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.

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

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 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.

A 67-year-old male had undergone bilateral lung transplantation for chronic obstructive pulmonary disease 11 months before the current presentation. He was admitted with a 5-day history of cough with sputum, and a 2-day history of fever. Computed tomography (CT) of the chest revealed rapidly progressive bilateral diffuse "ground glass" opacities. Despite anti-infective therapy and methylprednisolone pulse therapy, his condition deteriorated, necessitating endotracheal intubation with mechanical ventilation and veno-venous extracorporeal membrane oxygenation (V-V ECMO) for life support. A bedside cryobiopsy was undertaken, with pathology confirming the organizing pneumonia diagnosis. Comprehensive treatment was continued: methylprednisolone, tacrolimus for immunosuppression, and prophylactic anti-infectives. His partial pressure of oxygen in the blood by the fraction of inspired oxygen ratio and imaging findings improved gradually. ECMO support was discontinued after 2 weeks, and he was discharged 1-month later, resuming normal daily activities. At 2-month follow-up, he exhibited improved exercise tolerance. Chest CT showed bilateral upper-lobe emphysema (predominantly upper-lobe reticular shadows) and significant bilateral upper-lobe pleural thickening. After 12 months of fllow-up, a diagnosis of chronic lung allograft dysfunction was made based on imaging findings and the trajectory of pulmonary function.