Narrow-Band Imaging in Head and Neck Carcinomas: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to assess the diagnostic performance of narrow-band imaging (NBI) in monitoring patients with head and neck carcinomas posttreatment and to compare it with that of white light endoscopy (WLE). DATA SOURCES: PubMed, Embase, Web of Science (WOS), Cochrane Library, China Biology Medicine disc (CBM disc), China National Knowledge Internet (CNKI), Wanfang Data, China Science and Technology Journal Database (CSTJ), Chinese Clinical Trial Register. REVIEW METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), literature published before July 2024 was searched. Patients who underwent surgery, radiotherapy (RT), or chemo-RT for head and neck carcinomas with posttreatment follow-up using NBI were analyzed. The main outcomes were sensitivity, specificity, and diagnostic odds ratio (DOR) for NBI and WLE in posttreatment follow-up. RESULTS: The sensitivity, specificity, and DOR for NBI and WLE in posttreatment follow-up for head and neck carcinomas were 95% (95% confidence interval [CI]: 88%-98%), 96% (95% CI: 92%-98%), 433 (95% CI: 120-1560) and 72% (95% CI: 49%-87%), 72% (95% CI: 4%-99%), 7 (95% CI: 0-191). Additionally, the area under the curve (AUC) values for NBI and WLE were 0.99 (95% CI: 0.97-0.99) and 0.75 (95% CI: 0.71-0.79), respectively. The number of lesions and patients, treatment modality, follow-up time, disease, and endoscopic system might be sources of heterogeneity. CONCLUSION: Compared to WLE, NBI demonstrated superior diagnostic performance in follow-up patients with head and neck carcinoma posttreatment. NBI offers technical support and a clinical foundation for early detection of head and neck carcinoma recurrence. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Comparison of learning curves and related postoperative indicators between endoscopic and robotic thyroidectomy: a systematic review and meta-analysis.

BACKGROUD: Endoscopic thyroidectomy (ET) and robotic thyroidectomy (RT) yield similar perioperative outcomes. This study investigated how the learning curve (LC) affects perioperative outcomes between ET and RT, identifying factors that influence the LC. MATERIALS AND METHODS: Two researchers individually searched PubMed, EMBASE, Web of Science, and Cochrane Library for relevant studies published until February 2024. The Newcastle-Ottawa Scale assessed study quality. Random effects model was used to compute the odds ratio and weighted mean difference (WMD). Poisson regression comparison of the number of surgeries (NLC) was required for ET and RT to reach the stable stage of the LC. Heterogeneity was measured using Cochran's Q. Publication bias was tested using funnel plots, and sensitivity analysis assessed findings robustness. Subgroup analysis was done by operation type and patient characteristics. RESULTS: This meta-analysis involved 33 studies. The drainage volume of ET was higher than that of RT (WMD=-17.56 [30.22, -4.49]). After reaching the NLC, the operation time of ET and RT was shortened (ET: WMD=28.15[18.04, 38.26]; RT: WMD=38.53[29.20, 47.86]). Other perioperative outcomes also improved to varying degrees. Notably, RT showed more refined central lymph node resection(5.67 vs. 4.71), less intraoperative bleeding (16.56 mL vs. 42.30 mL), and incidence of transient recurrent laryngeal nerve injury(24.59 vs. 26.77). The NLC of RT was smaller than that of ET(Incidence-rate ratios [IRR]=0.64[0.57, 0.72]). CUSUM analysis (ET: IRR=0.84[0.72, 0.99]; RT: IRR=0.55[0.44, 0.69]) or a smaller number of respondents (ET: IRR=0.26[0.15, 0.46]; RT: IRR=0.51[0.41, 0.63]) was associated with smaller NLC. In RT, transoral approach (IRR=2.73[1.96, 4.50]; IRR=2.48[1.61, 3.84]) and retroauricular approach (RAA) (IRR=2.13[1.26, 3.60]; IRR=1.78[1.04, 3.05]) had smaller NLC compared to bilateral axillo-breast and transaxillary approach (TAA). In ET, the NLC of RAA was smaller than that of TAA (IRR=1.61[1.04, 2.51]), breast approach(IRR=1.67[1.06, 2.64]), and subclavian approach(IRR=1.80[1.03, 3.14]). CONCLUSIONS: Rich surgical experience can improve surgical results of ET and RT. After reaching the NLC, the perioperative outcomes of RT are better than those of ET. Study subjects, surgical approaches, and analysis methods can affect NLC.

