Clinical prognostic significance of xeroderma pigmentosum group C and IFN­Î³ in non­small cell lung cancer.

Lung cancer is the most common cancer in the world due to its high incidence and recurrence. Genetic instability is one of the main factors leading to its occurrence, development and poor prognosis. Decreased xeroderma pigmentosum group C (XPC) expression notably enhances the stem cell properties of lung cancer cells and increases their proliferation and migration. Additionally, patients with lung cancer and low XPC expression had a poor prognosis. The purpose of the present study was to analyze the effect of XPC and IFN-γ on the clinical prognosis of patients with non-small cell lung cancer (NSCLC). Lung adenocarcinoma specimens were collected from a total of 140 patients with NSCLC. Additionally, from these 140 patients, 48 paracarcinoma tissue specimens were also collected, which were later used to construct tissue microarrays. The expression of XPC and IFN-γ in cancer tissues and in paraneoplastic tissues was detected using immunohistochemistry. The prognosis and overall survival of patients were determined through telephone follow-up. The results showed a positive correlation between expression of XPC and IFN-γ in NSCLC. Additionally, high expression of both markers was associated with a favorable prognosis in patients with NSCLC. The aforementioned findings suggest that the expression of XPC and IFN-γ has prognostic value in clinical practice and is expected to become a marker for clinical application.

Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear. AIM: To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats. METHODS: A T2DM rat model was induced via a high-glucose and high-fat diet, combined with a low-dose streptozotocin injection. T2DM rats were divided into DJB operation and Sham operation groups. DJB surgical intervention was carried out on T2DM rats. The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis. Proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry, quantitative real-time PCR, Western blotting, and immunofluorescence. RESULTS: Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery, compared to the T2DM-Sham groups of rats. Oxidative stress-related proteins (glucagon-like peptide 1 receptor, Nrf2, and HO-1) were significantly increased (P < 0.05) in the hypothalamus of rats with T2DM after DJB surgery. DJB surgery significantly reduced (P < 0.05) hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin (IL)-1ß and IL-6. DJB surgery significantly reduced (P < 0.05) the expression of factors related to neuronal injury (glial fibrillary acidic protein and Caspase-3) in the hypothalamus of T2DM rats and upregulated (P < 0.05) the expression of neuroprotective factors (C-fos, Ki67, Bcl-2, and BDNF), thereby reducing hypothalamic injury in T2DM rats. CONCLUSION: DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.

Fibro-adipose vascular anomaly (FAVA) - diagnosis, staging and management.

BACKGROUND: The diagnosis and treatment of fibro-adipose vascular anomaly (FAVA) of the limb remains challenging since this entity is rare and complex. This paper is aimed to describe the clinical and imaging features, staging and management of this underrecognized disease of the limb. MATERIAL AND METHOD: Patients diagnosed with FAVA and managed between September 2019 and May 2022 in department of pediatric surgery & vascular anomalies of Xi'an international medical center hospital were retrospectively reviewed. Data extracted include age at presentation, previous diagnosis, affected muscles, symptoms, previous treatment, our management, and follow-up. RESULTS: Thirty-two patients with FAVA were diagnosed and managed in our center. There was a female sex predominance, with 23 female (72%) and 9 male (28%) in the cohort. Only one lesion was noticed during infancy; the remaining presented at age 1 to 20 years (median, 7 years). The most commonly involved muscles were gastrocnemius (14/32, 44%) and soleus (13/32, 40%). Swelling (mass), pain and contractures were the most common presentations. MRI featured a heterogeneous and ill-defined intramuscular high signal intensity. Diseases were staged according to clinical features: stage I (pain stage, n = 4), stage II (contracture stage, n = 20) and stage III (deformity stage, n = 8). Patients with stage I disease underwent radical resection and obtained a cure. Patients with stage II disease received radical resection and possible Achilles lengthening, having an outcome of cure. Personalized treatment was required in patients with stage III disease, including radical/partial/staged resection, Achilles lengthening/tenotomy, joint capsulotomy, neurolysis/neurectomy, tendon transfer, stretching exercises, and oral sirolimus/alpelisib. Significant improvement of symptoms was achieved in most. CONCLUSION: The most distinct features of FAVA include enlarging mass, severe pain and contracture. Based on distinct clinical and radiologic features, it is not difficult to make the diagnosis of FAVA. Earlier awareness of this disease can reduce misdiagnoses. Surgery-based comprehensive management can typically improve pain and contracture. Oral sirolimus or alpelisib plays an important role in treatment of unresectable lesions and major nerve involvement. Surgery alone can be curative in early stage FAVA.

