Objective To evaluate the role of brain-derived neurotrophic factor (BDNF) in inflammatory pain in rats. Methods Sixty female SD rats weighing 150-180 g in which intrathecal (IT) catheters were successfully placed without complication were randomly divided into 5 groups (n= 12 each): group Ⅰ sham operation; group Ⅱ sham operation + IT anti-BDNF antibody; group Ⅲ inflammatory pain; group Ⅳinflammatory pain + IT control IgG and group Ⅴ inflammatory pain + IT anti-BDNF antibody. Inflammatory pain was induced by injecting complete Freund's adjuvant (CFA) into ankle joint cavity of left hindpaw, while in sham operation group equal volume of normal saline was injected instead of CFA. Anti-BDNF antibody or control IgG 15 μg/10 μl was injected IT once a day for 3 days after inflammatory pain was induced. Paw withdrawal latency to thermal stimuli (PWTL) was measured one day before and at 3, 5, 7, 10 and 14 d after inflammatory pain was induced. The rat was sacrificed on 3 rd day of IT anti-BDNF antibody or control IgG injection. The lumbar segment L4-6 of the spinal cord was removed for detection of the expression of BDNF and p-ERK1/2 by immunohistochemistory and Western blot. Results Intra-articular CFA injection significantly increased the expression of BDNF and p-ERK1/2 in the spinal cord in group Ⅲ as compared with sham-operated animals in group Ⅰ . IT antiBDNF antibody injection significantly suppressed the expression of BDNF and p-ERK1/2. PWTL was significantly shortened after intra-articular CFA injection in group Ⅲ as compared with group Ⅰ . IT anti-BDNF antibody reversed the inflammation-induced thermal hyperalgesia in group Ⅴ but IT control IgG did not. Conclusion BDNF in the spinal cord may be involved in inflammatory pain through p-ERK1/2 signal transduction pathway.

Objective To study the prevention effects of AduoLa Fuzhenglin(ADL)Oll the brain injury induced by microwave radiation in rats.Methods A total of 140 male Wismr rats were divided randomly into 5 groups,including control group,microwave exposed group,low dosage(0.75 g·kg-1·d-1)group.middle dosage(1.5 g·kg-1·d-1)group and high dosage(3 g·kg-1·d-1)group.Rats in three ADL groups were lavaged with ADL per day for 2 weeks before radiation.After administration,rats were exposed to microwave at 30 mW/cm2 for 15 min.The abilities of learning and memory were detected by Morris water maze,and the contents of amino acids neurotransmitter of hippocampus were detected by HPLC, then the histology and uhrastrncture of hippocampus were observed with light and electron microscope at 6 h,7 and 14 d after exposure.Results The abilities of learning and memory were declined(F=0.000-0.043,P<0.05)from 6 h to 7 d after exposure,and the contents of four kinds of amino acid neurotransmitter in hippocampus were decreased,of which GLU,GLY and GABA were decreased significantly(F=0.000-0.007,P<0.01)at 6h after exposure,then tissue edema,neuronal degeneration,neuron mitoehondria swelling and cavitation,endocytoplasmie rotieulum broaden,synaptic cleft blurred,and perivascular space widen were found in the hippocampus at 6 h and 7 d after exposure.The changes in low dosage group were similar to those of the radiation group.However,in middle and high dosage groups,the abilities of learning and memory were normal to some extent with the significant differences compared to the radiation group from 6 h to 7 d after exposure(F=0.015-0.028.P<0.05).The contents of four kinds of amino acid neurotransmitter were not decreased,especially GLU contents close tO normal level.There were significant differences between middle and high dosage groups and radiation group at 6 h after exposure(F=0.000-0.042,P<0.05).Moreover,no obvious injury in the hippocampus was observed in middle and high dosage groups at 6 h and 7 d after exposure.Conclusions Exposure to 30 mW/cm2 microwave radiation could decrease the abilities of learning and memory,induce amino acid neurotransmitter turbulence,and injure the histology and uhrastructure of hippocampus.ADL at the dosages of 1.5 and 3 g·kg-1·d-1 would have preventive effects on the injury induced by microwave exposure.The concentration of 1.5 g·kg-1 ·d-1 of ADL might be the effective dosage to prevent the brain damage after microwave exposure.

