[Research progress on AMPK activation in nonalcoholic fatty liver disease].

Nonalcoholic fatty liver disease (NAFLD) occurrence and progression are associated with lipid accumulation, insulin resistance, inflammation, liver damage, fibrosis, and other factors. AMP-dependent protein kinase (AMPK) is a key molecule that regulates bioenergy metabolism and participates in multiple biological processes, including lipid metabolism, autophagy, inflammation, and cell apoptosis. Promoting AMPK activation can reduce hepatic lipid accumulation and insulin resistance, alleviate the development of NAFLD, reduce liver inflammation and fibrosis, and inhibit the progression of NAFLD to nonalcoholic steatohepatitis.

Effects of milk powder intervention on bone mineral density and indicators related to bone metabolism in Chinese adolescents.

The study is to determine the effects of milk powder on bone density and metabolism in healthy adolescents. Vitamin D and calcium supplements increased IGF-1 but did not affect bone mineralization or turnover. Higher vitamin D in combination with sufficient calcium supplementation in such populations requires attention. INTRODUCTION: Both calcium and vitamin D play an important role in bone mineralization in adolescents. METHODS: In this one and a half-year randomized controlled trial, 232 participants (aged 12-15 years) were randomly assigned to three intervention groups receiving milk powder fortified with vitamin D 400 IU plus calcium 300, or 600, or 900 mg [Ca3D (n = 54), Ca6D (n = 56), and Ca9D (n = 49)], or one control group maintaining habitual diet [control (n = 73)]. Bone turnover markers, serum intact PTH, 25(OH)D, and IGF-1 levels were measured at baseline and one and a half years, and bone mineral contents and bone areal mineral density were measured by Dual-energy X-ray absorptiometry (DXA) at baseline, one year, and one and a half years. RESULTS: Baseline average serum 25(OH)D level and calcium intake were 29.4 nmol/L and 363.5 mg/day, respectively. There was a significant increase in bone turnover, total body, hip, lumbar spine bone mineral density (BMD), and total body BMC as well as slight fluctuations in 25(OH)D levels over one and a half years without between-group differences. Significantly decreased serum PTH level was only observed in the Ca6D group (31%, p < 0.0001), in which the intervention effect was also significant (p = 0.0029) compared with the control group. IGF-1 levels increased significantly in all intervention groups (18.5 to 22.8%, p < 0.05) but decreased in the control group (16.5%, p < 0.05), and the group by time interaction was also significant (p = 0.0029). CONCLUSIONS: Our study showed that in healthy adolescents with low vitamin D status and calcium intake, mild vitamin D and mild to modest calcium supplements increased IGF-1 but did not affect bone mineralization or turnover. Higher vitamin D in combination with sufficient calcium supplementation in such populations requires attention.

Attenuating Neuronal Autophagy Alleviates Inflammatory Injury in OGDDeprived Co-culture of HT22 with BV2.

Neuronal CX3CL1 suppressed microglial inflammation by binding to its receptor CX3CR1 expressed on microglia. Neuronal autophagy was prominently activated by cerebral ischemia, whereas CX3CL1 expression in autophagic neurons was conversely down-regulated to exacerbate microglial inflammation. Accordingly, this study was meant to investigate whether ischemia-activated microglial inflammation could be repressed by promoting CX3CL1 expression via the attenuation of neuronal autophagy. Immunofluorescence showed that autophagy predominantly occurred in neurons but barely in microglia. Western blot and immunofluorescence demonstrated that attenuating HT22 autophagy significantly increased its CX3CL1 expression and subsequently mitigated the BV2-mediated inflammatory responses, as indicated by decreased inflammatory factors of NF-κB-p65, IL-6, IL-1ß, TNF-α, and PGE2. Meanwhile, CCK-8, Nissl staining, and FJC staining showed that an OGD (Oxygen-glycogen deprivation)-created neuronal injury was greatly alleviated by CX3CL1-suppressed microglial inflammation. Contrarily, elevating HT22 autophagy markedly decreased its CX3CL1 expression, which consequently worsened microglial inflammation and the neuronal injury. Our data suggests that attenuating neuronal autophagy may be an effective method to alleviate a microglial inflammatory injury after an ischemic stroke.

