Case report of avascular necrosis of the glans penis after PAE embolization.

BACKGROUND: Prostate artery embolization (PAE) is a relatively safe and effective alternative method for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. The adverse events caused by PAE are primarily mild, including urinary tract infection, acute urinary retention, dysuria, fever, etc. Severe complications, such as nontarget organ embolism syndrome or penile glans ischemic necrosis, are rare. Here, we report a case of severe ischemic necrosis of the glans penis after PAE and review the literature. CASE PRESENTATION: An 86-year-old male patient was admitted to the hospital due to progressive dysuria with gross hematuria. The patient underwent placement of a three-way urinary catheter to facilitate continuous bladder flushing, hemostasis, and rehydration. After admission, his hemoglobin decreased to 89 g/L. After an examination, the diagnosis was benign prostatic hyperplasia with bleeding. During communication with the patient regarding treatment, he requested prostate artery embolization due to his advanced age and concomitant disease status. He underwent bilateral prostate artery embolization under local anesthesia. His urine gradually turned clear. However, on the 6th day after embolization, the glans gradually showed ischemic changes. On the 10th day, there was partial necrosis and blackening of the glans. The glans completely healed, and the patient was able to urinate smoothly on the 60th day after local cleaning and debridement, the administration of pain relief, anti-inflammatory and anti-infection agents, and external application of burn ointment. CONCLUSION: Penile glans ischemic necrosis after PAE is rare. The symptoms include pain, congestion, swelling, and cyanosis in the glans.

Exploration the global single-cell ecological landscape of adenomyosis-related cell clusters by single-cell RNA sequencing.

Background: Adenomyosis (AM) is a common benign uterine disease that threatens the normal life of patients. Cells associated with microenvironmental immune ecology are crucial in AM, although they are not as well understood at the cellular level. Methods: Single-cell sequencing (scRNA-seq) data were used to construct an AM global single-cell map, to further identify relevant cell clusters and infer chromosomal copy number variation (CNV) in AM samples. The biological functions of cell clusters were explored and cellular evolutionary processes were inferred by enrichment analysis and pseudotime analysis. In addition, a gene regulatory network (GRN) analysis was constructed to explore the regulatory role of transcription factors in AM progression. Results: We obtained the expression profiles of 42260 cells and identified 10 cell clusters. By comparing the differences in cell components between AM patients and controls, we found that significant abundance of endometrial cells (EC), epithelial cells (Ep), endothelial cells (En), and smooth muscle cells (SMC) in AM patients. Cell clusters with high CNV levels possessing tumour-like features existed in the ectopic endometrium samples. Moreover, the Ep clusters were significantly involved in leukocyte transendothelial cell migration and apoptosis, suggesting an association with cell apoptosis and migration. En clusters were mainly involved in pathways in cancer and apoptosis, indicating that En has certain malignant features. Conclusion: This study identified cell clusters with immune-related features, investigated the changes in the immune ecology of the microenvironment of these cells during AM, and provided a new strategy for the treatment of AM.

Sesquiterpenoid-rich Essential Oils from Two Magnolia Plants: Contact and Repellent Activity to Three Stored-product Insects.

