OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance （IR） in type 2 diabetes mellitus （T2DM） rats. METHODS T2DM rat model was established by intraperitoneal injection of 30 mg/kg streptozotocin combined with high-fat and high-sugar diet. The rats were randomly divided into normal control group， model group， Qingxue xiaozhi jiangtang formula low-dose and high-dose groups （6.525， 13.05 g/kg， calculated by raw material） and metformin group （positive control， 0.18 g/kg）， with 8 rats in each group. Administration groups were given relevant medicine intragastrically； normal control group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 6 weeks. Body mass and fasting blood glucose （FBG） were determined， and oral glucose tolerance test was conducted. Serum fasting insulin （FINS） level was measured to calculate the insulin resistance index （HOMA-IR） and insulin sensitivity index （ISI）. Additionally， the level of serum lipids， liver function， oxidative stress indicators and inflammatory factors were assessed. The phosphorylation levels of kinase R-like endoplasmic reticulum kinase （PERK） and forkhead box O1 （FOXO1） protein in liver tissue of rats were determined. RESULTS Compared with model group， the body weight， ISI， the levels of high-density lipoprotein cholesterol and superoxide dismutase were increased significantly in Qingxue xiaozhi jiangtang formula high-dose group and metformin group （P＜0.05）； FBG， blood glucose level at 120 minutes of glucose loading， area under the curve of glucose， FINS， HOMA-IR， low-density lipoprotein cholesterol， total cholesterol， triglyceride， alanine transaminase， aspartate transaminase， alkaline phosphatase， malondialdehyde， interleukin-6， tumor necrosis factor-α， and C-reactive protein levels were significantly reduced （P＜ Δ0.05）； the pathological damage of liver tissue had significantlyimproved， and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased （P＜0.05）. CONCLUSIONS Qingxue xiaozhi jiangtang formula can regulate glucose and lipid metabolism， inflammation factor and oxidative stress levels， and alleviate insulin resistance in T2DM rats. Its mechanism of action may be related to the inhibition of the PERK/FOXO1 signaling pathway.

ObjectiveTo investigate the effects of jujuboside A （JuA） on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment （VCI） and explore the potential mechanisms by which JuA treats VCI. MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group （n=10）， a blank control group （n=10）， and a modeling group （n=30）. The rats in the modeling group underwent bilateral carotid artery ligation （2-VO） for the modeling of VCI. After stabilization， the VCI rats were randomized into model， JuA （20 mg·kg^-¹）， and donepezil （0.45 mg·kg^-¹） groups. After 4 weeks of gavage， the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β （GSK-3β）， cAMP response element-binding protein （CREB）， B cell lymphoma-2 （Bcl-2）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β， p-GSK-3β， p-CREB， Bcl-2， PI3K， p-PI3K， Akt， and p-Akt in the hippocampal tissue. ResultCompared with the sham operation group， the model group exhibited declines in the learning and memory abilities （P<0.01）， neuronal damage and decreased neurons in the hippocampal CA1 region （P<0.01）， up-regulation in the mRNA level of GSK-3β （P<0.01）， and down-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2， as well as the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.01）. In comparison to the model group， both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities （P<0.05， P<0.01）， with reduced neuronal damage and increased neurons （P<0.05， P<0.01）. In addition， the two groups showed down-regulation in the mRNA level of GSK-3β （P<0.01） and up-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2 and the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.05， P<0.01）. There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities， neuron count， and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors. ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway， reducing the apoptosis of hippocampal neurons， and alleviating the hippocampal neuronal damage.

