Objective To investigate the effects of 13-hexyl-berbefine hydroehlofide (HB-13) and 13-hexyl-paimatine hydrochloride (HP-13) on the activation of nuclear factor-kappa B (NF-kB) and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in a human keratinocyte cell line, HaCaT stimulated by tumor necrosis factor alpha (TNF-α). Methods HaCaT cells were cultured in the presence of various concentrations (0.39, 0.78, 1.56 μg/mL) of HB-13 or HP-13 for 120 minutes followed by the stimulation with recombinant human TNF-α for 120 minutes (in phosphorylatEd-IkB-α test) or 15 minutes (in phosphorylated-p38 test). Then, HaCaT cells were disrupted, total protein was extracted, and the expressions of phosphorylated I B-α and phosphorylated p38 were detected with Western blot. HaCaT cells receiving neither pretreatment nor stimulation served as blank control, untreated HaCaT cells stimulated by rhTNF-α as stimulator control, and HaCaT cells pretreated with turmeric root tuber and stimulated by rhTNF-α as positive control. Results From 0.39 to 1.56 μg/mL, both HB-13 and HP-13 significantly inhibited the expression of p-IkB-α in HaCaT cells stimulated by rhTNF-α, and a nonsignificant dose-dependent trend was observed for their inhibitory effect, with the ICo value being 0.441 μg/mL for I-IB-13 (r = -0.990, n = 3, P > 0.05) and 0.832 μg/mL for HP-13 (r = -0.992, n = 3, P > 0.05). In contrast, neither 1-113-13 nor HP-13 within the experiment concentration range had a significant effect on the expression of p-p38 in HaCaT cells stimulated by rhTNF-α (P > 0.05). Conclusions Within the experimental concentration range, both HB-13 and HP-13 can inhibit the activation of NF-kB in HaCaT cells induced by TNF-α signal, but neither of them suppress the phosphorylation of p38MAPK induced by TNF-α signal in HaCaT cells.

Objective To investigate the effects of triptolide on the expression of a series of proteins associated with interferon-γ (IFN-γ)signaling in HaCaT keratinocytes.Methods After pretreatment with difrerent dosages of triptolide(10-10-10-7 mol/L),HaCaT cells were stimulated by recombinant human IFN-γ(rhIFN-γ,500 U/mL)for various periods followed by the collection of cells.Then,total protein was extracted from these cells and subjected to Western blotting for the detection of expression of interferon-γ receptor α(IFN-γRα),phosphorylated Janus kinase 2(pJAK2)and suppressor of cytokine signaling (SOCS1).Results Triptolide at the concentrations of 10-8 mol/L and 10-7 mol/L significantly inhibited the IFN-γRα expression upregulated by rhIFN-γ(both P＜0.05).The expression of pJAK2 induced bv rhIFN-γ was also suppressed by triptolide at the concentrations of 10-9 moI/L and 10-8 mol/L(both P＜0.05).The inhibition of triptolide on IFN-γRα and pJAK2 expression was dose-dependent and the 50%inhibitory concentrations(IC50 value)were 1.37×10-8 mol/L and 2.83×10-9 mol/L,respectively.On the contrary,triptolide upregulated the expression of SOCS1 stimulated by rhIFN-γ at the concentrations of 10-10,10-9 and 10-8 mol/L(P＜0.05,0.05,0.01,respectively)with the 50%effective dosage(ED50 value)at 3.32 × 10-11 mol/L.Conclusions By inhibiting the expression of IFN-γRα as well as phosphorylation of JAK2 and upregulating the expression of SOCS1,triptolide inhibits the phosphorylation of STAT-1,resulting in the inhibition of genetic transcription of multiple inflammatory factors induced by IFN-γ signaling in HaCaT keratinocytes,and the inhibition probably contributes to the efficacy of triptolide in the treatment of IFN-γ-dependent inflammatory skin disorders,such as psoriasis.

