A brainstem peptide system activated at birth protects postnatal breathing.

Among numerous challenges encountered at the beginning of extrauterine life, the most celebrated is the first breath that initiates a life-sustaining motor activity1. The neural systems that regulate breathing are fragile early in development, and it is not clear how they adjust to support breathing at birth. Here we identify a neuropeptide system that becomes activated immediately after birth and supports breathing. Mice that lack PACAP selectively in neurons of the retrotrapezoid nucleus (RTN) displayed increased apnoeas and blunted CO2-stimulated breathing; re-expression of PACAP in RTN neurons corrected these breathing deficits. Deletion of the PACAP receptor PAC1 from the pre-Bötzinger complex-an RTN target region responsible for generating the respiratory rhythm-phenocopied the breathing deficits observed after RTN deletion of PACAP, and suppressed PACAP-evoked respiratory stimulation in the pre-Bötzinger complex. Notably, a postnatal burst of PACAP expression occurred in RTN neurons precisely at the time of birth, coinciding with exposure to the external environment. Neonatal mice with deletion of PACAP in RTN neurons displayed increased apnoeas that were further exacerbated by changes in ambient temperature. Our findings demonstrate that well-timed PACAP expression by RTN neurons provides an important supplementary respiratory drive immediately after birth and reveal key molecular components of a peptidergic neural circuit that supports breathing at a particularly vulnerable period in life.

The astrocytic Na+ -HCO3 - cotransporter, NBCe1, is dispensable for respiratory chemosensitivity.

The interoceptive homeostatic mechanism that controls breathing, blood gases and acid-base balance in response to changes in CO2 /H+ is exquisitely sensitive, with convergent roles proposed for chemosensory brainstem neurons in the retrotrapezoid nucleus (RTN) and their supporting glial cells. For astrocytes, a central role for NBCe1, a Na+ -HCO3 - cotransporter encoded by Slc4a4, has been envisaged in multiple mechanistic models (i.e. underlying enhanced CO2 -induced local extracellular acidification or purinergic signalling). We tested these NBCe1-centric models by using conditional knockout mice in which Slc4a4 was deleted from astrocytes. In GFAP-Cre;Slc4a4fl/fl mice we found diminished expression of Slc4a4 in RTN astrocytes by comparison to control littermates, and a concomitant reduction in NBCe1-mediated current. Despite disrupted NBCe1 function in RTN-adjacent astrocytes from these conditional knockout mice, CO2 -induced activation of RTN neurons or astrocytes in vitro and in vivo, and CO2 -stimulated breathing, were indistinguishable from NBCe1-intact littermates; hypoxia-stimulated breathing and sighs were likewise unaffected. We obtained a more widespread deletion of NBCe1 in brainstem astrocytes by using tamoxifen-treated Aldh1l1-Cre/ERT2;Slc4a4fl/fl mice. Again, there was no difference in effects of CO2 or hypoxia on breathing or on neuron/astrocyte activation in NBCe1-deleted mice. These data indicate that astrocytic NBCe1 is not required for the respiratory responses to these chemoreceptor stimuli in mice, and that any physiologically relevant astrocytic contributions must involve NBCe1-independent mechanisms. KEY POINTS: The electrogenic NBCe1 transporter is proposed to mediate local astrocytic CO2 /H+ sensing that enables excitatory modulation of nearby retrotrapezoid nucleus (RTN) neurons to support chemosensory control of breathing. We used two different Cre mouse lines for cell-specific and/or temporally regulated deletion of the NBCe1 gene (Slc4a4) in astrocytes to test this hypothesis. In both mouse lines, Slc4a4 was depleted from RTN-associated astrocytes but CO2 -induced Fos expression (i.e. cell activation) in RTN neurons and local astrocytes was intact. Likewise, respiratory chemoreflexes evoked by changes in CO2 or O2 were unaffected by loss of astrocytic Slc4a4. These data do not support the previously proposed role for NBCe1 in respiratory chemosensitivity mediated by astrocytes.

[Development of Nasal Continuum Minimally Invasive Surgical Robot System].

