The nucleus tractus solitarii (NTS) is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity. Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure (BP). Here, we investigated whether phenylethanolamine N-methyltransferase (PNMT)-expressing NTS (NTS^PNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTS^PNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTS^PNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTS^PNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTS^PNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex. Overall, we revealed the neuronal phenotype- and circuit-specific mechanisms underlying the contribution of NTS^PNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism* ; Blood Pressure/physiology* ; Phenylethanolamine N-Methyltransferase/metabolism* ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism*

Humans ; Mycobacterium tuberculosis/genetics* ; Microspheres ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Fluoroquinolones ; Drug Resistance, Bacterial/genetics* ; Tuberculosis, Multidrug-Resistant/microbiology*

Objective: To report the clinical features and genetic variations of monogenic lupus caused by DNASE1L3 deficiency and to introduce preliminary experience on diagnosis and treatment for this disease. Methods: Clinical data of 3 children from the same pedigree were collected who were diagnosed with DNASE1L3 defect-associated monogenic lupus in August 2020 by Department of Pediatrics, Peking Union Medical College Hospital referred from Department of Pediatrics, Boai Hospital of Zhongshan. DNA was extracted from the peripheral blood of the patients and their parients to perform genetic analysis and confirmation. Six interferon-stimulated genes were relatively quantified to examine the activation of the type I interferon signaling. "DNASE1L3" "systemic lupus erythematosus" and "SLE" were searched in PubMed, Wangfang Data, CNKI databases for related reports from database established date to June 2022. Spectrum of genetic variations and clinical phenotypes were analyzed in combination with this pedigree. Results: Case 1, a 14-year-old girl with edema, hematuria, and heavy proteinuria, presented with membranous nephropathy. Case 2, the 12-year-old younger brother of case 1 with hematologic, cardiac, pulmonary, renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody and low complement C3, manifested with systemic lupus erythematosus. Case 3, the 8-year-old younger sister of case 1 with hematologic, cardiac, pulmonary and renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody, and low complement C3 and C4, manifested with systemic lupus erythematosus. Genetic testing revealed that all 3 patients carried homozygous deletions in exons 3 and 4 on DNASE1L3 gene. Interferon scores were elevated in case 1, 2 and their parents but normal in case 3. All 3 patients were diagnosed with monogenic lupus caused by DNASE1L3 defects. Literature searching identified 10 relevant publications in English and 0 publication in Chinese, involving 42 patients from 18 pedigrees (including the 3 cases from this pedigree). Nine variants were found: c.289_290delAC (p.T97Ifs*2), c.643delT (p.W215Gfs*2), c.320+4delAGTA, c.321-1G>A, Ex5 del, c.433G>A, c.581G>A (p.C194Y), c.537G>A (p.W179X), and Ex3-4 del. The hotspot variants were c.643delT (43% (36/84)) and c.289_290delAC (36% (30/84)). Kidney was affected in 31 cases (74%) of the 42 cases. Among the 25 patients, joints were affected in 16 cases (64%), fever were reported in 13 cases (52%) hematologic system was involved 13 cases (52%), rash was present in 10 cases (40%), intestinal tract was involved in 8 cases (32%), lungs were involved in 6 cases (24%), eyes were involved in 4 cases (16%), and the heart was involved in 4 cases (16%). The 2 cardiopulmonary affected patients from literature showed poor prognosis, with 1 died, and 1 right heart failure. Conclusions: The clinical manifestations of monogenic lupus caused by DNASE1L3 defect are highly heterogenous, primarily with renal, blood, joint, intestinal, and cardiopulmonary involvement. There is no correlation between the genotype and the phenotype. DNASE1L3 defects were predominantly mediated by null varations including nonsense, splicing, frameshift and exon deletions. The hotspot variants are c.643delT and c.289_290delAC. DNASE1L3 defects should be cautioned in early-onset lupus-like patients with renal, joint and hematologic involvement. Cardiopulmonary involved patients require close monitoring for poor prognosis. Copy number variations should be carefully analyzed after negative whole exome sequencing.
Male ; Child ; Humans ; Homozygote ; Complement C3 ; Antibodies, Antinuclear ; DNA Copy Number Variations ; Sequence Deletion ; Interferons ; Lupus Erythematosus, Systemic/genetics* ; Antiviral Agents ; Endodeoxyribonucleases

