ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus（h-RLF）， formulate relevant quality standards， and explore its improving effect and mechanism on mice with ulcerative colitis（UC） induced by dextran sodium sulfate（DSS）. MethodsTaking the content of polysaccharides and water-soluble extract as the indexes， L₉（3⁴） orthogonal test was used to optimize parameters of the amount of honey bran， frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process， and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups， including the blank group， model group， mesalazine group（0.13 g·kg^-1）， RLF group（3.77 g·kg^-1）， bran-fried RLF group（3.77 g·kg^-1）， h-RLF low， medium and high dose groups（1.89， 3.77， 7.54 g·kg^-1）， with 10 mice in each group. The mice in the blank group were free to drink pure water， and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration， and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index（DAI） was calculated. After the administration， the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin（HE） staining. The levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65（p-NF-κB p65）， Toll-like receptor 4（TLR4）， p-p38 mitogen-activated protein kinase（p-p38 MAPK）， p-extracellular signal-regulated kinase（p-ERK） and p-c-Jun N-terminal kinase（p-JNK） proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF， and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows：the polysaccharide content should not be less than 25% based on anhydrous glucose（C₆H₁₂O₆）， the content of water-soluble extract should not be less than 38%， the moisture content should not be more than 12.0%， the total ash content should not be more than 5.0%， and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang， Hubei province was better. Animal experiments showed that compared with the blank group， the DAI score of the model group was significantly increased， the levels of TNF-α， IL-1β and IL-6 in the colon tissue were significantly increased， the IL-10 level was significantly decreased， the colonic mucosa was seriously damaged， accompanied by a large number of inflammatory cell infiltration， tissue congestion and a significant reduction in glands， and the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins were significantly increased（P<0.01）. Compared with the model group， each administration group could alleviate the symptoms of colonic ulcer， the structure of colonic crypt was basically intact， and the glands were arranged in an orderly manner. Among them， the high-dose group of h-RLF had a better effect， which could significantly reduce the DAI score and the levels of TNF-α， IL-1β and IL-6 in colon tissue（P<0.01）， and significantly increase the level of IL-10（P<0.01）， alleviate the colonic mucosal injury， and effectively inhibit the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins（P<0.01）. ConclusionThe key parameters of the processing technology of h-RLF are determined， and the optimized technology is stable and feasible. The established quality standard is simple and reliable， and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC， and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.

ObjectiveBased on the conjoint analysis of transcriptome and metabolome， the key genes in the phenylpropanoid biosynthesis pathway of Lonicera macranthoides were explored， which provided a basis for further exploring the synthesis and regulation mechanism of phenylpropanoid compounds in "Xianglei" L. macranthoides. MethodsThe stem， leaves， and three flowering flowers of "Xianglei" L. macranthoides were selected as experimental materials to construct transcriptome and metabolome. The transcriptome and metabolomics were conjointly analyzed by the Kyoto Encyclopedia of Genes and Genomes （KEGG） database and weighted correlation network analysis （WGCNA）， and the key genes in the phenylpropanoid biosynthesis pathway of L. macranthoides were explored. ResultsIn this study， 77 differential phenylpropanoids and 315 differential genes were found. Through the joint analysis of transcription and metabolism， nine key differential metabolites and four key genes related to them were finally discovered. Among them， cinnamic acid， 5-O-caffeoylshikimic acid，sinapyl alcohol， and chlorogenic acid were higher in flowers， and the content of the iconic effective component， namely chlorogenic acid，decreased sharply during the withering period. Caffeic acid，ferulic acid， 5-hydroxyconiferaldehyde，p-coumaryl alcohol， and syringin were higher in leaves. These four key genes belong to the cinnamic alcohol dehydrogenase （CAD） family， 4-coumaric acid： Coenzyme A （4CL） family， hydroxycinnamyl transferase （HCT） family， and L-phenylalanine ammonlyase （PAL） family genes. ConclusionAmong the four key genes excavated from L. macranthoides， TRINITY_DN42767_c0_g6 is related to the synthesis of p-coumaryl alcohol and sinapyl alcohol. TRINITY_DN43525_c4_g1 uses caffeic acid，ferulic acid，and cinnamic acid as substrates to catalyze the next reaction. TRINITY_DN47958_c3_g4 correlates with the synthesis of 3-p-coumaroyl quinic acid and caffeoyl-CoA， and TRINITY_DN52595_c1_g2 correlates with cinnamic acid synthesis. These findings provide a basis for further exploring the synthesis and regulation mechanism of phenylpropanoids in "Xianglei" L. macranthoides.

