OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

Liver cancer is one of the most common malignant tumors worldwide. Currently, the available treatment methods cannot fully control its recurrence and mortality rate. Establishing appropriate animal models for liver cancer is crucial for developing new treatment technologies and strategies. The patient-derived xenograft (PDX) model preserves the tumor's microenvironment and heterogeneity, which makes it advantageous for biological research, drug evaluation, personalized medicine, and other purposes. This article reviews the development, preparation techniques, application fields, and challenges of PDX models in liver cancer, providing insights for the research and exploration of PDX models in diagnostic and therapeutic strategies of liver cancer.
Liver Neoplasms/drug therapy* ; Animals ; Humans ; Xenograft Model Antitumor Assays/methods* ; Mice ; Disease Models, Animal

Objective:To establish a tumor tissue xenograft (PDX) model derived from liver cancer patients and explore the factors affecting tumorigenicity of liver cancer in the PDX model.Methods:The hepatocellular carcinoma tissues were inoculated subcutaneously in the axilla of NPG mice using the tissue block method to establish a PDX model. The demographic characteristics and related clinical examination data of 60 hepatocellular carcinoma patients were collected using the electronic medical record system and comprehensive medical information system of Beijing You'an Hospital, affiliated to Capital Medical University. The hepatocellular carcinoma samples of 24 cases were sequenced using the Oak Wing TM-808 gene detection reagent and high-throughput sequencing technology. SPSS 17.0 statistical software was used for statistical analysis, and the count data were analyzed using the χ2 test. Results:The tumorigenicity rate of PDX samples from 60 patients with liver cancer was 35% (21/60). The average tumorigenic duration in the PDX-P0 generation was 110.71±50.45 days. There were statistically significant differences ( P<0.05) corresponding to Edmondson grade ( χ2=5.910, P=0.015) and Ki67 expression ( χ2=4.615, P=0.032) among PDX with tumorigenicity and without tumorigenicity between the liver cancer samples. There was no statistically significant difference in gene mutation (TOP25) among PDX with tumorigenicity and without tumorigenicity between liver cancer samples. Conclusion:The factors affecting the tumorigenicity of liver cancer in PDX models are complex. The high pathological grade and strong Ki67 expression may be the key factors for the completion of liver cancer in PDX models.

Objective:To establish a tumor tissue xenograft (PDX) model derived from liver cancer patients and explore the factors affecting tumorigenicity of liver cancer in the PDX model.Methods:The hepatocellular carcinoma tissues were inoculated subcutaneously in the axilla of NPG mice using the tissue block method to establish a PDX model. The demographic characteristics and related clinical examination data of 60 hepatocellular carcinoma patients were collected using the electronic medical record system and comprehensive medical information system of Beijing You'an Hospital, affiliated to Capital Medical University. The hepatocellular carcinoma samples of 24 cases were sequenced using the Oak Wing TM-808 gene detection reagent and high-throughput sequencing technology. SPSS 17.0 statistical software was used for statistical analysis, and the count data were analyzed using the χ2 test. Results:The tumorigenicity rate of PDX samples from 60 patients with liver cancer was 35% (21/60). The average tumorigenic duration in the PDX-P0 generation was 110.71±50.45 days. There were statistically significant differences ( P<0.05) corresponding to Edmondson grade ( χ2=5.910, P=0.015) and Ki67 expression ( χ2=4.615, P=0.032) among PDX with tumorigenicity and without tumorigenicity between the liver cancer samples. There was no statistically significant difference in gene mutation (TOP25) among PDX with tumorigenicity and without tumorigenicity between liver cancer samples. Conclusion:The factors affecting the tumorigenicity of liver cancer in PDX models are complex. The high pathological grade and strong Ki67 expression may be the key factors for the completion of liver cancer in PDX models.

