[Research advances in immunosenescence and inflammation in lung diseases].

The world's population is ageing at a rate unprecedented in human history. As the number of older people increases, so does the prevalence of lung disease in the elderly, making it essential to understand the pathophysiology of elderly patients with lung disease. Age-related changes in immune system function and lung parenchyma occur throughout a person's life. Immunosenescence refers to the tendency for innate and adaptive immunity to decline in the elderly. As we age, changes in the innate and adaptive immune systems can lead to dysregulation and reduced immune function. A low-level chronic inflammatory state is known as inflamm-aging and is driven by immunosenescence. This review discusses the role of immunosenescence and inflamm-aging in pulmonary diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and lung infections. Understanding the different manifestations of lung diseases between the elderly and the young, finding new therapeutic sites, or improving clinical outcomes in hospitalized patients will provide clinicians with new ideas.

[Clinical characteristics and outcome analysis of COVID-19 patients with pulmonary tuberculosis].

Coronavirus disease (COVID-19) and tuberculosis (TB) are two respiratory infectious diseases with a high incidence of transmission, mainly via respiratory droplets and both can weaken the immune system and lower the number of CD4+T cells in patients. COVID-19 can occur before, at the same time or after the diagnosis of TB. Patients with pulmonary TB are more likely to have co-infection when they have a history of epidemiological exposure to COVID-19. At present, many cases of nosocomial infection of COVID-19 caused by ineffective prevention and control measures in tuberculosis hospitals have been reported successively at domestic and overseas. Therefore, it is urgent to strengthen the prevention and control of nosocomial infections in tuberculosis hospitals. The superposition of the two diseases can lead to a worsening prognosis, aggravating the patient's condition and making treatment more difficult. In addition, in the context of the new coronavirus epidemic, early recognition of co-infection with new coronavirus should be made when TB patients in chest hospitals present with symptoms such as aggregated fever or progressive disease. At the same time, we should focus on identifying the clinical and imaging manifestations of TB and COVID-19 co-infection. At present, research on COVID-19 complicated with pulmonary TB is scarce, and there are disputes on many aspects. As a country with a high prevalence of tuberculosis, it is of great practical significance to identify the clinical characteristics, outcomes, and treatment of the two infectious diseases in China.

[Application of serum markers in medullary thyroid carcinoma].

Objective: To discuss the diagnostic value of calcitonin(CT), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), pro-gastrin releasing peptide (Pro-GRP) and chromogranin A (CgA) in the identification of medullary thyroid carcinoma (MTC). Methods: The CT levels in 105 cases of MTC, 50 cases of papillary thyroid carcinoma, 10 cases of thyroid follicular carcinoma, 5 cases of undifferentiated thyroid carcinoma, 50 cases of benign thyroid diseases, 30 cases of non-thyroid malignant tumors and 50 cases of healthy controls were measured from February 2017 to August 2019 at the Department of Clinical Laboratory, Cancer Hospital affliated to Fudan University. Additionally, 79 cases of MTC, 30 cases of non-MTC thyroid malignant tumors and 30 healthy controls were selected for the measurement of CEA, NSE, Pro-GRP and CgA levels. The receiver operating curve was utilized to clarify the area under the curve (AUC), sensitivity, and specificity of each indicator to distinguish between different groups. Results: The medians of CT concentrations in the group of MTC patients was 607.2 (152.5,2 777.5)pg/ml, which was statistically significantly higher than that of the subjects in the group of papillary thyroid carcinoma 1.48 (0.5,2.91)pg/ml, follicular thyroid carcinoma 1.90 (0.82,2.99)pg/ml, undifferentiated thyroid carcinoma 0.50 (0.50,4.93)pg/ml, benign thyroid disease 1.30 (0.50,2.79)pg/ml, non-thyroid malignancies 1.36 (0.50,2.89)pg/ml and healthy controls 2.05 (0.89,3.18)pg/ml. The sensitivity, specificity and AUC of CT to distinguish MTC vs. non-MTC patients was 96.2%, 99.3% and 0.99, respectively. The maximum diameter (>1 cm, P=0.001, OR=15.74) and number (>1, P=0.04, OR=3.4) of nodules were two independent risk factors for elevated CT. CEA (AUC=0.94), NSE (AUC=0.65), Pro-GRP (AUC=0.94) and CgA (AUC=0.83) could all distinguish MTC vs. non-MTC thyroid malignancies. The AUC, sensitivity and specificity by combining CT, CEA, NSE, Pro-GRP and CgA to differentiate MTC vs. non-MTC thyroid malignancies was 1, 100% and 100%, respectively. Conclusions: CT, CEA, NSE, Pro-GRP and CgA may be helpful for the auxiliary diagnosis of MTC. The combination of these indicators in the diagnosis of MTC has high sensitivity and specificity.

