Objectives:To analyze the clinical features and prognosis of patients with medullary thyroid carcinoma combined with papillary thyroid carcinoma (combined carcinoma).Methods:The clinical data of 24 patients admitted to Tianjin Medical University Cancer Hospital from Nov 2012 to Dec 2019 were retrospectively analyzed. The treatment methods, pathological results, and prognosis of all patients were examined.Results:The results showed that combined carcinoma accounted for 10.0% (24/241) of all medullary thyroid carcinoma cases. In the combined cancer group, 45.8% (11/24) patients had lymph node metastasis, and the type of metastasis matched the largest lesion. There were no significant differences in gendex ratio ( χ2=0.164, P>0.05), age at onset ( t=1.381, P>0.05), maximum diameter of lesion ( Z=-1.733, P>0.05), multifocality ( χ2=2.695, P>0.05), and lymph node metastasis in the central ( χ2=1.625, P>0.05) and lateral neck regions ( χ2=1.537, P>0.05) between combined cancer patients and those with MTC alone. The median follow-up time for the 24 patients was 77.6 months. Local recurrence was observed in 2 cases, while no distant metastasis was found. There were no significant differences in disease-free survival, disease-specific survival, and overall survival between combined cancer and pure MTC groups (all P>0.05). Conclusion:The pathological characteristics and prognosis of medullary thyroid carcinoma combined with papillary thyroid carcinoma are similar to those of pure MTC. Therefore, clinical treatment decisions can be similar to pure MTC.

Objective:To analyze the surveillance data of Kashin-Beck disease (KBD) in Shandong Province, master the changes of KBD, and provide scientific basis for formulating prevention and control strategies of KBD and adjustment of the prevention and control focus of KBD.Methods:According to the requirements of the "National KBD Monitoring Plan" and the "Shandong KBD Monitoring Plan", from 2016 to 2020, the disease monitoring was carried out in the villages of KBD areas in Shandong Province, including the number of clinical positive cases, the number of X-ray positive cases, and the number of metaphyseal positive cases. The detection rate was calculated, and the dynamic changes of the disease was analyzed macroscopically.Results:From 2016 to 2020, a total of 1 816 children aged 7 - 12 years were clinically examined in Shandong Province, and no child with KBD was found. A total of 1 224 children were examined by X-ray, among which 1 positive patient was found in 2016 and 2017, respectively, both of whom were metaphyseal changes, with a total detection rate of 0.16%. There were 367 adult patients with KBD in Shandong Province, including 304 patients with grade Ⅰ, 47 patients with grade Ⅱ and 16 patients with grade Ⅲ. All villages in the KBD areas in Shandong Province had reached the elimination standard, with the elimination rate of 100%.Conclusion:No clinical case of KBD is detected in children aged 7 - 12 years in Shandong Province from 2016 to 2020, which has reached the elimination standard and is in a continuous elimination state.

Ovarian cancer is the third-most-common malignant reproductive tumor in women. According to the American Cancer Society, it has the highest mortality rate of gynecological tumors. The five-year survival rate was only 29% during the period from 1975 to 2008 (Reid et al., 2017). In recent decades, the five-year survival rate of ovarian cancer has remained around 30% despite continuous improvements in surgery, chemotherapy, radiotherapy, and other therapeutic methods. However, because of the particularity of the volume and location of ovarian tissue, the early symptoms of ovarian cancer are hidden, and there is a lack of highly sensitive and specific screening methods. Most patients have advanced metastasis, including abdominal metastasis, when they are diagnosed (Reid et al., 2017). Therefore, exploring the mechanism of ovarian cancer metastasis and finding early preventive measures are key to improving the survival rate and reducing mortality caused by ovarian cancer.
B7-H1 Antigen/biosynthesis* ; Cell Proliferation/drug effects* ; Chemokines/biosynthesis* ; Female ; Humans ; Ovarian Neoplasms/pathology* ; Survival Rate ; Up-Regulation

