OBJECTIVE To investigate the mechanism of pachymic acid on renal injury in pregnancy induced hypertension （PIH） rats by regulating the silent information regulator transcript 1/peroxisome proliferator-activated receptor γ coactivator-1α （Sirt1/PGC-1α） pathway. METHODS Pregnant SD rats were prepared by co-caging and PIH model was induced using N-nitro-L- arginine methyl ester （L-NAME） method. PIH rats were randomly divided into model group， L-pachymic acid （low-dose pachymic acid， 10 mg/kg） group， H-pachymic acid （high-dose pachymic acid， 20 mg/kg） group， and H-pachymic acid+EX527 （20 mg/kg pachymic acid+10 mg/kg EX527） group， with 6 rats in each group. Another 6 normal pregnant rats were selected as blank group. Each group was given relevant medicine or solvent intragastrically or intraperitoneally daily， once a day， for 28 consecutive days. After the last administration， 24 h urinary protein and tail artery systolic blood pressure （SBP） were measured in pregnant rats from each group， along with the levels of serum creatinine （Scr）， blood urea nitrogen （BUN），uric acid （UA）， and cystatin C （Cys-C）. The contents of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and 8-hydroxy-2′-deoxyguanosine （8-OHdG） in renal tissue， as well as the mRNA and protein expression levels of Sirt1 and PGC-1α， were also determined. Meanwhile， renal histopathological changes in rats from each group were evaluated using hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. RESULTS Compared with model group， L-pachymic acid group and H-pachymic acid group exhibited significant decreases in 24 h urine protein quantification， tail artery SBP， Scr， BUN， UA， Cys-C levels， glomerulosclerosis index score of renal tissue， renal tubular injury score， the percentage of PAS positive area， MDA and 8-OHdG （P＜0.05）. Conversely， the contents of SOD and GSH-Px， along with the mRNA and protein expression levels of Sirt1 and PGC-1α， were significantly increased （P＜0.05）. Moreover， these improvements were more pronounced in H-pachymic acid group （P＜0.05）. Compared with H-pachymic acid group， the aforementioned indicators in pregnant rats from the H-pachymic acid+EX527 group showed significant reversal （P＜0.05）. CONCLUSIONS Pachymic acid significantly ameliorates renal injury induced by PIH in rats， potentially through activation of the Sirt1/PGC-1α pathway.

CD8⁺ T cell-based immune-therapeutics, including immune checkpoint inhibitors and adoptive cell therapies (tumor-infiltrating lymphocytes (TILs), T cell receptor-engineered T cells (TCR-T), chimeric antigen receptor T cells (CAR-T)), have achieved significant successes and prolonged patient survival to varying extents and even achieved cure in some cases. However, immunotherapy resistance and tumor insusceptibility frequently occur, leading to treatment failure. Recent evidences have highlighted the ponderance of tumor cells metabolic reprogramming in establishing an immunosuppressive milieu through the secretion of harmful metabolites, immune-inhibitory cytokines, and alteration of gene expression, which suppress the activity of immune cells, particularly CD8⁺ T cells to evade immune surveillance. Therefore, targeting tumor cell metabolic adaptations to reshape the immune microenvironment holds promise as an immunomodulatory strategy to facilitate immunotherapy. Here, we summarize recent advances in the crosstalk between immunotherapy and tumor reprogramming, focusing on the regulatory mechanisms underlying tumor cell glucose metabolism, amino acid metabolism, and lipid metabolism in influencing CD8⁺ T cells to provide promising metabolic targets or combinational strategies for immunotherapy.

Objective To investigate the effect of NK cells on the proliferation of four kinds of colorec-tal cancer(CRC)lines,and to explore the feasibility of adoptive NK cell immunotherapy in the treatment of CRC so as to provide an experimental basis for the diagnosis and treatment of CRC.Methods Peripheral blood mononuclear cells were isolated by the Ficoll density gradient centrifuge method,which were in vitro in-duced to activate as the NK cells and amplified.The CCK-8 method was used to detect the effect of NK cells on the proliferation of CRC cell lines RKO,HCT15,HCT116 and LoVo.The inhibition rate of NK cells on CRC cell lines was statistically analyzed and compared.Results The inhibitory rate of NK cells against the same target cells was significantly different at different effect target ratios(P＜0.05).Under different num-ber of target cells(5 × 103 vs.1 × 104),the inhibitory rate of NK cells against RKO(effect-target ratio 0.4∶1),HCT15(effect-target ratio 0.4∶1 and 0.2∶1),HCT116(effect-target ratio 3.2∶1,1.6∶1,0.8∶1,0.4∶1 and 0.2∶1)and LoVo(effect-target ratio 1.6∶1,0.8∶1,0.4∶1,0.2∶1 and 0.1∶1)were significantly different(P＜0.05),while no statistical differences were found among other groups(P＞0.05).The effect-target ratio corresponding to the maximum inhibitory rate of NK cells against four CRC cell lines was 12.8∶1 under different target cell numbers.Conclusion Adoptive NK cell immunotherapy has an impor-tant significance for the early intervention and treatment of CRC,moreover 12.8∶1 may be a safe and effec-tive effect-target ratio.

