BACKGROUND:Rheumatoid arthritis is an inflammatory disease.Many studies have shown that wogonin has a good anti-inflammatory effect on rheumatoid arthritis,but its exact efficacy and specific mechanism of action remain to be clarified. OBJECTIVE:To investigate the mechanism of wogonin ameliorating joint inflammation by regulating endoplasmic reticulum stress pathway in rats with collagen-induced arthritis. METHODS:(1)At the animal level:Female Wistar rats were divided into healthy control group,arthritis model group and wogonin treatment group.Rat models of arthritis in the latter two groups were established by subcutaneous injection of bovine type Ⅱ collagen and adjuvant.In the wogonin group,wogonin was given by gavage for 28 consecutive days after modeling.During this period,the rats in each group were weighed,and arthritis score and ankle swelling were measured every 7 days.After the experiment,the pathological changes of the joint were observed,the mRNA and protein levels of endoplasmic reticulum stress pathway GRP78 and CHOP were detected by qRT-PCR,western blot,and immunohistochemistry.(2)At the cellular level,cell counting kit-8 was used to detect the cytotoxic effect of wogonin on fibroblast-like synoviocytes from rats with collagen-induced arthritis.The fibroblast-like synoviocytes induced by thapsigargin were treated with different concentrations of wogonin.The levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant were detected by ELISA,and the intracellular reactive oxygen species in each group were determined by DCFH-DA probe method.The mRNA and protein levels of GRP78,IRE1α,XBP1s and CHOP were detected by qRT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the healthy control group,arthritis index score and ankle swelling degree in the arthritis model group were increased(P<0.01),synovial hyperplasia,inflammatory cell infiltration,cartilage destruction and bone erosion were observed in pathological sections,and the mRNA and protein expressions of GRP78 and CHOP in the ankle were significantly increased(P<0.01),which were mainly located in synovial tissue and articular surface.Compared with the arthritis model group,the arthritis index score and ankle swelling degree in the wogonin treatment group were decreased(P<0.05),synovial hyperplasia and the number of inflammatory cells were decreased,cartilage destruction and bone erosion were alleviated,the mRNA and protein expression levels of GRP78 and CHOP in the ankle were decreased(P<0.05),particularly in synovial tissue and on the articular surface.There was no significant difference in body mass among the three groups(P>0.05).In the cell experiment,200 μmol/L wogonin significantly reduced the survival rate of fibroblast-like synoviocytes(P<0.01).Compared with the blank control group,the levels of interleukin-1β,tumor necrosis factor-α,content of reactive oxygen species,and mRNA and protein expression of GRP78,IRE1α,XBP1s,and CHOP in the thapsigargin group were significantly increased(P<0.05);compared with the thapsigargin group,50 and 100 μmol/L wogonin significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant(P<0.05,P<0.01),and 100 μmol/L wogonin significantly reduced the content of reactive oxygen species(P<0.01)and down-regulated the mRNA and protein expression levels of GRP78,IRE1α,XBP1s and CHOP(all P<0.05).These results suggest that wogonin can effectively alleviate joint inflammatory responses in rats with collagen-induced arthritis,and the endoplasmic reticulum stress pathway may be the key target of its intervention.

BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.

AIM: To analyze the prevalence, severity, types, and correction of astigmatism in children, and provide scientific evidences for the prevention and treatment of refractive errors.METHODS: This cross-sectional study included 29 153 children aged 6-12 years from Xi'an and Lantian County, Shaanxi Province, China. Visual acuity and non-cycloplegic refraction were measured. Astigmatism was defined as an absolute cylindrical power ≥0.5 D in the right eye. Differences in astigmatism severity, type distribution, and refractive correction were analyzed across age, gender, and region.RESULTS:The prevalence of astigmatism increased with age, peaking at 11 years old(62.88%). Boys(57.10%)had a higher prevalence than girls(54.86%), and the municipal areas(58.29%)had a higher prevalence than county areas(51.75%). Mild astigmatism was the most common(63.82%), with moderate astigmatism increasing with age. The highest prevalence of high astigmatism was observed in 11-years-old children(9.68%). Compound myopic astigmatism(59.28%)and mixed astigmatism(25.16%)were the most frequent types. With increasing age, compound myopic astigmatism increased, while simple myopic, simple hyperopic, and compound hyperopic astigmatism decreased. Mixed astigmatism increased from ages 6 to 7, but declined from ages 7 to 12. For astigmatic axis types, with-the-rule astigmatism was the most prevalent(81.06%)and increased with age, peaking at 11 years(85.74%). Against-the-rule astigmatism showed a declining trend, while oblique astigmatism remained relatively stable. Distribution differences in astigmatism types and axes by gender and region were observed. Significant differences in astigmatism severity, types, and axis types across different ages, genders, and regions were observed(all P<0.05). The overall refractive correction rate for children with astigmatism was only 40.18%.CONCLUSION: The overall prevalence of astigmatism among children aged 6-12 years in Shaanxi Province was 56.02%, with higher prevalence observed in boys and in municipal areas. Age, gender, and region significantly influenced the prevalence of astigmatism. Notably, less than half of the children with astigmatism received refractive correction, highlighting the need for increased attention from parents and relevant authorities.

