Metabolic mechanisms of thyroid cancer in different background using ultra-high performance liquid chromatography combined with mixed four-stage poles time-of-flight mass spectrometry / 中华内分泌代谢杂志

Objective:To analyze the metabolic mechanism of papillary thyroid cancer(PTC) in normal and Hashimoto′s thyroiditis(HT) background, and to explore the relationship between HT and PTC.Methods:This study included a matched sample set collected from Tianjin Medical University General Hospital between January 2018 and January 2019, consisting of PTC and paracancular tissue from 31 cases with coexisting HT(HT group), and 30 cases without(NC group), all confirmed pathologically following thyroidectomy. The ultra-high performance liquid chromatography combined with mixed four-stage poles time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to acquire data from the samples. Metabolite differences between the two groups were compared, aiming to identify distinct metabolic mechanisms of PTC under different backgrounds. Metabolic pathway analysis was conducted using Metabo-Analyst 5.0 to explore relevant metabolic pathways.Results:The HT group and NC group shared 7 common differentially expressed metabolites, including arginine, glutamic acid, cysteine, citric acid, malic acid, uracil, and taurine. Logistic regression model combined with receiver operating characteristic(ROC) analysis of these 7 biomarkers yielded excellent discriminatory capacity for PTC(area under ROC curve of HT group and NC group were 0.867 and 0.973, respectively). The common metabolic pathways were taurine and hypotaurine metabolism, arginine biosynthesis, alanine, aspartic acid and glutamic acid metabolism, arginine and proline metabolism, and glutamine and glutamic acid metabolism. The specific metabolic pathways in HT group were aminoacyl tRNA biosynthesis, glycine, serine, and threonine metabolism.Conclusion:The metabolic profiles of thyroid cancer exhibit significant differences between cases with normal backgrounds and those with HT. The specific pathways for PTC and HT are aminoacyl tRNA biosynthesis and the metabolism of glycine, serine, and threonine.

Propensity score matching study on the relationship between 131I treatment and male prognosis in postoperative differentiated thyroid cancer patients / 中华核医学与分子影像杂志

Objective:To study whether male was the risk factor for prognosis of patients with differentiated thyroid cancer (DTC) after 131I treatment based on propensity score matching (PSM) method. Methods:From April 2016 to January 2021, 1 677 patients (age: 11-84 (43.9±12.5) years) with DTC who underwent total thyroidectomy and received 131I treatment in Tianjin Medical University General Hospital were retrospectively enrolled and patients were divided into male group ( n=546) and female group ( n=1 131). The evaluation results of patients were divided into excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR) and structural incomplete response (SIR). Among them, ER and IDR were divided into good prognosis group, and BIR and SIR were divided into poor prognosis group. The PSM method was adopted to process all data to reduce the influence of data bias and confounding variables. χ2 test was used for data analysis. Multivariate logistic regression was used to analyze the risk factors affecting prognosis, and ROC curve was used to analyze the relationship between stimulated thyroglobulin (sTg) level and poor prognosis. Results:Before PSM, the proportion of male patients with poor prognosis was significantly higher than that of female patients (21.2%(116/546) vs 14.0%(158/1 131); χ2=17.53, P=0.001). After PSM, there was no difference in the proportion of poor prognosis between male and female groups (19.9%(107/537) vs 15.6%(84/537); χ2=5.43, P=0.143). Multivariate logistic regression analysis showed that male (odds radio ( OR)=1.439 (95% CI: 1.016-2.038), P=0.040), high T stage(T3+ T4 stage)( OR=1.816 (95% CI: 1.273-2.590), P=0.001), N1b stage ( OR=1.766 (95% CI: 1.233-2.530), P=0.002), M1 stage ( OR=9.833 (95% CI: 3.190-30.309), P<0.001) and sTg level ( OR=1.035 (95% CI: 1.029-1.042), P<0.001) were risk factors for poor prognosis before PSM, while high T stage (T3+ T4 stage)( OR=1.870 (95% CI: 1.212-2.886), P=0.005), M1 stage ( OR=8.993 (95% CI: 2.434-33.225), P=0.001), sTg level ( OR=1.040 (95% CI: 1.030-1.049), P<0.001) were still risk factors, and N1b stage ( OR=1.459 (95% CI: 0.938-2.270), P=0.094), male ( OR=1.383 (95% CI: 0.912-2.096), P=0.127) were no longer risk factors for poor prognosis after PSM. ROC curve analysis showed that the cut-off value of sTg was 10.25 μg/L, with the sensitivity of 81.0%(222/274) and the specificity of 84.2%(1 181/1 403). Conclusions:After reduction of selection bias by PSM, male is no longer a risk factor for prognosis after 131I treatment of DTC. In addition, high T stage(T3+ T4 stage), M1 stage and sTg≥10.25 μg/L were risk factors for poor prognosis.