OBJECTIVE: To compare the clinical efficacy of staged surgery on Sanders Ⅳ calcaneal fractures with soft tissue Ⅲ swelling. METHODS: The clinical data of 76 patients with Sanders type Ⅳ closed calcaneal fracture with soft tissue three-degree swelling treated from June 2017 to May 2020 was retrospectively analyzed, including 54 males and 22 females, aged from 25 to 50 (38.16±10.24) years. The patients were divided into observation group and control group according to different treatment methods. Twenty-four patients in the observation group were treated by staged surgery stageⅠclosed prying traction reduction and Kirschner wire fixation, stageⅡopen reduction and internal fixation with titanium plate, including 17 males and 7 females, aged from 25 to 50 (36.12±9.56) years. There were 52 patients in the control group, including 37 males and 15 females, aged from 25 to 50 (38.32±10.67) years, these patients were treated with open reduction and internal fixation with titanium plate after the dermatoglyphic signs appeared. The swelling subsidence time, the length of hospitalization days, and the incidence of postoperative incision complications were compared between two groups. The Bhler angle, Gissane angle, and calcaneal varus angle were measured by X-ray before and 6 months after operation. American Orthopedic Foot and Ankle Society (AOFAS) about the ankle hindfoot score was used to evaluate the clinical efficacy. RESULTS: All 76 patients were followed up for 8 to 12 (9.52±2.01) months. The swelling subsidence time and hospitalization days in observation group were (12.12± 3.24) d and (24.53±6.44) d, respectively, which in control group were (15.16±4.16) d and (29.46±9.61) d, with statistical difference between two groups ( CONCLUSION Compared with open reduction and internal fixation with titanium plate after the appearance of dermatoglyphic signs, staged surgery for Sanders type Ⅳ calcaneal fractures with soft tissue three-swelling does not increase the risk of soft tissue complications, and can significantly shorten the patient's swelling subsidence time and hospitalization days, improve the quality of fracture reduction and short term function, and relieve pain.
Ankle Injuries ; Calcaneus/surgery* ; Female ; Foot Injuries ; Fractures, Bone/surgery* ; Humans ; Male ; Retrospective Studies

OBJECTIVES: To study the effects of parent-child painting and creative crafting therapy on the core symptoms of preschool children with mild-to-moderate autism spectrum disorder (ASD) and the parenting stress and hope level of their mothers. METHODS: A total of 56 preschool children with mild-to-moderate ASD and their mothers were divided into an experimental group and a control group using the block randomization method, with 28 pairs in each group. The subjects in the control group received an applied behavior analytic intervention and those in the experimental group received parent-child painting and creative crafting therapy in addition to the intervention in the control group. The intervention time was 20 weeks for both groups. Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Parenting Stress Index-Short Form (PSI-SF), and Herth Hope Index (HHI) were used to evaluate the core symptoms of children and the parenting stress and hope level of their mothers before and after 20 weeks of intervention. RESULTS: Forty-nine child-mother pairs completed the study (25 pairs in the intervention group and 24 pairs in the control group). The children in the experimental group had significantly lower scores of social interaction, language, social communication, and social motivation and total scores of ABC and SRS compared with those in the control group ( CONCLUSIONS The combination of applied behavior analytic intervention with parent-child painting and creative crafting therapy can more effectively improve the core symptoms and social interaction of preschool children with mild-to-moderate ASD, reduce the parenting stress of mothers and improve their hope level.
Autism Spectrum Disorder/therapy* ; Child, Preschool ; Female ; Humans ; Mothers ; Parent-Child Relations ; Parenting ; Prospective Studies

