The predictors of long-term outcomes after targeted therapy for primary Aldosteronism.

Unilateral primary aldosteronism is thought to be a surgically curable disease, and unilateral adrenalectomy is the mainstay treatment. The Primary Aldosteronism Surgical Outcome (PASO) consensus was developed to assess clinical and biochemical outcomes to standardize the classification of surgical outcomes. However, fewer than half of patients are cured of hypertension after adrenalectomy; therefore, preoperative patient counseling and evaluation might be necessary. Moreover, current studies show that genetic mutations and histopathology classification are associated with the treatment outcome. The Task Force of Taiwan PA recommends using a specific scoring system, including the PASO score and nomogram-based preoperative score, to predict the clinical outcome before adrenalectomy. Herein, we discuss the associations of current histopathological classification and specific somatic gene mutations with clinical outcomes after surgery.

End-to-end interstitial fibrosis assessment of kidney biopsies with a machine learning-based model.

BACKGROUND: The extent of interstitial fibrosis in the kidney not only correlates with renal function at the time of biopsy but also predicts future renal outcome. However, its assessment by pathologists lacks good agreement. The aim of this study is to construct a machine learning-based model that enables automatic and reliable assessment of interstitial fibrosis in human kidney biopsies. METHODS: Validated cortex, glomerulus and tubule segmentation algorithms were incorporated into a single model to assess the extent of interstitial fibrosis. The model performances were compared with expert renal pathologists and correlated with patients' renal functional data. RESULTS: Compared with human raters, the model had the best agreement [intraclass correlation coefficient (ICC) 0.90] to the reference in 50 test cases. The model also had a low mean bias and the narrowest 95% limits of agreement. The model was robust against colour variation on images obtained at different times, through different scanners, or from outside institutions with excellent ICCs of 0.92-0.97. The model showed significantly better test-retest reliability (ICC 0.98) than humans (ICC 0.76-0.94) and the amount of interstitial fibrosis inferred by the model strongly correlated with 405 patients' serum creatinine (r = 0.65-0.67) and estimated glomerular filtration rate (r = -0.74 to -0.76). CONCLUSIONS: This study demonstrated that a trained machine learning-based model can faithfully simulate the whole process of interstitial fibrosis assessment, which traditionally can only be carried out by renal pathologists. Our data suggested that such a model may provide more reliable results, thus enabling precision medicine.

One year follow-up of US-Guided radiofrequency ablation for low-risk papillary thyroid microcarcinoma: The first experience in Taiwan.

BACKGROUND: The incidence of papillary thyroid microcarcinoma (PTMC) has increased rapidly in recent decades, with a favorable overall prognosis. We aimed to evaluate the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for treating low-risk PTMC in Taiwan. METHODS: This prospective study included patients with PTMC who were ineligible or refused surgery and underwent US-guided RFA between October 2018 and June 2020. US and computed tomography (CT) were performed before RFA to assess tumor lesions and exclude cervical lymph node metastasis. Sequential US follow-up following RFA was performed after 1, 3, 6, and 12 months, and yearly thereafter. Volume reduction ratio (VRR) and complete disappearance rate of tumor at one year were evaluated. RESULTS: 13 PTMCs in 12 patients were enrolled with a mean follow-up of 16.2 ± 8.1 months (range, 1-24 months). The median largest tumor diameter and tumor volume before RFA were 0.76 cm and 0.15 ml (range, 0.02-0.37 ml). The median (interquartile range, IQR) volume and VRR at 12 months post-RFA were 0 (0, 0.03) ml (p = 0.033) and 100% (84.26%, 100%) (p = 0.008). Eight tumors (61.54%) were completely disappeared at 12 months post-RFA and no tumor recurrence, lymph nodes, or distant metastasis were noted. All tumors were successfully treated without complications. CONCLUSION: Minimally invasive US-guided RFA is an effective and safe alternative for low-risk PTMC, resulting a satisfied VRR.

Radiofrequency ablation for treatment of thyroid follicular neoplasm with low SUV in PET/CT study.

