[Association of temperament type and mother's emotional state with acute respiratory infection in children].

OBJECTIVE: To explore the correlation of temperament type and mother's emotional state with acute respiratory tract infections in children so as to provide evidence for comprehensive treatment of the infections. METHODS: A total of 200 children aged between 3 and 6 were enrolled in this study from two kindergartens of Guangzhou and Hengyang. The mothers were invited to complete a questionnaire of the children's general information followed by assessment using children's temperament scale and the Depression-Anxiety-Stress Scale. RESULTS: The total incidence of acute respiratory infection was significantly higher in children with a hard- to-raise temperament than the easy- to-raise children (P < 0.05); the incidences of acute rhinitis, acute pharyngitis, acute laryngitis and acute bronchitis were all significantly higher in the hard-to-raise children (P < 0.05). A significant positive correlation was identified between the total number of episodes of acute respiratory tract infection in children and their mothers' stress and anxiety levels (P < 0.01). Acute rhinitis and acute tracheitis in the children were both positively correlated with the mothers' stress scores (P < 0.05), while acute pharyngitis and acute laryngitis were positively correlated with the mothers' anxiety scores (P < 0.05), while acute bronchitis was positively correlated with the mothers' stress and anxiety scores (P < 0.05). Multiple linear regression analysis with the factors influencing the types of acute respiratory tract infections in children as the independent variables suggested that the easy-to-raise type of temperament was a protective factor against acute rhinitis in children (P < 0.05), while mothers' anxiety was a risk factor of acute laryngitis in children (P < 0.05); the mothers' stress was a risk factor for acute bronchitis in children (P < 0.05). CONCLUSION: Acute respiratory tract infection in children is closely related to the temperament type of the children and the emotional state of the mothers, which are important therapeutic targets in comprehensive interventions of acute respiratory tract infection in children.

Association of genetic variants in the Sirt1 and Nrf2 genes with the risk of metabolic syndrome in a Chinese Han population.

BACKGROUND: Metabolic syndrome (MetS) is a complex of interrelated risk factors, including central adiposity, increased blood pressure, hyperglycemia, elevated triglyceride levels and low high-density lipoprotein. Few studies have reported the genetic variants in the Sirt1 and Nrf2 genes (Sirt1 rs7895833 A > G, Sirt1 rs2273773 C > T and Nrf2 rs6721961 C > A) that increase the risk of type 2 diabetes mellitus and are correlated with some glycemic and metabolic traits in the Chinese Han population. METHODS: Our study recruited 141 individuals with MetS and 549 individuals without MetS to investigate the associations between three single nucleotide polymorphisms (SNPs) of Sirt1 and Nrf2 and the risk of MetS in a Chinese Han population using the PCR-CTPP method. RESULTS: This research showed that the risk of MetS was 2.41 times higher for the AA genotype (P = 0.038) and 1.94 times higher for the AG genotype (P = 0.016) compared with carriers of the GG genotype. The serum levels of low-density lipoprotein cholesterol and HOMA-IR were significantly higher (P < 0.05) in carriers of the AA genotype of Sirt1 rs7895833 than in carriers of the AG and GG genotypes in the general population. The serum level of total cholesterol in the AA genotype was lower (P = 0.033) than that in the other two genotypes. However, the genotype frequencies of Sirt1 rs2273773 and Nrf2 rs6721961 in the MetS group were not significantly different from those in the control subjects, and those two genetic variants were not correlated with metabolic traits. CONCLUSIONS: These results underscore the contributions of SNPs of Sirt1 rs7895833 to MetS susceptibility as well as glycemic and metabolic traits in a Chinese population.

Critical Analysis of Apixaban Dose Adjustment Criteria.

