[Molecular epidemiological study on rubella virus circulating in Yunnan Province during 2011-2021].

Objective: To understand the genotype distribution and transmission pattern of rubella virus (RuV) circulating in Yunnan Province. Methods: Throat swab samples were collected from rubella outbreaks and sporadic cases in nine prefectures/cities of Yunnan Province from 2011 to 2021. Virus isolation, amplification of target genes and sequence determination were performed on the RuV-positive samples. The genotypes and lineages of Yunnan strains were determined by comparing them with the reference strains, and further phylogenetic analysis was performed with Yunnan strains and strains circulating in other provinces of China during the same period. Results: RuV circulating in Yunnan province during 2011-2021 showed significant genetic diversity, and three lineages, 1E-L1, 2B-L1 and 1E-L2, were detected. Two lineage-switches were also identified, including the conversion of 1E-L1 to 2B-L1 between 2012 and 2013, and the replacement of 2B-L1 to 1E-L2 after 2018. The time of the switches was basically consistent with the outbreak in Yunnan province in 2012 and the time of the rubella reemergence and epidemic between 2018 and 2019. The amino acid sequence of RuV virus strains in Yunnan province was highly conserved, and no important functional regions were changed. Conclusions: The transmission pattern of RuV in Yunnan province is generally consistent with the epidemic trend of RuV in other provinces of China.

[Demographic characteristics and associated influencing factors in treated patients with chronic hepatitis B with hypoviremia : a single-center retrospective cross-sectional study].

Objective: To investigate the demographic characteristics and clinical influencing factors which associates with the occurrence probability of persistent or intermittent hypoviremia (LLV) in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs). Methods: A single-center retrospective analysis was performed on patients with CHB who received outpatient NAs therapy for≥48 ± 2 weeks. According to the serum hepatitis B virus (HBV) DNA load at 48±2 weeks treatment, the study groups were divided into LLV (HBV DNA < 20 IU/ml and < 2 000 IU/ml) and MVR group (sustained virological response, HBV DNA < 20 IU/ml). Demographic characteristics and clinical data at the start of NAs treatment (considered as baseline) were retrospectively collected for both patient groups. The differences in the reduction of HBV DNA load during treatment was compared between the two groups. Correlation and multivariate analysis were further conducted to analyze the associated factors influencing the LLV occurrence. Statistical analysis was performed using the independent samples t-test, c2 test, Spearman analysis, multivariate logistic regression analysis, or area under the receiver operating characteristic curve. Results: A total of 509 cases were enrolled, with 189 and 320 in the LLV and MVR groups, respectively. Compared to patients with MVR group at baseline: (1) the demographics characteristics of patients showed that LLV group was younger in age (39.1 years, P = 0.027), had a stronger family history (60.3%, P = 0.001), 61.9% received ETV treatment, and higher proportion of compensated cirrhosis (20.6%, P = 0.025) at baseline; (2) the serum virological characteristics of patients showed that LLV group had higher HBV DNA load, qHBsAg level, qHBeAg level, HBeAg positive rate, and the proportion of genotype C HBV infection but decreased HBV DNA during treatment (P < 0.001) at baseline; (3) the biochemical characteristics of patients showed that LLV group had lower serum ALT levels (P = 0.007) at baseline; (4) the noninvasive fibrosis markers of patients showed that LLV group were characterized by high aspartate aminotransferase platelet ratio index (APRI) (P = 0.02) and FIB-4 (P = 0.027) at baseline. HBV DNA, qHBsAg and qHBeAg were positively correlated with LLV occurrence (r = 0.559, 0.344, 0.435, respectively), while age and HBV DNA reduction were negatively correlated (r = -0.098, -0.876, respectively). Logistic regression analysis showed that ETV treatment history, high HBV DNA load at baseline, high qHBsAg level, high qHBeAg level, HBeAg positive, low ALT and HBV DNA level were independent risk factors for patients with CHB who developed LLV with NAs treatment. Multivariate prediction model had a good predictive value for LLV occurrence [AUC 0.922 (95%CI: 0.897 ~ 0.946)]. Conclusion: In this study, 37.1% of CHB patients treated with first-line NAs has LLV. The formation of LLV is influenced by various factors. HBeAg positivity, genotype C HBV infection, high baseline HBV DNA load, high qHBsAg level, high qHBeAg level, high APRI or FIB-4 value, low baseline ALT level, reduced HBV DNA during treatment, concomitant family history, metabolic liver disease history, and age < 40 years old are potential risk factors for developing LLV in patients with CHB during the therapeutic process.

