[Efficacy of venetoclax-based induction regimen in newly diagnosed pediatric acute myeloid leukemia].

Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [M (Q1, Q3)] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P>0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P=0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference (P=0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission (OR=0.126, 95%CI: 0.025-0.629). FLT3 mutation was not conducive to morphological remission (OR=5.832, 95%CI: 1.778-19.124) and negative MRD (OR=4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.

[Research progress on the pathogenic mechanisms, diagnosis and treatment of McCune-Albright syndrome].

McCune-Albright syndrome is a rare chimeric disorder due to mutations in the postzygotic GNAS gene. It belongs to the group of guanine nucleotide-binding protein diseases, affecting a wide range of individuals. It is characterized by fibrous dysplasia, café-au-lait skin macules, and precocious puberty with other variable clinical manifestations. At present, there are difficulties in the molecular diagnosis of McCune-Albright syndrome, and there is a lack of effective clinical treatments to halt or reverse the course and regression of the disease. This article summarizes the clinical manifestations, diagnosis, pathogenic molecular mechanisms, treatment and relevant fertility guidelines of McCune-Albright syndrome, with a view to further research and therapy of McCune-Albright syndrome.

[Investigation on reproductive health status of women workers in different positions in oilfield enterprises].

Objective: The status and influencing factors of reproductive health (including menstrual period and gynecological diseases) of female workers in different positions of oilfield enterprises were analyzed. Methods: From January to December 2020, a total of 979 female workers in an oil field were selected as research objects by the judgment sampling method, and the "Female Reproductive Health Survey" was used as the investigation tool to investigate the demographic characteristics, menstrual status and gynecological diseases. The influential factors were analyzed by 2-test and logistic regression analysis. Results: The prevalence of abnormal menstruation was 26.1% (256/979), dysmenorrhea 53.1% (520/979), and gynecological diseases 54.34% (532/979). The prevalence of breast disease was 23.39% (229/979), uterine disease 11.03% (108/979), cervical disease 10.32% (101/979), and HPV infection 7.97% (78/979). Age, the nature of the job and whether occupational harmful factors were clear were the influencing factors of gynecological diseases (P=0.001, 0.000, 0.007). Age, job nature, working hours and work intensity were the influencing factors of abnormal menstruation (P=0.005, 0.000, 0.000, 0.010) . Conclusion: The reproductive health status of female workers in different positions of oil field enterprises is not optimistic, and the reproductive health status of female workers in professional and technical positions needs to be improved.

Experimental Evidence of Intrinsic Current Generation by Turbulence in Stationary Tokamak Plasmas.

High-ß_{θe} (a ratio of the electron thermal pressure to the poloidal magnetic pressure) steady-state long-pulse plasmas with steep central electron temperature gradient are achieved in the Experimental Advanced Superconducting Tokamak. An intrinsic current is observed to be modulated by turbulence driven by the electron temperature gradient. This turbulent current is generated in the countercurrent direction and can reach a maximum ratio of 25% of the bootstrap current. Gyrokinetic simulations and experimental observations indicate that the turbulence is the electron temperature gradient mode (ETG). The dominant mechanism for the turbulent current generation is due to the divergence of ETG-driven residual flux of current. Good agreement has been found between experiments and theory for the critical value of the electron temperature gradient triggering ETG and for the level of the turbulent current. The maximum values of turbulent current and electron temperature gradient lead to the destabilization of an m/n=1/1 kink mode, which by counteraction reduces the turbulence level (m and n are the poloidal and toroidal mode number, respectively). These observations suggest that the self-regulation system including turbulence, turbulent current, and kink mode is a contributing mechanism for sustaining the steady-state long-pulse high-ß_{θe} regime.

[Clinical features and prognosis of patients with leptomeningeal metastases].

