OBJECTIVE To evaluate the comprehensive value of novel oral anticoagulant drugs （NOACs） after major orthopedic surgery. METHODS The evaluation evidence was collected through literature research； evidence and value：impact on decision-making （EVIDEM） framework was introduced to integrate the evaluation process； the multi-criteria decision analysis （MCDA） method was used to construct a multi-dimensional evaluation system； the weights assigned to each evaluation criterion were determined by the combination of Delphi method and analytic hierarchy process， and the rivaroxaban， dabigatran and apixaban were comprehensively evaluated. RESULTS The clinical comprehensive evaluation system of NOACs after major orthopedic surgery was successfully established， and the final clinical comprehensive evaluation weights of NOACs （rivaroxaban， dabigatran， apixaban） after major orthopedic surgery were calculated， with scores of 0.399 7 for rivaroxaban， 0.244 4 for apixaban， and 0.355 9 for dabigatran， indicating that rivaroxaban demonstrated the highest overall clinical value. Among them， rivaroxaban had the highest weight score in the evaluation of pharmaceutical characteristics， cost-effectiveness and other attributes in a single dimension. In terms of efficacy and safety evaluation， apixaban had the highest weighting score. CONCLUSIONS Among NOACs， rivaroxaban is more suitable for routine anticoagulation management after major orthopedic surgery， especially in terms of pharmacological properties， cost-effectiveness and other attributes.

Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.

Methods: (i) Animal experiments. This study conducted experiments using specific pathogen-free (SPF) grade male C57BL/6J wild-type (WT) mice and APP/PS1 double transgenic mice. The animals were divided into three groups: WT group (WT mice, n = 5, receiving distilled water daily), APP/PS1 group (APP/PS1 double transgenic mice, n = 5, receiving distilled water daily), and BSTSD group [APP/PS1 double transgenic mice, n = 5, treated with BSTSD suspension at a dosage of 27 g/(kg·d) for 90 d]. Cognitive function was assessed using the Morris water maze (MWM). Post-experiment, hippocampal tissues were collected for analysis of pyramidal cell and synaptic morphology through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). (ii) Cell experiments. The HT-22 cells were divided into control group (untreated), Aβ25-35 group (treated with 20 μmol/L Aβ25-35 for 24 h), icariin group (pre-treated with 20 μmol/L icariin for 60 min, followed by 20 μmol/L Aβ25-35 for an additional 24 h), and icariin + LY294002 group [treated with 20 μmol/L icariin and 20 μmol/L LY294002 (an inhibitor of the phosphoinostitide 3-kinases (PI3K) signaling pathway) for 60 min, then exposed to 20 μmol/L Aβ25-35 for 24 h], and cell viability was measured. Western blot was used to detect the expression levels of synapse-associated proteins [synaptophysin (SYP) and postsynaptic density-95 (PSD-95)] and PI3K signaling pathway associated proteins [phosphorylated (p)-PI3K/PI3K, p-protein kinase B (Akt)/Akt, and p-mechanistic target of rapamycin (mTOR)/mTOR]. Results: (i) Animal experiments. Compared with APP/PS1 group, BSTSD group showed that escape latency was significantly shortened (P < 0.01) and the frequency of crossing the original platform was significantly increased (P < 0.01). Morphological observation showed that pyramidal cells in the hippocampal CA1 region were arranged more regularly, nuclear staining was uniform, and vacuole-like changes were reduced after BSTSD treatment. TEM showed that the length of synaptic active zone in BSTSD treatment group was increased compared with APP/PS1 group (P < 0.01), and the width of synaptic gap was decreased (P < 0.01). (ii) Cell experiments. Icariin had no obvious toxicity to HT-22 cells when the concentration was not more than 20 μmol/L (P > 0.05), and alleviated the cell viability decline induced by Aβ25-35 (P < 0.01). Western blot results showed that compared with Aβ25-35 group, the ratios of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in icariin group were significantly increased (P < 0.01), while the protein expression levels of SYP and PSD-95 were increased (P < 0.01). These effects were blocked by LY294002 (P < 0.01). Conclusion BSTSD and icariin enhance cognitive function and synaptic integrity in AD models and provide potential therapeutic strategies through activation of the PI3K/Akt/mTOR pathway.

