[Application of failure mode and effect analysis in reducing the risk of nosocomial infection].

Objective: To explore the effect of failure mode and effect analysis (FMEA) in the management of nosocomial infection, and provide reference for the effective prevention and control of nosocomial infection. Methods: Using FMEA to identify, analyze, evaluate and screen out the high-risk events of nosocomial infection in January 2020, from which two hospital level priority improvement projects of hand hygiene compliance and blood-borne occupational exposure were determined. After risk control and intervention measures, the effects before and after improvement were compared. Results: Except for the lack of incentive mechanism and insufficient communication between medical and nursing teams, the differences in hand hygiene compliance and blood-borne occupational exposure risk priority coefficients before and after the implementation of FMEA were statistically significant (P<0.05) . After the implementation of FMEA, the hand hygiene compliance was 74.92% (79375/105953) , which was significantly higher than 68.40% (58361/85328) before the implementation of FMEA, and the difference was statistically significant (χ(2)=996.55, P<0.01) . The incidence of blood-borne occupational exposure after the implementation of FMEA was 3.85% (80/2080) , which was lower than the 6.16% (123/1998) before the implementation of FMEA, and the difference was statistically significant (χ(2)=11.49, P<0.01) . Conclusion: FMEA has a good effect in nosocomial infection management. It can identify and evaluate the risk of nosocomial infection prospectively, so as to control the risk effectively.

The Pituitary Tumors and Their Tumor-Specific Microenvironment.

Pituitary tumors develop within a macroenvironment and microenvironment that favor their overall survival. Given the pituitary gland's unique anatomic, histological, and physiological properties, the role of the TME in the pituitary tumors is central. This chapter summarizes the body of literature investigating the role of each component of the TME in relation to tumors of the pituitary and its intimate association with tumorigenesis, maintenance, and progression.

Quantum Spin Hall Effect and Tunable Spin Transport in As-Graphane.

Tunable spin transport in nanodevices is highly desirable to spintronics. Here, we predict existence of quantum spin Hall effects and tunable spin transport in As-graphane, based on first-principle density functional theory and tight binding calculations. Monolayer As-graphane is constituted by using As adsorbing on graphane with honeycomb H vacancies. Owing to the surface strain, monolayer As-graphane nanoribbons will self-bend toward the graphane side. The naturally curved As-graphane nanoribbons then exhibit unique spin transport properties, distinctively different from the flat ones, which is a two-dimensional topological insulator. Under external stress, one can realize tunable spin transport in curved As-graphane nanoribon arrays. Such intriguing mechanical bending induced spin flips can offer promising applications in the future nanospintronics devices.

Population pharmacokinetics and Bayesian estimation of tacrolimus exposure in Chinese liver transplant patients.

WHAT IS KNOWN AND OBJECTIVES: Tacrolimus (TAC) is widely used as part of immunosuppressive regimens. There is great interindividual variation on the disposition of TAC. The aim of this study was to develop a population pharmacokinetic (PPK) model for Chinese liver transplant patients and evaluate genetic polymorphism and other possible factors on the PK parameters. The exposure of TAC is to be estimated through Bayesian modelling. METHODS: A total of 47 sets of rich-time PK and 1234 conventional therapeutic drug monitoring (TDM) data were collected from 125 Chinese liver transplant patients. The pathophysiological data of these patients were recorded. CYP3A5*3 and ABCB1 genotypes were determined for each patient. The PPK model for TAC was established by nonlinear mixed-effects modelling (nonmem). The impact of pathophysiology and genotype on PPK parameters was evaluated. Bayesian estimators for the area under concentration-time curve (AUC) of TAC were validated. RESULTS: A two-compartment model with lag time was found to be the most suitable model for the pooled full PK and TDM data for Chinese liver transplant patients. The CL/F, V2 /F, Q/F, V3 /F, Ka and lag time were 17.4±0.81 L/h, 165±44.1 L, 54.9±25.8L/h, 594±87.5 L, 0.51±0.095 L/h and 1.57±0.34 h. Post-operative day (POD), creatinine clearance (CLcr) and ABCB1 C3435T genotypes were found to have significant influences on CL/F (P<.01). ABCB1 C3435T genotypes showed a significant correlation with V2 /F (P<.01). C0 -C2 and C0 -C2 -C4 were shown to be suitable for the estimation of AUC in Chinese liver transplant patients. WHAT IS NEW AND CONCLUSION: A PPK model for TAC was established successfully in Chinese liver transplant patients. POD, CLcr and ABCB1 C3435T genotypes were shown to have significant effects on CL/F. The AUC of TAC in Chinese liver transplant patients could be estimated through Bayesian modelling, based on which individualized immunosuppressive regimens can be designed.

