Despite breakthroughs in immunotherapy for solid tumors, significant variations in treatment efficacy persist. Up to 80% of cancer patients suffer from malnutrition, which leads to: lymphoid atrophy and reduced T-cell reserves; deficiency of substrates required for T-cell activation and expansion; concurrent inflammation hindering T-cell infiltration into tumors; and cachexia accelerating PD-1 antibody clearance. Clinical studies confirm that severe malnutrition significantly impairs immune responses and increases the risk of treatment toxicity. Therefore, implementing standardized nutritional therapy is crucial for optimizing the reserve, activation, expansion, and infiltration capacity of immune cells, thereby providing a sound immune system foundation for immunotherapy. Immunonutrition therapy, by enhancing immunonutrients such as arginine, omega-3 polyunsaturated fatty acids, and nucleotides, reduces the secretion of pro-inflammatory mediators and promotes T-cell activation and proliferation. This enhances anti-tumor immune responses, prolongs survival, and advances cancer treatment towards multimodal combination and precision approaches.

Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

By reviewing the physical biological research on the activation of acupoint effects by acupuncture， this paper explains the activation mechanism from the perspective of the generation and transmission of mechanical signals caused by acupuncture， and reveals the physical-chemical coupling processes in the acupoint microenvironment. Future research should focus on locally mechanosensitive cells， further exploring how acupuncture mechanical signals trigger dynamic changes in cells and molecules in the acupoints， and the physical-chemical information transduction mechanism， which will provide scientific evidence for the acupoint activation during acupuncture. Related studies will contribute to a deeper understanding of the scientific principles behind acupuncture and promote its clinical application and development.

Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

Objective To investigate the protective effects of butyrate on sepsis-related myocardial dys-function.Methods Thirty healthy 8-week-old male Sprague-Dawley rats were randomly divided into three groups:sham operation group(SH,n=10),sepsis group(CL,n=10),and butyrate group(BU,n=10).The CL and BU groups underwent cecal ligation and puncture(CLP)to establish sepsis models,while the SH group received the same surgical procedure without cecal ligation or puncture.Within 30 minutes post-opera-tion,the SH and CL groups received 5 mL normal saline via gavage,whereas the BU group was administered 5 mL sodium butyrate solution(500 mg/kg)in normal saline.Cardiac output(CO)and ejection fraction(EF)were compared among the three groups.Myocardial histopathological injury was assessed by HE staining,and mitochondrial ultrastructural damage was observed by electron microscopy.Serum levels of brain natriuretic peptide(BNP),cardiac troponin Ⅰ(cTnⅠ),and butyrate were compared among groups.Western blot analysis was performed to detect and compare the expression levels of long-chain acyl-CoA synthetase 4(ACSL4)and glutathione peroxidase 4(GPX4)in myocardial tissues.Results After intervention,the BNP and cTnⅠ levels in the CL group were higher than those in the SH group,while CO and EF were lower than those in the SH group(P＜0.05).The BNP and cTnⅠ levels in the BU group were lower than those in the CL group,whereas CO and EF levels were higher than those in the CL group(P＜0.05).HE staining of myocardial tissues re-vealed more severe inflammatory cell infiltration and myocardial cell edema in the CL group compared with the SH group,while the BU group showed reduced inflammatory cell infiltration.Mitochondrial membrane in-tegrity was impaired in the CL group manifested by unclear cristae,swelling,vacuolar degeneration and rup-ture,whereas mitochondrial damage was attenuated in the BU group.Serum butyrate levels were measured as(61.7±21.6)μg/mL,(95.3±16.6)μg/mL and(302.2±49.7)μg/mL in the CL,SH and BU groups respec-tively(P＜0.05).The ACSL4 expression in the CL group was higher than that in the SH group,while GPX4 protein expression was lower than that in the SH group(P＜0.05).The BU group exhibited lower ACSL4 expression and higher GPX4 protein expression compared with the CL group(P＜0.05).Conclusion Buty-rate can ameliorate myocardial injury in septic rats,and its protective effect may be associated with the inhibi-tion of myocardial ferroptosis.