Stored products have been damaged by insects. Multiple approaches for pest management are employed. Among these approaches, botanical insecticide is an emerging one. This work investigated the pest management potential of Magnolia coriacea and Magnolia macclurei essential oils (EOs) to three major stored-product insects, namely the red flour beetle, cigarette beetle and booklouse. Magnolia coriacea and M. macclurei EOs showed promising contact toxicity to the cigarette beetle, with LD50 values of 11.7 and 12.3 µg/adult. The contact toxicity of M. coriacea EOs to the booklouse (LC50 = 95.5 µg/cm2) was much stronger than that of M. macclurei EOs (LC50 = 245.4 µg/cm2). To explore the contribution of individual compounds to insecticidal activity of EOs, chemical analysis was performed by GC-MS. Results showed that nerolidol (27.84%), agarospirol (18.34%), elixene (15.84%) and helminthogermacrene (12.69%) were major compounds of M. coriacea EOs, ß-guaiene (60.31%) and elixene (20.42%) dominated in M. macclurei EOs. Nerolidol and ß-guaiene showed contact activity to three insect species. Nerolidol showed stronger contact toxicity to the red flour beetle and cigarette beetle than M. coriacea EOs did, both samples were similar to the booklouse. ß-Guaiene was much stronger to the red flour beetle and booklouse, but weaker to the cigarette beetle than M. macclurei EOs did. The repellent effects of EOs and compounds were at various levels. Generally, results suggested that the contact toxic potential of samples could serve as management for the cigarette beetle and booklouse, while repellent effect would be used to control the red flour beetle.

Measuring upper limb function and patient reported outcomes after major breast cancer surgery: a pilot study in an Asian cohort.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Major breast cancer surgery especially with axillary lymph node dissection (ALND), is associated with upper limb functional decline. Majority of studies are conducted in Western population and may not be applicable to Asians. This pilot study aims to evaluate whether major breast surgery results in upper limb functional impairment in a cohort of Asian women with breast cancer. METHODS: This is a prospective cohort study of 41 patients who underwent 44 major breast surgeries from April 2018 to August 2019. Main inclusion criteria were patients over 21 years of age undergoing major breast surgery for breast cancer. Major breast surgery was defined as wide local excision (WLE) or mastectomy. Main exclusion criteria were patients with pre-existing neurological or rheumatological co-morbidities affecting upper limb function or previous trauma with resulting deformities to the upper limbs. Patients underwent early rehabilitation from post-operative day 1. Shoulder flexion and abduction active range of motion (AROM) and QuickDASH disability score were assessed 1 week before surgery, post-operative week 2 and week 6. Baseline demographics and peri-operative data were also collected. RESULTS: Median age was 62.5 years. There were 16 (36.4%) wide local excisions and 28 (63.6%) simple mastectomies. Two (4.5%) cases had neoadjuvant chemotherapy. Fifteen (34.1%) cases had ALND. At post-operative week 6, shoulder flexion was comparable to baseline (p = 0.775), while abduction improved from baseline (p = 0.016). However, QuickDASH disability score was significantly worse at post-operative week 6 compared to baseline (median score 2.5 vs 0, p = 0.027). Subgroup analysis of patients with ALND demonstrated significantly worse QuickDASH disability score at post-operative week 6 (p = 0.010) but not for patients with only sentinel lymph node biopsy (p = 0.396). CONCLUSION: This pilot study in an Asian cohort found that patients were able to regain AROM of shoulder after major breast surgery at post-operative week 6 but had a worse QuickDASH disability score, especially in the subgroup with ALND. Aggressive and early rehabilitation should be encouraged. However, a longer follow-up is required to evaluate long term functional outcomes.

LTBP2 knockdown by siRNA reverses myocardial oxidative stress injury, fibrosis and remodelling during dilated cardiomyopathy.

