ObjectiveTo investigate the expression of serum Aldo-keto reductase family 1 member B10 （AKR1B10） in patients with hepatocellular carcinoma （HCC） in northern China， and to provide a new and valuable biomarker for the clinical diagnosis of HCC. MethodsThis study was conducted among 102 patients with HCC， 119 patients with benign liver disease， and 132 patients with other malignant tumors who attended The Affiliated Hospital of Chengde Medical University and 148 healthy individuals who underwent physical examination from May 2020 to May 2024. ELISA and chemiluminescence were used to measure the serum levels of AKR1B10 and alpha-fetoprotein （AFP）. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between three groups and further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to assess diagnostic efficiency. ResultsThe expression level of AKR1B10 was 3 053.79 （1 475.67‍ ‍—‍ ‍4 605.86） pg/mL in the HCC group， 1 324.42 （659.68‍ ‍—‍ ‍2 023.88） pg/mL in the benign liver disease group， 660.68 （377.56‍ ‍—‍ ‍2 087.77） pg/mL in the other malignant tumor group， and 318.30 （82.73‍ ‍—‍ ‍478.82） pg/mL in the healthy group， with a significant difference between the four groups （H=240.86， P<0.001）， and further comparison between two groups showed that the HCC group had a significantly higher level than the other three groups （all P<0.001）. The ROC curve analysis of the HCC group and the other three groups showed that serum AKR1B10 had an optimal cut-off value of 1 584.97 pg/mL in the diagnosis of HCC， with an AUC of 0.86 （95% confidence interval ［CI］： 0.82‍ ‍—‍ ‍0.90）， a sensitivity of 74.3%， and a specificity of 85.2%. Compared with each indicator alone， a combination of AKR1B10 and AFP could improve the sensitivity （81.8%） and specificity （91.4%） of HCC diagnosis. AKR1B10 had an AUC of 0.84 （95%CI： 0.78‍ ‍—‍ ‍0.90） in the diagnosis of patients with early- or middle-stage HCC， with a sensitivity of 76.2% and a specificity of 81.2%. AKR1B10 had an AUC of 0.85 （95%CI： 0.77‍ ‍—‍ ‍0.92） in the diagnosis of patients with AFP-negative HCC， with a sensitivity of 81.6% and a specificity of 79.9%. ConclusionAKR1B10 is a promising serological marker for the diagnosis of HCC， and a combination of AKR1B10 and AFP can improve the detection rate of HCC patients in northern China， especially those with early- or middle-stage HCC and AFP-negative HCC.

Objective To evaluate the performance of two immunochromatography kits (lateral flow immunoassay) in detecting carbapenemases in carbapenem-resistant Enterobacterales (CRE).Methods A total of 390 nonduplicate clinical isolates of Enterobacterales were collected and tested.The carbapenemase gene was identified by polymerase chain reaction (PCR).The five common carbapenemases were tested by two immunochromatography kits.Results Overall,213 of the 390 Enterobacterales isolates were CRE and 177 strains were carbapenem-susceptible based on antimicrobial susceptibility testing.PCR assay confirmed that 207 of the 213 CRE strains carried carbapenemase genes,including KPC genotype in 119 strains,NDM genotype in 71 strains,IMP genotype in 9 strains,OXA-48-like genotype in 7 strains,both KPC and NDM genes in 1 strain,while none of the five common carbapenemases in 6 CRE strains.Two immunochromatography kits were used simultaneously to test the production of carbapenemases.The results of the two commercial kits were 100％ consistent with PCR results.The sensitivity and specificity of the two kits were 100％ (95％ CI,97.7％-100％) and 100％ (95％ CI,97.4％-100％) in detection of the five carbapenemases.Conclusions The immunochromatography method is rapid and easy to operate,and can be used to detect the production of carbapenmases in clinical isolates.

