Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ² test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9^th to <10^th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ²=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ²=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ²=1.878, P=0.171; χ²=0.078, P=0.780; χ²=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

BACKGROUND: Infant adipose-derived mesenchymal stem cells (ADSCs) collected from excised polydactyly fat tissue, which was surgical waste, could be cultured and expanded in vitro in this study. In addition, the collecting process would not cause pain in the host. In this study, the proliferation, reduction of senescence, anti-oxidative ability, and differentiation potential in the infant ADSCs were compared with those in the adult ADSCs harvested from thigh liposuction to determine the availability of infant ADSCs. METHODS: Proliferation was determined by detecting the fold changes in cell numbers and doubling time periods.Senescence was analyzed by investigating the age-related gene expression levels and the replicative stress. The superoxide dismutase (SOD) gene expression, adipogenic, neurogenic, osteogenic, and tenogenic differentiation were compared by RTqPCR. The chondrogenic differentiation efficiency was also determined using RT-qPCR and immunohistochemical staining. RESULTS: The proliferation, SOD (SOD1, SOD2 and SOD3) gene expression, the stemness-related gene (c-MYC) and telomerase reverse transcriptase of the infant ADSCs at early passages were enhanced compared with those of the adults’Cellular senescence related genes, including p16, p21 and p53, and replicative stress were reduced in the infant ADSCs. The adipogenic genes (PPARγ and LPL) and neurogenic genes (MAP2 and NEFH) of the infant ADSC differentiated cells were significantly higher than those of the adults’ while the expression of the osteogenic genes (OCN and RUNX) and tenogenic genes (TNC and COL3A1) of both demonstrated opposite results. The chondrogenic markers (SOX9, COL2 and COL10) were enhanced in the infant ADSC differentiated chondrogenic pellets, and the expression levels of SODs were decreased during the differentiation process. CONCLUSION Cultured infant ADSCs demonstrate less cellular senescence and replicative stress, higher proliferation rates, better antioxidant defense activity, and higher potential of chondrogenic, adipogenic and neurogenic differentiation.

OBJECTIVE: To confirm the therapeutic effect of recombinant human thrombopoietin (rhTPO) on rhesus monkeys irradiated with 5.0 Gy ⁶⁰Co γ-ray, and provide experimental basis for clinical treatment of similar patients. METHODS: Fourteen adult rhesus monkeys were irradiated with ⁶⁰Co γ-ray on both sides at the dose of 5.0 Gy (dose rate 69.2 cGy/min) to establish the acute radiation sickness model. The monkeys were divided into irradiation group (n=5), rhTPO 5 μg/kg group (n=4) and rhTPO 10 μg/kg group (n=5). Two hours after irradiation, the three groups of monkeys were injected with saline 0.1 ml/kg, rhTPO 5 μg/kg（0.1 ml/kg） and rhTPO 10 μg/kg(0.2 ml/kg), respectively. The general signs, survival, peripheral hemogram and serum biochemistry of rhesus monkeys were observed before and after irradiation, and the differences between rhTPO group and irradiation control group were compared. RESULTS: After total body irradiation with 5.0 Gy⁶⁰Co γ-ray, rhesus monkeys successively showed fever, hemorrhage, sharp decrease of whole blood cell counts in peripheral blood and disorder of serum biochemical indexes. Compared with the irradiated control group, a single intramuscular injection of rhTPO 5 μg/kg or 10 μg/kg 2 hours after irradiation could improve the symptoms of fever and bleeding, increase the nadir of peripheral red blood cells and platelets counts, shorten the duration of hemocytopenia, and advance the time for blood cells to return to the pre-irradiation level. The serum biochemical results showed that rhTPO could improve the abnormality of serum biochemical indexes in rhesus monkeys induced by 5.0 Gy total body irradiation to some extent. Compared with the two administration groups, the therapeutic effect of rhTPO 10 μg/ kg was better. CONCLUSION A single injection of rhTPO 5 μg/ kg or 10 μg/ kg 2 hours after irradiation can alleviate the injury of multilineage hematopoiesis and promote the recovery in monkeys irradiated by 5.0 Gy γ-ray. It also improves animal signs and has obvious therapeutic effect on acute radiation sickness.
Humans ; Animals ; Macaca mulatta ; Radiation Injuries