Gastrointestinal involvement in Klippel-Trénaunay syndrome: pathophysiology, evaluation, and management.

Klippel-Trénaunay syndrome is typically a complex combined capillary-lymphatic-venous malformation in lower limb. Gastrointestinal involvement is not infrequent in Klippel-Trénaunay syndrome. Rectal bleeding is the most common complication. In recent years, this condition has been increasingly reported. However, most authors simply described extreme manifestations or various combinations of clinical observations. The underlying pathophysiology of gastrointestinal involvement in Klippel-Trénaunay syndrome has been underrecognized. Pathophysiologically, some seemingly adequate managements are pitfalls in treatment. Anorectosigmoid vascular malformations in KTS have distinct and more complicated pathophysiologies than anorectal vascular malformation. Once understanding the pathophysiology, some patients can be successfully managed with a staged plan in our practice. Therefore, recognizing the pathophysiologies of gastrointestinal involvement is needed to evaluate, prevent pitfalls, and determine adequate managements for practitioners. Because of the complexity and rarity of this condition, prospective controlled study or a large cohort of patients is impossible. Based on literature review and our practice, we discuss pathophysiologies, evaluation, pitfalls, and treatment strategies for gastrointestinal involvement in Klippel-Trénaunay syndrome.

Endoscopic Resection for Vascular Anomalies in Children: A New Standard.

OBJECTIVE: To report an innovative endoscopic surgery for subcutaneous vascular malformations and intramuscular fibro-adipose vascular anomaly (FAVA) at our center. BACKGROUND: Historically, open surgical resection has been the treatment of choice. Recent advances in minimally invasive surgery have led to the successful application of endoscopic resection techniques for the surgical management of diseases of soft tissue. METHODS: Patients who underwent endoscopic resection of vascular anomalies were included in this retrospective review. Data were extracted from our Vascular Anomalies Center database between September 2019 and October 2022, including sex, age, symptoms, diagnosis, sites of surgery, previous treatment, surgery, and follow-up. RESULTS: There were 13 females and 15 males in the current study, with ages ranging from 1 to 17 years. The diagnoses included microcystic lymphatic malformation (LM) (n = 8), Klippel-Trénaunay syndrome (n = 7), venous malformation (n = 6), FAVA (n = 6), and mixed cystic LM (n = 1). Surgical sites included the lower extremity (n = 24), abdominal wall (n = 2), upper extremity (n = 1), and thoracic wall (n = 1). Five patients had an intramuscular lesion (FAVA). The endoscopic technique used 2 or 3 small ports in a gas inflation manner. Surgery included thrombectomy, radical resection, and debulking of vascular anomalies. Postoperative sclerotherapy with bleomycin was performed through a drainage tube in 6 patients with microcystic LM. Technical success was obtained in 27 patients. The conversion to open surgery was performed in one patient owing to the deep location of the lesion. No wound-related complication was observed. CONCLUSIONS: Endoscopic surgery is a minimally invasive, effective, and safe treatment for subcutaneous vascular malformations and intramuscular FAVA. This approach can set a new standard that minimizes wound complications and reduces recovery time in patients undergoing resection for benign soft-tissue lesions.

Polysaccharides from Holothuria leucospilota Relieve Loperamide-Induced Constipation Symptoms in Mice.

A vital bioactive component of marine resources is Holothuria leucospilota polysaccharides (HLP). This study examined whether HLP could regulate intestinal flora to treat loperamide-induced constipation. Constipated mice showed signs of prolonged defecation (up by 60.79 min) and a reduced number of bowel movements and pellet water content (decreased by 12.375 and 11.77%, respectively). The results showed that HLP treatment reduced these symptoms, reversed the changes in related protein expression levels in the colon, and regulated the levels of active peptides associated with the gastrointestinal tract in constipated mice, which significantly improved water-electrolyte metabolism and enhanced gastrointestinal motility. Meanwhile, it was found that intestinal barrier damage was reduced and the inflammatory response was inhibited through histopathology and immunohistochemistry. As a means to further relieve constipation symptoms, treatment with low, medium, and high HLP concentrations increased the total short-chain fatty acid (SCFA) content in the intestine of constipated mice by 62.60 µg/g, 138.91 µg/g, and 126.51 µg/g, respectively. Moreover, an analysis of the intestinal flora's gene for 16S rRNA suggested that the intestinal microbiota was improved through HLP treatment, which is relevant to the motivation for the production of SCFAs. In summary, it was demonstrated that HLP reduced loperamide-induced constipation in mice.

Curettage and sclerotherapy technique: A hybrid approach to superficial lymphatic malformation.