Alzheimer′s disease (AD) is a neurodegenerative disorder. In the past few decades, the exact mechanisms underlying the onset of the disease have remained unclear, and treatment options are still lacking. Due to the inability of two-dimensional cell and animal models to fully simulate the pathogenesis of AD, there have been shortcomings in clinical trials of new drugs. The development of organoids and organ-on-a-chip technologies has improved the dilemma of AD research, providing reliable in vitro research models for studying pathogenic mechanisms and drug screening. This article elaborates on the applications and progress of organoids and organ-on-a-chip in AD modeling, pathogenesis, and drug development, and discusses the current limitations of organoids and organ-on-a-chip and their future perspectives.

Microcephaly is a common pediatric neurodevelopmental disorder with complex etiology. In recent years, with the development of brain organoid technology, there has been rapid progress in understanding the pathogenesis and treatment strategies of microcephaly using this technology. This article elucidates the advantages of brain organoids over traditional experimental models, reviews the research progress of brain organoid technology in disease modeling and drug screening for various causes of microcephaly, and discusses the limitations and future prospects of brain organoids.

In recent years， the incidence and mortality rates of cancer have been increasing， posing a serious threat to human health. Western medicine mainly uses treatments such as surgical resection， chemotherapy， immunotherapy and targeted therapy， but they are prone to complications， drug resistance and adverse reactions. A growing number of studies have shown that traditional Chinese medicine has obvious advantages in the treatment of cancer， reducing the recurrence rate of cancer and improving the quality of survival of patients. Cellular senescence refers to a state of irreversible cell cycle growth arrest when cells cease to proliferate after a limited number of divisions， resulting in a decline in cell proliferation and differentiation capacities and physiological functions， accompanied by morphological changes such as flattening and multinuclear morphology. At the molecular level， it shows increased expression of DNA damage-related genes， reduced expression of cell cycle-related factors and significant secretory activity. The malignant development of cancer is closely related to cellular senescence. With the increasing number of cancer cell proliferation， cancer-related genes undergo continuous mutations， freeing them from cellular senescence and thus achieving unlimited proliferation. Through recent studies， it has been found that induction of tumor cell senescence， possibly through modulation of cellular DNA damage， cell cycle arrest and senescence-associated secretory phenotype （SASP）， which converts the suppressive immune tumor microenvironment to an activated immune tumor microenvironment and thus reverses the escape of tumor cell senescence， is a promising strategy for cancer therapy. However， the mechanism of cellular senescence in cancer progression is not fully understood， especially the anti-cancer role played by traditional Chinese medicine in regulating cellular senescence. This article summarized and concluded the specific molecular mechanisms of cellular senescence， the role of cellular senescence in cancer progression， and the mechanism of anti-cancer effects of traditional Chinese medicine based on cellular senescence from the perspective of regulating cellular senescence， with a view to providing ideas and methods for the anti-cancer effects of traditional Chinese medicine and the development of new drugs.

Objective To evaluate the performance of two immunochromatography kits (lateral flow immunoassay) in detecting carbapenemases in carbapenem-resistant Enterobacterales (CRE).Methods A total of 390 nonduplicate clinical isolates of Enterobacterales were collected and tested.The carbapenemase gene was identified by polymerase chain reaction (PCR).The five common carbapenemases were tested by two immunochromatography kits.Results Overall,213 of the 390 Enterobacterales isolates were CRE and 177 strains were carbapenem-susceptible based on antimicrobial susceptibility testing.PCR assay confirmed that 207 of the 213 CRE strains carried carbapenemase genes,including KPC genotype in 119 strains,NDM genotype in 71 strains,IMP genotype in 9 strains,OXA-48-like genotype in 7 strains,both KPC and NDM genes in 1 strain,while none of the five common carbapenemases in 6 CRE strains.Two immunochromatography kits were used simultaneously to test the production of carbapenemases.The results of the two commercial kits were 100％ consistent with PCR results.The sensitivity and specificity of the two kits were 100％ (95％ CI,97.7％-100％) and 100％ (95％ CI,97.4％-100％) in detection of the five carbapenemases.Conclusions The immunochromatography method is rapid and easy to operate,and can be used to detect the production of carbapenmases in clinical isolates.

