[A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors].

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase â study].

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION: Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.

[Death-related risk factors analysis of surgical treatment of myocardial infarction combined with ventricular septal rupture].

Objective: To in vestigate the death-related risk factors of surgical treatment of myocardial infarction (MI) combined with ventricular septal rupture (VSR). Methods: The clinical data of patients (68 cases) with ventricular septal rupture after myocardial infarction (PI-VSR) from January 2008 to December 2020 in Beijing Anzhen Hospital were retrospectively selected and analyzed. We followed up the surviving patients and divided them into the survival group and the death group according to the perioperative and follow-up results. The univariate analysis was performed on various indicators, and the Cox regression analysis was used to analyze the risk factors related to postoperative death. Results: A total of 68 patients (42 were male and 26 were female, with age 44-82 (64.3±8.2) years after surgical treatment of myocardial infarction combined with ventricular septal rupture were enrolled, 9 patients died during the perioperative period, 59 surviving patients were followed up for 0.1-10.5 years(mean, 4 years), and 7 deaths during follow-up. Based on this, 52 patients were selected as the survival group while 16 patients as the death group. The results of univariate analysis showed that age, VSR to operation time less than 7 days, killip grade ≥ grade 3, cardiogenic shock, preoperative use of IABP, emergent surgery were related to postoperative death. The factors with P<0.2 factors in univariate analysis were selected into the multivariate Cox regression analysis. Age ([OR=1.110(1.012-1.217), P=0.026], platelet count [OR=0.990(0.981-0.999), P=0.031], D dimer (OR=1.002[1.001-1.003], P=0.003), cardiogenic shock (OR=6.084[1.729-21.405], P=0.005) were independent risk factors for postoperative death. All patients were followed up, the survival rate of 2-year, 4-year, 6-year, 8-year, and 10-year was 77.5%, 77.5%, 71.0%, 71.0%, and 71.0%, respectively. Conclusions: Age, platelet count, D-dimer, and cardiogenic shock are risk factors for death after surgical treatment of myocardial infarction combined with ventricular septal rupture. Surgery is an effective method for the treatment of myocardial infarction combined with ventricular septal rupture. Long-term prognosis of the surviving patients during perioperative are relatively better.

[Clinical analysis of intravenous-cardiac leiomyomatosis].

Objective: To summarize the clinical characteristics, treatment and prognosis of patients with right intravenous-cardiac leiomyomatosis, and provide references for clinical diagnosis and management. Methods: The clinical data of 22 patients who were admitted to Department of Cardiac Surgery in Beijing Anzhen Hospital from November 2009 to July 2019 were retrospectively reviewed. The long-term prognosis of the patients was also evaluated. Results: All patients were women, with an age of (48.1±6.3) years. The clinical manifestations of patients lacked specificity. Among them, 14 patients had a history of uterine leiomyoma, 12 had hysterectomy, and 5 had abortions. Twenty patients underwent tumor resection. One-stage operation was performed in 15 cases, while staging surgery was performed in 5 cases. Ten cases underwent tumor resection under cardiopulmonary bypass. One case underwent a tricuspid valve annuloplasty at the same time. There was no death early in postoperative period. Early complications included deep venous thrombosis (2 cases), type Ⅱ atrioventricular block (1 case), pleural effusion (1 case) and incision infection (1 case). In the long-term follow-up (3 years), one case died of tumor recurrence-associated circulatory failure. Among the rest of the patients, the quality of life was satisfying, and cardiac function was between grade Ⅰ and Ⅱ, with no recurrence or metastasis. Conclusions: Patients with intravenous-cardiac leiomyomatosis are lack of specific manifestations. Early diagnosis is crucial for the treatment of this disease. Tumor resection is an effective treatment, which can improve the quality of life and long-term survival of patients.

[Short-term clinical safety and efficacy of No-touch great saphenous vein harvesting technique for off-pump coronary artery bypass grafting].