OBJECTIVES: To evaluate the feasibility of radiofrequency ablation (RFA) on follicular neoplasm with low standard uptake value (SUV) in a Positron emission tomography (PET/CT) study. METHODS: From January 2018 to July 2019, 86 consecutive patients were diagnosed with follicular neoplasm. Of the patients, 28 with PET/CT scans were enrolled in this study. All patients received ultrasound, fine/core needle aspiration, and PET/CT scan prior to treatment. In accordance with previous studies, we recommended 6 patients who had follicular neoplasm with SUVmax ≥5 undergo surgical resection due to an elevated suspicion of malignancy. For 22 patients SUVmax <5, RFA was performed using the moving shot technique. Ultrasound was performed 6 to 12 months after each procedure. RESULTS: Statistically significant volume reductions during follow-up between values prior to RFA and 12 months post RFA were demonstrated (12.6 ± 20.9 vs. 2.4 ± 3.0 cm3, p < 0.001). Volume reduction ratios at 6-12 months (mean: 10.1 months) after RFA were 73.3% ± 17.7%. One patient presented with vocal cord palsy and recovered within 3 months after RFA. No postprocedural hypothyroidism occurred in the RFA patients. CONCLUSIONS: By using PET/CT, we can select patients with low SUV follicular neoplasm. RFA offers a safe and feasible alternative treatment option for patients unsuitable or unwilling to undergo surgery.KEY POINTSBy using positron emission tomography-computed tomography, we can distinguish low SUV follicular neoplasm for radiofrequency ablation.For low SUV follicular neoplasm, RF ablation offers a safe and effective alternative treatment option for patients unsuitable or unwilling to undergo surgery.

Topical tacrolimus and steroids modulate T cells in acute rejection of hand allotransplantation: Two case reports.

Acute rejection is not uncommon after vascularized composite allotransplantation. We reported the effects of adjunctive topical immunosuppressant with topical tacrolimus (Protopic®) and steroid cream (Clobetasol®) in the management of acute rejection in two hand transplantation patients. Case 1 is a 45-year-old male with distal forearm deficit 4 years ago and Case 2 is a 30-year-old male with a proximal forearm deficiency 2 years ago, respectively. Both of them suffered from occupational accident and received hand allotransplantation. Induction was performed with antithymocyte globulins and methylprednisolone. Maintenance therapy consisted of tacrolimus (FK506), mycophenolate mofetil, and prednisone. Both cases experienced acute rejection, which we treated with topical tacrolimus and Clobetasol for 2 weeks, combined with systemic immunosuppressant maintenance therapy without adding pulse-steroid therapy. Clinically, both cases recovered after adjunctive treatments. The skin biopsies showed significantly decreased perivascular lymphocyte infiltration after topical treatment. Immunohistochemical staining showed that CD3+ T-cells and CD20+ B-cells were suppressed in the recovery phase. FoxP3-positive regulatory T cells were increased after treatment. Topical tacrolimus and Clobetasol as an adjunctive treatment with maintenance systemic immunosuppressives may be useful to control acute rejection, which correlated with modulation of lymphocyte activation, especially T cells. The treatment needs further investigation with gaining more comparable data.

MicroRNA-29a Attenuates Diabetic Glomerular Injury through Modulating Cannabinoid Receptor 1 Signaling.

Diabetic nephropathy often leads to end-stage renal disease and life-threatening morbidities. Simple control of risk factors is insufficient to prevent the progression of diabetic nephropathy, hence the need for discovering new treatments is of paramount importance. Recently, the dysregulation of microRNAs or the cannabinoid signaling pathway has been implicated in the pathogenesis of various renal tubulointerstitial fibrotic damages and thus novel therapeutic targets for chronic kidney diseases have emerged; however, the role of microRNAs or cannabinoid receptors on diabetes-induced glomerular injuries remains to be elucidated. In high-glucose-stressed renal mesangial cells, transfection of a miR-29a precursor sufficiently suppressed the mRNA and protein expressions of cannabinoid type 1 receptor (CB1R). Our data also revealed upregulated CB1R, interleukin-1ß, interleukin-6, tumor necrosis factor-α, c-Jun, and type 4 collagen in the glomeruli of streptozotocin (STZ)-induced diabetic mice, whereas the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) was decreased. Importantly, using gain-of-function transgenic mice, we demonstrated that miR-29a acts as a negative regulator of CB1R, blocks the expressions of these proinflammatory and profibrogenic mediators, and attenuates renal hypertrophy. We also showed that overexpression of miR-29a restored PPAR-γ signaling in the renal glomeruli of diabetic animals. Collectively, our findings indicate that the interaction between miR-29a, CB1R, and PPAR-γ may play an important role in protecting diabetic renal glomeruli from fibrotic injuries.

