Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy.

The identification of patient-derived, tumor-reactive T cell receptors (TCRs) as a basis for personalized transgenic T cell therapies remains a time- and cost-intensive endeavor. Current approaches to identify tumor-reactive TCRs analyze tumor mutations to predict T cell activating (neo)antigens and use these to either enrich tumor infiltrating lymphocyte (TIL) cultures or validate individual TCRs for transgenic autologous therapies. Here we combined high-throughput TCR cloning and reactivity validation to train predicTCR, a machine learning classifier that identifies individual tumor-reactive TILs in an antigen-agnostic manner based on single-TIL RNA sequencing. PredicTCR identifies tumor-reactive TCRs in TILs from diverse cancers better than previous gene set enrichment-based approaches, increasing specificity and sensitivity (geometric mean) from 0.38 to 0.74. By predicting tumor-reactive TCRs in a matter of days, TCR clonotypes can be prioritized to accelerate the manufacture of personalized T cell therapies.

The combination treatment of oncolytic adenovirus H101 with nivolumab for refractory advanced hepatocellular carcinoma: an open-label, single-arm, pilot study.

BACKGROUND: H101, an innovative oncolytic adenovirus, has shown potential in modifying the tumor microenvironment from immunologically 'cold' to 'hot'. When combined with nivolumab, a programmed cell death protein 1 inhibitor, this synergy may offer substantial therapeutic benefits beyond the capabilities of each agent alone. PATIENTS AND METHODS: In this pilot study, we assessed the efficacy and safety of combining H101 with nivolumab in advanced hepatocellular carcinoma (HCC) patients who failed prior systemic therapy. The participants received initial oncolytic virus (OV) pretreatment with intratumoral H101 injections (5.0 × 1011 vp/0.5 ml/vial, two vials per lesion) on days 1 and 3. Combination therapy started on day 8, with H101 administered every 2 or 4 weeks and nivolumab (240 mg) injections every 2 weeks. Treatment continued up to 12 months or until disease progression, intolerable toxicity, consent withdrawal, or study conclusion. The primary endpoint was the objective response rate (ORR). RESULTS: Between March 2020 and March 2022, 18 of 21 screened patients were assessable, showing an ORR of 11.1% [two cases of partial response (PR) and five cases of stable disease], with extrahepatic injections often leading to favorable outcomes. The disease control rate stood at 38.9%, with a 6-month survival rate of 88.9%. Median progression-free survival was 2.69 months, and overall survival (OS) was 15.04 months. Common adverse events included low-grade fever (100%) and pain related to centesis (33.3%), and no grade 3/4 events were reported. Significantly, local H101 injection showed potential in reversing immune checkpoint inhibitor resistance, evidenced by over 2.5 years of extended OS in PR cases with low α-fetoprotein. Additionally, decreasing neutrophil-to-lymphocyte ratio during OV pretreatment may predict positive outcomes. CONCLUSIONS: This study demonstrates the potential efficacy of combining H101 with nivolumab in treating refractory advanced HCC, with well-tolerated toxicities.

[A single-center study on the oncological outcomes of active surveillance of thyroid nodules measuring≤1 cm with highly suspicious ultrasound features].

