Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

Objective:To explore the clinical features and genetic etiology for a child with developmental delay, impaired growth, facial dysmorphism, and axonal neuropathy (DIGFAN).Methods:A child who was admitted to the Second Affiliated Hospital of Guangxi Medical University on March 22, 2021 was selected the study subject. Clinical data of the child was collected. Following extraction of genomic DNA, the child and his parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 10-year-and-9-month-old boy, had manifested with short stature, intellectual disability, delayed speech, motor and language development, and facial dysmorphism. WES and Sanger sequencing revealed that he has harbored a novel de novo c. 800T>C (p.Leu267Pro) variant of the MORC2 gene. The Leucine at position 267, which is highly conserved among various species, is located in the S5 domain of ribosome protein in the ATPase binding region of MORC2. And the Leu267Pro may affect the function of MORC2 by altering the spatial conformation and activity of ATPase. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 800T>C variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). Conclusion:The MORC2: c. 800T>C (p.Leu267Pro) variant probably underlay the pathogenesis of DIGFAN syndrome in this child.

Objective To explore the clinical significance regarding monitoring circulating tumor cells in early stage lung adenocarcinoma.Methods From November 2015 to January 2018,48 patients with stage Ⅰ lung adenocarcinoma were included in the study.BCAR1 expression in CTCs in peripheral blood were detected by using CanPatrolTM and RNA in situ hybridization detection.Results Among the 48 cases,CTCs and BCAR1 (+)-CTCs were detected in 41 cases(85.4％) and 30 cases(62.5％),respectively.Number of BCAR1 (+)-CTCs seemed to be significantly positively related to that of CTCs.BCAR1 (+)-CTCs were more likely to appear in the M-CTCS and E&M-CTCS.BCAR1 (+)-CTCs remarkably increased in three relapsed cases.Furthermore,there were 19 stable cases who had postoperative CTCs data:(1) in 12 patients,either CTCs or BCAR1 (+)-CTCs were significantly reduced or remained stable;(2) in 7 cases,CTCs increased,but BCAR1 (+)-CTCs remained stable in 2 cases,reduced in 1 case,and the other 4 cases underwent close follow-up.Conclusion Evaluation of BCAR1 (+)-CTCs possibly can be contributive to prediction of early lung adenocarcinoma recurrence or metastasis.

Objective To evaluate the sensitivity and specificity of enzyme assays,and to provide disease spectrum of lysosomal storage diseases (LSDs).Methods Three thousand three hundred and sixty-four high risk individuals were screened for 24 LSDs at Guangzhou Women and Children's Medical Center between January 2009 and December 2016.Twenty-two kinds of enzyme activities from peripheral blood leucocytes or plasma were measured by using the fluorometry or colorimetry of corresponding artificial substrates,screening for 24 LSDs diseases.Measurement data were represented by (x) ± s,and count data were expressed as a percentage or composition ratio.Results A total of 283 subjects were diagnosed with 18 different kinds of LSDs,and the positive rate of high-risk screening was 8.4％.Among the identified patients,172 cases (60.8％) were mucopolysaccharidosis (MPS),79 cases (27.9％) were sphingolipidoses,18 cases (6.4％) were Pompe diseases,10 cases (3.5％) were affected with mucolipidoses,3 cases (1.1％) were glycoprotein storage diseases,and 1 case(0.4％) was Wolman disease.Of the MPS cases,there were 75 cases of MPS Ⅱ (43.6％),45 cases of MP5 ⅣA (26.2％),24 cases of MPS Ⅵ (14.0％) and 20 cases of MPS Ⅰ (11.6％).Gaucher disease (23/79 cases,29.1％) and metachromatic leukodystrophy (MLD) (21/79 cases,26.6％) were common in sphingolipidoses group.Both the sensitivity and specificity of enzyme assays on peripheral blood leucocytes for LSDs were 100％.Conclusions The most common kinds of LSDs are MPS Ⅱ,MPS Ⅳ A,MPS Ⅵ,Gaucher disease,MLD and Pompe disease.Leukocyte enzymology analysis of high-risk screening LSDs has high sensitivity and specificity.