Objective: To evaluated early clinical outcomes of saphenous vein grafts harvested with a No-touch technique in off-pump coronary artery bypass graft (OPCABG) surgery. Methods: A total of 124 patients with three-vessel disease undergoing OPCABG by No-touch technique between June and November 2017 in Beijing An Zhen Hospital were respectively reviewed. Results: The average age of patients was (60.7±10.3) years, and 80 cases (64.5%) were male, with the average body mass index (BMI)of (25.4±2.5) kg/m(2,) the mean preoperative left ventricular ejection fraction (LVEF) of (58.0±7.0%). The operative time was (4.0±0.4) hours, and 16 cases (12.9%) were harvested for whole vein grafts. The number of vein grafts and venous anastomoses was 144 and 284, respectively. There were 16 cases of single bridge NTSVG-LAD, 4 cases of single bridge NTSVG-D, 99 cases of sequential bridge NTSVG-OM-PDA, 5 cases of sequential bridge NTSVG-OM-PLV, 4 cases of sequential bridge NTSVG-OM-RCA, 16 cases of sequential bridge NTSVG-D-OM-PDA. The mean flow volume of No-touch vein grafts was (51.9±2.4) ml/min. There was no death case in hospital. Postoperative re-exploration for hemorrhage of anastomosis happened in 1 case (0.8%), which was caused by pericardial tamponade due to insufficiency of hemostasis in internal mammary bed. There were 1 case of bad wound healing of lower extremity incision (0.8%). A total of 124 cases were followed up after operation, and the follow-up rate was 100%. There was one all-cause death (0.8%) 27 days after the operation. Conclusion: The short-term clinical observation of the application of No-touch great saphenous vein harvesting technique for OPCABG is safe and effective.

Tacrolimus population pharmacokinetics according to CYP3A5 genotype and clinical factors in Chinese adult kidney transplant recipients.

WHAT IS KNOWN AND OBJECTIVES: Tacrolimus is characterized by a narrow therapeutic index and a considerable inter- and intraindividual pharmacokinetic variability. The aim of our study was to develop a population pharmacokinetic model of tacrolimus in adult kidney transplant of Chinese patients, identify factors especially CYP3A5*3 genetic polymorphism that explain variability, and determine dosage regimens. METHODS: Pharmacogenomic data obtained from 83 Chinese kidney transplant patients treated with tacrolimus were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Trough blood concentration data were collected from all of the patients during the 12 months of post-transplantation days and were analysed using the nonlinear mixed-effects modelling program. After building the final model, 1000 bootstraps were performed to validate the final model. RESULTS AND DISCUSSION: A one-compartment model with first-order absorption and elimination adequately described the pharmacokinetics of tacrolimus. In this study, we observed that POD, HCT and CYP3A5*3 genotype were determinant factors in CL/F and POD related with V/F of tacrolimus significantly. The final model with the clearance covariates was presented as: Cl/F=THETA(1)*EXP(THETA(4)*(83/POD))*(39.1/HCT)**THETA(5)*EXP(THETA(6)*CYP3A5), and the final model with the volume covariates was presented as: Vd/F=THETA(2)*POD**THETA(3). The Ka was fixed to 4.5 h-1 . WHAT IS NEW AND CONCLUSION: The HCT, CYP3A5*3 genetic polymorphism and POD contributed to the interindividual variability of oral tacrolimus in Chinese adult renal transplant patients.

[Safety and efficacy of off-pump coronary artery bypass grafting in octogenarians].

