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.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans ; Peptides/pharmacology* ; Animals ; Neoplasms/drug therapy* ; Drug Discovery ; Neurodegenerative Diseases/drug therapy* ; Diabetes Mellitus/drug therapy*

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: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

Objective To investigate the role of matrix GLA protein(MGP)in the pathogenesis of idiopathic calcium oxalate kidney stones(ICOS),and to find potential biomarkers for early diagnosis and disease evaluation.Methods A total of 120 patients admitted to our hospital from September 2021 to September 2023 were prospectively included,of which 60 patients with ICOS were in the calculus group and 60 patients without calculus were in the control group.Serum biochemical indexes and immunohistochemical scores of the two groups were detected,urinary MGP levels were determined by ELISA,and MGP mRNA and protein expression in renal papilla tissues were detected by qPCR and Western blot.The independent risk factors of ICOS were screened by Logistic regression analysis,and the prediction model was drawn by nomogram.Results Compared with control group,urinary MGP content in calculus group was decreased[(1 805.91±244.44)pg/ml vs.(2 014.79±252.14)pg/mnl,P＜0.05).Expression of MGP mRNA and MGP protein in renal papillae decreased(0.89±0.15 vs.1.00±0.00,P=0.001)and decreased(0.87±0.18 vs.1.00±0.00,P＜0.05).MGP immunohistochemical scores of renal tissue were decreased[4(2-6)scores vs.6(4-8)scores,P＜0.001].Multivariate analysis showed that urinary calcium(OR=1.370),urinary MGP(OR=1.127),renal papilla MGP relative expression level(OR=27.532)and renal tissue MGP immunohistochemical score(OR=1.359)were independent risk factors for ICOS.Area under ROC curve of the nomogram prediction model built based on the above factors is 0.839,indicating that the model has good differentiation ability in risk prediction.Conclusion MGP is closely related to the pathogenesis of ICOS.Urinary and renal tissue MGP levels may be potential biomarkers for early diagnosis and disease assessment of ICOS.

Objective To compare the differences in clinical features and treatment choices between periph-eral spondyloarthritis(pSpA)and axial spondyloarthritis(axSpA),and better understand the clinical charac-teristics and medication needs of pSpA.Methods Our study is a retrospective cohort study.The patients who first visited the First Medical Center of Chinese PLA General Hospital between January 2016 and December 2022 and were diagnosed with axSpA or pSpA according to the classification criteria established by the Assess-ment of SpondyloArthritis International Society were selected as the study subjects.Demographic data,clinical characteristics,laboratory tests,and treatment information of these patients were obtained through the electronic medical records management system and the intelligent management system for spondyloarthritis.The research compared the distribution of swollen and tender joints between pSpA and axSpA patients,as well as that between pSpA1(excluding patients with psoriatic arthritis)and axSpA patients.Additionally,we analyzed differences in clinical features and treatment options among these groups.Results A total of 1639 pa-tients were included in the study,of which 184 had pSpA(including 97 with psoriatic arthritis),and 1455 had axSpA.Compared to axSpA patients,pSpA patients had fewer male patients(62.5％vs.79.7％,P＜0.001),later onset age(33.8 years vs.22.0 years,P＜0.001),shorter diagnostic delays(6.0 months vs.14.2 months,P=0.004),more associated peripheral arthritis(71.7％vs.9.3％,P＜0.001)and dac-tylitis(6.5％vs.0.3％,P＜0.001),more cases of psoriasis(52.7％vs.1.1％,P＜0.001)and a more common family history of psoriasis(11.4％vs.3.4％,P＜0.001).pSpA patients had higher levels of in-flammatory markers but a lower positive rate of human leukocyte antigen(HLA)-B27(43.5％vs.87.4％,P＜0.001).A positive HLA-B27 was associated with an earlier onset age,fewer cases of psoriasis,and a fami-ly history of ankylosing spondylitis.pSpA patients had a higher proportion of using conventional synthetic dis-ease-modifying antirheumatic drugs(csDMARDs),biologic disease-modifying antirheumatic drugs(bDMARDs),and oral glucocorticoids,and they also more frequently used a combination of bDMARDs and csDMARDs(19.0％vs.12.2％,P=0.009)or multiple csDMARDs(65.8％vs.12.5％,P＜0.001).Compared to axSpA patients,pSpA1 patients(excluding psoriatic arthritis)did not show significant differences in the prevalence of psoriasis,uveitis,family history of psoriasis,or the use of bDMARDs,but the subgroup analysis of other variables was consistent with the results of pSpA patients.Conclusions pSpA patients tend to have a later onset of disease,a lower proportion of male and HLA-B27 positivity,more associ-ated peripheral arthritis,dactylitis,psoriasis,and a more common family history of psoriasis.The disease bur-den in terms of treatment for pSpA is not lower than that for axSpA.Due to the presence of more peripheral symptoms,psoriasis,and higher levels of inflammation,they also require more medication.

