Exogenous melatonin enhances soybean (Glycine max (L.) Merr.) seedling tolerance to saline-alkali stress by regulating antioxidant response and DNA damage repair.

Saline-alkali (SA) stress induces excessive reactive oxygen species (ROS) accumulation in plant cells, resulting in oxidative damages of membranes, lipids, proteins, and nucleic acids. Melatonin has antioxidant protection effects in living organisms and thus has received a lot of attention. This study aimed to investigate the effect and regulating mechanism of melatonin treatment on soybean tolerance to SA stress. In this study, cultivars Heihe 49 (HH49, SA-tolerant) and Henong 95 (HN95, SA-sensitive) were pot-cultured in SA soil, then treated with MT (0-300 µM) at V1 stage. SA stress induced ROS accumulation and DNA damage in the seedling roots of both cultivars, causing G1/S arrest in HN95 and G2/M arrest in HH49. Melatonin treatment enhanced the activity of antioxidant enzymes in soybean seedling roots and reduced ROS accumulation. Additionally, melatonin treatment upregulated DNA damage repair genes, thus enhancing the reduction of DNA oxidative damage under SA stress. The effects of melatonin treatment were manifested as decreased RAPD polymorphism, 8-hydroxy-2'-deoxyguanine (8-OH-dG) level, and relative density of apurinic sites (AP-sites). Meanwhile, melatonin treatment partially alleviated the SA-induced G1/S arrest in HN95 and G2/M arrest in HH49, thus enhancing soybean seedling tolerance to SA stress.

An analysis of stimulation methods used in rehabilitation equipment for children with cerebral palsy.

Objective: This paper summarizes the research progress into stimulation methods used in rehabilitation equipment for pediatric cerebral palsy (CP) for the past 20 years from 2003 to 2023. We also provide ideas for innovative research and development of artificial intelligence-based rehabilitation equipment. Methods: Through a certain search strategy, Keywords are searched in the China National Knowledge Network Database (CNKI), the Wanfang Database knowledge service platform, the Chongqing VIP information service, PubMed, Web of Science, Cochrane, ScienceDirect, Medline, Embase, and IEEE database. A total of 3,049 relevant articles were retrieved, and 49 articles were included that mentioned research and development of rehabilitation equipment. We excluded articles that were not specific to children with CP, were duplicated or irrelevant literature, were missing data, the full article was not available, the article did not describe the method of stimulation used with the rehabilitation equipment on children with CP, were not Chinese and English, and were the types of reviews and commentaries. Results: Physical stimulation is the main stimulation method of rehabilitation equipment for children with CP. Force stimulation is the main mode of physical stimulation, and there are 17 articles that have verified the clinical efficacy of force stimulation-based equipment. Conclusion: Research on the stimulation mode of pediatric cerebral palsy rehabilitation equipment is likely to focus on simulating the force of the Chinese medicine called "tuina manipulation." When this method is combined with artificial intelligence and personalized direction we believe this will lay the foundation for future development of a novel therapy for children with CP.

Enhancing the Development and Growth of Infant Cerebral Palsy Rats Using Selective Spinal Manipulations.

Cerebral palsy (CP) is a refractory pediatric disease with a high prevalence, high disability rate, and difficult treatment. A variety of treatments are currently used for CP. The treatment involves drug and non-drug therapy. Traditional Chinese medicine external therapy is a very distinctive treatment method in non-drug therapy. As one of the external therapies of traditional Chinese medicine, massage is used in treating cerebral palsy and has good efficacy, small side effects, and strong operability. As a part of TCM external therapy, selective spinal manipulation can effectively promote the growth and development of infant rats with cerebral palsy.The operation was mainly divided into four steps: first, the rubbing method was applied to the spine and both sides of the spine for 1 min. The pressing and kneading method was applied to the spine for 5 min, and the muscles on both sides of the spine for 5 min. Second, pressing and kneading the sensitive local acupoints in the spine for 2 min were performed. Thirdly, the affected limb was treated by twisting method for 1 min. Fourth, the rubbing method was applied to a midline from the forehead to the back of the brain for 1 min. This study aimed to use selective spinal manipulation to treat infant rats with cerebral palsy. The weight, Rotarod test, Foot-fault score, and growth hormone of infant rats with cerebral palsy were detected to understand the effect of selective spinal manipulation on the growth and development of infant rats with cerebral palsy. The results showed that it can promote weight gain, improve balance ability and motor function, promote growth and development of infant cerebral palsy rats, promote growth hormone secretion, and increase the temperature of sensitive parts of the back.