Objective: To discuss the clinical safety and efficacy about off-pump coronary artery bypass grafting (OPCABG) in octogenarians. Methods: From June 2005 to July 2014, 252 patients (male 208, female 44, with a mean age of 81.7 years old) underwent OPCABG in Beijing Anzhen Hospital who were aged 80 years or older were enrolled. Results: Eight (3.2%) patients were diagnosed as single vessel coronary artery disease (CAD), 29 cases (11.5%) were diagnosed as bifurcation vessel CAD, and 215 cases (85.3%) were multivessel CAD. One hundred and one cases (40.1%) were diagnosed as left main artery disease, among which 51 cases (20.2%) had old myocardial infarction. Two hundred and forty-eight patients belonged to Canadian Cardiovascular Society (CCS) classⅠ-Ⅲ and 4 cases to CCS class Ⅳ. One hundred and forty-five cases belonged to New York Heart Association (NYHA) classⅠ-Ⅱ and 107 cases to NYHA class Ⅲ-Ⅳ. Mean graft number was 3. Two hundred and six patients (81.7%) received total vein graft operation. Intra-aortic balloon pump (IABP) was used in 43 patients (17.1%). In-hospital death occurred in 15 cases (6.0%). Major in-hospital complications included reoperation (16 cases), re-intubation (16 cases), dialysis (11 cases), sternum infection (2 cases), atrial fibrillation (63 cases). The follow-up time was from 1 to 11 years (with a mean time of 6 years). All-cause mortality was 18.1% (43 cases). The major out-of-hospital complications included recurrent myocardial infarction (3 cases), stroke (3 cases), re-admission (27 cases) and recurrent angina pectoris (20 cases). Conclusion: OPCABG is safe and effective for myocardial revascularization in patients aged 80 years and over.

Bulk signatures of pressure-induced band inversion and topological phase transitions in Pb(1-x)Sn(x)Se.

The characteristics of topological insulators are manifested in both their surface and bulk properties, but the latter remain to be explored. Here we report bulk signatures of pressure-induced band inversion and topological phase transitions in Pb(1-x)Sn(x)Se (x=0.00, 0.15, and 0.23). The results of infrared measurements as a function of pressure indicate the closing and the reopening of the band gap as well as a maximum in the free carrier spectral weight. The enhanced density of states near the band gap in the topological phase gives rise to a steep interband absorption edge. The change of density of states also yields a maximum in the pressure dependence of the Fermi level. Thus, our conclusive results provide a consistent picture of pressure-induced topological phase transitions and highlight the bulk origin of the novel properties in topological insulators.

Study on bending behaviour of nickel-titanium rotary endodontic instruments by analytical and numerical analyses.

AIM: To develop analytical models and analyse the stress distribution and flexibility of nickel-titanium (NiTi) instruments subject to bending forces. METHODOLOGY: The analytical method was used to analyse the behaviours of NiTi instruments under bending forces. Two NiTi instruments (RaCe and Mani NRT) with different cross-sections and geometries were considered. Analytical results were derived using Euler-Bernoulli nonlinear differential equations that took into account the screw pitch variation of these NiTi instruments. In addition, the nonlinear deformation analysis based on the analytical model and the finite element nonlinear analysis was carried out. Numerical results are obtained by carrying out a finite element method. RESULTS: According to analytical results, the maximum curvature of the instrument occurs near the instrument tip. Results of the finite element analysis revealed that the position of maximum von Mises stress was near the instrument tip. Therefore, the proposed analytical model can be used to predict the position of maximum curvature in the instrument where fracture may occur. Finally, results of analytical and numerical models were compatible. CONCLUSION: The proposed analytical model was validated by numerical results in analysing bending deformation of NiTi instruments. The analytical model is useful in the design and analysis of instruments. The proposed theoretical model is effective in studying the flexibility of NiTi instruments. Compared with the finite element method, the analytical model can deal conveniently and effectively with the subject of bending behaviour of rotary NiTi endodontic instruments.

Integrating tumor mutational burden and transcriptome expression into prediction of immune checkpoint inhibitor response and prognosis of patients with colon cancer.

