TDZD-8 alleviates delayed neurological sequelae following acute carbon monoxide poisoning involving tau protein phosphorylation.

Objective: Acute carbon monoxide （CO）poisoning can cause delayed neurological sequelae (DNS). Glycogen synthase kinase 3ß (GSK-3ß) /Tau protein pathway is reported to play a key role in neurological abnormalities. In the present study, we aimed to determine the role of GSK-3ß/Tau in DNS following acute CO poisoning.Methods: 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a specific non-competitive inhibitor of GSK-3ß, was used to inhibit GSK-3ß. Twenty-four male Sprague-Dawley rats were randomly assigned to the three groups: Control group, CO group and CO-TDZD-8 group. Rats breathed 1000 ppm CO for 40 minutes and then 3000 ppm for up to 20 minutes until they lost consciousness. TDZD-8 (1 mg/kg) was administered intravenously three times after the end of CO exposure at 0, 24, 48 hours late. Learning and memory abilities were observed using the Morris Water Maze (MWM). Brain histological changes were evaluated by hematoxylin-eosin staining. Moreover, the expression levels of Tau and GSK-3ß were detected after acute carbon monoxide poisoning.Results: TDZD-8 significantly attenuated the learning and memory dysfunction induced by acute CO poisoning, ameliorated the histology structure of damaged neural cells in cortex and hippocampus CA1 area. TDZD-8 clearly decreased p-Tau expression, reversed the reduction of p-GSK-3ß induced by acute CO poisoning.Conclusions: The therapeutic effect of TDZD-8 in alleviating DNS caused by acute CO poisoning is related to the inactivation of Tau by intensifying the level of GSK-3ß phosphorylation.

Combining conventional ultrasound and ultrasound elastography to predict HER2 status in patients with breast cancer.

Introduction: Identifying the HER2 status of breast cancer patients is important for treatment options. Previous studies have shown that ultrasound features are closely related to the subtype of breast cancer. Methods: In this study, we used features of conventional ultrasound and ultrasound elastography to predict HER2 status. Results and Discussion: The performance of model (AUROC) with features of conventional ultrasound and ultrasound elastography is higher than that of the model with features of conventional ultrasound (0.82 vs. 0.53). The SHAP method was used to explore the interpretability of the models. Compared with HER2- tumors, HER2+ tumors usually have greater elastic modulus parameters and microcalcifications. Therefore, we concluded that the features of conventional ultrasound combined with ultrasound elastography could improve the accuracy for predicting HER2 status.

An interpretable machine learning approach for predicting 30-day readmission after stroke.

BACKGROUND: Stroke is the second leading cause of death worldwide and has a significantly high recurrence rate. We aimed to identify risk factors for stroke recurrence and develop an interpretable machine learning model to predict 30-day readmissions after stroke. METHODS: Stroke patients deposited in electronic health records (EHRs) in Xuzhou Medical University Hospital between February 1, 2021, and November 30, 2021, were included in the study, and deceased patients were excluded. We extracted 74 features from EHRs, and the top 20 features (chi-2 value) were used to build machine learning models. 80% of the patients were used for pre-training. Subsequently, a 20% holdout dataset was used for verification. The Shapley Additive exPlanations (SHAP) method was used to explore the interpretability of the model. RESULTS: The cohort included 6,558 patients, of whom the mean (SD) age was 65 (11) years, 3,926 were males (59.86 %), and 132 (2.01 %) were readmitted within 30 days. The area under the receiver operating characteristic curve (AUROC) for the optimized model was 0.80 (95 % CI 0.68-0.80). We used the SHAP method to identify the top 10 risk factors (i.e., severe carotid artery stenosis, weak, homocysteine, glycosylated hemoglobin, sex, lymphocyte percentage, neutrophilic granulocyte percentage, urine glucose, fresh cerebral infarction, and red blood cell count). The AUROC of a model with the 10 features was 0.80 (95 % CI 0.69-0.80) and was not significantly different from that of the model with 20 risk factors. CONCLUSIONS: Our methods not only showed good performance in predicting 30-day readmissions after stroke but also revealed risk factors that provided valuable insights for treatments.

