Successful treatment of auto-trilevel positive airway pressure plus trazodone for obstructive sleep apnea complicated by anxiety disorder: a case report.

Obstructive sleep apnea (OSA) is a highly prevalent type of sleep-disordered breathing, which is often comorbid with affective disorders such as anxiety. A 61-year-old woman who was diagnosed with OSA affected by anxiety disorder complained of poor sleep quality at night and anxiety symptoms, and showed chest tightness, dyspnea, snoring, and apnea events during sleep. The patient initially received treatment with positive airway pressure (PAP) combined with trazodone, and subsequently switched to auto-trilevel PAP (AtPAP) combined with trazodone therapy. The initial attempt to treat the patient's disease by auto-adjusting PAP combined with trazodone failed because of central sleep apnea (CSA), which frequently occurred at night. After switching to AtPAP combined with trazodone therapy, CSA was effectively eliminated. In addition, sleep quality, hypoxia, and anxiety disorders were improved. The first report of successful therapy of AtPAP combined with trazodone for OSA complicated by anxiety disorder provides a new therapeutic strategy for this patient population.

T cell receptor repertoire as a novel indicator for identification and immune surveillance of patients with severe obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is the most prevalent sleep disturbance that affects approximately 936 million people worldwide and leads to extensively increased incidence of cardiovascular disease, metabolic syndrome, neurological disorders, and traffic accidents. Severe OSA patients suffer a significantly higher risk of complications and worse comorbidity outcomes. Notwithstanding, with inadequate access to contact diagnosis based on polysomnography (PSG), numerous patients with severe sleep apnea have not been diagnosed, especially during the pandemic. Moreover, how the T cell immunity is impaired in OSA remains largely unknown. Methods: We primarily investigated the T cell receptor (TCR) repertoires of 50 patients with severe OSA, 23 patients with mild-to-moderate OSA, 23 patients without OSA, and 157 healthy individuals, from their peripheral blood. Firstly, we compared the clinical characteristics, blood cell counts, the ratio of neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and CD4+/CD8+T cell count between groups. Then, we compared the diversity, clonotypes, unique VJ alleles in patients with different disease severity. Furthermore, by identifying a series of disease-associated amino acid sequences, we employed a repeated hold-out machine learning strategy to explore the optimal algorithm for calculating the TCR repertoire characteristic Index (OSA-TCI). We further confirmed its relation with clinical features by linear regression analysis. Moreover, in followup of severe OSA patients who accepted adherent non-invasive ventilation, we assessed the changes of TCR repertoires, OSA-TCI, ESS, NLR, PLR, and CD4+/CD8+T after therapy. Results: We found an unexpected increase in diversity and clonotypes in the TCR repertoire of OSA patients. Furthermore, we successfully developed a novel indicator termed OSA-TCI to summarize the unique repertoire alteration, which provided 90% of sensitivity and 87% of specificity in distinguishing severe OSA. In rationalization, OSA-TCI was found correlated to AHI, BMI, hemoglobin, N1, N2 percentage of sleep, snoring, smoking and lowest oxygen saturation, but only independently related to AHI (R = 0.603) and smoking (R = 0.22). Finally, we observed OSA-TCI in the eight severe patients decreased significantly after home noninvasive ventilation for three months during follow-up, consistently in line with the TCR repertoire improvement. In contrast, NLR, PLR, and the ratio of CD4+/CD8+T cell count were found useless to diagnose and therapeutic surveillance of severe OSA. Conclusions: Our study is the first to unveil the TCR repertoire alteration in OSA, indicates possible insidious autoimmune mechanisms underlying OSA, and suggests that TCR repertoires serve as a convenient peripheral blood biomarker for OSA assessment without long-time contact and facility/instrument occupation. It may shed light on future diagnostic, immunological, pathophysiological, and prognostic research on OSA.

Development and Validation of a Diagnostic Nomogram for Pneumocystis jirovecii Pneumonia in Non-HIV-Infected Pneumonia Patients Undergoing Oral Glucocorticoid Treatment.