Objective: To investigate the oncological outcomes of active surveillance (AS) in patients showing thyroid nodules measuring≤1 cm with highly suspicious ultrasound features. Methods: A prospective single-center cohort study. A total of 534 patients with highly suspicious thyroid nodules (2015 American Thyroid Association Nodule Sonographic Patterns and Risk of Malignancy: High Suspicion) were enrolled in this study, the patients received AS at Peking Union Medical College Hospital between January 2017 and November 2022 to assess oncological outcomes (disease progression, recurrence/metastasis rate, etc). The patients were followed up every 6 months for physical examination and neck ultrasound examination. And the value of tumor volume changes in evaluating tumor enlargement was explored too. Results: There were 413 females and 121 males in this cohort, with a mean age of (42.6±11.8) years. During a median follow-up period of 45.6 months (ranged from 3.5 to 176.0 months), disease progression occurred in 26 patients (4.9%) with highly suspicious thyroid nodules, characterized by a minimum 3-mm increase in tumor diameter in 19 patients (3.6%) and lymph node metastases in 7 patients (1.3%). Forty-seven (8.8%) patients opted for delayed surgery, with 29 patients due to a change in preference. There was no significant differences in pathologic and follow-up outcomes between patients with disease progression and preference change. Patients aged≤40 years had a higher cumulative incidence of 5-year disease progression than those aged>40 years (4.9% vs 1.9%, P=0.060). No patients experienced distant metastases or deaths. Among the 595 high-risk thyroid nodules with continuous volume assessment results and an increase in nodule diameter of less than 3 mm (including all high-risk nodules in patients with single or multiple nodules), 184 (30.9%) and 79 (13.3%) nodules exhibited volume increases of more than 50% and 100%, respectively, in multiple measurements. Among the nodules with volume changes exceeding 50% and 100%, the proportion of nodules with a baseline tumor diameter of≤0.5 cm was significantly higher than those with a diameter of>0.5 cm, at 69.0% vs 31.0% (P<0.001) and 77.2% vs 22.8% (P<0.001), respectively. Conclusions: Active surveillance in patients with highly suspicious subcentimeter thyroid nodules has good short-term oncological outcomes and can be considered a safe alternative to surgery. Due to the large variability in the measurement results of tumor volume, it is not suitable as an indicator for evaluating tumor enlargement.

Anterolateral thigh flap with a central hole for the repair of extensive oral defects in patients treated for chemotherapy-induced trismus.

Trismus is a rare complication of chemotherapy. The usefulness of a modified anterolateral thigh (ALT) flap for the repair of extensive oral defects in patients treated for chemotherapy-induced trismus was evaluated. Between 2019 and 2021, three patients with chemotherapy-induced trismus underwent scar excision. A thinned ALT flap with a central hole was designed to repair the resultant oral mucosal defects. The patients were followed up for a mean 9.3 months (range 4-18 months). The mean pre- and intraoperative maximum inter-incisal opening (MIO) was 0.7 cm (range 0-2.0 cm) and 3.6 cm (range 3.4-3.7 cm), respectively, indicating a significant operative effect. MIO at the latest follow-up was 2.4 cm (range 1.5-3.5 cm). All of the flaps survived without complications. All patients achieved a good diet and were satisfied with the aesthetics. Thorough excision of the perioral scar and restoration with a modified ALT flap achieved satisfactory mouth opening and cosmetic effects in patients with chemotherapy-induced trismus.

[Xanthoceras sorbifolium Bunge flower extract inhibits benign prostatic hyperplasia in rats].

OBJECTIVE: To assess the inhibitory effect of the extract of Xanthoceras sorbifolium Bunge flower against benign prostatic hyperplasia (BPH) and explore its possible mechanism. METHODS: MTT assay was used to examine the effect of the extract of Xanthoceras sorbifolium Bunge flower on proliferation of benign prostatic hyperplasia cells (BPH-1), and cell apoptosis and cell cycle changes following the treatment were analyzed using annexin V/PI double staining and flow cytometry. The protein expression levels of Bcl-2, Bax, caspase-3, PI3K and AKT in the treated cells were detected using Western blotting. A rat model of BPH established by subcutaneous injection of testosterone propionate was treated with the flower extract for 28 days, and pathological changes in the prostate tissue were observed with HE staining. The protein expression levels of Bcl-2, Bax, caspase3 and PI3K/AKT in the prostate tissue were detected with Western blotting. RESULTS: Within the concentration range of 125-1000 µg/mL, the flower extract of Xanthoceras sorbifolium Bunge significantly inhibited the proliferation of BPH-1 cells and caused obvious cell cycle arrest at G0/G1 phase; the apoptotic rate of the cells was positively correlated with the concentration of the flower extract (P < 0.05). Bcl-2, p-PI3K and p-AKT expression levels were significantly down-regulated and Bax and caspase-3 expression levels were significantly increased in the cells after treatment with the flowers extract (P < 0.05). In the rat models of BPH, the rats treated with the flowers extract at moderate and high doses showed obviously decreased expressions of p-AKT and Bcl-2 and an increased expression of Bax in the prostate tissue; a significantly lowered p-AKT expression was observed in the prostate tissue of rats receiving the low-dose treatment (P < 0.05). CONCLUSION: The flower extract of Xanthoceras sorbifolium Bunge has a inhibitory effect on BPH both in vitro and in rats, suggesting its potential value in the development of medicinal plant preparations for treatment of BPH.

