AIM:Hepatotoxicity of Brucea javani-ca picryl with broad-spectrum anticancer effect in nude mice based on hepatic drug metabolizing en-zyme CYP450 activity.METHODS:Fifty-six nude mice were randomly divided into blank group,Bru-cea javanica low-dose group(2 mg/kg),Brucea ja-vanica high-dose group(4 mg/kg),and cisplatin group(2 mg/kg),with 14 mice in each group.The blank group was injected with the same amount of normal saline every 3 days for 6 weeks.Calculate the mortality rate of nude mice in each group,ob-serve the general growth state of nude mice,re-cord the weight change of nude mice before and af-ter administration,weigh and record the liver weight after taking materials,and calculate the liv-er coefficient(liver weight/weight mass×100％),ob-serve and record the liver color and morphology.Hematoxylin-eosin(HE)staining was used to ob-serve the pathological changes of liver tissue.De-tection of alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),lactate dehydrogenase(LDH),alkaline phosphatase(AKP)and albumin(ALB)levels in serum of nude mice by ELISA.Real-time PCR and Western blot were used to detect the mRNA and protein expression levels of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6 and CYP2C9,which were key enzymes of drug metabolism in nude mice liver.RESULTS:Compared with the blank group,the mortality rate of nude mice in the low-dose Brucea javanica bitter alcohol group was 0,the growth state was good,the diet,movement,and mental state were normal,the weight change and liver coefficient ratio were consistent,the liver color was ruddy,the liver lobule morphology was complete under the microscope,the structure was clear,the liver cells were arranged regularly,and there was no inflammatory cell infiltration.There was no significant difference in the content of ALT,AST,LDH,AKP,and ALB.There was no significant difference in the mRNA and protein expression of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9(all P＞0.05).Compared with the blank group,the mortality rate of nude mice in the high-dose group of Brucea javanica bitter alcohol was 14.3％,the growth state was slightly poor,the diet,movement,and mental state were reduced,the weight growth was slow,the liver coefficient ratio was increased,the liver color was reddish brown,some liver lobule boundaries were unclear,a small number of liver cells were loosely arranged,the contents of ALT,AST,LDH,AKP,and ALB were signif-icantly increased,the mRNA levels of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9 were significantly reduced,and the protein expres-sions of CYP2E1,CYP3A11,CYP1A2,and CYP2D6 were significantly reduced(all P＜0.05 or P＜0.01),but there was no statistical difference in the mRNA and protein expression of CYP2C19,and the pro-tein expression of CYP2C9(P＞0.05).Compared with the blank group,the mortality rate of nude mice in the cisplatin group was 35.7％,the growth state was poor,the diet,action,and mental state were low,the weight gain was less,the liver coefficient ratio was significantly increased,the liver color was dark red,the liver sinusoids and central veins were congested,the hepatocytes were disordered,the nuclei were consolidated and contracted,and the arrangement was loose,the contents of ALT,AST,LDH,AKP,and ALB were significantly increased,and the mRNA and protein expressions of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9 were significantly reduced(all P＜0.05 or P＜0.01).CONCLUSION:The dose of Brucea javanica bitter alcohol is correlated with hepatotoxicity to nude mice.High doses of Brucea javanica bitter alcohol have hepatotoxicity to nude mice,which may be re-lated to reducing serum levels of ALT,AST,LDH,AKP,and ALB,inhibiting the expression of multiple subtypes of enzymes in the key enzyme CYP450 of liver drug metabolism,and then reducing the me-tabolism of toxic substances.

