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.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective:To explore effects and mechanisms of medium and low doses X-ray irradiation on polarization type changes of tumor associated macrophages(TAMs).Methods:Mouse RAW264.7 macrophage line was cultured with supernatant of 4T1 tumor cell culture(4T1-TCS)of mouse breast cancer,and induced to M2 TAMs.On this basis,medium and low doses X-ray irra-diation was conducted,and NO was detected by Griess method,CD86 and CD206 were detected by flow cytometry.ELISA was use to detect cytokines IL-10 and IL-12p70,immunofluorescence was use to detect iNOS and Arg-1.Western blot was used to detect polariza-tion related pathway proteins,and whether medium and low doses of radiation could alter polarization type of TAMs was observed.Results:4T1-TCS induced TAM had decreasing NO secretion and increasing CD206 and Arg-1 expressions,iNOS expression was decreased;with low doses irradiation(0.075 Gy,0.5 Gy,1 Gy)of TCS-TAM,compared with non irradiation group,NO secretion,expressions of CD86,CD206,Arg-1 and iNOS showed no significant changes;medium doses(2 Gy,4 Gy,6 Gy)of irradiation on TCS-TAM resulted in increased secretion of NO,and flow cytometry results showed increased expressions of CD86,decreased CD206 expression;immunofluorescence results showed an increase in iNOS expression and a decrease in Arg-1 expression in cells;ELISA results showed an increase in secretion of IL-12p70 by cells and a decrease in secretion of IL-10.Western blot results showed that NOX2,ATMS1981*,IRF5 proteins expressions were increased.Conclusion:4T1-TCS can successfully induce macrophage RAW264.7 polarize into M2 phenotype,while low dose irradiation has no significant effect on polarization phenotype of TCS-TAM.Medium dose irradiation can induce TCS-TAM polarization into M1 phenotype that inhibits tumor growth,and reversal mechanism of polarization may be related to IRF5 pathway.

Objective:To understand the psychosomatic experience and needs of patients with lumbar cistern drainage after transnasal endoscopic sinus surgery in neurosurgery while lying in bed.Methods:Using the purposeful sampling method, one-to-on, face-to-face semi-structured interviews were conducted among 12 patients with lumbar cistern catheter drainage who were treated in Beijing Tiantan Hospital Affiliated to Capital Medical University from July to August 2020. Colaizzi phenomenology study was used to analyze the interview data, and summarized the themes.Results:The experience and needs of patients with lumbar cistern catheterization during the catheter placement were summarized into 3 themes. Obvious physical and mental discomfort: pain, discomfort of body position restriction, expectation minimization constraint scheme. Knowledge and cognitive needs: understand the reasons for intubation, intubation time and precautions. Affectionate and professional care needs: eager for professional care and more attention from medical staff, eager to be accompanied by family member to achieve greater improvement of comfort.Conclusions:Clinical nursing should be based on the patient′s psychosomatic feelings and needs, actively explore personalized intervention measures suitable for patients with lumbar cistern drainage, and formulate corresponding predictive care content to improve patients′ compliance, comfort and satisfaction.

BACKGROUND: Severe hand-foot-and-mouth disease (HFMD) is a life-threatening contagious disease among young children and infants. Although enterovirus A71 has been well acknowledged to be the dominant cause of severe HFMD, there still remain other unidentified risk factors for severe HFMD. Previous studies mainly focused on identifying the individual-level risk factors from a clinical perspective, while rare studies aimed to clarify the association between regional-level risk factors and severe HFMD, which may be more important from a public health perspective. METHODS: We retrieved the clinical HFMD counts between 2008 and 2014 from the Chinese Center for Disease Control and Prevention, which were used to calculated the case-severity rate in 143 prefectural-level cities in mainland China. For each of those 143 cities, we further obtained city-specific characteristics from the China City Statistical Yearbook (social and economic variables) and the national meteorological monitoring system (meteorological variables). A Poisson regression model was then used to estimate the associations between city-specific characteristics (reduced by the principal component analysis to avoid multicollinearity) and the case-severity rate of HFMD. The above analysis was further stratified by age and gender to examine potential modifying effects and vulnerable sub-populations. RESULTS: We found that the case-severity rate of HFMD varied dramatically between cities, ranging from 0 to 8.09%. Cities with high case-severity rates were mainly clustered in Central China. By relating the case-severity rate to city-specific characteristics, we found that both the principal component characterized by a high level of social and economic development (RR = 0.823, 95%CI 0.739, 0.916) and another that characterized by warm and humid climate (RR = 0.771, 95%CI 0.619, 0.960) were negatively associated with the case-severity rate of HFMD. These estimations were consistent across age and gender sub-populations. CONCLUSION Except for the type of infected pathogen, the case-severity rate of HFMD was closely related to city development and meteorological factor. These findings suggest that social and environmental factors may also play an important role in the progress of severe HFMD.
Adolescent ; Child ; Child, Preschool ; China/epidemiology* ; Cities/epidemiology* ; Female ; Hand, Foot and Mouth Disease/virology* ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Risk Factors

