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Background@#Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), serve as valuable prognostic indicators in various cancers. This multicenter, retrospective cohort study assessed the treatment outcomes of lenvatinib in 71 patients with radioactive iodine (RAI)-refractory thyroid cancer, considering the baseline inflammatory biomarkers. @*Methods@#This study retrospectively included patients from five tertiary hospitals in Korea whose complete blood counts were available before lenvatinib treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated based on the median value of inflammatory biomarkers. @*Results@#No significant differences in baseline characteristics were observed among patients grouped according to the inflammatory biomarkers, except for older patients with a higher-than-median NLR (≥2) compared to their counterparts with a lower NLR (P= 0.01). Patients with a higher-than-median NLR had significantly shorter PFS (P=0.02) and OS (P=0.017) than those with a lower NLR. In multivariate analysis, a higher-than-median NLR was significantly associated with poor OS (hazard ratio, 3.0; 95% confidence interval, 1.24 to 7.29; P=0.015). However, neither the LMR nor the PLR was associated with PFS. A higher-than-median LMR (≥3.9) was significantly associated with prolonged OS compared to a lower LMR (P=0.036). In contrast, a higher-than-median PLR (≥142.1) was associated with shorter OS compared to a lower PLR (P=0.039). @*Conclusion@#Baseline inflammatory biomarkers can serve as predictive indicators of PFS and OS in patients with RAI-refractory thyroid cancer treated with lenvatinib.

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We present a rare case of acute thyrotoxicosis in a man with horse-induced neck trauma. A 60-year-old man presented to our emergency department with a head and neck injury caused by a horse kick. Computed tomography revealed a hematoma in the right thyroid gland. Ultrasonography of the neck revealed a 1.4 cm sized heterogenous hypoechoic lesion with an irregular margin in the right lower pole, suggestive of a thyroid hematoma. A thyroid function test revealed elevated free thyroxine and free triiodothyronine levels and suppressed thyrotropin levels. A Tc-99m thyroid scan showed a mild diffuse decreased uptake in the thyroid gland, especially in the right lower pole. We monitored the thyroid function test results, which took 2 months to recover to the normal range. This case indicates that awareness of thyroid dysfunction and monitoring of thyroid function are vital in patients with neck trauma.

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Purpose@#Invasive ductal carcinoma (IDC) accounts for 90% of triple-negative breast cancer (TNBC). IDC is mainly derived from the breast ductal epithelium which is innervated by the 4th to 6th thoracic sympathetic nerves. However, little is known about the contribution of the interactions between sympathetic nerves and breast cancer cells to the malignant progression of TNBC. @*Methods@#The expression levels of the β2 -adrenergic receptor (β2 -AR, encoded by ADRB2 gene), nerve growth factor (NGF), and tropomyosin receptor kinase A (TrkA) were determined using immunohistochemistry (IHC). NGF expression levels in the serum were compared by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was assessed using the Cell Counting Kit-8 assay. The β2 -AR, NGF, p-ERK, and p-CERB expression levels were determined using western blotting. TNBC cells and neuronal cells of the dorsal root ganglion (DRG) in 2-day-old Sprague Dawley rats were co-cultured. Using norepinephrine (NE), NGF, and β2 -AR, NGF/TrkA blocker pretreatments, the axon growth of each group of DRG neuron cells was detected by immunofluorescence analysis. @*Results@#The sympathetic adrenergic neurotransmitter NE activated the ERK signaling pathway in TNBC cells. NE/β2 -AR signaling promotes NGF secretion. NGF further facilitates the malignant progression of TNBC by increasing sympathetic neurogenesis. In the coculture assay, the sympathetic adrenergic NE/β2 -AR signal pathway also enhanced NGF secretion. NGF binds TrkA in DRG neurons and promotes axonal growth. @*Conclusion@#These results suggest that NE/β2 -AR pathway promotes cell proliferation and NGF production in triple-negative breast cancer.

