Acne vulgaris and rosacea are common inflammatory complications of the skin, both characterized by abnormal infiltration of immune cells. The two diseases can be differentiated based on ...characteristic profile of the immune cell infiltrates at the periphery of disease lesions. In addition, dysregulated infiltration of immune cells not only occur in the acne lesions but also in non-lesional areas of patients with the disease, thus characterizing the immune infiltration in these sites can further enhance our understanding on the pathogenesis of acne.
Five microarray data-sets (GSE108110, GSE53795, GSE65914, GSE14905 and GSE78097) were downloaded from Gene Expression Omnibus. After removing the batch effects and normalizing the data, we applied the CIBERSORT algorithm combined with signature matrix LM22, to describe 22 types of immune cells' infiltration in acne less than 48 hour (H) old, in comparation with non-lesional skin of acne patients, healthy skin and rosacea (including erythematotelangiectatic rosacea, papulopustular rosacea and phymatous rosacea) and we compared gene expression of Th1 and Th17-related molecules in acne, rosacea and healthy control.
Compared with the non-lesional skin of acne patients, healthy individuals and rosacea patients, there is a significant increase in infiltration of neutrophils, monocytes and activated mast cells around the acne lesions, less than 48 H after their development. Contrarily, few naive CD4+ T cells, plasma cells, memory B cells and resting mast cells infiltrate acne sites compared to the aforementioned groups of individuals. Moreover, the infiltration of Regulatory T cells (Tregs) in acne lesions is substantially lower, relative to non-lesional sites of acne patients and skin of healthy individuals. In addition, non-lesional sites of acne patients exhibit lower infiltration of activated memory CD4+ T cells, plasma cells, memory B cells, M0 macrophages, neutrophils, resting mast cells but higher infiltration of Tregs and resting dendritic cells relative to skin of healthy individuals. Intriguingly, we found that among the 3 rosacea subtypes, the immune infiltration profile of papulopustular rosacea is the closest to that of acne lesions. In addition, through gene expression analysis of acne, rosacea and skin tissues of healthy individuals, we found a higher infiltration of Th1 and Th17 cells in acne lesions, relative to non-lesional skin areas of acne patients.
Our study provides new insights into the inflammatory pathogenesis of acne, and the difference between acne and rosacea, which helps in differentiating the two diseases. Our findings also guide on appropriate target therapy of the immune cell infiltrates in the two disease conditions.
Cholestasis is a common feature of liver injury, which manifests as bile acid excretion and/or enterohepatic circulation disorders. However, very few effective therapies exist for cholestasis. ...Recently, 18β-Glycyrrhetinic acid (18b-GA), a major metabolic component of glycyrrhizin, which is the main ingredient of licorice, was reported to protect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. However, its protective mechanism remains unclear. We hypothesized that 18b-GA may stimulate the signaling pathway of bile acid (BA) transportation in hepatocytes, resulting its hepatoprotective effect. According to the results, 18b-GA markedly attenuated ANIT-induced liver injury as indicated the hepatic plasma chemistry index and histopathology examination. In addition, the expression levels of nuclear factors, including Sirt1, FXR and Nrf2, and their target efflux transporters in the liver, which mainly mediate bile acid homeostasis in hepatocytes, significantly increased. Furthermore, we first revealed that 18b-GA treatment significantly activated FXR, and which can be significantly reduced by EX-527 (a potent and selective Sirt1 inhibitor), indicating that 18b-GA activates FXR through Sirt1. Taken together, 18b-GA confers hepatoprotection against ANIT-induced cholestasis by activating FXR through Sirt1, which promotes gene expression of the efflux transporter, and consequently attenuates dysregulation of bile acid homeostasis in hepatocyte compartments.
