In vivo delivery process and regulating mechanisms of lipid-based nanomedicines / 药学学报

Lipid-based nanocarrier is a classic drug delivery system with great biocompatibility and biodegradability. It can effectively reduce the toxicity of anti-tumor and anti-infective drugs in clinical practice. However, it has not yet met the clinical demand for enhanced therapeutic efficacy, and the clinical application is still very limited. The complex in vivo delivery process of lipid-based nanomedicine and the reciprocal interactions with body lead to unexpected changes in in vivo performance of nanomedicine and seriously hinder clinical translation. Therefore, the in-depth study of the relationships among intrinsic properties of lipid-based nanomedicine, the in vivo delivery process, and the regulatory mechanisms will not only provide guidance for the rational design of nanocarriers, but also promote the clinical translation and precision medicine of new lipid-based nanomedicine. In this review, we summarize the in vivo delivery process, regulating factors and intervention strategies for the in vivo delivery of lipid-based nanomedicine.

Puncture and Needle Picking Action of Venipuncture Manipulator / 医用生物力学

Objective To propose a new multi-joint series venipuncture system, explore the mechanics and kinematics-based related control problems involved in needle insertion and needle picking during the puncture process, and verify feasibility of this system. Methods A puncture manipulator was built, and needle displacement control algorithm was proposed by combing with the puncture mechanics model. The the forward kinematics was calculated by using DH method, so as to obtain the tip coordinates. Then the inverse kinematics was calculated by using the geometric method. The forward and inverse processes were closely connected. The position error of the end coordinates before and after needle picking was compared by using the method of kinematics positive solution-inverse solution-re-positive solution. Finally, experimental verification and simulation were conducted by combining with the physical object. Results Through simulation and experiments, accuracy of the theoretical model was verified. The needle insertion algorithm could be used to achieve success with only one needle insertion, which provided theoretical basis for the control of robot arm. The position error before and after needle picking could be controlled within 1 mm from the end trajectory. The end needle tip of robot arm was almost kept fixed during the needle picking process. Therefore, this needle picking scheme was feasible and could basically verify that the needle picking action of robot arm met the accuracy and safety requirements. Conclusions The venipuncture manipulator truly simulates the needle insertion and needle picking action during the puncture process, and can safely and accurately realize the needle insertion and needle picking action with needle tip as the fixed point, indicating that it has certain clinical value.

Clinical features and prognosis analysis of 31 cases of extramedullary plasmacytoma of the head and neck / 中华放射肿瘤学杂志

Objective:To investigate the clinical features, treatment options and prognostic factors of extramedullary plasmacytoma of the head and neck.Methods:Clinical data of 31 cases of extramedullary plasmacytoma of the head and neck treated in Eye Ear Nose and Throat Hospital of Fudan University from January 2005 to January 2020 were retrospectively analyzed. According to the involvement sites, the lesions were divided into the Waldeyer's ring involvement and non-involvement groups. The differences between two groups were compared by one-way ANOVA. The overall survival (OS) was analyzed by Kaplan-Meier method. The OS rate and local recurrence free survival (LRFS) rate between two groups were compared by log-rank test.Results:All 31 patients received radiotherapy. The median follow-up time was 98 months (7-192 months). Among them, 16 patients received radiotherapy and surgery, 10 patients received radiochemotherapy, and 2 patients received surgery and radiochemotherapy. Waldeyer's ring involvement was found in 15 patients, and Waldeyer's ring was not involved in 16 patients. The 10-year OS rate was 84.8%. Two cases showed local recurrence and 2 cases progressed to multiple myeloma. The 10-year OS rate in patients ≤55 years old was 100% vs. 67% in those >55 years old ( P=0.039). The 10-year OS rates in patients with and without Waldeyer's ring involvement were 93.3% vs. 75.2% ( P=0.031). The 10-year LRFS rate in patients with Waldeyer's ring involvement was 100% vs. 66.7% in those without Waldeyer's ring involvement ( P=0.022). The 10-year OS rate was 95% and 35.7% for patients with longest diameter of tumor ≤5 cm and >5 cm before radiotherapy, respectively ( P=0.02). Conclusions:Extramedullary plasmacytoma of the head and neck patients with longest diameter of tumor ≤5 cm obtain higher 10-year OS rate. Those with Waldeyer's ring involvement have better 10-year OS and LRFS rates.

Research progress of CAR-T in the treatment of esophageal squamous cell carcinoma / 国际肿瘤学杂志

Chimeric antigen receptor T cell (CAR-T) therapy, an emerging immunotherapy, has achieved remarkable results in the treatment of hematologic tumors. However, it's limited in the treatment of solid tumors such as esophageal squamous cell carcinoma due to various factors. Clarifying the reasons for the limitation of CAR-T therapy and exploring the corresponding solutions can provide new ideas and insights for the treatment of esophageal squamous cell carcinoma.