Prevotella intermedia Aggravates Subclinical Hypothyroidism.

Subclinical hypothyroidism (SCH) has been shown to be associated with microbiota. However, the association between SCH and oral microbiota has not yet been elucidated. The results of our previous clinical studies showed that Prevotella intermedia was abundant in the oral microbiota of SCH patients. This study aimed to investigate the relationship between SCH and oral microbiota, verify the pathogenicity of P. intermedia in SCH, and preliminarily explore the possible mechanism. The SCH mouse model with oral application of P. intermedia was established, and the variance in the mouse oral microbiota and changes in thyroid function and metabolism were detected in mice. Student's t test and analysis of variance were used for statistical analysis. Oral application of P. intermedia changed the composition of the oral microbiota of SCH mice, which enhanced the damage to the thyroid and decreased the expression of functional genes of the thyroid. Moreover, P. intermedia decreased oxygen consumption and aggravated glucose and lipid metabolism disorders in SCH mice. Glucose tolerance and insulin tolerance decreased, and the triglyceride content of the liver and inflammatory infiltration in adipose tissue increased in SCH mice after P. intermedia stimulation. Mechanistically, P. intermedia increased the proportion of CD4+ T cells in cervical lymph nodes and thyroids in SCH mice. Th1 cells were suggested to play an important role in the pathogenesis of SCH involving P. intermedia. In conclusion, P. intermedia aggravated SCH manifestations, including thyroid dysfunction and glucose and lipid metabolism disorders, by causing immune imbalance in mice. This study sheds new light on the pathogenesis of SCH from the perspective of oral microbiota.

[Characteristics and clinical significance of wideband tympanometry of otitis media with effusion in young children].

Objective: To study the characteristics of wideband tympanometry(WBT) and its application value in the diagnosis of otitis media with effusion(OME) in young children. Methods: We compared wideband acoustic energy absorbance(EA) under peak pressure in young children with OME(190 ears) and healthy control subjects(121 ears) from Ninth People's Hospital of Shanghai Jiaotong University School of Medicine between January 2018 and June 2020. Both groups were divided into three groups, 1-6 months, 7-36 months and 37-72 months. SPSS 20.0 statistical software was used to analyze and compare the EA parameters between OME children of different months and the control group. Receiver operating characteristic (ROC)curve was used to analyze the diagnostic value of WBT in young children with OME. Results: There were significant differences in EA among three OME groups from 500 Hz to 2 000 Hz(P<0.05).Compared with the control groups, EA of 1-6 m OME group decreased significantly below 4 000 Hz(P<0.05), EA of 7-36 m OME group decreased significantly at 545-1 600 Hz(P<0.05), EA of 37-72 m OME group decreased significantly above 545 Hz(P<0.05).ROC curve indicated that EA at 1 000 Hz had the greatest diagnostic value (AUC was 0.890), followed by 1 500 Hz and the range of 500-2 000 Hz (AUC was 0.883 and 0.881, respectively).EA at 1 000 Hz with a cutoff value of 0.55 had the best diagnostic sensitivity of 90.8%, which was higher than conventional tympanometry (85.8%). The maximum AUC (0.932) could be obtained by combining EA, peak pressure and admittance amplitude of 226 Hz tympanometry as predictors. Conclusions: EA is significantly decreased in young children with OME. Compared with the conventional single frequency tympanometry, WBT is more accurate in the diagnosis of OME in young children, and the prediction accuracy would be better if combined with 226 Hz tympanometry.

Comparative analysis of time-scaling properties about water pH in Poyang Lake Inlet and Outlet on the basis of fractal methods.

