Economic burden of pertussis in children: A single-center analysis in Hangzhou, China.

The "reemergence of pertussis" has elicited international concerns, occurring paradoxically amidst the expansion of immunization programs. This study was aimed to evaluate quantitatively the economic burden and identify the determinants that influence the cost associated with treating pertussis in Chinese children. We evaluated the economic burden by Chinese children diagnosed with pertussis at the Children's Hospital, Zhejiang University School of Medicine in 2022. Direct medical expenses and the utilization of medical resources attributed to pertussis were calculated. A generalized linear regression model was applied to analyze the determinants that were associated with the direct medical expenses among patients. Among the 1110 pertussis patients included in the study, 1060 were outpatients and 50 were inpatients. The average direct medical cost was ¥1878.70(i.e. $279.33). Living in urban areas (OR:1.27, p = .04), complications (OR:1.40, p < .001), hospitalization (OR:10.04, p < .001), and ≥ 3 medical visits (OR:3.71, p < .001) were associated with increased direct medical expenses. Having received four doses of the pertussis vaccine was associated with reduced direct medical expenses (OR:0.81, p = .04). This study underscores a substantial economic burden of pertussis in Hangzhou, with pronounced implications for patients residing in urban areas, experiencing complications, requiring hospitalization, having multiple medical consultations, or lacking comprehensive pertussis vaccination.

Acceptance of influenza vaccination and associated factors among teachers in China: A cross-sectional study based on health belief model.

Teachers played an important role on the transmission of influenza in schools and communities. The study aims to investigate the influenza vaccination coverage and the factors determining flu vaccination acceptance among teachers in Hangzhou, China. A total of 1039 junior high school teachers in Hangzhou were recruited. The self-made questionnaire was used to investigate the influenza vaccine coverage among teachers and the influencing factors of influenza vaccination acceptance. Univariate analysis using the chi-square test and multivariable analysis using binary logistic regression were conducted to determine the relative predictors. The Influenza vaccine coverage among teachers was 5.9% (62/1039). 52.9% of teachers had the intention to receive influenza vaccine, 25.3% (247/977)/21.8% (213/977) of participants was hesitant/did not have the intention to get influenza vaccine. The top three sources for teachers to gain knowledge about influenza were website (72%), TV/radio (66.1%) and social media (58%). Whether get influenza vaccination before, knowledge about influenza and influenza vaccine, the beliefs for the likelihood of catching flu, the severity of getting flu, the effectiveness of influenza vaccine, the possibility of side effects after vaccination, and the troublesome of vaccination, doctors' recommendation, as well as the situation of vaccination among other teachers were the associated factors of influenza vaccination acceptance. The influenza vaccination coverage was low but the intentions were relatively high among junior high school teachers. Future research should focus on the relationship between vaccination acceptance and behavior to increase influenza vaccination rates.

Analysis of 13-valent pneumococcal polysaccharide conjugate vaccine among children born in Hangzhou from 2017 to 2021.

Background: 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) has been introduced in Hangzhou since 2017, whereas its current immunization state in children is not clear. Therefore, this study aims to describe the PCV13 vaccination distribution among children born in Hangzhou from 2017 to 2021 to provide data for reducing vaccination differences among different populations. Methods: Descriptive epidemiology was used for data analysis and PCV13 vaccination related information of children was collected from children vaccination management system of Zhejiang Province (ZJCVMS). Results: Among the 649,949 children born in Hangzhou from 2017 to 2021, 169,230 were vaccinated with an average full course vaccination rate of 26.0%. The full course vaccination rates in 5 years were different (P = 0.000) with an increasing trend (P fortrend < 0.01). The first dose vaccination rates were different in 5 years (P = 0.000) with an increasing trend (P fortrend < 0.01). The distribution of age when first dose PCV13 was administered varied, most people at 2 months and least people at 5 months. The full course vaccination rate varied by areas, highest in central urban areas and lowest in remote areas respectively (all P-value < 0.05). Overall, the full course vaccination rate of PCV13 was higher in the registered residence population than the non-registered residence population, which was 136,693 (31.4%) and 32,537 (15.1%) respectively (P = 0.000). The full course vaccination rates were the same between men and women (P = 0.502), which was 87,844 for men (26.0%) and 81,386 for women (26.1%). Conclusion: Although the number of people who received PCV13 full course vaccination and received the first dose vaccination showed yearly increasing trends in Hangzhou, the full course vaccination rate for the whole population was relatively low. In addition, the PCV13 vaccination rates also differed by geography and household registration status. Measures such as expanding vaccination publicity or including national immunization should be taken to increase vaccination rates and reduce the differences in vaccination among groups with different characteristics.

