[A case of pleural metastasis of malignant peripheral nerve sheath tumor].

Malignant peripheral nerve sheath tumor (MPNST) frequently metastasizes to the lungs, although pleural metastasis is rare. This article reported a case of pleural metastasis of MPNST. The patient was a young man who presented with 1 week of shortness of breath with dry cough. He had a history of malignant peripheral nerve sheath tumor. The patient was diagnosed with MPNST pleural metastasis after a thoracoscopic pleural biopsy, which revealed short spindle cell hyperplasia, immunohistochemical staining for S-100(+), SOX-10(+), Ki-67(+) with a positive index of 20%, and H3K27Me3(-) in the pleural pathology.

[Analysis of adverse late-term pregnancy outcomes after cervical cold knife conization].

Objective: To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization. Methods: The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed. Results: (1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm3 and cone size <2 cm3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference (P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm (RR=3.084, 95%CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm3 and those with cone size ≥2 cm3 (RR=1.700, 95%CI: 0.935-3.092; P=0.077). Conclusion: The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.

[Efficacy and safety of venetoclax combined with hypomethylating agents in the treatment of 83 patients with higher-risk myelodysplastic syndromes].

Objective: This study aimed to evaluate the efficacy and safety of venetoclax (VEN) combined with hypomethylating agents (HMA) in the treatment of higher-risk myelodysplastic syndromes (HR-MDS) and analyze the factors influencing their therapeutic effect. Methods: The clinical data of 83 patients with HR-MDS who were diagnosed at the First Affiliated Hospital of Zhengzhou University between November 2019 and May 2023 were retrospectively analyzed. All patients were treated with VEN combined with HMA. The Kaplan-Meier method was used to depict the survival curves, and the log-rank test was used to compare survival between the groups. Results: The median age was 57 (15-82) years old, and 51 patients (61.4%) were male. Forty-five patients (54.2%) were initially treated with HMA, 23 (27.7%) received ≤4 cycles of HMA, and 15 (18.1%) demonstrated HMA failure. At the median follow-up of 10.3 (0.6-34.4) months, the overall response rate (ORR) was 62.7% (52/83), including 18 patients (21.7%) with a complete response (CR), 14 (16.9%) with a bone marrow CR (mCR) with hematological improvement, and 20 (24.1%) with a mCR. The ORR of patients with initial treatment, ≤4 HMA cycles, and HMA failure were 66.7%, 60.9%, and 53.3%, respectively (P=0.641). The median overall survival time was 14.6 (95% CI 7.2-22.0) months, and the median progression-free survival time was 8.9 (95% CI 6.7-11.1) months. The multivariate analysis showed that serum alkaline phosphatase (ALP) ≥90 U/L (OR=14.574, 95% CI 3.036-69.951, P=0.001), TP53 mutation (OR=13.052, 95% CI 1.982-85.932, P=0.008), and U2AF1 mutation (OR=7.720, 95% CI 1.540-38.698, P=0.013) were independent risk factors for poor efficacy of VEN combined with HMA. Hematological toxicity occurred in all patients, and the incidence of treatment-induced grade 3-4 leukopenia was 48.2% (40/83). Infection was the most common non-hematological adverse event, mainly pulmonary infection (31.3%) . Conclusion: VEN combined with HMA had a high response rate in patients with HR-MDS, both at initial treatment and with HMA failure. ALP ≥ 90 U/L, TP53 mutation, and U2AF1 mutation were independent risk factors for non-response to treatment.

[Clinical features of SF3B1 mutation in patients with myelodysplastic syndrome with excess blasts].

