Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

【Objective】 To investigate the development of adaptability in children aged 2 - 6, and to explore its influencing factors, so as to provide reference for promoting the development of adaptability in young children. 【Methods】 Data were from the National Nutrition and Health Systematic Survey for Children in China, and 3 319 children aged 2 - 6 and their parents from 28 sites across 14 provinces were recruited in this study.The Development Scale for Children Aged 0 - 6 years (WS/T 580-2017) was used to measure the developmental quotient of children′s adaptive ability, and a survey questionnaire was used to collect relevant information about children and their parents. 【Results】 Among 3 319 children aged 2 - 6, the proportion of slightly low or low level of adaptability, moderate adaptability development, good and excellent adaptability development was 7.68%,66.25% and 26.06%, respectively.The proportion of children aged 5 - 6 with good and excellent adaptability was lower in 3-year-old and 4-year-old groups (χ²=59.29, P<0.05).Multiple stepwise linear regression showed that children′s gender (β=0.06), gestational age of birth (β=-0.05), only child (β=-0.04), left-behind child (β=-0.04), the main caregiver (β=-0.06), and the education level of parents (β=0.09, 0.10), whether parents actively pay attention to children′s emotions (β=-0.06) and whether children play with homemade toys (β=-0.04) were the influencing factors of children′s adaptive development quotient.Girls, full-term children, only children, non-left-behind children, children with parents as main caregivers, parents with a high level of education, parents who often take the initiative to pay attention to children′s emotions, and children who play with homemade toys had a higher level of adaptability development quotient. 【Conclusions】 The development level of adaptability in children aged 2 - 6 in China is mostly above the average level and is related to multiple factors.Targeted intervention work can be carried out on relevant factors in order to promote the development of children′s adaptability.

Allogeneic hematopoietic stem cell transplantation is an effective method for treating various hematological diseases. Membranous nephropathy is the second leading cause of novo glomerular disease after transplantation. Protocadherin FAT1 is a target antigen for diagnosing membranous nephropathy, primarily related to hematopoietic stem cell transplantation. Here we report a rare case of membranous nephropathy after hematopoietic stem cell transplantation. The target antigen of membranous nephropathy was confirmed to be FAT1 by pathology combined with mass spectrometry analysis. The nephrotic syndrome achieved partial remission after corticosteroid combined with cyclosporine treatment, and the patient's condition was stable during follow-up.

Objective:To study the epidemiological and clinical characteristics of brucellosis in Xinjiang Uygur Autonomous Region.Methods:A retrospective analysis method was used to collect medical records of 581 patients with brucellosis who visited the Xinjiang Uygur Autonomous Regional People's Hospital from January 2009 to December 2019. Demographic and epidemiological characteristics, clinical symptoms and signs, and laboratory test results of the patients were analyzed.Results:Among 581 patients with brucellosis, the male to female ratio was 2.8 ∶ 1.0 (428 ∶ 153). The age was (44.41 ± 16.25) years old, ranging from 1 - 83 years old, and mainly concentrated in 35 - 60 years old, accounting for 70.91% (412/581). The ethnic distribution was dominated by Uyghur, accounting for 50.60% (294/581). The occupational distribution was mainly farmers, accounting for 43.20% (251/581). A total of 186 patients had a clear history of contact with cattle and sheep, accounting for 32.01% (186/581). The clinical stage was dominated by patients in the acute stage, accounting for 55.25% (321/581). There were 48 cases of complications, accounting for 8.26%(48/581). The main clinical symptom of brucellosis patients was pain and fever, accounting for 73.67% (428/581) and 66.61% (387/581), respectively. Laboratory tests were dominated by increased blood sedimentation and C-reactive protein, accounting for 29.09% (169/581) and 23.06% (134/581), respectively. The positive rate of Brucella culture was low, accounting for 4.48% (26/581). Conclusions:The majority of brucellosis patients in Xinjiang Uygur Autonomous Region are young and middle-aged males, with the main occupation being farmers. The clinical symptoms are mostly pain and fever. The positive rate of Brucella culture in patients is relatively low. It is recommended to combine epidemiological and clinical features for diagnosis to reduce missed diagnosis and misdiagnosis, and detect and treat it early.