Apixaban is indicated for the prevention of ischemic stroke in non-valvular atrial fibrillation (NVAF), as well as for the prevention and treatment of venous thromboembolism (VTE). Dose adjustment is based on age, weight, and serum creatinine in NVAF, while there are no recommended adjustment criteria for VTE. Such adjustment is unconventional compared to other commonly used medications. The objective of this manuscript is to critically analyze each apixaban dosing adjustment criterion and its associated outcomes. PubMed articles from March 2013 to March 2020 were selected with search terms "apixaban," and "dose adjustment," "adjustment," or "adjustment criteria." Pharmacokinetic studies demonstrated increased apixaban exposure in patients >65 years of age, those with extreme body weights, and those with advanced renal impairment, though post-hemodialysis dosing may off-set the elevated apixaban exposure. However, clinical data show that among patients >75 years, <60 kg, and with estimated glomerular filtration rate <50 mL/min, including those on dialysis, there is no reduction in apixaban safety or efficacy. Published literature describes variable dosing strategies utilized in clinical practice. Overall, apixaban dose adjustment criteria may need to be re-evaluated.

Curriculum Design and Scholarship for New Educators: A Professional Development Workshop for Medical Students.

Introduction: Medical students' professional development includes their role as educators. Despite greater opportunities to join medical education curriculum development, medical students' engagement in these activities remains limited. A recent national study on student leadership in curricular change revealed a formal lack of leadership and training in medical education as significant barriers. Medical students' unawareness of how to disseminate curricula as educational scholarship and its value to their careers also restricts the fullness of their formation as educators. Methods: We designed a 3-hour, interactive, project-focused conference workshop for medical students without prior knowledge in curriculum development. Of participants, 64 worked in 10 groups creating medical curricula using Kern's six-step approach in student-facilitated breakout sessions. Completed group projects were presented, including brief action plans for transforming their work into scholarship. The workshop was evaluated using a mixed-methods approach. Results: Of survey respondents, 44 mostly medical students, faculty, and administrators from different institutions rated the workshop as a very positive experience, and the pacing of the breakout groups as effective. A notable increase in self-reported mastery, as measured by learning objectives aligned with Kern's six-step model, was recorded from student respondents as compared to faculty. A sense of readiness to participate in curricular decisions either at the home institution or in individual career paths was evident from narrative comments. Discussion: Our workshop provided medical students with a foundation in curriculum development and educational scholarship. Session design provided flexibility in the pace of breakout sessions and allowed in-depth discussion of educational topics.

Dissecting the Role of VicK Phosphatase in Aggregation and Biofilm Formation of Streptococcus mutans.

VicRK (WalRK or YycFG) is a conserved 2-component regulatory system (TCS) that regulates cell division, cell wall biosynthesis, and homeostasis in low-GC Gram-positive bacteria. VicRK is also associated with biofilm formation of Streptococcus mutans on the tooth surface as it directly regulates the extracellular polysaccharide (EPS) synthesis. Of the 2 components, VicK possesses both autokinase and phosphatase activities, which regulate the phosphorylation and dephosphorylation of the regulator VicR in response to environmental cues. However, the dual mechanism of VicK as the autokinase/phosphatase in regulating S. mutans' responses is not well elucidated. Previously, it has been shown that the phosphatase activity depends on the PAS domain and residues in the DHp domain of VicK in S. mutans. Specifically, mutating proline at 222 in the PAS domain inhibits VicK phosphatase activity. We generated a VicKP222A mutant to determine the level of VicR-P in the cytoplasm by Phos-tag sodium dodecyl sulfate polyacrylamide gel electrophoresis. We show that in VicKP222A phosphatase, attenuation increased phosphorylated VicR (VicR-P) that downregulated glucosyltransferases, gtfBC, thereby reducing the synthesis of water-insoluble polysaccharides (WIS-EPS) in the biofilm. In addition, VicKP222A presented as long-rod cells, reduced growth, and displayed asymmetrical division. A major adhesin of S. mutans, SpaP was downregulated in VicKP222A, making it unable to agglutinate in saliva. In summary, we have confirmed that VicK phosphatase activity is critical to maintain optimal phosphorylation status of VicR in S. mutans, which is important for cell growth, cell division, EPS synthesis, and bacterial agglutination in saliva. Hence, VicK phosphatase activity may represent a promising target to modulate S. mutans' pathogenicity.

[PTX3 promotes proliferation, invasion and drug resistance of neuroblastoma cells in children by regulating TLR4/NF-κB signaling pathway].