[Smoking relapse rate and influencing factors in smokers aged 15 years and above in China].

Objective: To describe the relapse status of smokers aged ≥15 years in China, and investigate the main factors influencing their relapse behavior. Methods: The data of this study cames from the 2018 China Adult Tobacco Survey, covering 400 committees or villages in 200 districts or counties in 31 provinces (autonomous regions and municipalities) of China. The relevant data of smoking and relapsing in residents aged ≥15 years were collected by face-to-face interview. Software SAS 9.4 was used to clean and analyze the data, and logistic regression model was used to analyze the influencing factors for relapse rate. Results: A total of 19 376 questionnaires were completed, with a response rate of 91.50%. In 2018, 66.05% of smokers aged ≥15 years in China had smoking relapse, in whom 66.59% were males and 55.79% were females. In all age groups, the age group 15-24 years had the highest smoking relapse rate (82.63%). Multivariate analysis showed that the younger age 15-24 years (OR=4.618,95%CI:1.981-10.763), e-cigarette use (OR=9.782,95%CI:3.139-30.490), and tobacco advertising, promotion and sponsorship in the past 30 days (OR=1.710,95%CI:1.291-2.265) were associated with higher smoking relapse rate. Compared with people who were allowed smoking at home or those without smoking limit, the smoking relapse rate in people who were not allowed to smoke at home (OR=0.562, 95%CI: 0.439-0.719) or those with smoking limit (OR=0.487, 95%CI: 0.366-0.647) was lower. Conclusion: The smoking relapse rate in Chinese smokers is high, especially in young people. It is suggested to conduct targeted intervention based on the results of this study to reduce the smoking relapse rate and help achieve the smoking control goal in Healthy China 2030.

[Study on smoking behavior and its changes among Chinese people aged 15 years and above in 2018].

Objective: To describe the current status of smoking among Chinese people aged 15 and above and analyze its epidemic evolution. Methods: A stratified multi-phased randomized cluster sampling design of the Global Adult Tobacco Survey was used. The cross-sectional survey was conducted from July to December 2018, covering 200 districts/counties in 31 provinces of China. Field data was collected through in-house face-to-face interviews by trained investigators using a tablet computer. 19 376 individual questionnaires were completed, with an overall response rate of 91.50%. The data were weighted for complex sampling and analyzed with SAS 9.4. Results: In 2018, the current smoking prevalence of adults aged 15 and above was 26.59%, with that higher among males (50.47%) than among females (2.07%) and higher among those in rural (28.87%) than among those in urban areas (25.05%). The quitting rate was 20.10%, with a higher rate among females (30.22%) than males (19.64%). However, there was no significant difference between rural and urban areas (P=0.864). Compared with the previous data, the smoking rate tends to drop, with a substantial decrease among the 25-44 age groups and 45-64 age groups. The most significant decline occurs among those with higher education (Junior college and above). In addition, in 2018, current daily smokers aged 15 and above in China started to smoke daily at an average age of 20.95 years old. For current smokers, 16.00 cigarettes were consumed each day on average. Conclusion: Although the current smoking prevalence among the Chinese population aged 15 and above tends to decrease, the decreasing speed is too slow to achieve the target set in the Healthy China Action (2019-2030). Consequently, much more effective efforts to control tobacco need to be enforced.

[Quit intention and smoking cessation behavior of current smokers aged 15 years and above in China, 2018].

