Identification of key genes in chronic intermittent hypoxia-induced lung cancer progression based on transcriptome sequencing.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased risk of lung cancer mortality. Nevertheless, little is known about the underlying molecular mechanisms. This research aimed to investigate differentially expressed genes (DEGs) and explore their function in Lewis lung carcinoma (LLC)-bearing mice exposed to chronic intermittent hypoxia (CIH) by transcriptome sequencing. METHODS: Lung cancer tissues in LLC-bearing mice exposed to CIH or normoxia were subjected for transcriptome sequencing to examine DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were employed to explore the function of DEGs. To evaluate the prognostic value of DEGs, the Kaplan-Meier survival analysis in combination with Cox proportional hazard model were applied based on The Cancer Genome Atlas. RESULTS: A total of 388 genes with 207 up-regulated and 181 down-regulated genes were differentially expressed between the CIH and normoxia control groups. Bioinformatics analysis revealed that the DEGs were related to various signaling pathways such as chemokine signaling pathway, IL-17 signaling pathway, TGF-ß signaling pathway, transcriptional misregulation in cancer, natural killer cell mediated cytotoxicity, PPAR signaling pathway. In addition, the DEGs including APOL1, ETFB, KLK8, PPP1R3G, PRL, SPTA1, PLA2G3, PCP4L1, NINJ2, MIR186, and KLRG1 were proven to be significantly correlated with poorer overall survival in lung adenocarcinoma. CONCLUSIONS: CIH caused a significant change of gene expression profiling in LLC-bearing mice. The DEGs were found to be involved in various physiological and pathological processes and correlated with poorer prognosis in lung cancer.

[Clinical effectiveness evaluation of gingival recession by using perioscope as an adjunct to non-surgical periodontal therapy].

PURPOSE: To investigate the effects of ultrasonic scaling and root planning(SRP) assisted by perioscope on gingival recession of maxillary lateral incisor. METHODS: Thirty-six outpatients with moderate to advanced chronic periodontitis from the Department of Periodontology at Dental and Ophthalmic Clinic of Putuo District from June 2020 to December 2020 were collected as research objects. Periodontal treatment was carried out according to a single-blind split-mouth self-control design randomly with(experimental group, namely perioscope group) or without(control group, namely SRP group) periodontal endoscope．The labial periodontal probing depth (PD), labial attachment loss (AL) and gingival recession(GR) in the maxillary lateral incisors were recorded at baseline, 3 and 6 months, and compared among groups by SPSS 22.0 software package. RESULTS: There was no significant difference between perioscope group and SRP group at baseline. ΔGR (the recession extent of gum within two observation time) in perioscope group was significantly smaller than that in SRP group at 3 months（P<0.05）. There was no significant difference in other periodontal indicators at 3 and 6 months between the 2 groups after treatment, but it can be found that the degree of PD reduction and AL improvement in perioscope group was more than those in SRP group, this trend was most obvious at 3 months. PD and AL were significantly different between baseline and 3 months or 6 months in the two groups. There were significant differences in ΔGR at 3 months and 6 months between the two groups. CONCLUSIONS: Compared with routine SRP, the extent of root surface debridement with perioscope-assisted SRP is thorough and less invasive, and the reduction of gingival recession of labial surface of maxillary lateral incisor at 3 months is significantly less; thus, the aesthetic effect is prominent.

C-arm-based flat-panel detector cone-beam computed tomography venography in the diagnosis of iliac vein compression syndrome.

