Background: Local hyperthermia is recommended for the treatment of patients with fixed cutaneous sporotrichosis, though the effectiveness and mechanisms of action remain elusive. While neutrophils represent the main inflammatory cells associated with sporotrichosis lesions, the issue of whether hyperthermia is involved with interactions between neutrophils and Sporothrix globosa remains unclear. Objective: To evaluate the effect of local hyperthermia on sporotrichosis and determine whether local hyperthermia involves effects of neutrophils against Sporothrix. Methods: For the in vivo study, mice were infected with yeast cells of S. globosa followed by treatment with local hyperthermia. In vitro, an isolated S. globosa strain was co-cultured with or without neutrophils and subjected under different temperatures. Immunofluorescence was used to assess the formation of neutrophil extracellular trap (NETs) were formed under these different culture conditions and the number of fungi colony forming units were compared. Results: Hyperthermia was significantly more effective in clearing the lesions in the mouse model, as compared to sham treatment. Neutrophils failed to exert any fungicidal effects against S. globosa in response to hyperthermia. Moreover, NETs were formed after interactionwith S. globosa, and the percentage of NETs formed was not significantly different at 41o C or 37o C. Conclusion While hyperthermia could serve as an effective therapy for fixed cutaneous sporotrichosis, this ability does not involve the formation of NETs.

OBJECTIVETo study the effect of electroacupuncture on proprioception in cynomolgus monkeys after unilateral anterior cruciate ligament (ACL) injury.

METHODSTwenty-seven cynomolgus monkeys were randomized equally into 3 groups, namely unilateral ACL injury with electroacupuncture group, unilateral ACL injury model group and blank control group. One week after modeling, the monkeys in electroacupuncture group were treated daily for 12 weeks with electroacupuncture at the acupoints Wei Yang, Yin Gu, Xi Yangguan and Qu Quan. At 4, 8, and 12 weeks during the treatment, the changes in the somatosensory evoked potentials (SEPs) and motor nerve conduction velocity (MCV) of the nerves of the ACL were examined with neural electrophysiological method; the changes in the morphology and the total and variable number of the proprioceptors in the ACL were observed with gold chloride staining. RESULTS; In the mokeys in the model group, the incubation period of the SEPs and MCV on the injured side of the knee were significantly extended and the amplitudes were decreased with the passage of time (P<0.05). Intervention with electroacupuncture significantly reduced the incubation period and increased the amplitudes of the SEPs and MCV (P<0.05). The total number of the proprioceptors in the ACL was significantly decreased and the variable number of the proprioceptors in ACL was increased with time in the monkeys in the model group (P<0.05); electroacupuncture intervention obviously slowed the reduction rate of total number of the proprioceptors (P<0.05) but without affecting the variable number of the proprioceptors (P>0.05). CoONCLUSION: ACL injury causes attenuation of the proprioception on the injury side, and electroacupuncture intervention can produce a positive effect on the proprioception in cynomolgus monkeys.

Background::Hyperthermia in combination with DnaJA4-knockout (KO) obviously affects the anti-viral immunity of HaCaT cells. The mechanisms of this process are not yet fully explored. However, it is known that DnaJA4 interacts with actin cytoskeleton after hyperthermia. Our aim was to investigate the effects of DnaJA4 on F-actin in HaCaT cells following hyperthermia.Methods::Wild-type (WT) and DnaJA4-KO HaCaT cells were isolated at either 37°C (unheated) or 44°C (hyperthermia) for 30 min followed by testing under conditions of 37°C and assessing at 6, 12, and 24 h after hyperthermia. The cytoskeleton was observed with immunofluorescence. Flow cytometry and Western blotting were used to detect the expression of F-actin and relevant pathway protein.Results::DnaJA4-KO and hyperthermia changed the cytoskeleton morphology of HaCaT cells. F-actin expression levels were elevated in DnaJA4-KO cells compared with WT cells (6364.33 ± 989.10 vs. 4272.67 ± 918.50, P < 0.05). In response to hyperthermia, F-actin expression levels of both WT and DnaJA4-KO cells showed a tendency to decrease followed by an obvious recovery after hyperthermia (WT cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.34 ± 0.02 vs. 0.24 ± 0.01, 0.31 ± 0.01, P < 0.001, P < 0.05; DnaJA4-KO cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.44 ± 0.01 vs. 0.30 ± 0.01, 0.51 ± 0.02, P < 0.001, P < 0.01). WT cells restored to baseline levels observed in the unheated condition, while DnaJA4-KO cells exceeded baseline levels in the recovery. As the upstream factors of F-actin, a similar profile in rho-associated serine/threonine kinase 1 (ROCK 1) and RhoA expressions was observed after hyperthermia. While E-cadherin expression was decreased in response to hyperthermia, it was increased in DnaJA4-KO cells compared with WT cells. Conclusions::Hyperthermia affects the expression levels of F-actin in HaCaT cells. DnaJA4 knockout increases the expression of F-actin in HaCaT cells after hyperthermia. DnaJA4 regulates the expressions of F-actin and the related pathway proteins in response to hyperthermia in HaCaT cells.

