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.

[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.

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.

[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.

[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 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.

[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.

[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.

[Quality of life analysis of teachers in a primary school in Chengdu].

Objective:To investigate the prevalence of voice disorder and quality of life in the primary school teachers in a certain district of Chengduand examine the correlation between two voice-specific questionnaires.Method:Random sampling survey included 389 teachers from a certain district of Chengdu.Twelve item general health questionnaire(GHQ-12),voice handicap index 10(VHI-10) and voice-related quality of life (V-RQOL) were investigated and routine examination of throat with electronic fiber laryngoscopy were carried out for teachers.Result:There were 189 teachers who had voice disorders(voice disorders group),and 200 teachers who did not have voice disorders(control group).②The total score's difference of V-RQOL and VHI-10,functional(F) and emotion(E) dimensions in VHI-10 between two groups were statistically significant(P<0.05),however,there were no statistically significant difference of GHQ-12 between two groups. The total score of GHQ-12 was positively correlated with VHI-10(r=0.194,P <0.05),while the total score of V-RQOL was negatively correlated with GHQ-12(r=-0.209,P<0.05) and VHI-10 (r=-0.586, P <0.05).Conclusion:Voice disorders can affect teachers' psychology and voice related quality of life.Although the VHI-10 and V-RQOL had correlation,the correlation is not strong.So it is recommended combine VHI-10 and V-RQOL when the quality of life of voice disorders is evaluated.

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.

Early-life lead exposure affects the activity of TNF-alpha and expression of SNARE complex in hippocampus of mouse pups.

This study aims to investigate the effects of maternal lead exposure on learning and memory ability and the protein expression of TNF-alpha and SNARE complex (SNAP-25, VAMP-2, and Syntaxin 1A) in hippocampus of mice offspring. Pb exposure was initiated from beginning of gestation to weaning. Pb acetate administered in drinking solutions was dissolved in distilled deionized water at 0.1%, 0.5%, and 1% groups, respectively. On the PND21, the learning and memory ability of mouse pups was tested by water maze test, and the Pb levels in their blood and hippocampus were also determined. The protein expression of TNF-alpha and SNARE complex in hippocampus was measured by immunohistochemistry and Western blotting. The Pb levels in blood and hippocampus of all exposure groups were significantly higher than control group (P < 0.05). In the water maze test, the performances of 0.5% and 1% groups were worse than that of control group (P < 0.05). The expression of TNF-alpha, Syntaxin 1A, and VAMP-2 was increased in Pb-exposed groups comparing control group (P < 0.05), but the expression of SNAP-25 was decreased (P < 0.05). Up-regulation of TNF-alpha and disturbance of SNARE expression in the hippocampus of pups may contribute to impairment of learning and memory ability associated with maternal Pb exposure.