Prediction of transition metal carbonitride monolayers MN4C6 (M = Cr, Mn, Fe, and Co) made up of a benzene ring and a planar MN4 moiety.

Based on first-principles calculations, we predict a class of graphene-like magnetic materials, transition metal carbonitrides MN4C6 (M = Cr, Mn, Fe, and Co), which are made up of a benzene ring and an MN4 moiety, two common planar units in the compounds. The structural stability is demonstrated by the phonon and molecular dynamics calculations, and the formation mechanism of the planar geometry of MN4C6 is ascribed to the synergistic effect of sp2 hybridization, M-N coordination bond, and π-d conjugation. The MN4C6 materials consist of only one layer of atoms and the transition metal atom is located in the planar crystal field, which is markedly different from most two-dimensional materials. The calculations indicate that MnN4C6, FeN4C6, and CoN4C6 are ferromagnetic while CrN4C6 has an antiferromagnetic ground state. The Curie temperatures are estimated by solving the anisotropic Heisenberg model with the Monte Carlo method.

α-Terpineol affects social immunity, increasing the pathogenicity of entomopathogenic nematodes to subterranean termites (Isoptera).

Biocontrol of subterranean termites is largely impeded by their social immune responses. Studies on biocontrol agents combined with natural insecticides and their possible effects on the immune defense mechanisms of termites are limited. In this study, we investigated the effects of a combined biocontrol strategy using a plant-derived insect ATPase inhibitor, α-terpineol, with the entomopathogenic nematodes (EPNs) Steinernema carpocapsae against the subterranean termite Coptotermes formosanus Shiraki. Survival assays showed that even a low lethal concentration of α-terpineol significantly increased the EPNs-induced virulence in C. formosanus. α-terpineol treatment majorly inhibited the activity of Na+- K+- ATPase, which disturbed the EPNs-induced enhancement of locomotor activity and grooming behavior in termites treated with the combined strategy. Furthermore, the combination treatment had a synergistic inhibitory effect on innate immune responses in C. formosanus, which were measured as changes in the expression of immune-related genes and activities of immune system enzymes. In conclusion, α-terpineol can weaken the immune defense of termites against EPNs at low lethal concentrations, and is a suitable non-synthetic insecticide to prove the biocontrol efficiency of EPNs on C. formosanus. This study provides a theoretical basis and technical reference for a novel biocontrol strategy that promises to overcome the problems of host immune defense in termites.

Unveiling the role of GAS41 in cancer progression.

GAS41, a member of the human YEATS domain family, plays a pivotal role in human cancer development. It serves as a highly promising epigenetic reader, facilitating precise regulation of cell growth and development by recognizing essential histone modifications, including histone acetylation, benzoylation, succinylation, and crotonylation. Functional readouts of these histone modifications often coincide with cancer progression. In addition, GAS41 functions as a novel oncogene, participating in numerous signaling pathways. Here, we summarize the epigenetic functions of GAS41 and its role in the carcinoma progression. Moving forward, elucidating the downstream target oncogenes regulated by GAS41 and the developing small molecule inhibitors based on the distinctive YEATS recognition properties will be pivotal in advancing this research field.

Effectiveness of the recurrent laryngeal nerve monitoring during endoscopic thyroid surgery: systematic review and meta-analysis.

