Pharmacological treatment of Tourette's syndrome: from the past to the future.

Tourette's syndrome (TS) is a neuropsychiatric disease featuring tics and vocal tics, with a prevalence of approximately 1%, including 75% of the total number of male patients. TS seriously disturbs the patients' career, education, and life and brings a serious and unbearable psychological burden to the patients themselves and their families. At present, there are no specific clinical medications recommended for treating TS. Therefore, it is necessary to select the appropriate medication for symptomatic treatment based on the doctor's personal experience and the patient's symptoms, with the main goal of relieving symptoms, thus improving the patient's social skills and psychological problems. Here we conducted a comprehensive search on PubMed to review and organize the history and current status of the development of drug therapy for TS through a timeline format. We also systematically evaluated the effects of each drug for TS treatment to summarize the current problems and new research directions and to provide some ideas for clinical treatment.

Unveiling Gambogenic Acid as a Promising Antitumor Compound: A Review.

Gambogenic acid is a derivative of gambogic acid, a polyprenylated xanthone isolated from Garcinia hanburyi. Compared with the more widely studied gambogic acid, gambogenic acid has demonstrated advantages such as a more potent antitumor effect and less systemic toxicity than gambogic acid according to early investigations. Therefore, the present review summarizes the effectiveness and mechanisms of gambogenic acid in different cancers and highlights the mechanisms of action. In addition, drug delivery systems to improve the bioavailability of gambogenic acid and its pharmacokinetic profile are included. Gambogenic acid has been applied to treat a wide range of cancers, such as lung, liver, colorectal, breast, gastric, bladder, and prostate cancers. Gambogenic acid exerts its antitumor effects as a novel class of enhancer of zeste homolog 2 inhibitors. It prevents cancer cell proliferation by inducing apoptosis, ferroptosis, and necroptosis and controlling the cell cycle as well as autophagy. Gambogenic acid also hinders tumor cell invasion and metastasis by downregulating metastasis-related proteins. Moreover, gambogenic acid increases the sensitivity of cancer cells to chemotherapy and has shown effects on multidrug resistance in malignancy. This review adds insights for the prevention and treatment of cancers using gambogenic acid.

Trends, Influence Factors, and Doctor-Patient Perspectives of Web-Based Visits for Thyroid Surgery Clinical Care: Cross-Sectional Study.

BACKGROUND: In recent years, the new generation of telecommunication technologies has profoundly changed the traditional medical industry. To alleviate the medical difficulties faced by patients with thyroid diseases, hospitals have opened web-based visits and actively combined online-to-offline outpatient services. OBJECTIVE: This study aims to explore differences between office and web-based outpatient services from doctors' and patients' perspectives, illustrate the effect of the COVID-19 pandemic on outpatient services, and provide clues for improving the online-to-offline mode of care for patients with thyroid diseases. METHODS: We collected the complete web-based and office outpatient records of the Thyroid Surgery Center of West China Hospital. A total of 300,884 completed patient encounters occurred (201,840 office visits and 99,044 web-based visits) from January 1, 2019, to May 31, 2022. We performed logistic regression to evaluate the association between the chosen visit type and patients' sociodemographic characteristics. RESULTS: The number of web-based visits rapidly increased since March 2020 and reached 45.1% (4752/10,531) of all encounters in December 2021. The COVID-19 pandemic dramatically accelerated the development of web-based visits. Web-based visits were preferred by patients 18-45 years old (odds ratio [OR] 2.043, 95% CI 1.635-2.552, P<.001), patients with relatively high-paying jobs (technical staff: OR 1.278, 95% CI 1.088-1.479, P=.003; office clerk: OR 1.25, 95% CI 1.07-1.461, P=.005; national public servant: OR:1.248, 95% CI 1.042-1.494, P=.02), and patients living in Sichuan Province (excluding Chengdu; OR 1.167, 95% CI 1.107-1.23, P<.001). The medicine cost (P<.001) and examination cost (P<.001) of office visits were significantly higher than those of web-based visits. CONCLUSIONS: Web-based outpatient visits have increased rapidly in recent years, and the COVID-19 pandemic has boosted their development. The preference for web-based visits was influenced by the socioeconomic and demographic characteristics of both patients and doctors.