Purpose: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic but potentially fatal infection with increasing prevalence in HIV-free patients. Glucocorticoid therapy is one of the most important risk factors for PJP. The delay in diagnosis contributes to poor outcomes. Hence, the aim of this study was to develop and validate a nomogram for the diagnosis of PJP in patients with non-HIV-infected pneumonia who are undergoing oral glucocorticoid treatment. Patients and Methods: This study was a retrospective, cross-sectional research. The development group included 434 patients who were admitted with pneumonia from 6 hospitals. Demographics, symptomatic features, laboratory and computed tomography data were analyzed using the least absolute shrinkage and selection operator (LASSO) to select potential diagnostic indicators. Binary logistic regression was used to develop a diagnostic nomogram. Another 119 patients with pneumonia admitted at Sichuan Provincial People's Hospital was used as the validation group. The diagnostic performance of the nomogram was measured by area under the receiver-operating-characteristics curve (AUC), calibration curves, and the net benefit by decision curve. Results: PJP prevalence was 25.3% in the development group. LASSO regression revealed that age, lymphocyte count, fever, dry cough, respiratory failure, ground-glass opacity in lungs, glucocorticoid therapy duration, and immunosuppressive therapy were indicators of PJP. The nomogram showed robust discrimination, with an AUC of 0.82 (95% CI 0.77-0.86) in the development group and an AUC of 0.87 (95% CI 0.80-0.94) in the validation group, both showing acceptable calibration. In the decision curve analysis, our model consistently achieved a greater net benefit across almost all ranges of clinical thresholds. Conclusion: We developed a nomogram with good diagnostic power for PJP diagnosis in pneumonia patients receiving oral glucocorticoids. This nomogram may help promote timely treatment of PJP and thus reduce the mortality rate in these patients.

Analysis of TUBB4A gene variant in a patient with adolescent-onset hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a patient with adolescent-onset hypomyelinated leukodystrophy with atrophy of basal ganglia and cerebellum (H-ABC).@*METHODS@#A patient who was diagnosed with H-ABC in March 2018 at the First Affiliated Hospital of Nanjing Medical University was selected as the study subject. Clinical data was collected. Peripheral venous blood samples of the patient and his parents were collected. The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.@*RESULTS@#The patient, a 31-year-old male, had manifested with developmental retardation, cognitive decline and abnormal gait. WES revealed that he has harbored a heterozygous c.286G>A variant of the TUBB4A gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Analysis with SIFT online software indicated the amino acid encoded by this variant is highly conserved among various species. This variant has been recorded by the Human Gene Mutation Database (HGMD) with a low population frequency. The 3D structure constructed by PyMOL software showed that the variant has a harmful effect on the structure and function of the protein. According to the guidelines formulated by the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic.@*CONCLUSION@#The c.286G>A (p.Gly96Arg) variant of the TUBB4A gene probably underlay the hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum in this patient. Above finding has enriched the spectrum of TUBB4A gene variants and enabled early definitive diagnosis of this disorder.

Case Report: Successful Treatment of Pulmonary Talaromyces marneffei Infection with Posaconazole in a Renal Transplant Recipient.

Talaromyces marneffei (T. marneffei), formerly Penicillium marneffei, is a dimorphic fungus prevalent in Southeast Asia that can cause severe systemic infection, especially in immunocompromised patients. There are few reports about the use of posaconazole in T. marneffei infection. Here, we present a case of pulmonary T. marneffei infection in a renal transplant recipient. The patient responded rapidly to oral posaconazole administration but experienced serum creatinine fluctuation because of the interaction between posaconazole and immunosuppressants. Seven months after adjusting the dose of immunosuppressants, the patient recovered completely. Posaconazole is a potentially promising therapy for T. marneffei infection, but it should be administered under close monitoring.

Association between Working Hours and Anxiety/Depression of Medical Staff during Large-Scale Epidemic Outbreak of COVID-19: A Cross-Sectional Study.

