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Objective: To study the role of CK19 in the survival of patients diagnosed with DPHCC in Fujian, China, which has a high incidence of hepatocellular carcinoma (HCC). Methods: Patients with DPHCC ( n =84) who had undergone surgical interventions at the 900th Hospital of Joint Logistic Support Force between 2013 and 2019 were retrospectively analyzed using the log-rank test and Kaplan-Meier method. Univariate and multivariate Cox model analyses were also conducted to further understand the correlation between CK19 and patient survival. Results: (1)Tumor size, differentiation, peripheral hepatic fibrosis, liver capsule invasion, microvascular invasion (MVI) and serum CA-199 level showed a correlation with CK19, as per the outcomes of Chi-squared tests. (2)According to the univariate analysis, the expression of CK19, MVI, the number of tumor lesions, necrosis, differentiation, peripheral hepatic fibrosis, and serum levels of both alpha-fetoprotein (AFP) and CA-199 showed a strong correlation with overall survival. (3)Necrosis and serum AFP levels were strongly related to an increased risk of death, according to the multivariate analysis. Conclusions: The expression of CK19 may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival.

Background: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine)., Methods: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log 10 plaque forming units (PFU; low-dose v7D group), 3·9 log 10 PFU (medium-dose v7D group), and 4·2 log 10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434., Findings: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related., Interpretation: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future., Funding: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests J-ZJ, J-LH, and X-ZY are employees of and have stock options in Beijing Wantai. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants., (© 2024. The Author(s).)

Background: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times., Method: Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups., Results: Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P < 0.05). After adjustment for the confounding factors, high proportion of breastfeeding were identified as protective factors and long fasting time before NEC were identified as risk factors for LO-NEC; early feeding were identified as protective factors and low gestational age, grade III ~ IV neonatal respiratory distress syndrome (NRDS), high accumulation of the MCT/LCT emulsion in the first week were identified as risk factors for LO-NEC occurring between 8 ~ 14d. Logistic regression analysis showed that LO-NEC was a risk factor for late-onset sepsis, parenteral nutrition-associated cholestasis, metabolic bone disease of prematurity, and extrauterine growth retardation., Conclusion: Actively preventing premature birth, standardizing the treatment of grade III ~ IV NRDS, and optimizing enteral and parenteral nutrition strategies may help reduce the risk of LO-NEC, especially those occurring between 8 ~ 14d, which may further ameliorate the short-term clinical outcome of VPIs., Trial Registration: ChiCTR1900023418 (26/05/2019)., (© 2024. The Author(s).)

Background: Hyperglycemia in pregnancy (HGP) has generally been considered a risk factor associated with adverse outcomes in offspring, but its impact on the short-term outcomes of very preterm infants remains unclear., Methods: A secondary analysis was performed based on clinical data collected prospectively from 28 hospitals in seven regions of China from September 2019 to December 2020. According to maternal HGP, all infants were divided into the HGP group or the non-HGP group. A propensity score matching analysis was used to adjust for confounding factors, including gestational age, twin or multiple births, sex, antenatal steroid administration, delivery mode and hypertensive disorders of pregnancy. The main complications and the short-term growth status during hospitalization were evaluated in the HGP and non-HGP groups., Results: A total of 2,514 infants were eligible for analysis. After matching, there were 437 infants in the HGP group and 874 infants in the non-HGP group. There was no significant difference between the two groups in main complications including respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus, culture positive sepsis, intraventricular hemorrhage, periventricular leukomalacia, anemia, feeding intolerance, metabolic bone disease of prematurity, or parenteral nutrition-associated cholestasis. The incidences of extrauterine growth retardation and increased growth retardation for weight and head circumference in the non-HGP group were all higher than those in the HGP group after matching ( P  < 0.05)., Conclusions: HGP did not worsen the short-term outcomes of the surviving very preterm infants, as it did not lead to a higher risk of the main neonatal complications, and the infants' growth improved during hospitalization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Li, Shen, Zhang, Mao, Liu, Chang, Ye, Qiu, Ma, Cheng, Wu, Chen, Chen, Xu, Mei, Wang, Xu, Ju, Tong, Lin and Wu.)

Pulmonary nodules are a common complication in solid organ transplant recipients, and may have various underlying causes, with Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) being one of them. Given the rarity of this entity, we describe the diagnosis and therapeutic interventions for post-transplant EBV-SMT in two individuals. Both cases involved female patients who were diagnosed with multiple pulmonary nodules 60 months and 116 months, respectively, after receiving living-related kidney transplantation. Pathological examination revealed a spindle cell tumor, with immunophenotype and EBV in situ hybridization supporting the diagnosis of EBV-SMT. After diagnosis, these two patients underwent intervention by decreasing their intake of immunosuppressants. As of the latest follow-up, the patients' lesion size remained stable, and their overall condition was favorable. We also reviewed literature about the morphological and molecular pathological features of EBV-SMT and highlighted the diagnosis and differential diagnosis of pulmonary spindle cell lesions especially in the setting of immunosuppression.

Background: To analyze the real-world growth pattern of very premature infants (VPI) with small for gestational age (SGA) after birth by using the ΔZ value of weight at discharge., Methods: The clinical data were collected from 28 hospitals in China from September 2019 to December 2020. They were divided into the EUGR(Extrauterine Growth Restriction) and the non-EUGR group according to the criterion of ΔZ value of weight at discharge < -1.28., Results: This study included 133 eligible VPI with SGA. Following the criterion of ΔZ value, the incidence of EUGR was 36.84% (49/133). The birth weight, the 5-min Apgar score, and the proportion of male infants in the EUGR group were lower (P < 0.05). The average invasive ventilation time, cumulative duration of the administration of antibiotics, blood transfusion time, blood transfusion ratio, and total days of hospitalization were significantly higher in the EUGR group (P < 0.05). In the EUGR group, several factors exhibited higher values (P < 0.05), including the initiation of enteral feeding, the volume of milk supplemented with human milk fortifier (HMF), the duration to achieve complete fortification, the cumulative duration of fasting, the duration to achieve full enteral feeding, the length of parenteral nutrition (PN), the number of days required to attain the desired total calorie intake and oral calorie intake, as well as the age at which birth weight was regained. The average weight growth velocity (GV) was significantly lower in the EUGR group (P < 0.001). The incidences of patent ductus arteriosus with hemodynamic changes (hsPDA), neonatal necrotizing enterocolitis (NEC) stage≥ 2, late-onset sepsis (LOS), and feeding intolerance (FI) in the EUGR group were higher (P < 0.05). Multivariate logistic regression analysis showed that birth weight, male, and GV were the protective factors, while a long time to achieve full-dose fortification, slow recovery of birth weight, and NEC stage ≥2 were the independent risk factors., Conclusion: SGA in VPI can reflect the occurrence of EUGR more accurately by using the ΔZ value of weight at discharge. Enhancing enteral nutrition support, achieving prompt and complete fortification of breast milk, promoting greater GV, reducing the duration of birth weight recovery, and minimizing the risk of NEC can contribute to a decreased occurrence of EUGR., Trial Registration: CHICTR, ChiCTR1900023418. Registered 26/05/2019, http://www.chictr.org.cn ., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To investigate the association between the expression of long non-coding RNA genes and the HULC rs7763881 polymorphism, recurrence, and metastasis after radical resection in patients with hepatocellular carcinoma (HCC). Methods: Paraffin tissue samples were selected from 426 cases diagnosed with HCC between January 2004 to January 2012. The expression of different genotypes of HULC gene locus rs7763881 in paraffin tissues was detected by PCR, and the association between different genotype expressions and clinical case characteristics of HCC [gender, age, TNM stage, alpha-fetoprotein, tumor maximum diameter (cm), vascular invasion, tumor capsule, tumor grade] was analyzed. Cox proportional risk regression model was used to analyze the correlation between different genotypes and clinicopathological features, prognosis, and recurrence. Survival analysis between different genotypes was performed using the Kaplan-Meier method for a parallel log-rank test. Results: There were 27 (6.3%) cases in the whole group who lost to follow-up. A total of 399 (93.7%) specimens were included in the study, and 105 (26.3%), 211 (52.9%) and 83 (20.8%) were included in the rs77638881 AA, AC, and CC genotypes, respectively. Kaplan-Meier curve showed that the postoperative overall survival and recurrence-free survival rate were significantly higher in patients with the AA than AC/CC genotype ( P < 0.05). Univariate analysis showed that the AC/CC genotype was closely related to tumor vascular invasion and recurrence or metastasis of HCC ( P < 0.05). Cox multivariate analysis results showed that patients with the AA genotype were taken as references, and the results showed that the risk of recurrence and metastasis in patients with the CA/CC genotype increased to varying degrees, with statistical significance ( P < 0.05). Conclusion: The rs7763881 polymorphic loci located on the HULC gene are closely related to HCC recurrence and metastasis after radical resection. Thus, it may be an indicator for evaluating HCC recurrence and metastasis.

