In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe₃O₄@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe₃O₄@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe₃O₄@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T₂ magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe₃O₄@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.

[This corrects the article DOI: 10.1016/j.apsb.2022.08.024.].

Objective:To explore the mediating effects of self-control and rumination between neuroticism and insomnia in college students.Methods:A cross-sectional survey was conducted among 767 college students from a university in Sichuan province with Chinese big five personality inventory-15, insomnia severity index, ruminative responses scale, and self-control scale.Results:The prevalence of insomnia was 36.6% among college students.The scores of neuroticism (9.63±3.41), rumination (22.27±5.44) and ISI (6.61±4.28) were positively correlated with each other ( r=0.281-0.389, P<0.01), while each of them was negatively correlated ( r=-0.453--0.194, all P<0.01) with self-control (60.71±9.41). Analysis of mediating effects revealed that neuroticism not only directly affected insomnia, but also indirectly affected insomnia through the mediating effects of rumination and self-control respectively. Conclusion:Self-control and rumination have mediating effects between neuroticism and insomnia in college students.

Objective To investigate the prevalence of nutritional risk,undernutrition and nutritional support among elderly inpatients with coronary heart disease in 11 tertiary A hospitals in China.Methods Records of elderly patients under the age of 90 with coronary heart disease were collected between March 2012 and May 2012 from 11 tertiary A hospitals in China following the direction of diagnosis related group of Beijing government.Results A total of 1 279 consecutive cases were recruited with the average age 74 years old (65-89).The total nutritional risk prevalence was 28.14％ (360/1 279).The prevalence of nutritional risk and nutritional risk score ≥ 5 increased with age.The prevalence of nutritional risk (12.88％ vs.30.08％ vs.42.28％) and nutritional risk scored ≥5 (10.86％ vs.18.61％ vs.27.78％)increased with age.Judging from BMI,most patients were overweight or obese (BMI ≥ 24 kg/m2),accounting for 53.0％ of the total,and prevalence of nutritional risk in this subgroup was 15.12％ (96/635).The prevalence of nutritional risk in patients with normal BMI was 34.24％.The prevalence of undernutrition defined as BMI＜ 18.5 kg/m2 was 4.25％ (51/1 279),among which patients with score ≥ 5 account for 64.7％ (33/51).The prevalence of undernutrition defined as nutritional impairment score =3 was 7.58％ (97/1 279).In patients with nutritional risk,57 were administrated nutrition support (16.6％);in patients without nutritional risk,21 received nutrition support,mostly parenteral nutrition (16 cases,76.2％).In patients with nutritional risk [(79.46± 7.19) years vs.(76.40± 6.16) years],there were statistically significant difference between those who received nutrition support and those who did not in terms of age and the ratio of patients with nutritional risk scored≥5 (35.1％ vs.17.1％) (P =0.001,P=0.002).Conclusions The prevalence of nutritional risk in patients with coronary heart disease was high.The prevalence of undernutrition was low.Prevalence of overweight and obese was high,but there was still nutritional risk in this group of patients.The patients who received nutrition support were older and had high nutritional impairment score,but the indication is not rationale.

