Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Bronchial asthma （asthma for short） is a common clinical respiratory disease mainly characterized by chronic airway inflammation， with complicated pathogenesis and a long treatment cycle. It is lingering and difficult to be cured， and lack specific drugs. Oxidative stress is a new focus in the research on the pathogenesis of asthma and a potential key target for the treatment. Under physiological conditions， the oxidative and antioxidative systems in the body are in a dynamic balance， and the two antagonize each other to maintain normal life activities. In the case of asthma attack， oxidation products such as reactive oxygen species （ROS）， malondialdehyde （MDA）， and nitric oxide （NO） are produced excessively， while the content of antioxidants such as superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） is reduced. As a result， the oxidation exceeds the removal of oxidation products， which aggravates oxidative stress. In addition， the overproduction of ROS activates oxidative stress-related signaling pathways to produce pro-inflammatory factors， exacerbating inflammation， which leads to lung and airway tissue damage. In recent years， traditional Chinese medicine has garnering increasing attention because of the unique advantages in the treatment of asthma， especially in regulating redox balance， alleviating oxidative stress in asthma patients， and reducing inflammation. On the one hand， by inhibiting the mitogen-activated protein kinase （MAPK） and transcription factor （NF）-κB signaling pathways， traditional Chinese medicine can reduce the content of oxidation products and pro-inflammatory factors from the source. On the other hand， by activating the nuclear factor-erythroid 2-related factor 2 （NrF2） signaling pathway， traditional Chinese medicine can elevate the levels of antioxidant enzymes and enhance the antioxidant system to neutralize the excessive accumulation of oxidation products. Therefore， the adjustment of redox balance state by traditional Chinese medicine may be a new means and a new direction for the prevention and treatment of asthma in the future. This paper summarizes the oxidative stress-related pathways in the pathogenesis of asthma and reviews the latest research progress in the regulation of oxidative stress-related pathways by Chinese medicine extracts and prescriptions in the treatment of asthma， with a view to providing a fuller， more solid， and more scientific theoretical basis for the clinical and basic research on the prevention and treatment of asthma by traditional Chinese medicine.

Objective Hypertriglyceridemic waist(HW),hypertriglyceridemic waist-to-height ratio(HWHtR),and waist-to-hip ratio(WHR)have been shown to be indicators of cardiometabolic risk factors.However,it is not clear which indicator is more suitable for children and adolescents.We aimed to investigate the relationship between HW,HWHtR,WHR,and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods This was a national cross-sectional study.Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China.Demographics,physical activity,dietary intake,and family history of chronic diseases were obtained through questionnaires.ANOVA,x2 and logistic regression analysis was conducted. Results A significant sex difference was observed for HWHtR and WHR,but not for HW phenotype.The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents(HW:OR = 12.22,95%CI:9.54-15.67;HWHtR:OR = 9.70,95%CI:6.93-13.58).Compared with the HW and HWHtR phenotypes,the association between risk of cardiometabolic health risk factors(CHRF)clustering and high WHR was much weaker and not significant(WHR:OR = 1.14,95%CI:0.97-1.34). Conclusion Compared with HWHtR and WHR,the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.

AIM To investigate the variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip.METHODS UPLC-MS/MS was adopted in the content determination of formononetin,ononin,calycosin,calycosin-7-glucoside,medicarpin,genistein,luteolin,liquiritigenin,isoliquiritigenin,vanillic acid,ferulic acid,γ-aminobutyric acid,adenosine and betaine,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition to explore differential components.RESULTS After rubbing strip,formononetin,calycosin,liquiritigenin and γ-aminobutynic acid demonstrated increased contents,along with decreased contents of ononin,calycosin-7-glucoside and vanillic acid.The samples with and without rubbing strip were clustered into two types,calycosin-7-glucoside,formononetin,γ-aminobutynic acid,vanillic acid,calycosin-7-glucoside and formononetin were differential components.CONCLUSION This experiment clarifies the differences of chemical constituents in Hedysari Radix before and after rubbing strip,which can provide a reference for the research on rubbing strip mechanism of other medicinal materials.

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

The tannin content of sorghum seeds had a significant impact on the wine's quality during the brewing process.Additionally,when used as a feed ingredient,the tannin content had a major impact on feed consumption.Thus the tannin content of sorghum has a substantial impact on its quality and application.To quickly and nondestructively determine the tannin content of sorghum,near-infrared spectroscopy was combined with chemometrics in this study,which eliminated the need for time-consuming and costly conventional approaches.Following the spectra's preprocessing,anomalous samples were removed by using a combination of Gaussian process regression(GPR)and Monte Carlo cross-validation(MCCV).The sample set was then randomly divided into a modeling set and a prediction set,with feature wavelength selection carried out using the elimination of uninformative variables(UVE)method.Subsequently,a GPR model was developed,and its performance was compared with partial least squares regression(PLSR)and support vector machine regression(SVR)models.The results indicated that the GPR model outperformed the PLSR and SVR models in all aspects.The optimized GPR model,generated following pre-processing process such as Detrending and Savitzky-Golay smoothing,elimination of anomalous samples,and selection of feature wavelengths,demonstrated superior performance,with model set determination coefficient(Rc2),prediction set determination coefficient(RP2),and relative percent deviation(RPD)values of 0.9979,0.9529,and 4.8453,respectively.These findings validated the effectiveness of the GPR regression model,which integrated near-infrared spectroscopy with chemometrics,for the rapid and non-destructive detection of sorghum tannins.

Objective To investigate the factors influencing the occurrence of small for gestational age(SGA)at different degrees and provide a basis for early identification of severe SGA cases.Methods Neonatal and maternal prenatal information were retrospectively collected from January 2018 to December 2022 at Peking University People's Hospital.The neonates were divided into three groups:severe SGA group(birth weight below the 3rd percentile for gestational age and sex),mild SGA group(birth weight ≥3rd percentile and＜10th percentile),and non-SGA group(birth weight ≥10th percentile).An ordered multinomial logistic regression model was used to analyze the factors influencing the occurrence of SGA at different degrees.Results A total of 14 821 neonates were included,including 258 cases(1.74％)in the severe SGA group,902 cases(6.09％)in the mild SGA group,and 13 661 cases(92.17％)in the non-SGA group.The proportions of preterm births and stillbirths were higher in the severe SGA group compared to the mild SGA and non-SGA groups(P＜0.0125).The proportion of neonatal asphyxia was higher in both the severe SGA and mild SGA groups compared to the non-SGA group(P＜0.0125).Ordered multinomial logistic regression analysis showed that maternal pre-pregnancy underweight(OR=1.838),maternal pre-pregnancy obesity(OR=3.024),in vitro fertilization-embryo transfer(OR=2.649),preeclampsia(OR=1.743),connective tissue disease during pregnancy(OR=1.795),nuchal cord(OR=1.213),oligohydramnios(OR=1.848),and intrauterine growth restriction(OR=27.691)were all associated with a higher risk of severe SGA(P＜0.05).Maternal parity as a multipara(OR=0.457)was associated with a lower likelihood of severe SGA(P＜0.05).Conclusions Maternal pre-pregnancy underweight,maternal pre-pregnancy obesity,in vitro fertilization-embryo transfer,preeclampsia,connective tissue disease during pregnancy,oligohydramnios,nuchal cord,and intrauterine growth restriction are closely related to the occurrence of more severe SGA.Maternal parity as a multipara acts as a protective factor against the occurrence of severe SGA.[Chinese Journal of Contemporary Pediatrics,2024,26(3):262-268]

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.