Humans ; Hydrogen-Ion Concentration ; Malassezia ; growth & development ; physiology ; Staphylococcus epidermidis ; growth & development ; physiology

OBJECTIVETo determine the effect of gonadotropin releasing hormone agonist (GnRHa), by itself alone or in combination with recombinant human growth hormone (rhGH), on height in young girls (bone age≥10 years) with idiopathic central precocious puberty (ICPP).

METHODSEighty girls with ICPP (9.0±0.7 years old) from six medical centers across Southeast and Southwest China participated in this study. They were allocated to treatment with GnRHa+rhGH (n=31) and GnRHa (n=49) respectively. Girls in the GnRHa+rhGH group (bone age 11.18 ±0.53 years) were treated with GnRHa for 25.29±6.92 months and rhGH for 12.87±7.02 months. Girls in the GnRHa group (bone age 11.03 ±0.50 years) were treated with GnRHa for 25.96±8.95 months. The height standard deviation for bone age (HtSDS-BA), predicted adult height, near-adult height and net height increase before and after treatment were recorded for girls in both groups.

RESULTSHtSDS-BA was significantly improved after treatment for both groups (P<0.01) and the HtSDS-BA value was superior in the GnRHa+rhGH group over the GnRHa group (P<0.01). Values in near adult height (157±6 cm vs 157±4 cm), net height increase after treatment (4.68 cm vs 3.89 cm), and predicted adult height after drug withdrawal (161±5 cm vs 158±5 cm) were higher in the GnRHa+rhGH group than the GnRHa group, but the differences were not significant.

CONCLUSIONSBoth GnRHa plus rhGH and GnRHa alone can improve the near adult height in girls with ICPP with a bone age ≥10 years to a similar extent. Adult height predicted based on bone age in ICPP girls following drug withdrawal is usually overestimated and precautions should be taken when this parameter is used.

Body Height ; drug effects ; Child ; Female ; Gonadotropin-Releasing Hormone ; analogs & derivatives ; pharmacology ; Human Growth Hormone ; pharmacology ; Humans ; Puberty, Precocious ; drug therapy ; physiopathology

BACKGROUNDAtopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing.

METHODSHaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-γ (IFN-γ). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real-time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry.

RESULTSIL-4/13 significantly reduced, while IFN-γ significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-γ significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-γ increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions.

CONCLUSIONSOur results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.

