Effects of early cognitive rehabilitation training on cognitive function and quality of life in critically ill patients with cognitive impairment: A randomised controlled trial.

BACKGROUND: Patients often develop cognitive dysfunction during admission to the ICU and after being transferred out of the ICU, which leads to physical disorders, sleep disorders, and psychological stress.Cognitive rehabilitation training can significantly improve patients' planning, decision-making ability, and executive function. OBJECTIVE: The aim of this study was to explore the role of early cognitive rehabilitation training in improving cognitive impairment in critically ill patients. METHODS: This study was a prospective, randomised, controlled clinical trial conducted from January 2017 to June 2021. Critically ill patients with cognitive impairment admitted to the Department of Intensive Care Medicine of The Third Hospital of Mianyang were randomly divided into the control (n = 68) and intervention groups (n = 68). Cognitive rehabilitation training (including digital operating system training, music therapy, aerobic training, and mental health intervention) was applied to the patients in the intervention group for 6 months, while the control group did not receive any cognitive intervention. Before 3 and 6 months after enrolment, the Montreal Cognitive Assessment and the 36-Item Short Form Health Survey Scale were used to evaluate cognitive function and quality of life, respectively, in both groups. RESULTS: A total of 136 critical patients were included in the final analysis. There were no significant differences in sex, age, years of education, complications, intensive care unit hospitalisation time, mechanical ventilation time, or the total score of the Montreal Cognitive Assessment scale when transferred out of the intensive care unit in 24 hours between the two groups. Six months later, the results of the follow-up showed that the cognitive function score in the intervention group was significantly higher than that in the control group (26.69 ± 2.49 vs. 23.03 ± 3.79). The analysis of quality of life showed that the scores in all areas in the intervention group improved. There were significant differences in physical functioning (69.02 ± 8.14 vs. 63.38 ± 11.94), role physical (62.02 ± 12.18 vs. 58.09 ± 8.83), general health (46.00 ± 15.21 vs. 40.38 ± 13.77), vitality (61.00 ± 11.01 vs. 54.38 ± 13.80), social functioning (70.00 ± 10.29 vs. 64.41 ± 13.61), role emotional (78.00 ± 8.00 vs. 72.15 ± 12.18), and mental health (71.00 ± 12.33 vs. 55.37 ± 10.76) between the two groups (P < 0.05). CONCLUSION: Early cognitive rehabilitation training can improve cognitive impairment in critically ill patients and their quality of life.

PTEN/PI3K/mTOR/B7-H1 signaling pathway regulates cell progression and immuno-resistance in pancreatic cancer.

BACKGROUND/AIMS: Patients of Pancreatic Cancer with B7-H1 over-expression usually have a poor prognosis. In our previous study, the expression of PTEN and B7-H1 were significantly correlated to the carcinogenesis in pancreatic carcinoma. In this study, we investigated the role of the PTEN/mTOR/B7-H1 pathway in immune-resistance, immune escape and progression of pancreatic cancer. METHODOLOGY: siRNAs targeting PTEN were designed, and transfected into pancreatic cancer cell lines. Transwell chamber invasion assay, CCK-8 proliferation assay and siRNA interference assay were used to explore the effect of PTEN on PI3K signaling. Expression of protein and mRNA of the factors involved in PTEN/mTOR/B7-H1 pathway were examined by RT-PCR and Western blot. T Cells apoptosis assay were performed by flow cytometer. RESULTS: Our study demonstrated that B7-H1 was regulated by PTEN through the PI3K/AKT pathway. Loss of PTEN promoted cell proliferation, cell invasion and led to significant increases in the levels of Phospho-AKT, Phospho-mTOR, phospho-S6K1 and B7-H1 proteins. In addition, the increased expression level of B7-H1 when PTEN was knockdown induced T lymphocyte apoptosis. CONCLUSION: Our results demonstrated deletion of PTEN in pancreatic cancer cells induced the expression of B7-H1, which contributed to immune suppression and increased cancer progression and invasion.

Preoperative evaluation with T-staging system for hilar cholangiocarcinoma.

AIM: To investigate the clinical value of T-staging system in the preoperative assessment of hilar cholangiocarcinoma. METHODS: From March 1993 to January 2006, 85 patients who had cholangiocarcinoma diagnosed by operative tissue-biopsy were placed into one of three stages based on the new T-staging system, and it was evaluated the resectability and survival correlated with T-staging. RESULTS: The likelihood of resection and achieving tumor-free margin decreased progressively with increasing T stage (P < 0.05). The cumulative 1-year survival rates of T1, T2 and T3 patients were 71.8%, 50.8% and 12.9% respectively, and the cumulative 3-year survival rate was 34.4%, 18.2% and 0% respectively; the survival of different stage patients differed markedly (P < 0.001). Median survival in the hepatic resection group was greater than in the group that did not undergo hepatic resection (28 mo vs 18 mo; P < 0.05). The overall accuracy for combined MRCP and color Doppler Ultrasonagraphy detecting disease was higher than that of combined using CT and color Doppler Ultrasonagraphy (91.4% vs 68%; P < 0.05 ). And it was also higher in detecting port vein involvement (90% vs 54.5%; P < 0.05). CONCLUSION: The proposed staging system for hilar cholangiocarcinoma can accurately predict resectability, the likelihood of metastatic disease, and survival. A concomitant partial hepatectomy would help to attain curative resection and the possibility of long-term survival. MRCP/MRA coupled with color Doppler Ultrasonagraphy was necessary for preoperative evaluation of hilar cholangiocarcinoma.