Objective To evaluate the improvement in the quality of early postoperative recovery in patients undergoing cardiac valve surgery with remimazolam-based fast-track anesthesia,and to provide a reference for the clinical optimization of fast-track anesthesia and Enhanced Recovery After Surgery(ERAS)protocols.Methods We selected elective surgery patients undergoing median sternotomy for cardiac valve replacement and/or repair under general anesthesia with extracorporeal circulation.Based on routine anesthesia assessment and fast-track anesthesia suitability assessment,a total of 228 patients were strictly enrolled according to the inclusion and exclusion criteria and randomly divided into two groups:the Remimazolam group(n=114)and the Propofol group(n=114).Patients in the Remimazolam group were induced and maintained with remimazolam for anesthesia,while patients in the control group were administered propofol.We recorded the general information and surgical data of the patients;the QoR-15 scores before surgery(1 day preoperatively),1 day postoperatively,3 days postoperatively,and 1 day before discharge;as well as hemodynamic parameters at key time points after admission,the incidence of hypotension and bradycardia after anesthesia,the duration of surgery,anesthesia duration,postoperative mechanical ventilation time,ICU stay,postoperative hospital stay,and the incidence of perioperative cardiovascular adverse events and the incidence of early postoperative complications.Results There was no statistically significant difference in general data and QoR-15 scores between the two groups 1 day before surgery(P>0.05).The QoR-15 score of the Remima-zolam group 1 day before discharge was higher than that of the Propofol group,with a statistically significant differ-ence(P<0.05),but the difference was less than the minimum clinically important difference,which is less than 8,indicating no significant clinical benefit.One minute after intubation and one minute after skin incision,the heart rate in the Propofol group slowed down and the Mean Arterial Pressure(MAP)significantly decreased,with a statis-tically significant difference between the groups(P<0.05);there was no statistically significant difference in heart rate and MAP at other times.The incidence of intraoperative hypotension and bradycardia was lower in the Remima-zolam group than in the Propofol group,with a statistically significant difference(P<0.05).The duration of postop-erative mechanical ventilation,ICU stay,postoperative hospital stay,and the rate of re-intubation were all shorter in the Remimazolam group than in the Propofol group,and the success rate of fast-track anesthesia was higher in the Remimazolam group,with a statistically significant difference(P<0.05).There was no statistically significant difference in the incidence of perioperative complications between the two groups.Conclusions Compared with the commonly used intravenous anesthetic propofol,the remimazolam-based fast-track anesthesia regimen did not signifi-cantly improve the postoperative recovery quality scores in patients undergoing cardiac valve surgery.However,remimazolam had advantages in maintaining hemodynamic stability,increasing the success rate of fast-track anesthe-sia,shortening postoperative ICU stay and hospital stay,and is a viable intravenous anesthetic option for cardiac surgery patients.