BACKGROUND: C-arm-based flat-panel detector cone-beam computed tomography (CBCT) venography has never been used in the management of iliac vein compression syndrome (IVCS). This study aimed to determine the technical feasibility and safety of CBCT venography in the diagnosis of IVCS compared with conventional venography (CV). METHODS: Twenty patients with clinical manifestations of lower extremity venous insufficiency were prospectively enrolled between May 2018 and December 2018. Each patient underwent both CV and CBCT venography. The feasibility and safety of CBCT venography were assessed by technical success rate and complication rate. The relationships between the clinical indexes and the results of CBCT venography and CV were analyzed with correlation analysis. The consistency of the diagnosis of IVCS using each modality was analyzed by the kappa test. RESULTS: The technical success rate was 100% for CBCT venography and for CV, without any complications. Compared with CV, CBCT venography was able to show more details of adjacent tissues which might be helpful for making etiological diagnosis. The stenosis rate under CBCT venography had excellent consistency with that under CV (kappa = 0.78, Chi-square test). The stenosis rate under CBCT venography was positively correlated with the presence of collateral veins (odds ratio 1.12, 95% confidence interval: [1.00, 1.26], P = 0.049), while the stenosis rate under CV was not. Unexpectedly, only one patient had a venous pressure gradient of more than 2 mmHg (1 mmHg = 0.133 kPa). CONCLUSIONS: For the diagnosis of IVCS, C-arm-based CBCT venography was technically feasible, with good safety. The presence of collateral veins on CBCT was clinically significant. A C-arm fluoroscopy-based technique that combines CV and CBCT might be a promising protocol for the management of IVCS during a single session.

A COVID-19 patient with multiple negative results for PCR assays outside Wuhan, China: a case report.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency of major international concern. Real-time RT-PCR assays are recommended for diagnosis of COVID-19. Here we report a rare case of COVID-19 with multiple negative results for PCR assays outside Wuhan, China. CASE PRESENTATION: A 32-year old male was admitted to our hospital because of 6 days of unexplained fever on January 29, 2020. He had come from Wuhan city 10 days before admission. Five days before admission, no abnormality was noted in laboratory test, chest radiography, and nasopharyngeal swab test for the SARS-CoV-2 nucleic acid. The patient was treated with ibuprofen for alleviating fever. On admission, chest computed tomography showed multiple ground-glass opacities in right lower lung field. COVID-19 was suspected. Three times of nasopharyngeal swab specimens were collected after admission. However, none of the specimens were positive. The patient was confirmed with COVID-19 after fifth SARS-CoV-2 nucleic acid test. He was treated with lopinavir/ritonavir, recombinant human interferon alfa-2b inhalation, methylprednisolone. After 18 days of treatment, he was discharged with improved symptoms, lung lesions and negative results of nasopharyngeal swab. CONCLUSION: This case reminds clinician that a patient with high clinical suspicion of COVID-19 but multiple negative RT-PCR result should not be taken out of isolation. A combination of patient's exposure history, clinical manifestations, laboratory tests, and typical imaging findings plays a vital role in making preliminary diagnosis and guide early isolation and treatment. Repeat swab tests are helpful in diagnosis for this kind of patients.

The effect of continuous positive airway pressure on circulating malondialdehyde among obstructive sleep apnea patients: a meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) has been demonstrated to be associated with an increase of oxidative stress. However, whether circulating malondialdehyde (MDA), a widely used biomarker of oxidative stress, could be reduced by the treatment of OSA by continuous positive airway pressure (CPAP) is debated. The present meta-analysis was performed to determine the effect of CPAP treatment on circulating MDA among patients with OSA. METHODS: A systematic search of PubMed, Embase, and Web of Science was performed for literature covering the period between 1967 and August 2019. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-CPAP therapy. RESULTS: A total of 10 studies with 220 patients were included in this meta-analysis. A significant decrease in circulating MDA was observed after CPAP treatment (SMD = 1.164, 95% CI = 0.443 to 1.885, z = 3.16, p = 0.002) in OSA patients. Subgroup analyses revealed that CPAP therapy was associated with a significant decrease of circulating MDA in elder (SMD = 1.629, 95% CI = 0.265 to 2.994, z = 2.34, p = 0.019), more obese patients (SMD = 0.954, 95% CI = 0.435 to 1.473, z = 3.61, p = 0.000), more severe OSA patients (SMD = 0.879, 95% CI = 0.421 to 1.336, z = 3.76, p = 0.000), patients with therapeutic duration ≥ 3 months (SMD = 1.867, 95% CI = 0.563 to 3.172, z = 2.80, p = 0.005), and patients with good compliance (SMD = 1.004, 95% CI = 0.703 to 1.305, z = 6.54, p = 0.000). CONCLUSIONS: This meta-analysis suggested that CPAP therapy exerted significant lowering effects on circulating MDA, especially in elder, more obese, and more severe OSA patients and patients with good compliance as well as longer duration of CPAP application.