AIM:Hepatotoxicity of Brucea javani-ca picryl with broad-spectrum anticancer effect in nude mice based on hepatic drug metabolizing en-zyme CYP450 activity.METHODS:Fifty-six nude mice were randomly divided into blank group,Bru-cea javanica low-dose group(2 mg/kg),Brucea ja-vanica high-dose group(4 mg/kg),and cisplatin group(2 mg/kg),with 14 mice in each group.The blank group was injected with the same amount of normal saline every 3 days for 6 weeks.Calculate the mortality rate of nude mice in each group,ob-serve the general growth state of nude mice,re-cord the weight change of nude mice before and af-ter administration,weigh and record the liver weight after taking materials,and calculate the liv-er coefficient(liver weight/weight mass×100％),ob-serve and record the liver color and morphology.Hematoxylin-eosin(HE)staining was used to ob-serve the pathological changes of liver tissue.De-tection of alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),lactate dehydrogenase(LDH),alkaline phosphatase(AKP)and albumin(ALB)levels in serum of nude mice by ELISA.Real-time PCR and Western blot were used to detect the mRNA and protein expression levels of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6 and CYP2C9,which were key enzymes of drug metabolism in nude mice liver.RESULTS:Compared with the blank group,the mortality rate of nude mice in the low-dose Brucea javanica bitter alcohol group was 0,the growth state was good,the diet,movement,and mental state were normal,the weight change and liver coefficient ratio were consistent,the liver color was ruddy,the liver lobule morphology was complete under the microscope,the structure was clear,the liver cells were arranged regularly,and there was no inflammatory cell infiltration.There was no significant difference in the content of ALT,AST,LDH,AKP,and ALB.There was no significant difference in the mRNA and protein expression of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9(all P＞0.05).Compared with the blank group,the mortality rate of nude mice in the high-dose group of Brucea javanica bitter alcohol was 14.3％,the growth state was slightly poor,the diet,movement,and mental state were reduced,the weight growth was slow,the liver coefficient ratio was increased,the liver color was reddish brown,some liver lobule boundaries were unclear,a small number of liver cells were loosely arranged,the contents of ALT,AST,LDH,AKP,and ALB were signif-icantly increased,the mRNA levels of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9 were significantly reduced,and the protein expres-sions of CYP2E1,CYP3A11,CYP1A2,and CYP2D6 were significantly reduced(all P＜0.05 or P＜0.01),but there was no statistical difference in the mRNA and protein expression of CYP2C19,and the pro-tein expression of CYP2C9(P＞0.05).Compared with the blank group,the mortality rate of nude mice in the cisplatin group was 35.7％,the growth state was poor,the diet,action,and mental state were low,the weight gain was less,the liver coefficient ratio was significantly increased,the liver color was dark red,the liver sinusoids and central veins were congested,the hepatocytes were disordered,the nuclei were consolidated and contracted,and the arrangement was loose,the contents of ALT,AST,LDH,AKP,and ALB were significantly increased,and the mRNA and protein expressions of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9 were significantly reduced(all P＜0.05 or P＜0.01).CONCLUSION:The dose of Brucea javanica bitter alcohol is correlated with hepatotoxicity to nude mice.High doses of Brucea javanica bitter alcohol have hepatotoxicity to nude mice,which may be re-lated to reducing serum levels of ALT,AST,LDH,AKP,and ALB,inhibiting the expression of multiple subtypes of enzymes in the key enzyme CYP450 of liver drug metabolism,and then reducing the me-tabolism of toxic substances.

AIM:To investigate the anti-fibrotic effect of Panax notoginseng saponins(PNS)in arecoline(ANE)-induced oral submucous fibrosis,and to analyze the effect of PNS on nuclear factor E2-related factor 2(Nrf2)/glu-tamate-cysteine ligase catalytic subunit(GCLC)signaling pathway.METHODS:CCK-8 assay was used to evaluate the effects of different concentrations of PNS and arecoline on the survival rate of human immortalized keratinocyte cell line Ha-CaT.The results of CCK-8 were used to select 75 mg/L arecoline,and 25,50 and 100 mg/L PNS as subsequent experi-mental concentrations.The cells were set as blank control group,model group,and low,medium and high doses(25,50 and 100 mg/L)of PNS groups.The protein and mRNA expressions of collagen type I(COL-I),E-cadherin,Nrf2,GCLC and glutathione reductase(GR)in each group were detected by Western blot and RT-qPCR.Immunofluorescence method was used to detect the entry of Nrf2 into the nucleus.Biochemical kits were used to detect the content of glutathione(GSH),nicotinamide adenine dinucleotide phosphate(NADPH)and malondialdehyde(MDA),and superoxide dis-mutase(SOD)activity in each group of cells.DCFH-DA fluorescent probe was used to detect the content of intracellular reactive oxygen species(ROS).RESULTS:Compared with the blank control group,the protein and mRNA expression of COL-I in the model group was up-regulated,and the protein and mRNA levels of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were down-regulated.The content of NADPH,MDA and ROS in the cells increased,and the content of GSH and the activity of SOD was significantly reduced.Compared with the model group,the protein and mRNA expression of COL-I was down-regulated,and the protein and mRNA expression of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were up-regulated in PNS 50 and 100 mg/L groups.Compared with the model group,the content of NADPH,MDA and ROS in cells decreased,and the content of GSH and the activity of SOD was significantly enhanced(P<0.05 or P<0.01).CON-CLUSION:Panax notoginseng saponins have anti-fibrosis effects in HaCaT cells,and their mechanism may be related to the activation of Nrf2/GCLC signaling pathway,thereby resisting oxidative stress and improving oral submucosal fibrosis.