Objectives: The management of enteral nutrition in very preterm infants (VPIs) is still controversial, and there is no consensus on the optimal time point after birth at which enteral nutrition can be started. The aim of this study was to investigate the effect of early initiation of enteral nutrition on the short-term clinical outcomes of VPIs., Methods: Data of infants (n = 2514) born before 32 wk of gestation were collected from 28 hospitals located in seven different regions of China. Based on whether enteral feeding was initiated within or after 24 h since birth, the infants were divided into an early initiation of enteral feeding (EIEF) group and a delayed initiation of enteral feeding (DIEF) group., Results: Compared with the DIEF group, the EIEF group was more likely to tolerate enteral nutrition and had less need for parenteral nutrition (all P < 0.05). The EIEF group was associated with lower incidence rates of feeding intolerance, extrauterine growth restriction (EUGR), and late-onset sepsis (LOS) (all P < 0.05). There was no significant difference in the incidence of necrotizing enterocolitis (NEC) (Bell stage ≥2) between the two groups (P = 0.118). The multivariate logistic regression analysis revealed that EIEF was a protective factor against EUGR (odds ratio [OR], 0.621; 95% confidence interval [CI], 0.544-0.735; P < 0.001), feeding intolerance (OR, 0.658; 95% CI, 0.554-0.782; P < 0.001), and LOS (OR, 0.706; 95% CI, 0.550-0.906; P = 0.006)., Conclusions: Early initiation of enteral feeding was associated with less frequency of feeding intolerance, EUGR, and LOS, and it may shorten the time to reach total enteral feeding without increasing the risk of NEC., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Despite the success in decreasing varicella-related disease burden, live-attenuated Oka vaccine strain of varicella-zoster virus (vOka) remains neuro-virulence and may establish latency and reactivate, raising safety concerns. Here we aimed to evaluate the safety and immunogenicity of a skin- and neuro-attenuated varicella vaccine candidate (v7D)., Methods: This is a randomized, double-blind, placebo-controlled, dose-escalation and age de-escalation phase 1 clinical trial conducted in Liuzhou, China (ChiCTR1900022284). Eligible healthy participants aged 1-49 years, with no history of varicella vaccination and had no history of varicella or herpes zoster were sequentially enrolled and allocated to subcutaneously receive one of the three doses (3.3, 3.9, and 4.2 lg PFU) of v7D, vOka or placebo in a dose-escalation and age de-escalation manner. The primary outcome was safety, assessed by adverse events/reactions within 42 days after vaccination and serious adverse events (SAEs) throughout six months after vaccination. The secondary outcome was immunogenicity, assessed by the VZV IgG antibodies measured with fluorescent antibody to membrane antigen (FAMA) assay., Findings: Between April 2019 and March 2020, totally 224 participants were enrolled. Within 42 days post-vaccination, the incidences of adverse reactions were 37.5%-38.7% in the three doses of v7D groups which were similar to that of the vOka (37.5%) and placebo (34.4%) groups. No SAE has been judged as causally related to vaccination. At 42 days post-vaccination, 100% of children aged 1-12 years in the per-protocol set of immunogenicity cohort of the v7D groups became seropositive. Meanwhile, in the intent-to-treat set of immunogenicity cohort of subjects aged 1-49 years, the geometric mean increases of the three groups of v7D vaccine were 3.8, 5.8 and 3.2, respectively, which were similar to that of the vOka vaccine group (4.4) and significantly higher than that of the placebo group (1.3)., Interpretation: The candidate v7D vaccine has been preliminarily shown to be well-tolerated and immunogenic in humans. The data warrant further evaluation of the safety advantage and efficacy of v7D as a varicella vaccine., Funding: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, and Beijing Wantai CO., LTD., Competing Interests: The authors declare the following financial interests/personal relationships that may be considered potential competing interests: The study funder, Beijing Wantai Biological Pharmacy Enterprise, prepared the vaccines in the phase 1 trial. Q-Q S, J-Z J, J-L H, Y-M L and X-Z Y are employees of Beijing Wantai Biological Pharmacy Enterprise. X-Z Y and Y-M L have stock options in Beijing Wantai Biological Pharmacy Enterprise CO. All other authors declare no competing interests., (© 2023 The Author(s).)

Objectives: To study the value of functional echocardiographic parameters in predicting refractory septic shock in neonates., Methods: A total of 72 neonates with septic shock were enrolled. According to the highest value of septic shock score, they were divided into two groups: refractory ( n =30) and non-refractory ( n =42). The two groups were compared in terms of clinical data, laboratory findings, and functional echocardiographic parameters. The receiver operating characteristic (ROC) curve was used to evaluate the performance of functional echocardiographic parameters in predicting refractory septic shock., Results: Compared with the non-refractory group, the refractory group had significantly lower cardiac output and cardiac index (CI) and a significantly higher mean arterial pressure (MAP)/CI ratio ( P <0.05). CI had a cut-off value of 2.6 L/(min·m 2 ), a sensitivity of 79%, a specificity of 83%, and an area under the ROC curve (AUC) of 0.841 in predicting septic shock-related death ( P <0.05), and MAP/CI ratio had a cut-off value of 11.4, a sensitivity of 83%, a specificity of 73%, and an AUC of 0.769 ( P <0.05). CI had a cut-off value of 2.9 L/(min·m 2 ), a sensitivity of 69%, a specificity of 69%, and an AUC of 0.717 in predicting all-cause death within 28 days ( P <0.05)., Conclusions: CI and MAP/CI ratio can be useful for early prediction of septic shock-related death in neonates.