Resveratrol pretreatment mitigates LPS-induced acute lung injury by regulating conventional dendritic cells' maturation and function.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a severe syndrome lacking efficient therapy and resulting in high morbidity and mortality. Although resveratrol (RES), a natural phytoalexin, has been reported to protect the ALI by suppressing the inflammatory response, the detailed mechanism of how RES affected the immune system is poorly studied. Pulmonary conventional dendritic cells (cDCs) are critically involved in the pathogenesis of inflammatory lung diseases including ALI. In this study, we aimed to investigate the protective role of RES via pulmonary cDCs in lipopolysaccharide (LPS)-induced ALI mice. Murine ALI model was established by intratracheally challenging with 5 mg/kg LPS. We found that RES pretreatment could mitigate LPS-induced ALI. Additionally, proinflammatory-skewed cytokines decreased whereas anti-inflammatory-related cytokines increased in bronchoalveolar lavage fluid by RES pretreatment. Mechanistically, RES regulated pulmonary cDCs' maturation and function, exhibiting lower level of CD80, CD86, major histocompatibility complex (MHC) II expression, and IL-10 secretion in ALI mice. Furthermore, RES modulated the balance between proinflammation and anti-inflammation of cDCs. Moreover, in vitro RES pretreatment regulated the maturation and function of bone marrow derived dendritic cells (BMDCs). Finally, the adoptive transfer of RES-pretreated BMDCs enhanced recovery of ALI. Thus, these data might further extend our understanding of a protective role of RES in regulating pulmonary cDCs against ALI.

Beneficial Effects of Theta-Burst Transcranial Magnetic Stimulation on Stroke Injury via Improving Neuronal Microenvironment and Mitochondrial Integrity.

Recent work suggests that repetitive transcranial magnetic stimulation (rTMS) may beneficially alter the pathological status of several neurological disorders, although the mechanism remains unclear. The current study was designed to investigate the effects of rTMS on behavioral deficits and potential underlying mechanisms in a rat photothrombotic (PT) stroke model. From day 0 (3 h) to day 5 after the establishment of PT stroke, 5-min daily continuous theta-burst rTMS (3 pulses of 50 Hz repeated every 200 ms, intensity at 200 G) was applied on the infarct hemisphere. We report that rTMS significantly attenuated behavioral deficits and infarct volume after PT stroke. Further investigation demonstrated that rTMS remarkably reduced synaptic loss and neuronal degeneration in the peri-infarct cortical region. Mechanistic studies displayed that beneficial effects of rTMS were associated with robust suppression of reactive micro/astrogliosis and the overproduction of pro-inflammatory cytokines, as well as oxidative stress and oxidative neuronal damage especially at the late stage following PT stroke. Intriguingly, rTMS could effectively induce a shift in microglial M1/M2 phenotype activation and an A1 to A2 switch in astrocytic phenotypes. In addition, the release of anti-inflammatory cytokines and mitochondrial MnSOD in peri-infarct regions were elevated following rTMS treatment. Finally, rTMS treatment efficaciously preserved mitochondrial membrane integrity and suppressed the intrinsic mitochondrial caspase-9/3 apoptotic pathway within the peri-infarct cortex. Our novel findings indicate that rTMS treatment exerted robust neuroprotection when applied at least 3 h after ischemic stroke. The underlying mechanisms are partially associated with improvement of the local neuronal microenvironment by altering inflammatory and oxidative status and preserving mitochondrial integrity in the peri-infarct zone. These findings provide strong support for the promising therapeutic effect of rTMS against ischemic neuronal injury and functional deficits following stroke.

Photobiomodulation Therapy Attenuates Hypoxic-Ischemic Injury in a Neonatal Rat Model.

Photobiomodulation (PBM) has been demonstrated as a neuroprotective strategy, but its effect on perinatal hypoxic-ischemic encephalopathy is still unknown. The current study was designed to shed light on the potential beneficial effect of PBM on neonatal brain injury induced by hypoxia ischemia (HI) in a rat model. Postnatal rats were subjected to hypoxic-ischemic insult, followed by a 7-day PBM treatment via a continuous wave diode laser with a wavelength of 808 nm. We demonstrated that PBM treatment significantly reduced HI-induced brain lesion in both the cortex and hippocampal CA1 subregions. Molecular studies indicated that PBM treatment profoundly restored mitochondrial dynamics by suppressing HI-induced mitochondrial fragmentation. Further investigation of mitochondrial function revealed that PBM treatment remarkably attenuated mitochondrial membrane collapse, accompanied with enhanced ATP synthesis in neonatal HI rats. In addition, PBM treatment led to robust inhibition of oxidative damage, manifested by significant reduction in the productions of 4-HNE, P-H2AX (S139), malondialdehyde (MDA), as well as protein carbonyls. Finally, PBM treatment suppressed the activation of mitochondria-dependent neuronal apoptosis in HI rats, as evidenced by decreased pro-apoptotic cascade 3/9 and TUNEL-positive neurons. Taken together, our findings demonstrated that PBM treatment contributed to a robust neuroprotection via the attenuation of mitochondrial dysfunction, oxidative stress, and final neuronal apoptosis in the neonatal HI brain.

