Preparation of hepatocellular carcinoma mRNA vaccines based on potential tumor targets and immunophenotypes.

Background: With the development of messenger RNA (mRNA)-based therapeutics for malignant tumor, mRNA vaccines have shown considerable promise for tumor immunotherapy. Immunophenotypes can reflect the tumor microenvironment, which might have a significant influence on the effect of immunotherapy. This study seeks to discover and validate effective antigens that can be employed to develop mRNA vaccines for hepatocellular carcinoma (HCC) and to construct immunophenotypes and immune landscapes to identify potential beneficiaries. Methods: RNA sequencing (RNASeq) data, mutation information, and clinical information were obtained from HCC patients and control cases from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium - Liver Cancer (ICGC-LIRI) and Gene Expression Omnibus (GEO) cohorts. Gene Expression Profiling Interactive Analysis (GEPIA2.0), cBioPortal for Cancer Genomics (cBioPortal), Tumor IMmune Estimation Resource (TIMER2.0), and immunohistochemistry (IHC) were employed to discover tumor antigens. ConsensusClusterPlus was employed to perform consistency matrix building and immunophenotypic clustering. Single sample gene set enrichment analysis (ssGSEA), ESTIMATE and monocle2 were employed to map immune cell distribution. Weighted correlation network analysis (WGCNA) was employed to identify potential gene modules that influence the efficacy of mRNA vaccines. Results: Six antigen targets were discovered in the TCGA cohort, including AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1, which were associated with antigen-presenting cell infiltration and poor prognosis. IHC scores of AURKA, CDC25C and MCM3 were higher in tumor tissues, and high scores of AURKA and CDC25C indicated poor prognosis in the validation cohort. Five immunophenotypes derived from TCGA-LIHC and ICGC-LIRI cohorts were consistent. Furthermore, increased expression of blue and black modules may reduce vaccine responsiveness. Conclusions: AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1 may be potential targets for mRNA vaccine development for HCC, especially AURKA and CDC25C. HCC patients with IS1 and IS5 subtypes perhaps present an autoimmunosuppressed state, then IS2 and IS3 subtypes perhaps the potential beneficiaries.

[Clinical efficacy of Longjintonglin Capsules on chronic prostatitis with damp-heat stasis syndrome Re-evaluation based on multicenter real-world study].

OBJECTIVE: To re-evaluate the clinical efficacy of Longjintonglin Capsules (LJTL) in the treatment of chronic prostatitis with damp-heat stasis syndrome. METHODS: This multicenter real-world study included 1 352 cases of chronic prostatitis with damp-heat and stagnation syndrome treated with LJTL (3 capsules once, tid, 30 minutes after meals, for 2 four-week courses) in addition to routine treatment. Before and after treatment, we analyzed the NIH-CPSI scores, the scores of Chinese medicine symptom quantitative classification and changes in individual symptom scores, and observed adverse reactions to medication. RESULTS: The total effectiveness rate of LJTL was 93.64%. Compared with the baseline, the NIH-CPSI scores were significantly decreased after treatment (ï¼»24.27 ± 6.04ï¼½ vs ï¼»8.17 ± 4.21ï¼½, P < 0.05), and so were the scores on the pain symptoms (ï¼»9.63 ± 3.65ï¼½ vs ï¼»3.02 ± 2.23ï¼½, P < 0.05), voiding symptoms (ï¼»5.65 ± 2.15ï¼½ vs ï¼»1.62 ± 1.36) and quality of life (ï¼»8.96 ± 2.32ï¼½ vs ï¼»3.16 ± 1.89ï¼½, P < 0.05). The effectiveness rate of LJTL was 95.9% on the Chinese medicine symptom frequent urination, 90.4% on painful urination, and 91.4% scanty dark urine, with a total effectiveness rate of 82.4% － 95.9%, all with statistically significant difference in comparison with the baseline (P < 0.05). CONCLUSION: Longjintonglin Capsules combined with routine treatment can significantly improve the clinical symptoms of chronic prostatitis with damp-heat stasis syndrome, especially effective on the symptoms of frequent urination, painful urination and scanty dark urine. Besides, it recommendable for its antidepressant and antianxiety effects, and the effect of improving the quality of life of the chronic prostatitis patients with damp-heat stasis.