AIM: Dilated cardiomyopathy (DCM) is characterised by left ventricular dilation and associated with systolic dysfunction. Recent evidence has reported the high expression of latent transforming growth factor beta binding protein 2 (LTBP2) in heart diseases, which may play a role in regulating multiple biological functions of myocardial cells. Thus, this study set out to investigate the molecular mechanism and effects of LTBP2 in myocardial oxidative stress injury, fibrosis and remodelling in a rat model of DCM, with the involvement of NF-κB signalling pathway. METHODS: The rat model of DCM was treated with si-LTBP2 and/or activator of NF-κB signalling pathway to examine the haemodynamic indexes, cardiac functions, oxidative stress injury, fibrosis and remodelling. Moreover, in vitro experiments were conducted to verify the regulatory role of LTBP2 and NF-κB signalling pathway in DCM. RESULTS: LTBP2 was up-regulated in DCM rats. After LTBP2 was knocked down, haemodynamic indexes, HW/BW ratio, collagen volume fraction (CVF) level, positive expression of LTBP2, levels of reactive oxygen species (ROS), malondialdehyde (MDA), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), tumour necrosis factor beta 1 (TGF-ß1) and brain natriuretic peptide (BNP) were all decreased. Meanwhile, levels of LTBP2, Col-I, Col-III, p65 and p52 were also reduced, while HW, BW and levels of SOD and TAOC were increased. In contrast, activation of NF-κB signalling pathway reversed effects of LTBP2 gene silencing. These findings were confirmed by in vivo experiments. CONCLUSIONS: LTBP2 silencing can attenuate myocardial oxidative stress injury, myocardial fibrosis and myocardial remodelling in DCM rats by down-regulating the NF-κB signalling pathway.

Atorvastatin suppresses vascular hypersensitivity and remodeling induced by transient adventitial administration of lipopolysaccharide in rats.

BACKGROUND: The phenotypic transition of vascular smooth muscle cells (VSMCs) from a contractile to a proliferative state markedly affects the pathophysiology of cardiovascular diseases. The adventitial inflammation can promote neointimal formation and vascular remodeling. We used direct administration of lipopolysaccharide (LPS) into the periphery of the carotid artery to investigate the influence of transient adventitial inflammation on vascular remodeling and its potential mechanism. METHODS: Male 15-week-old Wistar rats were randomly assigned to four groups with six rats in each group. The rats of groups I and II were administered distilled water, and group III and IV were treated with fasudil and atorvastatin respectively. All treatments were given daily for 11 days. On day 8, the adventitia in group I was injected with 5 µL sterile saline, and the group II-IV were injected with 5 µL sterilized LPS. The carotid blood flow and femoral blood pressure were measured in vivo, and the thickness of vascular intima and middle layer was measured in vitro. Serum interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) were determined using enzyme-linked immunosorbent assay (ELISA) assay. And the Rho-associated coiled-coil-containing protein kinase 2 (ROCK2), myosin phosphatase target subunit 1 (MYPT1), myosin light chain (MLC), myocardin, SM-α actin or glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were detected by western blot. The comparisons were made by one-way analysis of variance with Bonferroni's post hoc test. A value of P<0.05 was considered to represent a statistically significant difference. RESULTS: Transient adventitial inflammation induced by LPS caused no obvious change in basal blood flow, but did lead to vascular hypersensitivity to serotonin. Morphological examinations revealed that the medial layer was the only domain affected, and showed VSMC proliferation and rearrangement. LPS increased serum IL-6 and TNFα contents, ROCK2 expression and activity, and caused changes in the expression levels of some stereotypical VSMC genes. Similar to the Rho-kinase inhibitor fasudil, atorvastatin completely restored the morphological alterations, even increased blood flow. CONCLUSIONS: Our study confirms the beneficial effect of atorvastatin on the vascular system in terms of morphology and function.

Effects of surface modification of PLGA-PEG-PLGA nanoparticles on loperamide delivery efficiency across the blood-brain barrier.

