Programmed death-1 (PD-1) is an inhibitory immune checkpoint that binds to programmed death-ligand 1 (PD-L1) to regulate the immune response and maintain immune system homeostasis of the immune system. Through overexpression of PD-L1, tumor cells bind to PD-1 on the surface of immune cells, inhibiting the activity and function of immune cells, leading to immune escape of cancer cells and tumor progression. Gastrointestinal cancer is a common malignancy with a high mortality rate worldwide, and the effectiveness of current systematic treatment options is limited. In recent years, immune checkpoint inhibitors (ICIs) such as PD-1/PD-L1 inhibitors have attracted much attention in cancer therapy. Immunotherapy has been incorporated into the treatment of some gastrointestinal malignancies. Different from traditional treatment, it uses various means to stimulate and enhance the immune function of the body to achieve the therapeutic purpose of controlling and eliminating tumor cells. However, although PD-1/PD-L1 inhibitors have shown potential in the treatment of gastrointestinal tumors, the efficacy of single inhibitor therapy is limited, which may be due to the ability of tumors to escape immune attack through other pathways after inhibitor treatment, or the presence of other immunosuppressive factors. For example, PD-1 and PD-L1 inhibitors can be combined with other immune checkpoint drugs, molecularly targeted drugs, or chemotherapy drugs to simultaneously act on different immune pathways and improve the comprehensive effect of immunotherapy. However, to achieve an effective combination therapy, we need to delve into the specific mechanisms of action of the PD-1/PD-L1 axis in the development and progression of gastrointestinal tumors, which can help to develop the best treatment strategy and provide individualized treatment options for the appropriate patient population. Therefore, future studies should focus on the regulatory mechanisms of PD-1/PD-L1 axis and evaluate the therapeutic effects of different treatment combinations on gastrointestinal tumors. In this paper, we review the research progress of PD-1/PD-L1 axis in tumorigenicity and its mechanism, and review the single and combined treatment strategies of PD-1 and PD-L1 inhibitors in gastrointestinal tumors.

PI3Kγ and PI3Kδ have important regulatory roles in the immune system, and targeting these two subtypes helps to reshape the tumor microenvironment. PI3Kγ and PI3Kδ are potential targets for tumor immunotherapy. In this study, a series of new pyrazolopyrimidine derivatives were designed and synthesized on the basis of our previously reported PI3K inhibitors, resulting in the discovery of compound 16l as a potent and selective PI3Kγ/δ dual inhibitor. Compound 16l demonstrated strong biochemical potencies against PI3Kγ and PI3Kδ with IC₅₀ values of 0.11 and 0.79 nmol·L^-1. In cell-based assays, it potently inhibited the PI3Kγ and PI3Kδ mediated Akt S473 phosphorylation with EC₅₀ values of 3 and 7 nmol·L^-1. In vivo, compound 16l exhibited acceptable pharmacokinetic properties in Sprague-Dawley (SD) rats and suppressed the tumor growth in a MC38 syngeneic mouse model. The animal experiments were approved by the Animal Ethics Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (approval number: DWLL-2000-06). In addition, no appreciable human ether-a-go-go-related gene (hERG) inhibition was observed for compound 16l even at 30 μmol·L^-1. These results suggested that compound 16l might be a potential research tool for studying the PI3Kγ/δ mediated signaling pathways.

