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.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

Objective:To investigate the therapeutic effects of internal fixation via the posterolateral combined posteromedial approach in the treatment of posterior pilon fracture (Klammer type Ⅲ).Methods:A retrospective study was performed to analyze the 69 posterior pilon fractures (Klammer type Ⅲ) which had been treated by internal fixation with hollow screws or a buttress plate at Department of Orthopaedic Trauma, Yantai Shan Hospital from January 2015 to January 2020. There were 36 males and 33 females with an age of (45.3±10.0) years and duration from injury to surgery of (6.0±1.5) d. They were assigned into 2 groups according to different surgical approaches. The observation group (41 cases) was treated through the posterolateral combined posteromedial approach while the control group (28 cases) through the posterolateral approach alone. The therapeutic effects were evaluated by comparing the 2 groups in terms of incision length, intraoperative bleeding, operation time, fracture union time, fracture reduction (evaluated by the Burrwell-Charnley radiological score), the ankle-hindfoot score of American Orthopaedic Foot and Ankle Society (AOFAS) and complications.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All the 69 cases were followed up for (16.9±4.0) months, revealing primary healing of all the incisions and no vascular injury or wound infection. The incision length [(11.2±1.8) cm] and operation time [(76.0±6.6) min] in the observation group were significantly shorter than those in the control group [(12.4±1.9) cm and (79.7±6.8) min], the excellent and good rate of reduction in the observation group (97.6%, 40/41) was significantly higher than that in the control group (89.3%, 25/28), and the ankle-hindfoot scores of AOFAS at 1, 3 and 12 months after operation in the observation group [(78.4±5.6), (79.5±2.8) and (86.9±2.1)] were significantly higher than those in the control group [(75.2±5.5), (78.0±3.2) and (85.8±2.3)] (all P<0.05). There was no significant difference in the intraoperative bleeding between the 2 groups ( P>0.05). In the control group, 2 patients developed numbness in the dorsum of foot, which gradually disappeared after 3 months of treatment, but no other complications like persistent pain or flexor contracture within 1 year after operation. Conclusion:In the treatment of Klammer type Ⅲ posterior pilon fracture, the posterolateral combined posteromedial approach can result in satisfactory therapeutic effects, because the surgical approach can fully expose the fracture and facilitate better reduction.

Objective:Childhood traumatic experiences greatly influenced the brain network activities of patients with depression,and there is an urgent need to explore the temporal dynamics for these changes.This study aims to investigate the abnormalities of resting-state electroencephalogram(EEG)microstates in eye-open state of depressed adolescents and to explore the correlations between their EEG microstates and the childhood traumatic experience. Methods:Using resting-state EEG microstate analysis,we explored the temporal dynamics of brain activity in patients with adolescent depression.This study selected 66 adolescents with depression as a patient group,and 27 healthy adolescents as a healthy control group.A modified k-means clustering algorithm was used to classify the 64-channel resting-state EEG data into different microstates.Independent sample t-tests were used to compare the microstate parameters between the 2 groups and further assciations between these parameters and childhood traumatic experience in patients were explored via using Spearman correlation. Results:In this study,significant differences were observed in the occurrence and transition probabilities of EEG microstates between the healthy control and the patient group.Notably,there was a statistically significant difference(P＜0.05)in the occurrence of microstate A across 2 groups,exhibiting a negative correlation with the emotional abuse component within the childhood trauma scores(Spearman's rho=-0.31,P=0.013).Furthermore,patient-specific,non-random transitions from microstate B to A(Spearman's rho=-0.30,P=0.015)and C to A(Spearman's rho=-0.31,P=0.013)were inversely associated with the scores of emotional abuse factors from childhood trauma in the patient group,showing statistically significant differences when comparing to the healthy controls(P＜0.05).Upon stratification into quartiles based on the emotional abuse factor scores,the occurrence of microstate A,as well as the transition rates from microstates B to A and C to A,retained statistical significance following adjustment for multiple comparisons(all P＜0.05). Conclusion:The abnormal temporal dynamics in brain networks of adolescents with depression are linked to childhood emotional abuse.Those who have suffered severe emotional abuse may show greater impairments in the brain's visual and central executive networks.EEG microstate analysis could be a potential tool for detecting adolescent depression with severe childhood trauma.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Monkeypox is a zoonotic disease.Previous studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians′ understanding of monkeypox and achieve early detection, early diagnosis, early treatment and early disposal, the committee composed of more than 40 experts in the related fields of infectious diseases, pediatrics, infection control and public health formulate this expert consensus, on the basis of the latest clinical management and infection prevention and control for monkeypox released by the World Health Organization (WHO), the guidelines for diagnosis and treatment of monkeypox (version 2022) issued by National Health Commission of the People′s Republic of China and other relevant documents.During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis and differential diagnosis, treatment, discharge criteria, prevention, case management process and key points of prevention and control about monkeypox.