Myocardial fibrosis （MF）， characterized by decreased cardiac function and myocardial compliance， is a pathological process and a progression factor in various cardiovascular diseases. The nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） inflammasome is closely related to the development of MF. Recent studies have shown that traditional Chinese medicine （TCM） can regulate the NLRP3 inflammasome to alleviate MF. Based on this， this article systematically summarizes the research progress on the mechanisms by which TCM regulates the NLRP3 inflammasome to improve MF. It is found that active ingredients of TCM， such as alkaloids （lycorine，vincristine，bufalin）， saponins （astragaloside Ⅳ， diosgenin，ginsenoside Rg3）， terpenoids （celastrol，oridonin）， and phenols （polydatin，curcumin，phloridzin） as well as TCM formulas （Zhachong shisanwei pills，Zhilong huoxue tongyu capsules， Luqi formula） can inhibit the activation of the NLRP3 inflammasome， thereby suppressing the release of inflammatory factors such as interleukin-1β and IL-18， reducing inflammatory damage to myocardial tissue， alleviating excessive deposition of the extracellular matrix， and thus exerting the effect of improving MF.

Background During pregnancy, negative emotions such as anxiety and depression may induce cortisol disruption. Cortisol can be transmitted to the fetus through the placental barrier, thereby affecting the neurodevelopment of the offspring. Objective To investigate the relationship between placental cortisol, maternal depression during pregnancy, and neurodevelopment of 3-month-old infants. Methods From September 2022 to September 2023, 171 pregnant women ordered routine prenatal checks at the obstetrics outpatient department of a tertiary hospital in Ningxia were selected using a prospective cohort design. After providing informed consent, these women participated in a questionnaire survey that covered general individual characteristics, prenatal depression, and sleep quality. At birth, placental samples were collected to measure cortisol levels using ELISA kits. Follow-up assessments on the neurodevelopmental of 3-month-old infants were conducted using the Warning Sign for Children Mental and Behavioral Development. LASSO regression analysis was conducted to screen the influencing factors of depression during pregnancy. Huber regression analysis was then applied to assess potential linear relationship between depression during pregnancy and placental cortisol levels. Log-binomial regression was used to analyze the linear relationships between cortisol levels and neurodevelopmental delay in 3-month-old infants. Additionally, a mediation effect model was fitted using R 4.3.3 to assess possible mediating role of cortisol in the association between prenatal depression and neurodevelopmental delay in 3-month-old infants. Results The positive rate of prenatal depression was 33.33%. Nine factors affecting prenatal depression were identified by LASSO regression, including rural residence, high school education or above, extroverted personality characteristics, moderate early pregnancy reactions, baby sex expectation, prenatal anxiety, family dysfunction, exposure to stressful life events during pregnancy, and moderate prenatal sleep quality. The Huber regression model showed a positive linear correlation between prenatal depression and placental cortisol (P<0.05). With or without controlling confounding factors, the results of log-binomial regression modeling showed that cortisol levels were associated with a reduced risk of neurodevelopmental delay in 3-month-old infants (crude model: RR=0.988, 95%CI: 0.9768, 0.9996, P＜0.05; adjusted model: RR=0.988, 95%CI: 0.9764, 0.9993, P＜0.05). A mediating effect of placental cortisol between prenatal depression and the risk of neurodevelopmental delay in 3-month-old offspring was found statistically significant (P=0.045), accounting for 67.0% of the total effect. Conclusion Prenatal depression is associated with elevated placental cortisol levels, and higher cortisol levels are found to be related to a lower risk of neurodevelopmental delay in infants. Placental cortisol mediates the relationship between prenatal depression and infant neurodevelopment.

