Objective To develop an oxybutynin nanotransdermal formulation with high skin permeability based on cubsomes carrier.Methods The oxybutynin loaded cubsomes(OXY-CS)was prepared by ultrasonic method.Using particle size,polydispersity index and encapsulation efficiency as evaluation indexes,stirring temperature,stirring time,stirring speed,ultrasound time,ultrasound power,glycerol monooleate/poloxamer 407 ratio(GMO/F127),carrier(GMO+F127)/drug ratio and drug concentration were optimized.The effects of drug concentration,permeation promoter and gel matrix type on skin permeability were investigated using cumulative permeation and skin retention as evaluation indicators.Results The prepared OXY-CS had small particle size and high encapsulation efficiency at stirring temperature of 50℃,stirring time of 30 min,stirring speed of 1 000 r/min,ultrasound time of 10 min,ultrasound power of 100 W,GMO/F127 ratio of 2∶1,carrier/drug ratio of 3∶1 and drug concentration of 1％,respectively.OXY-CS had high cumulative penetration and skin retention at concentration ≥ 3％.The addition of a permeation promoter to OXY-CS did not increase the cumulative penetration of the drug.The skin permeability of oxybutynin cubsomes gel made with carbomer was significantly better than those of other gel matrices.Conclusion In this study,oxybutynin is made into a topical cubsomes gel,which is expected to reduce the incidence of adverse effects associated with oral administration.

Objective To investigate the protective effect of recombinant Schistosoma japonicum cystatin(rSj-Cys)against acute liver injury induced by lipopolysaccharide(LPS)and D-GalN in mice.Methods Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling(n=18),and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling.The survival of the remaining 10 mice in each group within 24 h was observed.Serum levels of ALT,AST,TNF-α and IL-6 of the mice were measured,and liver pathologies was observed with HE staining.The hepatic expressions of macrophage marker CD68,Bax,Bcl-2 and endoplasmic reticulum stress(ERS)-related proteins were detected using immunohistochemistry or immunoblotting,and TUNEL staining was used to detect hepatocyte apoptosis.Results The survival rates of PBS-and rSj-Cys-treated mouse models of acute liver injury were 30%and 80%at 12 h and were 10%and 60%at 24 h after modeling,respectively;no death occurred in the two control groups within 24 h.The mouse models showed significantly increased serum levels of AST,ALT,IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax,lowered expression of Bcl-2,increased hepatocyte apoptosis,and up-regulated expressions of ERS-related signaling pathway proteins GRP78,CHOP and NF-κB p-p65.Treatment of the mouse models significantly lowered the levels of AST,ALT,IL-6 and TNF-α,alleviated liver pathologies,reduced hepatic expressions of CD68,Bax,GRP78,CHOP and NF-κB p-p65,and enhanced the expression of Bcl-2.In the normal control mice,rSj-Cys injection did not produce any significant changes in these parameters compared with PBS.Conclusion rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS,attenuating inflammation and inhibiting hepatocyte apoptosis.

Objective To investigate the protective effect of recombinant Schistosoma japonicum cystatin(rSj-Cys)against acute liver injury induced by lipopolysaccharide(LPS)and D-GalN in mice.Methods Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling(n=18),and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling.The survival of the remaining 10 mice in each group within 24 h was observed.Serum levels of ALT,AST,TNF-α and IL-6 of the mice were measured,and liver pathologies was observed with HE staining.The hepatic expressions of macrophage marker CD68,Bax,Bcl-2 and endoplasmic reticulum stress(ERS)-related proteins were detected using immunohistochemistry or immunoblotting,and TUNEL staining was used to detect hepatocyte apoptosis.Results The survival rates of PBS-and rSj-Cys-treated mouse models of acute liver injury were 30%and 80%at 12 h and were 10%and 60%at 24 h after modeling,respectively;no death occurred in the two control groups within 24 h.The mouse models showed significantly increased serum levels of AST,ALT,IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax,lowered expression of Bcl-2,increased hepatocyte apoptosis,and up-regulated expressions of ERS-related signaling pathway proteins GRP78,CHOP and NF-κB p-p65.Treatment of the mouse models significantly lowered the levels of AST,ALT,IL-6 and TNF-α,alleviated liver pathologies,reduced hepatic expressions of CD68,Bax,GRP78,CHOP and NF-κB p-p65,and enhanced the expression of Bcl-2.In the normal control mice,rSj-Cys injection did not produce any significant changes in these parameters compared with PBS.Conclusion rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS,attenuating inflammation and inhibiting hepatocyte apoptosis.

