[Clinical management and prognosis for descending necrotizing mediastinitis].

Objective: To investigate the clinical characteristics, treatment experiences and prognostic factors for descending necrotizing mediastinitis (DNM). Methods: A retrospective analysis was performed on the data of 22 patients with DNM diagnosed and treated in Henan Provincial People's Hospital from January 2016 to August 2022, including 16 males and 6 females, aged 29-79 years. After admission, all patients underwent CT scanning of the maxillofacial, cervical, and thoracic regions to confirm their diagnoses. Emergency incision and drainage were performed. The neck incision was treated with continuous vacuum sealing drainage. According to the prognoses, the patients were divided into cure group and death group, and the prognostic factors were analyzed. SPSS 25.0 software was used to analyze the clinical data. Rusults: The main complaints were dysphagia (45.5%, 10/22) and dyspnea (50.0%, 11/22). Odontogenic infection accounted for 45.5% (10/22) and oropharyngeal infection accounted for 54.5% (12/22). There were 16 cases in the cured group and 6 cases in the death group, with a total mortality rate of 27.3%. The mortality rates of DNM typeⅠand typeⅡwere respectively 16.7% and 40%. Compared with the cured group, the death group had higher incidences for diabetes, coronary heart disease and septic shock (all P<0.05). There were statistically significant differences between the cure group and the death group in procalcitonin level (50.43 (137.64) ng/ml vs 2.92 (6.33) ng/ml, M(IQR), Z=3.023, P<0.05) and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score (16.10±2.40 vs 6.75±3.19, t=6.524, P<0.05). Conclution: DNM is rare, with high mortality, high incidence of septic shock, and the increased procalcitonin level and APACHE Ⅱ score combined diabetes and coronary heart disease are the poor prognostic factors for DNM. Early incision and drainage combined with continuous vacuum sealing drainage technique is a better way to treat DNM.

[Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population].

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

[Clinical analysis of 5 cases of dural arteriovenous fistulas complained of pulsatile tinnitus].

Objective: The clinical characteristics of dural arteriovenous fistula with pulsatile tinnitus were analyzed to deepen the understanding of the disease. Methods: The clinical data of five patients complained of pulsatile tinnitus and diagnosed dural arteriovenous fistula in Henan People's Hospital from May 2013 to June 2018 were retrospectively analyzed, including 3 males and 2 females, aged 27-65 years. Results: The main clinical symptoms of the five patients were continuous pulsatile tinnitus, accompanied/not accompanied by headache, memory decline, etc., with a course of three months to 20 years. They were diagnosed as dural arteriovenous fistula by digital subtraction angiography, and three cases of tinnitus disappeared and two cases of tinnitus were relieved after embolization. Conclusions: The dural arteriovenous fistula is a rare and complicated disease. When the patient complain of the pulsatile tinnitus, the related etiology should be considered and managed properly.

[Analyses of diagnosis and treatment of foreign body aspiration in children with tracheobronchial variations].

Objective: To investigate the key issues in the diagnosis and treatment of foreign body aspiration in children with tracheobronchial variations. Methods: A retrospective study was performed for 11 pediatric patients who were treated in Department of Otorhinolaryngology and Head and Neck Surgery, Henan Province People's Hospital after a diagnosis of foreign body aspiration with tracheobronchial variations between January 2015 and December 2017. There were 7 males and 4 females among the 11 cases of foreign body aspiration with tracheobronchial variations, ranging between 9 months and 11 years of age. Results: Among 11 cases, the types of variationswere tracheal bronchus in 9 cases, bridging bronchus in 1 case and simple tracheal stenosis in 1 case. All of the pediatric patients were under general anesthesia, and the foreign bodies were removed by bronchoscopy successfully with no significant complications. Conclusions: The possibility of tracheobronchial variations should be considered in children with recurrent wheezing and poor efficacy of regular treatment before foreign body aspiration. Removal of foreign body via rigid bronchoscope under general anesthesia is a safe and effective treatment. These children are needed to combine the situation oftracheobronchial variations and the location of foreign bodies to guide the operation, and strengthened the perioperative treatment.

[Diagnosis and therapy strategy of acute invasive fungal rhino-sinisitis].

