Necrostatin-1 prevents skeletal muscle ischemia reperfusion injury by regulating Bok-mediated apoptosis.

BACKGROUND: Receptor interacting serine/threonine kinase 1 (RIPK1) mediates apoptosis by regulating the classic proapoptotic effectors Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak). Although Bcl-2-related ovarian killer (Bok) is structurally similar to Bak and Bax, it is unclear whether it mediates apoptosis in skeletal muscle ischemia reperfusion (IR) injury. We hypothesized that by regulating Bok-mediated apoptosis, inhibiting RIPK1 with necrostatin-1 would reduce skeletal muscle IR injury. METHODS: Rats were randomized into four groups: sham (SM), IR, IR treated with necrostatin-1 (NI), or vehicle dimethyl sulfoxide (DI). For the IR group, the right femoral artery was clamped for 4 hours and then reperfused for 4 hours, and for the NI and DI groups, necrostatin-1 (1.65 mg/kg) and the equal volume of dimethyl sulfoxide were intraperitoneally administered prior to IR induction. The structural damage of muscle tissue and protein expression of Bok, Bcl-2, and cleaved caspase-3 were investigated, and apoptotic cells were identified with terminal dUTP nick-end labeling (TUNEL) staining. In vitro, human skeletal muscle cells (HSMCs) were exposed to 6 hours of oxygen-glucose deprivation followed by normoxia for 6 hours to establish an oxygen-glucose deprivation/reoxygenation (OGD/R) model. To determine the role of Bok, cell viability, lactate dehydrogenase (LDH) release, and flow cytometry were examined to demonstrate the effects of necrostatin-1 and Bok knockdown on the OGD/R insult of HSMCs. RESULTS: Necrostatin-1 pretreatment markedly reduced IR-induced muscle damage and RIPK1, Bok, and cleaved caspase-3 expression, whereas upregualted Bcl-2 expression (p < 0.05). Furthermore, necrostatin-1 prevented mitochondrial damage and decreased TUNEL-positive muscle cells (p < 0.05). In vitro, HSMCs treated with necrostatin-1 showed reduced Bok expression, increased cell viability, and reduced LDH release in response to OGD/R (p < 0.05), and Bok knockdown significantly blunted the OGD/R insult in HSMCs. CONCLUSION: Necrostatin-1 prevents skeletal muscle from IR injury by regulating Bok-mediated apoptosis.

Prevalence and impact of non-alcoholic fatty liver disease in patients with papillary thyroid carcinoma.

PURPOSE: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. Non-alcoholic Fatty Liver Disease (NAFLD) was possibly among the risk factors for thyroid carcinoma. It is uncertain whether NAFLD is associated with the aggressiveness of PTC. METHODS: We obtained data on patients with PTC who had undergone surgery at the First Affiliated Hospital of Wenzhou Medical University between January 2020 and February 2022. Pre-and post-operative data were obtained from electronic medical records and analyzed. Patients were split into two groups based on the NAFLD diagnostic criteria and compared using univariate and multivariate analysis through a logistic regression model. RESULTS: In all, 3468 patients with PTC were included in this study, of which 594 (17.1%) were diagnosed with NAFLD. NAFLD was found to be an independent risk factor for lymph node metastasis (OR = 1.285 95% CI: 1.052-1.570), incidence of BRAF V600E mutation (OR = 1.504, 95% CI: 1.148-1.972) and later tumor stage at diagnosis (OR = 2.310, 95% CI: 1.700-3.139) in PTC. The association mentioned above remained significant in subgroups of patients with Hashimoto's thyroiditis (HT), hypertension, diabetes (DM), high triglyceride (TG) levels, low levels of high-density lipoprotein-cholesterol (HDL-C), and high body mass index (BMI). In subgroup of female rather than male, NAFLD was an independent risk factor for lymph node metastasis (OR = 1.638 95% CI: 1.264-2.123), incidence of BRAF V600E mutation (OR = 1.973, 95% CI: 1.368-2.846) as well as later tumor stage (OR = 2.825, 95% CI: 1.964-4.063) in PTC. However, NAFLD was not a risk factor for the larger tumor size (>1 cm), extra-thyroidal extension (ETE), or multifocality in PTC. CONCLUSION: Our cross-sectional study indicated that there is a strong association of NAFLD with higher incidence of lymph node metastasis, higher incidence of BRAF V600E mutation and later TNM stage than non-NAFLD in females with PTC.

Efficacy and safety of sympathetic radiofrequency thermocoagulation in the treatment of cold hypersensitivity.

