Addressing the influencing path of social noise exposure risk perception on noise mitigation behavior.

Noise interference has become a common health risk in population-densified urban areas where social noise occurs frequently. However, the influence of an individual's perception of social noise exposure risk on reactive behavior remains unknown. This study developed an integrative psychosocial perspective-based model that includes constructs from two theoretical frameworks (the Theory of Planned Behavior and the Value-Belief-Norm theory) to analyze noise risk perception and behavioral intention for social noise mitigation. Haidian District, Beijing, was selected as the case study area and 300 questionnaires were distributed. The results showed that personal attributes had significant effects on residents' noise exposure risk perception and noise-mitigation behavioral intentions. Noise perception, as represented by awareness of consequences and ascription of responsibility, was significantly related to noise mitigation behavioral intention. Awareness of consequences directly positively influenced behavioral intention (ß = 0.235, p < 0.001) and indirectly positively influenced behavioral intention through the mediating effect of the ascription of responsibility, which accounted for 24 % of the total effect of awareness of consequences on behavioral intention. This study provides valuable insights into the risks of social noise and encourages adaptive measures to reduce it.

Graph-based pan-genomes: increased opportunities in plant genomics.

Due to the development of sequencing technology and the great reduction in sequencing costs, an increasing number of plant genomes have been assembled, and numerous genomes have revealed large amounts of variations. However, a single reference genome does not allow the exploration of species diversity, and therefore the concept of pan-genome was developed. A pan-genome is a collection of all sequences available for a species, including a large number of consensus sequences, large structural variations, and small variations including single nucleotide polymorphisms and insertions/deletions. A simple linear pan-genome does not allow these structural variations to be intuitively characterized, so graph-based pan-genomes have been developed. These pan-genomes store sequence and structural variation information in the form of nodes and paths to store and display species variation information in a more intuitive manner. The key role of graph-based pan-genomes is to expand the coordinate system of the linear reference genome to accommodate more regions of genetic diversity. Here, we review the origin and development of graph-based pan-genomes, explore their application in plant research, and further highlight the application of graph-based pan-genomes for future plant breeding.

[Protective effects of genistein on Aß25₋35-induced PC12 cell injury via regulating CaM-CaMKIV signaling pathway].

Genistein is a kind of isoflavone compounds， also called phytoestrogens， with clinical effects on cardiovascular disease， cancer and postmenopausal-related gynecological diseases， and also has the potentiality in the prevention and treatment of Alzheimer's disease(AD). In this study， the protective effect of genistein on Aß25₋35-induced PC12 cell injury and effect on CaM-CaMKIV signaling pathway were observed to investigate its mechanism for AD. PC12 cells were cultured in vitro and then the safe concentration of genistein and the modeling concentration and optimal time point of administration of Aß25₋35 were screened by MTT assay. After being pretreated with different concentrations of genistein(25， 50， 100 µmol·L⁻¹) on PC12 cells， the AD model of PC12 cells was induced by Aß25₋35. Then the survival rate of cells was detected by MTT assay; morphological change of cells was observed under the inverted microscope， and apoptosis of cells was assessed by AO/EB fluorescence staining; the neuroprotective effects of genistein on AD cell model were observed and the optimal concentration of genistein was determined. Expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau were detected by qRT-PCR and Western blot assay， respectively. The results showed that as compared with the blank group， the cell survival rate was decreased; the cell damage and apoptosis were increased; and the expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau were increased in AD model group. Genistein could significantly improve the cell survival rate， reduce the cell damage and apoptosis of AD cell model， and significantly down-regulate the expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau of AD cell model. These results indicated that genistein has obviously neuroprotective effect on the AD cell model induced by Aß25₋35， and the mechanism may be related to the down-regulation of CaM-CaMKIV signaling pathway and Tau protein expression.

CLEC4D as a Novel Prognostic Marker Boosts the Proliferation and Migration of Gastric Cancer via the NF-κB/AKT Signaling Pathway.