Whether tumor mutational burden (TMB), which refers to the total number of somatic or acquired mutations per million bases in a particular region of the tumor genome, can serve as a predictive biomarker of immune checkpoint inhibitor (ICI) therapy for colon cancer remains unclear. Hereby, we retrospectively investigated the differentially expressed genes (DEGs) based on the level of TMB and tried to established a risk score model as a novel biomarker. The DNA mutation data were retrieved from the Masked Somatic Mutation in Genomic Data Commons data portal of the Cancer Genome Atlas, where the RNA sequencing data, clinical information, and survival outcomes of patients were downloaded. Patients with incomplete clinical information were excluded. The immune score and stromal score were calculated to investigate immune infiltration. The patients were grouped into TMB-high group and the TMB-low group based on the median value of TMB. An immune relevant gene set was obtained from the Immunology Database and Analysis Portal to identify immune-related DEGs. The Cox proportional hazard model and nomogram were applied to establish the risk model. In results: the TMB value was associated with age (p≤0.001), clinical stage (p≤0.001), N stage (p≤0.001), M stage (p=0.003), and immune score (p≤0.001). Twenty-nine immune-related DEGs were identified as enriched in immune response-related function or pathway and tumorigenesis signaling. Nine of 29 were determined to establish a riskScore model. The riskScore suggested a positive relationship with the TMB value (p=0.033), immune score (p≤0.001), and tumor immune dysfunction and exclusion (TIDE) (p=0.002) and presented an independent prognostic factor (p≤0.001, HR=1.04), which predicted the overall survival with good specificity. We concluded that the combination of TMB with transcriptome expression has a predictive and prognostic value for patients treated with ICIs.

[Clinicopathological features and survival analysis of gastric cancer patients with neuroendocrine differentiation after radical resection].

Objective: To compare the clinicopathological characteristics and the prognosis of gastric adenocarcinoma patients with and without neuroendocrine differentiation (NED) after radical gastrectomy plus D2 lymph node dissection. Methods: A retrospective cohort study was performed. The inclusion criteria were as follows: (1) patients who underwent radical resection of gastric cancer plus D2 lymph node dissection and were confirmed as gastric adenocarcinoma by postoperative pathology and received immunohistochemical examination of neuroendocrine markers Syn and/or CgA; (2) patients aged 20 to 75 years with normal organ function; (3) patients who did not receive neoadjuvant chemotherapy or radiotherapy before operation; (4) patients with postoperative pathological stage I to III according to the 8th edition of tumor staging system of American Joint Committee on Cancer (AJCC); and (5) patients who completed adjuvant chemotherapy according to the postoperative pathological stage. Those who had other malignant tumors in the past 5 years and who could not be followed up according to the required rules were excluded. According to the above criteria, the clinicopathological characteristics of gastric cancer patients who underwent radical resection plus D2 lymph node dissection in Zhongshan Hospital of Fudan University from January 2010 to June 2017 were collected and compared. All patients were followed up till June 2020. The disease-free survival (DFS) and overall survival (OS) between the patients with and without NED were compared, and the effect of NED on the prognosis was corrected by Cox proportional hazards model. The propensity score matching method was used for sensitivity analysis. Results: A total of 539 patients were enrolled in this study, including 35 with NED and 504 without NED. Compared with the patients without NED, the patients with NED were older [(65.0±7.5) years vs. (54.5±11.3) years, t=-7.681, P<0.001], had higher proportion of undergoing proximal gastrectomy [22.9% (8/35) vs. 7.6% (36/504), χ(2)=10.335, P=0.006], higher proportion of intestinal-type based on Lauren classification [77.1% (27/35) vs. 42.5% (214/504), χ(2)=14.553, P<0.001], and higher proportion of pathologic stage III [65.7% (23/35) vs. 27.6% (139/504), χ(2)=25.653, P<0.001]. The 3-year DFS of patients with NED and those without NED was 48.9% (95% CI: 33.8%-70.8%) and 37.4% (95% CI: 32.9%-42.5%) respectively, and no significant difference was found (P=0.44). The 3-year OS was 56.1% (95% CI: 39.9%-79.1%) and 64.3% (95% CI: 59.3%-69.7%) respectively, and no significant difference was found as well (P=0.32). Univariate and multivariate analyses showed that NED was not an independent risk factor for DFS and OS (all P>0.05). Sensitivity analysis showed that there was no significant difference in DFS and OS between the two groups after propensity score matching. Conclusion: Compared with patients without NED, patients with NED were older at onset, had a higher proportion of proximal gastrectomy, intestinal-type, and later diagnostic stage, but the survival prognosis had no significant difference with that of patients without NED.

