ObjectiveTo investigate the value of baseline red cell distribution width （RDW） and alkaline phosphatase （ALP） level after ursodeoxycholic acid （UDCA） treatment for one month in predicting the response to UDCA treatment in patients with primary biliary cholangitis （PBC）. MethodsA retrospective analysis was performed for the data of 127 patients with PBC who were diagnosed in Department of Hepatology， The Third People’s Hospital of Jiangsu University， from January 2015 to July 2022， with data collected at baseline， after one month of treatment， and after one year of follow-up. Based on the Paris-I criteria， the patients were divided into good response group and poor response group， and the two groups were analyzed in terms of clinical and laboratory features and their association with response to UDCA. The Logistic regression method was used to investigate the independent risk factors for response to UDCA treatment. The area under the ROC curve （AUC） was used to determine the optimal cut-off values of related indicators； the patients were divided into two groups based on such values， and the two groups were compared in terms of baseline indicators and response. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the good response group， the poor response group had significantly higher levels of total bilirubin， aspartate aminotransferase/alanine aminotransferase， ALP， RDW， and RDW-CV at baseline and a significantly higher level of ALP after one month of UDCA treatment （Z=-4.792， -3.697， -2.399， -4.102， -3.220， and -4.236， all P<0.05）. Compared with the good response group， the poor response group had significantly lower levels of albumin， hemoglobin， lymphocytes， hematocrit， and body mass index at baseline （Z=-3.592， -3.603， -2.602， -3.829， -2.432， all P<0.05）， as well as significantly lower levels of prealbumin， albumin/globulin ratio， apolipoprotein A， and free triiodothyronine at baseline （t=4.530， 3.402， 3.485， and 3.639， all P<0.001）. Compared with the poor response group， the good response group had a significantly lower proportion of patients with liver cirrhosis， gallstones/cholecystitis， or anemia （χ²=20.815， 3.892， and 12.283， all P<0.05）. Baseline RDW （odds ratio ［OR］=1.157， 95% confidence interval ［CI］： 1.028‍ — ‍1.301， P=0.015） and ALP level after one month of treatment （OR=1.012， 95%CI： 1.005‍ — ‍1.020， P=0.002） were independent risk factors for response to UDCA， with an AUC of 0.713 and 0.720， respectively. The patients with baseline RDW≥upper limit of normal （ULN） and ALP≥2.2×ULN after one month of UDCA treatment had a lower UDCA response rate （42.6% vs 8.2%， χ²=20.813， P<0.001）. ConclusionPatients with baseline RDW≥ULN and ALP≥2.2×ULN after one month of UDCA treatment tend to have a low biochemical response rate to UDCA.

Objective:To establish high performance liquid chromatography (HPLC) wavelength switching method to simultaneously determine the contents of chlorogenic acid, hydroxysafflor yellow A, ferulic acid, Nicotiflorin, Osthole and columbianadin in Tongluo Zhibi Prescription.Methods:The column was XBridge C18 column (250 mm × 4.6 mm, 5 μm); the mobile phase was acetonitrile (A)-0.1% phosphate water (B); gradient eluted, with flow rate: 1 ml/min, column temperature: 30 °C, detection wavelength 330 nm (0-14 min detection of chlorogenic acid, 15-80 min detection of ferulic acid, Nicotiflorin, Osthole, and columbianadin), 403 nm (14-15 min detection of hydroxysafflower yellow pigment A).Results:Chlorogenic acid, hydroxyrhodopsin A, ferulic acid, kaempferol 3-O-rutinoside, serpentin, and dihydroeurobicarpus angelicus acid ester showed good linearity ( R2 ≥ 0.999 8) within 0.029 7-1.485 0, 0.030 0-1.500 0, 0.009 9-0.495 0, 0.017 5-0.875 0, 0.028 4-1.420 0, 0.013 7-0.685 0 μg, respectively. The precision, stability (24 h), repeatability relative standard deviation ( RSD) were all <2%. The average spiked recoveries were all in the range of 95%-105%, and the RSDs were all in the range of 0.32%-1.67%. In 10 batches of test samples of Tongluo Zhibi Prescription, the content of the above six components, including chlorogenic acid, was determined to be 0.221 60, 0.314 30, 0.085 10, 0.032 95, 0.043 87, 0.026 21 mg/g in the following order. Conclusion:The established HPLC wavelength switching method is fast, simple and accurate, which can be used for simultaneous determination of the content of the above six components in Tongluo Zhibi Prescription, which provides reference for quality monitoring and new dosage form research of Tongluo Zhibi Prescription.

