Analysis of clinical characteristics of thyroid phenotype in Pendred syndrome based on multiple databases.

OBJECTIVE: This study aimed to provide statistical data support for the development of thyroid phenotype-related follow-up and reference for follow-up duration and project selection by analyzing the clinical characteristics of thyroid phenotype in Pendred syndrome (PDS) based on multiple databases. MATERIALS AND METHODS: PDS-related pathogenic or possibly/pathogenic mutations were searched by Deafness Variation Database (DVD), ClinVar, and PubMed databases, the mutation sites were counted and the characteristics and thyroid phenotypes were analyzed. RESULTS: The median age of hearing phenotype onset in PDS cases reported in multiple databases was 1.0 (1.0, 2.0) years, the median age of thyroid phenotype onset was 14.5 (5.8, 21.0) years, and the median age that thyroid phenotype was more delayed than hearing phenotype was 10.0 (4.0, 17.0) years. There were significant differences in the distribution of onset time between the two phenotypes (Z=-4.560, p<0.01). In these patients, the positive rates of goiter, thyroid nodules, abnormal thyroid function, and perchlorate discharge test (PDT) were 78%, 78%, 69%, and 78%, respectively. Moreover, the number of thyroid phenotype-positive items in the genotype group with frameshift mutation was not significantly higher than that in the group without frameshift mutation (Z=-1.452, p=0.147). CONCLUSIONS: The early missed diagnosis of PDS may be due to the late onset of thyroid phenotype and the non-100% positive rate of examination items. Therefore, multi-item follow-up of the thyroid gland into adulthood will benefit patients. At present, the relationship between genotype and phenotype is still unclear, and prognosis cannot be determined according to genotype.

[Effects of orlistat and metformin on metabolism and gonadal function in overweight or obese patients with polycystic ovary syndrome].

The aim of this study was to assess the effects of orlistat or metformin treatment on lipid and glucose metabolism, and gonadal function in obese/overweight women with polycystic ovary syndrome (PCOS). A total of 39 patients diagnosed with PCOS were randomly (digital table method) divided into orlistat treatment group (20 cases) and metformin treatment group (19 cases). Compared with those before, treatment with either orlistat or metformin significantly reduced body weight, body mass index (BMI), hip circumferences, and serum insulin levels of the PCOS patients both at the end of 3 months and 6 months (P<0.05). No significant differences could be viewed between orlistat and metformin treated subjects. Moreover, orlistat treatment significantly lowered the levels of low-density lipoprotein cholesterol, total cholesterol, fasting blood glucose, and homeostasis model assessment-insulin resistance (HOMA-IR) (P<0.05), while there were no significant changes in above parameters with metformin treatment. The improvement of menstrual cycle was observed after 6-month treatment in both groups (P<0.05). However, changes in polycystic ovarian morphology by ultrasound were only observed in orlistat treated group. In conclusion, orlistat is comparable with metformin in weight loss and improvement of insulin resistance and menstrual cycle, and is superior to metformin in improvement of lipid metabolism in overweight/obese PCOS patients.

[Changes in platelet related parameters in obese patients after sleeve gastrectomy].

To compare changes in platelet related parameters in obese patients before and after sleeve gastrectomy (SG), we retrospectively analyzed the clinical data of 31 obese patients who underwent SG in Peking Union Medical College Hospital from December 2012 to September 2020. Results showed that compared with those before surgery, platelet count (PLT) decreased significantly at 2-12 weeks of follow-up (P=0.009), while platelet distribution width (PDW), mean platelet volume (MPV), and large platelet ratio (P-LCR) increased significantly at the same periods of follow-up after operation (P<0.001). However, the levels of PDW, MPV, and P-LCR began to decrease at 16-55 weeks when compared with those at 2-12 weeks of follow-up (P<0.01). PLT was positively correlated with white blood cells and neutrophils at 2-12 weeks of follow-up and positively correlated with high sensitivity C-reactive protein at 16-55 weeks of follow-up after operation (P<0.05).