Cuproptosis-Related 4-Gene Risk Model for Predicting Immunotherapy Drug Response and Prognosis of Kidney Renal Clear Cell Carcinoma / 中国医学科学杂志(英文版)

Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.

Clinical and bronchoscopy features of tracheobronchial tuberculosis in children / 中国当代儿科杂志

OBJECTIVES@#To study the clinical and bronchoscopic characteristics of tracheobronchial tuberculosis (TBTB) in children and to identify factors influencing residual airway obstruction or stenosis.@*METHODS@#The clinical data of children with TBTB were retrospectively collected. The children were divided into two groups based on the last bronchoscopic result within one year of follow-up: a group with residual airway obstruction or stenosis (n=34) and a group without residual airway obstruction or stenosis (n=58). A multivariate logistic regression analysis was used to identify the factors influencing residual airway obstruction or stenosis in children with TBTB. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of the factors influencing residual airway obstruction or stenosis in children with TBTB.@*RESULTS@#A total of 92 children with TBTB were included, and the main symptoms were cough (90%) and fever (68%). In children under 1 year old, the incidence rates of dyspnea and wheezing were significantly higher than in other age groups (P<0.008). Chest CT findings included mediastinal or hilar lymph node enlargement (90%) and tracheobronchial stenosis or obstruction (61%). The lymphatic fistula type was the main type of TBTB observed bronchoscopically (77%). All children received interventional treatment, and the effective rate was 84%. During one year of follow-up, 34 children had residual airway obstruction or stenosis. The TBTB diagnostic time and the initiation of interventional treatment were significantly delayed in the group with residual airway obstruction or stenosis compared with the group without residual airway obstruction or stenosis (P<0.05). The multivariate logistic regression analysis showed that the TBTB diagnostic time was closely related to residual airway obstruction or stenosis in children (P<0.05). ROC curve analysis showed that at the cut-off value of 92 days of TBTB diagnostic time, the area under the curve for predicting residual airway obstruction or stenosis in children with TBTB was 0.707, with a sensitivity of 58.8% and a specificity of 75.9%.@*CONCLUSIONS@#The clinical manifestations of TBTB are nonspecific, and symptoms are more severe in children under 1 year old. TBTB should be suspected in children with tuberculosis and chest imaging indicating airway involvement. Delayed diagnosis of TBTB is associated with the development of residual airway obstruction or stenosis.

Resting-state electroencephalogram relevance state recognition of Parkinson's disease based on dynamic weighted symbolic mutual information and k-means clustering / 生物医学工程学杂志

At present, the incidence of Parkinson's disease (PD) is gradually increasing. This seriously affects the quality of life of patients, and the burden of diagnosis and treatment is increasing. However, the disease is difficult to intervene in early stage as early monitoring means are limited. Aiming to find an effective biomarker of PD, this work extracted correlation between each pair of electroencephalogram (EEG) channels for each frequency band using weighted symbolic mutual information and k-means clustering. The results showed that State1 of Beta frequency band ( P = 0.034) and State5 of Gamma frequency band ( P = 0.010) could be used to differentiate health controls and off-medication Parkinson's disease patients. These findings indicated that there were significant differences in the resting channel-wise correlation states between PD patients and healthy subjects. However, no significant differences were found between PD-on and PD-off patients, and between PD-on patients and healthy controls. This may provide a clinical diagnosis reference for Parkinson's disease.

Construction of an online nomogram of risk factors for postoperative delirium in elderly patients with hip fracture / 中华创伤骨科杂志