The effects of monotherapy with erythropoietin in neonatal hypoxic-ischemic encephalopathy on neurobehavioral development: a systematic review and meta-analysis.

OBJECTIVE: Previous systematic review has shown the safety and efficiency of EPO (erythropoietin) for neonatal hypoxic-ischemic encephalopathy (HIE). To date, the evidence is limited that EPO is beneficial to therapeutic hypothermia as an adjuvant. There has not a brief discussion about the neuroprotection effects of EPO without hypothermia. To evaluate the long-term prognosis of HIE treated with EPO alone, we carried out this study that can be a supplement to the previous meta-analysis. MATERIALS AND METHODS: 7 databases (including PubMed, EMBASE, Cochrane, CKNI, CBM, WanFang, and VIP) and the ClinicalTrials.gov were retrieved from inception to 1 March 2020. The inclusion criteria were RCTs with EPO treatment without hypothermia. The outcomes were tested by using the Bayley Scales of Infant Development (BSID), including the Bayley Mental Development Index Score (MDI) and the Bayley Psychomotor Development Index Score (PDI). This meta-analysis was done to compare the Risk Ratio (RR) for the scores of BSID less than 70 after over 6 months of follow-up. RESULTS: 11 RCTs (1099 newborns) were included, excluding deaths and lost visits, and 917 patients finally were performed the statistical analysis. In neonatal HIE infants, investigation results showed a lower risk of cognitive impairment and psychomotor disability with EPO monotherapy. The pooled event rates of MDI <70 saw a reduction of 36% (95% CI 24%-54%) compared to the control group. There was a decrease of 37% (95% CI 24%-56%) of Psychomotor abnormal (PDI <70) in the EPO group. CONCLUSIONS: EPO administration alone could improve the scores of mental and psychomotor in neonates with HIE. However, the level of evidence is low to moderate for the insufficient sample size, so large-scale, multicenter clinical trials are still needed.

[Three-dimensional finite element analysis of the stress distribution of bone tissue around porous titanium implant].

Objective: To analyze the stress distribution of different types of bone tissue around porous titanium implant in different mechanical loads and to further evaluate the biomechanical properties of porous titanium implant. Methods: Finite element (FE) models of implant restorations for the maxillary first premolar was established, and the diameter of implants in the models was 4.1 mm. Five models was constructed according to diameter of implant central pillar and the thickness of outer porosity: solid group (group A), central pillar 1.5 and 3.1 mm and outer porosity 30% (group B and C), central pillar 1.5 and 3.1 mm and outer porosity 40% (group D and E). Different loads (150 N vertical force, 50 N lateral force) were applied to the occlusal surface of implant restorations in type Ⅲ bone and maximal von Mises stress was evaluated. Meanwhile, a couple of simplified maxillary part models varied in four types of bone were constructed with the implants bearing load of simulation ultimate force to evaluate the stress distribution of different types of bone. Results: With different mechanical loading, the stress value of bone tissue around porous implant (group B-E) was greater than that in the solid structure (group A). Under the load of simulation ultimate force, the maximum stress of the bone rised with the increase of porosity and thickness of the porous implant. And the maximum stress value of the surrounding bone tissue changed with the change of bone. Under vertical loading, the maximal von Mises stress of the bone around solid implants of group A was 17.56 MPa, which was a little lower than that of group B and C. And the maximal equivalent von Mises stress of group D and E was 69.24 MPa. The results of lateral force and simulation ultimate force loading were similar. The stress of the bone tissue around implant increased with the decrease of bone quality. The maximum stress value of group D implant was 134.95 MPa. Conclusions: Porous structure of the implant is conducive to transmit stress to surrounding bone tissue and increases the mechanical stimulation of bone. However, if the value and direction of load are inappropriate or quality of bone is poor, pathological stress may be produced.