Purpose: The functions of C-type lectin domain family 4 member D (CLEC4D), one member of the C-type lectin/C-type lectin-like domain superfamily, in immunity have been well described, but its roles in cancer biology remain largely unknown. Patients and Methods: This study aims to explore the role of CLEC4D in gastric cancer (GC). Bioinformatics preliminarily analyzed the expression of CLEC4D in gastric cancer. Immunohistochemical staining was used to detect the expression level and clinical pathological characteristics of CLEC4D in gastric cancer. The biological function of CLEC4D in gastric cancer cell lines was verified through in vitro and in vivo experiments. Results: In this study, CLEC4D expression was found to be markedly increased in gastric cancer (GC) tissues compared with matched normal gastric tissues, and high CLEC4D expression independently predicted unfavorable overall survival in patients with GC. Knockdown of CLEC4D markedly inhibited GC cell proliferation and migration. Mechanistically, CLEC4D knockdown deactivated the Akt and NF-κB signaling pathways in GC cells. Conclusion: Together, these results demonstrate that aberrantly increased CLEC4D expression promotes cancer phenotypes via the Akt and NF-κB signaling pathways in GC cells.

Oncogenic and immunological role of EDIL3 in human tumours: From pan-cancer analysis to validation in gastric cancer.

Background: Epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) is a secreted extracellular matrix protein implicated in diverse physiological and pathological processes including embryonic development, angiogenesis, and anti-inflammatory responses. Recent reports have indicated that EDIL3 play critical roles in carcinogenesis and progression of many cancers. Herein, we performed a pan-cancer investigation to study the potential functions of EDIL3 in various cancers and experimentally validate its function in gastric cancer (GC). Methods: We analysed EDIL3 expression profiles in different tumours using The Cancer Genome Atlas database. The Kaplan-Meier Plotter was used to investigate the prognostic value of EDIL3, while receiver operating characteristic curve was performed to analyze its diagnostic efficacy. Several bioinformatics tools were used to study the association between EDIL3 and promoter methylation, gene enrichment analysis, immune infiltration, immune-related genes, and drug sensitivity. Molecular biology experiments were conducted to validate the tumorigenic effects of EDIL3. Results: EDIL3 is variably expressed in different cancers and is closely associated with clinical outcomes. An inverse correlation between EDIL3 and DNA methylation has been observed in 13 cancers. Enrichment analysis indicated that EDIL3 is correlated with many cellular pathways such as extracellular matrix receptor interactions and focal adhesion. EDIL3 was tightly associated with immune infiltration and immune checkpoints. EDIL3 knockdown can promote GC calls apoptosis while preventing proliferation, migration, and invasion in vitro. Conclusion: EDIL3 is a promising prognostic, diagnostic, and immunological biomarker in various cancers, which could be applied as a new target for cancer therapy.

Overexpression of stathmin 1 is associated with poor prognosis of patients with gastric cancer.

Recently, stathmin 1 has been proposed to function as an oncogene based on some relevant studies in multiple types of human cancers. However, the role of stathmin 1 in gastric cancer carcinogenesis has not been elucidated yet. The aim of this study was to investigate the expression of stathmin 1 as well as its association with overall survival of gastric cancer patients. The expression of stathmin 1 was detected by real-time quantitative reverse transcription polymerase chain reaction and Western blotting in gastric cancer and adjacent nontumor tissues. In addition, stathmin 1 expression was analyzed by immunohistochemistry in paraffin samples from 210 primary gastric cancer patients. The expression levels of stathmin 1 mRNA and protein in gastric cancer tissues were both significantly higher than those in adjacent nontumor tissues. In addition, the expression of stathmin 1 is correlated with Lauren's classification, depth of invasion, lymph node metastases, and tumor node metastasis (TNM) stage (all P < 0.05). Univariate analysis showed that high stathmin 1 expression was associated with poor prognosis in gastric cancer patients (P = 0.040). Multivariate analysis demonstrated that only lymph node metastasis and TNM stage were the independent prognostic indicators for gastric cancer. Stathmin 1 expression status is not an independent prognostic factor for patients with gastric cancer. Further subgroup analysis revealed that stathmin 1 expression was significantly correlated with prognosis in diffuse type gastric cancer. This research showed that the stathmin 1 overexpression might play an important role in the pathogenesis and subsequent progression of gastric cancer. Stathmin 1 could also be a potential therapeutic target in gastric cancer, especially for diffuse type gastric cancer.