Background: The incidence of extrauterine growth retardation (EUGR) varies considerably in different countries due to the distinct definitions and inclusion criteria of individual studies. Most studies included small for gestational age (SGA) very preterm infants (VPIs), resulting in a higher incidence of EUGR. Experts have suggested the accurate definition of "EUGR" in SGA infants is not "true EUGR". The postnatal growth curve of multiple premature births also differs from that of singletons. As far as we know, there is no study about relationship between singleton-non-SGA preterm infants and EUGR., Objectives: To analyze the factors influencing EUGR among VPIs who were singleton-non-SGA in China., Methods: A prospective-multicenter study was conducted in 28 hospitals distributed through China from September 2019 to December 2020. The clinical data on singleton-non-SGA among VPIs were divided into EUGR group (n = 692) and non-EUGR group (n = 912)., Results: Compared to non-EUGR group, the mean gestational age (GA), mean birth weight (BW) and percentage of BW in Fenton curve in EUGR group were lower (P < 0.001 for all). The incidence of EUGR among distinct GA groups (classifications of GA < 28weeks, 28-28 +6 weeks, 29-29 +6 weeks, 30-30 +6 weeks and 31-31 +6 weeks) and distinct BW groups (classifications of BW<1000 g, 1000-1249 g, 1250-1499 g, 1500-1999g and 2000-2500 g) were statistically significant (P = 0.004 and P <.001). Logistic regression analysis indicated that later addition of human milk fortifier (HMF), later attainment of HMF sufficient fortification, later return to BW, more accumulative days of fasting, longer duration of parenteral nutrition, total duration of oxygen support and moderate/severe bronchopulmonary dysplasia (BPD) were risk factors for the development of EUGR in singleton-non-SGA VPIs (P < 0.001, P = 0.002, P < 0.001, P = 0.002, P = 0.017, P = 0.003 and P = 0.002, respectively). The use of full-course antenatal steroids, greater BW as a percentile of the Fenton curve, breastfeeding initiation and faster average velocity of weight growth effectively protected against EUGR (P = 0.008, P < 0.001, P < 0.001 and P < 0.001, respectively)., Conclusions: The overall incidence of EUGR was 43.1% among singleton-non-SGA VPIs in China. Raising the full-course antenatal steroids usage, reducing the incidence of moderate and severe BPD, attaching importance to the management of enteral nutrition in VPIs and increasing the weight growth velocity can reduce the incidence of EUGR., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

In order to understand the interspecific and ecological relationships of Michelia odora (extremely small population) community and strengthen the protection of wild M. odora resources in Junzifeng Nature Reserve, we studied the niche characteristics and interspecific associations of dominant tree species. The results showed that M. odora , Machilus chekiangensis , Schima superba , and Alniphyllum fortunei had obvious niche breadth advantages, which were the constructive species of the community. Among the 190 groups of species pairs among the 20 dominant tree species, 50.5% of species pairs had niche overlap value greater than 0.5. The degree of ecological niche differentiation among species was general. M. odora had large niche overlap with other 19 species, indicating a competitive risk when resources were insufficient. The overall associations of dominant tree species were significantly positive, indicating the community was at the late stage of relatively stable succession. The results of χ 2 test, asso-ciation coefficient, and Pearson correlation coefficient showed that all the significance ratios of interspecific association were lower, and that the independence among species was relatively strong. There was a positive correlation between interspecific association and niche overlap. The M. odora community was relatively mature, with full utilization of resources and stable interspecific relationship. To promote the rejuvenation and create a good habitat of M. odora population, the population size with large overlap with M. odora niche and significant negative association could be appropriately limited, while that with positive interaction could be increased.

Objective: To investigate the incidence and related factors of extrauterine growth retardation (EUGR) and "true EUGR" in very preterm infants (VPI) from different regions of China., Materials and Methods: Clinical data of VPI were prospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. The infants were divided into a small for gestational age (SGA) group or non-SGA group at birth, with non-SGA infants at 36 weeks of gestation or at discharge being further divided into a EUGR group or a non-EUGR group. Infants in the EUGR and non-SGA group were defined as "true EUGR." The general information of VPI, such as maternal complications during pregnancy, use of enteral nutrition and parenteral nutrition, and complications during hospitalization were compared between the groups., Results: Among the 2,514 VPI included in this study, 47.3, 41.5, and 33.3% of VPI were below the 10th percentile, and 22.6, 22.4, and 16.0% of VPI were below the 3rd percentile for weight, height, and head circumference at 36 weeks of gestation or at discharge, respectively, by the percentile on the 2013 Fenton curve. The incidences of EUGR and "true EUGR" evaluated by weight were 47.3 and 44.5%, respectively. Univariate analysis showed that there were statistically significant differences in the aspects of perinatal and nutritional characteristics, treatment, and complications between the groups. Multivariate analysis showed that in non-SGA infants, the cumulative caloric intake during the first week was a protective factor for "true EUGR," while days to reach total enteral nutrition, late initiation of human milk fortifier, and moderate to severe bronchopulmonary dysplasia were independent risk factors for "true EUGR.", Conclusion: More attention should be paid to the nutritional management of VPI to prevent "true EUGR." Cumulative caloric intake should be ensured and increased during the first week, total enteral nutrition should be achieved as early as possible, human milk fortifier should be added early, and moderate to severe bronchopulmonary dysplasia should be prevented. These strategies are very important for reducing the incidence of "true EUGR" in VPI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shen, Wu, Mao, Liu, Chang, Zhang, Zheng, Ye, Qiu, Ma, Cheng, Wu, Chen, Chen, Xu, Mei, Wang, Xu, Ju, Chen, Tong and Lin.)

With the increase in extremely low birth weight (ELBW) infants, their outcome attracted worldwide attention. However, in China, the related studies are rare. The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units in Guangdong Province of China during 2008-2017 were analyzed. A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76% to 62.02%. Increased survival is closely related to birth weight (BW), regional economic development, and specialized hospital. The incidence of complications was neonatal respiratory distress syndrome (85.2%), oxygen dependency at 28 days (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days). A total of 768 ELBW infants died after treatment withdrawal, for reasons of economic and/or poor outcome. The number of ELBW infants is increasing in Guangdong Province of China, and the overall survival rate is improving steadily., (© 2022. The Author(s).)

Objective: Nutritional deficiency soon after birth is a risk factor of chronic lung disease (bronchopulmonary dysplasia, BPD). Afflicted infants are further prone to inadequate growth during hospitalization (extrauterine growth restriction, EUGR). This multi-center retrospective study investigated risk factors of EUGR, specifically in very preterm infants with BPD., Method: Data of infants with BPD who were born less than 32 weeks gestation (n = 1010) were collected from 7 regions of China. All infants were non-small for gestational age at birth. Infants were characterized as EUGR or non-EUGR at 36 weeks gestation or discharge, or stratified by gestational age or birthweight. Logistic regression analysis was applied., Results: In 65.5% of the population, the BPD was mild. Infants with severe BPD (8.3%) had the highest rate of EUGR (72.6%, P < 0.001). Groups stratified by gestational age did not differ in rates of EUGR, but the birthweight of the EUGR group was significantly lower than that of the non-EUGR (P < 0.001). Birthweights of < 1000, 1000-1499, and ≥ 1500 g showed EUGR rates of 65.9%, 43.4%, and 23.8%, respectively (P < 0.001). Overall, the independent risk factors of EUGR were: moderate-to-severe BPD, gestational hypertension, cesarean section, cumulative fasting time, time required to achieve 110 kcal/kg/d, and hemodynamically significant patent ductus arteriosus (hsPDA)., Conclusion: In very preterm infants with BPD, the lower the birthweight or the more severe the BPD, the greater the risk of EUGR. In those with hsPDA, or moderate-to-severe BPD, it is especially important to prevent EUGR through perinatal management, enteral nutrition, and nutritional strategies., (© 2022. The Author(s).)

Objectives: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China., Methods: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group ( n =1 189) and non-EUGR ( n =1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined., Results: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR ( P <0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR ( P <0.05)., Conclusions: It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

Objectives: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China., Methods: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups., Results: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth ( P <0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group ( P <0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia ( P <0.05)., Conclusions: There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Without approved vaccines and specific treatments, COVID-19 is spreading around the world with above 26 million cases and approximately 864 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 - Gly548 of spike protein of SARS-CoV-2 linked with Gln830 - Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5) were expressed and renatured. The antigenicity and immunogenicity of S1-4 were evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency was measured preliminarily by microneutralization assay (MN50). The soluble S1-4 and S1-5 protein was prepared to high homogeneity and purity. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity supplemented with Th1-type immunity. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralizing antibody titer 256. Recombinant SARS-CoV-2 RBD with a built in T helper epitope could stimulate both strong humoral immunity supplemented with cellular immunity in mice, demonstrating that it could be a promising subunit vaccine candidate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease., Competing Interests: The authors have declared that no competing interests exist.

