[Anatomical elucidation and histological study of pelvic autonomic nerve-plane based female fresh cadaver].

Objective: To investigate the rationality of nerve-plane sparing radical hysterectomy (NPSRH) for cervical cancer by observing the anatomical and histological characteristics of pelvic autonomic plane based on fresh cadaver. Methods: From October 2015 to September 2020, 14 fresh female cadavers were anatomically and histologically studied in the Laboratory of Anatomy and Embryology Department, Peking Union Medical College, Chinese Academy of Medical Sciences. The median age of the specimens was 79 years (range: 67 to 92 years). Twenty-eight hemi-pelvic specimens were obtained from 14 fresh female cadavers. NPSRH procedures were simulated in 8 hemi-pelvic cavities to prove its feasibility. Detailed dissection was conducted to recognize nerve plane and to observe the distribution of pelvic nerves in 10 hemipelvis. In the other 10 hemipelvis, whole parametrium tissue was taken from the crossing of ureter and the uterine artery to the ureterovesical entrance and be embedded, then continuous section was performed, and was stained by hematoxylin-eosin staining (HE) to observe the relationship of nerves and vessels. Immunohistochemical staining of S100, tyrosine dehydrogenase (TH), and vasoactive intestinal peptide (VIP) were performed to count and distinguish sympathetic and parasympathetic nerves, respectively. Results: (1) The pelvic autonomic nerve-plane was completely preserved in 7 of 8 hemipelvis by simulating NPSRH. (2) After detailed dissection in 10 hemipelvis, it was found that hypogastric nerve, pelvic splanchnic nerve, and their confluence of inferior hypogastric plexus were distributed in a planar statelocating in the ureteral mesentery and its caudal extension. This nerve plane showed a cross relationship with deep uterine vein and its branches. The bladder branches and vesical venous plexus were closely related to the inferior hypogastric plexus. The middle vesical vein and inferior vesical vein were intact in 7 of 10 hemipelvis, and either vesical vein was missing in 3 of them. It was observed that the vesical venous plexus communicated with the deep uterine vein trunk on the medial side of the nerve plane in 6 hemipelvis, while flowed into the deep uterine vein on the lateral side of the nerve plane in 2 hemipelvis, and in the other 2 hemipelvis it directly flowed into the internal iliac vein. (3) It was revealed that autonomic nerves were continuously distributed beneath the ureteral with sagittal plane by HE staining. The average nerve content below the ureteral width was 70.9% of the total in nerve plane by S100 staining. TH and VIP staining showed that the average number of sympathetic fibers was 13.5 and parasympathetic fibers was 8.2, reminding sympathetic predominated. Conclusion: Pelvic autonomic nerves are mainly distributed within the mesangial plane below the ureter, which provides an anatomic justification for NPSRH.

Isothiazolinones Common in Children's Toy Slime.

BACKGROUND: Contact dermatitis to homemade slime has been frequently reported, with isothiazolinones as a likely sensitizer. Little is known on the presence of these preservatives in commercial, store-bought slime products. OBJECTIVES: The aims of the study were to review the literature on "slime dermatitis" and to assess for the presence of isothiazolinones in commercially available slime products and homemade slime components. METHODS: An experimental, colorimetric spot test was used to verify the presence of isothiazolinones in 38 slime products of the 16 best-selling commercial slime kits, 1 finished homemade slime, and 4 common components of homemade slime. High-performance liquid chromatography with UV detection was performed on 8 commercial slime products. RESULTS: According to the spot test, 27 (71%) of the 38 commercial slime products contained isothiazolinones. High-performance liquid chromatography with UV detection analyses indicated, however, that false-positives and false-negatives readily occur: isothiazolinone content was correctly identified in only 4 (50%) of the 8 samples. CONCLUSIONS: This study is the first to demonstrate the presence of isothiazolinones in commercial slime toys. Although the colorimetric spot test may have some utility as a screening assay, it is far from specific and likely not sensitive enough to reliably identify methylisothiazolinone.

[Open nerve-plane sparing radical hysterectomy in locally advanced cervical cancer: evaluation on efficacy and long-term survival outcomes].