[Three-dimensional finite element analysis of four-implants supported mandibular overdentures using two different attachments].

Objective: To compare the biomechanical characteristics of four-implants mandibular overdentures supported by Locator attachment or bar-clip attachment under different mechanical loads using three-dimensional finite element analysis method. Methods: Two different models of four-implants supported mandibular overdentures using Locator attachment and bar-clip attachment (hereinafter called Locator model and bar-clip model) were established. Each model was subjected to five different mechanical loading conditions: 100 N vertical loading in central incisor (vertical load of incisor), 100 N vertical loading or oblique loading in canine (vertical or oblique loads of canines), 100 N vertical or oblique loading in mandibular first molar (vertical or oblique loads of mandibular first molar). The stress distributions in implants, peri-implant bone and mucosa were recorded under the above five conditions to evaluate the effects of different attachments on the biomechanical properties of implant-supported mandibular overdentures. Results: Regardless of loading conditions and types of attachments, the stress concentration in implants were located at the neck of implants, and the stress concentration in peri-implant bone was located in the cortical bone. The stress values in mucosa were always much smaller than those in implants and cortical bone. Regardless of loading positions (on canine or on mandibular first molar), the maximum stress at the bone interface around the implant under lateral loading was much higher than that under vertical loading. Under various loading conditions, the stress in implants and cortical bone of the Locator model (the highest von Mise stress value was respectively 79.5 and 22.3 MPa) were lower than that of bar-clip model (the highest von Mise stress value was 110.3 and 28.7 MPa respectively) while the maximum compressive stress in mucosa (0.198 MPa) in Locator model was slightly higher than that in the bar-clip model (0.137 MPa). Conclusions: In clinical practice, the lateral force applied to the implant-retained overdenture should be minimized to avoid complications caused by pathological loads. Under the same loading condition, the stress distributions in overdenture using Locator attachment are more dispersed, which is more conducive to long-term stability of implants.

Fos-like immunoreactivity in central auditory neurons of the mouse.

Fos-like immunoreactivity was used to study sound-induced activation of neurons in the auditory brainstem. Immunoreactivity was assayed with a polyclonal antibody to Fos. In response to 6-kHz tone bursts, the pattern of staining was a band of immunoreactive neurons positioned at the tonotopically appropriate position within the cochlear nucleus and the inferior colliculus. The band was narrow at low sound pressure levels but wider along the tonotopic axis at higher sound levels. In response to noise bursts, the pattern was broader and often extended throughout the auditory nuclei. Often within this broad pattern were "sub-bands" of immunostained neurons, interspersed with bands of unstained neurons. With increasing sound pressure levels above 35-55 dB, the number of Fos-like immunoreactive neurons increased for the cochlear nucleus, superior olivary complex, and inferior colliculus. In the cochlear nucleus and inferior colliculus, the stained cells were small, and hence their activity would be difficult to sample in electrophysiological studies. In the medial nucleus of the trapezoid body, the stained neurons had larger somata and other characteristics of principal cells. Anesthesia with Nembutal or Avertin, but not with ketamine or urethane, decreased the number of Fos-like immunoreactive neurons in the cochlear nucleus. The different anesthetics produced more variable results in the inferior colliculus. In anesthetized, monaurally stimulated animals, the presence of staining in the contralateral cochlear nucleus indicates that some Fos-like immunoreactivity may be mediated by descending or commissural systems. These observations indicate that Fos assays are useful for studying the pattern of neuronal activation in the auditory system and may also be useful in studying the descending auditory pathways.