Objective: To investigate the effect of pentraxin 3 (PTX3) on the proliferation, invasion and drug resistance of pediatric neuroblastoma cells and its mechanism. Methods: si-RNA (si-RNA group), si-PTX3 (si-PTX3 group), siRNA+ pcDNA3.1 (siRNA+ pcDNA3.1 group), si-PTX3+ pcDNA3.1 (si-PTX3+ pcDNA3.1 group), siRNA+ pcDNA3.1-Toll-like receptor 4 (siRNA+ pcDNA3.1-TLR4 group) and si-PTX3+ pcDNA3.1-TLR4 (si-PTX3+ pcDNA3.1-TLR4 group) were transfected into SH-SY5Y cells. Collected 32 cases of tumor tissue and cancerous tissue in children with childhood neuromaternal cells who were treated at Zhumadian center hospital from July 2016 to August 2019. Real-time fluorescent quantitative polymerase chain (RT-qPCR) reaction and immunohistochemistry experiments were used to detect the protein expressions of PTX3 in neuroblastoma tissues and normal tissues. 5-Ethynyl-2'-deoxyuridine (EdU) was used to detect the proliferation effect of PTX3 on neuroblastoma cell SH-SY5Y. Western blot experiment was used to detect the protein expression levels of vascular endothelial growth factor (VEGF), resistance-related proteins including P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP-1), and invasion-related protein matrix metalloproteinase-1 (MMP-1). Results: PTX3 mRNA expressions in neuroblastoma tissues were 0.87±0.07, higher than 0.13±0.06 of normal tissues, and the differences were statistically significant (P<0.05), The expression of the immunohistochemistry test PTX3 protein was consistent with the qRT-PCR results. Compared with the si-RNA group (0.95±0.08; 1.02±0.10), the mRNA and protein expressions of PTX3 in the si-PTX3 group (0.25±0.05; 0.45±0.66) decreased, the differences were statistically significant (all P<0.05). The number of EdU positive cells, invasion rate, VEGF, MMP-1, P-gp and MRP-1 protein expressions in si-RNA group were (31.86±1.86)%, (28.12±2.96)%, (0.58±0.07), (0.44±0.06), (0.46±0.08) and (0.51±0.05), respectively, higher than (19.73±1.22)%, (8.45±1.06)%, (0.25±0.05), (0.19±0.03), (0.19±0.06) and (0.16±0.07) in si-PTX3 group, and the differences were statistically significant (all P<0.05). The Number of EdU positive cells [(19.49±1.68)%], invasion rate [(8.48±1.36)%], VEGF protein expression (0.10±0.15), P-gp (0.18±0.07) , TLR4 (0.45±0.06), p-p65 (0.25±0.05) protein expressions in si-PTX3+ pcDNA3.1 group were relatively lower compared with siRNA+ pcDNA3.1 group [(38.21±2.67)%, (26.39±2.14)%, 0.49±0.05, 0.52±0.06, 0.93±0.14 and 0.82±0.06] (all P<0.05). The number of EdU-positive cells [(62.73±5.18)%], invasion rate [(50.45±3.25)%], VEGF protein expression (2.17±0.17), P-gp (2.15±0.16), TLR4 (2.68±0.16), p-p65 (2.48±0.13) protein expressions in the siRNA+ pcDNA3.1-TLR4 group increased compared with siRNA+ pcDNA3.1 group (all P<0.05). Conclusions: Inhibition of PTX3 can inhibit the proliferation and invasion of neuroblastoma cells SH-SY5Y, and reduce drug resistance. Its mechanism may be achieved by regulating the TLR4/NF-κB signaling pathway. This result can provide a new perspective for pediatric neuroblasts tumor diagnosis and clinical treatment.

[The prognostic value of cloned genetic mutations detected by second-generation sequencing in RUNX1-RUNX1T1 positive acute myeloid leukemia patients receiving intensive consolidation therapy].