Summary Acute invasive fungal rhino-sinisitis(AIFRS) is a kind of acute fungus infectious disease.It ofen deteriorates rapidly and abruptly,which occurs in the nose and sinuses with somepeople who have low immunological function.This paper reviewed the progress about the acute invasive fungal rhino-sinisitis's clinical characteristics,diagnosis,treatment and prognosis to improve the level of early diagnosis and reduce the mortality.

[Endoscopic sinus surgery for the treatment of invasive fungal sinusitis].

Objective:To explore the early diagnosis, the treatment and theprognosis of invasive fungal rhinosinusitis.Method:By summarizing the clinical data of 18 patients, CT and MRI images, pathological diagnosis and follow-up results to analysis the early diagnosis and the treatment.Result:All 5 patients with invasive fungal sinusitis were infected with mucor, 3 of whom died of intracranial complications. Among 13 patients with chronic invasive fungal rhinosinusitis, 9 were aspergillus, 3 were mucor, and 1 was negative. There were 9 cases of diabetes, 1 cases of ankylosing spondylitis, 3 cases of hypoproteinemia, 1 cases of organ transplantation, and 1 cases of leukemia. There were 3 cases of death who unenforced the operation, 15 patients received enlarged endoscopic surgery, postoperative antifungal therapy. Followed up 1-3 years, relapse in 3 cases, 1 case of death.Conclusion:The diagnosis of FRS needs to be combined with clinical manifestations, imaging features and pathological findings. The treatment requires surgery to completely remove diseased tissue (enlarged sinus open surgery) combined with antifungal use in sufficient quantities.

Protective role of curcumin on renal ischemia reperfusion injury via attenuating the inflammatory mediators and Caspase-3.

Renal ischemia/reperfusion (I/R) damage may arise due to nephron sparing surgery in patient with a solitary kidney of restricted renal parenchymas. Apoptosis, inflammation and oxidative stress play a significant role in the expansion of renal dysfunction following renal I/R. The aim of the current investigation was to particularize the potential effect of curcumin against hypoxia induced renal injury. The albino Wistar rats divided into groups and each group contains six rats. They groups are normal control; disease control; curcumin (5 mg/kg per day) and another group orally treated with curcumin (10 mg/kg per day) for two weeks before induction of renal I/R. The renal and serum samples were collected and used for the biochemical estimation. The renal tissue was further used for the histopathological estimation. The result of the current investigation demonstrated that the curcumin significantly (P<0.01) attenuated I/R induced renal injury in a dose-dependent way. It also causes significant (P<0.01) reduction in the serum creatinine, blood urea nitrogen level and also suppressed the kidney injury molecules-1. Additionally, it also causes significant inhibition of the malonaldehyde, caspase-3, myeloperoxide, lactose dehydrogenase and interferon-gamma together with enhanced interlukin-10 content.

[Voice acoustic study of plasma radiofrequency ablation for the treatment of laryngeal premalignant lesions].

Objective:To study the voice function effect of low temperature plasma radiofrequency ablation in the treatment of patients with laryngeal premalignant lesions. Method:Fifty cases of laryngeal premalignant lesions were treated with low temperature plasma radiofrequency ablation. All of the patients were examined by electronic laryngoscopy and acoustic analysis(F0，Jitter，Shimmer，NNE，HNR) in 2 weeks,1 month,3 months after surgery. Voice acoustic results were compared with a control group of 50 normal adults for the further analysis. Result:Fifty patients with laryngeal premalignant lesions were treated by low temperature plasma radiofrequency ablation.The result showed that 47 patients(94%)were successfully decannulated without serious complications, such as dyspnea, aphonia and anterior glottic stenosis. Acoustic analysis showed that F0,Jitter,Shimmer and NNE were significantly different from normal 2 weeks after surgery（P<0.01）.Voice function recovered weakly 1 month after operation（P<0.05）.There were no significant differences in the vocal parameters between plasma radiofrequency ablation group and control group 3 months after surgery(P>0.05). Conclusion:Radiofrequency coblation was a safe,minimally invasive and effective surgical method and can be widely used to treat laryngeal premalignant lesions．.

Comparison of dual-source parallel radio frequency transmission liver MRI at 3.0 T with conventional MRI.