[Methylene blue play a role in preventing septic liver injury by inducing macrophage polarization].

Thirty mice were used to establish a sepsis model with cecal ligation and puncture. 15 mg/kg methylene blue or isotonic saline were injected intraperitoneally to observe liver tissue pathological changes. Changes in macrophage frequency and expressional condition of M1 and M2-type hepatic inflammatory factors were detected. After LPS stimulation, the expression level of macrophage inflammatory factor were detected. The results showed that the pathological liver injury was significantly reduced in the MB mice group (P < 0.05), and the frequency of liver macrophage was not statistically significantly different (P > 0.05). MB elevation had promoted the expression of M2-type hepatic inflammatory factor (P < 0.05) and macrophage inflammatory factor (P < 0.05). MB can play a role in preventing septic liver injury by inducing macrophages polarization to M2-type.

[Incidence and risk factors for cardiovascular events in patients hospitalized with community-acquired pneumonia].

Objective: To explore the incidence, risk factors of cardiovascular events (CVE) and their impact on 30-day mortality in patients hospitalized with community-acquired pneumonia (CAP). Methods: This is a multicenter, retrospective study. Patients hospitalized with CAP from 5 teaching hospitals in Beijing, Shandong and Yunnan provinces during 1 January 2013 to 31 December 2015 were included and clinical data were retrieved from the Hospital Information System (HIS), and patients were divided into CVE group and non-CVE group. Age, sex, comorbidities, pneumonia severity index(PSI)/CURB-65 score, routine blood test, biochemical examinations, radiological findings on admission and mortality on 30-day after admission were analyzed. The primary endpoint was acute CVE during hospitalization, the secondary endpoint was 30-day death after admission. Multivariate Cox regression analysis was used to explore the risk factors for CVE. Kaplan-Meier survival curve was used to compare the difference on 30-day mortality between CVE patients and non-CVE patients by Log-rank test. Multivariate Cox regression model was used to assess the impact of CVE on the 30-day mortality among CAP patients after adjustment with age, sex, comorbidities, PSI/CURB-65 score. Results: A total of 3 561 CAP patients were included into the final analysis, including 210 (5.9%) patients in CVE group and 3 351 (94.1%) patients in non-CVE group. Compared with patients in non-CVE group, patients in CVE group were older (P<0.001), prevalence of hypertension, coronary heart disease, chronic heart failure, cerebrovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, aspiration risk and bedrid were significantly higher (all P<0.001); prevalence of CURB-65 score 3-5 and PSI risk class Ⅳ/Ⅴ were also significantly higher (both P<0.001). The proportion of axillary temperature<36 ℃, respiratory rate≥30 beats/minutes, confusion, leukocytes>10×10(9)/L, hemoglobin<100 g/L, platelets>300×10(9)/L, albumin<35 g/L, blood urea nitrogen>7 mmol/L, fasting blood glucose>11 mmol/L, serum C-reaction protein>100 mg/L, serum procalcitonin≥2 µg/L, arterial pH<7.35, arterial PO(2)/FiO(2)≤300 mmHg (1 mmHg=0.133 kPa), and multilobar infiltrates and pleural effusion on chest X-ray or CT scan were significantly higher in CVE group than in non-CVE group(all P<0.05); the 30-day mortality was significantly higher in CVE group than in non-CVE group(P<0.001). The incidence of CVE was significantly higher in patients with cardiovascular and cerebrovascular disease(CVD) than in patients without CVD (13.9%(150/1 079) vs. 2.4%(60/2 482), χ(2)=178.737, P<0.001). Meanwhile, the incidence of CVE increased with PSI in patients with Ⅰ/Ⅱ, Ⅲ and Ⅳ/Ⅴ class, respectively(χ(2)=228.350, P<0.001); and CURB-65 score 0-1, 2 and 3-5, respectively (χ(2)=387.154, P<0.001). Cox regression analysis revealed that age (HR=1.05, 95%CI 1.02-1.09, P=0.002), coronary heart disease (HR=1.88, 95%CI 1.01-3.51, P=0.048), chronic heart failure (HR=4.25, 95%CI 1.89-9.52, P<0.001), PSI risk class (HR=1.66, 95%CI 1.50-2.62, P=0.029) and serum procalcitonin≥ 2 µg/L (HR=3.72, 95%CI 1.60-8.66, P=0.002) were independent risk factors for CVE in CAP patients. Kaplan-Meier curve showed that the survival probability of patients with CVE was significantly lower than patients without CVE (P<0.001). After adjustment for age, sex, comorbidities and PSI/CURB-65 score, Cox regression model showed that CVE was associated with increased 30-day mortality in CAP patients (HR=6.05, 95%CI 3.11-11.76, P<0.001). Conclusions: Although the incidence of CVE is not high in Chinese patients hospitalized with CAP, CVE is common in patients with severe pneumonia and in patients with CVD. Age, cardiovascular disease, PSI risk class and serum procalcitonin are the risk factors for CVE in this patient cohort. CVE is related to increased 30-day mortality in CAP patients.