Objective:To prepare advanced platelet-rich fibrin (A-PRF)/chitosan thermosensitive hydrogel (hereinafter referred to as composite hydrogel) and explore the effects of composite hydrogel on full-thickness skin defect wound healing in diabetic rats.Methods:This study was an experimental study. The composite hydrogel with porous mesh structure and thermosensitive characteristics was successfully prepared, containing A-PRF with mass concentrations of 10, 15, 20, 50, and 100 g/L. Diabetic model was successfully established in male Sprague-Dawley rats aged 6-8 weeks by intraperitoneal injection of streptozotocin, and 4 full-thickness skin defect wounds were established on the back of each rat (finally the model was successfully established in 36 rats). Three wounds of each rat were divided into blank group (no drug intervention), positive control group (dropping recombinant human granulocyte-macrophage stimulating factor gel), and chitosan hydrogel group (dropping chitosan hydrogel solution). Thirty rats were collected, and the remaining one wound of each rat (totally 30 wounds) was divided into 10, 15, 20, 50, and 100 g/L composite hydrogel groups, with 6 wounds in each group, which were dropped with composite hydrogel solution containing 10, 15, 20, 50, and 100 g/L A-PRF, respectively. Taking the remaining six rats, the remaining one wound from each rat was dropped with composite hydrogel solution containing 100 g/L A-PRF. On 14 d after injury, 6 rats with one wound dropped with composite hydrogel containing 100 g/L A-PRF were selected for hematoxylin-eosin (HE) staining to observe the inflammation, hemorrhage, or necrosis of the heart, liver, spleen, lung, and kidney. On 10 d after injury, 6 rats with one wound dropped with composite hydrogel containing 15 g/L A-PRF were selected to observe the blood perfusion of wounds in the four groups (with sample size of 6). On 7 and 14 d after injury, the wound healing rates in the eight groups were calculated. On 14 d after injury, the wound tissue in the eight groups was taken for HE and Masson staining to observe the formation of new epithelium and collagen formation, respectively; the positive expressions of CD31 and vascular endothelial growth factor A (VEGFA) were detected by immunohistochemistry, and the percentages of positive areas were calculated; the protein expressions of CD31 and VEGFA were detected by Western blotting; the mRNA expressions of CD31 and VEGFA were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction method (with all sample sizes of 4).Results:On 14 d after injury, no obvious inflammation, hemorrhage, or necrosis was observed in the heart, liver, spleen, lung, and kidney in the 6 rats. On 10 d after injury, the blood perfusion volume of wound in 15 g/L composite hydrogel group was significantly more than that in blank group, positive control group, and chitosan hydrogel group, respectively (with P values all <0.05). On 7 and 14 d after injury, the wound healing rates of blank group were (26.0±8.9)% and (75.0±1.8)%, which were significantly lower than those of positive control group, chitosan hydrogel group, and 10, 15, 20, 50, and 100 g/L composite hydrogel groups, respectively ((45.8±3.2)%, (49.8±3.7)%, (51.2±2.9)%, (68.5±2.4)%, (68.8±1.5)%, (72.7±2.1)%, (75.0±3.7)% and (79.1±1.9)%, (77.2±1.7)%, (82.3±1.3)%, (89.6±1.9)%, (89.8±1.3)%, (87.3±1.1)%, (87.9±1.3)%), P<0.05; the wound healing rates of positive control group, chitosan hydrogel group, and 10 g/L composite hydrogel group were significantly lower than those of 15, 20, 50, and 100 g/L composite hydrogel groups ( P<0.05). On 14 d after injury, the wound epithelialization degrees of 15, 20, 50, and 100 g/L composite hydrogel groups were higher than those of the other 4 groups, the new microvascular situation was better, and the collagen was more abundant and arranged more neatly. On 14 d after injury, the percentages of CD31 and VEGFA positive areas in wounds in positive control group and the percentage of VEGFA positive area in wounds in chitosan hydrogel group were significantly higher than those in blank group ( P<0.05), the percentage of VEGFA positive area in wounds in 10 g/L composite hydrogel group was significantly higher than that in blank group, chitosan hydrogel group, and positive control group (with P values all <0.05), and the percentages of CD31 and VEGFA positive areas in wounds in 15, 20, 50, and 100 g/L composite hydrogel groups were significantly higher than those in blank group, positive control group, chitosan hydrogel group, and 10 g/L composite hydrogel group ( P<0.05). On 14 d after injury, the protein and mRNA expressions of CD31 and VEGFA in wound tissue in chitosan hydrogel group, positive control group, and 10 g/L composite hydrogel group were significantly higher than those in blank group ( P<0.05); the protein expression of VEGFA in wound tissue in 10 g/L composite hydrogel group was significantly higher than that in positive control group ( P<0.05), and the mRNA expressions of CD31 and VEGFA in wound tissue in 10 g/L composite hydrogel group were significantly higher than those in positive control group and chitosan hydrogel group ( P<0.05); the protein and mRNA expressions of CD31 and VEGFA in wound tissue in 15, 20, 50, and 100 g/L composite hydrogel groups were significantly higher than those in blank group, positive control group, chitosan hydrogel group, and 10 g/L composite hydrogel group ( P<0.05); the mRNA expressions of CD31 and VEGFA in wound tissue in chitosan hydrogel group were significantly lower than those in positive control group ( P<0.05). Conclusions:The composite hydrogel has high biological safety, can improve wound blood perfusion, effectively promote the formation of blood vessels and collagen in wound tissue, thus promoting the wound healing of full-thickness skin defects in diabetic rats. 15 g/L is the optimal mass concentration of A-PRF in composite hydrogel.

