ObjectiveTo investigate the functional role and underlying molecular mechanisms of fumarylacetoacetate hydrolase （FAH） in the progression of glioblastoma （GBM）. MethodsDifferential expression analysis was performed on the TCGA-GBM， GSE4290， and GSE116520 datasets. Weighted gene co-expression network analysis （WGCNA） was used to identify key modules， and Cox regression and risk modeling were used to screen prognostic genes. Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels. The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases. The functional role of FAH was validated by in vitro and in vivo experiments， and pathway analysis was performed to explore the underlying mechanisms. ResultsA total of 152 overlapping genes were identified across the three GBM datasets （P<0.05）. WGCNA revealed that the turquoise module was most strongly associated with tumor purity， stromal score， immune score， and ESTIMATE score （P<0.001）. Compared with normal tissues， three prognostic genes （CTSD， FAH， and THBD） were upregulated in GBM and correlated with immune infiltration （P<0.05）. FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues， and its expression was significantly associated with age stratification and TP53 mutation （P<0.05）. CCK-8 assay results showed that， compared with the shNC group， the proliferative activity of GBM cells in the shFAH group was reduced （P<0.001）. Transwell migration and invasion assays demonstrated that， relative to the shNC group， the numbers of migrated and invaded cells in the shFAH group decreased （P<0.05）. Western blot analysis revealed that the protein expression levels of PI3K， p-AKT， and p-mTOR in the shFAH group decreased compared with those in the shNC group （P<0.05）. In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight significantly decreased in the shFAH group compared with the shNC group （P<0.001）. ConclusionFAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic target for GBM.

ObjectiveTo investigate the efficacy and safety of atezolizumab combined with bevacizumab versus sintilimab combined with bevacizumab biosimilar in the treatment of patients with unresectable hepatocellular carcinoma （HCC） in a real-world setting， and to provide a reference for clinical practice. MethodsA retrospective analysis was performed for 130 patients with unresectable HCC who were treated in Beijing Ditan Hospital， Capital Medical University， from January 2020 to January 2026， and all patients received the first-line systemic therapy with immune checkpoint inhibitors combined with bevacizumab or its biosimilar. According to the treatment regimen， the patients were divided into atezolizumab+bevacizumab group （T+A group with 51 patients） and sintilimab+bevacizumab biosimilar group （Shuangda group with 79 patients）. The primary endpoint was progression-free survival （PFS）， and secondary endpoints included objective response rate （ORR）， disease control rate （DCR）， and safety profile. The independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between the two groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used for survival analysis， and the Log-rank test was used for comparison between groups. ResultsThe T+A group had a median PFS of 297.00 days （95% confidence interval ［CI］： 195.44 — 398.56）， and the Shuangda group had a median PFS of 236.00 days （95%CI： 165.10 — 306.90）， with no significant difference between the two groups （P=0.668）. There were no significant differences between the T+A group and the Shuangda group in ORR （56.9% vs 45.6%， χ²=1.581， P=0.209）， DCR （76.5% vs 77.2%， χ²=0.010， P=0.922）， and the incidence of adverse events （96.08% vs 94.94%， P>0.05）. ConclusionFor unresectable HCC patients without prior systemic treatment， atezolizumab combined with bevacizumab can achieve a comparable PFS to sintilimab combined with bevacizumab biosimilar.

Objective:To explore the value of lymphocyte subsets in predicting the efficacy and prognosis of non-small cell lung cancer(NSCLC)patients receiving programmed death receptor 1(PD-1)monoclonal antibody(mAb)combined with chemotherapy.Methods:A retrospective analysis was conducted on the clinical data of 50 NSCLC patients diagnosed and treated with PD-1 mAb combined with chemotherapy at the Second Hospital of Lanzhou University from January 2022 to December 2023.Peripheral blood lymphocyte subsets(including total T cells,CD4+T cells,CD8+T cells,NK cells,total B lymphocytes,and CD4+/CD8+T cell ratio)were collected before and after two cycles of treatment.After two cycles of treatment,imaging examination was performed to evaluate the therapeutic efficacy,dividing patients into disease control(DC)group and disease progression(PD)group.The relationship between lymphocyte subset levels and the short-term efficacy in NSCLC patients was analyzed using chi-square test,rank sum test,and Logistic regression analysis.The value of lymphocyte subsets in predicting patients'progression-free survival(PFS)was explored using Kaplan-Meier method.Results:PD-1 mAb combined with chemotherapy significantly influenced the immune status of NSCLC patients.After treatment,the peripheral blood CD4+T cells and CD4+/CD8+T cell ratio significantly increased(both P<0.01),while the level of CD8+T cells decreased.In terms of short-term efficacy,the proportion of CD4+T cells and the CD4+/CD8+T cell ratio in the DC group were significantly higher than those in the PD group(both P<0.01).Logistic multivariate analysis showed that the CD4+/CD8+T cell ratio was an independent factor affecting the efficacy of PD-1 mAb combined with chemotherapy.ROC curve analysis showed that the area under the curve(AUC)for CD4?/CD8? T cell ratio variation was 0.820(>0.5),with a cut-off value of 0.15.Patients with a the CD4+/CD8+T cell ratio increase of≥0.15 had a longer PFS.Conclusion:The proportion of CD4+T cells,CD8+T cells,and the CD4+/CD8+T cell ratio in peripheral blood can predict the efficacy and prognosis of PD-1 mAb combined with chemotherapy in advanced NSCLC patients.