Objective: To investigate the relationship between socioeconomic status (SES) and all-cause mortality in patients with type 2 diabetes. Methods: A total of 17 553 patients with type 2 diabetes were recruited under the National Basic Public Health Service Project in Changshu county, Qingjiangpu district, and Huai'an district in Huai'an city of Jiangsu province as participants. Latent class analysis was applied to classify the individuals based on five socioeconomic indicators. Then, Cox proportional hazards regression models were used to estimate the associations of different levels of SES with all-cause mortality, and stratified analysis was performed according to age and area. Results: Among 100 529.08 person-years of the fo1low-up, the median follow-up time was 5.7 years, and 1 829 deaths occurred during the follow-up period. According to the relevant results of the latent class model, the model of the "three classes" was the best. The related population was then divided into low SES (8 256 people, 47.0%), medium SES (4 427 people, 25.2%), and high SES groups (4 870 people, 27.8%). Compared to patients with high SES, the multivariate-adjusted hazard ratio (95%CI) of all-cause mortality associated with low SES for males and females were 1.84 (1.53-2.21) and 1.41 (1.51-1.72), respectively. Stratified analysis showed that the hazard ration (95%CI) of all-cause mortality associated with low SES for males and females were 1.99 (1.12-2.95) and 2.01 (1.20-3.23), respectively, in people younger than 60 years old, and were 1.90 (1.57-2.31) and 1.40 (1.13-1.73) in people over 60 years old. The HR values (95%CI) for all-cause mortality associated with low SES for the male and females were 1.54 (1.17-2.04) and 1.27 (1.02-1.59) in the urban population with 2.11 (1.55-2.85) and 2.64 (1.17-3.35) in rural population, respectively. Conclusions: Lower SES increased the risk of all-cause mortality in type 2 diabetic patients, which is more significant in younger and rural populations.
United States ; Female ; Humans ; Male ; Middle Aged ; Latent Class Analysis ; Diabetes Mellitus, Type 2 ; Prospective Studies ; Social Class ; Income

Objective: To investigate the feasibility of endoscopic lateral neck dissection via the breast and transoral approaches (ELNDBTOA) for papillary thyroid carcinoma (PTC). Methods: From February 2015 to April 2019, 10 patients with PTC (cN1b) including 1 male and 9 females aged from 22 to 53 years old received ELNDBTOA in the General Surgery Department of Zhongshan Hospital, Xiamen University. Total thyroidectomy, the central lymph node dissection and the selective neck dissection (levels Ⅱ, Ⅲ and Ⅳ) were performed endoscopically via the breast approach, and then the residual lymph nodes were dissected via transoral approach. The medical records, operation time, blood loss, complications and postoperative follow-up outcomes were analyzed retrospectively. SPSS 22.0 software package was used for statistical processing of clinical data of patients. Results: All cases were successfully treated with ELNDBTOA without transfer to open surgery. The average operative time was (362.5±79.7) min, the blood loss was (23.0±14.9) ml, and the postoperative hospital stay was (5.1±1.3) days. The mean number of harvested cervical lymph nodes were (34.2±25.8), and the mean number of positive lymph nodes were (6.5±4.9). Lymph nodes were dissected by the further dissection via oral approach in 6 patients and a total of 9 lateral lymph nodes were havested from 2 of the 6 patients, with 3 positive lymph nodes. Two patients had transient skin numbness in the mandibular area and recovered within two weeks. One patient developed transient hypoparathyroidism and recovered within two months. No secondary bleeding, recurrent laryngeal nerve paralysis, chylous leakage, neck infection, permanent hypoparathyroidism or other complications were observed. The follow-up time was from 16 to 66 months with a median of 42.5 months, no tumor recurrence or metastasis occurred, and also no obvious deformity, abnormal sensation or movement in the chest, neck and mouth was observed. Conclusions: ELNBTOA is safe and feasible, with good cosmetic outcome.
Adult ; Female ; Humans ; Lymph Nodes ; Male ; Middle Aged ; Neck Dissection ; Retrospective Studies ; Thyroid Cancer, Papillary/surgery* ; Thyroid Neoplasms/surgery* ; Thyroidectomy ; Young Adult

Guided by cell-based anti-anaphylactic assay, eighteen cage-like monoterpenoid glycosides (1-18) were obtained from the bioactive fraction of P. lactiflora extract. Among these, compounds 1, 5, 6, 11, 12, 15, and 17 significantly reduced the release rate of β-HEX and HIS without or with less cytotoxicity. Furthermore, the most potent inhibitor benzoylpaeoniflorin (5) was selected as the prioritized compound for the study of action of mechanism, and its anti-anaphylactic activity was medicated by dual-inhibiting HDC and MAPK signal pathway. Moreover, molecular docking simulation explained that benzoylpaeoniflorin (5) blocked the conversion of L-histidine to HIS by occupying the HDC active site. Finally, in vivo on PCA using BALB/c mice, benzoylpaeoniflorin (5) suppressed the IgE-mediated PCA reaction in antigen-challenged mice. These findings indicated that cage-like monoterpenoid glycosides, especially benzoylpaeoniflorin (5), mainly contribute to the anti-anaphylactic activity of P. lactiflora by dual-inhibiting HDC and MAPK signal pathway. Therefore, benzoylpaeoniflorin (5) may be considered as a novel drug candidate for the treatment of anaphylactic diseases.
Animals ; Glucosides ; Mice ; Mice, Inbred BALB C ; Molecular Docking Simulation ; Monoterpenes ; Paeonia ; Plant Roots

