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.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective To evaluate the surgical treatments of refractory sclerosing peritonitis related peritoneal dialysis.Methods Clinical data of 15 patients with refractory sclerosing peritonitis related to peritoneal dialysis treated in the General Surgery Department of the 900th Hospital of the Joint Logistics Support Force of the People's Liberation Army from June 30,2014 to May 30,2018.Among them,5 cases underwent"open abdomen peritoneal catheter removal+intestinal adhesiolysis+abdominal infection flushing and drainage with catheter",4 cases underwent"laparoscopic peritoneal catheter removal+intestinal adhesiolysis+abdominal infection flushing and drainage with catheter",3 cases underwent"laparoscopic peritoneal dialysis catheter removal+abdominal infection flushing and drainage with catheter",2 cases underwent"open abdomen peritoneal dialysis catheter removal+abdominal infection flushing and drainage with catheter",and 1 case underwent"laparoscopic examination combined with laparotomy exploration and removal of lower abdominal catheter+intestinal adhesiolysis+abdominal infection flushing and drainage with catheter".Age,gender,clinical symptoms,abdominal CT examination,peripheral blood routine,blood biochemistry,blood C-reactive protein(CRP),white blood cells,biochemistry,and aetiology of peritoneal dialysis fluid were collected and followed up,and the therapeutic effect was evaluated.Results 15 patients were transferred to the Department of Surgery after ineffective treatment in the Department of Internal Medicine.Preoperatively(after 5 days of antibiotic treatment)compared to before antibiotic treatment,there were no significant changes in blood WBC,blood NEUT％,CRP,and peritoneal fluid WBC(P＞0.05).Laparoscopic exploration or laparotomy exploration was performed,during which the peritoneal dialysis catheter was removed and the abdominal infection focus was cleared.A pelvic cavity washout drainage tube was left in place postoperatively.Fourteen patients had a good recovery after surgery,with effective control of peritonitis symptoms and no complications such as intestinal obstruction or enterocutaneous fistula.After the removal of the peritoneal dialysis catheter,all patients switched to hemodialysis.A comparison of inflammatory markers before and after surgery showed a significant decrease after surgery.Three days postoperatively compared to before surgery(after 5 days of antibiotic treatment),there were no significant changes in blood WBC,blood NEUT％,CRP,and peritoneal fluid WBC(P＞0.05).Seven days postoperatively compared to before surgery(after 5 days of antibiotic treatment),there was a significant decrease in blood WBC[(7.43±2.65)× 109/L VS(10.17±5.24)× 109/L],blood NEUT％[(88.23±9.02)％VS(85.07±11.57)％],and CRP[(152.88±113.01)mg/L VS(114.49±92.97)mg/L](P＜0.05);the peritoneal fluid WBC at 7 days postoperatively showed no significant change compared to before surgery(after 5 days of antibiotic treatment)(P＞0.05).The cases were followed up for at least 22 months,and 13 patients did not experience peritonitis or intestinal obstruction again.One patient died 39 days after surgery due to multiple organ failure,and one patient died from other causes after a 2-year follow-up.Conclusion For refractory sclerosing peritonitis related peritoneal dialysis that is ineffective in medical conservative treatment,On the basis of reasonable and effective antibiotics to control infection,surgical intervention should be actively carried out and surgical methods such as surgery should be used to control the progress of peritonitis,reduce mortality and improve the cure rate.

