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BACKGROUND: The causes of vitamin B12 (B12) deficiency are varied and mainly related to gastric disorders. Glossitis is a common oral manifestation of B12 deficiency and is often first seen by dentists. This study aimed to investigate the correlation between B12 deficiency-related glossitis (B12-def glossitis) and gastric serum biomarkers [gastrin-17(G17), pepsinogen I (PGI), pepsinogen II (PGII), and anti-Helicobacter pylori (H. pylori) antibodies], and preliminarily discuss the etiology of B12-def glossitis. METHODS: A cross-sectional study was conducted in patients complaining of glossodynia, burning sensation, or severe recurrent oral ulcers, but patients with a history of gastrectomy were excluded. All subjects underwent a uniform oral examination and hematological tests. RESULTS: Of 243 patients, 133 with B12-def glossitis were in the case group, and 110 with other oral mucosal diseases (non-glossitis) and normal B12 levels were in the control group. In the case group, 84.2% (112/133) showed high G17 and low PGI levels (G17hi PGIlow ). Univariate logistic regression showed that G17hi PGIlow was a high-risk factor for B12-def glossitis (OR: 92.44; 95% CI: 35.91, 238.02). Subgroup analyses in the case group showed that the G17hi PGIlow group presented with lower B12 levels and a lower positive rate of anti-H. pylori antibodies compared to the non-G17hi PGIlow group. CONCLUSION: Gastric serum biomarkers in patients with B12-def glossitis generally showed G17hi PGIlow , suggesting possible atrophy of gastric corpus and fundus mucosa. The G17hi PGIlow and non-G17hi PGIlow groups may represent different etiologies of B12 deficiency.

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Objective To analyze the medication rules of Professor HUANG Feng for the treatment of low back pain using data mining methods.Methods The information of prescriptions for the effective cases of outpatients with low back pain treated by Professor HUANG Feng were collected and screened.Microsoft Excel 2019 was used to analyze the frequency of medication and the distribution of properties,flavors and meridian tropism of the drugs in the included prescription.IBM SPSS Modeler 18.0 was used for association rule analysis,and IBM Statistics 26.0 was used for cluster analysis.Results A total of 239 prescriptions and 75 Chinese medicines were included.There were 23 high-frequency Chinese medicines with the medication frequency being or over 20 times,and the top 10 Chinese medicines were Glycyrrhizae Radix et Rhizoma,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma,Zanthoxyli Radix,salt-processed Achyranthis Bidentatae Radix,Rehmanniae Radix,Dipsaci Radix,Coicis Semen,and Salviae Miltiorrhizae Radix et Rhizoma.The medicines were mainly warm in nature,and were sweet,bitter and pungent in flavor.Most of the drugs had the meridian tropism of liver,stomach and spleen meridians.Among the drug combinations obtained from association rule analysis with the top 20 highest support,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma and Zanthoxyli Radix were the core drugs.Cluster analysis yielded 6 clustering combinations.Conclusion For the treatment of low back pain,Professor HUANG Feng follows the principle of"treatment adapting to the climate,individuality,and environment"and"treating the root cause of the disease",usually adopts the drugs for activating blood,moving qi and relieving pain,nourishing the liver and kidney,and also uses the medicines for replenishing qi and strengthening the spleen.The ideas of HUANG Feng for the treatment of low back pain can be used as a reference for the clinical treatment.

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BACKGROUND:Intramedullary nail has achieved a good clinical result in the treatment of femoral shaft fractures,but some patients still have aseptic nonunion due to mechanical instability.The femur is the longest and largest bone in the human body,but there are few studies on whether the fracture of the femur has different biomechanical results in different areas and the influence of different inserting methods on the stability of fracture fragments in different areas. OBJECTIVE:To analyze the biomechanical characteristics of anterograde and retrograde intramedullary nails in the treatment of different areas of femoral shaft fractures,and to evaluate the best way of insertion to reduce the incidence of nonunion. METHODS:CT data of a healthy volunteer were selected to import into the software of Mimics 19.0 and Geomagic studio 2017 to extract and optimize the three-dimensional model of the right femur.The anterograde and retrograde intramedullary nail models were built with Solidworks 2017 software and assembled with femoral shaft fracture models at different fracture areas according to standard surgical techniques.The models were imported into Abaqus 2017 software in STEP format to set material attribute parameters,boundary conditions,load and submit calculation,and the results were viewed in the visualization module.Among them,the antegrade and retrograde intramedullary nails of the upper femoral shaft fracture were A1 and A2 models,B1 and B2 models in the middle segment,and C1 and C2 models in the lower segment. RESULTS AND CONCLUSION:(1)In models A1,B1 and C2,the overall stress distribution of the femur was more uniform,and the placement,the displacement and angle of the fracture site,and inversion angle of the proximal femoral bone fragment were smaller.(2)For the upper and middle femoral shaft fractures,the anterograde intramedullary nail has a better biomechanical effect.For lower femoral shaft fractures,a retrograde intramedullary nail is preferable.