Objective: To evaluate the security and clinical outcomes of open nerve-plane sparing radical hysterectomy (NPSRH) for operable locally advanced cervical cancer, compared with conventional radical hysterectomy (CRH). Methods: All 389 cases with International Federation of Gynecology and Obstetrics (FIGO, 2009) stage Ⅰb2 and Ⅱa2 cervical cancer were retrospectively analyzed in Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences between January 2008 and December 2014. Of all the patients, 69 cases underwent laparotomic NPSRH, and other 320 cases underwent CRH. Patients' general characteristics and intraoperative parameters were evaluated between the two groups. Basic clinical and pathological informations between the two groups were matched. After median 82 months' follow-up,disease-free survival (DFS), overall survival (OS), and postoperative recovery of bladder function were compared between the two groups. Results: (1) Compared to CRH group, NPSRH group had less intraoperative bleeding [(366±302) vs (457±301) ml; t=2.305, P=0.022], and a little bit longer operation time [(262±51) vs (245±52) minutes; t=2.621, P=0.009]. (2) Compared to CRH group, NPSRH group had shorter duration of urethral catheterization [(11±9) vs (16±7) days; t=3.906, P<0.01], and better postoperative bladder sensation and function in one year (6.1% vs 16.0%; χ2=4.418, P=0.036). (3) The 5-year DFS rate and 5-year OS rate of all patients were 89.6% and 89.9%, respectively. Either preserving pelvic autonomic nerves or not had little effect on the 5-year DFS rate (NPSRH vs CRH: 90.9% vs 89.4%; P=0.714) or on 5-year OS rate (NPSRH vs CRH: 90.0% vs 89.9%; P=0.910) for locally advanced cervical cancer. Univariate analysis showed that lymphatic vascular space infiltration (LVSI) and pelvic lymphatic metastasis were significantly correlated with prognosis (P<0.05). Multivariate analysis showed that pelvic lymphatic metastasis was the independent prognostic factor of 5-year DFS rate (HR=1.31, 95%CI: 1.01-1.68, P=0.040) as well as 5-year OS rate (HR=1.30, 95%CI: 1.01-1.67, P=0.046) for locally advanced cervical cancer. Conclusion: Open NPSRH is feasible for patients with locally advanced cervical cancer, which could improve both short-term and long-term bladder function, and is not a risk factor for the prognosis of patients.

Establishing a three-generation prospective study: Bogalusa daughters.

OBJECTIVE: The Developmental Origins of Disease hypothesis has spurred increased interest in how prenatal exposures affect lifelong health, while mechanisms such as epigenetics may explain the multigenerational influences on health. Such factors are not well captured within conventional epidemiologic study designs. We explored the feasibility of collecting information on the offspring and grand-offspring of participants in a long-running study. DESIGN: The Bogalusa Heart Study is a study, begun in 1973, of life-course cardiovascular health in a semirural population (65% white and 35% black). MAIN MEASURES: Female participants who had previously provided information on their pregnancies were contacted to obtain contact information for their daughters aged 12 and older. Daughters were then contacted to obtain reproductive histories, and invited for a clinic or lab visit to measure cardiovascular risk factors. RESULTS: Two hundred seventy-four daughters of 208 mothers were recruited; 81% (223) had a full clinic visit and 19% (51) a phone interview only. Forty-five percent of the daughters were black, and 55% white. Mean and median age at interview was 27, with 15% under the age of 18. The strongest predictors of participation were black race, recent maternal participation in the parent study, and living in or near Bogalusa. Simple correlations for cardiovascular risk factors across generations were between r = 0.19 (systolic blood pressure) and r = 0.39 (BMI, LDL). CONCLUSION: It is feasible to contact the children of study participants even when participants are adults, and initial information on the grandchildren can also be determined in this manner.

[Comparative study of three-dimensional versus two-dimensional laparoscopic C1 radical hysterectomy for cervical cancer].