BACKGROUND: Thyroid disease is a common endocrine disorder, and thyroid surgeries and postoperative complications have increased recently. This study aimed to explore the effectiveness of intraoperative nerve monitoring (IONM) in endoscopic thyroid surgery using subgroup analysis and determine confounding factors. MATERIALS AND METHODS: Two researchers individually searched for relevant studies published till November 2022 in the PubMed, Embase, Web of Science and Cochrane Library databases. Eventually, eight studies met the inclusion criteria. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. The odds ratio or risk difference were calculated using fixed-effects models. The weighted mean difference of continuous variables was calculated. Subgroup analysis was performed according to the disease type. RESULTS: Eight eligible papers included 915 patients and 1242 exposed nerves. The frequencies of transient, permanent and total recurrent laryngeal nerve (RLN) palsy were 2.64, 0.19 and 2.83%, respectively, in the IONM group and 6.15, 0.75 and 6.90%, respectively, in the conventional exposure group. In addition, analysis of the secondary outcome indicators for the average total length of surgery, localisation time of the RLN, recognition rate of the superior laryngeal nerve and length of incision revealed that IONM reduced the localisation time of the RLN and increased the identification rate of the superior laryngeal nerve. Subgroup analysis showed that IONM significantly reduced the incidence of RLN palsy in patients with malignancies. CONCLUSIONS: The use of IONM significantly reduced the incidence of transient RLN palsy during endoscopic thyroid surgery, but it did not significantly reduce the incidence of permanent RLN palsy. However, the reduction in the total RLN palsy was statistically significant. In addition, IONM can effectively reduce the location time of the RLN and increase the recognition rate of the superior laryngeal nerve. Therefore, the application of IONM for malignant tumours is recommended.

SiO2/hyaluronic acid nanoparticles carry CaO2, DOX and p53 plasmid to effectively achieve ion interference/chemical/gene multimodal therapy of lung cancer.

Monotherapy of lung cancer shows limited therapeutic effects due to its poorly targeted enrichment and low bioavailability. Using nanomaterials as carriers to form drug delivery systems has become a popular method to improve the targeting of anticancer drug therapy and patients' safety. However, the uniformity of the loaded drugs and the unsatisfactory effects are still the bottleneck in this field up to now. This study aims to construct a novel nanocomposite carrying 3 different types of anticancer drugs to enhance treatment efficacy. Herein, mesoporous silica (MSN) with high loading rate was constructed by dilute sulfuric acid thermal etching as the framework. Hyaluronic acid (HA) was loaded with CaO2, p53 and DOX to construct nanoparticle complexes-SiO2@CaO2@DOX@P53-HA. First, MSN was proved to be a porous sorbent with a mesoporous structure through BET analysis. The images obtained from the uptake experiment clearly show the gradual enrichment of the DOX and Ca2+ within the target cell. For in vitro experiments, the pro-apoptotic effects of SiO2@CaO2@DOX@P53-HA significantly increased compared to that of the single-agent group at different time points. Furthermore, in the tumor-bearing mouse experiment, the tumor volume was remarkably inhibited in the SiO2@CaO2@DOX@P53-HA group compared to that in the single-agent group. By observing the pathological sections of the euthanized mice, it is obvious that the tissues of the mice treated with the nanoparticles were more intact. Based on these beneficial results, it is believed that multimodal therapy is a meaningful treatment strategy for lung cancer.

Xenorhabdus bovienii subsp. africana subsp. nov., isolated from Steinernema africanum entomopathogenic nematodes.

Four Gram-negative bacterial strains isolated from Steinernema africanum entomopathogenic nematodes were biochemically and molecularly characterized to determine their taxonomic position. Results of 16S rRNA gene sequencing indicated that they belong to the class Gammaproteobacteria, family Morganellaceae, genus Xenorhabdus, and that they are conspecific. The average 16S rRNA gene sequence similarity between the newly isolated strains and the type strain of its more closely related species, Xenorhabdus bovienii T228T, is 99.4 %. We therefore selected only one of them, XENO-1T, for further molecular characterization using whole genome-based phylogenetic reconstructions and sequence comparisons. Phylogenetic reconstructions show that XENO-1T is closely related to the type strain of X. bovienii, T228T, and to several other strains that are thought to belong to this species. To clarify their taxonomic identities, we calculated average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values. We observed that the ANI and dDDH values between XENO-1T and X. bovienii T228T are 96.3 and 71.2 %, respectively, suggesting that XENO-1T represents a novel subspecies within the X. bovienii species. Noteworthy, the dDDH values between XENO-1T and several other X. bovienii strains are between 68.7 and 70.9 % and ANI values are between 95.8 and 96.4 %, which could be interpreted, in some instances, as that XENO-1T represents a new species. Considering that for taxonomic description the genomic sequences of the type strains are compared, and to avoid future taxonomic conflicts, we therefore propose to assign XENO-1T to a new subspecies within X. bovienii. ANI and dDDH values between XENO-1T and any other of the species with validly published names of the genus are lower than 96 and 70 %, respectively, supporting its novel status. Biochemical tests and in silico genomic comparisons show that XENO-1T exhibit a unique physiological profile that differs from all the Xenorhabdus species with validly published names and from their more closely related taxa. Based on this, we propose that strain XENO-1T represents a new subspecies within the X. bovienii species, for which we propose the name X. bovienii subsp. africana subsp. nov, with XENO-1T (=CCM 9244T=CCOS 2015T) as the type strain.