Intestinal mucositis is a common side effect of anticancer regimens that exerts a negative impact on chemotherapy. Superoxide dismutase (SOD) is a potential therapy for mucositis but efficient ...product is not available because the enzyme is degraded following oral administration or induces an immune reaction after intravascular infusion. Multi-modified Stable Anti-Oxidant Enzymes
(MS-AOE
) is a new recombinant SOD with better resistance to pepsin and trypsin. We referred it as MS-SOD to distinguish from other SODs. In this study we investigated its potential to alleviate 5-FU-induced intestinal injury and the mechanisms. An intestinal mucositis model was established in C57/BL6 mice by 5-day administration of 5-FU (50 mg/kg every day, ip). MS-SOD (800 IU/10 g, ig) was given once daily for 9 days. 5-FU caused severe mucositis with intestinal morphological damage, bodyweight loss and diarrhea; MS-SOD significantly decreased the severity. 5-FU markedly increased reactive oxygen species (ROS) and inflammatory cytokines in the intestine which were ameliorated by MS-SOD. Furthermore, MS-SOD modified intestinal microbes, particularly reduced Verrucomicrobia, compared with the 5-FU group. In Caco2 cells, MS-SOD (250-1000 U/mL) dose-dependently decreased tBHP-induced ROS generation. In RAW264.7 cells, MS-SOD (500 U/mL) had no effect on LPS-induced inflammatory cytokines, but inhibited iNOS expression. These results demonstrate that MS-SOD can scavenge ROS at the initial stage of injury, thus play an indirect role in anti-inflammatory and barrier protein protection. In conclusion, MS-SOD attenuates 5-FU-induced intestinal mucositis by suppressing oxidative stress and inflammation, and influencing microbes. MS-SOD may exert beneficial effect in prevention of intestinal mucositis during chemotherapy in clinic.
In this study, we aimed to enhance the treatment protocols and help understand the harm caused by the accidental ingestion of magnetic beads by children.
Data were collected from 72 children with ...multiple gastrointestinal perforations or gastrointestinal obstructions. The 72 pediatric patients were divided into a perforation and a non-perforation group. The data collected for the analysis included the gender, age, medical history, place of residence (rural or urban), and symptoms along with the educational background of the caregiver, the location and quantity of any foreign bodies discovered during the procedure, whether perforation was confirmed during the procedure, and the number of times magnetic beads had been accidentally ingested.
The accuracy rate of preoperative gastrointestinal perforation diagnosis via ultrasound was 71%, while that of the upright abdominal X-ray method was only 46%. In terms of symptoms, the risk of perforation was 13.844 and 12.703 times greater in pediatric patients who experienced vomiting and abdominal pain with vomiting and abdominal distension, respectively, compared to patients in an asymptomatic state. There were no statistical differences between the perforation and the non-perforation groups in terms of age, gender, medical history, and the number of magnetic beads ingested (P > 0.05); however, there were statistical differences in terms of white blood cell count (P = 0.048) and c-reactive protein levels (P = 0.033). A total of 56% of cases underwent a laparotomy along with perforation repair and 19% underwent gastroscopy along with laparotomy. All pediatric patients recovered without complications following surgery.
Abdominal ultrasonography and/or upright abdominal X-ray analyses should be carried out as soon as possible in case of suspicion of accidental ingestion of magnetic beads by children. In most cases, immediate surgical intervention is required. Given the serious consequences of ingesting this type of foreign body, it is essential to inform parents and/or caregivers about the importance of preventing young children from using such products.
•The most frequent causative agents in our study were antibiotics, antiepileptic drugs, and nonsteroidal anti-inflammatory drugs.•The overall survival rate in this cohort was better than that ...reported and the predicted SCORTEN.•Infection was a common complication in SJS/TEN patients, especially in lower respiratory tract and skin.•Blood glucose level, the use of corticosteroid and the total body surface area (TBSA) were significantly related to infection.
Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. The use of corticosteroids and the management of complications (e.g. infection) in SJS/TEN remains controversial.
A retrospective study was performed among 213 patients with SJS/TEN who were hospitalized in our department between 2008 and 2018, to investigate the causative agents, clinical characteristics, complications, and prognoses of SJS/TEN mainly treated by systemic corticosteroids combined with intravenous immunoglobulin (IVIG).
The causative drugs of SJS/TEN in these patients mainly consisted of antibiotics (61/213, 28.6%), anticonvulsants (52/213, 24.4%), and nonsteroidal anti-inflammation drugs (24/213, 11.3%), among which carbamazepine was the most frequently administered drug (39/213, 18.3%). There were significant differences in the maximum dosage, time to corticosteroid tapering, and the total dosage of corticosteroid between the SJS group and the TEN group, as well as among the three groups (P = 0.000), whereas in the initial dose of corticosteroid was not statistically significant among the three groups (P = 0.277). In a series of 213 cases, 18.4 cases (8.6%) were expected to die based on the score for the toxic epidermal necrolysis (SCORTEN) system, whereas eight deaths (3.8%) were observed; the difference was not statistically significant (P = 0.067; SMR = 0.43, 95% CI: 0.06, 0.48). The most common complications were electrolyte disturbance (174/213, 81.7%), drug-induced liver injury (64/213, 30.0%), infection (53/213, 24.9%), and fasting blood sugar above 10 mmol/L (33/213, 15.5%). Respiratory system (22/213, 10.3%) and wound (11/213, 5.2%) were the most common sites of infection. Multivariate logistic regression analysis indicated that the maximum blood sugar (≥10 mmol/L), the time to corticosteroid tapering (≥12 d), the maximum dosage of corticosteroid (≥1.5 mg/kg/d), and the total body surface area (TBSA) (≥10%) were defined as the most relevant factors of the infection.
