Dopamine and cyclic adenosine monophosphate-regulated phosphoprotein with an apparent Mr of 32000 promotes colorectal cancer growth.

BACKGROUND: Dopamine and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein with an apparent Mr of 32000 (DARPP-32) is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain. However, recent studies have shown that DARPP-32 is also expressed in other tissues, including colorectal cancer (CRC), where its function is not well understood. AIM: To explore the effect of DARPP-32 on CRC progression. METHODS: The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays. The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, while apoptosis was measured by flow cytometry. The migratory and invasive potential of CRC cell lines were determined using wound healing and transwell chamber assays. In vivo studies involved monitoring the growth rate of xenograft tumors. Finally, the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses. RESULTS: DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC. Overexpression of DARPP-32 was shown to promote cancer cell proliferation, migration, and invasion and reduce apoptosis. DARPP-32 knockdown resulted in the opposite functional effects. Mechanistically, DARPP-32 may regulate the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in order to carry out its biological function. CONCLUSION: DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.

A novel colorectal anastomotic method in natural orifice specimen extraction surgery for colorectal cancer.

PURPOSE: We introduced a novel colorectal anastomotic technique, double-angle anastomosis combined with the double stapling technique (DAA-DST), to simplify the anastomosis step during natural orifice specimen extraction surgery (NOSES) and compared its safety and effectiveness with purse string anastomosis combined with the double stapling technique (PSA-DST). METHODS: Between January 2018 and March 2021, 63 patients with colorectal cancer underwent NOSES with DAA-DST or PSA-DST. We compared the perioperative and oncological outcomes between the groups. RESULTS: There were no significant differences in the operation time, blood loss, time to first passage of flatus and excrement or hospital stay duration between PSA-DST and DAA-DST groups. The overall postoperative complication rates were similar (DAA-DST vs PSA-DST, 21.2% vs 26.7%, p = 0.78), including the rate of anastomotic leakage (6.1% vs 10%, p = 0.91). The rate of successful DAA-DST was higher than that of PSA-DST (100% vs 93.3%). The DAA-DST group had a lower rate of positive drain fluid culture than the PSA-DST group (18.2% vs 26.7% p = 0.61). Recurrence (3.01% vs 6.67%, p = 0.93) and metastasis rates (6.06% vs 6.67%, p = 0.98) were similar between the groups. CONCLUSION: DAA-DST is a safe and effective procedure and can simplify the procedure of NOSES.

Successful reversal of ostomy 13 years after Hartmann procedure in a patient with colon cancer: A case report.

BACKGROUND: The Hartmann procedure is currently recognized as a common, safe, and feasible surgical procedure. However, its reversal rate is low, and the optimal timing for Hartmann reversal surgery is controversial. CASE SUMMARY: A 65-year-old man came to our hospital with a complaint of an intestinal fistula next to the stoma. The patient had undergone a Hartmann procedure 13 years prior. We performed colonoscopy, computed tomography, and other diagnostics before successfully reversing the stoma. CONCLUSION: Although the optimal time for Hartmann procedure reversal is controversial, time may ultimately not be a factor in the success of reversal.

Colonic pouch confers better bowel function and similar postoperative outcomes compared to straight anastomosis for low rectal cancer.

BACKGROUND: With advancements in laparoscopic technology and the wide application of linear staplers, sphincter-saving procedures are increasingly performed for low rectal cancer. However, sphincter-saving procedures have led to the emergence of a unique clinical disorder termed anterior rectal resection syndrome. Colonic pouch anastomosis improves the quality of life of patients with rectal cancer > 7 cm from the anal margin. But whether colonic pouch anastomosis can reduce the incidence of rectal resection syndrome in patients with low rectal cancer is unknown. AIM: To compare postoperative and oncological outcomes and bowel function of straight and colonic pouch anal anastomoses after resection of low rectal cancer. METHODS: We conducted a retrospective study of 72 patients with low rectal cancer who underwent sphincter-saving procedures with either straight or colonic pouch anastomoses. Functional evaluations were completed preoperatively and at 1, 6, and 12 mo postoperatively. We also compared perioperative and oncological outcomes between two groups that had undergone low or ultralow anterior rectal resection. RESULTS: There were no significant differences in mean operating time, blood loss, time to first passage of flatus and excrement, and duration of hospital stay between the colonic pouch and straight anastomosis groups. The incidence of anastomotic leakage following colonic pouch construction was lower (11.4% vs 16.2%) but not significantly different than that of straight anastomosis. Patients with colonic pouch construction had lower postoperative low anterior resection syndrome scores than the straight anastomosis group, suggesting better bowel function (preoperative: 4.71 vs 3.89, P = 0.43; 1 mo after surgery: 34.2 vs 34.7, P = 0.59; 6 mo after surgery: 22.70 vs 29.0, P < 0.05; 12 mo after surgery: 15.5 vs 19.5, P = 0.01). The overall recurrence and metastasis rates were similar (4.3% and 11.4%, respectively). CONCLUSION: Colonic pouch anastomosis is a safe and effective procedure for colorectal reconstruction after low and ultralow rectal resections. Moreover, colonic pouch construction may provide better functional outcomes compared to straight anastomosis.