Objective To compare the pathological status of gastric mucosa and the expression of HH-PTCH-SMO-GLI(Hedgehog signaling pathway)and NOX/NF-κB/STAT1 signaling pathways in Hp and non-HP infected CAG patients,and to explore the biological mechanism of Hp promoting the"inflammatory cancer transformation"of CAG.Methods 43 patients with CAG who met the criteria were enrolled and divided into CAG with Hp infection group(Hp+ CAG group,n=21)and CAG without Hp infection group(HP-CAG group,n=22).The histological changes of gastric mucosa were observed by hematoxylin-eosin(HE)staining.Western blot was used to detect the relative expression levels of NOX1,NOX2,NOX4,STAT1,P65 and P-P65 in gastric mucosa.Real-time fluorescence quantitative PCR(RT-qPCR)was used to detect Gli1 mRNA,Gli2 mRNA,Gli3 mRNA,Shh mRNA,Smo mRNA,Ptch mRNA,NOX1 mRNA,NOX2 mRNA,NOX4 mRNA and NF-κB mRNA in gastric mucosa The mRNA level.Results HE staining results of gastric tissues in the two groups:In the Hp+CAG group,gastric epithelial cells were partially necrotic and shed,the surface was not smooth,the number of glands was reduced and disordered,intestinal metaplasia was observed,and diffuse lymphocyte and neutrophil infiltration were observed in the lamina proper.The degree of lymphocyte and neutrophil infiltration in HP-CAG group was lighter than that in Hp+CAG group.RT-qPCR results:Compared with HP-CAG group,the levels of Gli1 mRNA,Shh mRNA,Smo mRNA and Ptch mRNA in gastric mucosa of Hp+CAG group were significantly decreased(P<0.01).The levels of Gli2 mRNA,Gli3 mRNA,NOX1 mRNA,NOX2 mRNA,NOX4 mRNA and NF-κB mRNA were significantly increased(P<0.01).Western blot detection results:Compared with hP-CAG group,the relative expression levels of NOX1/GAPDH,NOX2/GAPDH,NOX4/GAPDH and P-P65/GAPDH in gastric mucosa of Hp+CAG group were significantly increased(P<0.01),and the STAT1 level was significantly decreased(P<0.01).There was no significant difference in the relative expression of P65/GAPDH between the two groups(P>0.05).Conclusion Hp infection may cause long-term inflammation of gastric mucosa,promote atrophy and intestinal metaplasia,and increase the risk of cancer by inhibiting hH-PTC-SMO-GLi signaling pathway and abnormal activation of NOX/NF-κB/STAT1 signaling pathway.

The fundamental pathogenic mechanisms of inflammatory bowel disease(IBD),a chronic inflammatory illness affecting the gastrointestinal tract,are still not fully understood.Dipeptidyl peptidase Ⅳ(DPP-4)is a glycoprotein found on the cell surface that has signaling and enzymatic properties.In addition,there is growing evidence from animal models and clinical trials that DPP-4 inhibitors have potential impacts beyond only lowering blood sugar levels,such as immunomodulatory and anti-inflammatory capabilities.This article reviews the biological properties of DPP-4 and its research progress in the diagnosis and treatment of IBD.It also discusses the mechanism of DPP-4 in IBD,aiming to provide a more in-depth understanding of the role of DPP-4 in IBD.