OBJECTIVE: To describe the curettage and sclerotherapy technique, a hybrid approach to treatment for superficial lymphatic malformations. METHODS: A retrospective analysis of a lymphatic malformation data base was performed. Patients with superficial lymphatic malformation treated by curettage and sclerotherapy technique with bleomycin were included in this study. Safety and efficacy of the curettage and sclerotherapy technique with bleomycin were evaluated. RESULTS: Between September 2019 and October 2021, 10 consecutive patients (male/female ratio: 4:6; mean age, 10.9 years; range, 3-35 years) presented with superficial lymphatic malformations that were subsequently treated by curettage and sclerotherapy technique with bleomycin. All lesions were located on the trunk and extremities. Each patient received one treatment session and a mean follow-up of 12 months. We observed minor complications. No postoperative infections occurred in this series. No patient developed skin ulceration or necrosis. Scarring and recurrence occurred in one patient. Complete regression was confirmed for all 10 patients by photographic evaluation. CONCLUSION: A curettage and sclerotherapy technique is proposed to treat superficial lymphatic malformation in this study. This technique seems to be safe and highly effective.

Liposuction-Like Sclerotherapy Technique for Microcystic Lymphatic Malformation.

Background The treatment for microcystic lymphatic malformation (LM) remains challenging. We describe the liposuction-like sclerotherapy technique, a new treatment for extensive microcystic LM. Methods LM data was retrospectively reviewed. This study included patients with a microcystic LM component treated by liposuction-like technique with bleomycin sclerotherapy. Results Between June 2016 and October 2019, 39 consecutive patients (male/female ratio: 21:18; mean age, 33.6 months; range: 5 months to 15 years) with microcystic LM were treated by liposuction-like sclerotherapy (LS-LS) technique. Fifty-six sessions of LS-LS were performed (mean of 1.44 sessions per patient; range: one to four sessions). Follow-up ranged 6-30 months (mean of 21 months). We observed no major complications. Transient minor complications included: postoperative noninfectious fever, vomiting, temporary skin edema, pigmentation, mild local depressions, and/or irregularities, and a small hyperpigmented scar at the incision. No postoperative infection, skin ulcer, or necrosis occurred. The patients' symptoms were successfully resolved or stable. A sub-complete response and partial response were observed for 26 (76%) and 13 patients (33%), respectively. Conclusion The LS-LS technique for microcystic LMs is safe, feasible, and effective. This technique is an effective intervention with which it is possible to manage and potentially cure microcystic LM clinically.

The expression of VISTA on CD4+ T cells associate with poor prognosis and immune status in non-small cell lung cancer patients.

Besides the two main histologic types of papillary thyroid carcinoma (PTC), the classical PTC (CL-PTC) and the follicular variant PTC (FV-PTC), several other variants are described. The encapsulated FV-PTC variant was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its similarities to benign lesions. Specific molecular signatures, however, are still unavailable. It is well known that improper DNA repair of dysfunctional telomeres may cause telomere-related genome instability. The mechanisms involved in the damaged telomere repair processing may lead to detrimental outcomes, altering the three-dimensional (3D) nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific 3D nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples, and the telomere length of NIFTP overlaps with that of the FTA histotype. In contrast, there was no association between BRAF expression and telomere length in all tested samples. These preliminary findings reinforce the view that NIFTP is closer to non-malignant thyroid nodules and confirm that PTC features short telomeres.

Internal Iliac Vein Reflux: An Underrecognized Pathophysiology in Klippel-Trénaunay Syndrome With Pelvis Involvement.

Background and objective Internal iliac vein reflux (IIVR) has been underrecognized in Klippel-Trénaunay syndrome (KTS) with pelvis involvement. In this study, our aim was to report clinical and radiological characteristics, modified phlebography technique, and diagnostic and treatment algorithm and outcomes of IIVR in KTS patients with pelvis involvement. Materials and methods KTS patients diagnosed between May 2014 and January 2021 were retrospectively analyzed. The medical records and imaging studies of all patients with KTS of the lower extremities were included and reviewed. KTS was defined as the triad of capillary malformation, venous malformation, and limb overgrowth. Pelvis involvement was evaluated with MRI. Phlebography was performed if IIVR was suspected. IIVR ablation and sclerotherapy were performed if IIVR was confirmed in KTS patients with external genitalia/perineum manifestation and bleeding. Patients were followed up via outpatient consultations. Episodes of gross bleeding were specifically investigated. Results A total of 211 patients with lower limb KTS diagnosed by our team were included in the study. Unilateral IIVR was diagnosed in 97 patients, and bilateral IIVR in two patients; 117 KTS patients were managed with radiological intervention and/or hybrid surgery by our team. Eleven patients underwent an IIVR ablation procedure due to recurrent bleeding from pelvic organs. Postprocedural complications included transient fever (n=2) and mild anaphylactic reaction (n=1). A small hyperpigmented scar at the incision and/or accessing site was noticed in patients receiving bleomycin during the procedure (n=6). Bleeding episodes and anemia resolved in all patients during the follow-up period. Correspondingly, the involved IIV and its tributaries were found to have disappeared on imaging during the follow-up. Conclusion IIVR is common in KTS patients, and it can cause bleeding from pelvic organs. Bleeding can be managed with IIVR ablation and sclerotherapy in KTS with pelvis involvement.