The mortality of patients in this study was lower than that predicted by SCORTEN, although there was no significant difference between them. Hyperglycemia, high-dose corticosteroid, and the TBSA were closely related to the infections of patients with SJS/TEN.
•First humanized rabbit anti-VEGF monoclonal antibody used for eye diseases.•Quickly diffuse and distribute in ocular tissues.•Long half-life of TMAB001 in ocular tissues compared to some other ...drugs.
TMAB001 is a humanized rabbit monoclonal antibody (mAb) designed to bind and neutralize human vascular endothelial growth factor (VEGF)-165. The purpose of the study was to investigate the pharmacokinetics (PK) and ocular tissue distribution after a single intravitreal (IVT) dose in rabbits and monkeys.
Rabbits (2.5 mg/eye; n = 40) and monkeys (2.5 mg/eye; n = 12) received TMAB001 as a bilateral IVT dose. TMAB001 concentrations were measured in ocular tissues in all rabbits and monkeys by enzyme-linked immunosorbent assay (ELISA). TMAB001 and VEGF concentrations were measured in serum of monkeys by ELISA.
Following a single bilateral IVT injection of TMAB001 2.5 mg/eye, the highest concentration was in vitreous humor, followed by retina and choroid, and the lowest concentration was in lens. In rabbits, TMAB001 was still detectable in ocular tissues at day 21 after single IVT dose, with the highest level in the vitreous humor and then retina, with longest t1/2 in aqueous humor and shortest t1/2 in choroid. In monkeys, tmax in serum was 43 h and t1/2 was approximately 5.5 days. Cmax in serum was much lower than that in vitreous, nearly 1/200. After IVT injection of TMAB001, total VEGF concentrations in serum and ocular tissues increased over time. VEGF concentration in retina and choroid increased over time, up to 336 h after administration.
This study demonstrated that TMAB001 could reach the drug target sites–retina and choroid after a single bilateral IVT administration in rabbits and monkeys, with a long t1/2 in vitreous humor. TMAB001 also showed strong capability to neutralize VEGF. The study further confirmed that full-length antibodies can also efficiently diffuse and distribute in ocular tissues.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening severe adverse drug reactions. The use of corticosteroids and intravenous immunoglobulin (IVIg) in ...SJS/TEN remains controversial.
In this single-center, observational, propensity-matched, retrospective study, we collected a total of 224 patients with SJS/TEN who were hospitalized in our department from 2008 to 2019; according to treatment with IVIg combined with corticosteroids or with corticosteroids alone, patients were divided into combination therapeutic group (163 patients) and monotherapeutic group (61 patients). Patients from the two groups were matched by their propensity score in blocks of 2:1. Comparisons of the clinical characteristics and prognoses between propensity-matched SJS/TEN patients treated with IVIg combined with corticosteroids and corticosteroids alone were made.
After our propensity matching, a total of 145 patients were yielded, including 93 patients treated with IVIg and 52 patients not treated with IVIg. All of the 23 variables reflected good matching between patients treated with/without IVIg, and no significant difference was observed. Although there was no significant difference between the totally predicted and actual mortality in both of our groups, the actual mortality was lower than it was predicted in patients treated with IVIg
> 0.250, the standardized mortality ratio (SMR) was 0.38, 95% CI 0.00-0.91 and patients treated without IVIg (
= 1.000, the SMR was 0.75, 95% CI 0.00-1.76). IVIg tended toward reducing the time to arrest of progression by 1.56 days (
= 0.000) and the length of hospital stay by 3.37 days (
= 0.000). The mortality rate was 45% lower for patients treated with IVIg combined with corticosteroids than those only treated with corticosteroid therapy, although it was not statistically significant (
= 0.555). The incidence of skin infections was significantly lower in the combined therapy group (
< 0.025), and the total infection rate of patients treated with combination therapy tended to decrease by 67% compared to patients treated with corticosteroids alone (
= 0.047).