Objective: To describe the current situation on quit intention and quit attempts among current smokers aged 15 years and above in China and explore the main factors affecting their smoking cessation behaviors. Methods: The subjects were people aged 15 years and above in China. A stratified multi-phased randomized cluster sampling method was used. The survey covered 200 districts/counties in 31 provinces (autonomous regions and municipalities directly under the central government), including 19 376 people under investigation. The data were weighted with SAS 9.4 for complex sampling analysis, and the frequency and weighted component ratio were used for description. The influencing factors were studied using the Rao Scott χ2 test and unconditional multivariate logistic regression. Results: Among current smokers, 6.63% reported that they planned to quit smoking in the next month, 5.44% for men and 8.49% for women. 17.96% of the current smokers made quit attempts in the past 12 months, with 17.80% men and 22.15% women. People who smoke occasionally (OR=3.42, 95%CI: 2.09-5.59) made quit attempts in the past (OR=4.91, 95%CI: 0.33-0.52) and knew that smoking would lead to three diseases (OR=2.24, 95%CI: 1.48-3.40) had higher quit intention. People who occasionally smoke (OR=1.68, 95%CI: 1.20-2.34) received smoking cessation suggestions from medical staff (OR=1.96, 95%CI: 1.62-2.37), were a ware of that smoking causes three diseases (OR=1.63, 95%CI: 1.32-2.02) and had smoking prohibition regulations in indoor areas of their homes, had a higher rate of quit attempts. Conclusion: Providing effective smoking cessation intervention services and creating a supportive tobacco control environment are significant in promoting smoking cessation behavior.

[Secondhand smoke exposure and its influencing factors among Chinese people aged 15 years and above in 2010 and 2018].

Objective: To investigate secondhand smoke (SHS) exposure among non-current smokers aged 15 and over and its influencing factors in China in 2010 and 2018. Methods: The 2010 and 2018 China Adult Tobacco Surveys used multistage stratified cluster random sampling methods to obtain national representative samples across 31 provinces (autonomous regions and municipalities) in China. This study selected non-current smokers aged 15 and over as the research subjects to describe the general demographic characteristics, perceptions of SHS hazards, attitudes towards smoking bans in indoor areas in public places, and SHS exposure and the smoking restriction regulations in different places. The Rao-Scott χ2 test was used to compare the rates, and the unconditional logistic regression was used to analyze the influencing factors of SHS exposure. All the subjects in the analysis were weighted based on a complex sampling design. Results: Among non-current smokers aged 15 and over, from 2010 to 2018, the percentage of indoor smokers had decreased from 84.7% to 71.9%. The rates of people who saw smoking in various places declined with a statistically significant difference (P<0.001). The exposure to SHS for females, people aged 45-64, teachers, medical staff, workers in enterprises, businesses, waiters, and people who live in rural and central areas declined. The differences were statistically significant (P<0.05). In 2018, the percentage of SHS exposure for those who reported a comprehensive smoking ban in households or allowed smoking in certain areas was lower than for those who reported allowed or without a smoking ban. Among those aged 25-44, SHS exposure for those who reported complete smoking prohibition in workplaces was lower than those who reported allowed or without smoking prohibition (OR=0.65, 95%CI: 0.49-0.87). The proportion of SHS exposure for those who believe that smoking should not be allowed in indoor areas of 0-5 public places is higher than that smoking should not be allowed in the indoor spaces of 8 public places (OR=2.13, 95%CI: 1.35-3.36). Among people aged 45-64, the proportions of SHS exposure for teachers (OR=0.37, 95%CI: 0.17-0.78) and medical staff (OR=0.35, 95%CI: 0.16-0.76) and staff working in agriculture, forestry, animal husbandry, fishery, and water conservancy were lower than governmental staff (OR=0.49, 95%CI: 0.29-0.84). Conclusions: Data from the decreased exposure of Chinese non-current smokers aged 15 and over to SHS suggests the initial achievement through constructing a smoke-free environment, but continued efforts are needed. It is necessary to actively advocate for smoke-free families, strengthen publicity and education on the hazards of tobacco and SHS, and improve the skills of non-smokers in rejecting SHS exposure.

[Analysis of exposure to tobacco advertisement and promotion among Chinese adults aged 15 years and above, 2010 and 2018].