Objective: To compare the clinical effects and the subjective perception of surgeons with three-dimensional (3D) and two-dimensional (2D) laparoscopic C1 radical hysterectomy surgeries for cervical cancer. Methods: The retrospective cohort study was conducted. The clinicopathological data of 101 patients with cervical cancer who received C1 laparoscopic radical hysterectomy (C1-LRH) surgery from June 2015 to August 2017 were collected. Of all patients, 42 cases undergoing 3D laparoscopic surgery and 59 cases undergoing 2D laparoscopic surgery were respectively allocated into the C1-3DLRH group or C1-2DLRH group. The clinical effect and the subjective perception of surgeons were compared between the two groups. Results: (1) There was no significant difference between the C1-3DLRH group and C1-2DLRH group in terms of age, body mass index (BMI), International Federation of Gynecology and Obstetrics (FIGO) stage, pathologic type, etc. (all P>0.05). Compared with C1-2DLRH group, the operation time was significantly shortened [(192±54) vs (221±54) minutes, P<0.01], blood loss was significantly less [(102±88) vs (167±117) ml, P<0.01], and the success rate of inferior hypogastric plexus (IHP) bladder branch preservation was significantly increased [86% (36/42) vs 66% (39/59), P<0.05] in C1-3DLRH group. There were no significant difference in the number of lymph nodes, the incidence of operative complications, the infection rate, the time of catheterization and the length of hospitalization between the two groups (all P>0.05). The long-term bladder function was evaluated at the twelfth month after operation, 39 patients in the C1-3DLRH group and 53 patients in the C1-2DLRH group were completed the survey. The results showed that 13% (5/39) of the patients in the C1-3DLRH group had long-term bladder dysfunction, which was lower than that 21% (11/53) of the C1-2DLRH group, but there was no significant difference between the two groups (χ(2)=0.980, P=0.322). (2) A total of 251 laparoscopic surgeons questionnaires were eligible. The incidence of side effects in the first and second generation of 3D and 2D laparoscopic surgeons was 20.4% (10/49), 6.9% (6/87) and 3.5% (4/115), respectively. The incidence of side effects in the first generation of 3D laparoscopic surgeons was higher than that in the second generation of 3D (χ(2)=5.463, P=0.019) and 2D laparoscopic surgeons (χ(2)=12.475, P<0.01). There was no difference between the second generation of 3D and 2D laparoscopic surgeons (χ(2)=1.208, P=0.272). Conclusions: 3D laparoscopy is advantageous to the preservation of autonomic nerve in C1-LRH operation and may improve the quality of operation compared with 2D laparoscopy. The second generation of 3D laparoscopic device might overcome the side effects of the surgeons.

Magnetic resonance spectroscopy may serve as a presurgical predictor of somatostatin analog therapy response in patients with growth hormone-secreting pituitary macroadenomas.

PURPOSE: Somatostatin analogs (SSAs) are considered one of the most effective medical treatments for patients with growth hormone-secreting pituitary adenomas (GH-PAs). The postoperative electron microscopy (EM) pathological subtype and SSTR2 expression in the tumor are the most established predictors of patient response to SSA therapy. The aim of this study was to evaluate how will magnetic resonance spectroscopy (MRS) measurements before surgery predict the EM pathological subtypes and SSTR2 expression of tumors, and thereby serve as an indicator for the therapeutic sensitivity to SSAs of patients with GH-PAs. METHODS: Eighteen patients with GH pituitary macroadenomas who underwent transsphenoidal surgery were included in this retrospective study. The preoperative MRS data and T2 signal intensity were obtained from patients by 1.5 T MR spectroscopy of the sellar mass. The EM pathological subtypes of tumors were determined after surgery through examination of cell granulations. The expressions of somatostatin receptor 2 (SSTR2), SSTR5, P21, P27, and Ki-67 were evaluated by immunohistochemistry. RESULTS: The MRS parameters that were found to significantly predict the EM pathological subtypes of tumors, as calculated by the receiver operating characteristic curve, were the choline (Ch) value at 3140.5 MR units (sensitivity 69.2%, specificity 100%) and the choline/creatine (Ch/Cr) ratio at 1.27 (sensitivity 92.3%, specificity 100%). Further, the Ch/Cr ratio, but not other MRS data, was shown to negatively correlate with the expression of SSTR2 (P = 0.02). The Ch/Cr ratio was also found to positively correlate with the Ki-67 value (P < 0.05) and T2 signal (P < 0.05), but not with other factors that were examined in this study. Moreover, the Ch/Cr ratio could predict the EM pathological subtypes of tumors with an accuracy of 83.3% (5/6) for patients with an isointense T2 signal. CONCLUSION: The Ch/Cr ratio by MRS could effectively predict the tumor subtype and was significantly correlated with the expression of SSTR2, which was consistent with other predictors. It was also able to distinguish the patients with isointense T2 signals. Our results provide a potentially new and non-invasive method to predict the response to SSAs in patients with GH pituitary macroadenomas.