Role of Proximal Intestinal Glucose Sensing and Metabolism in the Blood Glucose Control in Type 2 Diabetic Rats After Duodenal Jejunal Bypass Surgery.

BACKGROUND: Although gastric surgery can significantly improve blood glucose homeostasis in type 2 diabetes mellitus (T2DM), its mechanism remains unclear. This study evaluated the role of intestinal glucose sensing, glucose transport, and metabolism in the alimentary limb (A limb) of T2DM rats after duodenal jejunal bypass (DJB) surgery. METHODS: A T2DM rat model was induced via a high-glucose high-fat diet and low-dose streptozotocin injection. The diabetic rats were divided into two groups: the DJB surgery (T2DM-DJB) group and the sham surgery (T2DM-Sham) group. Wistar rats were used as wild-type control (Control). Small animal PET was used to assess the change in glucose metabolic status in the intestine. The intestinal villi height and the number of EECs after DJB were evaluated. The expressions of sweet taste receptors (T1R2/T1R3), glucose transporters (SGLT1/GLUT2), and key enzymes involved in glucose metabolism (HK2, PFK2, PKM2, G6Pase, and PCK1) in the A limb after DJB was detected by Western blot and qRT-PCR. RESULTS: Small animal PET analysis showed the intestinal glucose metabolism increased significantly 6 weeks after DJB surgery. The intestinal villi height and the number of EECs in the A limb 6 weeks after surgery increased significantly in T2DM-DJB rats comparing to T2DM-Sham rats. The mRNA and protein expression of T1R1/T1R3 and SGLT1/GLUT2 were downregulated in DJB-T2DM rats, while enzymes involved in glucose metabolism was upregulated in the A limb in T2DM-DJB rats. CONCLUSION: Proximal intestinal glucose sensing and metabolism play an important role in blood glucose homeostasis by DJB.

XPC Protein Improves Lung Adenocarcinoma Prognosis by Inhibiting Lung Cancer Cell Stemness.

Objective: Xeroderma Pigmentosum Complementation Group C (XPC) is a protein involving in nucleotide excision repair (NER). XPC also plays an important role in the lung cancer occurrence with the mechanism remian unclear up to date. Studies showed that the increased stemness of lung cancer cells is related to the recurrence and metastasis of lung cancer. This study aimed to study and analyze the correlation of XPC with lung cancer stem cell biomarkers expression and the overall survival (OS) of lung adenocarcinoma patients. Methods: 140 cases of clinical lung adenocarcinoma tissue samples and 48 cases of paired paracancerous tissue samples were made into tissue microarray. Immunohistochemistry (IHC) was used to detect the expression of XPC and CD133 in cancer and paracancerous tissues. Semi-quantitative analysis and statistics were performed by Pannoramic Digital Slide Scanner. The expression of XPC and CD133 in fresh tissues was verified by Western blotting assay. siXPC was used to knock down XPC in lung cancer cell lines to study the effect of XPC on the expression of lung cancer stem cell biomarkers and the ability of cell invasion. And shXPC was used to knockdown XPC in A549 and H1650 to study the effect of XPC on the expression of lung cancer stem cell biomarkers. Results: IHC and Western blotting results showed that XPC expression significantly decreased, while CD133 expression significantly increased in cancer tissues comparing to paracancerous tissues (P XPC < 0.0001, P CD133 = 0.0395). The high level of XPC in cancer was associated with a better prognosis (Log-rank p = 0.0577) in lung adenocarcinoma patients. Downregulation of XPC in lung cancer cells showed increased expression of cancer stem cell biomarkers and the increased cell invasion abilities. Conclusion: It is suggested that XPC can exert the ability of anti-tumor formation, tumor invasion and metastasis inhibition, and prognostic survival improvement in lung adenocarcinoma patients by regulating the stemness of lung cancer cells.

(Pro)renin receptor antagonist PRO20 attenuates nephrectomy-induced nephropathy in rats via inhibition of intrarenal RAS and Wnt/ß-catenin signaling.