In order to improve the operation difficulties in the narrow space of the nasal maxillary sinus, the nasal continuum minimally invasive surgical robot system is designed. The ball-and-socket joints and NiTiNol tubes are used as the main body of the continuum structure to improve the degree of freedom. The hardware systems and software systems are designed. The security control policies are planned. Finally, the robot confirmed prototype experiments are conducted and the feasibility of continuum robot confirmed through master-slave control experiment and animal experiment.

Clinical characteristics, risk factors, immune status and prognosis of secondary infection of sepsis: a retrospective observational study.

BACKGROUND: Secondary infection has a higher incidence in septic patients and affects clinical outcomes. This study aims to investigate the clinical characteristics, risk factors, immune status and prognosis of secondary infection of sepsis. METHODS: A four-year retrospective study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between January, 2014 and January, 2018. Clinical data were acquired from medical records. CD14+ monocyte human leukocyte antigen-D related (HLA-DR) expression and serum cytokines levels were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA) respectively. RESULTS: A total of 297 septic patients were enrolled, 92 of whom developed 150 cases of secondary infections. Respiratory tract was the most common site of secondary infection (n = 84, 56%) and Acinetobacter baumanii the most commonly isolated pathogen (n = 40, 31%). Urinary and deep venous catheterization increased the risk of secondary infection. Lower HLA-DR expression and elevated IL-10 level were found in secondary infection group. The expected prolonged in-hospital stay owing to secondary infection was 4.63 ± 1.87 days. Secondary infection was also associated with higher in-hospital, 30-day and 90-day mortality. Kaplan-Meier survival analysis and Log-rank test revealed that secondary infection group had worse survival between day 15 and day 90. CONCLUSIONS: Urinary and deep venous catheterization increased the risk of secondary infection, in which underlying immunosuppression might also play a role. Secondary infection affected the prognosis of septic patients and prolonged in-hospital length of stay.

Clinical characteristics and prognosis of serous body cavity effusions in patients with sepsis: a retrospective observational study.

BACKGROUND: Cavity effusion is common in patients with infectious diseases. However, the incidence rate and characteristics of serous cavity effusions (SCE) in septic patients are not clear to date. The objective of this study was to investigate the incidence and characteristics of SCE in septic patients and to explore the correlations between the bloody effusions and the illness severity/prognosis in septic patients. METHODS: From January 2010 to January 2015, a total of 214 patients with severe sepsis and septic shock were enrolled in this retrospective observational study. Thoracentesis or abdominal paracentesis was performed in 45 septic patients because of massive pleural effusions or ascites. The serum concentrations of VEGF, VEGFR, Ang, sICAM-1, sVCAM-1, E-selectin, Serpine1 and VE-cadherin in 45 septic patients underwent paracentesis were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Of the 214 septic patients, 155 (72.4%) had SCE according to imaging or ultrasound manifestations. 45 subjects with SCE underwent therapeutic thoracentesis or abdominal paracentesis. Effusion laboratory analysis showed that exudates were predominant when compared with transudates (95.6% vs. 4.4%), and 16 (35.6%) patients suffered bloody effusions. Compared with patients with non-bloody effusions, those with bloody effusions showed higher critical illness scores (13 vs. 17 for APACHE II; 7 vs. 9 for SOFA), and higher mortality (6.9% vs. 62.5%). Moreover, patients with bloody effusions had delayed TT and APTT, increased D-dimer concentration, and higher serum levels of CRP and PCT (P < 0.05). In addition, the serum levels of Ang2, sVCAM-1 and E-selectin were significantly higher in patients with bloody effusions than in those with non-bloody effusions (P < 0.05). However, the serum level of VEGFR2 was lower in patients with bloody fluids (P = 0.025). CONCLUSIONS: The incidence of serous cavity effusion is high in patients with sepsis. The septic patients with bloody effusions suffer a more inflammatory burden and a worse prognosis compared to septic patients with non-bloody effusions.

Electrical stimulation characteristics of denervated orbicularis oculi muscle.