In this study, we developed a nanoparticle system for drug delivery across the blood-brain barrier (BBB). The nanoparticle consisting of loperamide and poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer were prepared by the nanoprecipitation method; then the nanoparticles were coated with poloxamer 188 or polysorbate 80. The effects of poloxamer 188 or polysorbate 80 on the physicochemical and pharmaceutical properties of the coated nanoparticles were investigated. Loperamide, which does not cross the blood-brain barrier (BBB) but exerts antinociceptive effects after direct injection into the brain, was encapsulated by different polymeric materials and used as a model drug. The in vitro BBB penetration study shows that the surfactant-coated PLGA-PEG-PLGA nanoparticles could have penetration of 14.4-21.2%, which was better than the PLGA-PEG-PLGA nanoparticles (PEP) (8.2%) and the PLGA nanoparticles (PN) (4.3%). The biopsy studies also confirm that the PEP coated by surfactant could increase the penetration. The results of nanoparticles accumulation in brain tissue show that the PEP coated by surfactant had a much higher concentration than both the PEP and the PN. Moreover, the maximal possible antinociception effect (MPE) for the surfactant-coated PEP was 21-35% at 150 min after administering the drug intravenously, which was significantly better than just the PEP (MPE: 11.6%). The results of the formalin test show that the surfactant-coated PEP administered intravenously 150 min prior to the formalin injection could greatly reduce the pain response in the first phase. The results demonstrate that the surfactant-coated PEP could help to deliver loperamide across the BBB.

Inflammation inhibitory effects of sirolimus and paclitaxel-eluting stents on interleukin-1ß-induced coronary artery in-stent restenosis in pigs.

BACKGROUND: Coronary artery in-stent restenosis (ISR) and late stent thrombosis remain as important complications of stenting. The inflammation reactions to sirolimus and paclitaxel-eluting stents were investigated in a swine stenosis model induced by interleukin (IL)-1ß. METHODS: Mini pigs (n = 12; 2-3 months old and weighing 25-30 kg) were subjected to thoracotomy. Segments (10 mm) of the mid left anterior descending coronary artery and left circumflex coronary artery were exposed and aseptically wrapped with a cotton mesh soaked with IL-1ß (5 µg). After 2 weeks, the animals were anesthetized and quantitative coronary arteriography (QCA) was performed. The stenosis sites were randomized into three groups for stent insertion: a sirolimus-eluting stent (SES) group (Firebird(TM), n = 7), a paclitaxel-eluting stent (PES) group (TAXUS(TM), n = 9), and a bare-metal stent (BMS) group (YINYITM, Dalian Yinyi Biomaterials Development Co., Ltd, China, n = 8). The three different stents were randomly implanted into stenosis segments. Expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), P-selectin and vascular cell adhesion molecule-1 (VCAM-1) was determined by reverse transcription-coupled polymerase chain reaction (RT-PCR). RESULTS: QCA showed severe stenosis in IL-1ß treated segments. The SES and PES groups showed lower 1-month angiographic late lumen loss (LLL) within the stent and the lesion compared with BMS (P < 0.05) by follow-up QCA. The SES showed lower LLL than that of PES in reducing 1-month inflammation lesions in pigs by follow-up QCA ((0.15 ± 0.06) mm vs. (0.33 ± 0.01) mm, P < 0.0001). The neointimal hyperplasia areas in SES and PES showed lower than those of BMS (SES (11.6 ± 1.7) mm(2), PES (27.2 ± 1.6) mm(2) vs. BMS (76.2 ± 1.3) mm(2), P < 0.0001). The mRNA expression of MCP-1 by RT-PCR in SES and PES showed lower than that of BMS at 30 days after stenting (SES 0.20 ± 0.03, PES 0.48 ± 0.49 vs. BMS 0.58 ± 0.07, P < 0.05). Levels of VCAM-1 in SES were significantly lower than those of PES and BMS (SES 0.35 ± 0.08 vs. PES 0.65 ± 0.13, BMS 0.70 ± 0.06, P < 0.05). Histochemical immunostaining of vessel walls showed lower inflammatory chemokine MCP-1 expression in the SES and PES groups compared with BMS. CONCLUSION: SESs were superior in reducing 1-month angiographic LLL in inflammation lesions in pigs, strongly suggesting that SESs can suppress inflammatory reactions in ISR at multiple points.

[Preliminary investigation on the dynamic change in epidermal stem cells under mechanical stress in vivo].

