Monosodium urate (MSU)-induced the gouty arthritis (GA) model was used to investigate the effect of Nod-like receptor protein 3 (NLRP3) inhibitor N14 in alleviating GA. Firstly, the effect of NLRP3 inhibitor N14 on the viability of mouse monocyte macrophage J774A.1 was examined by the cell counting kit-8 (CCK-8) assay. The expression of mature interleukin 1β (IL-1β) and cysteinyl aspartate specific proteinase-1 (caspase-1) p20 in the cell supernatant and the expression of NLRP3, caspase-1 and pro-IL-1β proteins in the cell lysates was detected by Western blot for the inhibitory effect of N14 on the MSU-induced NLRP3 inflammasome activation in J774A.1 cells. Animal behavioral tests were used to detect redness, swelling, heat and pain in mice with gouty arthritis. Hematoxylin-eosin (H&E) staining revealed pathologic changes and inflammatory infiltration in foot sections. Protein expression of NLRP3, caspase-1, and pro-IL-1β in mouse hind paw tissues were assessed by Western blot. The effect of N14 on the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (CRE), urea, and uric acid (UA) was investigated by the MSU-induced gouty arthritis model in mice. All animal experiments in this paper were approved by the Scientific Ethics Review Board of Qingdao Marine Biomedical Research Institute (grant No. E-MBWNL-2024-20). The experimental results showed that N14 did not exhibit cytotoxicity in mouse monocyte macrophage J774A.1 cells at concentrations up to 100 μmol·L^-1, and N14 effectively prevented MSU-induced activation of NLRP3 inflammasome. In the mouse gouty arthritis model, N14 significantly ameliorated the redness, swelling, heat and pain caused by GA, and down-regulated the levels of NLRP3 inflammasome-associated proteins in mouse hind paw tissues. Meanwhile, N14 appeared to be well tolerated, as it did not significantly affect various biochemical indices in mouse plasma. In conclusion, N14 effectively alleviated GA in mice by inhibiting the NLRP3 inflammasome pathway, which is important for both prevention and treatment of related diseases.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

ObjectiveTo investigate the clinical value of DR corneal suture ring localization and CT 3D reconstruction localization of orbital foreign bodies. MethodsRetrospective analysis was performed on patients （51 cases） suspected of ocular foreign bodies admitted to our hospital from January 2016 to December 2020 At the same time， DR corneal suture ring localization and CT three-dimensional reconstruction localization of orbital foreign bodies were performed， and the detection rate of foreign bodies by the two methods was calculated to analyze the location of ocular foreign bodies. ResultsThere were 38 cases of intraorbital foreign body identified by DR corneal suture ring localization method， and 46 cases of intraorbital foreign body identified by CT three-dimensional reconstruction localization method. The accuracy of CT three-dimensional reconstruction localization method was 90.20%， which was higher than that of DR corneal suture ring localization method 74.51% （P<0.05）. Intraocular foreign bodies in 23 cases could be distinguished by DR corneal suture ring localization， and 25 cases by CT 3D reconstruction localization. The maximum diameter of intraocular foreign bodies that could be distinguished by CT 3D reconstruction localization was （2.65±0.14） mm. The diameter of intraspherical foreign body was （2.94±0.36） mm （P<0.05） lower than that which could be distinguished by DR corneal suture ring localization method. The results of DR corneal suture ring localization of orbital foreign body showed no difference compared with the results of CT 3D reconstruction localization （P>0.05）. Forty cases of high density images inside and outside the eye could be clearly distinguished by CT 3D reconstruction. By using DR corneal suture ring localization method， 23 cases were confirmed to be intraocular high-density shadows， and 15 cases could not be confirmed to be intraocular high-density shadows （P < 0.05）. ConclusionsFor the location of intraorbital foreign bodies， CT three-dimensional reconstruction can be used as a conventional method for locating ocular foreign bodies with high resolution and accuracy， and can detect fine metal particles inside the eyeball. Meanwhile， for a few small foreign bodies in the iris root， ciliary body and lateral suspension ligament， it is necessary to locate orbital foreign bodies with DR corneal suture ring.