Objective: To investigate the prognostic value of clonal gene mutations detected by second-generation sequencing in patients with positive RUNX1-RUNX1T1 acute myeloid leukemia (AML) who received high-dose chemotherapy or autologous transplantation (intensive consolidation therapy) in the first complete remission (CR(1)) state. Methods: 79 AML patients with positive RUNX1-RUNX1T1 who received intensive consolidation therapy in CR(1) state from July 2011 to August 2017 were analyzed retrospectively. Kaplan-Meier curve and Cox regression model were used to figure out the effect of leukocyte counts at onset and gene mutations for prognosis. Results: C-KIT, FLT3, CEBPA and DNMT3A gene mutations were found in 25 (31.6%) , 6 (7.6%) , 7 (8.9%) and 1 (1.3%) patient among the population. Mutations in C-KIT exon17 and C-KIT exon8 were detected in 19 (24.1%) and 5 (6.3%) cases, respectively, and mutations of FLT3-ITD were confirmed in 5 (6.3%) cases. The higher leukocyte counts presented at onset of leukemia, the shorter overall survival (OS) was seen in these patients (P=0.03) . Patients with C-KIT exon17 mutation had significantly shorter OS (P=0.01) and disease free survival (DFS) (P=0.006) compared with those without gene mutations, and patients with FLT3-ITD gene mutation got the inferior OS (P=0.048) and DFS (P=0.071) . Conclusion: In AML patients with positive RUNX1-RUNX1T1 receiving intensive consolidation therapy, the white blood cell counts at onset of leukemia, C-KIT mutations in exon 17, and FLT3-ITD gene mutations suggest poor prognosis, which would contribute to elaborate risk stratification, personalized treatment and predict prognosis for these patients.

Pollution status of the Yellow River tributaries in middle and lower reaches.

To determine the water quality status of the primary tributaries in middle and lower reaches of the Yellow River Basin, water collected from the confluence of the ten tributaries and some physical, chemical and biological parameters were analyzed, and then water quality index and health risk were evaluated. Of the ten main tributaries in the middle and lower reaches, only the Qingshui River had water of medium quality in the upper reaches, while all the other tributaries contributed water of poor quality. The Jindi and Dawen rivers in the lower reaches had the poorest water quality, especially the Jindi River. TP, TN, BOD5, COD, TOC and coliform bacteria exceeded the national criteria by 155%, 1%, 97.5%, 35.5%, 114.2%, and 80%, respectively. Cluster analysis indicated that industrial, agricultural, and domestic sewage, along with industrial waste gas, were the main sources of pollution in these tributaries. An analysis of the bacterial community structure showed that the Jindi River was the most polluted and had the largest species diversity and richness of bacteria. Also, its number of pathogenic microorganisms was much higher than that of other areas, and the bacterial functional genes of related metabolic pathways were significantly enriched. This was in sharp contrast with that of the Qingshui River, which had the best water quality. We suggest more specifics policy should be taken for different tributaries, and poor water quality of Jindi and Dawen River should be further studied to explore the most suitable pollution control methods.

Three kinds of ammonia oxidizing microorganisms play an important role in ammonia nitrogen self-purification in the Yellow River.

To develop the microbial resources of the Yellow River, seven water samples were collected along the Lanzhou region of the river from upstream to downstream for testing. Analysis of various physico-chemical indexes was conducted, and key parameters influencing the water quality were selected through principal component analysis, after which the decisive factors impacting water quality were determined by correlation and regression analysis. The results indicated that (1) DO, NH3-N, NO2--N, TN, TC, As, Cr6+ and Pb were the main physico-chemical factors influencing water quality in the Lanzhou region, with NH3-N having the greatest effect. (2) Ammonia-oxidizing microorganisms [ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), and anaerobic ammonia-oxidizing bacteria (AMX)] were found to mediate the transformation of NH3-N in the studied section. AOA was the primary microbe community among the two aerobic ammonia-oxidizing microorganisms (AOA and AOB) in the Yellow River. (3) Phylogenetic analysis showed that there were some known groups, and there were still many unknown species in the water of the studied section, especially within the AMX population. (4) Correlation analysis revealed that AOA has strong adaptability to unhealthy environments, and that some environmental factors (higher concentrations of carbon, nitrogen and some heavy metals) could increase the AOA gene abundance. Overall, these results suggested there are rich ammonia-oxidizing microbial resources, especially AOA, in the Lanzhou section of the Yellow River, which have the potential for application in nitrogen sewage treatment.

[Clinical features and pathological analysis of lacrimal gland occupying lesions in 91 cases].