Role of high ubiquitin-conjugating enzyme E2 expression as a prognostic factor in nasopharyngeal carcinoma.

The incidence of nasopharyngeal carcinoma (NPC) in Southeast Asia and Taiwan is high due to epidemiological factors. Cisplatin-based chemoradiotherapy is an important treatment strategy with excellent outcomes for patients with NPC. However, the outcomes for patients who are refractory to cisplatin-based therapy are poor. Methods for risk stratification of patients with NPC undergoing cisplatin-based chemoradiotherapy require to be investigated. A previous study indicated that ubiquitin-conjugating enzyme E2 B (UBE2B) was able to regulate alkylating drug sensitivity in NPC cells. In the present study, the clinical significance of UBE2B expression in patients with NPC was analyzed. Analysis of the two available NPC datasets containing the UBE2B expression profile (GSE12452 and GSE68799) was performed to evaluate the UBE2B expression levels in NPC tissues compared with nasopharyngeal mucosal epithelial tissues. Furthermore, immunohistochemical staining was performed using anti-UBE2B antibodies on samples from 124 patients with NPC who underwent cisplatin-based chemoradiotherapy. Disease-specific survival (DSS), distant metastatic-free survival (DMeFS) and local recurrence-free survival (LRFS) of patients with high and low UBE2B expression was analyzed. Furthermore, the associations between UBE2B expression and the biological behavior of NPC cells were investigated in vitro. Using public NPC datasets and in vitro studies, it was identified that UBE2B expression levels were increased in NPC tumor tissues compared with those in mucosal epithelial tissues. The cell proliferation ability was decreased in UBE2B-deficient NPC cells as compared with that in UBE2B-proficient cells. Immunohistochemical analysis of 124 NPC tissues from patients who underwent cisplatin-based chemoradiotherapy indicated that high UBE2B expression levels were associated with poor DSS, DMeFS and LRFS. Multivariate regression analysis of factors influencing survival also confirmed that high UBE2B expression levels were a statistically significant independent risk factor for poor clinical outcomes in terms of DSS [hazard ratio (HR), 1.955; 95% CI 1.164-3.282], DMeFS (HR, 2.141; 95% CI 1.206-3.801) and LRFS (HR, 2.557; 95 CI 1.313-4.981). In vitro analysis indicated that O6-methylguanine-DNA methyltransferase attenuated cisplatin sensitivity induced by knockdown of UBE2B in NPC cells. In conclusion, the present study demonstrated that high UBE2B expression is associated with poor clinical outcomes for patients with NPC treated with cisplatin-based chemoradiotherapy.

Age as a modifier of the effects of chemoradiotherapy with infusional 5-fluorouracil after D2 dissection in gastric cancer.

Adjuvant concurrent chemoradiotherapy (CCRT) is the standard care for patients with resected advanced gastric cancer, but its survival benefits remain undetermined in patients undergoing D2 lymph node dissection (D2 dissection). We evaluated safety and efficacy of adjuvant CCRT with 5-fluorouracil (5-FU) versus chemotherapy alone in 110 gastric cancer patients with D2 dissection treated in Taiwan between January 2009 and January 2013. All the 71 patients receiving adjuvant CCRT were treated with daily infusional 5-FU and radiotherapy. Adjuvant CCRT was associated with higher risks of major hematologic (56.3% vs. 23.8%, p = 0.002) and gastrointestinal (46.9% vs. 14.3%, p = 0.027) toxicities and death (12.5% vs. 0.0%, p = 0.041) in patients above 70 years old, but this was not the case in those ≤70 years of age. Univariate Cox proportional regressions identified adjuvant CCRT as a factor for better overall survival (OS) (hazard ratio [HR]=0.52; 95% confidence interval [CI]: 0.27-0.99) and disease-free survival (DFS) (HR=0.46, 95% CI: 0.24-0.88), but it was not a significant factor for OS or DFS after adjusting for other factors in the multivariate analysis. However, in stratified analyses by age, we found adjuvant CCRT was an independent prognostic factor for better OS (HR=0.07; 95% CI: 0.01-0.38) in patients ≤70 years old, but not in those above 70 years of age. Therefore, it was concluded that age may to be a modifier of the effects of adjuvant CCRT.

