Effect of nerve growth factor on elderly degenerative knee osteoarthritis pain / 中国骨伤

OBJECTIVE@#To explore effect of nerve growth factor (NGF) antibody on knee osteoarthritis (KOA) pain model was evaluated by in vitro model.@*METHODS@#Thirty male SPF rats aged 28-week-old were divided into blank group (10 rats with anesthesia only). The other 20 rats were with monoiodoacetate (MIA) on the right knee joint to establish pain model of OA, and were randomly divided into control group (injected intraperitoneal injection of normal saline) and treatment group (injected anti-NGF) intraperitoneal after successful modeling, and 10 rats in each group. All rats were received retrograde injection of fluorogold (FG) into the right knee joint. Gait was assessed using catwalk gait analysis system before treatment, 1 and 2 weeks after treatment. Three weeks after treatment, right dorsal root ganglia (DRG) were excised on L4-L6 level, immunostained for calcitonin gene-related peptide (CGRP), and the number of DRGS was counted.@*RESULTS@#In terms of gait analysis using cat track system, duty cycle, swing speed and print area ratio in control and treatment group were significantly reduced compared with blank group (P<0.05). Compared with control group, duty cycle and swing speed of treatment group were significantly improved (P<0.05), and there was no significant difference in print area ratio between treatment group and blank group (P>0.05). The number of FG-labeled DRG neurons in control group was significantly higher than that in treatment group and blank group (P<0.05). The expression of CGRP in control group was up-regulated, and differences were statistically significant compared with treatment group (P<0.05).@*CONCLUSION@#Intraperitoneal injection of anti-NGF antibody inhibited gait injury and upregulation of CGRP in DRG neurons. The results suggest that anti-nerve growth factor therapy may be of value in treating knee pain. NGF may be an important target for the treatment of knee OA pain.

Dietary patterns of preschool children based on factor analysis combined with cluster / 公共卫生与预防医学

Objective To investigate the dietary intake of preschool children in Northwest China, and provide scientific basis for studying the dietary patterns and characteristics of preschool children and formulating targeted dietary interventions. Methods Using the self-designed “Semi-quantitative Food Frequency Questionnaire for Preschool Children in Northwest China“, a convenient sampling method was used to investigate the dietary intake of children aged 3 to 7 years in Northwest China. The factor analysis combined with the cluster method was used to extract the dietary pattern. Results Through factor analysis of the average daily food intake of preschool children, the results show that the KMO test value was 0.82, Bartlett’s test value was 4 528.97, and the associated probability was <0.001, so factor analysis can be performed. In order to obtain more typical factor components so that the results were easier to explain, under the guidance of nutrition experts, the first 4 common factors were finally retained for analysis, and the cumulative variance contribution rate was 62.17%. On this basis, the number of clusters was 4, and the K-means cluster analysis method was used to cluster the factor scores of various foods for preschool children. According to the proportions of various foods and the characteristics of the foods, The dietary patterns of preschool children can be divided into staple food-based dietary patterns, high-protein dietary patterns, healthy dietary patterns, and high-sugar dietary patterns. Conclusion Using factor analysis method, the scores of each food factor of preschool children were continuous variables, and the results were highly repeatable, and subsequent analysis can be carried out. The factor analysis combined with cluster analysis method extracting the dietary pattern of preschool children that had certain degree of science. According to the characteristics of the four dietary patterns extracted in this study, children's dietary interventions can be targeted to promote children's physical and mental health.

Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis / 中西医结合学报

BACKGROUND@#The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear.@*OBJECTIVE@#This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects.@*SEARCH STRATEGY@#PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022.@*INCLUSION CRITERIA@#Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included.@*DATA EXTRACTION AND ANALYSIS@#Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response.@*RESULTS@#Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response.@*CONCLUSION@#Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.

