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.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Administration, Topical ; Alopecia/drug therapy* ; China ; Double-Blind Method ; Fibroblast Growth Factors/therapeutic use* ; Hair ; Humans ; Male ; Minoxidil/therapeutic use* ; Treatment Outcome

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease with 2% to 3% prevalence worldwide and a heavy social-psychological burden for patients and their families. As the exact pathogenesis of psoriasis is still unknown, the current treatment is far from satisfactory. Thus, there is an urgent need to find a more effective therapy for this disease. Keratin 17 (K17), a type I intermediate filament, is overexpressed in the psoriatic epidermis and plays a critical pathogenic role by stimulating T cells in psoriasis. Therefore, we hypothesized that inhibiting K17 may be a potential therapeutic approach for psoriasis. This study aimed to investigate the therapeutic effect of K17-specific small interfering RNA (siRNA) on mice with imiquimod (IMQ)-induced psoriasis-like dermatitis. METHODS: Eight-week-old female BALB/c mice were administered a 5% IMQ cream on both ears to produce psoriatic dermatitis. On day 3, K17 siRNA was mixed with an emulsion matrix and applied topically to the left ears of the mice after IMQ application every day for 7 days. The right ears of the mice were treated in parallel with negative control (NC) siRNA. Inflammation was evaluated by gross ear thickness, histopathology, the infiltration of inflammatory cells (CD3+ T cells and neutrophils) using immunofluorescence, and the expression of cytokine production using real-time quantitative polymerase chain reaction. The obtained data were statistically evaluated by unpaired t-tests and a one-way analysis of variance. RESULTS: The severity of IMQ-induced dermatitis on K17 siRNA-treated mice ears was significantly lower than that on NC siRNA-treated mice ears, as evidenced by the alleviated ear inflammation phenotype, including decreased ear thickness, infiltration of inflammatory cells (CD3+ T cells and neutrophils), and inflammatory cytokine/chemokine expression levels (interleukin 17 [IL-17], IL-22, IL-23, C-X-C motif chemokine ligand 1, and C-C motif chemokine ligand 20) (P < 0.05 vs. the Blank or NC siRNA groups). Compared to the NC siRNA treatment, the K17 siRNA treatment resulted in increased K1 and K10 expression, which are characteristic of keratinocyte differentiation (vs. NC siRNA, K17 siRNA1 group: K1, t = 4.782, P = 0.0050; K10, t = 3.365, P = 0.0120; K17 siRNA2 group: K1, t = 4.104, P = 0.0093; K10, t = 4.168, P = 0.0042; siRNA Mix group: K1, t = 3.065, P = 0.0221; K10, t = 10.83, P < 0.0001), and decreased K16 expression, which is characteristic of keratinocyte proliferation (vs. NC siRNA, K17 siRNA1 group: t = 4.156, P = 0.0043; K17 siRNA2 group: t = 2.834, P = 0.0253; siRNA Mix group: t = 2.734, P = 0.0250). CONCLUSIONS Inhibition of K17 expression by its specific siRNA significantly alleviated inflammation in mice with IMQ-induced psoriasis-like dermatitis. Thus, gene therapy targeting K17 may be a potential treatment approach for psoriasis.
Animals ; Dermatitis ; Disease Models, Animal ; Female ; Humans ; Imiquimod ; Inflammation ; Keratin-17/genetics* ; Mice ; Mice, Inbred BALB C ; Psoriasis/genetics* ; RNA, Small Interfering/genetics* ; Skin