ObjectiveBased on non-targeted metabolomics， to analyze the regulation of endogenous differential metabolites in serum of type 2 diabetes mellitus（T2DM） rats by Fuling Yunhua granules， and to clarify the metabolic pathways through which this granules exerted its effect on improving T2DM. MethodSeventy SD rats， half male and half female， were randomly divided into the control group， model group， and high， medium， low dose groups of Fuling Yunhua granules（20.70， 10.35， 5.18 g·kg^-1 in raw drug amount） and the positive drug group（pioglitazone hydrochloride tablets， 8.1 mg·kg^-1）. Except for the control group， other groups were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ） to establish a T2DM rat model. After successful modeling， the treatment groups were administered the corresponding drugs by gavage， and the control group and model group were treated with an equal volume of saline by gavage， once/d， for 28 d. Fasting blood glucose（FBG） and glycosylated hemoglobin A1c（GHbA1c） levels were measured in all groups of rats during the administration period， and hematoxylin-eosin（HE） staining was used to observe the pathomorphological changes in the pancreatic tissues of rats at the end of the administration period. The endogenous metabolite levels in rat serum were detected by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-LTQ-Orbitrap MS）， and the data were processed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential metabolites were identified by the Human Metabolome Database（HMDB） and the Kyoto Encyclopedia of Genes and Genomes（KEGG）， and screened for differential metabolites with variable importance in the projection（VIP） value>1， P<0.05， and fold change（FC）<0.6 or FC>1. And the metabolic pathway enrichment analysis of the screened differential metabolites was performed by MetaboAnalyst 5.0， then the screened differential metabolites were diagnosed and evaluated by the receiver operating characteristic（ROC） curves. ResultCompared with the control group， the FBG level of rats in the model group increased significantly（P<0.01）， the GHbA1c content tended to increase， but the difference was not statistically significant， and the pancreatic tissue of rats was obviously damaged， the number of pancreatic islets decreased， and the pancreatic β-cells were obviously reduced， atrophied and enlarged. Compared with the model group， the FBG levels of rats in the high dose group of Fuling Yunhua granules and the positive drug group were significantly reduced after 2 weeks of administration（P<0.05， P<0.01）， the GHbA1c content of rats in the high dose group of Fuling Yunhua granules was significantly reduced（P<0.05）， and the pancreatic tissue lesions of rats in the different dose groups of Fuling Yunhua granules were reduced. The results of non-targeted metabolomics showed that 46 differential metabolites were significantly changed in the model group compared with the blank group. Pathway enrichment analysis found that T2DM mainly affected biological processes including biosynthesis of primary bile acid， D-amino acid metabolism， steroid hormone biosynthesis， and glycerophospholipid metabolism in rats. Compared with the model group， the levels of 8 differential metabolites in the high dose group of Fuling Yunhua granules were significantly adjusted， and the pathway enrichment analysis found that D-amino acid metabolism， retinol metabolism， glycine， serine and threonine metabolism， tryptophan metabolism and other metabolic pathways were mainly involved. ROC curves further analysis revealed that the four characteristic differential markers of 11-cis-retinol， D-piperidinic acid， D-serine， and p-cresol sulfate had high diagnostic value for the treatment of T2DM with Fuling Yunhua granules. ConclusionFuling Yunhua granules can improve the symptoms of T2DM rats by regulating the amino acid metabolic and retinol metabolic pathways through the modulation of endogenous differential metabolites.

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.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

With the widespread use of carbapenem antibiotics,the clinical detection rate of carbapenem-resistant Gram-negative bacilli has shown a significant increase.Carbapenem-resistant Gram-negative bacilli isolates are often extensively or fully resistant,resulting in limited antimicrobial treatment options and high morbidity and mortality rates,posing a serious public health threat.The clinical treatment of carbapenem-resistant Gram-negative bacilli includes the use of single or combination antimicrobials such as polymyxin,tigecycline,and fosfomycin.A number of new antimicrobials and therapeutic approaches are under development.The clinical management of carbapenem-resistant Gram-negative infections is severely challenged by the limited choice of antimicrobial agents.Therefore,this article reviews the current status and progress of antimicrobial treatment for carbapenem-resistant Gram-negative bacilli to providing clinical reference.

The regulatory requirements of 3D printing products were introduced.The risks during the production of 3D printed navigational template for orthopedic surgery were summarized in terms of data acquisition,medical-industrial intera-ction design,3D printing,post-processing and sterilization.Some quality control measures were proposed from the aspects of quality control of raw materials,validation of data and software,verification of printing process parameters,post-processing method and verification,sterilization verification and testing of semi-finished and final products,so as to enhance the safety and effectiveness of 3D printed navigational template for orthopedic surgery.[Chinese Medical Equipment Journal,2024,45(5):80-85]

Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L⁻¹ NaAsO₂ model group (NaAsO₂), 50 mg·L⁻¹ NaAsO₂+10 mg·kg⁻¹ GBE intervene group (NaAsO₂+GBE), and 10 mg·kg⁻¹ GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L⁻¹ NaAsO₂, or given intraperitoneal injection of normal saline containing 10 mg·kg⁻¹ GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L⁻¹ NaAsO₂ group (NaAsO₂), 8 μmol·L⁻¹ NaAsO₂ + 200 mg·L⁻¹ GBE intervene group (NaAsO₂+GBE), and 200 mg·L⁻¹ GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO₂ group exhibited an elevated blood glucose compared to the control group, and the NaAsO₂+GBE group showed a decreased blood glucose compared to the NaAsO₂ group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO₂ group and NaAsO₂+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO₂ groups compared to the control groups, which was alleviated in the NaAsO₂+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO₂+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.