After Treatment with Methylene Blue is Effective against Delayed Encephalopathy after Acute Carbon Monoxide Poisoning.

Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) is the most severe and clinically intractable complication that occurs following acute CO poisoning. Unfortunately, the mechanism of DEACMP is still vague. Growing evidence indicates that delayed cerebral damage after CO poisoning is related to oxidative stress, abnormal neuro-inflammation, apoptosis and immune-mediated injury. Our recent report indicated that methylene blue (MB) may be a promising therapeutic agent in the prevention of neuronal cell death and cognitive deficits after transient global cerebral ischaemia (GCI). In this study, we aimed to investigate the potential of MB therapy to ameliorate the signs and symptoms of DEACMP. Rats were exposed to 1000 ppm CO for 40 min. in the first step; CO was then increased to 3000 ppm, which was maintained for another 20 min. The rats were implanted with 7-day release Alzet osmotic mini-pumps subcutaneously under the back skin, which provided MB at a dose of 0.5 mg/kg/day 1 hr after CO exposure. The results showed that MB significantly suppressed oxidative damage and expression of pro-inflammatory factors, including tumour necrosis factor-α and interleukin (IL)-1ß. MB treatment also suitably modulated mitochondrial fission and fusion, which is helpful in the preservation of mitochondrial function. Furthermore, MB dramatically attenuated apoptosis and neuronal death. Lastly, behavioural studies revealed that MB treatment preserved spatial learning and memory in the Barnes maze test. Our findings indicated that MB may have protective effects against DEACMP.

Rigid laryngoscope manifestations of 61 cases of modern laryngeal tuberculosis.

The present study investigated the clinical characteristics and diagnosis of modern laryngeal tuberculosis (TB). A total of 61 patients that were pathologically diagnosed with laryngeal TB between 1998 and 2012 were retrospectively analyzed using laryngoscopy methods. The primary symptoms of laryngeal TB observed in the present study include hoarseness and sore throat, and in the majority of cases, laryngeal TB was not associated with pulmonary TB (ratio 41/61, 67.2%). Systemic symptoms included low-grade fever and night sweats, which were rarely observed (20/61, 32.8%). Laryngoscopy results were summarized into 3 types: Edema type (24 cases), proliferation type (34 cases) and ulcer exudation type (3 cases). The positive rate of purified protein derivative (PPD) examination was 86.9%, which was 63.9% for sputum bacterium analysis. Pathological analysis indicated that there were a large number of phagocytes and giant cell reactions, stroma hyperplasia of epithelioid cells, and the Langhans cells constituted of granuloma and necrotic tissue, with caseous necrosis as a typical manifestation. Modern laryngeal TB is characterized by severe local symptoms like hoarseness and sore throat and mild systemic symptoms like fever and night sweat, and the diagnosis is based on patient history, laryngoscopy analysis, and PPD and sputum bacteria examinations used in combination. However, pathological biopsies and acid-fast bacilli examinations are required for the final diagnosis.

Functional research and molecular mechanism of Kainic acid-induced denitrosylation of thioredoxin-1 in rat hippocampus.

Thioredoxin-1 (Trx1) has long been recognized as a redox regulator, and is implicated in the inhibition of cell apoptosis. Trx1 is essential for the maintenance of the S-nitrosylation of molecules in cells. The S-nitrosylation of Trx1 is essential for the physiological function such as preservation of the redox regulatory activity. The mechanisms underlying Trx1 denitrosylation induced by kainate acid (KA) injection still remain uncharacterized. Our results showed that the S-nitrosylation levels of Trx1 were decreased subsequent to KA injection and that the glutamate receptor 6 (GluR6) antagonist NS102 could inhibit the denitrosylation of Trx1. Moreover, the denitrosylation of Trx1 following KA treatment could be suppressed by the Fas ligand (FasL) antisense oligodeoxynucleotides (AS-ODNs), the Trx reductase (TrxR) inhibitor dinitrochlorobenzene (DNCB), or the Nitric oxide (NO) donors sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO). Subsequently, these mechanisms were morphologically validated by cresyl violet staining, in situ TUNEL staining to detect the survival of CA1 and CA3/DG pyramidal neurons. NS102, FasL AS-ODNs, GSNO and SNP could provide neuroprotection of the pyramidal neurons of CA1 and CA3/dentate gyrus (DG) regions by attenuating Trx1 denitrosylation. Our results also showed that the denitrosylation of Trx1 induced by KA injection can active the caspase-3 which results in apoptosis.