Objective: To describe the clinical manifestations, neuroimaging, cerebrospinal fluid(CSF) cytology and prognosis of Leptomeningeal metastases(LM). Methods: The clinical manifestations, imaging features and CSF cytology of LM patients admitted to Henan Provincial People's Hospital from May 1, 2015 to May 31, 2020 were retrospectively analyzed. The overall survival (OS) was evaluated by the time from the diagnosis of LM to death. Results: A total of 88 patients with LM were enrolled in the study, and the median age was 59 years (range:28-78 years). There were 42 males (47.7%) and 46 females (52.3%). According to the pathological classification, it was lung cancer in 58 cases (65.9%), gastric cancer in 13 cases (14.8%), breast cancer in 7 cases (8.0%), melanoma in 1 case, esophageal cancer in 1 case, gallbladder cancer in 1 case, renal cell carcinoma in 1 case, double source cancer in 2 cases, and unknown source in 4 cases. The median Karnofsky Performance Scale (KPS) score was 50. LM was the initial manifestation of cancer in 34 patients. All patients had LM-related clinical symptoms, including headache in 73 cases (83.0%), nausea and vomiting in 63 cases (71.6%), abnormal physical and mental behaviors in 37 cases (42.0%), seizure in 41 cases (46.6%). Cranial nerve involvement was observed in 23 patients (39.0%) and spinal nerve involvement in 20(33.9%). There were 61 patients (83.6%) who showed neuroimaging features of LM. Tumor cells or atypical cells were found in 90.8% of patients for the first time, and activated monocytes in 47 cases (54.7%). The median OS was 13.0 weeks (95%CI:2.9-23.1) with the 1-year survival rate of 19.1%. Univariate analysis of survival indicated that lung cancer, lower KPS score, tyrosine kinase inhibitors (TKIs) and whole brain radiotherapy were favorable predictors of survival (P<0.05). Conclusions: The overall prognosis of LM is poor. Good physical condition, TKIs treatment and whole brain radiotherapy might improve clinical outcomes of LM patients.

[Visualization analysis of relevant literature on occupational health risk assessment from 2010 to 2019].

Objective: To understand the research status of occupational health risk assessment in recent ten years. Methods: In April 2020, the literatures related to occupational health risk assessment published by CNKI and Web of Science core collection (WoSCC) databases from 2010 to 2019 were searched, and Excel 2016 software was used to organize the literature, CiteSpace 5.6.R2 software was used for visual analysis. Results: A total of 58 Chinese literatures and 407 English literatures were included. The authors of the high frequency posts were Zhang Meibian, and Alessandro Marinaccio, and the publishing institutions were mainly the National Institute for Occupational Health and Poison Control of Chinese Center for Disease Control and Prevention and Finnish Institute Occupational Health. The Chinese journal with the most articles was Chinese Journal of Industrial Hygiene and Occupational Diseases, and the English journal was Safety Science. Chinese high-frequency keywords mainly included risk assessment, occupational health, occupational exposure. English high-frequency keywords mainly included occupational health, risk, risk factor. The prominent words in Chinese literature were occupational health, coal dust, occupational hazards, occupational health and occupational disease hazards; Risk assessment, worker, exposure, heart disease, cardiovascular disease and so on were prominent words in English literature. Conclusion: The main research keywords in the field of occupational health risk assessment at home and abroad focus on occupational health and risk assessment, but the research direction and focus are slightly different.

The role of Sigma-1 receptor agonist in hepatic ischemiareperfusion injury.

Sigma-1 receptor (Sig-1R) is a ligand-operated protein that modulates activity of various proteins. It is expressed within the endoplasmic reticulum membranes of multiple organs. We examined the role of Sig-1R in hepatic ischemia-reperfusion injury (IRI). We studied IRI indicators in Sig-1R-/- mice and compared them with wild-type controls. In addition, we assessed the influence of Sig-1R agonist, fluvoxamine, on IRI in both types of animals. We found that Sig-1R-/- mice exhibited significantly decreased liver damage after hepatic IRI as compared to wild-type mice. This effect was manifested by decreased serum levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT), myeloperoxidase (MPO), and supernatant level of lactate dehydrogenase (LDH), decreased endothelial glycocalyx shedding indexed by decreased serum levels of heparan sulfate and syndecan-1, slightly improved liver histology and reduced metalloproteinase-9 expression. Furthermore, in comparison to Sig-1R-/- mice, fluvoxamine significantly increased serum levels of AST, ALT, MPO, and LDH in wildtype animals in a dose-dependent manner at 6 h after IRI. Our findings demonstrate that the absence of Sig-1R provides a protective effect during hepatic IRI. Sig-1R-mediated signaling pathways may play distinct roles in IRI in different organs. The dynamic interaction between Sig-1R and other signaling molecules in different organs needs to be examined further.

[Effects of down-regulation of IGF2 gene on the biological characteristics of HCT116 colon cancer stem cells].