Objective:To investigate the clinical efficacy and safety of pulmonary rehabilitation in elderly patients with chronic obstructive pulmonary disease(COPD)who are undergoing long-term home oxygen therapy.Methods:The study included a total of 60 elderly patients with COPD who were successfully discharged after receiving treatment at the First Hospital of Shanxi Medical University from November 2021 to October 2022.The enrolled patients were randomly divided into two groups: the pulmonary rehabilitation group and the control group, with 30 patients in each group.The allocation was determined using a random number table and prospective research methods.Patients in the pulmonary rehabilitation group underwent a 12-week pulmonary rehabilitation training program, while patients in the control group received pulmonary rehabilitation education and nutrition education.The general data of the two groups of patients were compared, including lung function parameters[forced expiratory volume in one second(FEV 1), forced vital capacity(FVC), forced expiratory volume in one second to forced vital capacity ratio(FEV 1/FVC), and percentage of predicted forced expiratory volume in one second(FEV 1%pred)], blood gas analysis[partial pressure of arterial oxygen(PaO 2), partial pressure of arterial carbon dioxide(PaCO 2), arterial oxygen saturation(SaO 2)], 6-minute walking distance(6MWD), grip strength, 5-round sit to stand test(5R-STST), modified British medical research council(mMRC)score, COPD assessment test(CAT)score, closed cycles test(CCT), Berg balance scale(BBS), and safety measures.These parameters were assessed before and after the intervention. Results:A total of 29 patients in the pulmonary rehabilitation group and 28 patients in the control group completed the study.The general data between the two groups showed no significant difference(all P>0.05).After the intervention, patients in the pulmonary rehabilitation group showed improvements in FEV 1/FVC, PaO 2, PaCO 2, SaO 2, 6MWD, grip strength, 5R-STST, CAT, CCT, and BBS( t=-2.242, -4.630, W=-3.439, t=-6.512, -10.563, -6.197, W=-3.968, t=10.847, -7.334, W=-4.189, all P<0.05).Additionally, 6MWD, CAT, and CCT showed significant improvement after the intervention compared to the control group( t=-2.104, 2.183, 2.106, all P<0.05).No training-related adverse effects were observed during the study. Conclusions:The 12-week pulmonary rehabilitation program is shown to be effective for elderly patients with COPD who are undergoing long-term home oxygen therapy.This program helps to improve respiratory function, systemic symptoms, exercise endurance, muscle strength, and balance function.It is designed to be simple and easy to implement, allowing patients to achieve their training goals and improve their clinical symptoms.Additionally, the program has been found to be safe and well-tolerated by patients, making it a valuable intervention that should be promoted and widely applied.

Objective:To explore the application value of two-dimensional speckle tracking echocardiography (2D-STE) in measuring the global longitudinal peak strain of the right atrium (PRAGLS) in normal fetuses and evaluating PRAGLS in assessing right atrial function in fetuses with moderate and severe tricuspid regurgitation (TR).Methods:A total of 25 fetuses diagnosed with moderate and severe TR, who underwent fetal echocardiography at Run Run Shaw Hospital, Zhejiang University College of Medicine between October 2020 and May 2022, were selected as the case group. Their gestational age ranged from 25.00(24.00, 30.00)weeks. Additionally, 100 normal singleton fetuses were chosen as the control group, with a gestational age of 25.83(23.00, 28.75)weeks. Standard basal or apical four-chamber clips were acquired and inputted into TOMTEC-ARENA offline cardiac analysis software for analysis. The fetal PRAGLS values of the two groups were obtained, as well as the routine obstetric ultrasound measurements and fetal echocardiographic parameters of both groups: fetal heart rate (FHR), biparietal diameter (BPD), femur length (FL), aortic annulus inner diameter (AO), pulmonary annulus inner diameter (PA), PA/AO ratio, right atrial end-systolic length (RAESL), right atrial end-systolic diameter (RAESD), right atrial end-systolic area (RAESA), right ventricular end-diastolic diameter (RVEDD), and tricuspid annular plane systolic excursion (TAPSE). The peak TR velocity and pressure gradient were simultaneously measured in the case group.The differences in fetal PRAGLS and other parameters between the two groups were compared and analyzed. The correlation between fetal PRAGLS and gestational age (GA) and routine measurements was assessed for both groups. Intra- and inter-observer repeatability tests were conducted using the intragroup correlation coefficient (ICC).Results:A significant difference in PRAGLS was observed between the two groups ( t=11.55, P<0.01). The TAPSE difference between the two groups was also statistically significant ( Z=3.45, P=0.01). Notable differences were found in AO, PA, PA/AO, RAESL, RAESD, and RAESA between the two groups (all P<0.05), but no significant differences were identified in age, GA, FHR, BPD, FL, and RVEDD between the two groups (all P>0.05). PRAGLS in the control group exhibited a moderate negative correlation with GA ( r=-0.47, P<0.01) and were correlated with BPD, FL, AO, PA, RAESL, RAESD, RAESA, and RVEDD ( r=-0.50, -0.46, -0.39, -0.43, -0.45, -0.36, -0.43, -0.32, all P<0.05). No significant correlation was observed with maternal age, FHR, PA/AO, and TAPSE (all P>0.05). No significant correlation between PRAGLS and GA or other conventional parameters was found in the case group (all P>0.05). The inter-measurer and intra-measurer ICC of PRAGLS in the control group were 0.87 and 0.79, respectively, while the inter-measurer and intra-measurer ICC of PRAGLS in the case group were 0.94 and 0.97, respectively, demonstrating good consistency. Conclusions:2D-STE exhibits strong feasibility and reproducibility in assessing fetal atrial function.Fetuses with moderate and severe TR display decreased PRAGLS, suggesting impaired right atrial reservoir function. Right atrial strain introduces a novel method for evaluating fetal cardiac function.