Intranasal Delivery of a Caspase-1 Inhibitor in the Treatment of Global Cerebral Ischemia.

Caspase-1 is an enzyme implicated in neuroinflammation, a critical component of many diseases that affect neuronal degeneration. However, it is unknown whether a caspase-1 inhibitor can modify apoptotic neuronal damage incurred during transient global cerebral ischemia (GCI) and whether intranasal administration of a caspase-1 inhibitor is an effective treatment following GCI. The present study was conducted to examine the potential efficiency of post-ischemic intranasal administration of the caspase-1 inhibitor Boc-D-CMK in a 4-vessel occlusion model of GCI in the rat. Herein, we show that intranasal Boc-D-CMK readily penetrated the central nervous system, subsequently inhibiting caspase-1 activity, decreasing mitochondrial dysfunction, and attenuating caspase-3-dependent apoptotic pathway in ischemia-vulnerable hippocampal CA1 region. Further investigation regarding the mechanisms underlying Boc-D-CMK's neuroprotective effects revealed marked inhibition of reactive gliosis, as well as reduction of the neuroinflammatory response via inhibition of the downstream pro-inflammatory cytokine production. Intranasal Boc-D-CMK post-treatment also significantly enhanced the numbers of NeuN-positive cells while simultaneously decreasing the numbers of TUNEL-positive and PARP1-positive cells in hippocampal CA1. Correspondingly, behavioral tests showed that deteriorations in spatial learning and memory performance, and long-term recognition memory following GCI were significantly improved in the Boc-D-CMK post-treated animals. In summary, the current study demonstrates that the caspase-1 inhibitor Boc-D-CMK coordinates anti-inflammatory and anti-apoptotic actions to attenuate neuronal death in the hippocampal CA1 region following GCI. Furthermore, our data suggest that pharmacological inhibition of caspase-1 is a promising neuroprotective strategy to target ischemic neuronal injury and functional deficits following transient GCI.

Transplantation of VEGF-mediated bone marrow mesenchymal stem cells promotes functional improvement in a rat acute cerebral infarction model.

Vascular endothelial growth factor (VEGF) stimulation and bone marrow mesenchymal stem cell (BMSC) transplantation have been implicated in the treatment of acute cerebral infarction for their pivotal roles in behavioral recovery, neuroprotection, neurogenesis, and angiogenesis. However, the effects of BMSC transplants are likely limited because of low transplant survival after acute cerebral infarction, and delivery of VEGF alone also has limited effects on recovery because the protein is cleared quickly. This study attempted to explore whether VEGF could be transferred into BMSC via an adenovirus and whether transplanting VEGF-transfected BMSC into the rat brain provides sufficient neuroprotection after transient middle cerebral artery occlusion. The adenovirus carried VEGF into BMSC (Ad-VEGF-BMSC), and purified adenovirus was transferred into BMSC (Ad-BMSC). Western blots were used to detect the expression of VEGF protein after transfection. Rats exposed to 90-min middle cerebral artery occlusion (MCAO) were treated with Ad-VEGF-BMSC, Ad-BMSC, BMSC and Dulbecco's Modified Eagle's Medium (DMEM) after ischemia reperfusion for 24h. The Sham group only received surgery. After transplantation of Ad-VEGF-BMSC into the perifocal area of the ischemic rat brain, we found increased expression and secretion of VEGF and BDNF as well as a higher level of MAP2, increased microvascular density, improved behavioral function and enhanced BMSC survival. Our results indicated that transplantation of Ad-VEGF-BMSC improved ischemic neurological deficiency after MCAO in rats. This finding provides a potential valuable therapeutic intervention for cerebral ischemic diseases.

Low-level laser therapy for beta amyloid toxicity in rat hippocampus.