Objective: To exploring the clinical features of SF3B1-mutated myelodysplastic syndrome with excess blasts (MDS-EB) and analyzing the association between SF3B1 mutation, and efficacy and prognostic significance for patients with MDS-EB. Methods: This was a retrospective case series study. The clinical data of 266 patients with MDS-EB diagnosed in the First Affiliated Hospital of Zhengzhou University between April 2016 and November 2021 were analyzed. The observed indicators included blood routine counts, mutated genes, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and leukemia-free survival (LFS). The Kaplan-Meier method was used to depict the survival curves. The Log-rank test method was equally used to compare survival across groups and performed the Cox proportional hazard regression model for prognostic analysis. Results: In 266 patients with MDS-EB, 166 (62.4%) were men, and the median age was 57 (17-81) years. Moreover, there were included 26 and 240 patients in the SF3B1-mutated and SF3B1 wild-type groups. Patients in the SF3B1-mutated group were older [median age 65 (51, 69) years vs. 56 (46, 66) years, P=0.033], had higher white blood cell (WBC) counts [3.08 (2.35, 4.78) × 109/L vs. 2.13 (1.40, 3.77) × 109/L], platelet (PLT) counts [122.5 (50.5, 215.0) ×109/L vs. 49.0 (24.3, 100.8) × 109/L], absolute neutrophil counts (ANC) [1.83 (1.01, 2.88) × 109/L vs. 0.80 (0.41, 1.99) × 109/L]and occurrence of DNMT3A mutation [23.1% (6/26) vs. 6.7% (16/240)] (all P<0.05). The ORR were similar in both groups after 2 and 4 cycles of therapy (P=0.348, P=1.000). Moreover, the LFS (P=0.218), PFS (P=0.179) and OS (P=0.188) were similar across the groups. Univariate Cox analysis revealed that SF3B1 mutation did not affect the prognosis of patients with MDS-EB (OS: P=0.193; PFS: P=0.184). Conclusions: Patients with SF3B1 mutation were older, with greater WBC, PLT, and ANC, and SF3B1 mutation easily co-occurred with DNMT3A mutation. From this model, there were no significant differences in efficacy and survival of MDS-EB with or without SF3B1 mutation.

Long-term Cardiovascular Risks of Gonadotropin-releasing Hormone Agonists and Antagonists: A Population-based Cohort Study.

AIMS: Gonadotropin-releasing hormone (GnRH) agonists and antagonists, critical medications for prostate cancer (PCa) treatment, may differ in cardiovascular safety. This prospective cohort study aimed to compare the long-term cardiovascular risks between GnRH agonists and antagonists. MATERIALS AND METHODS: Patients with PCa receiving GnRH agonists or antagonists during 2013-2021 in Hong Kong were identified. Patients with <6 months' prescriptions, who were switching between drugs, had missing baseline prostate-specific antigen level or had a prior stroke or myocardial infarction were excluded. Patients were followed up until September 2021. The primary outcome was major adverse cardiovascular events (MACE) as in the PRONOUNCE trial (MACEPRONOUNCE), i.e. a composite of all-cause mortality, stroke and myocardial infarction. The secondary outcome was MACECVM, i.e. a composite of cardiovascular mortality, stroke and myocardial infarction. Inverse probability treatment weighting was used to balance covariates between groups. The Log-rank test was used to compare the cumulative freedom from the primary outcome between groups. RESULTS: In total, 2479 patients were analysed (162 GnRH antagonist users and 2317 agonist users; median age 75.0 years, interquartile range 68.0-81.6 years). Inverse probability treatment weighting achieved good covariate balance between groups. Over a median follow-up duration of 3.0 years (interquartile range 1.7-5.0 years), 1115 patients (45.0%) had MACEPRONOUNCE and 344 (13.9%) had MACECVM. GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.027). However, no differences were observed within 1 year of follow-up (MACEPRONOUNCE: Log-rank P = 0.308; MACECVM: Log-rank P = 0.357). Among patients without cardiovascular risk factors at baseline, GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.001), whereas no differences were observed in those with such risk factor(s) (MACEPRONOUNCE: Log-rank P = 0.569; MACECVM: Log-rank P = 0.615). CONCLUSIONS: GnRH antagonists may be associated with higher long-term, but not short-term, cardiovascular risks than agonists in Asian patients with PCa, particularly in those without known cardiovascular risk factors.

[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[Clinical features and survival analysis of microscopic polyangiitis-associated interstitial lung disease:a retrospective study of 28 patients].