Objective To evaluate the clinical value of neutrophil CD64(nCD64)index as a novel biomark-er in the differential diagnosis of acute and chronic brucellosis.Methods A total of 38 patients with acute bru-cellosis and 48 patients with chronic brucellosis diagnosed in the People's Hospital of Xinjiang Uygur Autono-mous Region from February 2021 to July 2023 were included.Peripheral blood of the patients was collected and nCD64 index was detected by flow cytometry,and the correlation between nCD64 index and disease severi-ty was analyzed.Receiver operating characteristic(ROC)curve was used to analyze the sensitivity and the specificity of nCD64 index in differentially diagnosing acute and chronic brucellosis.Meanwhile,Rose-Bengal Plate Test(RBPT)and Standard Tube Agglutination Test(SAT)were used as controls to evaluate the clini-cal diagnostic value of the three.Results The nCD64 index of acute brucellosis patients was higher than that of chronic brucellosis patients(U=216.00,P<0.001),and the index was positively correlated with the sever-ity of the disease(r=0.670,P<0.001).The ROC curve analysis results showed that the area under the curve of nCD64 index in the differential diagnosis of acute and chronic brucellosis was 0.882(95%CI:0.811-0.952,P<0.001),the cut-off value was 2.81,and sensitivity,specificity,positive predictive value,negative predictive value and accuracy were 83.3%,81.6%,80.4%,81.9%and 82.6%,respectively.The efficacy of nCD64 index in differential diagnosis of nCD64 index was significantly better than those of the qualitative tests of RBPT and SAT.Conclusion nCD64 index has favourable sensitivity and specificity in the differential diag-nosis of acute and chronic brucellosis,and tends to reflect the severity of the disease.It has clinical value in the differential diagnosis of acute brucellosis and chronic brucellosis,and plays an important role in the early diag-nosis and treatment effect monitoring of brucellosis.

Objective To investigate the characteristics of changes in interleukin(IL)-33 and regulatory T(Treg)cells in brucellosis,to verify the regulatory effect of IL-33 on Treg cells,so as to clarify the immune mechanism of IL-33 on Treg cells in brucellosis.Methods The peripheral blood of 39 patients with brucellosis treated in the People's Hospital of Xinjiang Uygur Autonomous Region from January to December 2021(the brucellosis group)and 42 healthy controls(the healthy control group)who underwent physical examination during the same period were collected.The serum IL-33 level was detected by AimPlex kit,and the proportion of Treg cells was detected by flow cytometry.Peripheral blood mononuclear cell(PBMC)was extracted and cultured in vitro to observe the proportion and mRNA expression levels of forkhead box protein P3(Foxp3)after stimulation and blocking of IL-33.Results Compared with the healthy control group,the level of IL-33 and the proportion of Treg cells in brucellosis group were significantly increased,with statistical significance(P＜0.05).In vitro tests showed that the Foxp3 proportion and mRNA expression level of PBMC in the two groups were significantly increased after IL-33 stimulation,and significantly decreased after IL-33 blocking,with statistical significance(P＜0.001).Conclusion IL-33 and Treg cells increased significantly in brucellosis patients,and IL-33 promoted the immune function of Treg cells.Blocking IL-33 is expected to be a potential target for immunotherapy of brucellosis.