Clinical characteristics of patients with thyroid nodules and differentiated thyroid cancer with different body mass index / 中华核医学与分子影像杂志

Objective:To explore the association between body mass index (BMI) and the incidence of thyroid nodules, the clinical characteristics and efficacy evaluation of differentiated thyroid cancer (DTC), respectively.Methods:Clinical data of 1 375 healthy people (1 031 males, 344 females, age: (43.5±10.6) years) who underwent routine physical examination (PE) and 1 450 patients (490 males, 960 females, age: (44.3±12.4) years) with medium-high risk DTC in Tianjin Medical University General Hospital from April 2016 to July 2020 were analyzed retrospectively. PE and DTC patients were classified into underweight group (BMI<18.5 kg/m 2), normal weight group (18.5≤BMI<24.0 kg/m 2), overweight group (24.0≤BMI<28.0 kg/m 2) and obesity group (BMI≥28.0 kg/m 2) respectively. χ2 test was employed to analyze the relation between BMI and thyroid nodules (with/without), BMI and clinical characteristics and efficacy evaluation of DTC, respectively. Logistic regression analysis was used to analyze the independent risk factors for the occurrence of thyroid nodules and the aggressiveness of DTC. Results:Among PE, there were 779 cases with nodules, and 596 cases without nodules. Comparing with those without nodules, more overweight and obese were found in PE cases with nodules (42.1%(328/779) vs 37.2%(222/596), 24.5%(191/779) vs 20.5%(122/596); χ2=13.42, P=0.004). Higher risk of developing thyroid nodules was related with older age and lower thyroid stimulating hormone (TSH) level (odds ratio ( OR): 1.044, 0.919, 95% CI: 1.029-1.060, 0.845-0.999; P<0.001, P=0.046). People with high-risk nodules were more likely to be obese than those with intermediate and lower risk nodules (5/15 vs 24.3% (186/764); χ2=21.11, P<0.001). Among 1 450 DTC patients, comparing with patients with normal weight, patients in the overweight and obesity groups were more likely to have central regional lymph node metastasis ( OR: 1.418, 1.427, 95% CI: 1.075-1.870, 1.044-1.952; P values: 0.013, 0.026), and patients in obese group were with greater risk of lesions being bilateral ( OR=0.696, 95% CI: 0.519-0.934; P=0.016). BMI was not related with the efficacy evaluation of DTC ( χ2=9.13, P=0.425). Conclusions:The incidence of thyroid nodules in people with high BMI is higher. DTC patients with high BMI may have more aggressive incidence. But BMI has no correlation with the efficacy evaluation of DTC patients after treatment.

Targeting TSHR and ICAM-1 for treatment of Graves′ disease in BALB/c mice / 中华核医学与分子影像杂志

Objective:To explore new methods of treating Graves′ disease (GD) by targeting thyroid stimulating hormone receptor (TSHR) and intercellular adhesion molecule-1 (ICAM-1).Methods:The small interfering RNA (siRNA) targeting TSHR and the ICAM-1 monoclonal antibody (mAb) were designed and synthesized. Thirty GD model mice were randomly divided into siRNA treatment group, ICAM-1 mAb treatment group, and untreated GD group (10 mice in each group), and 10 normal mice were taken as blank control. Serum thyroxine (T 4), thyroid stimulating hormone (TSH), TSH receptor-stimulating antibody (TSAb) and TSH-stimulation blocking antibody (TSBAb) were measured before and after treatment. At the end of the treatment, body mass and heart rate of mice in each group were measured, and thyroid uptake of 99Tc mO 4-, thyroid size and pathological changes were evaluated. Independent-sample t test, paired t test and one-way analysis of variance were used to analyze data. Results:After three treatments, the body mass of mice in siRNA group and ICAM-1 mAb group were significantly lower than that of normal mice ( F=3.50, P=0.025); the heart rates of the mice in two groups were significantly lower than that of untreated GD mice ( F=24.73, P<0.001). Heart rate of mice treated with siRNA decreased significantly, close to that of normal mice. After treatment, the serum T 4((27.58±1.94) vs (65.71±6.89) μg/L, (27.24±3.50) vs (70.84±8.46) μg/L), TSAb ((331.44±43.38) vs (457.33±45.85) mU/L, (275.16±45.80) vs (443.91±42.32) mU/L) and TSBAb ((13.94±1.11) vs (15.83±5.92) mU/L, (14.59±1.02) vs (17.05±6.16) mU/L) levels of mice in both siRNA group and ICAM-1 mAb group significantly decreased ( t values: 4.45-10.87, all P<0.05), while the serum TSH levels of mice in two groups significantly increased ((0.13±0.05) vs (0.04±0.05) mU/L, (1.46±0.34) vs (0.06±0.03) mU/L; t values: -2.22, -5.87, P values: 0.007, <0.001). The elevated TSH level and decreased TSAb level of mice treated with ICAM-1 mAb were significantly different from those treated with siRNA ( t values: 1.03, -1.63, P values: 0.002, 0.031). After treatment, the uptake of 99Tc mO 4- in part of the thyroid lobes of mice was decreased, and the enlargement degree of the corresponding lobes was reduced. The thyroid pathology of mice in the treated groups showed that the absorption vacuoles of thyroid follicles were reduced, and the phenomenon of thinner colloids was improved. No obvious damage was observed in the heart, liver and kidneys of the mice. Conclusions:Both the siRNA targeting TSHR and ICAM-1 mAb have therapeutic effects on GD model mice. The siRNA is better at controlling heart rate, and ICAM-1 mAb is better at increasing TSH and decreasing TSAb. Each of the above treatment methods is safe and effective, which can provide new ideas for GD targeted therapy.