MAC30 Knockdown Inhibits Proliferation and Enhance Apoptosis of Gastric Cancer by Suppressing Wnt/ß-Cateninsignaling Pathway.

Gastric cancer is one of the most frequently diagnosed cancer and poses a serious threat to health system in the world. Upregulation of meningioma-associated protein (MAC30) has been found in many solid tumors and can regulate the proliferation, differentiation, and apoptosis of different tumor cells. Quantitative polymerase chain reaction (qPCR) was used to detect the expression of MAC30 in 68 patients with gastric cancer and their adjacent tissues. Lentiviral vector pGCSIL-shMAC30-GFP of the RNA interference (RNAi) of the MAC30 gene was transfected into gastric cancer BGC-823 cell line and the expression of lentivirus label protein GFP was observed via fluorescence microscope, while cell proliferation and apoptosis were determined with flow cytometry and MTT assay, respectively. Also, related protein expressions on Wnt/ß-catenin signaling pathway were analyzed by Western blot method. The expression of MAC30 was abnormally elevated in gastric cancer tissues, while interfering of its expression could significantly inhibit the proliferation of gastric cancer BGC-823 cell line. However, the promotion of apoptosis by mitochondrial pathway was mediated by Bax/Bcl-2 upregulation. Present work showed the effect of downregulated MAC30 expression on proliferation and apoptosis of gastric cancer cell through Wnt/ß-catenin signaling pathway. Thus, this investigation provides an experimental basis for future development of chemotherapeutic agent on gastric cancer.

High expression of eukaryotic initiation factor 3M predicts poor prognosis in colon adenocarcinoma patients.

Eukaryotic initiation factor 3 subunit M (EIF3M) is required for key steps in the initiation of protein synthesis, and dysregulation of EIF3M is associated with tumorigenesis. This study aimed to explore the clinicopathological and prognostic role of EIF3M in patients with colon adenocarcinoma. A total of 82 pathology specimens, 20 freeze-thawed tumors and 80 healthy controls were used to investigate the expression of EIF3M in colon adenocarcinoma through immunohistochemistry, western blotting, RT-qPCR and ELISA. In addition, Kaplan-Meier curves and Cox regression analysis were used to analyze overall survival (OS) and disease-free survival (DFS). Furthermore, the Oncomine database was used for analyzing EIF3M expression. The positive rate of EIF3M in colon adenocarcinoma was higher compared with that in normal colon tissues (62.20% vs. 29.27%; P<0.001). The mean score of EIF3M was also higher in colon adenocarcinoma compared with normal colon tissue (17.28±10.05 vs. 6.53±4.87; P<0.001). The levels of EIF3M expression in freeze-thawed tumors and serum from 20 patients with colon adenocarcinoma were higher than those in normal tissues and serum from healthy controls, respectively (P<0.001). In addition, positive expression of EIF3M was associated with tumor size (P=0.002) and Dukes' stage (P<0.001). In multivariate Cox regression analysis, EIF3M expression was an independent prognostic factor for OS (P=0.003) and DFS (P=0.001). Oncomine database analysis showed a higher expression of EIF3M expression in colon adenocarcinoma compared with normal colon tissues, colon squamous cell carcinomas or gastrointestinal stromal tumors. In conclusion, EIF3M expression was associated with tumor size and Dukes' stage in colon adenocarcinoma. Hence, EIF3M is a potential prognostic indicator for colon adenocarcinoma.

Efficacy of Entomopathogenic Nematodes Against the Tobacco Cutworm, Spodoptera litura (Lepidoptera: Noctuidae).