Differential Effects of Statins on Inflammatory Interleukin-8 and Antimicrobial Peptide Human Β-Defensin 2 Responses in Salmonella-Infected Intestinal Epithelial Cells.

Alternative therapies are needed to reduce the use of antibiotics and incidence of drug-resistant Salmonellosis. Previous studies have revealed important roles of statins in regulating innate immunity. Therefore, we investigated the effects of statins on innate immunity in Salmonella-infected intestinal epithelial cells (IECs), which are involved in mucosal innate immunity. SW480 cells and Akt siRNA- or vitamin D receptor (VDR) siRNA-transfected SW480 cells were infected by wild-type S. Typhimurium strain SL1344 in the presence or absence of statins. The mRNA or protein expression was analyzed by real-time quantitative PCR or western blot analysis, respectively. Simvastatin or fluvastatin caused IL-8 (interleukin-8) suppression, but increased hBD-2 mRNA expression in Salmonella-infected SW480 cells. Both statins enhanced phosphorylated Akt and VDR expressions. Akt or VDR knockdown by siRNA counteracted the suppressive effect of simvastatin on IL-8 expression, whereas VDR knockdown diminished the enhanced hBD-2 expression in Salmonella-infected SW480 cells. Therefore, we observed differential regulation of statins on inflammatory IL-8 and anti-microbial hBD-2 expressions in Salmonella-infected IECs via PI3K/Akt signaling and VDR protein expression, respectively. The enhanced activity of antimicrobial peptides by statins in Salmonella-infected IECs could protect the host against infection, and modulation of pro-inflammatory responses could prevent the detrimental effects of overwhelming inflammation in the host.

FDG PET using SUVmax for preoperative T-staging of esophageal squamous cell carcinoma with and without neoadjuvant chemoradiotherapy.

BACKGROUND: Accurate T-staging is pivotal for predicting prognosis and selecting appropriate therapies for esophageal squamous cell carcinoma (ESCC). The diagnostic performance of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for its T-staging is uncertain. We investigated use of FDG PET/CT for preoperative T-staging of patients with ESCC. METHODS: Patients with ESCC given preoperative FDG PET/CT scans, either with (CRT[+] group) or without (CRT[-] group) neoadjuvant chemoradiotherapy, were retrospectively reviewed. Maximal standardized uptake value (SUVmax) of the primary tumors on FDG PET/CT scans were measured, and histopathological results were used as the reference standard. The associations between pathological T-stage and potential factors of age, tumor location, tumor grade, tumor size, and tumor SUVmax were analyzed. The cut-off levels of SUVmax for predicting different T-stages and for residual viable tumors after neoadjuvant chemoradiotherapy were determined using receiver operating characteristic analyses. RESULTS: We enrolled 103 patients (45 in the CRT[-] group; 58 in the CRT[+] group). SUVmax, an independent predictive factor, positively correlated with the pathological T-stage in both groups (CRT[-] group: ρ = 0.736, p < 0.001; and CRT[+] group: ρ = 0.792, p < 0.001). The overall accuracy of the PET/CT with thresholded SUVmax for predicting the pathological T-stage was 73.3% in the CRT[-] group (SUVmax of T0: 0-1.9, T1: 2.0-4.4, T2: 4.5-6.5, T3: 6.6-13.0, T4: >13.0) and 67.2% in the CRT[+] group (SUVmax of T0: 0-3.4, T1: 3.5-3.9, T2: 4.0-5.5, T3: 5.6-6.2, T4: > 6.2). For CRT[-] group, the accuracy using an SUVmax cut-off of 4.4 to differentiate early (T0-1) from locally advanced disease (T2-4) was 82.2% (95% CI, 71.1-93.4%). For CRT[+] group, the accuracy using an SUVmax cut-off of 3.4 to predict residual viable tumors (non-T0) after completion of chemoradiotherapy was 82.8% (95% CI, 73.0-92.5%). CONCLUSIONS: The FDG avidity of a primary esophageal tumor significantly positively correlated with the pathological T-stage. PET/CT with thresholded SUVmax was useful for predicting T-stage and differentiating residual viable tumors.