Polychromatic emission in a wide energy range from InP-InAs-InP multi-shell nanowires.

InP-InAs-InP multi-shell nanowires (NWs) were grown in the wurtzite (WZ) or zincblende (ZB) crystal phase and their photoluminescence (PL) properties were investigated at low temperature (≈6 K) for different measurement geometries. PL emissions from the NWs were carefully studied in a wide energy range from 0.7 to 1.6 eV. The different features observed in the PL spectra for increasing energies are attributed to four distinct emitting domains of these nano-heterostructures: the InAs island (axially grown), the thin InAs capping shell (radially grown), the crystal-phase quantum disks arising from the coexistence of InP ZB and WZ segments in the same NW, and the InP portions of the NW. These results provide a useful frame for the rational implementation of InP-InAs-InP multi-shell NWs containing various quantum confined domains as polychromatic optically active components in nanodevices for quantum information and communication technologies.

[Clinical characteristics and prognosis of long-term glucocorticoid users with community-acquired pneumonia].

Objective: To explore the clinical features, etiological features and prognostic risk factors of long-term glucocorticoid users with community-acquired pneumonia (CAP). Methods: A retrospective study included 100 long-term glucocorticoid users with CAP (G-CAP group) from 11 hospitals of China between January 2014 and December 2014, while 100 non-immunocompromised patients with community-acquired pneumonia were enrolled as controls (nICH-CAP group). Characteristics including age, gender, underlying diseases, corticosteroids, symptoms, disease severity, imaging manifestations, etiology, respiratory failure, mechanical ventilation, whether the application of vasoactive drugs, antibiotics application, hospital mortality rate between the two groups were compared, and the prognostic factors of G-CAP were investigated using Logistic regression. Results: The peripheral blood lymphocytes[1.06(0.70, 1.68) vs 1.44 (0.87, 1.98)]in G-CAP group was less than nICH-CAP group (P<0.05). CT with pulmonary interstitial change (28.6% vs 9.9%), the proportion of patients with respiratory failure (25.0% vs 7.0%), mechanical ventilation (9.0% vs 2.0%), noninvasive mechanical ventilation (12.0% vs 2.0%), septic shock (9.0% vs 2.0%), and the hospital mortality rate (13.0% vs 3.0%) in G-CAP group were significantly higher than in nICH-CAP group (all P<0.05). Bacterial infection accounted for the highest proportion of infection (61.3%) in G-CAP group, but also virus infection (19.4%) and mixed infection (16.1%). Pseudomonas accounted for the highest proportion (47.4%) in bacterial infection of G-CAP. Logistic regression analysis showed that peripheral blood lymphocytes (OR=0.004, 95% CI: 0.000-0.234; P<0.05) and respiratory failure (OR=17.766, 95% CI: 4.933-131.0; P<0.05) were independent predictors of death in G-CAP group. Conclusions: The proportion of severe pneumonia and the mortality rate of patients with G-CAP are higher than the patients with nICH-CAP. Lymphopenia and respiratory failure are associated with poor outcome of patients with G-CAP.