Objective To explore the differentially expressed mRNAs and related biological processes and pathways in fractional low-dose ionizing radiation (LDIR)-induced senescence of normal human bronchial epithelial (HBE) cells by high-throughput mRNA sequencing and bioinformatics techniques. Methods Senescence-associated β-galactosidase staining and senescence-associated secretion phenotype gene mRNA and protein expression levels were measured at 24 and 48 h after irradiating HBE cells 7 times at doses of 0, 50, 100, and 200 mGy, respectively. The differentially expressed genes were screened by high-throughput sequencing for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results The senescence-positive area of fractional low-dose irradiated HBE cells increased in a dose-dependent manner (P < 0.05). The mRNA levels and protein expression of transforming growth factor-β1(TGF-β1) and matrix metalloproteinase-9(MMP-9) genes were increased in the 100 mGy × 7 and 200 mGy × 7 groups at 24 and 48 h after the end of irradiation compared with the control group. High-throughput sequencing showed that there were 882, 475, and 1205 differentially expressed mRNAs in each dose group compared with the control group. GO analysis showed that the differentially expressed mRNAs in each dose group were mainly enriched in biological processes such as cell cycle regulation, regulation of nitrogen compound metabolic process, regulation of cell division and response to stimulus. KEGG analysis showed that the differentially expressed mRNAs were mainly enriched in the pathways of cell cycle, cell senescence, and ferroptosis. Conclusion Fractional LDIR induced senescence in HBE cells, and differentially expressed mRNA-associated biological processes and pathways in senescent cells are related to cell cycle and cell senescence.

Objective To study the evaluation value of lung injury score(LIS)and advanced glycation end products(AGEs)expression levels on the prognosis of elderly patients with sepsis-related acute lung injury/acute respiratory distress syndrome(ALI/ARDS).Methods A total of 98 elderly patients with sepsis-related ALI/ARDS admitted to First Branch of the First Affiliated Hospital of Chongqing Medical University from March 2019 to April 2021 were selected as the research group,and the patients were divided into two sub-groups according to their survival within 30 d after admission:the survival group(55 cases)and the death group(43 cases).Another 51 elderly patients with non-ALI/ARDS sepsis admitted to First Branch of the First Affiliated Hospital of Chongqing Medical University in the same period were selected as the control group.After admission,the clinical data of patients were recorded,and the levels of serum creatinine,troponin I,B-type brain natriuretic peptide(BNP),serum C-reactive protein(CRP)and procalcitonin(PCT)were de-tected.Enzyme-linked immunosorbent assay was used to determine the levels of AGEs in patients'serum.The LIS score was evaluated by LIS scale.With clinical factors as independent variables and prognosis as dependent variables,Logistic regression curve was used to analyze the death factors of elderly sepsis-related ALI/ARDS patients.Results AGEs levels,LIS scores,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores decreased sequentially in the death group,survival group,and control group(all P<0.05).The levels of lactic acid,blood glucose,troponin I,PCT,BNP and CRP in arterial blood of patients in the death group were significantly higher than those in the survival group and the control group(P<0.05).The results showed that arterial lactate,blood glucose,troponin I,PCT,BNP,CRP,AGEs,APACHE Ⅱ score,and LIS score were all independent risk factors for mortality in elderly sepsis-related ALI/ARDS patients(P<0.05).The area under the curve(AUC)of LIS score predicting prognosis in elderly sepsis-related ALI/ARDS pa-tients was 0.857(95%CI:0.821-0.911),and AUC of serum AGEs was 0.861(95%CI:0.809-0.908).LIS score and AGEs level had certain predictive value for the prognosis of elderly sepsis-related ALI/ARDS pa-tients.Conclusion The LIS score and AGEs level of the elderly patients with sepsis-related ALI/ARDS are independent risk factors of death,which have important predictive value for prognosis.

Objective: To understand the oral health status and associated factors of preschool children with disabilities in Bengbu City, so as to provide evidence for preventing dental caries in children with disabilities. Methods: From September 2021 to March 2022, a total of 405 preschool children with disabilities from two rehabilitation institutions in Bengbu were randomly selected for oral health examination, questionnaire survey and physical examination. The caries prevalence rate among disabled children was analyzed. After grouping based on childrens BMI, the correlation between body mass index (BMI) and dental caries among children was explored. Multivariate binary Logistic regression analysis was employed to investigate the factors associated with dental caries occurrence in children. Results: The prevalence of dental caries in preschool children with disabilities was 74.07%, with rates of 71.01% for boys and 77.27% for girls. There was a significant difference in caries prevalence between boys and girls aged 5（66.67%，88.24%） (χ2=7.53, P<0.05). There were significant differences in the dmft index among different BMI groups (underweight: 240, normal weight: 606, overweight:30,obese:60,H=35.66,P<0.05). BMI was negatively correlated with dmft（r=-0.50，P＜0.01）. Frequent tooth brushing (2-3 times daily), the use of fluoride toothpaste, limited intake of sugary foods (< 2 times/d) in the past six months, and exclusively breastfeeding within first six months were negatively correlated with the occurrence of dental caries in disabled children (OR=0.09，0.41，0.24, P＜0.05). Sleep forward to eat，parental education level of junior high school or lower, and parental education of vocational school or high school were positively correlated with dental caries (OR=3.18，5.95，3.99，66.95，7.75，P＜0.05). Conclusions The caries prevalence rate of disabled children in Bengbu City is high and is influenced by multiple factors. It is time to strengthen the oral health training for parents and teachers in educational institutions, pay attention to childrens oral health care, and help disabled children improve their quality of life.

