Objective To investigate the effect of protein kinase C (PKC)ζinhibitor T5450996 on the proliferation and invasion of skin squamous carcinoma cell line A-431. Methods PKCζinhibitor T5450996 was screened through Z′-LYTE?kit. Cell proliferation assay and cell cycle analysis were used to observe the effects of T5450996 on the proliferation of skin squamous carcinoma A-431 cells. Scratch assay and invasion assay were used to explore the effects of T5450996 on the migration and invasion of skin squamous carcinoma A-431 cells. Results The PKCζinhibitor T5450996 can inhibit the activity of PKCζkinase, and the IC50 value of T5450996 was about 35μmol/L. Compared to the control group, 35μmol/L and 70 μmol/L concentrations of T5450996 significantly suppressed the proliferation of A-431 cells and blocked the cell cycle of A-431 cells. The results of scratch assay and invasion assay indicated that the migration and invasion capacities of A-431 cells were markedly impaired after the treatments with 35μmol/L and 70μmol/L concentrations of T5450996 (P<0.05). However, 20μmol/L concentration of T5450996 showed no significant effect (P>0.05). Conclusion PKCζinhibitor T5450996 significantly inhibits the proliferation and invasion capacities of skin squamous carcinoma cell line A-431, and which may be a small molecular inhibitor with potential applications in the future.

Objective: To study the effect of tripterygium wilfordii polyglycosidium (TWP) on atopie dermatitis (AD) by detecting the expression of IL-2,IL-4,IFN-γ and IL-IO mRNA. Methods: RT-RCR was used to detect the mRNA of IL-2,IL-4, IFN-γ and IL-10 in peripheral blood mononuelear cells (PBMC)of AD cultured with different concentrations of TWP.ResuRs:(1)The expression of IL-2 was significantly different between the high concentration group and other groups(P＜0.05 or P＜0.01 ), and between the control group and the middle concentration group (P＜0.01). (2)The expression of IL-4 was significantly different between the three different concentration groups (P＜0.01 ). (3) The expression of IFN-γmRNA was significantly different between the high concentration group and the control, the low, the middle concentration groups (P＜0.05 or P＜0.01 ). (4)There was no significant difference in expression of IL-10 mRNA between the high concentration group and the middle concentration group (P＞0.05), there was significant difference among the other groups (P＜0.05 or P＜0.01).Conclusion: TWP can suppress the expression of IL-2, IL-4, IFN-γand IL-10 mRNA, but the low concentration of TWP can suppress the high-level expression of IL-4 and IL-10mRNA in vitro.

Objective Callus induction and plantlets regeneration of Pogostemon cablin(Blanco)Benth.are studied to establish a high-efficiency regeneration system for tissue culture.Methods The leaf segments,nodular stem segments,stem segments and root tips from Pogostemon cablin(Blanco)Benth.were cultured in vitro.The factors which affect the induction,multiplication and differentiation of callus were studied.Results Benzylaminopurine(BA) or thidiazuron(TDZ) combined with ?-naphthylacetic acid(NAA) was helpful to induce callus.The optimal concentrations of BA were 0.2～0.5mg/L.Nodular stem segments and stem segments were the most suitable explants for callus induction.The medium containing BA and NAA promoted the multiplication of callus.The multiplication rate and differentiation rate of 30-day callus were much higher than those of 60-day callus.BA was helpful to induce callus differentiation.The callus from leaf segments exerted a higher differentiation rate.Conclusion A high-efficiency regeneration system of callus induction and plant regeneration from Pogostemon cablin(Blanco)Benth.has been established.

ObjectiveTo investigate the influence of TGF-β receptor subtypes expression and their downstream signaling Smad proteins on rat renal interstitial fibrosis induced by unilateral ureteral obstruction(UUO).MethodsA total of 90 rats were randomly divided into three groups:normal control(CON),sham operation (SOR) and UUO group,and sacrificed 1,3,7,14 and 21 days after operation.Serum creatinine and urea nitrogen were detected to assess renal function.PAS and Masson staining were performed to observe histological damage in the kidneys.Quantitative RT-PCR was used to define expression of mRNA encoding TGF-β receptor subtypes and their downstream signaling Smad proteins in kidney tubular cells.Real-time PCR,Western blotting and immunofluorescence were used to monitor the time-related expression of the TGF-β receptor subtypes and their downstream signaling Smad proteins in kidney.ResultsCompared with the CON group,serum creatinine and urea nitrogen in UUO groups increased at day 3 after operation (P＜0.05) and reached their peak 21 days after operation (P＜0.01).Obvious inflammatory cell infiltration was observed in UUO group 3 days after operation,while renal tubular atrophy and renal interstitial fibrosis were observed in UUO group14 days after operation.The mRNA expressions of ALK-5,ALK-7 and TGF-βR Ⅱ increased significantly in UUO group 3 days after operation (all P＜0.05) and reached their peaks 14 days after operation (all P＜0.01).The mRNA expression of ALK-6 decreased significantly in UUO group 3 days after operation(P＜0.05) and reached its lowest level 14 days after operation (P＜0.01).The changes in the protein level of those receptors were consistent with their mRNA expressions.The protein expressions of Smad2/3 and p-Smad2/3 increased significantly in UUO group at day 3(all P＜0.05) and reached their peak at day 14 after operation(all P＜0.01).ConclusionExpressions of TGF-β receptor subtypes ALK-5,ALK-6,ALK-7,TGF-βR Ⅱ and their downstream signaling Smad2 and Smad3 proteins may influence the progress of renal interstitial fibrosis,tubular atrophy and inflammatory cell infiltration in UUO model rats.

