Intraoperative application of optical coherence tomography for lung tumor.

On-site instant determination of benign or malignant tumors for deciding the types of resection is crucial during pulmonary surgery. We designed a portable spectral-domain optical coherence tomography (SD-OCT) system to do real-time scanning intraoperatively for the distinction of fresh tumor specimens in the lung. A total of 12 ex vivo lung specimens from six patients were enrolled. Three patients were diagnosed with invasive adenocarcinoma (IA), while the others were benign. After OCT-imaged reconstruction, we compared the qualitative morphology of OCT and histology among malignant, benign, and normal tissues. In addition, through analysis of the quantitative data, a discrete difference in optical attenuation coefficients around the junctional surface was shown by our data processing. This study demonstrated a feasible OCT-assisted resection guide by a rapid on-site tumor diagnosis. The results indicate that future deep learning of OCT-captured image systems able to improve diagnostic and therapeutic efficiency is warranted.

Nasopharyngeal Large Cell Neuroendocrine Carcinoma Synchronized With Nasopharyngeal Squamous Cell Carcinoma: A Case Report and Review of Literature.

Neuroendocrine carcinomas (NECs) are poorly differentiated neuroendocrine tumors of the upper respiratory tract. We present an extremely rare case of nasopharyngeal large cell neuroendocrine carcinoma (LCNEC) synchronized with nasopharyngeal squamous cell carcinoma (SCC). Both SCC and LCNEC are associated with Epstein-Barr virus (EBV) infection, supported by the positive result of Epstein-Barr encoding region in-situ hybridization. Strong correlation is found between EBV infection and nasopharyngeal malignancies. Furthermore, the EBV status might be a crucial prognostic factor in nasopharyngeal LCNEC. EBV-positive LCNEC is effective to chemoradiotherapy, and may have preferable outcome than EBV-negative LCNEC arising in the nasopharynx or other sites. The recognition of the EBV status is important for patients to receive appropriate treatment.

Insulinoma-associated Protein 1 Expression and Its Diagnostic Significance in Female Genital Tract Neuroendocrine Carcinomas.

Neuroendocrine carcinomas (NECs) are rare, but aggressive malignant tumors of the female genital tract, especially in the uterine the cervix. Beside histologic morphology, positivity of neuroendocrine markers with immunohistochemistry plays an important role in diagnosis of NECs. Insulinoma-associated protein 1 (INSM1) is a novel marker reported to be widely expressed in a variety of neuroendocrine tumors. A previous study also suggested INSM1 has superior performance to conventional neuroendocrine markers in cervical NECs. In our present study, comparison between immunomarkers was performed in female genital tract NECs. Forty-nine patients with gynecologic NECs (4 vagina, 39 cervix, 5 endometrium, 1 ovary) were included from 1993 to 2019 at our center. Immunohistochemistry was performed with INSM1, CD56, synaptophysin (SYN), chromogranin-A (CgA), and thyroid transcription factor 1 (TTF1). The results show INSM1 has superior sensitivity and intensity compared with CD56, SYN, CgA, and TTF1 in cervical small cell NECs, but not in large cell NECs. In contrast to cervical NECs, INSM1 immunohistochemistry shows only focal and weak staining in endometrial NECs. Our result suggested INSM1 is a sensitive marker which can be used as first-line test in histologic suspicious cervical cases, especially small cell NECs. However, negative INSM1 stain does not exclude the possibility of NECs. In endometrial NECs, conventional panel with CD56, SYN, CgA has better diagnostic performance than INSM1 alone.

Concurrent bilateral testicular hamartomas and serous borderline tumors in a patient with complete androgen insensitivity syndrome: a case report and review of the literature.

We report a case of complete androgen insensitivity syndrome (CAIS) accompanied by serous borderline tumors in a 75-year-old patient. Müllerian epithelial tumors are extremely rare condition in CAIS patients with only a few case reports. We report a case of late-diagnosed testicular feminization with hamartomas, and the first report of serous tumor with borderline malignant potential in such cases.

The use of dehydroepiandrosterone-treated rats is not a good animal model for the study of metabolic abnormalities in polycystic ovary syndrome.

OBJECTIVE: Hyperandrogenism is the hallmark of polycystic ovary syndrome (PCOS). The use of dehydroepiandrosterone (DHEA)-treated rats is thought to be a suitable animal model to study PCOS. In the present study, we assessed the severity of reproductive and metabolic abnormalities in DHEA-treated rats. MATERIAL AND METHODS: Immature female Sprague-Dawley rats were divided into control and DHEA-treated groups. Reproductive parameters including estrus cycle and sex hormones were measured after sexual maturity. Adiposity, insulin sensitivity, and plasma lipid profiles were analyzed to assess metabolic profiles. After sacrifice, the insulin signaling pathway and lipogenic genes were analyzed by immunoblotting and polymerase chain reaction, respectively. RESULTS: An abnormal estrus cycle was observed in the DHEA-treated rats. DHEA treatment also increased plasma testosterone levels and caused multiple cystic follicle formation, which is compatible with the definition of PCOS. There were no significant changes in fasting glucose, fasting insulin, plasma lipid profiles, and blood pressure levels. The adiposity of the DHEA-treated rats was also lower than in the control rats. Moreover, glucose tolerance and insulin sensitivity were only mildly impaired in the DHEA-treated rats after oral glucose tolerance and insulin tolerance tests, even though insulin signaling in skeletal muscles was decreased in the DHEA-treated group. CONCLUSION: DHEA-treated rats had reproductive abnormalities which mimicked symptoms of human PCOS. In metabolic parameters, DHEA treatment did not show insulin resistance in the female rats, suggesting that the use of DHEA-treated rats is not a good animal model for the study of metabolic abnormalities in PCOS.