Objective: To explore the clinical features, laboratory examination and imaging features of microscopic polyangiitis (MPA)-associated interstitial lung disease (ILD), and to perform survival analysis. Methods: The records of 28 patients with MPA-ILD who were treated at the Affiliated Hospital of Medical School of Ningbo University were reviewed retrospectively from August 2014 to November 2021. The patients' clinical features, laboratory parameters, pulmonary function test, echocardiography, chest CT scan findings and therapeutic regimen were analyzed, and the relevant data were statistically analyzed. Results: There were 18 males and 10 females, with an average age of (70.1±9.3) years. Among them, 13 patients had a history of smoking. The main clinical manifestations were cough (14/28), fever (12/28), chest tightness, shortness of breath (12/28) and hemoptysis (3/28). Sixteen patients had renal involvement, and 78.57% (22/28) and 89.28% (25/28) of the patients had elevated C-reactive protein (CRP) and ESR respectively. Sixteen (16/28) patients had increased rheumatoid factor (RF), and the positive rate of myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) was 82.12% (23/28). 96.43% (27/28) of ILDs were diagnosed before or at the same time as MPA. The chest radiological pattern was mainly usual interstitial pneumonia (UIP) or UIP-like (15/28), followed by nonspecific interstitial pneumonia (NSIP) (8/28). Compared with non-UIP-like patients, UIP or UIP-like patients were older (P=0.018), and had higher serum LDH level (P=0.041), but serum creatinine level was significantly lower (P=0.041). Univariate and multivariate survival analysis showed that inappropriate treatment (HR=9.81, 95%CI: 1.68-57.29, P=0.011) and elevated serum LDH (HR=4.11, 95%CI: 0.99-17.00, P=0.051) were independent risk factors for shortened survival of MPA-ILD, while elevated RF (HR=0.22, 95%CI: 0.06-0.91, P=0.037) was a protective factor for prolonged survival. Conclusions: MPA-ILD patients had fewer systemic vasculitis symptoms. Most of the ILD patients were diagnosed before or at the same time as MPA. The chest radiological pattern was mainly UIP or UIP-like, followed by NSIP. Early use of glucocorticoids combined with immunosuppressant or rituximab could improve the survival rate of MPA-ILD. The elevated serum LDH was an independent risk factor for shortened survival of MPA-ILD, while elevated RF was a protective factor for prolonged survival.

[Correlation between professional quality of life and social support of Chinese nurses: a meta-analysis].

Objective: To systematically evaluate the correlation between professional quality of life and social support of Chinese nurses based on Pearson and Spearman correlation coefficients. Methods: In databases including PubMed, Cochrane Library, CINAHL, Medline, CBM, CNKI、Wanfang, and other databases were searched by computer for the literatures on correlation between Chinese nurses' professional quality of life and social support from January 2005 to July 2020. The Chinese and English search terms are "nurse" "professional quality of life" "empathy satisfaction" "empathy fatigue" "professional quality of life" "ProQOL" "comparison satisfaction" "comparison fatigue" "social support" "competent social support" "SSRS" "PSSS", etc. Literatures were screened according to the inclusion and exclusion criteria. After evaluating quality and extracting data, meta-analysis was conducted using RevMan 5.3 software. Results: A total of 12 studies were included. The meta analysis showed that nurses' compassion satisfaction, burnout, secondary traumatic stress were related to social support, summary r were 0.35, -0.26 and -0.23 respectively. The correlation between compassion satisfaction and social support were increased with sample, the south was higher than the north, and comprehensive departments were higher than other departments (P<0.05) . The correlation between burnout and social support were increased with time and sample, and the south was higher than the north, oncology was higher than others, non-random sampling was higher than random sampling, using ProQOL and Perceived Social Support Scale (PSSS) was higher than Professional Quality of Life Scale (ProQOL) and Social Support Racting Scale (SSRS) (P<0.05) . The correlation coefficient between secondary traumatic stress and social support in oncology was higher than others, random sampling was higher than non-random sampling, using ProQOL and PSSS was higher than ProQOL and SSRS (P<0.05) . Conclusion: There is a positive and weak correlation between compassion satisfaction and social support, and a negative and weak correlation between burnout and secondary traumatic stress and social support. There are differences in different time, research design, region and department.

