OBJECTIVETo investigate the dynamic correlation between pre-S1 antigen, pre-S2 antigen and HBV DNA in the serum of chronic hepatitis B (CHB) patients undergoing nucleoside analogue therapy.

METHODS12 CHB patients with transient virological response after lamivudine treatment, and 20 patients treated with adefovir for 5 years were recruited in this study. Serum samples were collected at four time points when HBV DNA fluctuated sharply during lamivudine treatment, and at 0, 8, 12, 28, 52, 104, 156, 208, 260 weeks following adefovir treatment. HBV DNA was quantified by real-time PCR, pre-S1 and pre-S2 antigens were detected by ELISA.

RESULTSThe titers of pre-S1 and pre-S2 antigens were not correlated with the HBV DNA level in the serum of lamivudine treated patients. Only in one case of the adfovir treated patients, the decrease of pre-S1 and pre-S2 antigens was in parallel with the decrease of HBV DNA. Linear regression analysis indicated that neither pre-S1 antigen nor pre-S2 antigen was correlated with HBV DNA in the serum of lamivudine or adfovir treated patients (P more than 0.05).

CONCLUSIONOur results indicate that the titers of pre-S1 and pre-S2 antigens are not correlated with the serum HBV DNA in CHB patients undergoing nucleoside analogue therapy. Neither pre-S1 nor pre-S2 is a good predictor for the outcome of nucleoside analogue treatment.

DNA, Viral ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Real-Time Polymerase Chain Reaction

OBJECTIVETo investigate the expression of TGF-betaR I, Smad2, Smad3 and Smad7 in keloids, normal scars and normal skins. Discuss the significance of these proteins in the course of keloid.

METHODSImmunohistochemistry method was used to detect the expression intensity and distribution of these proteins in above 3 kinds of different tissues in 44 cases. Statistics was used to analyze the data.

RESULTSThe expression of TGF-betaR I were much stronger in keloid than in the other two tissues. The expression of Smad7 were lower in keloids. The increase expression of Smad2,3 were not obvious, but they were found to accumulate in the nucleus.

CONCLUSIONSThe results indicate that over-expression of TGF-betaR I, low-expression of Smad7 and accumulation of Smad2,3 may be one of the etiological factors of keloids. This research may provide a new idea to prevent and treat keloids or other fibrosis diseases in the future.

Adolescent ; Adult ; Female ; Humans ; Keloid ; metabolism ; Male ; Middle Aged ; Protein-Serine-Threonine Kinases ; metabolism ; Receptors, Transforming Growth Factor beta ; metabolism ; Smad2 Protein ; metabolism ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; Young Adult

OBJECTIVETo study the effect of salvianolic acid B (SAB) and curcumin, the extracts of Salvia Miltiorrhiza and Curcuma Longa, on the proliferation and activation of hepatic stellate cell (HSC), and the extracellular signal regulated kinase (ERK) expression in it.

METHODSRat's HSC-T6 were cultured and treated by SAB or curcumin. The inhibitory effect on cell proliferation was determined by 3-(4, 5-dimthyl-2-2thiazoly)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) colorimetry, and the expression levels of alpha smooth actin (alpha-SMA), collagen type I, and ERK were determined by Western blot.

RESULTSSAB and curcumin inhibited the proliferation and activation of rat's HSC-T6 in dose-dependent fashion and significantly reduced the expression level of alpha-SMA (P < 0.01). Curcumin significantly reduced the expression of collagen type I (P < 0.05). Both SAB and curcumin showed insignificant effect on the ERK expression level, but they could significantly reduce the level of phosphorylated-ERK expression, showing significant difference as compared with that in the control group (P < 0.01 and P < 0.05 respectively).

CONCLUSIONSAB and curcumin could significantly inhibit the proliferation, activation of HSC, and the production of type I collagen in HSC, the mechanism may be associated with their inhibition on ERK phosphorylation.

