This study explores the mechanism of Guben Jiannao Liquid on Alzheimer's disease(AD) by regulating autophagy based on the liver kinase B1(LKB1)/adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) pathway. Male SD rats were randomly divided into the blank group, model group, low-dose and high-dose groups of Guben Jiannao Liquid, and rapamycin group, with 10 rats in each group. Except for the blank group, all other groups of rats were injected bilaterally in the hippocampus with β-amyloid(Aβ)_(1-42) to establish the AD model. The low-dose(6.21 g·kg~(-1)) and high-dose(12.42 g·kg~(-1)) groups of Guben Jiannao Liquid and rapamycin group(1 mg·kg~(-1)) were given the corresponding drugs by gavage, and the blank and model groups were given an equal volume of saline by gavage for four weeks. Morris water maze was used to test the learning and memory ability of rats in each group; hematoxylin-eosin(HE) and Nissl staining were used to observe the morphological and quantitative changes of neurons and Nissl bodies in the CA1 region of rat hippocampus; immunohistochemistry was utilized to detect Aβ-positive cell expression in the CA1 region of rat hippocampus; transmission electron microscopy was employed to observe ultrastructural changes in rat hippocampal tissue, and Western blot was used to examine the protein expression levels of LKB1, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, p62, and LC3-Ⅱ in the hippocampal tissue of the rats. The results showed that compared with those in the blank group, rats in the model group had elevated evasion latency and decreased number of platform transversal and residence time in the platform quadrant. The number of neurons in the hippocampal area was reduced, and the morphology was impaired. The average integral optical density value of Aβ-positive cells was elevated; the expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were decreased, and the expression levels of p-mTOR/mTOR and p62 were increased. Compared with those in the model group, rats in the low-dose and high-dose groups of Guben Jiannao Liquid had shorter evasion latency, higher number of platform transversal, longer residence time in the platform quadrant, increased number of neurons, decreased expression of Aβ-positive cells and average integral optical density values, and increased number of autophagic lysosomes in hippocampal tissue. The expression levels of LKB1, Beclin1, and LC3-Ⅱ were elevated in the hippocampus of rats in the low-dose group of Guben Jiannao Liquid. The expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were elevated in the hippocampal tissue of rats in the high-dose group of Guben Jiannao Liquid, and the expression levels of p-mTOR/mTOR and p62 were decreased. The findings suggest that Guben Jiannao Liquid can improve cognitive impairment in AD rats, and its mechanism of action may be related to the activation of the LKB1/AMPK/mTOR signaling pathway and the up-regulation of autophagy level.
Animals ; Alzheimer Disease/physiopathology* ; Male ; TOR Serine-Threonine Kinases/genetics* ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Protein Serine-Threonine Kinases/genetics* ; AMP-Activated Protein Kinases/genetics* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; AMP-Activated Protein Kinase Kinases ; Humans ; Hippocampus/metabolism*

OBJECTIVE: To investigate the influencing factors of differentiation syndrome (DS) during induction chemotherapy for acute promyelocytic leukemia (APL), and establish a prediction model for DS in newly diagnosed APL patients, in order to guide clinical treatment. METHODS: The clinical data of 324 newly diagnosed APL patients were retrospectively analyzed, and the patients were divided into DS group and non-DS group according to whether or not DS was present. Statistically significant factors from comparison of the two groups were selected and included in univariate and multivariate logistic regression to explore the influencing factors of DS in APL. R software was used to build the nomogram model, Bootstrap method was used for internal verification, and concordance index (C-index) and calibration curve were used to evaluate the accuracy of the model. RESULTS: The incidence of DS in 324 patients with newly diagnosed APL was 30.86% (100/324). Univariate logistic regression analysis showed that high risk, delayed retinoic acid, no hormonal prophylaxis, combined with disseminated intravascular coagulation, increased white blood cell count (WBC) at initial diagnosis and neutrophil count, prothrombin prolongation, decreased fibrinogen and albumin (ALB), increased proportion of bone marrow original cells, increased proportion of peripheral blood original cells, and increased peak of WBC after chemotherapy were risk factors for DS in newly diagnosed APL patients (all P < 0.01). Multivariate logistic regression analysis showed that the increased peak value of WBC after chemotherapy, prophylactic use of hormone, and ALB level were independent factors influencing the occurrence of DS in newly diagnosed APL patients (all P < 0.01). The C-index of DS in APL predicted by the nomogram model was 0.847(95%CI : 0.786-0.908). The calibration curve showed that the nomogram was in good agreement with the actual incidence of DS. CONCLUSION The independent influencing factors of DS in newly diagnosed APL are the increased peak value of WBC after chemotherapy, ALB and prophylactic use of hormone. The nomogram model based on the above factors can predict the risk of DS in APL patients, which is consistent with clinical observation.
Humans ; Leukemia, Promyelocytic, Acute/drug therapy* ; Nomograms ; Retrospective Studies ; Male ; Female ; Logistic Models ; Middle Aged ; Induction Chemotherapy ; Adult