Surgical treatment and prognosis values of extranodal extension to recurrent laryngeal nerve in papillary thyroid carcinoma.

PURPOSE: Recurrent laryngeal nerve (RLN) invasion by extranodal extension (ENE) is a rare condition that may occur in papillary thyroid cancer (PTC), and it has never been characterised in the literature.Our research aims to investigate the clinical significance of ENE to RLN including its effect on vocal cord function, relationship with the aggressive behaviour of PTC, and optimal surgical methods. METHODS: A total of 3119 patients, including 2868 patients without RLN invasion, 251 patients with RLN invasion [categorised into the ENE invasion group (n = 55) and extrathyroidal extension (ETE) invasion group (n = 196)] were analyzed retrospectively. Data on clinicopathological characteristics, vocal cord paralysis (VCP), postoperative complications, surgical methods, rates of recurrence and metastasis were collected. Predictive disease-free survival (DFS) was analysed using the Kaplan-Meier method. RESULTS: The ENE invasion group showed a similar rate of VCP and DFS compared with the ETE invasion group (P = 0.15, P = 0.38, respectively). Sharp separation applied on the invaded nerves preserves the visual integrity of the RLN without significantly reducing the DFS (P > 0.05). ETE or ENE to RLN, lymph nodes metastasis (LNM), and T4 stage were independent factors for total recurrence [P = 0.04, hazard ratio (HR), 1.97 (1.04-3.75); P = 0.00, HR, 4.63 (2.24-9.54); P = 0.00, HR, 3.63 (1.94-6.77); P = 0.00, HR, 6.1 (3.24-11.50)]. RLN invasion, both by ETE or ENE, was significantly associated with reduced DFS (P = 0.00; P = 0.00, respectively). CONCLUSIONS: ENE to RLN, while rare, has not previously been well-studied. Our interesting premise and important findings including ENE to RLN has the same poor prognostic impact on recurrence as does invasion of the RLN by ETE and surgical management for the invaded RLN that preserves its visual integrity without compromising DFS. Those novel findings indicate that ENE to RLN could be considered as an additional factor beyond post-operative disease status and risk stratification, and it would be a valuable addition to further individualise treatment/surveillance for PTC.

A nomogram model based on the preoperative clinical characteristics of papillary thyroid carcinoma with Hashimoto's thyroiditis to predict central lymph node metastasis.

OBJECTIVE: Preoperative prediction of central lymph node (LN) metastasis in papillary thyroid carcinoma (PTC) with Hashimoto's thyroiditis (HT) provides an important basis for surgical decision-making, especially regarding the extent of tumour resection. We aimed to develop and validate a nomogram model for the preoperative assessment of central LN metastasis. METHODS: We retrospectively collected the data of 994 PTC patients with HT who underwent surgery at the West China Hospital from January 2008 to December 2017. Among them, 606 patients who underwent surgeries relatively earlier comprised the training cohort for nomogram development, while the other 388 who underwent surgeries relatively later formed the validation cohort to validate the model's performance. Univariate and multivariate logistic regression analyses were conducted using the data of the two respective cohorts, as well as the data of the combined cohort. The relevant preoperative potential risk factors include demographic characteristics, medical history information, thyroid function test, ultrasound characteristics and BRAF V600E gene detection. A nomogram model was subsequently developed. The performance, discrimination and calibration of the nomogram model were assessed in the training and validation cohorts and in the combined cohort. RESULTS: The central LN metastasis rate of PTC with HT was 49.7% (301/606) and 48.7% (193/388) in the training and validation cohorts, respectively. The univariate and multivariate logistic regression analyses indicated that younger age, normal body mass index, BRAF V600E mutation, larger maximum diameter, left lobe tumour, aspect ratio >1, capsular invasion and calcification were significant risk factors for central LN metastasis in PTC patients with HT. The preoperative nomogram showed good calibration and discrimination for the training and validation cohorts, as well as for the combined data set. CONCLUSION: The nomogram we developed and validated with a comprehensive set of preoperative factors is effective in predicting central LN metastasis in PTC patients with HT.

Role of the 2018 American Thyroid Association statement on postoperative hypoparathyroidism: a 5-year retrospective study.