OBJECTIVE: To evaluate the protective effects of salvianolate on percutaneous coronary intervention (PCI) related myocardial injury or myocardial infarction after elective PCI in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients. METHODS: A total of 149 patients with NSTE-ACS who underwent elective PCI were enrolled. The patients were randomly allocated in a 1:1 ratio to the salvianolate group (74 cases) or the control group (75 cases). After exclusion criteria of coronary angiography, 60 patients with PCI therapy remained in the salvianolate group and 68 in the control group. The incidence and the severity of PCI related myocardial injury or myocardial infarction, in addition to major adverse cardiac events (MACEs) during 1 year follow-up after PCI were studied between the two groups. Multivariate logistic regression analysis was used to determine the independent factors for PCI related myocardial injury or myocardial infarction after elective PCI. RESULTS: Compared with the control group, salvianolate treatment reduced the incidence of PCI related severe myocardial injury or myocardial infarction (11.7% vs. 26.5%, P=0.035). The rate of MACEs or all-cause death within 1 month or 1 year after the procedure was not significantly different between the two groups. CONCLUSIONS Periprocedural treatment with salvianolate reduces the incidence of PCI related severe myocardial injury or myocardial infarction, although it does not influence clinical prognosis. [Chinese clinical trial registry: ChiCTR1800016992].

Purpose: Transarterial chemoembolization (TACE) delivers cytotoxic drugs intra-arterially and induces ischemic necrosis by arterial embolization. Embolization is achieved using a variety of agents that differ widely in particle size and range, deformation, and in vivo arterial distribution. The clinical significance of these differences has not been thoroughly characterized. The present study is to compare the efficacy of Embosphere and Embozene microspheres in TACE therapy for hepatocellular carcinoma. Materials and Methods: This retrospective study includes 108 hepatocellular carcinoma (HCC) patients who received TACE/doxorubicin with Embozene (70 patients) or Embosphere (38 patients) at a single medical center. Patient outcomes, including liver function, tumor size, tumor response, and complications after treatment, were analyzed. The change in total target lesion size and tumor response was evaluated according to embolization agent and clinical characteristics. Results: The postoperative glutamate oxaloacetate transaminase (mean, 194.5 vs. 147.5; p=0.032) and bilirubin (mean, 1.11 mg/dL vs. 0.73 mg/dL; p=0.016) were higher among patients treated with Embozene, the decrease in the number (55.86±25.55% vs. 41.81±38.51%, p=0.027) and size (56.37±25.91 mm vs. 43.44±37.89 mm, p=0.001) of liver tumors relative to baseline was greater in these patients than in those treated with Embosphere. These greater antitumor effects were achieved using lower doses of doxorubicin than for treatment with Embozene. Minor complications were more common among patients treated with Embosphere than with Embozene. Conclusion These results suggest that Embozene is more efficacious than Embosphere for HCC treatment using TACE/doxorubicin.

Objective Studies are rarely reported on the effect of short peptides of the pigment epithelium derived factor (PEDF) on the proliferation of human cutaneous squamous (SCL-1) cells. The purpose of this study is to investigate segmented cloning and expression of the PEDF protein and observe its effect on the proliferation of human SCL-1 cells. Methods The target genes of PEDF1, PEDF2 and PEDF3 were amplified by PCR and the recovered fragments subjected to double digestion of NheⅠ and Hind Ⅲ and inserted into the pET28a(+) plasmid. The product was transformed into human E coli BL21 and induced to express, followed by isolation and purification of the fusion protein. CCK-8 assay was used to detect the proliferation of the SCL-1 cells with PEDF1, PEDF2 and PEDF3 at 100, 400, 800 and 1000 nmol/L at 24, 48 and 72 hours. Results The prokaryotic expression vectors of PEDF1, PEDF2 and PEDF3 were successfully constructed, and their fusion proteins prepared, with the molecular weight of 18 000, 17 000 and 13 000, respectively. The proliferation of the SCL-1 cells was significantly decreased in the 800 and 1000 nmol/L PEDF3 groups compared with that in the 0 nmol/L PEDF3 group at 24 hours (0.16 ± 0.03 and 0.78 ± 0.07 vs 1.00 ± 0.00, P < 0.05), inhibited in a concentration-dependent manner in the 400, 800 and 1000 nmol/L PEDF3 groups at 48 hours (P < 0.05), markedly lower in the 800 and 1000 nmol/L PEDF3 groups at 72 hours (0.53 ± 0.05 and 0.51 ± 0.05) than in the in the 400 and 0 nmol/L PEDF3 groups (0.60 ± 0.05 and 1.00 ± 0.00) (P < 0.05). Conclusion The PEDF fusion proteins were successfully segmentally cloned and expressed and PEDF3 inhibited the proliferation of SCL-1 cells, which has paved the ground for further screening of active functional short peptides of PEDF.