[Effect of perforator flap of the proper digital artery of the ulnar or radial side of finger in the treatment of webbed scar contracture of the same finger in child].

Objective: To explore the effect of the perforator flap of the proper digital artery on the ulnar or radial side of the finger in the treatment of webbed scar contracture of the same finger in child. Methods: From January 2012 to January 2016, 26 children who were treated with dressing change after burn of finger and then had webbed scar contracture along with growth and development were hospitalized in our unit, involving a total of 50 fingers. There were 14 males and 12 females among the children aged from 2 to 14 years. After the scar was dissected and released, the wound area ranged from 1.6 cm×1.0 cm to 5.0 cm×2.6 cm. The perforator flap of the proper digital artery of the ulnar or radial side of the same finger was used to repair the wound. The flap area ranged from 1.8 cm×1.0 cm to 4.6 cm×1.8 cm. The donor sites were sutured directly. The residual wounds in donor and recipient sites were repaired by full-thickness skin graft collected from inguinal area/adjacent area or adjacent perforator flap. The postoperative development and function of the fingers were followed up and observed. The range of motion of the fingers was evaluated according to the Chinese Medical Association Hand Surgery Society's upper limb functional evaluation trial standard, the Kantor Scar Cosmesis Assessment and Rating Scale was used to score the scar of finger, and the latest data were recorded. Results: The flaps and skin grafts survived successfully after operation. The patients were followed up for 6 to 24 months. The perforator flaps of the proper digital artery on the ulnar or radial side of the finger survived well at the latest follow-up, with good color and texture and a two-point discrimination distance of 9 to 12 mm. There was no contracture of the fingers, a little pigmentation in the skin graft area, no flexion deformity of the fingers, no lateral bending of the fingers to the flap-harvesting side, and no scar contracture at the webs of the fingers. Compared with that of healthy side, the development of finger was not obviously abnormal. The range of motion of the fingers was excellent in 38 fingers and good in 12 fingers, and the scar score of the fingers was 2-3 points in 31 fingers, 4-7 points in 15 fingers, and 8-10 points in 4 fingers. Conclusions: The efficacy of perforator flap of the proper digital artery of the ulnar or radial side of finger in the treatment of the webbed scar contracture of the same finger in child is reliable, with high postoperative survival rate of the flap, better color and texture, and fewer complications, which can avoid the risk of re-contracture of the finger in a short period after operation, and does not affect the growth and development of the finger.

[Effects of free mini-flap on tibial side of third toe on repairing skin and soft tissue defect of finger pulp at the end of finger].

Objective: To investigate the effects of free mini-flap on tibial side of third toe on repairing skin and soft tissue defect of finger pulp at the end of finger. Methods: From August 2013 to May 2017, 18 patients with skin and soft tissue defect of finger pulp at the end of finger were admitted to our unit, with 12 men and 6 women aged 16 to 54 years. As the skin and soft tissue defect sites, there were 3 cases of thumb, 8 cases of index finger, 4 cases of middle finger, and 3 cases of ring finger. The area of defects ranged from 2.0 cm×1.4 cm to 3.5 cm×2.4 cm. Free mini-flaps on tibial side of third toes were designed according to area and shape of defects, and the length and width of flaps were 0.1 to 0.2 cm longer than the length and width of the defects, respectively. The area of flaps ranged from 2.1 cm×1.5 cm to 3.7 cm×2.6 cm. The end-to-end anastomosis of subcutaneous veins of flaps and superficial veins of the finger-palm side or superficial dorsal digital vein, the end-to-end tension-free anastomosis of the base metatarsal arteries on tibial side of third toe and proper digital arteries of recipient finger were performed. Besides, anastomosis of base metatarsal nerve on tibial side of third toe and proper digital nerve of recipient finger was performed. The donor sites on feet were sutured directly or repaired with full-thickness skin grafts on medial upper leg of the same side. The survival of flaps after operation and the follow-up of patients were observed. Results: All flaps survived well, with good blood supply. Among the 18 patients, 2 patients lost to follow-up, and 16 patients were followed up for 4 to 36 months. The shape and texture of flaps were good. After reconstruction, finger pulps at the end of finger were plump, with fingerprint. Function of the finger restored well, and the two-point discriminatory distances of flaps were 5 to 10 mm. The donor sites on feet of 14 patients healed after the operation, the other 2 patients had necrosis on edge and central area of skin grafts, and the necrotic area healed after dressing change. The skin graft areas on feet were wear-resistant, with slight damage to donor sites and did not influence shoes wearing and walking. Besides, patients did not feel uncomfortable. Conclusions: Skin and soft tissue defects of finger pulp at the end of finger repaired by free mini-flaps on tibial side of third toe are with good shape and slight damage to donor sites, and the operation is simple. It is worthy of popularization and application in clinic.