OBJECTIVESTo investigate the expression of Survivin in patients with extrahepatic cholangiocarcinoma (EHCC) and its relationship with clinicopathological features of EHCC, and the correlation between the expression of Survivin and lymph node micrometastasis, tumor markers, and the prognosis of EHCC.

METHODSThe expression of Survivin protein in paraffin-embedded specimens of 59 patients with EHCC and their 20 para-carcinoma tissues were evaluated by S-P method of immunohistochemical staining. The correlation between the expression of Survivin and the lymph node micrometastasis, clinicopathological features of EHCC and the prognosis of EHCC were analyzed.

RESULTSThe positive expression rate of Survivin protein was 67.8% (40/59) in paraffin-embedded specimens of 59 patients with EHCC and was 20.0% (4/20) in para-carcinoma tissues, and difference between carcinoma tissues and para-carcinoma tissues was significant (P<0.01). Histological differentiation in EHCC had a negative correlation with the expression of Survivin protein, while the expression of Survivin protein in EHCC had a positive correlation with TNM of EHCC, lymphatic vessel infiltration, lymph node metastasis and perineural invasion (P<0.05). The serum CA19-9 levels in the positive group with expression of Survivin protein was (290,300+/-55 500) U/L and was obviously higher than that in the negative group [(113,300+/-31,400) U/L, P<0.05]. The mean survival time of the patients with negative expression of Survivin protein was higher than that of the patients with positive expression (43.5 vs. 21.1 months, P<0.01). Screened to significance univariate, the multivariate analysis through Cox proportional hazard model analysis showed that lymph node metastasis, residual tumor margins, and expression of Survivin protein were independent prognosis factors of the patients with EHCC (P<0.05, P<0.01, P<0.01).

CONCLUSIONSThe expression of Survivin protein in EHCC has a negative correlation with histological differentiation, while has a positive correlation with lymphatic vessel infiltration and serum CA19-9 concentrations. The expression of Survivin protein maybe an independent prognosis factor of the patients with EHCC.

Adult ; Aged ; Aged, 80 and over ; Bile Duct Neoplasms ; metabolism ; pathology ; Bile Ducts, Extrahepatic ; Cholangiocarcinoma ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Prognosis

Objective: To investigate the survival time of multidrug-resistant tuberculosis (MDR-TB) patients and the influential factors in Wuhan. Methods: The relevant information were collected from TB management information system, cause of death reporting system and medical records by trained doctors. The univariate and multivariate Cox proportional hazards model were applied to analyze the factors affecting survival time of patients. Results: A total of 552 patients with MDR-TB were included in the analysis. After the diagnosis of MDR-TB, the cumulative survival rates from the first year to the third year were 0.94, 0.88, and 0.80, respectively. The mortality density of MDR-TB patients was 6.52/100 person-years, and the median survival time was (89.52±1.85) months. Kaplan-Meier analysis showed that the cumulative survival rate of the standardized treatment group was significantly higher than that of the non-standardized treatment group (Log rank=101.070, P<0.001). Compared with the patients aged <30 years, the HR of the patients aged 30-years and ≥60 years were 2.987 (95%CI: 1.268-7.036), 4.957 (95%CI: 1.942-12.653). Compared with the patients with the education level of high school and above, the HR of the patients with education level of junior high school/primary school and below were 1.908 (95%CI: 1.152-3.160), 1.681(95%CI: 1.033-2.735). Compared with the patients without diabetes, the HR of the patients with diabetes was 1.961(95%CI: 1.347-2.854). Compared with the patients without other serious diseases, the HR of the patients with other serious diseases was 2.597 (95%CI: 1.820-3.706). Compared with the patients who had been treated less than one time, the HR of the patients having previous treatment with more than 2 times was 1.611 (95%CI: 1.077-2.409). Compared with patients receiving standard MDR regimen treatment, the HR of the patients receiving no standard MDR regimen treatment was 3.155 (95%CI: 2.132-4.670). Conclusions The cumulative survival rate of MDR-TB patients without standard treatment was significantly lower than that of patients with standard treatment. Older age, low educational level, diabetes mellitus, other serious diseases, more than two times treatment in the past, and receiving no multi-drug resistance regimen treatment were the risk factors affecting the survival of MDR-TB patients.

