Specific genetic aberrations of parathyroid in Chinese patients with tertiary hyperparathyroidism using whole-exome sequencing.

Background: Tertiary hyperparathyroidism (THPT) is a peculiar subtype of hyperparathyroidism that usually develops from chronic kidney disease (CKD) and persists even after kidney transplantation. Unlike its precursor, secondary hyperparathyroidism (SHPT), THPT is characterized by uncontrolled high levels of calcium in the blood, which suggests the monoclonal or oligoclonal proliferation of parathyroid cells. However, the molecular abnormalities leading to THPT have not yet been fully understood. Methods: In this study, we analyzed DNA samples from hyperplastic parathyroid and corresponding blood cells of 11 patients with THPT using whole-exome sequencing (WES). We identified somatic single nucleotide variants (SNV) and insertions or deletions variants (INDEL) and performed driver mutation analysis, KEGG pathway, and GO functional enrichment analysis. To confirm the impact of selected driver mutated genes, we also tested their expression level in these samples using qRT-PCR. Results: Following quality control and mutation filtering, we identified 17,401 mutations, comprising 6690 missense variants, 3078 frameshift variants, 2005 stop-gained variants, and 1630 synonymous variants. Copy number variants (CNV) analysis showed that chromosome 22 copy number deletion was frequently observed in 6 samples. Driver mutation analysis identified 179 statistically significant mutated genes, including recurrent missense mutations on TBX20, ATAD5, ZNF669, and NOX3 genes in 3 different patients. KEGG pathway analysis revealed two enriched pathways: non-homologous end-joining and cell cycle, with a sole gene, PRKDC, involved. GO analysis demonstrated significant enrichment of various cellular components and cytobiological processes associated with four genes, including GO items of positive regulation of developmental growth, protein ubiquitination, and positive regulation of the apoptotic process. Compared to blood samples, THPT samples exhibited lower expression levels of PRKDC, TBX20, ATAD5, and NOX3 genes. THPT samples with exon mutations had relatively lower expression levels of PRKDC, TBX20, and NOX3 genes compared to those without mutations, although the difference was not statistically significant. Conclusion: This study provides a comprehensive landscape of the genetic characteristics of hyperplastic parathyroids in THPT, highlighting the involvement of multiple genes and pathways in the development and progression of this disease. The dominant mutations identified in our study depicted new insights into the pathogenesis and molecular characteristics of THPT.

Engineering a functional thyroid as a potential therapeutic substitute for hypothyroidism treatment: A systematic review.

Background: Hypothyroidism is a common hormone deficiency disorder. Although hormone supplemental therapy can be easily performed by daily levothyroxine administration, a proportion of patients suffer from persisting complaints due to unbalanced hormone levels, leaving room for new therapeutic strategies, such as tissue engineering and regenerative medicine. Methods: Electronic searches of databases for studies of thyroid regeneration or thyroid organoids were performed. A systematic review including both in vitro and in vivo models of thyroid regenerative medicine was conducted. Results: Sixty-six independent studies published between 1959 and May 1st, 2022 were included in the current systematic review. Among these 66 studies, the most commonly involved species was human (19 studies), followed by mouse (18 studies), swine (14 studies), rat (13 studies), calf/bovine (4 studies), sheep/lamb (4 studies) and chick (1 study). In addition, in these experiments, the most frequently utilized tissue source was adult thyroid tissue (46 studies), followed by embryonic stem cells (ESCs)/pluripotent stem cells (iPSCs) (10 studies), rat thyroid cell lines (7 studies), embryonic thyroid tissue (2 studies) and newborn or fetal thyroid tissue (2 studies). Sixty-three studies reported relevant thyroid follicular regeneration experiments in vitro, while 21 studies showed an in vivo experiment section that included transplanting engineered thyroid tissue into recipients. Together, 12 studies were carried out using 2D structures, while 50 studies constructed 3D structures. Conclusions: Each aspect of thyroid regenerative medicine was comprehensively described in this review. The recovery of optimal hormonal equilibrium by the transplantation of an engineered functional thyroid holds great therapeutic promise.

A systematic review and meta-analysis of nab-paclitaxel mono-chemotherapy for metastatic breast cancer.

