Fatty acid degradation driven by heat during ripening contributes to the formation of the "Keemun aroma".

Ripening refers to the process of chemical change during the refinement of Keemun black tea (KBT) and is crucial in the formation of Keemun Congou black tea's quality. In this study, the aroma composition of KBT during the ripening was analyzed. Sensomics indicated that ripening strengthened the coconut and fatty aroma of KBT and contributed to the decrease of green aroma substances, resulting in a shift of the overall aroma type of KBT to an integrated aroma profile, which was consistent with sensory evaluation. Changes in fatty acid content and the results of in vitro addition simulation tests confirmed that heat causes highly degradation of fatty acids into fatty aroma volatiles, which is a key driver of the formation of "Keemun aroma" quality. This study revealed the mechanism behind the formation of KBT's integrated "Keemun aroma" quality and the mode of thermal degradation of major fatty acids.

Optimization of Conditions of Zanthoxylum Alkylamides Liposomes by Response Surface Methodology and the Absorption Characteristics of Liposomes in the Caco-2 Cell Monolayer Model.

Zanthoxylum alkylamides, as a numbing substance in Zanthoxylum bungeanum has many physiological effects. However, the numbing taste and unstable properties limited its application. This study aimed to optimize the preparation process of Zanthoxylum alkylamides liposomes by response surface methodology (RSM) and to investigate the in vitro absorption characteristics of the liposomes through the Caco-2 cell monolayer model. The process parameters of liposomes were as follows: Zanthoxylum alkylamides was 15 mg, phospholipid-feedstock ratio was 6.14, phospholipid-cholesterol ratio was 8.51, sodium cholate was 33.80 mg, isopropyl myristate was 29.49 mg, and the theoretical encapsulation efficiency of the prepared liposomes could reach 90.23%. Further, the particle size of the liposomes was 155.47 ± 3.16 nm, and the ζ-potential was -34.11 ± 4.34 mV. Meanwhile, the liposomes could be preserved for 14 days under the condition that the content of Zanthoxylum alkylamides was less than 2 mg/mL and the preservation temperature was lower than 25 °C. Moreover, the uptake characteristics of the Zanthoxylum alkylamides liposomes in the Caco-2 cell monolayer model were also investigated. The results showed that the Zanthoxylum alkylamides liposomes could be taken up and absorbed by Caco-2 cells. Also, the Zanthoxylum alkylamides liposomes had a better uptake performance than the unembedded Zanthoxylum alkylamides and conformed to the passive uptake.

Preparation of starch-palmitic acid complexes by three different starches: A comparative study using the method of heating treatment and autoclaving treatment.

Recent research emphasizes the growing importance of starch-lipid complexes due to their anti-digestibility ability, prompting a need to explore the impact of different starch sources and preparation methods on their properties. In this study, starch-palmitic acid (PA) complexes were prepared by three different starches including Tartary buckwheat starch (TBS), potato starch (PTS), and pea starch (PS) by heating treatment (HT) and autoclaving treatment (AT), respectively, and their physicochemical property and in vitro digestibility were systematically compared. The formation of the starch-PA complex was confirmed through various characterization techniques, including scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffraction. Among the complexes, the PTS-PA complex exhibited the highest complexation index over 80 %, while the PS-PA complex had the lowest rapid digestible starch content (56.49-59.42 %). Additionally, the complexes prepared by AT exhibited higher resistant starch content (41.95-32.46 %) than those prepared by HT (31.42-32.49 %), while the complexes prepared by HT held better freeze-thaw stability and hydration ability than those prepared by AT. This study highlights the important role of starch sources in the physicochemical and digestibility properties of starch-lipid complex and the potential application of AT in the preparation of novel resistant starch.

Dynamic assessment of seawater quality based on semi-partial subtraction set pair potential method and game theory.