Interventional effect of asiaticosdide on rats exposed to silica dust / 中华劳动卫生职业病杂志

Objective: To investigate the effect of asiaticoside for fibrosis in lung tissues of rats exposed to silica and to explore its possible mechanism. Methods: 144 SD male rats were randomly divided into control group, model group, positive drug control group, asiaticoside high-dose group, medium-dose group and low-dose group, each group included 24 rats. Rats in the control group were perfused with 1.0 ml of normal saline, and the other groups were given 1.0 ml 50 mg/ml SiO(2) suspension. Gavage of herbal was given from the next day after model establishment, once a day. Rats in the positive drug control group were administration with 30 mg/kg tetrandrine and rats in the low-dose group, medium-dose group and high-dose group were given 20 mg/kg, 40 mg/kg and 60 mg/kg asiaticoside for fibrosis respectively. Rats in the control group and the model group were given 0.9% normal saline. The rats were sacrificed in on the 14th, 28th and 56th day after intragastric administration and collect the lung tissues to detect the content of hydroxyproline, TGF-β(1) and IL-18, observe the pathological changes of the lung tissues by HE and Masson staining and determine the expressions of Col-I, a-SMA, TGF-β in lung tissues by Western Blot. Results: On the 14th day, 28th day and 56th day after model establishment, the lung tissues of rats in the model group showed obvious inflammatory response and accumulation of collagen fibers, and the degree of inflammation and fibrosis increased with time. The intervention of asiaticoside could effectively inhibit the pathological changes of lung tissues. The contents of hydroxyproline, IL-18 and TGF-β1 in lung tissues of model group were higher than those in the control group (P<0.05) , while the level of hydroxyproline, IL-18 and TGF-β1 in asiaticoside groups were significantly decreased, and the difference was statistically signicant (P<0.05) . Compared with the control group, the expression levels of Col-I, TGF-β1and α-SMA in lung tissue of model group were increased (P<0.05) , while the expression level of Col-I, TGF-β1 and α-SMA were decreased after the intervention of asiaticoside, and the difference was statistically signicant (P<0.05) . Conclusion: Asiaticoside can inhibit the increase of Col-I, TGF-β1 and α-SMA content in the SiO(2)-induced lung tissues of rats, reduce the release of TGF-β1 and IL-18 inflammatory factors in lung tissue, and then inhibit the synthesis and deposition of extracellular matrix in rat lung tissue, and improve silicosis fibrosis.

Short-term effect of targeted drugs on quality of life in patients with radioactive iodine-refractory differentiated thyroid cancer / 中华核医学与分子影像杂志

Objective:To analyze the short-term effect of targeted drugs on quality of life in patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC).Methods:From February 2020 to April 2022, 19 RAIR-DTC patients (10 males, 9 females; age (54.5±14.5) years) who received targeted drugs therapy (sorafenib, lenvatinib or anlotinib) in Tianjin Medical University General Hospital were prospectively enrolled. The thyroglobulin (Tg) levels prior and 1, 3, 6 months post the targeted treatment, and the adverse events were measured and recorded. Response evaluation criteria in solid tumors (RECIST) 1.1 version was used to evaluate the treatment response. The quality of life based on five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) was monitored prior and 3 months post the targeted treatment, and the prevalence rates of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were analyzed, and the scores of health assessment were assessed. Paired t test, Kruskal-Wallis rank sum test and χ2 test were used to analyze data. Results:The prevalence rates of mobility (8/19), self-care (6/19), usual activities (10/19), pain/discomfort (10/19), and anxiety/depression (12/19) in 3 months post treatment were higher than those prior treatment (1/19, 1/19, 1/19, 2/19, 2/19; χ2 values: 4.38-11.31, all P<0.05). The score of health assessment prior treatment was (84.37±6.25), which was higher than that at 3 months post treatment (71.63±9.14; t=5.02, P=0.001). After targeted treatment, 10 patients were with skin toxicity, 8 patients were with hypertension, 8 patients were with weight loss, 7 patients were with diarrhea, 6 patients were with fatigue, 5 patients were with hepatic dysfunction, 2 patients were with proteinuria, 2 patients were with muscle pain and 1 patient was with oral ulcer. Of 19 patients, 17 insisted on continuing treatment, and the other two stopped treatment. The Tg levels at 1, 3 and 6 months post treatment were 56.26(44.60, 210.50), 53.36(41.25, 203.07) and 54.35(34.71, 223.52) mg/L, respectively, which were lower than the level prior treatment with no significant difference (110.16(49.63, 294.50) mg/L; H=2.42, P=0.490). After 3 months of targeted treatment, the progression-free survival (PFS) rate was 16/17, including 7 patients with partial response (PR), 9 patients with stable disease (SD), and 1 patient with progression of disease (PD). After 6 months of targeted treatment, the PFS rate was 10/17, including 5 patients with PR, 5 patients with SD, and 7 patients with PD. Conclusion:After 3-6 months of targeted treatment, the tumor markers of most patients are decreased with metastases improved, but the adverse events of targeted drugs have a great impact on quality of life in patients with RAIR-DTC.

Association between urinary iodine concentration and radioactive iodine therapeutic response in patients with differentiated thyroid cancer / 中华核医学与分子影像杂志

Objective:To explore the impact of urinary iodine concentration (UIC) on response to 131I treatment in differentiated thyroid cancer (DTC) patients with different risk stratifications. Methods:A total of 181 patients with DTC (75 males, 106 females, age: (44.1±12.5) years), who received the first 131I treatment in Tianjin Medical University General Hospital between January 2018 and February 2019, were retrospectively analyzed. Patients were divided into low- to intermediate-risk and high-risk groups. The treatment response was categorized into excellent response (ER) and non-excellent response (non-ER). Factors being evaluated including age, sex, preablative stimulated thyroglobulin (ps-Tg), UIC, etc. Mann-Whitney U test, χ2 test and logistic regression analysis were used for data analysis. Results:The UIC and ps-Tg in the low- to intermediate-risk group ( n=113) was 111.60(55.80, 204.65) μg/L and 2.08(0.63, 4.91) μg/L, respectively. Compared with the ER subgroup ( n=86), non-ER subgroup ( n=27) had higher UIC and ps-Tg level ( z values: -2.585, -4.511, both P<0.05). In the high-risk group ( n=68), UIC was 115.40(61.23, 167.28) μg/L and ps-Tg was 16.65(4.52, 43.45) μg/L. Compared with the ER subgroup ( n=20), non-ER subgroup ( n=48) had higher ps-Tg level ( z=-4.677, P<0.01), while the UIC was not significantly different between ER and non-ER subgroups ( z=-0.013, P>0.05). The multivariate logistic analysis indicated the ps-Tg level was the significant variable for non-ER in low- to intermediate-risk group (odds ratio( OR)=6.157(95% CI: 1.046-36.227); OR=22.965(95% CI: 3.591-146.857), both P<0.05) and high-risk group ( OR=9.696 (95% CI: 1.379-68.169), P<0.05); a high UIC could be an indicator of non-ER only in the low- to intermediate-risk group ( OR=3.715(95% CI: 1.201-11.488), P<0.05). Conclusions:The non-ER is associated with UIC in the low- to intermediate-risk group; however, UIC does not affect the non-ER in the high-risk group. Higher ps-Tg level is associated with non-ER in patients with low- to intermediate-risk and high-risk DTC.