Modified endoscopic submucosal tunnel dissection for large esophageal submucosal gland duct adenoma: A case report.

BACKGROUND: With the recent improvement of endoscopic techniques, endoscopic ultrasound-guided fine needle aspiration and endoscopic submucosal tunnel dissection (ESTD) have been widely used for accurate diagnosis and dissection acceleration of esophageal tumors. CASE SUMMARY: We used a modified submucosal tunnel technique during endoscopic en bloc resection in a 58-year-old man with large esophageal submucosal gland duct adenoma (ESGDA). During modified ESTD, the oral end of the involved mucosa was cut transversely, followed by a submucosal tunnel created from the proximal to the distal end, and the anal end of the involved mucosa blocked by the tumor was incised. As a result of retaining submucosal injection solutions using the submucosal tunnel technique, it was possible to reduce the amount of injection required and increase the efficiency and safety of dissection. CONCLUSION: Modified ESTD is an effective treatment strategy for large ESGDAs. Single-tunnel ESTD appears to be a time-saving procedure compared with conventional endoscopic submucosal dissection.

Gas-alternating-water infusion method with/without internal traction assistance: a novel technique of endoscopic submucosal dissection for large colorectal tumors regardless of gravity direction.

Introduction: Endoscopic submucosal dissection (ESD) using underwater technique has been developed to make colorectal ESD easier and safer. We have carried out a novel technique of colorectal ESD using gas-alternating-water infusion method for en-bloc resection of large colorectal tumors. Aim: To evaluate the feasibility and safety of colorectal ESD using the gas-alternating-water infusion method (GAW-ESD) with or without internal traction assistance depending on the level of exposure of the submucosal space, for large colorectal tumors (≥ 3 cm in size). Material and methods: All 8 patients were kept in the left lateral position during GAW-ESD as follows: (1) C-shaped mucosal incision. (2) The colorectal lumen was instilled with normal saline. Then the mucosal flap on the lower side of gravity was created with the help of buoyancy, followed by a V-shaped dissection both below and above the liquid surface, if necessary, assisted by internal traction using one-matching-many repositionable clips attached to one rubber band. (3) The post-ESD defect was closed underwater using repositionable clips. Results: GAW-ESD was performed successfully in 8 patients, five without internal traction, three with internal traction. The en-bloc resection rate was 100%. No perforation occurred. Only 1 patient suffered from post-ESD bleeding, which was resolved by endoscopic clipping. Conclusions: GAW-ESD with/without internal traction is safe and effective for en-bloc resection of large colorectal tumors, with the advantages of quick gas/liquid switch, stable platform, fixed position, buoyancy effect, counteraction design, dissection acceleration, heat-sink effect, optical zoom effect, and downsizing effect.

miR-204-5p promotes preeclampsia serum-induced injury in human umbilical vein endothelial cells through regulation of the PTPRJ/Notch axis.