Spodoptera litura (F.) is an obnoxious cosmopolitan pest that causes serious damage to different economic crops. Entomopathogenic nematodes (EPN) have the potential to control the S. litura larvae. Fifteen EPN isolates were screened, and Steinernema sp. 64-2, four isolates of S. carpocapsae (Weiser), S. longicaudum (Shen & Wang) X-7, and two isolates of H. indica (Poinar, Karunaka & David) were found to cause higher mortality of the second, third, and fourth instars of S. litura than the other tested isolates, with larval mortality rates > 90% after 48 h of exposure. An exposure rate of 12.5 infective juveniles per larva was enough for S. carpocapsae A24, All, and G-R3a-2 and S. longicaudum X-7 to cause 100% mortality of the second instar, and for S. longicaudum X-7 and H. indica 212-2 to cause 100% mortality of the third instar. Five EPN isolates were tested on their virulence at different temperatures and found that all the five EPN isolates performed well against the S. litura larvae at 25 and 30°C, but were not active at 10 and 15°C. Two S. carpocapsae isolates (All and Mex) were virulent against the S. litura larvae at lower temperatures. The five tested EPN isolates were also found to have the ability to infect and kill the pupae of S. litura in the laboratory. The present study further proves that EPN are effective at controlling S. litura, which may partially substitute the use of chemical insecticides, thus reduce the overuse of chemical insecticides.

A new physical-cognitive scale for assessment of frailty in Chinese Han elderly.

Objective: To develop a physical- cognitive scale for assessment of frailty and compare the clinical features between the new scale and the conventional Fried criteria. Methods: 1757 individuals aged 70-84 were analyzed. Participants reporting three or more Fried phenotypes were grouped as frail patients (FP) whereas others as non-frail (NF). A score of Hasegawa's dementia scale (HDS-R) higher than 21.5 were classified as non-cognitive impairment group (NCI) group. By combining the cognitive and frailty criteria, participants manifesting three or more positive components out of the six were categorized into the Physical-cognitive frailty group (Pc-F) while others into non- Pc-F (Pc-NF). Results: Of all the participants, 46.7% (820) were males and 53.3% (937) were females. The mean age was 75.33 ± 3.90. 10.1% (178/1757) were evaluated as FP patients. The prevalence of CI was 53.2%; CI was much higher in the frail group (77.0%) than in the non-frail group (50.5%). Based on the new Pc-F scale, 163 out of 1579 NF participants were identified as Pc-F, and the prevalence of Pc-F reached 19.4% (341/1757). In the Pc-F group, there are more females, patients of advanced age, diabetes, stroke, CHD, CKD, metabolic syndrome, and high hs-CRP. Within the Pc-F group, patients with CI showed a higher incidence of exhaustion, low activity, weakness, and slowness than those without CI. Conclusions: Our study revealed a significantly worse status in frail participants with CI than without. Our new scale shows a stronger correlation between frailty and complications than the classic phenotype.

Hypermethylation of CDH13, DKK3 and FOXL2 promoters and the expression of EZH2 in ovary granulosa cell tumors.

Aberrant epigenetic modification is associated with the development and progression of cancer. Hypermethylation of tumor suppressor gene promoters and cooperative histone modification have been considered to be the primary mechanisms of epigenetic modification. Ovary granulosa cell tumors (GCTs) are relatively rare, accounting for ~3% of all ovarian malignancies. The present study assessed hypermethylation of the cadherin 13 (CDH13), dickkopf WNT signaling pathway inhibitor 3 (DKK3) and forkhead box L2 (FOXL2) promoters in 30 GCT tissues and 30 healthy control tissues using methylation-specific polymerase chain reaction analysis. The data showed that the frequencies of CDH13, DKK3 and FOXL2 promoter methylation were significantly higher in the GCT tissues, compared with the healthy control tissues (86.67, vs. 23.33%; 80, vs. 26.67% and 66.67, vs. 20%, respectively; P<0.001). Immunostaining of enhancer of zeste homolog 2 (EZH2), a histone H3K27 methyltransferase, showed that the EZH2 protein was expressed in 11 of the 30 GCT tissue samples, whereas no EZH2 protein was expressed in the 30 healthy control tissues (P<0.01). These data suggested that hypermethylation of the CDH13, DKK3 and FOXL2 gene promoters, and overexpression of the EZH2 protein were involved in the development of GCT.

Increased Activity of Src Homology 2 Domain Containing Phosphotyrosine Phosphatase 2 (Shp2) Regulates Activity-dependent AMPA Receptor Trafficking.

