Background Some occupational asthma patients have a high risk of poor prognosis, and early assessment and screening of the high-risk groups with poor prognosis are crucial. Objective To evaluate the prognostic value of serum histone deacetylase 2 (HDAC2) and soluble suppression of tumorigenicity 2 (sST2) in occupational asthma patients. Methods An occupational asthma group containing 100 occupational asthma patients admitted to Baodi District People's Hospital of Tianjin between March 2020 and March 2023 were divided into a mild group of 38 cases, a moderate group of 40 cases, and a severe group of 22 cases, and re-divided into a good prognosis group of 66 cases and a poor prognosis group of 34 cases. During the same period, 98 ordinary asthma patients were recruited as the ordinary asthma group and 98 healthy individuals as the healthy control group. A multivariate logistic regression analysis was performed to investigate the relationships of prognosis with HDAC2, sST2, patients separated from allergen after diagnosis, age, body mass index (BMI), gender, smoking history, years of work, family history of asthma, allergy history, good medication adherence, regular follow-up visits. Receiver operating characteristic (ROC) curve was used to evaluate potential predictive value of serum HDAC2 and sST2, and Z-test was used to compare the area under the curve (AUC). Results The serum HDAC2 concentration [(11.13±2.26) ng·L⁻¹] in the occupational asthma group was lower than that in the ordinary asthma group and the healthy control group [(16.72±3.15), (22.75±4.92) ng·L⁻¹], while the sST2 concentration [(16.64±3.47) ng·L⁻¹] in the occupational asthma group was lower than that in the ordinary asthma group and the healthy control group [(12.49±2.31), (9.04±1.98) ng·L⁻¹] (F=256.623, 201.091; P<0.05). The serum HDAC2 concentration [(7.60±1.67) ng·L⁻¹] in the severe group was lower than that in the moderate and the mild groups [(10.02±2.35), (14.34±3.88) ng·L⁻¹], while the sST2 concentration [(24.65±6.31) ng·L⁻¹] in the severe group was lower than that in the moderate and the mild groups [(16.88±3.50), (11.75±3.09) ng·L⁻¹](F=41.731, 67.564; P<0.05). The serum HDAC2 and the proportion of patients separated from allergen after diagnosis in the poor prognosis group were lower than those in the good prognosis group [(8.19±1.94) vs (12.64±3.29) ng·L⁻¹, 64.71% vs 93.94%], and the serum sST2 in the poor prognosis group was higher than that in the good prognosis group [(21.67±5.86) vs (14.05±3.62) ng·L⁻¹] (t/χ²=7.253, 12.177, 8.020; P<0.05). HDAC2 and sST2 were associated with poor 6-month prognosis in the occupational asthma patients (P<0.05). The AUCs for predicting poor prognosis in the occupational asthma patients by serum HDAC2 and sST2 concentrations alone and in combination were 0.826, 0.838, and 0.902, respectively. Conclusion The serum HDAC2 concentration decreases and the sST2 concentration increases in patients with occupational asthma, and these two indicators may have important predictive value for poor disease prognosis.

Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease with complex and diverse pathogenesis， and there is no effective treatment or specific drugs for its clinical treatment. In recent years， its incidence has been on the rise， and it has become the earnest expectation of medical researchers in China and abroad that related patients could be treated. AMP-activated protein kinase （AMPK） functions to regulate cellular energy homeostasis and mitochondrial homeostasis. When activated， it has a good intervention effect on NAFLD progression with lipid metabolism disorders and mitochondrial homeostasis disorders. For NAFLD， the activation of AMPK can inhibit the production of new lipogenesis in the liver， promote the oxidation of fatty acids in the liver， and enhance the mitochondrial function of adipose tissues. As a key target of metabolic diseases， AMPK can also improve apoptosis， liver fibrosis， autophagy， and inflammation. Traditional Chinese medicine （TCM） is good at treating diseases from multiple targets and multiple pathways and is also commonly used in the treatment of chronic liver disease in clinical practice. A large number of in vitro and in vivo experimental studies on NAFLD have shown that TCM monomers have good prospects for the treatment of NAFLD through the AMPK signaling pathway， including glycosides， phenols， alkaloids， flavonoids， quinones， terpenoids， and lignans， which are natural activators of AMPK. This study reviewed the research progress on TCM monomers in regulating the AMPK pathway to prevent and treat NAFLD， providing a broader perspective for TCM treatment of NAFLD.

