Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Flavonoid 3-O-glucosyltransferase (3GT) is a key enzyme in the glucosidation of anthocyanins. To investigate the 3GT gene in rhododendron, we cloned an open reading frame (ORF) of 3GT gene (named Rh3GT) from Rhododendron hybridum Hort (Red cultivar) and then characterized this gene and the deduced protein in terms of the biochemical characteristics, expression level, and enzymatic function. The results showed that Rh3GT had a full length of 993 bp and encoded 330 amino acid residues. The deduced protein was hydrophilic, stable, weak acid, belonging to the glycosyltransferase family (GT-B type), with glutamine (Q) at position 44 in the PSPG box. The phylogenetic analysis showed that Rh3GT was most closely related to Vc3GT from Vaccinium corymbosum and Vm3GT from Vaccinium myrtillus. Rh3GT was expressed in the stems, leaves, and flowers and almost not expressed in the roots, with the highest expression level in petals during full blooming stage. Introduction of pCAMBIAL1302-Rh3GT into petals significantly up-regulated the expression level of Rh3GT and increased the total anthocyanin accumulation. Rh3GT was successfully expressed in Escherichia coli BL21 in the form of inclusion bodies with a size of about 36 kDa. The results of HPLC showed that the recombinant Rh3GT after denaturation, purification, and dilution could catalyze the synthesis of cyanidin and UDP-glucose to synthesize cyanidin 3-O-glucoside, indicating that the expressed protein had 3GT activity. This study provides basic data for further studying the molecular regulation mechanism of anthocyanin biosynthesis and theoretical support for molecular breeding of rhododendron.
Rhododendron/classification* ; Glucosyltransferases/metabolism* ; Cloning, Molecular ; Escherichia coli/metabolism* ; Recombinant Proteins/biosynthesis* ; Anthocyanins/biosynthesis* ; Phylogeny ; Plant Proteins/metabolism* ; Amino Acid Sequence

Objective:To explore the properties of gelatin-polyethylene glycol hydrogel loaded with silver nanoparticle (AgNP) Chlorella (hereinafter referred to as the composite hydrogel) and its effects on healing of infected full-thickness skin defect wounds in mice. Methods:The research was an experimental research. The simple gelatin-polyethylene glycol hydrogel (hereinafter referred to as the simple hydrogel) and the composite hydrogel were prepared, and the appearance and injectability of the two hydrogels were observed at 55 and 37 ℃, and under the irradiation of 808 nm near-infrared light, respectively. An electronic universal testing machine was employed to assess the tensile and compressive stress-strain properties of both types of hydrogels at room temperature. Additionally, the cyclic compressive stress-strain properties of the composite hydrogel were examined at 80% of the maximum compressive stress. Staphylococcus aureus or Escherichia coli solution was added to phosphate buffer solution (PBS), simple hydrogel, and composite hydrogel, respectively. The part of composite hydrogel containing Staphylococcus aureus or Escherichia coli solution was irradiated with near-infrared light for 5 minutes. After each sample was incubated for 6 h, the dilution plating method was used to detect and calculate the mortality rates of the two bacteria at 24 h of culture ( n=5). The discarded foreskin tissue was taken from a 6-year-old healthy boy admitted to the Department of Urology of the First Affiliated Hospital of Naval Medical University for circumcision. Primary human fibroblasts (HFbs) were isolated using the enzyme extraction method, routinely cultured to the 3 rd to 6 th passages for subsequent cellular experiments. Composite hydrogel extracts with final mass concentrations of 100.0, 50.0, 25.0, 12.5, and 0 mg/mL were respectively prepared and used to culture HFbs, and the cell proliferation after 24 h of culture was detected using a cell counting kit 8 ( n=3). A total of twenty 6-8 weeks old C57BL/6J female mice were utilized, and a full-thickness skin defect was surgically created on the back of each mouse. The wounds were infected with Staphylococcus aureus solution. The infected mice were divided into blank control group, simple hydrogel group, composite hydrogel group, and combined treatment group according to the random number table, and the wounds were treated with PBS, simple hydrogel, composite hydrogel, and composite hydrogel+light irradiation (under the irradiation of 808 nm near-infrared light for 5 min), respectively, with 5 mice in each group. On post injury day (PID) 0 (immediately after the first wound treatment), 3, 7, and 14, an overall assessment of wound exudation and healing were conducted, and the wound healing rates on