OBJECTIVETo estimate the association between overweight, obesity and the risk of breast cancer in Chinese female population.

METHODSLiteratures published in China and abroad about overweight, obesity and breast cancer risk among Chinese females were searched. We used "breast cancer", "overweight", "obesity", "weight", "body mass index" and "risk factors" as keywords, to retrieve papers in Chinese literature databases including CNKI, Wanfang and Weipu database. The same strategy was used to retrieve English papers in English literature database including Embase database, PubMed, Science Direct, Elsevier and Cochrane database, supplemented by literature tracing method. Time range was from the founding of each database to April 2012. A total of 124 research papers were collected. Using Stata11.2 software, meta-analysis was conducted, combined odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the associations between overweight, obesity and the risk of breast cancer in Chinese female population.

RESULTSEighteen studies were included in meta-analysis, among them 12 studies were in Chinese and 6 were in English, with a number of 7217 cases and 81 605 controls. Results showed a 7.7% increased risk of breast cancer among overweight or obesity women (OR = 1.08, 95%CI: 1.04 - 1.12). Compared with normal BMI women, the OR (95%CI) of overweight or obesity women were 1.07 (1.03 - 1.11) and 1.56 (1.29 - 1.84) before and after the adjustment of menopausal status.

CONCLUSIONOverweight, obesity may be important risk factors of breast cancer in Chinese female population. The intervention and control activities may reduce the risk of breast cancer at population level.

Asian Continental Ancestry Group ; Breast Neoplasms ; epidemiology ; China ; epidemiology ; Female ; Humans ; Obesity ; epidemiology ; Overweight ; epidemiology ; Risk Factors

Objective:To study the clinical application of ultrasound-guided puncture and catheter tip positioning in peripherally inserted central catheter (PICC) among very/extremely low birth weight infants (VLBWI/ELBWI).Method:From January 2019 to August 2020, VLBWI/ELBWI admitted to NICU of our hospital and received PICC were prospectively enrolled in the study. Based on the last digit of medical record number was odd or even, the infants were assigned into ultrasound group and X-ray group. In the ultrasound group, puncture and catheter tip positioning were performed at bedside guided by ultrasound, while in the X-ray group, these procedures were performed empirically. The differences of catheterization procedure duration, first-time success rate, the visibility of catheter tip, primary dislocation rate, secondary dislocation rate and complication rate were compared between the two groups using SPSS 25.0.Result:A total of 118 premature infants were enrolled, including 57 cases in ultrasound group (50 cases VLBWI and 7 cases ELBWI) and 61 cases in X-ray group (54 cases VLBWI and 7 cases ELBWI). The catheterization procedure duration [(23.2±7.1) min vs. (34.1±7.5) min], first-time success rate (93.0% vs. 65.6%), the visibility of catheter tip (96.5% vs. 83.6%), primary dislocation rate (7.0% vs. 24.6%) and complication rate (7.0% vs. 21.3%) in ultrasound group were all better than X-ray group ( P<0.05). For ELBWI, the above five indexes in the ultrasound group were better than the X-ray subgroup ( P<0.05). For VLBWI, only the catheterization procedure duration and first-time success rate were better in the ultrasound group than the X-ray group ( P<0.05). Conclusion:Ultrasound-guided PICC catheterization in VLBWI/ELBWI is convenient and accurate, which can improve success rate, reduce radiation exposure and repeated catheterization injury. Timely tracking and adjustment of the catheter under ultrasound can reduce complications after catheterization. This technique is worth popularizing among VLBWI/ELBWI.