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Background@#Immunoglobulin G4 (IgG4)-related disease is an entity that can involve the thyroid gland. The spectrum of IgG4-related thyroid disease (IgG4-RTD) includes Hashimoto thyroiditis (HT) and its fibrotic variant, Riedel thyroiditis, as well as Graves’ disease. The early diagnosis of IgG4-RTD is important because it is a medically treatable disease, and a delay in the diagnosis might result in unnecessary surgery. We present a case series of IgG4-RTD with a review of the literature. @*Methods@#We retrospectively reviewed the clinical presentation and the radiological and pathological findings of patients diagnosed with IgG4-RTD between 2017 and 2021 at a tertiary medical center in Korea. We also conducted a literature review of IgG4-RTD. @*Results@#Five patients were diagnosed with IgG4-RTD during the study period. The patients’ age ranged from 31 to 76 years, and three patients were men. Most patients visited the clinic for a neck mass, and hypoechogenic nodular lesions were observed on neck ultrasonography. Three patients had IgG4 HT, and two patients had IgG4 Riedel thyroiditis. All patients developed hypothyroidism that necessitated L-thyroxine replacement. The diagnosis of IgG4-RTD was confirmed after a pathological examination of the surgical specimen in the first two cases. However, the early diagnosis was possible after a core needle biopsy in three clinically suspected patients. @*Conclusion@#The diagnosis of IgG4-RTD requires clinical suspicion combined with serology and histological analyses using IgG4 immunostaining. The early diagnosis of IgG4-RTD is difficult; thus, biopsy with IgG4 immunostaining and serum IgG4 measurements will help diagnose patients suspected of having IgG4-RTD.

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Objective:To observe the efficacy and safety of different doses of esketamine in the prevention and treatment of shivering after epidural anesthesia during cesarean section.Methods:Ninety women with American Society of Anesthesiologists grade Ⅰ to Ⅱ who underwent cesarean section from February to April 2021 in Dalian Women and Children′s Medical Center (Group) were divided into three groups by random digits table method: 0.9% sodium chloride group (group C, 30 cases); 0.25 mg/kg esketamine group (K1 group, 30 cases); esketamine 0.50 mg/kg group (K2 group, 30 cases). After epidural anesthesia, each group was given the drugs in the trial plan intravenously. General condition, shivering, sedation, Apgar score, psychiatric symptoms, nausea and vomiting were observed and recorded.Results:Finally, 81 cases were completed, including 27 cases in group C, 28 cases in group K1, and 26 cases in group K2. Shivering assessment: there was no grade 2/3 shivering in K1 group and K2 group, but the incidence of grade 2/3 shivering in C group was 25.93% (7/27) and 70.37% (19/27) the difference was statistically significant ( P<0.05). Sedation assessment: in the groups of K1 and K2, incidences of mild/moderate sedation were 92.86% (26/28)/7.14% (2/28) and 3.85% (1/26)/96.15% (25/26), respectively, obviously higher than those of group C, the differences were statistically significant ( P<0.01); there were no significant differences in the incidences of maternal mental symptoms, nausea and vomiting, and Apgar score of newborns among the three groups ( P>0.05). Conclusions:0.25 and 0.50 mg/kg esketamine are effective in preventing and treating shivering after cesarean section with epidural anesthesia without obvious adverse reactions.

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BACKGROUND: The study aimed to evaluate the inhibitory effect of tamarixetin on the production of inflammatory mediators in immunoglobulin E /antigen-induced mouse bone marrow-derived mast cells (BMMCs). MATERIAL AND METHODS: Tamarixetin isolated from Inula japonica was infected into BMMCs. The inhibitory effect of tamarixetin were analyzed by quantifying ß-hexosaminidase, eicosanoid generation, intracellular calcium measurement, and Western blot analysis. RESULTS: Tamarixetin effectively decreased degranulation and the eicosanoid generation such as leukotriene C4 and prostaglandin D2 in BMMCs. To elucidate the mechanism involved, we investigated the effect of tamarixetin on the phosphorylation of signal molecules. Tamarixetin inhibited the phosphorylation of protein kinase B (Akt) and its downstream signal molecules including IκB kinase and nuclear factor-κB. Besides, tamarixetin downregulated the phosphorylation of cytosolic phospholipase A2 and p38 mitogen-activated protein kinase.Conclusion: In summary, tamarixetin inhibits degranulation and eicosanoid generation through the phospholipase Cγ1 as well as Akt pathways. It could be potential for the prevention of allergic inflammatory diseases in BMMCs.

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Background@#The association between Graves’ disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography. @*Methods@#Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules). @*Results@#Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020). @*Conclusion@#The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.

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Background@#Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis. @*Methods@#This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009. @*Results@#The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS). @*Conclusion@#The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nation-wide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging.