OBJECTIVE It's known that post-retrieval extinction but not extinction alone could erase fear memory.However,whether the coding pattern of original fear engrams is remod-eled or inhibited remains largely unclear.Here we try to investigate whether the coding pattern of memory engrams is altered during post-retrieval extinction induced memory updating.METHODS To answer the question,by using activity-depen-dent neuronal-tagging technology,neuronal trac-ing technique combined with optogenetic manipu-lation and in vivo calcium imaging,we identified the fear and extinction cells in PrL and BLA and investigated the dynamic encoding of memory engram ensembles in the PrL and BLA during CS versus US initiated memory updating.RESULTS We found increased reactivation of engram cells in the prelimbic cortex and basolat-eral amygdala during memory updating.More-over,conditioned stimulus and unconditioned stimulu sinitiated memory updating depend on the engram cells reactivation in the prelimbic cor-tex or basolateral amygdala respectively.Finally,we found memory updating causes increased overlapping between fear and extinction cells and the original fear engrams encoding was altered during memory updating.CONCLUSION Our data provide the first evidence to show the overlapping ensembles between fear and extinc-tion cells and functional reorganization of original engrams underlying conditioned stimulus and unconditioned stimulus initiated memory updating.

Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macro-phages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative acti-vation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.

Objective:To explore the association between weight status and early changes in blood pressure, cardiac structure and function in children at 4 years of age.Methods:A cross-sectional study of the relationship between weight status and cardiovascular parameters was performed on the platform of "Shanghai Birth Cohort" in Shanghai Xinhua Hospital between 2017 and 2020. Height, weight, blood pressure and echocardiography were measured in 1 477 children at 4 years of age. According to body mass index (BMI), participants were classified into five groups: underweight, lean, normal weight, overweight and obese. Blood pressure, cardiac structure and function indexes were compared among different groups using one-way ANOVA. The associations between blood pressure, cardiac structure and function and weight status in children were analyzed by linear regression models. Multivariate logistic regression models were used to analyze whether weight status was an independent risk factor for elevated blood pressure or left ventricular hypertrophy (LVH) in children.Results:A total of 1 477 children including 772 boys and 705 girls were included in this study. There were 115 overweight and obese boys (14.9%) and 68 overweight and obese girls (9.6%). The majority of children had normal weight (916 cases, 62.0%), followed by underweight (303 cases, 20.5%), overweight (130 cases, 8.8%), lean (75 cases, 5.1%), and obese (53 cases, 3.6%). With the increase of BMI, systolic blood pressure, diastolic blood pressure, left ventricular mass index (LVMI), left ventricular posterior wall thickness in systole, left ventricular posterior wall thickness in diastole, left ventricular diameter in end-systole, left ventricular diameter in end-diastole, interventricular septum thickness in systole and left ventricular ejection fraction showed significantly positive trend, and the differences among the groups were significant (F=31.73, 6.59, 14.22, 4.96, 3.01, 31.50, 39.79, 5.91, 3.09, all P<0.05). Multiple linear regression showed that overweight and obese were all positively associated with systolic blood pressure (β=5.2, 95% CI 3.6-6.8), LVMI (β=1.9, 95% CI 0.8-3.1), left ventricular diameter in end-systole (β=1.3, 95% CI 0.9-1.8), and left ventricular diameter in end-diastole (β=1.6, 95% CI 1.0-2.2). In the Logistic regression model, compared with normal weight children, overweight ( OR=2.37, 95% CI 1.37-4.41) and obese children ( OR=10.90, 95% CI 4.47-26.60) both had significantly increased risk of elevated blood pressure. However, the risk of LVH did not significantly increased. Conclusions:Overweight and obesity in 4-year-old children are associated with increased blood pressure, increased left ventricle diameter and LVMI. Overweight and obesity are independent risk factors for elevated blood pressure in children at 4 years of age.