The assessment of seawater quality is a complex process as it involves the influence of several factors and is characterized by dynamic changes in these factors. Herein, a novel model coupled with the semi-partial subtraction set pair potential method (SSSPP) and game theory was discussed for the dynamic assessment of seawater quality. In the proposed model, the identity-discrepancy-contrary degrees were calculated to construct the evaluation matrix, and then the classification and the dynamic risk trends of the seawater quality were determined. A case study and comparison with the single-factor approach and Nemerow index evaluation method were carried out to confirm the accuracy and dependability of the suggested model. The results indicate that the proposed method can be used to measure trends in seawater quality evolution and also to diagnose key indicators affecting seawater quality. It provides a new and effective way to accurately identify the quality of seawater and its trends.

Interphase Engineering Enhanced Electro-chemical Stability of Prelithiated Anode.

Prelithiation is an essential technology to compensate for the initial lithium loss of lithium-ion batteries due to the formation of solid electrolyte interphase (SEI) and irreversible structure change. However, the prelithiated materials/electrodes become more reactive with air and electrolyte resulting in unwanted side reactions and contaminations, which makes it difficult for the practical application of prelithiation technology. To address this problem, herein, interphase engineering through a simple solution treatment after chemical prelithiation is proposed to protect the prelithiated electrode. The used solutions are carefully selected, and the composition and nanostructure of the as-formed artificial SEIs are revealed by cryogenic electron microscopy and X-ray photoelectron spectroscopy. The electrochemical evaluation demonstrates the unique merits of this artificial SEI, especially for the fluorinated interphase, which not only enhances the interfacial ion transport but also increases the tolerance of the prelithiated electrode to the air. The treated graphite electrode shows an initial Coulombic efficiency of 129.4%, a high capacity of 170 mAh g-1 at 3 C, and negligible capacity decay after 200 cycles at 1 C. These findings not only provide a facile, universal, and controllable method to construct an artificial SEI but also enlighten the upgrade of battery fabrication and the alternative use of advanced electrolytes.

Traditional Chinese Medicine formula, Sanwujiao granule, attenuates ischemic stroke by promoting angiogenesis through early administration.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke (IS) is one of the most lethal diseases with the insufficient pharmacology therapeutic approach. Sanwujiao granule (SW) is widely used for IS in China with little known about its underlying mechanism. AIM OF THE STUDY: To investigate the characteristics of therapeutic effects and potential mechanisms of SW against IS. MATERIALS AND METHODS: The fingerprint of SW was applied by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Three different drug treatment strategies, including prophylactic administration, early administration and delayed administration, were applied in rats' permanent middle cerebral occlusion (pMCAO) model. The Garcia neurological deficit test, adhesive removal test, rotarod test, TTC and TUNEL staining were performed to evaluate the pathological changes. The transcriptomic analysis was used to predict the potential mechanism of SW. The vascular deficiency model of Tg(kdrl:eGFP) zebrafish larvae and oxygen-glucose deprivation model on bEnd.3 cells were used to verify SW's pharmacological effect. qRT-PCR, immunofluorescent staining and Western Blot were applied to detect the expression of genes and proteins. The network pharmacology approach was applied to discover the potential bioactive compounds in SW that contribute to its pharmacological effect. RESULTS: SW early and delayed administration attenuated cerebral infarction, neurological deficit and cell apoptosis. The transcriptomic analysis revealed that SW activated angiogenesis-associated biological processes specifically by early administration. CD31 immunofluorescent staining further confirmed the microvessel intensity in peri-infarct regions was significantly elevated after SW early treatment. Additionally, on the vascular deficiency model of zebrafish larvae, SW showed the angiogenesis effect. Next, the cell migration and tube formation were also observed in the bEnd.3 cells with the oxygen-glucose deprivation induced cell injury. It's worth noting that both mRNA and protein levels of angiogenesis factor, insulin-like growth factor 1, were significantly elevated in the pMCAO rats' brains treated with SW. The network pharmacology approach was applied and chasmanine, karacoline, talatisamine, etc. were probably the main active compounds of SW in IS treatment as they affected the angiogenesis-associated targets. CONCLUSIONS: These results demonstrate that SW plays a critical role in anti-IS via promoting angiogenesis through early administration, indicating that SW is a candidate herbal complex for further investigation in treating IS in the clinical.

Degradation and Transformation Mechanisms of Zanthoxylum Alkylamides Exposed to UVB Light.