The protective effect of catechin on acute high-altitude hypoxic injury / 中国药理学通报

Aim To study the protective effect of catechin on acute altitude injury in rats. Methods Rats were randomly divided into six groups: control group, altitude hypoxia model group, rhodiola capsule group, low -, middle-and high dose of catechin groups. After three days of preventive administration, animals were rushed to 4 010 m altitude. After five days of continuous administration, abdominal aortic blood of rats was collected for blood gas detection. Cardiac, brain and lung tissues were collected for HE staining to observe the pathological changes. MDA content, GSH content, NO content, SOD activity of myocardial, brain and lung tissues were detected, so were IL-6 and TNF-α content in serum. Results Compared with the control group, blood oxygen saturation of rats of altitud hypoxia model group was significantly reduced, while myocardial, brain and lung tissues were damaged to different degrees. MDA and NO content increased, while GSH content and SOD activity decreased. The serum inflammatory factors TNF-α and IL-6 levels were elevated significantly. After catechin treatment, blood oxygen saturation of hypoxia rats significantly increased (P < 0. 05). HE staining results showed that myocardial, brain and lung tissue injury was alleviated to some extent. MDA, NO, IL-6 and TNF-α content were down-regulated, while GSH content and SOD activity were up-regulated respectively. Conclusions Catechin can resist high altitude hypoxia and protect the main organs from hypoxia injury in rats acute exposed to altitude, which is related to alleviating oxidative stress and inflammation caused by acute hypoxia exposure.

The protective effect of betelnut polyphenols on exercise-induced fatigue at high altitude and its network pharmacology in rats / 中国药理学通报

Aim: To explore the protective effect of betelnut polyphenols on high altitude exercise-induced fatigue in rats, and to select the main targets to carry out network pharmacology research to preliminarily explore its protective mechanism. Methods: We compared the protective effects of areca catechu polyphenols on high altitude exercise fatigue in rats in low, medium and high dose groups (400, 800, and 1600 mg·kg

The value of nomogram for predicting microvascular invasion based on clinical and Gd-EOB-DTPA-enhanced magnetic resonance imaging features / 中华肿瘤杂志

Objective: To investigate the risk factors of microvascular invasion (MVI) in China liver cancer staging system stage Ⅰa (CNLC Ⅰa) hepatocellular carcinoma (HCC), and develop a nomogram for predicting MVI based on clinical and radiographic data. Methods: This retrospective study focused on CNLC Ⅰa HCC patients who underwent radical resection at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2020. Patients' clinical characteristics and laboratory test results and pre-surgery gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging results were collected. The clinical and radiographic risk factors for MVI were identified by univariate and multivariate logistic regression analyses and used for the construction of the predictive nomogram. The nomogram model was then internally validated, and its performance was assessed. Results: A total of 104 patients were divided into the MVI-positive group (n=28) and the MVI-negative group (n=76). Multivariate logistic regression analysis at the P<0.1 level identified serum alpha-ferroprotein >7 ng/ml, total bilirubin >21 μmol/L, prothrombin time >12.5 s, non-smooth margin, and incomplete or absent capsule as risk factors of MVI, based on which a nomogram model was built. The model achieved an area under the curve (AUC) value of 0.867 (95% confidence interval, 0.791-0.944) in the internal validation. The sensitivity and specificity of the nomogram model were 0.786 and 0.829, respectively, with the prediction curve nearly overlapping the ideal curve. Based on the Hosmer-Lemeshow test, the predicted and real results were not significantly different (P=0.956). Conclusions: The probability of MVI of CNLC Ⅰa HCC can be objectively predicted by the monogram model that quantifies the clinical and radiographic risk factors. The model can also help clinicians select individualized surgical plans to improve the long-term prognosis of patients.

Placebo Response among Different Types of Sham Acupuncture for Low Back Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials / 中国结合医学杂志

