Efficacy of endoscopic porcine small intestinal submucosa graft myringoplasty: a retrospective comparative study.

BACKGROUND: The surgical outcomes following tympanic membrane (TM) repair are affected by many factors. OBJECTIVES: To evaluate the efficacy of endoscopic porcine small intestine submucosa graft (PSISG) myringoplasty by comparing with endoscopic myringoplasty with temporal fascia (TF) and perichondrium (PC). METHODS: We conducted a retrospective comparative study that a total of 98 patients with TM perforations were included. The patients underwent endoscopic myringoplasty using PSISG, TF or PC as the graft. The closure rate, hearing outcomes, operative time and complications in three groups were compared. RESULTS: At 3 months postoperatively, the closure rate were 85.2% (23/27), 92.1% (35/38) and 87.9% (29/33) in the PSISG, TF and PC groups respectively (p = .667); Hearing improved after surgery in three groups (p < .001), and showed no significant difference among the three groups. The mean operative time of the PSISG group was shorter than autologous TF (p < .001) and PC groups (p < .001) in this study; No operative or postoperative complications were found among the three groups. CONCLUSION: Compare to autologous temporal fascia or perichondrium, the PSISG appears to be an effective and safe material for TM perforations closure. Endoscopic PSISG myringoplasty may be an alternative technique for repairing TM perforations, especially for revision cases.

Meniere's Disease Patients with Distinct Sac Pathoanatomic Findings React Differently to Endolymphatic Duct Blockage.

OBJECTIVES: To explore the possible difference in response to endolymphatic duct blockage (EDB) treatment in patients with Meniere's disease (MD) with distinct pathoanatomic characteristics of the sac. METHODS: In a total of 24 patients with MD receiving EDB treatment, the dynamics of the vertigo attack, hearing, vestibular function, and endolymph hydrops (EH) before surgery and 40 months following surgery in patients with normoplastic extraosseous portion of endolymphatic sac (eES) were compared with that in patients with atrophic eES. RESULTS: A higher prevalence of complete vertigo control, better cochlear and vestibular function, and lower endolymph to vestibule-volume ratio were found in patients with normoplastic eES than in those with atrophic eES. Moreover, the reversal of EH was found in a total of six patients in normoplastic eES group, but no reversal of EH was detected in the atrophic eES group after surgery. CONCLUSIONS: A difference in response to EDB treatment was shown in the MD patients with normoplastic eES and those with atrophic eES; the reversal of EH was found in the normoplastic eES group, but not in the atrophic eES group after surgery, suggesting two distinct pathologies in the eESs may underlie the pathogenesis of EH in two subgroups of MD patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2761-2769, 2023.

Up-Regulated Expression of Interferon-Gamma, Interleukin-6 and Tumor Necrosis Factor-Alpha in the Endolymphatic Sac of Meniere's Disease Suggesting the Local Inflammatory Response Underlies the Mechanism of This Disease.

Background: Immune mediated inflammatory changes affecting the endolymphatic sac (ES) may underlie the pathology of Meniere's disease (MD). The aim of the present study was to explore the differentially expressed cytokines in ES luminal fluid (ELF) of patients with MD, and the correlation between the expression of cytokines in the ELF with that in the serum was determined by quantitatively analyzing the cytokines in human ELF and serum. Methods: Human ELF, serum and ES tissues were collected from patients with unilateral MD and patients with acoustic neuroma (AN) during surgery. The Simoa Cytokine 6-Plex Panel kit was used to analyze the levels of cytokines in the ELF and blood samples of the patients. Immunohistochemistry and immunofluorescence were subsequently used to validate the relative expression levels of the cytokines in MD. Results: Significant differences were identified in the expression levels of interferon-γ (IFN-γ) (P < 0.001), interleukin (IL)-6 (P = 0.008) and tumor necrosis factor-α (TNF-α) (P = 0.036) in the luminal fluid of the ES comparing between the MD and AN groups. By contrast, the levels of IFN-γ, IL-10, IL-12p70, IL-17A, IL-6 and TNF-α in the serum of the MD group were not significantly different from those of either the AN group or healthy control subjects. In addition, no significant correlations in the expression levels of cytokines compared between the ELF and serum were found for the patients in either the MD or the AN group. Finally, the detection of positive expression of TNF-α, IL-6 and IFN-γ in the epithelial cells of the majority of ES specimens from patients with MD confirmed the up-regulated expression of these cytokines in the ES of patients with MD. Conclusions: The identification of up-regulated expression levels of TNF-α, IL-6 and IFN-γ in the ELF in the present study has provided direct evidence for an increased immunologic activity in the microenvironment of the ES in patients with unilateral MD, may suggest the local inflammatory response underlies the mechanism of this disease.