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Background@#The clinical outcomes of delayed radioiodine remnant ablation (RRA) therapy in patients with low-risk papillary thyroid carcinoma (PTC) are unclear. We aimed to evaluate the clinical impact of the interval between total thyroidectomy (TT) and RRA therapy in patients with low-risk PTC. @*Methods@#We included 526 patients who underwent TT and RRA for low-risk PTC with a primary tumor size of >1 cm between 2000 and 2012. Patients were divided into the early (3 months after TT considering other prognostic factors.

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Background@#The clinical outcomes of delayed radioiodine remnant ablation (RRA) therapy in patients with low-risk papillary thyroid carcinoma (PTC) are unclear. We aimed to evaluate the clinical impact of the interval between total thyroidectomy (TT) and RRA therapy in patients with low-risk PTC. @*Methods@#We included 526 patients who underwent TT and RRA for low-risk PTC with a primary tumor size of >1 cm between 2000 and 2012. Patients were divided into the early (3 months after TT considering other prognostic factors.

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Background@#The study aimed to compare the prognostic value of the 4th edition of World Health Organization classification (WHO-2017) with the previous WHO classification (WHO-2004) for follicular thyroid carcinoma (FTC). @*Methods@#This multicenter retrospective cohort study included 318 patients with FTC from five tertiary centers who underwent thyroid surgery between 1996 and 2009. We evaluated the prognosis of patients with minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTC according to WHO-2017. Further, we evaluated the proportion of variation explained (PVE) and Harrell’s C-index to compare the predictability of disease-free survival (DFS) and disease-specific survival (DSS). @*Results@#In total, 227, 58, and 33 patients had MI-, EA-, and WI-FTC, respectively. During a median follow-up of 10.6 years, 46 (14.5%) patients had disease recurrence and 20 (6.3%) patients died from FTC. The 10-year DFS rates of patients with MI-, EA-, and WI-FTC were 91.1%, 78.2%, and 54.9%, respectively (P<0.001, PVE=7.1%, C-index=0.649). The corresponding 10-year DSS rates were 95.9%, 93.5%, and 73.5%, respectively (P<0.001, PVE=2.6%, C-index=0.624). The PVE and C-index values were higher using WHO-2017 than using WHO-2004 for the prediction of DFS, but not for DSS. In multivariate analysis, older age (P=0.02), gross extrathyroidal extension (ETE) (P=0.003), and distant metastasis (P<0.001) were independent risk factors for DSS. @*Conclusion@#WHO-2017 improves the predictability of DFS, but not DSS, in patients with FTC. Distant metastasis, gross ETE and older age (≥55 years) were independent risk factors for DSS.

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Background@#The optimal dose of radioactive iodine (RAI) therapy for N1b papillary thyroid carcinoma (PTC) is controversial. We evaluated the clinical outcome of N1b PTC patients treated with either 100 or 150 mCi of RAI. @*Methods@#We retrospectively analyzed N1b PTC patients who underwent total thyroidectomy and postoperative RAI therapy at a tertiary referral center between 2012 and 2017. As the baseline characteristics differed between treatment groups, we performed exact matching for various pathological factors according to RAI dose. We evaluated the response to therapy and recurrence-free survival (RFS) in the matched patients. Structural recurrent/persistent disease was defined as new structural disease detected after initial therapy, which was confirmed by cytology or pathology. @*Results@#Of the total 436 patients, 37 (8.5%) received 100 mCi of RAI and 399 (91.5%) received 150 mCi of RAI. After an exact 1:3 matching, 34 patients in the 100 mCi group and 100 patients in the 150 mCi group remained. There was no significant difference in response to therapy between the groups in the matched population (P=0.63). An excellent response was achieved in 70.6% (n=24) of patients in the 100 mCi group and 76.0% (n=76) in the 150 mCi group. Two (5.9%) patients in the 100 mCi group and four (4.0%) in the 150 mCi group had recurrence and there was no significant difference in RFS between the groups in the matched population (P=0.351). @*Conclusion@#There were no differences in response to therapy and RFS in N1b PTC patients according to RAI dose.

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Colon interposition is a surgical procedure used for maintenance of luminal conduit after esophagectomy. Although epithelial neoplasia, such as adenoma and adenocarcinoma, may develop in the interposed colon, there are only few case reports on the condition. Due to the rarity of this condition, there is no definite consensus on recommending screening endoscopy for the early detection of neoplasia in the interposed colons. Here, we report a case of intramucosal adenocarcinoma in an interposed colon. Initial endoscopic resection for this tumor failed to accomplish complete resection. A subsequent endoscopic resection was performed 1 month later and complete resection was achieved. Based on our experience and recommendation on screening endoscopy for gastric cancer in Korea, we suggest that regular screening esophagogastroduodenoscopies should be performed following esophagectomy to detect early neoplasia in the stomach and interposed colon and avoid adverse results induced by delayed detection.