OBJECTIVES: Preeclampsia (PE) remains the leading cause of high morbidity and mortality in pregnancy. Injury of human umbilical vein endothelial cells (HUVECs) contributes to PE initiation. This study aims to analyze the molecular mechanism of PE-induced injury in HUVECs. METHODS: HUVECs were cultured with serum collected from PE patients and healthy pregnant women. PE-treated HUVECs were transfected with miR-204-5p inhibitor, si-protein tyrosine phosphatase receptor J (PTPRJ), and FLI-06 (Notch signaling pathway inhibitor). Cell viability, apoptosis, migration, and angiogenesis were determined using the cell counting kit-8 method, flow cytometry, wound healing assay, tube formation assay, and ELISA. The binding relationship between miR-204-5p and PTPRJ 3'UTR sequence was verified using dual-luciferase reporter assay. The expressions of miR-204-5p, PTPRJ, Notch, and HES1 were determined using qRT-PCR and Western blot analysis. RESULTS: miR-204-5p levels were higher in PE serum. PE-treated HUVECs showed elevated miR-204-5p expression and apoptosis and reduced migration, angiogenesis and VEGF level. miR-204-5p inhibition alleviated HUVEC injury and upregulated PTPRJ transcription. Silencing PTPRJ partly reversed the protecting role of miR-204-5p inhibition in HUVECs. PTPRJ downregulation or FLI-06 treatment limited the expressions of Notch and HES1 and blocked the activation of the Notch signaling pathway, consequently promoting HUVEC injury. CONCLUSIONS: miR-204-5p inhibited PTPRJ transcription and the activation of the Notch signaling pathway, thereby enhancing HUVEC injury.

Intrapartum and early postpartum glycemic profiles in women with gestational diabetes mellitus: an observational study.

BACKGROUND: Data on the glycemic profile of pregnant women with gestational diabetes mellitus (GDM) during the perinatal period are sparse. This study described the intrapartum and early postpartum glucose profiles among pregnant women with GDM, and analyzed factors potentially affecting glycemic parameters during the period. METHODS: This was a prospective observational study conducted from March 2020 to November 2021. Pregnant women with GDM receiving lifestyle interventions alone during pregnancy and matched women with non-diabetic pregnancies (NDPs) were enrolled from among patients admitted to the obstetrics department for childbirth. Glucose monitoring was performed via a flash glucose monitoring (FGM) system on admission, and glucose readings during labor and early postpartum were analyzed. The clinical characteristics and FGM-based parameters of participants in the two groups were compared. RESULTS: A total of 124 participants (mean age: 29.5 ±â€Š3.5 years, 92 [74.2%] primipara) were included in the final analysis. A total of 17,571 glucose readings were retrieved. There were no significant differences in clinical characteristics between the GDM (n = 60) and NDP (n = 64) groups. The average glucose level was 92.2 mg/dL, and the level was higher in the GDM group (95.5 ±â€Š12.1 mg/dL vs. 89.1 ±â€Š13.4 mg/dL, P = 0.008) during the intrapartum and early postpartum periods. The data were split into the intrapartum period (from the start of labor to delivery of the placenta) and the early postpartum period (within 24 h after placental delivery) for analysis. During intrapartum, women with GDM exhibited glycemic profiles and fluctuations similar to those in the NDP group. However, women with GDM had higher postpartum glucose levels (97.7 ±â€Š13.4 mg/dL vs. 90.8 ±â€Š15.3 mg/dL, P = 0.009), a longer time spent >140 mg/dL (8.7 ±â€Š9.3% vs. 5.9 ±â€Š10.3%, P = 0.011), and greater glycemic fluctuations than those with NDP. Postpartum hyperglycemia in GDM might be associated with high parity and postprandial glucose abnormalities in GDM screening tests. CONCLUSION: Compared to those with normoglycemia, pregnant women with GDM receiving lifestyle interventions alone had similar intrapartum glucose profiles but higher early postpartum glucose levels and greater glucose variability, providing evidence for modification of the current perinatal glucose monitoring strategy for GDM. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR2000030972.

Purse-indigitation mechanical anastomosis vs. traditional mechanical anastomosis undergoing McKeown esophagectomy: a retrospective comparative cohort study.