OBJECTIVE: To observe the distribution of epidermal stem cell (ESC) after soft tissue expansion, and to explore dynamic change in ESC under mechanical stress and kinetic mechanism of skin expansion. METHODS: Skin samples were collected from patients after expansion of the scalp. They were divided into three groups: A group (scalp harvested 3 cm away from the center of dilator), B group (scalp tissues at the edge of dilator), and control group (scalp without dilatation). The tissue structures were observed with optical microscope with HE staining. The distribution and differentiation characteristics of cell keratin 19 (CK19) positive cells were observed with inverted phase contrast microscope after immunohistochemistry staining. RESULTS: HE staining showed that the epidermis was thickened and distributed densely with uneven, rugged and increased layers in A, B groups. With immunohistochemistry staining, CK19 positive cells appeared in multilayers in basal membrane, a few of them were in cluster or dispersed , with" hollowing" structure formation. These phenomena were not seen in control group. CONCLUSION: ESC can proliferate with abnormal distribution and "hollowing" structure formation after mechanical dilatation, which may be related to dynamic changes in basal layer cells.

[Constitutive characteristics and change trend of gynecological malignant tumors in 8009 hospitalized patients in Guangxi Zhuang Autonomous Region].

OBJECTIVE: To investigate the constitutive characteristics and the change trend of gynecologic malignant tumors in hospitalized patients in Guangxi Zhuang Autonomous Region over the recent 20 years. METHODS: Clinical data of 8009 in-patients who suffered from gynecologic malignant tumors in 23 hospitals from 1985 to 2004 in Guangxi Zhuang Autonomous Region were analyzed, with respect to the tumor types and change trend. RESULTS: (1) The leading 4 types of malignant tumors were cervical cancers, ovarian cancers, endometrial cancers, and malignant trophoblastic tumors according to the constitutive ratios of the tumors. The constitutive ratio of cervical cancer patients rose year by year, from 17.48% during the 1985-1989 period to 49.25% during the 2000-2004 period (P < 0.01). While the constitutive ratio of malignant trophoblastic tumors dropped year by year. The changes of ovarian cancer, endometrial cancer, vulvar and vaginal carcinomas, and sarcoma of the uterus were not obvious (P > 0.05). (2) The occurring age of cervical cancers became younger obviously, from > or = 60 years old dropped to < 40 years old. (3) Cervical cancers were found mainly in urban residents in the former 10 years, the constitutive ratio being 67.1%; while in the latter 10 years it gradually shifted to rural residents, accounting for 52.6% of the total gynecological tumors. (4) Patients were usually at stages II, III, IV when they visited a doctor for their diseases. Especially for ovarian cancer, malignant trophoblastic tumors, sarcoma of the uterus, these patients were in the intermediate or advanced stage when they were diagnosed, mainly because of lack of obvious symptoms. The constitutive ratio of these advanced patients was over 60%. CONCLUSIONS: We should strengthen the screening program of cervical cancer, and pay more attention to prevention and control of other gynecological reproductive organ tumors at the same time. On the other hand, we should explore better tumor markers, new methods of diagnosis and treatment to improve early diagnosis and treatment of gynecologic malignant tumors.

[Pitavastatin enhances angiogenesis and perfusion in a murine mode of limb ischemia].