Repeat hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma: retrospective multicentre study.

BACKGROUND: The therapeutic value of repeat hepatic resection (rHR) or radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) is unknown. This study aimed to investigate the safety and efficacy of rHR or RFA. METHODS: This was a retrospective multicentre study of patients with recurrent HCC within the Milan criteria who underwent rHR or RFA at nine university hospitals in China and Italy between January 2003 and January 2018. Survival after rHR or RFA was examined in unadjusted analyses and after propensity score matching (1 : 1). RESULTS: Of 847 patients included, 307 and 540 underwent rHR and RFA respectively. Median overall survival was 73.5 and 67.0 months after rHR and RFA respectively (hazard ratio 1.01 (95 per cent c.i. 0.81 to 1.26)). Median recurrence-free survival was longer after rHR versus RFA (23.6 versus 15.2 months; hazard ratio 0.76 (95 per cent c.i. 0.65 to 0.89)). These results were confirmed after propensity score matching. RFA was associated with lower morbidity of grade 3 and above (0.6 versus 6.2 per cent; P < 0.001) and shorter hospital stay (8.0 versus 3.0 days, P < 0.001) than rHR. CONCLUSION: rHR was associated with longer recurrence-free survival but not overall survival compared with RFA.

Long non-coding RNA HOXB-AS1 promotes proliferation, migration and invasion of glioblastoma cells via HOXB-AS1/miR-885-3p/HOXB2 axis.

Long non-coding RNAs (lncRNAs) have been proved to play important roles in carcinogenesis and development of numerous cancers, but their biological functions in glioblastoma remain largely unknown. In this study, we found HOXB-AS1 was highly expressed in human glioblastoma tissues and cell lines, and was associated with survival time of patients. Our results showed HOXB-AS1 knockdown inhibited proliferation via inducing S phase cell cycle arrest, and suppressed migration ability of cells. In terms of mechanism, HOXB-AS1 were mainly located in cytoplasm and functioned as ceRNA via sponging of miR-885-3p. We proved inhibition of miR-885-3p antagonized the effects of HOXB-AS1 konckdown and promoted the proliferation and migration of glioblastoma. Finally, we found the sponging of miR-885-3p by HOXB-AS1 could further affecting the expression of HOXB2. Taken together, we demonstrated that HOXB-AS1/miR-885-3p/HOXB2 axis could regulate the proliferation and migration of glioblastoma, which could serve as a potential biomarker for glioblastoma patients.

Systematic review of risk factors of hepatocellular carcinoma after hepatitis B surface antigen seroclearance.

There is no consensus about factors that increase risk of hepatocellular carcinoma (HCC) among patients with chronic hepatitis B who have achieved seroclearance of hepatitis B surface antigen (HBsAg). To assess the available evidence about risk factors for HCC after HBsAg seroclearance, Scopus, EMBASE, PubMed and Cochrane Library databases were systematically searched for relevant studies published through 15 September 2017. A total of 28 studies involving more than 105 411 patients with chronic hepatitis B were included. HBsAg seroclearance occurred spontaneously in 7656, while it occurred after interferon or nucleos(t)ide analogue therapy in 1248. The rate of HBsAg seroclearance was 6.77%. Incidence of HCC was significantly lower among patients who experienced HBsAg seroclearance than among those who remained HBsAg-positive (1.86% vs 6.56%, P < .001). Risk factors of HCC occurrence included cirrhosis (incidence with vs without: 9.51% vs 1.66%), male gender (2.34% vs 0.64%) and age ≥ 50 year at HBsAg seroclearance (2.34% vs 0.63%) (all P < .001). The available evidence suggests that HCC can develop at a low rate after HBsAg seroclearance, so periodic surveillance is recommended, especially for male patients, patients with cirrhosis and patients who experience HBsAg seroclearance when at least 50 years old.