[Effects of combined transplantation of rat Schwann cells and fibroblasts on nerve regeneration of denervated perforator flaps in rats and the mechanism].

Objective: To explore the effects of combined transplantation of the rat Schwann cells and fibroblasts (Fbs) on the nerve regeneration of denervated perforator flaps in rats and the mechanism. Methods: (1) Fbs were isolated from the trunk of 2 Sprague-Dawley (SD) rats embryos of 14-16 days' pregnancy and cultured, and the morphology of the cells was observed. The third passage of cells were used for subsequent experiments. The protein expressions of fibronectin and Ephrin-B2 were observed by immunohistochemical method. The mRNA expression of Ephrin-B2 was detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction (n=3). (2) Schwann cells were isolated from the bilateral sciatic nerves and brachial plexus nerves of 45 SD rats born for 1-3 days and cultured, and the morphology of the cells was observed. The third passage of cells were used for subsequent experiments. The rate of S100 positive cells was detected by immunofluorescence method and flow cytometer, with sample numbers of 9 and 3 respectively. (3) In Dulbecco's modified Eagle medium (DMEM) high glucose medium, 1 mL Fbs and 1 mL Schwann cells both in the concentration of 1×10(5) cells/mL were co-cultured as Schwann cells+ Fbs co-culture group, and 2 mL Schwann cells in the concentration of 1×10(5) cells/mL were cultured alone as Schwann cells alone culture group, with 5 wells in each group. The clusters of Schwann cells in the two groups were observed and counted under inverted phase contrast microscope at post culture hour (PCH) 6 and 24 respectively. The clusters of Schwann cells in Schwann cells+ Fbs co-culture group were observed by immunofluorescence method at PCH 24 too. The protein expressions of EphB2, Sox2, and N-cadherin in Schwann cells of two groups at PCH 24 were detected by Western blotting (n=20). (4) Totally 100 8-week-old male SD rats were selected, and an in situ replanted peritoneal denervated perforator flap was made in each rat. According to the random number table, the rats were divided into simple flap group, Fbs alone transplantation group, Schwann cells alone transplantation group, Schwann cells+ Fbs co-transplantation group, with 25 rats in each group. Flaps of rats in Fbs alone transplantation group and Schwann cells alone transplantation group were injected with 0.4 mL Fb and 0.4 mL Schwann cells respectively (2×10(6) cells each). Flaps of rats in Schwann cells+ Fbs co-transplantation group were injected with 0.4 mL Fbs and Schwann cells mixed cells (totally 2×10(6) cells, cell number ratio: 1∶1), and flaps of rats of simple flap group were injected with the same volume of DMEM high glucose medium. On post injection day (PID) 2, 5, 7, 9, and 14, 5 rats in each group were selected respectively according to the random number table. The flap tissue was collected, and the number, diameter, and arrangement of regenerated nerves were observed by immunofluorescence method. Data were processed with completely random designed t test, analysis of variance for repeated measurement, t test, and Bonferroni correction. Results: (1) The third passage of cells isolated and cultured from the rat embryo trunks were uniform in size and shape, long spindle-shaped, with a large proportion of nuclei. Strong positive expressions of fibronectin and Ephrin-B2 protein in cells were observed, and the mRNA expression of Ephrin-B2 was 0.004 1±0.000 8. The cells were identified as Fbs. (2) After 5 days of culture, the primary cells isolated from the sciatic nerves and brachial plexus nerves of neonatal rats were elongated in cell bodies and grew in nest, fence, or vortex-like shape. The third passage of cells were detected by immunofluorescence method and flow cytometer, and the corresponding S100 positive cell rates were (95.9±1.0)% and (95.8±1.1)% respectively. The cells were identified as Schwann cells. (3) At PCH 6 and 24, the cluster numbers of Schwann cells in Schwann cells+ Fbs co-culture group were significantly higher than those of Schwann cells alone culture group (t=6.500, 10.614, P<0.01). At PCH 24, the Schwann cells in Schwann cells+ Fbs co-culture group aggregated into clusters, Fbs dispersed around the Schwann cell clusters, and the protein expressions of EphB2, N-cadherin, and Sox2 in Schwann cells were significantly higher than those in Schwann cells alone culture group (t=2.975, 19.717, 11.159, P<0.05 or P<0.01). (4) On PID 2, a small number of scattered, disordered, short, and thin nerve fibers were observed in the flap tissue of rats in the four groups. From PID 5 to 14, the number of nerve fibers in the flap tissue of rats of Schwann cells+ Fbs co-transplantation group increased gradually, and the nerve fibers were with long diameter and arranged orderly. The number of nerve fibers in the flap tissue of rats of Schwann cells alone transplantation group increased, but the nerve fibers were with short diameter and arranged disorderly, and the number was smaller than that of Schwann cells+ Fbs co-transplantation group. In simple flap group and Fbs alone transplantation group, the nerve fibers in the flap tissue of rats gradually degenerated with gradually decreased number or even disappeared. Conclusions: The combined transplantation of Fbs and Schwann cells in rats can regulate Schwann cells migration and clustering by activating Ephrin/Eph-Sox2-N-cadherin signaling pathway, thus promoting the orderly nerve regeneration of denervated perforator flaps in rats.