OBJECTIVE: The objective of our study was to evaluate the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) among < 5-year-old children in three provinces of China during 2020-2024 via a propensity score-matched test-negative case-control study. METHODS: Electronic health records and immunization information systems were used to obtain data on acute gastroenteritis (AGE) cases tested for rotavirus (RV) infection. RV-positive cases were propensity score matched with RV-negative controls for age, visit month, and province. RESULTS: The study included 27,472 children with AGE aged 8 weeks to 4 years at the time of AGE diagnosis; 7.98% (2,192) were RV-positive. The VE (95% confidence interval, CI) of 1-2 and 3 doses of RV5 against any medically attended RV infection (inpatient or outpatient) was 57.6% (39.8%, 70.2%) and 67.2% (60.3%, 72.9%), respectively. Among children who received the 3rd dose before turning 5 months of age, 3-dose VE decreased from 70.4% (53.9%, 81.1%) (< 5 months since the 3rd dose) to 63.0% (49.1%, 73.0%) (≥ 1 year since the 3rd dose). The three-dose VE rate was 69.4% (41.3%, 84.0%) for RVGE hospitalization and 57.5% (38.9%, 70.5%) for outpatient-only medically attended RVGE. CONCLUSION Three-dose RV5 VE against rotavirus gastroenteritis (RVGE) in children aged < 5 years was higher than 1-2-dose VE. Three-dose VE decreased with time since the 3rd dose in children who received the 3rd dose before turning five months of age, but remained above 60% for at least one year. VE was higher for RVGE hospitalizations than for medically attended outpatient visits.
Humans ; Rotavirus Vaccines/immunology* ; China/epidemiology* ; Case-Control Studies ; Child, Preschool ; Infant ; Rotavirus Infections/epidemiology* ; Male ; Propensity Score ; Female ; Vaccine Efficacy ; Gastroenteritis/virology* ; Vaccines, Attenuated ; Rotavirus

Background and objective Metabolic change is one of the important characteristics of radiation pneu-monitis.Radiotherapy,as a conventional method for the treatment of thoracic tumors,can not only effectively kill tumor cells,but also cause adverse reactions such as local inflammation and fibrosis,which leads to limited therapeutic effect and profound impact on the quality of life of patients.Therefore,it is of great significance to explore the metabolic changes caused by radio-therapy.The aim of this study was to investigate the effects of X-ray irradiation on the metabolism of a mouse lung epithelial cell line(murine lung epithelial-12,MLE12).Methods MLE12 cells were cultured in vitro and randomly divided into radiation group(IR)and control group(NC).Cells in the IR group were irradiated at a dose of 10 Gy using a Hitachi X-ray irradiator.Cell supernatant samples were collected at 48 h after irradiation.Metabolomic analysis of the samples was performed by liq-uid chromatograph mass spectrometer(LC/MS).Results LC/MS metabolomics analysis revealed the metabolic changes of MLE12 cells at 48 h after irradiation.A total of 38 secretory metabolites were altered in the IR group compared with the NC group.According to the annotation of Kyoto Encyclopedia of Genes and Genomes(KEGG)database,the differential metabo-lites are mainly involved in nucleotide metabolism,amino acid metabolism and lipid metabolism,among which the difference in nucleotide metabolism is the most significant.Conclusion The metabolism ofMLE12 cells was significantly affected by X-ray irradiation,mainly affecting the nucleotide metabolic pathways,including purine and pyrimidine metabolites and related meta-bolic pathways.