Reasonable sampling scheme is the important basis for establishing reliable population pharmacokinetic model. It is an effective method for estimation of population pharmacokinetic parameters with sparse data to perform population pharmacokinetic analysis using the nonlinear mixed-effects models. We designed the sampling scheme for amlodipine based on D-optimal sampling strategy and Bayesian estimation method. First, optimized sample scenarios were designed using WinPOPT software according to the aim, dosage regimen and visit schedule of the clinical study protocol, and the amlodipine population model reported by Rohatagi et al. Second, we created a NONMEM-formatted dataset (n = 400) for each sample scenario via Monte Carlo simulation. Third, the estimation of amlodipine pharmacokinetic parameters (clearance (CL/F), volume (V/F) and Ka) was based on the simulation results. All modeling and simulation exercises were conducted with NONMEM version 7.2. Finally, the accuracy and precision of the estimated parameters were evaluated using the mean prediction error (MPE) and the mean absolute error (MAPE), respectively. Among the 6 schemes, schemes 6 and 3 have good accuracy and precision. MPE is 0.1% for scheme 6 and -0.6% for scheme 3, respectively. MAPE is 0.7% for both schemes. There is no significant difference in MPE and MAPE of volume among them. Therefore, we select scheme 3 as the final sample scenario because it has good accuracy and precision and less sample points. This research aims to provide scientific and effective sampling scheme for population pharmacokinetic (PK) study of amlodipine in patients with renal impairment and hypertension, provide a scientific method for an optimum design in clinical population PK/PD (pharmacodynamics) research.
Adult ; Age Factors ; Alanine Transaminase ; blood ; Amlodipine ; pharmacokinetics ; pharmacology ; Antihypertensive Agents ; pharmacokinetics ; pharmacology ; Bayes Theorem ; Body Weight ; Calcium Channel Blockers ; pharmacokinetics ; pharmacology ; Humans ; Hypertension ; metabolism ; Metabolic Clearance Rate ; Middle Aged ; Models, Biological ; Monte Carlo Method ; Nonlinear Dynamics ; Renal Insufficiency ; metabolism ; Software

BACKGROUNDPyroptosis is the term for caspase-1-dependent cell death associated with pro-inflammatory cytokines. The role of alveolar macrophage (AM) pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains unclear.

METHODSC57BL/6 wild-type mice were assigned to sham, lipopolysaccharide (LPS) + vehicle, LPS + acetyl-tyrosyl-valyl- alanyl-aspartyl-chloromethylketone (Ac-YVAD-CMK) and LPS + Z-Asp-Glu-Val-Asp-fluoromethylketone groups. Mice were given intraperitoneal (IP) injections of LPS. Drugs were IP injected 1 h before LPS administration. Mice were sacrificed 16 h after LPS administration, and AMs were isolated. Western blot analysis for active caspase-1 and cleaved caspase-3, evaluation of lung injury and a cytokine release analysis were performed. AMs were treated with LPS and adenosine triphosphate (ATP); caspase-1-dependent cell death was evaluated using flow cytometry; the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) pyroptosomes were examined by immunofluorescence.

RESULTSThe expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group. In the ex vivo study, the caspase-1/propidium iodide-positive cells, caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation. The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death. Ac-YVAD-CMK also reduced the lung injury, pulmonary edema and total protein in bronchoalveolar lavage fluid (BALF). In addition, Ac-YVAD-CMK significantly inhibited interleukin-α2 (IL-1α2) release both in serum and BALF and reduced the levels of IL-18, tumor necrosis factor-α± (TNF-α±), High Mobility Group Box 1 (HMGB1) in BALF during LPS-induced ALI/ARDS.

