Traditional Chinese medicine in thyroid-associated orbitopathy.

PURPOSE: Orbital fibroblasts (OF) are considered the central target cells in the pathogenesis of thyroid-associated orbitopathy (TAO), which comprises orbital inflammation, orbital tissue edema, adipogenesis, fibrosis, oxidative stress and autophagy. Certain active ingredients of traditional Chinese medicine (TCM) demonstrated inhibition of TAO-OF in pre-clinical studies and they could be translated into novel therapeutic strategies. METHODS: The pertinent and current literature of pre-clinical studies on TAO investigating the effects of active ingredients of TCM was reviewed using the NCBI PubMed database. RESULTS: Eleven TCM compounds demonstrated inhibition of TAO-OF in-vitro and three of them (polydatin, curcumin, and gypenosides) resulted in improvement in TAO mouse models. Tanshinone IIA reduced inflammation, oxidative stress and adipogenesis. Both resveratrol and its precursor polydatin displayed anti-oxidative and anti-adipogenic properties. Celastrol inhibited inflammation and triptolide prevented TAO-OF activation, while icariin inhibited autophagy and adipogenesis. Astragaloside IV reduced inflammation via suppressing autophagy and inhibited fat accumulation as well as collagen deposition. Curcumin displayed multiple actions, including anti-inflammatory, anti-oxidative, anti-adipogenic, anti-fibrotic and anti-angiogenic effects via multiple signaling pathways. Gypenosides reduced inflammation, oxidative stress, tissue fibrosis, as well as oxidative stress mediated autophagy and apoptosis. Dihydroartemisinin inhibited OF proliferation, inflammation, hyaluronan (HA) production, and fibrosis. Berberine attenuated inflammation, HA production, adipogenesis, and fibrosis. CONCLUSIONS: Clinical trials of different phases with adequate power and sound methodology will be warranted to evaluate the appropriate dosage, safety and efficacy of these compounds in the management of TAO.

Effects of probiotic/prebiotic/synbiotic supplementation on blood glucose profiles: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Previous studies have evaluated the effects of probiotic/prebiotic/synbiotic supplementation on blood glucose profiles among diabetic patients. However, the results were inconsistent. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A systematic searching from PubMed, ISI Web of Science, Embase, and Cochrane Central was conducted to identify high-quality clinical trials investigating the effect of probiotic/prebiotic/synbiotic supplementation on blood glucose profiles [including fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR)] up to December 2020. Subgroup analyses by types or durations of probiotic/prebiotic/synbiotic supplementation were conducted to investigate the different effects among different populations. RESULTS: A total of 39 trials with 3517 participants were included in the final analyses. Among patients with type II diabetes (T2DM), the summarized standardized mean differences (SMDs) and 95% confidential intervals (95% CIs) of FBG, HbA1c, and HOMA-IR were -0.30 (95% CI: -0.65 to 0.05), -0.59 (95% CI: -0.88 to -0.30), and -0.68 (95% CI: -1.13 to -0.23), respectively. Among patients with gestational diabetes (GDM), the summary SMDs of FBG, HbA1c and HOMA-IR were -0.67 (95% CI: -1.23 to -0.11), -0.24 (95% CI: -0.57 to 0.08), and -1.06 (95% CI: -1.72 to -0.40), respectively. Similar improvements in blood glucose profiles were also found among persons with prediabetes or gestational woman with normal glucose, but not among patients with type I diabetes. Subgroup analyses showed similar results of probiotic supplementation for patients with T2DM and probiotic/synbiotic supplementation for patients with GDM. CONCLUSION: Probiotic/prebiotic/synbiotic supplementation might improve the blood glucose profiles among patients with T2DM/GDM, persons with prediabetes, or gestational woman with normal glucose. Trials with more sophisticated design are needed to validate the results in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020161975.

[Salvianolic acid B and its magnesium salt inhibit SARS-CoV-2 infection of Vero-E6 cells by blocking spike protein-mediated membrane fusion].