Objective: To investigate the exposure to tobacco advertisements and promotions among Chinese adults aged 15 and above, identify the publicity channels and forms of tobacco advertising and promotion in 2010 and 2018, and implicate further tobacco control measures in China. Methods: A multistage, stratified, randomized cluster sampling design was used in 2010 and 2018 China Adult Tobacco Survey, with national representativeness. 13 354 and 19 376 permanent residents were selected in the 2010 and 2018 surveys. SAS 9.4 software was applied for data analysis, and all the data were weighted based on a complex sampling design. Rao Scott χ2 test was used for group comparison of a single factor. Results: In 2010 and 2018, 19.61% and 18.14% of the survey respondents did see tobacco advertising and promotion. From 2010 to 2018, there was no significant change in the situation of tobacco advertisements and promotions. Among those who had gone to a cigarette shop, the proportion of seeing tobacco advertisements increased from 29.28% in 2010 to 43.28% in 2018. Among those who had seen tobacco advertisements on TV, the rate fell from 50.93% in 2010 to 28.58% in 2018. Among those who had gone to movie theaters, the proportion of seeing tobacco advertisements increased from 2.17% in 2010 to 9.89% in 2018. Among those who had used the Internet, the proportion of seeing tobacco advertisements online rose from 19.20% in 2010 to 42.30% in 2018. In terms of tobacco promotion, the percentages of people who had seen tobacco promotions, cigarette price discounts, cigarette discount coupons, gifts, and other preferential activities in various places in the past 30 days were 4.99% vs. 9.30%, 0.78% vs. 4.09%, 0.04% vs. 0.33% and 0.98% vs. 3.33% in 2010 and 2018, respectively (P<0.001). Conclusions: Tobacco advertising and promotion are still prevalent in China, with no significant change in 2010 and 2018. Tobacco advertising and promotion have been with the constant changes and development of media platforms. It is necessary to improve the implementation of relevant policies, comprehensively ban tobacco advertisements and promotions, and strengthen the supervision of ads and promotions.

The mechanism of Epimedium in the treatment of coronary atherosclerotic heart disease based on network pharmacology, molecular docking, and in vitro studies.

OBJECTIVE: There are many challenges related to the treatment of coronary atherosclerotic heart disease (CAD). Studies have confirmed that Epimedium extract inhibits myocardial injury induced by myocardial ischaemia, but the mechanism of action remains unclear. This study aimed at analysed the effective components and mechanisms of Epimedium in treating CAD based on network pharmacology and molecular docking studies and to verify the mechanism in vitro. MATERIALS AND METHODS: The TCMSP and UniProt databases were used to filter for the active components and drug targets of Epimedium. The GeneCards database was used to screen disease targets associated with CAD. The intersection of the drug targets of Epimedium and the disease targets of coronary heart disease was studied to identify the targets of Epimedium in the treatment of CAD. Cytoscape software was used to establish and analyse an activity-target network. The STRING database was used to analyse a protein-protein interaction (PPI) network, and proteins in the PPI network were visualized in the R language. Bioconductor software was used for GO function and KEGG pathway enrichment analyses, and visualization analysis was performed in the R language. PyMOL software was used to verify the molecular docking between selected active components of Epimedium and the targets of CAD, and the potential key effective components of Epimedium in the treatment of coronary heart disease were identified. The involvement of the PI3K/Akt pathway was validated by Western blot analysis. RESULTS: (1) Twenty-three active compounds, including Epimedium glycoside, quercetin, luteolin, and olive resin, were screened out. There were 68 common targets of Epimedium and CAD, including IL-6, ESR1, RELA, FOS, NCOA1, CCND1, EGFR, MAPK8, VEGFA, and CASP8. The potential signaling pathways involved in the treatment of CAD by Epimedium included the human cytomegalovirus infection pathway, the PI3K-Akt signaling pathway, the TNF signaling pathway, and the HIF-1 signaling pathway. (2) Luteolin, quercetin, sitosterol, and anhydroicaritin showed strong binding to targets of CAD based on molecular docking studies. (3) Epimedium extract increased the expression of PI3K, Akt and P-Akt but decreased the expression of IL-6  in vitro. CONCLUSIONS: (1) Icariin, quercetin and luteolin may act on target proteins, including IL-6, ESR1, EGFR, MAPK8, VEGFA and CASP8, to participate in the regulation of the human cytomegalovirus infection pathway, the PI3K-Akt signaling pathway, the TNF signaling pathway and other signaling pathways in order to effectively treat CAD. (2) In vitro studies confirmed that Epimedium extract can treat CAD by upregulating PI3K, Akt and P-Akt protein expression and downregulating IL-6 protein expression in SD rat cardiomyocytes.

[Risk factors affecting graft survival after parathyroidectomy and parathyroid autotransplantation in patients on maintenance hemodialysis].

