Illness narratives serve as an entry point that combines patients’ micro-level experiences with macro-level power structures in the medical field and are also an important aspect of medical ethics and narrative medicine research. Based on the existing meaning of illness narratives， the significant importance of focusing on the broader concept of illness narratives was emphasized. Drawing on Foucault’s theory of power， it was found that illness narratives， beyond reflecting the pain caused by the disease itself， should also focus on the dominant role of power structures in the modern medical field over illness narratives， and explore how to reduce the domination of power. Inspired by the concepts of ethics and survival aesthetics in Foucault’s late thought， this paper explored the possibility of transcending power domination and reconstructing subjectivity through self-technology reinforcement such as patient illness narratives in the medical field. Finally， from the perspectives of both medical service provision and patient needs， illness narratives and the practice of narrative medicine were reflected and summarized， hoping that narrative medicine can contribute to the return of individual subjectivity with a broad ethical meaning in the medical field.

Objective The study aims to investigate the immunological functions of the nucleocapsid (N) protein of the novel coronavirus Omicron (BA.1, BA.2) and evaluate the differences among different N proteins of mutant strains in immunogenicity. Methods By aligning sequences, the mutation sites of the Omicron (BA.1, BA.2) N protein relative to prototype strain of the novel coronavirus (Wuhan-Hu-1) were determined. The pET-28a-N-Wuhan-Hu-1 plasmid was used as template to construct pET-28a-BA.1/BA.2-N through single point mutation or homologous recombination. The three kinds of N protein were expressed in prokaryotic system, purified through Ni-NTA affinity chromatography, and then immunized into mice. The titer and reactivity of the polyclonal antibody, as well as the expression level of IL-1β and IFN-γ in mouse spleen cells, were detected using indirect ELISA and Western blot assay. Results The constructed prokaryotic expression plasmids were successfully used to express the Wuhan-Hu-1 N, BA.1 N, and BA.2 N proteins in E.coli BL21(DE3) at 37 DegreesCelsius for 4 hours. The indirect ELISA test showed that the titers of polyclonal antibody prepared by three N proteins were all 1:51 200. All three N proteins can increase the expression of IFN-γ and IL-1β cytokines, but the effect of Omicron N protein in activing two cytokines was more obvious than that of Wuhan-Hu-1 N protein. Conclusion The study obtained three new coronavirus N proteins and polyclonal antibodies, and confirmed that mutations in the amino acid sites of the N protein can affect its immunogenicity. This provides a basis for developing rapid diagnostic methods targeting N protein of different novel coronavirus variants.
Animals ; Mice ; SARS-CoV-2/genetics* ; Coronavirus Nucleocapsid Proteins/immunology* ; Nucleocapsid Proteins/isolation & purification* ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Mice, Inbred BALB C ; Interferon-gamma/metabolism* ; Interleukin-1beta/metabolism* ; Female ; Escherichia coli/metabolism* ; Mutation ; Humans

Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorate obesity. Our previous studies revealed that (Ex-4)₂-Fc, a long-acting GLP-1RA we developed, depends on the leptin pathway to treat obesity. However, the mechanisms linking (Ex-4)₂-Fc and leptin resistance remain largely unclear. To address this question, we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota, as increasing evidence indicates an important link between the gut microbiota and obesity. This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs. We found that (Ex-4)₂-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila (Am). In addition, (Ex-4)₂-Fc did not respond well in antibiotic-treated (ATB) Obese mice. Subsequent studies have shown that this defect can be overcome by gavage with Am. In addition, we found that Am enhanced (Ex-4)₂-Fc therapy by producing the metabolite inosine. Inosine regulates the macrophage adenosine A2A receptor (A2A) pathway to indirectly reduce leptin levels in adipocytes Thus, elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective To analyze the evaluation value of serum troponin Ⅰ(TnⅠ)combined with soluble CD163(sCD163)in the disease condition and prognosis of the patients with acute cholecystitis.Methods The clinical data of 125 patients with acute cholecystitis admitted and treated in the hospital from October 2022 to October 2023 were retrospectively collected.The patients were divided into the mild group(n=33),moderate group(n=51)and severe group(n=41)according to the severity of disease condition.The levels of serum TnⅠ,sCD163,interleukin(IL)-6,C reactive protein(CRP),total bilirubin(TBIL)and alanine aminotrans-ferase(ALT)were detected.The patients were divided into the good prognosis group(n=95)and poor prog-nosis group(n=30)according the occurrence of complications such as abdominal pain,dyspepsia and cholan-gitis within postoperative 3 months.The preoperative indicators were compared between the two groups.The influencing factors of prognosis in the patients were evaluated by the logistic regress analysis.The receiver op-erating characteristic(ROC)curve was used to analyze the diagnostic efficiency of TnⅠ and sCD163 in evalua-ting the disease condition and prognosis of the patients.Results The levels of TnⅠ,sCD163,IL-6,CRP,TBIL and ALT in the mild group were(0.78±0.23)μg/L,(25.01±3.15)mg/L,(62.52±7.61)pg/mL,(32.47±4.11)mg/L,(35.65±4.61)μmol/L and(79.75±7.23)U/L respectively,which were lower than those in the moderate group and severe group(P＜0.05).The TnⅠ level in the good prognosis group was(0.99±0.37)μg/L,which was lower than(1.82±0.51)μg/L in the poor prognosis group(P＜0.05);the sCD163 level in the good prognosis group was(27.46±3.50)mg/L,which was lower than[(33.12±4.13)mg/L]in the poor prognosis group(P＜0.05).The logistic analysis showed that TnⅠ,SCD163,IL-6,CRP,TBIL and ALT all were the important factors affecting the prognosis in the patients;the ROC curve showed the area under the curve(AUC)of TnⅠ combined with SCD163 for evaluating the disease condition was 0.966(95％CI:0.937-0.995),which for evaluating the prognosis was 0.948(95％CI:0.903-0.993).Conclusion Serum TnⅠ com-bined with sCD163 has a high application value in the assessment of the disease condition and prognosis in the patients with acute cholecystitis.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

