Objective To analyze the risk factors for extrauterine growth retardation(EUGR)in late preterm infants appropriate for gestational age.Methods The clinical data in 1 402 preterm infants appropri-ate for gestational age delivered and hospitalized in this hospital from January 2016 to June 2022 were analyzed retrospectively.They were divided into the EUGR group(n=244)and the non-EUGR group(n=1 158)ac-cording to whether or not the body weight at discharge was below the 10th percentile of the growth curve for the same gestational age at the same period based on the Fenton's preterm growth curve.The clinical data of preterm infants and mothers of the two groups were collected.The risk factors for EUGR occurrence in pre-mature infants were analyzed.Results Among 1 402 preterm infants appropriate for gestational age,EUGR occurred in 244 cases with the EUGR incidence rate of 17.4％.The EUGR incidence rate had no statistical difference among the different fetal ages of premature infants(P＞0.05).The EUGR incidence rate had sta-tistical difference among different birth weights of premature infants(P＜0.05).The logistic regression anal-ysis showed that male(OR=1.694,95％CI:1.144-2.507),low birth weight(OR=0.989,95％CI:0.988-0.991),feeding intolerance(OR=2.719,95％CI:1.234-5.990),short gestational weeks(OR=0.146,95％CI:0.103-0.207)and hospitalization duration extension(OR=1.073,95％CI:1.031-1.117)were the risk factors for EUGR occurrence in late premature infants appropriate for gestational age in discharge.The sub-group analysis showed that male,low birth weight,feeding intolerance and hospitalization duration extension were the risk factors for EUGR occurrence in the preterm infants with gestational ages of 34-＜36 weeks(P＜0.05).Low birth weight and feeding intolerance only affected the preterm infants≥36 weeks of gesta-tional age(P＜0.05).Conclusion Strengthening the pregnant duration health care and active nutritional sup-port after birth may reduce the risk of EUGR occurrence in late premature infants.

Objective We aimed to investigate the effects of Biejiajian Pills on MHCC-97H hepatoma cells and whether Biejiajian Pills regulate the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway through miR-885-5p.Methods SPF SD rats (n = 10) were randomly divided into the blank group and the Biejiajian Pills (1.1 g/kg) group to prepare blank and Biejiajian Pills-containing serum. MHCC-97H cells in the logarithmic growth phase were divided into the model group, blank serum groups with different concentrations (5％, 10％, 15％, and 20％), the serum containing Biejiajian Pills group, and the blank group without cells. Cell proliferation was detected by the CCK-8 assay, and the optimal intervention time and concentration of drug-containing serum were screened. MHCC-97H cells were divided into the blank control group (no intervention), the Biejiajian Pills-containing serum group (20％ Biejiajian Pills-containing serum), the miR-885-5p mimics group (transfected with miR-885-5p mimics), the miR-NC group (transfected with miR-885-5p NC), and the Biejiajian Pills-containing serum + miR-885-5p mimics group (treated with 20％ Biejiajian Pills-containing serum and transfected with miR-885-5p mimics). Cells in each group were cultured for 72 hours. A dual luciferase reporter assay was conducted to verify the targeting relationship between miR-885-5p and EGFR. Cell proliferation was detected by the CCK-8 assay, cell migration and invasion abilities were detected by the cell scratch assay and the Transwell invasion assay. Annexin V-APC/PI double staining was performed to detect the apoptosis level, and real-time fluorescence quantitative PCR (RT-qPCR) analysis was conducted to determine the mRNA expression levels of miR-885-5p, EGFR, MEK, and ERK1/2. The expression levels of EGFR, p-EGFR, MEK, p-MEK, ERK1/2, p-ERK1/2, matrix metalloproteinase 1 (MMP1), and CyclinD1 were determined by Western blotting analysis. The subcutaneous tumor model of MHCC-97H hepatoma cells in nude mice was established by subcutaneous injection to observe the inhibitory effect of Biejiajian Pills of different doses(0.55,1.1,2.2 g/kg).Results The optimal concentration and intervention time of Biejiajian Pills-containing serum were 20％ and 72 hours, respectively. Meanwhile, the dual luciferase reporter assay showed that miR-885-5p could directly target EGFR. No statistical significances between the blank control group and the miR-NC group were observed (P>0.05). Compared with the blank control group, the proliferation rates of MHCC-97H hepatoma cells in the Biejiajian Pills-containing serum group, the miR-885-5p mimics group, and the Biejiajian Pills-containing serum + miR-885-5p mimics group were significantly decreased (P<0.01), and their migration and invasion abilities were significantly decreased (P<0.05, P<0.01). At the same time, the protein expression levels of CyclinD1 and MMP1, which are closely related to cell proliferation and invasion, were significantly downregulated (P<0.05, P<0.01). The proportions of late apoptotic cells and the proportion of total apoptotic cells were significantly increased (P<0.01). In the Biejiajian Pills-containing serum group, the miR-885-5p mimics group, and the Biejiajian Pills-containing serum + miR-885-5p mimics group, miR-885-5p mRNA was significantly upregulated (P<0.01) and EGFR, MEK, and ERK1/2 were significantly downregulated at the mRNA level (P<0.05, P<0.01). EGFR, MEK, and ERK1/2 phosphorylation was inhibited (P<0.01), and the Biejiajian Pills-containing serum + miR-885-5p mimics group showed the best effect (P<0.05, P<0.01). The subcutaneous liver tumor model in nude mice verified that Biejiajian Pills can inhibit tumor growth in a dose-dependent manner. Conclusion Biejiajian Pills can promote apoptosis of MHCC-97H hepatoma cells and inhibit their proliferation, invasion, and migration. The mechanism may be related to the targeted regulation of the EGFR/MAPK/ERK signaling pathway by miR-885-5p.

