Angiotensin-converting enzyme - human amniotic mesenchymal stem cells improve pulmonary vascular remodeling in rats with pulmonary hypertension by promoting angiogenesis and counteracting inflammation.

OBJECTIVES: Human Amniotic Mesenchymal Stem Cells (hAMSCs) have strong multidirectional differentiation ability. Studies have found that transfection of target genes into target cells by lentivirus can enhance the differentiation potential of the cells. Angiotensin-Converting Enzyme 2 (ACE2) was found to improve vascular remodeling. Research is lacking on ACE2-hAMSCs. Therefore, this study aimed to investigate the ability to improve pulmonary arterial hypertension using ACE2-hAMSCs. METHODS: Lentiviruses overexpressing ACE2 were mixed with hAMSCs. Then, ACE2-hAMSCs and hAMSCs with good growth in logarithmic growth phase were collected. We detected their migration and angiogenesis. RT-qPCR technology was used to detect the expression levels of genes related to angiogenesis, and inflammation in the two cell lines, and western-blotting was used to detect the expression levels of ACE2. As an animal study, 21 rats were randomly divided into four different groups. Right heart hypertrophy, pulmonary angiogenesis, and serum inflammatory factors were measured before dissection. H&E staining was used to observe the inflammatory infiltration of lung tissues. RESULTS: The migration and angiogenesis of ACE2-hAMSCs were strongerthan that of hAMSCs alone. The expressions of genes in ACE2-hAMSCs were higher, and the expression of ACE2 protein in ACE2-hAMSCs was less. H&E staining showed that the inflammatory infilration of lung tissue in ACE2-hAMSCs groups was significantly improved. In addition, the ACE2-hAMSCs group had stronger pro-angiogenesis and anti-inflammatory effects. CONCLUSION: These results suggest that ACE2-hAMSCs can repair pulmonary vascular endothelial cell injury caused by pulmonary hypertension by promoting angiogenesis and anti-inflammatory ability. This shows that ACE2-hAMSCs have stronger ability to improve pulmonary vascular remodeling than hAMSCs alone.

Advanced penile cancer with multiple metastases and self-amputation of penis: A rare case report.

Penile cancer is a rare malignancy with poor prognosis. Advanced penile cancer that invades the penile shaft and causes urinary retention could be rarely seen. We reported a 72-year-old male suffered from advanced penile cancer with penile self-amputation and acute urinary retention. We reckoned the self-amputation of penis as a new sign of advanced penile cancer.

Successful Kidney-Sparing Systemic Therapy for a High-Risk Ureteral Carcinoma Case.

Upper tract urothelial carcinoma (UTUC) refers to the malignancies located from renal calices toward the end of the ureter and could be classified as renal pelvis carcinoma and ureteral carcinoma. For high-risk UTUC cases with a normal contralateral kidney, radical nephroureterectomy is the standard treatment. As for low-risk UTUC cases or solitary kidney cases, kidney-sparing therapy may be a better choice. Besides, to prevent postoperative recurrence, systemic therapy should be applied, though the investigation is still ongoing. In this case report, we reported a rare case diagnosed with high-risk ureteral carcinoma, but he underwent kidney-sparing therapy due to chronic kidney disease. Recurrence has occurred after segmental ureterectomy. But through the utilization of ablation, bladder instillation, and tislelizumab, endoscopy and CT were normal in the follow-up (the patient refused to take washings from the upper urinary tract) for more than a year. In all, the utilization of ureteroscopic retrograde tumor ablation, BCG bladder instillation, and tislelizumab injection to treat high-risk ureteral carcinoma for kidney-sparing therapy have filled in the gap in this field, which should be promoted to help more patients in similar situations.

Allele-specific polymerase chain reaction can determine the diplotype of NUDT15 variants in patients with childhood acute lymphoblastic Leukemia.