PID 7 and 14 were calculated ( n=5). On PID 14, hematoxylin-eosin staining was performed to observe histopathological changes in the mouse wound. Results:Both simple hydrogel and composite hydrogel were in a solution state at 55 ℃ and transition to a gel state when cooling to 37 ℃. After the two hydrogels were irradiated by near-infrared light, only the composite hydrogel reheated up and returned to the solution state again with injectability. The maximum tensile stress of the composite hydrogel was up to 301.42 kPa, with a corresponding strain of 87.19%; the maximum compressive stress was up to 413.79 kPa, with a corresponding strain of 91.67%, which was similar to the tensile and compressive properties of the simple hydrogel. After 10 compression cycles, the maximum compressive stress of the composite hydrogel still reached 84.1% of the first compressive stress. After 24 h of culture, the mortality rate of Staphylococcus aureus treated with simple hydrogel was significantly higher than that treated with PBS ( P<0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel alone were significantly higher than those treated with simple hydrogel ( P<0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel+light irradiation were significantly higher than those treated with composite hydrogel alone ( P<0.05). After 24 h of culture, compared with that cultured in composite hydrogel immersion solution with final mass concentration of 0 mg/mL, the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentrations of 25.0 and 50.0 mg/mL was significantly enhanced ( P<0.05), while the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentration of 100 mg/mL was significantly decreased ( P<0.05). On PID 0 and 3, more purulent secretions were seen in the wounds of mice in blank control group and simple hydrogel group, while only a small amount of exudate was observed in the wounds of mice in composite hydrogel group, and no obvious infection was observed in the wounds of mice in combined treatment group. On PID 7 and 14, the wound healing rates of mice in simple hydrogel group were significantly higher than those in blank control group ( P<0.05); the wound healing rates of mice in composite hydrogel group were significantly higher than those in simple hydrogel group ( P<0.05); the wound healing rates in combined treatment group were significantly higher than those in composite hydrogel group ( P<0.05). On PID 14, the wounds of mice in blank control group exhibited a high infiltration of inflammatory cells with no new epithelial layer observed; the wounds of mice in simple hydrogel group displayed a short length of newly formed epithelium with a small amount of inflammatory cells; the wounds of mice in composite hydrogel group exhibited continuous formation of new epithelium and a large amount of immature granulation tissue; the wounds of mice in combined treatment group showed continuous epithelialization with less immature granulation tissue. Conclusions:The prepared composite hydrogel exhibits excellent thermosensitivity, photothermal properties, and injectability, as well as excellent mechanical properties, antibacterial properties, and biocompatibility, and can promote the healing of infected full-thickness skin defect wounds in mice.

Objective:To observe the effect of enriched rehabilitation on dual-task gait disorder after a transient ischemic attack (TIA) and explore its mechanism.Methods:Sixty TIA patients were randomly divided into a control group and an observation group, each of 30. Another 30 healthy counterparts were selected to form a healthy control group. All of the TIA patients were given routine medication to lower blood pressure and improve brain function, while the observation group was additionally provided with enriched rehabilitation training for 12 weeks. Before and after the intervention, the gait and cognitive functioning of all of the subjects were quantified and their event-related potentials (P300s) and serum brain-derived neurotrophic factor (BDNF) levels were also measured.Results:Before the treatment there were significant differences between the TIA groups and healthy controls in all of the measurements, but there were no significant differences between the control and observation groups. After the treatment, no significant improvement was observed in any of the control group′s results, but there was significant improvement in the observation group′s gait parameters, cognitive functioning, average serum BDNF concentration and in the average latency and amplitude of its P300 signals.Conclusions:Enriched rehabilitation can improve the gait of TIA patients, perhaps through increasing their serum BDNF concentration and improving their cognition.

