The relationship between baseline peripheral blood indicators and treatment response of patients with anti-PD-1 treatment was analyzed using unpaired t-test. Subsequently, the Cox proportional risk regression model was used to explore the clinical prognostic factors that may affect anti-PD-1 immunotherapy by univariate and multivariate analysis. The clinical prognostic factors included baseline data and baseline peripheral blood indexes such as anti-PD-1 treatment lines, Eastern Cooperative Oncology Group performance status (ECOG PS), combined positive score (CPS), expression of human epidermal growth factor receptor 2 (Her-2), EBER status, pathological types, other metastatic lesions, ascites content before immunotherapy, with or without abdominal drainage during anti-PD-1 treatment, blood lipid indicators, inflammatory indicators, and tumor indicators. Results:Kaplan-Meier survival statistics showed similar OS (15.9 vs. 15.2 months, P=0.600) in patients with anti-PD-1 therapy compared to those without anti-PD-1 therapy. Patients with baseline high-density lipoprotein (HDL) ≥0.97 mmol/L ( n=22) demonstrated a significantly longer median OS compared to those with HDL＜0.97 mmol/L (15.2 vs. 13.5 months; P=0.018). Similarly, the cohort with apolipoprotein A1 (ApoA1) levels ≥0.86 g/L ( n=21) showed superior survival outcomes, with a median OS of 17.7 months versus 12.3 months in the ApoA1＜0.86 g/L group ( n=20; P=0.006). In contrast, elevated baseline alpha-fetoprotein (AFP) levels ( n=2) were associated with markedly reduced survival (median OS: 5.7 vs. 15.2 months in normal AFP group, n=37; P=0.005). Notably, elevated pretreatment ApoA1 levels correlated with enhanced immunotherapy response ( P=0.017). Multivariate Cox regression analysis revealed that ApoA1 deficiency (≥0.86 g/L) independently predicted better OS following PD-1 antibody therapy ( HR=0.35, 95% CI: 0.12-0.98, P=0.046) in gastric cancer patients with PM. Conclusions:In our study, it is first proposed that ApoA1 could be a significant predictor of the survival advantages of immunotherapy in gastric cancer patients with PM.

The aim of this study is to investigate the inhibitory effects and mechanism of three or-ganic acids,including formic acid(FA),butyric acid(BA)and lactic acid(LA),on the pathogenic-ity of Salmonella enteritidis(SE),Escherichia coli(EC)and Staphylococcus aureus(SA).The growth of pathogens was detected by Minimum Inhibitory Concentration(MIC)and Oxford Cup antimicrobial zone assays.The motility of pathogens was detected by soft agar plate method,and the biofilm of pathogens was detected by crystal violet staining.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to measure the expression levels of genes related to the patho-genicity of SE.The results showed that FA and BA significantly inhibited the growth of SE,EC and SA,and FA had a superior inhibitory effect on EC(MIC:0.25 g/L;inhibition zone:20.0 mm)and SA(MIC:0.5 g/L;inhibition zone:25.0 mm).In addition,the three organic acids significantly inhibited the motility of SE,EC and SA as accessed by swimming and swarming assays,and FA showed the best inhibition effect.Besides,the three organic acids,especially FA,markedly inhibited the biofilm formation of SE,EC and SA.Finally,our results showed that the three organic acids in-hibited the expression of the main virulence genes encoded by SPI-1(InvA,InvF,SopE,SopB,SipB,HilA and SipA),SPI-2(SopD2),pili-related genes(FliF,LpfA,SefA and FimF)and flagellum-related genes(FlhD,FliC and FliD)of SE.This study demonstrates that FA,BA,and LA significantly inhibited the growth and pathogenicity of the four pathogens,among which FA showed the most obvious effect on inhibiting the growth,motility,biofilm formation and virulence gene expression.Our study provided a theoretical basis for the application of organic acids in the field of animal husbandry.