Objective: To analyze the pathogenesis, histopathological classification and clinical features of lacrimal gland occupying lesions. Methods: This was a retrospective case series study. Clinical data of 91 patients (102 eyes) with lacrimal gland area occupying diseases who received ophthalmic surgery in the Second People's Hospital of Yunnan Province from January 2014 to November 2018 were retrospectively analyzed, including patients' age, reasons for treatment, gender, imageological examination data and pathological diagnosis results. All patients had more than one medical imaging examination results and histopathological diagnosis results. Results: Among 91 cases, 46 patients (50.5%) were male and 45 (49.5%) were female. The age distribution ranged from 1.1 years to 72 years old, with an average age of 43 years. All of benign tumors added up to 58 cases (63.7%). Pleomorphic adenoma (43 cases, 47.3%), dermoid cyst (6 cases, 6.6%), and inflammatory pseudotumor (6 cases, 6.6%) were the most common cases in the benign lacrimal gland occupying tumors. There were 33 cases (36.3%) of malignant tumors. Adenoid cystic carcinoma (15 cases, 16.5%), adenocarcinoma (6 cases, 6.6%) and lymphoma (5 cases, 5.5%) had the highest incidence among the malignant lacrimal gland occupying tumors. The most common reason for seeking medical treatment was exophthalmos (50 cases, 54.9%; 30 cases were pleomorphic adenoma). Brow arch mass (22 cases, 24.2%) and pain in and around the eye (9 cases, 9.9%; 5 cases were adenoid cystic carcinoma) were also major reasons. Conclusions: The most common benign lacrimal gland area occupying lesion in surgery patients of Yunnan is pleomorphic adenoma, which more occurred in patients with exophthalmos as the main symptoms. The most common malignant tumor in the lacrimal gland area is adenoid cystic carcinoma and the most common reason to seek medical advice was pain in and around the eye. (Chin J Ophthalmol, 2019, 55:842-846).

Modulating cAMP responsive element binding protein 1 attenuates functional and behavioural deficits in rat model of neuropathic pain.

OBJECTIVE: Chronic neuropathic pain (NP) has become a worldwide public health problem. This study was aimed to establish graded NP model to investigate the effect of CREB1 on nerve repair and NP after peripheral nerve injury. MATERIALS AND METHODS: Based on NP model, we measured the 50% paw withdrawal threshold (PWT) of rat hind paws and sciatic functional index (SFI). Luxol fast blue staining was performed to measure the ratio of distal myelin sheath to proximal (DPR). The c-Fos, GFAP, CX3CR1 and IBA-1 expressions in spinal cord were measured by Western blot. The expression levels of CREB1 and ATF-3 in dorsal root ganglion (DRG) were both measured. Intrathecal injection was performed by using recombinant CREB, or anti-CREB antibody for NP model, respectively. The above indexes were detected. RESULTS: In NP model, the 50% PWTs and DPR were gradually reduced and SFI was increased. The c-Fos, GFAP, CX3CR1 and IBA-1 expressions were increased compared to control group. The CREB1 and ATF-3 expressions in DRG showed gradually increase. With the injection of recombinant CREB, the similar changes were found in rats compared with NP model. While after anti-CREB1 antibody injection, all effects of CREB1 were impaired. Likewise, anti-CREB1 antibody treatment increased 50% PWT and DPR, decreased SFI, decreased expressions of c-Fos, GFAP, CX3CR1 and IBA-1. Besides, ATF-3 expression was inhibited by CREB1 suppression. CONCLUSIONS: CREB1 involved in the regulation of NP and nerve repair process, suggesting that CREB1 has potential as a new target for the treatment of chronic NP.

Laparoscopic appendiceal interposition pyeloplasty for long ureteric strictures in children.