BACKGROUND: Although various clinical trials and real-life studies have tried to explore the value of nab-paclitaxel mono-chemotherapy for metastatic breast cancer (MBC), the safety and efficacy of nab-paclitaxel remain unclear which need to be systematically evaluated. METHODS: Electronic searches for prospective clinical trials evaluating nab-paclitaxel monotherapy for MBC were performed. Requisite data were extracted, integrated and analysed from the included studies according to the different study designs using systematic review and meta-analysis. Meta-regression and subgroup analysis were further performed to explore the potential risk factors affecting each individual outcome of interest following nab-paclitaxel monotherapy. RESULTS: Twenty-two studies with 3287 MBC patients were included. A total of 1685 MBC patients received nab-paclitaxel as first-line therapy, 640 patients as further-line therapy, and 962 patients as mixed-line therapy. A total of 1966 MBC patients (60.40%) received nab-paclitaxel weekly, 1190 patients (36.56%) received nab-paclitaxel triweekly and 99 patients (3.04%) received nab-paclitaxel biweekly. The overall incidence rates of all-grade neutropenia, leukopenia, peripheral sensory neuropathy, and fatigue were 52% (95% CI, 38-66%, I2 = 98.97%), 58% (95% CI, 43-73%, I2 = 97.72%), 58% (95% CI, 48-68%, I2 = 97.17%), and 49% (95% CI, 41-56%, I2 = 94.39%), respectively. The overall response rate (ORR) was 40% (95% CI, 35-45%, I2 = 98.97%), and the clinical benefit rate (CBR) was 66% (95% CI, 59-73%, I2 = 98.97%) following nab-paclitaxel monotherapy. The median progression-free survival (PFS) was 7.64 months (95% CI, 6.89-8.40 months, I2 = 92.3%), and the median overall survival (OS) was 24.51 months (95% CI, 21.25-27.78 months, I2 = 92.7%). Treatment line, human epidermal growth factor receptor-2(Her-2)-negative status and dosage were found to be sources of heterogeneity among the included studies. According to the meta-regression and subgroup analysis, grade 3/4 neutropenia occurred less frequently in Her-2-negative patients than in the entire population (P = 0.046). Patients who received first-line nab-paclitaxel monotherapy showed a higher ORR (P = 0.006) and longer PFS (P = 0.045). Efficacy outcomes were not affected by the administration schedule. However, within the same schedule, patients appeared to have a superior ORR (P = 0.044) and longer PFS (P = 0.03) with an increasing dosage of nab-paclitaxel administered. CONCLUSIONS: The benefits brought by nab-paclitaxel mono-chemotherapy in the treatment of MBC are considerable while the harm is generally manageable. Further study and validation are needed to figure out the roles which the dosage, schedule and other factors play actually in nab-paclitaxel chemotherapy.

ADRB2 is a potential protective gene in breast cancer by regulating tumor immune microenvironment.

BACKGROUND: Breast cancer (BRCA) is the leading cause of cancer death among females. Studies suggested that ß-adrenoceptors involved in tumor progression by regulating immune system. However, how ADRB2 affects the immune infiltration in BRCA is still being unraveled. METHODS: Expressions of ADRB2 in multiple tissues, cancers and blood cells were analyzed by using the Human Protein Atlas and UALCAN database. Expression differentiation of ADRB2 in tumor microenvironment (TME) of BRCA was detected in TISCH database. Correlations between ADRB2 and immune cell infiltration were analyzed by TIMER 2.0, and co-expression genes of ADRB2 were obtained from the cBioPortal website. Functional enrichment analyses and protein-protein interactions were constructed as well. Finally, the potential mechanisms of ADRB2 and candidate drugs targeting BRCA were discussed by using the Metascape, STITCH and Cmap tools. RESULTS: ADRB2 was significantly down-regulated in BRCA, and lower ADRB2 expression often resulted in worse prognosis in BRCA patients. ADRB2 was mainly expressed in breast tissue and blood. Among blood cell subtypes and TME of BRCA, ADRB2 was specifically expressed in T cell subtypes. Also, ADRB2 expression level was positively correlated with the infiltration levels of immune cells such as CD4+ T cell, CD8+ T cell, Tγδ and myeloid DC while negatively correlated with Treg, Tfh and myeloid-derived suppressor cell. Furthermore, functional enrichment analyses revealed that most enriched pathways were immune-related, especially in T cell-related pathways. Also, transcription factors (TFs) analyses showed that most downstream TFs regulated by ADRB2 were immune-related, and most candidate drugs had promising anti-tumor effects. CONCLUSIONS: In conclusion, ADRB2 was a potential protective gene in BRCA, and it might play a vital role in regulating immune responses. The expression level of ADRB2 was positively correlated with immune cells infiltration in BRCA, especially for T cells. Therefore, ADRB2 would be a target for boosting immunotherapy effects in BRCA.

The predictive factors for postoperative hypoparathyroidism and its severity on the first postoperative day after papillary thyroid carcinoma surgery.