Mercaptopurine intolerance is an adverse effect of mercaptopurine administration in pediatric patients with acute lymphoblastic leukemia (ALL). NUDT15 variants have emerged as major determinants of mercaptopurine intolerance, especially in the Asian population. Two variants, c.55_56insGAGTCG in exon 1 and c.415C > T in exon 3, were commonly detected in the same allele, named NUDT15*1/*2. Although rare, compound heterozygous mutations also occur, with the two variants on different alleles (NUDT15*3/*6), which may confer tolerance to considerably lesser mercaptopurine dosage. Sanger sequencing or pyrosequencing can determine the NUDT15 variants but not the phase. Here, we designed an allele-specific PCR (AS-PCR) with locked nucleic acid-modified primers. A cohort of 63 patients harboring heterozygous c.55_56insGAGTCG and c.415C > T NUDT15 variations was selected for haplotyping using AS-PCR. Of the 63 patients, 60 harbored the NUDT15*1/*2 variant and three harbored compound heterozygous mutations, including two NUDT15*3/*6 and one NUDT15*2/*7 variants. These findings suggest that AS-PCR can determine NUDT15 diplotype and identify patients with compound heterozygous NUDT15 variants, which may enable precise genetic diagnosis of NUDT15. Nevertheless, a larger clinical trial is required to understand the clinical significance of NUDT15*3/*6 in pediatric patients with ALL because of its low incidence rate and challenges in detecting this variant.

Gas-Liquid-Solid Migration Characteristics of Gas Hydrate Sediments in Depressurization Combined with Thermal Stimulation Dissociation.

The exploitation of natural gas hydrate is always hindered by the migration of water and sands due to gas production. Depressurization combined with thermal stimulation is an effective method for hydrate dissociation. This paper reported the influence of gas-liquid-solid migration on morphological change of hydrate sediments in natural gas production using visualization method. Different backpressures combined with thermal stimulation methods were applied to simulate natural gas hydrate exploitation. Pressure compensation was first employed to study sediment recovery features. The expansion rate of a porous medium layer under combined dissociation and different backpressure (4.5, 3.5, 2.5, 1.5, and 0.1 MPa) was discussed. A 176% hydrate sediment expansion rate was found after the combined dissociation at 0.1 MPa. In addition, it was observed that the height of the water layer above the porous media after pressure compensation was gradually reduced with a decrease in backpressure and eventually disappeared at 0.1 MPa. It was also found that the disappearing water layer caused an anomalous memory effect phenomenon. Expansion and subsidence of sediments provide a better reference for hydrate exploitation and geological safety.

Sesamin inhibits lipopolysaccharide-induced proliferation and invasion through the p38-MAPK and NF-κB signaling pathways in prostate cancer cells.

Sesamin, a lipid-soluble lignan, is one of the major constituents of sesame. Previous studies have reported that sesamin induces growth inhibition in human cancer cells, particularly prostate cancer cells. In the present study, we mainly explored the mechanism underlying the protective effect of sesamin on prostate cancer cell proliferation and invasion induced by lipopolysaccharide (LPS). We found that the proliferation of PC3 cells, as determined using the MTT assay, and the expression of cyclin D1, COX-2, Bcl-2 and survivin proteins elevated by LPS were distinctly inhibited by sesamin in a dose-dependent manner. Meanwhile, the ability of PC3 cell invasion, as determined using the Transwell assay and the expression of matrix metalloproteinase 9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) proteins increased by LPS were obviously reduced by sesamin in a dose-dependent manner. In addition, the accumulation of TGF-α and interleukin-6 (IL-6) production induced by LPS in the culture supernatant was found to be decreased dose-dependently with sesamin pretreatment in PC3 cells using the enzyme-linked immunosorbent assay (ELISA) kit. Furthermore, phosphorylation of the p38 protein and nuclear factor (NF)-κB activity in the PC3 cells were enhanced by LPS and further inhibited with sesamin, SB203580 pretreatment or p38-siRNA transfection, respectively. Sesamin or SB203580 pretreatment obviously inhibited PC3 cells-derived tumor growth induced by LPS in vivo. Taken together, these results suggest that the potential ability of sesamin to downregulate the secretion of cytokines and the expression of cell proliferative- and invasive-related gene products induced by LPS was shown to be via the p38 mitogen-activated protein kinase (p38-MAPK) and NF-κB signaling pathways, which may be one of the mechanisms of the anticancer activity of this sesamin agent in prostate cancer cells.

Synthesis of biocontrol macromolecules by derivative of chitosan with surfactin and antifungal evaluation.