Objective:To evaluate the effect of N-acetylcysteine (NAC) in relieving discomfort symptoms after esophageal Lugol′s iodine staining.Methods:From April 1 to September 30, 2023, a total of 204 subjects who received endoscopy at the First Affiliated Hospital of Shihezi University were enrolled. All the subjects were stained with 10 mL 1.5% compound iodine solution after endoscopy. According to random number table method, the 204 subjects were randomly divided into two groups which received 20 mL 0.9% sodium chloride solution (sodium chloride group, 103 cases) and 10% NAC (NAC group, 101 cases) to neutralize the iodine, respectively. The primary outcome indicators of the subjects of the two groups were analyzed, including the incidence of retrosternal burning sensation and pharyngeal discomfort 15 and 30 min after spraying the neutralization solution, and the degree of discomfort was evaluated by visual analogue scale (VAS). Fisher′s exact probability method and non-parametric test were used for statistical analysis.Results:The incidence of retrosternal burning sensation and pharyngeal discomfort 15 and 30 min after spraying the neutralization solution in the sodium chloride group were higher than those in the NAC group (15 min: 17.5% (18/103) vs. 2.0% (2/101), 10.7% (11/103) vs. 1.0% (1/101); 30 min: 11.7%(12/103) vs. 1.0% (1/101), and 5.8% (6/103) vs. 0 (0/101)), and the differences were statistically significant (Fisher′s exact probability method, P<0.001, =0.005, =0.003, and =0.029). There was no significant difference in the VAS score 15 min after spraying neutralization solution between the sodium chloride group and the NAC group (3.00 (3.00, 4.25) vs. 4.00 (3.00, 5.25), P>0.05). At 30 min after spraying the neutralization solution, the VAS score of the sodium chloride group was higher than that of the NAC group (4.00(3.75, 5.00) vs. 1.50(1.00, 1.50)), and the difference was statistically significant ( Z=-2.37, P=0.007). Conclusion:NAC can effectively relieve the discomfort caused by esophageal iodine staining.

Objective:To evaluate the effect of N-acetylcysteine (NAC) in relieving discomfort symptoms after esophageal Lugol′s iodine staining.Methods:From April 1 to September 30, 2023, a total of 204 subjects who received endoscopy at the First Affiliated Hospital of Shihezi University were enrolled. All the subjects were stained with 10 mL 1.5% compound iodine solution after endoscopy. According to random number table method, the 204 subjects were randomly divided into two groups which received 20 mL 0.9% sodium chloride solution (sodium chloride group, 103 cases) and 10% NAC (NAC group, 101 cases) to neutralize the iodine, respectively. The primary outcome indicators of the subjects of the two groups were analyzed, including the incidence of retrosternal burning sensation and pharyngeal discomfort 15 and 30 min after spraying the neutralization solution, and the degree of discomfort was evaluated by visual analogue scale (VAS). Fisher′s exact probability method and non-parametric test were used for statistical analysis.Results:The incidence of retrosternal burning sensation and pharyngeal discomfort 15 and 30 min after spraying the neutralization solution in the sodium chloride group were higher than those in the NAC group (15 min: 17.5% (18/103) vs. 2.0% (2/101), 10.7% (11/103) vs. 1.0% (1/101); 30 min: 11.7%(12/103) vs. 1.0% (1/101), and 5.8% (6/103) vs. 0 (0/101)), and the differences were statistically significant (Fisher′s exact probability method, P<0.001, =0.005, =0.003, and =0.029). There was no significant difference in the VAS score 15 min after spraying neutralization solution between the sodium chloride group and the NAC group (3.00 (3.00, 4.25) vs. 4.00 (3.00, 5.25), P>0.05). At 30 min after spraying the neutralization solution, the VAS score of the sodium chloride group was higher than that of the NAC group (4.00(3.75, 5.00) vs. 1.50(1.00, 1.50)), and the difference was statistically significant ( Z=-2.37, P=0.007). Conclusion:NAC can effectively relieve the discomfort caused by esophageal iodine staining.