Objective To investigate the risk factors for carbapenem-resistant Acinetobacter baumannii(CRAB)bloodstream infection in intensive care units(ICU)and construct a nomogram prediction model.Methods A retrospective analysis was conducted on the medical records of patients with CRAB bloodstream(BSI)infection in the ICU ward of the First Afliated Hospital,Sun Yat-sen University from January 1,2018 to December 31,2023.Cox regression analysis was usedo determine the risk factors for death in patients with CRAB bloodstream infection and to construct a nomogram.prediction model.The predictive ability of the no-mogramprediction model was evaluated by drawing calibration curves,receiver operating characteristic(ROC)curves,and consistency index(C-index).Results Septic shock(HR=7.770,95％CI:1.852-32.593)was an independent risk factor for mortality in patients with CRAB bloodstream infections,and hospitalisation day＞14 d(HR=0.331,95％CI:0.165-0.665)was an independent protective factor for mortality in patients with CRAB bloodstream infections.A nomogram was constructed based on the above factors,with a C-index of 0.725(95％CI:0.652-0.798).The predictive efficacy of patient survival rates at 20 d and 30 d was 0.831(95％CI:0.752-0.910)and 0.826(95％CI:0.715-0.937),respectively.The calibration curve was well fit-ted.Conclusion Septic shock was an independent risk factor for mortality in patients with CRAB bloodstream infections,and hospitalisation days＞14 d was an independent protective factor for mortality in patients CRAB BSI infections.The nomogram prediction model constructed accordingly has good predictive value for the sur-vival rate of patients in the intensive care unit who undergo CRAB bloodstream infections.

Objective To develop models for predicting response to chemotherapy combined with immunotherapy in patients with esophageal squamous carcinoma with various machine learning algorithms,and then select the optimal model.Methods A retrospective study was performed for 174 patients with esophageal squamous cell carcinoma undergoing chemotherapy combined with immunotherapy admitted in Department of Thoracic Surgery of the First Affiliated Hospital of Army Medical University from January 2022 to December 2023.The CT scans and clinical information were collected before treatment.They were randomly divided into a training set(n=122)and a testing set(n=52)in a ratio of 7∶3.CT radiomic features were extracted and selected,and then 5 machine-learning algorithms were employed to establish the prediction models,including radiomics model and clinical-radiomics model.Five-fold cross-validation was conducted on the training set,and the performance of the prediction models was evaluated on the testing set using receiver operating characteristic(ROC)curve and the F1 score.The best-performing model was further explained using local interpretable model-agnostic explanations(LIME)algorithm.Results Among the 174 patients,115(66.1%)achieved clinical remission.From the clinical information and CT images,1 clinical features and 10 radiomic features were identified.The area under of ROC curve(AUC)for the radiomics and clinical-radiomics models was 0.750(95%CI:0.616～0.883),and 0.766(95%CI:0.637～0.895),respectively.The F1 score of the optimal clinical-radiomics model was 0.829.LIME algorithm indicated that this best model demonstrated reliability in predicting individual samples.Conclusion The clinical-radiomics prediction model based on machine learning algorithm performs well,and can provide a reference for doctors'clinical decision-making by predicting the response to chemotherapy combined with immunotherapy in patients with esophageal squamous cell carcinoma.

Atherosclerosis(AS)is the common pathological basis of ischemic cardiovascular diseases,and its formation mechanism is complex.Western medical treatment has problems such as a long cycle and a high relapse rate.Ethnic medicine is an important part of traditional medicine,which has unique efficacy in treating cardiovascular diseases.Studies have shown that the Mongolian medicine Eldon-Uriel regulates blood lipids and improves blood rheology in the treatment of AS.This paper aims to pro-vide new ideas for the prevention and treatment of AS by collecting,organizing,and summarizing the relevant literature on Eldon-Uriel and introducing its unique concept,mechanism of action,and clinical studies in the treatment of AS.