OBJECTIVE To establish and validate a rat liver micronucleus test(LMNT)method based on fixation of liver tissue with 4%neutral formaldehyde(HCHO fixation)for preparation of hepa-tocytes(HEPs).METHODS ①The LMNT based on neutral HCHO fixation(HCHO fixation-LMNT)was established using the liver micronucleus positive compound N-nitrosodiethylamine(DEN).SD rats were divided into female and male groups,and each group was randomly subdivided into the vehicle control group and DEN 12.5 mg·kg-1 group,with five rats in each.The rats were ig administered with normal saline and DEN once a day for 14 consecutive days,after which liver tissues were collected.Some of the tissue was digested with collagenase to prepare HEP suspension,and the remaining tissue was used to prepare HEP suspension with HCHO fixation.After staining with SYBR Gold,the number of micronucleated hepatocytes(MN-HEP)and the number of HEPs in the mitotic phase were counted under a microscope.The micronucleus rate of HEP(MN-HEP rate)and the mitotic index were calculated,and an MN-HEP rate>0.07%was considered positive.②Male SD rats were divided into the quinoline(30,60,120 mg·kg-1)group,N-nitrosoopyrrolidine(NPYR,25,50,100 mg·kg-1)group,vehicle control group(deionized water for NPYR,and corn oil for quinoline),and positive control DEN(12.5 mg·kg-1)group,with 5-6 rats per group,and were ig administrated for 15 consecutive days.Body mass was recorded daily,and at the end of the experiment,the liver was removed to record the total liver weight,and calculate the liver coefficient.Liver function-related serum biochemical indicators including glutamic-pyruvic transaminase(GPT),glutamic-oxaloacetic transaminase(GOT)activities,and levels of total bili-rubin(T-BIL)were measured and direct bilirubin(D-BIL)using an automatic biochemical analyzer.The MN-HEP rate was determined using the collagenase digestion and HCHO fixation methods,and the peripheral blood MN assay and hepatocellular carcinoma comet assay were conducted to evaluate the genotoxicity of quinoline and NPYR.RESULTS ① Compared with the corresponding vehicle control groups(0.069%and 0.030%),the MN-HEP rate of male rats treated with DEN by formalin-LMNT was 1.10%,and the MN-HEP rate of female ones was 0.82%,both significantly increased(P<0.05).Com-pared with corresponding vehicle control groups(0.060%and 0.030%),the MN-HEP rate of male rats treated with DEN by collagenase digestion-LMNT was 1.45%,and that of female rats was 0.46%,both significantly increased(P<0.05),which were considered positive.The MN-HEP rate of male rats was significantly higher than that of females with both methods(P<0.05).There was no significant differ-ence in mitotic indexes between the DEN groups by collagenase digestion-LMNT and HCHO fixation-LMNT in male and female rats compared to corresponding vehicle control groups.② Compared to the vehicle control group,the body mass of rats in the NPYR 50 and 100 mg·kg-1 groups was significantly reduced 7 to 14 days into the ig administration(P<0.01),and the DEN group showed a significant reduction at days 8 to 14(P<0.01).The body mass of rats in the quinoline 120 mg·kg-1 group was signifi-cantly reduced 4 to 14 days into the ig administration(P<0.01),and the DEN group showed a signifi-cant reduction at days 10 to 14(P<0.05).Compared to the vehicle control group,both the liver weight and liver coefficient were significantly reduced in the NPYR 100 mg·kg-1 group(P<0.01)and the DEN group(P<0.05).The liver weight(P<0.01)and liver coefficient(P<0.05)were significantly increased in the quinoline 60 and 120 mg·kg-1 groups.Compared to the vehicle control group,the serum T-BIL level was significantly increased in the DEN group(P<0.01),and the activities of GPT and GOT,as well as the levels of D-BIL and T-BIL,were significantly increased in the NPYR 100 mg·kg-1 group(P<0.01).There were no significant changes in the NPYR 25,50 mg·kg-1 groups or any of the dose groups of quinoline.The MN-HEP rate by HCHO fixation-LMNT for NPYR was slightly higher than that by collage-nase digestion-LMNT,both considered positive.Compared with corresponding control group,the MN-HEP rate by formalin-LMNT for NPYR and the MN-HEP rate by collagenase digestion for NPYR were both significantly increased(P<0.05).The MN-HEP rate by HCHO fixation-LMNT for quinoline was comparable to that by collagenase digestion-LMNT,both considered positive.Compared with corresponding vehicle control group,the MN-HEP rate by HCHO fixation-LMNT for quinoline and the MN-HEP rate by collagenase digestion-LMNT for quinoline were both significantly increased(P<0.05).The correlation between the MN-HEP rates based on HCHO fixation and collagenase digestion for NPYR and quinoline was good(R2=0.8614 and 0.9279,respectively).In the NPYR groups,the periph-eral blood micronucleus assay were negative,while the comet assay results were positive.In the quino-line group,both the peripheral blood micronucleus assay and the comet assay results were negative.CON-CLUSION The HCHO fixation-LMNT has been established and validated,and the sensitivity of the LMNT method based on HCHO fixation-LMNT for detection of hepatocarcinogens is higher than that of collagenase digestion-LMNT.