INTRODUCTION: (Pro)renin receptor has emerged as a new member of the renin-angiotensin system implicated in the pathogenesis of chronic kidney disease (CKD). Herein we report characterization of the therapeutic potential of (pro)renin receptor (PRR) antagonist PRO20 in 5/6 nephrectomy (5/6Nx) rats. METHODS: Male Wistar rats underwent 5/6Nx followed by treatment with vehicle or received daily injections of a PRR inhibitor PRO20 (700 µg/kg) via the 3 s.c. Sham group served as a control. RESULTS: As compared with the sham control, the 5/6Nx rats exhibited significant increases in proteinuria, glomerulosclerosis, tubular injury, and interstitial inflammation in the remnant kidneys. Treatment with PRO20 significantly attenuated these abnormalities, as evidenced by reduced expression of fibronectin, α-SMA, collagen 1, TGF-ß1, IL-6, IL-8, IL-1ß, MCP-1 and increased expression of E-cadherin. Increased urinary/renal levels of renin activity, angiotensinogen (AGT), and Angiotensin II (Ang II) by 5/6Nx, which were all ameliorated by PRO20. Renal PRR, the secreted proteolytic fragment of PRR (sPRR) in renal and urinary, were all elevated in 5/6Nx rats. Moreover, our results revealed that renal Wnt3A and ß-catenin expression were upregulated during 5/6Nx, which were all attenuated by PRO20. CONCLUSIONS: Overall we conclude that in vivo antagonism of PRR with PRO20 will improve 5/6Nx-induced CKD mainly through inhibition of intrarenal RAS and Wnt/ß-catenin signaling pathway.

Duodenal-Jejunal Bypass Ameliorates Type 2 Diabetes Mellitus by Activating Insulin Signaling and Improving Glucose Utilization in the Brain.

BACKGROUND: Duodenal-jejunal bypass (DJB) can dramatically improve type 2 diabetes independent of weight loss and food restriction. Increasing evidence has demonstrated that brain insulin signaling plays an important role in the pathophysiology of type 2 diabetes. This study explores whether the antidiabetic effect of DJB is involved in brain insulin signaling activation and brain glucose utilization. METHODS: A diabetic rat model was established by high-fat and high-glucose diet. DJB or sham surgery was performed in diabetic rats. 18F-FDG PET scanning was used to detect glucose uptake in different organs, particularly in the brain. The levels of glucose transporters, glucose utilization-related proteins (HK1 and PFK2), insulin, and insulin signaling pathway-related proteins (InsR, IRS1/2, PI3K, and p-Akt) in the brain tissues were evaluated and analyzed. RESULTS: The results showed that DJB significantly improved basal glycemic parameters and reversed the decreasing glucose uptake in the brains of type 2 diabetic rats. DJB significantly increased not only the expression levels of brain insulin, IRS1/2, PI3K, and p-Akt but also the levels of the glucose utilization enzymes HK1 and PFK2 in the brain. CONCLUSION: These results indicate that enhanced brain insulin signaling transduction and brain glucose utilization play important roles in the antidiabetic effect of DJB.

Sirolimus as initial therapy for kaposiform hemangioendothelioma and tufted angioma.

BACKGROUND: Sirolimus has been used to manage various complex vascular anomalies. Kaposiform hemangioendothelioma and tufted angioma may develop Kasabach-Merritt phenomenon in infancy. METHODS: We retrospectively reviewed the clinical and laboratory data of eight patients with kaposiform hemangioendothelioma and tufted angioma who were initially treated using oral sirolimus in our center, including six with Kasabach-Merritt phenomenon. RESULTS: Five girls and three boys seen between September 2012 and March 2015 were included. Age at initiation of sirolimus ranged from 30 days to 14 weeks (mean±SD 8.6 ± 3.5 weeks). Six of these eight patients had kaposiform hemangioendothelioma, and two had a tufted angioma. Platelet count before start of oral sirolimus ranged from 5 × 109 /L to 189 × 109 /L ((78.8 ± 65.2)×109 /L) and fibrinogen level from 68 to 215 mg/dL (123.1 ± 50.5 mg/dL). All patients received standard doses of sirolimus (0.05 mg/kg orally, twice daily) as initial therapy. All patients with thrombocytopenia or hypofibrinogenemia reached a normal platelet count and a normal fibrinogen level within 3 to 4 weeks after sirolimus treatment. Length of treatment ranged from 12 to 79 weeks (39.9 ± 15.3 weeks). Two patients developed grade 2 oral mucositis during treatment. CONCLUSION: Sirolimus as first-line therapy shows great promise in the treatment of kaposiform hemangioendothelioma and tufted angioma.