[Preparation, quality control and thyroid molecule imaging of solid-target based radionuclide ioine-124].

OBJECTIVE: To provide useful information for the further production and application of this novel radio-nuclide for potential clinical application. METHODS: 124Te (p,n) 124I nuclide reaction was used for the 124I production. Firstly, the target material, 124TeO2 (200 mg) and Al2O3 (30 mg) mixture, were compressed into the round platinum based solid target by tablet device. HM-20 medical cyclotron was applied to irradiate the solid target slice for 6-10 h with helium and water cooling. Then, the radiated solid target was placed for 12 h (overnight) to decay the radioactive impurity; finally, 124I was be purified by dry distillation using 1 mL/min nitrogen for about 6 hours and radiochemical separation methods. Micro-PET imaging studies were performed to investigate the metabolism properties and thyroid imaging ability of 124I.After 740 kBq 124I was injected intravenously into the tail vein of the normal mice, the animals were imaged with micro-PET and infused with CT. The micro-PET/CT infusion imaging revealed actual state 124I's metabolism in the mice. RESULTS: It was been successfully applied for 200 mg 124TeO2 plating by the tablet device on the surface of platinum. It showed smooth, dense surface and without obviously pits and cracks. The enriched 124Te target was irradiated for 6 to 10 hours at about 12.0 MeV with 20 µA current on HM-20 cyclotron. Then 370-1 110 MBq 124I could be produced on the solid target after irradiation and 370-740 MBq high specific activity could be collected afterdry distillation separation and radio-chemical purification.124I product was finally dissolved in 0.01 mol/L NaOH for the future distribution. The gamma spectrum of the produced 124I-solution showed that radionuclide purity was over 80.0%. The micro-PET imaging of 124I in the normal mice exhibited the thyroid and stomach accumulations and kidney metabolism, the bladder could also be clearly visible, which was in accordance with what was previously reported. To the best of our knowledge, it was the first production of 124I report in China. CONCLUSION: In this study, the preparation of 124TeO2 solid target was successfully carried out by using the tablet device. After irradiation of the 124TeO2 solid target and radio-chemical purification, we successfully produced 370-740 MBq high specific activity 124I by a cyclotron for biomedical application, and micro-PET imaging of 124I in normal mice exhibited the thyroid accumulations. Also, slight uptake in stomach were also monitored with almost nonuptake in other organs in the micro-PET imaging. The production of 124I is expected to provide a new solid target radionuclide for the scientific research and potential clinical application of our country.

[Analysis of measles immunity level and serological susceptibility among Yunnan residents aged ≥20 years].

Objective: To evaluate the population immunity to measles and explore the factors associated with measles susceptibility in Yunnan residents aged ≥20 years. Methods: 2 689 residents aged ≥20 years were selected by multistage stratified systematic randomized sampling in 252 villages of 42 counties in Yunnan Province between June and September in 2015. Each subject was surveyed by the same questionnaire, including general information, measles contained vaccine history, measles history, and 5 ml blood sample of each subject was collected. Serum IgG antibodies against measles virus were measured by ELISA. Positive was defined as the antibody concentration ≥250 mU/ml, and negative as <250 mU/ml. Non-conditional logistic regression model was used analyze the factors associated with measles susceptibility in adults. Results: Among 2 689 subjects, 1 214 were males (45.15%), and the overall positive rate of measles IgG antibody was 89.77%. Compared with subjects from the region where economic development was low, subjects from the region where economic development was moderate were likely to be susceptible to measles virus (OR=1.81, 95%CI: 1.33-2.47). Four age groups had higher risk of being susceptible to measles virus (compared with ≥40 years: 20-24 years old, OR=2.04, 95%CI: 1.26-3.31; 25-29 years old, OR=3.72, 95%CI: 2.37-5.86; 30-34 years old, OR=1.94, 95%CI: 1.22-3.09; 35-39 years old, OR=1.81, 95%CI: 1.07-3.05). Conclusion: Our results suggest that the serological susceptibility in adults (20-39 years), especially adults from the regions where the economic development was moderate, should be concerned. The additional vaccination strategy targeting young adults is important for reducing the risk of measles infection.