Objective To investigate the biomechanical effects of lingual metal-reinforced denture bases on edentulous implant-supported prostheses by three-dimensional finite element analysis,and provide references for the treatment of edentulous jaws.Methods Two implant-supported Locator-type overdenture models with lingual metal-reinforced and non-reinforced denture bases were constructed.A 150 N vertical load on the fovea of the posterior teeth,a 150 N oblique load on the fovea of the posterior teeth,and a 150 N vertical load on the anterior teeth were applied to simulate the centric occlusion,left and right lateral chewing,and anterior teeth cutting,and stresses on the tissues of two models were analyzed.Results When the posterior and anterior teeth were loaded vertically,the stress distribution on each organization was similar between the two denture base designs.The maximum stress difference was between 0 and 0.16 MPa.Under unilateral masticatory chewing,the range of stress concentration on denture base,implant and mucoperiosteum,and the maximum stress of the implant and peri-implant bone without metal reinforcement were significantly greater than those with metal reinforcement,and the maximum stress difference was between 0.59 MPa and 2.99 MPa.Conclusions Lingual metal-reinforced denture base can play a role in stress dispersion,or reduce the risk of bone resorption and denture base fracture to a certain extent.

BACKGROUND: The addition of growth factiors is commonly applied to improve the osteogenic differentiation of stem cells. However, for human pluripotent stem cells (hPSCs), their complex differentiation processes result in the unknown effect at different stages. In this study, we focused on the widely used bone forming peptide-1 (BFP-1) and investigated the effect and mechanisms of its addition on the osteogenic induction of hPSCs as a function of the supplementation period. METHODS: Monolayer-cultured hPSCs were cultured in osteogenic induction medium for 28 days, and the effect of BFP-1 peptide addition at varying weeks was examined. After differentiation for varying days (0, 7, 14, 21 and 28), the differentiation efficiency was determined by RT–PCR, flow cytometry, immunofluorescence, and alizarin red staining assays. Moreover, the expression of marker genes related to germ layers and epithelial-mesenchymal transition (EMT) was investigated at day 7. RESULTS: Peptide treatment during the first week promoted the generation of mesoderm cells and mesenchymal-like cells from hiPSCs. Then, the upregulated expression of osteogenesis marker genes/proteins was detected in both hESCs and hiPSCs during subsequent inductions with BFP-1 peptide treatment. Fortunately, further experimental design confirmed that treating the BFP-1 peptide during 7–21 days showed even better performance for hESCs but was ineffective for hiPSCs. CONCLUSION The differentiation efficiency of cells could be improved by determining the optimal treatment period.Our study has great value in maximizing the differentiation of hPSCs by adding osteogenesis peptides based on the revealed mechanisms and promoting the application of hPSCs in bone tissue regeneration.

ObjectiveIn view of the standardization of clinical diagnosis and treatment of the acute abdomen and the inheritance of diagnosis and treatment experience of prestigious veteran traditional Chinese medicine（TCM） doctors， a diagnosis and treatment reasoning algorithm based on association rule mining under incomplete evidence（AMIE）+ random walk was proposed to provide information services and technical support for primary doctors by recommending personalized diagnosis and treatment plans based on medical records. MethodThe experience of diagnosis and treatment of acute abdomen of prestigious veteran TCM doctors and the text data of clinical diagnosis and treatment guidelines of integrated TCM and western medicine were collected to complete the task of knowledge extraction and construct acute abdomen knowledge graph based on Neo4j. On the basis of ontology-supported rule-based reasoning， the rule reasoning based on similar syndromes was used to expand the syndrome combinations whose Jaccard similarity was greater than the threshold in the syndrome recommendation results. The semantic path coverage algorithm was used to calculate the semantic similarity between the symptom nodes. The symptom nodes were divided into 10 categories， and the symptom nodes in the same category were extended. The random walk algorithm was used to search the symptom nodes connected with the syndrome， and the connection rules between the syndrome and symptom nodes were extended to realize the knowledge reasoning of AMIE+ random walk. ResultThe acute abdomen knowledge graph included 1 320 nodes and 2 464 relationships. According to the link prediction evaluation index of knowledge reasoning， the reasoning results of the three algorithms in the auxiliary diagnosis and treatment of acute abdomen were compared. The AMIE+ random walk algorithm complemented the knowledge graph by extending the similar syndrome connection rules and the syndrome-symptom connection rules. Compared with the knowledge reasoning algorithm based on ontology rules， the area under the curve （AUC） was 15.18% higher and the accuracy was 30.36% higher， which achieved more accurate and effective knowledge inference. ConclusionThis study used knowledge graph technology to visualize the diagnosis and treatment of acute abdomen with TCM and western medicine， assisting primary clinicians in intuitively viewing the diagnosis and treatment process and data relationship. The proposed diagnosis and treatment reasoning algorithm can realize the personalized diagnosis and treatment plan recommendation at the level of "disease-syndrome-diagnosis-treatment-prescription"， which can assist primary doctors in disease diagnosis and treatment and clinical decision-making， contribute to the knowledge sharing and application of diagnosis and treatment experience and clinical guidelines of prestigious veteran TCM doctors， improve the level of primary clinical diagnosis and treatment， and promote the normalization and standardization of the diagnosis and treatment process of acute abdomen with integrated TCM and western medicine.

