Assessing hydrological connectivity for natural-artificial catchment with a new framework integrating graph theory and network analysis.

Anthropogenic activities alter the underlying surface conditions and arrangements of landscape features in a drainage basin, interfering with the pollutant (e.g., dissolved nitrogen, phosphorus) transport network configuration and altering the hydrological response. Assessing the impact of anthropogenic activities on hydrological connectivity for natural-artificial catchment is critical to understand the hydrological-driven ecosystem processes, services and biodiversity. However, quantifying this impact at catchment scale remains challenging. In this study, a new framework was proposed to quantify the impact of anthropogenic activities on hydrological connectivity combined with graph theory and network analysis. This framework was exemplified in a natural-artificial catchment of the Yangtze River basin of China. Based on remote sensing and field-investigated data, three transport networks were constructed, including natural transport network (N1), ditch-road transport network (N2), and terrace-dominated transport network (N3), which reflected the different human intervention. The results showed that human intervention improved the connectivity of the nodes and enhanced the complexity of the catchment transport network structure. Anthropogenic activities significantly decreased the hydrological structural connectivity of the catchment. In particular, compared with the N1 network, the critical nodes for hydrological connectivity which were judged by connectivity indexes were reduced by 92.94% and 95.29% in the N2 and N3 network, respectively. Furthermore, the ditch-road construction had a greater impact than terraces in decreasing hydrological structural connectivity at catchment scale. This framework has proven effective in quantifying the hydrological connectivity analysis under different human intervention at the catchment scale and facilitates the improvement of catchment management strategies.

[ANXA8 Regulates Proliferation of Human Non-Small Lung Cancer Cells A549 via EGFR-AKT-mTOR Signaling Pathway].

Annexin A8 (ANXA8) is a member of the annexin family, which had been reported to regulate multiple cancer cellular processes including proliferation, metastasis and inflammation. However, the specific role of ANXA8 in lung cancer cell biology remains unknown. Our previous transcriptome study revealed that ANXA8 mRNA was downregulated in curcumin analog (MHMD) -treated human non-small lung cancer cells (A549 cell line). Here, we continued to study the ANXA8 expression in A549 cells using reverse transcription-quantitative PCR and Western blotting, compared with that in human normal bronchial epithelium cells (BE-AS-2B cell line). Overexpression of ANXA8 via transfection of pEGFP-ANXA8 recombinant vector contributed to the proliferation and migration of A549 cells. Moreover, the cell cycle protein cyclin E1 was upregulated in ANXA8-transfected A549 cells. Knockdown of ANXA8 using an RNA interference technique decreased A549 cell viability and restrained their migration in vitro. The expression levels of multiple cellular factors, including EGFR, PI3K, Akt, mTOR, p70S6K and 4EBP1, in the epidermal growth factor receptor (EGFR) signaling pathway were also altered by ANXA8 knockdown or overexpression in A549 cells, which confirmed the activation of the EGFR/Akt/mTOR signaling pathway by ANXA8. The present results provided evidence to support further investigation of the functional identification of ANXA8 in lung cancer cells in the future.

[Recommended intakes of protein and energy in patients with chronic kidney disease: from guidelines of KDOQI and KDIGO in 2020].

The recommended intakes of protein and energy play a key role in medical nutrition therapy (MNT) management in patients with chronic kidney disease (CKD). In September 2020, the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) released the clinical practice guideline for nutrition in CKD, which updated its previous version published 20 years ago. In October 2020, "Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group" published KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. The opinions and recommendations on protein and energy intakes from these two guidelines were different. This article compares and discusses the differences among various national and international guidelines so as to facilitate the clinical practice for CKD patients.

[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.

[Study on the mechanism of brain damage based on structural covariant network to evaluate the brain structure of nicotine addicts].

