[Advances in clinical prediction scores for prognosis of coronavirus disease-2019].

Coronavirus Disease-2019 (COVID-19) has been a major public health issue all over the world, placing a significant burden on available healthcare resources. The most common types of COVID-19 are the mild and common forms. Although the proportion of the severe-critical types is smaller, the rate of death is significantly higher and the medical resources required tend to be greater. Thus, a variety of scores based on other disease and COVID-19 were used to assess the risk of poor prognosis on the COVID-19, including the common scores for community-acquired pneumonia, sepsis and viral pneumonia. Unfortunately, the above scores often lacked an adequate description of the applicable population or were at high risk of bias with unknown applicability. Therefore, the article summarized the existing scores, aiming to provide a reference for clinical prognostic risk assessment.

Mercuric-sulphide based metallopharmaceutical formulation as an alternative therapeutic to combat viral and multidrug-resistant (MDR) bacterial infections.

According to the Global Antimicrobial Resistance and Use Surveillance System (GLASS) data, antibiotic resistance escalates more challenges in treatment against communicable diseases worldwide. Henceforth, the use of combinational antimicrobial therapy and metal-conjugated phytoconstituents composites are considered as alternatives. The present study explored the efficacy of mercuric-sulfide-based metallopharmaceutical, Sivanar Amirtham for anti-bacterial, anti-tuberculosis, anti-HIV therapeutics and toxicity profile by haemolytic assay, first of its kind. The anti-bacterial study was performed against both gram-positive and gram-negative pathogens including Staphylococcus aureus (ATCC 29213), Methicillin-resistant Staphylococcus aureus (MRSA: ATCC 43300), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (PA14) and Vibrio cholerae (MTCC 3905) by agar well diffusion assay, wherein the highest zone of inhibition was identified for MRSA (20.7 mm) and V. cholerae (34.3 mm) at 25 mg/mL. Furthermore, the anti-tuberculosis activity experimented by microtitre alamar blue assay against M. tuberculosis (ATCC 27294) demonstrated significant activity at the concentration range of 12.5-100 µg/mL. Additionally, the anti-HIV efficacy established by the syncytia inhibition method using C8166 cell lines infected with HIV-1IIIB, showed a significant therapeutic effect. The in-vitro toxicity assay proved Sivanar Amirtham to be non-haemolytic and haemocompatible. The physicochemical characterization studies revealed the nano-sized particles with different functional groups and the distinctive metal-mineral complex could be attributed to the multi-site targeting ability. The rationale evidence and scientific validation for the efficacy of Sivanar Amirtham ensures that it could be proposed as an alternative or adjuvant for both prophylactics and therapeutics to overcome HIV infection and antimicrobial resistance as well as the multi-drug resistance challenges.

Zika virus transmission via breast milk in suckling mice.

OBJECTIVES: Infectious Zika viral particles were detected in human milk; however, whether they can be transmitted via breastfeeding remains unknown, so our objective was to clarify this. METHODS: Here, in a natural breastfeeding model, wild-type (C57Bl/6; WT) or interferon α/ß (IFNα/ß) receptor-deficient (A129; KO) murine dams on day 1 post-delivery were infected with Zika virus (ZIKV) intraperitoneally, and the neonates were suckled. In a novel artificial feeding model, WT suckling mice at 1 day old were fed with ZIKV alone or ZIKV and human breast milk mixtures. Thereafter, the virus distribution, clinical progression and neuropathology in the WT or KO neonates were characterized to evaluate the risk of ZIKV transmission through breast milk. RESULTS: In natural breastfeeding, viral RNAs (8/8) and infectious viral particles (7/8) were extensively present in the mammary glands of KO dams. All tested KO neonates (5/5), and none of WT neonates (0/9), were infected with ZIKV. In artificial feeding, 100% of the WT neonates (two groups, 12/12 and 16/16) were infected and developed some signs of neurodegeneration. ZIKV tended to seed and accumulate in the lungs and were subsequently disseminated to other tissues in both 16 naturally suckled and 19 artificially fed infected neonates. As human breast milk was mixed with ZIKV and fed to WT neonates, 45% individuals (9/20) were infected; in the infected neonates, the viral spread to the brain was delayed, and the clinical outcomes were alleviated. CONCLUSIONS: These results demonstrated that suckling mice can be infected with ZIKV through suckling, and breast milk has potential antiviral activity, inhibiting ZIKV infection.

