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.

[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.

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.

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.

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.

[Advances in immunotherapy of extranodal NK/T cell lymphoma].

Extranodal NK/T-cell lymphoma (ENKTCL) is a relatively rare group of highly aggressive non-Hodgkin's lymphoma (NHL). The disease has rapid clinical progress, high degree of malignancy and poor prognosis. Traditional chemoradiotherapy regimens have not shown good efficacy. In recent years, the immunotherapy of tumors has developed rapidly. At present, it has shown strong therapeutic activity in the treatment of various solid tumors such as non-small cell lung cancer, prostate cancer, melanoma and kidney cancer. Multiple tumor immunotherapy drugs have been approved by the US Food and Drug Administration (FDA) for clinical use. This article reviews recent novel immunotherapeutic regimens of ENKTCL, hoping to change the treatment modality of this malignant disease.

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.

Over-expressed miR-27a-3p inhibits inflammatory response to spinal cord injury by decreasing TLR4.

OBJECTIVE: We investigate whether microRNA-27a-3p (miR-27a-3p) can inhibit the inflammatory response of spinal cord injury by negatively regulating toll-like receptor 4 (TLR4). PATIENTS AND METHODS: The quantitative Real-time polymerase chain reaction (qRT-PCR) assay was used to detect the expression of miR-27a-3p and TLR4 in serum samples from patients with spinal cord injury and in hydrogen peroxide-treated C8-B4 and C8-D1A cells. Dual luciferase reporter assays were used to detect targeted binding of TLR4 to miR-27a-3p. The protein expression of miR-27a-3p and TLR4 and the two inflammatory factors, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), were all detected by Western blot. RESULTS: TLR4 expression was elevated and miR-27a-3p was decreased in serum samples from patients with spinal cord injury and in hydrogen peroxide-treated C8-D1A and C8-B4 cells. Dual luciferase reporter assays results demonstrated that miR-27a-3p can bind to TLR4. Up-regulation of miR-27a-3p can decrease the expression of TNF-α and IL-6 and can also reduce TLR4 expression. After overexpression of TLR4, the expression of TNF-α and IL-6 were increased. CONCLUSIONS: miR-27a-3p can inhibit the inflammatory response of spinal cord injury by negatively regulating TLR4.

Autophagy regulates chemoresistance of gastric cancer stem cells via the Notch signaling pathway.

OBJECTIVE: Gastric cancer is the most common gastrointestinal malignancy and the leading cause of cancer-related deaths in East Asia. Increasing evidence has revealed that autophagy is closely associated with tumor initiation and progression. The present work aimed to investigate the role of autophagy in adjuvant chemotherapy for gastric cancer. MATERIALS AND METHODS: Gastric cancer stem cells (CSCs) were isolated from gastric cancer cell lines using the cell surface markers CD44 and CD54 and cultured in a three-dimensional cell culture system. Western blotting was used to detect their protein expression levels in gastric CSCs. In addition, the cells were treated with inhibitors to investigate the underlying mechanisms of autophagy. RESULTS: After isolation of gastric CSCs expressing CD44 and CD54, Western blot analysis showed that the levels of the autophagic marker LC3II were markedly enhanced in CD44+CD54+ gastric CSCs. Moreover, the ratio of LC3II/LC3I protein levels was higher in CD44+CD54+ gastric CSCs than in non-CSCs. By contrast, both a chemotherapeutic agent (5-fluorouracil) and autophagy inhibitor (chloroquine) exhibited an inhibitory effect on the cell viability of gastric CSCs, and their combination further enhanced such inhibitory effects. Mechanistically, the addition of Notch inhibitor decreased the cell viability of gastric CSCs treated with 5-fluorouracil and chloroquine. In addition, 5-fluorouracil and chloroquine both increased the expression of Notch1 in gastric CSCs. CONCLUSIONS: These findings show that autophagy regulated drug sensitivity of gastric cancer cells through the Notch signaling pathway.

[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.

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.

[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.