BACKGROUND@#Low back pain (LBP) is a prevalent and debilitating condition that poses a significant burden on healthcare systems. Acupuncture has been proposed as a promising intervention for LBP, but the evidence supporting its specific effect is insufficient, and the use of sham acupuncture as a control in clinical trials presents challenges due to variations in sham acupuncture techniques and the magnitude of the placebo effect.@*OBJECTIVE@#To investigate the magnitude of the placebo response of sham acupuncture in trials of acupuncture for nonspecific LBP, and to assess whether different types of sham acupuncture are associated with different responses.@*METHODS@#Four databases including PubMed, EMBASE, MEDLINE, and the Cochrane Library were searched through April 15, 2023, and randomized controlled trials (RCTs) were included if they randomized patients with LBP to receive acupuncture or sham acupuncture intervention. The main outcomes included the placebo response in pain intensity, back-specific function and quality of life. Placebo response was defined as the change in these outcome measures from baseline to the end of treatment. Random-effects models were used to synthesize the results, standardized mean differences (SMDs, Hedges'g) were applied to estimate the effect size.@*RESULTS@#A total of 18 RCTs with 3,321 patients were included. Sham acupuncture showed a noteworthy pooled placebo response in pain intensity in patients with LBP [SMD -1.43, 95% confidence interval (CI) -1.95 to -0.91, I2=89%]. A significant placebo response was also shown in back-specific functional status (SMD -0.49, 95% CI -0.70 to -0.29, I2=73%), but not in quality of life (SMD 0.34, 95% CI -0.20 to 0.88, I2=84%). Trials in which the sham acupuncture penetrated the skin or performed with regular needles had a significantly higher placebo response in pain intensity reduction, but other factors such as the location of sham acupuncture did not have a significant impact on the placebo response.@*CONCLUSIONS@#Sham acupuncture is associated with a large placebo response in pain intensity among patients with LBP. Researchers should also be aware that the types of sham acupuncture applied may potentially impact the evaluation of the efficacy of acupuncture. Nonetheless, considering the nature of placebo response, the effect of other contextual factors cannot be ruled out in this study. (PROSPERO registration No. CRD42022304416).

Pregnancy Benefit of Acupuncture on in vitro Fertilization: A Systematic Review and Meta-Analysis / 中国结合医学杂志

BACKGROUND@#Currently, more and more infertility couples are opting for combined acupuncture to improve success rate of in vitro fertilization (IVF). However, evidence from acupuncture for improving IVF pregnancy outcomes remains a matter of debate.@*OBJECTIVE@#To quantitatively summarized the evidence of the efficacy of acupuncture among women undergoing IVF by means of systematic review and meta-analysis.@*METHODS@#Four English (PubMed, Web of Science, EMBASE, and Cochrane Register of Controlled Clinical Trials) and Four Chinese databases (Wanfang Databases, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and SinoMed) were searched from database inception until July 2, 2023. Randomized controlled trials (RCTs) that evaluated the acupuncture's effects for women undergoing IVF were included. The subgroup analysis was conducted with respect to the age of participants, different acupuncture types, type of control, acupuncture timing, geographical origin of the study, whether or not repeated IVF failure, and acupuncture sessions. Sensitivity analyses were predefifined to explore the robustness of results. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR), and the secondary outcomes were ongoing pregnancy rate and miscarriage rate. Random effects model with I2 statistics were used to quantify heterogeneity. Publication bias was estimated by funnel plots and Egger's tests.@*RESULTS@#A total of 58 eligible RCTs representing 10,968 women undergoing IVF for pregnant success were identifified. Pooled CPR and LBR showed a signifificant difference between acupuncture and control groups [69 comparisons, relative risk (RR) 1.19, 95% confifidence intervals (CI) 1.12 to 1.25, I2=0], extremely low evidence; 23 comparisons, RR 1.11, 95%CI 1.02 to 1.21, I2=14.6, low evidence, respectively). Only transcutaneous electrical acupoint stimulation showed a positive effect on both CPR (16 comparisons, RR 1.17, 95%CI 1.06 to 1.29; I2=0, moderate evidence) and LBR (9 comparisons, RR 1.20, 95%CI 1.04 to 1.37; I2=8.5, extremely low evidence). Heterogeneity across studies was found and no studies were graded as high-quality evidence.@*CONCLUSION@#Results showed that the convincing evidence levels on the associations between acupuncture and IVF pregnant outcomes were relatively low, and the varied methodological design and heterogeneity might inflfluence the fifindings. (Registration No. PROSPERO CRD42021232430).

Comparison of single-course versus multiple course prophylactic intravesical instillation chemotherapy for bladder tumor recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: a systematic review and meta-analysis / 中华老年医学杂志