Establishment of a visualized nude mouse model of cervical carcinoma with high potential of lymph node metastasis via total orthotopic transplantation.

OBJECTIVE: To screen cervical carcinoma (CC) SiHa subgroups with high potential of lymphatic metastasis and establish a visualized nude mouse model of cervical carcinoma with a total orthotopic transplantation approach. METHODS: A cervical carcinoma SiHa subgroup with high potential of lymphatic metastasis was isolated by in vitro and in vivo primary culture and continuous passage screening of cervical carcinoma SiHa cells that stably expressed enhanced green fluorescent protein (EGFP). Forty male nude mice aged 6-8 weeks were equally randomized to group A receiving unscreened SiHa/EGFP cells, and group B received in vitro and in vivo screened SiHa/EGFP cells with high potential of lymph node metastasis. RESULTS: In the 20 animals of group A receiving orthotopic transplantation of unscreened SiHa/EGFP cells, the primary tumors were small; local lymph node metastasis was observed in five animals; local organ invasion and distal lymph node metastasis were observed in two animals; and no lung metastasis was observed. In the 20 animals of group B receiving screened SiHa/EGFP cells, local lymph node metastasis occurred in all animals; distal lymph node metastasis was observed in 18 animals; and lung metastasis was observed in seven animals. CONCLUSION: A cervical carcinoma SiHa subgroup with high potential of lymphatic metastasis was isolated and a visualized nude mouse model of cervical carcinoma with high potential of lymph node metastasis was established through total orthotopic transplantation successfully. This provided a good platform for the further study of cervical carcinoma-related mechanisms, especially mechanisms of lymphatic metastasis in cervical carcinoma.

Electrical performances and structural designs of copper bonding in wafer-level three-dimensional integration.

The integrity of bonded Cu interconnects in wafer-level three-dimensional integration has been investigated as the function of pattern size and density, as well as bonding process parameter. The desired pattern density coupled with the application of bonding process profile we developed gives optimal yield and alignment accuracy, and provides excellent electrical connectivity and contact resistance through the entire wafer. This result is a key milestone in establishing the manufacturability of Cu-based interconnections for 3D integration technology.

Fabrication of nano-scale Cu bond pads with seal design in 3D integration applications.

A method to fabricate nano-scale Cu bond pads for improving bonding quality in 3D integration applications is reported. The effect of Cu bonding quality on inter-level via structural reliability for 3D integration applications is investigated. We developed a Cu nano-scale-height bond pad structure and fabrication process for improved bonding quality by recessing oxides using a combination of SiO2 CMP process and dilute HF wet etching. In addition, in order to achieve improved wafer-level bonding, we introduced a seal design concept that prevents corrosion and provides extra mechanical support. Demonstrations of these concepts and processes provide the feasibility of reliable nano-scale 3D integration applications.

Pituitary metastasis: From pathology to clinical and radiological considerations.

