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 establish a pediatric rare disease catalog,analyze the current status of therapeutic drugs and their coverage of the medical insurance in China,and propose strategies to enhance drug accessibility.Methods Pediatric rare diseases were identified from China's two national rare disease catalogs combined with the EU Orphanet database,US FDA orphan drug database,and the Diagnosis and Treatment Standards for Rare Diseases in Children.We created a specialized drug catalog for pediatric rare diseases,then analyzed drug types(ATC classification),pricing,and medical insurance coverage using descriptive statistics based on Yaozhi.com drug bidding prices and the 2024 Drug of List National Basic Medical Insurance(NBMIDL).Drug affordability was assessed through annual treatment cost calculations.Results The national catalogs included 151 pediatric rare diseases(72.95%of listed conditions),spanning 13 disease systems.We identified 94 dedicated orphan drugs(by generic name)for these conditions,among which 43 were approved internationally but unavailable in China.The average unit price per package was 6 113.53 yuan.Overall NBMIDL coverage was 68.83%,but drugs priced above 7 000 yuan per unit had only 7.69%coverage.Annual treatment costs reached 4.54 million for laronidase(mucopolysaccharidosis).Conclusions Critical gaps persist in China's pediatric rare disease treatment landscape,including catalog deficiencies,inadequate coverage for high-cost drugs and insufficient domestic innovation.It is recommended to establish a list of orphan drugs for pediatric rare diseases,accelerate the import of foreign drugs and the local innovative drugs through policy incentives,optimizing medical insurance reimbursement mechanisms for pediatric rare disease drugs to comprehensively improve therapeutic accessibility.

Objective To explore the relationship between the degree of compression and shape grading of the cerebral cistern ambiens in hypertensive cerebral hemorrhage(HCH)patients after neural endoscopic intracranial hematoma evacuation(NEIHE)and prognosis.Methods 246 HCH patients who underwent NEIHE surgery from January 2020 to June 2023 were selected as the research subjects.According to the postoperative 6 month Glasgow outcome score(GOS),the patients were divided into good prognosis group(n=158)and poor prognosis group(n=88).Hierarchical regression model was used to analyze the relationship between clinical pathological features and the degree of compression and shape grading of the cerebral cistern ambiens.Multivariate logistic regression model was used to analyze the independent risk factors affecting the poor prognosis of patients with HCH after NEIHE,and a prediction model was constructed.Receiver operating characteristic curve(ROC curve)was drawn with poor prognosis as the outcome variable.Area under the curve(AUC),integrated discrimination improvement(IDI)and net reclassification improvement(NRI)of different prediction models were compared.Hosmer-Lemeshow was used to test the goodness of fit.Generalized additive model(GAM)was used to analyze the relationship between GOS and related factors.Results Compared with the good prognosis group,the poor prognosis group had more preoperative blood loss,lower preoperative Glasgow coma score(GCS),and higher proportion of patients with midline deviation,hypertension history ≥10 years,hemorrhage breaking into the brain ventricle,and operation time in the late stage,the differences were statistically significant(P＜0.05).Compared with the good prognosis group,the proportions of patients with ipsilateral and contralateral cerebral cistern ambiens compression of 3 to 4 points and the morphological classification of cerebral cistern ambiens of grade V in the poor prognosis group were higher,and the differences were statistically significant(P＜0.05).The location of bleeding,midline deviation,and intracranial pressure all had an impact on the degree of compression and morphological grading of the cerebral cistern ambiens,and the differences were statistically significant(P＜0.05).Multivariate Logistic regression analysis(model 2:including the degree of compression and shape grading of the cerebral cistern ambiens)showed that midline deviation,history of hypertension ≥10 years,preoperative bleeding volume＞37 mL,bleeding into the brain ventricles,preoperative GCS＜7 points,late surgical timing,degree of compression of the cerebral cistern ambiens(3 to 4 points on the same side of hematoma,3 to 4 points on the opposite side of hematoma),and grade V morphology were all risk factors influencing the poor prognosis of patients with HCH after NEIHE(P＜0.05).After incorporating the degree of compression and morphological grading of the cerebral cistern ambiens into model 1(excluding the degree of compression and shape grading of the cerebral cistern ambiens),the AUC increased to 0.812(95％CI:0.763～0.872),and both the IDI(0.081,95％CI:0.049～0.095)and NRI(0.611,95％CI:0.510～0.674)of the model improved,with statistically significant differences(P＜0.05).Compared with model 1,model 2 showed an increase in AUC(0.826,95％CI:0.771～0.863),IDI(0.085,95％CI:0.052～0.110),and NRI(0.628,95％CI:0.510～0.709),with statistically significant differences(P＜0.05).The Hosmer-Lemeshow test showed that model 2(P=0.878)had a better fit for predicting poor prognosis than model 1(P=0.691).GAM analysis showed that the higher the degree of compression and morphological grading of the cerebral cistern ambiens,the lower the GOS,and the difference was statistically significant(P＜0.05).ROC curve analysis showed that the combined application of degree of compression and morphological grading of the cerebral cistern ambiens had a high predictive value for poor prognosis,with AUC of 0.935(95％CI:0.890～0.971),sensitivity of 70.26％,and specificity of 93.84％.Conclusion The degree of compression and shape changes of the cerebral cistern ambiens in HCH patients after NEIHE are closely related to prognosis,and the combined application has certain predictive value for poor prognosis.The location of bleeding,midline deviation,intracranial pressure,and other factors significantly affect the compression degree and shape change of the cerebral cistern ambiens.