[Familial interstitial lung disease associated with surfactant protein C gene mutation in adults: report of two cases and literature review].

Objective: To improve the understanding of clinical manifestations, imaging findings, diagnosis and treatment of surfactant protein C gene (SFTPC) mutation associated with familial interstitial lung disease in adults. Methods: Two cases of adult SFTPC gene mutation associated with familial interstitial lung disease diagnosed in the Affiliated Hospital of Medical School of Ningbo University were analyzed retrospectively, and the literature was reviewed. The literatures were retrieved with "family interstitial lung disease" "SFTPC gene" "surface protein C gene" "SFTPC gene mutation associated with familial international lung disease" and "surface protein C gene mutation associated with familial international lung disease" in PubMed, Embase, Ovid, Wanfang database and China National Knowledge Infrastructure (CNKI). Results: There were two patients with familial interstitial lung diseases(one male and one female) with an average age of 27.5 years. Ⅱ-2 patient had symptoms of dry cough and shortness of breath, and Ⅱ-1 patient had no symptoms. There were multiple cysts and fine reticular shadows in both cases. Ⅱ-2 patient had multiple ground glass opacities in both lower lungs. TheⅡ-2 patient was diagnosed with usual interstitial pneumonia (UIP) by transbronchial lung cryobiopsy. A total of 35 patients were included in this literature review, including 20 males, with an average age of 33.5 years. Of all the patients, the clinical symptoms were described in 30 patients. The main manifestations were shortness of breath (22/30), dry cough (18/30), clubbing finger (12/30), and 30% (9/30) of them were found by chest computerized tomography (CT) without symptoms. There were 17 cases with detailed description of chest CT imaging. The most common chest CT findings were multiple intralobular reticular opacities (17/17), multiple cysts (12/17) and ground glass opacities (7/17). The main histopathological pattern was UIP (24/26). Conclusions: The main clinical manifestations of SFTPC gene mutation associated with familial interstitial lung disease in adults are shortness of breath, dry cough and clubbing fingers. The main manifestations are multiple cysts and intralobular reticular opacities in combination with multiple ground glass opacities. There is no specific drug in the treatment at present and early treatment with hydroxychloroquine may have better curative effect. When the imaging findings show multiple cysts and intralobular reticular opacities in combination with multiple ground glass opacities, especially the age of onset is less than 50 years old, this disease should be considered.

[Research progress and challenges of neoadjuvant therapy for esophageal squamous cell carcinoma].

Surgery is the main treatment for resectable esophageal squamous cell carcinoma. However, for patients with locally advanced lesions, surgery-based comprehensive treatment is the best treatment strategy. According to the results of some randomized controlled clinical studies and meta-analysis, preoperative neoadjuvant therapy is recommended to improve the survival rate of patients. Neoadjuvant therapy includes neoadjuvant chemotherapy, chemoradiotherapy, targeted therapy and immunotherapy. Great progress has been made in neoadjuvant therapy, but there are still many clinical problems that need to be solved urgently, including the efficacy and safety of neoadjuvant therapy, the choice of neoadjuvant regimen and treatment cycle, the best combination and advantages of multimodal treatment, and the selection of responders to treatment, etc. This article provides a systematic review of the latest developments and existing controversies in neoadjuvant therapy for esophageal squamous cell carcinoma.

Use of the supraclavicular artery island flap for reconstruction of maxillofacial defects: a case report and literature review.

BACKGROUND: Free flaps are widely used in maxillofacial reconstruction; however, this approach was not feasible in the current case. It was not possible because the free flap method requires microvascular anastomosis expertise, which is difficult, time-consuming and costly. CASE PRESENTATION: An 86-year-old woman suffered squamous cell carcinoma on the right side of her face, which resulted in a large soft-tissue defect. Here, we present a case of facial reconstruction from the inferior margin of the jaw to the top of the head. The size of the defect was 18.5 cm × 7.5 cm, which is rare for a patient of this age in the maxillofacial area. We used the supraclavicular artery island flap (SCAIFP) which measured 19.3 cm × 8.3 cm to repair the defect. After the operation, the flap survived without complications. Then, the patient was followed for 10 months and was satisfied with the aesthetic and functional results at the donor and recipient sites following the tumour resection. The tumour did not recur, and facial nerve function was preserved. CONCLUSION: Our results provide a new choice for the reconstruction of large defects of the head and face, and expand the potential applications of the SCAIFP.