Objective: To investigate the effect of down-regulation of insulin-like growth factor 2 (IGF2) gene on the biological characteristics of HCT116 colon cancer stem cells (CSCs). Methods: Flow cytometry sorting technology was used to isolate CSCs from colon cancer cell line HCT116 by a monoclonal antibody against CD133; serum free floating culture assay was used for the enrichment of CSCs. The proportion of CD133(+) cells was analyzed by flow cytometry; CSCs were identified by sphere culturing, immunofluorescence analysis and soft agar clone formation. RT-qPCR method was used to examine transcriptional level of IGF2 gene in CSCs. Western blotting was used to examine IGF2 protein expression in CSCs. siRNA was used to establish IGF2 transient knock down model in CSCs. Cell proliferation array, cell cycle and apoptosis analysis, cell invasion array and colony forming assay were used to further examine the role of IGF2 on the biological characteristics of colon CSCs. Results: CSCs were successfully isolated from HCT116 cell lines, which were cultured to form cell spheres in serum-free stem cell culture medium. We found that the morphology of sphere-forming-like cells after several passages maintained the same characteristics as that of the first passage. The results of immunofluorescence showed that CSC markers including CD133 and ALDH continued positively expressing on the cell surface of CSCs, and flow cytometry analysis showed that more than 90% of the spheroid cells remained CD133 positive. The clone formation rate of non-CSCs group and CSCs group were (28.10±2.66)% and (43.73±2.30)% respectively, with significant difference (P<0.01). The RT-qPCR results showed that the transcriptional level IGF2 gene in non-CSCs group and CSCs group were (1.06±0.24) and (2.17±0.51) respectively, with significant difference (P<0.05). The western blot results showed that the protein expression of IGF2 in CSCs group and non-CSCs group were (1.10±0.55) and (2.14±0.23) respectively, with significant difference (P<0.05). Knockdown of IGF2 significantly decreased the percentage of CD133(+) cells in CSCs and cell proliferation (P<0.01). Knockdown of IGF2 increased the percentage of G(2)/M phase (23.46% of siNC group vs 60.14% of siIGF2 group) and cell apoptosis (2.80% of siNC group vs 40.70% of siIGF2 group), while decreased the percentage of G(0)/G(1) phase (40.77% of siNC group vs 17.73% of siIGF2 group). The invasion results showed that the number of cells penetrating into the basement surface in siNC group and siIGF2 group was (109.00±16.37) and (54.00±8.19) respectively, with significant difference (P<0.01). The rate of sphere-forming of colon CSCs in siNC group and siIGF2 group were (51.70±7.42)% and (21.27±2.35)% respectively, with significant difference (P<0.01). The clone formation rate of siNC group and siIGF2 group were (37.20±3.87)% and (18.23±2.25)% respectively, with significant difference (P<0.01). Conclusion: IGF2 gene plays an important role in maintaining the biological characteristics of colon cancer stem cells and promoting self-renewal and stemness of colon CSCs.

[Study on occupational exposure characteristics of Polycyclic Aromatic Hydrocarbons in workers of Carbon Enterprises].

Objective: To investigate the characteristics of occupational exposure to polycyclic aromatic hydrocarbons (PAHs) in the workplace and for various types of work in a carbon enterprise based on the measurement data of various components of PAHs in the air from the workplace of the carbon enterprise, and to provide a scientific basis for protection against PAHs in this enterprise. Methods: In July 2017, a carbon enterprise in Shandong Province and its on-duty workers were chosen as subjects. On-site occupational hygiene investigation and high-performance liquid chromatography were used to investigate and determine the presence and concentrations of PAHs in various workshops and various types of work in the enterprise, and toxic equivalent quantity (TEQ) was used to evaluate the carcinogenic level of PAHs. Results: The components of PAHs with relatively high content in the air of the workplace in the carbon enterprise were fluoranthene, pyrene, benzanthracene, X, and benzo[a]pyrene, with mean concentrations of 1 485.66, 864.66, 805.35, 500.08, and 120.88 ng/m(3), respectively. There were significant differences between the three workshops in the concentrations of PAHs components (benzo[a]pyrene, benzanthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, X, fluoranthene, pyrene, fluorene, indenopyrene, and anthracene) and total TEQ (P<0.05) . The total TEQ of PAHs in the molding workshop was significantly higher than that in other workshops (P<0.05) . There were significant differences between different types of work in the exposure to pyrene and fluoranthene and TEQ (P<0.05) . Shaking-table operators, moving-sieve operators, batching operators, fabric workers, and hot-oil stove workers had higher exposure levels of PAHs. The exposure concentrations of benzo[a]pyrene and benzanthracene were highly correlated with total TEQ. Conclusion: The concentration of PAHs in the working environment of the carbon enterprise is generally higher; benzo[a]pyrene and fluoranthene are the PAHs components against which special protective measures need to be taken; molding workshops are the workshops that are most seriously endangered by PAHs; shaking-table operators are the type of workers needing special protection against PAHs. The occupational hazards of PAHs in the carbon industry cannot be ignored, against which corresponding protective measures should be formulated based on their exposure characteristics.