Detrended fluctuation analysis (DFA) and multifractal methods are applied to the time-scaling properties analysis of water pH series in Poyang Lake Inlet and Outlet in China. The results show that these pH series are characterised by long-term memory and multifractal scaling, and these characteristics have obvious differences between the Lake Inlet and Outlet. The comparison results suggest that monofractal and multifractal parameters can be quantitative dynamical indexes reflecting the capability of anti-acidification of Poyang Lake. Furthermore, we investigated the frequency-size distribution of pH series in Poyang Lake Inlet and Outlet. Our findings suggest that water pH is an example of a self-organised criticality (SOC) process. The results show that it is different SOC behaviours that result in the differences of power-law relations between pH series in Poyang Lake Inlet and Outlet. This work can be helpful to improvement of modelling of lake water quality.

Long noncoding RNA FAM201A involves in radioresistance of non-small-cell lung cancer by enhancing EGFR expression via miR-370.

OBJECTIVE: The aberrant expression of long noncoding RNAs (lncRNAs) is involved in the molecular regulation of non-small cell lung cancer (NSCLC). This study aims to investigate the biological interaction of lnc-FAM201A and its downstream factors and their impacts on the radiotherapy response of NSCLC. PATIENTS AND METHODS: Quantitative Polymerase Chain Reaction (qPCR) was used to determine the expression of FAM201A in NSCLC tissues. The Chi-square tests explored the association between FAM201A level and the poor clinicopathological characteristics (including radioresistance) of NSCLC. Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate various prognostic factors for overall survival (OS). The effect of FAM201A on OS was tested by the log-rank test. A549/SK-MES-1 cell lines transfected with short hairpin RNA (shRNA) were used to verify the promoting effects of FAM201A on radiotherapy resistance in vitro and in vivo. Cell apoptosis (analyzed by flow cytometry), cell proliferation (determined by Cell Counting Kit-8), and mice xenograft models were performed to confirm the results. The downstream targets of FAM201A were predicted by bioinformatics tools. Additionally, the Dual-luciferase reporter assay, qPCR, and Western blotting were performed to confirm their interaction. RESULTS: FAM201A was significantly upregulated in tissues obtained from NSCLC patients resistant to radiotherapy. Increased FAM201A expression was strongly associated with radioresistance and inferior survival in NSCLC, as demonstrated by clinical data. The silence of FAM201A could inhibit cell proliferation and further cell apoptosis of NSCLC cells under X-ray irradiation both in vitro and in vivo. Moreover, by competitively targeting miR-370, FAM201A elevated the epidermal growth factor receptor (EGFR) and the hypoxia-inducible factor 1alpha (HIF-1α) levels. After FAM201A knockdown, EGFR and HIF-1α were repressed with enhanced radiosensitivity. CONCLUSIONS: The interference of FAM201A impairs its suppression of miR-370, resulting in the upregulation of EGFR and HIF-1α and enhancement of radiosensitivity in NSCLC patients. Collectively, our results indicated that this regulatory axis might serve as a potential therapeutic target to increase the sensitivity of radiotherapy in NSCLC patients.

Two-photon graphene quantum dot modified Gd2O3 nanocomposites as a dual-mode MRI contrast agent and cell labelling agent.

For obtaining high-resolution macroscopical anatomical information and high sensitivity microscopical optical signals, it is highly desirable to develop dual-modality magnetic resonance imaging (MRI) and fluorescent probes in medical imaging simultaneously. In this study, Gd2O3 nanoparticles were modified with two-photon graphene quantum dots (GQD), integrating a magnetic resonance imaging (MRI) contrast agent with two-photon imaging functionality into one nanoprobe. A photoluminescence study indicated that the GQD modification process integrated MRI properties with both one-photon and two-photon imaging properties. Gd2O3/GQD nanocomposites showed a significantly improved longitudinal relaxivity (r1 = 15.995 mM-1 s-1) in comparison with commercial Magnevist (Gd-DTPA, r1 = 4.5 mM-1 s-1) and some reported papers. Excellent water solubility and good biocompatibility make Gd2O3/GQD nanocomposites an ideal dual-modal imaging agent, suggesting their potential and significant biological and clinical applications in the future.

[Effects of bimodal intervention on the development of auditory and speech ability in infants with unilateral cochlear implantation].