Objective This study aimed to explore the underlying mechanisms between parental neglect and depression of adolescents.Methods This study utilized data from the 2020 China Family Panel Studies(CFPS)and included 1902 adolescents aged 10～15.Correlation analysis,multivariable logistic regression,structural equation modeling,and the bootstrap method were employed to examine the relationships between parental neglect,social trust,and depressive symptoms in adolescents.Results This study found that the prevalence of depressive symptoms among adolescents was 10.9%.Parental neglect was associated with an increased risk of depressive symptoms(OR:1.772,95%CI:1.310～2.636),and social trust acted as a mediator between parental neglect and depressive symptoms(mediating effect:17.20%,P<0.001).Additionally,gender moderated the latter half of the mediation model(β:0.127,95%CI:0.016～0.236,P<0.001).Conclusion The experiences of parental neglect are closely related to higher levels of depressive symptoms among adolescents,with social trust serving as a mediating factor.This mediating effect of social trust is particularly significant among females.It is crucial to cultivate a supportive environment and develop a harmonious family atmosphere.

Objective To explore the role of X chromosome encoded epigenetic regulator UTX in NK cell-mediated anti-tumor activity.Methods Male Ncr1-iCre mice were crossed with female UTXfl/fl mice to generate F1 Ncr1-iCre+UTXfl/-male mice,which were further crossed with female UTXfl/fl mice to obtain male Ncr1-iCre-UTX fl/-control mice(M-Con)and NK-specific deletion of UTX male mice Ncr1-iCre+UTXfl/-(M-KO),as well as female Ncr1-iCre-UTXfl/fl control mice(F-Con)and UTX-deficient female mice Ncr1-iCre+UTXfl/fl(F-KO).UTX-deficient mice were injected with melanoma cell line B16F10 via tail vein to observe pulmonary metastatic tumor nodules.Moreover,flow cytometry was applied to detect the proportion and quantity of pulmonary NK cells(CD3-CD19-NK1.1+),maturation makers KLRG1 and CD11b,activation receptors NKG2D and CD69,and effector molecules,including perforin,granzyme B,CD107a,and IFN-γ.Then pulmonary NK cells were sorted and co-cultured with B16F10 cells,and the apoptosis of the melanoma cells was measured with flow cytometry.Results Compared with the M-Con mice,the M-KO mice presented less number of pulmonary tumor nodules(P<0.05),increased proportion and quantity of NK cells in the tumor microenvironment(P<0.01),though no obvious changes in the ratio of NK maturation makers KLRG1 to CD11b,enhanced expression level of cytotoxic molecule perforin(P<0.01),but no changes in the expression of effector molecule granzyme B,degranulation marker CD107a and cytokine IFN-γ in NK cells.Co-culture of NK cells and B16F10 cells promoted the apoptosis of tumor cells(P<0.05).Compared with the F-Con mice,the F-KO mice had no statistical difference in the number of pulmonary tumor nodules,but larger proportion and number of NK cells(P<0.05),decreased ratio of KLRG1 to CD11b(P<0.01),elevated level of perforin but decreased levels of granzyme B,CD107a and IFN-γ in NK cells(P<0.01).The co-culture of NK cells and B16F10 cells reduced the apoptosis of tumor cells in F-KO female mice(P<0.05).Conclusion NK-specific deletion of UTX regulates pulmonary metastasis of melanoma in a sex-dependent manner.

