[Longitudinal study on catch-up growth in preterm infants with small for gestational age at corrected ages 0-24 months]. / æ—©äº§å°äºŽèƒŽé¾„å„¿æ ¡æ­£0~24æœˆé¾„è¿½èµ¶ç”Ÿé•¿çš„çºµå‘ç ”ç©¶.

OBJECTIVES: To understand the growth and development status and differences between small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants during corrected ages 0-24 months, and to provide a basis for early health interventions for preterm infants. METHODS: A retrospective study was conducted, selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022, including 144 SGA and 680 AGA infants. The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared. RESULTS: The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months (P<0.05), while there were no significant differences between the two groups at corrected age 24 months (P>0.05). At corrected age 24 months, 85% (34/40) of SGA and 79% (74/94) of AGA preterm infants achieved catch-up growth. Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age <34 weeks and the AGA subgroups with gestational age <34 weeks and 34 weeks (P<0.05). In addition, the weight and length of the SGA subgroup with gestational age 34 weeks showed significant differences compared to the AGA subgroups with gestational age <34 weeks and 34 weeks at corrected ages 0-18 months and corrected ages 0-12 months, respectively (P<0.05). Catch-up growth for SGA infants with gestational age <34 weeks and 34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months, respectively. CONCLUSIONS: SGA infants exhibit delayed early-life physical growth compared to AGA infants, but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants. Catch-up growth can be achieved earlier in SGA infants with a gestational age of <34 weeks compared to those with 34 weeks.

The predictive value of YAP-1 and POU2F3 for the efficacy of immuno-chemotherapy in extensive-stage SCLC patients.

INTRODUCTION: Recently, several clinical trials of immunotherapy for extensive-stage small-cell lung cancer (ES-SCLC) have shown limited benefits because of unselected patients. Thus, we aimed to explore whether YES-associated protein 1 (YAP-1) and POU domain class 2 transcription factor 3 (POU2F3) could identify SCLC patients with durable benefits from immunotherapy as potential biomarkers. METHODS: We performed IHC of YAP-1 and POU2F3, and RNA-seq on tissues of ES- SCLC patients. An open-source plugin based on IHC-profiler was conducted to calculate the expression levels of YAP-1 and POU2F3. RESULTS: Patients with ES-SCLC were retrospectively investigated in the Guangdong Provincial People's Hospital from January 2018 to July 2021, and 21 patients whoever received atezolizumab plus etoposide/carboplatin (ECT) regimen also had tissue samples reachable. The median IHC-score of YAP-1 in responders (CR/PR patients) was significantly lower than in nonresponders (SD/PD patients) at 13.97 (95% CI: 8.97-16.30) versus 23.72 (95% CI: 8.13-75.40). The IHC-score of YAP-1 and PFS showed a negative correlation by Spearman (r=-0.496). However, POU2F3 did not show a correlation with efficacy. Besides, patients with YAP-1 high expression had IL6, MYCN, and MYCT1 upregulated, while analysis of immune cell infiltration only showed that M0 macrophages were significantly higher. CONCLUSIONS: The expression of YAP-1 negatively correlated with the efficacy of ECT in ES-SCLC patients while POU2F3 did not reveal the predictive value. However, prospective investigations with a large sample size are needed.

Osteogenic differentiation characteristics of hip joint capsule fibroblasts obtained from patients with ankylosing spondylitis.

BACKGROUND: Autoimmune disease are fairly common and one that has an excessive degree of disability is Ankylosing spondylitis (AS). As the main cells in connective tissues, fibroblasts may play important roles in AS ossification. The conducted research aims to establish the osteogenic disparity characteristics of fibroblasts cultured in vitro, obtained via AS patients hip joint capsule, as well as investigating the pathological osteogenic molecular workings of AS. METHODS: AS patients hip joint capsules were acquired and fracture patients as the control with the finite fibroblast line were established by using tissue culture method. AS fibroblast proliferation, cycle and apoptosis, expression of osteogenic marker genes, osteogenic phenotypes, and the activation degree of the bone morphogenetic protein (BMP)/Smads signalling pathway were detected by flow cytometry, western blotting and real-time fluorescent quantitative polymerase chain reaction. RESULTS: Proliferative activity in AS fibroblasts were abnormally high, and the apoptotic rate decreased. Compared with normal fibroblasts, the mRNA expression of osteogenic marker genes, expression of osteogenic phenotypes, protein expression of core-binding factor a1 (Cbfa1), Smad1, Smad4, Smad5, phosphorylated (p) Smad1, and pSmad5 in AS fibroblasts were higher; however, the expression of Smad6 was lower. Moreover, recombinant human bone morphogenetic protein-2(rhBMP-2) stimulated Cbfa1 expression by normal and AS fibroblasts through the BMP/Smads signalling pathway. CONCLUSIONS: The fibroblasts of hip joint capsules in patients with AS cultured in vitro have biologic characteristics of osteogenic differentiation and may be important target cells of AS ossification. The Activated BMP/Smads signalling pathway could potentially be a mechanism relating to fibroblasts differentiating into osteoblasts and an ossification mechanism for AS.