Small-cell neuroendocrine carcinoma of the rectum - a rare tumor type with poor prognosis: A case report and review of literature.

BACKGROUND: Small-cell neuroendocrine carcinoma (SNEC) of the rectum is a rare tumor associated with poor prognosis. CASE SUMMARY: We report a case of a 77-year-old male who came into our hospital because of blood with his stool. An endoscopy revealed a cauliflower-like neoplasm in his rectum. Imaging examination showed that the lesion in the upper rectum was likely rectal cancer, and there was no evidence of metastasis. The patient was treated with surgery. Pathological examination confirmed SNEC of the rectum and an R0 resection was achieved. However, 1 mo after the operation, the patient developed intestinal and ureteral obstructions due to peritoneal metastases. Finally, the patient died from renal failure. CONCLUSION: SNEC of the rectum is a high-grade carcinoma with an aggressive phenotype, and surgery should be cautiously considered.

The role of circulating miR-146a in patients with rheumatoid arthritis treated by Tripterygium wilfordii Hook F.

Rheumatoid arthritis (RA) is polygenic autoimmune disease with unclear etiology. MicroRNAs (miRNAs) play a critical role in the pathogenesis of RA. The objective of this study was to evaluate the role of miR-146a in patients with RA receiving Tripterygium wilfordii Hook F (TwHF) treatment.In total, 69 patients with RA and 69 healthy controls (HC) were included in the study, and patients with RA received TwHF treatment for 24 weeks. Blood samples were collected from RA patients and HC, and peripheral blood mononuclear cells (PBMCs) were isolated. Expression of miR-146a was analyzed in RA patients (baseline, 12 weeks and 24 weeks) and HC.Circulating miR-146a expression was markedly increased in patients with RA compared with healthy controls (P < .001), ROC analysis of miR-146a for diagnosis for RA showed that the AUC was 0.908 (95% CI: 0.862-0.955) with a sensitivity of 87.0% and a specificity of 82.6% at best cutoff. And miR-146a expression was positively associated with the DAS28 score and CRP level (P = .002 and P = .019). Moreover, miR-146a expression was markedly reduced after TwHF therapy (P < .001), and baseline miR-146a level was observed to present an increased tendency in responders compared with non-responders at 24 weeks (P = .066).Our study presented that circulating miR-146a level was correlated with risk and disease activity of RA patients by TwHF treatment, which could strikingly decrease expression of miR-146a in RA patients, and miR-146a may have a value in predicting clinical response of TwHF treatment. It indicates that circulating miR-146a plays a prominent role in RA patients treated by TwHF.

[Critical illness polyneuropathy in a patient with Parkinson disease: a case report and review of the literature].

OBJECTIVE: To report a case of critical illness polyneuropathy (CIP) with Parkinson disease and discuss the development, clinical features and early diagnosis of this condition. METHODS: The clinical data of a patient with CIP and Parkinson's disease and the relevant literature were reviewed. RESULTS: This case showed no typical disease course of sepsis, and the condition exacerbated rapidly. The patient presented initially with abnormal homeostasis, followed by rapid onset of respiratory muscle weakness to require mechanical ventilation, but no limb weaknesses were detected. Intravenous antibiotics and aggressive treatment of sepsis did not produce any positive responses to wean from mechanical ventilation. Examinations of creatine kinase and cerebrospinal fluid showed no abnormalities. Electromyography and nerve conduction studies demonstrated declined nerve conduction velocity and decreased sensory and motor muscle action potentials, suggesting the possibility of CIP. CONCLUSION: In patients with Parkinson disease, the occurrence of sepsis with prolonged mechanical ventilation and limb weakness indicates the necessity of neurophysiological examination, muscle biopsies and laboratory tests, which may help detect CIP in the early phase. Proper interventions of sepsis may reduce the likeliness of CIP. Elimination of the risk factors and aggressive management of sepsis can be effective measures for preventing CIP.

