Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Objective To observe the effects of auricular point sticking on chronic soft tissue injury of knee joint caused by military training.Methods A total of 77 patients with chronic soft tissue injury of the knee caused by military training admitted to No.901 Hospital of Joint Logistics Support Force from January to November 2022 were enrolled in this study.Auricular point sticking therapy was applied in all the patients.Visual analogue scale(VAS)score,the range of motion of the knees and knee temperature were recorded before and after treatment.Results The VAS score was 6.10±1.23,3.03±0.95,and 2.70±0.93 before treatment,15 min and 24 h after treatment,respectively.The VAS score after treatment were significantly lower than that before treatment(P<0.01).The range of motion of the knees was(79.08±11.59)°,(104.79±8.49)°,and(108.08±9.36)° before treatment,15 min and 24 h after treatment,respectively.The knee flexion after treatment were significantly higher than that before treatment(P<0.01).The knee temperature at 15 min after treatment was significantly higher than that before treatment([30.68±1.38]℃vs.[29.30±1.41]℃,P<0.01).Conclusion Auricular point sticking can reduce the pain of patients with chronic soft tissue injury of the knee and increase the range of joint motion.It is safe and simple and has good compliance.

ObjectiveTaking the oligosaccharides in Rehmanniae Radix（RR） as the research object， the content determination method based on high performance liquid chromatography-evaporative light scattering detection（HPLC-ELSD） and thin layer chromatography（TLC） identification method were established to explore the content and distribution of oligosaccharides in different RR herbs and decoction pieces. MethodA total of 10 batches of fresh and raw RR， 12 batches of RR decoction pieces and Rehmanniae Radix Praeparata（RRP） were collected. A TLC identification method for fructose， sucrose， manninotriose， raffinose and stachyose in RR was established by using silica gel G thin-layer plates with ethyl acetate-water-anhydrous formic acid-glacial acetic acid（12∶6∶5∶4） as the developing agent and 10% sulfuric acid-ethanol solution as chromogenic agent. A HPLC-ELSD was used to determine the contents of fructose， glucose， sucrose， melibiose， raffinose， manninotriose and stachyose in different RR herbs and decoction pieces. Then principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） were used to analyze the contents of 7 kinds of saccharides in RR herbs and decoction pieces， and the differential components were screened with the value of variable importance in the projection（VIP）>1. ResultThe results of TLC identification showed that fresh RR， raw RR and its decoction pieces showed spots of the same color on the corresponding positions with the control products of stachyose， raffinose and sucrose， while the TLC of RRP showed spots of the same color at corresponding positions to manninotriose and fructose controls. The results of methodological investigations of 7 analytes met the requirements of determination. Only glucose， sucrose， raffinose and stachyose were detected in 10 batches of fresh RR and 10 batches of raw RR herbs， the average contents of which were 0.84%， 4.62%， 2.42% and 57.90% in fresh samples， while those were 3.16%， 9.36%， 7.05% and 38.10% in raw samples， respectively. In 12 batches of RR decoction pieces， the contents of the above seven sugars（fructose， glucose， sucrose， melibiose， raffinose， manninotriose and stachyose） were 1.68%， 4.27%， 9.96%， 0.53%， 6.85%， 3.05% and 37.52%， respectively. In 12 batches of RRP， the contents of the above seven sugars were 10.62%， 11.01%， 1.25%， 3.35%， 1.12%， 28.16% and 6.39%， respectively. The results of multivariate statistical analysis showed that fresh RR， raw RR and RRP could be distinguished from each other by the contents of the 7 sugars， and the main differential components were stachyose， sucrose， raffinose and manninotriose. ConclusionIn terms of oligosaccharides， the contents and types of saccharides in different herbs and decoction pieces of RR are quite different， and the TLC identification method based on this can be used to distinguish raw RR from RRP， which can lay a foundation for improving the quality standard of RR and developing and applying oligosaccharides in different processed products of RR.