Case Report: sintilimab-induced Stevens-Johnson Syndrome in a patient with advanced lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) have been widely applicated in clinical therapy in recent years. Skin-related adverse reaction is one of the most common adverse events for ICIs. Stevens-Johnson syndrome (SJS) is one of the serious cutaneous reactions threatening the life. Here, we reported a case of 76-year-old male patient with poorly differentiated metastatic lung adenocarcinoma, after 9 weeks exposure of sintilimab (3 doses) combined with paclitaxel liposome after concurrent chemotherapy/radiotherapy, experienced Stevens-Johnson syndrome involving limbs, trunk, lip and the oral mucosa. Biopsy of the skin tissue showed infiltration of CD4 and CD8 positive T lymphocytes. We also found PD-L1 expression in the glands and the basal layer of the skin. This finding is distinct from the previously reported expression of PD-L1 on the surface of epidermal keratinocytes in patients with SJS due to immunotherapy.

EDIL3 is a potential prognostic biomarker that correlates with immune infiltrates in gastric cancer.

Background: EDIL3, which contains epidermal growth factor-like repeats and discoidin I-like domains, is a secretory protein that plays an important role in embryonic development and various illnesses. However, the biological function of EDIL3 in gastric cancer (GC) is still unclear. The objective of this research was to explore the role and potential mechanism of EDIL3 in GC. Methods: In this study, we used the GEPIA, HPA, MethSurv, SMART, STRING, GeneMANIA, LinkedOmics TIMER, TIMER2.0, TISIDB, and RNAactDrug databases to comprehensively analyze the roles of EDIL3 in GC. To validate the in silico findings, EDIL3 expression was measured in our collected GC tissues. Meanwhile, several in vitro experiments were performed to test the function of EDIL3 in GC. Results: We found that EDIL3 was highly expressed in GC and associated with adverse clinical features. In vitro assays revealed that EDIL3 promoted the proliferation, migration, and invasion of GC cells. The functions of EDIL3 and co-expression genes were significantly associated with extracellular structure organization and matrix receptor interaction. EDIL3 expression was positively associated with numerous tumor-infiltrating immune cells and their biomarkers. Conclusion: This study determined that EDIL3 may function as an oncogene and is associated with immune infiltration in GC. EDIL3 could be used as a potential therapeutic target for GC.

Telomere-to-telomere assembly of cassava genome reveals the evolution of cassava and divergence of allelic expression.

Cassava is a crucial crop that makes a significant contribution to ensuring human food security. However, high-quality telomere-to-telomere cassava genomes have not been available up to now, which has restricted the progress of haploid molecular breeding for cassava. In this study, we constructed two nearly complete haploid resolved genomes and an integrated, telomere-to-telomere gap-free reference genome of an excellent cassava variety, 'Xinxuan 048', thereby providing a new high-quality genomic resource. Furthermore, the evolutionary history of several species within the Euphorbiaceae family was revealed. Through comparative analysis of haploid genomes, it was found that two haploid genomes had extensive differences in linear structure, transcriptome features, and epigenetic characteristics. Genes located within the highly divergent regions and differentially expressed alleles are enriched in the functions of auxin response and the starch synthesis pathway. The high heterozygosity of cassava 'Xinxuan 048' leads to rapid trait segregation in the first selfed generation. This study provides a theoretical basis and genomic resource for molecular breeding of cassava haploids.

Transcutaneous vagus nerve stimulation for the treatment of depression: a study protocol for a double blinded randomized clinical trial.

BACKGROUND: Depressive disorders are the most common form of mental disorders in community and health care settings. Unfortunately, the treatment of Major Depressive Disorder (MDD) is far from satisfactory. Vagus nerve stimulation (VNS) is a relatively new and promising physical treatment for depressive disorders. One particularly appealing element of VNS is the long-term benefit in mood regulation. However, because this intervention involves surgery, perioperative risks, and potentially significant side effects, this treatment has been limited to those patients with treatment-resistant depression who have failed medication trials and exhausted established somatic treatments for major depression, due to intolerance or lack of response.This double-blinded randomized clinical trial aims to overcome these limitations by introducing a novel method of stimulating superficial branches of the vagus nerve on the ear to treat MDD. The rationale is that direct stimulation of the afferent nerve fibers on the ear area with afferent vagus nerve distribution should produce a similar effect as classic VNS in reducing depressive symptoms without the burden of surgical intervention. DESIGN: One hundred twenty cases (60 males) of volunteer patients with mild and moderate depression will be randomly divided into transcutaneous vagus nerve stimulation group (tVNS) and sham tVNS group. The treatment period lasts 4 months and all clinical and physiological measurements are acquired at the beginning and the end of the treatment period. DISCUSSION: This study has the potential to significantly extend the application of VNS treatment for MDD and other disorders (including epilepsy, bipolar disorder, and morbid obesity), resulting in direct benefit to the patients suffering from these highly prevalent disorders. In addition, the results of this double-blinded clinical trial will shed new light on our understanding of acupuncture point specificity, and development of methodologies in clinical trials of acupuncture treatment. TRIALS REGISTRATION: Clinical Trials. ChiCTR-TRC-11001201 http://www.chictr.org/cn/