BACKGROUND:The cryopreservation technology enables tissues/cells to be stored for a long time in a low-temperature environment while maintaining the integrity of their activity and function,which is of great significance for the construction of cell therapy,tissue engineering and biological sample banks.Cryoprotective agents often contain dimethyl sulfoxide and serum.To avoid the toxic side effects of dimethyl sulfoxide,the complexity of serum components and immune responses,although some finished cryoprotective agents have been marketed,they are faced with many difficulties such as high cost and limited application.Therefore,there is an urgent need to develop a cryoprotective agent with clear components and the ability to solve the above problems.OBJECTIVE:To evaluate the effects of a novel cryoprotectant on cryopreservation efficiency of different tissue and cell sources.METHODS:By applying the novel cryoprotectant as an experimental group with the commercially available and widely used cryoprotectant(control group)to umbilical cord Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,NK and CIK cells,comparative analyses were conducted in terms of cell morphology,number,viability,surface markers,differentiation potential,and cell-killing toxicity assay before cryopreservation and after resuscitation thawing.We confirmed the cryopreservation effect of the new cryoprotectant and its potential application value.RESULTS AND CONCLUSION:(1)The novel cryoprotectant facilitated the normal growth of cryopreserved Wharton's jelly tissue upon recovery,exhibiting mesenchymal stem cell morphology.No significant differences were observed between the experimental and control groups in terms of cell recovery rate,surface markers,and differentiation potential.(2)There was no significant difference in the number and viability of cells between the experimental group and the control group after cryopreservation of cord blood/peripheral blood mononuclear cells,and the cryo-resuscitated cell numbers and viability of derived NK cells/CIK cells did not show significant difference between the experimental and control groups.(3)For NK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportion of CD56+CD16+cell subpopulations between the experimental group and the control group.For CIK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportions of CD3+CD8+and CD3+CD56+cell subpopulations between the experimental group and the control group.(4)In terms of cytotoxicity testing,when the effective-target ratio of immune cells and melanoma cell line Mel624 was 20:1,whether it was NK cells/CIK cells derived from cord blood or peripheral blood mononuclear cells,there was no significant difference in the tumoricidal activity of cells between the experimental group and the control group.These findings suggest that the novel cryoprotectant can replace existing commercially available and widely used cryoprotectants,and is applicable to Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,as well as NK and CIK cells,providing a solid technical foundation for the scaling,standardization,and commercialization of universal cryoprotectants.

BACKGROUND:The cryopreservation technology enables tissues/cells to be stored for a long time in a low-temperature environment while maintaining the integrity of their activity and function,which is of great significance for the construction of cell therapy,tissue engineering and biological sample banks.Cryoprotective agents often contain dimethyl sulfoxide and serum.To avoid the toxic side effects of dimethyl sulfoxide,the complexity of serum components and immune responses,although some finished cryoprotective agents have been marketed,they are faced with many difficulties such as high cost and limited application.Therefore,there is an urgent need to develop a cryoprotective agent with clear components and the ability to solve the above problems.OBJECTIVE:To evaluate the effects of a novel cryoprotectant on cryopreservation efficiency of different tissue and cell sources.METHODS:By applying the novel cryoprotectant as an experimental group with the commercially available and widely used cryoprotectant(control group)to umbilical cord Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,NK and CIK cells,comparative analyses were conducted in terms of cell morphology,number,viability,surface markers,differentiation potential,and cell-killing toxicity assay before cryopreservation and after resuscitation thawing.We confirmed the cryopreservation effect of the new cryoprotectant and its potential application value.RESULTS AND CONCLUSION:(1)The novel cryoprotectant facilitated the normal growth of cryopreserved Wharton's jelly tissue upon recovery,exhibiting mesenchymal stem cell morphology.No significant differences were observed between the experimental and control groups in terms of cell recovery rate,surface markers,and differentiation potential.(2)There was no significant difference in the number and viability of cells between the experimental group and the control group after cryopreservation of cord blood/peripheral blood mononuclear cells,and the cryo-resuscitated cell numbers and viability of derived NK cells/CIK cells did not show significant difference between the experimental and control groups.(3)For NK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportion of CD56+CD16+cell subpopulations between the experimental group and the control group.For CIK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportions of CD3+CD8+and CD3+CD56+cell subpopulations between the experimental group and the control group.(4)In terms of cytotoxicity testing,when the effective-target ratio of immune cells and melanoma cell line Mel624 was 20:1,whether it was NK cells/CIK cells derived from cord blood or peripheral blood mononuclear cells,there was no significant difference in the tumoricidal activity of cells between the experimental group and the control group.These findings suggest that the novel cryoprotectant can replace existing commercially available and widely used cryoprotectants,and is applicable to Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,as well as NK and CIK cells,providing a solid technical foundation for the scaling,standardization,and commercialization of universal cryoprotectants.