This study was aimed to investigate the association between dyslipidemia and thyroid associated ophthalmopathy (TAO). We evaluated the relationship between dyslipidemia and TAO in 218 patients with Graves' disease (GD) and found that the serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in the GD subjects with TAO ( n= 110) were significantly increased [(5.32±1.39) mmol/L vs. (3.18±2.12) mmol/L, (2.98±0.75) mmol/L vs. (1.25±0.98) mmol/L] than those in the GD subjects without TAO ( n= 108). TC and LDL-C were positively correlated with the Clinical disease activity score (CAS) [TC ( r= 0.7, P= 0.03),LDL-C ( r= 0.82, P= 0.03)], and the levels of TC ( OR= 2.56, P= 0.02) and LDL-C( OR= 2.01, P= 0.015) were positively associated with TAO. These suggested that high serum cholesterol level is a novel risk factor for TAO, and management of blood lipids should be included in the treatment of TAO.

Background: We aimed to determine the safety and effectiveness of laparoscopic-assisted surgery (LAS) in visceral obesity patients with colorectal cancer (CRC)., Patients and Methods: We retrospectively collected the clinical data of consecutive patients who underwent colorectal surgery for CRC between August 2014 and July 2018. The third lumbar vertebra visceral fat area was measured to diagnose visceral obesity. One-to-one propensity score matching was performed to compare the short-term outcomes between the open surgery (OS) and LAS in visceral obesity patients. Univariate and multivariate analyses were performed to evaluate the risk factors of postoperative complications., Results: A total of 280 visceral obesity patients were included in this study with 140 patients for each group. Compared with the OS group, the LAS group had more lymph nodes harvested, longer surgical duration, and shorter postoperative hospital stay. The overall incidence of complications in OS was significantly higher than LAS (32.1 vs. 20.0%, P=0.021). Multivariate analysis revealed that age of at least 65 years (odds ratio: 1.950, 95% confidence interval: 1.118-3.403; P=0.019) was an independent risk factor for postoperative complications, whereas LAS (odds ratio: 0.523, 95% confidence interval: 0.302-0.908; P=0.021) was a protective factor., Conclusion: LAS in visceral obesity patients with CRC was a safer and less invasive alternative than open surgery, with fewer complications within the first 30 days postoperatively.

Previous studies have been indicated that tumor necrosis factor receptor-associated factor 6 (TRAF6)-induced inflammation leads to acute kidney injury (AKI). How microRNA (miR) contributes to this process is poorly defined. The aim of this study was to investigate whether miR-590-3p regulated lipopolysaccharide (LPS)-induced inflammatory response by inhibiting TRAF6. LPS-induced septic mice were treated with adenovirus expressing miR-590-3p (ad-miR-590-3p) via tail-vein injection. AKI was evaluated by examining serum cystatin C (CysC), serum β2-microglobulin (β2-MG), and blood urea nitrogen (BUN). The mRNA and protein levels were assayed by RT-qPCR and western blotting, respectively. The proliferation of podocytes was monitored using the MTT assay. Cell apoptosis was analyzed by flow cytometry. Survival outcomes in ad-miR-590-3p-transfected septic mice were markedly improved compared with mice with LPS-induced sepsis. Ad-miR-590-3p transfection significantly attenuated LPS-induced AKI, which was reflected by an improved glomerular filtration rate (GFR) as determined by measuring CysC, β2-MG, and BUN. Moreover, we observed that miR-590-3p was a novel regulator of TRAF6, binding to its 3'-untranslated regions (3'-UTRs). In vitro, a miR-590-3p gain-of-function mutation blocked LPS-induced podocyte growth inhibition and apoptosis, as well as overactivation of the inflammatory response. miR-590-3p has the ability to suppress LPS-induced AKI and podocyte apoptosis by targeting TRAF6. This might provide a novel strategy for the treatment of LPS-induced renal injuries.

In this study, effects of euphorbia kansui on serum levels of inflammatory factors in patients with severe acute pancreatitis were investigated, and the mechanisms underlying the role of Euphorbia kansui in the treatment of severe acute pancreatitis were discussed. 36 patients hospitalized in the Third Affiliated Hospital of Wenzhou Medical University from March 2017 to May 2018 due to severe acute pancreatitis were selected and divided into two groups using a randomized grouping method. ELISA (enzyme-linked immunosorbent assay) was used to detect expressions of various inflammatory cytokines, such as tumor necrosis factor α (TNF-α), soluble TNF receptors (sTNFR), nuclear factor-κB (NF-κB), interleukin-6 (IL-6), and interleukin-8 (IL-8), in the serum of patients at different time points. The results showed no significant difference between the two groups in terms of age, gender, predisposing factors, Balthaza CT scores, and APACHEII (Acute Physiology and Chronic Health Evaluation) scores. According to the experimental results, euphorbia kansui effectively reduced the expression of inflammation related cytokines, such as NF-κB, TNF-α, sTNFR, IL-6, and IL-8, in the serum of patients with severe acute pancreatitis. It was also proposed that euphorbia kansui hindered the release of inflammatory factors and treated SAP by inhibiting the activation of the NF-κB signaling pathway.

Intrahepatic cholangiocarcinoma is a relatively uncommon malignant neoplasm. We recently encountered an unusual case of intrahepatic cholangiocarcinoma that histologically resembled a thyroid carcinoma. A thorough review of the English literature revealed only 2 similar cases that have been previously reported. Immunohistochemical studies are imperative to confirm the diagnosis of cholangiocarcinoma and to exclude the possibility of metastatic thyroid carcinoma and other malignancies with thyroid-like features.

Objective: To investigate feasibility and curative effect of superselective arterial embolization for the treatment of massive haemorrhage from pelvic fracture., Methods: From March 2008 to February 2016, clinical data of 65 patients with massive haemorrhage from pelvic fracture were collected and analyzed, and patients were divided into non-embolic and embolic group according to whether perform vascular thrombosis. Thirty-three patients were in non-embolic group including 26 males and 7 females aged from 21 to 64 years old with an average of(39.2±5.7) years old, the time from injury to operation ranged from 1.1 to 4.8 h with an average of (2.2±0.4) h; 12 cases were type B and 21 cases were type C according to AO/Tile classification; injury severity score (ISS) ranged from 25 to 42 with an average of (37.7±7.5); shock index score ranged from 1.7 to 2.4 with an average of 2.1±0.3; treated with blood transfusion and fluid infusion. Thirty-two patients in embolic group, including 25 males and 7 females aged from 22 to 65 years old with an average of(38.1±4.5) years old; the time from injury to operation ranged from 1.2 to 4.8 h with an average of (2.1± 0.5) h; 14 cases were type B and 18 cases were type C according to AO/Tile classification; ISS ranged from 26 to 43 with an average of 38.9±4.5; shock index score ranged from 1.6 to 2.4 with an average of 2.2±0.2; treated by blood transfusion and fluid infusion with superselective arterial embolization. Blood transfusion volume, fluid infusion volume, shock correction time and survival rate were observed and compared, effective rate of hemostasis and postoperative complications were compared., Results: Thirty-seven artery were injured in embolic group, hemostasis were controlled at 3 h after operation, and hemodynamics turned to stable. There were significant difference in blood transfusion volume, fluid infusion volume, shock correction time between non-embolic and embolic group, and embolic group performed better. Survival rate in embolic group was also better than that of non-embolic group, and had significant difference. While there was obvious differences in complications(χ²=4.03, P =0.045)., Conclusions: Superselective arterial embolization for massive haemorrhage from pelvic fracture could effective hemostasis, reduce blood transfusion and fluid infusion volume and occurrence rate of shock, moreover improve survival rate and deserves promotion., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