Objective To investigate the association between gallstones (GS) and metabolic syndrome (MS) in southern Xinjiang, China, and to provide experience for the prevention and control of metabolic diseases in southern Xinjiang. Methods The patients with GS who visited First Division Hospital, Second Division Korla Hospital, and Third Division Hospital of Xinjiang Production and Construction Corps from March 2015 to March 2019 were enrolled as case group, and cluster sampling was used to select the individuals who underwent physical examination in Third Division 51st Regiment Hospital during the same period of time were enrolled as control group. According to inclusion and exclusion criteria, 1140 cases were enrolled in each group after 1∶ 1 matching based on age and sex. The t -test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; a logistic regression analysis was used to investigate the influencing factors for GS. Dummy variables were included by logistic regression to evaluate multiplicative interaction between MS components, and the parameter estimate and covariance matrix of the logistic regression model and interaction calculation table were used to calculate and evaluate additive interaction between MS components. Results The risk of GS in MS patients was 2.33 times that in non-MS patients (odds ratio [ OR ]=2.33, 95% confidence interval [ CI ]: 1.86-2.92). In addition, the components of MS also increased the risk of GS, including blood glucose ( OR =2.94, 95% CI : 2.36-3.68), blood pressure ( OR =1.50, 95% CI : 1.26-1.80), blood lipids ( OR =1.48, 95% CI : 1.25-1.75), and body mass index ( OR =1.44, 95% CI : 1.21-1.70). After adjustment for multiple factors, the risk of GS gradually increased with the increase in the number of metabolic abnormalities, i.e., one abnormality ( OR =1.55, 95% CI : 1.22-1.99), two abnormalities ( OR =2.13, 95% CI : 1.66-2.72), three abnormalities ( OR =3.48, 95% CI : 2.59-4.69), and four abnormalities ( OR =4.65, 95% CI : 2.79-7.84). No additive or multiplicative interaction was found between MS components. Conclusion GS is closely associated with MS in southern Xinjiang, and the risk of GS gradually increases with the increase in MS components. No additive or multiplicative interaction is found between GS and MS components.

  Objective  To evaluate the clinical and paraclinical features of Chinese patients with anti- LGI1 encephalitis.  Methods  Patients with memory deficits, psychiatric symptoms, seizures or altered level of consciousness, suspicious of encephalitis, at presentation to Peking Union Medical College Hospital were recruited between July 2013 and January 2018, and tested for anti-LGI1 antibodies in their serum and/or cerebrospinal fluid(CSF) samples. Patients with anti-LGI1 antibodies were enrolled. The demographic characteristics, clinical manifestations, laboratory examination results, neuroimaging features, immunotherapy, follow-up practices and outcomes for included patients were registered and analyzed.  Results  The study enrolled 120 patients, of whom 66.7% were male. The median age was 61 years (interquartile range [IQR]: 49-66 years). Seizures(65.0%) were the most common initial symptoms. Most patients developed seizures (95.0%), including faciobrachial dystonic seizures (54.2%), memory deficits (92.5%), and psychiatric symptoms (69.1%). Brain MRI and ¹⁸F-FDG PET / CT showed that the lesions were mainly located in unilateral or bilateral medial temporal lobes, and (or) basal ganglia. Of the patients, 95.0% received intravenous immunoglobulin (IVIg) or corticosteroids, 47.5% received mycophenolate mofetil as long-term immunotherapy, and no one received second-line immunotherapy. The median follow-up was 34.2 months(IQR: 22.0-45.6 months). 91.2% had a good outcome (modified Rankin Scale score≤2 points). Residual mild memory deficits were present in 47.8% of the patients. Nine deaths were documented. Relapses occurred in 24.8% of the patients in the first year. In total, 24 (20%)cases were young patients(onset age ≤45 years).There were fewer males among the younger patients(37.5% vs. 74.0%, P < 0.01). Besides, there were fewer younger patients with psychiatric symptoms(50.0% vs. 74.0%, P=0.02), hyponatremia(33.3% vs. 68.8%, P < 0.01), and abnormalities on brain ¹⁸F-FDG PET/CT(20.8% vs. 47.9%, P=0.02). The relapse-free survival rate was significantly higher in the young patients.  Conclusions  Elderly males were predominant in patients with anti-LGI1 encephalitis. Most patients developed symptoms of limbic encephalitis and/or FDBS during the disease course. Several patients were young adults and lacked typical symptoms. Neuroimaging features were consistent with the involvement of limbic system or basal ganglia. Patients with anti-LGI1 encephalitis respond well to immunotherapy, irrespective of the age.