[Experimental study on the immune response of fusion tumor vaccine of HepG2 and dendritic cells in vitro].

Objective: To estimate the immune response of HepG2/dendritic cell (DC) fusion cells vaccines against HepG2 cells in vitro. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors by Ficoll-Hypaque density-gradient centrifugation.Then DC were obtain from PBMCs by culturing in medium containing granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 5 days.DC and HepG2 fusion cells were induced by polythyleneglycol (PEG). The fusion cells were examined under fluorescence microscope by labeling DCs and HepG2 with green and red fluorescein, respectively, and then the fusion rates were analyzed by flow cytometry.The capacity of fusion cells to secrete interleukin (IL)-12 and stimulate the proliferation of T lymphocyte was assessed by ELISA and Flow cytometry, respectively.ELISPOT was used to assess the interferon gamma (IFN-γ) produced by cytotoxicity T lymphocyte (CTL), and the specific killing ability of fusion cells induce-CTL targeting HepG2 was estimated. Results: The fusion rate of HepG2/DC was 54.5%, and the fusion cells expressed a higher levels of DC mature marker CD80 and costimulatory molecules CD83, CD86 and MHC-Ⅰ, MHC-Ⅱ molecules HLA-ABC and HLA-DR than those in immature DCs (P<0.01). HepG2/DC showed a greater capacity to secrete high level of IL-12 (P<0.05) and activate proliferation of lymphocytes in vitro, as compared with DCs alone and DCs mix HepG2 (P<0.01). The HepG2/DC -activated CTL generated higher IFN-γ level and had a specific killing ability against HepG2 cells at the effecter/target ratio 30∶1 (31.4%±2.4%) and 100∶1 (57.6%±7.3%) (P<0.01). Conclusions: HepG2/DC fusion cells could efficiently stimulate T lymphocytes to generate specific CTL targeting HepG2 cells.It might be a promising strategy of immunotherapy for HCC.

Albumin-bilirubin versus Child-Pugh score as a predictor of outcome after liver resection for hepatocellular carcinoma.

BACKGROUND: The Child-Pugh (CP) score is used widely to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the albumin-bilirubin (ALBI) score has been validated as a predictor of overall survival in these patients. This study aimed to compare the ability of the ALBI and CP scores to predict outcomes in patients with HCC after liver resection with curative intent. METHODS: Consecutive patients who underwent liver resection with curative intent for HCC between January 2007 and July 2013 were included in this retrospective study. The performance of the ALBI score in predicting postoperative liver failure (PHLF) and long-term survival was compared with that of the CP score. RESULTS: A total of 1242 patients were enrolled. Of these, 166 (13·4 per cent) experienced PHLF. The area under the receiver operating characteristic (ROC) curve of the ALBI score for predicting PHLF was greater than that of the CP score (0·723 versus 0·607; P < 0·001). Similar to findings for CP grade, the incidence and severity of PHLF increased with increasing ALBI grade. The ALBI grade stratified patients into at least two distinct overall survival cohorts (P < 0·001), whereas the CP grade did not. The ALBI grade also classified patients with CP grade A disease into two distinct overall survival cohorts (P < 0·001), and overall survival rates in the group with poorer survival were similar to those in the majority of patients with CP grade B disease. Both CP and ALBI scores had low power in predicting disease-free survival. CONCLUSION: The ALBI grade predicted PHLF and overall survival in patients with HCC undergoing liver resection with curative intent more accurately than the CP grade.

De novo transcriptome analysis of tobacco seedlings and identification of the early response gene network under low-potassium stress.

