Objective:To evaluate the clinical efficacy of extensively hydrolyzed protein formula(eHF) in very low birth weight(VLBW) infants.Methods:A prospective controlled signal-center trial was conducted in this study, the preterm infants with gestational age of 28-33 weeks and birth weight of 999-1 500 g who were hospitalized at Department of Neonatology, Zhuhai Maternal Hospital within the first 12 hours between January and December 2018, were selected.They were assigned into breast feeding group(HM) and formula feeding group according to the mothers′ disease and parents′ breastfeeding willingness.The formula feeding group was assigned into eHF group and preterm formula (PF)group according to the parents′ breastfeeding willingness.The infants discharging or dead before achieving full feeding, discharging within 28 days after birth, with congenital malformation (complex congenital heart disease, digestive system malformation, etc) and severe sepsis were rolled out. Chi- square test and One- Way ANOVA were used for statistical analysis.Prospective study was conducted among the 3 groups comparing the incidence of feeding intolerance, duration of meconium discharge, the time to regain birth weight and reach full enteral feeding, average hospital stay, incidence of necrotizing enterocolitis of newborn(NEC), cholestasis and extrauterine growth retardation(EUGR), the growth rate of head circumference, length and weight in the first 4 weeks of life, and blood biochemical indices at the first 2 weeks and 4 weeks of life. Results:A total of 102 infants were enrolled, 35 cases in the eHF group, 37 cases in the PF group and 30 cases in the HM group.Compared with the PF group [54.0%(20/37 cases)], the eHF group[22.0%(8/35 cases)] and the HM group [16.7%(5/30 cases)] had lower incidence of feeding intolerance, and the differences were statistically significant( χ2=7.366, 9.901, all P<0.05). The time to regain birth weight[(8.9±1.8) d, (9.1±1.4) d vs.(10.8±2.9) d], time for achieving full enteral feeding [(42.8±2.8) d, (42.3±3.3) vs.(45.5±3.4) d], the duration of meconium discharge [(7.2±1.8) d, (6.6±1.8) d vs.(8.7±2.1) d], and average hospital stay [(52.9±1.1) d, (52.3±1.2) d vs.(54.1±1.2) d]in the eHF group and HM group were shorter than those in PF group, and the differences were statistically significant(all P<0.05); and there was no statistically significant difference between the eHF group and the HM group(all P>0.05). There was no statistically significant difference in the incidence of incidence of NEC, cholestasis and EUGR, the growth rate of head circumfe-rence, length and weight in the first 4 weeks of life, the serum albumin, creatinine, urea nitrogen at first 2 weeks and 4 weeks of life among the 3 groups (all P>0.05). Compared with the PF group, the serum total bilirubin levels in the eHF group and the HM group were lower at 2 weeks [(109.4± 4.6) μmol/L, (110.2±1.0) μmol/L vs.(115.0±7.6) μmol/L]and 4 weeks after birth[(79.3±9.7) μmol/L, (80.0±1.7) μmol/L vs.(81.5±8.4)μmol/L], and the differences were statistically significant(all P<0.05), but no statistically significant difference was found between the eHF goup and the HM group(all P>0.05). Conclusions:For VLBW infants, eHF can reduce feeding intole-rance, promote defecation, achieve full feeding faster, promote bilirubin metabolism, shorten hospital stay, does not affect growth and development in short-term.

Objective: To understand the level of nutritional literacy and its influencing factors among schoolage children in grades 4-9 in Guizhou Province, and to explore the relationship between nutritional literacy and physical health, so as to provide reference for improving nutritional literacy and physical health of schoolage children. Methods: Using multistage stratified cluster sampling method, 1 155 schoolage children in grades 4-6 in elementary school and grades 7-9 in secondary schools in three prefectural and municipal cities of Guizhou Province (Zunyi, Tongren, and Bijie) were sampled from February to July 2023, and were surveyed for nutritional literacy by using the "Food and Nutritional Literacy Questionnaire for Chinese Schoolage Children", and their physical health data (data on body measurement indicators, such as height, weight, lung capacity, and vertical jump) were obtained from the physical health surveillance platform. Pearson correlation analysis and binary Logistic regression modeling were used to explore the association between nutritional literacy and physical health. Results: The nutritional literacy score of the study population was (63.50±8.63), and the scores of each level of nutritional literacy in descending order were interactivity (66.09±13.99), functionality (63.84±8.80), and criticism (61.15±14.65); and the scores of cognitive domain of nutritional literacy, and skill domain were (64.71±10.77) (62.97±9.21); food selection, food preparation, and food intake dimension scores were (64.68±13.52) (56.39±12.17) (63.63±10.04), respectively. Differences in the total nutritional literacy scores of schoolaged children who were only children or not, by gender, ethnicity, grade level, primary caregiver, primary caregivers education, and family economic situation were statistically significant (t/F=2.88, -3.28, 5.02, 18.32, 4.67, 32.47, 32.53, P<0.05); the physical health pass rate was 85.8%, and the mean scores of the total physical health score, physical form, physical function, and physical fitness dimensions were (71.86±10.52) (93.29±12.06) (72.12±14.42) (67.26±13.13), respectively; after controlling for confounders, the nutritional literacy scores were positively correlated with physical health (OR=1.03, 95%CI=1.01-1.05, P<0.05). Conclusion Nutritional literacy scores of schoolage children in grades 4-9 in Guizhou Province are low, and there is a positive correlation between nutritional literacy and physical health in this school age children.

