OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy （DN）. METHODS From the perspective of healthcare service providers， a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months， a simulation period of 15 years and an annual discount rate of 5%. At the same time， one-way sensitivity analysis and probability sensitivity analysis were performed， and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan， and the accumulative utility was 8.052 4 quality-adjusted life year （QALYs）； the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan， and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value， DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio， but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients， finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.

Qualitative analysis of the ingredients absorbed into blood and their metabolites of Xihuang pill (XHP) were conducted using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) technology. Network pharmacology was used to explore the potential anticancer mechanisms of the ingredients against glioma, and their specific mechanisms were validated through molecular docking and experimental verification. SD rats were intragastrically administered with XHP, and rat serum samples were collected. Ingredients absorbed into blood and their metabolites were identified based on the retention time of chromatographic peaks, accurate molecular mass, characteristic fragment ions, and comparisons with reference substances and literature data. PharmMapper and SwissTarget Prediction databases were used to obtain the targets of the XHP-medicated serum, while GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases were used to obtain glioma disease targets. The "component-target" network relationship diagram was constructed using Cytoscape 3.9.1 software. The protein-protein interaction (PPI) network diagram was constructed using the STRING database, and the targets were analyzed using GO and KEGG analyses. Molecular docking was used to verify the binding ability of core targets with their corresponding compounds in XHP-medicated serum. The potential mechanism of the anti-glioma effect of 11-keto-β-boswellic acid (KBA), a representative component of XHP-medicated serum, was verified using CCK-8 and Western blot assays. A total of 40 compounds were identified in the XHP-medicated serum, including 28 prototype components and 12 metabolites. The network pharmacology results showed that elemonic acid, 3-acetyl-β-boswellic acid, KBA, α-boswellic acid, and other 5 compounds might be the active ingredients of XHP-medicated serum in the treatment of glioma. Glutathione reductase (GSR), glucose-6-phosphate dehydrogenase (G6PD), ATP-citrate lyase (ACLY), aldo-keto reductase family 1 member B1 (AKR1B1) and glutaredoxin (GLRX) were identified as key targets, involving pathways such as glutathione metabolism and the pentose phosphate pathway. Further cell experiments showed that KBA significantly inhibited the proliferation of T98G cells with an IC₅₀ of 30.96 μmol·L^-1, and KBA (30 μmol·L^-1) significantly downregulated the protein expression levels of GSR in T98G cells. In summary, XHP-medicated serum may exert its anti-glioma effect by regulating GSR and G6PD-targeted pathways involved in glutathione metabolism. These results provide valuable evidence for further investigating the mechanism of XHP in treating glioma. The animal welfare and experimental procedures were approved by the Ethical Committee of Laboratory Animals at Nanjing University of Chinese Medicine (approval No. ACU221001).

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To investigate the association between quantified CT (QCT)-measured body composition and metabolic syndrome (MS) components in obese populations before bariatric surgery.Methods:A cross-sectional study. A retrospective analysis was conducted on a cohort of 97 obese patients scheduled for weight-loss surgery at the First Affiliated Hospital of Wannan Medical College from January 2021 to March 2023. The patients′ body mass index (BMI), biochemical parameters and body composition measurements obtained by QCT were recorded. The patients were stratified into groups based on gender, obesity severity and the number of MS components. Differences in body composition among the groups were compared. Additionally, the correlations between each body composition parameter and metabolic indicators were analyzed. The diagnostic efficacy of each body composition parameter for identifying obese individuals with different MS components was assessed using receiver operating characteristic (ROC) curve analysis.Results:There were 75 females (77.3%). Male obese patients had higher total abdominal fat area [(693.23±148.90) vs (574.99±114.89) cm 2, t=-3.958, P<0.001], visceral fat area [(289.65±57.67) vs (195.60±57.37) cm 2, t=-6.753, P<0.001], fat content of pancreatic head [27.45%(21.65%, 45.48%) vs 21.60%(17.6%, 26.9%), Z=-2.675, P=0.007], and skeletal muscle index [73.36(68.74, 81.26) vs 61.52(55.74, 66.41) cm 2/m 2, Z=-5.246, P<0.001]. With the increase of obesity, abdominal fat mainly increases in subcutaneous fat. With the increase of MS components (MS2 group, MS3 group, MS4 group, MS5 group), the abdominal fat area, abdominal fat/subcutaneous fat, liver fat content, pancreatic head fat content, and skeletal muscle index of patients all increased accordingly. In diagnosing the presence of two components of MS, area under the curve of visceral fat area was the largest (AUC=0.706, 95% CI=0.577-0.834). For diagnosing the presence of three, four and five components of MS, area under curve of liver fat content were all the largest (MS3=0.712, 95% CI=0.605-0.818; MS4=0.652, 95% CI=0.537-0.766; MS5=0.706, 95% CI=0.576-0.836). Conclusion:There are differences in QCT body composition among obese patients with different MS components, and there is a correlation between each body composition and MS component. Among them, intra-abdominal fat area and liver fat content are of great value in evaluating obese patients with different MS components.