This research is to study the electrical stimulation characteristics of orbicularis oculi muscle and the characteristics of the mechanical contraction. We observed the stimulus current diffusion regularity and its relationship with mechanical contraction in the orbicularis oculi muscle using an electrode gathering line. Under different stimulus intensities of 2 or 4 mA, the closer the recording electrodes were to the stimulating electrode, the larger was the amplitude. When the recording electrode and stimulating electrode distance increased, the amplitude declined linearly with decreasing function. In addition, current conduction across the muscle fiber was studied. Under different stimulus intensities of 2 or 4 mA, it was found that the closer the recording electrodes were to the stimulating electrode, the larger was the amplitude. When the recording electrode and stimulating electrode distance increased, the amplitude declined linearly with decreasing function. The transverse current reached a maximum 4 mA range, and increasing the current intensity did not increase the propagation range. Under different stimulation intensities, the larger the stimulus intensity, the greater is the potential change and the faster is the attenuation. Longitudinal current, even in the range of 6 mm, can still record electrical activity. While a transverse current diffuser has a maximum range of 4 mm, increasing the current intensity does not increase the propagation range.

Meta-analysis of the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese.

Glutathione S-transferase T1 (GSTT1) null genotype has been proven to be associated with risks of many cancers. There were also many studies assessing on the association between GSTT1 null genotype and nasopharyngeal carcinoma risk in Chinese, but the findings from those studies were inconsistent. We performed a meta-analysis to provide a more precise assessment on the effect of GSTT1 null genotype on nasopharyngeal carcinoma risk. The PubMed and Wanfang databases were searched to identify eligible case-control studies on the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese. The pooled odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were used to assess the association. Eight case-control studies with a total of 3,702 individuals were finally included in the meta-analysis. Meta-analysis of a total of eight studies showed that GSTT1 null genotype was significantly associated with increased risk of nasopharyngeal carcinoma in Chinese (OR = 2.27; 95% CI 1.41-3.67; P = 0.001). The finding from cumulative meta-analysis showed that there was a trend of more obvious association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese as data accumulated by publication year. Therefore, the GSTT1 null genotype is significantly associated with increased risk of nasopharyngeal carcinoma in Chinese.

Liver-Selective Imidazolopyrazine Mitochondrial Uncoupler SHD865 Reverses Adiposity and Glucose Intolerance in Mice.

Excess body fat is a risk factor for metabolic diseases and is a leading preventable cause of morbidity and mortality worldwide. There is a strong need to find new treatments that decrease the burden of obesity and lower the risk of obesity-related comorbidities, including cardiovascular disease and type 2 diabetes. Pharmacologic mitochondrial uncouplers represent a potential treatment for obesity through their ability to increase nutrient oxidation. Herein, we report the in vitro and in vivo characterization of compound SHD865, the first compound to be studied in vivo in a newly discovered class of imidazolopyrazine mitochondrial uncouplers. SHD865 is a derivative of the furazanopyrazine uncoupler BAM15. SHD865 is a milder mitochondrial uncoupler than BAM15 that results in a lower maximal respiration rate. In a mouse model of diet-induced adiposity, 6-week treatment with SHD865 completely restored normal body composition and glucose tolerance to levels like those of chow-fed controls, without altering food intake. SHD865 treatment also corrected liver steatosis and plasma hyperlipidemia to normal levels comparable with chow-fed controls. SHD865 has maximal oral bioavailability in rats and slow clearance in human microsomes and hepatocytes. Collectively, these data identify the potential of imidazolopyrazine mitochondrial uncouplers as drug candidates for the treatment of obesity-related disorders.

Transient outwardly rectifying A currents are involved in the firing rate response to altered CO2 in chemosensitive locus coeruleus neurons from neonatal rats.