OBJECTIVE: To investigate the risk factors affecting the survival of parathyroid autograft following total parathyroidectomy combined with autologous sternocleidomastoid muscle transplantation (TPTX + AT) in patients on maintenance hemodialysis (MHD) complicated with secondary hyperparathyroidism (SHPT). OBJECTIVE: This retrospective study was conducted among the patients on maintenance hemodialysis with SHPT, who underwent successful parathyroidectomy and autotransplantation from January, 2010 to February, 2020 in our hospital. The clinical data and serum levels of calcium, phosphorus, intact parathyroid hormone, hemoglobin, and alkaline phosphatase (ALP) of the patients were collected. The enrolled patients were divided into survival group with bilateral forearm parathyroid hormone (iPTH) ratio > 1.5 and death group with a ratio < 1.5 at 2 weeks after surgery for comparison of the clinical data and perioperative indicators. The risk factors of postoperative parathyroid autograft survival were analyzed using logistic regression analysis. OBJECTIVE: A total of 87 patients were included in the study, among whom the graft survival rate after parathyroid transplantation was 78.16%. In both groups, serum levels of calcium, phosphorus, iPTH and ALP decreased and hemoglobin level increased significantly at 1 week and 1, 2, 3, 6 and 12 months after surgery (P < 0.01). Logistic regression analysis showed that serum ALP level was an independent risk factor for graft survival following parathyroid autotransplantation [OR=1.003, 95% CI: 1.001-1.005, P=0.004]. OBJECTIVE: TPTX+AT is a safe and effective treatment for SHPT, and parathyroid autografts are less likely to survive following parathyroid transplantation in patients with high preoperative level of ALP.

[Study on the method of detection of benzene exposure biomarkers by solid phase extraction-gas chromatography-tandem mass spectrometry].

Objective: A gas chromatography-tandem mass spectrometry detection method for benzene and its metabolites was established to provide methodological support and theoretical basis for the study of benzene toxicity mechanism. Methods: In August 2019 to March 2020, the animal model of containing high concentration of benzene by inhalation of poison through the respiratory tract of mice was established, taken the blood of mice after dyeing the poison, and the HLB solid phase extraction method was used to extract and purify the samples. The gas chromatography-tandem mass spectrometry detection method was used to qualitative and quantitative analysis of the target substances. After separated by HP-17MS capillary chromatographic column, the compounds were ionized with EI ion source, mass spectrometry detection was carried out by selective ion scanning method (SIM) , and quantification was carried out by external standard curve method. Results: Benzene and its metabolites (phenol, catechol, hydroquinone and m-trihydroxybenzene) in blood could be effectively separated and quasi deterministic and quantitative by this method. The regression equations and correlation coefficients of this method for detecting benzene and its metabolites were: benzene: y=3252.1x+1540, r=0.9993; phenol: y=2046.5x+1423, r=0.9991; catechol: y=1853.9x+945, r=0.9993; hydroquinone: y=1891.5x+840, r=0.9992; m-trihydroxybenzene: y=1052.4x+655, r=0.9991. The detection limits for benzene, phenol, catechol, hydroquinone and m-trihydroxybenzene were 0.03, 0.03, 0.05, 0.05 and 0.10 µg/g, respectively. And the lower limits of quantification were 0.10, 0.10, 0.15, 0.15 and 0.30 µg/g, respectively. The intra-assay precision interval was 2.64%-10.06%, the inter-assay precision interval was 1.37%-10.17%, and the spike recovery rate was 89.8%-102.3%. This method could be used to quantitatively detect benzene, phenol, catechol, hydroquinone and m-trihydroxybenzene in the blood of benzene-infected mice. Conclusion: Solid phase extraction-gas chromatography-mass spectrometry can be used for qualitative and quantitative detection of benzene and its metabolites (phenol, catechol, hydroquinone and m-trihydroxybenzene) accurately.

Mechanisms of regulating NIS transport to the cell membrane and redifferentiation therapy in thyroid cancer.