There are huge differences between tumor cells and normal cells in material metabolism, and tumor cells mainly show increased anabolism, decreased catabolism, and imbalance in substance metabolism. These differences provide the necessary material basis for the growth and reproduction of tumor cells, and also provide important targets for the treatment of tumors. Ferroptosis is an iron-dependent form of cell death characterized by an imbalance of iron-dependent lipid peroxidation and lipid membrane antioxidant systems in cells, resulting in excessive accumulation of lipid peroxide, causing damage to lipid membrane structure and loss of function, and ultimately cell death. The regulation of ferroptosis involves a variety of metabolic pathways, including glucose metabolism, lipid metabolism, amino acid metabolism, nucleotide metabolism and iron metabolism. In order for tumor cells to grow rapidly, their metabolic needs are more vigorous than those of normal cells. Tumor cells are metabolically reprogrammed to meet their rapidly proliferating material and energy needs. Metabolic reprogramming is mainly manifested in glycolysis and enhancement of pentose phosphate pathway, enhanced glutamine metabolism, increased nucleic acid synthesis, and iron metabolism tends to retain more intracellular iron. Metabolic reprogramming is accompanied by the production of reactive oxygen species and the activation of the antioxidant system. The state of high oxidative stress makes tumor cells more susceptible to redox imbalances, causing intracellular lipid peroxidation, which ultimately leads to ferroptosis. Therefore, in-depth study of the molecular mechanism and metabolic basis of ferroptosis is conducive to the development of new therapies to induce ferroptosis in cancer treatment. Ferroptosis, as a regulated form of cell death, can induce ferroptosis in tumor cells by pharmacologically or genetically targeting the metabolism of substances in tumor cells, which has great potential value in tumor treatment. This article summarizes the effects of cellular metabolism on ferroptosis in order to find new targets for tumor treatment and provide new ideas for clinical treatment.

Objective To assess the risk factors for carbapenem-resistant Acinetobacter baumannii(CRAB)bloodstream infection(BSI)and 28-day short-term mortality in elderly patients,and provide reference for the pre-vention and treatment of CRAB BSI.Methods Clinical data of patients aged ≥60 years and diagnosed with AB BSI in a hospital in Yulin City from January 2013 to December 2022 were retrospectively analyzed,including demogra-phic and microbiological characteristics,as well as clinical outcomes of the patients.Variables which were significant in univariate analysis were selected for multivariate analysis using binary logistic regression model and Cox propor-tional hazards model.Independent risk factors for infection were further determined,and survival analysis was per-formed using Kaplan-Meier curve.Results A total of 150 patients were included in the study,out of which 16 pa-tients(10.7％)had CRAB BSI and 134 had carbapenem-sensitive AB(CSAB)BSI.The 28-day short-term mortali-ty of AB BSI in elderly patients was 15.3％(23/150,95％CI:9.6％-21.1％),and the short-term mortality of CRAB BSI was higher than that of CSAB([56.3％,9/16]vs[10.4％,14/134]).Deep venous catheterization(OR:15.598,95％CI:1.831-132.910)and combined infections of other sites(OR:15.449,95％CI:1.497-159.489)were related to CRAB BSI in elderly patients.The independent risk factors for 28-day mortality in elderly patients with AB BSI were hemodialysis(OR:11.856,95％CI:2.924-48.076),intensive care unit admission(OR:9.387,95％CI:1.941-45.385),and pulmonary infection being suspected source of bacteremia(OR:7.019,95％CI:1.345-36.635).Conclusion The occurrence of CRAB BSI in elderly patients is related to the combined infection of other sites and deep vein catheterization.Hemodialysis,admission to ICU,and pulmonary infection being suspected source of bacteremia are independent risk factors for the prognosis of AB BSI in elderly patients.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