Objective: To evaluate the effectiveness of recombinant Mycobacterium tuberculosis fusion protein skin test (EC-ST) in screening for latent tuberculosis infection (LTBI) among HIV/AIDS patients, so as to provide insights into the applicability of EC-ST in LTBI screening among HIV/AIDS patients. Methods: From April to June 2023, HIV/AIDS patients under management and treatment in Yangzhou City, Jiangsu Province, were selected as study subjects. Basic information was collected through questionnaire surveys. LTBI was screened by EC-ST and interferon-gamma release assay (IGRA). Taking IGRA results as the diagnostic standard, the positive rate, sensitivity, specificity and consistency rate of EC-ST, and the impact of CD4+T lymphocyte (CD4) counts on the screening effect of EC-ST were analyzed. Results: A total of 523 HIV/AIDS patients were screened, including 458 males (87.57%) and 65 females (12.43%). The median age was 48.00 (interquartile range, 21.00) years. The positive rate of EC-ST was 7.27% and the positive rate of IGRA was 7.46%, with no statistically significant difference (P>0.05). The consistency rate of the two methods was 94.84%, and the Kappa value of 0.621 (95%CI: 0.489-0.752, P<0.05). The sensitivity of EC-ST was 64.10% and the specificity was 97.31%. Comparing the groups with CD4 counts <500 and ≥500 cells/μL, the consistency rates of the two methods were 95.32% and 94.44%, and the Kappa values were 0.568 and 0.650, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05). Comparing the groups with CD4 counts <200 and ≥200 cells/μL, the consistency rates of the two methods were 96.55% and 94.62%, and the Kappa values were 0.648 and 0.619, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05). Conclusion The effectiveness of EC-ST in screening for LTBI among HIV/AIDS patients is consistent with that of IGRA and is not affected by CD4 counts.

Sepsis is one of the common severe diseases caused by the dysregulated host response to infection， which seriously threatens the life and health of human beings all over the world. The incidence and mortality of the disease are extremely high， and it has always been an urgent problem to be solved in the field of acute and critical diseases. At present， anti-infection， fluid resuscitation， mechanical ventilation and other programs are most used in clinic to treat sepsis， but their poor prognosis and high cost and other issues remain to be resolved. Therefore， it is necessary to explore a new， efficient， safe and inexpensive drug and treatment model at this stage. The treatment of traditional Chinese medicine （TCM） is based on syndrome differentiation and holistic concept. It can effectively regulate the progression of sepsis， maintain the homeostasis of the body， and has fewer adverse reactions. It has achieved good clinical results. In recent years， a large number of studies have shown that TCM can reduce the inflammatory response by regulating the Toll-like receptor 4（TLR4） signaling pathway， thereby reducing the severity and mortality of sepsis patients. However， there is still a lack of systematic exposition of TCM regulating TLR4 signaling pathway in the treatment of sepsis. Therefore， this article summarizes the relationship between TLR4 signaling pathway and sepsis and the mechanism of TCM in the disease by searching and consulting relevant literature in recent years. It is found that some Chinese medicine monomers and active ingredients， Chinese medicine compounds and Chinese medicine preparations can effectively reduce systemic inflammatory response， repair organ damage and improve the prognosis of sepsis by inhibiting the activation of TLR4 signaling pathway. However， due to various limitations， some studies have directly focused on the differential expression and function of TLR4， ignoring the downstream molecular expression and phenotypic effects of TLR4. The alternative mechanism， relationship and specific molecular mechanism of the pathway are still unclear. There are problems such as unclear pharmacokinetics and unclear mechanism in the pro- and anti-inflammatory balance， which need to be further studied and explored in order to provide new ideas for the potential treatment and drug development for sepsis.

Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

Objective To analyze the epidemiological characteristics of syphilis in Yangzhou City from 2013 to 2023, to understand the syphilis epidemic trends, and provide a scientific basis for formulating prevention and control strategies. Methods Syphilis case reports in Yangzhou City from 2013 to 2023 were collected through the infectious disease surveillance module of the Chinese Center for Disease Control and Prevention Information System. The annual average reported incidence rate and annual average growth rate were calculated. Descriptive epidemiological methods were employed to analyze the overview of syphilis and its temporal, geographical and demographic distribution characteristics. Linear trend chi-square tests were conducted to analyze the syphilis epidemic trends. Results A total of 19, 457 syphilis cases were reported in Yangzhou City from 2013 to 2023, with an annual average reported incidence rate of 39.17/100, 000. The overall incidence of syphilis showed an upward trend, with the reported incidence rate increasing from 37.26/100, 000 in 2013 to 43.27/100, 000 in 2023 (χ²= 50.528, P < 0.001), representing an annual average growth rate of 1.51%. The majority of reported cases were latent syphilis, accounting for 64.99% (12, 646/19, 457). The number of reported cases of primary, secondary and congenital syphilis revealed an overall decreased trend, while the number of reported cases of tertiary and latent syphilis increased trend. There was no significant seasonality or periodicity in the reported incidence rate of syphilis in Yangzhou City from 2013 to 2023. The top three districts with the highest annual average reported incidence rates were the Development District, Guangling District and Hanjiang District, with incidence rates of 50.93/100, 000, 50.89/100, 000 and 43.18/100, 000, respectively. There were 10, 290 male syphilis cases (52.89%) and 9, 167 female syphilis cases (47.11%). The top three occupations were farmers (8, 682 cases), homemakers and unemployed individuals (5, 379 cases) and retired personnel (2, 559 cases), accounting for 85.42% (16, 620/19, 457) of the reported cases. Conclusion The incidence of syphilis in Yangzhou City generally shows an upward trend, and the disease epidemic spectrum changes annually, with latent syphilis currently being the primary form. The prevention and control situation is severe. Therefore, syphilis prevention and control efforts should be further strengthened to block its transmission and prevalence.