ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

OBJECTIVE T o assess the in vitro antimicrobial activity of aztreonam-avibactam against metallo-β—lacta-mase(MBL)-producing carbapenem-resistant Enterobacteriaceae(CRE)using different antimicrobial susceptibility testing methods,evaluate the consistency of results based on the latest breakpoints recommended by European Committee on Antimicrobial Susceptibility Testing(EUCAST),and analyze the clinical applicability.METHODS The imipenem-or meropenem-resistant Enterobacteriaceae strains were isolated from the clinical specimens of Bei-jing Chaoyang Hospital from Jan.2019 to Mar.2023,MBL-producing CRE were selected after they were con-firmed by colloidal gold immunoassay and Sanger sequencing as the study subjects.The minimum inhibitory con-centrations(MICs)of single aztreonam and aztreonam-avibactam compounds were determined by using broth mi-crodilution method.In addition,the disk diffusion method and the gradient diffusion method were employed to further detect the in vitro susceptibility to aztreonam-avibactam.RESULTS Among the 87 strains of MBL-producing CRE that were included in the study,Escherichia coli was the most common species,accounting for 44.83％.NDM-5 was the predominant carbapenemase type,detected in 48.28％of the isolates.According to the latest EUCAST break-points,6 isolates were aztreonam-avibactam-resistant strains based on broth microdilution method,all of which were E.coli,and the resistance rate was 6.90％(6/87).However,the resistance rate that was determined by the disk diffu-sion method was significantly higher(22.99％,20/87).Among these,14 strains was within the area of technical uncer-tainty/resistant,making result interpretation difficult.In addition,the categorical agreement between the gradient diffu-sion method and the broth microdilution method reached up to 98.85％.CONCLUSIONS Aztreonam-avibactam has high antimicrobial activity against MBL-producing CRE.However,based on the latest EUCAST breakpoints,the antimicrobial susceptibility testing by the disk diffusion method results of some strains are hard to interpret.It is necessary to integrate with other methods for further validation.

Objective To analyze the status quo and high-risk factors of hemorrhagic transformation(HT)in patients with acute cerebral infarction(ACI)treated with alteplase(rt-PA).Methods A total of 462 patients with ACI who were admitted to Hai'an People's Hospital and treated with rt-PA from June 2019 to June 2023 were retrospectively emrolled.According to the occurrence of HT,the patients were assigned to HT group(n=31)or non-HT group(n=431).The clinical data of the two groups were compared,and high-risk factors of HT in ACI patients treated with rt-PA were analyzed.Results The incidence of HT was 6.71%(31/462).Multivariate logistic analysis showed that increased systolic blood pressure(SBP),severe cerebral small vessel disease(CSVD),and increased neutrophil-to-lymphocyte ratio(NLR)were the high-risk factors of HT in patients with ACI after treatment with rt-PA(P＜0.05).Conclusion There is a high incidence of HT in patients with ACI after treatment with rt-PA,the levels of SBP,CSVD and NLR are the influencing factors,and they can provide a basis for prediction and clinical intervention.

[Objective] To investigate the implementation of emergency transfusion strategy of uncrossmatched type O suspended RBCs based on the single-center clinical practice, which is "emergency transfusion is initiated by the authorized doctor of the emergency department, and no more than 4 U of type O uncrossmatched suspended RBCs are issued within 15 minutes in the transfusion department"(referred as the Practice), so as to provide reference for blood management. [Methods] A retrospective analysis of the information of patients who received uncrossmatched type O suspended RBCs in West China Hospital of Sichuan University from August 2019 to April 2024 was conducted. The analysis included reasons for emergency blood transfusion, time of receiving transfusion application and blood distribution, total bilirubin, indirect bilirubin, lactate dehydrogenase before and after transfusion, blood group of patients, and disease outcome. [Results] From August 2019 to April 2024, 39 cases applied for emergency transfusion of type O suspended RBCs, and a total of 90 U uncrossmatched suspended RBCs were transfused. All patients were Rh(D) positive, including 14 cases of blood group A, 6 cases of blood group B, 16 cases of blood group O, 2 cases of blood group AB, one case of undetermined blood group, and 2 cases with positive antibody screening. The main cause of emergency transfusion of type O suspended RBCs was traffic accident, accounting for 46% (18/39), with a mortality rate at 51.28% (20/39). The cause of death was primary injury, and no adverse reactions were reported. There was no significant difference in total bilirubin (TBIL), indirect bilirubin (IBIL) and lactate dehydrogenase (LDH) before and after blood transfusion (P>0.05). The median duration from admission to receiving transfusion application was 30.20 minutes, and 5.30 minutes from receipt of the application to blood distribution. [Conclusion] The single-center based Practice is safe, but there is room for optimization before the link of blood transfusion application sent to the transfusion department when applying for emergency transfusion of type O suspended RBCs.