[A retrospective analysis of clinic-pathological characteristics and prognostic factors for 204 cases of primary gastric lymphoma].

OBJECTIVE: To explore the clinicopathological characteristics and prognostic factors of primary gastric lymphoma (PGL). METHODS: The clinical data of 204 patients with PGL was reviewed and analyzed. There were 106 males and 98 females, their age were 19 to 85 years (average age was 53.7 years). The Focal areas included gastric fundus lesions 41 cases (20.1%), stomach body lesions 127 cases (62.3%), distal gastric lesions 105 cases (51.5%), cardia lesions 13 cases (6.4%), duodenal bulb lesion 1 cases (0.5%). The clinical characteristics and the outcomes in patients with influence were analysed. RESULTS: In 204 PGL patients, the most common complaints were abdominal pain (62.3%) and weight loss (52.9%). Most of the PGL patients appeared ulcerative (76.0%) and results showed that 62.7% patients involved single location. As to the factors of cellulate grading and pathological characteristics, most patients (87.7%) show low-grade or intermediate-grade lymphoma, Musshoff stages I and II (74.0%). In 186 patients with complete follow-up data, survival rates of 1-, 3- and 5-year were 75.8%, 63.4% and 60.2% respectively. The median overall survival time was 50.0 months. In univariate survival analysis, age (χ(2) = 5.030), level of LDH (χ(2) = 40.084), cellulate grading (χ(2) = 35.238), Musshoff stage (χ(2) = 71.601), tumor diameter (χ(2) = 12.018) and option of managements (χ(2) = 14.140) were obviously correlated with the prognosis (all P < 0.05). Musshoff stage (RR = 2.230, 95%CI: 1.372 - 3.625) and cellulate grading (RR = 1.892, 95%CI: 1.010 - 3.543) were independent prognostic factors in multivariable analysis (both P < 0.05). There was no prognostic difference between surgery and chemotherapy in stage I and II (χ(2) = 1.223, P = 0.542). CONCLUSIONS: Musshoff stage and grade malignancy are independent prognostic factors. For patients with stage I and II, surgical resection is not the first-choice for clinical therapy.

In vitro and in vivo Evaluation of the Bioactive Nanofibers-Encapsulated Benzalkonium Bromide for Accelerating Wound Repair with MRSA Skin Infection.

Purpose: Developing the ideal drug or dressing is a serious challenge to controlling the occurrence of antibacterial infection during wound healing. Thus, it is important to prepare novel nanofibers for a wound dressing that can control bacterial infections. In our study, the novel self-assembled nanofibers of benzalkonium bromide with bioactive peptide materials of IKVAV and RGD were designed and fabricated. Methods: Different drug concentration effects of encapsulation efficacy, swelling ratio and strength were determined. Its release profile in simulated wound fluid and its cytotoxicity were studied in vitro. Importantly, the antibacterial efficacy, inhibition of biofilm formation effect and wound healing against MRSA infections in vitro and in vivo were performed after observing the tissue toxicity in vivo. Results: It was found that the optimized drug load (0.8%) was affected by the encapsulation efficacy, swelling ratio, and strength. In addition, the novel nanofibers with average diameter (222.0 nm) and stabile zeta potential (-11.2 mV) have good morphology and characteristics. It has a delayed released profile in the simulated wound fluid and good biocompatibility with L929 cells and most tissues. Importantly, the nanofibers were shown to improve antibacterial efficacy, inhibit biofilm formation, and lead to accelerated wound healing following infection with methicillin-resistant Staphylococcus aureus. Conclusion: These data suggest that novel nanofibers could effectively shorten the wound-healing time by inhibiting biofilm formation, which make it promising candidates for treatment of MRSA-induced wound infections.