OBJECTIVE: The investigate the inhibitory effects of the traditional Chinese medicine (TCM) monomer salvianolic acid B (Sal-B) and its magnesium salt Salvia Miltiorrhiza Polyphenolate Injection (ZDDY) against SARS-CoV-2 infection in vitro and explore the molecular mechanism. OBJECTIVE: The anti-SARS-CoV-2 activity of Sal-B and ZDDY was assessed using the authentic and pseudotyped SARS-CoV-2 infection assay. The antiviral targets of Sal-B were identified by molecular docking and molecular dynamics simulation. Circular dichroism spectroscopy was used to examine the structural characteristics of HR1 and HR2 regions of SARS-CoV-2 S protein, and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of Sal-B on virus-cell membrane fusion. Flow cytometry was carried out to analyze the effect of Sal-B on the binding of SARS-CoV-2 RBD to hACE2 receptor. OBJECTIVE: The median effective concentrations (EC50) of Sal-B and ZDDY against SARSCoV-2 infection in Vero-E6 cells were 55.47 µmol/L and 36.07 µg/mL, respectively. Both Sal-B and ZDDY successfully inhibited the entry of SARS-CoV-2 pseudovirus into the cells that stably expressed human ACE2 (ACE2/293T), with half maximal inhibitory concentrations (IC50) of 1.69 µmol/L and 24.81 µg/mL, respectively. Sal-B showed a binding affinity of -8.2 kcal/mol to the 6-helix bundle (6-HB) of SARS-CoV-2 S protein. Molecular dynamics simulation showed stable binding between Sal-B and the 6-HB of SARS-CoV-2 S protein at the predicted binding site. Sal-B disturbed the formation of the secondary structure of 6-HB in HR1P/HR2P mixture, resulting in a significantly lowered α-helicity (P < 0.05). Sal-B dose-dependently inhibited SARS-CoV-2 S protein-mediated cell-cell fusion, with an IC50 of 3.33 µmol/L. Sal-B showed no effect on RBD-Fc protein binding to the ACE2 receptor. OBJECTIVE: Sal-B and its magnesium salt ZDDY can inhibit the entry of SARS-CoV-2 in Vero-E6 cells in vitro by blocking SARS-CoV-2 spike protein-mediated virus-cell membrane fusion.

[Effect analysis of sequential laser application in treating the hypertrophic scars of burn children at early stage].

Objective: To explore the effects of sequential application of intensive pulsed light and carbon dioxide laser in treating the hypertrophic scars of burn children at early stage. Methods: A retrospective cohort before-after control study in the same patients was conducted. From January 2016 to December 2018, 145 burn children with hypertrophic scar at the early stage who met the inclusion criteria were admitted to the First Hospital of Jilin University, including 82 males and 63 females, aged 1 to 12 (3 (2, 6)) years. All the children were firstly treated with intense pulsed light therapy (no anesthesia or intravenous-inhalation combined anesthesia) at an interval of once per month, and then changed to carbon dioxide laser therapy (topical anesthesia or intravenous-inhalation combined anesthesia) when the degree of scar hyperemia was reduced, at an interval of once every 3 months, for a total of 3 times. Before the first intense pulsed light treatment (hereinafter referred to as before the first treatment) and 3 months after the last carbon dioxide laser treatment (hereinafter referred to as after the last treatment), scar scoring was evaluated by Vancouver Scar Scale (VSS), and scar hyperemia (denoted as hemoglobin level) was measured with Antera 3D® camera. The times of intense pulsed light, the time of single treatment, the anesthesia method, and the time of intravenous-inhalation combined anesthesia of intense pulsed light and carbon dioxide laser treatment were analyzed. After the last treatment, Likert Scale was used to evaluate the efficacy satisfaction of both doctors and patients. Adverse reactions were recorded during the treatment. Data were statistically analyzed with Wilcoxon signed rank sum test, and paired sample t test. Results: The color, vascular distribution, thickness, and softness scores, and total score in VSS scoring of scars of children after the last treatment were significantly lower than those before the first treatment (Z=-6.05, -10.34, -9.84, -9.28, -10.43, P<0.01). The hemoglobin level of scar of children after the last treatment was 1.86±0.24, significantly lower than 2.27±0.32 before the first treatment (t=17.65, P<0.01). A total of 411 times of intense pulsed light therapy were performed, (2.8±0.6) times per person, and the single treatment time was 35 (20, 45) s. There were 392 times (95.38%) without anesthesia, and 19 times (4.62%) with intravenous-inhalation combined anesthesia with time of 6 (5, 8) min. The single treatment time of carbon dioxide laser therapy was 5 (3, 10) min. There were 364 times (83.68%) of topical anesthesia and 71 times (16.32%) of intravenous-inhalation combined anesthesia with time of 10 (8, 15) min. After the last treatment, the efficacy satisfaction scores of doctors and patients were (4.3±0.7) and (3.8±1.0) points, respectively. Blisters occurred in 5 cases after intense pulsed light treatment, which were healed naturally after drainage. One child developed local skin infection, skin redness and swelling accompanied by purulent exudate after carbon dioxide laser treatment, which was improved after skin disinfection and external use of mupirocin ointment. No inflammatory pigmentation, worsening of hyperplasia of scar, erythema, or other skin adverse reactions or anesthetics-related adverse reactions occurred in any child. Conclusions: Sequential application of intense pulsed light and carbon dioxide laser to treat the hypertrophic scars of burn children at early stage can obviously improve the appearance and texture of scar, with higher satisfaction of doctors and patients and fewer adverse reactions.