BACKGROUND: Definitions of postoperative hypoparathyroidism (hypoPT) have never reached consent until the American Thyroid Association (ATA) statement was released, with new characteristics and challenges. METHODS: Patients with papillary thyroid carcinoma who underwent primary total thyroidectomy between January 2013 and June 2018 were retrospectively enrolled. Symptoms of hypocalcemia and their frequency were stringently followed. Patients were divided into groups according to the ATA statement. Incidence of postoperative hypoPT and serum parathyroid hormone levels accompanied by calcium levels, from 1-day to at least 24-month follow-up. RESULTS: A total of 1749 patients were included: 458 (26.2%) had transient and 63 (3.6%) had permanent hypoPT. Transient hypoPT was found in 363 (20.7%) patients with biochemical hypoPT, 72 (4.1%) with clinical hypoPT, and 23 (1.3%) with relative hypoPT; permanent hypoPT was detected in 8 (0.5%) patients with biochemical hypoPT, 55 (3.1%) with clinical hypoPT, and none with relative hypoPT. Female sex, age ≥ 55 years, unintentional parathyroid gland resection, and autotransplantation of ≥ 2 parathyroid glands were independent risk factors for transient biochemical hypoPT. Age ≥ 55 years, bilateral central neck dissection, and isthmus tumor location were independent risk factors for transient clinical hypoPT. A postoperative 1-day percentage of parathyroid hormone (PTH) reduction of > 51.1% was an independent risk factor for relative hypoPT (odds ratio, 4.892; 95% confidence interval, 1.653-14.480; P = 0.004). No independent risk factor for permanent hypoPT was found. CONCLUSION: ATA diagnostic criteria for postoperative hypoPT are of great value in differentiating patients by hypocalcemia symptoms and choosing corresponding clinical assistance; however, they may underestimate the actual incidence.

Predictors of thyroglobulin in the lymph nodes recurrence of papillary thyroid carcinoma undergoing total thyroidectomy.

BACKGROUND: To investigate the association between postoperative lymph nodes (LNs) recurrence and distinct serum thyroglobulin (Tg) levels in patients with papillary thyroid carcinoma (PTC). METHODS: This study included PTC patients who underwent total thyroidectomy (TT) with at least central neck dissection and then re-operated due to recurrence of LNs between January 2013 and June 2018. These patients were grouped by negative or positive serum Tg levels according to the American Thyroid Association guidelines. RESULTS: Of the 60 included patients, 49 underwent radioactive iodine (RAI) treatment. Maximum unstimulated Tg (uTg) ≥ 0.2 ng/mL were associated with larger diameter of recurrent LNs (P = 0.027), and higher rate of metastatic LNs (P < 0.001). Serum-stimulated Tg (off-Tg) ≥ 1 ng/mL (P = 0.047) and unstimulated Tg (on-Tg) ≥ 0.2 ng/Ml (P = 0.013) were associated with larger diameter of recurrent LNs. Number of metastatic LNs ≥ 8 was an independent predictor for postoperative maximum uTg ≥ 0.2 ng/mL (OR = 8.767; 95% CI = 1.392-55.216; P = 0.021). Ratio of metastatic LNs ≥ 25% was an independent predictor for off-Tg ≥ 1 ng/mL (OR = 20.997; 95% CI = 1.649-267.384; P = 0.019). CONCLUSION: Postoperative Tg-positive status was associated with larger size of recurrent LNs. Number of metastatic LNs ≥ 8 and ratio of metastatic LNs ≥ 25% were independent predicators for uTg-positive and off-Tg-positive status, respectively.

Conspicuousness and recurrence related factors of ultrasound-guided microwave ablation in the treatment of benign thyroid nodules.