Real-Time Motor Cortex Mapping for the Safe Resection of Glioma: An Intraoperative Resting-State fMRI Study.

BACKGROUND AND PURPOSE: Resting-state functional MR imaging has been used for motor mapping in presurgical planning but never used intraoperatively. This study aimed to investigate the feasibility of applying intraoperative resting-state functional MR imaging for the safe resection of gliomas using real-time motor cortex mapping during an operation. MATERIALS AND METHODS: Using interventional MR imaging, we conducted preoperative and intraoperative resting-state intrinsic functional connectivity analyses of the motor cortex in 30 patients with brain tumors. Factors that may influence intraoperative imaging quality, including anesthesia type (general or awake anesthesia) and tumor cavity (filled with normal saline or not), were studied to investigate image quality. Additionally, direct cortical stimulation was used to validate the accuracy of intraoperative resting-state fMRI in mapping the motor cortex. RESULTS: Preoperative and intraoperative resting-state fMRI scans were acquired for all patients. Fourteen patients who successfully completed both sufficient intraoperative resting-state fMRI and direct cortical stimulation were used for further analysis of sensitivity and specificity. Compared with those subjected to direct cortical stimulation, the sensitivity and specificity of intraoperative resting-state fMRI in localizing the motor area were 61.7% and 93.7%, respectively. The image quality of intraoperative resting-state fMRI was better when the tumor cavity was filled with normal saline (P = .049). However, no significant difference between the anesthesia types was observed (P = .102). CONCLUSIONS: This study demonstrates the feasibility of using intraoperative resting-state fMRI for real-time localization of functional areas during a neurologic operation. The findings suggest that using intraoperative resting-state fMRI can avoid the risk of intraoperative seizures due to direct cortical stimulation and may provide neurosurgeons with valuable information to facilitate the safe resection of gliomas.

[Comparison of efficacy between the serum cortisol and 24 hour urine free cortisol in combined dexamethasone suppression test in the diagnosis of Cushing syndrome].