Very-late-onset schizophrenia-like psychosis(VLOSLP)is considered the most common mental disorder in the elderly following dementia and depression, and its clinical symptomatology is different from that of schizophrenia with onset around the average age.The diagnostic classification system and prognosis of VLOSLP are very complicated, and it is still controversial whether it should be classified as a prodromal symptom of dementia or as a type of late-onset schizophrenia.This article reviewed studies concerning the epidemiology, clinical features, diagnosis, prognosis, and neuroimaging of VLOSLP, hoping to provide value as a reference for future clinical research and treatment.

Objective:To explore the risk factors of blood pressure fluctuations during the dialysis period in maintenance hemodialysis (MHD) patients and their impact on long-term survival.Methods:A total of 100 cases of MHD patients admitted to Anhui Linquan People′s Hospital from September 2020 to May 2022 were selected and divided into high fluctuation group (coefficient of variation in systolic blood pressure>8.64%) and non-high fluctuation group (coefficient of variation in systolic blood pressure ≤ 8.64%). The clinical data of the two groups were compared, and the LASSO model was used to conduct the preliminary screening for each risk factor. The nomogram prediction model of blood pressure fluctuation during the dialysis period was drawn, and the receiver operating characteristic (ROC) curve and calibration curve was drawn to obtain the prediction efficiency and calibration degree of the nomograph model. Kaplan-Meier survival curve was drawn to compare the 1-year survival status of the two groups.Results:The results of single factor analysis showed that body mass index, dialysis age, urea clearance index, ultrafiltration volume, serum calcium, serum albumin, serum phosphorus, serum sodium, total parathyroid hormone (iPTH), serum uric acid, serum creatinine, C-reactive protein, alkaline phosphatase, early diastolic maximum blood flow in the left ventricle (peak E)/atrial systolic maximum blood flow of mitral valve (peak A), and left ventricular ejection fraction (LVEF) were risk factors for blood pressure fluctuation during dialysis ( P<0.05). The prediction model of nomograph was drawn, and the consistency index (C-index) was 0.941, the prediction sensitivity was 88.40%, and the specificity was 91.20%. Kaplan-Meier survival curve analysis showed that the 1-year survival rate in the high fluctuation group was lower than that in the non-high fluctuation group ( P<0.05). Conclusions:Blood pressure fluctuation during dialysis in MHD patients is related to blood sodium, calcium and phosphorus, iPTH, blood uric acid, albumin, peak E/peak A, and LVEF, and can affect the prognosis of patients, and attention should be paid to the monitoring and control of above indexes of the patients in order to improve the prognosis.