The effect of hypercapnia on outwardly rectifying currents was examined in locus coeruleus (LC) neurons in slices from neonatal rats [postnatal day 3 (P3)-P15]. Two outwardly rectifying currents [4-aminopyridine (4-AP)-sensitive transient current and tetraethyl ammonium (TEA)-sensitive sustained current] were found in LC neurons. 4-AP induced a membrane depolarization of 3.6 ± 0.6 mV (n = 4), while TEA induced a smaller membrane depolarization of 1.2 ± 0.3 mV (n = 4). Hypercapnic acidosis (HA) inhibited both currents. The maximal amplitude of the TEA-sensitive current was reduced by 52.1 ± 4.5% (n = 5) in 15% CO2 [extracellular pH (pHo) 7.00, intracellular pH (pHi) 6.96]. The maximal amplitude of the 4-AP-sensitive current was reduced by 34.5 ± 3.0% (n = 6) in 15% CO2 (pHo 7.00, pHi 6.96), by 29.4 ± 6.8% (n = 6) in 10% CO2 (pHo 7.15, pHi 7.14), and increased by 29.0 ± 6.4% (n = 6) in 2.5% CO2 (pHo 7.75, pHi 7.35). 4-AP completely blocked hypercapnia-induced increased firing rate, but TEA did not affect it. When LC neurons were exposed to HA with either pHo or pHi constant, the 4-AP-sensitive current was inhibited. The data show that the 4-AP-sensitive current (likely an A current) is inhibited by decreases in either pHo or pHi. The change of the A current by various levels of CO2 is correlated with the change in firing rate induced by CO2, implicating the 4-AP-sensitive current in chemosensitive signaling in LC neurons.

Parylene-based implantable platinum-black coated wire microelectrode for orbicularis oculi muscle electrical stimulation.

A novel and simple process was proposed to fabricate a parylene-based platinum-black coated wire microelectrode for orbicularis oculi muscle electrical stimulation. Compared with conventional microelectrodes, wire microelectrodes would enable smaller wounds, increased ease of implantation, and improved cosmesis. Meanwhile, the circumferential electrode sites of this wire microelectrode fabricated by lift-off process would contribute to fully contact with tissue and reduction of electrode-tissue interface impedance. The width and the amount of electrode sites could be decided by the thickness and the amount of sacrificial layer, respectively. The platinum-black coatings were electroplated on electrode sites by applying a current pulse train in chloroplatinic acid solution with ultrasonic bath for further electrode-tissue interface impedance reduction and good mechanical stability of coatings. Electrode impedance at 1 kHz has been significantly reduced by 90%, and the cathodic charge storage capacity (CSCc) has been increased by 13 times. In addition, hematoxylin-eosin (HE) staining section of muscle demonstrated the good biocompatibility of this electroplated platinum-black. By applying a charge imbalanced biphasic stimulation waveform for orbicularis oculi muscle stimulation, the rabbits with facial paralysis rehabilitated the function of closing eyes. This kind of microelectrode will be promising for neuromuscular applications.

Development and experiments of a continuum robotic system for transoral laryngeal surgery.

PURPOSE: Currently, self-retaining laryngoscopic surgery is not suitable for some patients, and there are dead zones relating to surgical field exposure and operation. The quality of the surgery can also be affected by the long periods of time required to complete it. Teleoperated continuum robots with flexible joints are expected to solve these issues. However, at the current stage of developing transoral robotic surgery systems, their large size affects the precision of surgical operative actions and there are high development and treatment costs. METHODS: We fabricated a flexible joint based on selective laser melting technology and designed a shallow neural network-based kinematic modeling approach for a continuum surgical robot. Then, human model and animal experiments were completed by master-slave teleoperation to verify the force capability and dexterity of the robot, respectively. RESULTS: As verified by human model and animal experiments, the designed continuum robot was demonstrated to achieve transoral laryngeal surgical field exposure without laryngoscope assistance, with sufficient load capability to finish the biopsy of vocal fold tissue in living animals. CONCLUSION: The designed continuum robotic system allows the biopsy of vocal fold tissue without laryngoscope assistance. Its stiffness and dexterity indicate the system's potential for applications in the diagnosis and treatment of vocal fold nodules and polyps. The limitations of this robotic system as shown in the experiments were also analyzed.

Development and validation of a two-segment continuum robot for maxillary sinus surgery.