Since December 2019, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infections have raged globally for more than 2 years.China has always adopted scientific and effective prevention and control measures to achieved some success.However, with the continuous variation of SARS-CoV-2 cases and imported cases from abroad, the prevention and control work has become more difficult and complex.With the variation of the mutant strain, the number of cases in children changed, and some new special symptoms and complications were found, which proposed a new topic for the prevention and treatment of SARS-CoV-2 infection in children in China.Based on the third edition, the present consensus according to the characteristics of the new strain, expounded the etiology, pathology, pathogenesis, and according to the clinical characteristics and experience of children′s cases, and puts forward recommendations on the diagnostic criteria, laboratory examination, treatment, prevention and control of children′s cases for providing reference for further guidance of effective prevention and treatment of SARS-CoV-2 infection in children in China.

Objective:To evaluate the efficacy of botulinum toxin A injection therapy with ultrasound-guided for benign masseter hypertrophy.Methods:Twenty cases (40 sides) of masseter hypertrophy were injected with botulinum toxin A, among which 10 cases were taken as experimental group and the other 10 cases as control group. The experimental group had preoperative ultrasound examination to measure the thickness of masseter, and use ultrasound-guided precise injection during the operation, and then ultrasound recheck to measure the postoperative masseter thickness; The other 10 cases of control group adopt traditional 3-point injection method.Results:The masseter thickness of the two groups at different period of times after treatment was decreased ( P<0.001), the most obviously decrease happened 4-12 weeks after injection. The mean reduction was 26.8% at 4 weeks and 28.4% at 12 weeks after injection. Masseter muscle thickness recovered by 22% at 24 weeks and by 20% at 36 weeks. The average follow-up was 6.0±2.4 months with no serious complications occurred. In the control group, there was a partial masseter bulge in one case. The satisfactory rate of the patients in the experimental group was higher than that of the control group. Conclusions:Botulinum toxin A injection therapy with ultrasound-guided for benign masseter hypertrophy is an effective treatment, which is more accurate and effective than the traditional injection method.

Objective: To analyze the spatio-temporal distribution characteristics of new HIV/AIDS cases at ages of 50 years and older in Wenzhou City from 2006 to 2020, so as to provide insights into precise control of AIDS. Methods : The data of new HIV/AIDS cases aged 50 years and older in Wenzhou City from 2006 to 2020 were collected from the China Information System for Disease Control and Prevention. The temporal and spatial distribution characteristics of new HIV/AIDS cases at ages of 50 years and older were identified using global and local spatial autocorrelation analyses and spatial-temporal scan analysis. Results: Totally 1 917 new HIV/AIDS cases aged 50 years and older were detected in Wenzhou City from 2006 to 2020, and there were 179 new HIV/AIDS cases in 58 townships ( streets ) from 2006 to 2010, 643 cases in 113 townships ( streets ) from 2011 to 2015 and 1 095 cases in 147 townships ( streets ) from 2016 to 2020, respectively. The distribution of new HIV/AIDS cases appeared positive spatial autocorrelations from 2006 to 2010 ( Moran's I value=0.05, Z=1.976, P=0.046 ), from 2011 to 2015 ( Moran's I value=0.08, Z=2.314, P=0.028) and from 2016 to 2020 (Moran's I value=0.18, Z=3.956, P=0.003 ). Spatial-temporal scan analysis identified two clusters. The primary cluster mainly covered 70 towns ( streets ) in Lucheng Distrct, Ouhai District, Longwan District, Economic and Technical Development Region, Rui' an City and Pingyang County of Wenzhou City from January 1, 2014 to December 31, 2020, with a cluster radius of 34.30 km [log likelihood ratio ( LLR )=192.84, RR=2.60, P<0.001], and the secondary cluster was located in Hongqiao Township of Yueqing City from January 1, 2009 to December 31, 2015, with a cluster radius of 0 ( LLR=90.60, RR=7.27, P<0.001 ). Conclusions The number of new HIV/AIDS cases aged 50 years and older appeared a tendency towards a rise in Wenzhou City from 2006 to 2020, with spatial clusters that were predominantly identified in urban areas, Rui' an City and Pingyang County of Wenzhou City.