Objective To investigate the value of aspartate aminotransferase-to-platelet ratio index (APRI) in judging the indication for antiviral therapy [liver inflammation grade (G) ≥2 or fibrosis stage (S) ≥2] in patients with chronic HBV infection and alanine aminotransferase (ALT) ＜ 2 × upper limit of normal (ULN).Methods A retrospective analysis was performed for the clinical data of 207 patients with chronic HBV infection and ALT ＜ 2 × ULN who were admitted to Nanyang Central Hospital from January 2015 to June 2017,and according to liver inflammation grade and fibrosis stage,these patients were divided into G ＜ 2 + S ＜ 2 group with 87 patients and G ≥2 or S ≥2 group with 120 patients.The results of liver biopsy and laboratory examination were recorded,and APRI was calculated.The Spearman correlation analysis was performed to investigate the correlation of APRI with liver inflammation grade and fibrosis stage.The area under the receiver operating characteristic curve (AUC) was used to investigate the value of ALT,aspartate aminotransferase (AST),platelet count (PLT),and APRI in judging the indication for antiviral therapy in patients with ALT ＜ 2 × ULN.The t-test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results APRI was positively correlated with liver inflammation grade and fibrosis stage (r =0.661 and 0.597,P ＜0.001).Among ALT,AST,PLT,and APRI,APRI had the highest value in judging the indication for antiviral therapy,with AUCs of 0.913 in the G≥2 or S≥2 group,0.882 in the G≥2 group,and 0.881 in the S≥2 group.APRI had an AUC of 0.913 (95％ confidence interval:0.871-0.954) in predicting the indication in the G ≥ 2 or S ≥2 group at the optimal cut-off value of 0.5324;when APRI was ≥0.5324,the patients had marked liver histological changes,i.e.,G≥2 or S≥2,which met the indication for antiviral therapy.APRI had a sensitivity of 87.50％,a specificity of 89.66％,a positive predictive value of 92.11％,and a negative predictive value of 83.87％.Conclusion For patients with chronic HBV infection and ALT ＜ 2 × ULN,APRI has a good value in evaluating liver pathological changes and judging the timing of antiviral therapy and can reduce the frequency of invasive assessment of histological changes via liver biopsy.

BACKGROUND:Bone marrow mesenchymal stem cells can differentiate into hepatic stem cells in a specific environment, and participate in the repair and reconstruction of liver function.OBJECTIVE:To investigate the therapeutic effect of autologous bone marrow mesenchymal stem cell transplantation on decompensated hepatitis B.METHODS:Eighty-four patients with decompensated hepatitis B were randomly divided into two groups:normal group (n=42) with symptomatic treatment, and oral entecavir, Fuzheng Huayu Capsule; stem cell group (n=42) with the left and right hepatic artery transplantation of autologous bone marrow mesenchymal stem cells (1×106/kg) based on conventional treatments. Degree of liver fibrosis, liver function and score on Model for End-Stage Liver Disease (MELD) system, 1-year survival rate of patients were detected and analyzed with statistics before and 12, 24 weeks after treatment.RESULTS AND CONCLUSION:(1) Liver fibrosis after treatment in two groups:hyaluronic acid, laminin, type Ⅲ collagen and type IV collagen levels after treatment were lower than those before treatment in both two groups (P < 0.05), while these indexes in the stem cell group were lower than those in the normal group at 12 and 24 hours after treatment (P <0.05). (2) Liver function:after treatment, decreased alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels were found in both two groups (P < 0.05), and albumin, cholinesterase, prothrombin activity levels were higher than those before treatment (P < 0.05). The alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels in the stem cell group were lower than those in the normal group at 12 and 24 weeks after treatment, while the cholinesterase level was higher in the stem cell group (P < 0.05). (3) MELD scores:MELD scores were both decreased in the two groups after treatment (P < 0.05), and lower in the stem cell group compared with the normal group at 24 weeks after treatment (P < 0.05). (4) The 1-year survival rate was higher in the stem cell group (69%) than the normal group (50%; P < 0.05). To conclude, the use of autologous bone marrow mesenchymal stem cell transplantation in the treatment of hepatitis B can significantly improve the patients' liver fibrosis and liver function, and improve the 1-year survival rate of patients.

Objective To investigate the effect of stem cells transplantation on immune function,liver function and related indexes in the patients with end-stage liver disease(ESLD).Methods A total of 163 cases of ESLD in Nanyang Municipal Central Hospital of Affiliated Hospital of Zhengzhou University were selected and divided into 2 groups by the randomized single blind method.Eighty-one cases in the control group were given the conventional symptomatic treatment,while 82 cases in the observation group received bone marrow mesenchymal stem cell(BMSC) transplantation based on the control group.The changes of immune function,liver function,alpha fetoprotein(AFP),rate of prothrombin activity(PTA) and plasma total protein(TP) level before and after treatment were observed in the two groups.Results The immune function indexes CD3+,CD4+,CD8+,CD4+/CD8+,TP and PTA levels after treatment in the observation group were significantly higher than those before treatment and in the control group (P＜0.05),while the levels of AFP,alanine aminotransferase (ALT),aspartate aminotransferase (AST) and total bilirubin (TBIL)were lower than those before treatment in the same group and the control group(P＜0.05).There was no statistically significant difference in complication occurrence rate between the two groups(P＞0.05).Conclusion BMSC transplantation for treating ESLD can improve the immune function,improves the liver function and reduces the AFP level.