Objective:To investigate the effect of intradialytic cerebral blood flow (CBF) fluctuation on cognitive decline in middle-aged and elderly maintenance hemodialysis (MHD) patients.Methods:It was a prospective cohort study. MHD patients aged ≥50 years from Beijing Shijitan Hospital were enrolled from January 2023 to June 2023. Middle cerebral artery mean flow velocity (MFV) was serially monitored via transcranial Doppler (TCD) during dialysis sessions. Cognitive function was assessed at baseline and after 12-month follow-up using standardized neuropsychological tests: montreal cognitive assessment (MoCA), auditory verbal learning test (AVLT 5), complex figure test (CFT), trail making test-B (TMT-B), Stroop color and word test (SCWT), and symbol digit modalities test (SDMT). ΔMFV was calculated as pre-to-post dialysis MFV difference. Multivariable linear regression was used to analyze the association of ΔMFV and cognition.Results:A total of 121 MHD patients were recruited with an age of (63.63±8.44) years. There were 97 males (80.2%), and the dialysis vintage was (55.08±54.73) months. Significant intradialytic MFV reductions were observed ( P<0.05). At 12 months, cognitive decline manifested in global cognition (MoCA), memory (CFT-memory), executive function (TMT-B, SCWT-C, SCWT-T), attention (SDMT), visuospatial ability (CFT-copy)(all P<0.05). Multivariable linear regression analysis revealed ΔMFV independently predicted declines in: MoCA ( B=0.066, 95% CI 0.018-0.113, P=0.007), AVLT5 ( B=0.050, 95% CI 0.004-0.097, P=0.035), TMT-B ( B=-1.955, 95% CI -3.453--0.457, P=0.011), SCWT-C ( B=0.298, 95% CI 0.112-0.484, P=0.002), SCWT-T ( B=-1.371, 95% CI -2.303--0.439, P=0.004). Conclusions:Hemodialysis induces acute CBF reductions detectable by TCD. Cumulative intradialytic CBF fluctuations may accelerate cognitive deterioration in middle-aged and elderly MHD populations, particularly affecting memory and executive domains.

Objective To investigate the weight loss efficacy and mechanisms of oligopeptide-herbal medicine composite,and to provide new approaches for obesity treatment.Methods Twenty-three SPF female SD rats were randomly divided into control group(n=3)and modeling group(n=20).The control group was fed an ordinary diet for 6 consecutive weeks,and the modeling group was fed a high-fat diet for 6 consecutive weeks to establish a simple obesity rat model.After successful modeling,the modeling group was randomly divided into model group(n=10)and treatment group(n=10).The treatment group started anoint-and-massage therapy with oligopeptide-herbal medicine composite(3 g per rat per time,once a day,20 min each time),which was recorded as day 1.The control group and model group were not treated with oligopeptide-herbal medicine composite but received the same massage,and continued to be fed ordinary feed and high-fat feed respectively.Ten rats in the model group and ten in the treatment group were each divided into 3 groups,with 3,3,and 4 rats in each group.On days 3,6,and 9 after treatment,the rats in the three groups were weighed and cardiac blood collection was performed after isoflurane respiratory anesthesia.After euthanasia by cardiac bloodletting,abdominal subcutaneous adipose tissue(aSAT)and perirenal white adipose tissue(pWAT)samples were collected and weighed.Serum triglycerides(TG)and high-density lipoprotein cholesterol(HDL-C)levels were measured.Image J software was used to measure aSAT thickness and the diameter and area of perirenal white adipocytes and abdominal subcutaneous adipocytes.Immunofluorescence technique was used to observe the number of telocytes(TCs),cell junctions and exosomes per unit area of aSAT.Transmission electron microscopy was used to measure the length of telopodes(Tps)of dermal and subcutaneous TCs in abdominal skin,and to observe the distribution of exosome vesicles,rough endoplasmic reticulum,mitochondria,and cell junctions.Results Compared with the control group,the body weight of rats in the modeling group increased significantly(P＜0.05).Compared with the control group,rats in the model group showed a significant increase in serum TG level,a significant decrease in HDL-C level,and a significant increase in pWAT mass(all P＜0.05).Compared with the model group,the treatment group showed a significantly increased rate of body weight reduction,significantly decreased pWAT mass,significantly decreased serum TG level,and significantly increased HDL-C level(all P＜0.05).Compared with the model group,the treatment group showed significant reductions in aSAT thickness,as well as cell diameter and area in both aSAT and pWAT(all P＜0.05).Compared with the model group,the treatment group showed significantly increased number of TCs per unit area of aSAT,number of exosomes from TCs in aSAT,and Tps length(all P＜0.05).The treatment group showed an increasing trend in the numbers of mitochondria,rough endoplasmic reticulum,and cell junctions in TCs.Conclusion Oligopeptide-herbal medicine composite applied via anoint-and-massage therapy effectively improves obesity-related symptoms such as dyslipidemia and fat accumulation in obese rats by regulating TCs and their intercellular communication.