Objective: To explore the effects of bimodal intervention on the development of auditory and speech ability in the infants with unilateral cochlear implantation(CI). Methods: Total 35 bilateral profound sensorineural hearing loss infants with unilateral CI, aged 0.7 to 2.8 years old, were selected. The subjects were divided into two groups: the group with unilateral CI(cochlear implant alone, n= 15), and the bimodal group with CI and contralateral fitting hearing aid(n= 20). Their auditory and speech abilities were estimated at the different time points after switch-on(the 0th, 0.5th, 1st, 3rd, 6th, 12th, 18th, and 24th month, respectively) using Infant Toddler-Meaningful Auditory Integration Scale(IT-MAIS), Meaningful Use of Speech Scale(MUSS), Categories of Auditory Performance(CAP), and Speech Intelligibility Rating(SIR) scores. Results: The IT-MAIS scores of bimodal group after switch-on were higher than unilateral CI group(the 0.5th, 1st, 3rd, 6th, 12th, and 18th month), the statistical significances were identified at the 0.5th, 1st, 3rd, 6th, and 12th month, respectively(P<0.05). The CAP scores of bimodal group before CI operation and after switch-on(the 0.5th, 1st, 3rd, 6th, 12th, 18th and 24th month)were higher than unilateral CI group, the statistical significances were seen at the 3rd, 6th, 12th, 18th and 24th month after switch-on(P<0.05). The MUSS scores of bimodal group after switch-on were higher than unilateral CI group(the 1st, 3rd, 6th, 12th, 18th and 24th month), the statistical significances were found at the 12th, 18th and 24th month, respectively(P<0.05). The SIR scores of bimodal group after switch-on were higher than unilateral CI group(the 3rd, 6th, 12th, 18th and 24th month), and significant differences appeared at the 12th, 18th and 24th month after switch-on(P<0.05). Conclusion: Bimodal intervention could be helpful to the development of auditory and speech ability of infants.

Metformin reduces SATB2-mediated osteosarcoma stem cell-like phenotype and tumor growth via inhibition of N-cadherin/NF-kB signaling.

OBJECTIVE: To investigate the role of SATB2 in stem cell-like properties of osteosarcoma and identify new strategies to eliminate cancer stem cells of osteosarcoma. MATERIALS AND METHODS: Osteosarcoma cancer stem cells were derived by sarcosphere generation or chemo drug enrichment. SATB2 and pluripotency-associated gene expression in osteosarcoma CSCs were analyzed using qRT-PCR and Western blotting. The sphere formation assay, cell counting kit-8 assay and anti-chemotherapy proteins were used to measure the effects of altered SATB2, N-cadherin expression or metformin treatment in CSCs. Nude mice were injected with SATB2-deficient U2OS/MTX cells to assess the role of SATB2 in osteosarcoma growth and chemoresistance in vivo. Bioinformatics analyses were performed to identify SATB2 downstream target genes and immunochemistry to determine the correlation between SATB2 expression and patient outcome. Western blotting and luciferase reporter assays were used to examine the effects of N-cadherin and SATB2 inhibition on the NF-kB pathway. RESULTS: SATB2 was upregulated in osteosarcoma stem cells. Knockdown of SATB2 decreased sarcosphere formation, cell proliferation and stem cell-like gene expression in vitro, meanwhile reduced tumor growth and chemoresistance in vivo. High SATB2 expression in osteosarcoma patient samples was associated with poor clinical outcome. N-cadherin was one critical downstream target gene of SATB2 that mediated the stem cell-like phenotype. Reduction of SATB2 or N-cadherin resulted in NF-kB inactivation, which led to impaired osteosarcoma sphere formation and tumor cell proliferation. Metformin treatment of osteosarcoma cells enhanced the effects of chemotherapy via suppression of N-cadherin. CONCLUSIONS: SATB2 plays an important role in regulating osteosarcoma stem cell-like properties and tumor growth. The combination of conventional chemotherapy and metformin may be a promising therapeutic strategy for osteosarcoma patients.