OBJECTIVE To provide reference for basic analysis of the pharmacodynamic substance in Stahlianthus involucratus. METHODS Overall 24 SD male rats were randomly divided into blank group （purified water）， and administration group （ethanol extract of S. involucratus， 15.75 g/kg， calculated by crude drug）， with 12 rats in each group. They were given drug liquid/purified water intragastrically， twice a day， every 6-8 h， for consecutive 3 days. After medication， the blood， urine and fecal samples were collected from two groups of rats. UPLC-Q-Exactive-MS technology was used to identify the chemical constituents in the ethanol extract of S. involucratus， and metabolites in the blood， urine and fecal of rats after intragastrical administration of the ethanol extract of S. involucratus. Multivariate statistical analysis was employed to screen various serum metabolites. Metabolic pathways were analyzed by MetaboAnalyst 5.0 platform. RESULTS A total of 38 chemical constituents were identified from the ethanol extract of S. involucratus， including fourteen prototype components and three metabolites identified from 5 urine samples， nine prototype components identified from fecal samples， and ten prototype components and one metabolite identified from serum samples. A total of 71 differential metabolites were screened from two groups of rat serum samples， of which 44 differential metabolites， such as ferulic acid， glycyrrhizin， were up-regulated and 27 differential metabolites， such as arachidonic acid， phenylacetylglutamine， were down-regulated. The 71 differential metabolites were mainly enriched in 11 metabolic pathways， including phenylalanine metabolism， linoleic acid metabolism， arachidonic acid metabolism， and tryptophan metabolism. CONCLUSIONS Ferulic acid， liquiritigenin， isofraxidin and formononetin may be the material basis that directly exert pharmacological effects of S. involucratus. S. involucratus may exert anti-inflammatory effects by affecting metabolic pathways， including arachidonic acid metabolism and tryptophan metabolism.

OBJECTIVE To analyze the metabolites of Zhideke granules and speculate its metabolic pathway in rats in vivo. METHODS Male SD rats were randomly divided into blank group and administration group （Zhideke granules， 9.45 g/kg）； they were given ultrapure water or relevant medicine， twice a day， every 6-8 h， for 3 consecutive days. Serum， urine and feces samples of rats were collected， and their metabolites were identified by UPLC-Q-Exactive-MS technique after intragastric administration of Zhideke granules； their metabolic pathways were speculated. RESULTS After intragastric administration of Zhideke granules， 16 prototype components （i.g. irisflorentin， baicalin， chlorogenic acid） and 11 metabolites （i.g. hydration products of kaempferol or luteolin， methylation products of chlorogenic acid， and hydroxylation products of baicalin） were identified in serum， urine and feces of rats. Among them， 8 prototype components and 4 metabolites were identified in serum samples； 10 prototype components and 7 metabolites were identified in urine samples； 8 prototype components and 5 metabolites were identified in the fecal samples. CONCLUSIONS The metabolites of Zhideke granules in rats mainly include baicalin， irisflorentin，chlorogenic acid， and the main metabolic pathways included methylation， hydroxylation， glucuronidation.

Background Nonylphenol (NP) is a typical phenolic endocrine disruptor, and there are significant differences in NP concentration in different regions and water types. Objective To investigate the concentration of NP in three types (river, lake, and reservoir) of water sources in Hubei Province, and assess its ecological risk and population health risk. Methods Fifteen sampling points were set up at four river water sources (Liangtingshan Waterworks, Baishazhou Waterworks, Dijiao Waterworks, and Zongguan Waterworks), one lake water source (Liangzi Lake), and one reservoir water source (Fushui Reservoir). Water samples were collected from the 15 sampling points in June 2019 (wet season), October 2019 (level season), and December 2019 (dry season), respectively. The NP concentration in water samples was detected using ultra-high-performance liquid chromatography-tandem mass spectrometry, and the differences in NP concentration among groups were compared using variance analysis. The ecological risk and the health risk of NP were evaluated using risk quotient (RQ) and non-carcinogenic risk index (NCRI), respectively. Results The detection rate of NP was 100%, with an average concentration of (18.10±15.00) ng·L⁻¹ (5.45-92.71 ng·L⁻¹). The average concentrations of NP during the level, wet, and dry seasons were (11.52±5.31) ng·L⁻¹, (23.86±22.08) ng·L⁻¹, and (18.93±9.51) ng·L⁻¹, respectively, and the maximum concentrations were 24.62 ng·L⁻¹, 92.71 ng·L⁻¹, and 42.38 ng·L⁻¹, respectively. The variance analysis showed no statistical difference in the NP concentration in the samples from rivers, lakes, and reservoirs in different periods (P>0.05). Only the water samples from the water source serving the Zongguan Waterworks showed an RQ (0.19) greater than 0.1 during the wet season, indicating a moderate risk. The RQ values of other water samples were all less than 0.1, indicating an overall relatively low ecological risk. The highest NCRI values during the level, wet, and dry seasons were 0.1459, 0.5492, and 0.2511, respectively, all less than 1, indicating an acceptable health risk level. Conclusion The NP concentrations in all water sources in this study are at a relatively low level, which poses an acceptable risk level to human health.