Objective:To examine whether multiple-course prophylactic intravesical instillation chemotherapy is superior to single-course chemotherapy in preventing bladder tumor recurrence after radical nephroureterectomy(RNU)for primary upper tract urothelial carcinoma(UTUC).Methods:A comprehensive literature search was performed using the PubMed, Wanfang Data and China National Knowledge Infrastructure and all publications before March 2021 about clinical trials comparing the effects of single-course and multiple-course prophylactic intravesical instillation chemotherapy after RNU for UTUC were retrieved.Analysis was performed using Stata/SE 12.0.Results:Seven trials included a total of 998 patients, with 473 participants receiving multiple-course and 525 receiving single-course intravesical instillation chemotherapy.Bladder cancer recurrence occurred in 69 out of 473 patients(14.6%)with multiple-course chemotherapy and in 123 out of 525 patients(23.4%)with single-course chemotherapy.The absolute risk reduction was 8.8% and the relative risk reduction was 37.6%.Compared with a single-course instillation, the pooled OR of bladder cancer recurrence was 0.55(95% CI: 0.40-0.76, P<0.001)for multiple-course instillations.No serious adverse events were reported. Conclusions:Compared with single-course instillation chemotherapy, multiple-course prophylactic intravesical instillation chemotherapy significantly decreases the risk of bladder cancer recurrence in primary UTUC patients treated with RNU, indicating multiple intravesical instillation chemotherapy is superior to single instillation chemotherapy.

The value of nomogram for predicting microvascular invasion based on clinical and Gd-EOB-DTPA-enhanced magnetic resonance imaging features / 中华肿瘤杂志

Objective: To investigate the risk factors of microvascular invasion (MVI) in China liver cancer staging system stage Ⅰa (CNLC Ⅰa) hepatocellular carcinoma (HCC), and develop a nomogram for predicting MVI based on clinical and radiographic data. Methods: This retrospective study focused on CNLC Ⅰa HCC patients who underwent radical resection at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2020. Patients' clinical characteristics and laboratory test results and pre-surgery gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging results were collected. The clinical and radiographic risk factors for MVI were identified by univariate and multivariate logistic regression analyses and used for the construction of the predictive nomogram. The nomogram model was then internally validated, and its performance was assessed. Results: A total of 104 patients were divided into the MVI-positive group (n=28) and the MVI-negative group (n=76). Multivariate logistic regression analysis at the P<0.1 level identified serum alpha-ferroprotein >7 ng/ml, total bilirubin >21 μmol/L, prothrombin time >12.5 s, non-smooth margin, and incomplete or absent capsule as risk factors of MVI, based on which a nomogram model was built. The model achieved an area under the curve (AUC) value of 0.867 (95% confidence interval, 0.791-0.944) in the internal validation. The sensitivity and specificity of the nomogram model were 0.786 and 0.829, respectively, with the prediction curve nearly overlapping the ideal curve. Based on the Hosmer-Lemeshow test, the predicted and real results were not significantly different (P=0.956). Conclusions: The probability of MVI of CNLC Ⅰa HCC can be objectively predicted by the monogram model that quantifies the clinical and radiographic risk factors. The model can also help clinicians select individualized surgical plans to improve the long-term prognosis of patients.

Clinical analysis of 12 cases of primary urethral carcinoma / 中华老年医学杂志

Objective:To investigate the clinical features, diagnosis, treatment and prognosis of primary urethral carcinoma.Methods:The clinical and follow-up data of 12 patients with primary urethral carcinoma admitted to Beijing Hospital from July 2016 to December 2020 were retrospectively analyzed.Results:There were four males and eight females, with an average age of 66.3(53~75)years.Nine patients underwent magnetic resonance examination before operation, and eight patients presented with abnormal urethral signals.The clinical stage of female patients was generally later than those of male patients, and all patients received surgical treatment.Four male patients did not receive post-operative adjuvant treatment, and all of them attained disease-free survival.Among the eight female patients, four patients received postoperative adjuvant radiotherapy or chemotherapy, five patients had recurrence or metastasis during follow-up, and two patients died.Conclusions:The clinical stage of female urethral cancer is later than that of male.MRI examination is beneficial to the determination of local invasion of urethral cancer.For female proximal urethral cancer and male posterior urethral cancer, radical resection has a good therapeutic effect.

Comparison of complications and analysis of factors affecting renal function decline after laparoscopic radical cystectomy with different urinary diversion methods / 中华老年医学杂志