Iodine is an essential constituent of thyroid hormone. Active iodide accumulation in the thyroid is mediated by the sodium iodide symporter (NIS), comprising the first step in thyroid hormone biosynthesis, which relies on the functional expression of NIS on the cell membrane. The retention of NIS expressed in differentiated thyroid cancer (DTC) cells allows further treatment with post-operative radioactive iodine (RAI) therapy. However, compared with normal thyroid tissue, differentiated thyroid tumors usually show a decrease in the active iodide conveyance and NIS is generally retained within the cells, indicating that posttranslational protein transfer to the plasma membrane is abnormal. In recent years, through in vitro studies and studies of patients with DTC, various methods have been tested to increase the transport rate of NIS to the cell membrane and increase the absorption of iodine. An in-depth understanding of the mechanism of NIS transport to the plasma membrane could lead to improvements in RAI therapy. Therefore, in this review, we discuss the current knowledge concerning the post-translational mechanisms that regulate NIS transport to the cell membrane and the current status of redifferentiation therapy for patients with RAI-refractory (RAIR)-DTC.

[Comparison of endoscopic versus conventional surgery for benign parotid tumor: a metaanalysis].

To assess the efficacy and safety of endoscopic versus conventional surgery for benign parotid tumor.We searched the electronic databases including PubMed, Embase, Web of Science, CNKI and Wanfang Data for studies published before January, 2021. A meta-analysis was performed using Rev Man 5.3 software.We retrieved 8 eligible studies involving a total of 532 patients, and 4 of the studies were RCT. The results of meta-analysis showed that endoscopic surgery was better than conventional surgery in terms of incision length (WMD=- 5.73; 95% CI: - 6.84--4.62), intraoperative bleeding volume (WMD=-34.50; 95% CI: -49.09--19.91), postoperative drainage volume (WMD=- 21.72; 95% CI: - 29.31--14.12), subjective satisfaction with incision scar(WMD=2.23; 95%CI: 1.11-3.34), and temporary facial paresis (OR=0.37; 95%CI: 0.17-0.78). There were no significant differences in the operation time, salivary fistula, Frey's syndrome or tumor recurrence between the two groups.For treatment of benign parotid tumor, endoscopic surgery is a safe surgical procedure and is superior to conventional surgery in terms of incision length, operative bleeding volume, postoperative drainage volume, subjective satisfaction with incision scar, and temporary facial paresis.

Clinical significance of multi-slice spiral CT, MRI combined with gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer.

PURPOSE: To explore the application value of multi-slice spiral CT (MSCT), magnetic resonance imaging (MRI) combined with gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer. METHODS: The subjects of study were 109 gastric cancer patients with T stages admitted to our hospital for diagnosis and treatment from December 2016 to December 2018. All the patients were examined with MSCT, MRI and gastric contrast-enhanced ultrasonography before operation to observe corresponding imaging results. T staging of gastric cancer patients was conducted according to the examination results, which was then compared with postoperative pathological staging. It was performed to analyze the accuracy of the three diagnostic methods and combined diagnosis of gastric cancer T staging. RESULTS: The sensitivity of MSCT in the diagnosis of T staging of gastric cancer was 60.00%, 67.74%, 72.22%, 76.47%, the specificity was 95.24%, 88.46%, 86.30%, 94.56% and the diagnostic coincidence rate was 87.16%, 82.57%, 81.65%, 91.74%; the sensitivity of MRI in the diagnosis of T staging of gastric cancer was 68.00%, 70.97%, 77.78%, 76.47%, the specificity was 92.86%, 88.46%, 91.78%, 95.65%, and the diagnostic coincidence rate was 87.16%, 83.49%, 87.16%, 92.66%; the sensitivity of gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer was 80.00%, 83.87%, 86.11%, 82.35%, the specificity was 97.62%, 92.31%, 91.78%, 97.83%, and the diagnostic coincidence rate was 93.58%, 89.91%, 89.91%, 95.41%; the sensitivity of combined MSCT, MRI and gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer was 88.00%, 93.55%, 97.22%, 94.12%; the specificity was 100%, 97.44%, 95.89%, 98.91%; and the diagnostic coincidence rate was 97.25%, 96.33%, 96.33%, 98.17%, respectively. Statistical analysis revealed that the sensitivity, specificity and diagnostic coincidence rate of combined detection of the three methods were significantly higher than those of single detection (P < 0.05). CONCLUSION: Combined use of MSCT, MRI and gastric contrast-enhanced ultrasonography can significantly improve the diagnostic sensitivity, specificity and diagnostic coincidence rate of T staging of gastric cancer. It may provide a certain reference value for guiding the selection of clinical therapeutic approaches and evaluation of curative effect.