Effect of High Suspension and Low Incision Surgery Based on Traditional Ligation of Chinese Medicine in Treatment of Mixed Haemorrhoids: A Multi-centre, Randomized, Single-Blind, Non-inferiority Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To observe the clinical effect of high suspension and low incision (HSLI) surgery on mixed haemorrhoids, compared with Milligan-Morgan haemorrhoidectomy.@*METHODS@#A multi-centre, randomized, single-blind, non-inferiority clinical trial was performed. Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing Rectum Hospital, Air Force Medical Center of People's Liberation Army of China, and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018. By using a blocked randomization scheme, participants were assigned to two groups. The experimental group was treated with HSLI, while the control group was treated with Milligan-Morgan haemorrhoidectomy. The primary outcome was the clinical effect evaluated at 12 weeks after operation. The secondary outcomes included the number of haemorrhoids treated during the operation, pain scores, use of analgesics, postoperative oedema, wound healing, incidence of anal stenosis, anorectal manometry after operation, as well as surgical duration, length of stay and total hospitalization expenses. A safety evaluation was also conducted.@*RESULTS@#In total, 246 eligible participants were enrolled, with 123 cases in each group. There was no significant difference in the clinical effect between the two groups (100.00% vs. 99.19%, P>0.05). Compared with the control group, the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group (P0.05). The surgical duration and length of stay in the experimental group were significantly longer than those in the control group, and the total hospitalization expense was significantly higher than that in the control group (all P<0.05). No adverse events were reported in either group during the whole trial or follow-up period.@*CONCLUSION@#HSLI had the advantages of preserving the skin of anal canal completely, alleviating postsurgical pain and promoting rapid recovery after operation. (Registration No. ChiCTR1900022883).

The influence of age and thyroglobulin antibody positive level on the prognosis of differentiated thyroid cancer / 中华内分泌代谢杂志

Objective:To investigate the prognostic factors of differentiated thyroid cancer (DTC) patients with positive thyroglobulin antibody (TgAb) and varying ages after operation and 131I treatment. To explore the value of TgAb level and its change in the prognosis of DTC patients. Methods:Clinical data of 131 TgAb positive DTC patients were retrospectively analyzed. According to age, they were divided into young group(age<55 years, n=95) and elder group (age≥55 years, n=36). According to response, it was divided into excellent response group (110 cases) and non-excellent response group (21 cases). χ2 test and t test were used to compare the clinicopathological features between excellent response group and non-excellent response group. By logistic regression analysis, the independent risk factors affecting the prognosis of patients were analyzed. The receiver operating characteristic curve was used to determine the TgAb value of persistent or recurrent DTC, and the Kaplan-Meier regression curve was used to analyze the time of TgAb becoming negative. P<0.05 was statistically significant. Results:In young patients, the higher serum TgAb level before 131I treatment and the lateral lymph node metastasis were the independent influencing factors of poor prognosis [ OR=0.89(95% CI 0.83-0.95), OR=0.15(95% CI 0.05-0.52); both P<0.05]. In elder group, extraglandular invasion and higher serum TgAb before 131I treatment were associated with poorer prognosis [ OR=0.05(95% CI 0-0.83), OR=0.91(95% CI 0.76-1.13); P<0.05]. The serum TgAb thresholds for predicting DTC persistence/recurrence were 315.5 IU/mL(246.0 IU/mL in the young group and 516.5 IU/mL in the elder group). The mean time TgAb sera turned negative was (26.37±2.22) months [(23.28±2.37) months for young group and (32.64±4.07) months for elder group]. The TgAb decreased >50% in one year of the patients who had a lower probability of disease persistence/recurrence than the group without ( P<0.05). Conclusions:The high level of serum TgAb before 131I treatment and lateral lymph node metastasis were independent factors of poor prognosis in young patients, while in elder patients, extraglandular tumor invasion and the high level of serum TgAb before 131I treatment were independent factors of poor prognosis. The rate of TgAb change one year after treatment may be used as an early marker for predicting the disease status of TgAb positive patients.