PURPOSE: The purpose of the study was to investigate the predictive factors for hypoparathyroidism and its severity on the first postoperative day (POD1) after total thyroidectomy (TT) with or without central neck dissection (CND) in patients with papillary thyroid carcinoma (PTC). METHODS: From February 2014 to February 2019, 2550 PTC patients were admitted to our department. PTC patients who underwent TT were enrolled in this study. A parathyroid hormone (PTH) level lower than 15 pg/mL on POD1 was defined as hypoparathyroidism, and the severity of hypoparathyroidism was classified into three categories according to the level of PTH on POD1: mild hypoparathyroidism (10 pg/mL ≤ PTH < 15 pg/mL), moderate hypoparathyroidism (5 g/mL ≤ PTH < 10 pg/mL), and severe hypoparathyroidism (PTH < 5 pg/mL). Multiple clinical, pathological and surgical parameters of these two different groups were compared and analyzed to demonstrate the possible causes of hypoparathyroidism. Furthermore, patients who developed postoperative hypoparathyroidism were also included in a subgroup analysis according to the severity of their hypoparathyroidism. The underlying factors affecting different severities of hypoparathyroidism were also illustrated with univariate and multivariate analyses. RESULTS: Ultimately, 690 patients who underwent TT were enrolled in this retrospective study. Through the univariate analysis, different surgeons (P < 0.001), extent of CND (P = 0.009), prophylactic calcium supplementation (PCS) (P < 0.001), preoperative (pre-op) PTH level (P < 0.001), and pre-op phosphorus concentration (P = 0.022) were found to be significantly correlated with postoperative hypoparathyroidism. According to the multivariate analysis, PCS was the only independent high-risk factor for hypoparathyroidism. In the univariate analysis of patient subgroups with different severities of hypoparathyroidism, we demonstrated that the tumor T stage (P = 0.021) and pre-op PTH level (P < 0.001) were associated with the severity of hypoparathyroidism. Furthermore, after the multivariate analysis, hypertension (P < 0.001) and pre-op PTH (P < 0.001) were the two independent predictive factors for the severity of hypoparathyroidism after surgery. CONCLUSIONS: Postoperative PCS could increase the risk for PTC patients developing hypoparathyroidism after thyroid surgery. Patients with a history of hypertension and a relatively high pre-op PTH level may not develop severe hypoparathyroidism after TT with CND.

Application of carbon nanoparticles in localization of parathyroid glands during total parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: Intraoperative imaging is used to address the challenges of parathyroidectomy, but no standard modality has been established. This study aimed to assess whether carbon nanoparticle injection is useful in localizing parathyroid glands (PGs) during parathyroidectomy. METHODS: Patients who underwent total parathyroidectomy (TPTX) between September 2015 and November 2018 were included. The operative duration and intact parathyroid hormones (iPTH) were analyzed. RESULTS: A total of 61 patients were included; of these, 32 with carbon nanoparticle injection (TPTX + CN group) and 29 without (TPTX group). The operative duration in the TPTX + CN group was significantly shorter (90.6 ± 21.2 vs 101.4 ± 19.4 min, P = 0.042), which is more apparent in those with normal sized PGs. For those with four enlarged PGs, iPTH levels on 1 day and 1 year postoperatively were significantly lower in the TPTX + CN group (P = 0.032 and P = 0.036, respectively). CONCLUSION: Carbon nanoparticles are useful in the identification normal sized PGs and complete resection of enlarged PGs.

Comparison of Great Curvature Plication with Duodenal-Jejunal Bypass (GCP-DJB) and Sleeve Gastrectomy (SG) on Metabolic Indices and Gut Hormones in Type 2 Diabetes Mellitus Rats.

OBJECTIVE: The present study compared the therapeutic effects of great curvature plication with duodenal-jejunal bypass (GCP-DJB) and the commonly used sleeve gastrectomy (SG) in rats with type 2 diabetes mellitus (T2DM). METHODS: The rats were randomly divided into three groups: Control group (n = 6), SG group (n = 6), and GCP-DJB group (n = 6). Body weight, daily food intake, fasting blood glucose level, fasting insulin level, insulin resistance index, and fasting serum concentrations of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), and bile acid were measured. In addition, postoperative changes in body weight and daily food intake at 2, 4, 6, 8, 10, and 12 weeks were also recorded. At week 12, an oral glucose tolerance test (OGTT) and insulin release test were performed to determine glucose tolerance. The insulin resistance index (IRI) was also measured. The postprandial secretion curves and area under the curve (AUC) of GLP-1, gastric inhibitory polypeptide (GIP), PYY, and bile acid were also calculated. RESULTS: Before surgery, no significant differences in body weight, daily food intake, fasting blood glucose, fasting insulin, insulin resistance index, fasting GLP-1, PYY, and bile acid were found among the three groups (P > 0.05). At postoperative week 12, body weight and food intake in the SG and GCP-DJB groups were lower than those in the Control group (P < 0.05), and body weight in the GCP-DJB group was lowest (P < 0.05). Glucose tolerance, postprandial serum insulin (INS), GLP-1, PYY, and bile acid were significantly higher in the SG and GCP-DJB groups than in the Control group (P < 0.05). The parameters related to glucose metabolism in the GCP-DJB group were higher than those in the SG group with the exception of serum insulin (P < 0.05). In addition, IRI and GIP secretion were significantly lower in the SG and GCP-DJB groups than in the Control group (P < 0.05) and were lowest in the GCP-DJB group (P < 0.05). CONCLUSION: Both GCP-DJB and SG are surgical options for the treatment of T2DM. The underlying mechanism of these treatments may be related to the decrease in body weight, food intake, GIP, IRI, and the increase in INS, GLP-1, PYY, and bile acid. According to the various metabolic indicators related to the hypoglycemic effects in T2DM, GCP-DJB was superior to SG.