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a child with acute form of tyrosinemia type I (TYRSN1). METHODS: A child with TYRSN1 who presented at the Gansu Provincial Maternal and Child Health Care Hospital in October 2020 was selected as the subject. The child was subjected to tandem mass spectrometry (MS-MS) and urine gas chromatography-mass spectrometry (GC-MS) for the detection of inherited metabolic disorders, in addition with whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing. RESULTS: The child's clinical features included abdominal distension, hepatomegaly, anemia and tendency of bleeding. By mass spectrometry analysis, her serum and urine tyrosine and succinylacetone levels have both exceeded the normal ranges. WES and Sanger sequencing revealed that she has harbored c.1062+5G>A and c.943T>C (p.Cys315Arg) compound heterozygous variants of the FAH gene, which were inherited from her father and mother, respectively. Among these, the c.943T>C was unreported previously. CONCLUSION Considering her clinical phenotype and result of genetic testing, the child was diagnosed with TYRSN1 (acute type). The compound heterozygous variants of the FAH gene probably underlay the disease in this child. Above finding has further expanded the spectrum of FAH gene variants, and provided a basis for accurate treatment, genetic counseling and prenatal diagnosis for her family.
Female ; Humans ; Gas Chromatography-Mass Spectrometry ; Genetic Testing ; Mutation ; Phenotype ; Prenatal Diagnosis ; Tyrosinemias/genetics* ; Child

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

Objective:We conducted a real-world multi-center clinical study with a large sample size to comprehensively evaluate the performance of three commercial hepatitis C virus (HCV) core antigen assays. The study aimed to evaluate the performance for their use in HCV infection screening, and to provide clues for further improving the sensitivity and specificity of the assays.Methods:Key performance indicators including the lower limit of detection (LOD), diagnostic sensitivity, and specificity of three HCV antigen assays (the Architect, Laibo, and ChemClin HCV core antigen assays) were evaluated using commercial seroconversion panels reflecting early HCV infection and clinical routine serum samples of outpatients and inpatients from 3 tertiary hospitals from January 2018 to April 2022. Factors that affect the performance indicators were further investigated.Results:The window period for detecting HCV infection with the three antigen assays was equal to or slightly longer than that of the RNA assay, but all are shorter than that of the anti-HCV assay. There was a good linear positive correlation between HCV core antigen and HCV RNA levels in treatment naive patients with hepatitis C ( r=0.90, P<0.01). For the most common genotype 1b strain in China, the LOD of the three HCV assays were equivalent to 531 IU/ml (Architect), 3,698 IU/mL (Laibo), and 4,624 IU/mL (ChemClin) HCV RNA, respectively. Due to the skewed distribution of HCV RNA levels in treatment-naive hepatitis C patients, more than 95% of the patients had viral loads higher than 6 166 IU/ml. Therefore, the three HCV antigens assays still maintained a satisfactory diagnostic sensitivity (94.33%-99.40%). Among 54 immunodeficient patients (leukemia patients) with HCV infection, 9% (5/54) had negative anti-HCV results, while the HCV antigen assays found all these infectors. Through further experiments, we revealed the amino acid polymorphism in the core region of genotype 3 strain impaired the sensitivity of all three HCV antigen assays. In addition, the sensitivity of the two domestic assays was impaired by anti-HCV antibodies in the serum. The specificity of HCV antigen assays for diagnosing hepatitis C is 99.94% to 99.98%. The rheumatoid factors, autoantibodies, and other unknown interference substances can lead to a small number of low level, "false positive" antigen results. Conclusions:HCV core antigen assay may be used as a satisfactory approach of infection screening, especially for the immunodeficient patents. However, the sensitivity and specificity of the assays are influenced by multiple factors, which should be further improved.

Genomic studies of cancer cell alterations,such as mutations,copy number variations(CNVs),and translocations,greatly promote our understanding of the genesis and development of cancers.However,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties.To explore the 3D genome structure in clin-ical lung cancer,we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer,combining with RNA sequenceing analysis.We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells(1×104),compared the genome architecture between clinical samples and cell lines of lung cancer,and identified conserved and changed spatial chromatin structures between normal and cancer sam-ples.We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer.By integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene expression.We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures.Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.

Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.