ObjectiveTo investigate the influencing factors for chronic kidney disease (CKD) in patients with hepatitis B cirrhosis within 3 years. MethodsA total of 376 patients with hepatitis B cirrhosis who attended Beijing Ditan Hospital, Capital Medical University, from January 2014 to July 2017 were enrolled and followed up for 3 years, and according to the presence or absence of CKD, they were divided into CKD group with 23 patients and non-CKD group with 353 patients. Related general information and laboratory markers were collected. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups; a stepwise forward Cox regression analysis was used to screen out the independent influencing factors for CKD within 3 years in patients with hepatitis B cirrhosis. The area under the receiver operating characteristic curve (AUC) was used to investigate the value of the influencing factors in predicting CKD in patients with hepatitis B cirrhosis; the Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison of the cumulative incidence rate of CKD between the patients with different risks. ResultsThe multivariate Cox regression analysis showed that age (hazard ratio ［HR］=1.078, 95% confidence interval ［CI］: 1.007-1.114, P=0.026), albumin (Alb) (HR=0.923, 95% CI: 0.860-0.989, P=0.024), and estimated glomerular filtration rate (eGFR) (HR=0.977, 95% CI: 0.955-0.999, P=0.037) were independent influencing factors for CKD within 3 years in patients with hepatitis B cirrhosis. Age, Alb, and eGFR had a relatively good value in predicting CKD, with AUCs of 0.701, 0.710, and 0.706, respectively. The Kaplan-Meier survival curve showed that the patients with baseline age ≥55 years, Alb ＜32 g/L, and eGFR ≥60 ml·min-1·1.73 m-2 and ＜76 ml·min-1·1.73 m-2 had a higher risk of CKD (χ2=9647, 13621, and 30.940, all P＜0.05). ConclusionRenal function should be closely monitored for patients with old age and low Alb and eGFR levels.

OBJECTIVE： To systematically evaluate the efficacy and safety of risperidone versus haloperidol in the treatment of behavioral and psychological symptoms of dementia （BPSD）， and to provide evidence-based reference for clinical drug use. METHODS： Cochrane library， PubMed， EMbase， CNKI， CBM， Wanfang and VIP database were searched for the randomized controlled trials （RCT） on risperidone （trial group） versus haloperidol （control group） in the treatment of BPSD. After literature screening， data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0， Meta-analysis was performed by using Rev Man 5.3 software. RESULTS： A total of 26 studies were included， involving 2 219 patients. The results of Meta-analysis showed that the total response rate [RR＝1.11， 95％CI（1.05， 1.18）， P＝0.000 3] and CMAI score [SMD＝0.19， 95％CI（0.04， 0.34）， P＝0.01] in trial group were significantly higher than control group. MMSE score [SMD＝－0.32， 95％CI（－0.63， －0.01）， P＝0.04]， and the incidence of extrapyramidal reaction [RR＝0.39， 95％CI（0.31， 0.49）， P＜0.000 1]， gastrointestinal reaction [RR＝0.51， 95％CI（0.38， 0.68）， P＜0.000 1]， somnolence [RR＝0.47， 95％CI （0.25， 0.88）， P＝0.02]， thirst [RR＝0.50， 95％CI（0.33， 0.74）， P＝0.000 5] and constipation [RR＝0.33， 95％CI（0.20， 0.54）， P＜0.000 1] in trial group were significantly lower than control group. There were no statistical significance in BEHAVE-AD score [SMD＝0.03， 95％CI（－0.09，0.16）， P＝0.62] and the incidence of insomnia [RR＝1.26， 95％CI（0.76， 2.11）， P＝0.37]， headache/dizziness [RR＝0.65， 95％CI（0.38， 1.12）， P＝0.12] and tachycardia[RR＝0.40， 95％CI（0.12， 1.31）， P＝0.13] between two groups. CONCLUSIONS： The efficacy and safety of risperidone in the treatment of BPSD are signi- ficantly better than haloperidol， and risperidone can improve agitation behavior and general cognitive state of patients.