Objective: To establish the quality control methods for the standard decoction of Puerariae Thomsonii Radix.Method:According to the preparation principles for traditional Chinese medicine (TCM) standard decoction,13 batches of Puerariae Thomsonii Radix from different origins were analyzed under the chromatography conditions established in this study and verified with methodology.By referring to Chinese Pharmacopoeia of 2015,puerarin was used as a quantitative indicator to calculate the transfer rate.In this study,the structures of main chromatographic peaks were also identified to clarify the main chemical constituents in the standard decoction.Result:The 13 batches of medicinal herbs were identified as Puerariae Thomsonii Radix,with a recovery rate of 98.0%,and RSD of 1.1%,indicating that the method was accurate and reliable.The transfer rate ranged from 41.4% to 60.0%,and the extraction rate was within the range of 15.7%-34.3%.The corresponding fingerprints were prepared for 13 batches of the standard decoction,and their similarities were all greater than 90.0%.The chemical constituents from Puerariae Thomsonii Radix were identified by mass spectrometry analysis,including citric acid,4'-O-glucosyl puerarin/daidzein-4',7-diglucoside,3'-hydroxy puerarin/genistein puerarin,puerarin apioside,daidzin puerossid A and daidzein,etc.Conclusion: The 13 batches of Puerariae Thomsonii Radix decoction in different origins had consistent properties with the basic properties of medicinal decoction pieces.The established method of quality evaluation can be used to systematically evaluate the standard decoction,providing reference for quality control of related decoction preparations of Puerariae Thomsonii Radix.

Objective To establish the quality control method of Yinqiao Chaihuang Granules.Methods Lonicerae Japonicae Flos, Bupleuri Radix, Scutellariae Radix and Glycyrrhizae Radix et Rhizoma in Yinqiao Chaihuang Granules were identified by TLC, and the content of forsythoside A was detected by HPLC. Results Under the selected chromatographic conditions, TLC spots were clear, the separating was good, and non-interference was found in negative control. Forsythoside A in calibration curve showed good linearity in the range of 0.029 6–0.474 μg, with average recovery of 99.73%, RSD=1.18%. Conclusion The method is accurate and simple, which can be used for the quality control of Yinqiao Chaihuang Granules.

BACKGROUNDWith industrial and econom ic development in recent decades in South China, cancer incidence may have changed due to the changing lifestyle and environment. However, the trends of lung cancer and the roles of smoking and other environmental risk factors in the development of lung cancer in rural areas of South China remain unclear. The purpose of this study was to explore the lung cancer incidence trends and the possible causes of these trends.

METHODSJoinpoint regression analysis and the age-period-cohort (APC) model were used to analyze the lung cancer incidence trends in Sihui, Guangdong province, China between 1987 and 2011, and explore the possible causes of these trends.

RESULTSA total of 2,397 lung cancer patients were involved in this study. A 3-fold increase in the incidence of lung cancer in both sexes was observed over the 25-year period. Joinpoint regression analysis showed that while the incidence continued to increase steadily in females during the entire period, a sharp acceleration was observed in males starting in 2005. The full APC model was selected to describe age, period, and birth cohort effects on lung cancer incidence trends in Sihui. The age cohorts in both sexes showed a continuously significant increase in the relative risk (RR) of lung cancer, with a peak in the eldest age group (80-84 years). The RR of lung cancer showed a fluctuating curve in both sexes. The birth cohorts identified an increased trend in both males and females; however, males had a plateau in the youngest cohorts who were born during 1955-1969.

CONCLUSIONSIncreasing trends of the incidence of lung cancer in Sihui were dominated by the effects of age and birth cohorts. Social aging, smoking, and environmental changes may play important roles in such trends.

Aging ; China ; Female ; Humans ; Incidence ; Lung Neoplasms ; Male ; Risk Factors ; Smoking