Zanthoxylum oleoresin, a concentrated extract derived from Zanthoxylum bungeanum, is rich in non-volatile, intensely flavorful substances and amide compounds, such as hydroxy-α-sanshool, hydroxy-ß-sanshool, and hydroxy-ε-sanshool. The production process of Zanthoxylum oleoresin remains unstandardized, and there is still a lack of research on the precise classification and quantification of its key chemical constituents, as well as the stability of these compounds when produced using different extraction methods. This study utilized preparative liquid chromatography to extract and purify amide compounds from Zanthoxylum oleoresin, successfully isolating three sanshools: hydroxy-α-sanshool, hydroxy-ß-sanshool, and hydroxy-ε-sanshool. The stability of three these sanshools under UVB irradiation in different solvents was explored in UVB-simulated sunlight conditions to investigate the degradation or transformation mechanism of Zanthoxylum alkylamides under UVB irradiation. The findings indicate a rapid decrease in the hydroxy-α-sanshool content under UVB ultraviolet light, aligning with the second-order kinetics. This study revealed alterations in the contents of hydroxy-α-sanshool, hydroxy-ß-sanshool, and hydroxy-ε-sanshool and the formation of a new compound following exposure to UVB light. This new compound, along with the three sanshools, possesses a uniform m/z 264 and shares similar chemical structures. Further analysis also uncovered that these compounds are capable of undergoing isomerization reactions under UVB irradiation. This demonstrates that UVB irradiation of certain intensities can modify the concentrations and chemical structures of these Zanthoxylum alkylamides. These insights offer crucial guidance for future studies on the processing and preservation of Zanthoxylum alkylamides and their derivatives.

Assessing cell chimerism in an acute graft-versus-host disease model established in TLR4 knockout mice.

BACKGROUND: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. OBJECTIVE: To elucidate the role of Toll-like receptor 4 (TLR4), the major receptor for bacterial lipopolysaccharide, in the development of GVHD, we constructed a GVHD model in TLR4 knockout (TLR4-/-) mice and monitored the cell chimerism. METHODS: In this study, we used polymerase chain reaction to identify whether TLR4 knockout (TLR4-/-) mice were established. Before transplantation, we pretreated mice with irradiation so as to obtain an appropriate irradiation dose. Flow cytometry was applied to measure the chimerism status, the distributions of antigen-presenting cells (APCs), and T-cells in TLR4+/+ and TLR4-/- recipient mice. RESULTS: The general condition of TLR4-/- recipients was better than that of TLR4+/+ recipients, and the TLR4-/- recipient mice showed less severe GVHD manifestations than the TLR4+/+ recipient mice. Most of the APCs and T-cells in the host mouse spleen were derived from donor cells, and CD4+ T-cells, including memory T-cells, were in the majority in host mice. CONCLUSION: In general, our data show that TLR4 deletion attenuated GVHD development, which suggests that TLR4 could be used as a novel target and therapeutic paradigm in GVHD therapies.

ANTECEDENTES: La enfermedad de injerto contra huésped (EICH) es una complicación importante después del trasplante alogénico de células madre hematopoyéticas. OBJETIVOS: Para dilucidar el papel de TLR4, el principal receptor de LPS bacteriano, en el desarrollo de GVHD, construimos un modelo de GVHD en ratones knockout para TLR4 (TLR4-/-) y monitoreamos el quimerismo celular. MÉTODOS: En este estudio, usamos PCR para identificar si se establecieron ratones knockout para TLR4 (TLR4-/-). Antes del trasplante, pretratamos a los ratones con irradiación para obtener la dosis de irradiación adecuada. Se aplicó citometría de flujo para medir el estado de quimerismo, las distribuciones de APC y células T en ratones receptores TLR4+/+ y TLR4-/-. RESULTADOS: El estado general de los receptores de TLR4-/- fue mejor que el de los receptores de TLR4+/+, y los ratones receptores de TLR4-/- mostraron manifestaciones de GVHD menos graves que los ratones receptores de TLR4+/+. La mayoría de las APC y las células T en el bazo del ratón huésped se derivaron de las células del donante, y las células T CD4+, incluidas las células T de memoria, se encontraban en su mayoría en los ratones huéspedes. CONCLUSIÓN: En general, nuestros datos muestran que la eliminación de TLR4 atenuó el desarrollo de GVHD, lo que sugiere que TLR4 podría usarse como un nuevo objetivo y paradigma terapéutico en las terapias de GVHD.