Plasma Metabolic Profiling of Pediatric Sepsis in a Chinese Cohort.

Sepsis represents one of the most pressing problems in pediatrics, characterized by pathogenic bacteria invading the blood, growing and multiplying in the blood circulation, and ultimately causing severe infections. Most children with sepsis have a rapid disease onset and frequently exhibit sudden high fever or first chills. Here we performed comprehensive metabolomic profiling of plasma samples collected from pediatric sepsis patients to identify specific metabolic alterations associated with these patients (n = 84, designated as case subjects) as compared to healthy cohorts (n = 59, designated as control subjects). Diagnostic models were constructed using MetaboAnalyst, R packages, and multiple statistical methods, such as orthogonal partial least squares-discriminant analysis, principal component analysis, volcano plotting, and one-way ANOVA. Our study revealed a panel of metabolites responsible for the discrimination between case and control subjects with a high predictive value of prognosis. Moreover, significantly altered metabolites in sepsis survivors versus deceased patients (non-survivors) were identified as those involved in amino acids, fatty acids, and carbohydrates metabolism. Nine metabolites including organic acids and fatty acids were also identified with significantly higher abundance in sepsis patients with related microbes, implicating greater potentials to distinguish bacterial species using metabolomic analysis than blood culture. Pathway enrichment analysis further revealed that fatty acid metabolism might play an important role in the pathogenesis of sepsis.

Ultrasound in neonatal lung disease.

Lung diseases in neonates can be life-threatening condition and may result in respiratory failure and death. Chest X-ray is a traditional diagnostic technique that results in radiation exposure to patients. Lung ultrasound is a user-friendly imaging technique that has been increasingly used in clinical practice in recent years and presents the advantages of real-time imaging and without radiation. Here we review the sonographic appearances of common neonatal lung diseases and present demonstration of typical cases.

Bushen Qiangji Granule () medicated serum inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by inhibiting the BMP/Smads signal pathway in vitro.

OBJECTIVE: To explore the mechanism of Bushen Qiangji Granule (, BSQJ) in restraining the osteogenic differentiation of ankylosing spondylitis (AS) fifibroblasts. METHODS: Hip joint capsules were obtained from AS patients (n=10) receiving total hip replacement and healthy hip joint capsules from patients with hip fracture (n=10) receiving surgery as a control. Finite fifibroblast lines were established from these tissue samples to observe the effect of BSQJ on suppressing osteogenic differentiation of fifibroblasts. The expression of osteogenic marker gene corebinding factor a1 (Cbfa1) and Smad family proteins were examined by Western blot and real-time quantitative polymerase chain reaction (qPCR). RESULTS: The mRNA expression level of Cbfa1 was significantly higher in AS fibroblasts than that in normal fibroblasts and the expression of pSmad1, pSmad5, Smad4 and Cbfa1 in AS fibroblasts was also higher, demonstrating the activation of the BMP/Smads signal pathway in AS fifibroblasts. BSQJ-medicated serum not only restrained the mRNA and protein expression levels of Cbfa1 and inhibited protein expression level of Smad4 but also decreased the expression quantities of pSmad1 and pSmad5. CONCLUSIONS: BSQJ can inhibit osteogenic differentiation of AS fifibroblasts in vitro by suppressing the activation of the BMP/Smads signal pathway. This may be the important molecular mechanism of BSQJ in regulating AS ossifification.

Elemene, the essential oil of Curcuma wenyujin, inhibits osteogenic differentiation in ankylosing spondylitis.