The purpose of this study was to observe the expression of LINGO-1 after cerebral ischemia, investigate the effects of retinoic acid (RA) on the expression of LINGO-1 and GAP-43, and the number of synapses, and to emplore the repressive effect of LINGO-1 on neural regeneration after cerebral ischemia. The model of permanent focal cerebral ischemia was established by the modified suture method of middle cerebral artery occlusion (MCAO) in Sprague-Dawley (SD) rats. The expression of LINGO-1 was detected by Western blotting and that of GAP-43 by immunohistochemistry. The number of synapses was observed by transmission electron microscopy. The SD rats were divided into three groups: sham operation (sham) group, cerebral ischemia (CI) group and RA treatment (RA) group. The results showed that the expression level of LINGO-1 at 7th day after MCAO in sham, CI and RA groups was 0.266 ± 0.019, 1.215 ± 0.063 and 0.702 ± 0.081, respectively (P<0.01). The number of Gap-43-positive nerve cells at 7th day after MCAO in sham, CI and RA group was 0, 59.08 ± 1.76 and 76.20 ± 3.12 per high power field, respectively (P<0.05). The number of synapses at 7th day after MCAO was 8.42 ± 0.13, 1.74 ± 0.37 and 5.39 ± 0.26 per μm², respectively (P<0.05). It is concluded that LINGO-1 expression is up-regulated after cerebral ischemia, and RA inhibits the expression of LINGO-1, promotes the expression of GAP-43 and increases the number of synapses. It suggests that LINGO-1 may be involved in the pathogenesis of cerebral ischemia, which may provide an experimenal basis for LINGO-1 antogonist, RA, for the treatment of cerebral ischemia.
Animals ; Blotting, Western ; Brain Ischemia ; metabolism ; GAP-43 Protein ; genetics ; metabolism ; Gene Expression ; drug effects ; Male ; Membrane Proteins ; genetics ; Nerve Tissue Proteins ; genetics ; Neurons ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tretinoin ; pharmacology

BACKGROUNDGene therapy and epigenetic therapy have gained more attention in cancer treatment. However, the effect of a combined treatment of gene therapy and epigenetic therapy on head and neck squamous cell carcinoma have not been studied yet. To study the mechanism and clinical application, human laryngeal carcinoma cell (Hep-2) tumor-bearing mice were used.

METHODSA xenograft tumor model was established by the subcutaneous inoculation of Hep-2 cells in the right armpit of BALB/c nu/nu mice. The mice with well-formed tumor were randomly divided into six groups. Multisite injections of rAd-p53 and/or 5-aza-dC were used to treat tumor. Tumor growth was monitored by measuring tumor volume and growth rate. p53 and E-cadherin protein levels in tumor tissues were detected by immunohistochemical staining. The mRNA levels were monitored with FQ-PCR.

RESULTSGene therapy was much more effective than single epigenetic therapy and combined therapy. The gene therapy group has the lowest tumor growth rate and the highest expression levels of p53 and E-cadherin.

CONCLUSIONSThe combined treatment of gene and epigenetic therapy is not suggested for treating head and neck carcinoma, because gene therapy shows an antagonistic effect to epigenetic therapy. However, the mechanisms of action are still unclear.

Animals ; Azacitidine ; analogs & derivatives ; therapeutic use ; Cadherins ; analysis ; DNA Modification Methylases ; antagonists & inhibitors ; Epigenesis, Genetic ; Genes, p53 ; Genetic Therapy ; Humans ; Laryngeal Neoplasms ; genetics ; pathology ; therapy ; Male ; Mice ; Mice, Inbred BALB C ; Tumor Suppressor Protein p53 ; analysis ; Xenograft Model Antitumor Assays