Background: Postoperative anastomosis-related complication rates remain high in patients undergoing McKeown esophagectomy with cervical anastomosis, and the optimal anastomotic technique remains under debate. We describe a new method of anastomosis, referred to as purse-indigitation mechanical anastomosis (PIMA) by reinforcing esophagogastric anastomosis, which can be performed after minimally invasive surgery. This study was designed to compare its feasibility, efficacy, and safety with those of traditional mechanical anastomosis (TMA). Methods: Between September 2020 and January 2022, 264 patients undergoing McKeown esophagectomy at a single center were included. Demographic data, including patient age, sex, diagnosis, neoadjuvant chemotherapy/radiation therapy in cases of malignancy, comorbidities, and operation time, anastomotic time, estimated blood loss, post­operative complications were collected. Their medical records were retrospectively reviewed, analyzed and compared between the PIMA and TMA cohorts. Results: The baseline comparability of the PIMA and TMA before the comparisons is no statistical difference. Univariable analysis revealed significantly decreased anastomotic leak rate with PIMA compared to TMA (4.10% vs. 11.59%, P=0.04). No significant difference was demonstrated in total operation time, estimated blood loss, postoperative hospital stay, or pulmonary complications between PIMA and TMA (243.94±21.98 vs. 238.70±28.45 min; 201.10±67.83 vs. 197.39±65.13 mL; 8.83±2.77 vs. 9.35±3.78 days; 8.21% vs. 11.59%; all P>0.05). The incidence of postoperative pulmonary complications (3.44% vs. 50%) was significantly associated with an increased rate of anastomotic leak [odds ratio (OR): 15.50; 95% confidence interval (CI): 4.81-43.71; P<0.01]. Conclusions: PIMA is feasible, safe to perform, and demonstrated a leak rate less than half that of TMA in this study. PIMA may represent a superior alternative to standard esophagogastric cervical anastomosis techniques. Larger sample size and long-term survival are required to fully evaluate PIMA.

Small bowel preparations for capsule endoscopy with mannitol and simethicone: a prospective, randomized, clinical trial.

BACKGROUND AND OBJECTIVE: There is no consensus concerning small bowel preparation before capsule endoscopy (CE). This study evaluated the effects of 4 regimens on small bowel cleansing and diagnostic yield. METHODS: Patients were randomly divided into 4 groups. Group A consumed a clear liquid diet after lunch on the day before CE, followed by overnight fasting. Group B took 250 mL 20% mannitol and 1 L 0.9% saline orally at 05:00 hours on the day of the procedure. In group C, the same regimen was taken at 20:00 hours on the day before and at 05:00 hours on the day of CE. In group D, in addition to the group C regimen, 20 mL oral simethicone was taken 30 minutes before CE. RESULTS: Two hundred patients were prospectively enrolled, and 7 were excluded from the final analysis because of incomplete small bowel transit. No significant difference was noted among the 4 groups for small bowel transit time. Bowel preparation in group D was significantly better than for the other regimens for overall cleansing of the proximal small bowel, and showed improved overall cleansing of the distal small bowel when compared with 10-hours overnight fasting. Pathological lesions of the proximal and distal small bowel were, respectively, achieved in 82 and 74 patients, mostly distributed in group D. CONCLUSIONS: Small bowel preparation that involves split-dose oral mannitol plus single-dose simethicone for CE can improve mucosal visualization and subsequent diagnostic yield when compared with 10-hours overnight fasting.

The natural compound puerarin alleviates inflammation and apoptosis in experimental cell and rat preeclampsia models.

Puerarin (Pue), an isoflavone derived from Radix puerariae, exerts anti-apoptosis and anti-inflammatory effects. However, the protective effect of Pue on PE is still unknown. The present study aimed to investigate whether Pue alleviates symptoms of PE and suppresses inflammation and apoptosis in vitro and in vivo. A cell model of PE was established by exposing HTR8/SVneo cells to LPS and an RNA-SEQ study was performed in LPS-stimulated HTR8/SVneo cells. We also established a rat model of PE by injecting pregnant rats with LPS and the basic preeclamptic symptoms were evaluated. Additionally, the placental histology, placental inflammation cytokines, and apoptosis markers were also measured. Pue protected HTR8/SVneo cells from LPS-evoked cytotoxicity, decreased the levels of sFlt-1, ET-1, and tPA in HTR8/SVneo cells. RNA-SEQ results revealed the significant changes in the expression levels of hub genes (TNF, IL-6, Jun, and NFKBIA) related to multiple inflammatory pathways, including the TNF signaling pathway, IL-17 signaling pathway, inflammatory disease, and NF-κB signaling pathway. After administration of Pue, we observed that LPS-evoked PE symptoms (hypertension, proteinuria, and fetal growth restriction), were reversed. Besides, Pue improved placental pathology change and reducing placental sFlt-1, ET-1, and tPA mRNA expression. Abnormal placental inflammatory cytokines (TNF, IL-6, IFN-γ, and IL-4) and apoptosis markers (Bcl-2, Bax, caspase-3, caspase-8, and caspase-9) expressions in the LPS-treated group were reversed after Pue treatment. Our findings revealed that Pue plays beneficial roles in PE models, and therefore possesses the therapeutic potential for prevention and treatment of PE.