BACKGROUND:Immunotherapy with autologous immune cel s has been developed as a major adjuvant therapy for malignant tumors, but its mechanism of action has not been elucidated. OBJECTIVE:To investigate the relationship between cytokine-induced kil er cel secretion and apoptosis in human liver cancer stem cel s. METHODS:Human liver cancer stem cel s, HepG2 cel s, were isolated and enriched using serum-free suspension method. The peripheral blood mononuclear cel s from patients with liver cancer were induced byγ-interferon, CD3 monoclonal antibody and recombinant human interleukin-2 to form kil er cel s. Passage 1 liver cancer stem cel s were divided into control group (culture alone) and experimental group (co-culture of cytokines-induced kil er cel s and human liver cancer stem cel s). At 48 hours after culture, apoptosis in human liver cancer stem cel s was detected using flow cytometry, and expression of caspase-3 mRNA and protein was detected using RT-PCR and western blot, respectively. RESULTS AND CONCLUSION:The apoptotic rate in the control group was significantly lower than that in the experimental group (P<0.05). The expressions of caspase-3 at mRNA and protein levels were both higher in the experimental group than the control group (P<0.05). Experimental findings show that cytokines-induced kil er cel s can significantly promote apoptosis in human liver cancer stem cel s, and up-regulate the caspase-3 mRNA and protein expressions dramatical y.

Objective To analyse the effect of matrine on sex hormone level, metal ion content and soluble tumor necrosis factor receptor in male patients with liver cirrhosis.Methods 70 cases male patients diagnosed with liver cirrhosis of decompensation period were selected in the hospital and randomly divided into experimental group and control group, 35 cases in each group.The experimental group were treated with 250 mL matrine sodium chloride injection on the basis of conventional treatment and the control group were given equal 0.9%sodium chloride injection, once a day, intravenous drip for a consecutive treatment of 4 weeks.The liver function, sex hormone levels, metal ion content, and soluble tumor necrosis factor receptor indicators were detected before and after treatment in two groups.ResuIts Compared with control group, serum liver enzymes and total bilirubin in experimental group decreased (P<0.05);the content of serum testosterone increased and estradiol levels decreased (P<0.05);serum zinc, iron and magnesium content increased, manganese content decreased (P<0.05); serum soluble tumor necrosis factor receptor levels decreased (P<0.05). ConcIusion Matrine adjuvant therapy could regulate the level of sex hormone and metal ion in male patients with liver cirrhosis, reduce the level of soluble tumor necrosis factor receptor, improve liver function in patients with cirrhosis.

Objective To investigate the expression of proteinase active receptor 2(PAR2)protein in hepatocellular carcino-ma(HCC)and portal vessel tumor thrombosis(PVTT)to evaluate its clinical value.Methods Immunofluorescence,RT-PCR and Western blot were used to examine the expression of PAR2 protein in cancer tissue,tumor thrombosis and cancer-adjacent normal tissue from 21 patients with HCC.Results The expression pattern of PAR2 protein was different cancer tissue and cancer-adjacent normal tissue.PAR2 labeling index was significantly higher in cancer tissue and PVTT than cancer-adjacent normal tissue(P <0.05).Although PAR2 labeling index was lower in cancer tissue than in tumor thrombosis,no statistical significance was observed in PAR2 labeling index between them(P >0.05).Conclusion PAR2 is over-expressed in HCC and PVTT.PAR2 expression is re-lated with the development and progression of HCC.