Objective:To analyze the role of dandelion and mulberry leaf in the progression of acute myeloid leukemia(AML)by network pharmacology,and to clarify the active components and their mechanisms in treating AML.Methods:The active components of dandelion and mulberry leaf were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The targets were predicted by SwissTargetPrediction Database.The AML-related genes and protein targets were retrieved from the SymMap Database,the GeneCards Human Gene Database,the DisGeNET Database,and the Online Mendelian Inheritance in Man(OMIM)Database.The AML-related genes and target genes of dandelion and mulberry leaf were compared by comparative analysis and were identify by the enrichment genes,followed by Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis.The drug-active component-target network and protein-protein interaction(PPI)network were constructed by Cytoscape 3.8.0 software,and the core genes were selected by CytoNCA plugin;the molecular docking was conducted by AutoDock software.Results:After filtering by databases,39 active components were identified,and 148 common targets between dandelion-mulberry leaf and AML were collected.The GO functional enrichment analysis mainly involved cytokine-mediated signaling pathways,positive regulation of kinase activity,and oxidative stress responses.The KEGG signaling pathway enrichment analysis focused on the phosphatidylinositol 3 kinase/protein kinase B(PI3K-AKT)signaling pathway,the tumor necrosis factor(TNF)signaling pathway,and the Janus kinase/signal transducer and activator of transcription(JAK-STAT)signaling pathway.The key targets were identified by topological analysis including signal transducer and activator of transcription 3(STAT3),epidermal growth factor receptor(EGFR),protein kinase B1(AKT1),recombinant human epidermal growth factor(EGF),vascular endothelial growth factor A(VEGFA),oncogene MYC,tumor protein P53(TP53),mitogen-activated protein kinase 3(MAPK3),cysteiny asparate specific protease-3(CASP3),oncogene SRC,heat shock protein 90 alpha family class A member 1(HSP90AA1),tenascin XB1(CTNNB1),phosphoinositide kinase-3 catalytic subunit alpha(PIK3CA),interleukin 6(IL-6),TNF,mitogen-activated protein kinase 1(MAPK1),and phosphatidylinositide kinase-3 regulatory subunit 1(PIK3R1).The molecular docking results showed the highest affinity pairing to be taraxerol with MYC(-8.74 kcal·mol-1),and quercetin,kaempferol,luteolin,and artemetin demonstrated good binding affinities with various targets.Conclusion:The main active components of dandelion-mulberry leaf,such as quercetin,taraxerol,kaempferol,luteolin,and artemetin,may exert the anti-AML effect by regulating AKT1,STAT3,HSP90AA1,IL-6,and MAPK1;regulation the PI3K-AKT signaling pathway may be the critical mechanism of anti-AML effect by dandelion-mulberry leaf.

Objective To investigate the clinical significance of serum S100 calcium binding protein(S100 A4)and S100A12 in patients with severe traumatic brain injury(sTBI).Methods A total of 147 sTBI pa-tients admitted to Handan Central Hospital from March 2021 to March 2023 were selected as the sTBI group,and 50 healthy subjects who underwent physical examination in Handan Central Hospital during the same pe-riod were selected as the control group.The correlation between S100A4,S100A12 levels and brain injury markers and the influencing factors of early death in sTBI patients were analyzed,and the predictive value of serum S100A4 and S100A12 for early death in sTBI patients was studied.Results The serum levels of S100A4,S100A12,myelin basic protein(MBP),S100B and neuron specific enolase(NSE)in sTBI group were significantly higher than those in control group(P＜0.05).The serum levels of S100A4 and S100A12 were positively correlated with MBP,NSE and S100B in sTBI patients(P＜0.05).Multivariate Logistic regression analysis showed that decreased Glasgow coma scale(GCS)score on admission and increased serum levels of S100A4,S100A12,MBP,NSE and S100B were risk factors for early death in sTBI patients(P＜0.05).Receiv-er operating characteristic curve showed that the combination of serum S100A4 and S100A12 with GCS score,MBP,NSE and S100B was superior to any single detection in predicting early death in sTBI patients.Conclu-sion The serum levels of S100A4 and S100A12 are increased in sTBI patients,which are related to the aggra-vations of brain injury and early death.The combined detection of S100A4 and S100A12 has a good predictive value for early death in sTBI patients.