The First Hand Allotransplantation in Taiwan: A Report at 9 Months.

PURPOSE: Hand transplantations have been initiated and have been encouraged by promising results for more than 1 decade. The aim of this study was to present the first case of hand transplantation performed in Taiwan. MATERIALS AND METHODS: On September 3, 2014, we transplanted the left distal forearm and hand of a brain-dead managed 37 years to a man aged 45 years who had traumatic amputation of the distal third of his right forearm 30 years ago. The total ischemic time during the transplantation was 6 hours and 45 minutes. Immunosuppression included anti-thymocyte globulins, and methylprednisolone (Solumedrol) was used for the induction. Maintenance therapy included systemic tacrolimus, mycophenolic acid [mycophenolate mofetil (MMF)], and prednisone. A combination of systemic (tacrolimus/MMF/prednisolone) and topical immunosuppressant cream (clobetasol and tacrolimus) was applied if acute rejection occurred. Follow-up included routine posttransplant laboratory tests, skin biopsies, intensive physiotherapy, and psychological support. RESULTS: The initial postoperative course was uneventful. No surgical complications were observed. Immunosuppression was well tolerated using tacrolimus, MMF, and prednisone, except for some immune-related complications. One episode of mild clinical and histological signs of cutaneous rejection was seen at 105 days after surgery. These signs disappeared after pulse therapy with Solumedrol and the topical application of immunosuppressive creams (tacrolimus and clobetasol). One infection episode occurred due to local cellulitis and axillary lymphadenopathy on day 140 and was successfully treated with antibiotics. The patient developed cytomegalovirus infection at 7 months that responded to medication. Intensive physiotherapy led to satisfactory progress in motor functioning. Sensory progress (Tinel sign) was good and reached the wrist by 3 months for the median and ulnar nerves, and could be felt in the finger tip by 9 months in response to deep pressure and light touch sensations. The patient has a lateral pinch that allows him to pick up and grip objects during daily living, although his muscle power is still insufficient. CONCLUSIONS: Hand allotransplantation is technically feasible. Currently available immunosuppression methods seem to control vascularized composite tissue allotransplantation rejection. A combination of topical and systemic immunosuppressants is a useful method to prevent acute hand allotransplant rejection.

Thoracoscopic removal of hypertrophic mediastinal parathyroid glands in recurrent secondary hyperparathyroidism.

BACKGROUND: Hypertrophic mediastinal parathyroid glands (HMPGs) play a role in recurrent secondary hyperparathyroidism (SHPT). Thoracoscopic retrieval of HMPGs has been proposed. METHODS: Twelve patients with recurrent SHPT owing to HMPGs were enrolled. We divided the locations of HMPGs below the innominate vein and right to the ascending aorta as Zone I, those below the innominate vein and left to the ascending aorta as Zone II, and those between the aortic arch and pulmonary artery as Zone III. Sestamibi scans combined with computed tomography (CT) scans were arranged to identify the location of HMPGs. Three trocars of the right or left thoracoscopic approach were applied for Zone I or Zone II; four trocars of the left thoracoscopic approach were applied for Zone III. RESULTS: Sestamibi and CT scans could positively find the 15 parathyroid glands of the 12 patients. Thirteen HMPGs were retrieved successfully with a thoracoscopic approach. The mean operation time was 155 min (range 80-292) and the mean hospital stay was 5.9 days (4-8). After a mean follow-up of 29.6 months (3-61), calcium and intact parathyroid hormone levels returned to normal ranges in all patients except for one who preferred two-stage surgery. Neither perioperative mortality, nor major complications occurred. CONCLUSIONS: HMPGs in recurrent SHPT may be multiple. Sestamibi scans combined with CT scans can guide optimal approaches. The thoracoscopic approach provides a safe and feasible technique in retrieving HMPGs in Zones I or II using 3 trocars. For HMPGs in Zone III, they should be handled with care using 4 trocars.