Treatment With Bortezomib-based Therapy, Followed by Autologous Stem Cell Transplantation, Improves Outcomes in Light Chain Amyloidosis: A Retrospective Study.

BACKGROUND: The hematologic response is critical in patients with light chain amyloidosis because a good response is known to improve organ response and overall survival. We present a retrospective analysis to compare the hematologic and organ response in patients who received bortezomib-based therapy before autologous stem cell transplantation (ASCT) versus those who received non-bortezomib-based therapy before ASCT and those who underwent ASCT at diagnosis. PATIENTS AND METHODS: Of a total of 63 patients who underwent ASCT for light chain amyloidosis, 34 received bortezomib-based therapy before ASCT (Bor-ASCT) and 29 did not receive bortezomib therapy (non-Bor-ASCT). A greater number of patients had involvement of ≥ 3 organs and cardiac involvement in the Bor-ASCT group, suggesting a greater risk at baseline in the Bor-ASCT group. RESULTS: At 3, 6, and 12 months after ASCT, the hematologic response was better in the Bor-ASCT group, with a statistically significance difference at 6 months (partial response or better in 82% vs. 20%; P = .002) and 12 months (partial response or better in 76% vs. 33%; P = .02). Organ responses (66% vs. 21%; P < .001) and median overall survival (not reached vs. 53 months; P = .001) were also greater in the Bor-ASCT group. CONCLUSION: Our study has shown that bortezomib-based therapy before ASCT improves the hematologic response, organ response and overall survival, potentially by decreasing the light chain load before ASCT.

Study on the relationship between the RASSF10 gene and the biological behavior of hepatocellular carcinoma cells.

OBJECTIVE: To investigate the relationship between Ras association domain family gene 10 (RASSF10 gene) and the biological behavior of hepatocellular carcinoma (HCC), including proliferation, invasion, and metastasis. MATERIALS AND METHODS: HCC cell lines were generated with stable overexpression or low expression of RASSF10 protein. A cell line transfected with an empty vector was treated as control. At 12, 24, 48, and 72 h, the cell proliferation was determined by MTT assay, the invasion ability was determined by Transwell chambers, and the scratch assay was used to assess the migration ability. Additionally, cell lines were injected subcutaneously in the axillary fossa of nude mice aged 5-6 weeks. Tumors were measured weekly for 6 consecutive weeks to observe tumor volume, tumor growth rate, weight, and tumor metastasis in nude mice of the different groups. RESULTS: In both the control group and low expression group, cell proliferation rates, cell invasion, and migration abilities, increased over time but decreased over time in the overexpression group. At each time point, data in the overexpression group were markedly lower than those in the control group, and highest in the low expression group. The differences were statistically significant (p<0.05). In both control group and low expression group, tumor volume, tumor growth rate, weight, and tumor metastasis number were increased in nude mice over time, while they decreased in the overexpression group (except for tumor metastasis number). At each time point, data in the overexpression group were markedly lower than in the control group, and highest in the low expression group. The differences were statistically significant (p<0.05). CONCLUSIONS: Like a tumor suppressor gene, RASSF10 can inhibit the proliferation, invasion, and migration of HCC cells.

Functional characterization of Bombyx mori nucleopolyhedrovirus mutant lacking late expression factor 9.