Expression of cytokines in rat brain with focal cerebral ischemia after grafting with bone marrow stromal cells and endothelial progenitor cells.

BACKGROUND AIMS: This study aimed to observe nine factors expressed in rat ischemic brain after transplantation of bone marrow stromal cells (BMSC) and/or endothelial progenitor cells (EPC). These factors were vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-l), transforming growth factor-ß (TGF-ß), platelet-derived growth factor-BB (PDGF-BB), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). METHODS: Adult Wistar rats were divided randomly into four groups: a vehicle group, BMSC group, EPC group and BMSC combined with EPC group. The rats were subjected to middle cerebral artery occlusion (MCAO) then implanted intravenously with 3 × 10(6) BMSC, EPC, BMSC/EPC or phosphate-buffered saline (PBS) 24 h after MCAO. Neurologic functional deficits were measured on days 1, 7, 14, 28 after transplantation. On day 7 after transplantation, quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and Western blot were employed to detect the expression of VEGF, SDF-1, bFGF, IGF-l, TGF-ß, PDGF-BB, BDNF, GDNF and NGF. RESULTS: The neurologic evaluation found that the neurologic severity scores were no different between the four groups on day 1, and the scores of rats in the BMSC/EPC group were significantly lower than those of rats in the other groups on days 7, 14 and 28 after transplantation. The expressions of bFGF, VEGF and BNDF were significantly higher in the BMSC/EPC group compared with the other groups. CONCLUSIONS: The intravenous transplantation of BMSC combined with EPC could promote the functional rehabilitation of rats with focal cerebral ischemia, and the mechanism may be related to the enhanced expression of factors.

Functional endothelial progenitor cells derived from adipose tissue show beneficial effect on cell therapy of traumatic brain injury.

Endothelial progenitor cells (EPCs) are responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Adipose tissue (AT) is an abundant source of mesenchymal stem cells (MSCs), which have multipotent differentiation ability. We successfully derived EPCs from AT, which maintained a strong proliferative capacity and demonstrated the characteristic endothelial function of uptaking of acetylated low-density lipoprotein. They formed tube-like structures in vitro. Endothelial nitric oxide synthase (eNOS) gene expression in EPCs was similar to that in mature endothelial cells. Transplantation of EPCs derived from AT after the acute phase was applied in rats with traumatic brain injury (TBI). Transplanted EPCs participated in the neovascularization of injured brain. Improving functional recovery, reducement of deficiency volume of brain, host astrogliosis and inflammation were found. These results suggest that adult AT derived stem cells can be induced to functional EPCs and have beneficial effect on cell therapy.

Investigation of a plasmid containing a novel immunotoxin VEGF165-PE38 gene for antiangiogenic therapy in a malignant glioma model.

Inhibition of tumor neovascularization has profound effects on the growth of solid tumors. Our previous studies have shown the effect of VEGF165-PE38 recombinant immunotoxin on proliferation and apoptosis in human umbilical vein endothelial cells in vitro. In this study, we explored the direct inhibition of angiogenesis in chick chorioallantoic membrane and antiangiogenic therapy in a malignant glioma model. HEK293 cells were transfected with the pVEGF165PE38-IRES2-EGFP plasmid. ELISA was used to confirm the expression of VEGF165-PE38 in the transfected cells. These cells released 1396 + or - 131.9 pg VEGF165-PE38/1x10(4) cells/48 h into the culture medium and the supernatant was capable of inhibiting the growth of capillary-like structures in chick chorioallantoic membrane assay. In a murine malignant glioma model, plasmid was directly administered via multiple local intratumoral delivery. After day 16 the tumor volume in mice treated with pVEGF165PE38-IRES2-EGFP was significantly lower than that in mice in the control groups. Immunohistochemistry studies showed that the treated group had decreased expression of CD31. Quantitative analysis of microvessel density in the treated group was 1.99 + or - 0.69/0.74 mm(2), and was significantly lower than that in the control groups (9.33 + or - 1.99/0.74 mm(2), 8.09 + or - 1.39/0.74 mm(2) and 8.49 + or - 1.69/0.74 mm(2)). Immunohistochemistry analysis indicated that immunotoxin VEGF165-PE38 was distributed in the treated group in malignant glioma tissue. Our findings provide evidence that the in vivo production of VEGF165-PE38 through gene therapy using a eukaryotic expression plasmid had potential antiangiogenic activity in malignant glioma in vivo.

Adenoviral-mediated interleukin-18 expression in mesenchymal stem cells effectively suppresses the growth of glioma in rats.