A comparison of endolymphatic duct blockage, endolymphatic sac drainage and endolymphatic sac decompression surgery in reversing endolymphatic hydrops in Meniere's disease.

BACKGROUND: To explore the differences between endolymphatic duct blockage, endolymphatic sac drainage and endolymphatic sac decompression surgery in the reversal of endolymphatic hydrops (EH) in patients with intractable Meniere's disease (MD). METHODS: A total of 27 MD patients receiving endolymphatic duct blockage surgery (n = 10), endolymphatic sac drainage surgery (n = 9) and endolymphatic sac decompression surgery (n = 8) underwent gadolinium-enhanced inner ear magnetic resonance imaging (MRI) scans prior to, 2 weeks after and at > 12 months following surgery. RESULTS: In the group with endolymphatic duct blockage, the second MRI revealed no changes in EH, whereas the third MRI revealed a reversal of vestibular EH in 3 patients and a downgrading of cochlear hydrops in 2 of these 3 patients, who presented with an improvement in their hearing and complete control of vertigo. In the group with endolymphatic sac drainage, the second MRI showed a reversal of EH in 4 patients, and no changes in EH in the remaining 5 patients, whereas the third MRI showed that those 4 patients who presented with a reversal of EH at the second MRI stage remained unchanged except a recurrence of vestibular hydrops in 1 patient. All 4 patients exhibited a complete control of vertigo, but hearing improved in 1, worsened in 1 and remained unchanged in 2. In the group with endolymphatic sac decompression, both the second and third MRI examination revealed no reversal of EH. CONCLUSIONS: The present study has shown that both endolymphatic duct blockage surgery and endolymphatic sac drainage surgery have the potential to reduce EH in certain MD patients, but none of the patients receiving endolymphatic sac decompression surgery showed reversal of their EH.

A 90-day Sub-chronic Oral Toxicity Assessment of Mulberry Extract in Sprague Dawley Rats.

Mulberry extract from Fructus Mori contains an anthocyanin pigment and has been widely used as a food additive in China and other Eastern Asian countries. Only few research has been done on toxicological profiling of mulberry extract for its safety evaluation; however, the data is inconclusive. In the current study, mulberry extract of 4200, 1400, or 466 mg/kg were orally administrated to Sprague Dawley rats for 90 consecutive days followed by a recovery period of 28 days. No abnormalities were detected in body weights, food intake, ophthalmological, hematological, coagulation, clinical chemistry, and organ weights parameters. Discoloration of urine (red, purple, and brown) and feces (black), along with bedding material (purple) were observed in the 4200 mg/kg group. Further, microscopic examination revealed brown granules in the renal tubular cells for rats in 4200 and 1400 mg/kg groups. Since these changes were associated with excretory effect of the extract, the No Observed Adverse Effect Level was determined to be 4200 mg/kg, which was equivalent to the 1058.5 mg/kg of anthocyanin.

Tongxinluo promotes axonal plasticity and functional recovery after stroke.