Accurate diagnosis of colorectal cancer based on histopathology images using artificial intelligence.

BACKGROUND: Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses. METHODS: Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany. RESULTS: Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells. CONCLUSIONS: This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.

A Cross-Sectional Study of GLIM-Defined Malnutrition Based on New Validated Calf Circumference Cut-off Values and Different Screening Tools in Hospitalised Patients over 70 Years Old.

BACKGROUND AND AIMS: The Global Leadership Initiative on Malnutrition (GLIM) is new criteria for diagnosing malnutrition that need validation adjusted to race. Our aim is to determine the optimal reference values of calf circumference (CC), investigate the prevalence of GLIM-defined malnutrition based on different screening tools in inpatients over 70 years old in China and assess its relationship with clinical outcomes. METHODS: We designed two continuity studies by analyzing a prospective multicenter database. First, we estimated and validated the CC cut-off values by receiver operating characteristic analyses against in-hospital mortality. Then the patients who were at risk by NRS 2002, MNA-SF and MUST were assessed by the GLIM criteria using the new CC values. Some clinical parameters and outcome data were evaluated. RESULTS: The optimal cut-off values of CC were 29.6 cm for male patients and 27.5 cm for female patients. The prevalence of GLIM-defined malnutrition was 27.5% by using NRS2002, 32.6% by using MNA-SF and 25.4% by using MUST. Patients with GLIM-defined malnutrition showed significantly worse values in BMI, total protein, albumin, neutrophil/lymphocyte ratio, CC, rate of complication, in-hospital mortality, length of stay, and total hospital cost than normal patients. Multivariate logistic regression showed the odds ratio of in-hospital mortality was significantly associated with GLIM defined malnutrition by using MNA-SF [OR = 1.231, 95%CI (1.022, 1.484), P = 0.029]. CONCLUSIONS: The Chinese reference values of CC for inpatients over 70 years old were validated by in-hospital mortality, which could be implemented in GLIM criteria. And this population possessed a high prevalence of nutrition risk and malnutrition. GLIM criteria with MNA-SF seems to be the first choice to diagnose malnutrition.

Escenarios ocultos de la muerte materna: desde la mirada de mujeres sobrevivientes / Hidden scenarios of maternal death: from the gaze of surviving women

El propósito: develar los escenarios ocultos de la muerte materna ocurrida en los micromundos poco abordados en el estado Aragua durante el quinquenio 2011 ­2015.La muerte materna constituye un complejo problema de salud pública, un importante indicador de desarrollo humano, que muestra las más grandes inequidades entre países de diferentes niveles de desarrollo. El enfoque integrador transcomplejo, constituye un camino epistemológico para develar lo que poco se dice y se evidencia, partiendo de referentes multidimensionales que se explican en una dialógica de saberes que no se aplanan unos a los otros sino que se interceptan para hacer tangible las determinaciones socioculturales poco abordadas en las explicaciones de la muerte materna. Desde esta perspectiva epistemológica se hace posible evidenciar las tramas ocultas del discurso de la vida de las mujeres sobrevivientes a la muerte materna, debido a la posibilidad que esta visión de pensamiento brinda para identificar distintos tipos de discurso y las hipertrofias de los mismos, develadas desde interpretaciones que no solo son parte de los micromundos estudiados de las mujeres sino desde la maya de saberes que se imbrican para la comprensión de los testimonios de las informantes. Mediante la hermenéutica como metódica y la historia de vida, se desarrolló un proceso de interpretación y comprensión de los significados de la muerte materna, fundamentadas en sus puntos de encuentro, permitiendo visibilizar lo invisible, desde una postura intersubjetiva. Con técnica de observación, entrevistas enfocadas a: dos mujeres que sobrevivieron a la muerte materna, se obtuvieron las vivencias, lo percibido y recordado, logrando la retención de esa experiencia vivida, que fueron procesadas, encontrando algunos hallazgos como: inadecuada praxis en salud; violencia obstétrica, violencia de género, violencia institucional; creencias socioculturales y representaciones sociales en relación con el embarazo; cargas sociales, emocionales y de trabajo durante el embarazo.