Epidemiology of post-adolescence acne and adolescence acne in Singapore: a 10-year retrospective and comparative study.

INTRODUCTION: Acne vulgaris commonly affects adolescents. But recent reports suggest a rising prevalence of post-adolescence acne. While there are few reports on post-adolescence acne, there are even fewer reports comparing adolescence acne and post-adolescence. METHODS: Epidemiological data of adolescence (<25 years) and post-adolescence (≥25 years) acne patients diagnosed between 2004 and 2013 in a tertiary dermatology referral centre was analysed. From the pool of patients seen in 2010, 80 adolescence and 84 post-adolescence acne patients' epidemiological characteristics and treatment responses were analysed. RESULTS: During the 10-year study period, there was an increase in the number and proportion of acne cases. In 2004, 4447 (5.77%) of all new diagnoses made were of acne vulgaris. The proportion rose to 5723 (8.13%) in 2013. There were consistently more female than male acne patients. The proportion of post-adolescent cases remained constant at about 30% of all acne patients seen. Mean age of acne vulgaris patients decreased from 23.1 years in 2004 to 22.6 years in 2013. In the subgroup analysis, there were more males than females with adolescence acne (61.3% vs. 38.8%, P < 0.01) and more females with post-adolescence acne (69.0% vs. 31.0%, P < 0.01). Thirty-four (40.5%) post-adolescence acne patients had acne from adolescence persisting into adulthood. Comedonal acne was more prevalent in the adolescence acne patients (58.8% vs. 40.5%, P = 0.019), whereas cystic acne was more prevalent in post-adolescence patients (18.1% vs. 7.5%, P = 0.044). Systemic retinoids were more often used for treatment in the adolescence acne patients than post-adolescence acne patients (23.8% vs. 10.7%, P = 0.027). CONCLUSION: Acne predominantly affects adolescents but post-adolescence acne is not uncommon. For post-adolescence acne, females predominate over males. Inflammatory and cystic acne tends to be more predominant in post-adolescence acne patients, whereas comedonal acne is more often seen in adolescence acne patients.

Pressure tunes electrical resistivity by four orders of magnitude in amorphous Ge2Sb2Te5 phase-change memory alloy.

Ge-Sb-Te-based phase-change memory is one of the most promising candidates to succeed the current flash memories. The application of phase-change materials for data storage and memory devices takes advantage of the fast phase transition (on the order of nanoseconds) and the large property contrasts (e.g., several orders of magnitude difference in electrical resistivity) between the amorphous and the crystalline states. Despite the importance of Ge-Sb-Te alloys and the intense research they have received, the possible phases in the temperature-pressure diagram, as well as the corresponding structure-property correlations, remain to be systematically explored. In this study, by subjecting the amorphous Ge(2)Sb(2)Te(5) (a-GST) to hydrostatic-like pressure (P), the thermodynamic variable alternative to temperature, we are able to tune its electrical resistivity by several orders of magnitude, similar to the resistivity contrast corresponding to the usually investigated amorphous-to-crystalline (a-GST to rock-salt GST) transition used in current phase-change memories. In particular, the electrical resistivity drops precipitously in the P = 0 to 8 GPa regime. A prominent structural signature representing the underlying evolution in atomic arrangements and bonding in this pressure regime, as revealed by the ab initio molecular dynamics simulations, is the reduction of low-electron-density regions, which contributes to the narrowing of band gap and delocalization of trapped electrons. At P > 8 GPa, we have observed major changes of the average local structures (bond angle and coordination numbers), gradually transforming the a-GST into a high-density, metallic-like state. This high-pressure glass is characterized by local motifs that bear similarities to the body-centered-cubic GST (bcc-GST) it eventually crystallizes into at 28 GPa, and hence represents a bcc-type polyamorph of a-GST.