BACKGROUND: The aim of this study was to investigate the neural plasticity in contralesional cortex and the effects of tongxinluo (TXL) in cerebral ischemic rats. METHODOLOGY: We used stroke-prone renovascular hypertensive (RHRSP) cerebral ischemia rat models to study the effect of TXL and the underlying mechanisms. We performed foot-fault and beam-walking tests to evaluate the motor function of rats after cortical infarction. Biotinylated dextran amine (BDA) was used to track axonal sprouting and neural connections. RESULTS: TXL enhanced the recovery of motor function in cerebral infarction rats. TXL increased axonal sprouting in the peri-infarcted area but not in the corpus callosum, indicating in situ origination instead of crossing between cortical hemispheres through the corpus callosum. TXL promoted the sprouting of corticospinal axons into the denervated side of spinal gray matter. The synaptophysin (SYN)-positive intensity in the peri-infarcted area of TXL-treated group was greater than that in the vehicle group. We observed co-localization of SYN with BDA-positive fibers in the denervated spinal cord gray matter in the TXL group, suggesting that axonal remodeling and synaptic connections were promoted by TXL. CONCLUSION: TXL may promote the recovery of neurological function by promoting the axonal remodeling and synapse formation of motor neuronal fibers after focal cortical infarction in hypertensive rats.

Spontaneous Neuronal Plasticity in the Contralateral Motor Cortex and Corticospinal Tract after Focal Cortical Infarction in Hypertensive Rats.

OBJECTIVES: In this study, we investigated the spontaneous neural plasticity on the contralateral side in hypertensive rats, including the expression of nerve growth factors (synaptophysin [SYN] and growth-associated protein 43 [GAP-43]), and the association between nerve fiber sprouting and redistribution, and the recovery of motor functions following sensorimotor cortical infarction. METHODS: Initially, Sprague-Dawley rats were induced with renal hypertension by the bilateral renal arteries clips method. Further, they were induced with cerebral ischemia by the middle cerebral artery electrocoagulation method; 70 male rats completed the study. We compared the changes in the corticospinal tract (CST) and the expressions of SYN and GAP-43 on the contralateral side in rats with cerebral infarction using immunohistochemical staining, western blot, and biotinylated dextran amine (BDA) tracing analyses. The recovery of motor function in rats after cortical infarction was evaluated by the foot-fault and beam-walk tests. RESULTS: The motor behavior tests revealed that the motor function of rats could recover to various degrees after focal cortical infarction. Compared with the sham-operated group, the SYN and GAP-43 levels increased in the motor cortex of the opposite hemisphere within 28 days after middle cerebral artery occlusion (MCAO). The increase in SYN and GAP-43 expressions presented differently in layers Ⅱ, Ⅲ, and Ⅴ. The amount of BDA-positive fibers also increased significantly in the denervated cervical spinal gray matter on day 56 post-MCAO. CONCLUSIONS: The increases in SYN and GAP-43 on the contralateral side of the motor cortex could promote CST sprouting and rewiring in the spinal cord gray matter and also spontaneous motor function recovery after cortical infarction.

Value of CT and three-dimensional reconstruction revealing specific radiological signs for screening causative high jugular bulb in patients with Meniere's disease.

BACKGROUND: The aim of the present study was to investigate the pathological features of vestibular aqueduct (VA) related high jugular bulb (HJB) and explore the possible cause-consequence relation between HJB and endolymphatic hydrops (EH), and the potential specific radiological signs for screening causative HJB in Meniere's disease (MD). METHODS: High-resolution computed tomography (HRCT) and three-dimensional reconstruction (3DRC) were used to detect the anatomical variables associated with VA and jugular bulb (JB) in hydropic and non-hydropic ears. The presence or absence of EH in the inner ear was determined by gadopentetate dimeglumine-enhanced magnetic resonance imaging. The presence of different types of HJB, the anatomical variables of the VA and JB and the three types of anatomical relationship between the VA and HJB were compared between the hydropic and non-hydropic ears using the χ2 or Fisher's exact tests. P < 0.05 was considered to indicate a statistically significant difference. RESULTS: JB was classified as: Type 1, no bulb; type 2, below the inferior margin of the posterior semicircular canal (PSCC); type 3, between the inferior margin of the PSCC and the inferior margin of the internal auditory canal (IAC); type 4, above the inferior margin of the IAC. There were no significant differences in the presence of types 1, 2 and 3 JB between two groups. The presence of type 4 JB, average height of the JB and prevalence of the non-visualization of the VA in CT scans showed significant differences between two groups. The morphological pattern between the JB and VA revealing by 3DRC was classified as: Type I, the JB was not in contact with the VA; type II, the JB was in contact with the VA, but the latter was intact without obstruction; type III, the VA was obliterated by HJB encroachment. There were no significant differences in the presence of type I and II between two groups. Type III was identified in 5 hydropic ears but no non-hydropic ears, with a significant difference observed between the two groups. CONCLUSION: The present results showed that JB height and non-visualization of the VA on Pöschl's plane could render patients susceptible to the development of EH. A jugular bulb reaching above the inferior margin of the IAC (type 4 JB) could obstruct VA, resulting in EH in a few isolated patients with MD. VA obliteration revealed by 3DRC, as a specific radiological sign, may have the potential for screening causative HJB in MD.