OBJECTIVE: Microwave ablation (MWA) is a minimally invasive technique for the treatment of benign thyroid nodules. The purpose of this study was to evaluate efficacy and safety of ultrasound-guided MWA in the treatment of benign thyroid nodules, and to find out the recurrence related factors, so as to provide reference for future clinical work. METHODS: This study retrospectively analyzed the patients who received ultrasound-guided MWA for benign thyroid nodules in our hospital from October 2018 to March 2020. A total of 214 patients were included in the study. We assessed thyroid volume changes (represented by volume reduction ratio VRR), the energy per 1 mL reduction in nodular volume (represented by energy volume ratio ΔE), the serum levels of free triiodide thyroid hormone (FT3), free thyroxine (FT4), thyrotropin (TSH) and complications after MWA treatment. RESULTS: There were a total of 306 nodules in 214 patients, including 183 (85.51%) females and 31 (14.49%) males. The median diameter and volume of the nodule were 33 mm and 8.01 mL. The VRR at 1 month, 3 months, 6 months and 12 months were 40.79%, 60.37%, 74.59% and 85.60%, respectively. In addition, MWA had a better ablation effect for small nodules (initial volume ≤ 10 mL). In recurrent studies, we found that ΔE was an independent risk factor for benign thyroid nodules (P < 0.05). CONCLUSIONS: Ultrasound-guided MWA is effective and safe in the treatment of benign thyroid nodules. In addition, it has little damage to surrounding tissues and no effect on thyroid function. Especially, the nodules with smaller initial volume, the treatment is better. On the other hand, the energy per 1 mL reduction ΔE in nodular volume may be associated with nodular recurrence, which requires further follow-up for longer periods. At this stage, we consider that ultrasound-guided MWA can be used as one of the main clinical treatment methods for benign thyroid nodules.

Diagnostic reliability of elastography in thyroid nodules reported as indeterminate at prior fine-needle aspiration cytology (FNAC): a systematic review and Bayesian meta-analysis.

OBJECTIVES: To assess the diagnostic yields of elastography in thyroid nodules reported as indeterminate in FNAC according to guidelines. METHODS: Databases of Medline, Embase, and Cochrane Central were searched till 31 October 2019. Two different reviewers check the studies and extracted the data. The diagnostic accuracy and yield were quantitatively synthesized using Bayesian bivariate model in R. RESULTS: Twenty studies with 1734 indeterminate thyroid nodules undergoing elastography were included. The summary estimates of sensitivity and specificity were 0.766 (95% credible interval (CrI), 0.686-0.835) and 0.867 (95% CrI, 0.780-0.931), respectively. The summary estimate for diagnostic odds ratio (DOR) was 25.9 (95% CrI, 12.8-46.2). Summary receiver operating characteristic plots for elastography showed a right-diagonal curvilinear relationship, suggesting a trade-off between sensitivity and specificity, and the estimate of area under curve (AUC) was 0.743. The summary estimates for positive and negative likelihood ratios were 6.6 (95% CrI, 4.2-11.3) and 0.27 (95% CrI, 0.21-0.36), respectively. CONCLUSIONS: Elastography had fair diagnostic yields in indeterminate thyroid nodules. Shear wave elastography and strain ratio elastography could be more efficient in diagnosis and should evolve in the next years while combing elastography with ultrasound would contribute more to sensitivity and specificity currently. KEY POINTS: • Elastography has fair diagnostic yields in indeterminate thyroid nodules. • Shear wave elastography and strain ratio elastography are more efficient than real-time elastography. • Combining elastography and other ultrasound techniques improves evaluation of indeterminate thyroid nodules.

Effects of energy-based ablation on thyroid function in treating benign thyroid nodules: a systematic review and meta-analysis.

BACKGROUND: Whether thyroid function would be affected by ablation remains controversial. This systematic review and meta-analysis aimed to investigate the effects of energy-based ablation on thyroid function in treating benign thyroid nodules. METHODS: EMBASE, PubMed, Cochrane Library, and Web of Science databases were searched. The mean difference (MD) or standard MD (SMD) was applied to assess changes in thyroid function, thyroglobulin (Tg), and antibodies after ablation. RevMan version 5.3 was used for data synthesis. RESULTS: Forty-two studies involving 6380 patients were eligible. The pooled results revealed significant decrease of 1-day thyroid-stimulating hormone (95% CI, -0.67 to -0.14), significant increase of 1-day, 1-week, and 1-month free thyroxine (95% CI, 1.57 to 5.28; 95% CI, 0.61 to 2.42; 95% CI, -0.76 to -0.15), 1-day and 1-week Tg level (95% CI, 0.40 to 0.81; 95% CI, 0.21 to 1.29), 6-month anti-thyroglobulin antibodies (95% CI, 0.02 to 0.26), 1- and 3-month thyroperoxidase antibody (95% CI, 0.02 to 0.22; 95% CI, 0.17 to 0.43), and 1-day, 1-, and 3-month thyrotrophin receptor antibody (95% CI, 0.10 to 0.43; 95% CI, 0.00 to 0.30; 95% CI, 0.13 to 0.36) after ablation. No statistically significant differences were found in these six indicators in the longer term. The results of subgroup analysis were similar to the pooled results. No significant publication bias was found. CONCLUSIONS: Energy-based ablation was more likely to have negative effects on thyroid function and antibodies and led to transient increase in Tg level in the short term. However, most of the patients would not develop any thyroid dysfunction in the long-term follow-up.