Role of the nano amorphous interface in the crystallization of Sb2Te3 towards non-volatile phase change memory: insights from first principles.

The nano amorphous interface is important as it controls the phase transition for data storage. Yet, atomic scale insights into such kinds of systems are still rare. By first-principles calculations, we obtain the atomic interface between amorphous Si and amorphous Sb2Te3, which prevails in the series of Si-Sb-Te phase change materials. This interface model reproduces the experiment-consistent phenomena, i.e. the amorphous stability of Sb2Te3, which defines the data retention in phase change memory, and is greatly enhanced by the nano interface. More importantly, this method offers a direct platform to explore the intrinsic mechanism to understand the material function: (1) by steric effects through the atomic "channel" of the amorphous interface, the arrangement of the Te network is significantly distorted and is separated from the p-orbital bond angle in the conventional phase-change material; and (2) through the electronic "channel" of the amorphous interface, high localized electrons in the form of a lone pair are "projected" to Sb2Te3 from amorphous Si by a proximity effect. These factors set an effective barrier for crystallization and improve the amorphous stability, and thus data retention. The present research and scheme sheds new light on the engineering and manipulation of other key amorphous interfaces, such as Si3N4/Ge2Sb2Te5 and C/Sb2Te3, through first-principles calculations towards non-volatile phase change memory.

[Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy].

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

Insulin Resistance-Varying Associations of Adiposity Indices with Cerebral Perfusion in Older Adults: A Population-Based Study.

OBJECTIVES: Excessive accumulation of adipose tissue may accelerate brain aging, but the underlying mechanisms are poorly understood. Several adiposity indices were proposed to assess obesity, while their linkage with brain health in older adults remained unclear. Here we aimed to examine the associations of adiposity indices with global and regional cerebral blood flow (CBF) in older adults, while considering insulin resistance. DESIGN: This was a cross-sectional population-based study that included older adults derived from the baseline participants in the ongoing Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) study. SETTING AND PARTICIPANTS: The study included 103 Chinese rural-dwelling older adults (age≥60 years; 69.9% women) who underwent brain magnetic resonance imaging scans. METHODS: We estimated eight adiposity indices based on anthropometric measures. We automatically quantified global and regional CBF using the arterial spin labeling scans. Insulin resistance was assessed using the triglyceride-glucose index and then dichotomized into high and low levels according to the median. Data were analyzed using general linear model and voxel-wise analysis. RESULTS: Of the eight examined adiposity indices, only higher waist-to-height ratio (WHtR) and body roundness index (BRI) were associated with reduced global CBF (multivariable-adjusted ß-coefficients and 95%CI: -1.76; -3.25, -0.27 and -1.77; -3.25, -0.30, respectively) and hypoperfusion in bilateral middle temporal gyri, angular gyri and superior temporal gyri, left middle cingulum and precuneus (P<0.05). There were statistical interactions of WHtR and BRI with levels of insulin resistance on CBF, such that the significant associations of higher WHtR and BRI with lower global and regional CBF existed only in people with high insulin resistance (P<0.05). CONCLUSION: Higher WHtR and BRI are associated with cerebral hypoperfusion in older adults, especially in people with high insulin resistance. This may highlight the pathological role of visceral fat in vascular brain aging.

Role of electronic excitation in the amorphization of Ge-Sb-Te alloys.

First-principles molecular dynamics simulation reveals the effects of electronic excitation in the amorphization of Ge-Sb-Te. The excitation makes the phase change an element-selective process, lowers the critical amorphization temperature considerably, for example, to below 700 K at a 9% excitation, and reduces the atomic diffusion coefficient with respect to that of melt by at least 1 order of magnitude. Noticeably, the resulting structure has fewer wrong bonds and significantly increased phase-change reversibility. Our results point to a new direction in manipulating ultrafast phase-change processes with improved controllability.

