To develop a novel polyamino acid-based nanohydrogel drug delivery system for dexamethasone to enhance its delivery efficiency to the inner ear.

Objective: To investigate the association between dietary quality and overweight / obesity among primary school students, so as to provide a basis for the prevention and control of childhood obesity. Methods: In September 2022, third-grade students from six primary schools in Ningbo City, Zhejiang Province were selected by a random cluster sampling method. Data on gender, age, height, and weight were collected through questionnaire surveys and physical examinations. Body mass index (BMI) was calculated, and overweight and obesity were determined using gender- and age-specific BMI cut-off points. The Chinese dietary quality questionnaires was administered to assess the intake of health-promoting and restricted foods over the past 24 hours, thereby evaluating overall dietary quality. A multivariate logistic regression model was used to analyze the association between dietary quality and overweight / obesity among primary school students. Results: A total of 1 375 primary school students were included, comprising 722 (52.51%) boys and 653 (47.49%) girls, with a mean age of (8.47±0.30) years. Among them, 165 (12.00%) were overweight and 171 (12.44%) were obese. The score for health-promoting foods was (4.29±2.27) points. The median score of restricted foods was 2.00 (interquartile range, 3.00) points. The total dietary quality score was (10.84±2.42) points. Multivariable logistic regression analysis indicated that the restricted food score was positively associated with overweight (OR=1.073, 95%CI: 1.002-1.148), while the total dietary quality score was negatively associated with overweight (OR=0.911, 95%CI: 0.851-0.976). However, no statistically significant associations were observed between the health-promoting food score and overweight or obesity (both P>0.05), nor between the restricted food score or total dietary quality score and obesity (both P>0.05). Conclusion A higher intake of restricted foods was associated with an increased risk of overweight, while a better dietary quality was associated with a decreased risk of overweight among primary school students.

Traditional Chinese medicines (TCMs) possess a rich historical background, unique theoretical framework, remarkable therapeutic efficacy, and abundant resources. However, the modernization and internationalization of TCMs have faced significant obstacles due to their diverse ingredients and unknown mechanisms. To gain deeper insights into the phytochemicals and ensure the quality control of TCMs, there is an urgent need to enhance analytical techniques. Currently, two-dimensional (2D) chromatography, which incorporates two independent separation mechanisms, demonstrates superior separation capabilities compared to the traditional one-dimensional (1D) separation system when analyzing TCMs samples. Over the past decade, new techniques have been continuously developed to gain actionable insights from complex samples. This review presents the recent advancements in the application of multidimensional chromatography for the quality evaluation of TCMs, encompassing 2D-gas chromatography (GC), 2D-liquid chromatography (LC), as well as emerging three-dimensional (3D)-GC, 3D-LC, and their associated data-processing approaches. These studies highlight the promising potential of multidimensional chromatographic separation for future phytochemical analysis. Nevertheless, the increased separation capability has resulted in higher-order data sets and greater demands for data-processing tools. Considering that multidimensional chromatography is still a relatively nascent research field, further hardware enhancements and the implementation of chemometric methods are necessary to foster its robust development.