ObjectiveTo investigate the independent risk factors for poor prognosis in patients with acute pancreatitis （AP） by analyzing inflammatory factors， lung ultrasound （LUS） scores， and CT scores， to establish a nomogram prediction model， and to provide a basis for early clinical intervention. MethodsA total of 409 patients with AP who were admitted to Changshu Hospital Affiliated to Soochow University from January 2021 to October 2023 were enrolled as subjects， and they were divided into modeling group with 288 patients and validation group with 121 patients using the simple random sampling method at a ratio of 7∶3. According to the prognosis， each group was further divided into poor prognosis group and good prognosis group. The levels of C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α） were measured for both groups within 72 hours after admission， and LUS scores， modified CT severity index （MCTSI）， and extrapancreatic inflammation on computed tomography （EPIC） scores were assessed within 48‍ ‍—‍ ‍72 hours after admission. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. A LASSO regression analysis was used to screen for the variables that were included in the multivariate logistic regression model to identify the independent risk factors for the poor prognosis of AP， and then a nomogram prediction model was established. The receiver operating characteristic （ROC） curve and the calibration curve were used to assess the discriminatory ability and goodness of fit of the nomogram model， and a decision curve analysis was used to assess the clinical applicability of the model. ResultsAmong the 288 patients with AP in the modeling group， there were 33 （11.46%） in the poor prognosis group and 255 （88.54%） in the good prognosis group； among the 121 patients with AP in the validation group， there were 13 （10.74%） in the poor prognosis group and 108 （89.26%） in the good prognosis group. Compared with the good prognosis group， the poor prognosis group had significantly higher levels of CRP （Z=3.607， P<0.05）， IL-6 （Z=4.189， P<0.05）， and TNF-α （t=2.584， P<0.05）， and significantly higher scores of LUS （t=8.075， P<0.05）， MCTSI （t=5.929， P<0.05）， and EPIC （t=8.626， P<0.05）. The multivariate logistic regression analysis showed that CRP （odds ratio ［OR］=3.592， 95% confidence interval ［CI］： 1.272‍ ‍—‍ ‍10.138， P<0.05）， IL-6 （OR=4.225， 95%CI： 1.468‍ ‍—‍ ‍12.156， P<0.05）， TNF-α （OR=3.540， 95%CI： 1.205‍ ‍—‍ ‍10.401， P<0.05）， LUS （OR=7.094， 95%CI： 2.398‍ ‍—‍ ‍20.986， P<0.05）， MCTSI （OR=7.612， 95%CI： 2.832‍ ‍—‍ ‍20.462， P<0.05）， and EPIC （OR=11.915， 95%CI： 4.007‍ ‍—‍ ‍35.432， P<0.05） were independent risk factor for poor prognosis in patients with AP. A nomogram prediction model was established based on the above 6 indicators， which had an area under the ROC curve of 0.924 （95%CI： 0.883‍ ‍—‍ ‍0.964）， and the Youden index for the optimal cut-off value was 0.670， with a sensitivity of 0.909 and a specificity of 0.761. The calibration curve showed good consistency between the predicted and observed results in both the modeling group and the validation group. The decision curve analysis showed that the predictive model had certain clinical effectiveness. ConclusionThe nomogram model for predicting the risk of poor prognosis in AP patients based on CRP， IL-6， TNF-α， LUS score， MCTSI score， and EPIC score has relatively good predictive performance and can provide important strategic guidance for developing early intensified treatment regimens for AP patients in clinical practice.

Liver transplantation has currently become an important treatment for patients with end-stage liver disease or hepatocellular carcinoma (HCC), significantly improving patients’ prognosis. However, liver transplantation still facing many challenges, such as donor sources, liver preservation technology, transplant rejection, biliary complications and postoperative tumor recurrence after HCC liver transplantation, which urgently need to be solved and optimized. With the development of new technologies, liver transplantation in our country is facing new opportunities and challenges. Domestic research teams actively respond to the needs of the times and continuously promote innovation and breakthroughs in the basic research of liver transplantation. This article reviews the cutting-edge progress in the field of basic liver transplantation research in 2024 and evaluates the important research achievements obtained by Chinese research teams in this field. The systematic sorting out of these research advances not only helps to promote the integration of Chinese characteristic liver transplantation research into the international academic system and the docking of Chinese liver transplantation research with the global forefront, but also helps researchers and clinical surgeons to fully understand the current status of basic liver transplantation research in China, provides a clear direction for future basic research, and thus promotes the vigorous development of Chinese liver transplantation cause.