PURPOSE: A review of the literature with respect to pituitary metastases (PM) with clinical and radiological considerations are summarized to facilitate clinical decision making in the management of PM METHODS: A review of literature associated with PM and tumour to tumour metastases in the English literature was reviewed and summarized RESULTS: Pituitary metastases account for 1.0-3.6% of all surgically treated pituitary lesions. Often identified in parallel with extensive disseminated disease, once diagnosed, the prognosis is generally poor, although survival is highly heterogeneous and dependent on the primary tumor histology. Within this anatomical region is also the observation of tumor-to-tumor metastases and collision tumours. Both the tumor macro- and microenvironment play central roles to the progression of disease with distinctive radiological features that may suggest a metastatic sellar lesion as opposed to a primary pituitary lesion. Surgical resection is the first line of therapy followed by adjuvant chemoradiotherapy and endocrinological evaluation for hormonal supplementation CONCLUSION: PMs are relatively rare but important oncological entities representing disseminated disease in the majority of cases. Careful consideration of the relevant clinical history and radiological features can aid the clinician differentiate between a metastatic lesion to the pituitary region and a primary pituitary tumor. While surgical resection is first line therapy, stereotactic radiosurgery in carefully selected patients is emerging as a viable alternative.

[Investigation and analysis of tinnitus in diabetic patients].

Objective:To analyze the influencing factors of tinnitus in diabetic patients and the correlation between hearing loss and tinnitus.Method:Participants were patients with diabetes. Subjects were tested for hearing function and tinnitus symptoms by questionnaire and pure tone audiometry.Result:①112 patients (55 were men and 57 were women) were affected by tinnitus symptoms in 255 patients with diabetes，there were no significant differences between the number of male patients and female patients(P=0.278).②The incidence of tinnitus increased with age (≤30 year: 40%, 31-40 year :25%, 41-50 year: 27%, 51-60 year: 43%, >60 year: 55%),and there was significant differences in the number of patients among different age (P=0.001).③The incidence of tinnitus was no significant difference in diabetes patients with different educational level (P=0.648).④Totally 83 subjects who complained hearing impairment were tested for hearing loss by pure tone audiometry, while 113 (66%) of 172 subjects who insisted their hearing were normal had hearing loss. Of the subjects with normal hearing but tinnitus, 72% had hearing loss and 62% of patients without tinnitus actually had hearing loss.⑤There were statistically significant in patients with diabetes between the incidence of tinnitus and low/intermediate frequency hearing loss or high frequency hearing loss.Conclusion:The incidence of tinnitus symptoms is increased in patients with diabetes mellitus, which may be related to the age, the incidence of hearing loss,however, may be irrelevant to gender and educational level. Diabetic patients with tinnitus symptoms should be tested as soon as possible to achieve early intervention.

Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis.

Microbial communities reside in healthy tissues but are often disrupted during disease. Bacterial genomes and proteins are detected in brains from humans, nonhuman primates, rodents and other species in the absence of neurological disease. We investigated the composition and abundance of microbiota in frozen and fixed autopsied brain samples from patients with multiple sclerosis (MS) and age- and sex-matched nonMS patients as controls, using neuropathological, molecular and bioinformatics tools. 16s rRNA sequencing revealed Proteobacteria to be the dominant phylum with restricted diversity in cerebral white matter (WM) from MS compared to nonMS patients. Both clinical groups displayed 1,200-1,400 bacterial genomes/cm3 and low bacterial rRNA:rDNA ratios in WM. RNAseq analyses showed a predominance of Proteobacteria in progressive MS patients' WM, associated with increased inflammatory gene expression, relative to a broader range of bacterial phyla in relapsing-remitting MS patients' WM. Although bacterial peptidoglycan (PGN) and RNA polymerase beta subunit immunoreactivities were observed in all patients, PGN immunodetection was correlated with demyelination and neuroinflammation in MS brains. Principal component analysis revealed that demyelination, PGN and inflammatory gene expression accounted for 86% of the observed variance. Thus, inflammatory demyelination is linked to an organ-specific dysbiosis in MS that could contribute to underlying disease mechanisms.