Objective:To investigate the protective effect of naringenin on acute lung injury related with sepsis; To discuss its possible mechanism.Methods:Totally 30 male SD rats were randomly divided into sham-operation group, model group, naringin low-, medium- and high-dosage groups, with 6 rats in each group. The sepsis-related acute lung injury model was established by cecal ligation and puncture in all groups except the sham-operation group. After modeling, naringin low-, medium- and high-dosage groups were given naringin 20 mg/kg, 40 mg/kg and 80 mg/kg, respectively for gavage, while the sham-operation group and the model group were given the same volume of distilled water by gavage, once a day, for 2 days. Pathological changes in lung tissue were observed using HE staining. The levels of 1L-1, IL-6 and IL-18 in bronchoalveolar lavage fluid (BALF) were measured by ELISA; the expression of TNF-α in lung tissue was detected by immunofluorescence histopathology; the expressions of TGF-β1, TGF-βR1 and Smad2 were detected by Western Blot. An agonist group and a naringin plus agonist group were set up, with 6 mice in each group, and the expressions of TGF-β1 and Smad2 protein in the lung tissue of each group were detected by immunohistochemical staining to verify the effect of naringin on the expressions of TGF-β1 and Smad2 protein.Results:Compared with the model group, the pathological injury of lung tissue in naringin groups were obviously alleviated, and the levels of IL-1β, IL-6 and IL-18 in BALF decreased ( P<0.01), the protein expressions of TNF-α, TGF-β1, TGF-βR1 and Smad2 in lung tissue decreased ( P<0.01 or P<0.05). Further verification found that the expressions of TGF-β1 and Smad2 in the agonist group increased ( P<0.01), while the expressions of TGF-β1 and Smad2 in the naringin agonist group decreased ( P<0.01). Conclusion:Naringin can reduce the inflammatory response in the lung of the rats to protect against sepsis-related acute lung injury, and its protective effect could be related to the inhibition of the TGF-β1/Smad2 signaling pathway.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To evaluate the role of O-sialoglycoprotein endopeptidase (OSGEP) in hepatic ischemia-reperfusion injury (HIRI) and the relationship with oxidative stress in mice.Methods:Experiment Ⅰ Twenty-four SPF healthy male C57BL/6 mice, 12 wild-type and 12 OSGEP knockdown, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) by the random number table method: wild-type shamoperation group (Sham group), wild-type HIRI group (HIRI group), OSGEP knockdown+ sham operation group (Sham+ KD group) and OSGEP knockdown+ HIRI group (HIRI+ KD group). Ischemia-reperfusion model was prepared by blocking the hepatic artery and portal vein for 60 min followed by reperfusion in anesthetized animals, the blood vessels were only exposed without occlusion in Sham group and Sham+ KD group, and the blood vessels were clamped for 60 min followed by reperfusion in HIRI group and HIRI+ KD group. The mice were sacrificed after 6-h reperfusion to extract liver tissue samples for microscopic examination of histopathological changes (with an optical microscope after HE staining) which were evaluated using Suzuki score and for determination of the serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), level of reactive oxygen species (ROS) (using the DCFH-DA fluorescent probe method), contents of malondialdehyde (MDA) and glutathione(GSH) in liver tissues (using a colorimetric method) and expression of OSGEP (using Western blot). Experiment Ⅱ The well-growing AML12 cells were divided into 4 groups ( n=30 each) using a random number table method: control group (C group), oxygen-glucose deprivation/restoration (OGD/R) group, OGD/R+ OSGEP knockdown group (OGD/R+ KD group), and OGD/R+ OSGEP knockdown negative control group (OGD/R+ NC group). Group C was cultured under normal conditions. Group OGD/R was subjected to O 2-glucose deprivation for 6 h followed by restoration of O 2-glucose supply for 24 h in OGD/R group. In OGD/R+ KD group, stable transfection of AML12 cells with OSGEP knockdown was performed prior to the experiment, and the other procedures were the same as those previously described. The cell survival rate was measured by the CCK-8 assay, the release of lactate dehydrogenase (LDH) was measured, the DCFH-DA method was used to detect the levels of ROS, and the contents of MDA and GSH were determined using a colorimetric method. Results:Experiment Ⅰ Compared with Sham group, the expression of OSGEP was significantly down-regulated, the serum concentrations of AST and ALT, Suzuki score, levels of ROS and content of MDA were increased, and the GSH content was decreased in HIRI group ( P<0.05), and no significant change was found in each parameter in Sham+ KD group ( P>0.05). Compared with HIRI group, the serum concentrations of AST and ALT, Suzuki score, levels of ROS and content of MDA were significantly increased, and the GSH content was decreased in HIRI+ KD group ( P<0.05). Experiment Ⅱ Compared with group C, the expression of OSGEP was significantly down-regulated, the cell survival rate and GSH content were decreased, and the release of LDH, levels of ROS and content of MDA were increased in group OGD/R ( P<0.05). Compared with OGD/R group, the cell survival rate and GSH content were significantly decreased, and the release of LDH, levels of ROS and content of MDA were increased in OGD/R+ KD group ( P<0.05), and no significant change was found in each parameter in OGD/R+ NC group ( P>0.05). Conclusions:OSGEP plays an endogenous protective role in HIRI by inhibiting oxidative stress in mice.

Objective:To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis.Methods:C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×10 6 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson′s trichrome to assess the extent of renal fibrosis. Results:Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×10 6 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group ( P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group ( P<0.05), but increased again upon addition of SC79. Conclusion:Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