Baculoviridae is a family of invertebrate viruses with large double-stranded DNA genomes. Proteins encoded by some late expression factor (lef ) genes are involved in the regulation of viral gene expression. Lef-9 is one of four transcription-specific Lefs, which are components of the virus-encoded RNA polymerase, and can initiate and transcribe late and very late genes. As a multifunctional protein encoded by the Bombyx mori nucleopolyhedrovirus (BmNPV), Lef-9 may be involved in the regulation of viral propagation. However, the underlying mechanism remains unclear. To determine the role of lef-9 in baculovirus infection, lef-9-knockout virus (lef-9-KO-Bacmid virus) was constructed using the Red recombination system, and the Bac-to-Bac system was used to prepare lef-9-repaired virus (lef-9-Re-Bacmid virus). The lef-9-KO virus did not produce infectious viruses or show infection activity, while the lef-9-repaired virus recovered both. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of the transcription levels in wild-type-Bacmid, lef-9-KO-Bacmid, and lef-9-Re-Bacmid viruses showed that the lef-9-KO bacmid had little effect on viral genome replication. However, the transcription levels of the early and late viral genes, lef-3, ie-1, vp39, and p10, were significantly lower in BmN cells transfected with lef-9-KO-Bacmids than in the controls. Electron microscopy showed no visible enveloped virions in cells transfected with lef-9-KO-Bacmids, while many mature virions in cells transfected with lef-9-Re-Bacmid and wt-Bacmid were present. Thus, lef-9 was not essential for viral genome replication, but significantly affected viral gene transcription and expression in all periods of cell life cycle.

Role of Prognostic Nutritional Index in patients with gastric cancer: a meta-analysis.

INTRODUCTION: The aim of this study was to determine the role of Prognostic Nutritional Index in predicting gastric cancer. EVIDENCE ACQUISITION: Studies were searched in PubMed, EMBASE and ISI Web of Science. The hazard ratios and 95% confidence interval for survival estimate were extracted from the articles and the pooled HR was computed. EVIDENCE SYNTHESIS: Nine studies with 3203 participants met the inclusion criteria. Low PNI was associated with poor overall survival (pooled HR 1.92, 95% CI: 1.68-2.19). CONCLUSIONS: Prognostic Nutritional Index was an effective indicator for the prognosis of gastric cancer.

[Expression and clinical significance of ELOVL6 gene in high-grade serous ovarian carcinoma].

OBJECTIVE: To investigate the expression of elongation of very long-chain fatty acids family member 6 (ELOVL6) in high-grade serous ovarian carcinoma (HSOC), and explore the correlation between its expression and clinical prognosis in these patients. METHODS: The expression of ELOVL6 at mRNA and protein levels were respectively detected by reverse transcription (RT)-PCR and immune histochemistry method in 12 cases with normal ovarian tissues and 172 cases with HSOC from primary tumor site, forty of which had paired peritoneal metastatic tissues. RESULTS: (1) The results tested by RT-PCR showed that ELOVL6 expression in normal ovarian tissue was 4.8±1.1, while 1.2±0.7 in primary tumors and 1.8±0.9 peritoneal metastatic sites in HSOC. Compared with normal ovarian tissue, the level of ELOVL6 mRNA was significantly lower in HSOC (P<0.05). There was no significant difference between primary and peritoneal metastatic sites in HSOC (P=0.610). It was shown that ELOVL6 protein localized in cytoplasm of ovarian cancer cell by immunostaining assay. (2) ELOVL6 expression was observed in all normal ovarian tissue, 70.2% of G1-G2 and 48.8% of G3 HSOC (P<0.05). ELOVL6 expression in drug-resistant group were significantly lower than that in non-resistant group (39.1% vs 65.0%, P<0.01). The median disease-free survival was 41 months in the ELOVL6-positive group and 39 months in ELOVL6-negative group (P>0.05). The total median survival was 52 months in ELOVL6-positive group and 44 months in ELOVL6-negative group (P>0.05). CONCLUSION: Low expression of ELOVL6 may correlate with the poor differentiation and drug resistance in HSOC.

Childhood obesity patterns and relation to middle-age sleep apnoea risk: the Bogalusa Heart Study.