OBJECTIVE: To explore the effects of Elemene, the essential oil of Curcuma wenyujin, on Bone morphogenetic protein/drosophila mothers against decapentaplegic proteins (BMP/SMADs) signal pathway in ankylosing spondylitis (AS) fibroblasts. METHODS: Hip joint capsules were obtained from AS patients (n=10) receiving total hip replacement. Healthy hip joint capsules from patients with hip fracture (n=10) receiving surgery were included as a control. Primary fibroblast cell lines were established from these tissue samples. Fibroblasts were incubated with Elemene for 48 hours. The protein expression was detected by Western blot. The mRNA expression was detected by real-time fluorescent quantitative polymerase chain reaction (PCR). RESULTS: The results showed that the expression of proteins including SMAD1, pSMAD1, SMAD4 and Runt-related transcription factor 2 (RUNX2), and mRNA of RUNX2, which were over-expressed in AS fibroblasts were decreased in the AS fibroblasts cultured in medium with Elemene. CONCLUSIONS: Ele could have a hand in anti-osteogenic differentiation of AS fibroblasts by inhibiting the BMP/SMADs signal pathway and subsequently blocking expression of ossification marker genes RUNX2 that initiate the osteogenic differentiation.

Genetic polymorphisms in estrogen-related genes and the risk of breast cancer among Han Chinese women.

Exposure to high levels of estrogen is considered an important risk factor for susceptibility to breast cancer. Common polymorphisms in genes that affect estrogen levels may be associated with breast cancer risk, but no comprehensive study has been performed among Han Chinese women. In the present study, 32 single-nucleotide polymorphisms (SNPs) in estrogen-related genes were genotyped using the MassARRAY IPLEX platform in 1076 Han Chinese women. Genotypic and allelic frequencies were compared between case and control groups. Unconditional logistic regression was used to assess the effects of SNPs on breast cancer risk. Associations were also evaluated for breast cancer subtypes stratified by estrogen receptor (ER) and progesterone receptor (PR) status. Case-control analysis showed a significant relation between heterozygous genotypes of rs700519 and rs2069522 and breast cancer risk (OR = 0.723, 95% CI = 0.541-0.965, p = 0.028 and OR = 1.500, 95% CI = 1.078-2.087, p = 0.016, respectively). Subgroup comparisons revealed that rs2446405 and rs17268974 were related to ER status, and rs130021 was associated with PR status. Our findings suggest that rs700519 and rs2069522 are associated with susceptibility to breast cancer among the Han Chinese population and have a cumulative effect with three other identified SNPs. Further genetic and functional studies are needed to identify additional SNPs, and to elucidate the underlying molecular mechanisms.

Application of molecular imaging technologies in antitumor drug development and therapy.

Molecular imaging enables noninvasive characterization, quantification and visualization of biological and pathological processes in vivo at cellular and molecular level. It plays an important role in drug discovery and development. The skillful use of molecular imaging can provide unique insights into disease processes, which greatly aid in identifications of target. Importantly, molecular imaging is widely applied in the pharmacodynamics study to provide earlier endpoints during the preclinical drug development process, since it can be applied to monitor the effects of treatment in vivo with the use of biomarkers. Herein, we reviewed the application of molecular imaging technologies in antitumor drug development process ranging from identification of targets to evaluation of therapeutic effect.

CHRNA3 polymorphism modifies lung adenocarcinoma risk in the Chinese Han population.

Recent genome-wide association studies (GWASs) have identified 15q25.1 as a lung cancer susceptibility locus. Here, we sought to explore the direct carcinogenic effects of genetic variants in this region on the risk of developing lung adenocarcinoma (ADC). Five common SNPs (rs8034191, rs16969968, rs1051730, rs938682, and rs8042374) spanning the 15q25.1 locus were assayed in a case-control study examining a cohort of 301 lung ADCs and 318 healthy controls. Stratification analysis by gender, smoking status, and tumor, node, metastasis (TNM) classification, was performed. In addition, sections from ADC tissue and normal tissue adjacent to tumors were stained with an anti-CHRNA3 (cholinergic receptor nicotinic α3) antibody by immunohistochemistry in 81 cases. Our results demonstrate that rs8042374, a variant of the CHRNA3 gene, is associated with an increased risk of ADC with an OR of 1.76 (95% CI: 1.17-2.65, p=0.024). This variant was linked to a greater risk of ADC in female nonsmokers (OR (95% CI): 1.81 (1.05-3.12), p=0.032) and female stage I+II cases (OR (95% CI): 1.92 (1.03-3.57), p=0.039). Although located within the same gene, rs938682 showed protective effects for smokers, stage III+IV cases, and male stage III+IV cases. Additionally, the CHRNA3 protein level in ADC tissue was slightly higher than in the surrounding normal lung tissue, based on immunohistochemical analysis. Our results suggest that the CHRNA3 polymorphism functions as a genetic modifier of the risk of developing lung ADC in the Chinese population, particularly in nonsmoking females.

