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.

The essence of clinical practice guidelines lies in their recommendations. It is common to find strong recommendations supported by low-quality evidence in current published guidelines. There is a typical misunderstanding among medical professionals that without high-quality evidence, it is impossible to develop high-quality guidelines or only expert consensus can be developed. Based on the GRADE approach, this paper explains the concept and clinical significance of low-quality evidence, and introduces the methods for formulating recommendations based on low-quality evidence in guidelines, with the aim to provide reference for guideline developers and users in China.

Objective:To investigate the effect and the neural mechanisms of Apelin-13 on the behavior changes of posttraumatic stress disorder (PTSD) model mice.Methods:Totally 32 SPF grade male C57BL/6J mice aged 6 weeks were divided into 4 groups randomly ( n=8 in each group): control group, model group, normal saline group and Apelin-13 group.The mice model of PTSD was established by single-prolonged stress (SPS) method. The mice in normal saline group and Apelin-13 group were respectively given lateral ventricular microinjection of 0.9% sodium chloride solution (2 μL) and Apelin-13 (1.5 μg/μL, 2 μL)after PTSD modeling. The behaviors of mice were evaluated by open field test, elevated plus maze test and Morris water maze test.The morphological structure and numerical changes of hippocampal neurons were observed by hematoxylin and eosin (HE) staining.The expression of phosphoinositide 3-kinase(PI3K), phosphorylated-PI3K(p-PI3K), protein kinase B(Akt), phosphorylated-Akt (p-Akt), forkhead box O3a (FoxO3a), phosphorylated-FoxO3a(p-FoxO3a), autophagy-related proteins including microtubule-associated protein 1 light chain 3(LC3) and sequestosome 1(p62) were detected by Western blot. SPSS 26.0 software was used for data analysis.The escape latency data of repeated learning training in Morris water maze was conducted by repetitive measurement ANOVA.The comparison of other data among multiple groups was conducted by one-way ANOVA and further pairwise comparisons were conducted by LSD test and Tamhane test. Result:(1) Open field test results showed statistically significant differences in the central area activity distance and residence time in central area among mice in the four groups ( F=15.37, 9.63, both P<0.05). The central area activity distance ((0.06±0.03) m) and residence time ((2.48±1.02) s) of the mice in model group were lower than those of the control group ((0.19±0.05) m, (15.00±8.91) s)(both P<0.05). And the central area activity distance((0.12±0.04)m)and the residence time((13.56±7.64)s)were higher than those of model group((0.06±0.03)m, (2.48±1.02)s)and normal saline group((0.06±0.02)m, (2.82±1.52)s)(all P<0.05). Elevated plus maze test results showed statistically significant differences in the numbers and time entering open arms among the four groups ( F=10.74, 19.12, both P<0.05). The numbers((4.50±2.51) times) and the time ((26.95±17.48) s) entering the open arm of mice in model group were both lower than those of the control group ((13.75±4.71) times, (103.75±42.43)s) and Apelin-13 group ((10.00±5.18) times, (55.98±19.49) s) (all P<0.05). Morris water maze test results showed that in the 4-day learning and training phase, the time and group interaction of escape latency was not significant among the four groups ( F=1.15, P=0.34), but time main effect and group main effect were significant ( F=131.65, 16.98, both P<0.05). On the 2nd to 4th day, mice in model group showed significantly increased escape latency than mice in control group and Apelin-13 group(both P<0.05). And the numbers crossing original platform and the time in the target quadrant of Apelin-13 group were both higher than those of model group and normal saline group (all P<0.05). (2) HE staining results showed that neurons in the hippocampal CA1 and CA3 area of mice in model group and normal saline group were swollen and arranged loosely.The hippocampal neurons in control group and Apelin-13 group were arranged neatly and densely. (3) Western blot results showed statistically significant differences in the protein expression of p-PI3K, p-Akt, p-FoxO3a, p62 and the ratio of LC3Ⅱ/LC3Ⅰ among the four groups ( F=21.37, 37.35, 20.71, 13.26, 37.65, all P<0.05). The protein expression of p-PI3K, p-Akt, p-FoxO3a and p62 in Apelin-13 group((0.92±0.07), (0.90±0.09), (0.89±0.13), (1.03±0.08)) were higher than those in model group((0.59±0.04), (0.50±0.07), (0.49±0.11), (0.68±0.04)) and normal saline group((0.61±0.06), (0.50±0.08), (0.53±0.11), (0.70±0.05))(all P<0.05), and the ratio of LC3Ⅱ/LC3Ⅰ in Apelin-13 group(0.60±0.06) was lower than those in model group(0.92±0.10) and normal saline group(0.99±0.05) (both P<0.05). Conclusion:Apelin-13 can alleviate the anxiety-like behavior and impaired spatial learning and memory in PTSD model mice. The mechanism may be related to the up-regulation of PI3K/Akt/FoxO3a autophagy pathway.

