ObjectiveTo observe the protective effect of Erchentang （ECT） on SiO₂-induced lung injury in rats and to explore its underlying mechanism. MethodsA rat model of lung injury was established by a single intratracheal instillation of 50 mg·mL^-1 SiO₂ suspension. Thirty male Sprague-Dawley （SD） rats were randomly assigned to five groups： control， model， low and high-dose （4.5 g·kg^-1·d^-1 and 9 g·kg^-1·d^-1， respectively） ECT， and dexamethasone （0.2 mg·kg^-1·d^-1）. All the groups were treated for 4 consecutive weeks. Histopathological alterations in the lung tissue were examined by hematoxylin and eosin （HE） staining. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px） in the lung tissue were measured through biochemical assays. The expression of key molecules in the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway was determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， Western blot， and immunofluorescence assay. The primary active components of ECT were identified by ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and their binding affinity to Nrf2/HO-1 was assessed by molecular docking. Untargeted metabolomics of the lung tissue was performed based on UPLC-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and correlation analysis was performed to identify differential metabolites and parameters closely associated with the Nrf2/HO-1 pathway. ResultsCompared with the control group， the model group exhibited a reduction in body weight gain， an increase in lung index， increased MDA content， weakened SOD and GSH-Px activities in the lung tissue， down-regulated mRNA and protein levels of Nrf2 and protein levels of HO-1 and GPX4， and an up-regulated protein level of Keap1 （P<0.05， P<0.01）. Treatment with ECT attenuated the SiO₂-induced decline in body weight （P<0.05）， alleviated inflammatory cell infiltration and silicotic nodule formation in alveoli， and reduced the MDA content and enhanced the SOD and GSH-Px activities in the lung tissue （P<0.05， P<0.01）. UPLC-MS/MS and molecular docking revealed that core components of ECT， such as hesperidin and glycyrrhizic acid， displayed strong binding affinity to Nrf2/HO-1. Molecular biological experiments demonstrated that ECT promoted nuclear translocation of Nrf2， up-regulated the mRNA and protein levels of HO-1 and GPX4， and down-regulated Keap1 expression （P<0.05， P<0.01）. Metabolomic analysis indicated that ECT reversed the SiO₂-induced aberrant expression of metabolites， including linoleic acid and glutamine （P<0.05， P<0.01）. Correlation analysis showed that Nrf2 and HO-1 were positively correlated with SOD and GSH-Px （P<0.05， P<0.01）， but negatively correlated with glutamine and serine （P<0.05， P<0.01）. ConclusionECT may activate the Nrf2/HO-1 pathway through its core active components， thereby regulating oxidative stress and metabolic disorders to ameliorate SiO₂-induced lung injury in rats. This study provides experimental evidence for ECT in the prevention and treatment of occupational lung injury.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective:To explore the clinical and genetic characteristics of X-linked intellectual disability associated with HUWE1 gene variants.Methods:A cases series study retrospectively analyzed the clinical data of 6 children with HUWE1 gene variants. The children were identified from the Third Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Henan University of Chinese Medicine, and Guangzhou Women and Children′s Medical Center of Guangzhou Medical University between April 2021 and July 2023.The data included sex, age, dysmorphic features, intellectual and motor development, seizure history, neuroimaging findings, family history, and genetic results was analyzed.Results:A total of 6 children, including 5 boys and 1 girl. The age of onset ranged from 1 day to 3 years. All children presented with varying degrees of intellectual disability, with or without motor developmental delay. Dysmorphic features were observed in 4 children, including microcephaly in 3 children. Short stature were observed in 3 children. One child was diagnosed with autism spectrum disorders and 1 child had seizures. Two boys had relevant maternal family histories of febrile seizures and mild intellectual disability, respectively. Abnormal neuroimaging findings were presented in 4 children, including cerebral dysplasia (1 child), prominent supratentorial ventricles (1 child), and mild white matter demyelination (2 children). Whole-exome sequencing identified 5 missense variants and 1 in-frame deletion variant. Five variants were novel and previously unreported (c.12290C>T, c.12701T>C, c.9875C>T, c.9641A>T and c.10313_10315del). The variants in 4 boys were maternally inherited, while the remaining 2 children had de novo variants. The child with the in-frame deletion variant (c.10313_10315del) presented with the most severe phenotype, exhibiting symptoms from 1 day of age, absent cognitive development, feeding difficulties, and congenital laryngeal chondrodysplasia. He was lost to follow-up at 3 months of age after treatment was withdrawn. The age at the last follow-up for the remaining 5 children ranged from 2 years and 10 months to 17 years. A boy with seizures died at 2 years and 10 months of age. The remaining 4 children were able to walk independently at the last follow-up, although their developmental progress was slow. Conclusions:HUWE1 gene related X-linked intellectual disability is characterized by varying degrees of developmental delay and intellectual disability, frequently accompanied by microcephaly, short stature, and occasionally by seizures and autism spectrum disorders. Missense variants are more common and the in-frame deletion variant appears to be associated with a particularly severe phenotypic presentation.