Objective The aim is to investigate the association between body mass index (BMI) and risk of all-cause mortality among patients with type 2 diabetes. Methods A total of 17 638 patients with type 2 diabetes registered in the management of National Basic Public Health Services in two areas of southern and northern Jiangsu were recruited. Cox proportional risk regression model was used to calculate the hazard ratio(HR) value and 95% confidence interval (95% CI) of different BMI groups in the follow-up period. Results The subjects were followed up for a total of 77 451 person-years with an average duration of 4.39 years, and 1 274 patients died during the follow-up period. The number of death in low weight group (BMI<18.5 kg/m2), normal weight group (18.5 kg/m2≤BMI<24 kg/m2), overweight (24 kg/m2≤BMI<28 kg/m2) and obese group (BMI≥28 kg/m2) were 39, 575, 484 and 176 respectively.The corresponding mortalities were 15.6%, 9.5%, 6.2% and 5.1%, respectively. Compared to normal weight group, the adjusted HR of all-cause mortality in low weight, overweight and obese group were 1.66 (95% CI: 1.20-2.30), 0.68 (95% CI: 0.61-0.77), 0.58 (95% CI: 0.48-0.68), respectively. Conclusions Low-weight patients have the highest risk of all-cause mortality compared with normal counterparts, while both overweight and obese people have a lower risk of death. Overweight and obesity may reduce the risk of all-cause mortality in type 2 diabetic patients.

OBJECTIVETo investigate the role of Notch1 in the proliferation, migration and invasion of gastric cancer cells.

METHODSNotch1 expression was detected by RT-PCR and Western blot in four gastric cancer cell lines(SGC-7901, BGC-823, MKN-45 and MKN-28). The RNAi segments targeting Notch1 were designed and transfected into cell lines with the highest level of Notch1. The transcription and translation level of Notch1 expression was detected by real-time PCR and Western blot. The proliferation of transfected cells were determined by CCK8 test. Meanwhile, the migration and invasive ability of transfected tumor cells were detected by Transwell test.

RESULTSGastric cell line BGC-823 was selected with the highest expression of Notch1 at both mRNA level and protein level. The expression of Notch1 was significantly reduced after the transfection. The CCK8 test showed the growth rate was significantly reduced in RNAi group after two days(F=4.644, P=0.046). In migration test, the number of cells crossing through chambers in RNAi group(30.1±3.1) was significantly lower than that in the negative control group(44.5±3.2) and in the mock group(46.1±2.6)(P<0.05). In invasion test, the number of cells crossing through chambers in RNAi group(22.9±4.5) was also significantly lower than that in the negative control group (37.3±4.2) and in the mock group (37.8±3.7)(P<0.05).

CONCLUSIONDown-regulation of Notch1 inhibits the proliferation and reduces the ability of migration and invasion in gastric cell line BGC-823, suggesting that Notch1 may play an important role in the gastric carcinogenesis and metastasis.

Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Down-Regulation ; Humans ; Neoplasm Invasiveness ; RNA Interference ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Receptor, Notch1 ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms ; Transfection

OBJECTIVETo discuss the application of MRI in indirect temporomandibular joint injury without condylar fracture.

METHODSMRI examination on temporomandibular joint was conducted in 28 patients with indirect injury to temporomandibular joint without condylar fracture. The scanning sequence included T(1)WI, PDWI on oblique sagittal section at both open and closed mouth positions, and T(1)WI, T(2)WI on oblique coronal section. The MRI appearance was analyzed by 2 senior radiologists.

RESULTSAmong the 56 temporomandibular joints of 28 patients, 35 joints exhibited pathological changes on MRI, in which there were 9 bone injuries, 21 articular disc dislocation, 24 intracapsular hematocele and hydrops.

CONCLUSIONSMRI can clearly reveal bone injury, articular disc dislocation as well as articular capsule abnormality in the indirect injury of temporomandibular joint without condylar fracture. It is highly advocated in clinical use.

Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Maxillofacial Injuries ; diagnosis ; Middle Aged ; Temporomandibular Joint ; injuries