Tobacco is an economically important crop, and its potassium content can greatly affect the quality of tobacco leaves. However, the molecular mechanism involved in potassium starvation in tobacco has not been elucidated to date. In this study, Illumina (Solexa) sequencing technology was used to analyze the transcriptome of tobacco seedlings under low-potassium stress for 6, 12, and 24 h. After analysis, 107,824 assembled unigenes were categorized into 57 GO functional groups, and 31,379 unigenes (29.08%) were clustered into 25 COG categories. A total of 9945 genes were classified into 233 KEGG pathways, and 15,209 SSRs were found among the 107,824 unigenes. Between the two samples, 1034 genes were differentially expressed. Twelve randomly selected gene expression levels were analyzed by quantitative RT-PCR, and the results were highly consistent with those obtained by Solexa sequencing. Our results provide a comprehensive analysis of the gene-regulatory network of tobacco seedlings under low-potassium stress.

Identification of low potassium stress-responsive proteins in tobacco (Nicotiana tabacum) seedling roots using an iTRAQ-based analysis.

Potassium is one of the three main mineral nutrients, and is vital for leaf growth and the quality of tobacco (Nicotiana tabacum) plants. In recent years, the isobaric tags for relative and absolute quantitation (iTRAQ) method has been one of the most popular techniques for quantitative proteomic analysis. In this study, we used iTRAQ to compare protein abundances in the roots of control and low potassium-treated tobacco seedlings, and found that 108 proteins were differentially expressed between the two treatments. Of these, 34 were upregulated and 74 were downregulated, and 39 (36%) were in the chloroplasts. Kyoto Encyclopedia of Genes and Genomes pathway enrichment results suggested that metabolic pathways were the dominant pathways (10 upregulated and 14 downregulated proteins). Ten proteins involved in the pyruvate metabolism pathway increased their expression levels, and 17 upregulated proteins were enriched in the ribosomes category. To evaluate correlations between protein and gene transcript abundances, the expression patterns of 12 randomly chosen genes were examined. A quantitative real-time polymerase chain reaction revealed that the 12 genes were induced after low potassium treatment for 3, 6, 12, and 24 h. Our results demonstrate that low potassium levels affect protein profiles in tobacco roots.

[Comparison of the prognosis after hepatic resection for patients with Barcelona Clinical Liver Cancer Stage B hepatocellular carcinoma].

Objective: To compare the efficacy of hepatic resection (HR) in patients with Barcelona Clinical Liver Cancer (BCLC) Stage B hepatocellular carcinoma (HCC) and examine how that efficacy has changed over time in a large medical center. Methods: A consecutive sample of 918 patients with preserved liver function and large and/or multinodular HCC who were treated by initial HR were divided into three groups: those with a single tumor ≥5 cm in diameter (n=582), 2-3 tumors with a maximum diameter>3 cm (n=223), or>3 tumors of any diameter (n=113). Hospital mortality and overall survival (OS) in each group were compared for the years 2001-2007 and 2008-2013. Results: Patients with >3 tumors showed the highest incidence of hospital mortality of all groups (P<0.05). Kaplan-Meier survival analysis showed that OS varied across the three groups as follows: single tumor>2-3 tumors >3+ tumors (all P<0.05). OS rate at 5 years ranged from 24% to 41% in all three groups for the period 2001-2007, and from 35% to 46% for the period 2008-2013. OS was significantly higher during the more recent 6-year period in the entire patient population, those with single tumor, and those with 3+ tumors (all P<0.05). However, in patients with 2-3 tumors, OS was only slightly higher during the more recent 6-year period (P=0.084). Conclusions: Prognosis of three types of HCC was different. Patients with >3 tumors show the highest hospital mortality and lowest OS after HR. OS has been improving for all three types of HCC at our medical center as a consequence of improvements in surgical technique and perioperative management.

[Role of PI3K/AKT signaling pathway in clonogenicity and tumorigenicity of CD90+ stem-like cells of the hepatocellular carcinoma cell line MHCC-97H].