BACKGROUND: Obese adults have a higher risk of obstructive sleep apnoea (OSA); however, the relationship between childhood obesity and adult OSA risk is unclear. Objectives This study aimed to examine overweight/obesity (OW) in childhood and risk of OSA in middle age. METHODS: Childhood OW status was classified as never OW, weight cycling, persistent OW and incident OW. After 35 years of follow-up, high risk for OSA was determined by a positive score in ≥2 domains on the Berlin Questionnaire with obesity removed from scoring. RESULTS: At initial assessment, mean (SD) age was 9.9 (2.9) years, and 23.9% were OW. Overall, 25.7% had scores indicating a high risk for OSA. Compared with participants who were never OW, those with persistent OW and incident OW were 1.36 (95%CI: 1.04-1.77) and 1.47 (1.11-1.96) times more likely to be high risk for OSA, after adjustment for multiple risk factors and adult OW status. Participants with an OW duration of 1-4 years, 5-8 years, and 8+ years were 0.96 (0.44-2.09), 1.20 (0.70-2.04) and 1.52 (1.22-1.90) times more likely to be high risk for OSA compared with those who were never OW (P for trend: 0.0002). CONCLUSIONS: These results suggest that childhood OW is associated with a high risk of OSA in middle age.

Design of pulsed guiding magnetic field for high power microwave generators.

In this paper, we present a comprehensive study on designing solenoid together with the corresponding power supply system to excite pulsed magnetic field required for high power microwave generators. Particularly, a solenoid is designed and the excited magnetic field is applied to a Ku-band overmoded Cerenkov generator. It is found in experiment that the electron beam is properly guided by the magnetic field and a 1.1 GW high power microwave is achieved at a central frequency of 13.76 GHz. Pulsed solenoid system has the advantages of compactness and low energy consumption, which are of great interest for repetitive operation. The reported studies and results can be generalized to other applications which require magnetic fields.

Ritonavir-Mediated Induction of Apoptosis in Pancreatic Cancer Occurs via the RB/E2F-1 and AKT Pathways.

Recent observations suggest a lower incidence of malignancies in patients infected with HIV during treatment with Highly Active Anti-Retroviral Therapy (HAART) utilizing protease inhibitors. We investigated the effects of ritonavir, a FDA approved HIV protease inhibitor, on proliferation of pancreatic ductal adeno-carcinoma (PDAC) cell lines. Human PDAC cell lines BxPC-3, MIA PaCa-2, and PANC-1 were propagated under standard conditions and treated with serial dilutions of ritonavir. Ritonavir inhibited cell growth in a dose-dependent manner as well as activated the intrinsic apoptotic pathway in human pancreatic ductal adenocarcinoma (PDAC) cell lines. We observed down-modulation of cell-cycle promoting and up-regulation of cell-cycle inhibitory genes; enhanced interaction of retinoblastoma protein (RB) with E2F-1 transcription factor; inhibition of phosphorylation of RB, resulting in sequestration of E2F-1 and subsequent down-regulation of S phase genes; decreased interaction of E2F-1 with its consensus binding sites; inhibition of cell motility and invasiveness; and inhibition of the AKT pathway. Our results demonstrate a potential use of ritonavir as part of combination chemotherapy for PDAC. Since ritonavir is FDA approved for HIV, drug repositioning for PDAC would limit the costs and reduce risks.

Validation of recombinant Sendai virus in a non-natural host model.

We have previously shown that recombinant Sendai virus (SeV) vector, derived from murine parainfluenza virus, is one of the most efficient vectors for airway gene transfer. We have also shown that SeV-mediated transfection on second administration, although reduced by 60% when compared with levels achieved after a single dose, is still high because of the efficient transfection achieved by SeV vector in murine airways. Here, we show that these levels further decrease on subsequent doses. In addition, we validated SeV vector repeat administration in a non-natural host model, the sheep. As part of these studies we first assessed viral stability in a Pari LC Plus nebuliser, a polyethylene catheter (PEC) and the Trudell AeroProbe. We also compared the distribution of gene expression after PEC and Trudell AeroProbe administration and quantified virus shedding after sheep transduction. In addition, we show that bronchial brushings and biopsies, collected in anaesthetized sheep, can be used to assess SeV-mediated gene expression over time. Similar to mice, gene expression in sheep was transient and had returned to baseline values by day 14. In conclusion, the SeV vector should be strongly considered for lung-related applications requiring a single administration of the vector even though it might not be suitable for diseases requiring repeat administration.