Objective:To investigate the risk factors for postoperative delirium in the elderly patients with hip fracture and to construct an online nomogram of the risk factors.Methods:Retrospectively analyzed were the data of 483 elderly patients with hip fracture who had been treated with artificial joint replacement from May 2020 to August 2021 at Department of Orthopaedics (Department of Joint Surgery), Jinling Hospital Affiliated to Medical College of Nanjing University. There were 166 males and 317 females, aged from 61 to 99 years (average, 82.1 years). Fracture types: 333 femoral neck fractures and 150 intertrochanteric fractures. The patients were divided into a delirium group ( n=149) and a delirium-free group ( n=334) according to whether postoperative delirium occurred after surgery. The 2 groups were compared in terms of general data like age, gender, body mass index, and concomitant diseases, as well as in terms of indexes like pre-operative albumin, preoperative hemoglobin, and postoperative C-reactive protein (CRP). Factors with P < 0.05 were included in the multi-factor logistic regression analysis to screen out the risk factors for postoperative delirium. The "rms" package of R software was used to draw the nomogram; the Bootstrap method was used to repeat the sampling 1,000 times for evaluation, calculation of the consistency index ( CI), and drawing of the ROC curve and correction curve; the decision curve was plotted using the "rmda" package. Results:There were significant differences between the delirium group and the delirium-free group in age, preoperative anxiety, Alzheimer＇s disease, history of cerebrovascular disease, preoperative albumin, intraoperative hypotension and postoperative CRP ( P < 0.05). The multifactorial logistic regression analysis showed that high age, preoperative anxiety, Alzheimer＇s disease, preoperative albumin < 35 g/L, and postoperative CRP ≥90 mg/L were the risk factors for postoperative delirium in the elderly patients with hip fracture after artificial joint replacement ( P < 0.05). The area under the ROC curve of the nomogram constructed by incorporating the risk factors for postoperative delirium was 0.894 (95% CI: 0.865 to 0.923) with a CI of 0.889; the calibration curve showed that the calibration curve of this nomogram model tended to be close to the ideal curve. The decision curve analysis showed that the threshold value was 0.01 to 1.00, showing the net benefit rate of this nomogram model > 0 when used to predict the postoperative delirium in the elderly patients with hip fracture. Conclusions:High age, preoperative anxiety, Alzheimer's disease, preoperative albumin < 35 g/L, and postoperative CRP ≥90 mg/L may be the risk factors for postoperative delirium in the elderly patients with hip fracture after artificial joint replacement. The online nomogram based on these factors demonstrates a good value in prediction of postoperative delirium.

Research progress of microRNA in diagnosis and treatment of prostate cancer / 中国临床药理学与治疗学

Prostate cancer (PCa) is an epithelial malignancy that occurs in the prostate tissue and is the second most common cancer in men after lung cancer, affecting millions of men worldwide. MicroRNA (miRNA) is a non-coding small RNA of length 20-22nt that regulates gene expression post-transcriptionally. miRNAs are involved in the regulation of almost all important biological life processes such as cell cycle progression, cell proliferation, cell apoptosis, and cell migration. Recently, more and more studies have shown that miRNAs are involved in the occurrence of various human tumors including PCa. This review summarizes the current research progress of PCA-related miRNAs, and analyzes the role of malregulated miRNAs in the pathogenesis, diagnosis and treatment of PCa. In addition, the role of miRNA in the diagnosis and treatment of castration-resistant prostate cancer (CRPC) is emphasized.

Gonococcal infections of the penile skin and accessory glands in men: high-frequency ultrasound features and their clinical significance / 中华皮肤科杂志

Objective:To investigate ultrasonographic manifestations of gonococcal infections of the penile skin and accessory glands in men, and to assess their clinical significance.Methods:From January 2014 to January 2021, male patients with gonococcal infections of the penile skin and accessory glands were collected from Department of Dermatology, Changshu No.1 People′s Hospital. The diagnosis had been confirmed by laboratory examinations, and these patients had not received relevant treatment. The real-time ultrasound imaging system SIEMENS ACUSON X300 was used to examine the penile skin and accessory gland lesions infected with Neisseria gonorrhoeae, with the probe frequency ranging from 7.5 to 15 MHz. Patients with tubular anechoic fluid-filled areas on the high-frequency ultrasound images received a single dose of intramuscular ceftriaxone (1 g) ; those with oval-shaped anechoic fluid-filled areas on the high-frequency ultrasound images received incision and drainage followed by intramuscular injection of ceftriaxone at a dose of 1 g once a day for 5 consecutive days; those with hypoechoic or mixed echoic areas on the high-frequency ultrasound images received intramuscular injection of ceftriaxone at a dose of 1 g once a day for 5 consecutive days, and if the nodules did not regress after 1-month treatment, local resection would be performed. One month after the treatment, the patients were followed up, and the efficacy was evaluated. Results:A total of 32 male patients with gonococcal infections of the penile skin and accessory glands were collected. They were aged 28.54 ± 3.27 years, all had a history of non-marital sexual contact, and the duration from non-marital sexual contact to the onset of symptoms was 4.45 ± 1.03 days. The disease course was 8.64 ± 1.87 days. Lesions were all solitary, and located at the external urethral meatus in 16 cases (50.00%) , at the glans penis in 7 cases (21.88%) , beside the foreskin frenulum in 5 cases (15.62%) , and at the penile raphe in 4 cases (12.50%) . Sixteen patients (50.00%) presented with sinus-like lesions, 9 (28.13%) with abscesses, 7 (21.87%) with nodules, and all had tenderness on palpation. High-frequency ultrasound examination showed tubular anechoic fluid-filled areas in 16 cases (50.00%) , oval-shaped anechoic fluid-filled areas in 7 cases (21.88%) , hypoechoic areas in 5 cases (15.62%) , and mixed echoic areas in 4 cases (12.50%) . Gonococcal infections involved the cavernous body of the urethra in 16 cases (50.00%) , cavernous body of the penis in 5 cases (15.62%) , and subcutaneous tissue of the penis in 11 cases (34.38%) . After the treatment, all the patients were cured.Conclusion:High-frequency ultrasound can be used in the assessment of skin lesions and selection of treatment regimens for male patients with gonococcal infections of the penile skin and accessory glands.