Since its establishment in 2016, the National Rare Diseases Registry System of China (NRDRS) has accumulated valuable case data and bio-specimen for basic and clinical research on rare diseases in China. However, the emerging challenges in clinical diagnosis and treatment of rare diseases make it unable for data and resource platform to fully meet the diversified needs. Under this backdrop, we have developed a protocol to optimize and upgrade the system based on the core functions of the NRDRS platform. The goal is to leverage intelligent digital technologies to transform NRDRS into a new platform integrating multimodal data and auxiliary diagnostic and treatment functions. It is specified as the development and construction of "one platform and four intelligent tools." Currently, we have upgraded and developed NRDRS platform, intelligent tool for genotype-phenotype analysis of rare diseases, AI-assisted diagnostic tool for rare diseases, remote multidisciplinary diagnosis and teaching tool for rare diseases, drug screening and validation tool for rare diseases. The next step will focus on the promotion of the application of these tools in clinical settings in order to address the issue of severe imbalance in the allocation of resources for the diagnosis and treatment of rare diseases. This article provides an overview of the digital and intelligent upgrades of the NRDRS, the trials in applications in clinical settings, and direction in the future.

Objective: To analyze CD36 gene by PacBio Sequel Ⅱ the third-generation sequencing technology (TGS), including non-coding sequence, and to investigate the molecular mechanism of CD36 deficiency. Methods: Flow cytometry was performed in the southern Chinese population to detect the CD36 phenotype. Among them, 15 cases of CD36 type I deficiency, 15 cases of CD36 type Ⅱ deficiency, and 10 positive samples were selected. The TGS of the CD36 gene was performed and statistical analysis was conducted. Results: 40 samples (including 15 cases of type I deficiency, 15 cases of type Ⅱ deficiency, and 10 positive samples) were subjected by TGS of CD36 full-length sequences (except part of intron1). A total of 180 polymorphic loci were identified. Among them, 13 kinds were in the coding region, the rest were in non-coding region, with most mutations located in regulatory regions such as the 5′-UTR and 3′-UTR. Conclusion: The high polymorphism of CD36 non-coding regions, particularly in regulatory sequences, provides mechanistic insights into type Ⅱ CD36 deficiency.

Objective: To prepare platelet membrane biomimetic liposomes loaded with vincristine sulfate (VCR) for targeted delivery to tumor. Methods: Vincristine sulfate liposomes (LIPO) were prepared using the pH-gradient method, followed by the fusion of platelet membranes and subsequent drug loading to obtain platelet membrane biomimetic liposomes (PLM-LIPO). The particle size, polydispersity index (PDI), Zeta potential, and drug encapsulation efficiency (EE%) of both liposomes were characterized. The tumor-targeting capability was evaluated through in vitro cellular experiments and in vivo biodistribution studies. Results: The optimal preparation conditions for LIPO were determined as follows: DPPC-to-cholesterol molar ratio of 1∶1, internal aqueous phase of 0.3 M pH 4.0 citrate buffer, external aqueous phase of 1 M Na HPO solution, drug-to-lipid ratio of 1∶10, drug loading temperature of 60℃, and loading time of 10 minutes. The LIPO exhibited a mean particle size of (147.3±2.24) nm, PDI of 0.078±0.014, Zeta potential of (-3.54±0.75) mV, and EE% of 91.37±0.47. For PLM-LIPO, prepared via membrane fusion followed by drug loading, the mean particle size was (185.3±3.61) nm, PDI was 0.075±0.022, Zeta potential was (-18.91±1.54) mV, and EE% was 63.36±2.45. In the CD62P validation experiment, the fluorescence intensity of PLM-LIPO was five times higher than that of LIPO. In vitro cellular uptake experiments revealed that PLM-LIPO showed 1.3-fold and 1.2-fold higher uptake rates compared to LIPO at 6 h and 12 h, respectively. In vivo experiments demonstrated that 1h after administration, the accumulation of PLM-LIPO at tumor sites was 4-fold higher than that of LIPO and 6-7 times higher than that in healthy mice. Conclusion: The platelet membrane biomimetic liposomes loaded with vincristine sulfate were successfully developed. Both cellular uptake and tissue distribution studies confirmed the PLM-LIPO enhanced tumor-targeting capability.