Objective:To characterize the digital language markers in Alzheimer′s disease (AD) and mild cognitive impairment (MCI) patients, and to explore the pathological effect and aging effect on these markers.Methods:AD ( n=14) and MCI ( n=16) patients from memory clinic in Peking Union Medical College Hospital, age-matched cognitively normal elderly adults ( n=18) and youthful adults ( n=19) as controls participated in the study. The digital speech data of animal fluency test were collected. Novel language markers such as response time, semantic similarity and word frequency were analyzed in addition to the traditional word production, clustering and switching indicators by trained professionals. Multiple linear regression analysis with multiple comparison was used to test the associations of language markers with the cognitive status, adjusting for education. Results:The results of multiple regression analysis showed that, after adjusting for the years of education, statistically significant differences existed in 11 language markers among the four groups ( P<0.001), except for the effective word production in the last 15 s, cluster size, the first word response time and the average semantic similarity. Compared to other three groups, AD group differed significantly in effective word production, effective rate, repetitive rate, effective word production in the first 15 s, the number of subcategories, single word production time and inter-subcategory switching interval ( P<0.001). In addition, compared to cognitively normal youthful group, AD group had less number of switching and shorter semantic maximum distance ( P=0.001, P<0.001); both AD and MCI groups had longer intra-subcategory switching interval ( P<0.001, P=0.001); AD, MCI and cognitively normal elderly groups had significantly higher word frequency ( P<0.001); MCI group had significantly less number of effective word production and subcategories ( P=0.002, P=0.003); both MCI and cognitively normal elderly groups had significantly longer single word production time ( P<0.001). Conclusions:The performance of AD patients on the semantic fluency test task was affected by both pathological effect and normal aging effect. Pathological indicators included effective word production, effective rate, repetition rate, effective word production in the first 15 s, the number of subcategories, inter-subcategory switching interval and single word production time. These results provide a new approach to identify the specific effects of AD dementia.

Neurosurgery navigation system, which is expensive and complicated to operate, has a low penetration rate, and is only found in some large medical institutions. In order to meet the needs of other small and medium-sized medical institutions for neurosurgical navigation systems, the scalp localization system of neurosurgery based on augmented reality (AR) theory was developed. AR technology is used to fuse virtual world images with real images. The system integrates computed tomography (CT) or magnetic resonance imaging (MRI) with the patient's head in real life to achieve the scalp positioning. This article focuses on the key points of Digital Imaging and Communications in Medicine (DICOM) standard, three-dimensional (3D) reconstruction, and AR image layer fusion in medical image visualization. This research shows that the system is suitable for a variety of mobile phones, can achieve two-dimensional (2D) image display, 3D rendering and clinical scalp positioning application, which has a certain significance for the auxiliary neurosurgical head surface positioning.
