Intestinal microbiota via NLRP3 inflammasome dependent neuronal pyroptosis mediates anxiety-like behaviour in mice exposed to 3.5 GHz radiofrequency radiation.

The rapid development of 5G communication technology has increased public concern about the potential adverse effects on human health. Till now, the impacts of radiofrequency radiation (RFR) from 5G communication on the central nervous system and gut-brain axis are still unclear. Therefore, we investigated the effects of 3.5 GHz (a frequency commonly used in 5G communication) RFR on neurobehavior, gut microbiota, and gut-brain axis metabolites in mice. The results showed that exposure to 3.5 GHz RFR at 50 W/m2 for 1 h over 35 d induced anxiety-like behaviour in mice, accompanied by NLRP3-dependent neuronal pyroptosis in CA3 region of the dorsal hippocampus. In addition, the microbial composition was widely divergent between the sham and RFR groups. 3.5 GHz RFR also caused changes in metabolites of feces, serum, and brain. The differential metabolites were mainly enriched in glycerophospholipid metabolism, tryptophan metabolism, and arginine biosynthesis. Further correlation analysis showed that gut microbiota dysbiosis was associated with differential metabolites. Based on the above results, we speculate that dysfunctional intestinal flora and metabolites may be involved in RFR-induced anxiety-like behaviour in mice through neuronal pyroptosis in the brain. The findings provide novel insights into the mechanism of 5G RFR-induced neurotoxicity.

Impact of innovative immunization strategy on PCV13 vaccination coverage among children under 5 years in Weifang city, China: A retrospective study.

BACKGROUND: Pneumococcal Diseases (PDs) remains a serious public health problem around the world and in China. Pneumococcal vaccination is the most cost-effective measure to prevent PDs. In 2021, the government of Weifang City, Shandong Province, China introduced a free dose of domestic 13-valent Pneumococcal Conjugate Vaccine (PCV 13) to vaccinate registered children aged 6 months-2 years. This study aimed to evaluate the vaccination rate of PCV13 in children aged under 5 years before and after the vaccination program to provide evidences for further improving the prevention and control strategy for PDs. METHODS: We collected data from the children's vaccination information management system in Weifang City and analyzed the PCV13 vaccination coverage and characteristics in all vaccination clinics of Weifang City for children aged under 5 years. We compared the differences in vaccination rates by gender, birth year, manufacturer, and county before and after innovative immunization strategy. RESULTS: Among the included 593,784 children aged under 5 years, the PCV13 vaccination rate in Weifang was generally low before the innovative immunization strategy. Urban children had a higher PCV13 coverage than rural children (P < 0.001), and parents tended to vaccinate their children with imported PCV13.The full vaccination rate for domestic and imported PCV13 was 0.67 % and 1.70 %, respectively. After the vaccination program, the PCV13 coverage of children increased significantly in all counties within Weifang City (P < 0.001), especially for children above 12 months of age. Most parents preferred to vaccinate their children with domestic PCV13, and the full vaccination rate of domestic and imported PCV13 was 6.59 % and 0.16 %, respectively. CONCLUSIONS: The vaccination rate of PCV13 in children is still much lower than the global average, posting a severe health challenge that needs to be addressed thoroughly. To improve the prevention and control strategy for PDs, it is recommended to continue to explore other relevant incentives based on the innovative immunization strategy. Furthermore, it is also recommended that China should incorporate PCV13 into the National Immunization Programs (NIP) as soon as possible.

Effects of provisioning on the activity budget and foraging strategies of black-and-white snub-nosed monkeys (Rhinopithecus bieti) in the Baima Snow Mountain Nature Reserve, Yunnan, China.