Correlation between colonic secretion and colonic motility in rats: Role of ghrelin.

AIM: To explore the relationship between colonic secretory function and colonic motility. METHODS: Using a rat model chronically implanted with intracerebroventricular (ICV) and cecal catheters, we validated the correlation between colonic secretion and colonic motor functions, as well as the role of ICV injection volume. RESULTS: Compared to saline controls (5 µL/rat), ICV acyl ghrelin at 1 nmol/5 µL enhanced the total fecal weight, accelerated the colonic transit time, and increased the fecal pellet output during the first hour post-injection, while ICV des-acyl ghrelin at 1 nmol/5 µL only accelerated the colonic transit time. These stimulatory effects on colonic motility and/or secretion from acyl ghrelin and des-acyl ghrelin disappeared when the ICV injection volume increased to 10 µL compared with saline controls (10 µL/rat). Additionally, the ICV injection of 10 µL of saline significantly shortened the colonic transit time compared with the ICV injection of 5 µL of saline. The total fecal weight during the first hour post-injection correlated with the colonic transit time and fecal pellet output after the ICV injection of acyl ghrelin (1 nmol/5 µL), whereas the total fecal weight during the first hour post-injection correlated with the fecal pellet output but not the colonic transit time after the ICV injection of des-acyl ghrelin (1 nmol/5 µL). CONCLUSION: Colonic secretion does not always correlate with colonic motility in response to different colonic stimulations. Acyl ghrelin stimulates colonic secretion.

Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats.

PURPOSE: Urocortin 3 is a key neuromodulator in the regulation of stress, anxiety, food intake, gut motility, and energy homeostasis, while ghrelin elicits feeding behavior and enhances gastric emptying, adiposity, and positive energy balance. However, the interplays between urocortin 3 and ghrelin on food intake and gastric emptying remain uninvestigated. METHODS: We examined the differential effects of central O-n-octanoylated ghrelin, des-Gln14-ghrelin, and urocortin 3 on food intake, as well as on charcoal nonnutrient semiliquid gastric emptying in conscious rats that were chronically implanted with intracerebroventricular (ICV) catheters. The functional importance of corticotropin-releasing factor (CRF) receptor 2 in urocortin 3-induced responses was examined by ICV injection of the selective CRF receptor 2 antagonist, astressin2-B. RESULTS: ICV infusion of urocortin 3 opposed central acyl ghrelin-elicited hyperphagia via CRF receptor 2 in satiated rats. ICV injection of O-n-octanoylated ghrelin and des-Gln14-ghrelin were equally potent in accelerating gastric emptying in fasted rats, whereas ICV administration of urocortin 3 delayed gastric emptying. In addition, ICV infusion of urocortin 3 counteracted central acyl ghrelin-induced gastroprokinetic effects via CRF receptor 2 pathway. CONCLUSION: ICV-infused urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats. Our results clearly showed that enhancing ghrelin and blocking CRF receptor 2 signaling in the brain accelerated gastric emptying, which provided important clues for a new therapeutic avenue in ameliorating anorexia and gastric ileus found in various chronic wasting disorders.

Adipocytes play an etiological role in the podocytopathy of high-fat diet-fed rats.

Obesity is a risk factor that promotes progressive kidney disease. Studies have shown that an adipocytokine imbalance contributes to impaired renal function in humans and animals, but the underlying interplay between adipocytokines and renal injury remains to be elucidated. We aimed to investigate the mechanisms linking obesity to chronic kidney disease. We assessed renal function in high-fat (HF) diet-fed and normal diet-fed rats, and the effects of preadipocyte- and adipocyte-conditioned medium on cultured podocytes. HF diet-fed and normal diet-fed Sprague Dawley rats were used to analyze the changes in plasma BUN, creatinine, urine protein and renal histology. Additionally, podocytes were incubated with preadipocyte- or adipocyte-conditioned medium to investigate the effects on podocyte morphology and protein expression. In the HF diet group, 24 h urinary protein excretion (357.5 ± 64.2 mg/day vs 115.9 ± 12.4 mg/day, P < 0.05) and the urine protein/creatinine ratio were significantly higher (1.76 ± 0.22 vs 1.09 ± 0.15, P < 0.05), increased kidney weight (3.54 ± 0.04 g vs 3.38 ± 0.04 g, P < 0.05) and the glomerular volume and podocyte effacement increased by electron microscopy. Increased renal expression of desmin and decreased renal expression of CD2AP and nephrin were also seen in the HF diet group (P < 0.05). Furthermore, we found that adipocyte-conditioned medium-treated podocytes showed increased desmin expression and decreased CD2AP and nephrin expression compared with that in preadipocyte-conditioned medium-treated controls (P < 0.05). These findings show that adipocyte-derived factor(s) can modulate renal function. Adipocyte-derived factors play an important role in obesity-related podocytopathy.

