IKBKG is the essential modulator for nuclear factor-κB(NF-κB) signaling pathway, and mutations within this gene can lead to anhidrotic ectodermal dysplasia and immunodeficiency (EDA-ID). Here we report a male patient, who presented with mild frontal bossing, sparse hair, skin pigmentation, conical teeth, and recurrent infections involving bacteria, fungi, and viruses after one month of age, together with hypogammaglobulinemia. These symptoms were consistent with the phenotype of EDA-ID. Genetic analysis revealed a hemizygous mutation c.1249T > G (p.Cys417Gly) in exon 10 of the IKBKG gene in the patient. The mother of the patient was identified as heterozygous carriers of the same mutation. Immunological assessment revealed a significant reduction in memory B cells. The patient showed no skewed TCR diversity. PHA-induced T-cell proliferation was impaired. IFN-γ secretion by Th cells was significantly reduced after PHA stimulation. IκBα degradation rate retained the same in the patient. We summarized the clinical features of the patient and conducted immunological analysis, in order to increase pediatricians′awareness of this rare disease. For boys with early-onset recurrent infections together with ectodermal dysplasia, IKBKG mutation should be considered. In addition, genetic analysis is needed to exclude pseudogene interference and functional evaluations are required.

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Objective: To observe the therapeutic effect of mild moxibustion on irritable bowel syndrome (IBS) visceral hyperalgesiamodel rats and its regulatory effect on P2X3 receptors in the spinal cord, anterior cingutate cortex (ACC) and thalamic ventral posterolateral nucleus (VPL). Methods: Thirty 8-day-old newborn rats were randomly divided into a normal group (n=6) and a modeling group (n=24) according to the completely random number table method. Rats in the normal group were bred routinely, and those in the modeling group were subjected to preparing IBS chronic visceral hyperalgesia model using colorectal distention (CRD) in stimulation method. Rats successfully modelled were re-divided into a model group, a mild moxibustion group, a P2X3 receptor antagonist group, and a normal saline group according to the completely random number table method with 6 rats in each group. Rats in each group received corresponding interventions from the 37-day old, once a day for 7 consecutive days. Immunohistochemistry and Western blot assays were used to detect P2X3 protein expressions in the spinal cord, ACC and VPL of rats. Results: Under different intensities of CRD stimulation, the abdominal withdrawal reflex (AWR) scores of the model group were significantly increased versus the normal group (all P<0.05); the AWR scores of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group (all P<0.01). The P2X3 protein expressions in rat spinal cord, ACC and VPL tissues of the model group were significantly increased versus the normal group (all P<0.01); the P2X3 protein expressions in rat spinal cord, ACC and VPL tissues of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group (all P<0.01). Conclusion: Mild moxibustion can inhibit the P2X3 receptor expressions in the spinal cord, ACC, and VPL tissues of IBS visceral hyperalgesia model rats, which may be the mechanism of mild moxibustion in relieving the central sensitization of rats with IBS visceral hyperalgesia.

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P<0.01), increased cold spray scores(P<0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1β(IL-1β), and lactic acid(Lac) in extracellular fluids of SDH(P<0.05), dwindled tumor necrosis factor(TNF-α)(P<0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P<0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P<0.05) and CRE-M enabled the decrease in cold spray scores(P<0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P<0.05), and the levels of Glu in the extracellular fluids of SDH(P<0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P<0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P<0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.
Animals ; Central Nervous System Sensitization ; Neuralgia/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Signal Transduction ; Spinal Cord/metabolism*

ObjectiveWearing protective masks for a long time causes a large number of frontline health care workers to suffer different degrees of pressure injury or facial skin rupture in response to COVID-19. This paper aims to analyze the occurrence characteristics and related factors of pressure injury related to devices, and provide the basis for taking countermeasures. Methods There was online investigation of skin injuries caused by wearing protective equipment in medical staff. Descriptive analysis was carried out on the occurrence characteristics of pressure-induced injury, and influencing factors were analyzed through logistic regression model. ResultsThere were a total of 2901 valid questionnaires. The results showed that the incidence of pressure injury caused by protective equipment was 26.34%, mainly in the bridge of the nose (20.41%), cheek (20.23%), auricle (17.82%) and forehead (8.86%). Multivariate Logistic regression model analysis showed that the major associated factors, which presented increasing risk, were sweating and dampness (OR=12.72, 95%CI 8.36-17.30), wearing level-3 protective equipment (OR=3.55, 95%CI 2.47-5.08), wearing level-2 protective equipment (OR=3.37, 95%CI 2.47-4.60), wearing time (OR=1.29, 95%CI 1.05~1.58) and occupation (OR=1.57, 95%CI 1.00~2.49). Conclusion There is the high incidence of pressure injuries to health care workers caused by protective equipment against COVID-19. The main risk factors for facial stress injury of medical staff are sweating and dampness, wearing level-3 and level-2 protective equipment and wearing time.