The effectiveness of the combined problem-based learning (PBL) and case-based learning (CBL) teaching method in the clinical practical teaching of thyroid disease.

BACKGROUND: This study aimed to evaluate the effectiveness and efficiency of PBL-CBL combined teaching in thyroid surgery and make observations from the students' perspectives, based on their satisfaction with the learning process. METHODS: We prospectively enrolled 354 fourth-year students majoring in clinical medicine, along with 232 residents, from September 2014 to June 2019. These participants were randomly allocated into either the combined PBL-CBL teaching group or the traditional lecture-based classroom group to attend a course about thyroid nodules. Both pre- and post-class quizzes were conducted. An anonymous questionnaire was also administered to both groups to evaluate the students' perceptions and experiences. We compared the two teaching methods among all the students as well as with the fourth-year students and residents in subgroups. RESULTS: The traditional group's pre-class quiz scores were significantly higher than the PBL-CBL group's (as determined by a two-tailed t-test at a 95% confidence interval, T = 16.483, P < 0.001). After class, in the PBL-CBL group, the mean total quiz score and the basic knowledge and case analysis scores increased significantly (P < 0.001). The PBL-CBL group's performance improvement was significantly higher than the traditional group's (increasing from 52.76 to 70.51 vs. from 67.03 to 71.97). Furthermore, the scores for learning motivation, understanding, student-teacher interaction, the final examination, communication skills, clinical thinking skills, self-learning skills, teamwork skills, and knowledge absorption, as measured by the survey, were significantly higher in the PBL-CBL group than in the traditional group (P < 0.001). Meanwhile, the survey scores representing the amount of students' free time the course consumed were significantly lower in the PBL-CBL group than in the traditional group (P < 0.001). CONCLUSIONS: PBL combined with CBL may be an effective method for improving medical students' and residents' performance and enhancing their clinical skills.

Activation of GPER suppresses the malignancy of osteosarcoma cells via down regulation of IL-6 and IL-8.

Estrogenic signals can regulate the progression of osteosarcoma (OS) via classic estrogen receptor α/ß (ERα/ß). G protein-coupled estrogen receptor (GPER) can mediate the non-genomic effects of estrogen and regulate the progression of various cancers. Our present study revealed that the expression of GPER in OS cells and tissues was lower than that in their corresponding controls. Activation of GPER via its specific agonist G-1 can decrease the proliferation, migration, and invasion of OS cells. By screening the expression of cytokines involved in the progression of OS, we found that activation of GPER can inhibit the expression of interleukin-6 (IL-6) and IL-8 in OS cells. Recombinant IL-6 (rIL-6) or rIL-8 can attenuate G-1 suppressed migration of OS cells. Mechanically, activation of GPER can rapidly decease the phosphorylation and nuclear translocation of NF-κB in OS cells. While over expression of p65 significantly attenuated G-1 induced down regulation of IL-6/IL-8. Further, G-1 can decrease the activation of p38-MAPK, which can further shorten the half-life of IL-8 mRNA. Collectively, we revealed that GPER can suppress the migration and invasion of OS cells via inhibition of IL-6 and IL-8. It suggested that GPER might be a potential therapy target for OS treatment.

The effect and mechanism of millepachine-disrupted spindle assembly in tumor cells.

