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.

Objective:To evaluate the effects of low-frequency ultrasound on antibiotic susceptibility and biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli).Methods:After MRSA and E. coli were treated with low-frequency ultrasound with different parameters, they were divided into a group with different ultrasound durations and a group with different ultrasound powers. With the power parameter set at 100%, the former was divided into 5 subgroups: control, 1.0 min, 2.5 min, 5.0 min, and 10.0 min subgroups. The bacteria were sonicated for 0, 1.0, 2.5, 5.0, 10.0 min, respectively. The group with different ultrasound powers was also divided into 5 subgroups: control, 25% power, 50% power, 75% power, and 100% power subgroups. The bacteria were treated with ultrasonic powers of 0, 25%, 50%, 75%, and 100% for 5.0 min. The MRSA and E. coli corresponded to antibiotic susceptibility testing using vancomycin and meropenem. The number of bacteria surviving was assessed by colony counts. Confocal microscopy was used to observe the changes in biofilms co-cultured with 1/2 minimum inhibitory concentration (MIC) antibiotics after sonication.Results:The E. coli enhanced its susceptibility to meropenem after 5.0 min of high-power sonication while the susceptibility of MRSA to vancomycin was unaffected. The number of E. coli decreased significantly with increasing ultrasound time and power: the numbers of E. coli in the 1.0 min, 2.5 min, 5.0 min, and 10.0 min subgroups [(51.00±18.73), (30.00±9.17), (5.33±4.04), and (0.23±0.03)×10 4 CFU/mL] were significantly smaller than that in the control subgroup [(120.00±7.81)×10 4 CFU/mL], and the numbers of E. coli in the 25%, 50%, 75%, and 100% subgroups [(25.00±3.00), (8.00±2.65), (5.00±2.00), and (5.33±4.04)×10 4 CFU/mL] were significantly smaller than that in the control subgroup [(120.00±7.81)×10 4 CFU/mL] ( P<0.05). However, the number of MRSA was not significantly affected. After treatment with ultrasound combined with 1/2 MIC meropenem, the ratio of live/dead biofilm areas of E. coli decreased significantly with increasing ultrasound time and power: the proportions of E. coli in the 1.0 min, 2.5 min, 5.0 min and 10.0 min subgroups (66.10%±1.78%, 50.84%±7.99%, 60.98%±2.23%, and 29.20%±16.49%) were significantly smaller than those in the control subgroup (93.73%±0.44%), and the proportions of E. coli in the 25%, 50%, 75%, and 100% subgroups (75.23%±2.21%, 65.10%±1.25%, 57.34%±11.21%, and 60.98%±2.23%) were significantly smaller than that in the control subgroup (93.73%±0.44%) ( P<0.05). However, the MRSA live/dead biofilm area ratio was not significantly affected by the treatment with ultrasound combined with 1/2 MIC vancomycin. Conclusions:Low frequency ultrasound can effectively inhibit the growth of E. coli and significantly enhance its sensitivity to antibiotics, and its combination with antibiotics can inhibit the formation of bacterial biofilm. However, low frequency ultrasound or its combination with antibiotics has no significant effect on MRSA.