Objective:This study aimed to systematically evaluate the efficacy and safety of ivabradine in patients with dilated cardiomyopathy, and to provide evidence-based reference for clinical treatment.Methods:We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wan Fang, VIP databases from inception to 1 September 2021 for randomized controlled trials (RCTs) that compared conventional therapies and ivabradine with conventional therapies in dilated cardiomyopathy patients. Studies meeting the inclusion criteria were included and analyzed. After data extraction and literature quality evaluation, we use the Review Manager 5.4 to perform the meta-analysis and publication bias test.Results:5 studies enrolling 494 patients were included. Compared with conventional therapies (control group), ivabradine and conventional therapies (observation group) significantly reduced resting heart rate [ MD=-7.58, 95% CI(-12.40, -2.76), Z=3.08, P=0.002], left ventricular end diastolic diameter (LVEDD) [ MD=-4.48, 95% CI(-7.33, -1.64), Z=3.09, P=0.002], left ventricular end systolic diameter (LVESD) [ MD=-4.94, 95% CI(-7.29, -2.59), Z=4.12, P<0.001], B-type natriuretic peptide (BNP) [ MD=-212.39, 95% CI(-230.55, -194.23), Z=22.92, P<0.001], New York Heart Association (NYHA) class [ MD=-0.36, 95% CI(-0.44, -0.27), Z=8.46, P<0.001] and Minnesota Questionnaire Score [ MD=-10.43, 95% CI(-15.72, -5.13), Z=3.86, P=0.001]. The left ventricular ejection fraction (LVEF) levels [ MD=1.31, 95% CI(0.64, 1.97), Z=3.85, P=0.001], 6-minute walk test level (6MWT) [ MD=54.83, 95% CI(40.58, 69.08), Z=7.54, P<0.001], systolic blood pressure [ MD=4.72, 95% CI(0.91, 8.54), Z=2.43, P=0.02], the incidence of visual symptoms (phosphene) [ OR=7.22, 95% CI(1.32, 45.00), P=0.02] and symptomatic bradycardia [ OR=8.90, 95% CI(1.21, 65.75), P=0.03] in the observation group were higher than those in the control group after treatment. In addition, there were no significant difference in the incidence of acute event between the two groups [ OR=0.72, 95% CI(0.12, 4.29), P=0.72]. Conclusions:Meta analysis showed that ivabradine combined β receptor blockers can effectively reduce resting heart rate and improve cardiac function in patients with dilated cardiomyopathy, but may increase the incidence of hallucinations and symptomatic bradycardia.

Objective:To establish the acute symptomatic osteoporotic thoracolumbar fracture (ASOTLF) classification system, and to examine the reliability and evaluate the effect of clinical application.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 293 patients with osteoporotic thoracolumbar fracture(OTLF) admitted to Honghui Hospital from January 2016 to December 2018. There were 514 males and 779 females, aged 57-90 years [(71.4±6.3)years]. The T value of bone mass density was -5.0--2.5 SD [(-3.1±-0.4)SD]. According to the clinical symptoms a and fracture morphology, OTLF was divided into 4 types, namely type I(I occult fracture), type II(compressed fracture), type III (burst fracture) and type IV(unstable fracture). The type II was subdivided into three subtypes (type IIA, IIB, IIC), and the Type III into two subtypes (type IIIA, IIIB). of all patients, 75 patients (5.8%) were with type I, 500 (38.7%) with type II A, 134 (10.4%) with type IIB, 97 (7.5%) with type IIC, 442 (34.2%) with type IIIA, 27(2.1%) with type IIIB and 18 (1.4%) with type IV. After testing the validity of the classification, different treatment methods were utilized according to the classification, including percutaneous vertebroplasty (PVP) for Type I, PVP after postural reduction for Type II, percutaneous kyphoplasty (PKP) for Type IIIA, posterior reduction and decompression, bone graft fusion and bone cement-augmented screw fixation for Type IIIB, and posterior reduction, bone graft fusion and bone cement-augmented screw fixation for Type IV. The visual analog score (VAS), Oswestry disability index (ODI), Frankel grade of spinal cord injury, local Cobb Angle, and vertebral body angle (vertebral body angle) were recorded in all patients and in each type of patients before surgery, at 1 month after surgery and at the last follow-up. The neurological function recovery and complications were also recorded.Results:The patients were followed up for 24-43 months [(29.9±5.1)months]. A total of 3 000 assessments in two rounds were conducted by three observers. The overall κ value of inter-observer credibility was 0.83, and the overall κ value of intra-observer credibility was 0.88. The VAS and ODI of all patients were (5.8±0.7)points and 72.5±6.6 before surgery, (1.8±0.6)points and 25.0±6.3 at 1 month after surgery, and (1.5±0.6)points and 19.5±6.2 at the last follow-up, respectively (all P<0.05). The Cobb angle and vertebral body angle of all patients were (13.0±9.1)° and (8.0±4.6)° before surgery, (7.9±5.2)° and (4.6±2.9)° at 1 month after surgery, and (9.1±6.0)° and (5.8±3.0)° at the last follow-up, respectively (all P<0.05). At the last follow-up, VAS, ODI, Cobb Angle and VBA of each type of patients were significantly improved compared with those before surgery (all P<0.05). The spinal cord compression symptoms were found 1 patient with type IV and 5 patients with type IIIB preoperatively. At the last follow-up, neurological function improved from grade C to grade E in 1 patient and from grade D to grade E in 5 patients ( P<0.05). The lower limb radiation pain or numbness in 3 patients with type IV and 22 patients with type III preoperatively were fully recovered after surgical treatment at the last follow-up except for three patients. Conclusions:The ASOTLF classification is established and has high consistency and reliability. The classification-oriented treatment strategy has achieved a relatively satisfactory effect, indicating that the classification has a certain guiding significance for treatment of OTLF.