OBJECTIVE To compare the hepatotoxicity of raw Polygonum cuspidatum and its vinegar-processed， ginger- processed， and wine-processed products in mice. METHODS Acute toxicity was assessed using the maximum tolerated dose approach. Male Kunming mice were randomly assigned to blank group， raw drug group， vinegar-processed group， ginger-processed group and wine-processed group， with 16 mice in each group. Mice in the treatment groups received oral gavage of the corresponding preparation at a total dose of 192 g/kg （single gavage volume of 40 mL/kg， administered three times at 5-hour interval）. During the experiment， the mortality and general condition of mice in each group were observed. Eight mice from each group were sacrificed at 48 hours， and the remaining eight at 14 days after the last administration. Organ coefficients， serum biochemical indices and liver histopathology were compared among the groups. RESULTS No mortality was observed in any group throughout the study. At 4 hours after the last administration， mice in all treatment groups exhibited transient alterations in urine and feces， which resolved at 14 days after the last administration. No significant differences in body weight or average food intake were observed among groups at any time point （P＞0.05）. At 48 hours after the last administration， all treatment groups showed varying degrees of liver injury， most severe in the wine-processed group， followed by the raw drug group， and mildest in the vinegar- processed group. Compared with the blank group， liver coefficients were significantly elevated in the wine-processed group， while serum levels of alanine transaminase， aspartate transaminase， total bilirubin （TBil） and alkaline phosphatase （ALP） were significantly increased in the raw drug and wine-processed groups. Additionally， the serum levels of TBil and ALP were significantly elevated in the ginger-processed group （P＜0.05）. At 14 days after the last administration， liver histopathology and all quantitative indicators showed partial recovery. Serum levels of liver function parameters were markedly reduced compared with 48 hours after the last administration （P＜0.05）. CONCLUSIONS Both raw and processed P. cuspidatum exhibit hepatotoxicity， which is closely associated with the processing method， and the severity of hepatotoxicity follows the order： wine-processed product＞raw product＞ginger-processed product＞vinegar- processed product.

Neoadjuvant therapy for pancreatic cancer is undergoing a paradigm shift from conventional chemotherapy to precision medicine. This expert forum discussed cutting-edge issues in pancreatic cancer neoadjuvant therapy from an evidence-based perspective, incorporating the latest clinical research advances. We focused on innovative directions including immunotherapy combination strategies, liquid biopsy applications, artificial intelligence (AI)-assisted decision making, and individualized precision medicine. We proposed forward-looking concepts such as molecular subtyping-guided individualized treatment strategies, multi-omics integrated efficacy prediction models, and standardized multidisciplinary collaborative care systems. These innovative concepts will drive pancreatic cancer neoadjuvant therapy toward more precise and effective directions.

Objective:To investigate the impact of blood pressure outcomes on the risk of arteriosclerosis in non-hypertensive populations.Methods:This study was a retrospective cohort study. All data were derived from Kailuan Cohort. Non-hypertensive individuals who completed two brachial-ankle pulse wave velocity (baPWV) measurements between January 2014 and December 2019 (using the first measurement as the baseline and the second as the follow-up) were enrolled, and clinical data such as blood pressure and baPWV were collected. According to the blood pressure level at baseline and follow-up, participants were divided into new-onset hypertension group (no hypertension at baseline but diagnosed at follow-up) and non-hypertension group (no hypertension at both baseline and follow-up). Multiple linear regression and multivariate logistic regression were used to analyze the impact of new-onset hypertension on arteriosclerosis progression. Subgroup analysis further classified participants into six blood pressure transition categories: normal-maintained, normal-to-high-normal, normal-to-hypertensive, high-normal-to-normal, high-normal-maintained, and high-normal-to-hypertensive groups. Multivariate logistic regression analysis was used to assess the impact of different blood pressure outcomes on arteriosclerosis progression.Results:A total of 7 049 participants were enrolled, with the age of (40.45±9.04) years, including 3 645 males (51.71%). There were 800 cases in the new-onset hypertension group and 6 249 individuals in the non-hypertension group. During follow-up, arteriosclerosis occurred in 2 154 cases (30.56%). Multivariable linear regression analysis revealed a positive correlation between new-onset hypertension and baPWV levels. The baPWV in the new-onset hypertension group was significantly higher by 63.94 cm/s compared to the non-hypertension group ( β=63.94, P<0.01). Additionally, the risk of arteriosclerosis in the new-onset hypertension group was 2.09 times that of the non-hypertension group ( OR=2.09, 95% CI: 1.77-2.46, P<0.01). Subgroup analysis revealed significantly higher arteriosclerosis risks in normal-to-high-normal ( OR=1.65, 95% CI 1.38-1.98, P<0.01), normal-to-hypertensive ( OR=2.47, 95% CI 1.70-3.59, P<0.01), high-normal-maintained ( OR=1.50, 95% CI 1.21-1.86, P<0.01), and high-normal-to-hypertensive groups ( OR=2.86, 95% CI 2.20-3.73, P<0.01) than normal-maintained group, except for a non-significant difference in high-normal-to-normal group ( OR=0.95, 95% CI 0.74-1.20, P>0.05). Conclusion:Blood pressure outcome in non-hypertensive populations is closely related to arteriosclerosis risk. Progression to or maintenance of high-normal blood pressure or higher levels substantially increases arteriosclerosis risk, while regression from high-normal to normal blood pressure shows no significant increase in arteriosclerosis risk.