Caspase 14 ; metabolism ; Cell Line, Tumor ; Cells, Cultured ; Dermatitis, Atopic ; metabolism ; Humans ; Immunohistochemistry ; Interferon-gamma ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-4 ; metabolism ; Intermediate Filament Proteins ; metabolism ; Keratinocytes ; enzymology ; metabolism ; Proteinase Inhibitory Proteins, Secretory ; metabolism ; Serine Peptidase Inhibitor Kazal-Type 5 ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism

Objective To investigate the modulation effects of mesenchymal stem cells (MSCs)implantation on the collagen remodeling in myocardial infarction. Methods Acute myocardial infarction (AMI) was induced in SD rats by left anterior descending coronary artery ligation, and the animals were assigned randomly into the Sham group, M1 + PBS group and MI + MSCs group. Echocardiography and hemodynamic examinations were performed to evaluate the cardiac function. HE staining and Masson trichrome staining were used to evaluate the myocardial infarction size. Infarcted area and infarcted expansion index were calculated. The expression of collagens in infarcted hearts was evaluated by immunohistochemistry, RT-PCR and Western blot. Results ( 1 ) Infarct area was significantly reduced post MSCs transplantation [MI+MSCs vs. MI+PBS: (38.27 ±2.70)％ vs. (46.20±3. 17)％, P＜0.001].(2) Cardiac function was significantly improved post MSCs transplantation [MI + MSCs vs. MI + PBS: FS (％): 29.98±4.50vs. 23.43 ±3.34, P=0.005; LVSP(mm Hg,1 mm Hg=0.133 kPa): 113.63±10.81vs. 99.25±16.76, P＜0.05; LVEDP(mm Hg): 12.10±4.28 vs. 20.08 ±4.26, P＜0.05;+ dp/dtmax ( mm Hg/s) : 4616.63 ± 363.34 vs. 3912.75 ± 248. 79, P ＜ 0. 05 ; - dp/dtmax ( mm Hg/s) :4254.63 ±324. 34 vs. 3530. 88 ±309.71, P ＜ 0. 05]. (3) Collagen synthesis was enhanced in infarcted area and decreased in non-infarcted area post MSCs transplantation ( P ＜ 0. 05 ). Conclusions MSCs transplantation could enhance the collagen synthesis in infarcted area while decrease the deposition of collagen in non-infarcted area in this MI model. This may be one of the mechanisms by which ventricular remodeling is attenuated post MSCs transplantation.

Adolescent ; Adult ; Age Factors ; Child ; Female ; Humans ; Hyperthermia, Induced ; methods ; Male ; Middle Aged ; Sex Factors ; Warts ; therapy ; Young Adult

BACKGROUND: Catheter ablation is effective in restoring sinus rhythm and left atrial appendage closure (LAAC) is increasingly used for stroke prevention in patients with atrial fibrillation (AF). We aimed to observe the feasibility and safety of performing AF ablation and LAAC in a single (one-stop) procedure. METHODS: Consecutive AF patients who underwent the combined procedure of AF ablation and LAAC with WATCHMAN device between March 2017 and September 2018 were prospectively enrolled. Baseline and intra-procedural parameters were evaluated. Three-month and subsequent 1-year follow-up were performed in all and earlier-enrolled subjects, respectively. RESULTS: A total of 178 AF patients (94 males, 68.9 ± 8.1 years) underwent the one-stop procedure with CHA2DS2-VASc score 3.3 ± 1.5 and HAS-BLED score 1.6 ± 1.0, respectively. Pulmonary vein isolation was achieved in all patients while additional linear ablation was applied if the operator deemed necessary, yielding immediate ablation success rate of 98.9% (176/178). In the subsequent LAAC, satisfactory seal (residual leak <5 mm) was achieved in all patients. One stroke and four cardiac perforations occurred peri-operatively. At 3-month follow-up, sinus rhythm and satisfactory seal were maintained in 153/178 (86.0%) and 178/178 (100%) patients, respectively. One stroke and one delayed cardiac tamponade occurred, while no device-related thrombus or device migration was observed. During the 1-year follow-up for the earlier enrolled subjects, 52/72 (72.2%) of the patients maintained sinus rhythm. There was no stroke or systemic embolism observed. CONCLUSION Combining catheter ablation and LAAC in a single procedure can be successfully and safely performed in non-valvular AF patients of Chinese population.

Objective To quantitatively evaluate the associations of PM
Air Pollutants/toxicity* ; Air Pollution/adverse effects* ; Child, Preschool ; China ; Dermatitis, Atopic/epidemiology* ; Female ; Humans ; Male ; Outpatients ; Particulate Matter/analysis*