The purpose: to reveal the hidden scenarios of maternal death that occurred in the little-addressed micro-worlds in the state of Aragua during the five-years period 2011 -2015. Maternal death constitutes a complex public health problem, an important indicator of human development, which shows the most great inequities between countries of different levels of development. The integrative cross-complex approach constitutes an epistemological path to reveal what little is said and evidenced, starting from multidimensional references that are explained in a dialogic of knowledge that do not flatten each other but are intercepted to make sociocultural determinations tangible. little addressed in the explanations of maternal death. From this epistemological perspective, it is possible to reveal the hidden plots of the discourse of the lives of women survivors of maternal death, due to the possibility that this vision of thought offers to identify different types of discourse and their hypertrophy, revealed from interpretations that are not only part of the studied microworlds of the women but also from the Mayan knowledge that overlap for the understanding of the informants' testimonies. Through hermeneutics as a method and life history, a process of interpretation and understanding of the meanings of maternal death was developed, based on their meeting points, allowing the invisible to be made visible, from an intersubjective position. With observation technique, interviews focused on: two women who survived maternal death, the experiences were obtained, what was perceived and remembered, achieving the retention of that lived experience, which were processed, finding some findings such as: inadequate health praxis; obstetric violence, gender violence, institutional violence; sociocultural beliefs and social representations in relation to pregnancy; social, emotional and work burdens during pregnancy.

Subtype-specific risk factors for postmenopausal breast cancer: findings from the PLCO trial.

OBJECTIVE: The aim of this analysis is to evaluate the relative weight of different epidemiological risk factors on the development of different breast cancer subtypes (i.e. luminal, Her2+ overexpressed or triple negative). METHODS: De-identified datasets of female participants recruited within the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial were accessed. Multivariate Cox regression analysis was utilized to assess factors affecting the development of breast cancer (regardless of subtype). Additional multivariate analyses were conducted to assess factors affecting the development of the three principal subtypes of breast cancer (ER+/Her2- breast cancer; Her2 overexpressed breast cancer and ER-/Her2- breast cancer). RESULTS: A total of 73,570 eligible participants were evaluated in the current analysis of which 2370 participants subsequently developed breast cancer. The following factors were associated with a higher risk of ER+/Her2- breast cancer: white race (P < 0.001), nulliparity (P < 0.001), higher body mass index (P = 0.003), prior exposure to hormone treatment (P = 0.004) and breast cancer in first-degree female relatives (P < 0.001). The following factors were associated with a higher risk of Her2 overexpressed breast cancer: prior exposure to hormone treatment (P = 0.002) and breast cancer in first-degree female relatives (P = 0.001). The following factors were associated with a higher risk of ER-/Her2- breast cancer: black race (P = 0.013), younger age (P = 0.017) and breast cancer in first-degree female relatives (P 0.023). CONCLUSIONS: There is considerable heterogeneity in risk factors among patients with different subtypes of breast cancer. In particular, factors associated with high estrogen levels seem to be associated with luminal breast cancer rather than other breast cancer subtypes.

DGCR8 promotes the metastasis in triple-negative breast cancer by epigenetically regulating TGF-ß.