Objective To observe the effects of gene therapy and epigenetic therapy on the tumor growth of laryngeal carcinoma and the underlying mechanisms.Methods The animal model of human laryngeal carcinoma was established by the subcutaneous inoculation of Hep-2 cells at the right armpit of BALB/c nu/nu mice.The tumor-bearing mice were randomized into 4 groups,p53 therapy group ( rAd p53),epigenetic therapy group(5-aza-dC),combination therapy group (rAd-p53 + 5-aza-dC) and control group.The gene and protein expressions of molecular markers p53 and E-cadherin were detected by FQ-PCR and immunohistochemistry.Results By the day 20 of the treatments,the mean tumor volumes were (106.09±24.40)mm3 in p53 therapy group,(166.55 ± 40.11 )mm3 in epigenetic therapy group,(126.11 ±22.49 )mm3 in combination therapy group,and (252.83 ± 54.09 )mm3 in control group.Both gene therapy( F =37.30,P ＜ 0.05 ) and epigenetic therapy ( F =4.79,P ＜ 0.05 ) inhibited the growth of xenografted tumors,with an interaction effect( F =22.01,P ＜ 0.05 )between the two groups.The integral optical density value of p53 protein expression of p53 therapy group (628.07 ± 95.16 ) was significantly higher than that of combination therapy group (494.76 ± 100.22 ),( t =8.72,P ＜ 0.05 ).The integral optical density values of E-cadherin protein expression were 558.89 ± 97.58 in p53 therapy group,380.41 ± 90.60 in epigenetic therapy group,494.76 ± 102.88 in combination therapy group,and 162.60 ±40.38 in control group respectively,indicating the enhancements of E-cadherin protein expression by gene therapy( F =45.24,P ＜ 0.05 ) or epigenetic therapy ( F =5.73,P ＜ 0.05 ) and the existence of interaction effect( F =21.82,P ＜ 0.05 ) between gene therapy and epigenetic therapy.The expression levels of p53 gene were 4.43 ±0.12 in p53 therapy group,1.06 ±0.11 in epigenetic therapy group,3.51 ±0.10 in combination therapy group,and 1.09 ± 0.11 in control group,respectively,showing an interaction effect between gene therapy and epigenetie therapy( F =298.11,P ＜ 0.05 ).The expression levels of E-cadherin gene were 4.50 ±0.34 in p53 therapy group,2.02 ±0.16 in epigenetic therapy group,2.99 ±0.12 in combination therapy group,and 1.00 ± 0.11 in control group,respectively.The expression of E-cadherin gene was enhanced by gene therapy ( F =329.12,P ＜ 0.05 ) or epigenetic therapy ( F =88.57,P ＜ 0.05 ),with an interaction effect between the two therapies ( F =122.17,P ＜ 0.05 ).Conclusions Xenografled tumors of human laryngeal carcinoma cells are inhibited by gene therapy,the epigenetic therapy and the ombination therapy.The gene therapy was significantly better than the epigenetic therapy or the combination therapy.There might be antagonistic effect between p53 and 5-aza-dC.

OBJECTIVETo examine the effects of high and low concentrations of transforming growth factor (TGF) β(1) and insulin-like growth factor-I (IGF-I) on the extracelluar matrix synthesis of the self-assembled constructs of temporomandibular joint (TMJ) disc.

METHODSThe experimental groups of self-assembled constructs were exposed to IGF-I (10, 100 µg/L) and TGF-β(1) (5, 50 µg/L), the control groups were not added with any growth factors. All groups were examined at 3 and 6 weeks for gross morphological, histological, and biochemical changes. Safranin-O/fast green staining was used to examine glycosaminoglycan (GAG) distribution, picrosirius red and immunohistochemical staining to observe type I collagen distribution. Type I collagen contents were tested by ELISA assay kit, GAG contents were measured by Blyscan GAG assay kit, and the cell numbers were quantified with a Picogreen reagent kit.

RESULTSThe growth factor groups all upregulated the matrix synthesis of the self-assembled constructs compared with control groups. TGF-β(1) (5 µg/L) and IGF-I (10 µg/L) were the two most potent concentration in increasing type I collagen and GAG synthesis and cells proliferation. IGF-I group (10 µg/L) produced nearly 2 times (109.16 ± 5.12 µg) as much type I collagen as the control group (69.13 ± 5.94 µg) at 3 weeks. The matrix contents and the number of the proliferated cells in control group and all GF groups at 6 weeks were more than those at 3 weeks.

CONCLUSIONSIGF-I (10 µg/L) is the most beneficial growth factor and can be applied in tissue-engineering stratigies of the temporomandibular joint disc. At the same time, the exposure time of growth factors is another key factor that affects matrix synthesis of TMJ disc constructs.

Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Collagen Type I ; biosynthesis ; Extracellular Matrix ; metabolism ; Glycosaminoglycans ; biosynthesis ; Goats ; Insulin-Like Growth Factor I ; pharmacology ; Temporomandibular Joint Disc ; cytology ; metabolism ; Tissue Engineering ; methods ; Transforming Growth Factor beta1 ; pharmacology