Effects of Diet on Bile Acid Metabolism and Insulin Resistance in Type 2 Diabetic Rats after Roux-en-Y Gastric Bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is effective for the treatment of type 2 diabetes mellitus; however, the mechanism remains unclear. METHODS: The effects of RYGB on postprandial responses to three different diets (low carbohydrate (CH)-rich diet, high CH-rich diet, and fat-rich diet) of different nutritional composition in a Goto-Kakizaki (GK) diabetic rat model were assessed by measuring glucose tolerance, insulin resistance, incretin responses, and bile acid (BA) metabolism. RESULTS: GK-RYGB group rats lost weight and preferred low CH-rich diet, but there were no significant differences in BW among the different diets. Glucose tolerance and insulin resistance were improved in rats who underwent RYGB, together with higher levels of circulating BAs, plasma GLP-1, and PYY levels. GK-RYGB rats fed high CH-rich or fat-rich diet showed increased glucose level and insulin resistance, together with high plasma BA, GIP, and PYY levels compared to those fed a low CH-rich diet. CONCLUSION: RYGB improves glucose tolerance and insulin resistance which may be related to BA metabolism and hormone levels, and the nutrient composition of the diet affects the treatment effect of RYGB on T2DM.

Greater Curvature Plication with Duodenal-Jejunal Bypass: a Novel Metabolic Surgery for Type 2 Diabetes Mellitus.

OBJECTIVE: The study investigated the use of great curvature plication with duodenal-jejunal bypass (GCP-DJB) in a type 2 diabetic with obesity rat model. METHODS: Twenty-two Sprague-Dawley rats were given a high fat and sugar diet with subsequent intraperitoneal injection of a small dosage of streptozotocin (30 mg/kg) and randomly assigned to either GCP-DJB (n = 12) or Sham surgery (n = 10). Body weight, peripheral blood glucose, and fasting serum insulin were assayed, and insulin resistance index (IRI) was calculated, before and at 1, 2, 4, and 8 weeks after surgery. RESULTS: No differences were found in the preoperative characteristics of the two groups (P > 0.05). At week 1, the body weights decreased significantly, but there was no significant difference between the two groups (P > 0.05).The fasting blood glucose was significantly lower in the GCP-DJB than in the Sham group (P < 0.05), serum insulin levels were higher (P < 0.05), and IRI began to decline (P < 0.05). From 2 to 8 weeks, the body weight of Sham group gradually recovered and continued to rise, while the GCP-DJB group remained at a relatively lower state. Compared to the Sham group, the body weight, fasting blood glucose as well as IRI of GCP-DJB rats had significantly decreased (P < 0.05). But, the fasting insulin concentrations had significantly increased (P < 0.05). CONCLUSION: This novel GCP-DJB procedure established a stable animal model for the study of metabolic surgery to treat type 2 diabetes mellitus (T2DM).

Changes of Ghrelin/GOAT axis and mTOR pathway in the hypothalamus after sleeve gastrectomy in obese type-2 diabetes rats.

AIM: To examine the changes of the ghrelin/ghrelin O-acyltransferase (GOAT) axis and the mammalian target of rapamycin (mTOR) pathway in the hypothalamus after sleeve gastrectomy. METHODS: A total of 30 obese type-2 diabetes Sprague-Dawley (SD) rats, 6 wk of age, fed with high-sugar and high-fat fodder for 2 mo plus intraperitoneal injection of streptozotocin were randomly divided into three groups: non-operation group (S0 group, n = 10), sham operation group (Sh group, n = 10) and sleeve gastrectomy group (SG group, n = 10). Data of body mass, food intake, oral glucose tolerance test (OGTT), acylated ghrelin (AG) and total ghrelin (TG) were collected and measured at the first day (when the rats were 6 wk old), preoperative day 3 and postoperative week 8. The mRNA expression of preproghrelin, GOAT and neuropeptide Y (NPY), and protein expression of ghrelin, GOAT, GHSR and the mTOR pathway (p-Akt, p-mTOR and p-S6) were measured in the hypothalamus. RESULTS: SG can significantly improve metabolic symptoms by reducing body mass and food intake. The obese rats showed lower serum TG levels and no change in AG, but the ratio of AG/TG was increased. When compared with the S0 and Sh groups, the SG group showed decreased TG (1482.03 ± 26.55, 1481.49 ± 23.30 and 1206.63 ± 52.02 ng/L, respectively, P < 0.05), but unchanged AG (153.06 ± 13.74, 155.37 ± 19.30 and 144.44 ± 16.689 ng/L, respectively, P > 0.05). As a result, the ratio of AG/TG further increased in the SG group (0.103 ± 0.009, 0.105 ± 0.013 and 0.12 ± 0.016, respectively, P < 0.05). When compared with the S0 group, SG suppressed mRNA and protein levels of preproghrelin (0.63 ± 0.12 vs 0.5 ± 0.11, P < 0.05) and GOAT (0.96 ± 0.09 vs 0.87 ± 0.08, P < 0.05), but did not change NPY mRNA expression (0.61 ± 0.04 vs 0.65 ± 0.07, P > 0.05) in the hypothalamus. The protein levels of p-Akt, p-mTOR and p-S6 were higher in the SG group, which indicated that the hypothalamic mTOR pathway was activated after SG at the postoperative week 8. CONCLUSION: The reduction of ghrelin expression and activation of the mTOR pathway might have opposite effects on food intake, as SG improves obesity and T2DM.