Objective: To explore the neuromechanism of nicotine dependence, structural covariation networks (SCNs) based on voxel-based morphometry (VBM) were used to study the synergistic changes in gray matter volume in different cerebral cortices of nicotine dependent individuals. Methods: During the period from August 2016 to February 2018, a total of 118 long-term smokers and 57 non-smoking healthy controls (both 18-55 male volunteers) through online platforms and leaflets were recruited. The subjects were scanned with SIEMENS Skyro 3.0T magnetic resonance scanner and underwent routine MRI sequence (preliminary elimination of intracranial lesions) and 3D-T1 (3D-mprage) sequence structure. Two imaging experts used Matlab software platform to carry on segmentation by using SPM8, and to find out the differences between the two groups of brain regions, and differences in brain regions as region of interest (ROI) structure association network analysis. Results: The gray matter volume (GMV) of the right anterior central gyrus and the left inferior parietal lobe in the smoking group decreased(voxels size were 55 and 284, respectively), and no gray matter volume (GMV) area increased. The network structure of covariant analysis found that when the inferior parietal lobe as the seed points, the smoking group showed a rising trend in left parietal lobe and left temporal pole, bilateral middle temporal gyrus, left postcentral gyrus and right middle frontal gyrus gray matter volume, and a downtrend in the right side of the left medial frontal gyrus, superior parietal lobe, bilateral temporal gyrus, left cingulate gyrus and left cerebellum (central) compared with the control group. Conclusion: In long-term smokers, there is a volume change of gray matter in the brain structure. Abnormal changes in the structure covariant network of the inferior parietal lobe can lead to impaired brain function in nicotine dependent patients.

[PLA2G6 compound complicated mutation in an atypical neuroaxonal dystrophy pedigree].

Objective: To analyze the clinical presentation, imaging features, and the mutation of the pathogenic genes in a Chinese Han atypical neuroaxonal dystrophy pedigree. Methods: A family of atypical neuroaxonal dystrophy pedigree who came to Henan Provincal People's Hospital in July 2016 was included. Clinical presentation, imaging features of the pedigree were analyzed, and all exon gene detection of the proband was performed to capture the target variations, then verified by sanger sequence. Another 4 family members' and 100 normal healthy controls' gene sequence of the mutations were also verified. Results: The proband(Ⅱ(3)) of the family presented with walking unsteadily, intellectual disability, glossolalia, dystonia, epilepsy, and autonomic nervous dysfunction. The magnetic resonance imaging (MRI) of the proband showed cerebellar atrophy and iron deposit in basal ganglia. The gene detection showed the PLA2G6 gene compound complicated mutation of 80 codon p.A80T in the exon 3 and 331 codon p.D331Y in the exon 7. The two sisters of the proband (Ⅱ(1),Ⅱ(2)) had the same mutation, the father of the proband carried the p.A80T, however, the mother carried the D331Y mutation. One of the proband's sister (Ⅱ(1)), whose onset age was 10 years old, had the similar symptoms with the proband. The proband's another sister(Ⅱ(1)) had abnormal gait at 24 years old. However, the MRI of the two sisters all showed cerebellar atrophy. Conclusion: We report a PLA2G6 compound complicated mutation in an atypical neuroaxonal dystrophy Chinese family, that is the p. A80T and p.D331Y mutation, which may be a pathogenic mutation to cause the family's disease.

Alanine Scanning Mutagenesis of the MEDI4893 (Suvratoxumab) Epitope Reduces Alpha Toxin Lytic Activity In Vitro and Staphylococcus aureus Fitness in Infection Models.