Animals ; Cell Division ; drug effects ; Cell Line ; Curcuma ; Drugs, Chinese Herbal ; pharmacology ; Extracellular Matrix ; drug effects ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Hepatocytes ; drug effects ; enzymology ; Liver Cirrhosis ; drug therapy ; metabolism ; MAP Kinase Signaling System ; drug effects ; Phosphorylation ; drug effects ; Plant Extracts ; Rats ; Salvia miltiorrhiza ; Vasodilator Agents ; pharmacology

Objective To explore serum long stranded noncoding RNA (lncRNA) transcript 1 (PCAT-1) expression level of patients with multiple myeloma (MM) and clinical value.Methods 72 cases of patients with MM treated in the Second People's Hospital of Zhaoqing City were selected as the study objects,and 60 cases of normal subjects undergoing physical examination in the same period were as the control group.Serum lncRNA PCAT-1 expression was detected by RT-PCR method.The relationship between lncRNA PCAT 1 expression and clinical pathological parameters,treatment effect was analyzed,and 5 years survival was analyzed by using Kaplan-Meier,and survival difference was detected by using Log-Rank method.Results Serum PCAT-1mRNA expression in MM group (2.65 ± 0.64) was significantly higher than that in the control group (1.06 ± 0.23,t=18.276,P=0.000).There were no significant differences in sex,clinical stage and pathological types of hemoglobin,plasma cells,platelets,albumin,β2-MG and CRP between PCAT 1 mRNA high expression group and low expression group (x2 =0.001 ～ 3.345,all P ＞ 0.05).Ca2+ ≥ 10 mg/dl in the PCAT-1 high expression group (57.14％) was significantly higher than that in the low expression group (27.27％,x2 =5.229,P=0.022).There was no significant difference in treatment effect between PCAT-1 mRNA high expression group and low expression group (88.64 ％ vs 75.00％,x2 =2.291,P=0.130).PFS and OS expression in PCAT-1 high expression group were lower than that in the low expression group (x2 =7.269,P =0.007;x2 =9.190,P =0.002).COX risk regression multiple factor analysis showed that age and PCAT-1mRNA expression were independent prognostic factors influencing patients (OR =3.275,P =0.025,95％CI:2.691～3.761;OR=2.136,P=0.046,95％CI:2.034～2.685).Conclusion LncRNA PCAT-1 is highly expressed in serum of patients with multiple myeloma,and correlated with the prognosis of patients.

OBJECTIVETo investigate the effects of sleep deprivation on intelligence development in primary school students.

METHODSBetween June 2009 and April 2010, 316 grade 5 students aged 10-11 years were selected from four primary schools in four administrative districts of Changsha, China by stratified random sampling. The intelligence characteristics of children with varying degrees of sleep deprivation were investigated using the Chinese Wechsler Intelligence Scale for Children.

RESULTSA total of 286 valid questionnaires were received, with a response rate of 90.5%. The survey was comprised of a sleep deprivation group (sleep time <8 hours per night; n=180) and a control group (sleep time ≥8 hours per night; n=106). The sleep deprivation group had significantly lower subtest scores, verbal intelligence quotient (IQ) (VIQ), performance IQ (PIQ) and full scale IQ (P<0.05) and significantly lower verbal comprehension factor score and memory/attention factor score compared with the control group (P<0.05). Compared with the control group, the moderate sleep deprivation subgroup had significantly decreased VIQ and full scale IQ as well as verbal comprehension factor score and memory/attention factor score (P<0.05), and the severe sleep deprivation subgroup showed decreases in all scores (P<0.05). The sleep deprivation group and moderate and severe sleep deprivation subgroups had significantly higher proportions of children with VIQ-PIQ imbalance than the control group.

CONCLUSIONSSleep deprivation adversely affects intelligence development, especially VIQ, in primary school students, and the adverse effects of sleep deprivation are mainly seen in students with moderate and severe sleep deprivation.