Mice ; Animals ; Tandem Mass Spectrometry ; Alpha-Amanitin ; Chromatography, Liquid ; Metabolomics ; Chromatography, High Pressure Liquid/methods*

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.
Humans ; Pregnancy ; Female ; Hypertension, Pregnancy-Induced/diagnosis* ; Retrospective Studies ; Pre-Eclampsia/epidemiology* ; Risk Factors ; Incidence

Dof(DNA binding with one finger), a unique class of transcription factors in plants, play an important role in seed development, tissue differentiation, and metabolic regulation. To identify the number and function of Dof gene family members in Panax ginseng, this study identified the members of Dof gene family in P. ginseng and systematically analyzed their structures, evolution, functional differentiation, expression patterns, and interactions using bioinformatics methods at the transcriptome level. At the same time, the association analysis of Dof genes from P. ginseng with key enzyme genes for ginsenoside synthesis was carried out to screen the candidate PgDof genes involved in the regulation of ginsenoside biosynthesis. The results showed that there were 54 genes belonging to the Dof gene family in P. ginseng from Jilin. All PgDof genes had Zf-Dof conserved motifs, implying that they were evolutionarily conserved and could be divided into five groups. Expression pattern analysis confirmed that the expression of PgDof gene family members in different tissues, different year-old P. ginseng, and different farm varieties varied significantly. Simultaneously, as revealed by "gene-saponin content" and "gene-gene" linkage analysis, an important candidate PgDof14-1 gene involved in the regulation of ginsenoside biosynthesis was obtained. From the established genetic transformation system of this gene in the hairy roots of P. ginseng, a positive hairy root clone was determined. This study has laid a theoretical foundation for the study of Dof gene family in P. ginseng.
Gene Expression Profiling/methods* ; Gene Expression Regulation, Plant ; Ginsenosides ; Panax ; Plant Proteins/metabolism* ; Plant Roots/metabolism* ; Transcriptome

Objective: To evaluate the relationship between red blood cell folate (RBC folate) and the prognosis of low-grade cervical intraepithelial neoplasia (CIN 1). Methods: In the married women cohort established in 2014, 564 women with CIN 1 diagnosed by pathology were recruited. The demographic characteristics and factors of cervical intraepithelial neoplasia were collected. Meanwhile, the infection status of human papillomavirus (HPV) was detected by molecular diversion hybridization, and the level of RBC folate was measured by chemical photoimmunoassay. After 24 months of follow-up, pathological examination was performed again to observe the prognosis of participants. The women with reversal were taken as the control group,and those with continuous and progressive CIN 1 were taken as the case group respectively. The relationship between RBC folate and CIN 1 outcome was evaluated by logistic regression model. Results: 453 women completed the follow-up, aged (49.72±6.84) years old. CIN 1 was reversed in 342 women, continued in 58 cases and progressed in 53 cases. The RBC folate level M (Q_1,Q₃) were 399.01 (307.10, 538.97) ng/ml, 316.98 (184.74, 428.49) ng/ml and 247.14 (170.54, 348.97) ng/ml, respectively. With the decrease of RBC folate, the risk of continuous and progressive CIN 1 increased (all P<0.001), while the risk of reversal CIN 1 decreased gradually (P<0.001). Combined with high-risk human papillomavirus (HR-HPV) infection status, low level of RBC folate could increase the risk of CIN 1 progression regardless of HR-HPV infection (HR-HPV infection: OR=21.34, 95%CI: 3.98-114.54; HR-HPV uninfection: OR=11.15, 95%CI: 2.34-53.13). Conclusion: Low level of RBC folate could increase the risk of CIN 1 persistence and progression regardless of HR-HPV infection.
Adult ; Alphapapillomavirus ; Case-Control Studies ; Cervical Intraepithelial Neoplasia ; Erythrocytes ; Female ; Folic Acid ; Humans ; Male ; Middle Aged ; Papillomaviridae ; Papillomavirus Infections ; Uterine Cervical Neoplasms

Adult ; Aged ; China/epidemiology* ; Cohort Studies ; Female ; Humans ; Male ; Metabolic Syndrome/etiology* ; Middle Aged ; Parks, Recreational/supply & distribution* ; Prevalence ; Residence Characteristics/statistics & numerical data* ; Rural Population/statistics & numerical data* ; Young Adult

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.
Tibet ; Medicine, Tibetan Traditional ; Quality Control ; Pharmaceutical Research ; Drug Industry