New structural picture of the Ge2Sb2Te5 phase-change alloy.

Using electron microscopy and diffraction techniques, as well as first-principles calculations, we demonstrate that as much as 35% of the total Ge atoms in the cubic phase of Ge2Sb2Te5 locate in tetrahedral environments. The Ge-vacancy interactions play a crucial stabilizing role, leading to Ge-vacancy pairs and the sharing of vacancies that clusters tetrahedral Ge into domains. The Ge2Sb2Te5 structure with coexisting octahedral and tetrahedral Ge produces optical and structural properties in good agreement with experimental data and explains the property contrast as well as the rapid transformation in this phase-change alloy.

[The analysis of mutations in non-syndromic deafness gene SLC26A4 by next generation sequencing technology].

Objective:To analogize the distribution of nonsyndromic deafness gene SLC26A4 mutation and to characterize clinical profiles in patients with SLC26A4 mutation in order to understand their hereditary etiologies and provide evidence for deafness screening and accurate genetic counseling. Method: SLC26A4 gene was first analized by MALDI-TOF-MS technology to detect the hot mutation c.919-2A>G in 57 cases. There were 3 cases with homozygous mutation and 7cases with heterozygous mutation. Then 54 cases except for 3 cases with homozygous mutation were analyzed by targeted genomic capturing and next generation sequencing technologies(targeted DNA-Hiseq), 81 non-syndromic deafness genes and the chondiogene was designed to all their exons and their flanking intron(±10 bp) sequences. Sanger sequencing was used to confirm the variant by analyzing the DNAs sequences. Result: The carrying rates of SLC26A4 gene in the deafness were 26.32%, but SLC26A4 homozygous genes and compound heterozygous genes were 19.30%. They included 3 cases with c.919-2A>G and 1 case with c.754T>C pathogenic homozygous mutations. While in 7 cases with compound heterozygous there were 6 cases with two pathogenic mutation, there was 1 case with c.2168A>G pathogenic mutation the other likely pathogenic mutation c.1545-1546insC. The 11 cases all were diagnosed large vestibular aqueduct syndrome(LVAS). There were 4 cases with heterozygous that were not found large vestibular aqueduct. Conclusion: Pathogenic mutation of SLC26A4 is closely related to clinical phenotype of LVAS. The hot pathogenic mutation was c.919-2A>G of SLC26A4 gene. The next generation sequencing technology is available for the diagnosis of inherited hearing loss especially for LVAS.

[Trans-oral robotic submandibular gland removal].

Submandibular gland excision was performed on two patients using trans-oral robotic surgery (TORS). Complications such as the injury of marginal mandibular branch of facial nerve, ranula in the floor of the mouth, and postoperative hemorrhage were not observed. Visible cervical scar can be avoided and esthetic outcome can be expected by using this surgical modality.

Tripterygium glycoside fraction n2: Alleviation of DSS-induced colitis by modulating immune homeostasis in mice.