Intestinal absorption mechanisms of ginsenoside Rh2: stereoselectivity and involvement of ABC transporters.

This study investigated the absorption mechanism of ginsenoside Rh2 to clarify the reasons for its poor absorption. Transepithelial transport across Caco-2 cell monolayers, cellular uptake, and in situ rat intestinal perfusion were examined. Cellular uptake of Rh2 was linear from 1 to 50 µM at 4°C, whereas it was saturated when the concentration exceeded 10 µM at 37°C. At 37°C, the uptake at 10 µM was linear in 60 min. Intracellular exposure in 240 min was 2173.70 and 979.38 ng·min/µg for S and R isomers, respectively. Transepithelial permeability of Rh2 was about 10⁻8 to 10⁻7 cm/s. Efflux ratios were above 1.5. Sodium dodecyl sulfate, sodium citrate, and sodium deoxycholate had no effect on Rh2 permeability. After intestinal perfusion for 3 h, 9.1% of 20(R)-Rh2 and 15.7% of 20(S)-Rh2 were absorbed. Cyclosporine, quercetin, and probenecid could improve the cellular uptake, absorptive permeability, and intestinal absorption. Carrier-mediated transport was the major absorption mechanism. Rh2 was a substrate of ABC transporters. The ABC-transporter-mediated efflux and the poor permeability were the major reasons for Rh2 poor absorption. The stereoselective absorption was significant. R isomer exhibited lower absorption profiles in all the experiments, possibly due to more potent efflux.

Increased tau phosphorylation and beta amyloid in the hipocampus of mouse pups by early life lead exposure.

The aim of this study was to investigate the effects of maternal lead exposure on the learning and memory ability and expression of tau protein phosphorylation (P-tau) and beta amyloid protein (Abeta) in hippocampus of mice offspring. Pb exposure initiated from beginning of gestation to weaning. Pb acetate administered in drinking solutions was dissolved in distilled deionized water at the concentrations of 0.1%, 0.5% and 1% groups. On the 21 th of postnatal day, the learning and memory ability of the mouse pups was tested by Water Maze test and the Pb levels in blood and hippocampus of the offspring were also determined. The expression of P-tau and Abeta in hippocampus was measured by immunohistochemistry and Western blotting. The Pb levels in blood and hippocampus of all exposure groups were significantly higher than that of the control group ( P < 0.05). In Water Maze test, the performances of 0.5% and 1% groups were worse than that of the control group ( P < 0.05). The expression of P-tau and Abeta was increased in Pb exposed groups than that of the control group ( P < 0.05). Tau hyper-phosphorylation and Abeta increase in the hippocampus of pups may contribute to the impairment of learning and memory associated with maternal Pb exposure.

Eight novel MHC class I alleles identified in Chinese-origin rhesus macaques.

We report here the identification of four Mamu-A1 and four Mamu-B novel alleles of Chinese-origin rhesus macaques.

[A cmparative study of the voice function change in patients who underwent total thyroidectomy between preoperative and postoperative].

Objective:The aim of this study is to investigate the voice function change in patients who underwent total thyroidectomy between preoperative and the third day postoperative, Taking the result data to explore methods for voice protection and be valuable for clinical diagnose and treatment. Method:Three hundred and fifth-three patients with thyroid papillary carcinoma without preoperative vocal dysfunction were treated with total thyroidectomy and single or bilateral central cervical lymph node dissection. At preoperative and the third day postoperative, videostroboscopic, acoustic analysis, voice handicap index 10（VHI-10）are measured. Result: At the third day postoperative, 294 （83.29%）patients have voice symptoms，the most common voice disorder is hoarseness in 105 cases （35.71%），phonasthenia in 78 cases（26.53%），unable speak louderly in 53 cases （18.03%）, unable speak high-pitch in 24 cases （8.16%）, unable speak low-pitch in 29 cases （9.86%）, pronunciation leakage in 5 cases （1.70%）. Videostroboscopic examinations are normal in all patients at the third day postoperative. The total score of VHI-10, Physiology（P）, Emotion（E） dimensions in VHI-10 between preoperative and the third day postoperative are statistically significant （P<0.05）. For male patients, the acoustic analysis （fundamental frequency, Harmonicto Noise Ratio, Shimmer and Maximum phonation time） are statistically significant between preoperative and the third day postoperative （P<0.05）. For female patients, acoustic analysis （fundamental frequency, Harmonicto Noise Ratio, Shimmer, Jitter and Maximum phonation time） are statistically significant between preoperative and the third day postoperative （P<0.05）. Conclusion:These patients who underwent total thyroidectomy with bilateral or unilateral central partment lymph node dissection may develop voice complications even their recurrent laryngealnerve be undamaged during the surgery. Changes in surgery and voice may cause changes in the patient's psychology, suggesting that clinicians need to have adequate communication between doctors and patients before surgery, pay attention to the patient's voice quality and psychological changes, and give positive intervention.