Objective: To investigate whether acupoint penetration acupuncture (APA) could regulate chondrocyte autophagy and apoptosis via the PI3K/Akt-mTOR signaling pathway to reduce cartilage degeneration in knee osteoarthritis (KOA) rats. Methods: KOA was induced in rats via intra-articular injection of sodium iodoacetate resolution. Forty male Sprague-Dawley rats were randomly assigned to blank control, model, APA, electro-acupuncture (EA), and sham model groups (n = 8) and those in the APA and EA groups received their respective therapies. Following completion of the treatment course, histological examinations of cartilage and muscle were conducted. Levels of apoptosis- and autophagy-related factors, including Bax, Bcl-2, mTOR, ULK-1, and Beclin-1 protein, and mRNAs were assessed. Additionally, β-endorphin (β-EP) concentrations in the brain and serum were measured. Results: Histological analysis revealed that APA alleviated cartilage and muscle damage compared with the model group. APA inhibited cartilage degeneration by modulating the expression of apoptosis- and autophagy-related proteins and mRNA, thus preventing chondrocyte apoptosis. In the APA group, Bax and mTOR protein levels were significantly lower than those in the model group (both P = .024). Conversely, the Bcl-2 expression level was significantly higher than that in the EA group (P = .035). Additionally, ULK-1 expression was significantly lower than that in the EA group (P = .045). The mRNA level of Bax was significantly higher than that in the blank control group (P < .001). However, Beclin-1 levels were significantly higher than those in both the model and EA groups (both P < .001). ELISA results showed a significant decrease in the concentration of β-EP in the brains of the rats in the APA group compared with those in the model group (P = .032). Conclusions APA reduced osteoarthritis-related pain and alleviated cartilage damage by upregulating chondrocyte autophagy and down-regulating apoptosis via signaling pathways involving PI3K/Akt-mTOR in KOA rats.

Objective:To assess the effects of low temperature environment on skeletal and serum metabolites, and explore underlying mechanism.Methods:C57BL/6J mice were divided into normal temperature control group(control group) and intermittent low temperature exposure group(low temperature group). After 12 weeks of intervention, Micro-computed tomography(CT) was used to detect the bone microstructure. The mouse femur was stained by hematoxylin-eosin(HE) staining, tartrate-resistant acid phosphase(TRAP) staining, and type Ⅰ collagen staining. The serum metabolites were detected by liquid chromatography-mass spectrometry(LC-MS), comprehensive principal component analysis and random forest were used to identify potential biomarkers influencing bone metabolism in serum samples, and the metabolic pathways affecting bone metabolism were enriched through metabolic database analysis.Results:Micro-CT results showed that compared to the control group, the bone mineral density, bone volume/tissue volume, trabecular thickness, and trabecular number decreased(all P<0.05) in low temperature group of mice, while trabecular separation and bone surface/bone volume ratio increased(both P<0.05). The staining results of HE indicated that, compared with the control group, low temperature group exhibited disordered bone trabecular space structure, widened gaps, reduced unit area, and the presence of numerous adipose vacuoles. TRAP staining suggested that compared to the control group, low temperature group had an increased number of osteoclasts. The results of type Ⅰ collagen staining showed that the number of type Ⅰ collagen in the low temperature group was lower than that in the control group, and the structure was disordered. On the other hand, metabolomics identified 40 metabolites in serum, including deoxycholic acid, methionine, bilirubin, and salicylic acid, which are involved in lipid metabolism and amino acid metabolism. Conclusion:Low temperature leads to decreased bone mass, which may be related to the regulation of lipid metabolism and amino acid metabolism.

Fetal STR typing of aborted tissue has long been a major problem in forensic DNA.Especially for the first trimester abortion tissue,it is difficult to isolate the embryonic components by histomorphological means,resulting in the inability to accurately obtain the STR typing of the fetus.The mixed STR typing results of mother and fetus can provide a key basis for the identification of suspects in cases of rape-induced pregnancy.In this study,next generation sequencing was used to successfully detect mixed STR typing of mother and suspected fetus or single STR typing of suspected fetus in 4 rape-induced early pregnancy abortion tissues.Combined with Y-STR and flank sequence information,it provides a more comprehensive and reliable genetic basis for the identification of suspects.

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM. METHODS: Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells. RESULTS: In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS. CONCLUSION: Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy. REGISTERATION Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).