Provisioning can significantly affect the ranging patterns, foraging strategies, and time budget of wild primates. In this study, we document for the first time, the effects of provisioning on the activity budget and foraging effort in an Asian colobine. Over 3-years, we used an instantaneous scanning method at 10-min intervals to collect data on the activity budget of a semiprovisioned breeding band (SPB) of black-and-white snub-nosed monkeys (Rhinopithecus bieti) (42-70 individuals) at Xiangguqing (Tacheng), Yunnan, China. We then compared the effects of provisioning in our study band with published data on a sympatric wild nonprovisioned breeding band (NPB) of R. bieti (ca. 360 monkeys) at the same field site. The SPB spent 25.6% of their daytime feeding, 17.1% traveling, 46.9% resting, and 10.3% socializing. In comparison, the NPB devoted more time to feeding (34.9%) and socializing (14.1%), less time to resting (31.3%), and was characterized by a greater foraging effort (1.74 versus 0.96, foraging effort = (feeding + traveling)/resting; see Methods). There was no difference between bands in the proportion of their activity budget devoted to traveling (15.7% vs. 17.1%). In addition, the SPB exhibited a more consistent activity budget and foraging effort across all seasons of the year compared to the NPB. These findings suggest that the distribution, availability, and productivity of naturally occurring feeding sites is a major determinant of the behavioral strategies and activity budget of R. bieti. Finally, a comparison of our results with data on six nonprovisioned R. bieti bands indicates that caution must be raised in meta-analyses or intraspecific comparisons of primate behavioral ecology that contain data generated from both provisioned and nonprovisioned groups.

Effects of Repeated Co-Injections of Corticosteroids and Hyaluronic Acid on Knee Osteoarthritis: A Prospective, Double-Blind Randomized Controlled Trial.

BACKGROUND: We compared the effects of repeated co-injections of corticosteroids plus hyaluronic acid (HA) with the effects of HA injections alone in patients with knee osteoarthritis. METHODS: A double-blind randomized controlled trial was conducted between October 2016 and July 2017 at a medical center. Patients (n = 57) who fulfilled the clinical and radiographic criteria for knee osteoarthritis established by the American College of Rheumatology with a Kellgren-Lawrence score of 2 or 3 were included. They were assigned to either the HA group (n = 29) or corticosteroids plus HA group (n = 28), and injections were administered under ultrasound guidance once a week for 3 consecutive weeks. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were the primary outcomes. Physical functional performance (10-m fast walking and chair-rising time) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were secondary outcomes. The assessment was performed prior to injections, 1 week, and 1, 3, and 6 months after injections. Data were analyzed through repeated-measures analysis of covariance. RESULTS: Both groups experienced decreased pain and improved physical function and physical functional performance over time. We found significant group × time interaction effects favoring the corticosteroids plus HA group in WOMAC-pain (P = .005) and physical function (P = .005), chair-rising time (P = .032), and KOOS-pain (P = .001). CONCLUSIONS: Repeated co-injections of corticosteroids plus HA more effectively decreased pain and improved physical function and physical functional performance than injections of HA alone from 1 week through 6 months posttreatment.

Multi-generational Effects of Different Resistant Wheat Varieties on Fitness of Sitobion avenae (Hemiptera: Aphididae).

Crop resistance plays a role in preventing aphid damage, benefiting food production industries, but its effects are limited due to aphid adaptation and phenotypic plasticity. Therefore, furthering understanding of aphid-crop interactions will improve our ability to protect crops from aphids. To determine how aphids adapt to resistant varieties of wheat, Triticum aestivum L. over time, we performed a laboratory experiment to assess the multi-generational effects of three wheat varieties, Batis, Ww2730, and Xiaoyan22, with different resistance levels on the fitness of Sitobion avenae (Fab.) (Hemiptera: Aphididae). The results showed that Ww2730 and Xiaoyan22 were more resistant than Batis to S. avenae, regardless of whether the aphids were newly introduced or had been acclimated before being introduced to the three wheat varieties. However, the effect of resistance on aphid life-history traits was time dependent. Aphid weigh gain increased and they development faster of the acclimated generation compared to the newly introduced generation on all three varieties. And the fecundity on the three varieties and net reproduction rates on Batis and Xiaoyan22 significantly decreased. Aphid fitness in terms of individual life-history parameters improved, whereas aphid fitness in terms of reproductive decreased, and a convergence effect, the difference gaps and standard errors of all life-history traits among the three acclimated populations had narrowed and were less than those in the three first-generation populations, was observed during the 3-mo experimental period. We suggested that S. avenae could rapidly respond to wheat resistance through life-history plasticity.