Establishment and characterization of an experimental mouse model of allergic rhinitis.

Allergic rhinitis (AR) is a common worldwide disease. Animal studies on AR were adopted in various investigations. However, animal studies simply aimed at establishing an animal model for AR have been seldom seen. The purpose of this study was to introduce an easy-to-establish experimental mouse model of AR. To develop a mouse model of AR, 38 Balb/c mice were randomly assigned to two groups. Mice in the study group were sensitized by intraperitoneal (IP) injection of ovalbumin (OVA) on day 1 and 6, followed by continuous inhalation (IH) of OVA solution for 1 week (day 8-14) using a newly designed inhalation box. The control group mice received sensitization of IP normal saline and IH sterilized distilled water instead of OVA. Before and after sensitization, the frequencies of nasal symptoms (sneezing, nasal rubbing) were recorded and the serum levels of total immunoglobulin E (IgE) were evaluated using ELISA. Finally, the murine nasal mucosal tissues were stained by Giemsa solution to estimate the degree of mast cell infiltration. After sensitization by IP and IH OVA, the study group showed significant phenotypic changes including increased sneezing and rubbing. Pathological and cytological findings also confirmed significant elevated serum total IgE titer and local mast cell infiltration in the study group statistically. We successfully developed a workable experimental animal model for AR that was more easily sensitized using our new-designed inhalation box, with less stress and more precisely to be observed.

Renal MALT lymphoma associated with Waldenström macroglobulinemia.

Mucosa associated lymphoid tissue lymphoma (MALT lymphoma) is mostly seen in the gastrointestinal tract; origin from the kidney is extremely rare. Waldenström macroglobulinemia (WM) is a clinicopathologic syndrome denoted by the presence of monoclonal gammopathy in the serum, typically caused by lymphoproliferative disorder. Literature review did not find any report of renal MALT lymphoma accompanied by WM. Herein, for the first time, we report a 72 year-old female patient with a history of chronic kidney disease, presenting with solitary renal mass; MALT lymphoma was confirmed by pathological examination. A serology study identified the presence of WM. No manifestation of hyperviscosity syndrome was noted. Bone marrow biopsy disclosed the concurrent systemic involvement. Her treatment response was uneventful and the renal mass responded with regressive change in size after chemotherapy. The renal function remained stable during follow-up. MALT lymphoma should be considered as an underlying pathology of isolated renal mass. Furthermore, patients with MALT lymphoma should be screened for Waldenström macroglobulinemia and hyperviscosity syndrome.

Hepatoma-derived growth factor upregulation is correlated with prognostic factors of early-stage cervical adenocarcinoma.

Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor that plays an important role in the progression of different types of cancer. A total of 63 patients with early-stage cervical adenocarcinoma (Cx) were enrolled in this retrospective study. The expression of HDGF was significantly increased compared with adjacent non-tumor tissue samples (p < 0.001). Moreover, elevated nuclear HDGF levels were correlated with lymph-vascular space invasion (LVSI; p < 0.05), lymph node metastasis (LNM; p < 0.001), recurrence (p < 0.001) and advanced grade (AG; p < 0.001). The growth of cervical cancer cells (Hela cells) was enhanced by HDGF treatment. The HDGF mRNA and protein level were significantly higher in malignant cervical cancer cells compared with primary ones. By adenovirus gene delivery, HDGF overexpression enhanced, whereas HDGF knockdown perturbed the tumorigenic behaviors of cervical cancer cells. HDGF overexpression is common in early-stage cervical adenocarcinoma and is involved in the carcinogenesis of cervical adenocarcinoma. Cytoplasmic HDGF expression is strongly correlated with pelvic lymph node metastasis and recurrence, indicating that HDGF may serve as a novel prognostic marker for patients with Cx.