Traditional Chinese Medicine (TCM) has its own unique features in the treatment of post-stroke depression (PSD). The kidney is the congenital foundation and is closely related to the brain. Kidney deficiency runs through the entire course of stroke. Liver regulates the normal operation of qi in the human body, which is closely related to depression syndrome. Kidney deficiency and liver depression affect each other. The treatment of PSD with the Bushen Shugan (tonifying the kidney and soothing the liver) method has achieved good efficacy in clinic. The method of tonifying kidney and soothing liver can not only reflect the holistic view of TCM and the association of viscera, but also coordinate the relationship between body and spirit. In the future, the development direction of PSD in TCM research should be to further strengthen the concept of co-regulation of body and spirit and integration of brain and viscera.

BACKGROUND: Amygdala plays an important role in the neurobiological basis of panic disorder (PD), and the amygdala contains different subregions, which may play different roles in PD. The aim of the present study was to examine whether there are common or distinct patterns of functional connectivity of the amygdala subregions in PD using resting-state functional magnetic resonance imaging and to explore the relationship between the abnormal spontaneous functional connectivity patterns of the regions of interest (ROIs) and the clinical symptoms of PD patients. METHODS: Fifty-three drug-naïve, non-comorbid PD patients and 70 healthy controls (HCs) were recruited. Seed-based resting-state functional connectivity (rsFC) analyses were conducted using the bilateral amygdalae and its subregions as the ROI seed. Two samples t test was performed for the seed-based Fisher's z -transformed correlation maps. The relationship between the abnormal spontaneous functional connectivity patterns of the ROIs and the clinical symptoms of PD patients was investigated by Pearson correlation analysis. RESULTS: PD patients showed increased rsFC of the bilateral amygdalae and almost all the amygdala subregions with the precuneus/posterior cingulate gyrus compared with the HC group (left amygdala [lAMY]: t  = 4.84, P  <0.001; right amygdala [rAMY]: t  = 4.55, P  <0.001; left centromedial amygdala [lCMA]: t  = 3.87, P  <0.001; right centromedial amygdala [rCMA]: t  = 3.82, P  = 0.002; left laterobasal amygdala [lBLA]: t  = 4.33, P  <0.001; right laterobasal amygdala [rBLA]: t  = 4.97, P  <0.001; left superficial amygdala [lSFA]: t  = 3.26, P  = 0.006). The rsFC of the lBLA with the left angular gyrus/inferior parietal lobule remarkably increased in the PD group ( t  = 3.70, P  = 0.003). And most of the altered rsFCs were located in the default mode network (DMN). A significant positive correlation was observed between the severity of anxiety and the rsFC between the lSFA and the left precuneus in PD patients ( r  = 0.285, P  = 0.039). CONCLUSIONS Our research suggested that the increased rsFC of amygdala subregions with DMN plays an important role in the pathogenesis of PD. Future studies may further explore whether the rsFC of amygdala subregions, especially with the regions in DMN, can be used as a biological marker of PD.
Humans ; Panic Disorder ; Magnetic Resonance Imaging/methods* ; Amygdala ; Gyrus Cinguli ; Comorbidity