In order to obtain virus-like particles (VLPs) for prevention of bovine viral diarrhea virus 1 (BVDV-1), the C-E^rns-E1-E2 region was cloned into a pFastBacDaul vector for generating the recombinant Bacmid-BVDV-1 in DH10Bac Escherichia coli. The recombinant baculovirus Baculo-BVDV-1 was produced by transfecting the Sf9 cells with Bacmid-BVDV-1. The expressed protein and the assembled VLPs were determined by immunofluorescence, Western blotting and electron microscopy. Guinea pigs were immunized with inactivated VLPs coupled with the Montanide ISA-201 adjuvant. The immunogenicity of VLPs was evaluated by monitoring the humoral immune response with neutralizing antibody titer determination, as well as by analyzing the cell-mediated immune response with lymphocyte proliferation assay. The protective efficacy of VLPs was evaluated by challenging with 10⁶ TCID₅₀ virulent BVDV-1 strain AV69. The results showed that the recombinant Baculo-BVDV-1 efficiently expressed BVDV structural protein and form VLPs in infected Sf9 cells. The immunization of guinea pigs with VLPs resulted in a high titer (1:144) of neutralizing antibody, indicating an activated cellular immunity. Significantly lower viral RNA in the blood of the post-challenged immunized guinea pigs was observed. The successful preparation of BVDV VLPs with insect cell expression system and the observation of the associated immunogenicity may facilitate further development of a VLPs-based vaccine against BVD.
Animals ; Antibodies, Viral ; Diarrhea ; Diarrhea Virus 1, Bovine Viral ; Guinea Pigs ; Mineral Oil ; Viral Envelope Proteins ; Viral Vaccines

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

Objective:To dynamically monitor the prevalence and trend of dental fluorosis in children in Shandong Province, and to evaluate the prevention and control measures for drinking water-borne endemic fluorosis (referred to as drinking water-borne fluorosis), and to provide scientific basis for the next step.Methods:Totally 40 counties (cities, districts) were selected as project counties (cities, districts) from drinking water-borne fluorosis areas in Shandong Province in 2018, and all counties (cities, districts) were selected in 2019 and 2020, to investigate the situation of water improvement, detect water fluoride content, and investigate the prevalence of dental fluorosis in children aged 8 - 12 years.Results:From 2018 to 2020, the detection rates of dental fluorosis in children aged 8 - 12 years were 10.30% (503/4 884), 8.94% (25 895/289 539) and 8.66% (24 061/277 689), respectively, with statistically significant differences (χ 2 = 27.10, P < 0.001), and the dental fluorosis indexes were 0.21, 0.18 and 0.17, respectively. The total detection rates of dental fluorosis in children of different age groups in the 3 years were 7.26% (6 590/90 775), 7.97% (9 303/116 680), 9.29% (12 167/130 915), 9.29% (12 238/131 670) and 9.95% (10 161/102 072), the differences were statistically significant (χ 2 = 615.71, P < 0.001). In the 3 years, the total detection rate of dental fluorosis was 8.93% (28 101/314 737) in boys and 8.69% (22 358/257 375) in girls, the difference was statistically significant (χ 2 = 10.27, P = 0.001). In 2018 and 2019, the detection rates of dental fluorosis of children aged 8 - 12 years in water fluoride qualified villages [5.74% (235/4 095) and 7.98% (20 200/253 082)] were significantly lower than those in villages with excessive water fluoride [33.97% (268/789) and 15.62% (5 695/36 457), χ 2 = 570.61, 2 283.76, P < 0.001]. Conclusions:The prevalence of dental fluorosis among children aged 8 - 12 years has been effectively controlled, and remarkable results have been achieved in prevention and treatment of drinking water-borne fluorosis in Shandong Province. However, the detection rate of dental fluorosis among children in a few endemic villages is high, so it is necessary to continue to strengthen the monitoring of fluoride content in drinking water and the condition of dental fluorosis among children.