Alpha toxin (AT) is a cytolytic pore-forming toxin that plays a key role in Staphylococcus aureus pathogenesis; consequently, extensive research was undertaken to understand the AT mechanism of action and its utility as a target for novel prophylaxis and treatment strategies against S. aureus infections. MEDI4893 (suvratoxumab) is a human anti-AT IgG1 monoclonal antibody (MAb) that targets AT and is currently in phase 2 clinical development. As shown previously, the MEDI4893-binding epitope on AT is comprised of the highly conserved amino acid regions 177 to 200 and 261 to 271, suggesting these amino acids are important for AT function. To test this hypothesis and gain insight into the effect of mutations in the epitope on AT neutralization by MEDI4893, nine MEDI4893 contact residues in AT were individually mutated to alanine. Consistent with our hypothesis, 8 out of 9 mutants exhibited >2-fold loss in lytic activity resulting from a defect in cell binding and pore formation. MEDI4893 binding affinity was reduced >2-fold (2- to 27-fold) for 7 out of 9 mutants, and no binding was detected for the W187A mutant. MEDI4893 effectively neutralized all of the lytic mutants in vitro and in vivo When the defective mutants were introduced into an S. aureus clinical isolate, the mutant-expressing strains exhibited less severe disease in mouse models and were effectively neutralized by MEDI4893. These results indicate the MEDI4893 epitope is highly conserved due in part to its role in AT pore formation and bacterial fitness, thereby decreasing the likelihood for the emergence of MAb-resistant variants.

Multimechanistic Monoclonal Antibodies (MAbs) Targeting Staphylococcus aureus Alpha-Toxin and Clumping Factor A: Activity and Efficacy Comparisons of a MAb Combination and an Engineered Bispecific Antibody Approach.

Secreted alpha-toxin and surface-localized clumping factor A (ClfA) are key virulence determinants in Staphylococcus aureus bloodstream infections. We previously demonstrated that prophylaxis with a multimechanistic monoclonal antibody (MAb) combination against alpha-toxin (MEDI4893*) and ClfA (11H10) provided greater strain coverage and improved efficacy in an S. aureus lethal bacteremia model. Subsequently, 11H10 was found to exhibit reduced affinity and impaired inhibition of fibrinogen binding to ClfA002 expressed by members of a predominant hospital-associated methicillin-resistant S. aureus (MRSA) clone, ST5. Consequently, we identified another anti-ClfA MAb (SAR114) from human tonsillar B cells with >100-fold increased affinity for three prominent ClfA variants, including ClfA002, and potent inhibition of bacterial agglutination by 112 diverse clinical isolates. We next constructed bispecific Abs (BiSAbs) comprised of 11H10 or SAR114 as IgG scaffolds and grafted anti-alpha-toxin (MEDI4893*) single-chain variable fragment to the amino or carboxy terminus of the anti-ClfA heavy chains. Although the BiSAbs exhibited in vitro potencies similar to those of the parental MAbs, only 11H10-BiSAb, but not SAR114-BiSAb, showed protective activity in murine infection models comparable to the respective MAb combination. In vivo activity with SAR114-BiSAb was observed in infection models with S. aureus lacking ClfA. Our data suggest that high-affinity binding to ClfA sequesters the SAR114-BiSAb to the bacterial surface, thereby reducing both alpha-toxin neutralization and protection in vivo These results indicate that a MAb combination targeting ClfA and alpha-toxin is more promising for future development than the corresponding BiSAb.

[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.

[Effect of blood pressure control level on perinatal outcomes in women with mild-moderate gestational hypertension].