Objective To observe the effect of Danshen injection (DSI) on pulmonary fibrosis in silicosis mice, and to analyze the differential metabolic pathway on pulmonary fibrosis in silicosis using DSI by urine metabolomics. Methods The specific pathogen free C57BL/6J mice were randomly divided into control group, silicosis model group, DSI prevention group and DSI treatment group. The mice in the last three groups were given 1 mL silica suspension with a mass concentration of 50 g/L by the one-time non-exposed tracheal method, and the mice in the control group were not given any treatment. Subsequently, mice in the DSI prevention group and the DSI treatment group were given intraperitoneal injection of DSI with a dose of 5 mL/kg body weight from 24 hours after exposure to dust and from the 29th day after exposure to dust, respectively, once per day until the 56th day after exposure. Mice in the other two groups were not treated. After DSI intervention, the lung histopathological changes of mice in all groups were evaluated. The components of mouse urine metabolites were analyzed using ultra-high performance liquid chromatography-quadrupole-time-of-fight mass spectrometry method. Human Metabolome Database was used to screen the potential differential metabolites (DMs). The related metabolic pathways were analyzed using MetaboAnanlyst 5.0 Web analytics platform. Results The result of hematoxylin-eosin staining and Van Gieson staining of mouse lung tissues showed that the pulmonary alveolar structure destroyed, typical fibrotic nodules appeared, collagen fiber deposition increased, and clumpy accumulation in the silicosis model group, compared with the control group. Compared with the silicosis model group, the degree of pulmonary alveolar inflammation and fibrosis in the lung tissues of mice in the DSI prevention group was obviously reduced to close to the control group, while pulmonary alveolar inflammation and fibrosis in the lung tissues of mice in the DSI treatment group were also reduced, although the outcome was not as good as that in the DSI prevention group. The result of urine metabolomics analysis identified four DMs in the model group and control group, seven DMs were identified in the DSI prevention group and silicosis model group, seven DMs were identified in the DSI treatment group and silicosis model group. A total of three DMs pathways related to pulmonary fibrosis in silicosis model group and the protective effect of DSI prevention group were identified, including D-arginine and D-ornithine metabolism, folic acid biosynthesis and metabolism, pantothenate and succinyl coenzyme A biosynthesis pathways (all P<0.01). Conclusion DSI treatment in any time point can interfere the process of pulmonary fibrosis in the silicosis mice, while the interference is more effective in the DSI group treated right after dust-exposure. DSI interferes with the urinary metabolism pathway of silicosis mice, and the D-arginine and D-ornithine metabolism, folic acid biosynthesis and metabolism, pantothenate and succinyl coenzyme A biosynthesis pathways may participate in the inhibiting process of early pulmonary fibrosis in silicosis mice by DSI.

Objective To understand the characteristics of long-working hours exposure of medical staff,and analyze the impact of long-working hours exposure on mental health problems such as occupational stress,depression,fatigue accumulation,and insomnia.Methods The cluster random sampling method was used to select the medical staff of 12 tertiary general hospitals in Guangdong Province as the research subjects,and the"Core Scale of Occupational Stress Measurement"and other scales were used to evaluate their occupational mental health.Results The average working hours of medical staff per day were(8.99±2.18)h;2,094 people were exposed during long working hours,accounting for 78.96%.The results of binary logistics regression analysis showed that after excluding the influence of sociodemographic factors such as age,long working hours(weekly working hours greater than 40 h)were the risk factors for occupational stress,depressive symptoms and fatigue accumulation of medical staff(P<0.01),and the longer the working week,the higher the risk of occupational stress,depressive symptoms and fatigue accumulation.Weekly working hours greater than 48 hours are risk factors for insomnia(P<0.01).Conclusion Long working hours are common among delivery workers on food delivery platforms,and long working hours are a risk factor for occupational tension and fatigue.