Wild-Type P53 Induces Sodium/Iodide Symporter Expression Allowing Radioiodide Therapy in Anaplastic Thyroid Cancer.

AIMS: Anaplastic thyroid cancer(ATC) is one of the most aggressive solid tumors. Mutations in the p53 gene are common in anaplastic thyroid cancer, but the effects of p53 mutations are yet to be elucidated. Here, we investigated the role of p53 in ATC. METHODS: p53 mutation was detect by immunohistochemistry in ATC tissues. Expression of NIS were measured using immunohistochemistry, qRT-PCR, western blot, immunofluorescence in ATC tissues and cell line 8505c. Luciferase reporter assay was performed to examine the effect of wild-type p53 on NIS. Radioiodide uptake assay and flow cytometry analysis were used to detect the role of wild-type p53 on radioiodide uptake.and cell apoptosis in ATC cell line. RESULTS: We showed that the p53 mutation can be detected in ATC tissues. Furthermore, we demonstrated that wild-type p53 transactivated the NIS promoter. In 8505c cells transfected with wild-type p53, treatment with radioiodine resulted in increased radioiodine uptake and increased apoptotic cell death compared with 8505c cells harboring the p53 mutation. CONCLUSION: In summary, transfection with wild-type p53 can increase the therapeutic effect of radioiodine by regulating the expression of the NIS.

A novel surgical strategy for secondary hyperparathyroidism: Purge parathyroidectomy.

OBJECTIVE: This study was intended to demonstrate the feasibility and efficacy of purge parathyroidectomy (PPTX) for patients with secondary hyperparathyroidism (SHPT). METHODS: The "seed, environment, and soil" medical hypothesis was first raised, following review of the literatures, to demonstrate the possible causes of persistence or recurrence of SHPT after parathyroidectomy. Subsequently, the novel surgical strategy of PPTX was proposed, which involves comprehensive resection of the fibro-fatty tissues, including visible or invisible parathyroid, within the region surrounded by the thyroid cartilage, bilateral carotid artery sheath, and the brachiocephalic artery. The perioperative information and clinical outcomes of patients who underwent PPTX from June 2016 to December 2016 were analyzed. RESULTS: In total, PPTX was performed safely in nine patients with SHPT from June 2016 to December 2016. The operative time for PPTX ranged from 95 to 135 min, and blood loss ranged from 20 to 40 mL. No patients with perioperative death, bleeding, convulsions, or recurrent laryngeal nerve injury were reported. The preoperative concentration of PTH ranged from 1062 to 2879 pg/mL, and from 12.35 to 72.69 pg/mL on the first day after surgery. In total, 37 parathyroid glands were resected. The postoperative pathologic examination showed that supernumerary or ectopic parathyroid tissues were found within the "non-parathyroid" tissues in three patients. No cases encountered persistence or recurrence of SHPT, or severe hypocalcemia during the follow-up period. CONCLUSION: PPTX involves comprehensive resection of supernumerary and ectopic parathyroid tissues, which may provide a more permanent means of reducing PTH levels.