BACKGROUND: Existing rigid instruments have difficulties in backward inspection and operation. Moreover, the pathway to the maxillary sinus is curved and narrow, resulting in complex and repetitive manual operations. There is a necessity to develop a retro-flexing robot and achieve path-following motion. METHODS: A continuum robotic system is developed for maxillary sinus surgery (MSS). And the system adopts an anatomical constraint-based optimization of the follow-the-leader strategy to generate a safe control scheme along a given path. RESULTS: The accuracy of the system is evaluated, and the task of reaching deep-seated targets is performed in a constrained anatomical space. The simulations and experiments of the path-following motion have validated the feasibility of the proposed method. Furthermore, a preliminary porcine study is performed to assess the capability of instruments. CONCLUSIONS: The developed continuum robotic system can meet the requirements of MSS.

Changes in the levels of DNA methylation in testis and liver of SD rats neonatally exposed to 5-aza-2'-deoxycytidine and cadmium.

To investigate the changes in the levels of DNA methylation in the testis during development after neonatal transient exposure to DNA methyltransferase (DNMT) inhibitors, we orally administered Sprague-Dawley (SD) rats with 5-aza-2'-deoxycytidine (5-aza-CdR; 0.025 or 0.25 mg kg(-1)) or cadmium (Cd; 1, 2 or 4 mg kg(-1)) daily from days 3-7 postpartum (pp). Sperm numbers decreased at day 70 pp in all exposure groups. We then used a PCR-based assay, combined bisulfite restriction analysis (COBRA) and pyrosequencing to determine the degrees of DNA methylation. Both 5-aza-CdR and Cd reduced DNMT activity in vivo after 5 days' exposure at day 8 pp but not at day 70 pp. In contrast, the DNA methylation level of LINE-1 was not changed in the testis, either at day 8 pp or at day 70 pp. We observed increased apoptosis and an increase in the p53 mRNA level, accompanied by a decreased DNA methylation level in the p53 gene promoter region, at day 8 pp in testis for the 5-aza-CdR-exposed groups but not in the Cd-exposed group. The Cd-exposed group exhibited a degradation of seminiferous tubules and inhibition of a stepwise change in methylation in the coding region of c-fos in testis at day 70 pp. Because we observed toxic phenotype development accompanied by aberrant DNA methylation, DNA methylation may play a role in chemical induced testis damage, with different DNMT inhibitors affecting DNA methylation levels in gene- or stage-specific manner.

TRPM4 Contributes to Subthreshold Membrane Potential Oscillations in Multiple Mouse Pacemaker Neurons.

Select neuronal populations display steady rhythmic neuronal firing that provides tonic excitation to drive downstream networks and behaviors. In noradrenergic neurons of the locus coeruleus (LC), circadian neurons of the suprachiasmatic nucleus (SCN), and CO2/H+-activated neurons of the brainstem retrotrapezoid nucleus (RTN), large subthreshold membrane potential oscillations contribute to the pacemaker-like action potential discharge. The oscillations and firing in LC and SCN involve contributions from leak sodium (NALCN) and L-type calcium channels while recent work from RTN suggested an additional pivotal role for a secondary calcium-activated and voltage-gated cationic current sensitive to TRPM4 channel blockers. Here, we tested whether TRPM4 contributes to subthreshold oscillations in mouse LC and SCN. By RNAscope in situ hybridization, Trpm4 transcripts were detected in both cell groups. In whole-cell recordings from acute slice preparations, prominent voltage-dependent membrane potential oscillations were revealed in LC and SCN after blocking action potentials. These oscillations were inhibited by two chemically-distinct blockers of TRPM4, 9-phenanthrol (9-pt) and 4-chloro-2-[[2-(2-chlorophenoxy)acetyl]amino]benzoic acid (CBA). Under whole-cell voltage clamp, inward currents evoked by oscillation voltage waveforms were inhibited in LC by blocking L-type calcium channels and TRPM4. These data implicate TRPM4 in the large subthreshold membrane potential oscillations that underlie tonic action potential discharge in LC and SCN, providing a voltage-dependent and calcium-dependent cationic current to augment the depolarizing inward Na+ and Ca2+ currents previously associated with this distinctive electroresponsive property.

TRPM4 mediates a subthreshold membrane potential oscillation in respiratory chemoreceptor neurons that drives pacemaker firing and breathing.