Objective:To analyze the correlations between serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) and clinicopathological features in children and adolescents with papillary thyroid carcinoma (PTC).Methods:A retrospective analysis was conduced on the clinicopathological data of children and adolescents (age≤21 years old) with PTC admitted to Tianjin Medical University Cancer Hospital from 2011 to 2019, and then, we used χ 2 test or Fisher′s exact probability test to compare the differences in clinicopathological characteristics between groups with different TgAb and TPOAb status and multivariate logistic regression model analysis to evaluate independent predictors of cervical lymph node metastasis. Results:A total of 304 patients, including 89 males and 215 females, aged 5-21 years (median age 19 years), were enrolled in this study. The comparison between groups with different TgAb and TPOAb status showed that there were significant differences in gender, preoperative thyroglobulin (Tg) level, primary tumor location, number of primary tumors and maximum tumor diameter (all P<0.05), which suggested that TgAb +group ( n=81) and TPOAb +group ( n=84) had relatively better primary tumor characteristics. Patitents with TgAb +and TPOAb +were more common in females and their preoperative Tg level was mostly within the normal range, and there were significant differences in primary tumor location, number of primary tumors and maximum tumor diameter between TgAb +and TgAb -(223 cases) groups (all P<0.05). There was significant difference in the maximum tumor diameter between TPOAb +and TPOAb -(220 cases) groups ( P<0.05). Analysis of risk factors for cervical lymph node metastasis showed that independent risk factors for central lymph node metastasis were maximum tumor diameter>2 cm ( OR=2.84, 95% CI: 1.59-5.07, P<0.001) and extra-thyroid extension ( OR=0.32, 95% CI: 0.17-0.60, P<0.001), and independent risk factors for lateral neck lymph node metastasis included age≤14 years old ( OR=0.34, 95% CI: 0.18-0.67, P=0.002), preoperative Tg +( OR=2.16, 95% CI: 1.10-4.24, P=0.026) and maximum tumor diameter>2 cm ( OR=3.99, 95% CI: 2.33-6.82, P<0.001). Conclusion:It is recommended to test routinely serum TgAb and TPOAb before surgery in children and adolescents with PTC. Preoperative Tg +, age≤14 years, maximum tumor diameter>2 cm, and extra-thyroid extension are risk factors for cervical lymph node metastasis.

Objective:To explore the efficacy of fluorescent retroperitoneal lymph node dissection in the comprehensive treatment of lymph node recurrence after radical prostatectomy (RP).Methods:From January 2017 to December 2020, 25 patients with lymph node recurrence diagnosed by 68Ga-PSMA PET/CT after RP in our hospital were enrolled in this study. The patients were 67 (59-77) years old. The median PSA was 7.7 (0.5-12.6) ng/ml at lymph node recurrence, and was treated with androgen deprivation therapy (ADT), suggesting hormone-sensitive prostate cancer. Before recurrence, 4 cases were in T 2 stage, 17 cases in T 3, 4 cases in T 4, 10 cases in N 0, and 15 cases in N 1stage, 25 cases in M 0stage. 2 cases diagnosed as ISUP grade group <3, 9 cases in group 4, and 14 cases in group 5. The median time from radical resection to recurrence was 43 (27-56) months. All 25 cases were diagnosed as lymph node recurrence by 68Ga-PSMA PET/CT examination. Fluorescence retroperitoneal lymph node dissection was performed. Pelvic lymph nodes were detected in the dark field under the fluorescence mode, and positive lymph nodes were found. The white light mode was switched, and the lymph nodes were cleaned, and recorded. For metastatic lymph nodes indicated by preoperative PSMA PET/CT, routine dissection was performed regardless of whether the lymph nodes were fluorescently positive or not. The only routine examination was performed if there were no lymph nodes with fluorescently positive staining in other sites. Perioperative data, biochemical recurrence (BCR) rate, radiological recurrence (RAR) rate, and follow-up data were collected and analyzed. Results:25 patients were pathologically diagnosed with lymph node metastasis. The median lymph node dissection time was 21(15-28) min, estimated blood loss was 30(20-50) ml, hospital days was 4(3-5)d without any severe complications (