Objective To study the effect of limited fluid resuscitation (LFR) on coagulation in patients with severe traumatic brain injury (sTBI) and investigate its clinical significance.Methods Seventy-nine patients were assigned to low volume group (≤ 2 000 ml,40 cases) and high volume group (＞ 2 000 ml,39 cases) according to the random number table.LFR was performed for all patients.Prothrombin time (PT),partial thromboplastin time (APTT),thrombin time (TT) and fibrinogen (FIB) level were measured in both groups at different time points.Mean heart rate,blood pressure,blood gas values and blood electrolytes were monitored.Meantime,NICU days,hospital length of stay and incidence of multiple organ dysfunction syndrome (MODS) were recorded.Glasgow Outcome Scale (GOS) was evaluated.Results In constrast to high volume group,PT,APTT and TI were shortened and FIB was elevated in low volume group (P ＜ 0.05).But there were no significant differences between the two groups in NICU days [(13.84 ±3.02)d vs (15.28 ±3.79)d],hospital length of stay [(36.85 ±6.73)d vs (40.01 ± 7.21) d],MODS incidence (15.0％ vs 17.9％) and mortality (27.5％ vs 38.5％) (P ＞ 0.05).The chances of good recovery in low volume group was higher than that in high volume group (22.5％ vs 7.3％) (P＜0.05).Mean heart rate,blood pressure,blood electrolytes,and blood gas values did not differ significantly between the two groups (P ＞ 0.05).Conclusion For patients with sTBI,low volume LFR can ameliorate coagulation disorders and improve prognosis,indicating a safe and effective therapy.

Objective To study the effects of different concentrations of hypertonic saline (HS) and 20%mannitol on decreasing intracranial pressure (ICP) in patients with moderate-sever traumatic brain injury (TBI). Methods A total of 60 patients were randomly assigned into 7.5%HS group, 3%HS group and 20%mannitol group, 20 patients in each group. All of patients were treated with conventional treatment according to the diagnostic and treatment practices of TBI. When ICP was above 20 mmHg for more than 5 minutes, patients were administered corresponding hypertonic dehydrator. The levels of ICP, mean arterial pressure (MAP), cerebral perfusion pressure (CPP), urine volume per hour and serum sodium were monitored continuously within 6 hours after the initiation of therapy. Results All agents could significantly decrease the ICP (P<0.05), but the onset time in 7.5%HS group was less than that of the other two groups (P<0.05), and the decreased magnitude of ICP and the effective time of decreasing ICP in 7.5%HS group were more than those of the other two groups (P < 0.05). Both 7.5%HS and 3%HS could increase MAP and CPP. There was no statistical difference in serum sodium between both groups , but the diuretic effect in both groups was worse than that of 20%mannitol group. Conclusion The rapidly infusion of 7.5%HS could significantly decrease the ICP, increase the MAP and CPP without obvious side-effect in patients with moderate-sever TBI, and which is a safe and effective therapy for intracranial hypertension after traumatic brain injury .

Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.

Objective To indentify the cognitive status of Chinese patients to acne and the influencing factors to theirs' cognitive status,so as to provide solid evidences for the prevention and treatment of acne.Methods A self-designed questionnaire was made to conduct this survey of 16,156 acne patients,who seeked to the treatment in the dermatological departments from 112 hospitals in China.The survey consisted of several parts,including the general status of patients,the patients' cognition of occurrence,development and risk factors of acne,whether the first choice was seeking treatment at the hospital when the patients had acne and the condition of selection of skin care products.The factors were analyzed,which could impact the cognition of the patients' behavior of treatment,how did the patients' cognition to influence their medical behavior and skin care as well as the consistency of assessment of the severity of acne by doctors and patients themselves.Results The acne patients studied had the best knowledge of "acne is a skin disease","it not only occurs in the period of adolescence" and "the disease can be prevented and cured",which accordingly accounted for 80.65％,69.16％ and 65.49％ of the total patients respectively.However,the awareness of acne patients to heredity,high sugar and dairy products as risk factors for acne was insufficient,which accounted for 48.72％,42.40％ and 18.25％ of the total patients,respectively.Gender,age,educational level,occupation and health knowledge were the main factors affecting the cognitive level of patients;the survey also found that men,patient with educational level of junior high or even lower educational condition,occupation of labor workers or farmers and patients were lack of health education with poor knowledge of the genetics and dietary were risk factors for acne;patients with age over 36 years or with mild illness had poor knowledge of dietary risk factors for acne;the difference was statistically significant (P＜0.05).The analysis of the influence of cognitive status on medical treatment behavior and skin care showed that the better the cognition,the higher the probability of patients would choose medical treatment as the first choice as well as choosing functional skin care products;the difference was statistically significant (P＜0.05).The consistency of assessment of the severity of acne by doctors and patients was poor (Kappa value ＜0.4),and the assessment of severity of acne by patients was more serious than doctors' assessment.Conclusions Patient's cognitive status will affect their medical behavior and skin care,and there is also a phenomenon that patients have a more serious assessment of their acne condition.It is suggested that health education for acne patients should be strengthened in clinical medicine so as to improve their knowledge of acne as well as preventing from acne effectively.