The zinc finger transcription factor, KLF2, protects against COVID-19 associated endothelial dysfunction.

Coronavirus disease 2019 (COVID-19) is regarded as an endothelial disease (endothelialitis) with its patho-mechanism being incompletely understood. Emerging evidence has demonstrated that endothelial dysfunction precipitates COVID-19 and its accompanying multi-organ injuries. Thus, pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications. The objective of the present study is to evaluate whether kruppel-like factor 2 (KLF2), a master regulator of vascular homeostasis, represents a therapeutic target for COVID-19-induced endothelial dysfunction. Here, we demonstrate that the expression of KLF2 was reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules, ICAM1 and VCAM1. IL-1ß and TNF-α, two cytokines elevated in cytokine release syndrome in COVID-19 patients, decreased KLF2 gene expression. Pharmacologic (atorvastatin and tannic acid) and genetic (adenoviral overexpression) approaches to augment KLF2 levels attenuated COVID-19-serum-induced increase in endothelial inflammation and monocyte adhesion. Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function (vasodilation, anti-inflammation, antioxidant status, anti-thrombosis/-coagulation, anti-fibrosis, and reduced angiogenesis). Finally, knockdown of KLF2 partially reversed the ameliorative effect of atorvastatin on COVID-19-serum-induced endothelial inflammation and monocyte adhesion. Collectively, the present study implicates loss of KLF2 as an important molecular event in the development of COVID-19-induced vascular disease and suggests that efforts to augment KLF2 levels may be therapeutically beneficial.

Deep learning driven colorectal lesion detection in gastrointestinal endoscopic and pathological imaging.

Colorectal cancer has the second highest incidence of malignant tumors and is the fourth leading cause of cancer deaths in China. Early diagnosis and treatment of colorectal cancer will lead to an improvement in the 5-year survival rate, which will reduce medical costs. The current diagnostic methods for early colorectal cancer include excreta, blood, endoscopy, and computer-aided endoscopy. In this paper, research on image analysis and prediction of colorectal cancer lesions based on deep learning is reviewed with the goal of providing a reference for the early diagnosis of colorectal cancer lesions by combining computer technology, 3D modeling, 5G remote technology, endoscopic robot technology, and surgical navigation technology. The findings will supplement the research and provide insights to improve the cure rate and reduce the mortality of colorectal cancer.

Peroral traction-assisted natural orifice trans-anal flexible endoscopic rectosigmoidectomy followed by intracorporeal colorectal anastomosis in a live porcine model.