Effects of dendritic cells transfected with full length wild-type p53 and modified by bile duct cancer lysates on immune response.

BACKGROUND: Dendritic cells (DCs) are the most potent antigen-presenting cells and are actively used in cancer immunotherapy. Wild-type p53 can be recognized as an antigen and can induce specific cytotoxic T lymphocytes (CTLs) in the host body. The aim of this study was to investigate the effects of DCs transfected with full length wild-type p53 and modified by bile duct lysates on immune response. METHODS: The wild-type p53 was transducted to DCs with adenovirus, which were modified by bile duct lysates (Lywtp53DC). The concentration of the surface molecules (B7-1, B7-2, MHC-I, MHC-II) of all DCs was detected with fluorescence activated cell sorter (FACS), and the ability of the DCs to induce efficient and specific immunological response in anti-(51)Cr-labeled target cells was studied. BALB/c mice infected with the DCs and QBC939 were used. CTL response in mice immunized with Lywtp53DC and treatment of tumor-bearing mice with Lywtp53DC and CTL response in these mice were studied. RESULTS: The surface molecules of Lywtp53DC had a high expression B7-1 (86.70%+/-0.07%), B7-2 (18.77%+/-0.08%), MHC-I(87.20%+/-0.05%), MHC-II(56.70%+/-0.07%) with FACS. The T lymphocytes had a specific CTL lysing ability induced by Lywtp53DC, with a CTL lysis rate of 81%. The immune protection of Lywtp53DC group was obvious, and the tumor diameter of the Lywtp53DC group was 3.10+/-0.31 mm, 2.73+/-0.23 mm, 3.70+/-0.07 mm on days 13, 16 and 19, smaller than those of any control groups (P<0.05), DC, wtp53DC and LyDC. On the other hand, the growth rate of tumor of the Lywtp53DC group was slower than that of any other groups (P<0.05). CONCLUSION: Dendritic cells transfected with wild-type p53 and modified by bile duct lysates have specific CTL killing capability.

Effects of dendritic cells transfected with full-length wild-type p53 and stimulated by gastric cancer lysates on immune response.

AIM: To investigate the effects of dendritic cells (DCs) transfected with full-length wild-type p53 and stimulated by gastric cancer lysates on immune response. METHODS: The wild-type p53 was transduced to DCs with adenovirus, and the DCs were stimulated by gastric cancer lysates. The surface molecules (B7-1, B7-2, MHC-I, MHC-II) of all DCs were detected by FACS, and the ability of the DCs to induce efficient and specific immunological response in anti-51Cr-labeled target cells was studied. BALB/c mice injected with DCs and Mk28 were established, and CTL response in mice immunized with Lywt-p53DC was evaluated. Tumor-bearing mice were treated with Lywt-p53DC. RESULTS: The surface molecules of Lywt-p53DC had a high expression of B7-1 (86.70 +/- 0.07%), B7-2 (18.77 +/- 0.08%), MHC-I (87.20 +/- 0.05%) and MHC-II (56.70 +/- 0.07%); T lymphocytes had a specific CTL lysis ability induced by Lywt-p53DC; the CTL lysis rate was as high as 81%. The immune protection of Lywtp-53DC was obvious, the tumor diameter in Lywtp-53DC group was 3.10 +/- 0.31 mm, 2.73 +/- 0.23 mm, 3.70 +/- 0.07 mm on d 13, 16 and 19, respectively, which were smaller than control, DC, wtp53DC and LyDC group (P<0.05). Tumor growth rate in Lywtp53DC group was slower than that in other groups (P<0.05). CONCLUSION: DCs transfected with wild-type p53 and stimulated by gastric cancer lysates have specific CTL killing activity.

Effects of dendritic cells transfected with full length wild type P53 and modified by gastric cancer lysate on immune response.

To investigate the effects of dendritic cells (DCs) transfected with full length wild type p53 and modified by gastric cancer lysates on immune response, the wild type P53 was transducted to DCs with adenovirus, and the DCs were modified by gastric cancer lysates (Lywt-P53DC). The concentration of the surface molecules (B7-1, B7-2, MHC-I , MHC-II) of all DCs was determined by FACS, and the ability of the DCs to induce efficient and specific immunological response in anti-51Cr-labeled target cells studied. BALB/c mice model infected with DCs and Mk28 was established. CTL response in mice immunized with Lywt-p53DC and the effectiveness of Lywt-p53DC in the treatment of tumor-bearing mice was assayed. FACS revealed that the surface molecules of Ly-wt-P53 DC had a high expression: for B7-1 86.70% +/- 0.07%, B7-2 18.77% +/- 0.08%, MHC-I 87.20% +/- 0.05%, MHC-II 56.70%+/-0.07%; The T lymphocytes had a specific CTL lysing ability induced by Lywt-P53DC with the CTL lysis rate being 81%. The immune protective effect of Lywt-p53DC group was more obvious than any other groups (P<0.05). The tumor diameter in Lywt-p53DC group was 3.10+/-0.31 mm, 2.73+/-0.23 mm, 3.70+/-0.07 mm on the day 13, 16 and 19, smaller than DC, wtp53DC and LyDC groups (P<0.05). On the other hand, the growth rate of tumor in Lywt-p53DC group was slower than any other groups (P<0.05). It was suggested that DCs transfected with wild type P53 and modified by gastric cancer lysates had specific CTL killing capability.