Objective To investigate the efficacy of transcatheter closure of coronary artery fistula (CAF) by transthoracic echocardiography(TTE) and the role of TTE in this therapy. Methods CAF were occluded with transcatheter closure techniques in 17 patients. TTE was performed before and after the treatments. The key points were retrospectively analyzed including: the sites of CAF, the position and diameter of CAF,the shape and position of the devices after the intervention,the residual shunt,and cardiac chamber size. Results Before the therapy,TTE made definite diagnosis of CAF. All patients had lesions in single coronary artery, and the diameter of CAF was 2-14 (6.4 ± 3.5)mm. All patients underwent transcatheter closure successfully. TTE revealed the shunts disappear 1-4 days after the occlusion. During a follow-up period of 1- 29 (11.7± 7.9)months,no residual shunts, no complications, and normal size of thecardiac chambers were recognized by TTE. Conclusions The transcatheter closure of CAF has emerged as a less invasive, safe and effective strategy. Echocardiography has important role in primary screening of patients and the follow-up after the treatments.

Objective To evaluate the clinical effect and safety of percutaneous closure of patent foramen ovalein treatment of migraine.Methods We studied 23 patients with migraine who were tested positive in Contrast Transcranial Doppler (TCDc) at the Department of Neurology in Bethune First Hospital of Jilin University between 2010 May and 2011 November.Procedures of transcatheterclosure of patent foramen ovale were performed at Department of Cardiovascular Surgery.At varied time points post-surgery,the patients were re-examined by TCDc and transthoracic echocardiograph (TTE) and followed up by phone interviewed with Headache Impact Test-6 (HIT-6) questionnaire to elevate improvement of migraine.The data was analyzed statistically.Results Percutaneous closure was successful in all patients without major long-term side-effects.At follow-ups at 48-542 days ((247 ± 145) days) post-surgery,the scores of HIT-6 were reduced to 38-70 (51 ± 9),compared to the pre-operative scores of 42-76 (61 ± 8).Disability by migraine had significantly improved (t =4.80,P ＜ 0.05).In 6 patients with migraine with aura,the scores of HIT-6 were reduced to 46-56 (51 ± 3),from preoperative scores of 63-76 (69 ± 4) and their disability affected by migraine had significantly improved (t =6.80,P ＜0.05).In 17 patients with migraine without aura,the scores of HIT-6 after surgery were reduced to 36-70 (52-10) from the preoperative scores of 42-69 (60 ± 8) and disability affected by migraine in this group had significantly improved (t =3.77,P ＜0.05).Among 18 patients having MRI or CT examination before the operation,8 patients had neurological events (such as cerebral infarction,cerebral ischemia) with average age of (44 ± 7) years old.In this group,disability affected by migraine had significantly improved (the HIT-6 scores:49 ± 7 vs 58 ± 10,t =2.49,P ＜ 0.05).Conclusion Percutaneous closure of PFO showed significant improvement in migraine treatment and it is a safe procedure.

OBJECTIVE:To study the effects of taurine on oxidative stress and calcium overload induced by cerebral cortex contusion.METHODS:SD rats were randomly divided into normal control group,brain contusion model group,taurine groups(high dose,middle dose and low dose respectively),and nimodipine group.After being fed with corresponding drugs for7days,all rats were subjected to modeling by brain contusion.For intracellular calcium detection,rats were sacrificed2h after modeling,and the brain slices were prepared to fluorescence labeling and confocal microscopy detection.For the detection of oxidative stress,rats were sacrificed24h after modeling,the cortex of contusion side was homogenated and then the activity of superoxide dis?mutase(SOD)and content of malondialdehyde(MDA)were detected through biochemical method.RESULTS:Compared with model group,all taurine groups were shown to have markedly less MDA and intracellular calcium content,and the high dose group had markedly stronger SOD activity.CONCLUSION:Taurine is effective in counteracting the oxidative stress and calcium overload caused by brain contusion.