BACKGROUND: The Tripterygium glycosides (TG) is the main active extractive of Tripterygium wilfordii Hook F and is widely used in clinical practice to treat inflammatory diseases (including inflammatory bowel disease). However, due to its severe toxicity, TG is restricted to the treatment of many diseases. Therefore, it is necessary to study a new method to obtain the attenuated and synergistic extracts from TG. PURPOSE: Tripterygium glycosides-n2 (TG-n2) was obtained from TG by a new preparation method. In this study, we aimed to investigate the difference in the chemical compositions between TG and TG-n2, further explored its toxicity and therapeutic effects on DSS-induced colitis in mice. METHODS: The major chemical compositions of TG and TG-n2 were analyzed by ultra-performance liquid chromatography (UPLC). Subsequently, acute toxicity test was applied to evaluate the toxicity difference between TG and TG-n2. Dextran sulfate sodium (DSS)-induced acute colitis model was used to explore the therapeutic effect of TG and TG-n2 and their potential mechanisms of action. RESULTS: We found that the chemical compositions of TG-n2 is different from TG. The main difference is the ratio of triptriolide (T11) / triptolide (T9). Acute toxicity test proved that TG-n2 was less toxic than TG. Base on this, further studies showed that TG-n2 has a similar therapeutic effect as compared to TG on attenuating the symptoms of colitis, such as diarrhea, bloody stools, body weight loss, colonic atrophy, histopathological changes, inhibiting cytokines secretion and reducing absolute lymph number. In addition, TG and TG-n2 can increase the apoptosis of T lymphocyte in vivo. Further investigated showed that TG and TG-n2 could increase the expressions of Bax and p62 on CD3-positive T cells. CONCLUSION: This study showed that oral administration of TG-n2 is safer than TG. Moreover, the attenuated TG-n2 has the similar therapeutic effect on treating experimental colitis in mice when compared to TG. Its mechanism may be related to activating the expression of Bax in T cells and inducing T cells autophagy to regulate the survival of T lymphocytes in colitis mice, thus reducing inflammation in colon.

[Robotic-assisted supraomohyoid neck dissection via retroauricular hairline incision].

Objective: To explore the feasibility of using da Vinci Surgical System to perform supraomohyoid neck dissection (SOND) to avoid visible scar and reduce trauma. Methods: Between September 2017 and December 2018, twenty patients (two females and 18 males, mean age, 54.8 years) with oral cancer treated in the Department of Stomatology, Hainan Hospital of General Hospital of Chinese PLA were enrolled in this study. Eight patients were assigned into robotic surgery group, and received robot-assisted SOND with retroauricular hairline incision. After the da Vinci Surgical System robotic platform was positioned, the neck dissection was performed in level Ⅱb, Ⅱa, Ⅲ, Ⅰb and Ⅰa orderly from the near region to far region. The other 12 patients were assigned into traditional surgery group, and received SOND with a traditional incision. The operation time, bleeding and amount of lymph node dissected were compared between two groups. Results: All the 8 cases of robot-assisted SOND were completed smoothly. Operation time [(4.5±1.0) h] was significantly longer in robotic surgery group than that [(2.5±1.0) h] in traditional surgery group (P<0.05). The amount of bleeding in robotic surgery group [30.0 (27.5) ml] was significantly lower than that in traditional surgery group [(100.0 (87.5) ml, P<0.05]. There's no difference in the number of lymph nodes dissected between robotic surgery group (23.6±5.2) and traditional surgery group (22.8±6.0)(P>0.05). No postoperative hemorrhage, symptoms of nerve injury, flap necrosis and secondary healing were observed in robotic surgery group. Conclusions: SOND through retroauricular hairline incision is feasible with the assistance of da Vinci Surgical System. The main advantage of this method is superior esthetic effects due to a hidden incision with minimal bleeding. There was no obvious differences in the amount of lymph nodes dissected and postoperative complications between two methods. However, robotic surgery costs a significantly longer operation time than traditional neck dissection.

[Clinical and genetic characteristics of 62 children with mitochondrial epilepsy].