Glioma is the most common primary intracranial malignant tumor. Despite advances in surgical techniques and adjuvant radio- and chemotherapies, the prognosis for patients with glioma remains poor. We have explored the effects of using genetically modified mesenchymal stem cells (MSCs) to treat malignant glioma in rats. Mesenchymal stem cells isolated from Sprague-Dawley rats can directly suppress the growth of C6 cells in vitro. MSCs transplanted intratumorally can also significantly inhibit the growth of glioma and prolong survival in C6 glioma-bearing models. MSCs producing Interleukin-18 infected by adenoviral vector inhibited glioma growth and prolonged the survival of glioma-bearing rats. Transplantation of IL-18 secreting MSCs was associated with enhanced T cell infiltration and long-term anti-tumor immunity. Thus, IL-18 may be an effective adoptive immunotherapy for malignant glioma. When used in conjunction with MSCs as targeting vehicles in vivo, IL-18 may offer a promising new treatment option for malignant glioma.

Beneficial effect of autologous transplantation of bone marrow stromal cells and endothelial progenitor cells on cerebral ischemia in rabbits.

We tested the therapeutic effect of autologous transplanted bone marrow stromal cells (BMSCs) and endothelial progenitor cells (EPCs) on cerebral ischemia in rabbits. Rabbit permanent middle cerebral artery occlusion (MCAO) models were intravenously injected with ex vivo expanded autologous BMSCs (n = 8), EPCs (n = 8), or phosphate-buffered saline (n = 6). 14 days after the transplantation, both infusion groups witnessed a functional improvement, a decrease in the number of apoptotic cells and an increase in the microvessel density in the ischemic boundary area, as compared to vehicle-treated control group. The EPCs treated group also exhibited a diminished infarct area in comparison with the control group. Moreover, immunohistochemistry revealed that few transplanted BMSCs expressed markers for astrocytes (GFAP+) and neurons (NeuN+), and most of EPCs were capable of binding to UEA-1 lectin and were incorporated into capillaries. Our data suggest that both BMSCs and EPCs, despite differences in their action mechanism, can be functional cytoreagents for treatment of cerebral ischemia in rabbits.

Lack of telomerase activity in rabbit bone marrow stromal cells during differentiation along neural pathway.

OBJECTIVE: To investigate telomerase activity in rabbit bone marrow stromal cells (BMSCs) during their committed differentiation in vitro along neural pathway and the effect of glial cell line-derived neurotrophic factor (GDNF) on the expression of telomerase. METHODS: BMSCs were acquired from rabbit marrow and divided into control group, GDNF (10 ng/ml) group. Cytokine.NSCs medium (prepared by our lab, Patent No. ZL02134314. 4) supplemented with 10 percent fetal bovine serum (FBS) was used to induce BMSCs differentiation along neural pathway. Fluorescent immunocytochemistry was employed to identify the expressions of Nestin, neuron-specific endase (NSE), and gial fibrillary acidic protein (GFAP). The growth curves of the cells and the status of cell cycles were analyzed, respectively. During the differentiation, telomerase activities were detected using the telomeric repeat amplification protocol-enzyme-linked immunosorbent assay (TRAP-ELISA). RESULTS: BMSCs were successfully induced to differentiate along neural pathway and expressed specific markers of fetal neural epithelium, mature neuron and glial cells. Telomerase activities were undetectable in BMSCs during differentiation along neural pathway. Similar changes of cell growth curves, cell cycle status and telomerase expression were observed in the two groups. CONCLUSIONS: Rabbit BMSCs do not display telomerase activity during differentiation along neural pathway. GDNF shows little impact on proliferation and telomerase activity of BMSCs.

[Hemorheological changes in hot and humid environment].

OBJECTIVE: To observe the changes in hemorheology of human under hot and humid environment. METHODS: Ninety soldiers serving in the Nansha Islands were divided into veteran group, recruit group and urapidil-treated recruit group, all of whom were required to complete 3 000-meter running exercise in 20 min in hot and humid environment. Their hemorheology were examined before and after the exercise. RESULTS: There were significant difference in the hemorheology between the 3 groups (P<0.05) both before and after the exercise, and the changes were most obvious in the veteran group followed by the new recruit group and urapidil-treated recruit group. No significant differences in the plasma indexes were detected between the 3 groups. CONCLUSIONS: Hot and humid environment causes obvious changes in the hemorheology, for which veterans and recruits have different tolerances and adaptabilities. Uradipil may help lower the magnitude of the the hemorheological changes after exercise by reducing body metabolism.