OBJECTIVE: To evaluate the efficacy and safety of topical delivery of modified Da-Cheng- Qi Decoction (, MDCQD) by low-frequency ultrasound sonophoresis (LFUS) in patients with refractory metastatic malignant bowel obstruction (MBO) using an objective performance criteria (OPC) design. METHODS: Fifty patients with refractory metastatic MBO were enrolled in this open-label single-arm clinical trial. Alongside fasting, gastrointestinal decompression, glycerol enema, intravenous nutrition and antisecretory therapy, a 50 g dose of MDCQD (prepared as a hydrogel) was applied through topical delivery at the site of abodminal pain or Tianshu (S 25) using LFUS for 30 min, twice daily for 5 consecutive days. The overall outcome was the remission of intestinal obstruction, and improvement on abdominal pain, abdominal distention, nausea and vomiting scores. Indicators of safety evaluation included liver and renal function as well as blood coagulation indicators. RESULTS: Among 50 patients, 5 patients (10%) showed complete remission of intestinal obstruction and 21 patients (42%) showed improvement of intestinal obstruction. The overall remission rate of bowel obstruction was 52%. The results of the symptom score, based on the severity and frequency of the episode, are as follows: 26 patients (52%) showed improvment on symptom scores, 20 patients (40%) did not respond to treatment, and 4 patients (8%) discontinued treatment due to intolerance. No serious adverse effects or abnormal changes on liver and renal function or blood coagulation were observed. CONCLUSION Topical delivery of MDCQD at 100 g/day using LFUS can improve the treatment response in patients with refractory metastatic MBO.
Administration, Cutaneous ; Adult ; Aged ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Intestinal Neoplasms ; complications ; secondary ; Intestinal Obstruction ; drug therapy ; etiology ; Male ; Middle Aged ; Ultrasonic Therapy ; methods

BACKGROUND: Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown. METHODS: Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 μL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 μL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed. RESULTS: Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 down-regulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 down-regulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin β1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9). CONCLUSIONS Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis.

Asymptomatic Infections ; Betacoronavirus ; Carrier State ; Coronavirus Infections ; transmission ; Female ; Humans ; Middle Aged ; Pandemics ; Pneumonia, Viral ; transmission

Objective: To systemically investigate the volatile organic compounds (VOCs) of Viola yedoensis, and to compare the VOCs differences of V. yedoensis obtained by the needle trap, static headspace and hydrostillation methods. Method: The needle trap, static headspace and hydrostillation methods coupled with gas chromatography-mass spectrometer (GC-MS) were developed for isolation and identification of the VOCs in V. yedoensis. The relative content of each component was obtained by peak area normalization with a triple-bed needle packed with Tenax, Carbopack X and Carboxen 1000 sorbents. Result: The 112 compounds were trapped by using needle trap, mainly moderate volatile components, including aldehydes, ketones, alcohols, monoterpenes, sesquiterpenoids and aromatic compounds. The static headspace and hydrodistillation methods were allowed to obtain 37 (mainly the high-volatile components) and 78 compounds (mainly low-volatile components), respectively. Only 13 common volatile components were detected in all these three methods. Conclusion: The results clearly demonstrated that the needle trap method is an alternative method for sampling VOCs of herbs, characterized by fast analysis, simple operation, good enrichment effect and high sensitivity.These three methods for VOCs analysis are complementary for each other.

Objective To explore a more minimally invasive and economical treatment for atrial septal defect (ASD) through comparing the efficacy and safety in percutaneous transcatheter closure of atrial septal defect procedure,guided by transthoracic echocardiography(TTE) and transesophageal echocardiography(TEE).Methods From March 2014 to September 2017,197 patients with ASD who were feasible to treated with percutaneous transcatheter closure procedure evaluated by preoperative ~ were recruited.TTE showed ASD belonged to secundum(central type) with a maximal diameter range from 2 mm to 35mm,including 82 cases of the ASD without aortic rim.There were 106 patients(47males and 59 females including 37 ASD without aortic rim) with a mean age of 14.2 years(6 months-59 years) old and a mean body weight of 29.5(8.5-64.0)kg were performed percutaneous transcatheter closure of ASD guided by TEE under general anesthesia and endotracheal intubation,and 91 patients(41males and 50 females with 45 ASD without aortic rim inside) with a mean age of 13.8 years(9 months-65 years) old and a mean body weight of 30.4 (9.5-61.0)kg were treated with the percutaneous transcatheter procedure guided by TTE when patients in waking state of local anesthesia(general anesthesia were adopted in patients under 12 years old without intubation).The size of the occluder was selected on the basis of the maximal diameter plus 2-6mm.All 197 cases intraoperation and postoperation data were collected,including complications 、operation time 、operation room stay time and total cost.Results 1 patients in 106 cases of the the TEE group were transferred to small incision on the chest performing transthoracic transcatheter closure of ASD because the difficult stuck of the occluder.3 patients in TEE group transferred to repair under cardiopulmonary bypass(CPB) via small incision on the chest because the difficult stuck of the occluder even in using transthoracic transcatheter closure way.86 patiens in TTE group successfully treated with percutaneous transcatheter closure,and there were 5 failed cases including 2 patients who transferred to TEE guided because of the poor imaging of TTE,another 2 cases treated with transthoracic transcatheter closure of ASD because the difficult stuck of the occluder,and 1 patient performed ASD repair procedure under CPB via small incision on the chest because of the huge ASD without aortic rim and difficult stuck of the occluder.All the 197 patients were cured and discharge from hospital,and there were no complications.There was no significant difference in age,weight,and maximum diameter of ASD between TEE group and TTE group (P ＞ 0.05).Follow-ups were conducted by TTE at month 3 post-operation,and all 197 cases performed no residual shunt of ASD,there were no difference between 2 group.The stay time in the operation room was(68.2 ± 17.3) min in group TEE and (34.7 ± 16.8) min in group TTE,there was obviously shortened the stay time in operation room(P ＜0.01).The total cost of the TTE group was(24.2 ± 2.1) thousand yuan,and the group TEE was(29.3 ± 1.4) thousand yuan,and the cost was significantly reduced in TTE group (P ＜ 0.01).Conclusion The treatment of percutaneous transcatheter closure of ASD guided by TTE is effective and safe,and the feature of more non-invasive and socioeconomic benefits show a broad application prospect.