Peripheral injection of pancreatic polypeptide enhances colonic transit without eliciting anxiety or altering colonic secretion in rats.

Pancreatic polypeptide (PP) is a negative regulator of energy homeostasis that suppresses food intake and lowers body weight. Similar to other gastrointestinal-derived peptides, PP also modulates gastrointestinal motility and may be involved in the regulation of anxiety. Previous studies revealed that PP suppresses gastric emptying but increases colonic motility in mice. In our present study, we assessed the effect of PP on anxiety as well as colonic motility and secretory function. Intracerebroventricular and intravenous routes of PP were administered in conscious rats. Our results showed that intracerebroventricular administration of PP did not affect anxiety in the open field test. Intravenous injection of PP accelerated colonic transit, but did not significantly change fecal amount and fecal fluid composition. On the other hand, intracerebroventricular injection of PP did not alter colonic transit, fecal amount, or fluid composition. In conclusion, peripheral, but not central PP administration enhances colonic motility without eliciting anxiety or altering colonic secretion.

Differential modulation of endogenous cannabinoid CB1 and CB2 receptors in spontaneous and splice variants of ghrelin-induced food intake in conscious rats.

OBJECTIVE: Dysregulation of the endocannabinoid system can lead to the development of obesity and metabolic disorders. Endogenous endocannabinoids act on two cannabinoid receptor subtypes, type 1 (CB1) and type 2 (CB2), to exert their biological actions. The aim of this study was to determine whether CB1 and CB2 receptors modulate feeding behavior. METHODS: We investigated the different roles of CB1 and CB2 receptors in spontaneous and centrally administered splice variants of ghrelin, O-n-octanoylated ghrelin and des-Gln(14)-ghrelin, stimulation of food intake in conscious rats. RESULTS: Intraperitoneal (IP) injection of different doses of selective CB2 receptor antagonist AM-630 (0.3, 1, and 3 mg/kg) enhanced cumulative food intake during the first 12 h with a dome-shaped dose-response relationship in freely fed rats, with the most effective dose being 1 mg/kg. In comparison, the selective CB1 receptor antagonist AM-251 (0.3, 1, and 3 mg/kg, IP) dose-dependently suppressed the cumulative food intake in 16-h food-deprived rats. Centrally administered O-n-octanoylated ghrelin and des-Gln(14)-ghrelin-induced hyperphagic effects were counteracted dose-dependently by IP AM-251, but not AM-630. CONCLUSIONS: We demonstrated that the endogenous CB2 receptor plays a role in inhibiting food intake in the satiated state, whereas the CB1 receptor promotes food intake in the fasted condition. The induction of feeding by central acyl ghrelin is a CB1 receptor-dependent mechanism. Differentially nibbling CB1 and CB2 receptor subtypes may provide a new avenue to treating eating and metabolic disorders.

Losartan ameliorates renal injury, hypertension, and adipocytokine imbalance in 5/6 nephrectomized rats.

The mechanisms underlying insulin sensitivity and fat tissue distribution in chronic renal insufficiency remain unclear. Previous studies have shown the benefits of angiotensin II receptor blockers on moderately nourished to well-nourished patients with the metabolic syndrome. The current study explored the effect of losartan, the first selective angiotensin II receptor blocker, on insulin sensitivity and visceral fat tissue distribution in a 5/6 nephrectomized (N) rat model and investigated the expression of adipose tissue adipocytokines. Male Sprague-Dawley rats (200 g to 250 g) were subjected to 5/6 nephrectomy, and the adipocytes isolated from the visceral fat tissues were then studied. Results showed that desmin expression was significantly suppressed and systolic blood pressure was successfully normalized in the losartan-administered (NA) group. The weight of the visceral fat pad remarkably decreased in the N and NA groups (100 mg/500 ml drinking water) compared with the control group. The weight did not decrease further in the NA group compared with the N group. Insulin resistance was more remarkable in the N group compared with the control and NA groups. Moreover, the adipose tissue expression of adiponectin and leptin was downregulated whereas that of resistin was upregulated in the N group compared with the control group. However, the adiponectin, leptin, and resistin adipose tissue expression returned to their basal values in the NA group. These findings indicated that losartan administration ameliorated renal injury, systolic blood pressure, and adipocytokine imbalance of the adipose tissue in chronic renal insufficiency. Insulin sensitivity was not improved.