Indoor burning coal air pollution and lung cancer--a case-control study in Fuzhou, China.

A case-control study on risk factors for lung cancer was carried out in Fuzhou, China. One-hundred and two newly-diagnosed primary lung cancer cases in urban Fuzhou (78 male and 24 female cases) were matched with 306 population-based controls. The primary histological types were adenocarcinomas (57 cases, 55.9%) and squamous cell carcinomas (39 cases, 38.2%). Controls were obtained from the general population by random, stratified sampling and consisted of noncancer cases matched for sex, ethnicity and age. Cases and controls were interviewed by trained professionals using a standardized questionnaire. Information was obtained on: smoking habits, living conditions, history of respiratory diseases, air pollution, and 40 other variables. The data were evaluated by conditional logistic regression analysis. The major risk factors for lung adenocarcinoma were: indoor air pollution from burning coal, chronic bronchitis, and high economic income. The risk factors for lung squamous cell carcinoma were: amount of cigarettes smoked per day, "deep inhalation", a history of exposure to environmental tobacco smoke (ETS) before 20 years of age, burning coal indoors, and high economic income. The results showed that the major risk factors for lung cancer in Fuzhou were: burning coal indoors, smoking, exposure to ETS before 20 years of age, chronic bronchitis, and high economic income. Cigarette smoking significantly increased the risk of lung squamous cell carcinoma, but had no significant association with the risk of lung adenocarcinoma. In summary, our research supports the hypothesis that smoking and indoor air pollution are the major risk factors for lung cancer in Fuzhou. Burning coal indoors and smoking were associated with lung cancer mortality in a major city in southern China.

Diagnosis of hepatocellular carcinoma by quantitative detection of hepatoma-specific bands of serum gamma-glutamyltransferase.

Tissues of hepatocellular carcinoma (HCC) can express hepatoma-specific gamma-glutamyltransferase (GGT) and secrete GGT into circulating blood. Serum GGT was separated into several bands (up to 11), including hepatoma-specific bands (HSBs, I', II, and II') by a vertical slab electrophoresis assay of polyacrylamide stage gradient gel. In the present study, the HSBs of serum GGT were separated, and the HSB activity was quantitatively measured in 91 patients with HCC and compared with that of 106 patients with benign liver disease, 16 patients with extrahepatic tumors, and 30 healthy control subjects. Significant differences of the HSB activity were observed between the HCC group and each study group. An HSB activity greater than 5.5 U/L seems to be diagnostic of HCC. The quantitative method has a sensitivity of 85.3%, a specificity of 97.2%, a positive predictive value of 95.1%, a negative predictive value of 91.2%, and an accuracy of 92.5% for detecting HCC. No correlation was found between HSB activity and the serum alpha-fetoprotein (AFP) level or tumor size in patients with HCC. The quantitative analysis of HSB activity of GGT is superior to detection of the AFP concentration and is useful in early diagnosis of small HCC or AFP-negative HCC.

Reversible hearing impairment induced by lithium in the guinea pig.

Lithium salts remain one of the most widely used treatments for depressive illness. The mechanisms involved probably include reduction in free inositol. Visual perceptive disturbances can be a side effect of the treatment. We report here for the first time that chronic lithium treatment in the guinea pig induces a predominantly low frequency hearing loss and, in the longer term, loss of sensitivity is observed across the whole audiogram. The changes are reversed when treatment is arrested. The observations could be accounted for, at least partially, by a lithium-induced perturbation of the phosphoinositide cascade within the inner ear.

Average spectrum of cochlear activity: a possible synchronized firing, its olivo-cochlear feedback and alterations under anesthesia.