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Osteoporosis development is closely associated with oxidative stress and reactive oxygen species (ROS). Taurine has potential antioxidant effects, but its role in osteoblasts is not clearly understood. The aim of this study was to determine the protective effects and mechanisms of actions of taurine on hydrogen peroxide (H₂O₂)-induced oxidative stress in osteoblast cells. UMR-106 cells were treated with taurine prior to H₂O₂ exposure. After treatment, cell viability, apoptosis, intracellular ROS production, malondialdehyde content, and alkaline phosphate (ALP) activity were measured. We also investigated the protein levels of β-catenin, ERK, CHOP and NF-E2-related factor 2 (Nrf2) along with the mRNA levels of Nrf2 downstream antioxidants. The results showed that pretreatment of taurine could reverse the inhibition of cell viability and suppress the induced apoptosis in a dose-dependent manner: taurine significantly reduced H₂O₂-induced oxidative damage and expression of CHOP, while it induced protein expression of Nrf2 and β-catenin and activated ERK phosphorylation. DKK1, a Wnt/β-catenin signaling inhibitor, significantly suppressed the taurine-induced Nrf2 signaling pathway and increased CHOP. Activation of ERK signaling mediated by taurine in the presence of H₂O₂ was significantly inhibited by DKK1. These data demonstrated that taurine protects osteoblast cells against oxidative damage via Wnt/β-catenin-mediated activation of the ERK signaling pathway.

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Objective To explore the role of pregabalin on the expression of c-fos in spinal dorsal horn of the rat with neuropathic pain.Methods Thirty Wister rats (male) were divided into shamoperated group,model group and pregabalin group,with 10 cases in each group.The effect of the pregabalin on the heat pain threshold and expression of c-fos in spinal dorsal horn of the rat with neuropathic pain were observed.Results The heat pain threshold in model group at 3rd,4th,5th,6th,7th,10th and 14th day after operation was significantly lower than that in sham-operated group and pregabalin group at same time (P ＜ 0.05).The heat pain threshold in pregabalin group was lower than that in sham-operated group from 2nd day after operation,but there was no significant difference (P ＞0.05).At the 14th day after operation,the number of Fos-like-immunoreactivity (FLI) positive cells in sham-operated group,model group and pregabalin group was (16.4 ± 0.6),(66.7 ± 3.3) and (22.8 ± 1.5)cases,and the number of FLI positive cells in model group was significantly higher than that in shamoperated group and pregabalin group (P ＜ 0.05).Conclusions Pregabalin has analgesic activity on rat with neuropathic pain.Pregabalin activates spinal cord glial cells raisedby the injured peripheral nerve and infection,and also reduces the noxious stimulation of afferent pain to spinal dorsal horn neurons.

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Eight 1,6-O,O-diacetylbritannilactone (OABL) derivatives (compounds 1-8) were synthesized by esterification or reduction of 1-O-diacetylbritannilactone (ABL) isolated from Inula japonica.All derivatives were evaluated for their anti-inflammation activities through the determination of inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophages.As results,compounds 5-8 (IC50 ＜ 2 μmol/L) exhibited more potent inhibition of NO production activities than the lead compound OABL.