Somatostatin modulates the behavioral effects of dopamine receptor activation in parkinsonian rats.

Somatostatin may play a role in several neuropsychiatric disorders, including Parkinson's disease. Although functional interactions between somatostatinergic and dopaminergic transmitter systems have been well documented, no study has been conducted in animals with experimental Parkinsonism to explore the effects of somatostatin on dopamine receptor-mediated behavior. In the present study, rats with unilateral 6-hydroxydopamine-induced destruction of the medial forebrain bundle were assessed following administration of the dopamine(1/2) receptor agonist apomorphine. Ipsilateral intrastriatal infusion of somatostatin produced a dose-related inhibition of apomorphine-induced rotations with maximal effect at a dose of 7.5 microg in 2 microl. This inhibitory effect of somatostatin was antagonized by the somatostatin antagonist cyclo-somatostatin (0.1 microg in 2 microl, intrastriatally). Neither somatostatin (up to 15 microg in 2 microl) nor cyclo-somatostatin on its own induced rotations; similarly, this dose of cyclo-somatostatin did not affect apomorphine-induced rotations. From these results we suggest that exogenous somatostatin, by directly acting on its specific receptors in the striatum, inhibits the effects of dopamine receptor activation in parkinsonian rats. We conclude that therapies based on modulation of somatostatin may be worth exploring in the management of Parkinson's disease and other disorders of the basal ganglia.

Circadian rhythm in the responsiveness of central 5-HT2A receptor to DOI in rats.

The present study investigated the circadian variation in the behavioral response to the selective 5-HT2A/2C receptor agonist (+/-)-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI). Rats were subcutaneously injected with DOI at 0000, 0400, 0800, 1200, 1600, or 2000 hours. The wet-dog shake (WDS) response was counted following administration of DOI. A circadian rhythm that peaked during the late light period (0400 hours) and reached the lowest point during the late dark period (1600 hours), was observed in the DOI-induced WDS response. In a separate experiment, DOI was administered intra-cerebroventricularly at either 0400 or 1600 hours. The WDS response to the drug at 0400 hours was significantly higher than the response at 1600 hours. These results suggest that the function of the central 5-HT2A receptor exhibits a circadian rhythm.

Circadian and circannual rhythms in the function of central 5-HT1A receptors in laboratory rats.

In order to elucidate whether a circannual rhythm exists in the function of the central serotonin (5-HT) system, we examined the responsiveness of rats to a selective 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), at different hours of the day in different seasons. The results indicate that both a circadian rhythm and a circannual rhythm exist in the responsiveness. The phases of the circadian rhythm exhibit 1-year period variations, while those of the circannual rhythm exhibit 1-day period variations. These results will help to clarify the disparities among the reports on circadian and circannual rhythms in the phenomenon related to the central 5-HT system.

Circadian rhythm in the response of central 5-HT1A receptors to 8-OH-DPAT in rats.

Circadian rhythm in the behavioral responsiveness to the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was studied in rats. Rats were subcutaneously injected with 8-OH-DPAT at one of the following times of day: 0000, 0400, 0800, 1200, 1600, 2000 hours. The post-synaptic 5-HT1A receptor behavioral syndrome, that is, forepaw treading, head weaving, and flat body posture, were measured after the administration of 8-OH-DPAT. Circadian rhythms were found in each of the behavioral responses to 8-OH-DPAT. Peak responses were observed in the mid-dark phase (1200 hours) while the weakest responses were observed in the mid-light phase (0000 hours). In a subsequent experiment, 8-OH-DPAT was administered intracerebroventricularly during the mid-dark phase and the mid-light phase. The behavioral responses to the drug in the mid-dark phase were significantly higher than those in the mid-light phase. These results suggest that the function of central postsynaptic 5-HT1A receptor exhibits circadian rhythm.

Circadian rhythm in the response to intracerebroventricular administration of 8-OH-DPAT.