Debridement, antibiotics irrigation and implant retention for acute periprosthetic joint infection after primary total joint arthroplasty / 中华创伤骨科杂志

Objective:To analyze the clinical efficacy of debridement, antibiotics irrigation and implant retention (DAIR) in the treatment of acute periprosthetic infection (PJI) and to explore the risk factors leading to the failure of DAIR.Methods:From January 2010 to January 2021, 122 patients underwent DAIR for acute PJI at Department of Orthopedics, General Hospital of Eastern Theater of PLA. They were 55 males and 67 females, aged from 50 to 86 years (mean, 68.0 years). Their C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), body temperature, white blood cell count and visual analogue scale (VAS) were compared at admission and discharge to analyze the clinical efficacy of DAIR. The 122 patients were assigned into a cured group (81 cases) and an uncured group (41 cases). Risk factors were screened by univariate analysis out of their gender, age, body mass index, site of infection, type of infection (early postoperative infection or acute hematogenous infection), type of surgery (primary or revision), comorbidities, CRP, ESR, albumin and hemoglobin at admission, duration of symptoms, Staphylococcus aureus infection, multiple bacterial mixed infection, and preoperative sinus tract. For the factors of P<0.05, multivariate binary logistic regression analysis was used to determine the risk factors for failure of DAIR. Survival curves were plotted for the patients using DAIR failure as the endpoint event. Results:The CRP, ESR, VAS score, body temperature and white blood cell count at discharge in the 122 patients were significantly lower than the corresponding values at admission ( P<0.05). The success rate of DAIR was 66.39%(81/122). The multivariate binary logistic regression analysis suggested that duration of symptoms over 3 weeks( OR=1.230, 95% CI: 1.092~1.576, P=0.020), Staphylococcus aureus infection( OR=4.607, 95% CI: 2.057~10.318, P<0.001), preoperative sinus tract( OR=6.115, 95% CI: 2.630~14.220, P<0.001) and multiple bacterial mixed infection( OR=2.600, 95% CI: 1.131~5.977, P=0.020) were risk factors for DAIR failure; Kaplan-Meier survival curve also confirmed that the patients with Staphylococcus infection, multiple bacterial mixed infection, duration of symptoms over 3 weeks, or preoperative sinus tract had a significantly lower rate of survival than their controls ( P<0.05). Conclusions:For acute PJI, DAIR can be used to retain the prosthesis and control infection. However, DAIR is not recommended for the patients with Staphylococcus aureus infection, multiple bacterial mixed infection, symptoms lasting more than 3 weeks, or preoperative sinus formation.

Discussion on the application of simulation medicine teaching in clinical practice teaching of respiratory department / 中华医学教育探索杂志

Objective:To observe the application effect of simulation medicine teaching in clinical practice teaching of respiratory department.Methods:A total of 96 five-year undergraduate students of clinical medicine specialty from Batch 2018 were randomized into in two groups in average. The traditional teaching group conducted bedside teaching according to traditional teaching outline, and the simulation medicine group used simulated medical teaching method. The performances of theoretical knowledge and skill operations and the teaching satisfaction with the department were evaluated between the two groups. SPSS 22.0 was used for t test and chi-square test. Results:There was no significant difference in theoretical knowledge between the two groups, but the results of skill operation test and satisfaction with the department of the simulation medicine group were significantly better than those of the traditional teaching group, and the difference was statistically significant [(80.92±5.99) vs. (87.71±4.95), P<0.050; χ2=26.14, P<0.05]. Conclusion:Simulation medicine teaching is better than traditional teaching in clinical practice teaching of respiratory department, which can improve students' clinical skills and operation level, cultivate good clinical thinking for students, and improve their learning interests.

Prognosis factors for death within 90 days of discharge in patients with acute kidney injury requiring continuous renal replacement therapy after surgery for Stanford type A acute aortic dissection / 中华外科杂志