A functional variant of NEDD4L is associated with obesity and related phenotypes in a Han population of Southern China.

NEDD4L is a candidate gene for hypertension, both functionally and genetically. Recently, studies showed evidence for the association of NEDD4L with obesity, a key intermediate phenotype in hypertension. To further investigate the relationship between NEDD4L and body mass-related phenotypes, we genotyped three common variants (rs2288774, rs3865418 and rs4149601) in a population-based study of 892 unrelated Han Cantonese using the Sequenom MALDI-TOF-MS platform. Allele frequencies and genotype distribution were calculated in lean controls and overweight/obese cases and analyzed for association by the Chi-squared test and Logistic regression. Linear regression analysis was used to analyze the effect of individual genotypes on quantitative traits. Multivariate analyses demonstrated that the minor allele of rs4149601(A = 20.9%) was associated with a 2.60 kg, 2.78 cm and 0.97 kg/m2 decrease per allele copy in weight, waist and BMI, respectively. Carriers of this allele also had a significant lower risk of overweight/obesity (p < 0.0001, OR = 0.52, 95% CI: 0.37-0.74) as compared to non-carriers. However, no significant association between genotypes at rs2288774 and rs3865418 and covariate-adjusted overweight/obesity or any related phenotypes was observed. These results suggested that the functional variant of NEDD4L, rs4149601, may be associated with obesity and related phenotypes, and further genetic and functional studies are required to understand its role in the manifestation of obesity.

Molecular characterization of the envelope gene of dengue virus type 3 newly isolated in Guangzhou, China, during 2009-2010.

BACKGROUND: After an absence of 29 years, dengue virus type 3 (DENV-3) re-emerged in Guangzhou in 2009 and again in 2010. However, the geographical route by which the virus entered the city, and how it has changed genetically, remain unclear. Therefore, we carried out a comprehensive investigation into the molecular characteristics of the DENV-3 involved. METHODS: The envelope (E) genes of viruses isolated from dengue patients during the 2009-2010 epidemics were sequenced and compared with previously published E gene sequences of global representative DENV-3 strains available in GenBank, including isolates circulating in other provinces of China. RESULTS: A total of 13 isolates (seven from 2009 and six from 2010) were obtained from human serum samples. Phylogenetic analysis revealed that the isolates were grouped into three genotypes (I, III, and V) and then two clades within genotype III (genotype I from Indonesia, genotype III clade A from Côte d'Ivoire, genotype III clade B from Tanzania, and genotype V from Philippines). In addition, there were 1.3-9.0% and 0.5-3.9% differences in the nucleic and deduced amino acid sequences between the 2009 and 2010 strains, respectively. CONCLUSIONS: The DENV-3 viruses from the period 2009-2010 were not from the continuous spread of an epidemic strain or the re-emergence of the 2009 strains in the 2-year period. The introduction of different DENV-3 genotypes following more than one geographical route was an important contributing factor to the 2009-2010 dengue epidemics in Guangzhou.

Epidemiological, virological, and entomological characteristics of dengue from 1978 to 2009 in Guangzhou, China.

To understand its unprecedented resurgence, we examined the epidemiological, virological, and entomological features of dengue in Guangzhou during 1978-2009. Cases reported to the Guangzhou Centre for Disease Control and Prevention and data from virological and entomological surveillance were analyzed from three periods: 1978-1988, 1989-1999, and 2000-2009. Although cases decreased over time: 6,649 (1978-1988) to 6,479 (1989-1999) to 2,526 (2000-2009), geographical expansion resulted in districts with an average incidence >2.5/100,000, increasing from five (1978-1988, 1989-1999) to seven (2000-2009). Age distribution (mean age: 34.9 years) provided a trend of increasing dengue incidence among adults, and there was a significantly higher incidence among men with a sex ratio of 1.15:1 (P<0.001). Cases occurred from May through November with a peak between August and October, and a long-term trend was characterized by a three to five-year cyclical pattern. The most frequently isolated serotypes were DENV-2 (1978-1988) and DENV-1 (1989-1999 and 2000-2009). Seasonal fluctuations in immature densities of Aedes albopictus (sole transmission vector in Guangzhou) were consistent with the dengue seasonality. After a 30-year apparent absence, DENV-3 had reemerged in 2009. The current epidemiological situation is highly conducive to periodic dengue resurgences. Thus, a high degree of surveillance and strict control measures in source reduction should be maintained.