In a recent study, we observed circadian rhythms in the response to subcutaneous (s.c.) administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a serotonin (5-HT)1A receptor agonist, in rats. Although these results suggested a circadian rhythm in the function of the central 5-HT1A receptor, it was not possible to completely exclude drug disposition as the generating factor. The present study investigated circadian rhythms in the behavioral responses to intracerebroventricular administration of 8-OH-DPAT in rats. The results indicated the existence of circadian rhythms of a similar pattern to those observed in the forepaw treading and head weaving responses to s.c. administration of the drug. The flat body posture response observed following s.c. drug administration was not evident in the present study. These observations suggest that the central postsynaptic 5-HT1A receptor exhibits a circadian rhythm in its function.

The pharmacokinetics of lignocaine in humans during a computer-controlled infusion.

Several types of chronic pain syndromes are effectively treated with sodium channel blockers such as lignocaine. Further investigation of this therapeutic modality would be facilitated by refinement of the parameters describing lignocaine distribution and elimination. This would allow precise lignocaine infusion by a computer-controlled infusion to attain and maintain stable target lignocaine concentrations. Arterial blood samples were obtained at frequent intervals during a computer-controlled infusion of lignocaine in 12 adult human volunteers. Plasma lignocaine concentrations of 1, 2, 3, 4 and 5 microg/ml were targeted for 15 min at each concentration. A three-compartment mammillary pharmacokinetic model best described the resulting concentration vs time profile. A population pharmacokinetic analysis was performed using three different techniques; the two-stage, pooled and mixed effects modelling. There was marked overshoot of the plasma concentration above the target prior to refinement of the pharmacokinetic parameters. The best parameters of a three-compartment mammillary model fit to the measured concentration using the pooled data approach were: V(1) = 7.44, V(2) =11.5 and V(3) = 97.71; Cl(1) = 0.585, Cl(2) = 2.23 and Cl(3) =1.64 l/min. Similarly calculated parameters using NONMEM were V(1) = 6.99, V(2) =12.2 and V(3) =1341; Cl(1) = 0.703, Cl(2) =1.24 and Cl(3) =1.49 l/min. The addition of age as a covariate of the pharmacokinetic parameters improved the model in both cases. Height, lean body mass and body surface area as covariates of the pharmacokinetic parameters did not improve the predicted value of the model. Prospective testing of the pharmacokinetic parameters will be required to define whether they function well. The refinement of pharmacokinetic parameters for the computer-controlled intravenous infusion of lignocaine will facilitate further research in pain therapy. Published lignocaine pharmacokinetic values have a relatively large central volume of distribution, and hence, when implemented as a computer-controlled infusion, result in dramatic overshoot shortly after targeting a higher plasma concentration. In light of the long-lasting pain relief provided by sodium channel blockade in neuropathic pain states, overshoot of plasma concentrations must be avoided if the concentration vs effect relationship is to be defined.

Optical properties of porcine skin dermis between 900 nm and 1500 nm.

The weak absorption of shortwave infrared light by skin tissues between 700 and 1500 nm offers an important window for diagnosis by optical means. The strong scattering of shortwave infrared light by the skin, however, presents a challenge to the modelling of light propagation through the skin and the understanding of skin optics. We have measured the collimated and diffuse transmittance and diffuse reflectance of porcine skin dermis samples within 30 h post-mortem. Monte Carlo simulations have been performed to inversely determine the absorption coefficient, scattering coefficient and anisotropy factor of the dermis samples in the spectral range from 900 to 1500 nm. We further analyse the sensitivity of the values of the parameters to the experimental errors and inverse calculation procedures. The state of the cellular integrity of the skin samples following optical measurements was verified using transmission electron microscopy. These results were correlated to study post-mortem effects on the in vitro optical properties of porcine dermis. We concluded that for samples stored within crushed ice for up to 30 h post-mortem the wavelength dependence of optical properties of the dermis remains unchanged while the values of the parameters vary moderately due to modification of the water content of the tissue.