Mechanism of NLRX1 Mediating JNK Apoptosis Pathway to Participate in Functional Impairment of Cochlear Hair Cells in Mice with Senile Deafness.

To explore the mechanism of cochlear hair cell damage and study the prevention and treatment of sensorineural hearing loss, the effect of NLRX1 gene expression on the functional damage of cochlear hair cells in presbycusis was comprehensively analyzed. In the in vivo detection, C57BL/6 mice of different ages were used as experimental subjects. Cochlear tissues were taken after the hearing test of mice, and the number of cells and protein changes in NLRX1 immunofluorescence staining were detected. In the in vitro detection, the cochlear hair cell HEI-OE1 was used as the experimental object, and the cell proliferation activity was detected after overexpression or silencing of NLRX1.In the in vivo and in vitro experiments, the expression of JNK pathway-related proteins was simultaneously detected. The results of in vivo experiments showed that the hearing threshold of 270d -old mice was substantially greater than that of 15d-, 30d-, and 90d-old mice (P <0.05). I addition, with increasing age, the expression of p-JNK, Bcl-2, Bax, and Caspase-3 in the mouse cochlea gradually increased (P<0.05).In vitro experimental results showed that cell proliferation activity decreased after overexpression of NLRX1, and the expression of p-JNK, Bcl-2, Bax, and Caspase-3 was substantially decreased (P<0.05). Silencing NLRX1 can inhibit the above phenomenon, indicating that NLRX1 can inhibit the proliferation of hair cells in old mice through the activation of the JNK apoptosis pathway, thereby promoting the occurrence of sensorineural hearing loss.

Effects of Neurod1 Expression on Mouse and Human Schwannoma Cells.

OBJECTIVES: The objective was to explore the effect of the proneuronal transcription factor neurogenic differentiation 1 (Neurod1, ND1) on Schwann cells (SC) and schwannoma cell proliferation. METHODS: Using a variety of transgenic mouse lines, we investigated how expression of Neurod1 effects medulloblastoma (MB) growth, schwannoma tumor progression, vestibular function, and SC cell proliferation. Primary human vestibular schwannoma (VS) cell cultures were transduced with adenoviral vectors expressing Neurod1. Cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine (EdU) uptake. STUDY DESIGN: Basic science investigation. RESULTS: Expression of Neurod1 reduced the growth of slow-growing but not fast-growing MB models. Gene transfer of Neurod1 in human schwannoma cultures significantly reduced cell proliferation in dose-dependent way. Deletion of the neurofibromatosis type 2 (Nf2) tumor-suppressor gene via Cre expression in SCs led to increased intraganglionic SC proliferation and mildly reduced vestibular sensory-evoked potentials (VsEP) responses compared to age-matched wild-type littermates. The effect of Neurod1-induced expression on intraganglionic SC proliferation in animals lacking Nf2 was mild and highly variable. Sciatic nerve axotomy significantly increased SC proliferation in wild-type and Nf2-null animals, and expression of Neurod1 reduced the proliferative capacity of both wild-type and Nf2-null SCs following nerve injury. CONCLUSION: Expression of Neurod1 reduces slow-growing MB progression and reduces human SC proliferation in primary VS cultures. In a genetic mouse model of schwannomas, we find some effects of Neurod1 expression; however, the high variability indicates that more tightly regulated Neurod1 expression levels that mimic our in vitro data are needed to fully validate Neurod1 effects on schwannoma progression. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E259-E270, 2021.

Upregulated TRPC5 plays an important role in development of nasal polyps by activating eosinophilic inflammation and NF-κB signaling pathways.