Purpose::Road traffic injuries (RTIs) have been one of the most serious public health problems in China. The purpose of this study was to investigate the extent to which traffic investment affects traffic fatalities in China as well as regional differences.Methods::The cohort study analyzed the correlation between traffic investment and traffic fatalities, incorporating additional factors such as economic conditions, road infrastructure, population density, and lighting. The selected variables included the number of traffic fatalities, traffic investment, urban per capita road area, urban road length, road mileage, urban road lighting, population size, and per capita gross domestic product. Relevant data between 2004 and 2020 were collected for an analysis using a fixed effect regression model. A p < 0.05 is considered statistically significant. To reduce the heterogeneity caused by regional differences, the provinces were divided into 6 groups according to administrative districts, and the clustering standard error analysis was carried out. Results::Overall, there has been a significant improvement in road safety in China from 2004 to 2020, but some regions show an increase in traffic fatalities. The model reveals that traffic investment is significantly and positively correlated with the number of traffic fatalities. Holding all other factors constant, each 10,000 yuan increase in transport investment was associated with an average increase of 0.22 road traffic fatalities. In the analysis of regional differences, there was a significant positive correlation between traffic investment and traffic fatalities in the Northwest region and an increase of 10,000 yuan leads to an increase of 0.47. There was a significant negative correlation between road mileage, urban road lighting system, and population and traffic fatalities. For example, holding other factors constant, a 10,000 km reduction in road length would increase the number of traffic deaths by 45.56. The model results of urban per capita road area, urban road length, per capita gross domestic product, and the explained variables showed that p > 0.100, which was not statistically significant. Conclusions::Therefore, traffic investments are essential for governments to develop measures to enhance road safety and reduce the risk of road fatalities. Adjusting traffic road investment and other covariates is conducive to improving traffic safety and reducing the risk of road fatalities. The road safety situation in different regions of China varies greatly. Local governments should consider the actual conditions to provide better road safety configuration policies.

Objective To compare the dosimetric effects of volume modulated arc therapy(VMAT)and intensity modulated radiation therapy(I M RT)on the anal sphincter(AS)and its sub-structures in neoadjuvant radiotherapy for rectal cancer to facilitate the selection of radiotherapy techniques.Methods Fifty rectal cancer patients receiving neoadjuvant radiotherapy were selected,and 2 types of radiotherapy plans,including coplanar double full-arc VMAT and coplanar seven-field homo-geneous IMRT,were designed based on the CT images of the patients,respectively.Under the premise of ensuring that the irradiated doses to the target area and the major organs at risk reached the standard and met the clinical requirements,AS and its substructures were added as the organs at risk for dosimetric evaluation.The absolute dose parameters and relative dose parameters of AS and its substructures were counted by dose-volume histograms.Statistical analysis was performed using IBM SPSS 22.0 software.Results The VMAT plan had the relative dose parameters V20,V30,and V40 of AS and its substructures lower those of the IMRT plan,the differences were statistically significant(P＜0.05),while the differences in V5 and V 10 were not statistically significant(P＞0.05).The VMAT plan had the absolute dose parameterDmeanlower while the D2％slightly higher than those of the IMRT plan,the differences were statistically significant(P＜0.05).The difference in D98％between the two plans was not statistically significant(P＞0.05).Conclusion During rectal cancer radiotherapy VMAT generally behaves better than IMRT in protecting AS and its sub-structures and decreasing injuries of AS and its sub-structures dosimetrically.[Chinese Medical Equipment Journal,2024,45(8):63-67]