A combination of three probiotic strains for treatment of acute diarrhoea in hospitalised children: an open label, randomised controlled trial.

Acute diarrhoea continues to be a leading cause of morbidity, hospitalisation, and mortality worldwide, and probiotics have been proposed as a complementary therapy in the treatment of acute diarrhoea. The goal of this study is to assess the efficacy and safety of three combined probiotic strains, Bifidobacterium lactis Bi-07, Lactobacillus rhamnosus HN001, and Lactobacillus acidophilus NCFM, as an adjunct to rehydration therapy in treatment of acute watery diarrhoea in hospitalised children. Eligible diarrheal children were randomised into intervention group (IG, n=96, conventional treatment for diarrhoea in combination with probiotics) and control group (CG, n=98, conventional treatment for diarrhoea without probiotics). The primary assessments of this study were duration of diarrhoea and hospital stay and improvement in diarrhoea symptoms. Significantly more children in the IG showed improvements in diarrhoea (defined as a decrease of stool frequency to no more than four times per day and an improved stool consistency within 24-48 h after the treatment) than those in the CG (96.9 vs 79.6%, P<0.05). Children supplemented with the mixed strains had a 22.5 h shorter (121.4±13.7 h vs 143.9±19.8 h) mean duration of diarrhoea and 1.2 d shorter hospital stays (5.1±1.2 d vs 6.3±1.4 d) than children only receiving the rehydration therapy (P<0.05). The prevalence of constipation of children in the IG (3.1%) was markedly lower (P<0.05) than that of children in the CG (13.3%) after treatment. In conclusion, the mixture of three probiotic strains given to children aged 1-3 years resulted in shorter durations of diarrhoea and hospitalisation and a higher percentage of improved children.

Serum fibroblast growth factor 23 and mineral metabolism in patients with euthyroid Graves' diseases: a case-control study.

This study investigated the alterations of mineral metabolism in patients with Graves' disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status. INTRODUCTION: FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves' disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved. METHODS: A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups. RESULTS: Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group. CONCLUSION: Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations. TRIAL REGISTRATION: Registration number: NCT01660308 and NCT02620085.

L-theanine attenuates transport stress-induced impairment of meat quality of broilers through improving muscle antioxidant status.