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Purpose To investigate the distribution of polymorphisms of quinone oxidoreductase 1 (NQO1) C609T gene in breast cancer patients, and to analyze the relationship with breast cancer molecular subtype. Methods Genotyping of C609T rs1800566 lo-cus of NQO1 gene in peripheral blood of 248 cases of female breast cancer were detected using high-throughput TaqMan MGB real-time fluorescence quantitative PCR technology, while the detection of ER, PR, HER-2 and Ki-67 in cancerous tissues were used with immu-nohistochemical staining and FISH gene amplification. Results Among 248 cases of breast cancer patients, CC genotype accounted for 27. 42% (68/248), CT genotype accounted for 49. 60% (123/248), TT genotype accounted for 22. 98% (57/248), which con-sistent with Hardy-Weinberg equilibrium law genetic (P>0. 05). 5 cases of HER-2 (++) who did not undergo FISH testing were re-moved, all the rest were done with FISH detection. Luminal A type accounted for 15. 2% (37/243), Luminal B type accounted for 51. 4% (125/243), HER-2 overexpression type accounted for 19. 8% (48/243), basal cell type accounted for 13. 6% (33/243). Compared with patients carrying the CC genotype, ER and PR positive rates in breast cancer patients carrying CT and TT genotype was significantly higher (P0. 05). There was no statistically difference on distribution of C609T polymorphism of NQO1 gene among different molecular sub-types of breast cancer (P>0. 05). Conclusions Here is no relationship between C609T polymorphism of NQO1 gene and breast cancer molecular subtype, miss rate of NQO1 ( CT+TT) in basal cell carcinoma is lower, and its gene polymorphism may provide the reasonable explanation to the heterogeneity of breast cancer molecular subtype.

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Objective: To study changes of serum levels of hepatocyte growth factor (HGF), soluble intercellular adhesion molecule-1 (sICAM-1) in patients with essential hypertension (EH) and their significance. Methods: A total of 59 EH patients were selected, including 20 cases with EH stage 1 (EH stage 1 group), 19 cases with EH stage 2 (EH stage 2 group) and 20 cases with EH stage 3 (EH stage 3 group). Another 30 healthy subjects were regard as normal control group. Double antibody enzyme-linked immunosorbent sandwich assay was used to measure concentrations of HGF and sICAM-1 in all groups, and then the results were compared and analyzed. Results: Compared with normal control group, there were significant increase in serum levels of HGF [(641.65±142.90) pg/ml vs. (998.15±241.38) pg/ml] and sICAM-1 [(161.70±32.36) ng/ml vs. (327.17±31.28) ng/ml] in EH patients (P<0.01 both), and it’s more significant as blood pressure increased (P<0.01). HGF concentration was positively correlated with sICAM-1 concentration (r=0.317, P<0.01). Conclusion: HGF and sICAM-1 may participate in pathogenesis of hypertension, indicating that HGF plays an important role in restore of impaired endothelial cells in hypertension.

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Objective: To investigate effect of curcumin on serum gelatinases levels in patients with unstable angina pectoris（UAP）. Methods： A total of 80 UAP patients admitted from January 2010 to September 2010 were enrolled and randomly divided into curcumin treatment group (n=40) and routine treatment control group (n=40). Serum levels of gelatinases [contain matrix metalloproteinase（MMP）-2 and -9) of the two groups were measured before and 30d after treatment. Results：Compared with before treatment , after treatment, serum gelatinases levels significantly decreased [MMP-2：（52.64±6.77）ng/ml vs. （32.65±1.67）ng/ml，MMP-9：（56.75±7.34）ng/ml vs.（35±1.88）ng/ml ] (P<0.01) in curcumin treatment group (P<0.01), and they were significantly lower than those of routine treatment control group [MMP-2：（32.65±1.67）ng/ml vs.（37.78±2.76）ng/ml，MMP-9：（35±1.88）ng/ml vs.（40.23±1.95）ng/ml ] , P<0.05 all. Conclusion：Curcumin could decrease serum levels of gelatinases in patients with unstable angina pectoris, and possesses effect of stabilization coronary artery plaque.

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Objective:To investigate effect of curcumin on serum gelatinases level in patients with unstable angina pectoris (UAP). Methods:A total of 80 UAP patients admitted from January 2010 to September 2010 were enrolled and randomly divided into curcumin treatment group (n=40) and routine treatment control group (n=40). Serum levels of gelatinases [contain matrix metalloproteinase (MMP)-2 and -9] of the two groups were measured before and 30d after treatment.Results: Compared with before treatment , after treatment, serum levels of gelatinases significantly decreased [MMP-2:(52.64±6.77)ng/ml vs.(32.65±1.67)ng/ml,MMP-9:(56.75±7.34)ng/ml vs.(35±1.88)ng/ml]in curcumin treatment group (P<0.01), and they were significantly lower than those of routine treatment control group[MMP-2:(32.65±1.67)ng/ml vs.(37.78±2.76)ng/ml,MMP9:(35±1.88)ng/ml vs.(40.23±1.95)ng/ml]],P<0.05. Conclusion:Curcumin could decrease serum levels of gelatinases in patients with unstable angina pectoris, and possesses effect stabilizing coronary artery plaque.