Long term synaptic plasticity, such as long term potentiation (LTP), has been widely accepted as a cellular mechanism underlying memory. Recently, it has been unraveled that Shp2 plays a role in synaptic plasticity and memory in Drosophila and mice, revealing significant and conserved effects of Shp2 in cognitive function. However, the exact mechanism underlying this function of Shp2 in synaptic plasticity and memory still remains elusive. Here, we examine the regulation of Shp2 in hippocampal LTP and contextual fear conditioning. We find that Shp2 is rapidly recruited into spines after LTP induction. Furthermore, the phosphorylation level of Shp2 at Tyr-542 is elevated after LTP stimuli either in cultured hippocampal neurons or acute slices. Notably, contextual fear conditioning also regulates the phosphorylation level of Shp2 at Tyr-542, suggesting fine-tuned regulation of Shp2 in LTP and memory formation. By using a Shp2-specific inhibitor and adeno-associated virus-Cre mediated Shp2 knock-out in cultured neurons, we provide evidence that the phosphatase activity of Shp2 is critical for activity-dependent AMPA receptor surface trafficking. Collectively, our results have revealed a regulatory mechanism of Shp2 underlying LTP and memory, broadening our understanding of Shp2 in cognitive function.

[Clinical Research about Risk Factors and Reversible Predictors in Renal Impairment due to Multiple Myeloma].

OBJECTIVE: This study was aimed to investigate the risk factors of renal impairment and the predictive factors of renal function recovery so as to provide basis for its prevention and treatment. METHODS: Medical records of 161 patients with MM firstly diagnosed from January 2007 to April 2013 were analyzed retrospectively. Among them 58 cases accompanied with renal insufficiency (group A, others belong to group B) and 39 of them regain normal renal function after some treatment. The possible related renal impairment risk factors and reversible predictors were analyzed with chi-square test for significance firstly, then factors that have significant difference were entered into multivariate logistic regression analysis. RESULTS: Systolic blood pressure (SBP), hemoglobin, uric acid, blood calcium, phosphorus, serum ß2-microglobulin, urine ß2-microglobulin levels, M-component type, light chain type, nephrotoxic drug use, infection in group A had significant difference (P<0.05) compared with those in group B; the systolic blood pressure, diastolic blood pressure, platelet, globulin, blood calcium, and urine ß2-microglobulin levels, the chemotherapy applied and the response to chemotherapy in reversed group were significantly different from no-reversed group (P<0.05). Multivariate logistic regression showed that light chain type, Hb, uric acid, Ca were the independent risk factors for the development of renal failure in MM, and Ca, chemotherapy and the response to chemotherapy were the predictors of renal function recovery. CONCLUSION: High blood calcium, severe anemia, λ light chain, high uric acid are the independent risk factors of renal impairment in MM patients. Patients with high blood calcium before treatment easily regain normal renal function after effective chemotherapy. Bortezomib-based chemotherapy has higher response rate and higher reversal rate, and it may be related with its unique mechanism.

Whole lung lavage combined with Granulocyte-macrophage colony stimulating factor inhalation for an adult case of refractory pulmonary alveolar proteinosis.

BACKGROUND: Whole-lung lavage (WLL) is classically the first-line treatment for symptomatic pulmonary alveolar proteinosis (PAP). However, some patients require multiple WLLs because of refractory nature of their PAP. In this instance, these patients may benefit from new treatment regimens, and new therapies should be tried for these patients. CASE PRESENTATION: We describe a 47-year-old Chinese woman who was confidently diagnosed with pulmonary alveolar proteinosis (PAP) after bronchoalveolar lavage and transbronchial lung biopsy. The patient received four sessions of bilateral whole lung lavage (WLL) and one session of WLL in combination with plasmapheresis, each only producing short-term symptomatic relief. The patient was given a trial of combination therapy, which consisted of WLL and Granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation. The patient showed a gradual improvement in oxygenation and her daily activity, as well as a dramatic improvement in her pulmonary CT examination. CONCLUSION: Bilateral WLL, in combination with GM-CSF inhalation, may be an effective treatment option for severe refractory PAP.

Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-ß1-Smad4-PAI-1 axis.