Objective: To investigate the pathogen spectrum distribution and drug resistance of febrile neutropenic patients with hematological diseases in Shanghai. Methods: A retrospective study was conducted on the clinical isolates from the febrile neutropenic patients hospitalized in the departments of hematology in 12 general hospitals in Shanghai from January 2012 to December 2014. The drug susceptibility test was carried out by Kirby-Bauer method. WHONET 5.6 software was used to analyze pathogenic bacteria and drug susceptibility data. Results: A total of 1 260 clinical isolates were collected from the febrile neutropenic patients. Gram-positive bacteria accounted for 33.3% and Gram-negative bacteria accounted for 66.7%. Klebsiella pneumoniae (12.5%) , Stenotrophomonas maltophilia (9.5%) , Escherichia coli (9.1%) , Pseudomonas aeruginosa (8.7%) , Acinetobacter baumannii (6.6%) , Staphylococcus aureus (5.6%) and Enterococcus faecium (5.0%) were ranked in the first 7 of all pathogens. In the respiratory tract secretions specimens, non-fermented strains accounted for 56.2%. Stenotrophomonas maltophilia accounted for 15.2%. Enterobacteriaceae and coagulase-negative Staphylococci accounted for 42.3% (104/246) and 32.6% (85/246) respectively in blood samples. Enterobacteriaceae and Enterococcus bacteria accounted for 39.4% (76/193) and 28.5% (55/193) respectively in pus specimens. The detection rates of methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase negative Staphylococci (MRCNS) were 54.3% and 82.5%, respectively. Staphylococcus bacterial strain was not found to be resistant to linezolid, vancomycin and teicoplanin. The detection rate of Enterococcus vancomycin-resistant strains was 8.9%. Enterococcus was not detected resistance to oxazolidinone strains. Enterobacteriaceae bacteria were highly sensitive to carbapenems. The resistance rate of Pseudomonas aeruginosa to imipenem and meropenem was 34.1% and 15.8%, respectively. Stenotrophomonas maltophilia was more sensitive to minocycline hydrochloride, levofloxacin and sulfamethoxazole. The resistance rate of Acinetobacter baumannii only to cefoperazone-sulbactam was less than 10.0%. The antibiotic resistance rate of Klebsiella pneumoniae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa and Acinetobacter baumanii to most of common antibiotics was lower than that of the CHINET surveillance. Conclusions The pathogenic strain distribution in common infection sites of febrile neutropenic patients was characterized. Bacterial resistance surveillance was better than the CHINET nationwide large sample surveillance in China.

Objective To investigate the condition of flight fatigue and its relationship with mental health in the pilots of base transformation on the purpose of providing the reference for comprehensive intervention during the transformation.Methods Both 90 transformed and 90 nontransformed pilots were tested by fatigue assessment instrument (FAI) and symptom checklist 90 (SCL 90).Thirty-eight transformed and 38 non-transformed pilots were selected to continuously record ECG for 1 h for the analysis of heart rate variability (HRV).Correlation analysis was done on the condition of fatigue and mental health.Results ①FAI score results:the total score and factor 1,2,and 3 of FAI in transformed pilots was significantly higher than that in non-transformed pilots (t=1.981-4.570,P＜0.05).②HRV test:the standard deviation of R-R intervals,root mean square of the successive R R intervals difference,total power,low frequency,high frequency in transformed pilots was all significantly lower than that in non-transformed pilots (t=4.475-8.644,P＜0.01).The ratio of low frequency to high frequency of transformed pilots was significantly higher than that of non-transformed pilots (t=7.681,P＜0.01).③The total score and the score of factor 1,2,and 3 in FAI showed varied positive correlation with the total score and each score of factors in SCL-90 (r=0.165-0.452,P＜0.01 or 0.05).The score of factor 4 in FAI had weak positive correlation with the total score of SCL-90 and the score of sensitivity in interpersonal relationship,depression,hostility (r=0.158-0.175,P＜0.05).Conclusions The severity of flight fatigue in transformed pilots was significantly higher than that in non transformed pilots.The condition of flight fatigue is closely correlated with mental health.We should carry out comprehensive intervention based on psychological intervention to ensure the flight safety during transformation.