Average spectrum of electrophysiological cochlear activity (ASECA) recorded from the cochlea or the eighth nerve is related to firing of auditory neurons and has been used recently in search of an objective measure of tinnitus both in animal models and in humans. Little is known about neuro-sensory processes underlying the spectral features of ASECA. The present study used awake and/or anesthetized animals and investigated effects of various sounds presented contralaterally and ipsilaterally. Contralateral stimulation with noise bands at frequencies above about 8 kHz and below acoustic interaural cross-talk decreased the amplitude of the 1 kHz peak of ASECA. When presented ipsilaterally noises produced either an increase or a decrease of this spectral peak when the acoustic bandwidth was respectively above or below 1.5 kHz. Pure tones when presented contralaterally had no detectable effect. When presented ipsilaterally pure tones with frequencies higher than about 4 kHz decreased the 1 kHz peak of ASECA. The detailed time course of sound-induced variations of the 1 kHz peak was measured by time averaging. The resulting response patterns resemble PST histograms of the auditory nerve. Sedation and anesthesia deepened the 500 Hz trough of ASECA and shifted it towards 400 Hz. Sedation induced a diminution and anesthesia an almost complete suppression of the decrease of the 1 kHz peak induced by contralateral noise. Overall these data indicate that ASECA would reflect synchronized firings and they provide evidence for an influence of olivo-cochlear feedback sensitive to the state of awakeness.

[Prognosis decision system for acute myocardial infarction].

Prognosis Decision System (PDS) is a program that analyzes the prognosis of AMI basing on the presented prognostic risk-factors after the onset of symptoms in patients with AMIs. The model is represented by using both pattern recognition and logical judgement. The forecast exact rate of PDS reached 90% by analysis of 100 retrospective cases and 125 prospective cases. It is useful in reduction of early case fatality rate and prevention of sudden death during convalescence.

Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylate-induced tinnitus in rat.

Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG) expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc) and the early growth response gene-1 (Egr-1), appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS) paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC) and auditory cortex (AC), in contradiction of our hypothesis. Expression of N-methyl d-aspartate receptor subunit 2B (NR2B) was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus.

Telomerase inhibition alters telomere maintenance mechanisms in laryngeal squamous carcinoma cells.

BACKGROUND AND PURPOSE: Telomere length must be maintained throughout cancer cell progression and proliferation. In most tumours, telomerase activity maintains telomere length. Therefore, telomerase is a target for cancer treatments. However, some cancer cells maintain telomere length through an alternative mechanism termed 'alternative lengthening of telomeres'. To determine how telomerase inhibition relates to the initiation of the alternative lengthening of telomeres pathway, we investigated telomerase activity and telomere maintenance in Hep-2 cells with and without reduced telomerase activity. MATERIALS AND METHODS: We investigated telomerase activity levels in a normal Hep-2 cell line and in residual cells following telomerase inhibition treatment. Additionally, we looked for expression of a marker protein for the alternative lengthening of telomeres mechanism. RESULTS AND CONCLUSIONS: In the residual cells, telomerase activity was eliminated. However, these cells had higher levels of the alternative lengthening of telomeres biomarker, suggesting an alternative mechanism for telomere maintenance following telomerase inhibition. These results could have a major impact on the design of new cancer treatments.

Paradoxical long-term enhancement of distortion product otoacoustic emission amplitude after repeated exposure to moderate level, wide band noise in awake guinea pigs.

OBJECTIVE: Hearing sensitivity usually diminishes with noise exposure. In the present study, we examined the effect of 93 dB(A) wide band noise on cochlear micromechanical sensitivity in awake guinea pigs. METHODS: Animals were randomly assigned to groups receiving either single or repeated noise exposure. Distortion product otoacoustic emission amplitudes were recorded before, during and after noise exposure. RESULTS: Ninety-three decibel(A) wide band noise reduced the distortion product otoacoustic emission amplitudes at all tested frequencies. The distortion product otoacoustic emission amplitudes for higher frequencies showed a permanent reduction, whereas those for lower frequencies showed a temporary reduction. Distortion product otoacoustic emission amplitudes for middle frequencies showed prolonged enhancement after repeated noise exposure. CONCLUSION: Our results suggest that (1) it is likely that there are intermediate stages between permanent threshold shift and temporary threshold shift, and (2) long-term enhancement of distortion product otoacoustic emission amplitudes may be an indication of tinnitus generation.