Mechanism of curcumin in inhibiting silica-induced NLRP3 inflammasome activation in mouse alveolar macrophages / 中国职业医学

OBJECTIVE: To explore the molecular mechanism of curcumin in inhibiting the nucleotide-binding oligomerization domain like receptor family pyrin domain-containing(NLRP3) inflammatory bodies induced by silica(SiO_2) in mouse alveolar macrophages(AM). METHODS: AMs were isolated from the bronchoalveolar lavage fluid of specific pathogen free C57 BL/6 mice and divided into 6 groups. Among them, the AM of the control group received no stimulation; the AM in the SiO_2 stimulation group was stimulated with SiO_2 suspension at the final mass concentration of 50 mg/L; the AM in nuclear factor(NF-κB)inhibition group was pretreated with 5-(4-fluorophenyl)-2-urea-thiophene-3-formamide with a final concentration of 200 nmoL/L for 1 hour, the AM in the low-, medium-and high-dose curcumin groups were pretreated with curcumin with the final concentrations of 20, 40 and 50 μmol/L for 1 hour, respectively, and then stimulated with SiO_(2 )suspension with a final concentration of 50 mg/L. Samples were collected after 6 hours of incubation. The mRNA expression of NLRP3 inflammasome related genes such as NLRP3, Caspase-1 and interleukin(IL)-1β was detected by real-time fluorescence quantitative polymerase chain reaction. The secretion level of maturation IL-1β(mIL-1β) and IL-18 in AM was detected by enzyme-linked immunosorbent assay. The protein expression and secretion level of cleaved Caspase-1, precursor-IL-1β(pro-IL-1β) and mIL-1β were analyzed by Western blotting. RESULTS: The mRNA relative expression of NLRP3, Caspase-1 and IL-1β, and the secretion levels of mIL-1β and IL-18, and the protein relative expression of Caspase-1, pro-IL-1β and mIL-1β, as well as the secretion levels of cleaved Caspase-1 and mIL-1β increased in the SiO_2 stimulated group compared with the control group(P<0.05). Except for the relative expression and the secretion level of cleaved Caspase-1, the other 8 indexes in the NF-κB inhibition group were lower than that in the SiO_2 stimulation group(P<0.05). Except for the relative expression of cleaved Caspase-1 and mIL-1β proteins in the low-dose curcumin group, the relative expression of all the above 10 indexes was lower in the three curcumin treated groups than that in the SiO_2 stimulation group(P<0.05). In addition, all the above indexes decreased with the increase of curcumin intervention dose(P<0.05). The mRNA relative expression of NLRP3 and IL-1β, and the protein relative expression of pro-IL-1β increased in the medium-dose curcumin group(P<0.05), the secretion levels of mIL-1β and IL-18, as well as the protein relative expression and secretion levels of cleaved Caspase-1 and mIL-1β decreased(P<0.05), compared with the NF-κB inhibition group. CONCLUSION: Curcumin can inhibit SiO_2-induced AM NLRP3 inflammasome activation in a dose-response relationship. This process may be related to the inhibition of NF-κB signaling pathway by curcumin and the down-regulating NLRP3 inflammasome-related genes at the transcriptional level. The important mechanism may be that curcumin directly blocks the activation, assembly, and downstream shearing of NLRP3 in inflammasomes.

The role of high mobility group protein 1 in toluene diisocyanate-induced NLPR3 inflammasome activation in human bronchial epithelial cells / 中国职业医学

OBJECTIVE: To investigate the role of high mobility group protein 1(HMGB1) in toluene diisocyanate(TDI) induced nucleotide-binding oligomerization domain like receptor family pyrin domain-containing 3(NLRP3) inflammasome activation in human bronchial epithelial cells(HBECs). METHODS: i) The TDI-human serum albumin(HSA) stimulation experiment: the HBECs in logarithmic growth phase were randomly divided into control group, low-, medium-and high-dose groups that were pretreated with TDI-HSA with the final concentration of 0.00, 40.00, 80.00 and 120.00 mg/L for 12 hours. ii) The HMGB1 expression inhibition experiment: the HBECs in logarithmic growth phase were divided into control group, TDI-HSA group, TDI-HAS+negative-siRNA group, and TDI-HAS+HMGB1-siRNA group. The cells in TDI-HAS+negative-siRNA group and TDI-HAS+HMGB1-siRNA group were infected with HBECs with negative-siRNA lentivirus and HMGB1-siRNA lentivirus, respectively. Cells in these two groups and the TDI-HSA group were treated with 120.00 mg/L of TDI-HSA for 12 hours. The cells in the control group were not treated with TDI-HAS. iii) The expression of HMGB1, NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), pro-caspase-1 and caspase-1 p20 proteins in all groups were detected by Western blot. The number of NLRP3 and caspase-1 inflammasome in TDI-HSA stimulation experiment was observed by immunofluorescence method. RESULTS: i) TDI-HSA stimulation experiment: the relative protein expression of HMGB1 and ASC was higher in HBECs of medium-and high-dose groups than that of control group(all P values were <0.01). The relative protein expression of NLRP3 and casepase-1 p20 and the number of NLRP3-caspase-1 inflammasome were higher in HBECs of 3 dose groups than that of control group(all P values were <0.01). The number of NLRP3-caspase-1 inflammasome in HBECs increased obviously in low-, medium-and high-dose groups as compared to the control group(all P values were <0.05). The number of NLRP3-caspase-1 inflammasome in HBECs increased with the increase of TDI-HSA dose(all P values were <0.01). ii) The HMGB1 expression inhibition experiment: the relative protein expression of HMGB1, NLRP3, ASC, pro caspase-1 and caspase-1 p20 in HBECs were higher in the TDI-HSA group and TDI-HSA + negative-siRNA group than those of the control group(all P values were <0.01). The above indexes of HBECs were lower in the TDI-HAS + HMGB1-siRNA group than those in the TDI-HSA group and TDI-HSA + negative-siRNA group(all P values were <0.01).CONCLUSION: TDI treatment in HBECS can induce the increase of HMGB1 protein expression and activate NLPR3 inflammasome. Inhibition of HMGB1 expression can down-regulate the expression of NLPR3 and its related proteins.