[The application of parental version of pediatric voice-related quality of life in children with voice disorders].

Objective:To evaluate the influence of voice disorders on children's quality of life through the parental version of pediatric voice-related quality of life（pVRQOL）. Method:Three hundred and eighty-six children from August 2017 to December 2018 were enrolled in this study. A total of 214 parents of children had voice disorders（dysphonic group）, and 172 parents of children were without voice disorders（control group）. Both groups were filled out the questionnaire containing the parental version of pVRQOL. Result:① The most common disease in children with voice disorder was vocal fold nodule, and boys were more susceptible to voice disorder than girls（71.5%, 28.5%）; ②In dysphonic group, the scores of total（91.40±8.63, 97.94±4.23）, physiology and function（87.55±10.98, 96.99±6.10）, social emotion（98.86 ±3.29, 99.73±1.08） were lower than those in control group（P<0.01）; ③In dysphonic group, there was a correlation between the parents' overall evaluation of the children's voice quality and the three dimensions of the parental version of pVRQOL（total: r=-0.398, P<0.01, physical function: r=-0.448, P<0.01, social-emotion: r=-0.125, P<0.05）. Conclusion:Voice disorders could cause a negative impact on children's voice related quality of life. pVRQOL could be applied to assess the voice-related quality of life in children with voice disorders.

[The application of pediatric voice handicap index in children with voice disorders].

Objective: To access the influence of voice disorders on children's voice-related quality of life through the parental version of pediatric voice handicap index (pVHI). Methods: From April 2017 to March 2018, a total of 192 children with voice disorders (dysphonic group) and 111 children without voice disorders (control group) were enrolled in this work. Parents of children in both groups were asked for fill out the questionnaire containing the parental version of pVHI and the data of non-normal distribution were analyzed by Mann-Whitney U test. Spearman test was used for correlation analysis. Results: (1)Vocal cord nodule was the most common voice disorder in children, and boys were more susceptible to voice disorder than girls in this study (70.3%(135/192) vs 29.7%(57/192)). (2)The most common voice abuse or misuse habit was "Shouting loudly". (3)In dysphonic group, the scores of function, physiology, emotion and total were higher than those in control group (all P<0.05). (4)In dysphonic group, there was a weak correlation between the parents' overall evaluation of the children's voice status and the three dimensions of the parental version of pVHI (function: r=0.339, physiology: r=0.334, emotion: r=0.208, all P<0.001). Conclusions: Voice disorders can cause a negative impact on children's quality of life. Parental version of pVHI can be used to assess the voice-related quality of life in children with voice disorders.

[Research status and challenges of vocal cord leukoplakia].

Vocal cord leukoplakia is a clinical diagnosis defined as a whitish patch or a plaque on a mucosal surface. Because of the diversity of histopathological types, the complexity and unpredictability risks for malignant transformation, there are still many controversies about its histopathological classification, diagnosis and treatment. The aim of this article is to review the epidemiology, etiology, pathological classification, diagnosis, treatment and prognosis of vocal cord leukoplakia.

Bidirectional regulation of Munc13-3 protein expression by age and dark rearing during the critical period in mouse visual cortex.