Objective: To investigate the prognosis factors for death within 90 days after discharge in patients with acute kidney injury(AKI) treated requiring continuous renal replacement therapy(CRRT) undergoing surgery for acute Standford type A aortic dissection. Methods: The clinic data of 126 patients undergoing CRRT for postoperative AKI after acute type A aortic dissection surgery in the Center for Cardiac Intensive Care, Beijing Anzhen Hospital from July 2016 to February 2019 were analyzed retrospectively. There were 83 males and 43 females, aging (52.9±11.2) years(range: 25 to 70 years). The patients' demographic characteristics, disease-related information, perioperative data, laboratory indexes during CRRT, complications, and survival information within 90 days after discharge were recorded. Independent prognosis factors for death within 90 days of discharge were determined by Kaplan-Meier survival analysis, univariate and multifactorial Cox regression analysis. Results: Totally 57 of 126 patients(45.2%) died over the first 90 days after discharge. Kaplan-Meier survival analysis and univariate Cox regression analysis showed that there were significant differences between the non-survival and survival group including ≥65 years old, high lactate values 12 hours after CRRT, pulmonary infection, liver dysfunction, presence of permanent neurological complications, and postoperative ejection fraction(EF)<45%. Multifactorial Cox regression analysis revealed that ≥65 years old(HR=2.14, 95%CI: 1.09 to 4.21, P=0.03), high lactate values 12 hours after CRRT(HR=1.13, 95%CI: 1.06 to 1.20, P=0.01) and postoperative EF<45%(HR=2.21, 95%CI: 1.09 to 4.51, P=0.03) were independent prognosis factors for patients' death within 90 days after hospital discharge. Conclusions: ≥65 years old, high lactate values 12 hours after CRRT and postoperative EF<45% are independent prognosis factors for death within 90 days after discharge in patients undergoing CRRT for AKI after acute type A aortic dissection surgery. Proper identification and management of prognosis factors could be beneficial to improve patients' outcomes.

Experimental Study on Puncture Mechanical Properties of Biomimetic Materials / 医用生物力学

Objective To obtain a more suitable puncture method for venipuncture robot through experiments.Methods By using different puncture speeds and angles for biomimetic materials, the force-time curves by various puncture methods were obtained. Results During puncture process, with the increase of the puncture angle, a smaller puncture force was required. The faster puncture speed would lead to a larger puncture force. Conclusions The 40°-45° puncture angleand the 120-300 mm/min puncture speed should be used for designing the puncture method of venipuncture robot. The results provide references for selecting the puncture angle and speed of the venipuncture robot.

Changes and formation mechanism of plasma endothelial microparticles in patients with acute pancreatitis / 临床肝胆病杂志

Objective To investigate the changes and formation mechanism of plasma endothelial microparticles (EMPs) in patients with acute pancreatitis (AP). Methods Blood samples were collected from 60 patients with AP who were treated in The First Affiliated Hospital of Anhui Medical University from August 2020 to June 2021, and these patients were divided into mild acute pancreatitis (MAP) group with 23 patients, moderate-severe acute pancreatitis (MSAP) group with 23 patients, and severe acute pancreatitis (SAP) group with 14 patients; 20 individuals who underwent physical examination were enrolled as control group.Differential centrifugation was used to obtain platelet-poor plasma, flow cytometry was used to measure the level of CD31 + CD41 - EMPs, and ELISA was used to measure the levels of endothelin-1(ET-1), von Willebrand factor (vWF), nitric oxide (NO), and vascular cell adhesion molecule-1(VCAM-1).HUVECs were stimulated by the plasma of AP patients, and then flow cytometry and qRT-PCR were used to measure the changes in EMPs, reactive oxygen species (ROS), and mitochondrial membrane potential and the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1(ICAM-1), VCAM-1, NADPH oxidase, and P-selectin.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups and within each group.The chi-square test was used for comparison of categorical data between groups, and the Pearson correlation test was used for correlation analysis. Results Compared with the control group, the MAP, MSAP, and SAP groups had a significant increase in the level of EMPs (all P < 0.05).Compared with the MAP and MSAP groups, the SAP group had a significant increase in the level of EMPs (both P < 0.05).In the patients with AP, the level of EMPs was negatively correlated with Acute Physiology and Chronic Health Evaluation Ⅱ score, Bedside Index for Severity in Acute Pancreatitis, Ranson score, CT score, and C-reactive protein ( r =0.686 2, 0.777 3, 0.713 8, 0.771 8, and 0.473 9, all P < 0.01).Compared with the control group, the MAP, MSAP, and SAP groups had significant increases in the levels of ET-1, vWF, and VCAM-1 and a significant reduction in the level of NO (all P < 0.05).Compared with the control group, the MSAP and SAP groups had the plasma that promoted the release of a large amount of EMPs (both P < 0.05).Compared with the control group, all the other groups, except the MAP group in terms of VCAM-1 and eNOS, had significant increases in the mRNA expression levels of eNOS, iNOS, ICAM-1, P-selectin, VCAM-1, and NADPH oxidase (all P < 0.05).Compared with the HC group, the MAP, MSAP, and SAP groups and the LPS group had a significant increase in the level of ROS and a significant reduction in mitochondrial membrane potential in HUVECs (all P < 0.05). Conclusion There is a significant increase in the plasma level of EMPs in AP patients, which is correlated with the severity of pancreatitis.Meanwhile, the plasma of AP patients can promote the formation of EMPs in HUVECs in vitro, which may be associated with cell oxidative injury.