Effect of levosimendan on renal function in background of left ventricular dysfunction: a meta-analysis of randomized trials.

OBJECTIVE: Levosimendan, an inotrope, is widely used in the management of heart failure (HF) and cardiac surgery, but it remains uncertain whether levosimendan can improve renal function in patients with left ventricular dysfunction (LVD). METHODS: PubMed, Embase, and Cochrane CENTRAL from the inception to June 2020 were systematically screened for randomized controlled trials (RCTs) to investigate whether levosimendan offers kidney-related advantages in cardiovascular patients with LVD. We pooled the effects using a random-effect model. RESULTS: Twenty-eight studies enrolling 5069 patients were included. Levosimendan reduced the sCr (SMD -0.28, 95% CI (-0.48, -0.09), P = 0.005, I2 = 52.5%, high quality) and the risk of ARF (relative risk 0.75, 95%CI (0.60, 0.95), P = 0.017, I2 = 11.3%, moderate-quality) in patients with LVD compared with control group. The reduction of sCr was more pronounced in patients with a relatively higher baseline sCr level. For secondary outcomes, levosimendan therapy was associated with the improvement of GFR (SMD 0.32, 95%CI (-0.05, 0.68), P = 0.092, I2 = 55.1%, low-quality) and urine output (SMD 0.42, 95%CI (0.06, 0.79), P = 0.024, I2 = 50.0%, very low-quality), but there was no significant reduction in BUN (SMD -0.14, 95%CI (-0.97, 0.70), P = 0.774, I2 = 77.9%, very low-quality). CONCLUSIONS: Levosimendan might improve renal function of patients with LVD.

Comparison of the corticosteroid injection and hyaluronate in the treatment of chronic subacromial bursitis: A randomized controlled trial.

OBJECTIVE: To analyse the effectiveness of corticosteroid (CS) and hyaluronic acid (HA) subacromial - subdeltoid (SASD) injection compared with normal saline (NS) in patients with chronic subacromial bursitis (CSB). DESIGN: A prospective three-arm double-blinded randomised controlled trial. SETTING: Rehabilitation department of two teaching hospitals. SUBJECTS: Patients with CSB (N = 186) divided into CS (N = 68), HA (N = 60), and NS (N = 58) groups. INTERVENTIONS: Three SASD injections under ultrasound guidance: group A, 20 mg of triamcinolone; group B, 2.5 mL of HA; and group C, 2.5 mL of NS. OUTCOME MEASURES: The primary outcome measures were the pain visual analogue scale (VAS) score at eight weeks. The secondary outcomes were scores on the Shoulder Pain and Disability Index (SPADI) and Shoulder Disability Questionnaire. RESULTS: At eight weeks, the pain VAS scores during activity were 2.56 ± 2.29, 3.65 ± 2.50, and 4.71 ± 2.83 in the CS, HA, and NS groups, respectively (CS vs NS, P < 0.001; HA vs NS, P = 0.013; CS vs HA, P = 0.010). SPADI scores were 40.83 ± 21.75, 36.92 ± 22.78, and 33.35 ± 23.38 in the CS, HA, and NS groups, respectively (CS vs NS, P < 0.001; HA vs NS, P = 0.197; CS vs HA, P = 0.004). CONCLUSION: Ultrasound-guided corticosteroid injection into the subacromial - subdeltoid bursa was proven to be effective and superior to hyaluronic acid and normal saline injection for treating CSB. Hyaluronic acid injection was only marginally more effective than normal saline injection.Trial Registration: ClinicalTrials.gov: NCT02702206.

Stochastic Robust Team Tracking Control of Multi-UAV Networked System Under Wiener and Poisson Random Fluctuations.