Objective To promote the application of the best evidence for supportive care in the management of depression in patients with head and neck cancer, and to improve the quality of clinical care.Methods Follow the three stages of clinical evidence practice of Joanna Briggs Institute (JBI): baseline review, practice change and effect evaluation, the best evidence of supportive nursing in depression management for head and neck cancer patients were retrieved, and 4 quality review indicators were developed. A total of 50 hospitalized head and neck cancer patients and 12 nurses were selected to collect data by means of field observation, interviews and nursing records. The obstacles to the application of evidence were analyzed and a practical scheme was worked out.Results The nurse's implementation rate of the four review indicators increased from 0-90％ at the baseline review to 90％-100％ after the evidence was applied. Except for Indicator 3 "Indicators nurses introduced the pressure on patients and their families to face cancer", the implementation rates of the other three indicators were significantly improved (P<0.01). After the application of evidence, the incidence of depression was decreased (P<0.05). The score of Relaxation, Sleep and Fatigue Management Knowledge Questionnaire was (18.20±14.09) before the application of evidence, which was lower than that after the application of evidence (80.60±12.84), and the difference was statistically significant (t=-23.14, P<0.01). The nurses' score of Supportive Nursing Knowledge Questionnaire before the application of evidence was (63.83±10.78), which was lower than that after the application of evidence (95.5±3.18), and the difference was statistically significant (t=-9.76,P<0.01).Conclusions The evidence-based application program can standardize nurses' supportive nursing behaviors for patients with depressive symptoms, reduce the severity of depression, improve the self-support knowledge level, and improve the quality of depression management in hospitalized patients with head and neck cancer.

Background Studies confirmed that hydroxycamptothecin cause the apoptosis of human Tenon capsule fibroblasts (HTFs) by protein kinase R-like endoplasmic reticulum stress kinase (PERK) single pathway.Autophagy and apoptosis are programmed cell death following stress reaction,so they remain a close association.However,the effect of hydroxycamptothecin on the autophagy of HTFs and its mechanism are still unclear.Objective This study was to explore the promoting effect of PERK signal pathway on hydroxycamptothecin inducing the autophagy of HTFs.Methods This study procedure was approval by Ethic Committee of Nanjing Medical University.Human Tenon capsule tissue was obtained from fresh adult donors.HTFs were cultured and passaged by explant-culture method and identified by immunofluorescence for vimentin and keratin.pLVX-PERK lentiviral packed by 293T cells was transfected into HTFs to obtain stable PERK-knockout cell line by puromycin selection.Then the HTFs were treated with 0.10 g/L of hydroxycamptothecin for 5 minutes and consecutively cultivated for 24 hours,and the untreated cells were used as the control group.Western blot assay was used to detect the expressions of autophagy specific proteins in the cells,including autophagy related gene 5 (ATG-5),Beclin-1,light chain 3 (LC-3).Cyto-ID staining was used to identify the autophagosome in the cells.The experimental results were analyzed and compared between different treating groups.Results The gray scales for the expressions of Beclin 1,ATG-5,LC-3-Ⅰ and LC-3-Ⅱ proteins in HTFs were 0.365:±0.045,0.765 ±0.055,0.120±0.030 and 0.215 ±0.035 in the control group,and those in the hydroxycamptothecin treated group were 0.980±0.070,1.495±0.095,0.585±0.025 and 0.785±0.055,showing a significant decline in the hydroxycamptothecin treated group(P=0.018,0.022,0.007,0.013).The green fluorescence of the autophagosome was stronger in the hydroxycamptothecin treated group compared with the control group.Western blot revealed that the gray scale of PERK expression in the cells was 0.130±0.030 in the PERK-knockout group,with a significant reduce in comparison with 0.765 ±0.055 of the control group (P =0.010).However,no obvious distinctions were seen in the band intensities of the expressions of Beclin-1,ATG-5 and LC-3 proteins between the two groups.Western blot indicated that the grey scale of the PERK expression in the cells was 1.790± 0.060 in the 0.10 g/L hydroxycamptothecin group,which was significantly higher than 0.880 ± 0.070 of the control group (P =0.010).Expression levels (gray scales) of Beclin-1,ATG-5,LC-3-Ⅰand LC-3-Ⅱ in the PERK-knockout+ 0.10 g/L hydroxycamptothecin group were 0.475 ± 0.045,0.390 ± 0.040,0.055 ± 0.015 and 0.075 ± 0.025,which were significantly lowed in comparison with 0.955 ± 0.065,0.765 ± 0.055,0.155 ± 0.015 and 0.280 ± 0.030 of the control+ 0.10 g/L hydroxycamptothecin group (P =0.026,0.031,0.042,0.034).In addition,the fluorescence intensity of autophagosomes was weaker in the PERK-knockout+0.10 g/L hydroxycamptothecin group compared with the control+0.10 g/L hydroxycamptothecin group.Conclusions Hydroxycamptothecin induces the autophagy of HTFs by PERK signal pathway.