Objective To explore the process and main behavior characteristics of behavioral characteristics of patients with recurrent hypoglycemia in the degeneracy of blood glucose management.Methods A mixed-method convergent design was used to collect data.From June 2022 to April 2023,382 patients with recurrent hypoglycemia were admitted to the endocrine department of a tertiary hospital in Jiangsu were recruited to score of ego depletion.K-means clustering was conducted to analyze the distribution characteristics of patients'characteristics in blood glucose management.At the same time,19 patients who were selected from the participants of the quantitative study were recruited to attend semi-structured interviews.Results Quantitative results analysis:the average score of blood glucose management loss was(49.20±6.58),and the average scores of cognitive control,behavioral control and emotional control were(17.90±4.12),(15.49±3.64)and(15.81±3.58),respectively.The results of cluster analysis showed that behavioral characteristics could be divided into 3 groups:a cognitive depletion group,an emotional depletion group and a self-control group.Qualitative data analysis:the process of deterioration of management in patients included 3 major themes,including the antecedents of ego depletion,the process of ego depletion and the aftereffects of ego depletion.Analysis of the mixed results showed that the status of ego depletion is serious;patients ignore the behavioral elements of active participation in blood glucose management,show many irrational decision-making behaviors,and the degradation behavior characteristics of patients'blood glucose management are different.Conclusion The degeneration behavior of blood glucose management was serious and affected by single or multiple factors,continuously consuming self-control energy and causing ego depletion.To promote the long-term maintenance of blood glucose management,priority should be given to take actions to enhance patients'perceptions,emotion and behaviors,help them learn about the possible blood glucose changes,improve their understanding and recognition of the value of scientific management.

Over the past decade, research has increasingly identified unique dysregulations in lipid metabolism within the tumor microenvironment (TME). Lipids, diverse biomolecules, not only constitute biological membranes but also function as signaling molecules and energy sources. Enhanced synthesis or uptake of lipids in the TME significantly promotes tumorigenesis and proliferation. Moreover, lipids secreted into the TME influence tumor-resident immune cells (TRICs), thereby aiding tumor survival against chemotherapy and immunotherapy. This review aims to highlight recent advancements in understanding lipid metabolism in both tumor cells and TRICs, with a particular emphasis on exogenous lipid uptake and endogenous lipid de novo synthesis. Targeting lipid metabolism for intervention in anticancer therapies offers a promising therapeutic avenue for cancer treatment. Nano-drug delivery systems (NDDSs) have emerged as a means to maximize anti-tumor effects by rewiring tumor metabolism. This review provides a comprehensive overview of recent literature on the development of NDDSs targeting tumor lipid metabolism, particularly in the context of tumor immunotherapy. It covers four key aspects: reprogramming lipid uptake, reprogramming lipolysis, reshaping fatty acid oxidation (FAO), and reshuffling lipid composition on the cell membrane. The review concludes with a discussion of future prospects and challenges in this burgeoning field of research.