A novel method, real-time reverse transcription PCR (real-time RT-PCR) coupled with probe-melting curve analysis, has been established to detect two kinds of samples within one fluorescence channel. Besides a conventional TaqMan probe, this method employs another specially designed melting-probe with a 5' terminus modification which meets the same label with the same fluorescent group. By using an asymmetric PCR method, the melting-probe is able to detect an extra sample in the melting stage effectively while it almost has little influence on the amplification detection. Thus, this method allows the availability of united employment of both amplification stage and melting stage for detecting samples in one reaction. The further demonstration by simultaneous detection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in one channel as a model system is presented in this essay. The sensitivity of detection by real-time RT-PCR coupled with probe-melting analysis was proved to be equal to that detected by conventional real-time RT-PCR. Because real-time RT-PCR coupled with probe-melting analysis can double the detection throughputs within one fluorescence channel, it is expected to be a good solution for the problem of low-throughput in current real-time PCR., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The risk factors of high trait anger of juvenile offenders were explored through questionnaire study in a youth correctional facility of Hubei province, China. A total of 1090 juvenile offenders in Hubei province were investigated by self-compiled social-demographic questionnaire, Childhood Trauma Questionnaire (CTQ), and State-Trait Anger Expression Inventory-II (STAXI-II). The risk factors were analyzed by chi-square tests, correlation analysis, and binary logistic regression analysis with SPSS 19.0. A total of 1082 copies of valid questionnaires were collected. High trait anger group (n=316) was defined as those who scored in the upper 27th percentile of STAXI-II trait anger scale (TAS), and the rest were defined as low trait anger group (n=766). The risk factors associated with high level of trait anger included: childhood emotional abuse, childhood sexual abuse, step family, frequent drug abuse, and frequent internet using (P<0.05 or P<0.01). Birth sequence, number of sibling, ranking in the family, identity of the main care-taker, the education level of care-taker, educational style of care-taker, family income, relationship between parents, social atmosphere of local area, frequent drinking, and frequent smoking did not predict to high level of trait anger (P>0.05). It was suggested that traumatic experience in childhood and unhealthy life style may significantly increase the level of trait anger in adulthood. The risk factors of high trait anger and their effects should be taken into consideration seriously.

Biochar derived from various materials has been investigated with regard to its ability to decrease the bioavailability of heavy metals in contaminated soils, and thus reduce their potential to enter the food chain. However, little attention has been given to the adsorption capacity of untreated crop straws, which are commonly used as a biochar feedstock, especially in soils. Hence, this study was conducted to investigate the effect of crop straws on heavy metal immobilization and subsequent heavy metal uptake by maize and ryegrass in a soil artificially polluted by Cd and Pb. Bamboo biochar, rice straw, and wheat straw were mixed into soil four weeks before the experiment, enabling them to reach equilibrium at 2% (w/w), 1% (w/w), and 1% (w/w), respectively. The results showed that soil pH for both species was significantly increased by all treatments, except when wheat straw was used for ryegrass cultivation. Soil organic carbon was only improved in the rice straw treatment and the soil alkali-hydrolyzable N content was significantly decreased with all of the amendments, which may have contributed to the lack of an effect on plant biomass. Soil available Cd was significantly lower in the rice straw treatment than in the control soil, while Pb levels clearly decreased in wheat straw treatment. The Cd concentration in shoots of maize was reduced by 50.9%, 69.5%, and 66.9% with biochar, rice straw, and wheat straw, respectively. In addition, shoot Cd accumulation was decreased by 47.3%, 67.1%, and 66.4%, respectively. Shoot Pb concentration and accumulation were only reduced with the rice straw treatment for both species. However, metal uptake in plant roots was more complex, with increased metal concentrations also detected. Overall, the direct application of crop straw could be considered a feasible way to immobilize selected metals in soil, once the long-term effects are confirmed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Peroxisome proliferator activated receptor gamma (PPARγ) is a pleiotropic ligand activated transcription factor that acts in several tissues to regulate adipocyte differentiation, lipid metabolism, insulin sensitivity and glucose homeostasis. PPARγ also regulates cardiomyocyte homeostasis and by virtue of its obligate role in placental development is required for embryonic survival. To determine the postnatal functions of PPARγ in vivo we studied globally deficient neonatal mice produced by epiblast-restricted elimination of PPARγ. PPARγ-rescued placentas support development of PPARγ-deficient embryos that are viable and born in near normal numbers. However, PPARγ-deficient neonatal mice show severe lipodystrophy, lipemia, hepatic steatosis with focal hepatitis, relative insulin deficiency and diabetes beginning soon after birth and culminating in failure to thrive and neonatal lethality between 4 and 10 days of age. These abnormalities are not observed with selective PPARγ2 deficiency or with deficiency restricted to hepatocytes, skeletal muscle, adipocytes, cardiomyocytes, endothelium or pancreatic beta cells. These observations suggest important but previously unappreciated functions for PPARγ1 in the neonatal period either alone or in combination with PPARγ2 in lipid metabolism, glucose homeostasis and insulin sensitivity.

Objective: RNA-seq data of rectal adenocarcinoma (READ) were analyzed with bioinformatics tools to unveil potential biomarkers in the disease., Materials and Methods: RNA-seq data of READ were downloaded from The Cancer Genome Atlas (TCGA) database. Differential analysis was performed with package edgeR. False discovery rate (FDR) < 0.05 and |log2 (fold change)|>1 were set as cut-off values to screen out differentially expressed genes (DEGs). Gene coexpression network was constructed with package Ebcoexpress. Gene Ontology enrichment analysis was performed for the DEGs in the gene coexpression network with DAVID online tool. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was also performed for the genes with KOBASS 2.0., Results: A total of 620 DEGs, 389 up-regulated genes, and 231 down-regulated genes, were identified from 163 READ samples and 9 normal controls. A gene coexpression network consisting of 71 DEGs and 253 edges were constructed. Genes were associated with ribosome and focal adhesion functions. Three modules were identified, in which genes were involved in muscle contraction, negative regulation of glial cell proliferation and extracellular matrix organization functions, respectively. Several critical hub genes were disclosed, such as RPS2, MMP1, MMP11 and FAM83H. Thirteen relevant small molecule drugs were identified, such as scriptaid and spaglumic acid. A total of 8 TFs and 5 miRNAs were acquired, such as MYC, NFY, STAT5A, miR-29, miR-200 and miR-19., Conclusions: Several critical genes and relevant drugs, TFs and miRNAs were revealed in READ. These findings could advance the understanding about the disease and benefit therapy development.

Objective: To evaluate the incidence and risk factors of postoperative delirium in patients post permanent pacemaker implantation., Methods: Patients underwent permanent pacemaker implantation in our department from September 2013 to February 2015 were included in this study. Delirium was measured by the confusion assessment method on the first three postoperative days. All the patients were divided into the postoperative delirium group and the non-delirium control group according to whether new onset delirium was diagnosed. Risk factors significantly associated with postoperative delirium detected by univariate analysis were entered into multivariable analysis to define the independent predictors of postoperative delirium., Results: A total of 225 patients were enrolled in this study. The incidence of postoperative delirium was 5.3%. Patients developing postoperative delirium were older ((83±5) years vs. (74±11) years, P=0.002), had a significantly higher incidence of blood pressure fluctuations (58.3% (7/12) vs. 4.7% (10/213), P<0.001), hyponatremia (25.0% (3/12) vs. 5.2% (11/213), P=0.030) and had higher systolic blood pressure ((157±35) mmHg vs. (136±22)mmHg, 1 mmHg=0.133 kPa, P=0.007). However, patients developing postoperative delirium had lower preoperative average heart rate ( (47±18)bpm vs. (58±15)bpm, P=0.007). Multiple regression analysis showed that advanced age (OR= 2.984, 95% CI: 1.226-7.624, P=0.016) and blood pressure fluctuations (OR=27.393, 95% CI: 6.735-111.417, P<0.001) are the independent risk factors for pacemaker patients with postoperative delirium., Conclusion: Advanced age and blood pressure fluctuations are independent risk factors of postoperative delirium in patients post permanent pacemaker implantation.