Background: Cold hypersensitivity (CH) is a sensation of cold in the limbs and (or) body of a patient in an environment that is not considered cold by unaffected people, or a strong feeling of cold at a relatively low temperature. However, the currently available treatments are limited and often unsatisfactory. This study aimed to evaluate the clinical efficacy and safety of the sympathetic radiofrequency thermocoagulation (RF-TC) technique in patients with CH disorder. Methods: The study is a retrospective analysis. A total of 71 were entered into the final analysis and all patients underwent computed tomography-guided thoracic (lumbar) sympathetic nerve RF-TC on an elective basis. The values of terminal temperature (T) and perfusion index (PI) of patients before and after treatment were recorded. Patients were followed up clinically at regular intervals and their Visual Analog Scale (VAS) and Pittsburgh Sleep Quality Index (PSQI) scores were recorded to detect postoperative complications and assess patient satisfaction with the treatment. Results: All patients completed the radiofrequency treatment. Compared with the preoperative period, VAS and PSQI scores were significantly lower at all postoperative time periods (P < 0.001). Patients had significantly higher postoperative terminal temperatures and perfusion indices on the right and left sides than before surgery (P < 0.001). The overall patient satisfaction score was 4 (3-5) at 3 years of postoperative follow-up. There were 20 recurrences (28.2%). The main postoperative complications were postoperative local pain and compensatory hyperhidrosis. No other adverse events or deaths were observed. Conclusion: RF-TC for CH could be a feasible, effective, and safe treatment option to improve patients' symptoms of cold sensation. Yet, more researches are needed to verify this potentially efficient and standardized treatment.

Comparison of Analgesic Effects of Different Regional Blocks in Video-assisted Thoracic and Breast Surgeries: A Network Meta-analysis and Systematic Review.

BACKGROUND: Postoperative pain management in breast surgery and video-assisted thoracic surgeries (VATS) remains challenging. Oral or intravenous infusion of opioids were early treatments, but they can result in gastrointestinal reactions, respiratory inhibition, and other adverse reactions. In recent years, various regional block techniques have been employed for postoperative analgesia of these surgeries. However, a pair-wise meta-analysis cannot comprehensively rank and evaluate the analgesic effects and adverse events of various regional blocks. OBJECTIVE: The purpose of this network meta-analysis (NMA) was to compare the analgesic effects and adverse events of different regional block techniques after breast surgery and VATS. STUDY DESIGN: NMA of randomized controlled trials (RCTs) for comparing multiple regional block techniques in breast surgery and VATS. METHODS: Pubmed, Embase, and Cochrane databases were searched systematically for RCTs comparing analgesic effects and adverse events after breast surgery and VATS. After critical appraisal, a random-effects NMA was mainly used to compare all the regional blocks' analgesic effects and adverse events. The Population, Interventions, Comparators, Outcomes, and Study design (PICOS) framework was used to build the search strategies and present the results according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. The primary endpoint was opioid consumption within 24 hours after the operation; secondary endpoints included dynamic and static pain scores and the incidence of nausea and vomiting. This study is registered in the Prospective Register of Systematic Reviews (PROSPERO) with a PROSPERO number of CRD42021283907. RESULTS: A total of 21 clinical trials, including 1,284 patients and 6 different regional block techniques (paravertebral block pectoral nerve block serratus anterior plane block [SAPB], intercostal nerve block [ICNB], erector spinal plane block and thoracic epidural anesthesia), were included and analyzed. There was no significant difference between the consistent and the inconsistent models. Based on limited evidence, SAPB may be the most effective regional block technique for relieving postoperative pain, while ICNB had the lowest probability of nausea and vomiting. There was no significant difference in the pair-wise comparisons. In this study, we found no obvious publication bias. LIMITATIONS: Limitations include: morphine milligram equivalents were not used to calculate opioid consumption; the scales used in the studies were different; the number of studies and total sample size included was limited; non-English literature and gray literature were not included; more databases were not searched. CONCLUSIONS: After a comprehensive evaluation of postoperative analgesic effects and adverse events based on the NMA, we hypothesize that SAPB and ICNB have distinct advantages in postoperative analgesia and reduce the incidence of nausea and vomiting, respectively. However, conclusions drawn from more RCTs may be more convincing.

Correlation of Cystatin E/M with Clinicopathological Features and Prognosis in Triple-Negative Breast Cancer.