Temperature-dependent interphase formation and Li+ transport in lithium metal batteries.

High-performance Li-ion/metal batteries working at a low temperature (i.e., <-20 °C) are desired but hindered by the sluggish kinetics associated with Li+ transport and charge transfer. Herein, the temperature-dependent Li+ behavior during Li plating is profiled by various characterization techniques, suggesting that Li+ diffusion through the solid electrolyte interface (SEI) layer is the key rate-determining step. Lowering the temperature not only slows down Li+ transport, but also alters the thermodynamic reaction of electrolyte decomposition, resulting in different reaction pathways and forming an SEI layer consisting of intermediate products rich in organic species. Such an SEI layer is metastable and unsuitable for efficient Li+ transport. By tuning the solvation structure of the electrolyte with a lower lowest unoccupied molecular orbital (LUMO) energy level and polar groups, such as fluorinated electrolytes like 1 mol L-1 lithium bis(fluorosulfonyl)imide (LiFSI) in methyl trifluoroacetate (MTFA): fluoroethylene carbonate (FEC) (8:2, weight ratio), an inorganic-rich SEI layer more readily forms, which exhibits enhanced tolerance to a change of working temperature (thermodynamics) and improved Li+ transport (kinetics). Our findings uncover the kinetic bottleneck for Li+ transport at low temperature and provide directions to enhance the reaction kinetics/thermodynamics and low-temperature performance by constructing inorganic-rich interphases.

Polymer Competitive Solvation Reduced Propylene Carbonate Cointercalation in a Graphitic Anode.

Polymer electrolytes have been studied as an alternative to organic liquid electrolytes but suffer from low ionic conductivity. Propylene carbonate (PC) proves to be an interesting solvent but is incompatible with graphitic anodes due to its cointercalation effect. In this work, adding poly(ethylene oxide) (PEO) into a PC-based electrolyte can alter the solvation structure as well as transform the solution into a polymer electrolyte with high ionic conductivity. By spectroscopic techniques and calculations, we demonstrate that PEO can compete with PC in solvating the Li+ ions, reducing the Li+-PC bond strength, and making it easier for PC to be desolvated. Due to the unique solvation structure, PC-cointercalation-induced graphite exfoliation is inhibited, and the reduction stability of the electrolyte is improved. This work will extend the applications of the PC-based electrolytes, deepen the understandings of the solvation structure, and spur designs of advanced electrolytes.

Advances in oxidative stress in pathogenesis of diabetic kidney disease and efficacy of TCM intervention.

Diabetic kidney disease (DKD) is a common complication of diabetes and has become the leading cause of end-stage kidney disease. The pathogenesis of DKD is complicated, and oxidative stress is considered as a core of DKD onset. High glucose can lead to increased production of reactive oxygen species (ROS) via the polyol, PKC, AGE/RAGE and hexosamine pathways, resulting in enhanced oxidative stress response. In this way, pathways such as PI3K/Akt, TGF-ß1/p38-MAPK and NF-κB are activated, inducing endothelial cell apoptosis, inflammation, autophagy and fibrosis that cause histologic and functional abnormalities of the kidney and finally result in kidney injury. Presently, the treatment for DKD remains an unresolved issue. Traditional Chinese medicine (TCM) has unique advantages for DKD prevention and treatment attributed to its multi-target, multi-component, and multi-pathway characteristics. Numerous studies have proved that Chinese herbs (e.g., Golden Thread, Kudzuvine Root, Tripterygium glycosides, and Ginseng) and patent medicines (e.g., Shenshuaining Tablet, Compound Rhizoma Coptidis Capsule, and Zishen Tongluo Granule) are effective for DKD treatment. The present review described the role of oxidative stress in DKD pathogenesis and the effect of TCM intervention for DKD prevention and treatment, in an attempt to provide evidence for clinical practice.