OBJECTIVE: To observe the effect of heat-sensitive moxibustion at "Feishu" (BL13) on immunoinflammatory response in rats with allergic rhinitis (AR) based on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, so as to explore its underlying mechanism. METHODS: Thirty-two male SD rats were randomly divided into a blank group (6 rats) and a modeling group (26 rats). In the modeling group, AR model was prepared using systemic and local attack sensitization method with ovalbumin. The successfully-modeled rats were randomized into a model group (6 rats), a medication group (6 rats) and a moxibustion group (14 rats). In the moxibustion group, the suspending moxibustion was operated at bilateral "Feishu" (BL13), 40 min each time, once daily, for 21 consecutive days; during which, the temperature of the body and tail was recorded. During intervention, if the temperature of the body and tail increased by >1 ℃, the heat-sensitive reaction at the point was determined in the rats of the moxibustion group, and these rats were collected in a heat-sensitive moxibustion group (8 rats involved and 6 rats of them were randomly collected to ensure the sample-size consistency); and those without heat-sensitive moxibustion reaction were assigned to a traditional moxibustion group (6 rats). In the medication group, fluticasone propionate nasal spray was applied, 8 μL on each side, once daily and for 21 days. The behavioral score for AR symptoms after modeling and intervention, and the content of serum immunoglobulin E (IgE) after modeling were observed. After intervention, the histological morphology of the nasal mucosa was observed using HE staining, the positive expression of thymic stromal lymphopoietin (TSLP) in the nasal mucosa was detected using immunohistochemistry, the levels of IgE, interleukin (IL)-4, IL-5, IL-13 and interferon-γ (IFN-γ) were detected by ELISA, and the protein expression of the member 4 of tumor necrosis factor receptor superfamily (OX40), phosphorylated protein kinase B (p-AKT), phosphorylated phosphatidylinositol 3-kinase (p-PI3K) in nasal mucosa was detected by Western blotting. RESULTS: After modeling, the behavioral score of AR symptoms and serum IgE level in the modeling group were higher than those of the blank group (P<0.01), suggesting the success of AR modeling. After intervention, compared with the blank group, the behavioral score of AR symptoms was increased (P<0.01)；the nasal mucosa structure was disordered, the inflammatory infiltration was severe; the positive expression of TSLP in the nasal mucosa increased (P<0.01), the levels of serum IgE, IL-4, IL-5, and IL-13 elevated (P<0.01), and the level of IFN-γ decreased (P<0.01); and the protein expression of OX40, p-AKT, and p-PI3K in the nasal mucosa increased (P<0.05) in the model group. Compared with the model group, the behavioral score of AR symptoms was reduced (P<0.01); the nasal mucosa structure, inflammatory infiltration, and vascular dilation were ameliorated to varying degrees; the positive expression of TSLP in the nasal mucosa decreased (P<0.01); the content of serum IgE, IL-4, IL-5, and IL-13 decreased (P<0.05), and that of IFN-γ increased (P<0.05) in the medication, traditional moxibustion, and heat-sensitive moxibustion groups. Compared with the model group, the protein expression of p-AKT was reduced in the medication and traditional moxibustion groups (P<0.05), the protein expression of OX40, p-AKT, and p-PI3K in the nasal mucosa decreased in the heat-sensitive moxibustion group (P<0.05). When compared with the medication group, the positive expression of TSLP in the nasal mucosa was reduced (P<0.05) in the heat-sensitive moxibustion group. In comparison with the traditional moxibustion group, the content of serum IL-13 was reduced and the content of IFN-γ elevated in the heat-sensitive moxibustion and the medication groups (P<0.05), the protein expression of p-PI3K reduced in the medication group (P<0.05), and the positive expression of TSLP and the protein expression of OX40 and p-PI3K in the nasal mucosa were reduced in the heat-sensitive moxibustion group (P<0.05). CONCLUSION Heat-sensitive moxibustion at "Feishu" (BL13) can alleviate the symptoms of AR rats, ameliorate the inflammatory infiltration and telangiectasia of nasal mucosa, and inhibit immunoinflammatory response, which may be obtained by regulating PI3K/AKT signal pathway.
Animals ; Moxibustion ; Male ; Rats ; Signal Transduction ; Rats, Sprague-Dawley ; Rhinitis, Allergic/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Acupuncture Points ; Humans ; Phosphatidylinositol 3-Kinases/immunology* ; Phosphatidylinositol 3-Kinase/immunology*