The actual mortality rate of patients treated with corticosteroids alone or IVIg combined with corticosteroids tended to be lower than those predicted by TEN-specific severity-of-illness score (SCORTEN), although there was no significance. Compared with those treated by corticosteroids alone, combination therapy was prone to bring a better prognosis for SJS/TEN patients.
Introduction
This study aims to explore the theoretical method and clinical application of manipulation reduction for testicular torsion.
Methods
A total of 28 patients with testicular torsion were ...recruited from the Emergency Surgery Department of Beijing Children’s Hospital affiliated to Capital Medical University from July 2016 to July 2018. Among these patients, 22 patients (age: 10.80 ± 3.50 years old) were treated with manual reduction using the elastic retraction method and push-and-turn method. Observation indexes included dramatically alleviated or completely disappeared pain without general anesthesia; the spermatic cord being smooth and unknotted; the restoration of the suffered testis to normal anatomical position under ultrasonography monitoring; blood flow signals increased in the affected testis and epididymis, which was regarded as the main sign of a successful reduction.
Results
Among the 22 cases who received manual reduction, 19 patients were successfully treated (left side:
n
= 11, right side:
n
= 8) with a total success rate of 86.36%. The other three cases showed either incomplete (
n
= 2) or failed (
n
= 1) reposition. Among the 19 patients who were successfully treated by manual reduction, 2 of them did not undergo prophylactic orchiopexy, and no abnormalities were found during the follow-up.
Conclusion
The reduction of testicular torsion using the elastic retraction method and push-and-turn method may improve the success rate of the manual reduction of testicular torsion, especially for incomplete testicular torsion. Furthermore, manual reduction may help increase the rate of testicular salvage in a timely manner before emergency surgery. Hence, this skill should be extended to primary hospitals to reduce the possibility of testectomy caused by testicular torsion.
Monoclonal gammopathy of renal significance (MGRS) can present with different morphologic features and lead to kidney failure. The Henoch-Schönlein purpura nephritis (HSPN) that cannot be relieved by ...treatment with glucocorticoid and immunosuppressive agents suggests the presence of monoclonal gammopathy in adult patients. The present study reports on a single case of HSPN associated with IgA-κMGRS. The patient who suffered from recurrent skin purpura for 6 months and nephrotic syndrome for 2 months was admitted to our hospital. Bone marrow biopsy showed monoclonal gammopathy of undetermined significance. Kidney biopsy indicated a Henoch-Schönlein purpura nephritis (HSPN, ISKDC classified as type III) with positive staining with κ-light chain in the glomeruli and renal tubular epithelial cells. Furthermore, skin biopsy showed leukocytoclastic vasculitis and negative staining for Congo red and light chain. Given both the renal and cutaneous involvement, the patient was considered to have HSPN associated with IgA-κMGRS. The patient experienced an exacerbation in his purpura-like lesions and clinical status after treatment with glucocorticoid and immunosuppressive agents. Consequently, the patient was put on a regimen that included dexamethasone (20 mg on the 1st, 4th, 8th, and 11th days of each month, iv) and bortezomib (2.4 mg on the 1st, 4th, 8th, and 11th days of each month, iv). Eight weeks after treatment, he had complete resolution of his cutaneous purpura and his biochemical parameters improved. The latent presence of MGRS in cases of HSPN should be considered in adult patients. Increased cognizance and correct treatment options could improve patient outcomes.
Although gene therapy can cure patients with severe combined immunodeficiency (SCID) syndromes, the clinical occurrence of T cell malignancies due to insertional mutagenesis has raised concerns about ...the safety of gene therapy. Several key questions have remained unanswered: (i) are there unique risk factors for X-linked SCID (XSCID) gene therapy that increase the risk of insertional mutagenesis; (ii) what other genetic lesions may contribute to transformation; and (iii) what systems can be used to test different vectors for their relative safety? To address these questions, we have developed an XSCID mouse model in which both the Arf tumor-suppressor gene and the γc gene were ablated. Gene therapy in this animal model recapitulates the high incidence of integration-dependent, T cell tumors that was seen in the clinical trial. Ligation-mediated PCR analysis showed integration sites near or within established protooncogenes (Chd9, Slamf6, Tdel, Camk2b, and Ly6e), demonstrating that T cell transformation was associated with targeting of oncogene loci; however, no integrations within the Lmo2 locus were identified. The X-SCID background in transplanted cells was required for high rate transformation and was associated with expansion of primitive hematopoietic cells that may serve tumor precursors. This model should be useful for testing safety-modified vectors and for further exploring the risk factors leading to insertional mutagenesis in gene therapy trials.
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