This study was to investigate the effect of dietary L-theanine (THE) supplementation (0, 600 mg/kg) on growth performance, carcass traits, immune organ indexes, meat quality, and muscle antioxidant status of transported broilers. A total of 180 one-day-old male Ross 308 broilers were randomly allotted to 2 treatment groups including a THE-free group with 12 replicates of 10 birds each and a THE group with 6 replicates of 10 birds each. On the morning of day 42, after a 9-h fast, the birds of THE-free group were divided into 2 equal groups, and then all birds in the 3 groups were placed into 18 crates and were transported according to the following protocols: 0-h transport of birds in the THE-free group (control group), 3-h transport of birds in the THE-free group (T group), and 3-h transport of birds in the THE group (T + THE group). Results showed that dietary THE supplementation improved feed conversion ratio and birds' final body weight (P < 0.05), while transport and dietary THE supplementation did not affect carcass traits of broilers (P > 0.05). Transport increased bird live weight loss, drip loss, L*24 h, muscle malondialdehyde (MDA), protein carbonyl (PC) and lactate contents, while it decreased thymus, spleen, and bursa of Fabricius indexes, pH24h, a*, and muscle total antioxidant capacity (T-AOC), catalase (CAT), and glutathione peroxidase (GSH-PX) activities and glycogen content (P < 0.05). Nevertheless, compared with birds in the T group, birds in the T + THE group exhibited increased thymus, spleen, and bursa of Fabricius indexes, pH24h, a*24 h, and muscle T-AOC, CAT, and GSH-PX activities and glycogen content, and decreased drip loss, L*24 h, and muscle MDA, PC, and lactate contents (P < 0.05). This study provided the first evidence that dietary THE supplementation prevented transport-stress-impaired immune organ indexes and meat quality of broilers, and the reason for maintenance of meat quality by supplementation of THE may be partly ascribed to the changed muscle glycolysis metabolism and antioxidant status.

Effects of acarbose and siglitine on blood glucose fluctuation and islet ß-cell function in patients with type 2 diabetes mellitus.

The effects of acarbose and sitagliptin on blood glucose fluctuation and islet ß-cell function in patients with type 2 diabetes mellitus (T2DM) were studied. One hundred and three patients with poorly controlled T2DM with insulin aspart 30 were selected and randomly divided into three groups: group A [continuous subcutaneous insulin infusion (CSII) treatment group], group B (CSII combined with acarbose treatment), group C (CSII combined with sitagliptin treatment). The treatment lasted for two weeks and the clinical indicators in the three groups were measured. The insulin dosage was adjusted according to the blood glucose statuses of the three groups of patients. In the final three days, 72 h of continuous glucose monitoring (CGM) were carried out, and the OGTT test was performed again. The results showed that the MODD (absolute means of daily difference), intra-day blood glucose fluctuation indices [(24 h MBG (mean blood glucose), LAGE (largest amplitude of glycemic excursions) and MAGE (average blood glucose fluctuation)] and postprandial blood glucose fluctuation indices [PGS (postprandial glucose spike), △t, PPGE (postprandial glucose excursion) and T (time) total] in group C and group B were significantly lower than those in group A. Compared with group B, the difference in blood glucose fluctuation indices in group C was not statistically significant (P>0.05). The HOMA-islet (homeostasis model assessment of islet) (CP-DM) index and FC-P (Fasting c-peptide) levels in group C and group B were significantly higher than those in group A (P less than 0.01). The HOMA-IR (CP) index of groups B and C was significantly lower than that of group A (P less than 0.01), and there was no statistically significant difference between groups B and C (P less than 0.05). Sitagliptin combined with intensive insulin pump therapy can reduce blood glucose fluctuation throughout the day, reduce insulin dosage, improve islet B cell function and reduce hypoglycemia better than intensive insulin pump therapy alone.

Effect of l-theanine on the growth performance, immune function, and jejunum morphology and antioxidant status of ducks.