OBJECTIVE: To investigate the feasibility and effectiveness of absorbable anchor combined with Kirschner wire fixation in the reconstruction of extension function of old mallet finger. METHODS: Between January 2020 and January 2022, 23 cases of old mallet fingers were treated. There were 17 males and 6 females with an average age of 42 years (range, 18-70 years). The cause of injury included sports impact injury in 12 cases, sprain in 9 cases, and previous cut injury in 2 cases. The affected finger included index finger in 4 cases, middle finger in 5 cases, ring finger in 9 cases, and little finger in 5 cases. There were 18 patients of tendinous mallet fingers (Doyle type Ⅰ), 5 patients were only small bone fragments avulsion (Wehbe type ⅠA). The time from injury to operation was 45-120 days, with an average of 67 days. The patients were treated with Kirschner wire to fix the distal interphalangeal joint in a mild back extension position after joint release. The insertion of extensor tendon was reconstructed and fixed with absorbable anchors. After 6 weeks, the Kirschner wire was removed, and the patients started joint flexion and extension training. RESULTS: The postoperative follow-up ranged from 4 to 24 months (mean, 9 months). The wounds healed by first intention without complications such as skin necrosis, wound infection, and nail deformity. The distal interphalangeal joint was not stiff, the joint space was good, and there was no complication such as pain and osteoarthritis. At last follow-up, according to Crawford function evaluation standard, 12 cases were excellent, 9 cases were good, 2 cases were fair, and the good and excellent rate was 91.3%. CONCLUSION Absorbable anchor combined with Kirschner wire fixation can be used to reconstruct the extension function of old mallet finger, which has the advantages of simple operation and less complications.
Male ; Female ; Humans ; Adult ; Bone Wires ; Fracture Fixation, Internal ; Finger Injuries/surgery* ; Fractures, Bone/surgery* ; Tendon Injuries/surgery* ; Fingers ; Treatment Outcome ; Finger Joint/surgery*

Objective:To investigate the application value of laparoscopic pancreatic tumor enucleation (LapEN).Methods:The retrospective and descriptive study was conducted. The clinical data of 47 patients who underwent LapEN in Second Hospital of Hebei Medical University from September 2016 to June 2022 were collected. There were 18 males and 29 females, aged (49±12)years. Observa-tion indicators: (1) surgical situations; (2) postoperative complications; (3) postoperative recovery; (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All 47 patients underwent LapEN successfully, with the operation time as (135±19)minutes and the volume of intraoperative blood loss as 100(50,100)mL. (2) Postoperative complications. Of the 47 patients, there were 12 patients with postoperative pancreatic fistula, 3 patients with postoperative abdominal infection, 1 case with postoperative hemorrhage, 1 case with postoperative gastric emptying disorder. (3) Postoperative recovery. Of the 47 patients, there were 13 cases with pancreatic solid pseudopapillary neoplasm, 12 cases with insulinoma, 11 cases with pancreatic serous cystadenoma, 7 cases with pancreatic intraductal papillary mucinous neoplasm (branched type), 4 cases with pancreatic mucinous cyst-adenoma. The tumor diameter of 47 patients was 1.9(1.6,2.3)cm and all patients with R 0 resection. There was no patient with perioperative death in the 47 patients. The postoperative duration of hospital stay and total hospital expenses of 47 patients was (13±4)days and (6.8±1.2) ten thousand yuan, respectively. (4) Follow-up. All 47 patients were followed up for 14(range, 8?18)months. None of the 47 patients had new onset diabetes or situations required postoperative exocrine replacement therapy, and no patient died. Conclusion:LapEN is safe and feasible for patients with pancreatic benign tumor or low potential malignancy.