Objective:To explore the clinical and genetic characteristics of X-linked intellectual disability associated with HUWE1 gene variants.Methods:A cases series study retrospectively analyzed the clinical data of 6 children with HUWE1 gene variants. The children were identified from the Third Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Henan University of Chinese Medicine, and Guangzhou Women and Children′s Medical Center of Guangzhou Medical University between April 2021 and July 2023.The data included sex, age, dysmorphic features, intellectual and motor development, seizure history, neuroimaging findings, family history, and genetic results was analyzed.Results:A total of 6 children, including 5 boys and 1 girl. The age of onset ranged from 1 day to 3 years. All children presented with varying degrees of intellectual disability, with or without motor developmental delay. Dysmorphic features were observed in 4 children, including microcephaly in 3 children. Short stature were observed in 3 children. One child was diagnosed with autism spectrum disorders and 1 child had seizures. Two boys had relevant maternal family histories of febrile seizures and mild intellectual disability, respectively. Abnormal neuroimaging findings were presented in 4 children, including cerebral dysplasia (1 child), prominent supratentorial ventricles (1 child), and mild white matter demyelination (2 children). Whole-exome sequencing identified 5 missense variants and 1 in-frame deletion variant. Five variants were novel and previously unreported (c.12290C>T, c.12701T>C, c.9875C>T, c.9641A>T and c.10313_10315del). The variants in 4 boys were maternally inherited, while the remaining 2 children had de novo variants. The child with the in-frame deletion variant (c.10313_10315del) presented with the most severe phenotype, exhibiting symptoms from 1 day of age, absent cognitive development, feeding difficulties, and congenital laryngeal chondrodysplasia. He was lost to follow-up at 3 months of age after treatment was withdrawn. The age at the last follow-up for the remaining 5 children ranged from 2 years and 10 months to 17 years. A boy with seizures died at 2 years and 10 months of age. The remaining 4 children were able to walk independently at the last follow-up, although their developmental progress was slow. Conclusions:HUWE1 gene related X-linked intellectual disability is characterized by varying degrees of developmental delay and intellectual disability, frequently accompanied by microcephaly, short stature, and occasionally by seizures and autism spectrum disorders. Missense variants are more common and the in-frame deletion variant appears to be associated with a particularly severe phenotypic presentation.

Objective:To analyze the factors affecting the disappearance time of airway necrosis and repair time of airway scar stenosis in patients with ulceration necrosis tracheobronchial tuberculosis (TBTB Ⅱ) after standardized chemotherapy and bronchoscopic intervention.Methods:The clinical data of 222 TBTB Ⅱ patients admitted to Hunan Chest Hospital from January 2015 to December 2018 were collected, bronchoscopic interventional treatment was performed on time. The texture, blockage of lumen, granulation proliferation, airway stenosis of TBTB patients before treatment, the disappearance time of airway dead objects, scar repair time and stenosis degree after treatment were followed up. The disappearance time of airway necrosis and repair time of airway scar stenosis and its influencing factors were recorded and analyzed.Results:In 222 patients, 508 ulceration necrosis airway lesions were found under bronchoscopy, with a median of 2(1-6); 170(76.6%) cases of airway lesions had different degrees of stenosis before treatment. 79(35.6%) patients had tough necrosis, and 86(38.7%) patients had necrosis blocking the lumen; 132(59.5%) patients had granulomatosis. The disappearance time of airway necrosis after treatment was 1 to 32 weeks, and M( Q1, Q3) was 6(3, 9) weeks; the repair time of airway scar stenosis was 2 to 73 weeks, and M( Q1, Q3) was 14(10, 19) weeks; after treatment, there were 90.5%(201/222) patients with different degrees of scarring in the airways. Cox multiple analysis showed that the risk factor for the disappearance time of airway necrosis was tough tough necrosis ( HR=1.52, 95% CI: 1.10-2.10); the risk factor for the repair time of airway scar stenosis was the disappearance time of airway necrosis 6-9 weeks ( HR=2.73, 95% CI: 1.84-4.05). Conclusions:90.5% of patients with type Ⅱ TBTB developed airway scar stenosis after treatment. The median time for the disappearance of airway necrosis was 6 weeks, and the median time for the repair time of airway scar stenosis was 14 weeks. In the interventional process, attention should be paid to the removal of tough necrosis and the efficiency of necrosis removal to reduce the risk of airway scar stenosis.