Circadian rhythm in the hypothermic response to serotonin1A receptor agonist 8-OH-DPAT in rats.

In a recent study, we found a circadian rhythm in the serotonin (5-HT) syndrome (forepaw treading, head weaving, and flat body posture) in the response to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The present study examined the rhythm in the responsiveness to 8-OH-DPAT by observing hypothermia, another index of the 5-HT1A receptor function. Rats standardized to L(1800-0600) : D(0600-1800) were subcutaneously administered with 0.16 mg/kg 8-OH-DPAT at one of the following times of day: 00:00, 04:00, 08:00, 12:00, 16:00, 20:00 h. Two parameters of assessing the hypothermic response, the maximum decrease in temperature after the administration (MAXDT) and the area under the curve of the decrease in temperature (AUCDT), displayed significant circadian rhythms with the peaks in the middark phase (12:00 h). The waveform of the rhythms observed was similar to that of the rhythms that we observed previously in the 5-HT syndrome. The evidence presented here further supports that the central postsynaptic 5-HT1A receptor function exhibits a circadian rhythm.

Radiation dosimetry estimates for the PET serotonin transporter probe 11C-DASB determined from whole-body imaging in non-human primates.

The radiotracer 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile labelled in the N-methyl position (11C-DASB) is a selective radioligand for the in vivo quantification of serotonin transporters (SERTs) using positron emission tomography (PET). The current study quantified the distribution of activity in two rhesus monkeys after the injection of approximately 333 MBq (9 mCi) 11C-DASB. Whole-body images were acquired at 22 time points for a total of 120 min following injection of the radioligand. Source organs were identified at each time point from both tomographic images (using multiple regions of interest on each tomograph for each organ) and a single planar image (using a single region of interest for each organ). The peak activities in planar images in the five identified source organs (expressed as per cent injected dose (ID)) were lungs (24% ID at 1.5 min), kidneys (6.5% ID at 4 min), liver (8% ID at 3 min), brain (4% ID at 5 min) and spleen (0.42% ID at 3 min). Mono-exponential fitting of activity overlying the bladder suggested that approximately 14% of activity was excreted via the urine. The radiation burden to the body was calculated from residence times of these source organs and then scaled to corresponding human values. The calculated effective dose from tomographic and planar images was 6.0 and 6.4 microGy x MBq(-1) (22.3 and 23.7 mrad x mCi(-1)), respectively. The planar analysis was much easier to perform, and generally yielded slightly higher (i.e., more conservative) estimates of radiation burden than the tomographic analysis. The estimated radiation burden of 11C-DASB is relatively modest and would allow multiple scans per research subject per year.

[Establishment of the human stomach poorly-differentiated adenocarcinoma (PdGC-81) cell line and its biological character].

The gastric cancer specimen was obtained from a female patient, 65 years old. The metastatic node in the greater omentum, demonstrated by pathology as a poorly-differentiated adenocarcinoma, was cut into small cubes (1 mm3) and cultured. The human stomach poorly-differentiated adenocarcinoma cell line (PdGC-81) was thus established. It had been transferred for 83 generations during 13 months. This cell line showed the following characters: 1. The pathological features of the tumor transplanted in mice was similar to that of the original inoculated lesion. 2. Microscopically, the majority of the cells were elliptical and polygonal epithelial cells with abnormal mitotic figures and 2-4 nucleoli. 3. Electronmicroscopically, there were rich microvilli on the surface of the cells. Desmosomes and abundant ribosomes were also observed. 4. The growth curves of the 33rd and 65th passages were determined. They multiplied 23 and 21 times within 8 days, the doubling times were 41.4 and 43.4 hours. The mitotic indexes attained their peak on day 3 in 33rd passage (80.5%) and on day 4 in 65th passage (72%). 5. The numbers of the chromosomes ranged from 56 to 60. This cell line may be considered as the subtriploid.