OBJECTIVE: This present study aimed to investigate the relationship between working hours and anxiety/depression mood of medical staff in China during COVID-19 epidemic. METHODS: The cross-sectional interview study was conducted during the period between February 14th and February 29th, 2020. A total of 291 Chinese medical professionals were recruited from 4 cities and participated in the study. RESULTS: In 291 participants, 116 (40.0%) medical staff experienced anxiety and 151 (51.8%) underwent depressed mood. In male, the level of GAD-7 and PHQ-9 scores increased with the elevation of working hours per day (WHPD) (ß=0.579, p=0.003 and ß=0.943; p=0.001) respectively. In female, nonlinear relationship mode was demonstrated. The levels of GAD-7 and PHQ-9 scores increased with the elevation of working hours when it was above 5 hours (ß=1.432; p<0.001 and ß=1.177; p<0.001), but it did not have a significant association with WHPD when it was less than 5 (p>0.05). CONCLUSION: During the COVID-19 epidemic, we found a strong correlation between the psychological mood and WHPD. The correlation followed different modes in male and female medical workers. Enforcing an upper time limit of WHPD may help decrease the risk of pandemic-related psychological problems in medical workers.

KCNH2-3.1 mediates aberrant complement activation and impaired hippocampal-medial prefrontal circuitry associated with working memory deficits.

Increased expression of the 3.1 isoform of the KCNH2 potassium channel has been associated with cognitive dysfunction and with schizophrenia, yet little is known about the underlying pathophysiological mechanisms. Here, by using in vivo wireless local field potential recordings during working memory processing, in vitro brain slice whole-cell patching recordings and in vivo stereotaxic hippocampal injection of AAV-encoded expression, we identified specific and delayed disruption of hippocampal-mPFC synaptic transmission and functional connectivity associated with reductions of SERPING1, CFH, and CD74 in the KCNH2-3.1 overexpression transgenic mice. The differentially expressed genes in mice are enriched in neurons and microglia, and reduced expression of these genes dysregulates the complement cascade, which has been previously linked to synaptic plasticity. We find that knockdown of these genes in primary neuronal-microglial cocultures from KCNH2-3.1 mice impairs synapse formation, and replenishing reduced CFH gene expression rescues KCNH2-3.1-induced impaired synaptogenesis. Translating to humans, we find analogous dysfunctional interactions between hippocampus and prefrontal cortex in coupling of the fMRI blood oxygen level-dependent (BOLD) signal during working memory in healthy subjects carrying alleles associated with increased KCNH2-3.1 expression in brain. Our data uncover a previously unrecognized role of the truncated KCNH2-3.1 potassium channel in mediating complement activation, which may explain its association with altered hippocampal-prefrontal connectivity and synaptic function. These results provide a potential molecular link between increased KCNH2-3.1 expression, synapse alterations, and hippocampal-prefrontal circuit abnormalities implicated in schizophrenia.

Analysis of the Spatial and Temporal Evolution of Land Cover and Heat Island Effects in Six Districts of Chongqing's Main City.

The urban heat island effect has always been one of the hottest issues in urban development. In this study, Landsat images from the summers of 2001, 2004, 2009, 2014 and 2018 were used to identify land cover type in six districts of Chongqing's main city. Land cover was categorized as water, vegetation or impervious surface with the object-oriented method. Land surface temperature (LST) data was calculated with the atmospheric radiation transfer equation method, and was then divided into different heat island intensity grades. Next, the spatial and temporal changes in land cover type and heat island effect were analyzed in the six districts. Center migration analysis and heat island coefficients were used to quantitatively reflect the spatiotemporal evolution relationship between land cover and heat island effect. All six districts exhibited a trend of expanding impervious surface, with a 419.38% increase from 2001 to 2018, and shrinking vegetation, with a 17.81% decrease from 2001 to 2018. Also from 2001 to 2018, Yuzhong District had the most significant heat island effect, with a heat island coefficient 0.35 higher than the mean value of the whole study area. The impervious surface center migrated in different directions in each district. Both the direction and the corresponding velocity of the impervious surface and heat island centers were tightly correlated, with a correlation coefficient of 0.53. Relative heat island coefficients (the difference from the mean) of water ranged from -2.08 to -1.17 in different districts. That of impervious surface ranged from 1.60 to 1.93, and that of vegetation ranged from -0.22 to 1.09. The internal heterogeneity of land cover and heat island effect in Chongqing's main city was huge. This study quantitatively analyzed the evolution of the heat island effect in the study area to help provide each district with some targeted suggestions for future urban planning.