The α2δ-1 protein coded by Cacna2d1 is dramatically up-regulated in dorsal root ganglion (DRG) neurons and spinal dorsal horn following sensory nerve injury in various animal models of neuropathic pain. Cacna2d1 overexpression potentiates presynaptic and postsynaptic NMDAR activity of spinal dorsal horn neurons to cause pain hypersensitivity. The α2δ-1-NMDAR interaction promotes surface trafficking and synaptic targeting of NMDARs in neuropathic pain caused by chemotherapeutic agents and peripheral nerve injury, as well as in other pathological conditions such as in the paraventricular nucleus (PVN) with neurogenic hypertension and in the brain with ischemic stroke. The lentiviral transfection method was used to construct a human embryonic kidney HEK293T cell line that could stably express α2δ-1-NMDAR complex. A stably transfected cell line was observed by florescence microscope, and identified by RT-qPCR and Western blotting. The results showed that the HEK293T cell line was successfully transfected and the genes could be stably expressed. Subsequently, the transfected cell line was successfully developed into a target drug screening system using patch clamp techniques. It provides a promising cell model for further research on the interaction mechanism of α2δ-1-NMDAR complex and drug screening for chronic pain and related diseases with low side effects.
Analgesics/therapeutic use* ; Animals ; Drug Discovery ; HEK293 Cells ; Humans ; Neuralgia/metabolism* ; Receptors, N-Methyl-D-Aspartate/genetics*

ObjectiveTo investigate the effects of berbamine hydrochloride on sorafenib resistance in hepatocellular carcinoma cells and the underlying mechanisms. MethodThe sorafenib-resistant cell line SMMC-7721/S was selected by the concentration increment method starting at 1.25 μmol·L^-1 sorafenib. Both SMMC-7721 and SMMC-7721/S cells were treated with 0， 2.5， 5， 10， 15， 20 μmol·L^-1 sorafenib， and the cell counting kit-8 （CCK-8） assay was employed to determine the half maximal inhibitory concentration （IC₅₀） and calculate the resistance index （RI）. Western blot was conducted to compare the expression of proteins involved in autophagy and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway between SMMC-7721 and SMMC-7721/S cells. Furthermore， SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 2.5， 5， 10 μmol·L^-1 sorafenib， and the cell growth was assessed by the CCK-8 assay. In addition， SMMC-7721 and SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 5 μmol·L^-1 sorafenib， and the cell proliferation was examined by the colony formation assay. The immunofluorescence assays with Microtubule-associated protein 1 light chain 3 （LC3） and LysoTracker as probes were employed to assess the lysosomal acidification in SMMC-7721 cells treated with 5 μmol·L^-1 berbamine hydrochloride or 0.1 μmol·L^-1 autophagy inhibitor bafilomycin A1 （Baf）. Further， the expression of proteins involved in autophagy and PI3K/Akt/mTOR signaling pathway was determined by Western blot and compared between groups. ResultSorafenib showed the IC₅₀ of 9.56 mol·L^-1 （P<0.01） and 7.99 mol·L^-1 for SMMC-7721/S and SMMC-7721 cells， respectively， at 24 h. The resistance index （RI） of SMMC-7721/S for sorafenib was 1.20 （P<0.01）， which indicated mild resistance. Compared with SMMC-7721 cells， SMMC-7721/S cells exhibited up-regulated expression of p-mTOR， p-Akt， and LC3Ⅱ， down-regulated expression of p62 protein （P<0.01）， and unchanged Akt protein level. CCK-8 and colony formation assays demonstrated that the combination of berbamine hydrochloride and sorafenib exhibited a synergistic effect （Q>1.15）， with berbamine hydrochloride partially reversing the resistance of liver cancer cells to sorafenib. The immunofluorescence detection of LC3 revealed that berbamine hydrochloride and Baf significantly increased LC3 in SMMC-7721 cells. The detection with LysoTracker as the probe showed that berbamine hydrochloride inhibited the acidity of lysosomes in SMMC-7721 cells （P<0.01）， indicating the suppression of autophagy. Berbamine hydrochloride further enhanced the downregulation of p-mTOR and p-Akt protein levels and did not change the Akt protein level in SMMC-7721 cells exposed to sorafenib. Berbamine hydrochloride inhibited the increase in p-mTOR expression， down-regulated the p-Akt protein level， and did not change the total Akt protein level in the SMMC-7721/S cells exposed to sorafenib. ConclusionBerbamine hydrochloride can ameliorate the resistance of liver cancer cells to sorafenib by inhibiting cellular autophagy and the PI3K/Akt/mTOR signaling pathway.