BACKGROUND: Compared to traditional open surgery, laparoscopic surgery has become a standard approach for colorectal cancer due to its great superiorities including less postoperative pain, a shorter hospital stay, and better quality of life. In 2007, Whiteford et al reported the first natural orifice trans-anal endoscopic surgery (NOTES) sigmoidectomy using transanal endoscopic microsurgery. To date, all cases of NOTES colorectal resection have included a hybrid laparoscopic approach with the use of established rigid platforms. AIM: To introduce a novel technique of peroral external traction-assisted transanal NOTES rectosigmoidectomy followed by intracorporeal colorectal end-to-end anastomosis by using only currently available and flexible endoscopic instrumentation in a live porcine model. METHODS: Three female pigs weighing 25-30 kg underwent NOTES rectosigmoid resection. After preoperative work-up and bowel preparation, general anesthesia combined with endotracheal intubation was achieved. One dual-channel therapeutic endoscope was used. Carbon dioxide insufflation was performed during the operation. The procedure of trans-anal NOTES rectosigmoidectomy included the following eight steps: (1) The rectosigmoid colon was tattooed with India ink by submucosal injection; (2) Creation of gastrostomy by directed submucosal tunneling; (3) Peroral external traction using endoloop ligation; (4) Creation of rectostomy on the anterior rectal wall by directed 3 cm submucosal tunneling; (5) Peroral external traction-assisted dissection of the left side of the colon; (6) Trans-anal rectosigmoid specimen transection, where an anvil was inserted into the proximal segment after purse-string suturing; (7) Intracorporeal colorectal end-to-end anastomosis using a circular stapler by a single stapling technique; and (8) Closure of gastrostomy using endoscopic clips. All animals were euthanized immediately after the procedure, abdominal exploration was performed, and the air-under-water leak test was carried out. RESULTS: The procedure was completed in all three animals, with the operation time ranging from 193 min to 259 min. Neither major intraoperative complications nor hemodynamic instability occurred during the operation. The length of the resected specimen ranged from 7 cm to 13 cm. With the assistance of a trans-umbilical rigid grasper, intracorporeal colorectal, tension-free, end-to-end anastomosis was achieved in the three animals. CONCLUSION: Peroral traction-assisted transanal NOTES rectosigmoidectomy followed by intracorporeal colorectal end-to-end anastomosis is technically feasible and reproducible in an animal model and is worthy of further improvements.

SUMO4 M55V variant is associated with diabetic nephropathy in type 2 diabetes.

OBJECTIVE-SUMO4 mRNA was recently found to be mainly expressed in the kidney, and the methionine-to-valine substitution at codon 55 (M55V) variant of SUMO4 may induce higher nuclear factor-kappaB (NF-kappaB) activity. Because NF-kappaB is known to mediate the development of diabetic nephropathy, we examined the association between the SUMO4 M55V variant and the severity of diabetic nephropathy. RESEARCH DESIGN AND METHODS-We recruited a total of 430 patients with type 2 diabetes. The M55V (rs237025, 163A-->G) polymorphism of SUMO4 was genotyped by real-time PCR, and urine albumin concentration was measured by radioimmunoassay. RESULTS-The frequencies of SUMO4 AA, GA, and GG were 52.6, 40.7, and 6.7%, respectively, in the normoalbuminuric group; 45.5, 47.3, and 7.1% in the microalbuminuric group; and 36.9, 46.2, and 16.9% in the macroalbuminuric group. We detected a significant linear trend for SUMO4 genotype between the macroalbuminuric and normoalbuminuric groups. The mean urine albumin-to-creatinine ratio (42.3 +/- 108.82 mg/mmol) in the GG group was significantly higher than in the AA (14.9 +/- 51.49 mg/mmol) and GA (17.0 +/- 43.74 mg/mmol) groups. Multivariate logistic regression analysis showed the SUMO4 M55V variant to be independently associated with the severity of diabetic nephropathy. CONCLUSIONS-This study indicates that the SUMO4 gene M55V variant is associated with severity of diabetic nephropathy in patients with type 2 diabetes.

PD-1/PD-L1 regulates Treg differentiation in pregnancy-induced hypertension.

