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.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

Objective To investigate the protective effect of Gynostemma pentaphyllum on memory of individuals rapidly ascending to high altitudes.Methods Twenty-one healthy subjects were randomly divided into a G.pentaphyllum food group(n=12)and a control group(n=9).The first group consumed G.pentaphyllum food for seven consecutive days while the control group received placebos.Both groups ascended from the plains to an altitude of 3600 m.Memory function was assessed using the matching memory and sequential memory tests of a cognitive evaluation system on day 1 and day 7 on the plains,and at 24 and 48 h after ascending to the high altitude.Scores of acute mountain sickness symptoms were also recorded.Results After 24 h of stay at the high altitude,the score of headache of the G.pentaphyllum food group was significantly lower than that of the control group(P＜0.05).Cognitive test results showed that the matching memory accuracy and sequential memory accuracy of the control group at 24 and 48 h were significantly lower than those on the plains(P＜0.05).In contrast,the G.pentaphyllum food group performed significantly better than the control group in these metrics(P＜0.05).Conclusion Regular consumption of G.pentaphyllum food can effectively alleviate headache symptoms in individuals rapidly ascending to high altitudes and mitigate the decline in working memory,short-term memory,and memory spans caused by acute hypoxic exposure.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective The purpose of writing the"expert consensus on humanistic care for patients in hospice care"(hereinafter referred to as the"consensus")aims to standardize the practice of humanistic care in the field of hospice care,ensuring that humanistic care is integrated throughout the entire service process for hospice care patients and their families.Methods A systematic search was conducted in domestic and foreign databases for literature related to hospice care and humanistic care,including guidelines,expert consensuses,systematic reviews or Meta-analyses,and evidence summaries.High-quality evidence was evaluated,extracted,and summarized to form the initial draft of the"consensus".From June to October 2024,20 experts from the fields of hospice care,nursing humanities,and evidence-based nursing were invited to participate in 1 round of expert consultation.Among them,13 experts were selected for 2 rounds of expert demonstration meetings.After collating and analyzing the experts' opinions,the initial draft was revised and refined,ultimately resulting in the final version of the"consensus".Results The effective response rate of the consultation questionnaire was 100％,with expert authority coefficient of 0.880,judgment coefficient of 0.935,and familiarity level of 0.825.The Kendall harmony coefficient of the expert consultation was 0.134(P＜0.05).The"consensus"consisted of 13 aspects,including the targets and objectives,principles,institutional guarantees,environmental requirements,etc.Conclusion This"consensus"possesses strong scientific rigor and practicality,which can provide guidance and references for the practice of humanistic care in the field of hospice care,promoting the standardization and humanization of hospice care services.

Objective:To explore the application of the O-PIRTAS flipped classroom in teaching the course of "developmental psychology".Methods:This study involved second-year undergraduate students majoring in clinical psychology. The 26 undergraduate students enrolled in 2023 who participated in the late adulthood section of the course were selected as the experimental group (O-PIRTAS teaching), while the 25 undergraduate enrolled in 2022 in the same course were selected as the control group (traditional teaching). Assessments were conducted through closed-book tests and questionnaires. The student questionnaire evaluated their theoretical knowledge, class assessment, and class engagement. The teacher questionnaire assessed the completeness of the lecture, logical flow, and student engagement. SPSS 22.0 was used for t test. Results:In the theoretical examination, the experimental group showed significantly higher scores compared to the control group in knowledge application [(13.09±1.59) vs. (10.54±0.77)] and practical problem-solving ability [(8.27±0.57) vs. (6.95±0.32)]. In the questionnaire survey, 24 (92.00%) students in the experimental group expressed recognition of the flipped classroom mode. Teachers reported greater improvement in satisfaction with the classroom performance of the experimental group compared to the control group.Conclusions:O-PIRTAS flipped classroom improves the quality of teaching "developmental psychology", enhances student learning outcomes, and stimulates learning motivation.

Objective To investigate the effect of the rs3765467 polymorphism of glucagon-like peptide-1 receptor(GLP-1R)gene on the efficacy of Liraglutide(Lir)in patients with type 2 diabetes mellitus(T2DM)and metabolic associated fatty liver disease(MAFLD).Methods A total of 281 patients with T2DM from May 2022 to May 2023 were selected,including 125 patients with simple T2DM(T2DM group)and 156 patients with T2DM combined with MAFLD(T2DM+MAFLD group).120 healthy individuals during the same period were selected as the control(NC)group.The related indexes of glucose and lipid metabolism were detected.The polymorphism of GLP-1R gene rs3765467 was detected.Results BMI,FPG,HbA1c,HOMA-IR and TG in each group increased in turn(P<0.05),while the distribution frequency of genotype GG and allele G decreased in turn(P<0.05).TC and LDL-C in T2DM and T2DM+MAFLD groups were higher than those in NC group(P<0.05).TC and TG levels in genotype GA/AA patients were significantly higher than those in genotype GG patients(P<0.05).Compared with before treatment,the levels of BMI,FPG,HbA1c,HOMA-IR,TC,TG and LDL-C in T2DM patients with MAFLD were significantly decreased after Lir treatment(P<0.05).There was no significant difference in BMI and related indexes of glucose and lipid metabolism in GG and GA/AA patients before and after Lir treatment(P>0.05).Conclusions The distribution frequency of GG and G allele at rs3765467 of GLP-1R gene is reduced in T2DM patients with MAFLD.The carrying of allele A was associated with increased TC and TG levels,but did not affect the efficacy of Lir in reducing weight and improving glycolipid metabolism.