The pathophysiology of nasal polyps (NP) remains unclear, however, several ion channels may participate. Whether transient receptor potential canonical (TRPC) channel play a role in NP remains unknown. We investigated expression of TRPC, eosinophil infiltration, IL-6, and NF-κB in 58 patients with NP and 35 control subjects using hematoxylin-eosin (HE) staining, immunohistochemistry, real-time fluorescence quantitative reverse transcription PCR (real-time RT-PCR), Western blotting, and calcium imaging. Compared with normal nasal mucosa, TRPC5 mRNA and protein expression increased in NP. Eosinophil counts, IL-6 expression, and phosphorylation levels of NF-κB were higher in NP than in normal mucosa. TRPC5 expression was positively correlated with eosinophils, IL-6, and phosphorylation levels of NF-κB. Blocking of TRPC5 channel decreased store-operated calcium influx, IL-6 expression, and phosphorylation levels of NF-κB in blood eosinophils from patients with NP. In conclusion, TRPC5 was upregulated in NP and played an important role in development of NP by activating eosinophilic inflammation and NF-κB signal pathways.

Tim-3 expression predicts the abnormal innate immune status and poor prognosis of glioma patients.

Malignant glioma, the most common and devastating primary brain tumor, has serious effects on human health with high risk of recurrence and short survival periods. Recently, the exploitation of immunological mechanisms shed new lights for developing novel therapeutic strategies for glioma pathogenesis. Tim-3, a member of T cell immunoglobulin and mucin domain family, has been involved in multiple diseases, including tumor, by regulating the viability and function of immunocytes. In the present study, we detected Tim-3 expression on peripheral innate immunocytes from glioma patients and analyzed their correlation with clinical indices. We found that the number of CD3-CD56+ NK cells decreased in glioma patients. Compared with healthy controls, glioma patients had higher Tim-3 expression on peripheral CD3-CD56+ NK cells and CD14+ monocytes. Tim-3+ NK cells had decreased capability of IFN-r secretion, while Tim-3+ monocytes showed a M2-like phenotype. Importantly, Tim-3 level on both NK cells and monocytes positively correlated with the ratio of Ki-67+ tumor cells. Moreover, patients with high percentage of Tim-3+ monocytes showed high risk of recurrence or death. Our present work gives new insights into the innate immune mechanisms in glioma and might provide new evidences for the clinical practice of Tim-3-based immunotherapy in glioma.

Ferulic acid promotes survival and differentiation of neural stem cells to prevent gentamicin-induced neuronal hearing loss.

Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed. Gentamicin was used to induce neuronal hearing loss in mice, in the presence and absence of FA, followed by assessments of auditory brainstem response (ABR) and distortion product optoacoustic emissions (DPOAE) amplitude. FA promoted survival, neurosphere formation and differentiation of NSCs, as well as neurite outgrowth and excitability of in vitro neuronal network. Furthermore, FA restored ABR threshold shifts and DPOAE in gentamicin-induced neuronal hearing loss mouse model in vivo. Our data, for the first time, support potential therapeutic efficacy of FA in promoting survival and differentiation of NSCs to prevent gentamicin-induced neuronal hearing loss.

Prevalence of Mutations in Deafness-Causing Genes in Cochlear Implanted Patients with Profound Nonsyndromic Sensorineural Hearing Loss in Shandong Province, China.

The mutations of GJB2, SLC26A4, and mtDNA12SrRNA are the most common inherited causes of nonsyndromic sensorineural hearing loss (NSHL) in China, yet previous genetic screenings were mainly carried on patients with moderate-to-profound impairment. We aimed to detect the mutation frequencies in NSHL population within a more specified range of severity. Patients with profound NSHL who had undergone cochlear implantation in the Shandong Provincial Hospital (Shandong, China) were recruited. The majority (n = 472) were between 0.7 and 6 years old, and the remaining (n = 63) were between 6 and 70 years old. In total, 115 mutation alleles of the three genes were screened with SNP scan assay. Of the patients, 19.44% (104/535) were found to have GJB2 mutations, and the most common allele was c.235delC, followed by c.299_300delAT and c.109G>A. SLC26A4 mutations were detected in 13.46% patients (72/535), and the most common allele was c.919-2A>G (IVS7-2A>G), followed by c.1174A>T and c.2168A>G. Seven patients (1.31%) carried mutations in mtDNA12SrRNA, with the alleles of m.1555A>G and m.1494C>T. We found the allele frequency of c.109G>A (GJB2) was relatively lower in the profound NSHL population in comparison to the moderate-to-profound ones, and the c.1174A>T (SLC26A4) relatively higher. It suggests those mutations may be connected with the degree of deafness, which needs more observations and analyses to support.