Rearing in darkness slows the time course of the visual cortical critical period, such that at 5 weeks of age normal cats are more plastic than dark-reared cats, while at 20 weeks dark-reared cats are more plastic [Mower GD (1991) The effect of dark rearing on the time course of the critical period in cat visual cortex. Dev Brain Res 58:151-158]. Thus, genes that are important for visual cortical plasticity should show differences in expression between normal and dark-reared visual cortex that are of opposite direction in young versus older animals. Previously, we showed by differential display polymerase chain reaction and northern blotting that mRNA for Munc13-3, a mammalian homologue of the C. elegans uncoordinated (unc) gene, shows such bidirectional regulation in cat visual cortex [Yang CB, Zheng YT, Li GY, Mower GD (2002) Identification of Munc13-3 as a candidate gene for critical period neuroplasticity in visual cortex. J Neurosci 22:8614-8618]. Here, the analysis is extended to Munc13-3 protein in mouse visual cortex, which will provide the basis for gene manipulation analysis. In mice, Munc13-3 protein was elevated 2.3-fold in dark-reared compared with normal visual cortex at 3.5 weeks and 2.0-fold in normal compared with dark-reared visual cortex at 9.5 weeks. Analysis of variance of protein levels showed a significant interaction, indicating that the effect of dark rearing depended on age. This bidirectional regulation was restricted to visual cortex and did not occur in frontal cortex. Bidirectional regulation was also specific to Munc13-3 and was not found for other Munc13 family members. Munc13 proteins serve a central priming function in synaptic vesicle exocytosis at glutamatergic and GABAergic synapses and this work contributes to the growing evidence indicating a role of Munc13 genes in synaptic plasticity.

[Clinical and pathological analyses of 154 patients with white lesion of vocal cord].

Objective: To investigate the clinical and pathological features and prognosis of white lesion of vocal cord. Methods: One hundred and fifty-four cases of white lesion of vocal cord from January 2009 to February 2016 were retrospectively analysed. All the patients had undergone the resection of white lesion of vocal cord resection through retaining laryngoscope under general anesthesia with the specimens pathologically examined. Results: There were 148 males and 6 females in this study. The ages ranged from 36 to 83 years, and the median age was 54.5.There were 103(66.88%) long-term smokers, and 64(41.56%) long-term drinkers. Postoperative pathology showed that chronic mucosal inflammation in 19 cases (12.34%), squamous epithelial hyperplasia in 56 cases(36.36%), mild dysplasia in 25 cases(16.23%), moderate dysplasia in 34 cases(22.08%), severe dysplasia in 12 cases(7.79%), carcinoma in situ in 6 cases(3.90%), and invasive carcinoma in 2 cases(1.30%). The recurrence rate and canceration rate of chronic mucosal inflammation were 0. The recurrence rate of squamous epithelial hyperplasia was 10.71%, the canceration rate was 0.The recurrence rate of mild dysplasia was 8.00%, the canceration rate was 0. The recurrence rate of moderate dysplasia was 20.59%, the canceration rate was 8.82%. The recurrence rate of severe dysplasia was 25.00%, the canceration rate was 16.67%. Conclusions: White lesion of vocal cord is a predominantly male disease. Long-term smokering and drinking are one of common causes. The final diagnosis of white lesion of vocal cord relies on the pathology. Closed observation is necessary for theses dysplasia cases. The majority of which are benign, the operation effect is good.

[A comparative study of therapy effects between esomeprazole plus mosapride citrate and botulinum toxin injection on vocal process granuloma].

Objective:Anti-reflux medications or botulinum toxin A injections are the main current therapies for the definite vocal process granuloma. This studies is focusing on comparing the effects of proton pump inhibitors plus prokinetic agents with botulinum toxin A injections on vocal process granuloma. Method:Adult patients in our outpatient department (from December 2014 to June 2016) complaining of trachyphonia and/or abnormal pharyngeal sensations who were found to have contact granulomas (38 cases) were included. Patients were divided into two groups according to the treatment selected by themselves: esomeprazole with mosapride citrate (n=28) or botulinum toxin A injection (n=20). The reflux symptom index and reflux finding score determined by electronic fibrolaryngoscopy were utilized to assess efficacy. Result:There was no statistical difference on age, sex and reflux symptom index and reflux finding score before treatment between the two groups. Total effective rate in the esomeprazole with mosapride citrate group and the botulinum toxin A group were 96.43% and 45.00%, separately. The recorded symptoms after therapy resolved with a statistically significant improvement in the esomeprazole with mosapride citrate group. Conclusion:Combined proton pump inhibitor plus prokinetic drug therapy plays a significant role in the treatment of vocal process granulomas.