[Neuroimaging characteristics of cryptogenic stroke with and without patent foramen ovale].

Objective: To explore the neuroimaging characteristics associated with the presence of patent foramen ovale(PFO) for patients with cryptogenic stroke. Methods: We retrospectively collected the clinical and imaging data of cryptogenic stroke patients with PFO and without PFO from Henan Province People's Hospital from January 1, 2013 to June 30, 2017. Lesion patterns and pertinent vascular territory were compared between the two groups. Multivariate logistic regression analysis was used to explore the independent predictors for the presence of PFO. Results: A total of 54 cryptogenic stroke patients with PFO and 50 cases without PFO were recruited. Compared with PFO(-) stroke group, more patients in PFO(+ ) stroke group had migraine(P=0.036), and patients in PFO(+ ) stroke group had higher Risk of Paradoxical Embolism(RoPE) score(P=0.030). The lesion pattern of PFO(+ ) stroke was more frequently observed as multiple lesions in multicirculatory (P=0.035), and infarcts were more likely to be distributed in the vertebrobasilar artery territory (P=0.041); the most frequently involved vessel was the posterior cerebral artery region (P=0.006). More patients with PFO(+ ) stroke had old silent stroke lesion(P=0.021). On multivariate analysis, infarction distributed in the posterior cerebral artery region(OR=4.292, 95% CI 1.469-12.543, P=0.008), silent stroke lesion (OR=6.688, 95% CI 1.277-35.029, P=0.024), and high RoPE score (OR=1.393, 95% CI 1.026-1.893, P=0.034) were independent parameters that could predict the presence of PFO. Conclusions: Multiple lesions in multicirculatory and the posterior predominance are neuroimaging characteristics of cryptogenic stroke with PFO. Infarction distributed in the posterior cerebral artery region, silent stroke lesion and high RoPE score are independent predictors of the presence of PFO.

[Expression of CD117, MITF and NAT10 and their prognostic values in sinonasal mucosal melanoma].

Objective: To investigate the correlation between the expression of CD117, MITF, NAT10 and clinical parameters in sinonasal mucosal melanoma (SNMM). Methods: Formalin-fixed paraffin-embedded tumor specimens of 80 cases of SNMM at the Eye, Ear, Nose and Throat Hospital, Fudan University, from December 1999 to November 2013 were analyzed for CD117, MITF and NAT10 expression by immunohistochemistry. Results: There were 40 men and 40 women. The median age was 61 years, age 26 to 85 years. There was no correlation of the expression of CD117, MITF and NAT10 with the patients' age, gender, tumor site, stage, therapy method and brain metastases (P>0.05). The expression of MITF and NAT10 was associated with lymph node metastasis and the tumors were more likely to metastasize when MITF and NAT10 were positive. However, expression of CD117 had no correlation with lymph node metastasis. Log-rank test revealed that the expression of CD117 was correlated with both three-year and five survival rate (P=0.012, P=0.023; respectively) and patients with tumor having low expression of CD117 had the worse outcome. COX test revealed that low CD117 expression, advanced age and lymph node metastasis were independent risk factors (P<0.05). No significant association was found between the expression of CD117, MITF and NAT10 with disease free survival (P>0.05). Conclusions: Patients with SNMM expressing low level of CD117 have decreased survival rate. Tumors with high level of MITF and NAT10 expression are more likely to metastasize. The expression level of CD117 can be used as an important indicator for the patient survival, and the expression of MITF and NAT10 can be used as a predictor of tumor metastasis.