Chemometric Discrimination of Cichorium glandulosum Boiss. et Huet and Cichorium intybus L. via Their Metabolic Profiling, Antioxidative, and Hypoglycemic Activities.

Cichorium glandulosum Boiss. et Huet (CG) and Cichorium intybus L. (CI) are widely used as the main raw material of functional food with hepatoprotective and hypoglycemic effects. Due to the lack of comparison on the chemical ingredients and efficacy, they were often used imprecisely and interchangeably. It is necessary to distinguish between them. With the plant metabolomics based on high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) and multivariate chemometric techniques, the chemical ingredients were characterized and 59 compounds between CG and CI were classified. As for antioxidative and hypoglycemic activities in vitro, CI extraction exhibited better antioxidant activity than CG, while CG extraction showed stronger hypoglycemic activity. Furthermore, a bivariate correlation between the chemical composition and efficacy of the extract was also analyzed, and three differentially strong correlation components between CI and CG were prepared, and the antioxidative and hypoglycemic efficacies were compared in vivo and different active phenotypes were obtained. Finally, we revealed chemical and biological differences between CG and CI, providing a basis for achieving better quality control and developing more effective functional foods.

Electron beam irradiation pretreatment enhances the formation of granular starch-phenolics complexes.

Starch-phenolics complex generated by the interaction between starch and phenolic acids had improved characteristics than the native starch, but the efficient preparation of such complex is still challenging. In this study, we proposed a new method for the preparation of starch-phenolics complexes under the pretreatment of electron beam irradiation (EBI). Four structurally similar monomeric phenolic acids including gallic acid (GA), 3,4-Dihydroxy-5-methoxybenzoic acid (3MGA), syringic acid (SA) and vanillic acid (VA), which naturally existed in Tartary buckwheat (TB) seeds, were complexed with native and EBI-pretreated TB starch. The results showed that the complexation between starch and 3MGA was the strongest, more than 30 mg of 3MGA was complexed with 1 g of starch. The complexation did not affect the particle morphology and A-type structure of starch, but changed the crystal structure order and promoted the strength of hydrogen bond, which may lead to the formation of granular complex. EBI pretreatment can significantly promote the complexation by enhancing hydrogen bonds as indicated by a broader band at 3500 ∼ 3100 cm-1 in the FT-IR spectra. In addition, EBI pretreatment helped to build a tighter bond and higher crystallinity, increase the particle size and iodine binding capacity, and decrease turbidity to inhibit retrogradation of starch. The 1H NMR of complexes indicated that EBI pretreatment could provide more accessibility for starch to interact with phenolics by creating a spacious microenvironment for 1H (α1 â†’ 4). Above all, EBI pretreatment enhanced the formations of starch-phenolics complexes.

Research progress on components and mechanisms of neurotoxicity induced by traditional Chinese medicine.

Over the years, the safety of traditional Chinese medicine (TCM) has received widespread attention, especially the central nervous system-related adverse reactions. Indeed, the complexity of TCM has limited the widespread application of TCM. The article summarizes the main components associated with neurotoxicity, including alkaloids, terpenes, flavonoids, saponins, proteins, and heavy metals, by reviewing the literature on the neurotoxicity of TCM. It has been established that the neurotoxicity mechanisms mainly include mitochondrial damage, oxidative damage, inhibition of cell proliferation (including transcriptional and DNA damage), changes in cell membrane permeability, and apoptosis. By reviewing the latest literature, this paper provides the foothold for follow-up studies and can assist clinicians in preventing neurotoxicity via rational and safe TCM drug use.

Preparation of antifouling and highly hydrophobic cellulose nanofibers/alginate aerogels by bidirectional freeze-drying for water-oil separation in the ocean environment.