To assess the effects of parathyroidectomy (TPTX versus TPTX+AT) for Secondary Hyperparathyroidism in chronic renal failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Secondary Hyperparathyroidism (SHPT) requiring parathyroidectomy (PTX) occurs more commonly in patients with progressive chronic kidney disease and in those on long-term lithium therapy. Successful PTX often results in a dramatic drop of parathyroid hormone level, relieves the patient from clinical symptoms, and reduces mortality. However, there is an ongoing debate on the optimal surgical treatment of SHPT. Currently, no clinical guidelines or trials have definitely answered the question of whether Total Parathyroidectomy (TPTX) is superior or equal to Total Parathyroidectomy with Autotransplantation (TPTX + AT). OBJECTIVE: The aims of the study were to compare the efficacy of two different surgical procedures and to develop evidence-based practice guidelines for the treatment of SHPT. METHODS: Citations were identified in the Medline, Cochrane, EMBASE, and Chinese Biomedical Literature databases through November 2016. The Newcastle-Ottawa Scale (NOS) score was used to assess the methodological quality of the studies included. All data were analyzed using Review Manager 5.3. RESULTS: A total of nine cohort studies and one Randomized Controlled Trials (RCT), comprising 1283 patients, were identified. The NOS score of all the studies included was 5 or above. Compared with TPTX + AT, patients in the TPTX group had lower rates of "recurrence" (OR = 0.20; 95%CI, 0.11-0.38; P < 0.01), "recurrence or persistence" (OR = 0.18; 95%CI, 0.10-0.33; P < 0.01), "reoperation due to recurrence or persistence" (OR = 0.17; 95%CI, 0.06-0.54; P = 0.002), and shorter "operative time" (WMD = -17.30; 95%CI, -30.53 to -4.06; P < 0.05), except for a higher risk of "hypoparathyroidism" (OR = 2.97; 95%CI, 1.09-8.08; P = 0.01). However, none of the patients had developed permanent hypocalcemia or adynamic bone disease. No significant difference was found for "symptomatic improvement", "complications", "drug requirements", and "hospital stay" (P > 0.05). CONCLUSION: The findings indicate that TPTX is superior to TPTX + AT, while referring to the rate of recurrent SHPT. However, this conclusion needs to be tested in large-scale confirmatory trials. TPTX seems to be a feasible alternative therapeutic option for the surgical treatment of refractory SHPT.

Gut microbiota after Roux-en-Y gastric bypass and sleeve gastrectomy in a diabetic rat model: Increased diversity and associations of discriminant genera with metabolic changes.

Recent work with gut microbiota after bariatric surgery is limited, and the results have not been in agreement. Given the role of the gut microbiota in regulating host metabolism, we explored the effect of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on the modifications of gut microbiota with regard to the potential influence of food intake and/or weight loss and examined their links with host metabolism. Zucker diabetic fatty rats were divided into the following groups: RYGB; sham-operated with pair-fed as RYGB; sham-operated fed ad libitum; and SG. The metabolic effects and gut microbiota profile were analyzed 10 weeks postoperatively. Associations between discriminating genera and metabolic markers after RYGB were explored. The 2 procedures induced similar glucose improvement and increased flora diversity after 10 weeks compared with sham-operated groups. RYGB induced a marked higher relative abundance of Proteobacteria/Gammaproteobacteria and Betaproteobacteria and increased emergence of Fusobacteria and Clostridium, whereas SG resulted in more abundant Actinobacteria compared with other groups. Most of the 12 discriminant genera correlated with changes in metabolic phenotype, but only 28.6% of these correlations were independent of weight, and 4 discriminant genera still negatively correlated with serum insulin level independent of food intake and weight loss after RYGB. These data demonstrate that RYGB and SG surgery produced similar diversity but different microbiota compositions changes in Zucker diabetic fatty rats. These findings stimulate deeper explorations of functions of the discriminate microbiota and the mechanisms linking postsurgical modulation of gut microbiota and improvements in insulin resistance.

Long-term outcomes of cruroplasty reinforcement with composite versus biologic mesh for gastroesophageal reflux disease.

AIM: The aim of this study was to evaluate the issue of improvement of disadvantages of different type meshes. METHODS: A retrospective analysis was performed on 101 gastroesophageal reflux disease patients who underwent reinforcement of crura with or without prosthetic mesh. Three types of mesh, 4-ply biologic small intestine submucosa (SIS, Surgisis(®), since November 2010), 6-ply SIS (Biodesign™ Surgisis(®), since March 2011), and composite synthetic mesh (Crurasoft(®), since May 2010), were used. All patients were assigned to simple suture group (n = 35), 4-ply SIS group (n = 13), 6-ply Biodesign™ group (n = 26) or Crurasoft(®) group (n = 27). Postoperative follow-up was performed via clinical visit or phone call contact. Subjective assessment included dysphagia, patients' symptomatic outcome judgment according to Visick and patients' satisfaction. Objective evaluation included hiatal hernia recurrence according to upper endoscopy and barium contrast swallow. Follow-up was completed in 83 patients with a mean duration of 45 months (range 16-149 months). RESULTS: For the objective outcomes, although anatomic recurrence of hiatal hernia did not significantly differ between groups at 6 months postoperatively, long-term results showed a protective effect of mesh implantation on hernia recurrence (p = 0.047). For the subjective outcomes, the mesh group had a more significant improvement in Visick score (p = 0.020) compared to the simple suture group. Patient satisfaction was significantly higher in the mesh group (p = 0.014), and subgroup analysis showed a clear trend as follows: Crurasoft(®) ≈ Biodesign(®) > SIS(®). A higher frequency of postoperative dysphagia was presented in the Crurasoft group compared with other two groups at 6 months postoperatively, but the difference was not significant over time (p = 0.227). CONCLUSION: Mesh cruroplasty results in satisfactory symptom control with a low recurrence rate. 6-ply biologic mesh is promising with respect to the reduction in anatomic recurrences. Postoperative dysphagia does not occur commonly following mesh cruroplasty with PTFE/ePTFE mesh.