OBJECTIVE: To investigate the influence of the PI3K/AKT signaling pathway on the proportion and characteristics of the stem-like CD90(+) subpopulation of the human hepatocellular carcinoma (HCC) cell line MHCC-97. METHODS: MHCC-97H cultures were treated with the PI3K/AKT pathway inhibitor LY294002. The proportion of the CD90(+) subpopulation was determined by flow cytometry, and the expression of related proteins was measured by Western blot. The clonogenicity of CD90(+) and CD90(-) cells was measured by plate colony formation assay. The tumorigenicity was compared between CD90(+) and CD90(-) subpopulations (with different concentrations) in xenograft experiments in nude mice, and the changes in tumorigenicity after the addition of LY294002 were evaluated. The changes in the expression of CD90, SHP2, P-AKT, and AKT in CD90(+) and CD90(-) cell xenografts after the addition of LY294002 were examined. Data were analyzed using t test. RESULTS: LY294002 was capable of reducing the proportion of CD90(+) HCC stem cells from 2.98%±0.08% to 0.78%±0.08% (t = 32.400, P < 0.01) and reducing the clonogenicity of CD90(+) subpopulation from 95.13%±3.78% to 61.82%±7.23% (t = 7.617, P < 0.01). However, it showed no significant effect on the clonogenicity of CD90(-) subpopulation. LY294002 also reduced the tumorigenicity of CD90(+) subpopulation and the expression of CD90, SHP2, and P-AKT in related HCC stem cells, but it did not significantly affect the expression of AKT. LY294002 had no significant inhibitory effect on the tumorigenicity of CD90(-) cells. CONCLUSION: The CD90(+) subpopulation of MHCC-97H cells has the characteristics of stem cells and is dependent on the PI3K/AKT signaling pathway.

Meta-analysis of microsomal epoxide hydrolase gene polymorphism and the risk of breast carcinoma.

Carcinogenesis of breast carcinoma is very complicated. Previous studies have suggested conflicting results regarding the association between Tyr113His and His139Arg microsomal epoxide hydrolase (mEH) gene polymorphisms and risk of breast carcinoma. We conducted a meta-analysis to examine the relationship between these polymorphisms and breast carcinoma risk. We searched the PubMed, EMBASE, and Google Scholar databases to identify relevant studies. After extracting relevant data, the association between mEH polymorphisms and susceptibility to breast carcinoma was examined by meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association. Seven studies were identified that included 6357 cases and 8090 controls. The mEH His-allele was not associated with the risk of breast carcinoma based on the allelic contrast model (OR = 0.99, 95%CI = 0.94-1.04, P = 0.58), dominant genetic model (OR = 1.14, 95%CI = 0.88-1.48, P = 0.33), or recessive genetic model (OR = 1.03, 95%CI = 0.96-1.10, P = 0.43). Similarly, the mEH Arg-allele was not associated with breast carcinoma risk based on the allelic contrast model (OR = 0.97, 95%CI = 0.91-1.04, P = 0.44), dominant genetic model (OR = 1.01, 95%CI = 0.84-1.21, P = 0.94), or recessive genetic model (OR = 1.04, 95%CI = 0.96-1.12, P = 0.35). Subgroup analysis based on ethnicity showed no association between the polymorphisms and risk of breast carcinoma. Thus, the Tyr113His and His139Arg mEH polymorphisms may not be risk factors for breast carcinoma.

Chloroplast ultrastructure regeneration with protection of photosystem II is responsible for the functional 'stay-green' trait in wheat.

CN17 is a functional stay-green wheat variety that exhibits delayed leaf senescence and enhanced photosynthetic competence. To better understand these valuable traits, levels of chlorophyll a and b, soluble proteins, unsaturated fatty acids, and other components of CN17 were assayed. In addition, chloroplast ultrastructure, chloroplast number, and differences in gene expression between CN17 and a control variety, MY11, were examined. By 21 d post-anthesis (DPA), CN17 leaves exhibited a significantly higher maximal photochemical efficiency for photosystem II (PSII) (F(v) /F(m) ) and a significantly higher efficiency of excitation capture by open PSII reaction centres (F(v) '/F(m) '). In addition, chlorophyll degradation in CN17 was delayed by approximately 14 d, and was not blocked as observed in cosmetic stay-green phenotypes. The soluble protein content (Ps) of CN17 was higher than MY11 at all timepoints assayed, and the ratio of unsaturated to saturated fatty acids was significantly higher. CN17 also exhibited isolated granal lamellae associated with vesicles and diminished peroxidation, and between 35 and 42 DPA, a sharp decrease in chloroplast number was detected. Taken together, these results strongly support the hypothesis that chloroplast ultrastructure regeneration is responsible for the functional stay-green trait of CN17, and gene expression data provide insight into the mechanistic details.