Floralozone Ameliorated Atherosclerosis in Experimental Atherosclerotic Rats Involved with Sphingosine 1-Phosphate 1 Enhancement.

Atherosclerosis (AS) is a chronical pathological process of the arterial narrows due to the AS plaque formation. The aim of this study was to explore the therapeutic effect and the underlying mechanism of Floralozone on experimental atherosclerotic model rats. Experimental atherosclerotic model rats were induced by the right carotid artery balloon injury and intraperitoneal injection of vitamin D3 in rats after 4 weeks high-fat diet. The results exhibited that Floralozone could ameliorate vascular injury and vasorelaxation of descending aortas and increase the superoxide dismutase activity and the expression of sphingosine 1-phosphate (S1P) 1 and reduce the intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, interleukin (IL)-1, IL-6 level, and the malondialdehyde activity in experimental atherosclerotic rats. However, Fingolimod, an S1P1 inhibitor, could reverse these Floralozone effects in experimental atherosclerotic rats. Our results indicated that Floralozone could inhibit the atherosclerotic plaque formation and improves arterial stenosis and reduces endothelial dysfunction in experimental atherosclerotic rats, which might be involved with S1P1 enhancement.

Angiotensin II type 1 receptor blockers prevent aortic arterial stiffness in elderly patients with hypertension.

Backgrounds and aims: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blockers (ARBs) are potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of ARBs in aged patients with essential hypertension are not entirely investigated. Methods: The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension. Results: In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared to patients without essential hypertension. In correlation analysis, PWV was associated positively with age, hypertension duration, and carotid atherosclerosis. However, there was no relationship between PWV and gender in aged patients with essential hypertension. In a perspective study, 6-12 months administration of ARBs (losartan, 50 mg/day; telmisartan, 40 mg/day; valsartan 80 mg/day; irbesartan, 150 mg/day) remarkably reduced PWV in aged patients with essential hypertension. Regression analyses of multiple factors indicated that the effects of ARBs on arterial stiffness were not associated with the reduction of blood pressure. Conclusion: ARB treatment is a negative risk factor of arterial stiffness in aged patients with essential hypertension.

[Huanshao Capsules combined with levocarnitine for the treatment of asthenospermia, oligospermia and teratozoospermia].

OBJECTIVE: To observe the clinical effects of Huanshao Capsules (HSC) combined with levocarnitine (LC) on asthenospermia, oligospermia, teratozoospermia, and the semen parameters of the patients. METHODS: This randomized controlled clinical study included 186 infertility patients with spleen and kidney asthenia. We randomly divided them into three groups of equal number and treated them orally with HSC at the dose of 3 capsules tid, LC at 10 ml tid, and HSC+LC, respectively, all for 12 weeks. At 4, 8, and 12 weeks after treatment, we obtained the semen parameters from the patients and compared them among the three groups. RESULTS: Totally, 180 of the patients completed the study, 61 in the HSC, 59 in the LC and 60 in the HSC+LC group. After 12 weeks of medication, the patients of the HSC+LC group showed an increase of 42.77% in the semen volume, 142.37% in sperm concentration, 28.61% in sperm motility, and 24.39% in the percentage of grade a+b sperm and a decrease of 6.27% in the percentage of morphologically abnormal sperm as compared with the baseline (P <0.05). The patients treated with HSC+LC showed significantly more improvement in all the above parameters than those treated with LC alone (P <0.05) as well as in sperm motility and the percentage of progressively motile sperm than those treated with HSC alone (P <0.05). The HSC group exhibited remarkable improvement in the above parameters after treatment as compared with the baseline (P <0.05) and higher semen volume and sperm concentration than the LC group (P <0.05). CONCLUSIONS: Huanshao Capsulescombined with levocarnitinedeserves a wide clinical application as a safe and efficacious therapy forasthenospermia, oligospermia,and teratozoospermia.

Safety and efficacy of dehydrated ethanol soaking of the operative field in the treatment of spontaneous hepatocellular carcinoma rupture.