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We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m 2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.

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Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

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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.

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Hepatitis C virus (HCV) infection is one of the major etiologies of hepatocellular carcinoma (HCC) with approximately 30% of HCC being due to HCV infection worldwide. HCV eradication by antivirals greatly reduces the risk of HCC; nevertheless, HCC remains to occur in chronic hepatitis C (CHC) patients who have achieved a sustained virological response (SVR). The proportion of post-SVR HCC among newly diagnosed HCC patients is increasing in the direct-acting antiviral (DAA) era and might be due to preexisting inflammatory and fibrotic liver backgrounds, immune dysregulation between host and virus interactions, as well as host epigenetic scars, genetic predispositions and alternations. By means of applying surrogate markers and adopting risk stratification, HCC surveillance should be consistently performed in high-risk populations. In this review, we discuss the possible molecular mechanism, risk factors, and HCC surveillance strategy for HCC development after HCV eradication in CHC patients.

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Background/Aims@#Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. @*Methods@#We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. @*Results@#Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. @*Conclusions@#Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

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Objectives@#This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. @*Methods@#A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. @*Results@#The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. @*Conclusions@#This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

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Gamma delta (γδ) T-cell-based immunotherapy has shown favorable safety and clinical response in patients with multiple types of cancer. However, its efficiency in treating patients with solid tumors remains limited. In the current study, we investigated the function and molecular mechanism underlying gastric cancer (GC) cell-derived exosomal THBS1 in the regulation of Vγ9Vδ2 T cells. We found that GC cell-derived exosomal THBS1 markedly enhanced the cytotoxicity of Vγ9Vδ2 T cells against GC cells and the production of IFN-γ, TNF-α, perforin and granzyme B in vitro and elevated the killing effects of Vγ9Vδ2 T cells on GC cells in vivo. Mechanistically, exosomal THBS1 could regulate METTL3-or IGF2BP2-mediated m6A modification, further activating the RIG-I-like receptor signaling pathway in Vγ9Vδ2 T cells. Moreover, blocking the RIG-I-like receptor signaling pathway reversed the effects of exosomal THBS1 on the function of Vγ9Vδ2 T cells. In addition, THBS1 was expressed at low levels in GC tissues and was associated with an unfavorable prognosis in GC patients. In sum, our findings indicate that exosomal THBS1 derived from GC cells enhanced the function of Vγ9Vδ2 T cells by activating the RIG-I-like signaling pathway in a m6A methylation-dependent manner. Targeting the exosomal THBS1/m6A/RIG-I axis may have important implications for GC immunotherapy based on Vγ9Vδ2 T cells.

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Aims: To investigate adherence to oral anticoagulants among patients after mechanical heart valve (BHV) replacement and further examine the mediating role of medication belief in the relationship between knowledge and medication adherence. Background: The number of patients who undergo BHV replacement has increased in recent years. Short-term anticoagulant therapy is recommended for patients after BHV replacement. However, little is known about adherence to oral anticoagulant therapy and the underlying mechanisms among patients with BHV replacement. Methods: A cross-sectional study was conducted between September 2022 and November 2022. A convenience sample of 323 patients who underwent BHV replacement was recruited from a tertiary public hospital in Southwest China. Data were collected by using the 8-item Morisky Medication Adherence Scale, Beliefs about Medicines Questionnaire-specific, and the Knowledge of Anticoagulation Questionnaire. The mediation model was tested by Hayes's PROCESS macro. The STROBE checklist was used. Results: Approximately 17.3% of participants had low adherence, 47.1% had medium adherence, and only 35.6% reported high adherence to oral anticoagulants. Knowledge and necessity beliefs were positively related to medication adherence, while concern beliefs were negatively correlated with medication adherence. Medication belief mediated the relationship between knowledge and adherence to oral anticoagulants. Conclusion: Patients with BHV replacement demonstrated relatively low adherence to oral anticoagulant therapy. Efforts to enhance medication adherence should consider improving patients' knowledge and medication beliefs.