The Hazards of Probiotics on Gut-Derived Pseudomonas aeruginosa Sepsis in Mice Undergoing Chemotherapy.

Pseudomonas aeruginosa (P. aeruginosa) is a leading cause of nosocomial infections associated with a high mortality rate and represents a serious threat to human health and the increasing frequency of antimicrobial resistance. Cancer patients are more vulnerable to invasive infection due to ulcerative lesions in mucosal surfaces and immune suppression secondary to chemotherapy. In our in vitro study, we observed that probiotics have the potential to yield beneficial effects on intestinal epithelial cells infected with P. aeruginosa. Additionally, probiotics were found to confer advantageous effects on the innate immunity of mice suffering from Salmonella-induced colitis. As a result, we sought to investigate the impact of probiotics on gut-derived P. aeruginosa sepsis induced by chemotherapy. Following chemotherapy, gut-derived P. aeruginosa sepsis was induced in female C57BL/6 mice aged 6-8 weeks, which were raised under specific-pathogen-free (SPF) conditions in an animal center. Prior to the induction of the sepsis model, the mice were administered 1 × 108 colony-forming units (CFU) of the probiotics, namely Lactobacillus rhamnosus GG (LGG) and Bifidobacterium longum (BL) via oral gavage. We observed that LGG or BL amplified the inflammatory mRNA expression in mice undergoing chemotherapy and suffering from gut-derived P. aeruginosa sepsis. This led to a heightened severity of colitis, as indicated by histological examination. Meanwhile, there was a notable decrease in the expression of antimicrobial peptide mRNA along with reduced levels of zonulin and claudin-2 protein staining within mucosal tissue. These alterations facilitated the translocation of bacteria to the liver, spleen, and bloodstream. To our astonishment, the introduction of probiotics exacerbated gut-derived P. aeruginosa sepsis in mice undergoing chemotherapy. Conclusively, we must be prudent when using probiotics in mice receiving chemotherapy complicated with gut-derived P. aeruginosa sepsis.

Unveiling the Novel Benefits of Co-Administering Butyrate and Active Vitamin D3 in Mice Subjected to Chemotherapy-Induced Gut-Derived Pseudomonas aeruginosa Sepsis.

Cancer patients face increased susceptibility to invasive infections, primarily due to ulcerative lesions on mucosal surfaces and immune suppression resulting from chemotherapy. Pseudomonas aeruginosa (P. aeruginosa) bacteremia is notorious for its rapid progression into fatal sepsis, posing a significant threat to cancer patients, particularly those experiencing chemotherapy-induced neutropenia. This bacterial infection contributes significantly to morbidity and mortality rates among such individuals. Our latest report showed the mutually beneficial effects of postbiotic butyrate on 1,25-dihydroxyvitamin D3 (1,25D3)-controlled innate immunity during Salmonella colitis. Hence, we investigated the impact of butyrate and 1,25D3 on chemotherapy-induced gut-derived P. aeruginosa sepsis in mice. The chemotherapy-induced gut-derived P. aeruginosa sepsis model was established through oral administration of 1 × 107 CFU of the P. aeruginosa wild-type strain PAO1 in C57BL/6 mice undergoing chemotherapy. Throughout the infection process, mice were orally administered butyrate and/or 1,25D3. Our observations revealed that the combined action of butyrate and 1,25D3 led to a reduction in the severity of colitis and the invasion of P. aeruginosa into the liver and spleen of the mice. This reduction was attributed to an enhancement in the expression of defensive cytokines and antimicrobial peptides within the cecum, coupled with decreased levels of zonulin and claudin-2 proteins in the mucosal lining. These effects were notably more pronounced when compared to treatments administered individually. This study unveils a promising alternative therapy that involves combining postbiotics and 1,25D3 for treating chemotherapy-induced gut-derived P. aeruginosa sepsis.