Prospects for the targeted treatment research of TSHR and IGF-1R in Graves disease and Graves ophthalmopathy / 中华核医学与分子影像杂志

Anti-thyroid drug (ATD), radioactive iodine (RAI) and thyroidectomy are treatment options for Graves disease (GD). Treatment strategies for Graves ophthalmopathy (GO) patients include thyroid function control, oral or intravenous corticosteroids, orbital radiotherapy or orbital decompression surgery. However, current treatments for GD and GO are also less ideal because they target the signs and symptoms rather than the pathogenic mechanisms. The development of treatment strategies that targeting the thyroid-stimulating hormone receptor (TSHR) or insulin-like growth factor 1 receptor (IGF-1R) alone or in combination may yield effective and better tolerated treatments for GD and GO. This paper reviews the progress and limitations of the 2 methods.

Taking rivaroxaban is a risk factor for acute kidney disease and disorders in patients with coronary heart disease or non-valvular atrial fibrillation / 中华肾脏病杂志

Objective:To observe the risk of acute kidney disease and disorders (AKD) in patients with coronary heart disease or non-valvular atrial fibrillation who were taking rivaroxaban for the first time in our hospital.Methods:A retrospective case-control analysis was performed using the hospital database to screen for patients with coronary heart disease or non-valvular atrial fibrillation who were taking rivaroxaban for the first time for more than 3 months during January 1, 2018 to June 30, 2019. A total of 279 patients with serum creatinine reviewed within 3 months were as the rivaroxaban group, and 317 patients with coronary heart disease or non-valvular atrial fibrillation who did not take rivaroxaban during the same period in our hospital were selected as the control group. The general condition and the incidence of AKD were compared between the two groups, and the influencing factors of AKD were analyzed by logistic regression analysis.Results:The prothrombin time and international normalized ratio were higher in the rivaroxaban group than those in the control group (both P<0.01). There was no significant difference in age, gender, serum creatinine and urea level between the two groups. The incidence of AKD in the rivaroxaban group was 4.30%(12/279), and the incidence of AKD in the control group was 1.26%(4/317). The relative risk ( RR) of the two groups of patients was 3.409. Logistic regression analysis showed that older age (≥75 years old, OR=1.166, 95% CI 1.012-1.343, P=0.033) and diabetes ( OR=34.261, 95% CI 1.639-716.326, P=0.023) were risk factors for AKD in patients taking rivaroxaban. Rivaroxaban was a risk factor for AKD in patients with coronary heart disease or non-valvular atrial fibrillation ( OR=3.500, 95% CI 1.115-10.988, P=0.032). Conclusions:The incidence of AKD in patients taking rivaroxaban for the first time due to coronary heart disease or non-valvular atrial fibrillation was 4.30%. Taking rivaroxaban is a risk factor for AKD in patients with coronary heart disease or non-valvular atrial fibrillation. Older age and diabetes are the risk factors for AKD in the rivaroxaban group.

Effects of dezocine-remifentanil intravenous anaesthesia on perioperative signs, serum TNF-alpha and IL-6 in liver cancer patients undergoing radiofrequency ablation

Objective: To analyse the impact of dezocine-remifentanil intravenous anaesthesia on perioperative signs, serum tumour necrosis factor-alpha [TNF-alpha], and interleukin-6 [IL-6] in liver cancer patients undergoing radiofrequency ablation [RFA]

Study Design: An experimental study

Place And Duration Of Study: Renmin Hospital of Wuhan University, Wuhan, China, from January 2017 to February 2018

Methodology: Eighty patients with small hepatocellular carcinoma [SHCC] were selected as the research object. They were divided into Group A and Group B with the random number table method, with 40 cases in each group. Group A were given dezocine-remifentanil intravenous anaesthesia and Group B were given midazolam-remifentanil intravenous anaesthesia. Patients' situations in the surgery were compared between the two groups. Changes in heart rate [HR], mean arterial pressure [MAP] and blood oxygen saturation [SpO₂] were recorded before the surgery [T₀], at 5 minutes after the RFA [T₁] and at the end of the RFA [T₂]. Levels of tumour necrosis factor-alpha; [TNF-alpha;] and interleukin-6 [IL-6] on the 1² day after the RFA were compared between the two groups

Results: The wake-up time in Group A was shorter than Group B [p<0.001], and the VAS pain score in Group A was lower than Group B [p<0.001]. At T₁, the MAP in Group A was higher than Group B [p<0.001]. There was no significant difference in MAP between the two groups at T₀ and T₂ [p=0.881, 0.696, respectively]. At T₁ and T₂, the HR in Group A was lower than Group B [all p<0.001]. There was no significant difference in HR between the two groups at T₀ [p=0.684]. There was no significant difference in SpO₂ between the two groups at T₀, T₁ and T₂ [p=0.654, 0.884 and 0.798, respectively]. On the 1st day after the RFA, the level of TNF-alpha;, IL-6 in Group A were lower than those of Group B [all p<0.001]. There was no significant difference in the incidence of intraoperative complications between the two groups [p=0.644]

Conclusion: Compared with midazolam-remifentanil intravenous anaesthesia, the dezocine-remifentanil method has a better analgesic effect, shorter wake-up time, and can effectively regulate the expression of inflammatory cytokines TNF-alpha; and IL-6. However, the effect of remifentanil on the respiratory function is dose-dependent. Therefore, respiratory cycle monitoring and management should be strengthened during the surgery

Toluene diisocyanate induces inflammatory response and autophagy in human bronchial epithelial cells / 中国职业医学