Pregnancy-induced hypertension (PIH) causes significant maternal and fetal morbidity and mortality. A decreased number of regulatory T (Treg) cells is associated with the pathogenesis of PIH. The programmed cell death-1 (PD-1)/PD-ligand 1 (PD-L1) pathway is critical to normal pregnancy (NP) by promoting Treg cell development. However, the relationship between PD-1/PD-L1 and Treg differentiation in PIH has not been fully elucidated. In this study, venous blood was obtained from 20 NP and 58 PIH patients. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood. The levels of Treg-related cytokines (TGF-ß, IL-10, and IL-35) in serum and PBMCs were measured by ELISA. The percentage of Treg cells in PBMCs was assessed by flow cytometry. The mRNA levels of Treg-specific transcription factor Foxp3 in PBMCs, and PD-1 and PD-L1 in Treg cells were detected by qRT-PCR. The protein levels of PD-1 and PD-L1 in Treg cells were evaluated by western blot. The serum levels of TGF-ß, IL-10, IL-35, and Foxp3 mRNA expression and CD4+CD25+ Treg cell percentage in PBMCs were decreased in PIH. Furthermore, a significant increase of PD-1 in Treg cells was found in PIH compared with NP. In addition, PD-L1 Fc, an activator of PD-1/PD-L1 pathway, increased Treg cell percentage, enhanced Foxp3 mRNA expression, and elevated levels of TGF-ß, IL-10, and IL-35 in PBMCs. However, anti-PD-L1 mAb exerted a reverse effect. These findings revealed that PD-L1 Fc had a favorable effect on Treg cell differentiation, indicating a potential therapeutic value of PD-1/PD-L1 pathway for PIH treatment.

Primary aldosteronism caused by unilateral adrenal hyperplasia: rethinking the accuracy of imaging studies.

A rare type of aldosteronism, known as unilateral adrenal hyperplasia (UAH), is difficult to diagnose, not only because it fails to conform to the typical common subtypes, but also because imaging results are unreliable. We report 2 Taiwanese patients with UAH. Case 1 was a 44-year-old man with 2 episodes of hypokalemic paralysis. Hypertension and suppressed plasma renin activity (PRA) with elevated plasma aldosterone concentration (PAC) were observed. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) showed a right adrenal mass, but adrenal scintigraphy revealed no definite laterality. The patient underwent a laparoscopic right adrenalectomy. Adrenal cortical hyperplasia was discovered from results of the histologic analysis. Case 2 was a 33-year-old woman referred for hypokalemia, hypertension, and a left adrenal mass found on a CT scan. However, MRI revealed normal adrenal glands. The adrenal vein sampling for PAC showed overproduction of PAC from the left adrenal gland. A laparoscopic left adrenalectomy was done. Pathology results revealed micronodular cortical hyperplasia with central hemorrhage. Blood pressure, plasma potassium, aldosterone, and renin activity levels returned to normal after operation in both cases. Both patients have been well for 3 years and 16 months, respectively, after surgery. We review the literature and discuss the limitations of imaging studies.

Raman spectroscopy for early real-time endoscopic optical diagnosis based on biochemical changes during the carcinogenesis of Barrett's esophagus.

Raman spectroscopy is a spectroscopic technique based on the inelastic scattering of monochromatic light that represents the molecular composition of the interrogated volume to provide a direct molecular fingerprint. Several investigations have revealed that confocal Raman spectroscopy can differentiate non-dysplastic Barrett's esophagus from esophageal high-grade dysplasia and adenocarcinoma with high sensitivity and specificity. An automated on-line Raman spectral diagnostic system has made it possible to use Raman spectroscopy to guide accurate target biopsy instead of multiple random forceps-biopsies, this novel system is expected to improve in vivo precancerous diagnosis and tissue characterization of Barrett's esophagus.

Colossolactone H, a new Ganoderma triterpenoid exhibits cytotoxicity and potentiates drug efficacy of gefitinib in lung cancer.

Three pentacyclic triterpene dilactones were isolated from the fruiting bodies of Ganoderma colossum, a medicinal mushroom. Colossolactone H (colo H) as a new compound and the most cytotoxic among the isolates was studied for its anticancer mechanism and the potential use in cancer therapy. Gene expression profiling analysis indicated that treatment of lung cancer cells with colo H caused upregulation of 252 genes and downregulation of 398 genes. Gene ontology enrichment analysis indicated that the downregulated genes were the most significantly enriched in cell cycle progression, and the upregulated genes were significantly enriched in metabolic process, cellular response to stimulus, and oxidation reduction. Accordingly, colo H was found to halt cell growth and induce cell apoptosis via the elevation of cellular reactive oxygen species to cause DNA damage and the increase of tumor suppressor p53 protein. These events facilitate additive cytotoxicity of colo H and gefitinib for gefitinib-resistant H1650 lung cancer cells. Furthermore, combination of colo H and gefitinib effectively inhibited the growth of tumor xenografts in athymic mice. In addition to the efficacy in adjunctive cancer therapy, we have also demonstrated the isolation of colo H from cultivated G. colossum. Thus it is feasible to use colo H or Ganoderma colossum for cancer therapy.