Objective To observe the value of artificial intelligence iterative reconstruction(AIIR)combined with 60 kVp scanning in craniocervical CT angiography(CTA).Methods Eighty-six patients with suspected craniocervical vascular diseases were prospectively enrolled and randomly received routine-dose(120 kVp)or low-dose(60 kVp)scanning(each n=43),and contrast dosage and radiation dose were recorded.After scanning,hybrid iterative reconstruction(HIR)was used to reconstruct routine-dose images(group A),while HIR images(group B1)and AIIR images(group B2)were performed to reconstruct low-dose images,respectively.The overall imaging quality,visualization of targeted large and small vessels and diagnostic confidence scores,as well as image noise(SD),signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of targeted large vessels were compared among 3 groups.Results Contrast dosage and effective dose(ED)decreased by 36.52％ and 77.56％ in low-dose scanning compared with those in routine-dose scanning,respectively.No significant difference of subjective scoring of imaging quality indexes was found between groups B2 and A(all adjusted P＞0.05),which were both higher than those in group B1(all adjusted P＜0.05).SD of target large vessels in group B2 than that of most target large vessels in group A(all adjusted P＜0.05)except for aortic arch.SNR and CNR of target large vessels in group B2 were higher than those in group A and B1(all adjusted P＜0.05),while SD of target large vessels in group B2 were lower than in group B1.Conclusion AIIR combined with 60 kVp scanning in craniocervical CTA could meet diagnostic requirements of imaging quality and reduce contrast dosage and radiation dose.

Objective:To evaluate the effects of low-frequency ultrasound on antibiotic susceptibility and biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli).Methods:After MRSA and E. coli were treated with low-frequency ultrasound with different parameters, they were divided into a group with different ultrasound durations and a group with different ultrasound powers. With the power parameter set at 100%, the former was divided into 5 subgroups: control, 1.0 min, 2.5 min, 5.0 min, and 10.0 min subgroups. The bacteria were sonicated for 0, 1.0, 2.5, 5.0, 10.0 min, respectively. The group with different ultrasound powers was also divided into 5 subgroups: control, 25% power, 50% power, 75% power, and 100% power subgroups. The bacteria were treated with ultrasonic powers of 0, 25%, 50%, 75%, and 100% for 5.0 min. The MRSA and E. coli corresponded to antibiotic susceptibility testing using vancomycin and meropenem. The number of bacteria surviving was assessed by colony counts. Confocal microscopy was used to observe the changes in biofilms co-cultured with 1/2 minimum inhibitory concentration (MIC) antibiotics after sonication.Results:The E. coli enhanced its susceptibility to meropenem after 5.0 min of high-power sonication while the susceptibility of MRSA to vancomycin was unaffected. The number of E. coli decreased significantly with increasing ultrasound time and power: the numbers of E. coli in the 1.0 min, 2.5 min, 5.0 min, and 10.0 min subgroups [(51.00±18.73), (30.00±9.17), (5.33±4.04), and (0.23±0.03)×10 4 CFU/mL] were significantly smaller than that in the control subgroup [(120.00±7.81)×10 4 CFU/mL], and the numbers of E. coli in the 25%, 50%, 75%, and 100% subgroups [(25.00±3.00), (8.00±2.65), (5.00±2.00), and (5.33±4.04)×10 4 CFU/mL] were significantly smaller than that in the control subgroup [(120.00±7.81)×10 4 CFU/mL] ( P<0.05). However, the number of MRSA was not significantly affected. After treatment with ultrasound combined with 1/2 MIC meropenem, the ratio of live/dead biofilm areas of E. coli decreased significantly with increasing ultrasound time and power: the proportions of E. coli in the 1.0 min, 2.5 min, 5.0 min and 10.0 min subgroups (66.10%±1.78%, 50.84%±7.99%, 60.98%±2.23%, and 29.20%±16.49%) were significantly smaller than those in the control subgroup (93.73%±0.44%), and the proportions of E. coli in the 25%, 50%, 75%, and 100% subgroups (75.23%±2.21%, 65.10%±1.25%, 57.34%±11.21%, and 60.98%±2.23%) were significantly smaller than that in the control subgroup (93.73%±0.44%) ( P<0.05). However, the MRSA live/dead biofilm area ratio was not significantly affected by the treatment with ultrasound combined with 1/2 MIC vancomycin. Conclusions:Low frequency ultrasound can effectively inhibit the growth of E. coli and significantly enhance its sensitivity to antibiotics, and its combination with antibiotics can inhibit the formation of bacterial biofilm. However, low frequency ultrasound or its combination with antibiotics has no significant effect on MRSA.