OBJECTIVE: We investigated the effects of pitavastatin on angiogenesis and perfusion in C3H/He mice with unilateral hind limb ischemia. METHODS: C3H/He mice treated with saline (n = 15) or pitavastatin (1 mg.kg(-1).d(-1), n = 15) per gavage for 1 week underwent unilateral hind limb ischemia surgery and were treated for another 5 weeks. Hind-limb blood flow was measured by Laser Doppler perfusion imager (LDPI, ischemic/nonischemic limb, %) at baseline, immediately after ischemia and weekly thereafter for 5 weeks. Endpoints included local vessel counts by immunofluorescence, phospho-Akt positive cell counts by immunoenzyme histochemical technique, vascular endothelial growth factors (VEGFs) expression in ischemic limbs by Western blot and serum nitric oxide metabolite (NOx) by chrome dioxide Griess method. RESULTS: Lower extremity perfusion was significantly improved in pitavastatin treated mice vs. controls as measured by LDPI% at 1 week post ischemia and thereafter (P < 0.05). Pitavastatin treatment was associated with significantly increased capillary count [(47 +/- 11) vs. (26 +/- 14)/per high-power field (x 200), P < 0.05] and greater percentage of phospho-Akt positive cells [(6 +/- 1) vs. (2 +/- 0)/per high-power field (x 200), P < 0.05] in ischemic limbs. Serum NOx [(77.3 +/- 21.8) vs. (52.1 +/- 11.2) mol/L, P < 0.05) and VEGF protein expression in ischemic limbs were also significantly increased in pitavastatin group than those in control group. CONCLUSIONS: Pitavastatin enhances angiogenesis and perfusion in CsH/He mice with limb ischemia.

[The pro-angiogenesis effect of Pitavastatin in the Klotho gene-knockout mice].

AIM: To discuss the effect of Pitavastatin on angiogenesis in vivo and its mechanism in Klotho heterozygous deficient mice. METHODS: The heterozygous deficient Klotho mice (kl +/-) and wild mice (kl +/+) from the same litter were used to establish the animal model of hind-limb ischemia and grouped into control and Pitavastatin group, respectively. Hind-limb blood flow was evaluated using Laser Doppler perfusion imager (LDPI) before treatment and after operation of hind-limbs. The capillaries in muscle of limbs were counted by means of CD-31 labeled immuno-fluorescence. The phosphorylation of Akt (Protein kinase B) in cells was measured by direct immunohistochemical technique. The expression of vascular endothelial growth factors (VEGFs) in muscle of limbs was assessed using Western blotting. RESULTS: After treatment of Pitavastatin, the blood flow in ischemic limbs of the Kl +/- and wild mice improved obviously, the ratio of blood flow area in ischemic limb to that in non-ischemic limb increased and the density of capillaries increased in ischemic limbs of the Kl +/- and wild mice. Pitavastatin enhanced the phosphorylation of Akt and the expression of VEGF in ischemic limbs of the Kl +/- and wild mice. CONCLUSION: Pitavastatin has the pro-angiogenesis effect in vivo and the VEGF-p-Akt-NO pathway may be involved in the mechanism of the effect of Pitavastatin.

[Analysis of prognostic factors of malignant ovarian tumor after fertility-preserving treatment].

OBJECTIVE: To explore the prognostic factors of malignant ovarian tumor after fertility-preserving treatment. METHODS: 189 patients with malignant ovarian tumor who had undergone fertility-preserving management in the past 20 years were retrospectively analyzed. The correlative factors for survival, recurrence and reproductive status were evaluated. Among the patients, 136 cases suffered from ovarian germ cell tumor (OGCT), 31 cases suffered from ovarian sex cord-stromal tumor (OSCST), and 22 cases suffered from epithelial ovarian cancer (EOC). The median follow-up time of different groups was 50 months for OGCT, 46 months for OSCST, 45 months for EOC respectively. RESULTS: The 5-year survival rates for OGCT, OSCST and EOC groups were 94.0% (131/134), 77.1% (26/30) and 64.7% (16/21) respectively. The recurrent rates were 29.9% (40/134), 20.0% (6/30) and 47.6% (10/21) respectively. 46 babies were delivered during the follow-up period. Standard chemotherapy was the most important prognostic factor for OGCT. FIGO stage and standard chemotherapy were favourable factors for prognosis in OSCST group. The important prognostic factors included FIGO stage and standard comprehensive surgical staging for EOC. CONCLUSION: Fertility-preserving treatment should be considered for OGCT without limitation of FIGO stage, whereas it should be performed individually for OSCST and EOC. The treatment outcome for OGCT is the best, for EOC the worst.