Objective To investigate the effect of progesterone receptor membrane component 1(PGRMC1)mediated autophagy on the sensitivity of liver cancer cells to 125I particles irradiation.Methods Hepatoma cell lines Huh7 and LM3 were exposed to different doses(0,2,4,6 and 8 Gy)of 125I particles,and cell autophagy was observed by transmission electron microscopy(TEM).Then,autophagy inhibitor chloroquine(CQ),agonist rapamycin(Rapa),and PGRMC1 inhibitor AG-205 were used respectively to verify that PGRMC1-mediated autophagy plays a key role in the sensitivity of hepatocellular carcinoma cells to 125I particle irradiation.Cell proliferation,colony formation and apoptosis were detected by CCK-8 assay,clonal formation test and flow cytometry,respectively.The expression levels of PGRMC1,microtubule-associated protein light chain 3-Ⅰ(LC3-Ⅰ),LC3-Ⅱ and p62 were detected by Western blotting.Results Different doses of 125I particles irradiation significantly decreased the proliferation and clonogenesis of Huh7 and LM3 cells(P＜0.05),and increased the apoptotic cells(P＜0.01),in a dose-dependent manner.Compared with the 0 Gy group,the ratio of LC3-Ⅱ/LC3-Ⅰ in Huh7 and LM3 cells was obviously increased,and the expression of p62 was significantly down-regulated in the 6 Gy group.The proliferation capacity and clonal formation ability of Huh7 and LM3 cells were decreased significantly,and their apoptotic cells were increased notably in the 6 Gy+CQ group than the 6 Gy group,while the above results were on the contrary in the 6 Gy+Rapa group.The 6 Gy+AG205 group had notably decreased LC3-Ⅱ/LC3-Ⅰ ratio in the Huh7 and LM3 cells,up-regulated p62 expression,reduced cell proliferation capacity and clone formation ability,and enhanced cell apoptosis when compared with the 6 Gy group,and the above results of the 6 Gy+PGRMC1 group were opposite.Conclusion Increment of PGRMC1 induced by 125I irradiation can promote autophagy,increase the proliferation and clonogenesis,and reduce the apoptosis in hepatocellular carcinoma cells.

Objective:To investigate the risk factors of postoperative recurrence in patients with primary brain glioma and to construct a prediction model.Methods:A total of 98 patients with primary brain glioma treated by radical surgery in Nanchong Central Hospital from January 2018 to January 2021 were retrospectively included, and were divided into recurrent group (40 cases) and non-recurrent group (58 cases) according to whether there was recurrence or not during the follow-up period. The independent influencing factors for postoperative recurrence in patients with primary brain glioma were evaluated by multivariate logistic regression. Logistic prediction model of postoperative recurrence risk of patients with primary brain glioma was established, and the predictive efficacy of each index was calculated by receiver operator characteristic (ROC) curve.Results:There were statistically significant differences between recurrent group and non-recurrent group in glioma World Health Organization (WHO) grade ( χ2=12.48, P<0.001), isocitrate dehydrogenase (IDH) 1/2 mutation ( χ2=13.24, P<0.001), mean platelet volume (MPV) ( t=5.34, P<0.001), and MPV/platelet count (PLT) ( t=9.73, P<0.001). Multivariate analysis showed that WHO grade Ⅲ-Ⅳ ( OR=8.54, 95% CI: 1.62-44.99, P=0.011), IDH1/2 wild type ( OR=9.08, 95% CI: 1.68-49.19, P=0.010), low MPV ( OR=0.46, 95% CI: 0.21-0.99, P=0.048) and low MPV/PLT ( OR=0.02, 95% CI: 0.01-0.03, P<0.001) were independent risk factors for postoperative recurrence in patients with primary brain glioma. The logistic prediction model based on the above indicators was logit ( P) =11.78+2.15×WHO grade+2.21×IDH1/2 mutation situation-0.78×MPV-200.70×MPV/PLT ( R2=0.785). The ROC curve analysis results showed that WHO grade, IDH1/2 mutation, MPV, MPV/PLT, and logistic prediction model P-value could all be used to predict the risk of postoperative recurrence in patients with primary brain glioma; The areas under the curve were 0.681, 0.684, 0.783, 0.920 and 0.964, respectively. In the area under ROC curve comparison of each indicator, the predictive performance of the logistic regression model P-value was significantly higher than that of other indicators (all P<0.05) . Conclusion:Postoperative recurrence in patients with primary brain glioma may be related to glioma WHO grade, IDH1/2 mutation and platelet related laboratory indexes. The model constructed based on the above indicators can be used to predict the recurrence risk in patients with primary brain glioma after surgery.

Objective To investigate the current status and awareness of pharmaceutical services in hospitals in Guizhou province and to provide a reference for exploring and carrying out pharmaceutical service fees.Methods The questionnaire was designed by the"wjx.cn"website.Three kinds of questionnaires were designed for pharmacists,doctors,nurses,and patients as the research objects,with corresponding differences in some questions,and promoted on WeChat,Dingxiangyuan,and other network platforms.Results A total of 655 questionnaires were collected,and 639 valid questionnaires were recovered,with an effective recovery rate of 97.56%.324 pharmacists(50.70%),82 doctors and nurses(12.83%),233 patients(36.46%)were surveyed.The average approval score of these three groups of respondents on pharmaceutical service fees was 4.67,4.23,and 4.22,respectively(full score:5).Conclusions Overall,pharmacists'professional services have received support from medical staff and patients.However,patients'pharmaceutical service projects currently focus on dispensing services.The recognition of pharmacists'work and the public's awareness of pharmaceutical services can be improved by enhancing the professional ability of pharmacists,strengthening publicity and guidance,and exploring"Internet+pharmaceutical services",etc.,to promote the sustainable development of pharmaceutical services.