Objective To observe the value of artificial intelligence iterative reconstruction(AIIR)combined with 60 kVp scanning in craniocervical CT angiography(CTA).Methods Eighty-six patients with suspected craniocervical vascular diseases were prospectively enrolled and randomly received routine-dose(120 kVp)or low-dose(60 kVp)scanning(each n=43),and contrast dosage and radiation dose were recorded.After scanning,hybrid iterative reconstruction(HIR)was used to reconstruct routine-dose images(group A),while HIR images(group B1)and AIIR images(group B2)were performed to reconstruct low-dose images,respectively.The overall imaging quality,visualization of targeted large and small vessels and diagnostic confidence scores,as well as image noise(SD),signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of targeted large vessels were compared among 3 groups.Results Contrast dosage and effective dose(ED)decreased by 36.52％ and 77.56％ in low-dose scanning compared with those in routine-dose scanning,respectively.No significant difference of subjective scoring of imaging quality indexes was found between groups B2 and A(all adjusted P＞0.05),which were both higher than those in group B1(all adjusted P＜0.05).SD of target large vessels in group B2 than that of most target large vessels in group A(all adjusted P＜0.05)except for aortic arch.SNR and CNR of target large vessels in group B2 were higher than those in group A and B1(all adjusted P＜0.05),while SD of target large vessels in group B2 were lower than in group B1.Conclusion AIIR combined with 60 kVp scanning in craniocervical CTA could meet diagnostic requirements of imaging quality and reduce contrast dosage and radiation dose.

Biological toxins are toxic molecules produced by specific microorganisms,plants or animals.Due to their wide range of sources and high toxicity,the availability of protein and non-protein toxins is becoming increasingly important,some of which are used for military purposes and developed as biotoxin warfare agents.In this paper,the classification and mechanism of action of biological toxins are discussed.In addition,the strategies for prevention and control of biological toxins as well as their therapeutic applications are reviewed.

Objective:To explore the differential efficacies of conventional chemotherapy, autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for T lymphoblastic lymphoma (T-LBL) .Method:From January 2012 to December 2022, the relevant clinical data were retrospectively reviewed for 82 T-LBL patients hospitalized at Affiliated Tongji Hospital. According to different treatments, they were assigned into two groups of non-transplantation (49 cases) and transplantation (33 cases). The transplantation group was divided further into two groups of allo-HSCT (22 cases) and auto-HSCT (11 cases) according to different transplantation modes. In non-transplantation group, remission was induced mostly by cyclophosphamide+messosodium+doxorubicin+dexamethasone+vincrine/methotrexate+Hyper CAVD A/B. Six patients achieved remission based upon cyclophosphamide+cytarabine+6-mercaptopurine (CAT), etoposide+vincristine+doxorubicin+cyclophosphamide+cyclophosphamide+ prednisone (EPOCH), high-dose methotrexate+dexamethasone and vincristine+pirubicin+ cyclophosphamide+ pemasase+prednisone (VDCLP). The transplantation group underwent HSCT after multi-drug combination intensive induction therapy. Efficacy and survival were analyzed by observing the rates of overall survival (OS) and progression-free survival (PFS) .Result:There were 64 males and 18 females with a median age of 23 (11~74) year. Among them, 62 cases (75.61%) had clinical stage Ⅲ~Ⅳ. And 43 cases (53.44%) had systemic symptoms (B symptom) of fever, night sweats and weight loss at an onset of disease. Fifty cases (61.00%) had an involvement of bone marrow and 33 cases (80.5%) belonged to Ann Arbor stage Ⅲ and above. There were 65 cases (79.27%) with Eastern Cooperative Oncology Group (ECOG) score ≤2 and 17 cases (20.73%) with ECOG score >2. International Prognostic Index (IPI) was ≤3 (63 cases, 76.83%) and >3 (19 cases, 23.17%). Follow-up period was 27.5 (5~118) month. And 3-year OS and PFS were 53.64% (95% CI: 42.35%~64.62%) and 47.56% (95% CI: 36.53%~58.82%). Significant inter-group difference existed in 3-year OS[42.86% (95% CI: 29.12%~57.71%) vs 69.70% (95% CI: 51.13%~83.79%), P=0.014]and 3-year PFS was 38.76% (95% CI: 25.54%~53.76%) and 60.61% (95% CI: 42.24%~76.57%). And the difference was statistically significant ( P=0.032) . Conclusion:As a consolidation therapy, HSCT may improve the long-term outcomes of T-LBL patients as compared with chemotherapy alone.