Transcutaneous Electrical Acupoint Stimulation for Improving Postoperative Recovery, Reducing Stress and Inflammatory Responses in Elderly Patient Undergoing Knee Surgery.

Transcutaneous electrical acupoint stimulation (TEAS) is a form of acupuncture treatment that applies electrical stimulation on specific acupoint through cutaneous electrodes. This technique has been used for perioperative anesthesia management as part of after surgery recovery. However, to date, limited data are available for using the TEAS for postoperative recovery in elderly surgical patients. We conducted this prospective randomized sham-control trail to evaluate the efficacy of TEAS in a group of elderly patients receiving knee surgery under epidural anesthesia. 52 subjects were assigned to either the experimental group (Group E) or control group (Group C). The patients in Group E received TEAS at zusanli (ST36), sanyinjiao (SP6), neiguan (PC6), and quchi acupoints (LI11) 30min prior to the epidural anesthesia and postoperative day 1 and 2, while patients in Group C received sham TEAS on the same acupoints for 30min same as those of Group E. The primary endpoint was the Quality of Recovery-40 questionnaire (QR-40) and the secondary endpoints were the biomarkers level of stress and inflammatory responses and visual analogue scale (VAS). A one-way ANOVA (SNK method) was used in statistic, and p<0.05 is considered to be statistically significant. Our data showed that the QoR-40 was significantly lower in Group C than that in Group E at postoperative day 1 (p<0.05); Similarly, Cortisol (COR), Adrenocorticotropic Hormone (ACTH), and C-reactive protein (CRP) were significantly lower in Group E than those of Group C at postoperative day 1, 3, and 7 (p<0.05), while the neutrophil/lymphocyte ratio (N/L) was lower in Group E than that in Group C at postoperative day 1 and 3 (p<0.05). Our results showed that perioperative TEAS administration is able to facilitate the development of postoperative recovery of elderly patients, especially at the early stage after surgery. The reported results are likely to be mediated by the reduction of surgical inflammation and perioperative stress response.

Administrations of Preoperative Shenmai Injection and Postoperative Shenfu Injection, Two Ginseng Containing TCM Formulas, Improve Cognitive Dysfunction in Aged Rats.

Postoperative cognitive dysfunction (POCD) is one of the major complications in patients who have undergone surgeries. Reduction of surgery-induced inflammation and perioperative stress responses may prevent the development of POCD. As recent experimental data have suggested, Shenmai and Shenfu injections, two ginseng containing formulations, may improve cognition. We designed this study using aged rats as an experimental model to determine the effect of combined perioperative Shenmai injection and Shenfu injection in preventing the development of POCD and exploring the underlying mechanism of this intervention. Aged rats were randomized into one of the two groups. Rats in the experiment group received preoperative Shenmai injection and postoperative Shenfu injection while those of the control group did not receive this treatment. Study results indicate that the memory and cognitive ability of rats in the experiment group were significantly better than those of the control group at postoperative day 1 as well as at day 3. Plasma levels of neuron-specific enolase (NSE), S-100 [Formula: see text] protein, interleukin-6 (IL-6), tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), cortisol (COR), aldosterone (ALD), and adenocorticotropic hormone (ACTH) were significantly lower in the experiment group than in those of the control group (day 1 postoperatively). The plasma level of NSE on postoperative day 3 remained lower in the experimental group than in those of the control group. Our experimental results indicate that preoperative Shenmai and postoperative Shenfu injections facilitate conscious recovery and prevent postoperative cognitive decline. This anti-POCD effect may be a result of minimizing surgery-induced inflammation and reduction of perioperative stress responses by these injections.

Effects of apelin on retinal microglial cells in a rat model of oxygen-induced retinopathy of prematurity.