Objective:To investigate the diagnostic efficacy of targeted biopsy combined with regional systematic biopsy in prostate cancer(PCa)in patients with prostate imaging reporting and data system v2.1(PI-RADS v2.1)4-5.Methods:From January 2023 to October 2023,patients who underwent prostate biopsy for the first time with total prostate specific antigen(tPSA)≤20 ng/mL and had a multi-parametric magnetic resonance imaging(mpMRI)PI-RADS of 4-5 in Peking University First Hospital were prospectively collected.All the patients underwent transrectal ultrasound-guided cognitive fusion tar-geted biopsy(3 cores)followed by systematic biopsy(12 cores).Various hypothetical biopsy schemes were defined based on different biopsy sites.The detection effectiveness of targeted biopsy combined with regional systematic biopsy and other biopsy schemes for prostate cancer were compared using Cochran's Q and McNemar tests.Results:A total of 255 patients were enrolled,of whom 204(80.0％)were de-tected with prostate adenocarcinoma and 187(73.3％)were clinically significant with prostate cancer(csPCa).The detection rate of PCa with targeted biopsy was significantly lower than that of targeted biopsy combined with 12-core system biopsy(77.3％vs.80.0％,P=0.016),and 71.4％(5/7)of the missed patients was csPCa.There was no significant difference in the detection rate between targeted biopsy combined with 4-core regional system biopsy and 12-core system biopsy(P＞0.999),and 1 case of csPCa and clinically insignificant prostate cancer(cisPCa)were missed.There was no significant difference in the detection rate of PCa between targeted combined regional system biopsy and targeted combined lateral or traditional 6-core system biopsy and the number of cores were reduced.Missed diag-nosis of targeted biopsy was correlated with the maximum diameter of the lesion(OR=0.086,95％CI:0.013-0.562,P=0.010).For the patients with PI-RADS 5,only 1 case of PCa was missed in 122 cases by targeted biopsy alone.For patients with PI-RADS 4,6 PCa cases were missed among the 133 patients with targeted biopsy alone,and 1 case of csPCa and cisPCa were missed by targeted biopsy com-bined with regional system biopsy.The statistics of positive core counts for different biopsy schemes indi-cated that targeted combined regional systematic biopsy had a higher proportion of positive cores second only to targeted biopsy alone.Conclusion:Targeted biopsy combined with regional systematic biopsy has high diagnostic efficacy in patients with PI-RADS 4-5 and can be considered as one of the improved schemes for combined biopsy.Targeted biopsy alone is also a feasible option for patients for patients with a PI-RADS score of 5.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

This study adopted the policy text analysis method,review the historical background of the enactment,aimed to comparatively analyze the international pharmaceutical trade policies of the BRICS countries.The main objectives of the BRICS countries'international pharmaceutical trade policies included ensuring stable and accessible drug supply,expanding exports of domestic products and creating a favorable political environment.For these purposes,Brazil,Russia,and South Africa all ensure drug supply through substantial imports.However,they have also taken measures such as compulsory patent licensing and promoting localization of production by foreign companies to reduce import dependence.India,on the other hand,protects its domestic industry by resisting drug imports to ensure drug supply while simultaneously promoting the export of pharmaceutical products.China continually optimizes approval and data monitoring procedures to align with international standards,creating a favorable trade environment and expanding exports.China should further refine its international pharmaceutical trade policies while ensuring the autonomy of domestic drug research and supply,fostering stronger collaboration within BRICS nations and promoting global access to public healthcare products.