OBJECTIVE: To compare the sensitivity and specificity between the 24 hour urine free cortisol (24 h UFC) and serum cortisol in dexamethasone suppression test (DST) in the diagnosis of Cushing syndrome (CS). METHODS: Combined low dose DST (LDDST) and high dose DST (HDDST) were carried out in 67 cases of CS with surgically confirmed cases in recent 3 years(from January 2011 to November 2015). The serum cortisol and 24 h UFC were collected simultaneously for each subject and the sensitivity and specificity of serum cortisol and 24 h UFC were compared. RESULTS: There were Cushing disease (CD) group (n=53), ectopic adrenocorticotropic hormone (ACTH) syndrome group (n=7) and ACTH-independent Cushing syndrome group (n=7) according to the etiology of hypercorticordism.There were no significant differences among 3 groups in gender and age.The sensitivity of serum cortisol of different cut off points(50, 110, 140 nmol/L and 50% of control)after LDDST was 97.01%, 86.57%, 83.58% and 70.15% respectively.Meanwhile, the sensitivity of cutoff point of 24 h UFC <32 nmol in combined LDDST was 92.54% in the diagnosis of Cushing syndrome.There was no significant differences in two groups between serum cortisol <110 nmol/L and 24 h UFC <32 nmol.However, the sensitivity of serum cortisol <50 nmol/L was significantly higher than 24 h UFC<32 nmol (P<0.05). Furthermore, in combined HDDST, if the suppression rate was ≥50%, the sensitivity of serum cortisol and 24 h UFC in differentiating the etiology of Cushing disease was 60.38% and 90.57%, and the specificity was 91.43% and 96.00% respectively.There were significant differences between serum cortisol and 24 h UFC in both of sensitivity and specificity (both P<0.05). In addition, if the suppression rate of 24 h UFC in HDDST was adjusted to 60.85% according to receiver operating characteristic (ROC) curve, it could have the best levels of sensitivity (92.6%) with the specificity of 85.7%. If the suppression rate of serum cortisol was adjusted to 61.53% in HDDST according to ROC curve, it could have the best sensitivity (64.8%) with the specificity of 78.6% accordingly. CONCLUSION: In combined LDDST, the serum cortisol <50 nmol/L had a higher sensitivity than the 24 h UFC<32 nmol when they were used as the criteria in determining the diagnosis of CS.In HDDST, the sensitivity and specificity of suppression rate of 24 h UFC ≥50% were better than serum cortisol to differentiate the etiology of CS.

Zinc-alpha2-glycoprotein is involved in regulation of body weight through inhibition of lipogenic enzymes in adipose tissue.

CONTEXT: Zinc-alpha2-glycoprotein (ZAG) was found to influence lipolysis in adipose tissue and has recently been proposed as a candidate factor in the regulation of body weight. OBJECTIVE: To elucidate the association of serum ZAG level with body weight and percentage of body fat in normal, obese subjects and high-fat diet (HFD)-induced obese mice. DESIGN: The relationship between serum ZAG and obesity-related parameters was studied in 44 human subjects and 36 mice fed standard food and HFD. Furthermore, the effects of ZAG overexpression on adipose tissue of mice was also evaluated by using a liposome transfection method. RESULTS: Serum ZAG level was significantly lower in obese patients and obese mice in comparison to that in people and mice with normal weight. The further statistical analysis demonstrated that ZAG level was negatively correlated with body weight (r=-0.62, P<0.001), body mass index (r=-0.64, P<0.001), waist circumference(r=-0.68, P<0.001), hip circumference (r=-0.60, P<0.001), percentage of body fat (r=-0.52, P=0.03) and fat mass(r=-0.59, P=0.01) in human subjects after adjustment for age and sex. Furthermore, ZAG overexpression in mice reduced body weight and the percentage of epididymal fat. The decreased FAS, ACC1 and DGAT mRNA and the increased HSL mRNA were also observed in epididymal adipose tissue in ZAG overexpression mice. CONCLUSION: ZAG is closely linked to obesity. Serum ZAG level is inversely associated with body weight and percentage of body fat. The action of ZAG is associated with downregulated lipogenic enzymes and upregulated lipolytic enzyme expressions in adipose tissue of mice.