INTRODUCTION: The management of long ureteric strictures is very challenging, and ureteral substitution is necessary when end-to-end anastomosis can not be accomplished. OBJECTIVE: To evaluate the mid-term results of laparoscopic appendiceal interposition pyeloplasty in children with long ureteric strictures. METHODS: Between March 2010 and September 2016 four patients (median age 24 months, male/female 3/1) underwent laparoscopic appendiceal interposition pyeloplasty at the current hospital. Two patients had previously failed pyeloplasty, one had a traffic injury, and one had iatrogenic ureteral injury (Summary Table). The intraoperative, postoperative and follow-up results were analyzed. Success was defined as clinical (subjective) and radiologic (objective) resolution of the stricture. RESULTS: All surgeries were successfully completed without conversion. The mean stricture length was 4.5 cm. Two cases were right-sided strictures, and two were left-sided. The mean operative time and estimated blood loss were 238.5 min and 25.0 ml, respectively. No intraoperative complication was encountered. No Grade 3 or Grade 4 complication was observed after surgery. One was anastomosed in the antiperistaltic manner and three were in the isoperistaltic fashion. The mean postoperative hospital stay was 7.3 days. The success rate was 100% at a mean follow-up duration of 33.8 months. DISCUSSION: There is no consensus on the best surgical approach for long ureteric strictures. Ureteric replacement with intestinal segments or kidney autotransplantation is a viable alternative treatment to long ureteric strictures. However, both methods are technically challenging with significant complications. Appendiceal interposition to restore ureteral continuity has been described in adult patients. The current results demonstrated that laparoscopic appendiceal interposition pyeloplasty is a safe and feasible minimally invasive approach for the treatment of long ureteral strictures in children. CONCLUSIONS: Laparoscopic appendiceal interposition pyeloplasty was a viable minimally invasive alternative for children with long ureteric strictures on both left and right sides. Both isoperistaltic or antiperistaltic anastomosis were feasible.

Applying the zero-inflated Poisson model with random effects to detect abnormal rises in school absenteeism indicating infectious diseases outbreak.

Records of absenteeism from primary schools are valuable data for infectious diseases surveillance. However, the analysis of the absenteeism is complicated by the data features of clustering at zero, non-independence and overdispersion. This study aimed to generate an appropriate model to handle the absenteeism data collected in a European Commission granted project for infectious disease surveillance in rural China and to evaluate the validity and timeliness of the resulting model for early warnings of infectious disease outbreak. Four steps were taken: (1) building a 'well-fitting' model by the zero-inflated Poisson model with random effects (ZIP-RE) using the absenteeism data from the first implementation year; (2) applying the resulting model to predict the 'expected' number of absenteeism events in the second implementation year; (3) computing the differences between the observations and the expected values (O-E values) to generate an alternative series of data; (4) evaluating the early warning validity and timeliness of the observational data and model-based O-E values via the EARS-3C algorithms with regard to the detection of real cluster events. The results indicate that ZIP-RE and its corresponding O-E values could improve the detection of aberrations, reduce the false-positive signals and are applicable to the zero-inflated data.

[Anti-CD(25) monoclonal antibody as a salvage therapy for steroid-refractory acute graft-versus-host disease in 80 patients receiving allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the efficacy of anti-CD(25) monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 80 patients with SR-aGVHD from January 1st 2012 to December 31st 20l6 were enrolled in this study. Acute GVHD were classified as classic aGVHD (n=72) and late-onset aGVHD (n=8). Anti-CD(25) monoclonal antibodys (mAb) were administrated on days 1, 4, 8, 15, and 22. The efficacy of anti-CD(25) mAb was evaluated at day 28 after the initial treatment. The associated factors of clinical outcome were analyzed. Results: The overall response (OR) rate of anti-CD(25) mAb was 75% (60/80), with complete response (CR) rate, partial response (PR) rate and no response(NR) rate 52.5% (42/80), 22.5% (18/80), and 25% (20/80), respectively. GVHD-relapse was not observed with a median follow-up time of 394.5 days (range, 12-1 761 days). The 6-month overall survival (OS) rate was 68.4%(95%CI 63.2%-73.6%). The 1-year OS rate was 63.1% (95%CI 57.6%-68.6%), and 2-years OS rate was 50.7% (95%CI 44.3%-57.1%). Non-relapse mortality (NRM) rate of 1 and 3 years was 32.6% (95%CI 27.2%-38%) and 41.7% (95%CI 35.3%-48.1%), respectively. The 1 and 2 years cumulative incidence of chronic graft versus host disease (cGVHD) was 32.9% (95%CI 26.4%-39.4%) and 38.9% (95%CI 31.8%-46.0%). By univariate and multivariate analysis, liver involvement was an independent poor risk factor of SR-aGVHD (OR=4.66, 95%CI 1.145-18.962, P=0.032). Conclusion: Anti-CD(25) mAb serves as an alternative and effective salvage therapy for SR-aGVHD at present. Liver involvement is a predictive factor of poor response in patients with SR-aGVHD.