Objective: To summarize the clinical and genetic characteristics of children with mitochondrial epilepsy. Methods: Clinical data of 62 children who were clinically and genetically diagnosed with mitochondrial epilepsy by the Department of Neurology, Beijing Children's Hospital from October 2011 to December 2018 were analyzed retrospectively, and the control of epilepsy was followed up. T test or χ(2) test were used to analyze the related factors affecting the prognosis of epilepsy between the effective group and the ineffective group. Results: Of the 62 patients, 33 were male and 29 were female. The age of onset was 3.38 (0-12.00) years; for the type of seizures, 68% (42/62) of the patients had focal seizures, generalized or secondary generalized tonic-clonic seizures were seen in 32% (20/62), myoclonic seizures in 23% (14/62), spastic seizures in 7 cases, tonic seizures in 4 cases, absence seizure, atonic seizure and clonic seizure in 1 case each; 16 cases (26%) had status epilepticus, of whom 6 cases had epilepsia partialis continua; 52% (32/62) had 2 or more types of seizures. The clinical phenotypes were mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) in 29 cases, Leigh syndrome (LS) in 11 cases, combined oxidative phosphorylation deficiency in 6 cases, myoclonus epilepsy with ragged-red fibers in 5 cases, Alpers syndrome in 4 cases, pontocerebellar hypoplasia type 6 and mitochondrial DNA depletion syndrome 9 in 2 cases each, mitochondrial complex Ⅰ deficiency nuclear type 20, progressive cavitating leukoencephalopathy, and biotinidase deficiency in 1 case each. Of the 62 cases, 40 cases (65%) had mitochondrial DNA (mtDNA) variations, of which 26 cases had m.3243A>G variants, 6 cases had m.8344A>G variants, and 3 cases had m.8993T>G/C variants, m.3271T>C, m.3481G>A, m.3946G>A, m.13094T>C, m.14487T>C variant was in 1 case each; nuclear DNA (nDNA) variations were identified in 22 cases (35%), of which 7 cases carrying variations in mitochondrial ammonia acyl tRNA synthetase coding gene, mutations in POLG and the gene encoding complex Ⅰ were in 4 cases each, variations in SUCLG1 and SDHA genes were in 2 cases each, and variations in PDHA1, BTD and TRIT1 genes were in 1 case each. Forty-three patients were followed up, and the follow-up time was 20 (3-84) months. According to the follow-up results, the anti-epilepsy treatment was effective in 19 cases (44%) and ineffective in other 24 cases (56%). The onset age of the effective group was 3.42 (0-11.50) years and that of the ineffective group was 0.92 (0-9.50) years. The onset duration of the effective group was 0 (0-7.00) years and that of the ineffective group was 0 (0-4.83) years. There was no significant difference between the effective group and the ineffective group (t=1.662, 0.860; P=0.104, 0.395). In the effective group and the ineffective group, 12 cases and 9 cases used less than 2 kinds of antiepileptic drugs, 7 cases and 15 cases used more than or equal to 2 kinds of antiepileptic drugs, 13 and 15 cases had first epilepsy, 6 and 9 cases had non-first epilepsy, 14 and 11 cases had mtDNA variation, 5 and 13 cases had nDNA variation, respectively. There was no significant difference between the two groups (χ(2)=2.794, 0.164, 3.380; P=0.095, 0.686, 0.066). Conclusions: The types of seizures with mitochondrial epilepsy in children varied, with focal motor seizures being the most common, followed by generalized or secondary generalized tonic-clonic seizures. Most children have more than two types of seizures. MELAS is the most common clinical phenotype, followed by LS; mtDNA variation is the dominant gene variation, of which m.3243A>G variation is the most common hotspot variation, followed by gene variation encoding mitochondrial aminoacyl tRNA synthase.

MiR-608 exerts tumor suppressive function in lung adenocarcinoma by directly targeting MIF.

OBJECTIVE: Lung adenocarcinoma (LA) is considered as a highly aggressive disease with heterogeneous prognosis. The molecular mechanisms of LA progression remain elusive. Recent studies have shown that dysregulation of microRNAs (miRNAs) is prevalent in LA, playing a significant role in tumor progression. The present work aims to analyze the expression and function of miR-608 in LA. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT­PCR) assay and Western blot were performed to detect expressions of miR-608 and migration inhibitory factor (MIF). Luciferase reporter assays were carried out to investigate the regulatory effect of miR-608 on MIF. The cell invasion and the migration capabilities were detected by transwell assay. RESULTS: QRT-PCR indicated that miR-608 expressions in LA tissues were markedly reduced than that of the normal tissues. Moreover, the expression of MIF, a potential target gene of miR-608, was inversely associated with miR-608 expression in LA. Furthermore, miR-608 overexpression could inhibit LA invasion and migration, which was reversed by MIF knockdown. CONCLUSIONS: Our study revealed the mechanisms that miR-608 suppressed LA invasion and migration by targeting MIF, suggesting that miR-608/MIF axis could be used as a potential prognostic biomarker and therapeutic target for LA.