Brainstem networks that control regular tidal breathing depend on excitatory drive, including from tonically active, CO2/H+-sensitive neurons of the retrotrapezoid nucleus (RTN). Here, we examine intrinsic ionic mechanisms underlying the metronomic firing activity characteristic of RTN neurons. In mouse brainstem slices, large-amplitude membrane potential oscillations are evident in synaptically isolated RTN neurons after blocking action potentials. The voltage-dependent oscillations are abolished by sodium replacement; blocking calcium channels (primarily L-type); chelating intracellular Ca2+; and inhibiting TRPM4, a Ca2+-dependent cationic channel. Likewise, oscillation voltage waveform currents are sensitive to calcium and TRPM4 channel blockers. Extracellular acidification and serotonin (5-HT) evoke membrane depolarization that augments TRPM4-dependent oscillatory activity and action potential discharge. Finally, inhibition of TRPM4 channels in the RTN of anesthetized mice reduces central respiratory output. These data implicate TRPM4 in a subthreshold oscillation that supports the pacemaker-like firing of RTN neurons required for basal, CO2-stimulated, and state-dependent breathing.

Achieving reliability and high accuracy in automated protein docking: ClusPro, PIPER, SDU, and stability analysis in CAPRI rounds 13-19.

Our approach to protein-protein docking includes three main steps. First, we run PIPER, a rigid body docking program based on the Fast Fourier Transform (FFT) correlation approach, extended to use pairwise interactions potentials. Second, the 1000 best energy conformations are clustered, and the 30 largest clusters are retained for refinement. Third, the stability of the clusters is analyzed by short Monte Carlo simulations, and the structures are refined by the medium-range optimization method SDU. The first two steps of this approach are implemented in the ClusPro 2.0 protein-protein docking server. Despite being fully automated, the last step is computationally too expensive to be included in the server. When comparing the models obtained in CAPRI rounds 13-19 by ClusPro, by the refinement of the ClusPro predictions and by all predictor groups, we arrived at three conclusions. First, for the first time in the CAPRI history, our automated ClusPro server was able to compete with the best human predictor groups. Second, selecting the top ranked models, our current protocol reliably generates high-quality structures of protein-protein complexes from the structures of separately crystallized proteins, even in the absence of biological information, provided that there is limited backbone conformational change. Third, despite occasional successes, homology modeling requires further improvement to achieve reliable docking results.

Influence of persistent thyroxine reduction on spermatogenesis in rats neonatally exposed to 2,2',4,4',5,5'-hexa-chlorobiphenyl.

BACKGROUND: The aim of the present study is to determine the long-term testicular effects of neonatal exposure to PCB153. METHODS: Sprague-Dawley (SD) rats were treated by oral gavage with PCB153 in corn oil at doses of 0, 0.025, and 2.5 mg/kg per day from postnatal day 3 (PND 3) to PND7. The rats were sacrificed on PND 8 and PND 77. TUNEL in situ detection for testis apoptosis, immunohistochemical staining of thyroid gland for thyroxine (T4), semi-quantitative RT-PCR for mRNA expression, and radioimmunoassay (RIA) for serum hormone levels were performed. RESULTS: Neonatal treatment with PCB153 at both doses had no obvious effects on body weight, testis weight, testis histology, and germ cell apoptosis, but decreased T4 staining in thyroid gland was observed on PND 8. On PND 77, neonatal treatment with 2.5 mg/kg per day of PCB153 significantly reduced daily sperm product (DSP). Serum levels of thyroxine (T4) and free thyroxine (FT4) decreased, but there were no differences in thyroid-stimulating hormone (TSH) level between the control and exposed groups. Gap junction connexin43 (CX43) and cyclin-dependent kinase inhibitor (CDKI) P27kip1 mRNA expression, which was associated with Sertoli cell differentiation, was significantly reduced after PCB153 treatment on PND 8 but not on PND 77. Androgen-binding protein (ABP) and androgen receptor (AR) mRNA expression, which indicates Sertoli cell maturation, was suppressed on PND 77 after neonatal PCB153 exposure. CONCLUSIONS: The findings in this study suggest that neonatal exposure to PCB153 induces persistent T4 reduction, which disturbs Sertoli cell function, and subsequently results in alterations in adult spermatogenesis. Birth Defects Res (Part B) 89:18-25, 2010. (c) 2009 Wiley-Liss, Inc.