A Proposal for a Shared Medical School Curricular Ecosystem.

New digital platforms are transforming learning in higher education and providing high-quality education content at little or no cost. Educators can now reach large, even global audiences. Yet, many medical schools continue to develop and maintain custom but duplicative curricular content despite having limited faculty and financial resources. In addition, medical students are faced with a multitude of potentially unaligned curricula driven by the school, national licensing exams, and the students' own perceived clinical training needs. The authors propose the creation of a common curricular component ecosystem that is developed around consensus-built foundational learning objectives aligned with core competencies that must be acquired by all students graduating medical school. Identifying and developing common curricula with standardized learning outcomes ideally should involve leading medical education, accreditation, and certification bodies in the United States. Curriculum component standards will be necessary to enable curriculum development, sharing, and adoption at scale. A shared medical curriculum ecosystem would free up faculty time to develop high-value teaching activities at individual medical schools. Students would benefit from a consistent education experience that better aligns with national licensure exams. A shared, core curriculum system could begin to bend the cost curve for medical education in the United States and scale internationally to help address the increasing global shortage of health care workers.

Greater health risk in wet season than in dry season in the Yellow River of the Lanzhou region.

The Yellow River flows through Lanzhou city and is the only drinking water source for 3.6 million residents. Yet, little is known regarding the safety and quality of the Yellow River for resident consumption. To address this knowledge-gap, water samples were collected from different sites within this section during the dry and wet seasons. Physico-chemical parameters and microbial community metrics were analyzed to assess the health risk associated with this Chinese mother river. Water quality of the river was better during the dry season (March-April) than in the wet season (September-October). Fifteen conventional physico-chemical and biological indices, such as NH3-N, NO2--N, total nitrate (TN), five day biochemical oxygen demand (BOD5), chemical oxygen demand (COD), volatile phenol (VP), and coliform abundances, generally exceeded acceptable standards. The average abundance of coliforms was 2.8 times that of acceptable standards in the dry season and 4.6 times the standards in the wet season. The concentration of the toxic metal As was more than two times than that of the national standard in waters from the wet season. Microbial community analysis also indicated that community diversity and species richness were positively correlated with the concentrations of several physico-chemical parameters. The results indicate that As and Cr6+ pose potential risk for human health through consumption by residents. Further, the results indicated that human activities are the main causes of water pollution, and that long-term strict monitoring should be conducted to ensure the safety of drinking water consumption and the health of the environment.

PDZK1 inhibits the development and progression of renal cell carcinoma by suppression of SHP-1 phosphorylation.

Renal cell carcinoma (RCC) is one of the most aggressive urologic cancers, however, the mechanism on supporting RCC carcinogenesis is still not clear. By using gene expression profile analysis and functional clustering, PDZ domain-containing 1 (PDZK1) was revealed to be downregulated in human clear cell renal cell carcinoma (ccRCC) samples, which was also verified in several independent public ccRCC data sets. Using PDZK1 overexpression and knockdown models in ccRCC cell lines, we demonstrated that PDZK1 inhibited cell proliferation, cell cycle G1/S phase transition, cell migration and invasion, indicating a tumor-suppressor role in the development and progression of ccRCC. Our study further demonstrated that PDZK1 inhibited cell proliferation and migration of ccRCC via targeting SHP-1. PDZK1 was further identified to suppress cell proliferation by blocking SHP-1 phosphorylation at Tyr536 via inhibition of the association between SHP-1 and PLCß3, and then retarding Akt phosphorylation and promoting STAT5 phosphorylation in ccRCC cells. Moreover, the inhibitive effects of PDZK1 on SHP-1 phosphorylation and the tumor growth were verified in vivo by xenograft tumor studies. Accordingly, PDZK1 expression was negatively correlated with SHP-1 activation and phosphorylation, advanced pathologic stage, tumor weight and size, and prognosis of ccRCC patients. These findings have provided first lines of evidences that PDZK1 expression is negatively correlated with SHP-1 activation and poor clinical outcomes in ccRCC. PDZK1 was identified as a novel tumor suppressor in ccRCC by negating SHP-1 activity.