Beta amyloid (Aß) is well accepted to play a central role in the pathogenesis of Alzheimer's disease (AD). The present work evaluated the therapeutic effects of low-level laser irradiation (LLI) on Aß-induced neurotoxicity in rat hippocampus. Aß 1-42 was injected bilaterally to the hippocampus CA1 region of adult male rats, and 2-minute daily LLI treatment was applied transcranially after Aß injection for 5 consecutive days. LLI treatment suppressed Aß-induced hippocampal neurodegeneration and long-term spatial and recognition memory impairments. Molecular studies revealed that LLI treatment: (1) restored mitochondrial dynamics, by altering fission and fusion protein levels thereby suppressing Aß-induced extensive fragmentation; (2) suppressed Aß-induced collapse of mitochondrial membrane potential; (3) reduced oxidized mitochondrial DNA and excessive mitophagy; (4) facilitated mitochondrial homeostasis via modulation of the Bcl-2-associated X protein/B-cell lymphoma 2 ratio and of mitochondrial antioxidant expression; (5) promoted cytochrome c oxidase activity and adenosine triphosphate synthesis; (6) suppressed Aß-induced glucose-6-phosphate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase activity; (7) enhanced the total antioxidant capacity of hippocampal CA1 neurons, whereas reduced the oxidative damage; and (8) suppressed Aß-induced reactive gliosis, inflammation, and tau hyperphosphorylation. Although development of AD treatments has focused on reducing cerebral Aß levels, by the time the clinical diagnosis of AD or mild cognitive impairment is made, the brain is likely to have already been exposed to years of elevated Aß levels with dire consequences for multiple cellular pathways. By alleviating a broad spectrum of Aß-induced pathology that includes mitochondrial dysfunction, oxidative stress, neuroinflammation, neuronal apoptosis, and tau pathology, LLI could represent a new promising therapeutic strategy for AD.

Neuroprotective and Functional Improvement Effects of Methylene Blue in Global Cerebral Ischemia.

Transient global cerebral ischemia (GCI) causes delayed neuronal cell death in the vulnerable hippocampus CA1 subfield, as well as behavioral deficits. Ischemia reperfusion (I/R) produces excessive reactive oxygen species and plays a key role in brain injury. The mitochondrial electron respiratory chain is the main cellular source of free radical generation, and dysfunction of mitochondria has a significant impact on the neuronal cell death in ischemic brain. The aim of the present study is to investigate the potential beneficial effects of methylene blue (MB) in a four-vessel occlusion (4VO) GCI model on adult male rats. MB was delivered at a dose of 0.5 mg/kg/day for 7 days, through a mini-pump implanted subcutaneously after GCI. We first found that MB significantly improved ischemic neuronal survival in the hippocampal CA1 region as measured by cresyl violet staining as well as NeuN staining. We also found that MB has the ability to rescue ischemia-induced decreases of cytochrome c oxidase activity and ATP generation in the CA1 region following I/R. Further analysis with labeling of MitoTracker® Red revealed that the depolarization of mitochondrial membrane potential (MMP) was markedly attenuated following MB treatment. In addition, the induction of caspase-3, caspase-8, and caspase-9 activities and the increased numbers of TUNEL-positive cells of the CA1 region were significantly reduced by MB application. Correspondingly, Barnes maze tests showed that the deterioration of spatial learning and memory performance following GCI was significantly improved in the MB-treatment group compared to the ischemic control group. In summary, our study suggests that MB may be a promising therapeutic agent targeting neuronal cell death and cognitive deficits following transient global cerebral ischemia.

Methylene Blue promotes cortical neurogenesis and ameliorates behavioral deficit after photothrombotic stroke in rats.

Ischemic stroke in rodents stimulates neurogenesis in the adult brain and the proliferation of newborn neurons that migrate into the penumbra zone. The present study investigated the effect of Methylene Blue (MB) on neurogenesis and functional recovery in a photothrombotic (PT) model of ischemic stroke in rats. PT stroke model was induced by photo-activation of Rose Bengal dye in cerebral blood flow by cold fiber light. Rats received intraperitoneal injection of either MB (0.5mg/kg/day) from day 1 to day 5 after stroke or an equal volume of saline solution as a control. Cell proliferative marker 5-bromodeoxyuridine (BrdU) was injected twice daily (50mg/kg) from day 2 to day 8 and animals were sacrificed on day 12 after PT induction. We report that MB significantly enhanced cell proliferation and neurogenesis, as evidenced by the increased co-localizations of BrdU/NeuN, BrdU/DCX, BrdU/MAP2 and BrdU/Ki67 in the peri-infarct zone compared with vehicle controls. MB thus effectively limited infarct volume and improved neurological deficits compared to PT control animals. The effects of MB were accompanied with an attenuated level of reactive gliosis and release of pro-inflammatory cytokines, as well as elevated levels of cytochrome c oxidase activity and ATP production in peri-infarct regions. Our study provides important information that MB has the ability to promote neurogenesis and enhance the newborn-neurons' survival in ischemic brain repair by inhibiting microenvironmental inflammation and increasing mitochondrial function.