Objective:To investigate the effect of aucubin on behaviors and excessive activation of astrocytic in attention deficit/hyperactivity disorder (ADHD) model mice.Methods:Twelve wild-type C57BL/6 pregnant mice (female, clean grade) were intraperitoneally administered with esketamine (15 mg/kg) to establish an ADHD model in offspring mice. The offspring mice were divided into control+ saline group, control+ aucubin group, Ketamine+ saline group and Ketamine+ aucubin group according to the nest matching principle with 15 in each group.At 14 days after birth, mice in the control+ aucubin group and Ketamine+ aucubin group were administered with aucubin (5 mg/kg, once a day) by gavage for 5 days. Mice in control+ saline group and Ketamine+ saline group were administered with equal volume of 0.9% sodium chloride solution. The offspring mice were housed with their mothers in the same cage until 21 days after birth. Twenty-one days after birth, the offspring mice were evaluated by open field test and elevated plus maze tests. Immunofluorescence assay was used to detect the expression of glutamate decarboxylase 2 (GAD2), γ- aminobutyric acid (GABA) and glial fibrillary acidic protein (GFAP) in the amygdala. The morphological changes of astrocytes were quantitatively analyzed by Sholl analysis. GraphPad Prim 9.0.1 software was used for statistical analysis. The comparison of multiple groups was conducted by one-way ANOVA or Kruskal-Wallis test.Results:(1)The results of behavioral experiments showed that the total distance traveled in the open field test and the residence time in open arm of the elevated plus maze were statistically significant ( F=236.90, H=39.92, both P<0.001). The total distance ((7 044±249)mm, (22 891±2 175)mm, P<0.05) and the residence time in open arm(12.69(9.86, 17.24)s, 2.72(0.57, 3.87)s, P<0.05) of mice in Ketamine+ saline group were both higher than those in control+ saline group.The total distance((22 891±2 175)mm, (8 252±839)mm, P<0.05) and the the residence time in open arm(5.45(1.13, 10.99)s, 12.69(9.86, 17.24)s, P<0.05) of Ketamine+ aucubin group were both lower than those of Ketamine+ saline group.(2)The immunofluorescence results showed that the levels of GAD2, GABA and GFAP intensity in amygdala of mice in the four groups were statistically significant ( F=145.50, 50.08, 53.83, all P<0.05). Compared with control+ saline group, the fluorescence intensities of GAD2 ((100.00±9.60)%, (24.86±4.14)%, P<0.05) and GABA ((100.00±16.84))%, (25.48±5.70)%, P<0.05) of Ketamine+ saline group were down-regulated, and the GFAP((100.00±18.02)%, (223.80±25.85)%, P<0.05) was up-regulated. Compared with Ketamine+ saline group, the fluorescence intensities of GAD2 ((24.86±4.14)%, (56.08±6.55)%, P<0.05) and GABA((25.48±5.70)%, (52.59±15.74)%, P<0.05) in Ketamine+ aucubin group were up-regulated, but the fluorescence intensity of GFAP ((223.80±25.85)%, (157.10±22.10)%, P<0.05) was down-regulated.(3)Sholl analysis indicated that the number of the intersections between the astrocyte processes or the branches of astrocyte processes was statistically significant in the 4 groups ( F=12.47, P<0.05). Compared with control+ saline group, the number of the intersections in Ketamine+ saline group((2.07±0.48), (1.67±0.72), P<0.05) increased. While the number of the intersections in Ketamine+ aucubin group was lower than that of Ketamine+ saline group ((1.20±0.78), (2.07±0.48), P<0.05). Conclusion:Aucubin administration can alleviate ADHD-like behaviors in offspring mice, and the mechanism may be associated with the inhibition of excessive astrocytic activation.

Ischemic stroke(IS)is the main cause of neurological dysfunction in adults in China,and rapid,timely,and accurate prediction of post-stroke outcome and intervention treatment are crucial.Currently,the prognosis of ischemic stroke mainly relies on neuroimaging and clinical assessment,and there is still a lack of objective and simple rapid prediction tools.Recent studies have shown that early measurement of peripheral blood-derived biomarkers may be able to predict stroke patient outcomes,thereby optimizing stroke management,improving patient rehabilitation,and improving stroke outcomes.This article reviews the progress of studies on the correlation between peripheral blood biomarkers and clinical prognosis of ischemic stroke.

Objective:The aims of the study were to investigate the relationship among atherogenic index of plasma (AIP) and inflammatory adipocytokines with the severity of coronary artery calcification (CAC) score in coronary artery disease (CAD). And then we analyzed the diagnostic value of the new markers on CAC.Methods:A total of 241 patients with CAD diagnosed by coronary CT angiography (CTA) and coronary angiography in Baoding First Central Hospital from June 2019 to June 2020 were retrospectively enrolled. According to the presence of calcification in coronary CTA, they were divided into CAC group ( n=63) and non-CAC group ( n=178). The clinical data of the patients were collected, and the levels of serum inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). The correlation between CAC score and AIP and inflammatory cytokines was analyzed. The diagnostic value of AIP and inflammatory factors in the formation of CAC in patients with CAD. Results:The levels of AIP, serum osteoprotegerin (OPG) and oligomeric matrix protein (COMP) in CAC group were higher than those in non-CAC group, while the levels of serum fibroblast growth factor 21 (FGF21) were lower than those in non-CAC group, with statistically significant difference (all P<0.01). Correlation analysis showed that CAC score of CAD patients was positively correlated with AIP, OPG and COMP ( r=0.581, 0.451, 0.326, P<0.05), and negatively correlated with FGF21 ( r=-0.294, P<0.05). Receiver operating characteristic (ROC) curve analysis showed that AIP, OPG, COMP and FGF21 had diagnostic value for CAC in CAD patients (all P<0.05). AIP>0.387, OPG>5.150 ng/ml, FGF21>136.35 pg/ml, COMP>733.16 ng/ml were independent factors affecting the formation of CAC (all P<0.05). Conclusions:The increase of AIP and the change of inflammatory factors can be used as markers for the diagnosis of CAC formation in CAD patients.