Objective To study the effect of pain on the lumbar and hip joint moments in patients with lumbar disc herniation(LDH)while sitting and standing.Methods Dynamic data from 20 healthy controls and 20 patients with LDH were collected using an AMTI dynamometer.The differences in moments between the lumbar spine and hip joints in the sagittal and coronal planes for the two groups of subjects performing sitting-standing tasks were analyzed using statistical parameter mapping(SPM).Results Compared to the healthy control group,the LDH group showed a significant increase in the maximum lumbar flexion moment and the maximum hip adduction moment from standing to sitting(P＜0.05).SPM analysis showed that during the initial phase of standing(37％-42％),the hip abduction moment of the LDH group was significantly greater than that of the healthy control group(P=0.007).Conclusions Subjects with LDH have an unstable lumbar spine and pelvis during sitting and standing,especially at the stationary stage,which makes it difficult to achieve balance in their body.Therefore,increasing the hip abduction moment is necessary to maintain pelvic stability.During clinical evaluation and treatment,emphasis should be placed on the stable function of the spine and pelvis.

Objective:To understand the status and coping strategies of death anxiety among military nurses participating in emergency public health incident response, and to provide references for improving their coping abilities.Methods:A purposive sampling and snowball sampling method were used to select 15 nurses from multiple military hospitals who supported the emergency public health incident. One-on-one semi-structured interviews were conducted, and the Colaizzi's seven-step analysis method was used to analyze the interview data.Results:Four themes were identified: the occurrence of death anxiety at different time points; the presence of significant outbreaks of death anxiety; multiple factors that help military nurses alleviate death anxiety; and the intrinsic motivation and gains of military nurses participating in the response.Conclusions:It is crucial to monitor the occurrence and changes in death anxiety among nurses throughout the entire cycle of emergency public health incidents. Managers should focus on value guidance, leverage individual positive strengths to cope with death anxiety, enhance information and social support, reinforce training on infectious disease prevention and death education, and reduce the level of death anxiety among military nurses and improve their coping abilities.

Dry eye,also known as keratoconjunctivitis sicca,is clinically manifested as dry eyes,itching,burning,blurred vision and other symptoms,which seriously affects the life quality of patients.In recent years,the incidence of dry eye has increased year by year,and it has become one of the common clinical diseases in ophthalmology.At present,the treatment methods of dry eye mainly include drug treatment,surgical treatment and clinical nursing,among which drug is the most commonly used method for the treatment of dry eye.Therefore,this paper summarizes the application and research progress of clinical medication of dry eye based on permeation pathways and inflammatory pathways in recent years,so as to provide some ideas for the follow-up treatment of dry eye and drug development.

The solute carrier family 12(SLC12)of cation-chloride cotransporters(CCCs)comprises potassium chlo-ride cotransporters(KCCs,e.g.KCC1,KCC2,KCC3,and KCC4)-mediated Cl-extrusion,and sodium po-tassium chloride cotransporters(N[K]CCs,NKCC1,NKCC2,and NCC)-mediated Cl-loading.The CCCs play vital roles in cell volume regulation and ion homeostasis.Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues.In recent years,there have been considerable ad-vances in our understanding of CCCs'control mechanisms in cell volume regulations,with many tech-niques developed in studying the functions and activities of CCCs.Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs.These techniques include the ammonium pulse technique,radioactive or nonradioactive rubidium ion uptake-assay,and thallium ion-uptake assay.CCCs'activity can also be indirectly observed by measuring y-aminobutyric acid(GABA)activity with patch-clamp electrophysiology and intracellular chloride con-centration with sensitive microelectrodes,radiotracer 36Cl-,and fluorescent dyes.Other techniques include directly looking at kinase regulatory sites phosphorylation,flame photometry,22Na+uptake assay,structural biology,molecular modeling,and high-throughput drug screening.This review sum-marizes the role of CCCs in genetic disorders and cell volume regulation,current methods applied in studying CCCs biology,and compounds developed that directly or indirectly target the CCCs for disease treatments.