This study explores the effects of apelin on retinal microglial cells in rat models of oxygen-induced retinopathy of prematurity (ROP). Totally, 274 rats were selected for establishing oxygen-induced retinopathy (OIR) models, and 92 healthy rats for control group. OIR rats were assigned into OIR, 10-5 g/L apelin, 10-4 g/L apelin, and 10-3 g/L apelin groups. Immunohistochemistry was employed to determine morphology of microglial cells and cell number. CDllb, ionized calcium-binding adapter molecule 1 (IBA-1), TNF-α, and iNOS mRNA and protein expressions were identified using RT-qPCR and Western blotting, respectively. ELISA was employed to determine the levels of VEGF and glial fibrillary acidic protein (GFAP). The amoeboid microglial cells were found in the OIR and 10-3 g/L apelin groups, while bipolar microglial cells were found in the normal control, 10-5 g/L apelin and 10-4 g/L apelin groups. In the 1, 2, 3, and 4th week after apelin treatment, there were significantly decreased bipolar microglial cells, lower mRNA and protein expressions of CDllb, IBA-1, TNF-α and iNOS, and the levels of VEGF and GFAP in the 10-4 g/L apelin group than in the OIR, 10-3 g/L apelin and 10-5 g/L apelin groups. The differences between the normal control and 10-4 g/L apelin groups are not significant. Compared with the OIR group, the 10-5 g/L apelin and 10-3 g/L apelin groups presented decreased microglial cells and mRNA and protein expressions of CDllb, IBA-1, TNF-α, and iNOS. Appropriate concentration of apelin may reduce retinal microglial cells in a rat model of oxygen-induced ROP.

Protective role of mitochondrial K-ATP channel and mitochondrial membrane transport pore in rat kidney ischemic postconditioning.

BACKGROUND: Previous studies suggested that mechanical intervention during early reperfusion, or ischemia postconditioning (IPo), could protect kidneys against renal ischemia reperfusion injury (RIRI). However, the mechanisms responsible for this protection remain unclear. This study therefore investigated the protection afforded by IPo in rat kidneys in vivo, and the roles of mitochondrial K(ATP) channels (mitoK(ATP)) and mitochondrial permeability transition pores (MPTPs), by inhibiting mitoK(ATP) with 5-hydroxydecanoate (5-HD), and by directly detecting open MPTPs using calcein-AM and CoCl2. METHODS: Thirty-five male Sprague-Dawley rats were randomly assigned to sham-operation (S), ischemia-reperfusion (I/R), IPo, ischemia reperfusion with 5-HD (I/R + 5-HD), or IPo with 5-HD (IPo + 5-HD) groups. Rats in each group were sacrificed after 6 hours of reperfusion by heart exsanguination or cervical dislocation under anesthesia. RIRI was assessed by determination of creatinine and blood urea nitrogen (BUN), and by examination of histologic sections. The roles of mitoK(ATP) and MPTP were investigated by analyzing fluorescence intensities of mitochondria, mitochondrial membrane potential, intracellular reactive oxygen species (ROS) and intracellular calcium, using appropriate fluorescent markers. The relationship between apoptosis and RIRI was assessed by determining the apoptotic index (AI) of kidney tubular epithelial cells. RESULTS: The RIRI model was shown to be successful. Significantly higher levels of creatinine and BUN, and abnormal pathology of histologic sections, were observed in group I/R, compared with group S. 5-HD eliminated the renoprotective effects of IPo. Mitochondrial and mitochondrial membrane potential fluorescence intensities increased, and intracellular calcium, ROS fluorescence intensities and AI decreased in group IPo, compared with group I/R. However, mitochondrial and mitochondrial membrane potential fluorescence intensities decreased, and intracellular calcium and ROS fluorescence intensities and AI increased in group IPo + 5-HD, compared with group IPo. CONCLUSIONS: mitoK(ATP) and MPTPs participated in IPo-induced renoprotective mechanisms in rat kidneys subjected to RIRI, possibly through decreased renal tubular epithelial cell apoptosis.

[Development and genetic polymorphism of abnormal pronuclear zygotes after intracytoplasmic sperm injection].