ETA-mediated anti-TNF-α therapy ameliorates the phenotype of PCOS model induced by letrozole.

Chronic inflammation is a typical characteristic of polycystic ovary syndrome (PCOS), in which, tumor necrosis factor (TNF)-α plays an important role. We investigated whether anti-TNF-α therapy can alleviate the core phenotypes of PCOS. In pubertal female Wistar rats, release pellets of letrozole (LET) were administered continuously for 90 days to induce PCOS-like phenotypes, followed by treatment with etanercept (ETA), a TNF-α inhibitor. ETA significantly inhibited increases in body weight and androgen, TNF-α, and MCP-1 levels, excessive recruitment of lipid droplets, altered levels of pre-adipose differentiation markers, and abnormal development of follicles. In addition, TNF-α and testosterone (T) levels in the rat sera were significantly positively correlated. Further experiments were performed to investigate the relationship between TNF-α and androgen. Persistent exposure of the RAW 264.7 cell line to low doses of testosterone significantly enhanced TNF-α expression and activated the NF-κB signaling pathway, which were blocked by ETA. Furthermore, treatment with TNF-α promoted the production of testosterone in KGN granulosa cells by reducing CYP19A1 expression, whereas ETA treatment blocked this process. In conclusion, anti-TNF-α therapy with ETA may be an efficient method to alleviate PCOS, whose underlying mechanism may be associated with its ability to reduce excessive androgen levels.

Effects of cultivation environments on Dendrobium catenatum / 中国中药杂志

The study was aimed to clarify the effect of three cultivation environments on the growth and metabolism of Dendrobium catenatum C13 group. There were three different cultivation conditions including rock epiphytic cultivation, pear epiphytic cultivation and pot cultivation. Morphological characteristics and agronomic characters of D. catenatum were observed and measured. Microstructure, contents of polysaccharide and alcohol-soluble extracts were measured by paraffin section method, phenol-sulfuric acid method and hot-dip method, respectively. The result showed that the cultivation environment significantly affected the growth of D. catenatum, the leaves of D. catenatum that cultivated on the rock and pear were sparse and small, the stems were short and purple and the root system was developed. Compare with potted cultivation, D. catenatum from rock epiphytic cultivation and pear epiphytic cultivation showed the following characteristics in the microstructure: the upper epidermis became thicker, the epidermal hair in the epidermis became denser, stomatal showed smaller and denser, the cell wall of exodermis, endoderm and medulla became thicker, the cell of velamen, exodermis, endoderm and medulla were smaller and arranged more closely, but the cultivation environment did not produce specific tissue structure, mainly changed in the structural parameters of size and quantity. The growth environments also influenced contents of polysaccharides and alcohol-soluble extracts. The dontents of polysaccharides and alcohol-soluble extracts in D. catenatum from rock epiphytic were the highest, reached 37.34% and 11.66%, the second was pear epiphytic, both higher than pot cultivation, alcohol-soluble extracts contents in D. catenatum from rock epiphytic are more complex, which shows that rock epiphytic is conducive to the accumulation of secondary metabolites in D. catenatum.

Effects of sampling time on polysaccharides of Dendrobium catenatum under temperature-controlled condition / 中国中药杂志

In order to reveal the accumulation trend of polysaccharides in Dendrobium catenatum and determine the effect of sampling time on polysaccharides, D. Catenatum D21 clone was harvested from January to December after culturing for 2 to 5 months in the growth chamber with constant temperature. Polysaccharides were determined by phenol-sulfuric acid method and the monosaccharide compositions were analyzed by pre-column derivative-UPLC. The results showed that the content of polysaccharide and its key component mannose was positively correlated with the culture time, but the contents of polysaccharides in all kinds of culture peaked from 5 to 6 months, which were consistent with the trend of field planting. The results suggested that the trend of polysaccharide accumulation in the plant could be related to the life rhythm of the sensory seasons of D. catenatum, which was significantly affected by the harvesting season, even under the constant condition of the culture chamber.