国家自然科学基金项目(11932012、81400536),上海申康医院发展中心临床创新三年行动计划(SHDC2020CR3009A),上海交通大学医工(理)交叉基金(JYJC202130)

Objective:To analyze the clinical and laboratory characteristics of acute myeloid leukemia (AML) patients with NPM1 mutation, and to explore the prognostic factors.Methods:A total of 77 AML patients with NPM1 gene mutation admitted to Hebei Yanda Ludaopei Hospital from May 1st 2012 to December 31st 2021 were enrolled in the study, including 34 male and 43 female patients. The median age was 40 (3, 68) years old. Patients were selected and divided into 4 groups according to the morphological FAB classification. There were 29 cases (37.7%) of M1 type, 13 cases (16.9%) of M2 type, 23 cases (29.9%) of M4 type, and 12 cases (15.5%) of M5 type. The clinical characteristics, bone marrow/peripheral blood cell morphology, immunophenotype, cytogenetics, molecular biology and overall survival of different groups were retrospectively analyzed, and the risk factors affecting the prognosis of AML were also explored. Cox multivariate regression was used to analyze the clinical influencing factors of survival and prognosis.Results:The white blood cell counts were highest in M4 and M5 patients and lowest in M2 patients, while no significant difference in the red blood cell, hemoglobin, and platelet counts( P>0.05). Morphologically, there were significant differences in the percentage of blasts and blasts with cup-like nuclei on bone marrow (BM) and peripheral blood (PB). The proportion of blasts in BM and PB was the highest in M1 and the lowest in M2 ( P<0.001). The positive rate of blasts with cup-like nuclei was the highest in M1 and the lowest in M5 of BM ( P<0.001), while the highest in M2 and the lowest in M5 of PB ( P=0.006). The scores of myeloperoxidase and chloroacetate esterase were all the highest in M1 and the lowest in M5 ( P<0.001, 0.001, respectively). In terms of molecular biology, the occurence rate of blasts combined with DNMT3A mutation was the highest in M4 and the lowest in M2 ( P=0.044), while those combined with FLT3-ITD mutation was the highest in M4 and the lowest in M5 ( P=0.002). In immunophenotype, there were significant differences in the expression positivities of seven antigens including HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO ( P<0.05). Multivariate COX regression analysis showed that no recurrence after treatment ( P<0.001), complete remission after treatment ( P=0.015) and transplantation ( P<0.001) were correlated with overall survival (OS). No recurrence after treatment ( P=0.033), transplantation ( P=0.027), no mutation of FLT3-ITD ( P=0.040), and hemoglobin concentration ( P=0.023) were associated with relapse-free survival (RFS). Survival analysis by Kaplan-Meier curve showed that there was no significant difference in survival time between the M1, M2, M4 and M5 groups in OS and RFS. Conclusion:There were significant differences in the white blood count, the percentage of blasts and blasts with cup-like nuclear morphology, cytochemical staining (MPO integration, CE integration and percentage of NAS-DCE), gene mutation (DNMT3A and FLT3-ITD) and immunophenotypes (HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO) between the four groups. The multivariate analysis revealed that no recurrence after treatment and transplantation were independent prognostic factors in NPM1 mut AML patients. On the other hand, FLT3-ITD mutation and hemoglobin concentration were associated with RFS and complete remission after treatment was associated with OS in the entire NPM1 mut cohort.

Objective:To investigate the arthroscopic temporomandibular joint disc reduction on the outcome of orthodontic patients with anterior disc displacement without reduction.Methods:From January 2012 to December 2021, forty treated orthodontic patients with anterior disc displacement without reduction (unilateral/bilateral) and no obvious articular cartilage absorption were selected from Department of Orthodontics, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine. The patients were (17.5±3.8) years old (12-25 years old), including 8 males and 32 females. Twenty patients who had completed arthroscopic temporomandibular joint disc reduction were included in the control group, and twenty patients with untreated temporomandibular joint disc were included in the experimental group. Model measurement (including overjet, etc.), cephalometric analysis (including ANB angle, which was formed by subspinale, nasion and supramental, etc.) and temporomandibular joint magnetic resonance imaging (including measurement of the condyle height of the displacement sides) were used to compare the difference of two groups. Objective grading system was used to evaluate the efficacy of orthodontic treatment.Results:The overjet of the experimental group and the control group after orthodontic treatment was (2.19±0.76) and (1.92±0.94) mm, respectively. Both two groups achieved ideal overjet with no statistical difference ( t=1.02, P=0.314). The ANB angle difference before and after treatment in the control group (-1.97°±2.87°) was greater than that in the experimental group (0.09°±1.82°), and the difference was statistically significant ( t=2.72, P=0.010). The variation of condyle height before and after treatment was (0.30±1.11) mm in the experimental group and (0.82±1.25) mm in the control group, with no statistical significance ( t=1.80, P=0.076). The post-treatment objective grading system scores of the experimental group and the control group were 21.00 (16.00, 24.00) and 21.00 (17.00, 25.00), respectively, which had no statistical difference ( U=0.24, P=0.808). Conclusions:In orthodontic patients with anterior disc displacement without reduction and no obvious articular cartilage absorption, whether displaced discs are repositioned after arthroscopic surgery has no significant effect on the orthodontic treatment outcome.