A derivative of chitosan was prepared with chitosan and ß-cyclodextrins, which was synthesized by the immobilization reaction, as a carrier to adsorb surfactin produced from Bacillus amyloliquefaciens and got biological macromolecules. The antifungal activity against three sapstain fungi by a combination of macromolecules was tested. The results showed that the macromolecules inhibited the mycelium growth of sapstain fungi Lasiodiplodia rubropurpurea, L. crassispora, and L. theobromae by about 73.22%, 76.72%, and 70.22%, respectively. The macromolecules were relatively thermally stable with more than 50% of the antifungal activity even after being held at 121°C for 30 min. Meanwhile, the activity of the macromolecules remained more than 55% at a pH value ranging from 4 to 12. The macromolecules were resistant to hydrolysis by most protein-denaturing detergents and other enzymes. The results indicated the macromolecules might provide an alternative bioresource for the bio-control of sapstain.

LKB1 suppresses proliferation and invasion of prostate cancer through hedgehog signaling pathway.

Activation of the hedgehog (Hh) signaling pathway has been implicated in the development of many human malignancies. Hh signaling target genes, such as patched (PTCH), smoothened (SMO) and sonic hedgehog (SHH), are markers of Hh signaling activation in most Hh-associated tumors. The protein kinase LKB1 has been shown to slow proliferation and induce cell-cycle arrest in many cell lines. However, the function of LKB1 in prostate cancer development remains largely unclear. In this study, the expression of LKB1 in human prostate cancer tissue samples and prostate cancer cell lines was detected, and the effects of LKB1 on prostate cancer cell proliferation and invasion were evaluated. Moreover, the influence of LKB1 on target genes of the Hh signaling pathway was analyzed. The results indicated that knockdown of LKB1 expression by RNA interference promoted cell proliferation, colony formation and invasion. Meanwhile, we observed that LKB1 siRNA increased the expression of factors related to Hh signaling reporter activity in prostate cancer cells, including PTCH, SMO and SHH. These findings suggest that LKB1 is a putative tumor suppressor gene in prostate cancer, and that LKB1 is negatively correlated with the expression of Hh signaling related transcription factors. Our results suggest that LKB1 may inhibit tumorigenesis by regulating the Hh signaling pathway in certain cancers.

[Application value of scrotal ultrasonography in the etiological diagnosis of azoospermia].

OBJECTIVE: To evaluate the application of scrotal ultrasonography in the diagnosis of the causes of azoospermia. METHODS: We performed scrotal ultrasonography for 96 patients with azoospermia, and analyzed the ultrasonographic images in comparison with the results of the final diagnosis. RESULTS: Based on the characteristics of the ultrasonographic images, 35 of the cases were diagnosed as obstructive azoospermia and the other 61 as non-obstructive azoospermia, with an accuracy rate of 97.0%. The causes and sites of the lesions were manifested in 44.4% of the obstructive and 46.7% of the non-obstructive cases, with accuracy rates of 100% and 75.0%, respectively. As for the rest of the cases, scrotal ultrasonography helped narrow the scope of further examinations by giving directional indications. CONCLUSION: Scrotal ultrasonography is an essential means for the diagnosis of the causes of azoospermia, or for obtaining directional indications of its causes.

[Local thermotherapy with rabdosia liquid as prophylactic measure for recurrence of superficial urinary bladder carcinoma: a non-randomized contemporary controlled study].

OBJECTIVE: To compare the actions of local thermotherapy with rabdosia liquid and repeated perfusion of mitomycin C for the postoperative prophylaxis of superficial urinary bladder carcinoma. METHODS: In the prospective non-randomized contemporary controlled study, 123 patients were divided into 2 groups. The patients in group A received local thermotherapy with rabdosia liquid starting from 1-2 months after operation, once tri-monthly for one year. Those in group B received intravesical perfusion of mitomycin C, starting from 2 weeks after operation, once weekly, six times in total, thereafter once monthly for one year. The recurrence rate, disease free interval, and adverse reaction after operation were observed. RESULTS: The follow-up lasted for 10-45 months with the average of 28.6 +/- 5.8 months. The recurrence rates in group A and B were 5.0% and 14.3%, respectively. Significant difference was shown when compared by Kaplan-Meier analysis of disease free interval and the recurrence rate between the two groups (P < 0.05). The occurrence rates of cystitis, hematuria, vesical contracture, urethral stricture were 28.3%, 5.0%, 1.7%, 1.7%, respectively in group A, 25.4%, 4.8%, 0%, 0%, respectively in group B, showing no significant difference between the two groups (P > 0.05). CONCLUSION: The effect of local thermotherapy with rabdosia liquid is reliable in preventing the recurrence of superficial urinary bladder transitional cell carcinoma.