OBJECTIVE: To investigate the effect of toluene diisocyanate(TDI) on the activation of autophagy and expression of inflammatory cytokines interleukin(IL)-4 and IL-6 in normal human bronchial epithelial cells(16 HBE). METHODS: i) We prepared TDI-human serum albumin(HSA) and determined the mass concentration of TDI in TDI-HSA. ii) The cells were treated with TDI-HSA and HSA at concentrations of 0.00-400.00 mg/L for 12 hours. CCK-8 assay was used to determinate the cell viability, and TDI-HSA and HSA doses were selected for subsequent experiments. iii) The cells were treated with TDI-HSA and HSA at doses of 0.00-120.00 mg/L for 12 hours, and the levels of reactive oxygen species(ROS) in the cells were detected by flow cytometry. The levels of IL-4 and IL-6 in the cell supernatant were measured by enzyme-linked immunosorbent assay. iv) The cells were treated with TDI-HSA at doses of 0.00-120.00 mg/L for 12 hours, and the autophagy activity was observed under transmission electron microscope. Western blot was utilized to detect the expression of Beclin1, microtubule-associated protein 1 light chain(LC3β) and P62. RESULTS: i) The mass concentrations of TDI in 40.00, 80.00 and 120.00 mg/L TDI-HSA groups were 0.44, 0.89 and 1.33 mg/L respectively. ii) The results of CCK-8 showed that TDI-HSA and HSA at doses below 120.00 mg/L did not affect cell viability, and 0.00-120.00 mg/L was selected as the TDI-HSA and HSA treatment doses for subsequent experiments. iii) The level of ROS in cells and the levels of IL-4 and IL-6 in the supernatant of 16 HBE cells in the TDI-HSA group at 40.00, 80.00, and 120.00 mg/L were higher than that in HSA group at the same dose(P<0.01). The level of ROS in cells and the levels of IL-4 and IL-6 in the supernatant of 16 HBE cells increased with the increase of TDI-HSA doses(P<0.01). iv) Transmission electron microscopy showed that the number of autophagic lysosomes in 16 HBE cells increased significantly, and the number of mitochondrial vacuoles increased in 40.00, 80.00, 120.00 mg/L TDI-HSA group compared with 0.00 mg/L group. With the increase of TDI-HSA dose, the relative expression of Beclin1 protein and LC3β-Ⅱ/Ⅰ ratio in 16 HBE cell supernatant increased(P<0.05), and the relative expression of P62 protein decreased(P<0.05). CONCLUSION: TDI-HSA induces increased expression of ROS and inflammatory factors and induces autophagy activation in 16 HBE cells. Autophagy may be an important factor for the development of airway inflammation in TDI-induced occupational asthma.

The change of reactive oxygen species and cell cycle in bone marrow cells of mice with benzene-induced aplastic anemia / 中国职业医学

OBJECTIVE: To explore the effect of reactive oxygen species(ROS) and cell cycle in bone marrow cells in benzene-induced aplastic anemia(AA) mouse model. METHODS: Specific pathogens free male CD1 mice were randomly divided into control group and exposure group(n=10, each group). The mice in exposure group were subcutaneously injected with benzene at a dose of 2 mL/kg body weigh diluted 1 ∶1 in corn oil, while the mice in control group were treated with equal volume of corn oil, 3 times a week for a total of 25 times. After exposure, the blood routine and reticulocyte percentage of peripheral blood of mice were examined. The femur histopathology was performed. The levels of benzene and its metabolites hydroquinone, and phenol in blood, liver and bone marrow were tested by solid-phase extraction gas chromatography mass spectrometry. The level of ROS and the changes of cell cycle in bone marrow mononuclear cells(BMMNCs) were determined by flow cytometry. The protein expression of Cyclin D1 and cyclin-dependent kinase 4(CDK4) in BMMNCs was detected by Western blot. RESULTS: Since the 10 th benzene exposure, the body mass of mice in the exposure group was lower than that in the control group at the same time point(P<0.05). After the benzene exposure, all the counts of white blood cell, red blood cell, platelet, and hemoglobin level and reticulocyte percentage in peripheral blood of mice in the exposure group were decreased when compared with the control group(P<0.05). Bone marrow histopathological examination showed that bone marrow hematopoietic cells were decreased and non-hematopoietic cells were increased in the exposure group. In this study, a mouse model of AA induced by benzene was successfully established. The levels of benzene, hydroquinone and phenol in exposure group increased in blood, liver, and bone marrow compared to control group(P<0.05). Furthermore, the level of benzene from high to low were blood, liver and bone marrow, while the levels of hydroquinone and phenol were mainly stored in the blood and bone marrow in exposure group. Compared with the control group, the level of ROS, S phase fraction, and the relative protein expression of Cyclin D1 and CDK4 in BMMNCs increased, while the G1 phase fraction decreased in exposure group(P<0.01). CONCLUSION: The results suggest that benzene and its metabolites induce an increase of ROS level and S phase cell arrest, that play an important role in the pathogenesis and development of benzene-induced AA.

Relationship between plasma cytokine level and cognitive function in patients with stable schizophrenia / 中华行为医学与脑科学杂志

Objective To explore the relationship between plasma cytokine level and cognitive function in patients with stable schizophrenia and explore the possible role of cytokine in the occurrence mechanism of cognitive impairment in them.Methods A total of 75 stable patients who met the mental disorder diagnostic criteria of DSM-ⅣV (patient group) and 40 healthy people (control group) were included in the essay.The method of enzymelinked immunosorbent assay (ELISA) were used to detected the concentrations of plasma proinflammatory cytokines IL-1β,IL-8,TNF-α and IFN-γas well as the anti-inflammatory cytokines IL-10 in all research objects.The MATRICS Consensus Cognitive Battery (MCCB) was used to assess the cognitive function of patients.The relationship between plasma cytokines and cognitive function of patients were analyzed when the differences of the plasma cytokines concentrations were compared between the patient group and the control group.Results (1) Compared with the control group,plasma IL-8 (2.80 (2.13) pg/ml vs 0.23 (0.80) pg/ml),TNF-α (1.16 (0.47) pg/ml vs 0.67 (0.15) pg/ml) in the patient group showed statistically significant difference (P＜0.01).(2)In the partial correlation analysis of plasma cytokines and cognitive functions in patients,TNF-α was negatively correlated with the attention/vigilance dimensions(r=-0.29,P=0.03).Conclusion Stable schizophrenia patients have some problems with cytokine level.There is a correlation between TNF-α level and attention/vigilance dimensions.What's more,cytokine level immunological abnormalities may play some role in the development of cognitive impairment occurrence in patients.