l-theanine is a unique nonproteinogenic amino acid found in tea, and has recently received considerable attention because of its various biological activities. However, there is no available research report on the use of l-theanine as a feed additive in ducks. This study was conducted to investigate the potential benefits and appropriate dosages of l-theanine on the growth performance, immune function, serum biochemical parameters, and jejunum morphology and antioxidant capacity of ducks. A total of 600 1-day-old Chaohu ducks were randomly allocated into five dietary treatment groups supplemented with 0 (control group), 300, 600, 900 and 1500 mg/kg of l-theanine. Each group included five replicates of 24 birds each. Body weight at day 28 was increased (P<0.05) by l-theanine. From days 15 to 28, l-theanine elevated cumulative BW gain (BWG) and cumulative feed intake (FI), and decreased feed to gain ratio. From days 1 to 28, l-theanine elevated (P<0.05) cumulative BWG and cumulative FI. l-theanine elevated (P<0.05) the relative weight of bursa of Fabricus (day 14), thymus (day 14), spleen (day 28) and liver (day 28). On day 28, l-theanine decreased (P<0.05) serum glucose, uric acid, triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, insulin, interleukin-2 (IL-2) and IL-6 contents, and elevated (P<0.05) serum total protein, globulin (GLB), immune globulin A (IgA) and IgG contents, but only serum insulin, interferon-γ, tumor necrosis factor-α and IL-6 contents was decreased (P<0.05) and serum GLB and IgM content was elevated (P<0.05) by l-theanine on day 14. On day 14, l-theanine decreased (P<0.05) jejunum crypt depth, and elevated (P<0.05) jejunum villus height, villus height to crypt depth ratio (V/C), goblet cell number and total superoxide dismutase (T-SOD) activity. On day 28, l-theanine decreased (P<0.05) jejunum malondialdehyde content, and elevated (P<0.05) jejunum villus height, V/C, goblet cell number, and T-SOD, catalase and glutathione peroxidase activities. l-theanine levels caused quadratic effect on the growth performance, relative organ weight, serum parameters, jejunum morphology and antioxidant capacity. In conclusion, l-theanine can be used as a promising feed additive for ducks, and its optimal supplementation level was 600 to 900 mg/kg based on the current experimental condition.

[Transurethral flexible ureteroscopic holmium laser resection for tumors of renal pelvis: 6 cases report and literature review].

OBJECTIVE: To summarize the experience of flexible ureteroscopic holmium laser resection in treatment of renal pelvic carcinoma and to evaluate its value in treatment of renal pelvic carcinoma. METHODS: The clinical data of 6 patients with renal pelvic carcinoma treated in Peking University Third Hospital from January 2015 to January 2017 were retrospectively analyzed. The 6 patients were treated by the same experienced urologist and by flexible ureteroscopic holmium laser resection of renal pelvic tumors under general anesthesia. Regarding the intensity of the holmium laser, 10-30 W was generally used with settings of 0.5-1.5 J and 10-20 Hz. In general, a 200 µm end-firing holmium laser fiber was used. Narrow-band imaging (NBI) technique was applicated to search for tumors and check whether the excision was satisfactory. Routine "second flexible ureteroscopy" was performed after 4-6 weeks, and suspected lesions were referred for a biopy, then vaporized and cauterized. The ureteroscopy was examined every 6 months after operation, and color Doppler ultrasound, computed tomography urography (CTU) or magnetic resonance urography (MRU) were performed at the same time. The urine tumor cells were examined for 3 days before the operation, and the urine tumor markers, such as urinary nuclear matrix protein 22 (NMP22) were tested. For cases with highisk urothelial carcinoma and normal renal function, and 6 cycles of systemic adjuvant chemotherapy were performed after operation. RESULTS: All of the cases were successfully treated. The data were as follows: the operation time 77.5 min (45-115 min), the blood loss 10 mL (5-20 mL), and hospital stay after surgery 3 days (2-5 days). After 13-34 months' followp, two patients had recurrent tumor recurrence and underwent resection operation. Two patients received systemic adjuvant chemotherapy after operation. Case 5 was histopathologically high grade urothelial carcinoma, and 6 cycles of systemic chemotherapy were given after operation. Local recurrence occurred during chemotherapy, and then endoscopic operation was performed, and no recurrence occurred in the follow-up for 12 months after reoperation. In case 6, the pathology was low grade urothelial carcinoma, but the case was multiple tumors in the right renal calyx and the lower calyx. Then 6 cycles of systemic chemotherapy were given, and no recurrence was found in the followp for 13 months. CONCLUSION: Transurethral flexible ureteroscopic holmium laser resection is relatively safe for the treatment of renal pelvic carcinoma. It is suitable for special cases of solitary kidney and renal dysfunction, as well as for patients with low risk urinary tract epithelial tumors, but the recurrence rate is high, and the indications need to be strictly controlled. Patients with high-risk urothelial carcinoma who underwent endoscopic resection are advised to receive systemic adjuvant gemcitabine and cisplatin (GC) regimen after surgery, in order to increase the overall survival rate. Systemic chemotherapy combined with endoscopic operation may become a new treatment for upper tract urothelial carcinoma (UTUC).