Objective: To investigate the effect of blood pressure (BP) control level on perinatal outcomes in women with mild-moderate gestational hypertension (GHp). Methods: Totally, 344 women diagnosed initially as mild-moderate GHp who delivered in Peking University Third Hospital from January 2012 to December 2016 were recruited. They were divided into four groups according to the stabilized level of BP during pregnancy. (1) Group A: BP<130/80 mmHg (1 mmHg=0.133 kPa) ; (2) Group B: BP (130-139) / (80-89) mmHg; (3) Group C: BP (140-149) / (90-99) mmHg; (4) Group D: BP (150-159) / (100-109) mmHg. The clinical profile and incidence of severe GHp, pre-eclampsia with proteinuria (PE+Upro), severe pre-eclampsia (sPE), small-for-gestational age (SGA) were compared among the four groups. Student t-test was preformed to normal distributive data and Kruskal-Wallis test was used to non-normally distributed variables. Chi-square test was used in count data. Logistic regression analysis was adopted for multiple-factor analysis. Results: (1) The incidence of severe GHp in group A was lower than group B (P<0.05). The incidences of severe GHp and sPE in the group B was lower than those in group C (P<0.05). While there was no difference in the incidence of PE+Upro and SGA among the four groups (P>0.05). And the incidence of severe GHp in group D had no difference with group A, B, C (P>0.05). (2) In the 48 patients who used medications to control BP, the occurence of severe GHp in those whose initial BP was (140-149) / (90-99) mmHg was lower than those of ≥160/110 mmHg (P<0.05). But the incidence of severe GHp had no significant difference between patients whose initial BP was (140-149) / (90-99) mmHg and patients whose initial BP was (150-159) / (100-109) mmHg (P>0.05). The initial BP level had no impact on the incidence of PE+Upro, sPE and SGA (P>0.05). (3) Multivariate logistic regression analysis showed that the BP level before using medications (OR=3.566, 95%CI: 1.080-11.771, P=0.037) and the BP level maintained (OR=4.787, 95%CI: 1.115-20.551, P=0.035) were independent factor that affected the incidence of severe GHp. Edema (OR=2.651, 95% CI: 1.628-4.316 P=0.000), fetal growth restriction (FGR; OR=1.103, 95% CI: 1.427-5.914, P=0.002) and the onset gestational age of GHp (OR=0.755, 95%CI: 0.578-0.985, P=0.038) were independent factors that affected the incidence of PE+Upro. The tendency of FGR (OR=17.787, 95%CI: 1.833-40.396 P=0.000), history of PE (OR=5.294, 95%CI: 1.086-25.800, P=0.039) and the BP level during pregnancy (OR=2.109, 95%CI: 1.274-3.491, P=0.004) were independent factors affecting the incidence of sPE. FGR tendency was independent factor affecting the incidence of SGA (OR=25.622, 95%CI: 2.596-252.864, P=0.005). Conclusion: A satisfied control of BP is helpful to reduce severe GHp and sPE, but the incidence of SGA does not affected.

[Association between the time of sedentary behaviors and risk of type 2 diabetes].

Objective: To explore the relationship between the time of sedentary behaviors and the risk of type 2 diabetes mellitus (T2DM) among rural adults in Henan Province. Methods: A total of 1 227 adults from Houzhai village in Zhengzhou City and Qiaomiao village in Jiaozuo City in Henan Province were randomly selected to participate in the survey; each of them finished a questionnaire and accepted physical examination and test of biochemical indicators. The participants were divided into case and control groups according to whether suffering from T2DM. A Pearson linear correlation and linear regression model analysis were used to investigate the relevance between the time of sedentary behaviors and fasting plasma glucose (FPG); meanwhile, a multi factor logistic regression model was used to analyze the relationship between the time of sedentary behaviors and T2DM. Results: The average FPG level among the participants was (5.4±2.5) mmol/L, and the average time of sedentary behaviors was (234.5±156.5) min per day. The prevalence rate of T2DM in subgroups whose time of sedentary behaviors were separately 0-<2.5, 2.5-<4.5, 4.5-<6.5 and ≥6.5 h/day were 15.8% (72/457), 19.3% (73/379), 16.7% (35/210) and 20.4% (37/181), respectively. There was a linear regression relationship between the time of sedentary behaviors(x) and FPG(y), the regression equation was: y=5.081+0.001x (t=3.01, P=0.003). Logistic regression model analysis showed that participants whose time of sedentary behaviors ≥6.5 h/day had significantly higher risk of T2DM than those whose time of sedentary behaviors between 0-2.4 h/day (OR=1.77, 95%CI: 1.11-2.81) after age and gender adjusted. However, the associations only exist in males and adults ≥50 years old according to sex and age stratification. It showed that participants with sedentary time ≥6.5 h/day had significantly higher risk of T2DM than those with sedentary time between 0-<2.5 h/d, with the corresponding OR (95%CI) at 2.34 (1.21-4.52) and 2.22 (1.19-4.16), respectively. Conclusion: The prolonged sedentary time is a risk factor of type 2 diabetes. After stratification by gender and age, the correlation only found in males and adults aged ≥50 years old.