Objective:To compare the pathological results and complications of limited and extended pelvic lymph node dissection among high-risk prostate cancer patients, and to explore the risk factors that affect the rate of lymph node metastasis in high-risk prostate cancer patients.Methods:The data of 800 high-risk prostate cancer patients who underwent radical prostatectomy and pelvic lymph node dissection from January 2016 to December 2020 in three affiliated hospital of Sun Yat-sen University were analyzed retrospectively. According to the scope of pelvic lymph node dissection, they were divided into limited pelvic lymph node dissection (LPLND) group and extended pelvic lymph node dissection (EPLND) group. There were 172 patients underwent LPLND, and 628 patients underwent EPLND.The age of the patients in the LPLND group was 67 (62, 72) years old, diagnosed PSA 20.7 (10.9, 54.8) ng/ml. The biopsy Gleason score 6 in 22 cases, 7 in 59 cases, 8 in 56 cases and 9-10 in 35 cases.The clinical T stage: T 1 in 29 cases, T 2 in 102 cases, T 3 in 37 cases, T 4 in 4 cases; N 0 in 160 cases and N 1 in 12 cases. 50 patients received neoadjuvant hormonal therapy. The age of patients in the EPLND group was 67 (63, 72) years old, diagnosed PSA was 23.9 (14.0, 46.8) ng/ml. Biopsy Gleason Score 6 in 51 cases, 7 in 194 cases, 8 in 218 cases and 9-10 in 165 cases. Clinical T stage: T 1 in 114 cases, T 2 in 341 cases, T 3 in 144 cases, T 4 in 29 cases; N 0 in 526 cases and N 1 in 102 cases.158 patients received neoadjuvant hormonal therapy. There were no significant differences in the age, PSA, puncture Gleason score, clinical T stage, and whether or not to receive neoadjuvant hormonal therapy between the two groups of patients ( P>0.05). The difference in clinical N staging was statistically significant ( P=0.002). The number of postoperative lymph nodes, positive pelvic lymph nodes and postoperative complications and other related clinical and pathological data of the two groups were analyzed. Multivariate logistic regression was used to analyze the risk factors of patients with positive lymph nodes. Results:The median number of lymph nodes harvested [13(8, 19)vs. 6(4, 13), P<0.001] and the rate of positive lymph node cases[31.2%(196/628) vs. 10.5%(18/172), P<0.001] in the EPLND group was significantly higher than those in the LPLND group. Preoperative PSA, clinical N staging, Gleason score, and way of lymph node dissection were independent risk factors for postoperative positive pelvic lymph node in high-risk prostate cancer patients. Compared with the LPLND group, the ELPND group had a higher postoperative complication rate [19.9%(125/628) vs. 11.0%(11/172), P=0.007]. Conclusions:Compared with the LPLND, EPLND in high-risk prostate cancer patients can harvest more lymph nodes and increase the detection rate of positive lymph nodes. The complications of EPLND were higher than those of LPLND. Preoperative PSA, clinical N stage, Gleason score, and the way of lymph node dissection are independent risk factors for positive pelvic lymph node dissection.

Ferroptosis is a newly discovered regulatory cell death induced by the accumulation of iron-dependent lipid peroxides, with the morphological manifestations of decreased mitochondrial volume, increased mitochondrial membrane density, and reduction or disappearance of mitochondria. The mechanism of ferroptosis is mainly associated with disturbance of iron metabolism, imbalance of amino acid antioxidant system, and accumulation of lipid peroxides. Studies have shown that ferroptosis plays different roles in different liver diseases, and ferroptosis can participate in the progression of various liver inflammatory diseases and inhibit the formation of liver fibrosis, the development of hepatocellular carcinoma, and sorafenib resistance. This article summarizes the advances in the mechanism of ferroptosis and its role in liver diseases, so as to provide a reference for further research and treatment of liver diseases.