Objective:To investigate the expression changes of Hedgehog related factors (Ihh, Shh and Smo) in bone of rats with chronic fluorosis, and the significance.Methods:Thirty-six healthy SD rats were divided to three groups with the method of random digits table by body weight (100 - 120 g), 12 rats in each group, half male and half female. The rats of control were fed with tap water (NaF < 1 mg/L), and the experimental rats were exposed to NaF (low dose fluoride group: 5 mg/L, high dose fluoride group: 50 mg/L) added to the drinking water to establish the chronic fluorosis model. After the rats were raised for six months, 24-hour urine samples were collected and the femoral metaphysis of the rats was taken. Urine fluoride and bone fluoride were detected by fluorin ion selective electrode method. Bone tissues were stained with hematoxylin-eosin and observed under light microscope. The content of bone alkalinephosphatase (BALP) in rats' serum was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Ihh, Shh and Smo mRNA and protein in bone were detected by Real-time PCR and immunohistochemistry (IHC).Results:The contents of urine fluoride, bone fluoride and serum BALP were increased gradually in the control, low and high doses fluoride groups [urine fluoride: (1.37 ± 0.44), (5.96 ± 0.56), (7.60 ± 0.61) mg/L; bone fluoride: (306.04 ± 12.58), (652.91 ± 51.83), (1 094.11 ± 126.34) mg/kg; BALP: (27.78 ± 4.09), (46.59 ± 5.75), (57.45 ± 3.99) U/L, P < 0.05]. It could observed that bone sclerosis by light microscope in low and high doses fluoride groups. The expressions of Ihh, Shh and Smo mRNA in high dose fluoride group (1.39 ± 0.36, 0.56 ± 0.23, 0.40 ± 0.15) were higher than those of the control and low dose fluoride groups (0.73 ± 0.19, 0.92 ± 0.34; 0.19 ± 0.04, 0.36 ± 0.16; 0.14 ± 0.04, 0.24 ± 0.13; P < 0.05). The expression of Shh mRNA in low dose fluoride group was higher than that of the control group ( P < 0.05). The expressions of Ihh and Smo protein in high dose fluoride group (138.89 ± 3.72, 149.29 ± 7.63) were higher than those of the control and the low dose fluoride groups (127.39 ± 2.69, 134.81 ± 3.53; 129.64 ± 12.62, 139.07 ± 9.30), and the low dose fluoride group were higher than those of the control group ( P < 0.05). The expression of Shh protein in high dose fluoride group (141.26 ± 7.49) was higher than that of the control group (130.96 ± 11.10, P < 0.05). Conclusion:The expression of Hedgehog signaling pathway related factors in bone of rats with chronic fluorosis is changed, which indicates that bone formation can be affected by activation of Hedgehog signaling pathway induced by fluoride.