Objective To analyze the current status of serum calcium,phosphorus,and hemoglobin(Hb)levels in maintenance hemodialysis patients and identify related influencing factors.Methods Clinical data and related laboratory tests of maintenance hemodialysis patients were retrospective analyzed,clinical related indicators and target achievement rates among different serum calcium,phosphorus and Hb patients were analyzed,correlation and multiple linear regression analysis of serum corrected calcium,phosphorus and Hb and clinical indicators were performed.Results 217 maintenance hemodialysis patients,115(53.0％)cases were male,mean age was(55.88±13.54)years.The target achievement rates for serum corrected calcium,phosphorus,and Hb was 50.70％,24.00％,and 34.10％respectively.Multivariate linear regression analysis revealed that in maintenance hemodialysis patients,serum corrected calcium was independently positively correlated with bicarbonate and Hb;Serum phosphorus was independently positively correlated with creatinine,urea,and serum potassium,but negatively correlated with age;And Hb was independently positively correlated with total protein and serum corrected calcium,while being negatively correlated with C-reactive protein,β2 microglobulin,and parathyroid hormone.Conclusion The control target achievement rates for serum calcium,phosphorus,and Hb in maintenance hemodialysis patients at our center are low.Attention which should be paid to the related influencing factors of these indicators is beneficial to guide the control of complications and provide a reference for clinical disease management.

Objective The purpose of this study is to utilize CiteSpace visualization software for literature analysis to investigate published literature concerning geriatric pharmacy outpatient services,create a knowledge graph,and analyze and discuss the developmental process and relevant hotspots of geriatric pharmacy outpatient services in China.Methods Utilizing the China National Knowledge Infrastructure(CNKI)as the source database,a search for literature containing the core phrases"pharmacy outpatient",'pharmacist outpatient","drug outpatient","drug consultation outpatient"and"elderly"was conducted from the inception of the database to March 2024 for data extraction.CiteSpace was employed to generate a visual knowledge graph,analyze,and discuss key nodes such as authors,institutions,and keywords within the realm of geriatric pharmacy outpatient services.Results After screening based on inclusion criteria,a total of 396 articles were included in the study.Scholars such as Ge Weihong,Wu Qiuhui and Liu Yang have made significant contributions to the research field of geriatric pharmacy outpatient services.Drum Tower Hospital affiliated with Nanjing University Medical School,the Sixth People's Hospital affiliated with Shanghai Jiao tong University,Dali University rank as the top three publishing institutions in terms of publication volume.The most frequently occurring keywords in the published literature include"pharmaceutical services","clinical pharmacists","pharmacy clinics","rational drug use"and"pharmacists".Conclusion"Drug safety","survey questionnaires"and"tertiary hospitals"have emerged as prominent and evolving topics within the realm of geriatric pharmacy outpatient services in China in recent years.In general,there remains considerable potential for further development in both the scope and depth of outpatient services for the elderly in the field of pharmacy in China.

Objective To analyze the current status of serum calcium,phosphorus,and hemoglobin(Hb)levels in maintenance hemodialysis patients and identify related influencing factors.Methods Clinical data and related laboratory tests of maintenance hemodialysis patients were retrospective analyzed,clinical related indicators and target achievement rates among different serum calcium,phosphorus and Hb patients were analyzed,correlation and multiple linear regression analysis of serum corrected calcium,phosphorus and Hb and clinical indicators were performed.Results 217 maintenance hemodialysis patients,115(53.0％)cases were male,mean age was(55.88±13.54)years.The target achievement rates for serum corrected calcium,phosphorus,and Hb was 50.70％,24.00％,and 34.10％respectively.Multivariate linear regression analysis revealed that in maintenance hemodialysis patients,serum corrected calcium was independently positively correlated with bicarbonate and Hb;Serum phosphorus was independently positively correlated with creatinine,urea,and serum potassium,but negatively correlated with age;And Hb was independently positively correlated with total protein and serum corrected calcium,while being negatively correlated with C-reactive protein,β2 microglobulin,and parathyroid hormone.Conclusion The control target achievement rates for serum calcium,phosphorus,and Hb in maintenance hemodialysis patients at our center are low.Attention which should be paid to the related influencing factors of these indicators is beneficial to guide the control of complications and provide a reference for clinical disease management.