Objective To investigate the imaging feature of hippocampal sclerosis (HS), and evaluate the diagnostic value of double inversion recovery (DIR) sequence at 3.0 T MR for its diagnosis. Methods Twelve patients with unilateral HS proven by pathology and 12 healthy volunteers were enrolled. All patients received DIR, fluid attenuated inversion recovery (FLAIR) and T2 TSE sequences scans on oblique coronal plane vertical to the hippocampal axis on a 3.0 T MR scanner. Regions of interest (ROI) were set respectively in ipsilateral and contralateral hippocampi hippocampi in patients with HS, and the bilateral hippocampi in healthy volunteneers were placed respectively. Signal to noise ratio (SNR), contrast to noise ratio (CNR), ratio of signal intensity (RSI) and asymmetry index (AI) of each ROI in all hippocampi were calculated and compared among the three sequences. Statistical analysis was performed with one-way ANOVA. Results On DIR images, ipsilateral hippocampal lesions demonstrated extremely high signal intensity. Relative signal intensity of ipsilateral hippocampal lesions, contralateral hippocampi and the hippocampi in control groups healthy volunteneers were 1.50±0.05, 1.26±0.03, 1.18±0.05 (F=172.609,P=0.000), respectively. SNR of ipsilateral hippocampal lesions on DIR, FLAIR and T2 TSE sequences were 84.13±16.62, 50.90±12.38, 63.25±15.46 (F=15.185,P=0.000), respectively. CNR of hippocampus were 13.72±3.73, 6.67±3.02, 7.33±3.65 (F=14.985,P=0.000), respectively.In HS patients, RSI and AI of the ipsilateral hippocampal lesions and contralateral hippocampi among the three sequences did not show statistically significant difference(P=0.078). Conclusions HS manifests extremely high signal intensity on DIR images. On DIR images, the SNR and CNR of HS were higher than those on conventional MR sequences which provide valuable information for the diagnosis of HS.

Objective To investigate the evolution of monkey brain isehemic penumbra(IP)area.Methods Seyen monkeys were used to make middle cerebral artery occlusion(MCAO)model by interventional methods.CT perfnsion imaging,MR diffusion weighted-imaging (DWI),perfusion weighted imaging(PWI)and T2W1 were performed at 1,5,10;15,20 and 24 h after MCAO respectively.Four regions of interest of infarct lesion were measured.Point 1 was at the infarct core.point 3 was at the infamt margin,and point 2 was at the midpoint between point 1 and 3.Point 4 demonstrated normal signal intensity adjacent to high signal intensity.Parameters measured included cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), apparent diffusion coefficient (ADC) and negative enhancement integral (NEI).The relative ratios between infarct lesions and the corresponding contralateral normal brain were calculated(rCBF, rCBV, rMTY, rADC and rNEI).The IP areas were calculated by two methods: IP thresholds combined with self-made computer software, and PWI( MrlT)-DWI mismatch.ANOVA and ROC analysis were used. Results Five of 7 monkey MCAO models were made successfuUy. There were signitlcanfly difference of rCBF and rNEI within 20 h, of rCBV within 15 h, of rADC within 10 h, of rMTT at24 h (P＜0.05).ROI 1,2 and 3 values as following: rCBF: 1 h(0.160 ±0.034, 0.310 ±0.037,0.540±0.107), 5 h(0.098±0.029, 0.157 ± 0.052, 0.427 ±0.116), 10 h(0.072 ±0.023, 0.097 ±0.028, 0.209 ± 0.070), 15 h(0.054 ± 0.017, 0.069 ± 0.015, 0.166 ± 0.049), 20 h(0.038 ± 0.011,0.026± 0.007, 0.092±0.013); rNEI: 1 h(0.219 ± 0.085, 0.303 ± 0.099, 0.463 ± 0.132), 5 h (0.143±0.057, 0.195± 0.055, 0.348±0.127), 10 h(0.127 ± 0.029, 0.171 ± 0.058, 0.259 ±0.079), 15 h(0.128 ±0.024, 0.164 ±0.031, 0.217 ±0.030), 20 h(0.075±0.019, 0.147±0.058,0.129 ±0.045) ; rCBV: 1 h(0.594 ± 0.199, 0.804 ± 0.099, 1.021 ±0.169), 5 h(0.457±0.103,0.462±0.145, 0.815±0.201), 10 h(0.222 ±0.046, 0.249±0.065, 0.529 ±0.135), 15 h(0.201 ±0.047, 0.187 ±0.055, 0.361 ±0.083) ; rADC: 1 h(0.515 ±0.115, 0.667±0.097, 0.761 ±0.106),5 h(0.488 ±0.100, 0.539 ±0.107, 0.674 ±0.099), 10 h(0.456 ±0.057, 0.549 ±0.049, 0.590 ±0.081 ) ; 24 h rMTT(4.163 ± 1.179, 4.192± 1.607, 2.397±0.909).The thresholds of IP were 0.203 of rCBF, 0.483 of rCBV, 0.571 of rADC and 0.250 of rNEI respectively.The values measured using the method of IP thresholds combined with software were larger than PWI(MTr)-DWI mismatch region before 15 hours, but were smaller at 20 h and 24 h. The area of IP was 20%-38% of infarct area at 1 h,15%-35% at 5-10 h, 13%-25% at 15 h, 9%-15% at 20 h, and 3%-12% at 24 h.Conclusion The time window of IP in monkey MCAO model was 15%-20 hours.At the early phase of infarction, IP was present within the region of high signal intensity on DWI.PWI-DWI mismatch method could not estimate IP areas accurately.Areas evaluated with CT perfusion (MrIT) and DWI mismatch were much closer to the actual IP areas.