Oil spills frequently occur in the ocean, and adsorption is one of the effective ways to deal with oil spills. Compared with other adsorbent materials, biomass aerogel has superior selective adsorption capacity. CNF/SA aerogels with good mechanical properties (340 kPa at 90 % strain) and high adsorption capacity (88.91 g/g) were prepared by mixing cellulose nanofibers (CNF) with sodium alginate (SA) through bidirectional freeze-drying, ionic crosslinking, and surface modification to effectively solve the ocean oil spill problem. The bidirectional freeze-drying technology is a green and efficient technique for preparing layered microstructured composite aerogels. The prepared aerogels have a three-dimensional interpenetrating lamellar structure, low density (24.2 mg/cm3), high porosity (97.85 %), and high hydrophobicity (WCA = 144.5°), can be calibrated and used repeatedly. It has potential applications in water-oil separation and can be used as an absorbent for effectively treating oil spills in the ocean environment.

Comparing clinical features, severity and prognosis of autoimmune encephalitis and with and without oligoclonal bands.

Objective: This study aimed to examine the clinical distinctions among patients diagnosed with autoimmune encephalitis (AE) based on the presence or absence of cerebrospinal fluid (CSF) oligoclonal bands (OCBs). Additionally, it sought to explore the relationship between OCBs and the severity and prognosis of autoimmune encephalitis. Methods: A retrospective analysis was conducted on 94 patients diagnosed with AE at the People's Hospital of Zhengzhou University between October 2016 and June 2022. The patients were divided into OCB-positive and OCB-negative groups based on CSF-OCBs. Patient severity at admission was assessed utilizing the Clinical Assessment Scale for Autoimmune Encephalitis (CASE) and the modified Rankin scale (mRS). Additionally, some oligoclonal-positive patients underwent dynamic longitudinal analysis of cerebrospinal fluid test indices. The mRS score was ultimately employed to evaluate patients' short-term prognosis (6 months) and long-term prognosis (at least 12 months) following immunotherapy. Results: Of the 94 patients, 34 (36.2%) belonged to the OCB-positive group, while 60 (63.8%) belonged to the OCB-negative group. The group with anti-n-methyl-d-aspartate receptor (anti-NMDAR) encephalitis exhibited the highest rate of oligoclonal positivity at 27 (49.1%), followed by anti-aminobutyric acid B receptor (GABABR) encephalitis with 4 cases (30.8%), anti-contactin-associated protein-like 2 (CASPR2) encephalitis with 2 cases (20%), and anti-leucine-rich glioma inactivating protein 1 (LGI1) encephalitis with 1 case (6.25%). No statistically significant differences were found between the two groups regarding gender, age, prodromal symptoms, psychiatric disorders, seizures, language disorders, motor dysfunction, cognitive dysfunction, tumor incidence, and magnetic resonance imaging (MRI) abnormalities (p > 0.05). The OCB-positive group exhibited higher rates of autonomic dysfunction, intensive care unit (ICU) admission, CSF leukocytes, and IgG index compared to the OCB-negative group (p < 0.05). Additionally, the OCB-positive group had significantly higher median CASE and mRS scores prior to immunotherapy than the OCB-negative group (p < 0.001 and p < 0.001). Furthermore, in both short-term follow-up and long-term follow-up, the OCB-positive group had a significantly lower proportion of patients with a favorable prognosis compared to the OCB-negative group (50% vs. 71.7, 61.8% vs. 83.3%; p = 0.036, p = 0.002). Conclusion: Autonomic dysfunction, ICU admission, leukocytes in the cerebrospinal fluid, and elevated IgG index are more commonly observed in OCB-positive patients. OCB-positivity has also been linked to the severity and prognosis of AE, making it a potential biomarker. Initial OCB testing aids clinicians in identifying potentially critically ill patients early and monitoring disease progression, thereby optimizing clinical treatment decisions.