Exploration into the Anti-Rheumatoid Arthritis Mechanism of Ethyl Acetate Extract from Kadsura longipedunculata Finet et Gagnep / 中国药学杂志

OBJECTIVE: To research the effect and mechanism of ethyl acetate extract from Kadsura longipedunculata Finet et Gagnep. METHODS: The 70 SD male rats were randomly divided into 7 groups: normal control group, model group, tripterginum glycosides(TG) group, dexamethasone(DXM) group, ethyl acetate extract from Kadsura longipedunculata Finet et Gagnep. low, medium and high dosage groups(0.063, 0.126, 0.252 g·kg-1·d-1), the CIA(collagen induced arthritis) model of rats was adopted. Under 28 days intragastric administration, the rats' state, weight, degree of paw swelling, arthritis index and pathological changes of ankle joints were observed. Their serologic contents of interleukin 1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) were examined by means of ELISA, and the expression of NF-κB p65 mRNA in joint synovial tissues were tested via quantitative Real-time PCR method. RESULTS: The ethyl acetate extract from Kadsura longipedunculata Finet et Gagnep. is found obviously effective in inhibiting CIA rats' paw swelling, decreasing serologic content of IL-1β, IL-6, and TNF-α, as well as the expression of NF-κB p65 mRNA in synovial tissues.Its effect is dosage-related, and stronger than that of TG, weaker than that of DXM. CONCLUSION: Kadsura longipedunculata Finet et Gagnep. is, to some extent, effective against RA, the mechanism of which is related to the transcription of NF-κB p65.

CFTR Deletion in Mouse Testis Induces VDAC1 Mediated Inflammatory Pathway Critical for Spermatogenesis.

Cystic fibrosis is the most common genetic disease among Caucasians and affects tissues including lung, pancreas and reproductive tracts. It has been shown that Endoplasmic Reticulum (ER) stress and heat shock response are two major deregulated functional modules related to CFTR dysfunction. To identify the impact of CFTR deletion during spermatogenesis, we examined the expression of spermiogenesis-related genes in the testis of CFTR mutant mice (CF mice). We confirmed expression changes of MSY2, a germ cell specific RNA binding protein, resulting from deletion of CFTR in testis. Furthermore, real time PCR and Western blot results showed that an inflammatory response was activated in CF mice testis, as reflected by the altered expression of cytokines. We demonstrate for the first time that expression of MSY2 is decreased in CF mice. Our results suggest that CFTR deletion in testis influences inflammatory responses and these features are likely to be due to the unique environment of the seminiferous tubule during the spermatogenesis process. The current study also suggests avenues to understand the pathophysiology of CFTR during spermatogenesis and provides targets for the possible treatment of CFTR-related infertility.

Study of fetal lymphocyte of intrahepatic cholestasis of pregnancy / 中华妇产科杂志

Objective To explore effect of fetal lymphocyte on pathogenesis of intrahepatic cholestasis of pregnancy(ICP).Methods Twenty pregnant women with ICP and 20 normal pregnant women were enrolled in the study.The single mixed lymphocyte culture/reaction(MLC/MLR)was conducted using inactive lymphocyte obtained from maternal peripheral blood and lymphocyte of cord blood from fetus.Antigen-induced-lymphocyte-proliferation-reaction was used for dermic soluble antigen and decidual soluble antigen obtained from maternal blood and cord blood from fetus.The intense of proliferation was calculated and compared between normal and ICP-complicated pregnancies.Results(1)The level of intense of proliferation of fetal lymphocyte was significantly increased in ICP group 2.75?0.36 than those of normal control group 1.45?0.19 in single mixed lymphocyte culture(P＜0.05).(2)The level of intense of proliferation of fetal lymphocyte was significantly increased in ICP group 1.45?0.19 than those of normal control group 0.67?0.24 in decidual soluble antigen induced lymphocyte proliferation reaction(P＜0.05). (3)The level of intense of proliferation of fetal lymphocyte was significantly increased in ICP group(1.22?0.44)than those of normal control group(0.66?0.27)in dermic soluble antigen induced lymphocyte proliferation reaction.Conclusions(1)The fetal lymphocyte may be one of the effector cells in pathogenesis of ICP.(2)The disturbance of fatal-maternal immune-tolerance is one of the important mechanisms underlying ICP.