Objective:To compare the complications associated with various urinary flow diversion methods and identify the factors that contribute to the decline in renal function after radical total cystectomy for myoinfiltrating urothelial carcinoma.Methods:This study conducted a retrospective analysis on the clinical data of 46 patients with pathologically confirmed muscle-invasive bladder cancer.The patients underwent laparoscopic radical cystectomy with either ileal conduit diversion(n=21)or ureterocutaneous diversion(n=25)between January 2017 and December 2021.Perioperative data, postoperative pathology, postoperative complications, and follow-up results were compared between the two groups.Results:The study found significant differences between the two groups in terms of age[(67±6)years vs.(73±8)years, t=3.132, P=0.003], Charlson comorbidity index adjusted for age[(3.80±1.15) vs.(4.52±1.03), t=2.223, P=0.031], prognostic nutritional index[(48.81±5.74) vs.(43.64±4.74), t=3.347, P=0.002], operation time[(449±108)minutes vs.(326±130)minutes, P=0.001]], hospital stay[(20.1±11.1)days vs.(13.3±5.2)days, t=2.762, P=0.008], proportion of Clavien grade 3 or higher complications within 3 months after surgery(4/21 vs 0/25, χ2=2.105, P<0.05), and proportion of stoma-free patients(18/21 vs.5/25, χ2=6.373, P<0.01). According to Logistic multivariate analysis, perioperative blood transfusion and urinary tract infection were identified as independent risk factors for renal function decline 12 months after surgery.Escherichia coli was found to be the most common bacteria cultured from urinary tract infections in both groups after surgery. Conclusions:Laparoscopic radical cystectomy with ureterocutaneous diversion offers benefits such as shorter hospital stays and fewer perioperative complications for older and frail patients.However, a higher proportion of patients may require ureteral stenting.It is important to note that perioperative blood transfusion and urinary tract infection are major risk factors for renal function decline following radical cystectomy.

Guanxin Danshen Dripping Pills Improve Quality of Life and Cardiovascular Prognoses of CHD Patients after PCI with Anxiety or Depression (GLAD Study): A Randomized Double-Blind Placebo-Controlled Study / 中国结合医学杂志

OBJECTIVE@#To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).@*METHODS@#From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12.@*RESULTS@#In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred.@*CONCLUSIONS@#GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).

Analysis of 7 cases of delayed diagnosis of primary upper tract urothelial carcinoma with calculi / 现代泌尿外科杂志

【Objective】 To reduce the misdiagnosis rate by analyzing the clinical data of patients with primary upper tract urothelial carcinoma (UTUC) complicated with calculi. 【Methods】 Clinical data of 7 UTUC with calculi patients treated during Sep.2018 and Apr.2022 were retrospectively analyzed, including general data, time from visit to diagnosis, imaging data, urine exudation cytological results, surgical methods, pathological stages and follow-up data. 【Results】 The ratio of male to female was 3∶4, and the mean age was 66.4 (55-72) years. The initiate imaging examination results only showed calculi, but did not indicate suspicious tumor (including 1 case with missing data). The median time from the first visit to diagnosis was 12 months (5-36 months). Of all 7 cases, 2 (2/4) were clinically diagnosed by enhanced CT, 3 (3/4) by MRI, and 2 (2/7) by positive urine exudation cytology. All patients received surgical treatment. Postoperative pathology showed 85.71% (6/7) were high-grade UTUC. Postoperative staging was T1N0M0 in 4 cases, T3N0M0 in 2 cases, and T4N2M0 in 1 case. Adjuvant chemotherapy was conducted in 2 cases. During the median follow-up of 12 months (6-41), 1 case developed multiple systemic metastases in month 9, while the other cases had no recurrence or metastasis. 【Conclusion】 For UTUC patients without obvious filling defect on imaging, especially when ipsilateral calculi were complicated, misdiagnosis should be alerted for timely treatment and better prognosis.

Expressions of P53 and Ki-67 in prostate cancer and the clinicopathological significance / 现代泌尿外科杂志

【Objective】 To investigate the expressions of P53 and Ki-67 in prostate cancer (PCa)and to explore their correlation with the clinicopathological characteristics. 【Methods】 The expressions of P53 and Ki-67 in 90 PCa patients were detected with immunohistochemistry. Patients’ age, preoperative prostate-specific antigen (PSA) level, postoperative Gleason score, pathological stage, and invasion of neurovascular cancer embolus of all patients were recorded. The relationship of P53 expression with the above indexes was evaluated. 【Results】 The positive rates of P53 and Ki-67 were 27.8% (25/90) and 46.7% (42/90), respectively. The positive rate of P53 in pT2 and pT3-T4 stage groups were 19.7% (13/66) and 50.0% (12/24) (P=0.005), and the positive rate of Ki-67 were 36.4% (24/66) and 75.0% (18/24) (P=0.001), respectively. The positive rate of Ki-67 in Gleason score ≤6, ≤7 and ≥8 groups were 30.4%, 53.8% and 66.7%, respectively, with statistical difference. Positive expression of P53 was related to Ki-67 expression, but not to patients’ age, preoperative PSA level, postoperative Gleason score and nerve and invasion of neurovascular cancer embolus. 【Conclusion】 P53 expression is related to tumor stage and Ki-67, while Ki-67 expression is associated with tumor stage ang grade.