Although the absolute number of positive lymph nodes (LNs) has been established as 1 of the most important prognostic factors in rectal cancers, many researchers have proposed that the lymph node ratio (LNR) may have better predicted outcomes. We conducted a retrospective study to compare the predictive ability of LNR and ypN category in rectal cancer. A total of 264 locally advanced rectal cancer (LARC) patients who underwent preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) between 2005 and 2012 were reviewed. All patients were categorized into 3 groups or patients with metastatic LNs were categorized into 2 groups according to the LNR. The prognostic effect on overall survival (OS) and disease-free survival (DFS) was evaluated. With a median follow-up of 45 months, the OS and DFS were 68.4% and 59.3% for the entire cohort, respectively. The respective 5-year OS and DFS rates for the 3 groups (LNR = 0, 0 < LNR ≤ 0.20, and 0.20 < LNR ≤ 1.0) were as follows: 83.2%, 72.6%, and 49.4% (P < 0.001) and 79.5%, 57.3%, and 33.5% (P < 0.001), respectively. Multivariate analysis revealed that LNR and differentiation, but not the number of positive LNs, had independent prognostic value for OS (hazard ratio [HR] = 2.328, 95% confidence interval [CI]: 1.850-4.526, P < 0.001) and DFS (HR = 3.004, 95% CI: 1.616-5.980, P < 0.001). As for patients with positive LNs, the respective 5-year OS and DFS rates for the 2 groups (0 < LNR ≤ 0.20, and 0.20 < LNR ≤ 1.0) were 72.6% and 49.4% (P < 0.001) and 57.3% and 33.5% (P < 0.001), respectively. Multivariate analysis revealed that only LNR was an independent factor for OS (HR = 3.214, 95% CI: 1.726-5.986, P < 0.001) and DFS (HR = 4.230, 95% CI: 1.825-6.458, P < 0.001). Subgroups analysis demonstrated that the ypN category had no impact on survival whereas increased LNR was a significantly prognostic indicator for worse survival in the LNs < 12 subgroup. LNR is an independent prognostic factor in LARC patients treated with preoperative CRT followed by TME. It may be a better independent staging method than the number of metastatic LNs when <12 LNs are harvested after preoperative CRT.

Many studies have examined the association between the FABP2 (rs1799883) Ala54Thr gene polymorphism and type 2 diabetes mellitus risk (T2DM) in various populations, but their results have been inconsistent. To assess this relationship more precisely, A HuGE review and meta-analysis were performed. The PubMed and CNKI database was searched for case-control studies published up to April 2014. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 13 studies, comprising 2020 T2DM cases and 2910 controls were included. Overall, for the Thr carriers (Ala/Thr and Thr/Thr) versus the wild-type homozygotes (Ala/Ala), the pooled OR was 1.18 (95% CI = 1.04-1.34, P = 0.062 for heterogeneity), for Thr/Thr versus Ala/Ala the pooled OR was 1.17 (95% CI = 1.05-1.41 P = 0.087 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were found among Asians but not Caucasians. This meta-analysis suggests that the FABP2 (rs1799883) Ala54Thr polymorphisms are associated with increased susceptibility to T2DM risk among Asians but not Caucasians., (© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Breast cancer stem-like cells (BCSC) are crucial for metastasis but the underlying mechanisms remain elusive. Here, we report that tumor-infiltrating natural killer (NK) cells failed to limit metastasis and were not associated with improved therapeutic outcome of BCSC-rich breast cancer. Primary BCSCs were resistant to cytotoxicity mediated by autologous/allogeneic NK cells due to reduced expression of MICA and MICB, two ligands for the stimulatory NK cell receptor NKG2D. Furthermore, the downregulation of MICA/MICB in BCSCs was mediated by aberrantly expressed oncogenic miR20a, which promoted the resistance of BCSC to NK cell cytotoxicity and resultant lung metastasis. The breast cancer cell differentiation-inducing agent, all-trans retinoic acid, restored the miR20a-MICA/MICB axis and sensitized BCSC to NK cell-mediated killing, thereby reducing immune escape-associated BCSC metastasis. Together, our findings reveal a novel mechanism for immune escape of human BCSC and identify the miR20a-MICA/MICB signaling axis as a therapeutic target to limit metastatic breast cancer., (©2014 American Association for Cancer Research.)

Purpose: Fast-track surgery aims to attenuate the surgical stress response, reduce complications, and shorten hospital stay. The goal of the present meta-analysis is to assess the safety and effectiveness of fast-track surgery in patients undergoing gastrectomy for gastric cancer compared with conventional perioperative care., Methods: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and reference lists of the identified studies were searched to identify randomized clinical trials that compared fast-track surgery with conventional perioperative care in patients undergoing gastrectomy for gastric cancer., Results: Five studies with a total of 400 patients were included in the meta-analysis. Meta-analysis shows that postoperative hospital stay (weighted mean difference (WMD) -1.87 days, 95 % confidence interval (CI), -2.46 to -1.28 days, P < 0.00001), time to first passage of flatus (WMD -0.71 days, 95 % CI, -1.03 to -0.39 days, P < 0.0001), and hospital costs (WMD -505.87 dollars, 95 % CI, -649.91 to -361.84 dollars, P < 0.00001) were significantly reduced for fast-track surgery. No significant differences were found for readmission rates (relative risk (RR), 1.97 95 % CI, 0.37 to 10.64, P = 0.43) and total postoperative complications (RR, 0.99 95 % CI, 0.56 to 1.76, P = 0.97)., Conclusions: Fast-track surgery is safe and effective in gastrectomy for gastric cancer. Further randomized trials are needed to strengthen the conclusions.

Cancer stem cells (CSCs) constitute a subpopulation of cancer cells that have the potential for self-renewal, multipotent differentiation, and tumorigenicity. Studies on CSC biology and CSC-targeted therapies depend on CSC isolation and/or enrichment methodologies. Scientists have conducted extensive research in this field since John Dick's group successfully isolated CSCs based on the expression of the CD34 and CD38 surface markers. Progress in CSC research has been greatly facilitated by the enrichment and isolation of these cells. In this review, we summarize the current strategies used in our and other laboratories for CSC isolation and enrichment, including methods based on stem cell surface markers, intracellular enzyme activity, the concentration of reactive oxygen species, the mitochondrial membrane potential, promoter-driven fluorescent protein expression, autofluorescence, suspension/adherent culture, cell division, the identification of side population cells, resistance to cytotoxic compounds or hypoxia, invasiveness/adhesion, immunoselection, and physical property. Although many challenges remain to be overcome, it is reasonable to believe that more reliable, efficient, and convenient methods will be developed in the near future.