Identification and validation of a hub gene prognostic index for hepatocellular carcinoma.

Aims: We aim to provide new insights into the mechanisms of hepatocellular carcinoma (HCC) and identify key genes as biomarkers for the prognosis of HCC. Materials & methods: Differentially expressed genes between HCC tissues and normal tissues were identified via the Gene Expression Omnibus tool. The top ten hub genes screened by the degree of the protein nodes in the protein-protein interaction network also showed significant associations with overall survival in HCC patients. Results: A prognostic model containing a five-gene signature was constructed to predict the prognosis of HCC via multivariate Cox regression analysis. Conclusion: This study identified a novel five-gene signature (CDK1, CCNB1, CCNB2, BUB1 and KIF11) as a significant independent prognostic factor.

Lay abstract Given the poor success of traditional treatments in improving the prognosis of hepatocellular carcinoma (HCC), we need new techniques to improve survival. The new techniques must be checked for accuracy and we must assess whether we can utilize it to achieve individualized treatment. The finding of this study, which examined genetic differences between tumor tissues and normal tissues, is that patients with a high-risk genetic 'signature' have worse results and a shorter survival time than those with a low-risk profile. We first screen hub genes related to the survival status of HCC patients. Then we construct a risk score model to predict the prognosis of HCC and confirm that the model is highly credible. It is reasonable to believe that our risk score model has a high predictive value for the prognosis of HCC.

[The value of serum abnormal prothrombin in clinical application of hepatocellular carcinoma].

Objective: To examine the value of serum protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) detection in the early diagnosis and surveillance of hepatocellular carcinoma (HCC). Methods: The clinical data of 215 patients with HCC admitted to Department of Hepatobiliary-Pancreatic Surgery of China-Japan Union Hospital of Jilin University from October 2017 to May 2018 were analyzed retrospectively. There were 172 males and 43 females, aged of (59.0±9.3) years old (range 34 to 86 years old). In addition, there were 85 non HCC patients were enrolled in the control group, 42 males and 43 females, aged (54.2±11.3) years old (range 22 to 80 years old). The blood sample of 3 ml was drawn from the elbow vein at 6∶00 am on the next day of admission, and then was kept in low temperature away from light, and sent for PIVKA-Ⅱ detection on the same day. The positive value of AFP was ≥20 µg/L and PIVKA-Ⅱ was ≥32 AU/L. The data were analyzed statistically by χ(2) test, t test or rank sum test. The correlation between AFP, PIVKA-Ⅱ and tumor maximum diameter was analyzed by linear regression. Results: The sensitivity of PIVKA-Ⅱ detection only for the diagnosis of HCC in all stages was significantly higher than AFP or equivalent to AFP, the overall sensitivity of PIVKA-Ⅱ and AFP was 85.1% and 52.1%, respectively. But the specificity of PIVKA-Ⅱ was lower than that of AFP, they were 78.8% and 96.5%, respectively. In particularly, in the earlier stage of HCC (Ⅰa) , the sensitivity of PIVAK-Ⅱ to HCC was 64.5%, while the AFP was only 26.3%. Combined detection of PIVKA-Ⅱ and AFP significantly improved the diagnostic rate of HCC to 88.4%, and the specificity to 76.5%. Moreover, there was a positive correlation between PIVKA-Ⅱ level and the maximum tumor diameter (r(2)=0.587, P<0.05), but there was no correlation between the AFP level and the maximum tumor diameter (r(2)=0.296, P>0.05). The positive rate of PIVKA-Ⅱ in the diagnosis of HCC with vascular invasion was also significantly higher than that of AFP (P<0.01) . Conclusions: PIVKA-Ⅱ can be used as a serological marker for HCC screening and diagnosis. In particular, PIVKA-Ⅱ detection was significantly sensitive than AFP in the earlier stage of HCC. Combined detection of PIVKA-Ⅱ and AFP can effectively improve the diagnostic rate of HCC in all stages. The significant elevation of PIVKA-Ⅱ is also helpful to determine the tumor aggressiveness, vascular invasion and prognosis of HCC patients.