Procaspase-9 induces its cleavage by transnitrosylating XIAP via the Thioredoxin system during cerebral ischemia-reperfusion in rats.

Transnitrosylation is an important mechanism by which nitric oxide (NO) modulates cell signaling pathways. For instance, SNO-caspase-3 can transnitrosylate the X-linked inhibitor of apoptosis (XIAP) to enhance apoptosis. XIAP is a potent antagonist of caspase apoptotic activity. Decrease in XIAP activity via nitrosylation results in SNO-XIAP-mediated caspase activation. Considering the functional liaison of procaspase-9 and XIAP, we hypothesized that procaspase-9 nitrosylates XIAP directly. Our data confirmed that cerebral ischemia-reperfusion induced XIAP nitrosylation, procaspase-9 denitrosylation and cleavage. Interestingly, the time courses of the nitrosylation of procaspase-9 and XIAP were negatively correlated, which was more prominent after cerebral ischemia-reperfusion, suggesting a direct interaction. The nitrosylation of XIAP, as well as the denitrosylation and cleavage of procaspase-9, were inhibited by DNCB, TrxR1 AS-ODNs, or TAT-AVPY treatment. Meanwhile, DNCB, TrxR1 AS-ODNs, or TAT-AVPY also inhibited the decrease in hippocampal CA1 neurons induced by ischemia-reperfusion in rats. The denitrosylation and cleavage of procaspase-9 induced by OGD/reoxygenation in SH-SY5Y cells were inhibited when cells were co-transfected with wild-type procaspase-9 and XIAP mutant (C449G). These data suggest that cerebral ischemia-reperfusion induces a transnitrosylation from procaspase-9 to XIAP via the Trx system to consequently cause apoptosis. Additionally, Cys325 is a critical S-nitrosylation site of procaspase-9.

Role of Mitochondria in Neonatal Hypoxic-Ischemic Brain Injury.

Hypoxic-ischemia (HI) causes severe brain injury in neonates. It's one of the leading causes to neonatal death and pediatric disability, resulting in devastating consequences, emotionally and economically, to their families. A series of events happens in this process, e.g. excitatory transmitter release, extracelluar Ca2+ influxing, mitochondrial dysfunction, energy failure, and neuron death. There are two forms of neuron death after HI insult: necrosis and apoptosis, apoptosis being the more prevalent form. Mitochondria handle a series of oxidative reactions, and yield energy for various cellular activities including the maintainance of membrane potential and preservation of intracellular ionic homeostasis. Therefore mitochondria play a critical role in neonatal neurodegeneration following HI, and mitochondrial dysfunction is the key point in neurodegenerative evolution. Because of this, exploring effective mitochondria-based clinical strategies is crucial. Today the only efficacious clinic treatment is hypothermia. However, due to its complex management, clinical complication and autoimmune decrease, its clinical application is limited. So far, many mitochondria-based strategies have been reported neuroprotective in animal models, which offers promise on neonatal therapy. However, since their clinical effectiveness are still unclear, plenty of studies need to be continued in the future. According to recent reports, two novel strategies have been proposed: methylene blue (MB) and melatonin. Although they are still in primary stage, the underlying mechanisms indicate promising clinical applications. Every neurological therapeutic strategy has its intrinsic deficit and limited efficacy, therefore in the long run, the perfect clinical therapy for hypoxic-ischemic neonatal brain injury will be based on the combination of multiple strategies.

[Clinical observation on treatment of chronic suppurative otitis media caused large tympanic membranes perforation by ear-dropping with combined Chinese and Western drugs].