The Cold-Adapted, Temperature-Sensitive SARS-CoV-2 Strain TS11 Is Attenuated in Syrian Hamsters and a Candidate Attenuated Vaccine.

Live attenuated vaccines (LAVs) replicate in the respiratory/oral mucosa, mimic natural infection, and can induce mucosal and systemic immune responses to the full repertoire of SARS-CoV-2 structural/nonstructural proteins. Generally, LAVs produce broader and more durable protection than current COVID-19 vaccines. We generated a temperature-sensitive (TS) SARS-CoV-2 mutant TS11 via cold-adaptation of the WA1 strain in Vero E6 cells. TS11 replicated at >4 Log10-higher titers at 32 °C than at 39 °C. TS11 has multiple mutations, including those in nsp3, a 12-amino acid-deletion spanning the furin cleavage site of the S protein and a 371-nucleotide-deletion spanning the ORF7b-ORF8 genes. We tested the pathogenicity and protective efficacy of TS11 against challenge with a heterologous virulent SARS-CoV-2 D614G strain 14B in Syrian hamsters. Hamsters were randomly assigned to mock immunization-challenge (Mock-C) and TS11 immunization-challenge (TS11-C) groups. Like the mock group, TS11-vaccinated hamsters did not show any clinical signs and continuously gained body weight. TS11 replicated well in the nasal cavity but poorly in the lungs and caused only mild lesions in the lungs. After challenge, hamsters in the Mock-C group lost weight. In contrast, the animals in the TS11-C group continued gaining weight. The virus titers in the nasal turbinates and lungs of the TS11-C group were significantly lower than those in the Mock-C group, confirming the protective effects of TS11 immunization of hamsters. Histopathological examination demonstrated that animals in the Mock-C group had severe pulmonary lesions and large amounts of viral antigens in the lungs post-challenge; however, the TS11-C group had minimal pathological changes and few viral antigen-positive cells. In summary, the TS11 mutant was attenuated and induced protection against disease after a heterologous SARS-CoV-2 challenge in Syrian hamsters.

Evaluating smoking cessation service at an emergency department clinical observation unit.

OBJECTIVES: To evaluate the effectiveness of a pilot smoking cessation service in an emergency department (ED) clinical observation unit. STUDY DESIGN: A descriptive case series review was undertaken of smoking cessation service patients in the short-stay unit of an acute hospital in Singapore from July 1, 2018, to December 31, 2019. METHODS: Upon admission, ED nurses screen all patients regarding their current smoking status and implement the 5 A's framework, which involves the steps of Ask-Advise-Assess-Assist-Arrange. Patients in the "contemplation" and "preparation" stages were offered the following components: (1) a bedside counseling session by a pharmacist and (2) a follow-up appointment at an outpatient smoking cessation clinic. Postdischarge follow-up telephone calls at 1, 6, and 12 months were carried out as part of the study data collection to obtain abstinence information. RESULTS: Forty-seven patients were included in the study; the majority were male (n = 41; 87.2%). The median numbers of cigarettes smoked per day at baseline, 1 month, 6 months, and 12 months were 14, 5, 3, and 5, respectively. The overall point-prevalence abstinence rates over the same follow-up time points were 26.5%, 38.7%, and 31.3%, respectively. The proportions of patients lost to follow-up at 1 month, 6 months, and 12 months were 27.7%, 34.0%, and 31.9%, respectively. CONCLUSIONS: Given the small sample and high number of uncontactable patients, more research is needed to assess whether the trend toward increasing point-prevalence abstinence rate over time and the trend toward decreasing median number of cigarettes smoked are observed in a larger sample.

[A retrospective analysis of clinicopathological characteristics and prognostic factors of gastric stump cancer].