Millepachine (MIL) is a bioactive natural product that shows great potential for cancer treatment. Previous studies showed that MIL was a novel cancer drug candidate with a special structure. To provide reference for the research and development of MIL, we further investigated the mechanism of MIL inducing G2/M arrest and found MIL disrupted spindle assembly in tumor cells. In this study, we investigated the disrupting spindle assembly effects of MIL with a focus on its potential mechanism of action. First, we indicated that MIL did not inhibit microtubule polymerization from the results of in-vivo microtubule nucleation assay and microtubule polymerization in-vitro assay but delayed this process by inhibiting the production of ATP in tumor cells. Thereafter, we investigated the effect of MIL on the mitotic spindle. We found that MIL induced multipolar spindles by inhibiting the activity of Eg5 and inhibited mitotic spindle formation and chromatin condensation by the activation of the spindle assembly checkpoint (SAC) in tumor cells. These results established a novel function of MIL in regulating the assembly of mitotic spindle. As Eg5 and SAC are antitumor targets, effect of MIL on the Eg5 protein and SAC activation hinted that MIL has novel application in the development of antitumor drugs.

Transjugular intrahepatic portosystemic shunt versus open splenectomy and esophagogastric devascularization for portal hypertension with recurrent variceal bleeding.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) and open splenectomy and esophagogastric devascularization (OSED) are widely used to treat patients with portal hypertension and recurrent variceal bleeding (PHRVB). This study aimed to compare the effectiveness between TIPS and OSED for the treatment of PHRVB. METHODS: The data were retrospectively retrieved from 479 cirrhotic patients (Child-Pugh A or B class) with PHRVB, who had undergone TIPS (TIPS group) or OSED (OSED group) between January 1, 2010 and October 31, 2014. RESULTS: A total of 196 patients received TIPS, whereas 283 underwent OSED. Within one month after TIPS and OSED, the rebleeding rates were 6.1% and 3.2%, respectively (P=0.122). Significantly lower incidence of pleural effusion, splenic vein thrombosis, and pulmonary infection, as well as higher hepatic encephalopathy rate, shorter postoperative length of hospital stay, and higher hospital costs were observed in the TIPS group than those in the OSED group. During the follow-up periods (29 months), significantly higher incidences of rebleeding (15.3% vs 4.6%, P=0.001) and hepatic encephalopathy (17.3% vs 3.9%, P=0.001) were observed in the TIPS group than in the OSED group. The incidence of in-stent stenosis was 18.9%. The survival rates were 91.3% in the TIPS group and 95.1% in the OSED group. The long-term liver function did not worsen after either TIPS or OSED. CONCLUSION: For the patients with liver function in the Child-Pugh A or B class, TIPS is not superior over OSED in terms of PHRVB treatment and rebleeding prevention.

Hypomagnesemia predicts postoperative biochemical hypocalcemia after thyroidectomy.

BACKGROUND: To investigate the role of magnesium in biochemical and symptomatic hypocalcemia, a retrospective study was conducted. METHODS: Less-than-total thyroidectomy patients were excluded from the final analysis. Identified the risk factors of biochemical and symptomatic hypocalcemia, and investigated the correlation by logistic regression and correlation test respectively. RESULTS: A total of 304 patients were included in the final analysis. General incidence of hypomagnesemia was 23.36%. Logistic regression showed that gender (female) (OR = 2.238, p = 0.015) and postoperative hypomagnesemia (OR = 2.010, p = 0.017) were independent risk factors for biochemical hypocalcemia. Both Pearson and partial correlation tests indicated there was indeed significant relation between calcium and magnesium. However, relative decreasing of iPTH (>70%) (6.691, p < 0.001) and hypocalcemia (2.222, p = 0.046) were identified as risk factors of symptomatic hypocalcemia. The difference remained significant even in normoparathyroidism patients. CONCLUSIONS: Postoperative hypomagnesemia was independent risk factor of biochemical hypocalcemia. Relative decline of iPTH was predominating in predicting symptomatic hypocalcemia.

Evaluation of Total Flavonoids, Myricetin, and Quercetin from Hovenia dulcis Thunb. As Inhibitors of α-Amylase and α-Glucosidase.