AIM: Aim of the present study was to investigate the role of dual-source parallel Radio frequency (RF) and single-source excitation in liver imaging at 3.0 T MR. METHODS: This study was a retrospective analysis. One hundred and seven subjects underwent a 3.0 T TX MR scanning including axial spectrally selective attenuated inversion recovery (SPAIR) T2WI, axial DWI and coronal balanced-fast field echo (Balanced FFE). Each sequence was carried out with both single-source and dual-source RF excitation. Student's t test was used to compare whether there was difference between single-source and dual-source RF excitation in the image uniformity, single-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Wilcoxon signed rank test was used to determine whether there was difference between conventional and parallel transmission in the score of image quality. Reader agreement was assessed using the Cohen's Kappa test. RESULTS: For the image uniformity, there was significant difference between single-source and dual-source excitation (418.40±66.75 for single-source vs. 416.26±50.61 for dual-source, t=2.524, P<0.05). There also existed significant difference between single-source and dual-source excitation in SNR and CNR, respectively. The SNR and CNR of parallel transmission (22.03±12.16 and 18.33±10.01, respectively) were both higher than those of single transmission (20.36±11.21 and 15.22±8.95, respectively) (t=-2.630, P<0.05 for SNR and t=-4.238, P<0.05 for CNR). Image quality comparisons revealed significantly better results with dual-source than single-source RF excitation at SPAIR T2WI (1.4±0.42 vs. 1.81±0.27), DWI (1.08±0.46 vs. 1.63±0.36) and balanced FFE sequence (0.95±0.45 vs. 1.65±0.37, Z=-5.894, -5.801 and -6.985, respectively, P<0.01). In the comparison of image quality, the agreement between the two readers was very good (Kappa>0.8, P<0.05). CONCLUSION: Dual-source parallel RF excitation MR imaging in liver enables reducing dielectric shading, improving homogeneity of the RF magnetic induction field, and increasing SNR and CNR at 3.0 T.

State-Dependent Inhibition of Sodium Channels by Local Anesthetics: A 40-Year Evolution.

Knowledge about the mechanism of impulse blockade by local anesthetics has evolved over the past four decades, from the realization that Na+ channels were inhibited to affect the impulse blockade to an identification of the amino acid residues within the Na+ channel that bind the local anesthetic molecule. Within this period appreciation has grown of the state-dependent nature of channel inhibition, with rapid binding and unbinding at relatively high affinity to the open state, and weaker binding to the closed resting state. Slow binding of high affinity for the inactivated state accounts for the salutary therapeutic as well as the toxic actions of diverse class I anti-arrhythmic agents, but may have little importance for impulse blockade, which requires concentrations high enough to block the resting state. At the molecular level, residues on the S6 transmembrane segments in three of the homologous domains of the channel appear to contribute to the binding of local anesthetics, with some contribution also from parts of the selectivity filter. Binding to the inactivated state, and perhaps the open state, involves some residues that are not identical to those that bind these drugs in the resting state, suggesting spatial flexibility in the "binding site". Questions remaining include the mechanism that links local anesthetic binding with the inhibition of gating charge movements, and the molecular nature of the theoretical "hydrophobic pathway" that may be critical for determining the recovery rates from blockade of closed channels, and thus account for both therapeutic and cardiotoxic actions.

A Fuzzy Reasoning Design for Fault Detection and Diagnosis of a Computer-Controlled System.

A Fuzzy Reasoning and Verification Petri Nets (FRVPNs) model is established for an error detection and diagnosis mechanism (EDDM) applied to a complex fault-tolerant PC-controlled system. The inference accuracy can be improved through the hierarchical design of a two-level fuzzy rule decision tree (FRDT) and a Petri nets (PNs) technique to transform the fuzzy rule into the FRVPNs model. Several simulation examples of the assumed failure events were carried out by using the FRVPNs and the Mamdani fuzzy method with MATLAB tools. The reasoning performance of the developed FRVPNs was verified by comparing the inference outcome to that of the Mamdani method. Both methods result in the same conclusions. Thus, the present study demonstratrates that the proposed FRVPNs model is able to achieve the purpose of reasoning, and furthermore, determining of the failure event of the monitored application program.

Differential neurotoxicity of tricyclic antidepressants and novel derivatives in vitro in a dorsal root ganglion cell culture model.