Chemo-radiotherapy for advanced non-small cell lung cancer: concurrent or sequential? It's no longer the question: a systematic review.

There has been conflicting evidence concerning the best sequence of radiotherapy (RT) and chemotherapy (CT) for advanced non-small-cell-lung-cancer (NSCLC). To investigate whether current clinical trials can clarify this schedule and offer further bases for clinical decision making, we performed a systematic review of 11 trials (2,043 patients; concurrent-1,019, sequential-1,024) that compared concurrent RT-CT with sequential arm in advanced NSCLC patients. Primary end point was overall survival (OS). Pooled median ratios (MRs) and progression-free-survival ratios (FRs) for median survival and progression-free survival (PFS) were calculated using the weighted sum of the log ratio of MR and FR of individual study. Pooled odds ratios (ORs) for the objective response rate, relapse control rate, and toxic events were calculated using the Mantel-Haenszel estimate. Results confirmed that concurrent RT-CT determined a statistically significant increase in median survival time (16.3 vs. 13.9 months; MR = 1.17,95%CI:1.09-1.26), response rate (64.0% vs. 56.3%; OR = 1.38,95%CI:1.10-1.72), and tumor-relapse control (OR = 0.82,95%CI:0.69-0.97), though at the expense of increased hematological toxicity (neutropenia and thrombocytopenia) and non-hematological toxicity (nausea/vomiting, stomatitis, and esophagitis). Similar results were obtained from the sensitivity analysis of all Phase-III/trials designed to evaluate the primary end point of OS. Subgroup analysis revealed that concurrent strategy was mainly associated with improved loco-regional control (OR = 0.68,95%CI:0.52-0.87). However, no difference in PFS is shown. While careful interpretation of our conclusions is required because of potential bias, the present study, to some extent, exhibits the superiority of the concurrent arm over the sequential in the treatment of advanced NSCLC. Further improvements will be obtained by optimizing the conditions for a concurrent regimen.

Facts and fiction of the relationship between preexisting tuberculosis and lung cancer risk: a systematic review.

There has been conflicting evidence concerning the possible association between tuberculosis (TB) and subsequent risk of lung cancer. To investigate whether currently published epidemiological studies can clarify this association, we performed a systematic review of 37 case-control and 4 cohort studies (published between January 1966 and January 2009) and a meta-analysis of risk estimates, with particular attention to the role of smoking, passive smoking and the timing of diagnosis of TB on this relationship. Data for the review show a significantly increased lung cancer risk associated with preexisting TB. Importantly, the association was not due to confounding by the effects of tobacco use (RR=1.8, 95% confidence interval (CI)=1.4-2.2, among never smoking individuals), lifetime environmental tobacco smoke exposure (RR=2.9, 95%CI=1.6-5.3, after controlling) or the timing of diagnosis of TB (the increased lung cancer risk remained 2-fold elevated for more than 20 years after TB diagnosis). Interestingly, the association was significant with adenocarcinoma (RR=1.6, 95%CI=1.2-2.1), but no significant associations with squamous and small cell type of lung cancer were observed. Although no causal mechanism has been demonstrated for such an association, present study supports a direct relation between TB and lung cancer, especially adenocarcinomas.

[Meta-analysis on relationship between hyperhomocysteinemia and multiple sclerosis].

OBJECTIVE: To determine the relationship between hyperhomocysteinemia and multiple sclerosis (MS). METHODS: Cochrane, Medline, EMbase, Springerlink, Highwire, CBM, CNKI and some other databases were searched for literatures. Articles were identified using the Medical Subject Heading term "hyperhomocysteinemia, homocysteine, multiple sclerosis". The methodological quality of internalized literatures were evaluated, screened and heterogeneity tested. Case control studies involving unrelated subjects and valid data were extracted and analyzed in Stata 8.0. RESULTS: Nine studies were included in this review. The involved 1146 subjects were made of 676 patients and 470 controls. A meta-analysis showed that the level of homocysteine in MS was higher than that in controls (standardized mean difference 1.25, 95%CI: 0.48 - 2.01). The analytical result of sensitivity proved that the result of meta-analysis was coherent. CONCLUSION: Hyperhomocysteinemia is associated with MS, and it may contribute to the pathological course of MS.