OBJECTIVE To analyze the clinical characteristics of the 12 patients tested with Candida auris in a three-A hospital so as to provide guidance for prevention and control of nosocomial C.auris infection.METHODS The specimens sources and departments where the C.auris strains were isolated as well as the drug resistance were retrospectively collected from Zhongda Hospital Affiliated to Southeast University between Sep.2023 and Jun.2024.The clinical characteristics of the patients with C.auris infection were summarized.The epidemiological survey was conducted for the possibility of its transmission in hospitals,and the corresponding modified preven-tion measures were put forward.RESULTS Among the 12 patients who were tested with C.auris,10 were male,and 2 were female;the age ranged between 21 and 92 years old.Most of the patients were complicated with multi-ple underlying diseases and had the history of repeated hospitalization as well as the history of invasive operation procedures such as tracheotomy,urinary catheterization,gastric tube indwelling and venoarterial catheterization;in the meantime,other multidrug-resistant organisms(MDROs)and fungi were tested in those patients,and the patients used multiple types of antibiotics.Totally 16 strains of C.auris were isolated from the 12 patients with C.auris tested,62.50％(10/16)of which were isolated from urine specimens,18.75％(3/16)were isolated from sputum specimens,and 6.25％(1/16)were isolated from deep venous catheter,tissue biopsy and wound swab specimens.All of the 16 strains of C.auris were resistant to fluconazole and sensitive to caspofungin;4 strains were resistant to amphotericin B.Totally 2 patients had Candida auris infection,one was pulmonary infection,and the other was urinary tract infection,and the infection rate was 16.67％;both patients were cured.There were 10 cases of colonization,and the colonization rate was 83.33％.The result of epidemiological survey indicated that the C.auris that was tested in the No.8 patient may originate from the No.4 patient who carelessly brought from outside the hospital due to poor implementation of standardized prevention measures.CONCLUSIONS The patients tested with C.auris usually have complicated medical backgrounds.Although the colonized C.auris strains are dominant among the strains in the hospital,the related departments need to intensify the implementation of pre-vention measures so as to prevent the transmission of C.auris and pay special attention to the early identification and management of imported pathogens.

Objective:To construct a nomogram model for predicting the incidence of hepatocellular carcinoma based on serum abnormal prothrombin and alpha-fetoprotein and evaluate the predictive effect.Methods:Retrospective analysis of data from 351 patients with liver disease who received treatment at the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2023, including 285 males and 66 females, aged (52.9±11.9) years. Among the 351 patients, there were 229 cases (65.2%) of hepatocellular carcinoma, 87 cases (24.8%) of liver cirrhosis, and 35 cases (10.0%) of chronic hepatitis B. All patients were randomly divided into a training set ( n=245) and a testing set ( n=106) in a 7∶3 ratio without replacement sampling. The training set was used to construct the model, and the testing set was used to evaluate the model. At the same time, gender, age, disease type, and other indicators were compared between the two sets. The risk factors of hepatocellular carcinoma were analyzed by univariate and multivariate logistic regression based on the training set, and a nomogram was constructed to predict the incidence of hepatocellular carcinoma based on the multivariate results. Receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the predictive performance of nomogram, and decision curve analysis was used to evaluate the clinical applicability of the model. Results:There was no statistically significant difference in age, gender, disease type, etc. between the training and testing sets of patients (all P>0.05). Univariate logistic regression analysis showed that age, abnormal prothrombin logarithm (LnPIVKA-Ⅱ), alpha-fetoprotein logarithm (LnAFP), and diabetes were associated with hepatocellular carcinoma (all P<0.05). Multivariate logistic regression analysis showed that older age ( OR=1.07, 95% CI: 1.03-1.12), higher LnPIVKA-Ⅱ ( OR=2.97, 95% CI: 1.97-4.46), higher LnAFP ( OR=1.43, 95% CI: 1.11-1.84) and diabetes ( OR=5.17, 95% CI: 1.02-26.17) were risk factors for hepatocellular carcinoma (all P<0.05). Based on the above variables, a nomogram model for predicting the incidence of hepatocellular carcinoma was constructed. The area under the ROC curve analysis of the nomogram for predicting the incidence of hepatocellular carcinoma was 0.920 (95% CI: 0.886-0.953) in the training set and 0.934 (95% CI: 0.891-0.977) in the testing set. The calibration curve fit well with the standard curve, and the prediction was basically consistent with the actual situation. The decision curve analysis showed that the net benefit of the model was greater than 0 under most thresholds (0.1-1.0). Conclusion:The nomogram constructed based on age, LnPIVKA-Ⅱ, LnAFP and diabetes can effectively predict the incidence of hepatocellular carcinoma and has clinical applicability.