The treatment effect of the atopic dermatitis by electrolytic-reduction ion water lotion.

A female in her late 20s was diagnosed with systemic atopic dermatitis in another hospital 5 years earlier and treated by steroid ointment application to the affected areas and oral steroid administration. She visited our hospital due to the aggravation of dermatitis symptoms over the entire face from 1 week earlier. Lesions were present on the face, chest, neck, and bilateral upper limbs, and, in particular, facial dermatitis was extensive. A diagnosis of systemic atopic dermatitis complicated by infection was made. As oral drugs, a herbal medicine and steroid/antihistamine combination tablet were used. As topical drugs, an steroid/antibiotic combination ointment and vitamin E/A ointment were applied. In addition, injections for the treatment of allergic disease were used, and acidic electrolyzed water and an electrolyticreduction ion water (ERI) lotion were topically applied. While receiving the two types of oral drug, she received a subcutaneous injection once a week and the application of acidic electrolyzed water, ERI lotion, steroid/antibiotic combination ointment, and vitamin E/A ointment to the lesions twice a day. One week after the initiation of treatment, redness and swelling decreased. After 1 month, the swelling further decreased, but the redness remained. After 1.5 months, the redness further decreased, showing a favorable course. Three months after the initiation of treatment, slight redness remained, but the skin color was almost normal. This patient showed the improvement of skin redness and swelling and an almost normal skin state without pigmented scars. These results suggest the effectiveness of complex therapy consisting of a herbal medicine and steroid/antihistamine combination drug as oral drugs and an steroid/antibiotic combination ointment and vitamin E/A ointment as topical drugs, injections for allergic disease, and acidic electrolyzed water and ERI lotion for disinfection and skin care.

Epinephrine stimulates esophageal squamous-cell carcinoma cell proliferation via beta-adrenoceptor-dependent transactivation of extracellular signal-regulated kinase/cyclooxygenase-2 pathway.

Esophageal cancer is the sixth leading causes of cancer-related death in the world. It is suggested that beta-adrenoceptor is involved in the control of cell proliferation, but its role in the pathogenesis of esophageal cancer remains unknown. We therefore studied the role of beta-adrenergic signaling in the regulation of growth of an esophageal squamous-cell carcinoma cell line HKESC-1. Results showed that both beta(1)- and beta(2)-adrenoceptors were expressed in HKESC-1 cells. Stimulation of beta-adrenoceptors with epinephrine significantly increased HKESC-1 cell proliferation accompanied by elevation of intracellular cyclic AMP levels, which were abolished by beta(1)- or beta(2)-selective antagonists. Epinephrine also increased extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation as well as cyclooxygenase-2 (COX-2) and cytosolic phospholipase A(2) expression, which were blocked by beta(1)- or beta(2)-selective antagonists. Moreover, epinephrine increased cyclin D(1), cyclin E(2), cyclin-dependent kinase (CDK)-4, CDK-6, and E(2)F-1 expression and retinoblastoma protein phosphorylation at Ser807/811, all of which were abrogated by beta(1)-adrenoceptor antagonist. Furthermore, epinephrine increased the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1 and -2 in a beta(2)-adrenoceptor-, mitogen-activated protein kinase/ERK kinase (MEK)-, and COX-2-dependent manner. MEK or COX-2 inhibitor also significantly inhibited HKESC-1 cell proliferation induced by epinephrine. Collectively, we demonstrate that epinephrine stimulates esophageal squamous-cell carcinoma cell proliferation via beta-adrenoceptor-dependent transactivation of ERK/COX-2 pathway. Stimulation of beta(1)- and beta(2)-adrenoceptors also elicits a differential response on the expression of cell cycle regulators. These novel findings may shed new light on the understanding of beta-adrenergic signaling in the control of esophageal cancer cell growth.