Clinical features and long-term prognosis of primary biliary cholangitis in patients with past hepatitis B virus infection / 中华肝脏病杂志

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

Effects of altitude hypoxia on cerebral blood distribution of sodium valproate in mice / 中国药理学通报

Aim To investigate the effects of altitude hypoxia on serum sodium valproate eoncentration and eerebral blood distribution.Methods Male mice were divided into control group and plateau group.Each group was given sodium valproate orally and intrave¬nously, respectively.UFLC-MS/MS was used to deter¬mine the concentration of sodium valproate in plasma and brain, and Western blot was used to detect the ex¬pression of P-gp in BBB.Results Compared with the control group, the ratio of brain/blood drug concentra¬tion in plateau group was up-regulated by 44.0% , 57.9% , 176.8% and 184.5% at 10, 30, 60 and 120 min, respectively.The ratio of brain/blood drug con-centration increased by 33.9% , 50.6% and 125.6% at 60 min, 120 min and 240 min in plateau group, re¬spectively.Compared with the control group, the ex¬pression of P-gp protein in BBB of mice in altitude group was significantly down-regulated by 58.46% (P < 0.05 ).Conclusions Compared with the control group, the brain/blood drug concentration ratio of val¬proic acid increases in high altitude hypoxia environ¬ment.Meanwhile, it is found that P-gp expression lev-el decreased in the brain mierovessels of mice under high altitude hypoxia environment, and the cerebral and blood distribution of valproic acid in mic increases in high altitude hypoxia environment.

Diagnostic value of FibroTouch, FibroScan, and acoustic radiation force impulse for liver fibrosis in patients with primary biliary cholangitis / 临床肝胆病杂志

ObjectiveTo investigate the diagnostic efficiency of FibroTouch, FibroScan, and acoustic radiation force impulse (ARFI) for liver fibrosis in patients with primary biliary cholangitis (PBC). MethodsA retrospective analysis was performed for the patients who underwent liver biopsy and were then diagnosed with PBC in Beijing Friendship Hospital, Capital Medical University, from September 2014 to October 2018, and the METAVIR scoring system was used to evaluate the degree of liver fibrosis and inflammation. Within 1 week after liver biopsy, FibroTouch, FibroScan, and ARFI were used to measure liver stiffness (LS); with pathological results as the gold standard, the area under the ROC curve (AUC) was used to compare the value of FibroTouch, FibroScan, and ARFI in the diagnosis of liver fibrosis in PBC patients, and related influencing factors were analyzed; Youden index was used to calculate the cut-off values of LS for different degrees of liver fibrosis. The Kruskal-Wallis H test was used for comparison between multiple groups, and P value corrected by the Bonferroni method was used for further comparison between two groups. A Spearman correlation analysis was performed, and a multiple linear regression model was used for multivariate analysis. ResultsA total of 68 patients with PBC were enrolled in the study, among whom 13 had F0 liver fibrosis, 15 had F1 liver fibrosis, 18 had F2 liver fibrosis, 12 had F3 liver fibrosis, and 10 had F4 liver fibrosis. LS obtained by FibroTouch (FT-LS), LS obtained by FibroScan (FS-LS), and LS obtained by ARFI (ARFI-LS) were strongly positively correlated with the degree of liver fibrosis (r=0.798, 0.782, and 0.742, all P＜0.001). FT-LS had AUCs of 0.922, 0.881, and 0.926, respectively, in the diagnosis of F≥2, F≥3, and F=4 liver fibrosis, and the corresponding cut-off values were 10.5 kPa, 15.8 kPa, and 17.5 kPa, respectively; FS-LS had AUCs of 0.918, 0.878, and 0.939, respectively, in the diagnosis of F≥2, F≥3, and F=4 liver fibrosis, and the corresponding cut-off values were 10.1 kPa, 12.9 kPa, and 18.2 kPa, respectively; ARFI-LS had AUCs of 0.904, 0.869, and 0.928, respectively, in the diagnosis of F≥2, F≥3, and F=4 liver fibrosis, and the corresponding cut-off values were 1.45 m/s, 1.83 m/s, and 2.08 m/s, respectively. There was no significant difference in diagnosing the same stage of liver fibrosis between FibroTouch, FibroScan, and ARFI (P＞0.05). The multivariate analysis showed that degree of liver fibrosis (β=0.399, P＜0.001), total bilirubin (β=0.466, P＜0.001), and prothrombin time activity (β=-0.195, P=0.020) were influencing factors for FT-LS; degree of liver fibrosis (β=0370, P＜0.001), aspartate aminotransferase (β=0.450, P＜0.001), prothrombin time activity (β=-0.303, P=0.001), and alkaline phosphatase (β=-0.187, P=0.042) were influencing factors for FS-LS; degree of liver fibrosis (β=0.489, P＜0.001), aspartate aminotransferase (β=0.467, P＜0.001), and platelet count (β=-0.188, P=0.028) were influencing factors for ARFI-LS. ConclusionFibroTouch has similar efficiency to FibroScan and ARFI in the diagnosis of liver fibrosis in PBC patients, with relatively high diagnostic efficiency for significant liver fibrosis (F≥2) and liver cirrhosis (F=4), and therefore, it can be used as a reliable method for the diagnosis of liver fibrosis in PBC patients.