Objective To judge the effect of plasma exchange (PE) to the patients with severe hepatopath of nonage according to evaluating the change of the liver function of reserve with 13C-methacetin breath test. Methods There are two groups: the case group and the control group. Each group has 30 patients. The patients in the case group were treated by PE. All the patients received 13C-methacetin breath test at before or one week after treatment. MVmax40, CUM40 and CUM120 were present. At the same time, clinical symptoms, glutamate-pyruvate transaminase (ALT), total bilirubin (TBiL) and prethrombin active (PTA) were observed. Results MVmax40, CUM40, CUM120 and PTA were higher, ALT and TBiL were lower in the case group after treatment (t=4.679, 4.752, 5.048, 5.413, 6.208, 7.413, P=0.000,P<0.01). After a week, MVmax40, CUM40, CUM120 and PTA were higher, ALT and TBiL were lower in the case group than that in the control group (t=2.260, 2.247, 2.476, 4.017, 3.250, 3.658, P<0.05). The total effective rates in the case group and the control group were 83.3 % (25/30) and 43.3 % (13/30),which are significant different(χ2 10.335,P<0.01). Conclusion PE can im-prove the liver reservation functionin the severe hepatopath of nonage.

Objectives To observe the effects of varied doses of L-thyroxin sodium ( L-T4) on congenital hypothyroidism ( CH) and to determine appropriate dose for early therapeutic intervention. Methods Totally, 108 cases of confirmed CH were divided into two groups (54 in each group). All the cases were administered with L-T4 at varied doses( 10. 1? - 15. 0 ?g ? kg-1? d-1 for large-dose group and 6. 0 - 10. 0 ?g ?kg-1? d-1 for small-dose group) after their parents were trained for basic knowledge of CH by specialists. Their serum levels of T3, T4 and TSH, as well as their body height, weight and head circumference, were measured during follow-up. L-T4 was maintained at doses of 1. 0 - 4. 0 ?g ? kg -1 ? d-1 when their serum levels of T3, T4 and TSH returned to normal. Results All the 108 cases had their clinical symptoms quickly improved and development and growth accelerated after L-T4 substitution. Their serum level of T3 returned to normal in all cases, that of T4 did not return to normal in six cases of large-dose group and in 16 cases of small-dose group, and that of TSH did return to normal in 22 cases of large-dose group and in 39 cases of small-dose group, respectively, after one-month treatment, with a significant difference between the two groups. Cases in large-dose group gained more weight in average than those in small-dose group when they were three months old. Conclusions Early therapeutic intervention for babies with CH with L-thyroxin sodium of 10. 1 -15. 0 ?g ? kg-1? d-1 could quickly correct abnormal function of their thyroid and could avoid abnormal development of their intelligence due to CH.

Objective:To explore the concentration of monoamine neurotransmitter in serum and psychiatric symptoms such as anxiety and depression in infertility patients with and without PCOS(No-PCOS),and the relationship between them.Methods:30 infertility with PCOS were selected as experimental group(EG) and 30 infertility patients without PCOS as control group(CG).They were administered Symptom Checklist(SCL-90).Their monoamine neurotransmitter in serum were determined including norepinephrine(NE),3-methoxy-4-hydroxyphenylglycol(MHPG),5-hydroxytryptamine(5-HT),5-hydroxyindoleacetic acid(5-HIAA),dopamine(DA),homovanillic acid(HVA) and dihydroxy-phenyl acetic acid(DOPAC).Results:The findings indicated that the scores in anxiety and depression subscales of SCL-90 were significantly higher in the PCOS group than those in the No-PCOS(P