Child ; Female ; Humans ; Intelligence ; Male ; Sleep Deprivation ; psychology

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

OBJECTIVETo establish an in vitro model applicable for fatty liver lipotoxicity pharmacological research.

METHODSHepG2 cells were cultured with rat serum instead of fetal bovine serum and with long-chain free fatty acid (FFA) added. The tested indices were: the content of serum TNFa, cellular triglycerides (TG) content, Oil Red staining and ultrastructural changes; protein expression and gene expression of cellular TNFa, and the expression and distribution of cathepsin B (Ctsb).

RESULTSAfter incubation with FFA for 24 hours, the TG deposition of HepG2 in the model group increased markedly and TG content was 627.24 mg/g protein (t = 23.6, P less than 0.01), TNFa content in the cell supernatant also increased to 52.04 pg/mg protein (t = 2.6, P less than 0.05). Compared with those of the normal group, the protein expression and mRNA expression of cellular TNFa and Ctsb also increased significantly.

CONCLUSIONFFA could induce a model of HepG2 steatosis with TNFa secretion through the Ctsb signal pathway using rat serum in the culture media. The method is simple and economical, which is an ideal model applicable for fatty liver lipotoxicity pharmacological research.

Animals ; Disease Models, Animal ; Fatty Acids ; toxicity ; Hep G2 Cells ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; blood ; Tumor Necrosis Factor-alpha ; analysis

Animals ; Antioxidants ; pharmacology ; Apoptosis ; drug effects ; Atherosclerosis ; prevention & control ; Ceramides ; analysis ; Dietary Fats ; administration & dosage ; Emodin ; pharmacology ; Lipids ; blood ; Male ; Rabbits ; Signal Transduction ; Sphingomyelin Phosphodiesterase ; metabolism ; Sphingomyelins ; metabolism

INTRODUCTION: Family history of psychopathology is a risk factor for mood and anxiety disorders in children, but little is known about rates of parental psychopathology among treatment-seeking youth with affective disorders in the Asia Pacific region. This study examined patterns of emotional and behavioural problems in parents of clinically-referred youth in Singapore. We hypothesised that parents would have higher rates of affective disorders compared to the Singapore national prevalence rate of 12%. MATERIALS AND METHODS: In this cross-sectional study, 47 families were recruited from affective disorders and community-based psychiatry programmes run by a tertiary child psychiatry clinic. All children had a confirmed primary clinical diagnosis of depression or an anxiety disorder. Parents completed the Mini International Neuropsychiatric Interview (MINI) to assess for lifetime mood and anxiety disorders. They also completed the Adult Self Report (ASR) and Adult Behavior Checklist (ABCL) to assess current internalising and externalising symptoms. RESULTS: Consistent with our hypothesis, 38.5% of mothers and 10.5% of fathers reported a lifetime mood and anxiety disorder. Nearly 1/3 of mothers had clinical/subclinical scores on current internalising and externalising problems. A similar pattern was found for internalising problems among fathers, with a slightly lower rate of clinical/subclinical externalising problems. CONCLUSION Our findings are consistent with previous overseas studies showing elevated rates of affective disorders among parents - particularly mothers - of children seeking outpatient psychiatric care. Routine screening in this population may help to close the current treatment gap for adults with mood and anxiety disorders.
Adult ; Anxiety Disorders ; diagnosis ; epidemiology ; psychology ; Child ; Cross-Sectional Studies ; Family Health ; statistics & numerical data ; Female ; Humans ; Male ; Mood Disorders ; diagnosis ; epidemiology ; psychology ; Parent-Child Relations ; Parenting ; psychology ; Parents ; psychology ; Psychiatric Status Rating Scales ; Psychopathology ; Singapore ; epidemiology

COVID-19 ; Humans ; Kidney Transplantation ; Retrospective Studies ; SARS-CoV-2 ; Transplant Recipients