BACKGROUND: The aim of our study was to evaluate the clinical safety and value of ethanol surgical field infiltration (ESFI), combined with distilled water peritoneal lavage (DWPL), after hepatectomy in patients with hepatocellular carcinoma (HCC) rupture. METHODS: Rat liver tissue samples were soaked in dehydrated ethanol for different soaking times, and 18 rats were assigned to three groups that underwent different soaking methods of the hepatectomy cut surface. We retrospectively reviewed 45 patients who underwent hepatectomy for treatment of ruptured HCC. Among these, EFSI combined with DWPL was used in 21 patients (DAW group), with only DWPL used in the other 24 patients (DW group). Clinical outcomes were compared between the two groups. RESULTS: For in vitro experiments, the depth of coagulation degeneration and necrosis increased with the duration of soaking. For in vivo experiments, rats in all three groups survived until postoperative day 7 without significant postoperative complication. In patients, the rate of post-operation complication was comparable between the two groups (P = 0.398), with no between-group differences in liver function levels. The incidence of peritoneal dissemination was significantly higher for DW than DAW group (P = 0.037). Kaplan-Meier test identified dehydrated ethanol treatment as a significant factor of disease-free survival (DFS) (P = 0.036). On univariate analysis, dehydrated ethanol treatment was associated with better prognostic outcomes, although it was not retained as an independent factor of patient outcome. CONCLUSIONS: Dehydrated ethanol soaking of the cut surface of the hepatectomy could potentially lower the risk of metastasis and improve the effect of hepatectomy for ruptured HCC as well as showed potential therapeutic value for intraoperative iatrogenic rupture of HCC.

Long-term results of the paraesophagogastric devascularization with or without esophageal transection: which is more suitable for variceal bleeding?

BACKGROUND: It has been reported that the paraesophagogastric devascularization with esophageal transection procedure, also known as the modified Sugiura procedure, was effective in the treatment of variceal bleeding. However, it was not widely accepted by other surgeons because of the high rate of rebleeding, complications, and mortality. To discover the effects of the paraesophagogastric devascularization procedure and the modified Sugiura procedure, we retrospectively analyzed the outcomes of these two procedures. MATERIALS AND METHODS: During January 1990 and December 2009, 278 patients with variceal bleeding underwent devascularization after failed pharmacotherapy and endotherapy. In these 278 patients, 180 underwent paraesophagogastric devascularization without esophageal transection (group I), and the other 98 patients were subjected to the modified Sugiura procedure (group II). RESULTS: Postoperative mortality was 7.2% in group I, and 9.2% in group II (P = 0.563). The postoperative rebleeding rate in the two groups was 2.2 and 3.1%, respectively (P = 0.474). After a mean follow-up of 67.9 ± 37.3 months and 67.4 ± 44.6 months, respectively, esophageal transaction-related morbidity (leak, bleeding, and stricture) was 8.2% (8/98) in group II and 0% (0/180) in group I (P < 0.001). The overall rebleeding rate was 27% (41/152) in group I, and 27.2% (22/81) in group II (P = 0.976). The overall mortality was 28.3% (43/152) in group I, and 28.4% (23/81) in group II (P = 0.986). CONCLUSIONS: In the management of variceal bleeding, paraesophagogastric devascularization without esophageal transection is as effective and safe as devascularization with esophageal transaction, but with less esophageal transection-related morbidity.

Purification and Characterization of EGF-like Active Peptide from Calf Submaxillary Gland (c-EGF).

A peptide with M(r) of 6 kD and pI at 4.6 was purified from calf submaxillary gland by acid extraction, CM52 and DE52 ion exchange chromatography, Sephadex G 75 gel filtration and HPLC. Similar to rh- EGF, the peptide has such biological effects as the stimulation of the proliferation of NRK cells and fetal epithelial cells in vitro, the acceleration of incisor eruption and eyelid opening in new born mice and the stimulation of phosphorylation of the membrane protein of A 431 cells. The amino acid composition of this peptide is similar to that of rh-EGF, with both deficient in phenylalanine and threonine.