Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Objective:To analyze the relationship between neutrophil-to-lymphocyte ratio(NLR) and the levels of inflammatory factors in peripheral blood and the brain injuries of suppurative meningitis in neonates (NPM) and the value of joint prediction of hydrocephalus.Methods:Ninety-five children with NPM diagnosed and treated in the Affiliated Hospital of Jining Medical College from January 2020 to December 2022 were retrospectively selected, including 31 children with non-cerebral parenchymal injury (group A), accounting for 32.63%(31/95); 36 children with parenchymal injury and no hydrocephalus (group B), accounting for 37.89%(36/95); 28 children with brain parenchymal injury and hydrocephalus (group C), accounting for 29.47%(28/95). The clinical data, peripheral blood levels of NLR, interleukin 6(IL-6), hyper-sensitive C-reactive protein (hs-CRP) and procalcitonin (PCT) were compared among the three groups, and the influencing factors of hydrocephalus were analyzed by Logistic regression. Receiver operating characteristic (ROC) curve was used to analyze the value of changes(△, representing the absolute value of the difference between the corresponding indexes and 3 d after admission) in NLR, hs-CRP, IL-6 and PCT in predicting hydrocephalus in NPM alone and combination.Results:The incidence of respiratory failure and convulsion and the levels of NLR, hs-CRP, IL-6 and PCT in the group C were higher than those in the group B and A: 42.86%(12/28) vs. 13.89%(5/36), 6.45%(2/31); 42.86%(12/28) vs. 16.67%(6/36), 3.23%(1/31); 3.91 ± 0.71 vs. 3.12 ± 0.64, 2.16 ± 0.58; (98.21 ± 10.17) mg/L vs. (86.74 ± 9.30), (75.18 ± 8.42) mg/L; (40.73 ± 7.88) ng/L vs. (31.26 ± 6.45), (25.01 ± 5.19) ng/L; (13.26 ± 2.04) ng/L vs (11.83 ± 1.91), (9.45 ± 1.67) ng/L; the levels of NLR, hs-CRP, IL-6 and PCT in the group B were higher than those in the group A, there were statistical differences ( P<0.05). Logistic regression analysis showed that the levels of peripheral blood NLR and serum hs-CRP, IL-6 and PCT at admission were independent risk factors for hydrocephalus in children with NPM ( P<0.05). The △NLR, △hs-CRP, △IL-6 and △PCT of the children with hydrocephalus were lower than those without hydrocephalus: 0.73 ± 0.24 vs. 1.02 ± 0.31, (42.73 ± 13.08) mg/L vs. (69.56 ± 18.19) mg/L, (13.43 ± 4.22) ng/L vs. (19.86 ± 6.43) ng/L, (4.35 ± 1.34) ng/L vs. (6.58 ± 2.03) ng/L, there were statistical differences ( P<0.05). ROC curve analysis results showed that the AUC of △NLR, △hs-CRP, △IL-6 and △PCT combined to predict hydrocephalus in children with NPM was 0.903, which was greater than each single index ( P<0.05). Conclusions:The levels of NLR, hs-CRP, IL-6 and PCT in peripheral blood of children with NPM are significantly correlated with brain injuries, and have certain predictive efficacy in predicting the risk of hydrocephalus.

ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

Premature ovarian insufficiency(POI)is a disease that seriously affects the health and life of women,which is also one of the main causes of female infertility.The incidence of POI is increasing in recent years.The diagnostic criteria of POI are not uniform,and different diagnostic criteria have inconsistent thresholds for various indicators.Strict diagnostic criteria are more conducive to early detection and treatment of POI.At present,complementary and alternative therapies such as traditional Chinese medicine,acupuncture and moxibustion are widely used in the treatment of POI.This article reviewed the recent studies on the complementary and alternative therapy of traditional Chinese medicine in the treatment of POI,and finds that the dialectical treatment of traditional Chinese medicine is based on the perspective of traditional Chinese medicine theory and puts forward corresponding treatment plans for different dialectical types.For example,treatment from the kidney,tonifying kidney filling essence,regulating chongren;Treatment from the liver,soothing the liver,regulating qi,nourishing blood and softening the liver;Treatment from the heart and spleen,nourishing Yangming,tonifying the spleen and nourishing the heart.In terms of acupuncture treatment,regulating menstruation and promoting pregnancy and regulating the conception vessel and toning the governor vessel and toning the kidney are often used to treat POI.In addition,moxibustion regulates body function by stimulating the bladder meridian and conception vessel and governor vessel acupoints.Other methods,such as ear acupoint bean-pressing,acupoint thread-embedding and acupoint injection,have also shown potential in the treatment of POI.This article summarizes the role and characteristics of traditional Chinese medicine in the treatment of POI,in order to provide ideas and basis for clinical treatment of POI.