Comparison of cytokine expression and disease severity between plasma cell-dominant and eosinophil-dominant patients in chronic rhinosinusitis with nasal polyps.

PURPOSE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease characterized by inflammation of the nasal and sinus mucosa. The inflammatory patterns may differ among patients, leading to different subtypes based on the dominant inflammatory cell type. This study aimed to compare the differences in cytokine expression and disease severity between plasma cell-dominant and eosinophil-dominant subtypes in patients with CRSwNP. METHODS: This study included 53 CRSwNP patients and 19 control subjects who did not have asthma or a history of cigarette smoking. The expression of cytokines and inflammatory cells was assessed via enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. RESULTS: Among the cytokines analyzed, only IL-6 was significantly different between the two subtypes. A greater proportion of mast cells and IgE cells was present in plasma cell-dominant CRSwNP patients than in eosinophil-dominant group. For the three disease severity scores (LMK-CT, TPS and SNOT-22), objective scores (LMK-CT and TPS) were greater in the eosinophil-dominant CRSwNP group, while the opposite result was shown for the subjective score (SNOT-22). Additionally, the percentage of plasma cell-dominant cells was significantly positively correlated with disease severity according to the TPS and SNOT-22 scores. CONCLUSIONS: Our data revealed that plasma cell-dominant inflammation, a subtype of type 2 CRS, was significantly correlated with subjective disease severity. The study also highlights the role of IL-6, IgE and mast cells as distinguishing factors between eosinophil-dominant and plasma cell-dominant CRSwNP. This information could be useful for clinical diagnosis and personalized treatment.

Preoperative work-up and results of parathyroidectomy plus auto-transplantation for the elderly with secondary hyperparathyroidism.

BACKGROUND: Total parathyroidectomy for secondary hyperparathyroidism has low morbidity and mortality rates and requires a special workup in the preoperative period. METHODS: Neck echography and technetium-99m-sestamibi scintigraphy were performed preoperatively. Cardiac echography, a thallium-201 myocardial perfusion scan, and cardiac catheterization were performed if necessary. During surgery, we removed all the parathyroid glands and the upper thymus and autotransplanted 100 mg of the smallest gland into the subcutaneous tissue of the forearm. RESULTS: The success rate in three months after total parathyroidectomy was 91.7% without mortality. In the elderly (age ≤65 years, n = 35), bone pain, skin itching, general weakness, and insomnia improved three months after surgery, and grip strength increased significantly. One year after parathyroidectomy, the serum levels of Ca, P, alkaline phosphatase, and intact parathyroid hormone were all within the normal ranges. Except for the bone mineral density (BMD) of the radial distal one-third, the BMD of the lumbar spine (L2 to L4), femoral neck, femoral global, and radial global increased significantly. Furthermore, the bone density T-scores of the lumbar spine (L2 to L4), femoral neck, femoral global, radial distal one-third, and radial global improved significantly. CONCLUSIONS: After a meticulous preoperative workup, parathyroidectomy plus autotransplantation can be performed safely for the treatment of symptomatic secondary hyperparathyroidism in the elderly to improve their quality of life and decrease their incidence of bone fractures.

Toll-like receptor-4 agonist inhibits motility and invasion of hepatoblastoma HepG2 cells in vitro.