BACKGROUND: Among all kinds of breast cancer, triple-negative breast cancer (TNBC) is the most aggressive, with the poorest prognosis and highest mortality rates. Thus, novel biomarkers that personalize the therapeutic regimen and evaluate prognosis for TNBC patients should be determined. METHODS: We analyzed the cystatin E/M (CST6) expression profiles of 161 TNBC tissues and 14 noncancerous tissues through multiple statistical analyses. We also investigated the relationship of CST6 expression with clinical parameters and evaluated the prognostic value of CST6 in 161 TNBC patients. RESULTS: CST6, a member of the cystatin superfamily, was remarkably more up-regulated in TNBC tissues than in adjacent normal breast tissues. High CST6 expression was frequently observed in white people and associated with a high risk of lymph-node metastasis. Cox regression analysis confirmed that the high CST6 expression was an independent predictor of disease-free survival in TNBC. Kaplan-Meier analysis further revealed that high CST6 expression caused a low disease-free survival rate. CONCLUSION: CST6 is involved in the progression of TNBC and may act as a tumor-promoter gene. A systematic literature review shows that our study is the first to explore the relationship between CST6 and TNBC.

A scoring system is an effective tool for predicting central lymph node metastasis in papillary thyroid microcarcinoma: a case-control study.

BACKGROUND: The purpose of this study was to evaluate the clinicopathologic and ultrasonographic (US) characteristics and establish an effective scoring system for predicting central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma (PTMC). METHODS: A total of 498 patients with PTMC who underwent total thyroidectomy or lobectomy with therapeutic central lymph node dissection (CLND) were enrolled. Univariate and multivariate analyses were performed to find the independent predictors for CLNM based on clinicopathological and US characteristics. Using the standardized regression coefficient, a 10-point score system was constructed in line with these independent predictors. Then, the scoring system was evaluated for the diagnostic value in predicting CLNM. RESULTS: Tumor location (the lower polo), tumor size (>5 mm), extrathyroidal extension, margin (no well-defined), display of enlarged lymph node, and contact of >25% with the adjacent capsule were independent predictors for CLNM. Verifying the scoring system, a cutoff value of 5 points was found to be the best prediction for CLNM, the sensitivity and specificity were 64.7 and 80.5%, respectively, and the positive and negative predictive values were 77.3 and 69.0%, respectively. CONCLUSIONS: The points≤5 could be considered as a low risk for CLNM, and the points>5 could be identified as a high risk for CLNM. More advanced diagnostic approaches and prophylactic CLND are needed for patients with the points>5.

[Number of positive central cervical lymph nodes for predicting lateral cervical lymph node metastasis in patients with papillary thyroid carcinoma].

OBJECTIVE: The aim of this study was to evaluate the number of central cervical lymph node metastasis (CCLNM) in predicting lateral cervical lymph node metastasis (LCLNM) in patients with papillary thyroid carcinoma (PTC). METHODS: From January 2005 to October 2010, a total of 133 patients diagnosed as PTC underwent central and lateral cervical lymph node dissection were enrolled in this study. Quantitative analysis was performed to explore the correlation between the number of CCLNM and LCLNM. RESULTS: The sensitivity of central cervical node metastasis to predict lateral cervical node metastasis was 84.7%(61/72), and the positive predictive value (PPV) was 66.3% (61/92). The incidence of lateral cervical LNM was correlated with the number of CCLNM (r=0.911, P=0.004). The LCLNM rates in patients with number of CCLNM <2 and ≥ 2 were 54.5% (12/22) and 70.0% (49/70), respectively, with a non-significant difference (P=0.181). The LCLNM rates in patients with number of CCLNM < 3 and ≥ 3 were 50.0% (19/38) and 77.8% (42/54), showing a significant difference (P=0.006). The LCLNM rates in patients with number of CCLNM <4 and ≥ 4 were 55.1% (27/49) and 79.1% (34/43), with a significant difference (P=0.015). The LCLNM rates in patients with number of CCLNM <5 and ≥ 5 with the LLNM rate were 57.6% (34/59) and 81.8% (27/33), showing a significant difference (P=0.019). The LCLNM rates in patients with number of CCLNM <6 and ≥ 6 were 60.0% (39/65) and 81.5% (22/27), showing a significant difference (P=0.047). CONCLUSIONS: CCLNM has a significant association with LCLNM in patients with papillary thyroid carcinoma. LCLNM is mainly observed in patients with ≥ 3 CCLNM. Therefore, the number of CLNM ≥ 3 may be a valuable predictor of lateral cervical lymph node metastasis, and lateral cervical lymph node dissection should be considered.