An update on the management of thyroid nodules: rationalising the guidelines.

BACKGROUND: Guidance for the management of thyroid nodules has evolved over time, from initial evaluation based predominantly on clinical grounds to now including the established role of ultrasound and fine needle aspiration cytology in their assessment. There is, however, significant variation in the management of thyroid nodules depending on which national guidelines are followed. In addition, there are certain clinical situations such as pregnancy and paediatric thyroid nodules that have differing evaluation priorities. OBJECTIVES: This review aimed to provide an overview of currently accepted practices for the initial investigation and subsequent management of patients with thyroid nodules for the non-specialist. The review also addresses areas of variance between the systems in common clinical use, as well as newer, evolving technologies, including molecular testing in the evaluation of malignancy in thyroid nodules.

Therapeutic Outcome of Stereotactic Body Radiotherapy for Small Hepatocellular Carcinoma Lesions - A Systematic Review and Network Meta-analysis.

Surgical resection, stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) have seldom been compared for small hepatocellular carcinoma (HCC). We explored the treatment outcomes of SBRT for small HCC by conducting a network meta-analysis (NMA). We compared the efficacy and safety of surgical resection, RFA and SBRT for liver-confined small HCC (three or fewer lesions with a diameter ≤5 cm). The study endpoint included the odds ratios of the 1-, 3- and 5-year progression/recurrence/disease-free survival (disease progression-free survival; DPFS) and overall survival rates, as well as severe complications. Forty-five studies included 21 468 patients. In the NMA with comparable data, SBRT had comparable 1-, 3- and 5-year DPFS but significantly worse pooled long-term overall survival (3- and 5-year overall survival) than surgical resection (odds ratio 1.39, 95% confidential interval 1.3-1.89; odds ratio 1.33, 95% confidence interval 1.06-1.69, respectively). SBRT was associated with significantly better pooled 1-year DPFS compared with RFA (odds ratio 0.39, 95% confidence interval 0.15-0.97), with the remaining outcomes being comparable. SBRT had significantly less incidence of severe complications compared with surgical resection (odds ratio 0.62, 95% confidence interval 0.42-0.88) and RFA (odds ratio 0.2, 95% confidence interval 0.03-0.94). In conclusion, for small HCCs (≤5 cm) with one to three nodules, SBRT may be favourable to reduce the risks of severe complications. In terms of DPFS, SBRT may be recommended as an alternative first-line therapy for RFA and surgical resection. The results regarding overall survival should be interpreted with caution, considering the potentially uneliminated bias. There is a clear need for well-designed randomised trials to conclusively identify real differences in efficacy between these treatments, especially SBRT and surgical resection.

Adoptive immunotherapy for postoperative hepatocellular carcinoma: a systematic review.

The high risk of recurrence in post-operative hepatocellular carcinoma (HCC) highlights the need for an effective adjuvant treatment. A systematic review of randomised controlled trials (RCTs) was performed to evaluate the clinical efficacy of adjuvant adoptive immunotherapy (AIT) for post-operative HCC patients. Electronic (MEDLINE, EMBASE and Cochrane Library databases) and manual searches were conducted throughout May 2011 to identify RCTs evaluating postoperative AIT for patients with HCC. Methodological quality was assessed in accordance with the QUOROM statement. Four RCTs totalling 423 patients met the eligibility criteria. All RCTs reported significantly improved disease-free survival rate or reduced recurrence rate after treating with adjuvant AIT (p < 0.05). The overall survival rates of AIT group are slightly higher than those of the control group in one study. Moreover, AIT was a safe treatment, with fever as the main adverse effects. This study adds to the evidence that postoperative HCC patients treated with adjuvant AIT show an improvement in disease-free survival rate or recurrence rate.