[The progress in the diagnosis and management of orbital lymphoma].

Lymphoma is one of the most common malignant tumor of the orbit in adults. Orbital lymphoma mainly consists of extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue, follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, infrequent NK/T cell lymphoma and Burkitt lymphoma. Diagnosis on orbital lymphoma remains challenging in that it is difficult to distinguish it from benign lesions, especially for low degree lymphomas. Combined examinations of histological, cytological and molecular features are required to make final differentiation. There are many treatment options for diagnosis of orbital lymphoma, such as surgical resection, radiotherapy, chemotherapy, monoclonal antibody targeted therapy, immunotherapy. The appropriate scenario of treatment on orbital lymphoma should be made based on the Ann Arbor or TNM staging system to determine the stage of orbital lymphoma at the moment for maximizing the results. The latest concepts on diagnosis and management of orbital lymphoma are reviewed in this paper. (Chin J Ophthalmol, 2017, 53: 632-636).

Electrophoretic deposition of graphene oxide reinforced chitosan-hydroxyapatite nanocomposite coatings on Ti substrate.

Electrophoretic deposition (EPD) is a facile and feasible technique to prepare functional nanocomposite coatings for application in orthopedic-related implants. In this work, a ternary graphene oxide-chitosan-hydroxyapatite (GO-CS-HA) composite coating on Ti substrate was successfully fabricated by EPD. Coating microstructure and morphologies were investigated by scanning electron microscopy, contact angle test, Raman spectroscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis. It was found GO-CS surface were uniformly decorated by HA nanoparticles. The potentiodynamic polarization test in simulated body fluid indicated that the GO-CS-HA coatings could provide effective protection of Ti substrate from corrosion. This ternary composite coating also exhibited good biocompatibility during incubation with MG63 cells. In addition, the nanocomposite coatings could decrease the attachment of Staphylococcus aureus.

Prognostic role of the cancer stem cell marker CD44 in ovarian cancer: a meta-analysis.

This meta-analysis study aimed to investigate the correlation between CD44-positive cancer stem cells (CSCs) and clinicopathological features and its effect on the survival of ovarian cancer patients. A comprehensive literature search in the electronic databases, including PubMed, EMBASE, and Wanfang (up to December 1, 2015), was conducted. Publications assessing the clinical or prognostic significance of CD44 expression in ovarian cancer were identified and reviewed until December 1, 2015. A meta-analysis was then performed to examine the association between CD44 expression and clinical outcomes of ovarian cancer. A total of 8 publications comprising 957 cases satisfied the criteria and were included for this meta-analysis. Our results show that CD44 expression was not significantly associated with the tumor grade (OR = 2.31, 95%CI = 0.61-8.73, P = 0.22), age of the patients (OR = 0.89, 95%CI = 0.32- 2.53, P = 0.83), residual tumor size (OR = 1.01, 95%CI = 0.30-3.40, P = 0.99), or response to chemotherapy (OR = 3.49, 95%CI = 0.51-23.65, P = 0.20). However, our meta-analyses of the data from the identified studies demonstrate that CD44 expression was significantly correlated with tumor lymphatic metastasis (OR = 2.66, 95%CI = 1.36-5.22, P = 0.004), tumor TNM stage (OR = 2.34, 95%CI = 1.76-3.12, P < 0.00001), and decreased overall survival for ovarian cancer patients (RR = 1.47, 95%CI = 1.23- 1.74, P < 0.0001). In conclusion, our findings show that CD44-positive ovarian cancer patients exhibit worse prognosis, which was associated with common clinicopathological features and poor prognostic factors.

[Evaluation and establishment of Mongolian gerbil model of long-term infection of Helicobacter pylori with highly-expressed thioredoxin-1 gene].