Background: Enhanced recovery after surgery programs in colorectal surgery aim to attenuate the surgical stress response, reduce complications and shorten hospital stay., Objective: This study aimed to assess the safety and efficacy of enhanced recovery after surgery programs in colorectal surgery in comparison with traditional care., Data Sources: PubMed, Embase, and Cochrane databases were electronically searched (date range, January 1966 to July 2012)., Study Selection: Randomized controlled trials were selected that compared enhanced recovery after surgery programs with traditional care in elective colorectal surgery., Intervention: Articles were reviewed independently by 2 reviewers, who extracted the data and assessed the quality of the included studies. The outcome measures were analyzed, and the quality of evidence for each outcome was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation system., Main Outcome Measures: The primary outcome measures were primary and total postoperative hospital stay, readmission rates, total postoperative complications (including general and surgical complications), and mortality., Results: Thirteen studies (total, 1910 patients) were included in the meta-analysis. In comparison with traditional care, enhanced recovery after surgery programs were associated with significantly decreased primary hospital stay (weighted mean difference, -2.44 days; 95% CI, -3.06 to -1.83 days; p < 0.00001), total hospital stay (weighted mean difference, -2.39 days; 95% CI, -3.70 to -1.09 days; p = 0.0003), total complications (relative risk, 0.71; 95% CI, 0.58-0.86; p = 0.0006), and general complications (relative risk, 0.68; 95% CI, 0.56-0.82; p < 0.0001). No significant differences were found for readmission rates, surgical complications, and mortality., Limitations: This study was limited by the risk of bias in most included studies., Conclusions: Enhanced recovery after surgery programs are safe and effective, and increased implementation is justified for perioperative care in colorectal surgery. Future studies may examine the benefits of enhanced recovery after surgery programs in elderly patients and in other GI surgery.

Background: The safety and effectiveness of early oral feeding after colorectal surgery has not been determined. We performed a meta-analysis to evaluate surgical outcomes following early oral feeding compared with traditional oral feeding in patients undergoing elective colorectal surgery., Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials comparing the outcomes following early oral feeding versus traditional oral feeding in patients undergoing elective colorectal surgery. The trials must have reported at least one of the following end points: anastomotic dehiscence, pneumonia, wound infection, nasogastric tube reinsertion, vomiting, mortality, length of hospital stay, hospital costs, and quality of life., Results: Seven trials, which included a total of 587 patients, met our inclusion criteria. Compared with traditional oral feeding, early oral feeding reduced the length of hospital stay (weighted mean difference -1.58 days; 95% CI -2.77 to -0.39; p = 0.009) and the total postoperative complications (relative risk 0.70; 95% CI 0.50-0.98; p = 0.04). There were no significant differences in the risk of anastomotic dehiscence, pneumonia, wound infection, rate of nasogastric tube reinsertion, vomiting, or mortality., Conclusions: Early oral feeding is safe and effective in patients undergoing elective colorectal surgery., (Copyright © 2013 S. Karger AG, Basel.)

Objective: To investigate the clinicopathologic features, immunophenotyping, differential diagnoses and prognosis of histiocytic sarcoma (HS)., Methods: The clinical and pathologic findings of 4 cases of HS were reviewed. The samples were used for paraffin section, HE stain, immunohistochemistry stain by EnVision method, electron microscope observation. Follow-up information was available in all patients., Results: The age of patients, 2 males and 2 females, ranged from 22 to 65 years old (median, 43.25 years). The sites of involvement included lymph node (2 cases), skin or soft tissue (1 case) and colon (1 case). The tumor cells were widespread infiltration, diffused distribution, no adhesion to each other. Tumor cells were middling and large, round, orbicular-ovate, polygon, epithelium appearance, plentiful cytoplasm and acidophilia, cystose. Nucelus was round, orbicular-ovate, dissymmetry. Nuclear chromatin was vacuole appearance, basophilia nucleolus, caryocinesia and pathological mitotic figure. Three of the cases showed conjugate nuclei, increased pleomorphism with multinucleated tumor giant cell formation. Focal cytoplasmic with foamy appearance was identified in 2 cases. One case demonstrated foci of spindly sarcomatoid appearance. Hemophagocytosis was identified in 2 cases. The tumor cells of 4 cases were often accompanied by various numbers of inflammatory cells. Immunohistochemical study showed that all cases were diffusely positive for α-1-ACT, CD68, CDl63 and lysozyme. Three of 4 cases also expressed CD45, CD45RO. The electron microscope results of 4 cases showed that the tumor cells were plentiful cytoplasm and a few cytolysosome in the cytoplasm, and no birbeck cytorrhyctes, cell-cell junction and digitation. Amongst the 4 patients with follow-up information available, three died of the disease 6-13 months after diagnosis. One patient, whose lesion was localized at the skin and soft tissue, survived at the present time., Conclusion: HS was a scarce malignant tumor with mature histiocyte morphology and immunophenotype character. The diagnosis should be based on tissue morphology, immunohistochemistry and electron microscope observation to exclude other disorders.

The invasion of malignant glioma cells into the surrounding normal brain tissues is crucial for causing the poor outcome of this tumor type. Recent studies suggest that glioma stem-like cells (GSLCs) mediate tumor invasion. However, it is not clear whether microenvironment factors, such as tumor-associated microglia/macrophages (TAM/Ms), also play important roles in promoting GSLC invasion. In this study, we found that in primary human gliomas and orthotopical transplanted syngeneic glioma, the number of TAM/Ms at the invasive front was correlated with the presence of CD133(+) GSLCs, and these TAM/Ms produced high levels of TGF-β1. CD133(+) GSLCs isolated from murine transplanted gliomas exhibited higher invasive potential after being cocultured with TAM/Ms, and the invasiveness was inhibited by neutralization of TGF-β1. We also found that human glioma-derived CD133(+) GSLCs became more invasive upon treatment with TGF-β1. In addition, compared with CD133(-) committed tumor cells, CD133(+) GSLCs expressed higher levels of type II TGF-β receptor (TGFBR2) mRNA and protein, and downregulation of TGFBR2 with short hairpin RNA inhibited the invasiveness of GSLCs. Mechanism studies revealed that TGF-β1 released by TAM/Ms promoted the expression of MMP-9 by GSLCs, and TGFBR2 knockdown reduced the invasiveness of these cells in vivo. These results demonstrate that TAM/Ms enhance the invasiveness of CD133(+) GSLCs via the release of TGF-β1, which increases the production of MMP-9 by GSLCs. Therefore, the TGF-β1 signaling pathway is a potential therapeutic target for limiting the invasiveness of GSLCs.

Objective: To investigate the association between the genetic variant of miRNA-1 target gene COG6 rs9548934 C→T and the risk of premature coronary artery disease (pCAD)., Methods: This study included 226 pACD patients and 275 gender and age matched pCAD-free controls hospitalized in our hospital, diagnosis was made based on coronary angiography (CAG) results. The genotypes of miRNA-1 target gene COG6 rs9548934 C→T were detected by PCR-RFLP., Results: Compared with the wide genotype CC, subjects with the variant genotypes CT of rs9548934 C→T was associated with a 45% lower risk of pACD (adjusted OR = 0.55, 95%CI = 0.36 - 0.82, P = 0.003), and the subjects with CT/TT genotypes were also associated with a significantly lower risk of pACD (adjusted OR = 0.64, 95%CI = 0.44 - 0.92, P = 0.015). Using the median serum TG level (1.20 mmol/L) in control group as the cutoff value, subjects with higher serum TG levels were associated with increased risk of pACD after adjustment for age, gender and BMI (adjusted OR = 2.32, 95%CI = 1.57 - 3.41, P < 0.001). In addition, subjects with higher HDL-C levels were associated with significantly lower risk of pACD (adjusted OR = 0.48, 95%CI = 0.31 - 0.75, P = 0.001). Stratified analyses showed that the risk reduction for pCAD in CT/TT genotypes carriers was more significant in the female subjects (adjusted OR = 0.54, 95%CI = 0.30 - 0.97, P = 0.040), and in subjects with lower TG, TC, HDL-C and LDL-C levels (adjusted OR = 0.62, 95%CI = 0.39 - 0.98, P = 0.040; adjusted OR = 0.55, 95%CI = 0.35 - 0.85, P = 0.008; adjusted OR = 0.43, 95%CI = 0.22 - 0.87, P = 0.018; adjusted OR = 0.49, 95%CI = 0.32 - 0.75, P = 0.001, respectively)., Conclusion: The polymorphism of miRNA-1 target gene COG6 rs9548934C→T is associated with lower risk of pCAD, especially in female subjects and subjects with lower serum lipid levels.