Quantification of ambrisentan in human plasma by LC-MS/MS and its pharmacokinetic application / 中国临床药理学与治疗学

AIM: To establish an LC-MS/MS method to determine the concentration of ambrisentan in human plasma and apply it to the study of human pharmacokinetics. METHODS: After extracting ambrisentan and internal standard from human plasma by liquid-liquid extraction, chromatographic separation was performed on a Waters Symmetry C

Intrathecal injection of miR-125b mimic attenuates neuroinflammation after ischemia-reperfusion injury by inactivation of microglial NLRP3 inflammasome / 中国医师杂志

Objective:To observe and investigate the effect and mechanism of intrathecal injecting miR-125b mimic on regulating microglial and its-mediated NOD-like receptor protein 3 (NLRP3) inflammasome activation after spinal cord ischemia reperfusion injury (SCIRI) in rats.Methods:120 Sprague-Dawley (SD) rats were randomly divided into four groups: sham group (sham group, intrathecal injection of normal saline), injury group (IR group, intrathecal injection of normal saline), mimic group (IR+ intrathecal injection of miR-125b mimic) and control group (IR+ intrathecal injection of miR-125b control). In sham group, the aortic arch was exposed without clamping. In other groups, the aortic arch was clamped for 14 minutes, and then the artery clamp was removed to prepare SCIRI model. Rats in each group were given intrathecal injection for 3 consecutive days before operation, once a day. Immunofluorescence was used to observe the morphology of microglia and count the number of activated cells 48 hours after injury; double immunofluorescence was used to observe the distribution of Iba-1 and NLRP3 in cells. The protein expression of Iba-1, NLRP3 and cleaved caspase-1 in spinal cord were determined by Western blot, and the inflammatory factor IL-1 β was determined by enzyme linked immunosorbent assay (ELISA).Results:The activated microglias exhibited the amoeba morphology and increased Iba-1 fluorescence signal in immunofluorescence. The microglias in spinal dorsal horn of Sham group were all branched-like morphology and absent of the increased Iba-1 signal at 48 h post-IR. And the microglias in IR and control groups was all amoeba-like morphology with obviously increased number and intensity of Iba-1 signal, whereas in mimic group, the microglias were mixed morphology with the less increased number and intensity of Iba-1 signal ( P<0.05). And NLRP3 signals were mainly distributed in microglias with increased Iba-1 signal. Meantime, compared with Sham group, the protein expression of Iba-1, NLRP3, cleaved caspase-1 and IL-1β were significantly increased in IR group ( P<0.05). Compared with IR group, the above-mentioned protein expression were decreased in mimic group ( P<0.05). There were no statistical differences between IR and control groups in the above-mentioned protein levels ( P>0.05). Conclusions:Intrathecal injection of miR-125b mimic inhibits the SCIRI-induced microglial activation and then reduces NLRP3 inflammasome expression in spinal cords, thereby exerting an effective anti-inflammatory effects.