OBJECTIVE: To establish a Mongolian gerbils model by long-term infection of Helicobacter pylori (Hp) with highly-expressed thioredoxin-1 (Trx1) gene and to investigate the histopathological findings of gastric mucosa in Mongolian gerbils. METHODS: In this study, 75 healthy male Mongolian gerbils were randomly divided into 3 groups: Hp with highly-expressed Trx1 gene group (n=30), Hp with lowly-expressed Trx1 gene group (n=30), and control group (n=15). The animals underwent gastric perfusion of Hp suspension once a week for 5 weeks. The animals were sacrificed at the end of 4, 20, 34, 48, 70, and 90 weeks after inoculation for detecting Hp colonization by rapid urease test and Warthin-Starry silver staining and histological examination, respectively. RESULTS: (1) The Mongolian gerbil model of long-term infection of Hp with highly-expressed Trx1 gene and lowly-expressed Trx1 gene were successfully established. (2) The macroscopic mucosal lesions, including erythema, uneven, erosion, nodules, etc. could be observed in experimental groups. The severity of lesions and the time when lesions occurred in Hp with highly-expressed Trx1 gene group were heavier/earlier than that in Hp with lowly-expressed Trx1 gene group. (3) Histopathologically, the gastric mucosa of Hp with highly-expressed Trx1 gene group showed the mild dysplastic hyperplasia of epithelial cells 34 weeks after the Hp inoculation, and the time was in the 48th week in Hp with lowly-expressed Trx1 gene group. At the end of the 90th week after Hp inoculation, the gastric adenocarcinoma could be detected in the two experimental groups (71.4% vs. 42.8%). The difference between the two experimental groups did not reach statistical significance (P=0.592), which might be due to the small sample capacity and/or short observation time. In addition, there were 2 cases with severe epithelial dysplastic hyperplasia in Hp with highly-expressed Trx1 gene group, and only 3 cases with moderate epithelial dysplastic hyperplasia in Hp with lowly-expressed Trx1 gene group. The uninfected control animals showed no abnormal findings throughout the entire observation period. CONCLUSION: Hp with highly-expressed/lowly-expressed Trx1 gene colonizes stably in the glandular gastric mucosa of Mongolian gerbils. The histological changes after infection are similar to those of the Hp infected human being, and Hp with highly-expressed Trx1 gene cause the injury of gastric mucosa and the occurrence of gastric adenocarcinoma. Trx1 maybe the virulence factor that participates in the pathogenesis of gastric cancer and Hp expressing high levels of Trx1 should be highly toxic for gastric diseases in China.

[Clinical analysis of fourteen cases with neuromyelitis optica spectrum disorders].

Objective: To analysis the clinical manifestation, radiological data, laboratory findings of neuromyelitis optica spectrum disorders (NMOSD) to help physicians have a deeper understanding of the disease. Methods: The clinical manifestations, radiological data, laboratory findings of NMOSD patients from People's Hospital of Zhengzhou University between June 2015 and June 2016 were retrospectively analyzed. Results: Fourteen patients with NMOSD were enrolled, consisting of 3 males and 11 females. The onset age ranged from 15 to 62 years, in average 39.64. Among them, there was 1 case with history of hyperthyroidism, 3 cases with Sjögren syndrome (SS). Major clinical manifestations were vision loss in 4 cases, nausea and vomiting in 4 cases, limbs numbness and weakness in 6 cases. All the 14 patients were received the cerebrospinal fluidcell surface antigen antibody detection, and the results were strong positive 6 cases (6/14), positive 7 cases (7/14), weak positive 1 case (1/14). Abnormal signals in the thirdventricle, midbrain aqueduct, oblongata, pons and cervical, thoracic spinal cord were found by Magnetic Resonance Imaging (MRI). Fourteen patients were treated with glucocorticoid, among them 8 received immunosuppressive therapy. All the 14 patients were followed up, and 9 patients had different degrees of sequelae, including vision decline in 4 cases, numbness and weakness in 5 cases. Conclusions: Neuromyelitis optica spectrum disorders frequently occur in young female. Clinicians need to consider the possibility of NMOSD for acute or subacute blurred vision, nausea, vomiting, numbness and weakness of limbs or trunk and psychiatric symptoms. NMOSD can not be easily excluded for those special patients with atypical clinical manifestations, and relevant inspections should be performed as far as possible in order to make the correct diagnosis.