OBJECTIVE: To observe the therapeutic effect of the self-prepared ear dropping made by combined Chinese and Western drugs in treating chronic suppurative otitis media caused large tympanic membrane perforation. METHODS: Sixty-four patients were randomly divided into two groups, the treated group treated with the self-prepared ear-dropping and the control group treated with ear-dropping made by placebo, to observe the therapeutic effect and adverse reaction. RESULTS: In the 32 patients of the treated group, 15 patients were cured, the cured tympanic membrane was normal in shape and thickness in 11, scarred in 3, and thin and transparent in 1. The hearing was improved in all patients with cured tympanic membrane. But no one was cured in the control group. CONCLUSION: The self-prepared ear-dropping had good effect in treating tympanic membrane perforation, it is simple, cheap and no need of further operation.

[Clinical analysis of the diagnosis of laryngeal tuberculosis].

OBJECTIVE: To explore the clinical characteristic and diagnosis of modern laryngeal tuberculosis. METHOD: A retrospective research among 33 patients of laryngeal tuberculosis, with definitive pathological result, had been done in the laryngeal-endoscope room in our department. RESULT: The main symptoms of laryngeal tuberculosis are hoarseness and sore throat. Most of the patients did not accompany with pulmonary tuberculosis (TB) (63.6%). Few of them accompany with low-grade fever, night sweat and malnutrition (24.2%). There are three types in the laryngeal-endoscope vision: edema type, hyperplasia type and ulcer exudation type. The positive rates of PPD and phlegm bacteria examination are respectively 87.9% and 68.4%. There can be seen in the pathological slides the interstitial phagocytes and giant cell reaction. Granuloma consisting of epithelioid cell and Langhans' cells is coexistent with necrotic tissue. Cheese necrosis is the typical characteristic of the disease. CONCLUSION: Severe local symptoms of laryngeal with slightly general symptoms are the clinical characteristics of modern laryngeal tuberculosis. The diagnosis of it depends mainly on the process of the disease, laryngeal-endoscope examination and PPD examination combined with phlegm bacteria examination. And the final diagnosis is based on the pathological biopsy and tubercular bacillus culturing.

[Clinical therapeutic effects of staging tympanoplasty].

OBJECTIVE: To explore the clinic characteristic and curative effect of staging tympanoplasty for chronic suppurative otitis media and cholesteatoma otitis media. METHOD: Curative effects of 132 patients cured by staging tympanoplasty and 325 patients cured by no staging tympanoplasty were retrospectively analyzed. Curative effects include ABG value (the reduced value of air-bone conduct gaps after operation), recrudescence of cholesteatoma, tympanic membrane reperforation and wet ear after operation. RESULT: In staging tympanoplasty group, ABG is 28.4 dB, rate of tympanic membrane reperforation is 1.5%, recrudescence of cholesteatoma is 0% and rate of wet ear after operation is 0%. In no staging tympanoplasty group, ABG is 21.3 dB, rate of tympanic membrane reperforation is 2.2%, recrudescence of cholesteatoma is 4.0% and rate of wet ear after operation is 1.2%. CONCLUSION: The ABG, the rate of recrudescence of cholesteatoma in staging tympanoplasty group is much better than that in no staging tympanoplasty group. Tympanic membrane reperforation and wet ear after operation rate have no significant difference in statistic between two groups. We can conclude that staging operations will maintain and improve hearing level more effectively compare to no staging operation.

[Research on the change of PSG parameters of OSAHS patients before and after UPPP operation].

OBJECTIVE: To study the change of polysomnography (PSG) parameters of obstructive sleep apnea hypopnea syndrome (OSAHS) patients before and after uvulopalatopharyngoplasty (UPPP) operation. METHOD: Having PSG detection for this 20 OSAHS patients both before and after UPPP operation. RESULT: (1) After UPPP operation, AHI (P<0.01), average SaO2 (P<0.01), Min SaO2 (P<0.01), and apnea time contrast (P<0.05)have improvements; (2) After UPPP operation, the change of sleep stage mainly S2 stage replaced S stage. (3) In observation index of PSG, both the relationship between AHI and oxygen saturation and the relationship between AHI and apnea time have correlation, but correlation of the former has more significant difference in statistics. The change of AHI and MinSaO2 after UPPP operation has correlation also. The secant plane of oropharynx can be regarded as the predictive index for OSAHS severity and guideline for UPPP operation, but the change of oropharyngeal secant plane after operation can not be used as the predictive index for therapeutic effectiveness. CONCLUSION: So we treat oxygen saturation as a more sensitive marker than apnea time in predicting severity degree of OSAHS. After UPPP operation, the change of sleep stage mainly S2 replaced S1 stage.