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Objectives: To determine the protective effect of Apelin-13 on cardiac hypertrophy through activating the PI3K-AKT-mTOR signaling pathway. Materials and Methods: The phenylephrine-induced cardiomyocyte hypertrophy model was established in H9C2 cells in vitro. Electroporation transfection technology was utilized to prepare and screen the H9C2 cells inducing low expression of the angiotensin type one receptor-related protein (Si-APJ). H9C2 and Si-APJ cells were divided independently into five groups: the control group, the PE group, the PE+Apelin group, the PE+Rapa group, and the PE+Apelin+Rapa group. RT-PCR was performed to analyze the mRNA expression levels of myosin heavy chain 7 (MYH7). Expression of the PI3K/AKT/mTOR pathway proteins and MYH7 was investigated by western blot. Results: The expression of PI3K/AKT/mTOR phosphorylated proteins was significantly higher in the PE group compared with the PE+Apelin group in H9C2 cells (P<0.05). Conversely, in Si-APJ H9C2 cells, the expression of PI3K/AKT/mTOR phosphorylated proteins was decreased (P<0.05). In H9C2 cells, the expression of MYH7 protein was increased in the PE group compared with the control group (P<0.05). In the same cell line, the expression of MYH7 in the PE+Apelin group was decreased significantly compared with the PE group (P<0.05). In Si-APJ H9C2 cells, compared with the control group, the expression of MYH7 in the PE group still increased significantly (P<0.05). In contrast, in the same cell line, there was no statistically significant difference in MYH7 expression between the PE+Apelin, PE+Rapa, and PE+Apelin+Rapa groups compared to the PE group (P>0.05). Conclusion: Apelin-13 reduces PE-induced cardiac hypertrophy by activating the PI3K/AKT/mTOR signaling pathway.

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PURPOSE: Patients with obstructive sleep apnoea (OSA) have a high incidence of vascular endothelial injury. The most important pathophysiological feature of OSA is chronic intermittent hypoxia (CIH). This study aimed to investigate the mechanisms of CIH-related vascular endothelial injury. METHODS: IH exposure was applied to human umbilical vein endothelial cells (HUVECs). After modeling, cell viability, the expression levels of peroxisome proliferator activated receptor γ (PPARγ), apoptosis-associated proteins and mitochondrial division fusion proteins, and the levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assessed via Cell Counting Kit-8 (CCK-8), western blotting, fluorescent microscope, and flow cytometry, respectively. Rosiglitazone (PPARγ agonist), tempo (the mitochondrial-specific antioxidant), and tempo combined with PPARγ interfering RNA were used to treat HUVECs, respectively. RESULTS: After IH exposure, cell viability and levels of MMP decreased, cell apoptosis and ROS levels increased, and the expression levels of PPARγ decreased. Both tempo and rosiglitazone pretreatment ameliorated cell apoptosis and improved cell viability. In addition, mitochondrial function became better after tempo pretreatment. PPARγ interference reversed the protective effects of tempo on IH-related mitochondrial function injury and cell injury. CONCLUSIONS: PPARγ regulated the apoptosis and cell viability of IH-treated HUVECs by altering mitochondrial function. This finding clarifies the mechanism of CIH-related vascular endothelial injury.

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ObjectiveTo obtain high-quality chloroplast genome information on Stemona tuberosa and clarify its structure， sequence features， and phylogenetic status. MethodThe Illumina NovaSeq 6000 and PacBio RS Ⅱ platforms were used for library construction and sequencing of S. tuberosa， respectively. The data from both sequencing platforms were combined and subjected to bioinformatics analysis for genome assembly and base correction， resulting in a high-quality chloroplast genome. Subsequently， sequence features， repetitive sequences， gene diversity， and phylogeny were analyzed. ResultThe chloroplast genome size of S. tuberosa was determined to be 154 379 bp. The structure of the chloroplast genome followed the typical quadripartite circular form， consisting of a pair of inverted repeat regions （IRs） with a length of 27 074 bp， a small single-copy region （SSC） of 17 924 bp， and a large single-copy region （LSC） of 82 307 bp. The average GC content was 37.86%. A total of 121 genes were annotated， including 30 tRNA genes， four rRNA genes， and 87 protein-coding genes. Among them， six tRNA genes and 12 protein-coding genes contained introns. In the chloroplast genome of S. tuberosa， 49 long repetitive sequences and 59 single-nucleotide simple sequence repeats （SSRs） were identified. Comparative analysis of chloroplast genomes among four Stemona species revealed high diversity in the ycf1 and ndhF genes. The phylogenetic tree constructed based on the chloroplast genome showed consistent classification with the current taxonomic status of S. tuberosa. ConclusionThe high-quality chloroplast genome of S. tuberosa was successfully assembled， providing valuable information on the structure and sequence features of chloroplast genomes in four Stemona species， including S. tuberosa. These findings lay a foundation for the identification， evolution， and phylogenetic studies of medicinal plants in the genus Stemona.