A Chinese randomized prospective trial of floppy Nissen and Toupet fundoplication for gastroesophageal disease.

INTRODUCTION: To evaluate the clinical outcomes of laparoscopic floppy Nissen fundoplication (LNF) and laparoscopic Toupet fundoplication (LTF) for the treatment of gastroesophageal disease (GERD). METHODS: A total of 84 patients with GERD were randomized to either LNF (n = 43) or LTF (n = 41) between January 2010 and January 2013. The primary endpoint measures were the DeMeester score, distal esophageal amplitude (DEA), peristaltic frequency, lower esophageal sphincter pressure (LESP), short-term and long-term postoperative dysphagia and recurrence rate. The secondary endpoints were improvements in symptom scores and quality of life (QoL), and perioperative complications. RESULTS: LNF group had a lower DeMeester score and a higher LESP compared to LTF group after surgery (DeMeester score: P = 0.007; LESP: P = 0.027). The mean DEA and peristaltic frequency both improved significantly after surgery in 2 groups. There was no difference in the incidence of short-term adverse events (including dysphagia, heartburn, regurgitation et al.) between the two groups (P = 0.157). At the time of the latest follow-up, there was no difference in the incidence of symptomatic reflux symptom (heartburn and regurgitation) between the two groups (heartburn: P = 0.363; regurgitation: P = 1.000). A higher frequency of dysphagia was present in the LNF group compared with the LTF group (P = 0.023). DISCUSSION: LNF is associated with an excessive elevation of LESP which may lead to further persistent dysphagia. Partial fundoplication may provide adequate reflux control, improve esophageal body motility and minimize complications associated with an 'over-tight' fundal wrap. CONCLUSION: LTF seems to be as safe and effective on the long-term as LNF, but with a lower incidence of postoperative dysphagia (ChiCTR-TRC-13003945).

A Meta-Analysis of Randomized Controlled Trials to Compare Long-Term Outcomes of Nissen and Toupet Fundoplication for Gastroesophageal Reflux Disease.

AIM: In recent years, several studies with large sample sizes and recent follow-up data have been published comparing outcomes between laparoscopic Nissen fundoplication and laparoscopic Toupet fundoplication. It is now timely to be re-evaluated and synthesized long-term efficacy and adverse events of both total and partial posterior fundoplication. MATERIALS AND METHODS: Electronic searches for RCTs comparing the outcome after laparoscopic Nissen fundoplication and laparoscopic Toupet fundoplication were performed in the databases of MEDLINE, EMBASE, and the Cochrane Center Register of Controlled Trials. The data of evaluation in positive and adverse results of laparoscopic Nissen fundoplication and laparoscopic Nissen fundoplication were extracted and compared using meta-analysis. RESULTS: 13 RCTs were ultimately identified involving 814 (52.05%) and 750 (47.95%) patients who underwent laparoscopic Nissen fundoplication and laparoscopic Toupet fundoplication, respectively. The operative time, perioperative complications, postoperative satisfaction, recurrence, and the rates of medication adoption or re-operation due to recurrence were not significantly different between two groups. The two types of fundoplication both reinforced the anti-reflux barrier and elevated the lower esophageal sphincter pressure. However, rates of adverse results involving dysphasia, gas-bloat syndrome, inability to belch and re-operation due to severe dysphasia were significantly higher after LNF. In the subgroup analysis of wrap length≤2 cm, laparoscopic Nissen fundoplication was associated with a significantly higher incidence of postoperative dysphagia. However, in the subgroup wrap length>2 cm, the difference was not statistically significant. CONCLUSION: Laparoscopic Toupet fundoplication might be the better surgery approach for gastroesophageal reflux disease with a lower rate of postoperative adverse results and equal effectiveness as Laparoscopic Nissen fundoplication.

The role of carbon nanoparticles in identifying lymph nodes and preserving parathyroid in total endoscopic surgery of thyroid carcinoma.