Clinical study on the expression of Piezo1 in small intestinal mucosa of 57 patients with Crohn′s disease / 中华消化杂志

Objective:To investigate the expression of Piezo1 in small intestinal mucosal epithelial cells of patients with Crohn′s disease (CD) and its clinical correlation with CD.Methods:From January 1st 2010 to November 30th 2020, the clinical data including age, gender, disease location and biological behavior, etc of 57 patients with CD (CD group) who underwent surgery at The First Affiliated Hospital of Anhui Medical University were retrospectively. And at same time the normal samll intestinal epithelial tissues of 10 healthy individuals who underwent colonoscopy were collected as the healthy control group. The expression of Piezo1 in small intestinal epithelial cells of CD patients with different disease sites, biological behavior and disease activity were detected by immunofluorescence staining and hematoxylin-eosin staining. The histological score system and intestinal fibrosis score were used to analyze the inflammation and fibrosis of the intestinal tissues of patients with CD. Semi-quantitative analysis of Piezo1 in small intestinal epithelial cells was analyzed by ImageJ software. And the correlation between Piezo1 expression and clinical characteristics and pathological features of small intestine was also analyzed. Independent sample t test and analysis of variance were used for statistical analysis. Results:In CD group, there were 37 males (64.9%) and 20 females (35.1%). The age was (39.1±14.2) years old, ranged from 18 to 71 years old, and the average duration of the disease was (26.5±24.1) months. There were 29 cases (50.9%)of ileal type, 26 cases (45.6%) of ileocolonin type and 2 cases (3.5%) of colonic type. There were 12 cases (21.1%) of non-penetrating non-stenotic type, 31 cases (54.4%) of stenotic type and 14 cases (24.6%) of penetrating type. There were 47 cases (82.5%) with moderate activity and 10 cases (17.5%) with severe activity. There were 17 cases (29.8%) of moderate intestinal inflammation, 40 cases (70.2%) of severe intestinal inflammation. The score of intestinal fibrosis in six cases (10.5%) was 1, 28 cases (49.1%) was 2, 18 cases (31.6%) was 3, five cases was 4. The relative expression level of Piezo1 in intestinal mucosal epithelial cells of CD group was higher than that of healthy control group (12.9±4.6 vs. 8.5±1.1), the relative expression of Piezo1 in intestinal mucosal epithelia cells of stenotic type and penetrating type CD patients were both higher than that of non-penetrating and non-stenotic CD patients (12.6±3.8 and 9.8±2.4 vs. 6.0±1.3), and the differences were all statistically significant ( t=3.00, -3.66 and -3.32, all P<0.01). The relative expression of Piezo1 in small intestinal epithelial cells of CD patients with severe intestinal inflammation was higher than that of CD patients with moderate intestinal inflammation (13.1±4.0 vs. 9.7±3.1), and the difference was statistically significant ( t=-2.65, P<0.05). The relative expression levels of Piezo1 in small intestinal epithelial cells of patients with intestinal fibrosis score of 4, 3, 2 and 1 were 17.6±5.2, 12.6±1.7, 9.1±2.1 and 5.8±1.1, respectively; the relative expression levels of Piezo1 in intestinal epithelial cells of patients scored 4 were higher than that of patients scored 3, 2 and 1, and that of patients scored 3 was higher than patients scored 2 and 1, and that of patients scored 2 was higher than that of patients scored 1, and the differences were all statistically significant ( t=-2.98, -5.10, -3.84, 4.60, 6.55 and 2.56, all P<0.05). The relative expression of Piezo1 in intestinal mucosal epithelial cells was related to the severity of intestinal inflammation and fibrosis. The more severe the intestinal inflammation and fibrosis, the higher the relative expression of Piezo1 in intestinal mucosal epithelial cells. Conclusions:The relative expression of Piezo1 in small intestinal epithelial cells is related to the biological behavior and the severity of intestinal inflammation and fibrosis of CD. It is speculated that the expression of Piezo1 in small intestinal epithelial cells may be clinically related to the process of intestinal wall fibrosis in CD to some extent, however whether it plays an important role in the process of intestinal wall fibrosis in CD and its specific mechanism need to be further studied.