Patient-specific volumetric modulated arc therapy (VMAT) quality assurance (QA) process is an important component of the implementation process of clinical radiotherapy. The tolerance limit and action limit of discrepancies between the calculated dose and the delivered radiation dose are the key parts of the VMAT QA processes as recognized by the AAPM TG-218 report, however, there is no unified standard for these two values among radiotherapy centers. In this study, based on the operational recommendations given in the AAPM TG-218 report, treatment site-specific tolerance limits and action limits of gamma pass rate in VMAT QA processes when using ArcCHECK for dose verification were established by statistical process control (SPC) methodology. The tolerance limit and action limit were calculated based on the first 25 in-control VMAT QA for each site. The individual control charts were drawn to continuously monitor the VMAT QA process with 287 VMAT plans and analyze the causes of VMAT QA out of control. The tolerance limits for brain, head and neck, abdomen and pelvic VMAT QA processes were 94.56%, 94.68%, 94.34%, and 92.97%, respectively, and the action limits were 93.82%, 92.54%, 93.23%, and 90.29%, respectively. Except for pelvic, the tolerance limits for the brain, head and neck, and abdomen were close to the universal tolerance limit of TG-218 (95%), and the action limits for all sites were higher than the universal action limit of TG-218 (90%). The out-of-control VMAT QAs were detected by the individual control chart, including one case of head and neck, two of the abdomen and two of the pelvic site. Four of them were affected by the setup error, and one was affected by the calibration of ArcCHECK. The results show that the SPC methodology can effectively monitor the IMRT/VMAT QA processes. Setting treatment site-specific tolerance limits is helpful to investigate the cause of out-of-control VMAT QA.
Calibration ; Humans ; Quality Assurance, Health Care ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated

Objective: To investigate the expression and clinical significance of long-chain non-coding RNA brain cytoplasmic RNA 1 (BCYRN1) in serum of patients with non-small cell lung cancer. Methods: 74 patients with non-small cell lung cancer (NSCLC) diagnosed and treated in our hospital were selected as the experimental group, and 50 healthy subjects were selected as the control group. The expression of BCYRN1 in serum of NSCLC and control group was detected by real-time quantitative polymerase chain reaction (qRT-PCR). The patients′ clinical pathology data were collected and followed up. To analyze the relationship between the expression of serum BCYRN1 and clinicopathological parameters of NSCLC patients, and the relationship between BCYRN1 expression in the diagnosis and prediction of NSCLC prognosis. Results: The relative expression of BCYRN1 in serum of NSCLC patients was 2.84±0.95, which was significantly higher than that of healthy controls (1.16±0.50) (P<0.05). The level of serum BCYRN1 in patients with NSCLC with tumor size >3 cm was significantly higher than that in patients with tumor size ≤3 cm (P<0.05). The level of BCYRN1 in patients with tumor node metastasis (TNM) Ⅲ+ Ⅳ was significantly higher than that in patients with stage Ⅰ+ Ⅱ (P<0.05). Patients with low differentiation and positive lymph node metastasis had higher serum BCYRN1 than those with moderate to high grade and lymph node metastasis (P<0.05). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve was 0.847 (95% CI: 0.772-0.922, P=0.000), and the sensitivity and specificity were 68.9% and 88.0%, respectively. The median progression free survival (PFS) (15 vs 21 months) and overall survival (OS) (19 vs 28 months) of patients with high and low expression of BCYRN1 were statistically significant (P<0.05). High expression of BCYRN1 was an independent risk factor for overall survival in patients with NSCLC. Conclusions BCYRN1 is highly expressed in the serum of NSCLC patients, and high expression of BCYRN1 is closely related to the poor prognosis of patients with NSCLC. It can be used as a novel biomarker and diagnostic target for NSCLC.

Circular RNAs (circRNAs), covalently closed continuous RNA loops, are generated from cognate linear RNAs through back splicing events, and alternative splicing events may gener-ate different circRNA isoforms at the same locus. However, the challenges of reconstruction and quantification of alternatively spliced full-length circRNAs remain unresolved. On the basis of the internal structural characteristics of circRNAs, we developed CircAST, a tool to assemble alter-natively spliced circRNA transcripts and estimate their expression by using multiple splice graphs.Simulation studies showed that CircAST correctly assembled the full sequences of circRNAs with a sensitivity of 85.63％-94.32％and a precision of 81.96％-87.55％. By assigning reads to specific iso-forms, CircAST quantified the expression of circRNA isoforms with correlation coefficients of 0.85-0.99 between theoretical and estimated values. We evaluated CircAST on an in-house mouse testis RNA-seq dataset with RNase R treatment for enriching circRNAs and identified 380 cir-cRNAs with full-length sequences different from those of their corresponding cognate linear RNAs. RT-PCR and Sanger sequencing analyses validated 32 out of 37 randomly selected isoforms, thus further indicating the good performance of CircAST, especially for isoforms with low abundance. We also applied CircAST to published experimental data and observed substantial diversity in circular transcripts across samples, thus suggesting that circRNA expression is highly regulated. CircAST can be accessed freely at https://github.com/xiaofengsong/CircAST.