Objective:To analyze the relationship between neutrophil-to-lymphocyte ratio(NLR) and the levels of inflammatory factors in peripheral blood and the brain injuries of suppurative meningitis in neonates (NPM) and the value of joint prediction of hydrocephalus.Methods:Ninety-five children with NPM diagnosed and treated in the Affiliated Hospital of Jining Medical College from January 2020 to December 2022 were retrospectively selected, including 31 children with non-cerebral parenchymal injury (group A), accounting for 32.63%(31/95); 36 children with parenchymal injury and no hydrocephalus (group B), accounting for 37.89%(36/95); 28 children with brain parenchymal injury and hydrocephalus (group C), accounting for 29.47%(28/95). The clinical data, peripheral blood levels of NLR, interleukin 6(IL-6), hyper-sensitive C-reactive protein (hs-CRP) and procalcitonin (PCT) were compared among the three groups, and the influencing factors of hydrocephalus were analyzed by Logistic regression. Receiver operating characteristic (ROC) curve was used to analyze the value of changes(△, representing the absolute value of the difference between the corresponding indexes and 3 d after admission) in NLR, hs-CRP, IL-6 and PCT in predicting hydrocephalus in NPM alone and combination.Results:The incidence of respiratory failure and convulsion and the levels of NLR, hs-CRP, IL-6 and PCT in the group C were higher than those in the group B and A: 42.86%(12/28) vs. 13.89%(5/36), 6.45%(2/31); 42.86%(12/28) vs. 16.67%(6/36), 3.23%(1/31); 3.91 ± 0.71 vs. 3.12 ± 0.64, 2.16 ± 0.58; (98.21 ± 10.17) mg/L vs. (86.74 ± 9.30), (75.18 ± 8.42) mg/L; (40.73 ± 7.88) ng/L vs. (31.26 ± 6.45), (25.01 ± 5.19) ng/L; (13.26 ± 2.04) ng/L vs (11.83 ± 1.91), (9.45 ± 1.67) ng/L; the levels of NLR, hs-CRP, IL-6 and PCT in the group B were higher than those in the group A, there were statistical differences ( P<0.05). Logistic regression analysis showed that the levels of peripheral blood NLR and serum hs-CRP, IL-6 and PCT at admission were independent risk factors for hydrocephalus in children with NPM ( P<0.05). The △NLR, △hs-CRP, △IL-6 and △PCT of the children with hydrocephalus were lower than those without hydrocephalus: 0.73 ± 0.24 vs. 1.02 ± 0.31, (42.73 ± 13.08) mg/L vs. (69.56 ± 18.19) mg/L, (13.43 ± 4.22) ng/L vs. (19.86 ± 6.43) ng/L, (4.35 ± 1.34) ng/L vs. (6.58 ± 2.03) ng/L, there were statistical differences ( P<0.05). ROC curve analysis results showed that the AUC of △NLR, △hs-CRP, △IL-6 and △PCT combined to predict hydrocephalus in children with NPM was 0.903, which was greater than each single index ( P<0.05). Conclusions:The levels of NLR, hs-CRP, IL-6 and PCT in peripheral blood of children with NPM are significantly correlated with brain injuries, and have certain predictive efficacy in predicting the risk of hydrocephalus.