BACKGROUND AND OBJECTIVE: Tricyclic antidepressants are commonly employed orally to treat major depressive disorders and have been shown to be of substantial benefit in various chronic pain conditions. Among other properties they are potent Na+ channel blockers in vitro and show local anaesthetic properties in vivo. The present study aimed to determine their differential neurotoxicity, and that of novel derivatives as prerequisite for their potential use in regional anaesthesia. METHODS: To directly test neurotoxicity in adult peripheral neurons, the culture model of dissociated adult rat primary sensory neurons was employed. Neurons were incubated for 24 h with amitriptyline, N-methyl-amitriptyline, doxepin, N-methyl-doxepin, N-propyl-doxepin, desipramine, imipramine and trimipramine at 100 mumol, and at concentrations correlating to their respective potency in blocking sodium channels. RESULTS: All investigated substances showed considerable neurotoxic potency as represented in significantly decreased neuron numbers in cultures as compared to controls. Specifically, doxepin was more neurotoxic than amitriptyline, and both imipramine and trimipramine were more toxic than desipramine or amitriptyline. Novel derivatives of tricyclic antidepressants were, in general, more toxic than the parent compound. CONCLUSIONS: Tricyclic antidepressants and novel derivatives thereof show differential neurotoxic potential in vitro. The rank order of toxicity relative to sodium channel blocking potency was desipramine < amitriptyline < N-methyl amitriptyline < doxepin < trimipramine < imipramine < N-methyl doxepin < N-propyl doxepin.

The signaling network of tumor invasion.

The ability of a cell to invade its surroundings is an important hallmark of malignant tumors and results from aberrant cell signaling mechanisms. The signal transduction that leads to tumor invasion can be broken down into major pathways. Even though the pathway systems are distinct in themselves, none of these pathways operate independently when it comes to transmitting signals that culminate in an invasive phenotype. That is, the malignant change in one receptor not only leads to malignant changes directly downstream but can also affect the molecules of many other pathways. Three major pathway systems involved in tumor invasion are discussed in this review: the integrin system, the insulin-like growth factor system, and the Rho family GTPases. Here we see that although the individual signaling systems can each contribute to invasion, each system is networked to others and should not be considered isolated. Each system is first reviewed as independent contributors to an invasive phenotype and then discussed in the context of interacting pathways that collectively result in tumor invasion.

State-dependent block of human cardiac hNav1.5 sodium channels by propafenone.

State-dependent blockade of human cardiac hNav1.5 sodium channels by propafenone was studied using whole-cell patch clamp techniques. Both a direct investigation using cells with inactivation-deficient sodium channels and an algorithmic approach used on cells with wild-type channels revealed a rapid binding of propafenone to the open state. This occurs approximately 4000 and 700 times faster than the binding to the resting and inactivated state, respectively. An established mathematical "gating" model was modified to represent the experimental data.

Interactions of local anesthetics with voltage-gated Na+ channels.

Voltage-gated Na+ channels are dynamic transmembrane proteins responsible for the rising phase of the action potential in excitable membranes. Local anesthetics (LAs) and structurally related antiarrhythmic and anticonvulsant compounds target specific sites in voltage-gated Na+ channels to block Na+ currents, thus reducing excitability in neuronal, cardiac, or central nervous tissue. A high-affinity LA block is produced by binding to open and inactivated states of Na+ channels rather than to resting states and suggests a binding site that converts from a low- to a high-affinity conformation during gating. Recent findings using site-directed mutagenesis suggest that multiple S6 segments together form an LA binding site within the Na+ channel. While the selectivity filter may form the more extracellular-located part of this binding site, the role of the fast inactivation gate in LA binding has not yet been resolved. The receptor of the neurotoxin batrachotoxin (BTX) is adjacent to or even overlaps with the LA binding site. The close proximity of the LA and BTX binding sites to residues critical for inactivation, together with gating transitions through S6 segments, might explain the strong impact of LAs and BTX on inactivation of voltage-gated Na+ channels and might help elucidate the mechanisms underlying voltage- and frequency-dependent LA block.

Methanethiosulfonate-modification alters local anesthetic block in rNav1.4 cysteine-substituted mutants S1276C and L1280C.