Humans ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging ; Neurosurgery ; methods ; Scalp ; Tomography, X-Ray Computed

Objective To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in antileucine-rich glioma-inactivated 1 (LGI1) encephalitis by analyzing the clinical and immunologic data of patients treated with MMF in this prospective cohort of anti-LGI1 encephalitis.Methods Patients treated with MMF for more than one year in Peking Union Medical College Hospital were included in this study.MMF was given at a dosage of 1.5-3.0 g/d in the induction period (two to four months) and 0.75-2.00 g/d in the maintenance period.All the patients were followed up regularly.Modified Rankin Scale (mRS) score evaluation,serum IgG and peripheral CD19-positive B cells,CD4-positive T cells and CD8-positive T cells testing were performed every two months.Results Fifteen patients were included in this study who received first-line immunotherapy combined with MMF.No other second-line therapy including rituximab was used.Thirteen patients responded well to MMF combined with first-line immunotherapy (a decrease in mRS score of more than 1).All 15 patients had a good outcome (i.e.,a mRS score of 0-2),including nine patients without residual symptoms (a mRS score of 0).After 12 months of MMF treatment,CD19-positive B cells were significantly decreased (median 320 (227,628) × 106/L vs 152 (105,223) × 106/L;Z=-2.028,P=0.043),while serum IgG (9.07 (6.70,11.32) g/L vs 8.35 (6.63,10.69) g/L,P=0.144)),CD4-positive T cells (1 136 (736,1 432) × 106/L vs 1 055 (802,1 072) × 106/L,P =0.866) and CD8-positive T cells (627 (413,784) × 106/L vs 568 (393,743) × 106/L,P =0.735) were not significantly changed.Three patients relapsed and were treated with additional cycle of first-line immunotherapy and increased dosage of MMF (induction dosage) resulting in remission.CD19-positive B cells were tested to be increased during the patients' relapse.No serious adverse event was noted in all these patients.Conclusions MMF is safe and effective as a long-term immunotherapy in patients with anti-LGI1 encephalitis.MMF can be used as an add-on therapy to first-line immunotherapy for autoimmune encephalitis.CD19-positive B cell count should be monitored and used as a parameter to individualize dosage of MMF.

Objective The risk of current pancreaticojejunostomy is carefully considered from the perspective of the morphology of remnant pancreas,and we aimed to discuss the clinical outcomes of selecting different pancreaticojejunostomy techniques based on pancreatic morphology.Methods This was a prospective cohort study.The histopathology of remnant pancreatic tissues was categorized into four types based on preoperative radiological images and intraoperative palpation:Type Ⅰ:pancreas with hard texture in palpation,pancreatic atrophy,dilated pancreatic duct larger than 5 mm and remnant pancreatic surface ＜3 cm;Type Ⅱ:pancreas with hard texture in palpation,pancreatic atrophy and mild dilatation of pancreatic duct with the diameter of 3-5 mm and remnant pancreatic surface ＜3 cm;Type Ⅲ:pancreas with slightly hard texture,no atrophy,and normal or slightly dilated pancreatic duct with the diameter of 3-5 mm and remnant pancreatic surface ≥3 cm;Type Ⅳ:pancreas with soft texture,normal morphology and pancreatic duct.Results From January 2008 to August 2017,116 consecutive patients underwent pancreaticoduodenectomy in our center.Among them,10 patients with type Ⅰ underwent classic pancreatic ductal mucosa to mucosa anastomosis.19 patients with type Ⅱ underwent classic end to end invaginated pancreaticojejunostomy.45 patients with type Ⅲ underwent classic end to end invaginated pancreaticojejunostomy with overlapping U sutures;42 patients with type Ⅵ underwent total invaginated pancreaticojejunostomy.The post-operative pancreatic fistula occurred in 6 patients (5.2％) with one patient died.Postoperative bleeding occurred in 10 patients (8.6％),and gastroparesis occurred in 22 patients (19.0％).Overall complication rate was 33.6％.Conclusions Classification of pancreatic morphology based on preoperative radiological images and intraoperative palpation and the selection of corresponding pancreaticojejunostomy technique is theoretically rational and has the advantage of potentially reducing the risk of remnant pancreatic tissue.