In this article, a robust leader-follower tracking control scheme is proposed to deal with the stochastic multi-unmanned aerial vehicle (UAV) networked team tracking control problem to achieve a prescribed H∞ robust tracking performance. By taking the leader's desired path and every UAV networked system into account, the leader-follower tracking error networked system is constructed by arranging the UAVs network systems into a leader-follower formation. To effectively reduce the effect of the external disturbance on the team tracking process, a robust H∞ controller is proposed. With the help of the Itô-Lévy formula, the robust team tracking control design of the multi-UAV system is transformed to a Hamilton-Jacobin inequality (HJI)-constrained optimization problem. Since the HJI constraint cannot be easily solved, the Takagi-Sugeno (T-S) fuzzy interpolation method is employed to approximate the nonlinear networked system with a set of local linearized stochastic networked systems to simplify the design procedure. By the proposed T-S fuzzy control method, the H∞ robust leader-follower tracking control design of the stochastic multi-UAV networked system can be transformed to equivalent linear matrix inequalities (LMIs)-constrained optimization problem which can be efficiently solved by using the convex optimization techniques. Finally, a design example is given with simulation to illustrate the design procedure of the robust team tracking control of desired attitude and path and validate the effectiveness of the proposed robust H∞ team tracking control method of the multi-UAV networked system.

Meta-Analysis of Shrinkage Mode After Neoadjuvant Chemotherapy for Breast Cancers: Association With Hormonal Receptor.

Background: Patients with concentric shrinkage mode after neoadjuvant chemotherapy (NAC) is considered to be ideal candidates for breast conserving treatment (BCT). While, what proportion of patients would represent CSM have not been well defined. This study was conducted to pool the rates of concentric shrinkage mode (CSM) in patients undergoing NAC, determine the impact of hormonal receptor on the shrinkage mode after NAC and estimate the rates of the CSM in various subgroups. Methods: We conducted a systematic review following the guidelines for Meta-Analyses and Systematic reviews for the PRISMA guidelines. We systematically searched the literature about shrinkage mode after NAC from PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang database published from January 2002 to June 2020 on breast cancer shrinkage mode after NAC and carefully screened the literature by using eligibility criteria: (1) patients with primary breast cancer treated with NAC; (2) publications with available data of shrinkage mode measured by magnetic resonance imaging (MRI), or data of pathology and hormonal receptor. The association between shrinkage mode and hormonal receptor was estimated using Stata 15.1 software. Results: This analysis included a total of 2434 tumors from 23 papers. The included studies were heterogeneous (I2 = 89.4%, P<0.01). Random effects model was used to estimate the overall rates of CSM: 56.6% [95%CI (50.5%, 62.7%)]. According to the analysis of hormonal receptor, 10 of the paper was included for HR+ (hormone receptor positive) type analysis and the rate of CSM for HR+ type was 45.7% [95%CI (36.4%, 55.0%)]; 9 of the paper was used for HR- type (hormone receptor negative) analysis and the incidence of HR-CSM is 63.1% [95%CI (50.0%, 76.1%)]; with HR+ type as the control, the OR of the HR- CSM rate is 2.32 (1.32, 4.08) folds of HR+ type. From subgroup analyses, the CSM% of luminal A, luminal B, Her2+, and triple negative were 29.7% (16.5%, 42.8%); 47.2% (19.1%, 75.3%); 59.0% (39.7%, 78.3%); 66.2% (52.8%, 79.6%), respectively. Conclusions: Breast cancer patients undergoing NAC did not get an ideal odds ratio of CSM. The incidence of CSM in breast cancer after NAC is associated with hormonal receptor. Patients with triple-negative breast cancers have the highest rates of CSM after NAC. More care should be taken to select patients with the luminal subtypes for BCT throughout NAC.

Comparison of the effect of Western-made unloading knee brace with physical therapy in Asian patients with medial compartment knee osteoarthritis-A preliminary report.

PURPOSE: To compare the effect of unloading knee brace with physical therapy (PT) in Asian patients with osteoarthritis (OA) of the knee. METHOD: This is a non-random, two-group comparative study. Patients with medial compartment knee OA (n = 41) were assigned to either the brace group (n = 20) or PT group (n = 21). Patients in the brace group were fitted with an unloading knee brace for three months and the PT group received a 60-min session of physiotherapy over the affected knee, three times a week, for three months. The primary outcome measures were the pain visual analogue scale (VAS) and the Western Ontario McMaster University Osteoarthritis Index (WOMAC); the second outcome measures were the 36-item Short-Form Health Survey (SF-36) and patient's satisfaction. The patients were evaluated at baseline, and at one month and three months. RESULTS: Group comparison showed no significant difference regarding pain VAS, WOMAC, SF-36, and patient's satisfaction, except stiffness in WOMAC (P = .006) and social functioning in SF-36 (P = .007). Time and group interaction revealed significant differences only in general health (P = .007) and mental health (P = .006) of SF-36. Within-group comparison found that pain VAS and WOMAC decreased significantly at one months and three months in both groups. CONCLUSION: The effect of brace fitting in patients with knee OA was similar to that of physical therapy. A Western-made unloading knee brace is acceptable in some Asian people with knee OA. CLINICAL TRIAL REGISTRATION NUMBER: NCT02712710.