Safety reassessment of cinobufotalin injection: new findings into cardiotoxicity.

Cinobufotalin injection, a traditional Chinese medicine preparation, successfully used for several years, might induce cardiotoxicity. The aim of the study was to evaluate the cardiotoxicity of cinobufotalin injection and the cardiotoxicity-preventive effect of sodium phenytoin in vivo. According to the 4 × 4 Latin square design, four Beagle dogs were allocated into four dose levels of 0, 0.3, 1, and 3 g/kg in treatment phases I-IV (cinobufotalin injection) and 3 g/kg in treatment phase V (cardiotoxicity antidote). The following parameters and endpoints were assessed: clinical observations, body weight, indicators of myocardial injury, and electrocardiogram (ECG) parameters. The cinobufotalin injection-related changes were observed in clinical observations (rapid breathing pattern), indicators of myocardial injury (increased cardiac troponin I, creatine kinase isoenzymes, and aspartate aminotransferase), and ECG graphics (arrhythmia) at 3 g/kg concentration in treatment phases I-IV. The cardiotoxicity of cinobufotalin injection was attenuated by sodium phenytoin in treatment phase V. The results confirmed the cardiotoxicity of cinobufotalin injection, and they might bring information about the appropriate monitoring time points and cardiotoxicity parameters in clinical practices and shed light on the treatment of cardiovascular adverse reactions.

Association between blood pressure variability and the short-term outcome in patients with acute spontaneous subarachnoid hemorrhage.

The association between the fluctuation in blood pressure (BP) and the early outcomes of patients with subarachnoid hemorrhage (SAH) remains unclear. Our study aimed to evaluate the value of blood pressure variability (BPV) for predicting the short-term outcomes of patients with acute spontaneous SAH. We collected data from 303 patients hospitalized for acute spontaneous SAH. BP values were recorded at admission and subsequently every 2 h during the initial 24 h of hospitalization. BPV was determined as the standard deviation (SD), the difference between the maximum and the minimum (ΔBP), the coefficient of variation (CV), and successive variation (SV). The outcome at discharge was assessed according to the Glasgow Outcome Scale (GOS). The association between BPV and the outcome was identified by multivariable analysis. The findings showed that the parameters of systolic BPV were independently associated with the outcome in a graded fashion. The odds ratios (OR) for the highest tertiles were as follows: SD 13.9 (95% confidence interval [CI], 4.8-40.4), ΔBP 4.4 (95% CI, 1.6-11.9), CV 16.4 (95% CI, 5.6-48.8), SV 15.8 (95% CI, 5.3-46.9). However, there was no association between a poor outcome and diastolic BPV (all p > 0.05). In conclusion, systolic BPV within the first 24 h after admission was independently associated with the outcomes in SAH patients; the greater the variability was, the worse the outcome.

Clinical Features of Nephrotic Syndrome with Cerebral Hemorrhage.