Objective To investigate the epidemiological characteristics and diagnosis of imported Plasmodium malariae and P. ovale malaria cases in Anhui Province, Hubei Province, Zhejiang Province, Guangxi Zhuang Autonomous Region and Henan Province from 2014 to 2021, so as to provide insights into malaria control in these five provinces. Methods All data pertaining to malaria cases reported in five provinces of China were captured from Chinese Disease Control and Prevention Information System from 2014 to 2021, and the epidemiological characteristics of imported P. malariae and P. ovale malaria cases were analysed using a descriptive epidemiological method. The duration from onset of malaria to initial diagnosis, duration from initial diagnosis to definitive diagnosis, institutions of initial and definitive diagnoses, and proportion of correct malaria diagnosis at initial diagnosis were statistically analyzed. Results A total of 1 223 imported P. malariae and P. ovale malaria cases were reported in Anhui Province, Hubei Province, Zhejiang Province, Henan Province and Guangxi Zhuang Autonomous Region from 2014 to 2021, there were 158 P. malariae malaria cases (12.92%) and 1 065 P. ovale malaria cases (87.08%). Totally 98.53% (1 205/1 223) of the imported malaria cases were from Africa, with Angola (18.99%, 30/158), Nigeria (11.39%,18/158), Cameroon (10.76%, 17/158), Ghana (10.13%, 16/158) and the Democratic Republic of the Congo (10.13%,16/158) as predominant countries where P. malariae malaria cases were from, and Ghana (23.19%, 247/1 065), Cameroon (14.74%, 157/1 065), Nigeria (9.39%, 100/1 065) and Angola (6.95%, 74/1 065) as predominant countries where P. ovale malaria cases were from. There were significant differences in the duration from onset of malaria to initial diagnosis (χ² = 27.673, P = 0.000) and duration from initial diagnosis to definitive diagnosis of P. malariae and P. ovale malaria cases (χ² = 29.808, P = 0.000), and the proportions of correct initial diagnosis of P. malariae and P. ovale malaria cases were 38.61% (61/158) and 56.53% (602/1 065). There were 74.69% (118/158) of P. malariae malaria cases with definitive diagnosis in county-, city-, and province-level medical institutions, and 79.25% (844/1 065) of P. ovale malaria cases with definitive diagnosis in county- and city-level medical institutions and county-level centers for disease control and prevention. Conclusions The imported P. malariae and P. ovale malaria cases in Anhui Province, Hubei Province, Zhejiang Province, Henan Province and Guangxi Zhuang Autonomous Region from 2014 to 2021 were mainly returned from Africa and the proportion of correct diagnosis of P. malariae and P. ovale malaria was low at initial diagnosis. Persistent improvements in the diagnostic capability of malaria are required in medical institutions.

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.

To optimize the formulation and technology of oxymatrine-astragaloside IV coloaded liposomes (Om-As-Lip) based on quality by design (QbD) principles, and further to verify the feasibility of its amplification process, Om-As-Lip was prepared by ethanol injection combined with pH gradient method. The critical material attributions of Om-As-Lip were evaluated by dual-risk analysis tools and Plackett-Burman design (PBD). The formulation of Om-As-Lip was further optimized with the Box-Behnken design (BBD). The design space was also established based on the contour plots of BBD. In order to further investigate the amplification process of Om-As-Lip, the critical process parameters of high-pressure homogenization (HPH) were optimized by single-factor test, and the quality of the final product was also evaluated. The results of risk analysis and PBD confirmed that the astragaloside concentration, cholesterol concentration, and phospholipid ratio (HSPC∶SPC) were the ctitical material attributes. The model established by BBD had a good predictability, and the optimized mass ratio of As to phospholipids was 1∶40, cholesterol to phospholipids was 1∶10, HSPC to SPC was 51∶9. The design space of Om-As-Lip was as follows: the ratio of cholesterol to phospholipids was 1∶12-1∶5 and HSPC to SPC was 1∶7-17∶3. The optimized high-pressure homogenization pressure was 600 bar, temperature was 4 ℃, and cycle times was 6 times for HPH-Om-As-Lip. The quality of Om-As-Lip prepared based on the QbD concept can meet the expected CQAs, and the formulation and technology established can provide a reliable experimental basis for its future development and applications.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Molecular imprinting is a biomimetic technique that simulates the specific recognition of biological macromolecules such as antibody. Based on molecular imprinting and high-specificity affinity analysis,the biomimetic imprinting affinity analysis (BIA) possesses many advantages such as high sensitivity,strong tolerance,good specificity and low cost,and thus,it has shown excellent prospects in food safety detection,pharmaceutical analysis and environmental pollution monitoring. In this review,the construction methods of recognition interfaces for BIA were summarized,including bulk polymerization,electro-polymerization and surface molecular imprinting. The application of molecularly imprinted polymers in different analysis methods,such as radiolabeled affinity analysis,enzyme-labeled affinity analysis,fluorescence-labeled affinity analysis,chemiluminescence affinity analysis and electrochemical immunosensor was mainly discussed. Furthermore,the challenges and future development trends of BIA in practical application were elucidated. This review might provide new reference ideas and technical supports for the further development of BIA technique.