Malfunctioned gap junctional intercellular communication (GJIC) has been thought associated with malignant transformation of normal cells. However, the role of GJIC-related proteins such as connexins in sustaining the malignant behavior of cancer stem cells remains unclear. In this study, we obtained tumorspheres formed by glioma stem cells (GSCs) and adherent GSCs and then examined their GJIC. All GSCs showed reduced GJIC, and differentiated glioma cells had more gap junction-like structures than GSCs. GSCs expressed very low level of connexins, Cx43 in particular, which are key components of gap junction. We observed hypermethylation in the promoter of gap junction protein α1, which encodes Cx43 in GSCs. Reconstitution of Cx43 in GSCs inhibited their capacity of self-renewal, invasiveness, and tumorigenicity via influencing E-cadherin and its coding protein, which leads to changes in the expression of Wnt/β-catenin targeting genes. Our results suggest that GSCs require the low expression of Cx43 for maintaining their malignant phenotype, and upregulation of Cx43 might be a potential strategy for treatment of malignant glioma., (Copyright © 2011 AlphaMed Press.)

Objective: Postoperative fatigue syndrome (POFS) is a general and main complication after surgery. However, there is no stable and standardized animal model for POFS. The aim of the present study was to establish a rodent model of POFS by small intestinal resection, with POFS evaluated by acknowledged physical and behavioral methods., Material and Methods: Forty-two Sprague-Dawley rats were randomly divided into four groups according to the length of a "middle" small intestinal resection: 0% (sham group; i.e., laparotomy alone), 10%, 40% and 70% groups, with corresponding lengths of small intestinal resections. Following surgery, the general state of health was evaluated. Tail suspension test, open field test and Morris water maze test were used to evaluate the degree of POFS. Serum albumin, transferrin, prealbumin and fibronectin were measured to assess the nutritional status, and superoxide dismutase (SOD) and malondialdehyde (MDA) were also measured., Results: As compared with the other three groups, the 70% small intestinal resection group showed the worst general state of health, decreased strength of the tail suspension test and decreased score of Morris water maze test (p < 0.05) after operation. All rats in whom the small intestinal resection was done demonstrated a certain degree of malnutrition and behavior of depression, and the 70% resection group had the lowest levels of transferrin, prealbumin and fibronectin as compared with the other groups (p < 0.05), as well as decreased SOD and increased MDA in serum (p < 0.05)., Conclusions: Resection of 70% of the small intestine resulted in typical characteristics of POFS. As this procedure is simple, stable and easily reproducible, it may serve as a model for research on POFS.

Aim: To clone and express human alanine aminotransferase 2 (ALT2) in E.coli Rosetta (DE3), and to prepare monoclonal antibodies(mAb) against ALT2 for diagnostic purpose., Methods: The gene encoding alanine aminotransferase 2 (ALT2) was cloned from hepatoma carcinoma cell by RT-PCR, and then inserted into pET28a vector. Recombination plasmids (pET28a-ALT2) were transformed into E.coli BL21. Human ALT2 was expressed as His-tagged fusion proteins and purified by immobilized Ni(2+);-affinity chromatography. The purified fusion ALT2 protein was used as an antigen to prepare mAb against it., Results: The fusion ALT2 protein was expressed in recombinant E.coli Rosetta (DE3). The enzymatic activity of purified His-tag ALT2 is over 10 000 U/L. Mice were immunized with the purified fusion ALT2 protein, and 5 mAbs against ALT2 were generated., Conclusion: Two mAbs with high specificity for ALT2 were selected for further quantitative diagnostic reagent development.

Growing evidence suggests that myeloid-derived suppressor cells (MDSCs), which have been named "immature myeloid cells" or "myeloid suppressor cells" (MSCs), play a critical role during the progression of cancer in tumor-bearing mice and cancer patients. As their name implies, these cells are derived from bone marrow and have a tremendous potential to suppress immune responses. Recent studies indicated that these cells also have a crucial role in tumor progression. MDSCs can directly incorporate into tumor endothelium. They secret many pro-angiogenic factors as well. In addition, they play an essential role in cancer invasion and metastasis through inducing the production of matrix metalloproteinases (MMPs), chemoattractants and creating a pre-metastatic environment. Increasing evidence supports the idea that cancer stem cells (CSCs) are responsible for tumorigenesis, resistance to therapies, invasion and metastasis. Here, we hypothesize that CSCs may "hijack" MDSCs for use as alternative niche cells, leading to the maintenance of stemness and enhanced chemo- and radio-therapy resistance. The countermeasure that directly targets to MDSCs may be useful for against angiogenesis and preventing cancer from invasion and metastasis. Therefore, the study of MDSCs is important to understand tumor progression and to enhance the therapeutic efficacy against cancer., (Copyright 2010 Institute of Genetics and Developmental Biology and the Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

The effect of urea with 1% 3,4-dimethyl pyrazole phosphate (DMPP) on inorganic nitrogen runoff loss from agriculture field was determined in an undisturbed vegetable soil by using the simulated artificial rainfall method. The results show that, during the three simulated artificial rainfall period, the ammonium nitrogen content in the runoff water is increased 1.42, 2.82 and 1.95 times with the DMPP application treatment compared to regular urea treatment, respectively. In the urea with DMPP addition treatment, the nitrate nitrogen content is decreased 70.2%, 59.7% and 52.1% in the three simulated artificial rainfall runoff water, respectively. The nitrite nitrogen content is also decreased 98.7%, 90.6% and 85.6% in the three simulated artificial rainfall runoff water, respectively. The nitrate nitrogen and nitrite nitrogen runoff loss are greatly declined with the DMPP addition in the urea. Especially the nitrite nitrogen is in a significant low level and is near to the treatment with no fertilizer application. The inorganic nitrogen runoff loss is declined by 39.0% to 44.8% in the urea with DMPP addition treatment. So DMPP could be used as an effective nitrification inhibitor to control the soil ammonium oxidation, decline the nitrogen runoff loss, lower the nitrogen transformation risk to the waterbody and be beneficial for the ecological environment.

The application of nitrogen fertilizers leads to various ecological problems such as nitrate leaching. The use of nitrification inhibitors as nitrate leaching retardants is a proposal that has been suggested for inclusion in regulations in many countries. In this study, using a multi-layer soil column device, the influence of new nitrification inhibitor DMPP (3,4-dimethyl pyrazole phosphate) was studied for understanding the nitrogen vertical transformation and lowering the nitrate leaching at different soil profile depths. The results indicated that, within 60 d of experiment, the regular urea added 1.0% DMPP can effectively inhibit the ammonium oxidation in the soil, and improve the ammonium concentration in soil solution over the 20cm depths of soil profile, while decline the concentrations of nitrate and nitrite. No obvious difference was found on ammonium concentrations in soil solution collected from deep profile under 20cm depths between regular urea and the urea added 1.0% DMPP. There was also no significant difference for the nitrate, ammonium and nitrite concentrations in the soil solution under 40cm depths of soil profile with the increasing nitrogen application level, among the treatments of urea added 1.0% DMPP within 60 d. It is proposed that DMPP could be used as an effective nitrification inhibitor in some region to control ammonium oxidation and decline the ion-nitrogen leaching, minimizing the shallow groundwater pollution risk and being beneficial for the ecological environment.