Premature ovarian insufficiency(POI)is a disease that seriously affects the health and life of women,which is also one of the main causes of female infertility.The incidence of POI is increasing in recent years.The diagnostic criteria of POI are not uniform,and different diagnostic criteria have inconsistent thresholds for various indicators.Strict diagnostic criteria are more conducive to early detection and treatment of POI.At present,complementary and alternative therapies such as traditional Chinese medicine,acupuncture and moxibustion are widely used in the treatment of POI.This article reviewed the recent studies on the complementary and alternative therapy of traditional Chinese medicine in the treatment of POI,and finds that the dialectical treatment of traditional Chinese medicine is based on the perspective of traditional Chinese medicine theory and puts forward corresponding treatment plans for different dialectical types.For example,treatment from the kidney,tonifying kidney filling essence,regulating chongren;Treatment from the liver,soothing the liver,regulating qi,nourishing blood and softening the liver;Treatment from the heart and spleen,nourishing Yangming,tonifying the spleen and nourishing the heart.In terms of acupuncture treatment,regulating menstruation and promoting pregnancy and regulating the conception vessel and toning the governor vessel and toning the kidney are often used to treat POI.In addition,moxibustion regulates body function by stimulating the bladder meridian and conception vessel and governor vessel acupoints.Other methods,such as ear acupoint bean-pressing,acupoint thread-embedding and acupoint injection,have also shown potential in the treatment of POI.This article summarizes the role and characteristics of traditional Chinese medicine in the treatment of POI,in order to provide ideas and basis for clinical treatment of POI.

Objective:To discuss the clinical efficacy of minimally invasive pulmonary surfactant (PS) therapy technology (MIST) in the treatment of neonatal respiratory distress syndrome (NRDS) and analyze the high-risk factors for failure.Methods:A total of 91 NRDS infants treated in the Affiliated Hospital of Jining Medical College from July 2017 to July 2019 were selected as the research objects, and 46 cases were performed minimally MIST (MIST group), 45 cases performed intubate-surfactant-extubate to continuous positive airway pressure (INSURE group), the infants were given 70-100 mg/kg porcine pulmonary phospholipid injection through vascular catheter or endotracheal intubation, respectively. The clinical efficacy of the two groups was compared and the risk factors for failure in the treatment of NRDS by PS were analyzed.Results:The total operating time in the MIST group was longer than that in the INSURE group: (90.06 ± 14.38) min vs. (62.57 ± 11.44) min, there was statistical difference ( P<0.05). The duration of non-invasive auxiliary ventilation, total oxygen uptake time and length of hospitalization time in two groups had no significant differences ( P>0.05). The incidence of bronchopulmonary dysplasia in the MIST group was lower than that in the INSURE group :10.87%(5/46) vs. 31.11%(14/45), there was statistical difference ( χ2 = 5.64, P<0.05). Univariate analysis showed that the male, cesarean section, birth weight <1 500 g, maternal gestational diabetes, arterial partial blood oxygen pressure (PaO 2) <59 mmHg (1 mmHg = 0.133 kPa) before the application of PS, and PaO 2/inhaled oxygen concentration (FiO 2) <185 mmHg and arterial partial pressure of carbon dioxide>55 mmHg were high risk factors for failure ( P<0.05). Conclusions:Although the operation of MIST is difficult, it is safe and feasible. In clinical work, various risk factors should be comprehensively analyzed to select an appropriate early respiratory support model for NRDS children.

Objective:To explore the effect of mini-clinical evaluation exercise (Mini-CEX) combined with simulation teaching + case-based learning (CBL) in pediatric clinical teaching.Methods:A total of 60 medical students who practiced in Department of Pediatrics, Affiliated Hospital of Jining Medical College from August 2019 to August 2020 were selected as the research objects. According to different teaching methods, they were divided into control group ( n=30) and observation group ( n=30). The control group received traditional teaching, and the observation group received Mini-CEX combined with simulated teaching + CBL. The assessment results, comprehensive ability of medical interview, critical thinking ability and teaching satisfaction of the two groups were compared. SPSS 20.0 was performed for t-test and Chi-square test. Results:The test scores and total scores of the observation group were significantly higher than those of the control group ( P<0.05). After teaching, the Mini-CEX scores, the CTDI-CV (critical thinking disposition inventory Chinese version) scores and the total scores of the two groups increased significantly, and the above scores were significantly higher in the observation group than the control group ( P<0.05). The scores of the teaching program satisfaction questionnaire in the observation group were significantly higher than those in the control group ( P<0.05). Conclusion:The application of Mini-CEX combined with simulation teaching + CBL in pediatric clinical teaching can help to cultivate the medical interview ability, clinical practice ability and critical thinking ability of interns, improve the examination results, and improve the teaching satisfaction.