[Effects of voice therapy and psychological intervention on anxious and depressive in patients with voice disorders].

Objective:To investigatethe effect of voice therapy on anxious and depressive in patients with voice disorders.Method:The patients who received voicee therapy in our department from May 2014 to July 2016 were enrolled in our study and evaluated by self-rating anxiety scale (SAS) and self rating depression scale (SDS), before and after voice therapy.result:Before voicee therapy, the score of SAS and SDS were 47.52±11.15 and 48.63±8.70 respectively, which were higher than domestic norm (37.23±12.59 and 41.88±10.57 for SAS and SDS, respecative) with P< 0.05. After voice therapy, the score of SAS and SDS were 38.03±6.95 and 42.21±7.71, which were lower than the score of before voice therapy (P< 0.05). And compared with the domestic norm, the difference was not statistically significant (P> 0.05).Conclusion:The anxiety and depression scores of patients with voice disorders are higher than those of ordinary people. The voice therapy can effectively relieve anxiety and depression of patients with voice disease.

Demonstration of selective protein kinase C-dependent activation of Src and Lck tyrosine kinases during ischemic preconditioning in conscious rabbits.

Src tyrosine kinases have been shown to mediate cellular responses to stress in noncardiac cells. However, the effect of myocardial ischemia on Src tyrosine kinases is unknown. Furthermore, the identity of the tyrosine kinase(s) involved in the genesis of ischemic preconditioning (PC) remains obscure. Here, we present the first evidence that ischemic PC (6 cycles of 4-minute coronary occlusion and 4-minute reperfusion) induces selective activation of 2 members of the Src family of tyrosine kinases, Src and Lck, in the heart of conscious rabbits. The activation of Src in the particulate fraction was not evident at 5 minutes after ischemic PC but became apparent at 30 minutes (+119% versus control), whereas the activation of Lck in the particulate fraction was apparent both at 5 minutes (+103% versus control) and at 30 minutes (+89%) after ischemic PC. The activity of the other 5 members of the Src tyrosine kinases expressed in the rabbit heart (Fyn, Fgr, Yes, Lyn, and Blk) was not affected by ischemic PC. Ischemic PC had no effect on the activity of epidermal growth factor receptor kinases, either at 5 or at 30 minutes. The activation of Src and Lck was completely abrogated by the tyrosine kinase inhibitor lavendustin A, given at doses that have previously been shown to block the protective effect of ischemic PC in this same conscious rabbit model, suggesting that Src and Lck kinases are essential for the development of ischemic PC. The activity of the epsilon isoform of protein kinase C (PKC) in the particulate fraction increased at 5 minutes (+72%) and at 30 minutes (+67%) after ischemic PC. Pretreatment with lavendustin A had no effect on the activation of PKCepsilon, whereas pretreatment with the PKC inhibitor chelerythrine (given at doses that have previously been shown to block ischemic PC) blocked not only the activation of PKCepsilon but also that of Src and Lck, indicating that Src and Lck are downstream of PKCepsilon in the signaling cascade of ischemic PC. This study identifies a new component of the signaling mechanism of ischemic PC. The results support the concept that, in conscious rabbits, 2 specific members of the Src family of tyrosine kinases, Src and Lck, play an important role in the genesis of late PC by serving as downstream elements of PKC-mediated signal transduction.

[Head and neck alveolar soft-part sarcoma: a review in diagnosis and treatment].

Head and neck alveolar soft part sarcoma(ASPS) is a rare, distinctive sarcoma, typically occurring in infants and children.It displays a relatively fast clinical course, and the ultimate prognosis is poor and is often characterised by late metastases. It is now clear that they are caused by the formation of an ASPL TFE3 fusion gene,and the new molecular target therapies under study may change the possible approach to primary disease.The diagnosis and treatment of head and neck ASPS are reviewed in this article.

[Clinical analysis of plasma cell granuloma in nasal cavity and nasal sinus].

The plasma cell granuloma occurred in nasal cavity and sinus, which is rarely seen in clinical practice,the common clinical features included nasal congestion,nose bleeding,eye protrusion and olfactory impairment.Its clinical manifestations are similar to the clinical manifestations of malignant tumors, the correct diagnosis depends on histopathology and immunohistochemistry, and surgical treatment is the main method, can be supplemented by hormone therapy, radiotherapy,the prognosis could be better.