"Button and Buttonhole" Supramolecular Structure Enables the Self-Healing Behaviors of Functionalized Poly(ether sulfone) Membranes for Osmotic Power Generation.

Osmotic power generation has emerged as an advanced technology toward water-energy nexus to tackle global water pollution. It provides a sustainable use of salinity gradient from water resources yet encounters major obstacles caused by pressure-retarded osmosis (PRO) membrane fouling. Although membranes with good antifouling properties are widely studied, their antifouling functions are readily lost when scratches or detachments occur through physical damage during operation and chemical degradation by water and corrosive foulants. Consequently, it is important to develop antifouling membranes with autonomous self-healing capabilities. Herein, self-healable functionalized poly(ether sulfone) (PES) antifouling membranes have been fabricated via the sequential conjugation of the zwitterionic random copolymer [poly(1-(1-(1-adamantylcarbonyloxy)methyl)-3-vinylimidazolium bromide-co-1-(3-sulfopropyl)-3-vinylimidazolium-co-vinylamine)] (P(ADVI-co-SBVI-co-VA), abbreviated as PASV copolymer) and linear cyclodextrin polymer (LPCD) on polydopamine-preactivated PES supports. The self-healing behaviors rely on the judiciously designed "button-and-buttonhole" supramolecular network. Specifically, ß-cyclodextrins in LPCD and adamantines in PASV act as "buttonholes" and "buttons", respectively. Under physical and chemical damages, the ß-cyclodextrin "buttonhole" may sacrificially detach from the adamantine "button" of PASV but then recap another adamantine to restore the protective function. The antifouling and self-healing traits of as-functionalized PES-g-PASV-LPCD membranes were demonstrated by the superior antiprotein behaviors and improved antimicrobial performances on both nonaged and aged samples. In the PRO process, the modified membranes were effective in mitigating organic fouling and exhibited higher power density (79% of the initial value) than the nonmodified ones (47% of the initial value) in municipal wastewater testing. The strategy for engineering inherently healable and antifouling membranes paves a new pathway for the development of sustainable membranes for osmotic power production.

Hybrid light field head-mounted display using time-multiplexed liquid crystal lens array for resolution enhancement.

In recent years, head-mounted display technologies have greatly advanced. In order to overcome the accommodation-convergence conflict, light field displays reconstruct three-dimensional (3D) images with a focusing cue but sacrifice resolution. In this paper, a hybrid head-mounted display system that is based on a liquid crystal microlens array is proposed. By using a time-multiplexed method, the display signals can be divided into light field and two-dimensional (2D) modes to show comfortable 3D images with high resolution compensated by the 2D image. According to the experimental results, the prototype supports a 12.28 ppd resolution in the diagonal direction, which reaches 82% of the traditional virtual reality (VR) head-mounted display (HMD).

Morphometric studies of genus Placocheilus (Teleostei: Cypriniformes) from Red River, China.

It is practically difficult to differentiate Placocheilus robustus and Placocheilus caudofasciatus from Red River drainage of China. Without stated reasons, P. robustus has been assumed as the synonyms of P. caudofasciatus. The present study aims to decipher the morphological differences between two species so as to provide reliable clues for their classification by multivariate morphometry. A total of 72 specimens of two species in genus Placocheilus were examined. Besides morphological character comparisons, 10 anatomic landmarks were utilized and 23 frame structures and 15 general characters measured. The scatter plot results of principal component analysis showed that all specimens were clustered together and could not be defined as two distinct species. No significant morphological differences existed in four diagnostic characters between P. robustus and P. caudofasciatus. Thus the results of the present study fail to support P. robustus as a valid and independent species.