Type Ⅳ cardiorenal syndrome(CRS)is a subtype of CRS characterized by cardiac structural damage and/or functional decline secondary to chronic kidney disease.Clinically,it often manifests as fatigue,shortness of breath,edema,oliguria,and difficulty lying flat at night,which align with the TCM pattern of"deficiency of primordial qi and excess of yin-pathogenic fire".Li Dongyuan proposed the theory that"yin-pathogenic fire and primordial qi are opposites",emphasizing the dynamic relationship of"mutual growth and decline"between primordial qi and yin fire.From this perspective,the development and progression of Type Ⅳ CRS are believed to correspond to the fluctuations in the balance of primordial qi and yin-pathogenic fire.Based on this theory,the core pathogenesis of Type Ⅳ CRS is summarized as"imbalance between qi and fire",where"deficiency of primordial qi"is the root cause,often attributed to damage to the heart,spleen,and kidney,while"exuberance of yin-pathogenic fire"represents the pathological manifestation.In clinical practice,the treatment should focus on reinforcing primordial qi and subduing yin-pathogenic fire,with tailored approaches according to the stages of disease progression.In the early stage,when primordial qi lacks a foundation for generation and yin-pathogenic fire begins to emerge,the treatment should aim to consolidate the root of primordial qi and suppress the budding of yin-pathogenic fire.In the middle stage,when primordial qi is insufficiently produced and yin-pathogenic fire becomes predominant,the treatment should focus on nourishing the source of primordial qi and curbing the exuberance of yin-pathogenic fire.In the late stage,when primordial qi becomes dispersed and yin-pathogenic fire is unconstrained,the treatment should prioritize consolidating the foundation of primordial qi and restraining the chaotic movement of yin-pathogenic fire.

Type Ⅳ cardiorenal syndrome(CRS)is a subtype of CRS characterized by cardiac structural damage and/or functional decline secondary to chronic kidney disease.Clinically,it often manifests as fatigue,shortness of breath,edema,oliguria,and difficulty lying flat at night,which align with the TCM pattern of"deficiency of primordial qi and excess of yin-pathogenic fire".Li Dongyuan proposed the theory that"yin-pathogenic fire and primordial qi are opposites",emphasizing the dynamic relationship of"mutual growth and decline"between primordial qi and yin fire.From this perspective,the development and progression of Type Ⅳ CRS are believed to correspond to the fluctuations in the balance of primordial qi and yin-pathogenic fire.Based on this theory,the core pathogenesis of Type Ⅳ CRS is summarized as"imbalance between qi and fire",where"deficiency of primordial qi"is the root cause,often attributed to damage to the heart,spleen,and kidney,while"exuberance of yin-pathogenic fire"represents the pathological manifestation.In clinical practice,the treatment should focus on reinforcing primordial qi and subduing yin-pathogenic fire,with tailored approaches according to the stages of disease progression.In the early stage,when primordial qi lacks a foundation for generation and yin-pathogenic fire begins to emerge,the treatment should aim to consolidate the root of primordial qi and suppress the budding of yin-pathogenic fire.In the middle stage,when primordial qi is insufficiently produced and yin-pathogenic fire becomes predominant,the treatment should focus on nourishing the source of primordial qi and curbing the exuberance of yin-pathogenic fire.In the late stage,when primordial qi becomes dispersed and yin-pathogenic fire is unconstrained,the treatment should prioritize consolidating the foundation of primordial qi and restraining the chaotic movement of yin-pathogenic fire.