We previously showed that lysine substitutions at two residues in segment 6 of domain 3 in voltage-gated Na(+) channel rNav1.4 (S1276K, L1280K) reduced steady-state inactivated local anesthetic block. Here we studied cysteine substitutions at the same residues (S1276C, L1280C). We used whole-cell recordings to determine local anesthetic block (100 microM bupivacaine) before and after cysteine modification with 1.5 mM 2-aminoethyl methanethiosulfonate (MTSEA). Compared with rNav1.4, steady-state resting bupivacaine block at -180 mV was increased in S1276C, while inactivated block at -50 mV was not different in the mutants. After application of MTSEA at -160 mV, rNav1.4 showed enhanced bupivacaine block and a negative shift in V(1/2) of the bupivacaine affinity curve, while L1280C and S1276C showed a decrease in inactivated bupivacaine block after MTSEA. Application of MTSEA at 0 mV produced similar results in rNav1.4 and L1280C, but an opposite effect in S1276C, i.e., enhancement of bupivacaine block, with a large negative shift in V(1/2) of the bupivacaine affinity curve similar to that found in rNav1.4. We conclude that 1) MTSEA modification of 1276C or 1280C decreases inactivated bupivacaine block similar to that found in L1280K and S1276K, 2) residue 1276C is only accessible to MTS-modification in the resting state, and 3) MTSEA may modify a native cysteine in rNav1.4 that produces an allosteric, indirect effect on bupivacaine affinity.

Modifications of human cardiac sodium channel gating by UVA light.

Voltage-gated Na(+) channels are membrane proteins responsible for the generation of action potentials. In this report we demonstrate that UVA light elicits gating changes of human cardiac Na+ channels. First, UVA irradiation hampers the fast inactivation of cardiac Nav1.5 Na(+) channels expressed in HEK293t cells. A maintained current becomes conspicuous during depolarization and reaches its maximal quasi steady-state level within 5-7 min. Second, the activation time course is slowed by UVA light; modification of the activation gating by UVA irradiation continues for 20 min without reaching steady state. Third, along with the slowed activation time course, the peak current is reduced progressively. Most Na(+) currents are eliminated during 20 min of UVA irradiation. Fourth, UVA light increases the holding current nonlinearly; this phenomenon is slow at first but abruptly fast after 20 min. Other skeletal muscle Nav1.4 isoforms and native neuronal Na(+) channels in rat GH(3) cells are likewise sensitive to UVA irradiation. Interestingly, a reactive oxygen metabolite (hydrogen peroxide at 1.5%) and an oxidant (chloramine-T at 0.5 mM) affect Na(+) channel gating similarly, but not identically, to UVA. These results together suggest that UVA modification of Na(+) channel gating is likely mediated via multiple reactive oxygen metabolites. The potential link between oxidative stress and the impaired Na(+) channel gating may provide valuable clues for ischemia/reperfusion injury in heart and in CNS.

Local anesthetic properties of prenylamine.

BACKGROUND: Local anesthetics that produce analgesia of long duration with minimal impairment of autonomic functions are highly desirable for pain management in the clinic. Prenylamine is a known calcium channel blocker, but its local anesthetic blocking effects on voltage-gated sodium channels have not been studied thus far. METHODS: The authors characterized the tonic and use-dependent prenylamine block of native Na(+) channels in cultured rat neuronal GH3 cells during whole cell voltage clamp conditions and the local anesthetic effect of prenylamine by neurologic evaluation of sensory and motor functions of sciatic nerve during neural block in rats. RESULTS: Prenylamine elicits both use-dependent block of Na(+) channels during repetitive pulses (3 microm prenylamine produced 50% block at 5 Hz) and tonic block for both resting and inactivated Na(+) channels. The 50% inhibitory concentration for prenylamine was 27.6 +/- 1.3 microm for resting channels and 0.75 +/- 0.02 microm for inactivated channels. Furthermore, in vivo data show that 10 mm prenylamine produced a complete sciatic nerve block of motor function, proprioceptive responses, and nociceptive responses that lasted approximately 27, 34, and 24 h, respectively. Rats injected with 15.4 mm bupivacaine, a known local anesthetic currently used for pain management, had a significantly shorter duration of blockade (< 2 h) compared with rats injected with prenylamine. CONCLUSIONS: The data presented here demonstrate that prenylamine possesses local anesthetic properties in vitro and elicits prolonged local anesthesia in vivo.