Objective To evaluate the postoperative efficacy and safety of dexmedetomidine for cardiac surgery patients in intensive care unit. Methods A total of 90 cardiac surgery patients in the intensive care unit (ICU)were randomly assigned into dexmedetomidine group(D group,45 cases)and propofol group(P group,45 cases)to receive dexmedetomidine or propofol respectively for post-operative sedation. The ratio of sedation satisfac-tion was evaluated and calculated by Riker sedation-agitation scale(SAS),and the duration of mechanical ventila-tion,24-hour consumption of sufentanil,ICU staying time,and the incidences of side-effects(such as hypoten-sion,bradycardia,delirium etc)were recorded during the observation period. Results No significant differences were found in the ratio of sedation satisfaction and the incidences of bradycardia and delirium between the two groups (P > 0.05). The duration of mechanical ventilation and ICU staying time were significantly shorter in D group than that in P group(P<0.01),while the 24-hour consumption of sufentanil and the incidences of hypoten-sion and delirium were significantly lower than that in P group(P<0.05). Conclusion Using the dexmedetomi-dine as a postoperative sedation drug for post cardiac surgical patients in ICU is clinically effective and safe ,and the postoperative recovery of patients may be enhanced by the drug using.

Objective To investigate the relationships between septic shock and vascular endothelial cells (VECs)injury by measuring the plasma CEC,vWF,and NO in septic shock patients and to explore its potential clinical values. Methods 72 patients were divided into group A including 34 infection patients but without septic shock,and group B including 38 patients with septic shock. Circulating endothelial cell(CEC),von willebrand factor(vWF),and nitric oxide(NO)in plasma were measured in all patients at the time points of accessing ICU (T0)and 24 hours after staying in ICU(T1). And the blood pressures of studied patients were also recorded at the same time points. Results The levels of CEC and vWF at each observing time point were higher in group B than those in group A(P < 0.01),while the levels of NO were lower in group B than those in group A(P < 0.01). In group B,the levels of CEC and vWF at T1 were higher than those at T0(P<0.01),while the level of NO was low-er at T1 than that at T0(P<0.01). With contrary to those of group A,circulation conditions of group B were obvi-ously unstable and high doses of vasoactive agents were needed during the therapy period. MAP in group B at each time point was obviously lower than that in group A(P<0.05). There were 7 dead cases(18%)in group B but no death in group A during the whole therapy period. Conclusion Obvious injury of vascular endothelial cells exists in septic shock patients and the injury degree is related to the severity of the disease.