The efficacy of pedicle screw instrument in treatment of irreducible atlantoaxial dislocation.

OBJECTIVE: To explore the effect of pedicle screw instrument in treatment of irreducible atlantoaxial dislocation. PATIENTS AND METHOD: From June 2003 to February 2009, 14 cases of atlas dislocation with upper cervical cord compression were enrolled and anterior transoral soft tissue release combined with posterior reduction and pedicle screw fixation were performed. CT, MRI and radiograph were used preoperatively, and screw placement and bone graft were administered in all cases intraoperatively. Cervical collars were used for 3 months. RESULTS: Screws were successfully placed in atlas in all cases. The average follow-up period was 18 months. Bone fusion was observed in all cases without the following complications: neurologic symptoms, internal fixation failure and redislocation. Neurological recovery was observed in all 14 cases. CONCLUSIONS: Pedicle screw instrument has the following advantages in atlas and axis injury treatment: direct screw placement, short-segment fusion, intraoperative reduction and high fusion rate, which should be a better surgical method for the treatment of atlantoaxial dislocation.

Hepatic angiomyolipoma mimicking hepatocellular carcinoma: magnetic resonance imaging and clinical pathological characteristics in 9 cases.

Hepatic angiomyolipoma (HAML) is a rare mesenchymal tumor of the liver with marked histological diversity. The present study was to review the magnetic resonance imaging (MRI) and clinical pathological features of HAML resembling hepatocellular carcinoma (HCC). Nine patients who underwent surgical resection and had pathological diagnosis of HAML were retrospectively analyzed. All of 9 patients (5 males and 4 females) had a solitary hepatic mass with a median size of 4 cm (from 1.4 cm to 15.3 cm). Seven cases were identified as incidental liver tumors during health screening and 2 patients were diagnosed for hepatic mass when visited hospitals with unspecific abdominal discomfort. Before resection, 6 cases were diagnosed as HCC on MRI. MRI on chemical shift imagings showed a large amount of lipids in 5 cases. The enhancement pattern of MRI was classified into 2 types: in 2 cases, lesions with small or no vessels that demonstrated prolonged enhancement (1 mixed subtype and 1 myomatous subtype) and in 7 cases, lesions with abundant central vessels that show rapid washout (3 mixed subtypes and 4 myomatous subtypes) in the portal venous/delayed phase. All patients underwent resection of hepatic tumor and no recurrence was observed during follow-up (range: 2-24 months) of median 10 months. By immunohistochemistry, the tumor cells demonstrated positive immunostaining for human melanoma black-45, smooth muscle actin, and CD34. In conclusion, all of 9 patients with HAML presented with none or nonspecific clinical manifestations. The diagnosis of HAML relies on disease and immunohistochemistry, but not MRI due to its resemblance to HCC.

Hypomethylation of long interspersed nuclear element-1 promoter is associated with poor outcomes for curative resected hepatocellular carcinoma.

BACKGROUND: Epigenetic alterations are well documented in hepatocarcinogenesis. However, hypomethylation of long interspersed nuclear element 1(LINE-1) promoter and its relationship with clinicopathological features in hepatocellular carcinoma(HCC) remain unknown. METHODS: The bisulfite-specific PCR and DNA sequencing analysis was performed to assess the methylation status of LINE-1 promoter in a pilot cohort of 71 patients with HCC. Additionally,methylation levels of two hot CpG sites of LINE-1 promoter, site 7 and 18 were measured by real-time PCR and compared with clinicopathological parameters in a cohort of 172 HCC. All the patients included were in BCLC stage A or B. RESULTS: Most patients with HCC (87.3%) showed hypomethylation of LINE-1 promoter compared with HBV-related cirrhosis and normal controls (P < 0.001). The HCC patients with LINE-1 promoter hypomethylation had a median tumour-free survival (TFS) and overall survival (OS)post-resection of 22.0 (95% CI: 13.3­30.7) months and 35.0 (95% CI: 24.0­46.1) months, respectively, compared with 40 months and ~60 months for those with LINE-1 promoter hypermethylation (P < 0.05). Multivariate analyses showed that the hypomethylation level at CpG site 7 and 18 of LINE-1 promoter, along with tumour size and tumour differentiation, was independently associated with both TFS and OS for patients with HCC after resection. CONCLUSION: Promoter hypomethylation of LINE-1, especially at the CpG site 7 and 18, was associated with a poor prognosis in HCC.