OBJECTIVE: To compare the development of abnormal pronuclear zygotes after intracytoplasmic sperm injection (ICSI) and analyze their genetic polymorphism. METHODS: Four hundred and ninety three abnormal pronuclear zygotes after ICSI were divided into three groups based on the number of pronuclei: 347 nonpronuclear oocytes, 71 monopronuclear zygotes and 75 multipronuclear zygotes. All of them were cultured in the medium of Vitrolife G5 series(TM). Sixteen short tandem repeats (STR) of seven blastocysts were then analyzed by ABI3100. RESULTS: The cleavage rate of nonpronuclear group (25.4%) was lower than that of the others (P<0.01), the proportion of blocked embryos in nonpronuclear group (48.9%) was significantly higher than that of the others (P<0.05), but the blastocyst rate showed no significant difference in three groups (P>0.05). The genetic polymorphism of the 16 STRs showed that the blastocysts from the nonpronuclear and multipronuclear were diploid, and one of the blastocysts from nonpronuclear oocyte was Y-bearing. CONCLUSION: The zygotes with abnormal pronuclei after ICSI might have development potential, and the blastocysts from nonpronuclear oocytes and multipronuclear zygotes could be diploid.

[In vitro maturation of human oocytes from pregnant late term: a new source of oocytes].

OBJECTIVE: To investigate the in vitro maturation of human oocytes (IVM) from pregnant late term, natural cycles and Gn stimulating cycles and the effect of granulose cells on IVM from pregnant late term. METHODS: A total of 1086 immature oocytes were obtained including 633 oocyte-cumulus complexes (OCCs) and 453 denuded oocytes (DOs). OCCs were divided into pregnant late term group, natural cycle group and IVM group, and DOs were divided into pregnant late term group, natural cycle group and controlled ovarian hyperstimulation (COH) group. All the oocytes were matured in IVM culture system and fertilized by ICSI. The embryos were cultured to blastocyst stage except that those in IVM group were transferred into the uterus. The main outcomes were assessed including maturation rate (MR), fertilization rate (FR), cleavage rate (CR), and blastulation rate (BR) (natural cycle group, pregnant late term group and COH group) and pregnancy rate per transfer cycle (PR) of IVM group. RESULTS: MR of OCCs in pregnant late term group, natural cycle group and COH group was 74.3%, 76.9% and 82.2%, respectively, showing statistical difference between pregnant late term cycle group and IVM group. No statistical difference was observed in FR, CR or BR between the three groups. For IVM cycle group, clinical pregnancy rate of 20% per aspiration was achieved. For DOs, MR of COH group (86.0%) was significantly higher than that of the natural cycle group (72.5%) and pregnant late term group (72.7%) (P<0.01). FR, CR and BR showed no statistical difference among the 3 groups. No difference was found in MR, FR, CR and BR between OCCs group and DOs group from pregnant late term. CONCLUSIONS: The oocytes from pregnant late term have the same development potential as those from natural cycles or Gn stimulating cycles in vitro, and provide a new source of donor oocytes. Granulose cells do not affect the IVM from pregnant late term.

[Sperm acrosin activity helps predict IVF-ET outcome].

OBJECTIVE: To investigate the effect of sperm acrosin activity on the IVF-ET outcome. METHODS: We analyzed sperm parameters, morphology and acrosin activity for 909 infertile husbands by computer-assisted self-assessment (CASA), modified Papanicolaou staining and N-alpha-benzoyl-DL-arginine-p-nitroanilide (BAPNA), respectively, and detected the rates of fertilization, cleavage, quality embryos, embryo cryopreservation, implantation, clinical pregnancy and abortion. The wives were identified as normal or with mere oviduct problems. RESULTS: The rate of normal sperm morphology and sperm motility, vitality, rapid progressive velocity and concentration were significantly lower in the abnormal acrosin activity group than in the normal one (P < 0.01). Significant positive correlations were observed between acrosin activity and the above-mentioned semen parameters (P < 0.01). There were no significant differences in the number of retrieved eggs, the rates of cleavage, quality embryos, embryo cryopreservation, non-embryo transfer cycles and miscarriages, and the number of transferred embryos between the two groups (P > 0.05). The fertilization rate, the percentage of transfer cycles with only 1 embryo and the rate of implantation and clinical pregnancy were notably higher in the normal acrosin activity group than in the abnormal one (P < 0.01). CONCLUSION: Sperm acrosin activity is closely related with semen parameters, and it helps to predict the sperm fertilizing capacity and IVF-ET outcome.