Small incision releasing of transverse carpal ligament in diagnosis and treatment of mild carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is a medical condition due to compression of the median nerve as it travels through the wrist at the carpal tunnel. Few studies have been carried out to examine the effectiveness of mini-open technique for carpal tunnel release using minor wrist skin crease incision in patients with mild CTS. Therefore, the present study was designed to improve the neurophysiological parameters for the diagnosis of mild CTS, and to examine the effectiveness of small incision surgery for the clinical treatment of mild CTS. To this end, we applied the electrophysiological diagnosis of difference between median and ulnar palmar latencies (PMPU) and the difference of median and ulnar latencies from D4 stimulation (D4MD4U) in 80 patients with mild CTS, whom were diagnosed by hand surgeon at the First Hospital of Jilin University. Those patients showed normal in median nerve electrophysiological examination, and received minor wrist skin crease incision surgery. All patients were followed up and received electromyography (EMG) examination. We showed that D4MD4U and PMPU methods are sensitive diagnosis methods for mild CTS, and mini-open wrist crease incision is beneficial for the treatment of mild CTS in clinical settings.

[Clinical analysis of 9 cases with Anti-leucine-rich glioma inactivated 1 protein antibody associated limbic encephalitis].

Objective: This study was to describe the clinical characteristics of Anti-leucine-rich glioma inactivated 1 protein(LGI1) antibody associated limbic encephalitis. Methods: Clinical data including clinical features, laboratory and radiological findings, treatment and prognosis of the 9 patients were analyzed. Results: In all 9 cases, 6 cases experienced epileptic seizure, 5 cases had psychosis, 7 cases presented with memory impairment, 4 cases showed faciobrachial dystonic seizure, 2 had refractory hyponatremia. One case presented with typically acute Guillain-Barre syndrome (GBS). Anti-LGI1 antibody was detected in 6 cases in cerebrospinal fluid (CSF) samples and 9 in serum samples. Seven cases out of 9 had brain imaging abnormalities. All 9 cases found no evidence of tumors. Eight cases were given immune therapy. During a 1-16 months follow-up, 1 case had complete recovery, 5cases had various degree of sequelae , among whom 4 had memory disturbance and 1 case had changed personality. 2cases were lost to follow-up. Conclusions: Limbic encephalitis is the most common manifestation of anti-LGI1 antibody associated encephalitis. Faciobrachial dystonic seizure (FBDS) is a specific symptom which favors an early diagnosis. Tumor is uncommon to see. The disease has a relatively favorable prognosis while impaired memory can be seen as a common sequelae.

[Diagnostic value of clot burden score of susceptibility vessel sign in arterial thrombosis of acute ischemic stroke and its association with prognosis].

Objective: To analysis the value of susceptibility vessel sign (SVS) in susceptibility weighted imaging (SWI) in detecting thrombogenesis in middle cerebral artery (MCA) and its association with clinical prognosis. Methods: From December 2014 to December 2015 in People's Hospital of Zhengzhou University, we retrospectively examined clinical, imaging and experimental datafrom 104 consecutive patients with acute ischemic strokeand compared the consistency of detecting thrombus between SWI and magnetic resonance angiography (MRA) using Kappa analysis. Clot Burden Score (CBS) was used to analysis extent and scope of thrombus. The association between CBS and clinical prognosiswere analyzed by Spearman rank correlation. Results: Mean age was 60 years old of the 104 patients with acute cerebral infarction and female accounted for 32%. There were 39 patients (37.5%) with SVS positive in SWI and 32 patients (30.8%) with both SVS positive and MRA occlusion or severe stenosis. The consistency in predicting arterial thrombosis of occlusion or severe stenosis between MRA and SVS in SWI was statistically significant (Kappa=0.502, P<0.001). There were 6 cases with SVS positive and none stenosis in MRA, and all the clots in this 6 case were located in distal artery. CBS was significantly associated with 3-month outcome (Spearman ρ =-0.472; P<0.001). Conclusion: SWI is superior to MRA for the detection of intracranial distal thrombus in patients with acute ischemic stroke of the MCA territory. Higher clot burden(lower CBS) could be an important clinical tool to estimate poor outcome in patients with acutecerebral infarction.

[Expression and prognostic values of PD-1, PD-L1 and IDO-1 in sinonasal malignant mucosal melanoma].