Objective:To explore the causes and influencing factors of financial toxicity in young breast cancer survivors, and to provide evidence for intervention program development to improve financial toxicity in young breast cancer survivors.Methods:Using descriptive qualitative research methods, 29 young breast cancer patients from September to December 2021 in Breast Surgery Follow-up Clinic of Fudan University Shanghai Cancer Center were interviewed. The Nvivo 12.0 qualitative data analysis software was used to analyze the data.Results:Four themes were extracted as following, direct cost of cancer treatment was the primary cause of financial toxicity, indirect costs related to cancer and treatment cannot be ignored, long-term effects of cancer and treatment further exacerbated financial toxicity, and cancer-related financial toxicity was also influenced by a variety of other factors.Conclusions:Multiple causes affected the experience of financial toxicity in young breast cancer survivors. The occurrence and risks of financial toxicity in young breast cancer survivors should be assessed. Intervention and support should be provided to meet the needs of young breast cancer survivors.

Objective:To evaluate the effects of low-dose esketamine on remifentanil-induced postoperative hyperalgesia in the patients.Methods:Ninety-six American Society of Anesthesiologist Physical Status classificationⅠ or Ⅱ patients, aged 18-60 yr, with body mass index of 18-30 kg/m 2, scheduled for elective thyroidectomy under general anesthesia, were divided into 3 groups ( n=32 each) using a random number table method: control group (group C), esketamine administered before anesthesia induction group (group K1), and esketamine administered immediately after the end of surgery group (group K2). Esketamine 0.4 mg/kg was intravenously injected in group K1, and the equal volume of normal saline was given instead in C and K2 groups at 5 min before anesthesia induction. Anesthesia was induced by intravenous injection of propofol, remifentanil and rocuronium. Remifentanil was intravenously infused at a rate of 0.3 μg · kg -1·min -1 and 1.5%-2.5% sevoflurane was inhaled for anesthesia maintenance. Esketamine 0.4 mg/kg was intravenously injected in group K2 and the equal volume of normal saline was given instead in C and K1 groups immediately after the end of surgery. The mechanical pain thresholds of surgical incision and forearm of non-dominant hand were measured at 1 day before surgery and 30 min, 6 h, 24 h and 48 h after surgery, and flurbiprofen axetil was intravenously injected for rescue analgesia when the NRS score≥4 or the patient needed sedation. The intensity of pain was estimated using numeric rating scale at 30 min, 6 h, 24 h and 48 h after surgery. The intraoperative consumption of remifentanil, use of vasoactive drugs, recovery time, tracheal extubation time, duration of PACU stay, postoperative rescue analgesia and adverse reactions were recorded. Results:Compared with C group, the mechanical pain threshold around surgical incision and of the forearm of non-dominant hand was significantly increased at 30 min and 6 h after surgery in K1 and K2 groups ( P<0.05). Compared with C and K1 groups, the emergence time, tracheal extubation time, and duration of PACU stay were significantly prolonged, and the incidence of hallucinations and increased glandular secretion was increased in group K2 ( P<0.05). There were no significant differences in the consumption of remifentanil, intraoperative utilization rate of atropine and ephedrine, numeric rating scale scores at each time point after surgery, incidence of postoperative nausea and vomiting, and rate of rescue analgesia among the three groups ( P>0.05). Conclusions:Intravenous injection of small dose of esketamine (0.4 mg/kg) before anesthesia induction and immediately after the end of surgery can reduce postoperative hyperalgesia induced by remifentanil, and administration before anesthesia induction provides better efficacy in the patients.

OBJECTIVETo study the toxicity-attenuating effect and the dose-toxicity relationship of rhubarb by processing based on correspondence.

METHODThe effects of different processed materials of rhubarb on the hepatic and renal functions of mice was researched in a way of parallel comparison, as well as the chemical alteration induced by processing was observed. Correspondence analysis, a kind of multivariate statistical analysis, was performed to explore the dose-toxicity relationship of processed materials of rhubarb.

RESULTNo obvious toxic effect was found in mice after single intragastric administration of crude drug of rhubarb at dosage of 76 g x kg(-1), while some lesions to liver and kidney tissues were observed in mice after repeated administration of rhubarb and its processed materials for 14 days at the same dosage. In the correspondence analysis diagram, it could be deduced that there was definite dose-toxicity relationship of processed rhubarb as the distance between trial groups and control group increased along with the dosage and the toxicity. The distance of the processed rhubarb showed as the following consequence: crude drug of rhubarb > vinegar-processed rhubarb > alcohol-processed rhubarb > steamed rhubarb > carbonized rhubarb > Qingning pian. Theerefoer, the toxicity of processed rhubarb was much lower than that of crude drug and the extent of toxicity attenuation was related to the processing intensity. Meanwhile, the toxicity-attenuating effect of processed rhubarb was related to the decline of the contents of both anthraquinone glycosides and tannins, and the former was contributed remarkably to toxicity.

CONCLUSIONThe toxicity-attenuating effect of processed rhubarb was verified in this study and the toxicity of steamed rhubarb attenuated notably while the pharmacological substances degraded little. The correspondence analysis would be useful to assess the pharmacological and toxic effects with multiple indexes of traditional Chinese medicines.

Animals ; Chemistry, Pharmaceutical ; methods ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Female ; Kidney ; drug effects ; Liver ; drug effects ; Male ; Mice ; Random Allocation ; Rheum ; chemistry