Exposure Duration Is a Determinant of the Effect of Sinusoidal Electromagnetic Fields on Peak Bone Mass of Young Rats.

We proposed a three-step strategy to obtain the optimal therapeutic parameters, which is composed of large-scale screening at cellular level, verification in animal experiments, and confirmation by a clinical trial. The objective of the current study was to test the feasibility of our strategy. Newborn rat calvarial osteoblasts were treated by 50 Hz 1.8 mT sinusoidal electromagnetic fields (SEMFs) with 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 h/days, respectively. The osteogenic differentiation and maturation of the osteoblast were assayed and compared to obtain the optimal duration. One-month-old growing rats were then treated by the same SEMFs with 0.5, 1.5, and 2.5 h/days, respectively, and the peak bone mass was analyzed after 2 months. It was found that the optimal exposure duration to promote the osteogenic differentiation and maturation of osteoblasts was 1.5 h/days, judging by the increasing degrees of ALP activity, calcified nodules formed, the gene and protein expression levels of Runx-2, BMP-2, and Col-I, as well as the expression levels of signaling proteins of the BMP-2/Smad1/5/8 pathway. The highest increase of peak bone mass after 2 months was also obtained by 1.5 h/days, judging by the results of X-ray dual-energy absorptiometry, mechanical property analysis, micro-CT scanning, and serum bone turnover marker examinations. The above results indicated that exposure duration is a determinant for the therapeutic effect of EMFs, and the optimal therapeutic effects only can be obtained by the optimal exposure duration.

Delta-frequency stimulation of cerebellar projections can compensate for schizophrenia-related medial frontal dysfunction.

Schizophrenia involves abnormalities in the medial frontal cortex that lead to cognitive deficits. Here we investigate a novel strategy to normalize medial frontal brain activity by stimulating cerebellar projections. We used an interval timing task to study elementary cognitive processing that requires both frontal and cerebellar networks that are disrupted in patients with schizophrenia. We report three novel findings. First, patients with schizophrenia had dysfunctional delta rhythms between 1-4 Hz in the medial frontal cortex. We explored cerebellar-frontal interactions in animal models and found that both frontal and cerebellar neurons were modulated during interval timing and had delta-frequency interactions. Finally, delta-frequency optogenetic stimulation of thalamic synaptic terminals of lateral cerebellar projection neurons rescued timing performance as well as medial frontal activity in a rodent model of schizophrenia-related frontal dysfunction. These data provide insight into how the cerebellum influences medial frontal networks and the role of the cerebellum in cognitive processing.

Acupuncture in the neonatal intensive care unit-using ancient medicine to help today's babies: a review.

Acupuncture has been used for thousands of years in Eastern medicine for a variety of conditions and illnesses, including pain. Neonatal intensive care, on the other hand, is a relatively new branch of medicine that has emerged as the pivotal influence in increasing survival of critically ill newborn infants only within the last 50 years. Unfortunately, pain is an inevitable part of treatment in a neonatal intensive care unit (NICU). The control and prevention of pain remains a major issue for clinicians despite recognition and understanding of the myriad of short- and long-term problems that are associated with both pain and its treatment within the NICU environment. In this review, we examine the potential role of acupuncture to decrease and treat pain in babies requiring neonatal intensive care and discuss future therapeutic and research implications for the use of this ancient therapy within the modern environment of the NICU.

Epigenetic suppression of potassium-chloride co-transporter 2 expression in inflammatory pain induced by complete Freund's adjuvant (CFA).