Objective:To explore the value of X-ray signs with applying low dose of contrast agent to confirm successful puncture in direct shoulder MR arthrography.Methods:In total 669 patients who underwent shoulder MR arthrography in Peking University Third Hospital from January 2016 to August 2018 were retrospectively analyzed. All patients received the anterior approach puncture in shoulder arthrography. X-ray films were taken after 1-2 ml contrast agent was injected. Six X-ray signs of contrast agent distribution were recorded. MR arthrography findings were used to confirm whether the puncture was success. Kappa analysis was used to verify the consistency between each 2 signs. The accuracy rate of each X-ray sign to confirm the successful puncture was calculated. X-ray signs were paired to define the best diagnostic index of successful puncture.Results:Successful puncture was performed in arthrographies for all 669 cases .The displaying rates of six signs were as follows. Contrast agent distribution at overlapping humeral head away from the needle was 66.8% (447/669), in axillary recess was 64.7% (433/669), in glenohumeral space was 93.9% (628/669), in subscapular bursa was 69.8% (467/669), in sheath of long head tendon of biceps brachii (LHBT) was 1.9% (13/669), between LHBT and supraspinatus tendon was 17.2% (115/669). Consistency of each 2 signs was poor (Kappa<0.2), in which the poorest consistency was found between contrast agent overlapping humeral head away from the needle and contrast agent in glenohumeral space (Kappa=-0.115). With combining the above 2 signs, the accuracy rate for defining successful puncture was 100% (669/669).Conclusion:In direct shoulder arthrography by anterior approach, X-ray signs with low dose of contrast agent can be regard as the method to confirm successful puncture. The accuracy rate of the signs of contrast agent distribution at overlapping humeral head away from the needle or in glenohumeral space to define a successful puncture is 100%.

Abstract During the yellow fever epidemic in Angola in 2016, cases of yellow fever were reported in China for the first time. The 11 cases, all Chinese nationals returning from Angola, were identified in March and April 2016, one to two weeks after the peak of the Angolan epidemic. One patient died; the other 10 cases recovered after treatment. This paper reviews the epidemiological characteristics of the 11 yellow fever cases imported into China. It examines case detection and disease control and surveillance, and presents recommendations for further action to prevent additional importation of yellow fever into China.

Major hepatectomy (MH) is a common treatment for benign and malignant liver diseases. Controlled low central venous pressure (CLCVP) is an important measure to reduce the intraoperative blood loss and transfusion requirement during MH. In this paper, the application standard of CLCVP at MH is discussed, and the specific measures to achieve CLCVP including fluid restriction, drug application, body gesture adjustment, reduction of tidal volume, suspension of respiratory ventilation, and infrahepatic inferior vena cava clamping (complete and partial) are systematically summarized.

Objective: To investigate the change and association of glioma-associated oncogene homolog 1 (Gli1) and β-catenin on bone formation in rats with chronic fluorosis which were inhibited by cyclopamine (Cycl). Methods: Forty-eight Sprague-Dawley rats were evenly divided to four groups, including control, F, F+Cycl and F+DMSO groups. The control group were fed with tap water (NaF<1 ppm). The F, F+Cycl and F+DMSO groups were exposed to NaF (50 ppm) in drinking water as the chronic fluorosis model. Then the rats in F+Cycl or F+DMSO groups were injected by Cycl or DMSO after 6 months, respectively. Urine fluoride concentration was detected using fluorine ion selective electrode. The enzyme-linked immunosorbent assay (ELISA) was used to detect bone alkaline phosphatase (BALP). Bone tissues were stained with hematoxylin-eosin. The mRNA and protein expression of Gli1 and β-catenin in bone tissue were detected using real-time PCR, immunohistochemistry and Western blot. Results: Compared with the controls, the urine fluoride concentration and the width and volume of bone trabeculae were increased in the F, F+Cycl and F+DMSO groups, but no statistical difference among the 3 fluorosis groups. The concentration of BALP was increased in the F group and decreased in F+Cycl group (P<0.05). The expression of Gli1 and β-catenin mRNA and protein was higher in the F and F+Cycl groups than controls, but lower in the F+Cycl group than in the F group. There was positive correlation between the expression of Gli1 and β-catenin (r=0.476, P<0.05). The expression of Gli1 and β-catenin was also associated with BALP concentration and volume of bone trabeculae, respectively (r₁=0.457, r₂=0.466, r₃=0.581, r₄=0.554, respectively, P<0.05 for all). Conclusions The expression of Gli1 can be inhibited by Cycl. It may be involved in the bone formation of rats with chronic fluorosis. It may also affect the expression of β-catenin, which is an osteogenesis factor.