Morphological study of cultured cardiac ganglionic neurons from different postnatal stages of rats.

This study sought to establish a culture model of cardiac ganglia (CG) neurons of the Sprague-Dawley (SD) rat which could by used to study the distinct characteristics of CG neurons. After culturing, the morphology and immunocytochemistry of CG neurons obtained on different days after birth were compared. Samples of CG neurons were taken from the posterior atrial wall of rats aged 7, 14, 21 and 40 postnatal days (designated as P7, P14, P21 and P40, respectively). During 3-6 days of culture, the morphological changes of the cultured neurons were monitored using a light microscope. Immunocytochemical staining of the neurofilaments (NF-L, -M and -H) was performed to identify the CG neurons and the changes in morphology. The differences in size of the CG soma of each culture were compared by morphometry. Frozen sections of CG neurons were used as the in vivo control of the above experiments. The results showed that the rate of growth in size of the CG soma was highest in the P7 group, and was slower after weaning (21 days after birth). Cultured neurons were categorized into unipolar-like (Type I), multipolar-like (Type II), and bipolar-like (Type III) based on their morphological characteristics. In NF immuocytochemical staining, there were strong responses to NF-H and NF-M in all cultures, but not to NF-L. More specifically, responses to NF-H were mainly observed in perikaryons and neurites, whereas the responses to NF-M were mainly in perikaryons. The present study has established a culture system for cardiac ganglia neurons of SD rats. Our results show that the intracardiac neurons were still developing in their somata and the processes and that various responses to different antibodies of NF for CG neurons occurred in different postnatal stages in rats.

Adaptive postprocessing algorithms for low bit rate video signals.

A new adaptive postprocessing algorithm to enhance the quality of a noisy video sequence is presented. The algorithm recognizes that the visibility of noise depends on local signal characteristics. It therefore classifies the video signal into different classes and uses separate nonlinear filters matched to each class. The most general version of the algorithm employs motion-compensated frame averaging to improve picture quality in a first stage. A classification algorithm subsequently divides subblocks of pixels in the averaged frame into four classes: edge, smooth, nonsmooth with motion and nonsmooth without motion. Spatial algorithms that perform multilevel median filtering, double median filtering, and median filtering are used for pixels belonging to edge, smooth, and nonsmooth with motion categories. Pixels in the nonsmooth, unmoving category are left unfiltered to preserve corresponding image texture. In a simpler version of this four-class system, the motion cues and motion-compensated frame averaging are eliminated, and the purely spatial filtering is based on a three-class algorithm. When used at the output of a 3-D subband coder at 384 kbps, the spatial postfilter was shown to provide a consistent gain in subjectively evaluated picture quality. Twenty-five viewers participated in an experiment involving three coded sequences. In a pairwise comparison of postfiltered and unfiltered sequences, the postfiltered version was judged to be better in 63 out of 75 instances.

Fuzzy control stabilization with applications to motorcycle control.

This study develops fuzzy control that is designed with sliding modes to achieve stability of the fuzzy controller. Fuzzy control is formulated in the form of variable structure system (VSS) control. In contrast to previous works in which Lyapunov functions are used to examine the stability, the current study investigates the stability of fuzzy control from the viewpoints of differential geometric methods and the sliding mode theory. Best values for parameters in fuzzy control rules are determined with the aid of sliding modes. In order to improve control performance, a tuning algorithm is executed to adjust parameters for dealing with uncertainties and disturbances. Both computer simulations and experiments with regard to an inverted pendulum hinged to a rotating disk are carried out to validate the proposed method. This apparatus can to some extent represent cornering motion of a motorcycle on which a rider leans to maintain stability. Effects of rider's leaning angle on both stability and handling control are examined according to Bode plots.