Objective To observe the effects of brain-computer interface-controlled pedal training system on bal-ance function and serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)levels in ischemic stroke pa-tients.Methods Forty patients with ischemic stroke who were hospitalized from September 2022 to September 2023 were selected as observation subjects.The patients were equally divided into stroke control group and stroke experimental group according to the random number table method.At the same time,20 healthy subjects with similar gender and age were recruited as the healthy control group to collect relevant plantar pressure data.Patients in the stroke control group received conventional rehabilitation training including the upper and lower extremity active and passive motor training system,and the stroke experimental group replaced the upper and lower extremity active and passive motor training system in the stroke control group with the brain-computer interface-controlled pedal training system for rehabilitation treatment,and other things remained unchanged.Bilateral plantar pressure symmetry index(SI)and center of body pressure(COP)swing area were collected from both groups of stroke patients with eyes open and closed using the plantar pressure assessment system before and after 4 weeks of treatment.Fugl-meyer low-er extremity motor function score(FMA-LE)and berg balance scale(BBS)were used to evaluate the two groups of stroke patients.Serum IL-6 and TNF-α levels were also compared between the two groups before and after treat-ment.Results ① The SI value and COP swing area in the eyes open and closed state improved in both groups of stroke patients after treatment compared with that before admission,and the results of the stroke experimental group were better than those of the stroke control group(P＜0.05),but there was still a gap with the healthy control group(P＜0.05).②The BBS and FMA-LE scores of stroke patients in both groups were higher after treatment than before treatment,and the scores of the stroke experimental group were greater than those of the stroke control group,with statistically significant differences(all P＜0.05).③Serum IL-6 and TNF-α levels decreased in both groups of stroke patients after treatment compared with before,and the degree of decrease in serum IL-6 and TNF-αlevels in the stroke experimental group was greater than that in the stroke control group,and the difference was sta-tistically significant(P＜0.001,P＜0.05).Conclusion Brain-computer interface-controlled pedal training sys-tem has a facilitating effect on the recovery of balance function in hemiplegic patients with ischemic stroke,and its mechanism may be related to the reduction of serum IL-6 and TNF-α levels.

Objective To investigate the role of chemokine ligand 19 (CCL19) and protein kinase-B (AKT) signaling pathway in lung cancer development. Methods The human lung adenocarcinoma cell line, A549 cells, in logarithmic growth phase were randomly divided into five groups： blank control group, solvent control group, CCL19 treatment group, AKT inhibition group, and antibody neutralization group. The blank control group received no treatment. The other four groups were treated with dimethyl sulfoxide, CCL19, MK-2206 (AKT inhibitor), and a combination of CCL19 and MK-2206, respectively. Cell viability was assessed using the CCK-8 assay, while cell migration and invasion capabilities were evaluated using the cell scratch and transwell assays. The relative expression levels of Pan-AKT, p-AKT (Ser473), p-AKT (Thr308), E-cadherin (E-cad), N-cadherin (N-cad), and Snail proteins in A549 cells were detected using Western blotting. Lung cancer tissue samples from 60 patients with non-small cell lung cancer (NSCLC) were collected, and the expression of CCL19 and matrix metalloproteinase 9 (MMP9) proteins in the specimens was examined using immunohistochemistry. Results The survival rate of A549 cells in the AKT inhibition group and antibody neutralization group was lower than that in blank control group, solvent control group, and CCL19 treatment group (all P<0.05). The cell scratch assay result showed that the cell migration rate of the CCL19 treatment group was higher at 36.0 and 48.0 hours than those of the blank control group, solvent control group, AKT inhibition group, and neutralizing antibody group (all P<0.05). The Transwell assay result showed that the invasion amount of A549 cells in the AKT inhibition group was less than that in the CCL19 treatment group (P<0.05). Compared with the blank control group, the relative expression of E-cad protein in the CCL19 treatment group decreased, while the relative expression of p-AKT (Ser473), p-AKT (Thr308), N-cad and Snail proteins increased (all P<0.05). The relative expression of p-AKT (Ser473), p-AKT (Thr308), N-cad, and Snail proteins in A549 cells decreased (all P<0.05), and relative expression of E-cad protein increased (all P<0.05) in the AKT inhibition group and antibody neutralization group compared with the blank control group, solvent control group, and CCL19 treatment group. There was no significant difference in the expression of CCL19 and MMP9 in lung cancer tissues of NSCLC patients in Xuanwei City, Gejiu City, and other regions (all P>0.05). The expression of CCL19 and MMP9 in NSCLC patients with lymph node metastasis was higher than in patients without lymph node metastasis (all P<0.01). Conclusion CCL19 can promote the invasion and metastasis of lung cancer cells and induce epithelial-mesenchymal transition. Its expression level is related to lymph node metastasis in NSCLC patients. The AKT signaling pathway may be an important mechanism underlying lung cancer development.