OBJECTIVE: Breast cancer (BC) is one of the most ordinary fatal cancers. Recent studies have identified the vital role of genes in the development and progression of Tri-negative breast cancer (TNBC). In this research, DGCR8 was studied to identify how it functioned in the metastasis of TNBC. PATIENTS AND METHODS: DGCR8 expression of tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in 50 TNBC patients. Wound healing assay and transwell assay were used to observe the changes in the biological behaviors of TNBC cells through knockdown or overexpression of DGCR8. In addition, qRT-PCR and Western blot assay were performed to discover the potential target protein of DGCR8 in TNBC. RESULTS: DGCR8 expression level in TNBC samples was higher than that of adjacent ones. Besides, the migration ability and invasion ability of TNBC cells were inhibited after DGCR8 was silenced, while they were promoted after DGCR8 was overexpressed. In addition, TGF-ß was downregulated after silencing of DGCR8 in TNBC cells, while TGF-ß was upregulated after overexpression of DGCR8 in TNBC cells. Furthermore, TGF-ß was upregulated in TNBC tissues, which was positively associated with DGCR8. CONCLUSIONS: Our study uncovers a new oncogene in TNBC and suggests that DGCR8 can enhance TNBC cell migration and invasion via targeting TGF-ß, which provides a novel therapeutic target for TNBC patients.

Porphyromonas gingivalis Sphingolipid Synthesis Limits the Host Inflammatory Response.

Porphyromonas gingivalis, like other bacteria belonging to the phylum Bacteroidetes, synthesizes sphingolipids (SLs). However, their exact roles in microbial physiology and their potential role in mediating interactions with their eukaryotic host are unclear. Our working hypothesis for this study was that synthesis of SLs (host-like lipids) affords a mechanism that allows P. gingivalis to persist in homeostasis with its host. In a previous study, we deleted a gene (PG1780 in strain W83) predicted to encode a serine palmitoyl transferase (SPT)-the enzyme that catalyzes the first conserved step in the synthesis of SLs-and we determined that the mutant was unable to synthesize SLs. Here, we characterized the SPT enzyme encoded by PG1780, analyzed the impact of SPT deletion on P. gingivalis gene expression (RNA-Seq analysis), and began to define the impact of SL synthesis on its interactions with host cells. Enzymatic analysis verified that the protein encoded by PG1780 is indeed an SPT. RNA-Seq analysis determined that a lack of SL synthesis results in differential expression of extracytoplasmic function sigma factors, components of the type IX secretion system (T9SS), and CRISPR and cas genes. Our data demonstrate that when human THP1 macrophage-like cells were challenged with the wild type (W83) and the SL-null mutant (W83 ΔSPT), the SL-null strain elicited a robust inflammatory response (elevated IL-1ß, IL-6, IL-10, IL-8, RANTES, and TNFα) while the response to the parent strain W83 was negligible. Interestingly, we also discovered that SLs produced by P. gingivalis can be delivered to host cells independent of cell-to-cell contact. Overall, our results support our working hypothesis that synthesis of SLs by P. gingivalis is central to its ability to manipulate the host inflammatory response, and they demonstrate the integral importance of SLs in the physiology of P. gingivalis.

The most useful cranial ultrasound predictor of neurodevelopmental outcome at 2 years for preterm infants.

AIM: To determine the most important cranial ultrasound predictors of abnormality associated with neurodevelopmental outcome at 2 years of age in preterm infants. MATERIALS AND METHODS: A total of 343 preterm infants born between 2005 and 2010 and cared for in KK Women's and Children's Hospital, a tertiary paediatric hospital, with birth weight ≤1,250 g were assessed in this retrospective study. Serial cranial ultrasound examinations were examined for intraventricular haemorrhage and cystic periventricular leukomalacia. Ventricular-brain ratio on term equivalent cranial ultrasound was measured. Neurodevelopmental outcome was assessed by the performance on Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) at 2 years corrected age. Mental delay was defined as having a combined Bayley-III score (the average of cognitive and language scores) <80. RESULTS: The mean cognitive, language, and motor scores on Bayley-III in this cohort were 93±15, 83±18, and 92±15, respectively. Twenty-six percent of the preterm infants had mental delay and 4% had cerebral palsy. Ventricular-brain ratio >0.35 was the most significant factor associated with mental delay (odds ratio 5.28, 95% CI: 1.49-18.71, p=0.01). Other significant risk factors for mental delay were male gender, postnatal steroids, and necrotising enterocolitis, whereas maternal tertiary education was a protective factor against adverse outcome. CONCLUSION: Ventricular-brain ratio >0.35 on term-equivalent cranial ultrasound in preterm infants is the strongest predictor for mental delay on Bayley score at 2 years of age.