Objective: To investigate the correlation between the expression of programmed death-1(PD-1), PD ligand-1(PD-L1), indoleamine 2, 3-dioxygenase 1(IDO-1) and clinical parameters in sinonasal malignant mucosal melanoma (SNM). Methods: Samples from 86 SNM patients who did not receive immune-targeted therapy and radio-chemotherapy were analyzed for PD-1, PD-L1, and IDO-1 expression by immunohistochemistry. Results: High clinical/pathologic staging, brain metastases and advanced age were independent risk factors of poor prognosis. The overall survival rate of SNM without pigment was lower than that with pigment. PD-1, PD-L1 and IDO-1 expression was not correlated with tumor pigmentation, but correlated with different primary site.PD-1, PD-L1 and IDO-1 were expressed in 47.6% (41/86), 53.5% (46/86) and 58.1% (50/86)of SNM samples respectively. PD-1 was associated with brain metastasis. Negative expression of PD-1(P=0.031) and IDO-1(P=0.017 9) correlated with worse disease-free survival. No significant association was found between PD-L1 and prognosis. For stages Ⅲ, ⅣA and ⅣB patients, PD-1 expression was associated with better outcome (P=0.025), but PD-L1 negative and IDO-1 positive patients hadworse outcome (P>0.05). PD-1 positive and IDO-1 negative stage ⅣC patients had poorer overall survival. Conclusions: In SNM patients, clinical/pathologic staging, brain metastases, age and pigmentation were prognostic indicator. IDO-1 and PD-1 can also be used as reference to evaluate prognosis. Anti-IDO-1 targeted therapy may be suitable for middle to late stage patients, while advanced stage patients might benefit from anti-PD-1 targeted therapy. PD-1/PD-L1 and IDO-1 may be considered as joint targeted therapy.The predictive value of PD-L1 requires further study.

Co-suppression of vitamin C composite nano-drug carrier and its drug delivery to nidus in tumor cells.

This study aimed to discuss the co-suppression of vitamin C-contained composite nano-drug carrier and its drug delivery to nidus in tumor cells. Amphiphilic polymers PLA-block-PAAA and block polymer PLA-PEG4000-Maleimide, PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelles were prepared, and, PLA-block-PAAA polymer-coated Nile red nano-micelle, PLA-block-PAA and PLA-PEG4000-Maleimide composite nano-micelles as well as paclitaxel-carrying composite nano-micelle in different molar ratios were given stability tests. Lastly, PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelle cancer cells and paclitaxel-carrying composite nano-micelle cancer cells were given toxicity tests. Stability tests showed that self stability of PLA-block-PAAA (63/8) nano-micelle was not sufficient; the stability was good when the molar ratio of PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelle was 3:1; paclitaxel-carrying composite nano-micelle had good stability within 48 hours; PAAA segment had an inhibiting effect on C6 cancer cells and paclitaxel-carrying composite nano-micelle had a strong inhibiting effect also on tumors. After 24 hours, with the continuous release of paclitaxel, the tumor inhibiting effect of paclitaxel-carrying composite nano-micelle enhanced gradually, and the controlled-release of drugs had continuous inhibiting effect on tumor cells. Therefore, PAAA segment and paclitaxel had time-postponed synergistic effect. In conclusion, vitamin C-contained composite nanometer drug carrier materials can deliver anti-cancer drugs to nidus and thus inhibit tumor cells.

Identification and pathogenicity of Vibrio parahaemolyticus isolates and immune responses of Penaeus (Litopenaeus) vannamei (Boone).

Five different Vibrio parahaemolyticus strains (SH8, SH108, SH58, AH5 and GD10) isolated from the hepatopancreas of moribund shrimp in farms of mainland China were identified and capable of inducing massive mortality of Penaeus (Litopenaeus) vannamei. The immersion challenge results with five isolates indicated variance of virulence, while only GD10 caused massive sloughing of tubule epithelial cells which was recognized as the most significant symptom of AHPND. Differences in immune responses were detected of P. vannamei during 48 h post-infection (p.i.) by injection or immersion challenge with V. parahaemolyticus (SH8, SH108 and GD10) isolates. When injected SH8 and SH108 isolates, the expression of lysozyme (LSZ) showing statistically significant upregulation at 16 and 48 h p.i. and that of Toll-like receptors (TLR) showed statistically significant upregulation at 48 h p.i. When immersion challenge with the GD10 isolate, TLR were upregulated after 8 h p.i. challenge with 10(4)  cfu mL(-1) ; however, LSZ was downregulated when challenged with 10(3)  cfu mL(-1) . The results suggested that LSZ and TLR serve as crucial molecular markers of innate immunity in shrimp against V. parahaemolyticus infection. LSZ is a vital marker for acute bacterial infection, while TLR serves as a crucial marker for chronic infection.