Objective:This study aims to explore the synergistic effects of DIP and other medical insurance supply-side policies.Method:City A that has piloted DIP reform was set as the treatment group,and City B without reform was set as the control group.A total of 1 120 public medical institution samples from 2019 to 2022 were collected.The total medical expenses during hospitalization and some structural expenses were analyzed using DID method.Result:DIP had a significant inhibitory effect on the medical expenses,and the expenses of checkups and examinations during hospitalization in city A,but had no impact on the drug and the material expenses during hospitalization.Conclusion:DIP played a significant cost control role and effectively controlled the total medical expenses during hospitalization.The synergistic effects of price adjustment of medical services policy and national centralized drug/material procurement policy on cost control were insufficient.DIP synergized with other supply-side policies to promote rational medical cost structure.It is suggested that medical insurance departments should focus on the synergistic effects of medical insurance supply-side policies to jointly improve the efficiency of medical insurance fund utilization.

Objective:Analyze the medical reimbursement rate and influencing factors under the DIP payment method to refine the DIP payment policy,promote the optimization of internal operations in medical institutions,and ensure reasonable compensation.Methods:Based on the 2022 DIP fund settlement data from 196 medical institutions in City A,the study used multiple linear regression to analyze the factors affecting medical reimbursement rate and conducted a heterogeneity analysis for medical institutions of different levels.Results:The medical reimbursement rate for medical institutions in City A in 2022 was 103.32%.Medical institutions with lower CMI standardized inpatient costs,lower rates of deviation cases,tertiary care institutions,lower proportion of level-four surgeries,and lower ratios of resident to employee medical insurance cases have higher medical reimbursement rate(P<0.05).Heterogeneity analysis reveals that therates of deviation cases,the proportion of primary care diseases,the ratio of resident to employee medical insurance cases,and the low-standard admission rate have different impacts on medical institutions of different levels.Conclusion:Medical insurance departments should improve policies for primary care diseases,dynamically adjust disease catalogs and payment standards,optimize funding levels and institutional coefficients,and increase penalties for violations to ensure effective use of funds.Medical institutions need to strengthen their understanding of policies,focus on refined internal management,promote standardized and rational diagnosis and treatment through performance assessment transformation,and leverage their own advantages in medical services to reasonably increase the medical reimbursement rate.

ObjectiveRapid and accurate identification of body fluid traces at crime scenes is crucial for case investigation. Leveraging the speed and sensitivity of nucleic acid detection technology based on SHERLOCK, our research focuses on developing a peripheral blood SHERLOCK-HBA detection system to detect mRNA in forensic practice. MethodsShort crRNA fragments targeting the blood-specific mRNA gene HBA were designed and screened, alongside RPA primers. Optimal RPA primers were selected based on specificity and amplification efficiency, leading to the establishment of the RPA system. The most efficient crRNA was chosen based on relative fluorescence units (RFU) generated by the Cas protein reaction, and the Cas protein reaction system was constructed to establish the SHERLOCK-HBA detection method. The RPA and Cas protein reaction systems in the SHERLOCK detection system were then individually optimized. A total of 79 samples of five body fluids were tested to evaluate the method’s ability to identify blood, with further verification through species-specific tests, sensitivity tests, mixed spots detection, aged samples, UV-irradiated samples, and actual casework samples. ResultsThe SHERLOCK reaction system for the peripheral blood-specific marker HBA was successfully established and optimized, enabling detection within 30 min. The method demonstrated a detection limit of 0.001 ng total RNA, better than FOB strip method and comparable to RT-PCR capillary electrophoresis. The system could detect target body fluids in mixed samples and identify blood in samples stored at room temperature for three years and exposed to UV radiation for 32 h. Detection of 11 casework samples showed performance comparable to RT-PCR capillary electrophoresis. ConclusionThis study presents a CRISPR/Cas-based SHERLOCK-HBA detection system capable of accurately, sensitively, and rapidly identifying blood samples. Introducing CRISPR/Cas technology to forensic body fluid identification represents a significant advancement in applying cutting-edge molecular biology techniques to forensic science.The method’s simplicity, shorter detection time, and independence from specialized equipment make it promising for rapid blood sample identification in forensic cases.