Influence of indometacin on the level of platelet microparticles in patients with post-endoscopic retrograde cholangiopancreatography pancreatitis / 中华消化内镜杂志

To observe the effect of indomethacin suppository 100 mg before endoscopic retrograde cholangiopancreatography (ERCP) on the level of platelet microparticles (PMPs) in patients with post-ERCP pancreatitis (PEP). A total of 191 patients receiving ERCP were collected from June 2019 to October 2020 in the First Affiliated Hospital of Anhui Medical University and were randomly divided into the indometacin group ( n=96) and the control group ( n=95) by random number table method. The indometacin group received 100 mg indometacin suppositories before ERCP and the control group received placebo of equal quality. Levels of PMPs before operation, 3 hours and 24 hours after operation were measured by flow cytometry. The levels of IL-1, IL-6 and TNF-α in the plasma before ERCP, 3 hours and 24 hours after ERCP were also detected. The incidence of PEP in the indometacin group was 5.21% (5/96), which was significantly lower than that in the control group [13.68% (13/95), P=0.044]. The preoperative PMPs level in the indometacin group (1 910.01/μL) was slightly lower than that in the control group (2 351.87/μL) with no significant difference ( P>0.05). The PMPs levels in the indometacin group 3 hours and 24 hours after ERCP (1 671.47 /μL, 862.74/μL) were significantly lower than those of the control group (2 443.75/μL, 2 536.76/μL, both P<0.05). Inflammatory cytokines including IL-1, IL-6 and TNF-α showed the same tendency. Indometacin can reduce the incidence of PEP, for the reason that indometacin may decrease the levels of PMPs.

Effect of laparoscopic cholecystectomy combined with laparoscopic common bile duct exploration on pain stress and inflammatory factors in elderly patients with cholecystolithiasis and choledocholithiasis / 国际外科学杂志

Objective:To investigate the effect of laparoscopic cholecystectomy (LC) combined with common bile duct exploration (LCBDE) on pain stress and inflammatory factors in elderly patients with gallbladder stones and common bile duct stones.Methods:Eighty elderly patients with cholecystolithiasis and choledocholithiasis in Huadong Hospital Affiliated to Fudan University from January 2020 to January 2021 were selected. According to the surgical method, they were divided into observation group of 40 cases and control group of 40 cases. Patients in the observation group were treated with LC combined with LCBDE, and patients in the control group were treated with traditional open surgery. The perioperative indicators and complications, changes in pain stress and inflammatory factors before and 3 days after operation, and the quality of life before operation, 1 month after operation and 6 months after operation were compared between the two groups. Normally distributed measurement data were represented by mean±standard deviation ( Mean± SD), and t test was used to compare between groups. The chi-square test was used to compare the count data between groups. Results:The operation time, time to get out of bed, postoperative exhaust time, intraoperative blood loss, and postoperative complications in the observation group were (98.39±7.23) min, (1.56±0.37) d, (1.29±0.28) d, (38.94±5.64) mL, 5%, the control group were (107.53±9.98) min, (2.53±0.52) d, (2.16±0.34) d, (65.87±7.96) mL, 25%, the observation group were excellent in all indicators compared with the control group, the differences between the two groups were statistically significant ( P<0.05). After operation 3rd day, the serum 5-hydroxytryptamine, substance P and norepinephrine in the two groups were higher than before operation ( P<0.05); after operation 3rd day, serum 5-hydroxytryptamine, substance P and norepinephrine the observation group were (0.70±0.12) pg/mL, (175.42±17.87) ng/mL and (378.52±26.57) ng/mL, the control group were (1.02±0.18) pg/mL, (248.98±18.98) ng/mL, and (460.92±35.42) ng/mL. The indexes of the observation group were smaller than those of the control group, the differences between the two groups were statistically significant ( P<0.05). After operation 3rd day, the serum tumor necrosis factor-α, C-reactive protein and interleukin-6 in the two groups were higher than before operation ( P<0.05); after operation 3rd day, Serum tumor necrosis factor-α, C-reactive protein and interleukin-6 in the observation group were (108.76±10.86) pg/mL, (14.23±3.18) mg/L and (17.84±3.98) pg/mL, respectively, on the 3rd day after operation. The control group were (156.95±16.67) pg/mL, (26.52±4.59) mg/L and (28.53±5.67) pg/mL, the observation group indexes were all smaller than control group, the differences between the two groups were statistically significant ( P<0.05). The quality of life scores of the two groups at 1 month and 6 months after the operation were higher than before operation ( P<0.05); The quality of life scores of patients in the observation group at 1 month and 6 months after surgery were higher than control group ( P<0.05). Conclusion:LC combined with LCBDE treatment has little effect on pain stress and inflammatory factors in elderly patients with cholecystolithiasis and choledocholithiasis, and has fewer postoperative complications, and can improve the quality of life of patients.