Objective: To investigate the epidemiological characteristics of sexually transmitted diseases (STDs) in Zhejiang Province from 2018 to 2022, so as to provide insights into improving STDs prevention and control strategies. Methods: Data of syphilis, gonorrhea, condyloma acuminatum, genital herpes and genital Chlamydia trachomatis infections reported in Zhejiang Province from 2018 to 2022 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The temporal, spatial and population distribution of STDs were analyzed, and the trends in incidence of STDs were evaluated using annual percent change (APC). Results: A total of 386 770 STDs cases were reported in Zhejiang Province from 2018 to 2022, with mean annual reported incidence of 127.80/105. The mean annual reported incidence from high to low was syphilis (44.11/105), genital Chlamydia trachomatis infections (40.20/105), gonorrhea (24.92/105), condyloma acuminatum (13.32/105), and genital herpes (5.34/105). The incidence of STDs appeared a tendency towards a decline from 2018 to 2022 (APC=-9.332%, P<0.05), with an average annual growth rate of -9.41%. Syphilis (APC=-11.536%, P<0.05), condyloma acuminatum (APC=-7.509%, P<0.05), and genital Chlamydia trachomatis infections (APC=-9.009%, P<0.05) showed a appeared a tendency towards a decline. The top three highest reported incidence were reported in Hangzhou City (185.98/105), Taizhou City (133.85/105) and Lishui City (122.73/105), respectively. The mean annual reported incidence of females was higher than that of males (140.60/105 vs. 117.83/105; P<0.05). Most STDs cases were at ages of 20 to 49 years (265 314 cases, 68.60%). Farmers (118 096 cases, 30.53%), household and unemployed personnel (85 924 cases, 22.22%) were the predominant occupation. Conclusions The incidence of STDs appeared a tendency towards a decline in Zhejiang Province from 2018 to 2022, with regional differences in incidence. People at ages of 20 to 49 years, farmers, household and unemployed personnel are high-risk populations for STDs.

Objective:To investigate the iodine nutritional status of children in Qingdao City and the effects of prevention and treatment measures on iodine deficiency disorders (IDD), and to provide a scientific basis for guiding residents to scientifically supplement iodine, taking timely targeted prevention and control measures, and scientifically adjusting intervention strategies.Methods:According to "National Iodine Deficiency Disorders Surveillance Program (2016 edition)" and "Iodine Deficiency Disorders Surveillance Program of Shandong Province", from 2018 to 2020, using the cluster sampling method, children aged 8-10 years in Qingdao City were chosen to test their household salt iodine content and random urinary iodine content, and to examine their thyroid volume by B-ultrasonography, and the correlation between thyroid volume and physical development indexes was analyzed.Results:From 2018 to 2020, a total of 6 057 children were monitored, including 3 068 boys and 2 989 girls. The median of salt iodine and iodized salt iodine of children was 23.50 and 24.10 mg/kg. The qualified rate of iodized salt was 89.95% (4 832/5 372), the coverage rate of iodized salt was 88.69% (5 372/6 057), and the consumption rate of qualified iodized salt was 79.78% (4 832/6 057). There were significant differences in the qualified rate of iodized salt, the coverage rate of iodized salt and the consumption rate of qualified iodized salt between different years (χ 2 = 135.26, 314.71, 342.87, P < 0.001). A total of 6 057 urine samples were collected from children, and the median of urinary iodine was 193.92 μg/L, of which 16.2% (979/6 057) were < 100 μg/L, and 22.5% (1 361/6 057) were ≥300 μg/L. There were statistically significant differences in the medians of urinary iodine between different years, gender and whether eating iodized salt ( H/Z = 37.25,-3.89,-5.69, P < 0.001), the median of urinary iodine in boys was higher than that of girls, and the median of urinary iodine in eating iodized salt group was higher than that of eating non-iodized salt group. There was no significant difference in the median of urinary iodine between different age ( H = 4.33, P = 0.119). The rate of goiter in children was 3.45% (71/2 057), and the difference between different years was statistically significant (χ 2 = 42.68, P < 0.001). The incidence of goiter in 2020 [7.31% (45/616)] was significantly higher than that in 2018 and 2019 [2.81% (18/641), 1.00% (8/800), P < 0.001]. Thyroid volume of children was positively correlated with height and weight ( r = 0.20, 0.22, P < 0.001). Conclusions:The iodine nutritional level of children aged 8-10 years in Qingdao City is appropriate. However, the incidence of goiter in children in some years is relatively high. The qualified rate of iodized salt, the coverage rate of iodized salt and the consumption rate of qualified iodized salt are all lower than the national standard for elimination of IDD, which should be paid attention to.