OBJECTIVE: To explore the clinicopathological characteristics and prognostic factors of gastric stump cancer(GSC). METHODS: The clinical data of 138 patients with GSC treated from January 1992 to July 2008 were reviewed and analyzed. The patients included 122 males and 16 females with a mean age of 61.5 years, and the mean interval between the initial operation and second diagnosis was 21.9 years. RESULTS: The endoscopy and pathological examination showed Borrmann III/IV in 127 (92.7%) patients and undifferentiated carcinoma in 115 (83.3%) patients. The resectability and radical resectability rate were 72.4% and 59.4%. The 1-, 3- and 5-year survival rates was 59.2%, 30.1% and 14.2%, respectively. The median overall survival time was 19.4 months. Univariate Log-rank test indicated that Borrmann type, histological type, tumor diameter, TNM stage, depth of invasion, number of metastatic lymph node, distant metastasis and option of treatment were significant prognostic factors for GSC. While TNM stage, depth of invasion, distant metastasis and option of treatment were prognostic factors on multivariable analysis. The median survival time of patients underwent radical resection was significantly longer (36 months) than that of patients received palliative resection (8 months, P < 0.05) and chemotherapy only (5 months, P < 0.05). Among patients with a tumor of T4 stage, the median survival time was statistically prolonged by combined evisceration (18.6 months) when compared with the patients received palliative surgery. CONCLUSIONS: TNM stage, depth of invasion, distant metastasis and option of treatment are independent prognostic factors for GSC. Early diagnosis and radical resection may play an important role in improving the prognosis of GSC.

Wastewater SARS-CoV-2 monitoring as a community-level COVID-19 trend tracker and variants in Ohio, United States.

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 129 million confirm cases. Many health authorities around the world have implemented wastewater-based epidemiology as a rapid and complementary tool for the COVID-19 surveillance system and more recently for variants of concern emergence tracking. In this study, three SARS-CoV-2 target genes (N1 and N2 gene regions, and E gene) were quantified from wastewater influent samples (n = 250) obtained from the capital city and 7 other cities in various size in central Ohio from July 2020 to January 2021. To determine human-specific fecal strength in wastewater samples more accurately, two human fecal viruses (PMMoV and crAssphage) were quantified to normalize the SARS-CoV-2 gene concentrations in wastewater. To estimate the trend of new case numbers from SARS-CoV-2 gene levels, different statistical models were built and evaluated. From the longitudinal data, SARS-CoV-2 gene concentrations in wastewater strongly correlated with daily new confirmed COVID-19 cases (average Spearman's r = 0.70, p < 0.05), with the N2 gene region being the best predictor of the trend of confirmed cases. Moreover, average daily case numbers can help reduce the noise and variation from the clinical data. Among the models tested, the quadratic polynomial model performed best in correlating and predicting COVID-19 cases from the wastewater surveillance data, which can be used to track the effectiveness of vaccination in the later stage of the pandemic. Interestingly, neither of the normalization methods using PMMoV or crAssphage significantly enhanced the correlation with new case numbers, nor improved the estimation models. Viral sequencing showed that shifts in strain-defining variants of SARS-CoV-2 in wastewater samples matched those in clinical isolates from the same time periods. The findings from this study support that wastewater surveillance is effective in COVID-19 trend tracking and provide sentinel warning of variant emergence and transmission within various types of communities.

[Risk factors of early recurrence in patients with gastric cancer after curative resection].

OBJECTIVE: To analyze the clinical and pathologic influencing factors of early recurrence in patents with gastric cancer after radical gastrectomy. METHODS: Clinicopathological data of 141 patients with recurrence after curative gastrectomy for gastric cancer from January 2001 to December 2004 were analyzed retrospectively. Risk factors correlated with tumor early recurrence and survival difference between early recurrence group (< 1 year, 82 cases) and control group (1 year after, 59 cases) were assessed. RESULTS: The 1- and 3-year survival rates of in early recurrence group and control group were 36.6%, 2.4% and 100%, 45.8%, respectively (P < 0.05). The median survival time after recurrence in the two groups was 3, 5 months, respectively (P < 0.05). Univariate analysis showed that the age, tumor Borrmann type, tumor site, invasive depth, lymph node metastasis, pTNM stage, metastatic lymph node ratio, surgical procedure and intraperitoneal hyperthermic perfusion chemotherapy (IHPC) were significant factors associated with early recurrence after curative gastrectomy for gastric cancer (P < 0.05). Lymph node metastasis, metastatic lymph node ratio and IHPC were independent factors associate with early recurrence after curative gastrectomy on multivariate analysis (P < 0.05). CONCLUSIONS: The patients with early recurrence after the radical gastrectomy have a poorer survival compared with cases recur later. Lymph node metastasis, metastatic lymph node ratio and IHPC are independent factors associate with early recurrence after curative gastrectomy for gastric cancer.

Detection of Pathogenic Isoforms of IKZF1 in Leukemic Cell Lines and Acute Lymphoblastic Leukemia Samples: Identification of a Novel Truncated IKZF1 Transcript in SUP-B15.