Genome-wide identification, phylogenetic relationships, and expression analysis of the carotenoid cleavage oxygenase gene family in pepper.

Carotenoid cleavage oxygenases (CCOs) are a family of dioxygenases, which specifically catalyze the cleavage of conjugated double bonds in carotenoids and apocarotenoids in plants. In this study, genome-wide analysis of CCO genes in pepper plants was performed using bioinformatic methods. At least 11 members of the CCO gene family were identified in the pepper genome. Phylogenetic analysis showed that pepper and tomato CCO genes could be divided into two groups (CCDs and NCEDs). The CCD group included five sub-groups (CCD1, CCD4, CCD7, CCD8, and CCD-like). These results indicate that there is a close genetic relationship between the two species. Sequence analysis using the online tool, Multiple Expectation Maximization for Motif Elicitation (MEME), showed that the CCO proteins comprise multiple conserved motifs, with 20 to 41 amino acids. In addition, multiple cis-acting elements in the promoter of CCO genes were identified using the online tool PlantCARE, and were found to be involved in light responsiveness, plant hormone regulation, and biotic and abiotic stresses, suggesting potential roles of these proteins under different conditions. RNA-seq analysis revealed that the CCO genes exhibit distinct patterns of expression in the roots, stems, leaves, and fruit. These findings suggest that the CCO genes have important roles in the vegetative and reproductive development of pepper plants.

Role of TGFB1 polymorphism in the development of metastatic brain tumors in non-small cell lung cancer patients.

We conducted a case-control study to investigate the role of 3 single-nucleotide polymorphisms of the gene encoding transforming growth factor-b1 (TGFB1) in the development of metastatic brain tumors in non-small cell lung cancer patients. The polymorphisms in TGFB1 rs4803455, rs1800469, and rs1800470 were evaluated by polymerase chain reaction-restriction fragment length polymorphism. Odds ratios and their corresponding 95% confidence intervals were used to assess the influence of TGFB1 rs4803455, rs1800469, and rs1800470 on metastatic brain tumors. We found that cases were more likely to have a later disease stage when compared with control subjects, without brain metastasis. Individuals carrying the TGFB1 rs1800469 TT and CT+TT genotypes had an increased risk of developing brain metastasis compared with the rs1800469 CC genotype. Moreover, a significant interaction was observed between the rs1800469 polymorphism and disease stage. However, no significant association between polymorphisms rs4803455 and rs1800470 and the risk of developing brain metastasis were observed. We found that the TGFB1 rs1800469 polymorphism may be predictive biomarker for the risk of developing brain metastasis in non-small cell lung cancer patients.

Detection of the genetic variation of polygalacturonase-inhibiting protein gene 2 in autotetraploid alfalfa (Medicago sativa) using an improved SSCP technique.

In this study, 2 approaches were adopted to obtain good single-strand conformation polymorphism (SSCP) data for autotetraploid alfalfa; primers were added to PCR products, and fluorescent-labeled primers were utilized. PCR-SSCP conditions for a 331-bp fragment in the coding region of polygalacturonase-inhibiting protein gene 2 in alfalfa (MsPGIP2) were optimized, and the results showed that the best SSCP gel pattern could be obtained when the loading mixture was made by mixing 1 µL PCR products, 0.2 to 0.8 µL unlabeled primers (50 µM) and 4 to 16 µL loading buffer. Furthermore, the use of the fluorescent-labeled primers resulted in 2 separated electrophoresis images from 2 complementary single DNA strands, thus making the determination of alleles and idiotypes a relatively easy task. In addition, the results of sequencing prove that the determination of alleles and idiotypes were accurate based on SSCP analysis. Finally, a total of 9 alleles with 18 SNP sites were identified for MsPGIP2 in the alfalfa variety 'Algonquin'. In conclusion, MsPGIP2 possessed great genetic variation, and the addition of primers to the PCR products in combination with the fluorescent labeling of primers could significantly improve the sensitivity and resolution of SSCP analysis. This technique could be used for genetic diversity detection and marker-assisted breeding of useful genes in autopolyploid species such as alfalfa.