[Effect of prenatal stressful life event exposure on child emotional and behavioral problem at age 2-6 years].

Objective: To investigate the influence of prenatal stressful life event (SLE) exposure on child emotional and behavioral problem at age 2-6 years and identify the most risk exposure period. Methods: A total of 2 524 mother-child pairs were selected from Shanghai Maternal-Child Pairs Cohort based on pregnant women form 2016 to 2018 in Shanghai. Prenatal SLE exposure was assessed by Life Events Scale for Pregnant Women Questionnaire during the first and third trimester of pregnancy. Child emotional and behavioral problem was evaluated by Strengths and Difficulties Questionnaire at age 2-6 years. Multivariate binary logistic regression model and generalized estimating equation were conducted to quantify the association between prenatal SLE exposure and child emotional and behavioral problem at age 2-6 years, and identify the pregnancy period with strongest adverse effect. Results: The 2 524 mother-child pairs were divided into 4 groups: group with consistent low exposure to SLE (61.8%), group with high exposure to SLE in the first trimester (13.2%), group with high exposure to SLE in the third trimester (13.2%) and group with consistent high exposure to SLE (11.8%). The detection rates of emotional problem, hyperactivity, peer interaction problem and total difficulty score in children aged 3-6 years were highest in the group with consistent high exposure to SLE. Generalized estimating equation analysis showed that after controlling the confounding factors, compared with the consistent low exposure group, the children in the group with high exposure to SLE in the first trimester had significant increased risk for conduct problem at age 2-6 years (aOR=1.41, 95%CI:1.07-1.87). The children in the group with consistent high exposure to SLE were at increased risk for emotional problem, peer interaction problem, and high total difficulty score with the aOR of 1.41 (95%CI: 1.09-1.83), 1.46 (95%CI: 1.15-1.86) and 1.51(95%CI: 1.17-1.93). Conclusion: These findings indicated that prenatal exposure to SLE have adverse effect on child emotional and behavioral problem at age 2-6 years, especially the exposure in the first trimester.

[Clinical efficacy of allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome-evolved acute myeloid leukemia].

Objective: The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored. Methods: A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored. Results: Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade Ⅲ/Ⅳ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS (P<0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade Ⅲ or Ⅳ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS (P=0.001, HR=6.981, 95%CI 2.186-22.300; P=0.010, HR=6.719, 95%CI 1.572-28.711; P=0.026, HR=3.386, 95%CI 1.158-9.901; P=0.006, HR=0.151, 95%CI 0.039-0.581) . Conclusion: For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.

[Clinical analysis of allogeneic hematopoietic stem cell transplantation for seven cases of acute myeloid leukemia with BCR::ABL1 fusion].

Objective: To explore the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML) patients with BCR::ABL1 fusion. Methods: The clinical data of seven AML patients with BCR::ABL1 fusion from November 2012 to January 2022 were retrospectively analyzed, and their survival status was followed up. Results: The median age of patients at the time of diagnosis was 35 years. Four cases (57.1%) were diagnosed with high leukocyte counts. All cases were assayed as BCR::ABL1 positive and accompanied by four types of gene mutations (NPM1, RUNX1, ASXL1, PHF6) . Seven patients received tyrosine kinase inhibitor (TKI) combined with induction chemotherapy and bridged to allo-HSCT, and six patients received maintenance therapy with TKI. Before allo-HSCT, six patients achieved complete remission, and four patients achieved complete molecular remission (CMR) . After allo-HSCT, the three remaining cases also achieved CMR. All patients were in remission post-allo-HSCT. One case died of infection, and the remaining cases survived without relapse. The 3-year cumulative overall survival rate was (80.0±17.9) %. Conclusions: TKI combined with traditional chemotherapy could achieve a high response rate in AML patients with BCR::ABL1 fusion. In addition, allo-HSCT could enhance the molecular response rate. Maintenance therapy post-HSCT with TKI could improve prognosis.

[Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study].

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.