Targeted anti-tumor strategies based on the tumor-promoting mechanisms of B7H3: opportunities and challenges / 中国肿瘤生物治疗杂志

@#[摘 要] 以靶向PD-1/PD-L1和CTLA-4为代表的免疫检查点阻断治疗在实体瘤的治疗中取得了不俗疗效，但仅有不到30%的患者能够从中受益的现实表明，还存在其他免疫检查点分子介导的免疫抑制。B7H3属于免疫球蛋白超家族B7家族成员，与CTLA-4/PD-1主要表达在T细胞并介导后者的免疫抑制或耗竭不同，B7H3蛋白不仅诱导性表达在免疫细胞，还组成性高表达在多种肿瘤细胞和肿瘤相关脉管系统。B7H3不仅能够激活多条信号通路直接促进肿瘤细胞恶性表型，还可以通过重塑肿瘤免疫抑制微环境间接促进肿瘤的进展、转移和耐药。因此，基于B7H3的多项靶向抗肿瘤策略，包括特异性抗体、抗体偶联药物及CAR-T细胞等均已进入临床试验并展示出较好的应用前景。但总体而言，该领域的研究依然处于探索阶段，在相互作用受体的鉴定、降低毒性、打破耐药及联合用药策略优化等方面还面临着许多问题和挑战亟待突破。

Clinicopathological characteristics and prognostic factors of elderly small intestine adenocarcinoma using propensity score matching analysis: a study based on SEER database.

BACKGROUND: Small intestine adenocarcinoma (SIA) is a scant disease that has no adequate clinical trials, so its prognostic factors are still unclear, especially in elderly patients. In this article, we aimed to explore the clinicopathology presentation, treatments, outcomes, and predictors of small intestine adenocarcinoma patients aged 65 years or older. METHODS: We retrieved clinicopathology data of small intestine adenocarcinoma patients diagnosed between 2004 and 2015 from the Surveillance Epidemiology and End Results (SEER) database. We clarified patients into two groups: the surgery and the non-surgery group and conducted propensity score matching (PSM) to compare survival outcoming. We identified the prognostic indicators for cancer-specific survival (CSS) and overall survival (OS) by the Cox proportional hazards model. RESULTS: In total, 1018 eligible cases were enrolled, with a median survival of 16 months; the 3-year OS and CSS rates were 36% and 41.7%, and the 5-year OS and CSS rates were 26.5% and 33.3%. Multivariate analyses revealed that age, grade, tumor stage, surgery, and chemotherapy were independent prognostic factors for OS, while grade, tumor stage, surgery, radiation, and chemotherapy were independent factors for CSS. After PSM, only surgery and tumor stage (AJCC 6th) were independent prognostic factors for OS and CSS. CONCLUSION: Surgery could bring benefit to survival for elderly SIA patients, and the early stage of the disease was another significant prognostic factor.

Deficiency of tumor-expressed B7-H3 augments anti-tumor efficacy of anti-PD-L1 monotherapy rather than the combined chemoimmunotherapy in ovarian cancer.

As a high mortality gynecological malignancy, most ovarian cancer patients experience refractory to standard chemotherapy, current immunotherapy or chemoimmunotherapy in clinic and clinical trials. The underlying mechanisms and biomarkers predictive of response for patient selection is quite urgent. In this study, we found that the level of tumor-expressed B7-H3 is positively correlated with the poorer prognosis in ovarian cancer patients. Therapeutically, in syngeneic mouse model of ovarian cancer, deficiency of tumor-expressed B7-H3 significantly potentiates the anti-tumor efficacy of paclitaxel or PD-L1 blockade monotherapy. However, combination of paclitaxel plus anti-PD-L1 has no synergistic effects than PD-L1 blockade monotherapy. Mechanistically, deficiency of tumor-expressed B7-H3 attenuates inflammatory cytokine IL-6 production, upregulates type I interferon (IFN) expression and increases paclitaxel-induced tumor cells apoptosis via caspase 3 activation pathway, resulting in reprogramming the tumor microenvironment including increasing the infiltration of effector T lymphocytes and decreasing the recruitment of Ly6G+CD11b+ myeloid-derived suppressor cells (MDSCs) in vivo. Collectively, these results demonstrate that deficiency of tumor-expressed B7-H3 enhances the anti-tumor efficacy of paclitaxel or PD-L1 blockade monotherapy rather than their combined chemoimmunotherapy in ovarian cancer, suggesting that B7-H3 may be a potential predictive biomarker for beneficial patient stratification and a candidate therapeutic target in ovarian cancer.