Objective:To investigate the relationship between protein tyrosine phosphatase non-receptor type 1 (PTPN1) gene polymorphism and the risk of gestational diabetes mellitus (GDM).Methods:In this case-control study, 4 835 pregnant women who delivered from March, 2012 to July, 2014 in the Department of Gynecology and Obstetrics at the First Hospital of Shanxi Medical University were consecutively enrolled. Among them, 789 cases were diagnosed with GDM. A simple random sampling method was used to select 334 pregnant women with GDM as the case group, and 334 healthy pregnant women matched by maternal age, gestation time and residence were set as control. The DNA genotyping was performed in the subjects, and those with genotyping deletions10% were excluded; and finally, 322 and 317 subjects were included in case and control group, respectively. Under the codominant, dominant, recessive, and allelic genetic models, the unconditional logistic regression model was used to check the relationship between 13 candidate single nucleotide polymorphism (snp) loci in PTPN1 gene and the risk of GDM. The Haploview was used to analyze the relationship between haplotypes and risk of GDM, and multiple comparisons were adjusted with the false discovery rate (FDR) method.Results:The age of the 639 pregnant women analyzed in this study was (30.28±4.32) years. The proportions of pre-pregnancy body mass index (BMI)≥24.0 kg/m 2 and having a family history of diabetes were significantly higher in the GDM group compared to those in the control group (29.19% vs 16.72% and 13.04% vs 6.31%, respectively, both P0.05). The rs6096644 locus was positively associated with increased risk of GDM in co-dominant (GG vs AA, OR=2.76, 95% CI: 1.18-6.44) and recessive (GG vs AA+AG, OR=2.78, 95% CI: 1.20-6.46) genetic models (all q0.2). The rs6096655 locus was positively associated with increased risk of GDM in codominant (AA vs GG, OR=5.90, 95% CI: 1.27-27.36) and recessive (AA vs GG+GA, OR=5.50, 95% CI: 1.19-25.38) and alleles (A vs G, OR=1.51, 95% CI: 1.09-2.08) genetic models (all q0.2). The rs6013317 locus was associated with an increased risk of GDM in the allele (A vs G, OR=1.74, 95% CI: 1.15-2.63) genetic model (all q0.2). The GAGG haplotype and GGAG haplotype in haplotype block 1 (rs4811262, rs6096646, rs6096655, rs6013317), and the GGGA haplotype in haplotype block 2 (rs6068018, rs6123105, rs6013324, rs2869621) of the PTPN1 gene were all positively associated with an increased risk of GDM (all P0.05). Conclusion:PTPN1 gene polymorphisms may associated with risk of GDM, moreover, complex haplotype structures within the gene influence the risk of GDM.

Objective:To analyze the correlation between bone metabolism marker β-CTX and metabolic dysfunction-associated fatty liver disease (MAFLD) in postmenopausal women with type 2 diabetes mellitus (T2DM).Methods:In this retrospective cohort study, a total of 279 postmenopausal women with T2DM who were admitted to the Endocrinology Department of Shanxi Bethune Hospital from February 2023 to February 2024 were included. Among them, 152 patients had MAFLD. The bone metabolism markers were measured in all the subjects. The logistic regression analysis was used to assess the correlation between β-CTX and the risk of MAFLD.Results:In postmenopausal T2DM women, serum β-CTX level in the MAFLD group [352.50 (248.60, 442.95)pg/ml ] was significantly lower than that in the non-MAFLD group [643.20 (446.10, 781.90) pg/ml]( Z=-10.896, P0.05). Binary logistic regression analysis revealed that reduced β-CTX( OR=0.986, 95% CI:0.981-0.991), BMI( OR=1.232, 95% CI: 1.046-1.451) and fasting insulin (FINS)( OR=1.155, 95% CI: 1.041-1.281) were independent risk factors for the risk of MAFLD in postmenopausal T2DM women (all P0.05), and β-CTX was negatively correlated with the occurrence of MAFLD ( β=-0.013, P0.001). Additionally, in postmenopausal T2DM women with MAFLD, serum β-CTX level was significantly negatively correlated with BMI ( r=-0.191) and TG ( r=-0.128) (both P0.05). Conclusions:The bone metabolism index β-CTX in postmenopausal women with T2DM is significantly negatively correlated with the risk of MAFLD.