Objective:To explore the effects of occupational and recreational therapy on symptom distress and mental toughness in perioperative period for lung neoplasms patients.Methods:By adopt convenient sampling method, a total of 92 cases of lung tumor patients were collected the lung cancer department in Tianjin Medical University Cancer Institute & Hospital from December 2019 to September 2020 in pulmonary oncology department. They were divided into observation group and control group according to the order of admission, with 46 cases in each group. The patients in the control group received routine care, the observation group implemented occupational and recreational therapy based on the routine care. At enrollment and 1 month after discharge, the effects were assessed by Chinese Version of the MD Anderson Symptom Inventory (MDASI-C) and Connor-Davidson Resilience scale (CD-RISC), respectively.Results:After intervention, the symptom distress scores and life influence scores in MDASI-C were (4.45 ± 1.09) points and (5.24 ± 1.78) points in the observation group, significantly lower than in the control group (5.84 ± 1.67) points and (6.11 ± 1.32) points, the differences were statistically significant ( t=4.59, 2.59, both P<0.05); the scores of tenacity, power, optimism and total scores of CD-RISC in the observation group were (28.12 ± 4.39) points, (21.07 ± 5.57) points, (10.67 ± 3.03) points and (59.86 ± 8.29) points, significantly higher than in the control group (24.54 ± 4.16) points, (18.23 ± 4.21) points, (9.16 ± 2.47) points and (51.93 ± 5.99) points, the differences were statistically significant ( t values were 2.53-5.10, all P<0.05). Conclusions:Occupational and recreational therapy can effectively alleviate symptom distress and promote mental toughness of lung cancer patients in perioperative period.

【Objective】 To investigate the effect of leukocyte-depleted suspended red blood cells (lds-RBCs) storaged for different time on blood transfusion effect of patients with hematologic diseases and malignant tumors, as well as to evaluate the storage quality of lds-RBCs in blood stations. 【Methods】 Seven hospitals (4 tertiary-A hospitals and 3 secondary-A hospitals), applying for blood from our blood center, were selected. Blood transfusion cases (medical record) and related data (indicators) of patients with blood diseases and malignant tumors in those hospitals from December 2018 to May 2019 were collected, including disease diagnosis (type) before transfusion, demographic characteristics, date of solo transfusion of lds-RBCs, units of lds-RBCs [(1~2)U/bag, 1 U=200 mL whole blood], different storage duration (1~5 weeks) (bar code), and hemoglobin (Hb) 48 h before and after transfusion. The efficacy of lds-RBCs (storaged for different time) transfusion in patients with hematologic diseases and malignant tumors was evaluated by statistical analysis. 【Results】 A total of 3 557 patients with hematologic diseases and malignant tumors were enrolled in this study. No significant changes were noticed in transfusion efficacy by blood transfusion unit, gender and previous transfusion history (P > 0.05). The effective rate of lds-RBCs in patients with blood diseases and malignant tumors, stratified by storage duration, i. e. storaged for >1~2 weeks, >2~3 weeks, >3~4 weeks and more than >4~5 weeks, was 78.77% vs 77.68% vs 75.06% vs 70.37%, and 79.32% vs 76.73% vs 72.79% vs 67.65%, respectively(P<0.05), with lds-RBCs of 4-5 storage weeks presenting the lowest transfusion efficacy in both groups of patients. 【Conclusion】 The storage time of most lds-RBCs supplied by our center is moren than 3 weeks, and the transfusion effect of lds-RBCs stored for 5 weeks needs further observation. In order to ensure and improve the efficacy of blood transfusion, evidence-based medicine and information management are needed to help the clinical gasp the advantageous time of blood products and shorten the storage-to-transfusion time of red blood cells.