Expression of potential resistance genes to the English grain aphid, Sitobion avenae, in wheat, Triticum aestivum.

The English grain aphid, Sitobion avenae (F.) (Homoptera: Aphididae), is a dominant and destructive pest in wheat, Triticum estivum L. (Poales: Poaceae), production regions in China and other grain-growing areas worldwide. Patterns of gene expression of the S. avenae-resistant synthetic wheat line 98-10-35, the S. avenae-susceptible line1376, and their hybrid population, and the differences in segments between 98-10-35/1376 F3 resistant plants and resistant parents of 98-10-35, as well as those between the F3 resistant and susceptible populations, were examined with differential display reverse transcription PCR. The results showed that five patterns of differential expression were detected between the progeny and its resistant parents: 1) The gene was silenced in one of the parents; 2) Special expression showed in the progeny; 3) Expression was consistent with the resistant parents; 4) Up expression showed in the progeny but not in the parents; 5) Down expression showed in the progeny but not in the parents. Paired t-test results were not significant; however, the probability value (0.9158) indicated that gene expression on the RNA level were consistent with resistant bands found in F3 resistant individuals and resistant parents, as well as the F3 resistant and susceptible populations. For both the F3 of 98-10-35/1376 and the parents, the total number of amplified bands was 202, with an average of 25.3 per primer. The number of differential bands was 116, with an average of 14.5 per primer amplified and a polymorphism ratio of 56.3%. In the present study, differential expression genes in the resistant line 98-10-35 were all up-regulated. Among them, gene expression of resistant groups in the F3 population was in agreement with patterns 2, 3, and 4. However, the susceptible line 1376 did not have this gene expression on the RNA level. This pattern is expected to be used to select and analyze target genes from the same F3 population and the resistant parents. The results suggest that it can be employed as a new method for molecular assisted breeding.

Long interspersed nuclear element ORF-1 protein promotes proliferation and resistance to chemotherapy in hepatocellular carcinoma.

AIM: To clarify the specific roles and mechanisms of long interspersed nuclear element-1 ORF-1 protein [human long interspersed nuclear element-1 (LINE-1), ORF-1p] in chemotherapeutic drug resistance and cell proliferation regulation in hepatocellular carcinoma (HCC) cells. METHODS: MTT assays were performed to identify the effect of the chemotherapeutic drug toxicity on HepG2 cells. Cell proliferation inhibition and the IC50 were calculated by the Origin 8.0 software. Western blotting assays were performed to investigate whether LINE-1 ORF-1p modulates the expression of some important genes, including p53, p27, p15, Bcl-2, mdr, and p-gp. To corroborate the proliferation and anchor-independent growth results, the HepG2 cells were analyzed by flow cytometry to investigate the effect of LINE-1 ORF-1p on the apoptosis regulation. RESULTS: LINE-1 ORF-1p contributed to the resistance to several chemotherapeutic drugs (cisplatin and epirubicin) in HepG2 cells. The IC50 of the epirubicin and cisplatin increased from 36.04 nmol/L to 59.11 nmol/L or from 37.94 nmol/L to 119.32 nmol/L. Repression of LINE-1 ORF-1p expression by the siRNA could markedly enhance the response of HepG2 cells to the epirubicin and cisplatin. The IC50 correspondingly decreased from 28.06 nmol/L to 3.83 nmol/L or from 32.04 nmol/L to 2.89 nmol/L. Interestingly, down-regulation of LINE-1 ORF-1p level by siRNA could promote the response of HepG2 cells to the paclitaxel. The IC50 decreased from 35.90 nmol/L to 7.36 nmol/L. However, overexpression of LINE-1 ORF-1p did not modulate the paclitaxel toxicity in HepG2 cells. Further Western blotting revealed that LINE-1 ORF-1p enhanced mdr and p-gp gene expression. As a protein arrested in the nucleus, LINE-1 ORF-1p may function through modulating transcriptional activity of some important transcription factors. Indeed, LINE-1 ORF-1p promoted HepG2 cell proliferation, anchor-independent growth and protected the cells against apoptosis through modulating the expression of p15, p21, p53, and Bcl-2 genes. CONCLUSION: LINE-1 ORF-1p promotes HepG2 cell proliferation and plays an important role in the resistance of chemotherapeutic drugs. By establishing novel roles and defining the mechanisms of LINE-1 ORF-1p in HCC chemotherapeutic drug resistance and cell proliferation regulation, this study indicates that LINE-1 ORF-1p is a potential target for overcoming HCC chemotherapeutic resistance.