BACKGROUND: Expression of toll-like receptor-4 (TLR4) on tumor cells is known to mediate innate immune responses that influence tumor cell growth and migration. This study aimed to characterize TLR4 expression and elucidate its functional significance in human hepatoblastoma (HB) cells. PROCEDURE: Immunohistochemistry (IHC) was used to determine TLR4 expression level and its distribution pattern in HB liver tissues. Transcripts of tumor necrosis factor (TNF)-α, interleukin (IL)-8, matrix metalloproteinase (MMP)-2, MMP-13, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 in HB HepG2 cells with lipopolysacharide (LPS) treatment were measured by quantitative PCR. Soluble cytokines and peptides in conditioned media were measured by ELISA. MMP-2 activity was determined by using gelatin zymography. Cell motility and invasiveness was determined using wound healing migration and Matrigel invasion assays, respectively. RESULTS: TLR4 IHC staining demonstrated that TLR4 overexpression in HB liver tissues dramatically vanished after chemotherapy. In vitro study using an HB cell line, HepG2, showed that TLR4 agonist, LPS, significantly decreased transcripts of IL-8 and TNF-α, but did not affect MMP-13 mRNA level. By contrast, LPS only down-regulated IL-8 production and MMP-2 gelatinolytic activity. The latter might be in part due to the increased levels of MMP-2/TIMP-2 complex in conditioned media, thus leading to the decreased motility and invasiveness of HepG2 cells. CONCLUSIONS: HB cells overexpress TLR4, whereas TLR4 agonistic treatment inhibits migration and invasion of HB HepG2 cells. These findings suggest that TLR4 signaling pathway is a potential therapeutic target for control of HB tumor progression.

The Pivotal Role of Aryl Hydrocarbon Receptor-Regulated Tight Junction Proteins and Innate Immunity on the Synergistic Effects of Postbiotic Butyrate and Active Vitamin D3 to Defense against Microbial Invasion in Salmonella Colitis.

Our recent report illustrated the unitedly advantageous effects of postbiotic butyrate on active vitamin D3 (VD3)-orchestrated innate immunity in Salmonella colitis. There is growing awareness that aryl hydrocarbon receptor (AhR) can regulate intestinal immunity and barrier function, through modulating cecal inflammation and junction proteins expression. Hence, we researched the participation of AhR-regulated tight junction functions on the united effects of butyrate and VD3 on intestinal defense to Salmonella infection. Salmonella colitis model were elicited by oral gavage with 1 × 108 CFU of a S. typhimurium wild-type strain SL1344 in C57BL/6 mice. Before and after the colitis generation, mice were fed with butyrate and/or VD3 by oral gavage in the absence or presence of intraperitoneal injection of AhR inhibitor for 4 and 7 days, respectively. We observed that butyrate and VD3 could concert together to reduce the invasion of Salmonella in colitis mice by enhancing cecal cytokines and antimicrobial peptides expression and reducing zonulin and claudin-2 protein expressions in mucosal stain, compared to single treatment, which were counteracted by AhR inhibitor. It implies that AhR is involved in the united effects of butyrate and VD3 on the intestinal defense to Salmonella infection in colitis mice. This study discloses the promising alternative therapy of combining postbiotic and VD3 for invasive Salmonellosis and the pivotal role of AhR pathway.

The Critical Role of Acyl Hydrocarbon Receptor on the Combined Benefits of Postbiotic Propionate on Active Vitamin D3-Orchestrated Innate Immunity in Salmonella Colitis.

Our recent study observed the combined beneficial effects of postbiotic butyrate on active vitamin D3-orchestrated innate immunity to Salmonella Colitis. There is increasing interest in the role of acyl hydrocarbon receptor (AhR) on colitis and innate immunity. Therefore, we investigated the involvement of AhR in the effects. Salmonella colitis model is conducted with 6-8 w/o male C57BL/6 mice: Streptomycin (20 mg/mouse p.o.)-pretreated C57BL/6 mice were mock infected with sterile PBS or infected orally with 1 × 108 CFU of an S. typhimurium wild-type strain SL1344 for 48 h. Before and after the colitis induction, mice were oral gavage with active vitamin D3 0.2 µg/25 g mice (VD3) and/or postbiotics propionate (PP), in the absence of the presence of intraperitoneal injection of AhR inhibitor for 4 and 7 days, respectively. We observed AhR inhibitor counteracted the synergistic effects of PP and VD3 on reducing the severity of Salmonella colitis and body weight loss in C57BL/6 mice, reducing the cecal inflammatory but enhancing antimicrobial peptide mRNAs expression, and reducing the bacterial translocation in liver/spleen, compared to single treatment. It suggests the involvement of AhR on the synergistic effects of postbiotics PP and VD3 on the antibacterial and anti-inflammatory responses in Salmonella colitis and the potential biological treatment of Salmonella colitis.