[Toxic effect of neonatal exposure to 2,2',4,4',5,5'-hexa-chlorobiphenyl on spermatogenesis in rats].

OBJECTIVE: To determine the long-term testicular effect after neonatal exposure to 2,2', 4,4',5,5'-hexa-chlorobiphenyl (PCB153). METHODS: On birth day (Postnatal day 0, PNDO), the Sprague-Dawley (SD) male rats were mixed together and divided into 12 pups/litter. At PND1, the rats were grouped randomly into control and treatment groups according to different litters, 24 pups/group. They were treated by oral gavage with PCB153 in corn oil at doses of 0, 0.025, 0.250 and 2.500 mg/kg BW-day from PNDI to PND7. The rats were sacrificed at PND8 and PND90 by anesthesia. The testes were collected and weighed for histological examination and daily sperm production at PND8 or/and PND90. The epididymidis and the epididymidis cauda also were collected and weighed for determination the sperm counts at PND90. RESULTS: The body weight of 2.500 mg/kg dose group was decreased significantly from PND3 to PND8 compared with that of control (P < 0.05). At PND8, the loose structure in seminiferous cord and the spermatogonia with enlarged volume and detached from the cord were observed in 2.500 mg/kg dose group by light microscope and electronic microscopy. With the increase of exposure doses, the testicular daily sperm production (DSP) and the sperm counts of epididymidis cauda were decreased in dose-dependent manner at PND90. The DSP in 0.250 mg/kg [30 x 10(6)/testis(g)] and 2.500 mg/kg [18 x l0(6)/testis(g)] dose groups were significantly reduced compared with that of control [36 x 10(6)/testis(g)] (P < 0.05). And there was a significant reduction in the sperm counts of epididymidis cauda in 0.250 mg/kg [42 x 10(7)/epididymidis cauda (g)] and 2.500 mg/kg [18 x 10(7)/epididymidis cauda (g)] dose groups compared with that of control [51 x 10(7)/epididymidis cauda (g)] (P < 0.05). CONCLUSIONS: The spermatogenesis of adult testis is disturbed, which causes the decrease in the testicular DSP and the sperm counts of epididymidis cauda after neonatal exposure to PCB153. The long-term damage in male reproductive function is caused by neonatal exposure to chemicals.

Clinical characteristics and prognosis of community-acquired pneumonia in autoimmune disease-induced immunocompromised host: A retrospective observational study.

BACKGROUND: Community-acquired pneumonia (CAP) in autoimmune diseases (AID)-induced immunocompromised host (ICH) had a high incidence and poor prognosis. However, only a few studies had determined the clinical characteristics of these patients. Our study was to explore the characteristics and predictors of mortality in CAP patients accompanied with AID-induced ICH. METHODS: From 2013 to 2018, a total of 94 CAP patients accompanied with AID-induced ICH, admitted to Emergency Department of Zhongshan Hospital, Fudan University, were enrolled in this study. Clinical data and the risk regression estimates of repeated predictors were evaluated by generalized estimating equations (GEEs) analysis. An open-cohort approach was used to classify patient's outcomes into the survival or non-survival group. RESULTS: The hospital mortality of patients with CAP occurring in AID-induced ICH was 60.64%. No significant differences were found with respect to clinical symptoms and lung images between survival and non-survival groups, while renal insufficiency and dysfunction of coagulation had higher proportions in non-survival patients (P<0.05). Both noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) were performed more frequently in non-survival group (P< 0.05). By the multivariate GEEs analysis, the repeated measured longitudinal indices of neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR]=1.055, 95% confidence interval [95%CI] 1.025-1.086), lactate dehydrogenase (LDH) (OR=1.004, 95%CI 1.002-1.006) and serum creatinine (sCr) (OR=1.018, 95%CI 1.008-1.028), were associated with a higher risk of mortality. CONCLUSION: The CAP patients in AID-induced ICH had a high mortality. A significant relationship was demonstrated between the factors of NLR, LDH, sCr and mortality risk in these patients.