Level of vascular endothelial growth factor and its relationship with symptoms in stable schizophrenia. J / 中国神经精神疾病杂志

Objective To investigate the level of serum vascular endothelial growth factor (VEGF) in stable schizophrenia patients, and to explore the relationship between serum VEGF level and clinical symptoms. Methods Seventy-five patients with stable schizophrenia and 40 healthy controls were enrolled. The levels of serum VEGF were detected by flow multiplex protein analysis. The clinical symptoms of patients were assessed by positive and negative symptom scale (PANSS). Results The level of serum VEGF was significantly lower in patients group than in healthy control group [medians (lower and upper quartiles) were 3.77 (2.61, 5.14) pg/mL vs. 6.21 (4.37, 11.16) pg/mL, P＜0.01]. There was no significant difference in serum VEGF levels between patients with different gender, smoking or family history of mental illness (P＞0.05). The level of VEGF was negatively correlated with the total score of PANSS (r=-0.27, P=0.03), negative symptom subscale score (r=-0.25, P=0.04), lack of response score (r=-0.26, P=0.02), but not with other PANSS scores (P＞0.05). Conclusion The serum level of VEGF in patients with stable schizophrenia is lower than that in healthy control group. There is, to some degree, a relationship between the level of VEGF and the severity of clinical symptoms in patients with stable schizophrenia.

Preliminary analysis of differential expression of miRNA-423-5p and miRNA-26a-5p in lung tissue of early silicotic rats / 中华劳动卫生职业病杂志

Objective@#To screen the changes of microRNA (miRNA) expression profiles in lung tissues of early silicosis rats, and provide a basis for functional analysis of differential microRNA.@*Methods@#SPF Wistar male rats were randomly divided into a negative control group and SiO2-exposed groups, with 30 rats in each group. The model of silicosis in rats was established by intratracheal instillation of 1 ml SiO2 suspension, and the control rats were treated with 1mL in the same way to sterilize normal saline. The lung tissues of two group were collected at the 1, 7, 14, 21, 28 d after SiO2-exposed. Three of the rat lung tissues were used for pathological observation, and the other three were used to screen differentially expressed miRNAs in lung tissue by miRNA microarray technology. miRNA chip screening and RT-qPCR were used to verify the expression levels of miRNA-423-5p and miRNA-26a-5p in the two groups. miRNA-423-5p and miRNA-26a-5p are predicted by target genes and analyzed by GO (gene ontology) enrichment analysis and KEGG (kyoto encyclopedia of genes and genomes) pathway analysis.@*Results@#In the control group, the inflammatory response of lung tissue 21 and 28 days was significantly reduced compared with 1, 7 and 14 days, and the inflammatory cells infiltrated in the lung tissue of the SiO2-exposed rats. The rats in the control group had a small amount of collagen at 21 and 28 days, but a large amount of collagen fiber deposition began to appear in the lung tissue of rats exposed to SiO2 after 21 days. Compared with the control group, the expression levels of micro RNA-423-5p was significantly up-regulated and the expression of microRNA-26a-5p was significantly down-regulated in the SiO2-exposed rats lung tissues dust at different time points (P<0.05) .@*Conclusion@#The up-regulation of miRNA-423-5p and the down-regulation of miRNA-26a-5p in lung tissues of early silicotic rats may be related to the occurrence and development of early silicosis.

Repair effect of adipose-derived mesenchymal stem cells on lung injury in rats exposed to silica / 中华劳动卫生职业病杂志

Objective@#To observe the repairing effect of adipose mesenchymal stem cells (ADSCs) on lung injury induced by silica in rats.@*Methods@#Primary ADSCs-GFP was obtained from rats. ADSCs-GFP was injected into tail vein of silicosis model rats. The expression of green fluorescence in lungs was observed regularly to determine the homing ability of ADSCs. Primary ADSCs of rats were obtained and randomly divided into control group, exposure group, vehicle group and ADSCs group. Silicosis rat model was established by non-exposed tracheal drip method. 24 hours after silica exposure, rats in ADSCs group were injected with ADSCs of 1×106/kg body weight through tail vein, and the pathological changes of lung tissue were observed and evaluated 28 days after intervention. To explore the early intervention mechanism of ADSCs on pulmonary fibrosis in silicosis model rats, apoptosis-related proteins were detected by immunohistochemistry.@*Results@#28 days after exposure to silica, rats in the exposure group showed obvious pulmonary fibrosis. Compared with exposure group and vehicle group, ADSCs group showed less pulmonary inflammation, less silica nodules and less collagen deposition area. Immunohistochemical results showed that the expression of Caspase-3 and cytochrome C protein decreased and Bcl-2 protein increased after ADSCs transplantation.@*Conclusion@#ADSCs infusion has an obvious intervention effect on postponing early silicosis fibrosis in rats exposed to silica, and its mechanism is related to the regulation of apoptotic process.