Meige syndrome is one of the rare Diseases of neurology. It is a part of the group of segmental cranial dystonia, which affects more than two cranial muscle groups. Especially, blepharospasm is associated with another cranial dystonia. Currently, the etiology and pathogenesis of this disorder are not well-understood. Based on the theory of collaterals and the relationship between collateral disease and five zang organs,we try to classify the disease into the category of collateral disease, and hold that the mechasnism of disease is not only linked to brain, but also the five zang organs. The disorder of qi and blood leads to the "deficiency of qi and blood", "phlegm-damp" and "stagnant blood" in collateral. These pathological changes cause the deficiency of both qi and blood in brain marrow and tendon.We think that "unblocking and regulating the collterals"is the general program. Adjusting the five zang organs to heel the brain is the key point of the treatment. What's more, we create Tongmai Heluo Decoction to regulate qi and blood of the collateral. This decoction is composed of Huangqi Jianzhong Decoction with some herbal medicine for tonifying qi and activating blood. By adjusting the middle energizer, the qi and the qi movement of five zang organs are well regulated. We use this decoction effectively on refractory Meige syndrome.

Objective To investigate the risk factors of postoperative vitreous hemorrhage after minimal vitrectomy without endotamponade for proliferative diabetic retinopathy (PDR).Methods From June 2015 to June 2017,103 eyes of 103 patients with PDR diagnosed and underwent minimalvitrectomy in Henan Provincial People's Hospital were enrolled in the study.There were 58 males and 45 females,with the average age of 58.37± 10.14 years and diabetes duration of 8.7± 7.2 years.Baseline systemic parameters including sex,age,diabetes duration,hypertension,HbA1c,creatinine,whether received anticoagulants,ocular parameters including whether combined with vitreous hemorrhage,whether finished panretinal photocoagulation (PRP),whether received treatment of anti-VEGF,whether combined with iris neovascularization (NVI),lens status preoperatively,whether hypotony postoperatively and intraoperative parameters including whether disc neovascularization (NVD) bleeding,whether fibrovascular membrane (FVM) residual,laser points,whether combined with cataract phacoemulsification were identified by multivariate logistic regression analysis.Results Twenty-nine of 103 eyes (28.15％) developed PVH in 1 day to 6 months after surgery,with self absorption of 18 eyes and reoperation of 11 eyes.Univariate analysis showed there were significant differences in age (t=2.124,P=0.036),anti-VEGF(x2=7.105,P=0.008),NVD bleeding (x2=10.158,P=0.001) and FVM residual(x2=8.445,P=0.004) between patients with and without postoperative vitreous hemorrhage.Sex (x2=0.021,P=0.884),diabetes duration (t=0.87,P=0.386),hypertension (x2=2.004,P=0.157),HbA1c (t=1.211,P=0.229),creatinine (t=0.851,P=0.397),preoperative oral anticoagulants (x2=0.985,P=0.321),preoperative vitreous hemorrhage (x2=0.369,P=0.544),PRP (X2=1.122,P=0.727),NVI (x2=2.635,P=0.105),lens status (x2=0.172,P=0.679),hypotony postoperatively (x2=1.503,P=0.220),laser points (x2=1.391,P=0.238) and combined phacoemulsification surgery (x2=0.458,P=0.499) were not associated with PVH.Multivariate logistic regression analysis revealed the more PVH appeared in younger (OR=1.065,P=0.009) and NVD bleeding (OR=6.048,P=0.001) patients.Conclusion Younger age and NVD bleeding are the important risk factors for PVH after minimal vitrectomy without endotamponade in PDR.

Objective To investigate the effect of KRAS gene mutation and clinical factors on postopera-tive prognosis of rectal cancer patients and to explore their value in prognosis. Methods A total of 130 cases of rectal cancer patients from January to December 2010 were collected in the study. The tumor tissues sample was used to detect the KRAS gene mutation and 5-year follow-up was conducted. The correlation between KRAS gene mutation and clinical pathological features was analyzed.The clinic pathological factors that may affect the progno-sis were analyzed by survival analysis. Results Forty-five patients had mutations in No.2 expressed region of KRAS,with a mutation rate of 34.6%.KRAS gene mutation and stronger positive expression of EGFR(P<0.05), and multiple metastasis of tumor(P<0.05)were strongly coupled.The average survival of patients with wild-type KRAS gene was 57.5 months and that of patients with KRAS gene mutation 58.9 months but no significant differ-ence was observed(P>0.05).The TNM by high staging,multiple metastasis,lung metastasis and liver metasta-sis of cancer cells was closely related with poor postoperative prognosis of patients(P<0.05).The average surviv-al of postoperative patients in stage Ⅳ was 49months. Conclusions KRAS gene mutation in patients with rectal cancer after surgery is related with stronger positive expression of EGFR and multiple metastasis of cancer.TNM by high staging and metastatic sites affects the prognosis. The survival of rectal cancer after surgery in patients with stage Ⅳ are prolonged but the relation between KRAS genovariation and patients′ postoperative prognosis can not be determined.