CONCLUSIONSThis study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury. These preliminary findings may form the basis for further studies to evaluate this pathway as a target for prevention or reduction of ALI/ARDS.

Acute Lung Injury ; chemically induced ; prevention & control ; Amino Acid Chloromethyl Ketones ; pharmacology ; Animals ; Lipopolysaccharides ; toxicity ; Macrophages, Alveolar ; drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Oligopeptides ; pharmacology ; Pyroptosis ; drug effects

Objective:To develop a novel, flexible, dual-arm, master-slave digestive endoscopic minimally invasive surgical robot system named dual-arm robotic endoscopic assistant for minimally invasive surgery (DREAMS) and to evaluate its feasibility for endoscopic submucosal dissection (ESD) by using ex vivo porcine stomachs.Methods:A novel endoscopic robot (DREAMS) system was developed which was composed of a flexible two-channel endoscope, two flexible robotic manipulators, a master controller, a robotic arm, and a control system. A total of 10 artificial round-like lesions with diameters ranging from 15 to 25 mm were created (5 in gastric antrum and 5 in gastric body) by using fresh peeled stomach of healthy pigs as the model. Submucosal dissection was performed with the assistance of the DREAMS system by two operators. The main outcome was submucosal dissection speed, and the secondary outcomes included muscular injury rate, perforation rate, and grasping efficiency of the robot.Results:All 10 lesions were successfully dissected en bloc by using the DREAMS system. The diameter of the artificial lesions was 22.34±2.39 mm, dissection time was 15.00±8.90 min, submucosal dissection speed was 141.79±79.12 mm 2/min, and the number of tractions required by each ESD was 4.2 times. Muscular injury occurred in 4/10 cases of ESD. No perforation occurred. Conclusion:The initial animal experiment shows the DREAMS system is safe and effective.

Objective:To investigate the correlation between macular cherry red spot (CS) and severity of neurological manifestations in Chinese children with sialidosis (SD) type I.Methods:A evidence-based medical study. "China", "Sialidosis" and "Sialidoses" were used as Chinese and English search terms. The literature was searched in CNKI, Wanfang and PubMed. The cases were all from China and matched the diagnostic criteria. According to the presence or absence of CS in the fundus, the SD children were divided into a group with CS (+) and a group without CS (-), and the correlation between the occurrence of ocular CS and neurological manifestations was compared with meta-analysis by RevMan 5.3 software.Results:Sixty-eight studies were initially retrieved according to the search strategy, and 17 studies were finally included, and 5 studies with CS+ and CS- were meta-analyzed. Among the 43 patients, 28 were male and 15 were female, with a median age of 12 years. Visual impairment was observed in 37 cases (90.2%, 37/41, 2 cases not recorded), and CS was present in 24 cases (55.8%, 24/43). The most common neurological manifestation was myoclonus (97.7%, 42/43), followed by cerebellar ataxia (95.1%, 39/41, 2 cases not recorded) and seizures (91.4%, 32/35, 8 cases not recorded). Pathogenic NEU1 gene mutations were detected in 42 cases and one case was undocumented. The incidence of seizure in group CS+ (100%, 20/20) was higher than that in group CS- (80%, 12/15). Meta-analysis showed that there was no statistically significant difference between the incidence of myoclonus or ataxia [relative risk ( RR)=1.13, 95% confidence interval ( CI) 0.79-1.63, P=0.49] and seizure ( RR=1.13, 95% CI 0.84-2.06, P=0.24) among the children in the CS+ and CS- groups. Conclusions:The incidence of ocular CS in Chinese children with type I SD was 55.8%. There was no correlation with neurological manifestations, however the incidence of seizure was significantly higher in patients with CS than in others without CS.