This study was designed to investigate the inhibition effect and mechanism of total flavonoids, myricetin and quercetin extracted from Hovenia dulcis Thunb. on α-amylase and α-glucosidase in order to explore the potential use of Hovenia flavonoids in alleviating postprandial hyperglycemia. The results demonstrate that total flavonoids, myricetin, and quercetin were effective inhibitors of α-amylase with IC50 values of 32.8, 662 and 770 µg ml-1, respectively. And all three were effective inhibitors of α-glucosidase with IC50 values of 8, 3 and 32 µg ml-1, respectively. Enzyme kinetics tests and Lineweaver-Burk results showed the inhibition effects of total flavonoids, myricetin and quercrtin on α-amylase were all reversible and competitive, and the effects on α-glucosidase were all reversible but non-competitive. This study revealed that Hovenia flavonoids, especially myricetin, are effective and promising functional foods in alleviating type 2 diabetes mellitus.

[Effect of CD86 Gene Modified Recipient Dendritic Cell on Mix Cultured Donor-derived Islet with Recipient-derived Lymphocyte in vitro].

OBJECTIVE: To investigate the effect of CD86 gene modified recipient dendritic cell (DC) on mix cultured donor-derived islet with recipient-derived lymphocyte in vitro. METHODS: DCs were separated from bone marrow of BALB/c mice and identified by flow cytometry. Chemically synthesized CD86 siRNA was transferred into DC. Donor islets were separated from the pancreas of SD rats. Acridine orange (AO)/Propidium iodide (PI) staining was conducted to assess the viability of islets. Lymphocytes were collected from the spleen of SD rats and then co-cultured with CD86 gene modified recipient DCs. CD86 gene modified recipient DC, donor-derived islet (400 IEQ) and recipient-derived lymphocyte (1 x 10(6)) were mix cultured in vitro. Four groups were set: blank group (islets of SD rat only), control 1 group (islets of SD rat with splenic lymphocyte of BALB/c mice) , control 2 group (islets of SD rat, splenic lymphocyte of BALB/c mice with normal recipient DC) and experimental group (islets of rat, splenic lymphocyte of BALB/c mice with CD86 gene modified recipient DC). After 3 days culture, the cellular morphology of culture was observed with light inverted microscope. The levels of IL-2, IL-4, IL-10 and IFN-γ in the culture supernatant were tested, and islets viability was assessed by AO/PI staining. GSIS was conducted and stimulation index (SD was calculated. RESULTS: Typical DC morphology was found from the collected cells. The positive rates of CD1lc, CD80 and CD86 protein expression on DCs were 86.26% ± 9.73%, 72.64% ± 8.55% and 77.18% ± 10.23%, respectively. The positive rate of CD86 protein expression on DCs after transfection was 23.64% ± 5.25%. The viability of islets was over 95%. After 3 days culture, the level of IL-10 increased significantly and the levels of IL-2 and INF-γ decreased significantly in experimental group (vs. control 1 and control 2 groups, P < 0.05). The level of IL-4 was similar in control 1, control 2 and experimental groups, but the proliferation rate of lymphocyte in the experimental group was the lowest one, the viability of islets in the experimental group was the best and the SI was the highest. The levels of IL-2, IL-4, IL-10 and IFN-γ in the experimental group were higher than those in the blank group. CONCLUSION: CD86 gene modified recipient DC loaded with donor-derived antigen could protect the islet function in vitro to some extent.

Triple-layer duct-to-mucosa pancreaticojejunostomy with resection of jejunal serosa decreased pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Pancreatic fistula (PF) is one of the most common complications after pancreaticoduodenectomy (PD). We described a new method of pancreaticojejunostomy (PJ) developed by combining triple-layer duct-to-mucosa PJ with resection of jejunal serosa, which was named as modified layer-to-layer PJ (MLLPJ). The aim of the present study was to observe whether the new technique would effectively reduce the PF rate in comparison with two-layer duct-to-mucosa PJ (TLPJ). METHODS: Data on 184 consecutive patients who underwent the two methods of PJ after standard PD between January 1, 2010 and January 31, 2013 were collected retrospectively from a prospective database. The primary endpoint was the PF rate. The risk factors of PF were investigated by using univariate and multivariate analyses. RESULTS: A total of 88 patients received TLPJ and 96 underwent MLLPJ. Rate of PF for the entire cohort was 8.2%. There were 11 fistulas (12.5%) in the TLPJ group and four fistulas (4.2%) in the MLLPJ group (P = 0.039). Body mass index, pancreatic texture, pancreatic duct diameter, and methods of PJ anastomosis had significant effects on the formation of PF on univariate analysis. Multivariate analysis showed that pancreatic duct diameter ≤3 mm and TLPJ were the significant risk factors of PF. CONCLUSIONS: MLLPJ effectively reduces the PF rate after PD in comparison with TLPJ. Results confirm increased PF rates in patients with pancreatic duct diameter ≤3 mm compared with pancreatic duct diameter >3 mm.