Percutaneous transgastric endoscopic tube ileostomy in a porcine survival model.

AIM: To introduce natural orifice transgastric endoscopic surgery (NOTES) tube ileostomy using pelvis-directed submucosal tunneling endoscopic gastrostomy and endoscopic tube ileostomy. METHODS: Six live pigs (three each in the non-survival and survival groups) were used. A double-channeled therapeutic endoscope was introduced perorally into the stomach. A gastrostomy was made using a 2-cm transversal mucosal incision following the creation of a 5-cm longitudinal pelvis-directed submucosal tunnel. The pneumoperitoneum was established via the endoscope. In the initial three operations of the series, a laparoscope was transumbilically inserted for guiding the tunnel direction, intraperitoneal spatial orientation and distal ileum identification. Endoscopic tube ileostomy was conducted by adopting an introducer method and using a Percutaneous Endoscopic Gastrostomy Catheter Kit equipped with the Loop Fixture. The distal tip of the 15 Fr catheter was placed toward the proximal limb of the ileum to optimize intestinal content drainage. Finally, the tunnel entrance of the gastrostomy was closed using nylon endoloops with the aid of a twin grasper. The gross and histopathological integrity of gastrostomy closure and the abdominal wall-ileum stoma tract formation were assessed 1 wk after the operation. RESULTS: Transgastric endoscopic tube ileostomy was successful in all six pigs, without major bleeding. The mean operating time was 71 min (range: 60-110 min). There were no intraoperative complications or hemodynamic instability. The post-mortem, which was conducted 1-wk postoperatively, showed complete healing of the gastrostomy and adequate stoma tract formation of ileostomy. CONCLUSION: Transgastric endoscopic tube ileostomy is technically feasible and reproducible in an animal model, and this technique is worthy of further improvement.

Diadenosine tetraphosphate protects against injuries induced by ischemia and 6-hydroxydopamine in rat brain.

Diadenosine tetraphosphate (AP4A), an endogenous diadenosine polyphosphate, reduces ischemic injury in the heart. In this study, we report the potent and protective effects of AP4A in rodent models of stroke and Parkinson's disease. AP4A, given intracerebroventricularly before middle cerebral artery (MCA) ligation, reduced cerebral infarction size and enhanced locomotor activity in adult rats. The intravenous administration of AP4A also induced protection when given early after MCA ligation. AP4A suppressed terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) induced by hypoxia/reperfusion in primary cortical cultures, and reduced both ischemia-induced translocation of mitochondrial cytochrome c and the increase in cytoplasmic caspase-3 activity in vivo. The purinergic P2/P4 antagonist di-inosine pentaphosphate or P1-receptor antagonist sulfonylphenyl theophylline, but not the P2-receptor antagonist suramin, antagonized the effect of AP4A, suggesting that the observed protection is mediated through an anti-apoptotic mechanism and the activation of P1- and P4-purinergic receptors. AP4A also afforded protection from toxicity induced by unilateral medial forebrain bundle injection of 6-hydroxydopamine (6-OHDA). One month after lesioning, vehicle-treated rats exhibited amphetamine-induced rotation. Minimal tyrosine hydroxylase immunoreactivity was detected in the lesioned nigra or striatum. No KCl-induced dopamine release was found in the lesioned striatum. All of these indices of dopaminergic degeneration were attenuated by pretreatment with AP4A. In addition, AP4A reduced TUNEL in the lesioned nigra 2 d after 6-OHDA administration. Collectively, our data suggest that AP4A is protective against neuronal injuries induced by ischemia or 6-OHDA through the inhibition of apoptosis. We propose that AP4A may be a potentially useful target molecule in the therapy of stroke and Parkinson's disease.