The central role of HOTAIR in the malignancy of CD44+ human hypopharyngeal carcinoma cells.

Human hypopharyngeal carcinoma is one of the most common malignant tumors. CD44 could serve as a molecular marker to screen for cancer stem cells (CSCs) in hypopharyngeal cancer. The aim of this study was to identify the role of HOX transcript antisense RNA (HOTAIR) on cell proliferation and invasion in CD44+ FADU cells (human hypopharyngeal carcinoma cells). We also explored the underlying mechanism contributing to HOTAIR's observed effects. CD44+ FADU cells were sorted and purified by flow cytometry and infected with lentivirus stably expressing HOTAIR shRNA. Cell proliferation and invasion analyses were carried out with cell counting kit-8 (CCK-8) and Transwell assays. The expressions of downstream effectors of HOTAIR, including E-cadherin, ß-catenin, and vimentin were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Knockdown of HOTAIR markedly inhibited the proliferation and invasion of CD44+ FADU cells in vitro. HOTAIR depletion also increased the expressions of tumor suppressors E-cadherin and ß-catenin and decreased the expression of oncogenic vimentin at both mRNA and protein levels. Collectively, our results show that HOTAIR can suppress CD44+ FADU cells proliferation and invasion by regulating the expressions of E-cadherin, ß-catenin, and vimentin.

Green Tea Polyphenols Protects Cochlear Hair Cells from Ototoxicity by Inhibiting Notch Signalling.

Notch signalling pathway plays an essential role in the development of cochlea, which inhibits the proliferation of hair cells. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea, which presents strong antioxidant activation and has been applied for anti-cancer and anti-inflammatory. In this study, we treated the cochlear explant cultures with EGCG and found that EGCG can protect cochlear hair cells from ototoxic drug gentamicin. We demonstrated that EGCG could down-regulate the expression of Notch signalling pathway target genes, such as Hes1, Hes5, Hey1 and Hey5. However, the Notch pathway ligands such as Delta1, Jag1 and Jag2 were not affected by EGCG. To further illustrate the mechanism of recover cochlear hair cells, we demonstrated that EGCG inhibited the activity of γ-secrectase to suppress Notch signalling pathway and promoted the proliferation and regeneration of hair cells in the damaged cochlea. Our results suggest for the first time the role of EGCG as an inhibitor of the Notch signalling pathway, and support its potential value in hearing-impaired recovery in clinical therapy.

The expression of IL-2 and IL-4 in CD4(+) T cells from mouse lymph nodes and spleen during HSV-1-induced facial palsy.

OBJECTIVE: Herpes simplex virus 1 (HSV-1) is regarded as an important underlying cause of Bell's palsy, but the immunologic mechanism remains unknown. Here, we employed a mouse facial paralysis model to investigate the expressions of CD4(+) T lymphocytes and interleukin (IL)-2 and -4 in the left draining cervical lymph nodes (LCLN) and spleen, as well as the inhibitory effects of glucocorticoids (GCs). METHODS: HSV-1 was inoculated into the surface of the posterior auricle to generate the facial paralysis model. The paralyzed mice were divided into three groups; in one group without any treatment, mice were killed at different time points, and those in the other two groups were injected with methylprednisolone sodium succinate (MPSS) or with a combination of MPSS and GC receptor blocker (RU486). The expression levels of CD4(+) T lymphocytes and CD4(+)-IL-2(+) and CD4(+)-IL-4(+) cells in the LCLN and spleen were detected by fluorescence-activated cell sorting. RESULTS: Expression levels of CD4(+), IL-2, and IL-4 first increased then decreased in LCLN and spleen and peaked 5 and 7 days, respectively, after the manifestation of facial paralysis. All the data at the peak points were significantly different compared with control (p < 0.05), and these effects were inhibited by MPSS. CONCLUSION: Our results suggest that CD4(+), IL-2, and IL-4 participate in the HSV-1-induced facial paralysis immune response. MPSS can effectively attenuate HSV-1-mediated nervous system damage, which is associated with its inhibitory effect on expression of these inflammatory markers.