High intratumoral metastasis-associated in colon cancer-1 expression predicts poor outcomes of cryoablation therapy for advanced hepatocellular carcinoma.

BACKGROUND: Cryoablation is one of the local therapies for hepatocellular carcinoma (HCC), but its safety and effect has not been studied in patients with Child class A or B and Barcelona Clinic Liver Cancer (BCLC) stage C HCC. Metastasis-associated in colon cancer-1 (MACC1) overexpression has been associated with poor prognosis of HCC, but its predictive value to post-cryoablation outcomes remains unknown in patients with BCLC stage C HCC. METHODS: This study assessed the safety and outcomes of cryoablation measured by time to progression (TTP) and overall survival (OS), and predictive value of MACC1 mRNA and protein overexpression in tumorous tissue to post-cryoablation outcomes in 120 advanced HCC patients with child-pugh class A or B by quantitative polymerase chain reaction and immunohistochemical staining. The potenial correlation of MACC1 and c-Met expression to tumor cell proliferation and apoptosis was also analyzed. RESULTS: The cryoablation in patients with advanced unresectable HCC resulted in a median TTP and OS of 5.5 (4.2- 6.7) months and 10.5 (9.0-12.0) months, respectively and no significant complications, comparable to the historical report for RFA therapy. The MACC1 mRNA and nuclear protein expression was significantly increased in tumorous tissues in these patients than that in normal liver tissue controls. Higher expression of MACC1 mRNA and nuclear protein in tumorous tissues in these patients was associated with shorter post cryoablation median TTP and OS than that with lower MACC1 expression. CONCLUSIONS: Cryoablation is a safe and effective therapeutic option for patients with advanced HCC and Child-pugh class A or B cirrhosis; and a higher intratumoral expression of MACC1 or nuclear translocation predicts poor outcomes of cryotherapy in these patients.

Tumour seeding after percutaneous cryoablation for hepatocellular carcinoma.

AIM: To assess the rate and risk factors for tumour seeding in a large cohort of patients. METHODS: Over an 8-year period, 1436 hepatocellular carcinoma (HCC) patients with 2423 tumour nodules underwent 3015 image-guided percutaneous cryoablation sessions [1215 guided by ultrasonography and 221 by spiral computed tomography (CT)]. Follow-up CT or magnetic resonance imaging was performed every 3 mo. The detailed clinical data were recorded to analyse the risk factors for seeding. RESULTS: The median follow-up time was 18 (range 1-90) mo. Seeding was detected in 11 patients (0.76%) at 1-24 (median 6.0) mo after cryoablation. Seeding occurred along the needle tract in 10 patients and at a distant location in 1 patient. Seeded tumours usually showed similar imaging and histopathological features to the primary HCCs. Univariate analyses identified subcapsular tumour location and direct subcapsular needle insertion as risk factors for seeding. Multivariate analysis showed that only direct subcapsular needle insertion was an independent risk factor for seeding (P = 0.017; odds ratio 2.57; 95%CI: 1.47-3.65). Seeding after cryoablation occurred earlier in patients with poorly differentiated HCC than those with well or moderately differentiated HCC [1.33 ± 0.577 mo vs 11.12 ± 6.896 mo; P = 0.042; 95%CI: (-19.115)-(-0.468)]. CONCLUSION: The risk of seeding after cryoablation for HCC is small. Direct puncture of subcapsular tumours should be avoided to minimise seeding.