Objective: To analyze the effect of rapid convalescence surgery on plasma radical prostatectomy in elderly patients with prostate hyperplasia. Methods: A total of 140 elderly patients with prostate hyperplasia who underwent plasma prostatectomy in our hospital from January 2016 to August 2017 were selected as subjects. Divide them into control group (70 cases) and observation group (70 cases) according to random number table method. Patients in the control group were given routine care. The observation group gave a nursing model based on the concept of rapid rehabilitation surgery on the basis of the control group. Compared the bladder irrigation time, postoperative hospitalization time, catheter removal time, anal exhaust time, first time out of bed time, complication rate, postoperative Numerical Rating Scale (NRS) pain score, bladder spasm symptom score and quality of life score between the two groups. Results: The bladder irrigation time, postoperative hospital stay, urinary catheter removal time, anal exhaust time and first time to get out of the observation group were (23.94±3.75) h, (3.49±0.46) d, (3.11±1.50) d, 6.23±3.07) h and (24.70±3.62) d, while the control group were (76.42±9.55) h, (7.06 ±0.44) d, (6.74±2.06) d, (17.41±3.48) h and (90.58±9.75) d, the above observation indexes of the observation group were significantly lower than the control group, the difference was statistically significant (t=11.918-52.998, P<0.01). The incidence of postoperative bladder spasm, bloating, hemorrhage, lung infection and urinary tract infection in the observation group were 1.429% (1/70), 2.857% (2/70), 0, 2.857% (2/70) and 7.143% (5/70), respectively, while the control group were 11.429% (8/70), 14.286% (10/70), 8.571% (6/70), 15.714% (11/70) and 24.143% (19/70), respectively. The incidence of the above complications in the observation group was significantly lower than that of the control group, the difference was statistically significant (χ²=4.275-8.499, P<0.05 or 0.01). The NRS pain score, quality of life score and bladder spasm score were observed in the observation group (31.48±3.60), (1.89±1.03), (2.25±0.47) points, while the control group were (36.20±4.22), (2.77±1.84), and (3.79±0.81) points, respectively. The above three scores in the observation group were significantly lower than those in the control group, the difference was statistically significant (t=7.119, 3.491, 13.756, P<0.01).The nursing satisfaction of patients in the observation group was 95.71% (67/70) which was significantly higher than 80.00% (56/70) of the control group, the difference was statistically significant (χ²=6.695, P<0.05). Conclusions Rapid rehabilitation surgery for patients with advanced prostatic hyperplasia with plasma prostatectomy can speed up the recovery process, relieve postoperative pain, reduce the incidence of postoperative complications, harmonious doctor-patient relationship, improve the quality of life of patients, it is worthy of extensive clinical promotion.

Hyperuricemia contributes to renal inflammation. We aimed to investigate the role of Na⁺–K⁺–ATPase (NKA) in hyperuricemia-induced renal tubular injury. Human primary proximal tubular epithelial cells (PTECs) were incubated with uric acid (UA) at increasing doses or for increasing lengths of time. PTECs were then stimulated by pre-incubation with an NKA α1 expression vector or small interfering RNA before UA (100 μg ml⁻¹, 48 h) stimulation. Hyperuricemic rats were induced by gastric oxonic acid and treated with febuxostat (Feb). ATP levels, the activity of NKA and expression of its α1 subunit, Src, NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and interleukin 1β (IL-1β) were measured both in vitro and in vivo. Beginning at concentrations of 100 μg ml−1, UA started to dose-dependently reduce NKA activity. UA at a concentration of 100 μg ml⁻¹ time-dependently affected the NKA activity, with the maximal increased NKA activity at 24 h, but the activity started to decrease after 48 h. This inhibitory effect of UA on NKA activity at 48 h was in addition to a decrease in NKA α1 expression in the cell membrane, but an increase in lysosomes. This process also involved the subsequent activation of Src kinase and NLRP3, promoting IL-1β processing. In hyperuricemic rats, renal cortex NKA activity and its α1 expression were upregulated at the 7th week and both decreased at the 10th week, accompanied with increased renal cortex expression of Src, NLRP3 and IL-1β. The UA levels were reduced and renal tubular injuries in hyperuricemic rats were alleviated in the Feb group. Our data suggested that the impairment of NKA and its consequent regulation of Src, NLRP3 and IL-1β in the renal proximal tubule contributed to hyperuricemia-induced renal tubular injury.