Mucin gene expression in gallbladder epithelium with black pigment stone ascertained by in situ hybridization.

Black pigment stones are usually found in patients with liver cirrhosis or hemolytic disease. Mucoglycoproteins are present in a significant amount in black pigment stones and contribute to the matrix of gallstones. Epithelium of stone-containing gallbladders contains much more mucin than those without stones. In this study, we try to determine by in situ hybridization the mucin gene expression in black stone-containing gallbladders and try to find the diversity of mucin gene expression in gallbladders containing black pigment stones and those without stones. In situ hybridization with DIG-tailed oligonucleotides was performed on sections of paraffin-embedded tissues of gallbladders with black pigment stones (n = 10) and those without stones (n = 6) to identify the expression of MUC1, MUC2, MUC3, MUC4, MUC5B and MUC6 in gallbladder epithelium. The findings showed that (1) mRNA expression of MUC1, MUC3, MUC5B and MUC6 were found in all gallbladders with black pigment stones, while they were expressed in 33.3%, 83.3%, 83.3% and 66.7% respectively in those without stones. They were expressed more strongly and extensively in gallbladders with stones when compared to those without stones. (2) MUC2 and MUC4 labeling were absent in gallbladders without stones, while they were present in 20% and 60% of gallbladders with black pigment stones, respectively. We conclude that MUC3, MUC5B and MUC6 were the main mucin gene expression in either gallbladder with or without stones. Altered mucin gene expression occurred in gallbladders with black pigment stones, such as the presence of MUC2 and MUC4 and increased expression of MUC1, MUC3, MUC5B and MUC6 in black stone-containing gallbladders. The higher incidence and stronger labeling intensity of mucin gene expression of MUC2, MUC3, MUC5B and MUC6 in black stone-containing gallbladder may reflect abundant mucin content in these gallbladders. Increased expression of MUC2 and MUC4 in black stone-containing gallbladder epithelium indicated that intestinal metaplasia and altered mucin genes could occur in diseased gallbladders.

[Effect of lower body negative pressure and rotating-table simulated push-pull effect in flight on cardiovascular function].

Objective. To explore the effect of push-pull effect (PPE) simulated by lower body negative pressure (LBNP) rotating-table, and observe the physiological responses to push-pull maneuver. Method. A special LBNP rotating-table was used to simulate the push-pull maneuver. 8 healthy adults participated randomly in two experiments. One was simulated PPE test, which include a series of head-up stand (HUT, +1 Gz) for 1 min, then in head-down stand (HDT, -1 Gz) for 30 s and again in HUT combining LBNP (-50 mmHg) for 10 min. The other one was control test, which only consists of HUT combining LBNP (-50 mmHg) for 10 min. Changes of heart rate (HR), blood pressure (BP), basic impedance (Z0) , stroke output (SO) , cardiac output (CO) and total peripheral resistance (TPR) were monitored by electrical impedance instrument during the experiment. Result. During simulated PPE experiment, 3 subjects presented presyncopal symptoms, with average standing time of 8.99 +/- 1.47 min, while during control test, all the subjects completed HUT combining LBNP for 10 min. In simulated PPE experiment, as compared with HUT (control), HR, Z0 during HDT were significantly lowered, while SV and CO were increased significantly. During HUT + LBNP, HR, Z0 and TPR were significantly higher, while SV and CO were significantly lower than that of control and HDT. SBP was increased significantly than control value when "HUT + LBNP" started, but during the whole process of "HUT + LBNP ", it became significantly lowered. In control experiment, the above mentioned indexes showed the same trend of as change compared with the control, however, the percentage of the change was lower than simulated PPE test, the change percentage in HR was not including. Conclusion. After headstand, head-up stand combining LBNP caused cardiovascular function descends, the degree was larger than simple head-up stand combining LBNP. LBNP rotating-table can be used to simulated push-pull effect.