Objective To investigate the factors affecting the exposure of polymyxin B and the correlation between pharmacokinetic/pharmacodynamic(PK/PD)indexes and efficacy in patients with multidrug-resistant Gram-negative bacterial(MDR-GNB)infections.Methods This prospective study was conducted in patients who received polymyxin B to treat MDR-GNB infections in the intensive care unit of Nanjing Drum Tower Hospital,Medical College,Nanjing University from January 2021 to December 2023.Plasma concentrations of polymyxin B were analyzed using a high-performance liquid chromatography-tandem mass spectrometry,and the influencing factors of exposure were investigated.The predictive value of area under the concentration-time curve(AUC24h)and AUC24hto minimum inhibitory concentration ratio for efficacy was determined by the receiver operating characteristic curve.Results The median of AUC24h was 76.11(56.06,96.94)μg·mL-1·h in 96 patients with MDR-GNB infections.Patients in the high-dose group(≥ 150 mg·d-1)were more likely to have higher exposure of polymyxin B than those in the low-dose group(＜150 mg·d-1)(P＜0.05).The exposure in patients with renal replacement therapy was significantly de-creased(P＜0.01).However,increasing the dose in patients receiving renal replacement therapy had no significant difference on exposure.The ROC curve showed AUC24h/MIC was closely correlated with clinical efficacy in patients with MDR-GNB infections(AUCROC=0.724,P＜0.01)and the optimal cut-off value of AUC24h/MIC was 62.1.Subgroup analysis showed that the optimal cut-off values of AUC24h/MIC in patients with and without pulmonary infection were 70.8 and 61.5,respectively.The clinical effi-cacy rate was significantly higher in AUC24 h/MIC≥62.1 group,compared with those in AUC24 h/MIC＜62.1 group(72.88％vs.32.43％,P＜0.01).After treatment,the decreasing trend of inflammation indicators in AUC24 h/MIC≥ 62.1 group was superior to those in AUC24h/MIC＜62.1 group.Conclusion The dose and renal replacement therapy are the significant factors influencing the exposure of polymyxin B.AUC24 h/MIC with the target of 62.1 was the optimal exposure index to predict the efficacy in the treatment of MDR-GNB infections and the optimal threshold of AUC24h/MIC was higher in patients with pulmonary infections than in non-pulmonary patients,so therapeutic drug monitoring is recommended to adjust the AUC24h/MIC index to achieve individual-ized medication.

Objective This study aimed to explore the underlying mechanisms between parental neglect and depression of adolescents.Methods This study utilized data from the 2020 China Family Panel Studies(CFPS)and included 1902 adolescents aged 10～15.Correlation analysis,multivariable logistic regression,structural equation modeling,and the bootstrap method were employed to examine the relationships between parental neglect,social trust,and depressive symptoms in adolescents.Results This study found that the prevalence of depressive symptoms among adolescents was 10.9%.Parental neglect was associated with an increased risk of depressive symptoms(OR:1.772,95%CI:1.310～2.636),and social trust acted as a mediator between parental neglect and depressive symptoms(mediating effect:17.20%,P<0.001).Additionally,gender moderated the latter half of the mediation model(β:0.127,95%CI:0.016～0.236,P<0.001).Conclusion The experiences of parental neglect are closely related to higher levels of depressive symptoms among adolescents,with social trust serving as a mediating factor.This mediating effect of social trust is particularly significant among females.It is crucial to cultivate a supportive environment and develop a harmonious family atmosphere.

Objective:To explore drug detoxification motivation in methamphetamine-dependent female youth and its relationship with time perspective,perceived social support and emotion regulation strategies.Methods:To-tally 200 methamphetamine-dependent female youths under compulsory isolation were assessed with the Drug De-toxification Motivation Scale,Zimbardo Time Perspective Inventory-Chinese(ZTPI-C),Emotion Regulation Scale(ERS),and Perceived Social Support Scale(PSSS).Results:Multiple linear regression analysis showed that drug detoxification motivation scores were positively correlated with the scores of ERS reevaluation and expression inhi-bition,PSSS family support scores and level of education(β=0.24,0.16,0.20,0.16).Conclusion:Time perspec-tive,perceived social support and emotion regulation strategies are closely related to drug detoxification motivation in methamphetamine-dependent female youth.

Objective:To explore drug detoxification motivation in methamphetamine-dependent female youth and its relationship with time perspective,perceived social support and emotion regulation strategies.Methods:To-tally 200 methamphetamine-dependent female youths under compulsory isolation were assessed with the Drug De-toxification Motivation Scale,Zimbardo Time Perspective Inventory-Chinese(ZTPI-C),Emotion Regulation Scale(ERS),and Perceived Social Support Scale(PSSS).Results:Multiple linear regression analysis showed that drug detoxification motivation scores were positively correlated with the scores of ERS reevaluation and expression inhi-bition,PSSS family support scores and level of education(β=0.24,0.16,0.20,0.16).Conclusion:Time perspec-tive,perceived social support and emotion regulation strategies are closely related to drug detoxification motivation in methamphetamine-dependent female youth.