Objective To explore and study the new nationwide centralized volume-based procurement model of Chinese patent medicines(CPM),aiming further to promote the normalization and institutionalization of such procurement practices.Methods This study conducts a retrospective analysis of the entire 2023 national CPM procurement process,comparing it with the 19-province alliance procurement,the national chemical drugs procurement,and the national insulin special procurement and highlighting its similarities and differences.Results In contrast to the 19-province alliance procurement,the national CPM alliance procurement introduced a daily average cost rule to reduce the price selection deviation.It also improved and optimized the criteria for qualification,bidding unit formation principles,selection rules,resurrection mechanisms,and principles for allocating procurement volumes under agreements.A comprehensive analysis of the results from two rounds of CPM procurement indicates statistically significant differences in resurrection rates,brand substitution rates,and reduction in selected prices,with the national procurement outperforming the 19-province alliance procurement.Compared with the national chemical drugs and special insulin procurements,this procurement distinctly showcases its unique characteristics.Conclusion The new mode of the national CPM alliance procurement is innovative and has contributed valuable experiences towards the sustained advancement of CPM procurement and establishing a medical insurance payment standard system.

Objective Based on the traditional Chinese medicine theory of"simultaneous regulation of the liver and kidney,"this study integrated network pharmacology prediction,molecular docking,and animal experimental validation to analyze the multi-target regulatory network of Duzhong Xionghua(the male flower of Eucommia ulmoides)-Sanqi Hua(Sanchi flower)herb pair(hereinafter called"herb pair")in modulating glucolipid metabolic disorders in type 2 diabetes mellitus(T2DM),thereby elucidating its underlying molecular mechanism.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,China National Knowledge Infrastructure,VIP Database for Chinese Technical Periodicals,and Wanfang Data were used to obtain the active ingredients of the male flower of Eucommia ulmoides and Sanchi flower.PubChem Compound,SwissTargetPrediction,and SuperPred were used to screen and predict the targets of the drugs;The Human Gene Database,The Online Mendelian Inheritance in Man,and Therapeutic Target Database were used to screen the key gene targets of T2DM.A"component-target-pathway"network diagram was constructed using Cytoscape software,and Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were employed to identify the functions of the relevant target genes and pathways.Molecular docking was used to verify the binding activities of the core components and the key targets.For animal experiments,spontaneous T2DM model mice were used,in which the normal group consisted of six mice(wild type)from the same litter,and the 24 successfully modeled mice were randomly divided into model,metformin(0.26 g/kg),high-dose herb pair(2.6 g/kg),and low-dose herb pair groups(1.3 g/kg)according to the blood glucose levels and body weights,with six mice per group.The drugs were administered by gavage daily for six consecutive weeks.The body weight and fasting blood glucose(FBG)levels were measured weekly,and an oral glucose tolerance test was performed in the fifth week.At the end of drug administration,body weight,naso-anal length,liver and bilateral epididymal adipose mass were measured;pathological changes in the liver were observed using HE staining;serum levels of aspartate transaminase(AST),alanine amino-transferase(ALT),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected using colorimetric assay;and liver tissue phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase-3β(GSK-3β)signaling pathway protein expressions were determined using Western blotting.Results Network pharmacology screening identified 38 active components and 669 potential targets of the herb pair.Intersection analysis with 1,275 T2DM-related targets yielded 185 common targets.Protein-protein interaction network analysis and pathway enrichment revealed the PI3K/AKT signaling pathway as a key mechanism.Molecular docking confirmed the strong binding affinity of the core components to key targets such as AKT1,suggesting that the herb pair may activate the PI3K/AKT pathway and inhibit GSK-3β activity via beta-sitosterol etc.Animal experiments demonstrated that,compared with the model group,the metformin group exhibited reduced FBG,AST,and ALT levels(P<0.01),but failed to improve body weight,Lee's index,or epididymal fat coefficient.Both herb pair doses significantly lowered Lee's index,hepatic index,and the epididymal fat coefficient(P<0.01),with the low-dose herb pair group showing attenuated body weight gain in mice.In contrast,the high-dose herb pair group exhibited decreased FBG,improved glucose tolerance,reduced TC,TG,and LDL-C levels,and increased HDL-C level(all P<0.01).HE staining revealed that all metformin and the herb pair markedly restored hepatic structure and alleviated steatosis in model mice,with more pronounced effects in the high-dose group than in the low-dose group.Western blotting result indicated that in the low-dose herb pair group,phospho-PI3K(p-PI3K),AKT,and phospho-GSK-3β(p-GSK-3β)protein expressions significantly increased(P<0.05 or P<0.01),whereas GSK-3β decreased(P<0.05).The high-dose group exhibited enhanced PI3K,p-PI3K,AKT,phospho-AKT,and p-GSK-3β protein expressions(all P<0.01),accompanied by reduced GSK-3β expression(P<0.01).Conclusion The male flower of Eucommia ulmoides-Sanchi flower herb pair may ameliorate T2DM-related glucolipid metabolic disorders by modulating the PI3K/AKT/GSK-3β pathway.