Is laparoscopic approach for pancreatic insulinomas safe? Results of a systematic review and meta-analysis.

BACKGROUND: No consensus exists as to whether laparoscopic treatment for pancreatic insulinomas (PIs) is safe and feasible. The aim of this meta-analysis was to assess the feasibility, safety, and potential benefits of laparoscopic approach (LA) for PIs. The abovementioned approach is also compared with open surgery. METHODS: A systematic literature search (MEDLINE, EMBASE, Cochrane Library, Science Citation Index, and Ovid journals) was performed to identify relevant articles. Articles that compare the use of LA and open approach to treat PI published on or before April 30, 2013, were included in the meta-analysis. The evaluated end points were operative outcomes, postoperative recovery, and postoperative complications. RESULTS: Seven observational clinical studies that recruited a total of 452 patients were included. The rates of conversion from LA to open surgery ranged from 0%-41.3%. The meta-analysis revealed that LA for PIs is associated with reduced length of hospital stay (weighted mean difference, -5.64; 95% confidence interval [CI], -7.11 to -4.16; P < 0.00001). No significant difference was observed between LA and open surgery in terms of operation time (weighted mean difference, 2.57; 95% CI, -10.91 to 16.05; P = 0.71), postoperative mortality, overall morbidity (odds ratio [OR], 0.64; 95% CI, 0.35-1.17; P = 0.14], incidence of pancreatic fistula (OR, 0.86; 95% CI, 0.51-1.44; P = 0.56), and recurrence of hyperglycemia (OR, 1.81; 95% CI, 0.41-7.95; P = 0.43). CONCLUSIONS: Laparoscopic treatment for PIs is a safe and feasible approach associated with reduction in length of hospital stay and comparable rates of postoperative complications in relation with open surgery.

Post-marketing Safety Concerns of Teprotumumab: A Real-World Pharmacovigilance Assessment.

PURPOSE: Teprotumumab is the only drug approval by The US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED), which targets the insulin-like growth factor-1 receptor. This study aimed to identify potential safety signals of teprotumumab by analyzing post-marketing safety data from the FDA Adverse Event Reporting System (FAERS) database in 2023. METHODS: The case/non-case approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for adverse events (AEs) that numbered three or more. RESULTS: Total of 2158 cases were included in the analysis. Main safety signals identified were ear and labyrinth disorders, reproductive system and breast disorders, metabolism and nutrition disorders and gastrointestinal disorders. Specifically, autophony (ROR [95% CI] = 4188.34 [1403.29-12500.8]), eyelid retraction (ROR [95% CI] = 2094.17 [850.69-5155.29]), deafness permanent (ROR [95% CI] = 1552.35 [789.07-3053.98]), deafness bilateral (ROR [95% CI] = 73.12 [41.14-129.97]), inflammatory bowel disease (ROR [95% CI] = 23.26 [13.46-40.19]), hyperglycaemic hyperosmolar nonketotic syndrome (ROR [95% CI] = 17.75 [5.70-55.28]) and amenorrhoea (ROR [95% CI] = 47.98 [36.22-63.54]) showed significant safety signals of teprotumumab. CONCLUSIONS: This study identified ear and labyrinth disorders, reproductive system and breast disorders, as specific safety signals of teprotumumab. Clinicians and pharmacists should be vigilant regarding these AEs. However, available data are currently insufficient, and further pharmacovigilance and surveillance are needed to fully understand this issue.