Objective To explore the predictive value of sequential organ failure score(SOFA)combined with serum Clara cell protein 16(CC16)and angipoietin-2(Ang-2)in the prognosis of patients with acute respiratory distress syndrome(ARDS)caused by sepsis.Methods A total of 173 sepsis patients were divided into the concurrent group(n=76)and the non-concurrent group(n=97),based on whether ARDS occurred within 72 h after admission.According to the death situation within 30 days,patients in the concurrent group were divided into the death group(n=35)and the survival group(n=41).Enzyme-linked immunosorbent assay(ELISA)was used to detect serum CC16,Ang-2,C-reactive protein(CRP)and interleukin(IL)-6.The levels of triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)and white blood cell count(WBC)were detected by automatic biochemical analyzer and hemocytometer.SOFA scores were performed on patients at admission.The biochemical indexes,SOFA score,CC16 and Ang-2 levels were compared between the two groups,and the poor prognosis of the patients was analyzed.Binary Logistic regression was used for influencing factor analysis.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of related factors in the poor prognosis of patients with sepsis complicated by ARDS.Results The serum levels of CRP,IL-6,CC16,Ang-2 and SOFA scores were higher in the concurrent group than those in the non-concurrent group(P＜0.05).The SOFA score,mechanical ventilation time,CRP,CC16 and Ang-2 were higher in the death group than those in the survival group(P＜0.05).High SOFA score,CC16 and Ang-2 were independent risk factors for poor prognosis in the concurrent group(P＜0.05).The area under the curve(AUC)of SOFA score,serum CC16 and Ang-2 levels in predicting poor prognosis in patients with sepsis complicated with ARDS were 0.806(0.700-0.888),0.801(0.693-0.884),0.845(0.743-0.918)and 0.945(0.867-0.984),respectively.Conclusion SOFA score combined with changes in CC16 and Ang-2 expression levels can be used to comprehensively evaluate prognosis of patients with sepsis complicated with ARDS.

Objective To explore the predictive value of sequential organ failure score(SOFA)combined with serum Clara cell protein 16(CC16)and angipoietin-2(Ang-2)in the prognosis of patients with acute respiratory distress syndrome(ARDS)caused by sepsis.Methods A total of 173 sepsis patients were divided into the concurrent group(n=76)and the non-concurrent group(n=97),based on whether ARDS occurred within 72 h after admission.According to the death situation within 30 days,patients in the concurrent group were divided into the death group(n=35)and the survival group(n=41).Enzyme-linked immunosorbent assay(ELISA)was used to detect serum CC16,Ang-2,C-reactive protein(CRP)and interleukin(IL)-6.The levels of triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)and white blood cell count(WBC)were detected by automatic biochemical analyzer and hemocytometer.SOFA scores were performed on patients at admission.The biochemical indexes,SOFA score,CC16 and Ang-2 levels were compared between the two groups,and the poor prognosis of the patients was analyzed.Binary Logistic regression was used for influencing factor analysis.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of related factors in the poor prognosis of patients with sepsis complicated by ARDS.Results The serum levels of CRP,IL-6,CC16,Ang-2 and SOFA scores were higher in the concurrent group than those in the non-concurrent group(P＜0.05).The SOFA score,mechanical ventilation time,CRP,CC16 and Ang-2 were higher in the death group than those in the survival group(P＜0.05).High SOFA score,CC16 and Ang-2 were independent risk factors for poor prognosis in the concurrent group(P＜0.05).The area under the curve(AUC)of SOFA score,serum CC16 and Ang-2 levels in predicting poor prognosis in patients with sepsis complicated with ARDS were 0.806(0.700-0.888),0.801(0.693-0.884),0.845(0.743-0.918)and 0.945(0.867-0.984),respectively.Conclusion SOFA score combined with changes in CC16 and Ang-2 expression levels can be used to comprehensively evaluate prognosis of patients with sepsis complicated with ARDS.