Probability of clinically significant hearing recovery following salvage intratympanic steroids for sudden sensorineural hearing loss in the 'real world'.

OBJECTIVE: This study aimed to determine the probability of hearing recovery in patients with idiopathic sudden sensorineural hearing loss following salvage intratympanic steroids. METHOD: A retrospective review of all patients receiving salvage intratympanic steroid injections for idiopathic sudden sensorineural hearing loss was performed (January 2014 to December 2019). Twenty-two patients were identified, of whom 15 met inclusion criteria. Pre- and post-treatment audiograms were compared with the unaffected ear. Hearing recovery was categorised based on American Academy of Otolaryngology Head and Neck Surgery criteria. RESULTS: Only 1 patient out of 15 (6.7 per cent) made a partial recovery, and the remainder were non-responders. The median duration of time between symptom onset and first salvage intratympanic steroid treatment was 52 days (range, 14-81 days). No adverse reactions were observed. CONCLUSION: 'Real world' patients with idiopathic sudden sensorineural hearing loss present differently to those in the literature. Sudden sensorineural hearing loss should be diagnosed with care and intratympanic steroid injections initiated early if considered appropriate. Patients should make an informed decision on treatment based on prognostic factors and local success rates.

Pharmacokinetics of HupA-PLGA-NPs of different sizes in the mouse blood and brain determined by LC-MS/MS.

OBJECTIVE: Huperzine A, which was extracted from a Chinese herb, is a reversible and selective inhibitor of acetylcholinesterase (AChE), which is used as an anti-Alzheimer's drug that exerts evident pretreatment effects against exposure to organophosphate chemical warfare agents or pesticides. The aims of this study were to establish an LC-MS/MS method for the detection of HupA in biological samples and to investigate the pharmacokinetics of HupA polylactic-co-glycolic acid nanoparticles (HupA-PLGA-NPs) with different diameters in mice. MATERIALS AND METHODS: The proposed LC-MS/MS method was established by optimizing the MS conditions and validating the specificity, linear range, lower limit, precision, accuracy, matrix effects, absolute recovery, and sample stability of the method. ICR mice were divided into three treatment groups: the HupA control group, the 46.4-nm HupA-PLGA-NP group and the 208.5-nm HupA-PLGA-NP group. All the mice in the three groups were administered 0.5 mg/kg HupA via the tail vein. The pharmacokinetic parameters in plasma and the brain were detected by LC-MS/MS. Pharmacokinetic parameters were analyzed using PKS pharmacokinetic software, and the relative bioavailability and brain-targeted drug targeting efficiency (DTE) were also calculated. RESULTS: The distributions of HupA-PLGA-NP groups showed marked changes compared with that of HupA in mice in vivo, and the particle size of nanodrugs exerted a significant effect on the pharmacokinetic parameters in mice. The half-life (T1/2) values in plasma of the 46.4- and 208.5-nm HupA-PLGA-NPs were 1.53- and 1.96-fold longer than that of the HupA at the same dose. The bioavailabilities of the two nanoparticles were 1.93- and 2.19-fold higher than that of HupA, respectively. In the brain, the Tmax values of the two HupA-PLGA-NPs of different sizes was 1.25 h, which was clearly longer than that of HupA (0.5 h), and the corresponding T1/2 values were 12.53 h and 8.47 h, which were 1.82- and 1.23-fold higher than that of HupA (6.89 h). In addition, the brain targeting index of the 46.40-nm HupA-PLGA-NPs was 1.48, which revealed an evident brain-targeting effect. CONCLUSIONS: The LC-MS/MS method has the advantages of good specificity, high sensitivity and needing a low sample amount and is economical and particularly suitable for determining the drug content in plasma and brain samples. The NP size is associated with the distribution patterns of nanodrugs. Therefore, a particular NP size can be selected to maximize the pharmacodynamics effects and control the toxicity of nanodrugs.