Leukemia-associated alternative splicing of IKZF1 can result in proteins with loss of one to four copies of its N-terminal zinc finger domains (N-ZnF). The best characterized pathogenic splice isoforms, Ik-6 and Ik-8, have been commonly found in BCR-ABL1+ acute lymphoblastic leukemia (ALL) and a subset of BCR-ABL1-like ALL. Infantile and childhood ALL that express these pathogenic IKZF1 isoforms have shown inferior clinical outcomes and can be resistant to tyrosine kinase inhibitors. Using ALL cell lines, we designed and validated a method to detect abnormal IKZF1 transcripts. In the SUP-B15 leukemia cell line, we noted novel IKZF1 transcripts that include both an Ik-6 splice and a transcript with a 14 base pair insertion at the C-terminus. There was also increased IKZF2 protein in SUP-B15 as compared to other ALL lines. Expression of Ik-6 could be suppressed by treatment with the pro-apoptotic type II histone deacetylase inhibitor givinostat. In 17 adult ALL samples, we noted the Ik-6 isoforms in 6 of 15 BCR-ABL1-, and 1 of 2 BCR-ABL1+ cases, with Ik-8 also expressed in one case. Cases with Ik-6 expression showed inferior survival as well as older age at presentation, lower expression of CD10 and more commonly a diploid karyotype.

Ablation of the Brca1-Palb2 Interaction Phenocopies Fanconi Anemia in Mice.

Heterozygous mutations in the BRCA1 gene predispose women to breast and ovarian cancer, while biallelic BRCA1 mutations are a cause of Fanconi anemia (FA), a rare genetic disorder characterized by developmental abnormalities, early-onset bone marrow failure, increased risk of cancers, and hypersensitivity to DNA-crosslinking agents. BRCA1 is critical for homologous recombination of DNA double-strand breaks (DSB). Through its coiled-coil domain, BRCA1 interacts with an essential partner, PALB2, recruiting BRCA2 and RAD51 to sites of DNA damage. Missense mutations within the coiled-coil domain of BRCA1 (e.g., L1407P) that affect the interaction with PALB2 have been reported in familial breast cancer. We hypothesized that if PALB2 regulates or mediates BRCA1 tumor suppressor function, ablation of the BRCA1-PALB2 interaction may also elicit genomic instability and tumor susceptibility. We generated mice defective for the Brca1-Palb2 interaction (Brca1 L1363P in mice) and established MEF cells from these mice. Brca1 L1363P/L1363P MEF exhibited hypersensitivity to DNA-damaging agents and failed to recruit Rad51 to DSB. Brca1 L1363P/L1363P mice were viable but exhibited various FA symptoms including growth retardation, hyperpigmentation, skeletal abnormalities, and male/female infertility. Furthermore, all Brca1 L1363P/L1363P mice exhibited macrocytosis and died due to bone marrow failure or lymphoblastic lymphoma/leukemia with activating Notch1 mutations. These phenotypes closely recapitulate clinical features observed in patients with FA. Collectively, this model effectively demonstrates the significance of the BRCA1-PALB2 interaction in genome integrity and provides an FA model to investigate hematopoietic stem cells for mechanisms underlying progressive failure of hematopoiesis and associated development of leukemia/lymphoma, and other FA phenotypes. SIGNIFICANCE: A new Brca1 mouse model for Fanconi anemia (FA) complementation group S provides a system in which to study phenotypes observed in human FA patients including bone marrow failure.See related commentary by Her and Bunting, p. 4044.

[Overview of "tian-yin-yang" acupuncture, an acupuncture school of Huang's Zhuang medicine of Guangxi].

The theory of "tian-yin-yang" of Zhuang medicine was explored and the academic achievements and experience of professor HUANG Jin-ming were summarized to explain the theory and clinical characteristics of tian-yin-yang acupuncture, an acupuncture school of Huang 's Zhuang medicine of Guangxi. This acupuncture method is guided by the theory of "three-qi synchronization" and "tian-yin-yang" of Zhuang medicine, based on the theory of "three channels and two paths", with regulating qi as the method and regulating spirit as the basis. After the patient is calmed and resting, the micro needle shallow needling technique is adopted, mainly at the umbilical ring point, so as to achieve the purpose of regulating the mind and treating the root cause.