BACKGROUND Cerebral hemorrhage has been increasingly reported in patients with nephrotic syndrome (NS). However, the clinical features and pathogenesis of NS patients with cerebral hemorrhage remain unclear. MATERIAL AND METHODS From January 2007 to August 2017, continuous NS patients with cerebral hemorrhage at the First Affiliated Hospital of Guangxi Medical University were selected. The clinical manifestations, laboratory measurements, and neurological images of these patients were collected and analyzed. RESULTS Acute cerebral hemorrhage was recorded in 15 of 10 461 NS patients. The average age of these 15 patients (9 males and 6 females) was 50.87±23.27 years old. Among these 15 patients, conventional vascular risk factors were identified in 8 patients, hypoalbuminemia and proteinuria were recorded in all 15 patients, coagulopathy was observed in 9 patients, increased D-dimer level was recorded in 13 patients, hyperlipidemia was recorded in 11 patients, and impaired renal function was recorded in 9 patients. The hemorrhage developed in the lobe (n=9), basal ganglia (n=3), cerebellum (n=2), and cerebral hemisphere (n=1). Eight patients were in a coma on the day the cerebral hemorrhage occurred, while 12 patients had a poor prognosis after 30 days of hemorrhage onset. CONCLUSIONS Poor prognosis was recorded in NS patients with cerebral hemorrhage. Although conventional vascular risk factors have only been identified in 8 patients, biochemical abnormalities (hypoalbuminemia, proteinuria, elevated D-dimer, and hyperlipidemia) were recorded in the majority of these 15 patients. Furthermore, most of the hemorrhages developed in the lobes. Coagulopathy might be the potential pathogenesis of cerebral hemorrhage in NS patients.

The synthesis and antistaphylococcal activity of dehydroabietic acid derivatives: modifications at C12 and C7.

A series of 7-N-acylaminoethyl/propyloxime derivatives of dehydroabietic acid were synthesized and investigated for their antibacterial activity against Staphylococcus aureus Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108 and NRS-271). Most of the target compounds having trifluoromethyl phenyl/benzyl, halogen-substituted thiophenyl, benzothiophenyl or pyrrolyl moiety exhibited potent in vitro antibacterial activity. Among which, compounds 4m, 4x and 7j showed high antibacterial activity with minimum inhibitory concentration (MIC) values of 1.25-3.13 µg/mL against five multidrug-resistant S. aureus.

The synthesis and antistaphylococcal activity of dehydroabietic acid derivatives: Modifications at C-12.

A series of 12-oxime and O-oxime ether derivatives of dehydroabietic acid were synthesized and investigated for the antibacterial activity against Staphylococcus aureus Newman strain and five multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108, and NRS-271). The aromatic oximate derivative 11a showed the highest activity with MIC of 0.39-0.78µg/mL against S. aureus Newman. Of note, compounds 10b, 11 and 14 showed the most potent antibacterial activity against five multidrug-resistant S. aureus with MIC values of 1.25-3.13µg/mL. These results offered useful information for further strategic optimization in search of the antibacterial candidates against infection of multidrug-resistant Gram-positive bacteria.

Effects of Transportation on Antioxidant Status in Cynomolgus Macaques (Macaca fascicularis).

To evaluate the effects of transportation on oxidative stress in cynomolgus monkeys, we measured serum levels of reduced glutathione (GSH), malondialdehyde, and protein carbonyl (PC) and the activities of total antioxidant capacity (TAOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in cynomolgus macaques before transportation (day 0), on the day of arrival (day 1), and on days 7, 14, and 21 after transportation. Compared with that on day 0, TAOC and catalase activities on days 1, 7, and 14 after transportation were significantly decreased, reached their nadirs on day 7, and increased thereafter to reach their pretransportation levels by day 21 after transportation. Compared with day 0 levels, mean SOD activity and GSH concentration were decreased significantly on day 1; they thereafter increased to reach their pretransportation measures by day 7 after transportation. In contrast, PC and malondialdehyde concentrations in serum and the activity of GSH-Px were increased on day 1 compared with day 0 and thereafter decreased to reach their pretransportation levels by day 14 after transportation. In summary, GSH, TAOC, catalase, and SOD levels decreased and malondialdehyde, PC, and GSH-Px concentrations increased in cynomolgus macaques after transportation. These results suggest that transportation might imbalance oxidant and antioxidant levels to create excess oxidative stress in cynomolgus macaques. Therefore, cynomolgus macaques should have at least 21 d to recover after transportation and regain their healthy status.

Effects of Ketamine on Metabolomics of Serum and Urine in Cynomolgus Macaques (Macaca fascicularis).