Objective To observe the occurrence and evolution of persistent submacular fluid (SMF) after scleral buckling surgery (SB) in rhegmatogenous retinal detachment,and then to study the related factors of persistent SMF and the effect of persistent SMF on visual outcome.Methods Ninety eyes of 89 patients with rhegmatogenous retinal detachment which had been performed SB were included in this study.Best corrected visual acuity (BCVA),intraocular pressure,slit-lamp microscopy,three mirror contact lens,indirect ophthalmoscopy and B-scan ultrasonography were measured for all patients.There were 21 eyes with atrophic holes while 42 eyes with horse-shoe tears,22 eyes with old retinal detachment while 68 new suffered eyes.Thirty-two eyes underwent scleral encircling surgery (SE) and 58 eyes underwent segmental scleral buckling surgery (SSB).The patients were divided into SMF group and non-SMF (NSMF) group according to the results of optical coherence tomography (OCT) at 1 month postoperatively.Thorough ophthalmologic examinations were performd at 1,3,6 and 12 months after surgery to the patients,further observations were continued to carry out unless the abnormality had resolved for at least 6 months.Results Patients who underwent SE (20 eyes,62.5 ％) had a higher incidence of persistent SMF at 1 month after surgery than those who underwent SSB (23 eyes,39.7 ％),the difference was significant (x2 =5.024,P＜ 0.05).Persistent SMF was more frequent in eyes with atrophic holes (66.7％) than that with horseshoe tears (38.1％),the difference was significant (x2 =4.582,P＜0.05).Persistent SMF was found in 72.7％ old retinal detachment eyes and in 39.7％ new suffered eyes,showed a striking differences (x2=7.264,P＜0.01).There was no significant difference in BCVA among SE and SSB groups at every time point (t=0.659,0.699,1.108,1.037,1.902; P＞0.05).The SMF group have a similar BCVA with NSMF group 1 and 3 months after surgery (t=1.812,1.957; P＞0.05),whereas the SMF group showed worse BCVA than NSMF group from since 6 months after surgery (t=2.324,2.147,2.184; P＜0.05).Conclusions Persistent SMF is more frequent after SE than SSB,the type of retinal breaks and old retinal detachment may be the potential influencing factors.Persistent SMF after SB may affect the final visual outcome.

BACKGROUND:Stem cells have been shown to not only replace damaged cells, but also secrete trophic factors, bringing a bright future for the treatment of clinical spinal cord injury.
OBJECTIVE:To review the latest advances of bone marrow mesenchymal stem cells in animal and clinical research.
METHODS:A computer-based search of Kjmed and Wanfang databases was done for relevant articles published from April 2004 to April 2014 using the keywords of“stem cells, spinal cord injuries, embryonic stem cells, neural stem cells, mesenchymal stem cells”in English and Chinese, respectively.
RESULTS AND CONCLUSION:Total y 2 745 articles were initial y retrieved, and only 50 articles were included in result analysis. Bone marrow mesenchymal stem cells have become one of the most promising sources of stem cells in the treatment of spinal cord injury. Although the bone marrow mesenchymal stem cellin the treatment of spinal cord injury is stil in its infancy, it has certain effects on the repair of spinal cord injury. The mechanism of action of bone
marrow mesenchymal stem cells in the treatment of spinal cord injury is possibly related to the substitution effect, neurotrophic effects, suppression of the immune response and promoting axonal regeneration.