Objective:To explore the effects of foraging exercise (FE) on depressive-like behaviors and expression of transforming growth factor-β1 (TGF-β1) in hippocampus of rats with ischemic stroke after chronic stress.Methods:The right middle cerebral artery occlusion (MCAO) model was used in 30 male adult clean grade SD rats by suture method.According to the body weight, rats were evenly divided into stroke group ( n=10) and chronic unpredictable mild stimulation (CUMS) group ( n=20). Rats of CUMS group received stress induction 1 week after operation and lasted for 3 weeks. Then, according to random number generator of SPSS 24.0 software, the depression rats were divided into post-stroke depression (PSD) group( n=10) and FE groups ( n=10). The FE group received free FE intervention for 4 weeks. Body weight, water maze test, novelty inhibition feeding test (NSFT) and sucrose preference test (SPT) were performed at the end of the 1st, 4th and 8th week, respectively. The expression of TGF-β1 in hippocampus was detected by Immunohistochemistry (IHC) and Western blot (WB), and the levels of TGF-β1 and TNF-α in serum were detected by ELISA. SPSS 24.0 software was used for statistical analysis. The behavioral data were compared by two factor repeated measurement analysis of variance. One way ANOVA was used for comparison among groups, and LSD test was used for further pairwise comparison. Results:(1) The interaction between group and time had statistical significance on body weight, latency and food intake of NSFT and sucrose preference index(SPI) ( F=2.936-12.098, all P<0.05). After 4 weeks, compared with the stroke group((343.80±19.34)g, (12.10±6.97)s, (0.75±0.09)%), the body weight((307.80±17.23)g, (305.30±24.39)g), and SPI((0.52±0.06)%, (0.53±0.07)%) of PSD group and FE group were lower and the NSFT latency((21.70±7.02)s, (22.40±0.84)s) was longer (all P<0.05). After 8 weeks, SPI in FE group was higher than that in PSD group ( P=0.045). There were significant differences in body weight of three groups, NSFT latency and SPI of PSD group and FE group, and food intake of stroke and FE group ( F=8.478-196.548, all P<0.05). There was no interaction between group and time in the water maze test. Main effect of time ( P=0.034) and main effect of group ( P<0.01) had statistical significance on escape latency. The escape latency after 4 weeks was longer than that after 1 week ( P=0.003). The latency of PSD group was longer than that of stroke group ( P=0.005), and latency of FE group was shorter than that of the PSD group ( P<0.01). The main effect of group had statistical significance in the number of crossing quadrant ( P<0.01). The number of crossing quadrant of FE group was less than that of PSD group ( P<0.01). (2) Immunohistoche mistry staining showed that compared with the stroke group, the expression of TGF-β1 was down-regulated in 3 areas of hippocampus of PSD group (CA1, CA3 and DG) ( t=5.449-9.353, all P<0.01). Compared with stroke group, the expression of TGF-β1 of CA1 ( t=7.433, P<0.01) in FE group was down-regulated, but was up-regulated in CA3 ( t=3.342, P<0.05) of FE group. Compared with the PSD group, the expression of TGF-β1 was up-regulated in CA3 and DG of FE group ( t=7.811, 8.790, both P<0.01). (3) Western blot results: Compared with stroke group, the expression of TGF-β1 in hippocampus of PSD group was down-regulated ( t=3.255, P<0.01). Compared with the PSD group, the expression of TGF-β1 in hippocampus of FE group was up-regulated ( t=2.906, P<0.05). (4) ELISA detection showed that compared with the stroke group, the levels of TGF-β1 decreased ( t=2.224, P<0.05), but TNF-α increased ( t=6.127, P<0.01) in PSD group.Compared with the PSD group, the expression of TGF-β1 in FE group increased significantly ( t=4.417, P<0.01). Conclusion:Foraging exercise can improve the depressive behavior symptoms of ischemic stroke rats after chronic stress, and its mechanism may be related to the increasing expression of TGF-β1, which can alleviate the inflammatory reaction in hippocampus.

Background/Aims: Older adults are vulnerable to central obesity, while the association of changes in central fatness with risk of diabetes and metabolic control has not been investigated among this particular population. This study was aimed to address these issues. Methods: A total of 1,815 adults aged ≥ 60 years without diabetes at baseline were followed for 4 years. Incident diabetes was ascertained based on plasma glucose, hemoglobin A1c, medical history, and/or the use of anti-diabetic drugs. Central fatness was assessed by waist circumference (WC), waist-height ratio (WHtR), and body roundness index (BRI). Logistic regression analyses were used to assess the association of changes in central fatness with risk of diabetes, along with dose-response and mediation analyses. Results: During the 4-year follow-up, 177 participants developed diabetes. The risk of diabetes was increased by 42%, 41%, and 40% per 1 standard deviation increases in WC, WHtR, and BRI, respectively, in multivariable-adjusted models (all p < 0.01). Moreover, these relationships were all linearly-shaped (all pnonlinearity ≥ 0.11). Increases in WC, WHtR, and BRI correlated with increases in hemoglobin A1c, triglycerides-and-glucose index, triglycerides, white blood cell, and C-reactive protein (all p ≤ 0.04). Yet only changes in hemoglobin A1c and triglycerides-and-glucose index were identified as the possible mediators for risk of diabetes, with their mediating effect being about 35% and 21%, respectively. Conclusions Increases in central fatness were related to elevated risk of diabetes, and this association might be partly explained by the worsening of glycemic control and insulin resistance in older adults.