Objective To investigate the factors affecting the exposure of polymyxin B and the correlation between pharmacokinetic/pharmacodynamic(PK/PD)indexes and efficacy in patients with multidrug-resistant Gram-negative bacterial(MDR-GNB)infections.Methods This prospective study was conducted in patients who received polymyxin B to treat MDR-GNB infections in the intensive care unit of Nanjing Drum Tower Hospital,Medical College,Nanjing University from January 2021 to December 2023.Plasma concentrations of polymyxin B were analyzed using a high-performance liquid chromatography-tandem mass spectrometry,and the influencing factors of exposure were investigated.The predictive value of area under the concentration-time curve(AUC24h)and AUC24hto minimum inhibitory concentration ratio for efficacy was determined by the receiver operating characteristic curve.Results The median of AUC24h was 76.11(56.06,96.94)μg·mL-1·h in 96 patients with MDR-GNB infections.Patients in the high-dose group(≥ 150 mg·d-1)were more likely to have higher exposure of polymyxin B than those in the low-dose group(＜150 mg·d-1)(P＜0.05).The exposure in patients with renal replacement therapy was significantly de-creased(P＜0.01).However,increasing the dose in patients receiving renal replacement therapy had no significant difference on exposure.The ROC curve showed AUC24h/MIC was closely correlated with clinical efficacy in patients with MDR-GNB infections(AUCROC=0.724,P＜0.01)and the optimal cut-off value of AUC24h/MIC was 62.1.Subgroup analysis showed that the optimal cut-off values of AUC24h/MIC in patients with and without pulmonary infection were 70.8 and 61.5,respectively.The clinical effi-cacy rate was significantly higher in AUC24 h/MIC≥62.1 group,compared with those in AUC24 h/MIC＜62.1 group(72.88％vs.32.43％,P＜0.01).After treatment,the decreasing trend of inflammation indicators in AUC24 h/MIC≥ 62.1 group was superior to those in AUC24h/MIC＜62.1 group.Conclusion The dose and renal replacement therapy are the significant factors influencing the exposure of polymyxin B.AUC24 h/MIC with the target of 62.1 was the optimal exposure index to predict the efficacy in the treatment of MDR-GNB infections and the optimal threshold of AUC24h/MIC was higher in patients with pulmonary infections than in non-pulmonary patients,so therapeutic drug monitoring is recommended to adjust the AUC24h/MIC index to achieve individual-ized medication.

Objective:This study aimed to construct a risk prediction model for obstructive sleep apnea（OSA） related hypertension based on the nomogram, and to explore the independent risk factors for OSA-related hypertension, so as to provide reference for clinical treatment decision-making. Methods:The clinical data of OSA patients diagnosed by polysomnography from October 2019 to December 2021 were collected retrospectively and randomly divided into training sets and validation sets. A total of 1 493 OSA patients with 27 variables were included. The least absolute shrinkage and selection operator（Lasso） logistic regression model was used to select potentially relevant features and establish a nomogram for OSA-related hypertension.The performance and clinical benefits of this nomogram were verified in terms of discrimination, calibration ability and clinical net benefit. Results:Multivariate logistic regression showed that body mass index（BMI）, family history of hypertension, lowest oxygen saturation（LSaO2）, age and cumulative percentage of total sleep time with oxygen saturation below 90% were independent risk factors for OSA-related hypertension. Lasso logistic regression identified BMI, family history of hypertension, LSaO2 and age as predictive factors for inclusion in the nomogram. The nomogram provided a favorable discrimination, with a C-indexes of 0.835（95% confidence interval[CI ]0.806-0.863） 0.865（95%CI 0.829-0.900） for the training and validation cohort, respectively, and well calibrated. The clinical decision curve analysis displayed that the nomogram was clinically useful. Conclusion:Compared with cumulative percentage of total sleep time with blood oxygen saturation below 90%, LSaO2 may have a greater impact on the incidence of OSA-related hypertension, and the effects of different times and degrees of hypoxia on OSA-related hypertension should be further explored in the future. Apnea hypopnea index involvement is weak in predicting OSA-related hypertension, and the blood oxygen index may be a better predictor variable. Furthermore, we established a risk prediction model for OSA-related hypertension patients using nomogram, and demonstrated that this prediction model was helpful to identify high-risk OSA-related hypertension patients. This model can provide early and individualized diagnosis and treatment plans, protect patients from the serious.
Humans ; Sleep Apnea, Obstructive/complications* ; Nomograms ; Hypertension/epidemiology* ; Male ; Female ; Risk Factors ; Middle Aged ; Retrospective Studies ; Polysomnography ; Logistic Models ; Body Mass Index ; Adult