BACKGROUND/AIMS: Functional dyspepsia (FD) remains a great clinical challenge since the FD subtypes, defined by Rome III classification, still have heterogeneous pathogenesis. Previous studies have shown notable differences in visceral sensation processing in the CNS in FD compared to healthy subjects (HS). However, the role of CNS in the pathogenesis of each FD subtype has not been recognized. METHODS: Twenty-eight FD patients, including 10 epigastric pain syndrome (EPS), 9 postprandial distress syndrome (PDS), and 9 mixed-type, and 10 HS, were enrolled. All subjects underwent a proximal gastric perfusion water load test and the regional brain activities during resting state and water load test were investigated by functional magnetic resonance imaging. RESULTS: For regional brain activities during the resting state and water load test, each FD subtype was significantly different from HS (P < 0.05). Focusing on EPS and PDS, the regional brain activities of EPS were stronger than PDS in the left paracentral lobule, right inferior frontal gyrus pars opercularis, postcentral gyrus, precuneus, insula, parahippocampal gyrus, caudate nucleus, and bilateral cingulate cortices at the resting state (P < 0.05), and stronger than PDS in the left inferior temporal and fusiform gyri during the water load test (P < 0.05). CONCLUSIONS: Compared to HS, FD subtypes had different regional brain activities at rest and during water load test, whereby the differences displayed distinct manifestations for each subtype. Compared to PDS, EPS presented more significant differences from HS at rest, suggesting that the abnormality of central visceral pain processing could be one of the main pathogenesis mechanisms for EPS.
Brain ; Broca Area ; Caudate Nucleus ; Classification ; Dyspepsia ; Functional Neuroimaging ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Parahippocampal Gyrus ; Parietal Lobe ; Perfusion ; Prefrontal Cortex ; Sensation ; Somatosensory Cortex ; Visceral Pain ; Water

OBJECTIVE:To provide reference for comprehensive intervention and management of chronic disease in China.METHODS:The global chronic disease trends and disease burden were summarized;theoretical framework,practice and experience of international chronic disease management were summarized and analyzed as well as enlightenment on domestic chronic disease management.RESULTS&CONCLUSIONS:Worldwide prepresentative chronic disease theory model mainly involved USA chronic disease nursing model and WHO innovation care for chronic conditions.Main experience of international chronic disease management is that managing based on community,confirming preferential intervened disease types,adopting standardized clinical diagnosis and treatment pathway,designing rational transfer treatment system,providing patient self-management support.At pres ent,chronic disease management have been improved in China,but is still poor in community management.It is necessary to strengthen community medical staff training about chronic disease prevention and treatment and health education for social group.

OBJECTIVE:To establish a method for simultaneous determination of 6 residual organic solvents in aprepitant raw material as methanol,ethanol,acetone,isopropyl alcohol,methyl tert-butyl ether and tetrahydrofuran.METHODS:Headspace capillary gas chromatography was adopted.The determination was performed on DB-624 capillary column using temperature programming.The temperature of injector port was 180 ℃,and flame ionization detector was used with temperature of 260 ℃.Nitrogen was used as carrier gas with flow rate 3.0 mL/min.The spilt ratio was 5 ∶ 1,and head-space injection volume was 1.0 mL.The head-space equilibrium temperature was set at 80 ℃,and equilibrium time was 40 min.RESULTS:The linear ranges of methanol,ethanol,acetone,isopropyl alcohol,methyl tert-butyl ether,tetrahydrofuran were 6.052-605.232 μ g/mL (r=0.999 9),9.987-998.718 μg/mL(r=0.999 9),9.998-999.768 μg/mL(r=0.999 8),9.986-998.634 μg/mL(r=0.999 9),9.991-999.090 μg/mL (r=0.999 7),1.461-146.133 μg/mL(r=0.999 5),respectively.The limits of quantitation were 1.782 1,2.079 0,0.749 8,1.777 8,0.223 1,0.607 0 μg/mL;the limits of detection were 0.594 0,0.693 0,0.249 9,0.592 6,0.074 4,0.202 3 μg/mL,respectively.RSD of precision test was lower than 2.0％.Only acetone and isopropyl alcohol were detected in stability test and reproducibility tests,RSD＜2.0％.Their recoveries were 99.34-100.75％ (RSD=0.52％,n=9),98.20％-100.24％ (RSD=0.69％,n=9),98.07％-100.07％ (RSD=0.84％,n=9),99.86％-101.32％ (RSD=0.58％,n=9),97.87％-104.02％ (RSD=2.13％,n=9),98.26 ％-100.58 ％ (RSD =0.75 ％,n =9),respectively.CONCLUSIONS:The established method is simple,accurate and reproducible,and can be used for simultaneous determination of 6 residual organic solvents in aprepitant raw material.