BACKGROUND: Multiple mechanisms contribute to the stimulus-evoked pain hypersensitivity that may be experienced after peripheral inflammation. Persistent pathological stimuli in many pain conditions affect the expression of certain genes through epigenetic alternations. The main purpose of our study was to investigate the role of epigenetic modification on potassium-chloride co-transporter 2 (KCC2) gene expression in the persistence of inflammatory pain. METHODS: Persistent inflammatory pain was induced through the injection of complete Freund's adjuvant (CFA) in the left hind paw of rats. Acetyl-histone H3 and H4 level was determined by chromatin immunoprecipitation in the spinal dorsal horn. Pain behaviour and inhibitory synaptic function of spinal cord were determined before and after CFA injection. KCC2 expression was determined by real time RT-PCR and Western blot. Intrathecal KCC2 siRNA (2 µg per 10 µL per rat) or HDAC inhibitor (10 µg per 10 µL per rat) was injected once daily for 3 days before CFA injection. RESULTS: Persistent inflammatory pain epigenetically suppressed KCC2 expression through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in decreased inhibitory signalling efficacy. KCC2 knock-down caused by intrathecal administration of KCC2 siRNA in naïve rats reduced KCC2 expression in the spinal cord, leading to sensitized pain behaviours and impaired inhibitory synaptic transmission in their spinal cords. Moreover, intrathecal HDAC inhibitor injection in CFA rats increased KCC2 expression, partially restoring the spinal inhibitory synaptic transmission and relieving the sensitized pain behaviour. CONCLUSION: These findings suggest that the transcription of spinal KCC2 is regulated by histone acetylation epigenetically following CFA. SIGNIFICANCE: Persistent pain suppresses KCC2 expression through HDAC-mediated histone hypoacetylation and consequently impairs the inhibitory function of inhibitory interneurons. Drugs such as HDAC inhibitors that suppress the influences of persistent pain on the expression of KCC2 may serve as a novel analgesic.

The effects of air pollution on asthma hospital admissions in Adelaide, South Australia, 2003-2013: time-series and case-crossover analyses.

BACKGROUND: Air pollution can have adverse health effects on asthma sufferers, but the effects vary with geographic, environmental and population characteristics. There has been no long time-series study in Australia to quantify the effects of environmental factors including pollen on asthma hospitalizations. OBJECTIVES: This study aimed to assess the seasonal impact of air pollutants and aeroallergens on the risk of asthma hospital admissions for adults and children in Adelaide, South Australia. METHODS: Data on hospital admissions, meteorological conditions, air quality and pollen counts for the period 2003-2013 were sourced. Time-series analysis and case-crossover analysis were used to assess the short-term effects of air pollution on asthma hospitalizations. For the time-series analysis, generalized log-linear quasi-Poisson and negative binomial regressions were used to assess the relationships, controlling for seasonality and long-term trends using flexible spline functions. For the case-crossover analysis, conditional logistic regression was used to compute the effect estimates with time-stratified referent selection strategies. RESULTS: A total of 36,024 asthma admissions were considered. Findings indicated that the largest effects on asthma admissions related to PM2.5 , NO2 , PM10 and pollen were found in the cool season for children (0-17 years), with the 5-day cumulative effects of 30.2% (95% CI: 13.4-49.6%), 12.5% (95% CI: 6.6-18.7%), 8.3% (95% CI: 2.5-14.4%) and 4.2% (95% CI: 2.2-6.1%) increases in risk of asthma hospital admissions per 10 unit increments, respectively. The largest effect for ozone was found in the warm season for children with the 5-day cumulative effect of an 11.7% (95% CI: 5.8-17.9%) increase in risk of asthma hospital admissions per 10 ppb increment in ozone level. CONCLUSION: Findings suggest that children are more vulnerable and the associations between exposure to air pollutants and asthma hospitalizations tended to be stronger in the cool season compared to the warm season, with the exception of ozone. This study has important public health implications and provides valuable evidence for the development of policies for asthma management.

Investigation of the inhibitors of histone-lysine N-methyltransferase SETD2 for acute lymphoblastic leukaemia from traditional Chinese medicine.

Leukaemia is the leading cause of childhood malignancies. Recent research indicates that the SETD2 gene is associated with acute lymphoblastic leukaemia. This study aims to identify potential lead compounds from traditional Chinese medicine (TCM) using virtual screening for SET domain containing 2 (SETD2) protein against acute lymphoblastic leukaemia. Docking simulation was performed to determine potential candidates which obtain suitable docking poses in the binding domain of the SETD2 protein. We also performed molecular dynamics (MD) simulation to investigate the stability of docking poses of SETD2 protein complexes with the top three TCM candidates and a control. According to the results of docking and MD simulation, coniselin and coniferyl ferulate have high binding affinity and stable interactions with the SETD2 protein. Coniselin is isolated from the alcoholic extract of Comiselinum vaginatum Thell. Coniferyl ferulate can be isolated from Angelica sinensis, Poria cocos (Schw.) Wolf, and Notopterygium forbesii. Although S-adenosyl-L-homocysteine has more stable interactions with key residues in the binding domain than coniselin and coniferyl ferulate during MD simulation, the TCM compounds coniselin and coniferyl ferulate are still potential candidates as lead compounds for further study in the drug development process with the SETD2 protein against acute lymphoblastic leukaemia.