Objective To analyze serotype distribution, drug resistance, quinolone resistance gene carrying status and genetic relationship of foodborne Salmonella and human Salmonella isolates in Changzhou from 2012 to 2018, to provide scientific basis for the prevention and control of Salmonella. Methods The serum type was identified by serum agglutination and liquid chip. The antibiotic sensitivity was determined by micro broth dilution method. The quinolone antibiotic resistance gene was determined by gene sequencing method. The multilocus sequence typing ( MLST ) typing was performed on quinolone-resistant Salmonella, and the genetic relationship was analyzed by BioNumerics 8.0. Results A total of 10 and 36 serotypes were detected in 46 foodborne Salmonella strains and 152 human Salmonella strains, respectively. The dominant serotypes were Indiana Salmonella and Salmonella typhimurium. Erythromycin resistance rate was the highest in both Salmonella strains, and the proportion of multidrug-resistant bacteria was 93.47 % ( 43 / 46 ) and 80.92 % ( 123 / 152 ), respectively. 38 strains of quinolone-resistant foodborne Salmonella GyrA subunit mainly occurred double mutations Asp87Asn, Ser83Phe, ParC subunit mainly occurred single mutation Ser80Arg, 119 strains of quinolone-resistant human Salmonella qnrS gene detection rate was higher, reached 68.1 % ( 81 / 119 ) ; The dominant ST types of quinolone-resistant Salmonella from two sources were ST17 and ST19, respectively. Conclusions The antibiotic sensitivity of the two Salmonella resistant strains from Changzhou was the same ; Synergistic drug resistance, but both quinolone resistance genemutations and carry inconsistent ; The ST type distribution of quinolone resistant strains isalso inconsistent, and the genetic relationship is far. It is suggested that the probability of Salmonella resistant bacteria infection caused by food transmission in our region is small, and the treatment of the two should be differentiated.

Objective To probe into the feasibility and applicability of the foodborne food risk monitoring and sentinel hospital foodborne disease surveillance on the Salmonella serotype identification by liquid phase suspension array. Methods The serotyping of Salmonella isolates was performed by traditional glass agglutination test. Meanwhile, the liquid phase suspension array was operated to analyze the antigen O, H and AT for classification identification. Results From 2012 to 2019, a total of 215 strains of Salmonella were collected divided into 38 serotypes, 96% of them could be analyzed by SSA kit. The results of xMAP were in accordance with the traditional agglutination. 8 of the 11 strains which cannot be checked out by glass agglutination seemed to be easy detected by liquid phase suspension array. Conclusion The liquid phase suspension array has advantages of high throughput, high sensitivity and high specificity. It is able to detect the Salmonella serotype rapidly during a short time. Compared with the traditional serum agglutination method, the liquid phase suspension array has obvious advantages in detection time. It can be useful and important in the break out of foodborne disease caused by Salmonella spp.