Longevity assurance homolog 2 of yeast LAG1 (Lass2) gene is capable of suppressing the proliferation and metastasis of several types of tumours including liver cancer. In the present study, hepatocyte-specific Lass2-knockout (Lass2 KO) and wild-type (WT) mice were exposed to the carcinogen, diethylnitrosamine (DEN), to induced liver tumours. At week 23 following DEN injection, tumours were produced in 100% of the Lass2 KO mice and 21.4% of the WT mice. At week 40, 100% of the Lass2 KO mice and 78.6% of the WT mice developed tumours, with no distinct significant difference in tumour occurrences between the two genotypes; yet, tumours in the Lass2 KO mouse livers were more numerous and larger in size. Hepatocellular carcinoma (HCC) was confirmed by α-fetoprotein (AFP). PCNA and EdU assays indicated more active proliferation whereas TUNEL assay revealed decreased apoptosis in Lass2 KO livers, when compared with the WT control. The expression of plasminogen activator inhibitor type-1 (PAI-1), a tumour-promoting gene, in the liver tissues of the 2 genotypes was detected using qPCR and western blotting, showing that PAI-1 levels were significantly elevated in Lass2 KO livers at week 40 following DEN introduction. Moreover, the expression of PAI-1-related TGF-ß1, Smad-4 and -7 was detected, displaying an elevation in TGF-ß1 and Smad-4 (not including Smad-7) in the Lass2 KO livers. Our data demonstrates that i) Lass2 is a protective gene against DEN-induced liver tumourigenesis; and ii) upregulation of the TGF-ß1-Smad4-PAI-1 axis may contribute to the vulnerability of Lass2-knockout mice to DEN.

[Therapeutic effects and the underlying mechanism of umbilical cord-derived mesenchymal stem cells for bleomycin induced lung injury in rats].

OBJECTIVE: To study the efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for bleomycin-induced pulmonary fibrosis in mice. METHODS: UC-MSCs were isolated from the umbilical cord after parental consent. One hundred C57BL/6 mice were randomly divided into 4 groups (12 of these for preliminary experiment). Mice in the control group (n = 20) were instilled with PBS via trachea and NS was injected via the tail vein after 3 days. Mice in the stem cell group (n = 20) were instilled with PBS via trachea and were injected with MSC via the tail vein after 3 days. Mice in the bleomycin group (n = 24) were instilled with bleomycin via trachea and NS was injected via the tail vein after 3 days. Mice in the bleomycin plus stem cell group (n = 24) were instilled with bleomycin via trachea and were injected with MSCs via the tail vein after 3 days. All of the mice were sacrificed at the 21(th) day, and the lungs were immediately fixed with 4% paraformaldehyde for 48 h, embedded in paraffin and sectioned at 5 µmol/L thickness. The sections were stained with hematoxylin and eosin (H&E) and Masson-trichrome. Histopathological scoring of pulmonary fibrosis was performed according to Ashcroft's method. The concentrations of matrix metalloproteinases-2 and tissue inhibitor of metalloproteinase-1were determined using immunohistochemistry. RESULTS: Compared with the bleomycin group, MSC transplantation significantly reduced pulmonary inflammation, fibrosis and deposition of collagen in the bleomycin plus stem cell group [(1.55 ± 0.51) vs (2.16 ± 0.77), and (1.45 ± 0.60) vs (2.32 ± 0.82), respectively, P < 0.05]. There was no difference between the control group and the stem cell group [(0.35 ± 0.49) vs (0.37 ± 0.50), P > 0.05]. The expression of MMP-2 in the bleomycin plus stem cell group was lower than the bleomycin group [(1.59 ± 0.59) vs (2.37 ± 0.68), P < 0.05], but there was no difference between the control group and the stem cell group [(0.80 ± 0.69) vs (0.84 ± 0.77), P > 0.05]. The expression of TIMP-1 in the bleomycin plus stem cell group was higher than the bleomycin group [(1.95 ± 0.58) vs (0.79 ± 0.71), P < 0.05], but there was no difference between the control group and the stem cell group [(1.10 ± 0.72) vs (1.32 ± 0.58), P > 0.05]. CONCLUSION: UC-MSC transplantation could relieve bleomycin-induced fibrosing alveolitis in mice. The mechanism might be related to the expression of MMP-2 and TIMP-1. UC-MSC had no effect on normal lungs.