ObjectiveTo explore the mechanism of action of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata （CSFZ） in the treatment of acute-on-chronic liver failure （ACLF） through network pharmacology， molecular docking， and animal experiments. MethodsNetwork pharmacology was used to identify potential targets and related signaling pathways for the treatment of ACLF with CSFZ. Molecular docking was used to examine the binding activity of the core components with corresponding key targets. An ACLF rat model was established by subcutaneous and tail vein injections of bovine serum albumin combined with lipopolysaccharide （LPS） + D-galactosamine （D-GalN） intraperitoneal injection. A normal control group （NC）， a model group， a CSFZ group （CSFZ， 5.85 g·kg^-1）， and a hepatocyte growth-promoting granule group （HGFG， 4.05 g·kg^-1） were set up in this study. Pathological changes in rat liver tissue were observed using hematoxylin and eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interleukin-6 （IL-6）， B-cell lymphoma-2 （Bcl-2）， Caspase-3， and albumin （ALB）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to measure the mRNA and protein expression levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （p-PI3K）， and phosphorylated Akt （p-Akt）. ResultsNetwork pharmacology screening identified 49 active ingredients of CSFZ， 103 action targets， and 3 317 targets related to ACLF. Among these， 74 targets overlapped with CSFZ drug targets. Key nodes in the protein-protein interaction （PPI） network included Akt1， tumor necrosis factor （TNF）， IL-6， Bcl-2， and Caspase-3. Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis identified multiple signaling pathways， with the PI3K/Akt signaling pathway being the most frequent. Molecular docking showed that the core components of the drug exhibited good binding activity with the corresponding key targets. Animal experiments confirmed that CSFZ significantly improved liver tissue pathological damage in ACLF rats， reduced the release of inflammatory factors and liver cell apoptosis， and upregulated the expression levels of the PI3K/Akt signaling pathway. ConclusionThrough network pharmacology， molecular docking， and in vivo experiments， this study confirms the effect of CSFZ in reducing liver cell inflammatory damage and inhibiting liver cell apoptosis. The specific mechanism may be related to its involvement in regulating the PI3K/Akt signaling pathway.

Plasticity in the glutamatergic synapses on striatal medium spiny neurons (MSNs) is not only essential for behavioral adaptation but also extremely vulnerable to drugs of abuse. Modulation on these synapses by even a single exposure to an addictive drug may interfere with the plasticity required by behavioral learning and thus produce impairment. In the present work, we found that the negative reinforcement learning, escaping mild foot-shocks by correct nose-poking, was impaired by a single in vivo exposure to 20 mg/kg cocaine 24 h before the learning in mice. Either a single exposure to cocaine or reinforcement learning potentiates the glutamatergic synapses on MSNs expressing the striatal dopamine 1 (D1) receptor (D1-MSNs). However, 24 h after the cocaine exposure, the potentiation required for reinforcement learning was disrupted. Specific manipulation of the activity of striatal D1-MSNs in D1-cre mice demonstrated that activation of these MSNs impaired reinforcement learning in normal D1-cre mice, but inhibition of these neurons reversed the reinforcement learning impairment induced by cocaine. The results suggest that cocaine potentiates the activity of direct pathway neurons in the dorsomedial striatum and this potentiation might disrupt the potentiation produced during and required for reinforcement learning.

To investigate the clinical features and peripheral blood immune cell subsets ofelderly (≥60 years old) onset rheumatoid arthritis (EORA) patients.