[The diagnosis and treatment of primary thyroid lymphoma].

Primary thyroid lymphoma (PTL) refers to the malignant tumor of primary lymphoid tissue in the thyroid, accounting for approximately 5% of all thyroid malignancies and less than 3% of all extranodal lymphomas. PTL usually develops in females more than 50 years old. Most of PTL cases are non-Hodgkin's lymphomas. The major pathological subtypes are mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma. Treatment options for individual pathological subtypes are also different, so pathological diagnosis is very important. The main treatment options include surgical treatment, radiotherapy, chemotherapy, targeted therapy and combined therapy. The main aims of surgical treatment are to obtain a determined diagnosis and to relieve airway pressure, . The prognosis of PTL is generally excellent.

Identification and characterization of an atypical 2-cys peroxiredoxin from the silkworm, Bombyx mori.

Peroxiredoxins (Prxs) play an important role in the protection of insects against the toxicity of reactive oxygen species. Here, we identified and characterized a novel, atypical 2-cysteine (Cys) peroxiredoxin (BmPrx3) from an expressed sequence tag database in a lepidopteran insect, Bombyx mori. The BmPrx3 cDNA contained an open reading frame of 684 bp that encodes a 228-amino-acid protein with a calculated molecular mass of 25 kDa. Sequence comparison revealed that BmPrx3 belongs to the atypical 2-Cys Prxs. Quantitative real-time PCR revealed that BmPrx3 can be detected in all tissues and developmental stages. Recombinant BmPrx3 purified from Escherichia coli exhibited antioxidant activity that removed hydrogen peroxide and protected DNA from oxidative damage. Disc diffusion and viability assays revealed that recombinant BmPrx3 increased bacterial survival under H2 O2 -mediated oxidative stress. In addition, quantitative real-time PCR analysis indicated that BmPrx3 transcription levels were significantly increased in response to various oxidative stresses. Furthermore, BmPrx3 transcription levels in the midgut were regulated by bacterial infection. Taken together, these results suggest that BmPrx3 acts as an antioxidant enzyme to protect the silkworm from various oxidative stresses.

Upregulation of the oncoprotein SET determines poor clinical outcomes in hepatocellular carcinoma and shows therapeutic potential.

The SET protein is a potent inhibitor of protein phosphatase 2A (PP2A). Here, we report the oncogenic role of SET in hepatocarcinogenesis, clinical aggressiveness and anti-hepatocellular carcinoma (HCC) therapeutics. By analyzing samples obtained from 147 HCC patients, we found that SET overexpression was detected specifically in 30.6% HCC tumor samples, and was significantly associated with worse clinical features and high p-Akt expression in HCC tumors. Co-expression of SET and Akt predicted shorter post-operative recurrence-free survival in this cohort (P=0.045). Furthermore, SET was significantly associated with cell growth and hepatosphere formation. To elucidate the anti-HCC potential of targeting SET, we generated a novel SET antagonist, EMQA (N(4)-(3-ethynylphenyl)-6,7-dimethoxy-N(2)-(4-phenoxyphenyl) quinazoline-2,4-diamine). EMQA enhanced PP2A activity via disrupting SET-PP2Ac (catalytic domain of PP2A) binding in HCC cells, which restored PP2A-mediated p-Akt downregulation and promoted HCC cell death. In HCC cells or recombinant proteins expressing the N- and C- truncated forms of SET, only the C-terminal SET was required for EMQA targeting. Furthermore, combining sorafenib and EMQA showed good synergism in inhibiting HCC survival. Our findings suggested the oncogenic role of SET and the adverse prognostic value of SET overexpression in HCC. This alteration defines a subgroup of HCC patients who could benefit from SET antagonists, such as EMQA.