Value of carnitine palmitoyltransferase 1α expression for the assessment of the degree of renal fibrosis and the progression of chronic kidney disease / 中华肾脏病杂志

Objective:To study the relationship between the expression of carnitine palmitoyltransferase 1α (CPT1α) and progression of renal interstitial fibrosis and chronic kidney disease (CKD), and to evaluate the value of CPT1α as a biomarker in pathological diagnosis of renal interstitial fibrosis and CKD.Methods:As a retrospective cohort study, information of CKD patients dignosed with tubulointerstitial fibrosis by renal biopsy and receiving follow-up from March 1, 2010 to July 30, 2017 in the Second Affiliated Hospital of Nanjing Medical University were collected. Renal tissues were stained by immunohistochemistry to detect the expression of CPT1α protein and then divided into three groups according to the quartile of proportion of CPT1α positive staining cells, including group Q1(>67.89%), group Q2(49.84%-67.89%) and group Q3(<49.84%). The degree of renal interstitial fibrosis was measured by Masson staining and lipid deposition was represented by Bodipy staining. Messenger RNA of CPT1α and collagen as well as other extracellular matrix genes were detected by real time-PCR. Relationships between proportion of CPT1α positive staining cells and renal interstitial fibrosis and renal function were analyzed by linear regression analysis. The relationship between CPT1α positive cell number ratio and renal function progression was measured by Pearson correlation analysis and generalized linear model. The effect of lipid-lowering medicine on renal function of CKD patients was analyzed by paired comparative analysis.Results:Ninety patients with CKD were included in this study. Renal interstitial fibrosis and lipid droplets deposition area increased in Q2/Q3 group compared with Q1 group by Masson and Bodipy staining (all P<0.05). Messenger RNA level of extracellular matrix-related proteins increased in Q2/Q3 group by real time-PCR than those of Q1 group (all P<0.05). Linear regression analysis showed that fibrosis area was negatively correlated with the proportion of CPT1α positive staining cells ( r=-0.309, P<0.01). The baseline expression of CPT1α in renal issues was negatively related with serum creatinine (Scr) ( r=-2.801, P<0.001), positively related with estimated glomerular filtration rate (eGFR) ( r=1.240, P<0.001). After a medium follow-up of 3.47 years, CPT1α positive cell number ratio was positively correlated with eGFR change rate by Pearson analysis ( r=0.220, P=0.038). Paired stratified analysis showed that taking lipid-lowering medicines attenuated the decrease of eGFR in Q2 group and Q3 group but not in Q1 group (both P<0.05). Conclusions:The decline of CPT1α in renal tissues of CKD patients is associated with the increase of Scr, the decrease of eGFR and renal interstitial fibrosis. CPT1α is a promising molecular marker to evaluate the degree of renal fibrosis and the progression of CKD.

Clinical effects of ultrasound-guided intra-articular and coracohumeral ligament injections on frozen shoulder in the elderly / 中华老年医学杂志

Objective:To compare the clinical effects of ultrasound-guided intra-articular and coracohumeral ligament glucocorticoid injections versus ultrasound-guided intra-articular glucocorticoid injections alone on frozen shoulder in the elderly.Methods:A total of 44 patients with frozen shoulder admitted to the rehabilitation department of the Affiliated Hospital of Sichuan Nursing Vocational College from September 2019 to June 2020 were enrolled.They were randomly divided into the experimental group and the control group, with 22 patients in each group.The experimental group received two consecutive ultrasound-guided intra-articular injections and two coracohumeral ligament injections, while the control group received two consecutive ultrasound-guided intra-articular injections.The shoulder's passive range-of-motion(PROM), the 11-point numeric rating scale(NRS)as well as the Shoulder Pain and Disability Index(SPADI)were conducted before treatment, 1 week after the first treatment(1 week), 1 week after the second treatment(2 weeks)and 10 weeks after the second treatment(12 weeks).Results:There was no significant difference in baseline characteristics between the two groups(all P>0.05). Flexion, abduction, extension and external rotation increased whereas NRS and SPADI decreased after treatment, compared with pre-treatment in the experimental group( F=11.341, 20.965, 20.403, 32.470, 82.970 and 102.154, all P<0.05)and in the control group( F=7.012, 8.937, 23.265, 31.966, 52.500 and 41.356, all P<0.05). Compared with the control group, extension( t=0.365, 0.143 and 0.236, all P<0.05)and external rotation( t=0.205, 0.620 and 2.751, all P<0.05)increased at 1, 2 and 12 weeks after treatment.SPADI scores were lower in the experimental group than in the control group at 12 weeks after treatment( t=2.063, P=0.045). There was no significant difference in NRS, flexion or abduction between the two groups at any time point after treatment(all P>0.05). No serious adverse reactions occurred during treatment in either group. Conclusions:Both ultrasound-guided intra-articular injections plus coracohumeral ligament injections and ultrasound-guided intra-articular injections can effectively alleviate pain and improve function in elderly patients with frozen shoulder, but the former has better effects on extension.For patients with clear restricted extension and external rotation, ultrasound-guided intra-articular injections combined with coracohumeral ligament injections may achieve better clinical effects.