AIM: To evaluate the efficacy of carbon nanoparticles (CNs) in identifying lymph nodes and preserving parathyroids in endoscopic total thyroidectomy (ETT) with central neck dissection (CND), and to further explore the role of CNs in recovering postoperative parathyroid function. METHOD: Fifty-five patients with papillary thyroid carcinoma were randomized to either CN group (n = 28) or control group (n = 27). The primary outcome measures were pathological results (e.g., amount of incidental removed parathyroids and lymph nodes dissected) and follow-up results [e.g., recovery of serum calcium and parathyroid hormone (PTH) levels]. The secondary end-points were the rates of neuromuscular symptoms, in-hospital postoperative hormonal assay, and lymph node metastases. RESULTS: A total of 193 lymph nodes in the CN group and 123 lymph nodes in the control group were detected. The mean number of detected lymph nodes was significantly higher in the CN group than in the control group (P = 0.009). Parathyroids were present in the thyroid or central nodal specimens of five patients, which were all in the control group. The control group had a relatively higher incidence of incidental parathyroidectomy compared to the CN group (P = 0.023). Compared to the CN group, the incidence of paresthesia was higher in the control group even if not statistically significant. During follow-up, the serum calcium levels were higher in the CN group than in the control group; however, there was no statistically significant difference. For the serum PTH levels, the CN group recovered rapidly to the preoperative levels, whereas the control group climbed steadily to the normal range. The serum PTH levels in the CN group were apparently higher than in the control group at 1 week and 1 month postoperatively. CONCLUSION: CNs play an important role in protecting parathyroid glands, dissecting lymph nodes thoroughly, and promoting rapid recovery of parathyroid in ETT with CND (ChiCTR-TRC-14005042).

A meta-analysis of short-term outcomes of patients with type 2 diabetes mellitus and BMI ≤ 35 kg/m2 undergoing Roux-en-Y gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is effective for type 2 diabetes mellitus (T2DM) patients with a body mass index (BMI) >35 kg/m(2). It is unknown whether it benefits those with a BMI ≤ 35 kg/m(2). In the last decade, the effect of bariatric procedures on metabolic outcomes in individuals who underwent surgery outside National Institutes of Health (NIH) guidelines (BMI ≤ 35 kg/m(2)) was both interesting and controversial. OBJECTIVE: We performed a systematic analysis evaluating the effect of RYGB for T2DM patients with a BMI ≤ 35 kg/m(2). METHODS: We searched databases (Embase, Ovid, PubMed, China National Knowledge Infrastructure [CNKI], and Cochrane Library) and relevant journals between January 1980 and October 2013. Keywords used in electronic searching included 'diabetes', 'gastric bypass', 'BMI', and 'body mass index'. Inclusion criteria were as follows: (1) patients who underwent RYGB; (2) sample size ≥ 15; (3) patients with a BMI ≤ 35 kg/m(2); and (4) follow-up ≥ 12 months. Exclusion criteria were as follows: (1) data extracted from a database; (2) trials for sleeve gastrectomy; (3) trials for laparoscopic banding; (4) trials for bilio-pancreatic diversion; and (5) trials for duodenojejunal bypass. Participants and intervention type 2 diabetes patients with BMI ≤ 35 kg/m(2) who underwent RYGB. Two investigators reviewed all reported studies independently. Data were extracted according to previously defined endpoints. A meta-analysis was performed for these parameters, with homogeneity among different trials. RESULTS: Nine articles fulfilled inclusion criteria. After 12 months, patients with T2DM had a significant decrease in their BMI postoperatively (p < 0.00001, weighted mean difference [WMD] -7.42, 95 % confidence interval [CI] -8.87 to -5.97), and remission of diabetes (glucose: p < 0.00001, WMD -59.87, 95 % CI -67.74 to -52.01; hemoglobin A1c p < 0.00001, WMD -2.76, 95 % CI -3.41 to -2.11). There were no deaths in all trials, and the complication rate was between 6.7 and 25.9 %. Mean length of hospital stay was 2.00 to 3.20 days, and mean operative time was from 72.8 to 112.0 min. In terms of study limitations, publication and selection bias were unavoidable. Trials with small sample sizes were excluded, which may lead to a selection bias. CONCLUSION: RYGB was effective for T2DM patients with BMI ≤ 35 kg/m(2). Further clinical studies with long-term follow-up data are necessary to clarify this issue.

Use of a mini-instrument in endoscopic thyroidectomy via a breast approach to improve cosmetic outcomes.

The objective of this research was to evaluate the clinical benefits of using a mini-instrument during endoscopic thyroidectomy via a breast approach (ETBA). Surgery-related indices and cosmetic results were compared for 20 patients underwent ETBA with a mini-instrument (ETBA-m) and 20 patients who underwent standard ETBA (sETBA). Patients were closely matched in terms of age, gender, tumor size, and pathology. Patients who underwent sETBA had a significantly larger area of dissection and total length of incisions compared to patients who underwent ETBA-m (136.25 ± 19.22 cm(2)vs. 105.25 ± 9.54 cm(2), p < 0.001 and 2.66 ± 0.09 cm vs. 2.08 ± 0.24 cm, p < 0.001). All patients who underwent ETBA-m commented that they preferred their current cosmetic appearance after they were shown a picture of the scars of a patient who underwent sETBA. Results of this study revealed that use of a mini-instrument in ETBA is technically safe and feasible and it offers improved cosmetic outcomes compared to sETBA.