Objective:To explore the risk factors and outcomes of central nervous system(CNS)complications associated with hematopoietic stem cell transplantation(HSCT).Methods:A total of 550 recipient after HSCT in the department of hematology of Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 1 2019 to August 31 2021were enrolled.According to the occurrence of CNS complications, they were divided into the CNS group(24 cases)and the non CNS group(526 cases). The clinical information and prognosis were compared.We further analyzed the risk factors associated with CNS complications, and conducted multivariate logistic regression on statistically significant indicators.Cox regression analysis is conducted on prognostic factors such as age, gender and risk degree.Results:A total of 550 recipients were enrolled, of which 330 underwent allo-HSCT, and others received auto-HSCT.A total of 24 cases (4.36%)had CNS complications, of which 4 cases had 2 types of CNS complications.The type of CNS complications included intracranial infection(8 cases, 28.57%), transplantation-associated thrombotic microangiopathy(TA-TMA)(6 cases, 21.43%), central tumor invasion(4 cases, 14.29%), intracranial hemorrhage(4 cases, 14.29%), leucodystrophy(2 cases, 7.14%)and unexplained encephalopathy(4 cases, 14.29%). Logistic regression analysis of risk factors related to CNS complications showed that, Platelet implantation time( β=0.084, OR=1.088, P=0.048), CMV infection( β=1.295, OR=3.65, P=0.008)is positively correlated with the occurrence of CNS complications in HSCT recipients but age( β=-0.052, OR=0.949, P=0.004)is negatively correlated with it.Nine of the 24 cases(37.50%)who experienced CNS complications died, including 3 cases of intracranial infection, 3 cases of cerebral hemorrhage, 2 cases of TMA, and 1 case of unexplained encephalopathy.Platelet implantation time is an independent risk factor for poor prognosis of CNS complications in HSCT recipients. Conclusions:Our results indicated that, age, CMV infection and platelet implantation time were associated with the occurrence of CNS complications after HSCT.Platelet implantation time is an independent risk factor for poor prognosis of CNS complications in HSCT recipients.

Objective:To compare the clinical outcomes and safety of haploidentical donor (HID)and HLA-matched sibling donor(MSD)hematopoietic stem cell transplantation(HSCT)for severe aplastic anemia(SAA).Methods:From January 1, 2012 to December 31, 2019, retrospective review of clinical data was performed for 75 SAA patients undergoing HSCT at Department of Hematology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.Based upon donor sources, they were divided into two groups of MSD(49 cases)and HID (26 cases). And two groups were compared with regards to hematopoietic recovery, graft-versus-host disease(GVHD)infection and overall survival(OS).Results:Time of platelet and neutrophil engraftment of two groups was comparable(11 d vs.11 d, P=0.84; 11 d vs.12 d, P=0.08). Compared with HID group, MSD group had a lower incidence of acute GVHD(46.2% vs.18.4%, P=0.01)with a comparable incidence of grade Ⅱ-Ⅳ acute GVHD(26.9% vs.14.3%, P=0.24), grade Ⅲ-Ⅳ acute GVHD(15.4% vs.4.1%, P=0.09)and chronic GVHD(23.9% vs.23.1 %, P=0.71). A reactivation of CMV occurred in 27(55.1%)MSD and 22(84.6%)HID recipients( P=0.01). And the incidence of EB viremia was 69.4% and 61.5% respectively.After a median follow-up period of 54.0 and 18.5 months, the estimated 3-year OS rate of MSD and HID groups were 94.0% and 88.0% respectively ( P=0.35). Conclusions:HID HSCT is an effective and relatively safe option for SAA patients, especially for those in urgent need of treatment without MSD or refractory/relapse to immunosuppressive therapy.