The Clinical Relevance of Psammoma Body and Hashimoto Thyroiditis in Papillary Thyroid Carcinoma: A Large Case-control Study.

This study aims to investigate the impact of psammoma body (PB) on papillary thyroid carcinoma (PTC), and evaluate the association among PB, Hashimoto thyroiditis (HT), and other clinicopathologic characteristics in PTC patients.We conducted a retrospective case-control study involving 1052 PTC patients who underwent total thyroidectomy or lobectomy with lymph node dissection.Psammoma body was observed in 324 out of 1052 PTC (30.8%) patients. Ultrasonographic (US) calcification (P < 0.001), multifocality of the tumor (P = 0.047), lymph node metastasis (LNM) (P < 0.001), HT (P < 0.001), and Primary tumor (T), Regional lymph nodes (N), Distant metastasis (M) staging (P = 0.001) were significantly related to the presence of PB. The presence of PB was significantly associated with US microcalcification (P < 0.001). In the subgroup with HT, compared with the patients without PB, the patients with PB exhibited a higher frequency of central LNM (54.7% vs 32.1%; P < 0.001) and US microcalcification (94.7% vs 38.8%; P < 0.001), as well as smaller tumors (0.9 ±â€Š0.6 vs 1.3 ±â€Š0.9 cm; P < 0.001). In the subgroup without HT, the patients with PB displayed a higher incidence of lateral LNM (25.8% vs 14.6%; P < 0.001), US microcalcification (87.3% vs 52.5%; P < 0.001), and extrathyroidal extension (47.2% vs 34.8%; P = 0.001), as well as larger tumors (1.3 ±â€Š0.9 vs 1.0 ±â€Š0.8 cm; P < 0.001) than without PB. Moreover, in the subgroup with PB, the PTC patients with HT showed a higher LNM (77.9% vs 57.2%; P < 0.001) and a lower frequency of extrathyroidal extension (20.0% vs 47.2%; P < 0.001) than without HT.Psammoma body is a useful predictor of aggressive tumor behavior in PTC patients. HT with PB shows more aggressive behaviors than non-HT with PB in PTC patients.

A Case Report: The Diagnosis and Therapeutic Evaluation for a Rare Disease of Langerhans Cell Histiocytosis Involving Thyroid.

Langerhans cell histiocytosis (LCH) involving the thyroid gland is extremely rare. Currently, the diagnosis and therapeutic evaluation for LCH involving thyroid is a challenge.We reported a rare case of LCH involving thyroid, presenting as painless thyroid goiters, and successfully performed positron emission tomography/computed tomography (PET/CT) to make an accurate diagnosis and therapeutic evaluation for LCH.Although the histology or cytology is the golden standard for the diagnosis of LCH involving thyroid, the PET/CT should be keep in mind when LCH involving thyroid with inconclusive cytologic results. During the treatment of LCH, PET/CT can be performed to assess the therapeutic effect and select the most effective and reliable treatment for LCH.

Risk factors target in patients with post-thyroidectomy bleeding.

As the highly blood flow of thyroid gland post-thyroidectomy bleeding (PTB) is a serious and life-threatening complication. Our aim was to investigate factors that influenced bleeding after thyroidectomy. Between February 2008 and September 2012, the data of 4449 consecutive patients with thyroid diseases undergoing thyroidectomy were collected and analysed from the department of surgical oncology retrospectively. During the study period, 88 (2.0%) patients were identified to have clinically PTB. 6 risk factors were significantly related to PTB: gender (OR 3.243; 95% CI 2.078-5.061; P < 0.001), age (OR 1.025; 95% CI 1.006-1.043; P = 0.009), tumor size (OR 4.495; 95% CI 2.462-8.208; P < 0.001), postoperative hypertension (OR 2.195; 95% CI 1.006-1.043; P = 0.035), lymph node dissection (OR 3.384; 95% CI 2.146-5.339; P < 0.001) and Graves' disease (OR 3.744; 95% CI 1.920-7.303; P < 0.001). We addressed the most common explicit source of bleeding by reexploration: infrahyoid muscles (30/88), beside the laryngeal recurrent nerve (22/88), subcutaneous tissue (10/88) and superior pole (10/88). In our study, male gender, older age, tumor size > 3 cm, postoperative hypertension (SP > 150 mmHg), lymph node dissection and Graves' disease were independent risk factors for PTB. The sources of bleeding were identified more frequently in the infrahyoid muscles and beside the laryngeal recurrent nerve. It is helpful for surgeons to decide the potential bleeding points during the reexploration of PTB.