In this study, a metabolomics approach based on nuclear magnetic resonance spectroscopy and pertinent multivariate data analyses was used to evaluate the effect of ketamine on metabolic markers in cynomolgus macaques. Principal component analysis and orthogonal projection to latent structure with discriminant analysis showed that ketamine (10 mg/kg) induced metabolic perturbations. Compared with the control group, ketamine-treated macaques had lower serum levels of α-glucose, myoinositol, lactate and succinate and lower urine levels of pyruvate and lactate. In contrast, the levels of leucine in serum and arginine in urine were significantly higher in the ketamine group. Our results also demonstrated that a single injection of ketamine influenced the major energy and amino acid metabolic pathways in cynomolgus macaques. Our study suggests that these influences should be considered in the design of experiments and the interpretation related blood and urine data from ketamine-sedated cynomolgus macaques.

Analysis of prognostic factors of endoscopic optic nerve decompression in traumatic blindness.

CONCLUSIONS: Hemorrhage within the ethmoid and/or sphenoid sinus and an interval between the time of injury and the time of operation exceeding 3 days are the risk factors for the visual prognosis of traumatic blindness. OBJECTIVES: To investigate the therapeutic efficacy of endoscopic optic nerve decompression in the treatment of traumatic blindness and to evaluate the relevant prognostic factors. METHODS: Eighty-five cases of traumatic blindness were analyzed retrospectively. Univariate analysis and multiple logistic regression were performed to evaluate potential prognostic factors. RESULTS: The overall rate of vision acuity improvement was 44.7% (38 of 85). Univariate analysis indicated that hemorrhage within the ethmoid and/or sphenoid sinus was significantly associated with unrecovered visual acuity. However, multiple logistic regression analysis identified that an interval between the time of injury and the time of operation exceeding 3 days, and hemorrhage within the ethmoid and/or sphenoid sinus were significantly correlated with the efficacy of treatment of traumatic blindness.

Bacteriological and molecular identification of Bartonella species in cats from different regions of China.

With the improvements in diagnostic techniques, Bartonella henselae (B. henselae) infection has recently been recognized to cause a widening spectrum of diseases. Cats are the natural reservoir hosts of B. henselae. The current study aims to investigate the prevalence of B. henselae infection in the cat populations in China. Polymerase chain reaction (PCR) and bacterial cultures confirm that 12.7% of the tested cats were positive for the infection. Old age and outdoor exposure were statistically associated with the infection. Multilocus sequence typing and eBURST analysis of the cat isolates collected in the present study show that 65.4% of the isolates belong to sequence type 1 (ST1). Three new STs (ST16-18) were identified in Midwestern China. These results may aid our understanding of the population structure of B. henselae in China and the relationship between human and cat strains in subsequent studies.

Helper component-proteinase (HC-Pro) protein of Papaya ringspot virus interacts with papaya calreticulin.

Potyviral helper component-proteinase (HC-Pro) is a multifunctional protein involved in plant-virus interactions. In this study, we constructed a Carica papaya L. plant cDNA library to investigate the host factors interacting with Papaya ringspot virus (PRSV) HC-Pro using a Sos recruitment two-hybrid system (SRS). We confirmed that the full-length papaya calreticulin, designated PaCRT (GenBank accession no. FJ913889), interacts specifically with PRSV HC-Pro in yeast, in vitro and in plant cells using SRS, in vitro protein-binding assay and bimolecular fluorescent complementation assay, respectively. SRS analysis of the interaction between three PaCRT deletion mutants and PRSV HC-Pro demonstrated that the C-domain (residues 307-422), with a high Ca(2+)-binding capacity, was responsible for binding to PRSV HC-Pro. In addition, quantitative real-time reverse transcriptase-polymerase chain reaction assay showed that the expression of PaCRT mRNA was significantly upregulated in the primary stage of PRSV infection, and decreased to near-basal expression levels in noninoculated (healthy) papaya plants with virus accumulation inside host cells. PaCRT is a new calcium-binding protein that interacts with potyviral HC-Pro. It is proposed that the upregulated expression of PaCRT mRNA may be an early defence-related response to PRSV infection in the host plant, and that interaction between PRSV HC-Pro and PaCRT may be involved in plant calcium signalling pathways which could interfere with virus infection or host defence.