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Artesunate possesses the potential of intervening with glioma, however, its pharmacological mechanisms remain unclarified. Firstly, the effects of artesunate on cell activity, proliferation and apoptosis of U87 and U251 human glioma cells were explored. It was found that artesunate exerted stronger inhibitory effects on the activity and proliferation of U87 cells than U251 cells. It could significantly promote apoptosis in U87 cells (P < 0.05), while only high dose of artesunate can promote that of U251 cells (P < 0.01), detected by Hoechst and TUNEL cell apoptosis staining. Further, the differential expression gene sets between artesunate-sensitive and non-sensitive cell line, as well the therapeutic effects-related genes of artesunate were obtained through transcriptome sequencing and differential data analysis by using the lysates of U87 and U251 cells before and after artesunate treatment, aiming to explore the molecular mechanism of distinct artesunate sensitivity to two types of cells. Then, key putative targets that related to therapeutic effects were screened by constructing the interaction network of differential genes of three above comparison groups, and calculating their topological characteristics. Pathway enrichment analysis showed that those key putative targets were significantly enriched in several signaling pathways that were closely associated with the main pathological changes of glioma, among which apoptosis-related activating transcription factor 4 (ATF4)-DNA damage induced transcript 3 (DDIT3)- polyadenosine diphosphate ribose polymerase 1 (PARP1) signaling axis was the most enriched in. Molecular docking indicated that artesunate had fine binding affinities with ATF4 and DDIT3. Above all, this study preliminarily revealed that ATF4-DDIT3-PARP1 signaling axis is the target pathway of artesunate intervening with U87 glioma cells, and PARP1 may be an important gene for U251 cells to develop resistance to artesunate. Our results not only provide fundamental experimental evidence for artesunate as a potential therapeutic drug in glioma treatment, but shed light into overcoming drug resistance in its clinical therapy.

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Objective: To investigate the outcomes including major complications and prognosis of extremely preterm infants with gestational age ≤25+6 weeks. Methods: The cross-sectional study enrolled 233 extremely preterm infants with gestational age ≤25+6 weeks who were admitted to the Department of Neonatology of Shenzhen Maternity and Child Healthcare Hospital from January 2015 to December 2021. The clinical data including perinatal factors, treatments, complications, and prognosis were extracted and analyzed. These extremely preterm infants were also grouped according to gestational age and year of admission to further analyze their survival rate, major complications, causes of death, and long-term outcomes. The comparisons between the groups were performed with Chi-square test and Kruskal-Wallis. Results: Among these 233 extremely preterm infants, 134 (57.5%) were males and 99 (42.5%) females. The gestational age was (24.6±0.9) weeks, the birth weight was 710.0 (605.0,784.5) g, and the overall survival rate was 61.8% (144/233). Among the surviving extremely preterm infants, the earliest gestational age was 22+2 weeks and the lowest birth weight was 390 g. There were 17.6% (41/233) of extremely preterm infants had treatment withdrawn and were discharged in line with the will of guardians. Among the rest 192 extremely preterm infants managed with aggressive treatments, 14 (7.3%) died in hospital and 34 (17.7%) had treatment withdrawn later due to severe complications. Of the 192 extremely preterm infants, 144 (75.0%) survived, and the survival rate increased year by year (χ2=26.28, P<0.001) while the mortality decreased year by year (χ2=14.09, P=0.027). Among the survivors, 20.8%(30/144) had no major complications, and the incidence of complications was also negatively related with the gestational age (χ2=7.24, P=0.044), and the length of invasive ventilation was negatively related to the gestational age (χ2=29.14, P<0.001). In the group of less than 23+6 weeks, all extremely preterm infants had one or more major complications. The follow-up were completed in 122 infants and revealed that delayed motor development, language retardation, and hearing and vision impairment accounted for 17.2% (21/122), 8.2% (10/122) and 17.2% (21/122), respectively. Conclusions: Extremely preterm infants with gestational age ≤25+6 weeks are difficult to treat, but the survival rate of infants undergoing aggressive treatments increases year by year. Although the prevalence of major complications is still high, most extremely preterm infants have acceptable prognosis during follow-up.

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The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.

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OBJECTIVE To study the effects of Wubao capsule on airway inflammation in asthmatic model mice by regulating upstream and downstream cytokines of type Ⅱ innate lymphoid cells （ILC2s）. METHODS Totally 40 female BABL/c mice were randomly divided into normal group， model group， positive control group （dexamethasone 1 mg/kg）， Wubao capsule low-dose and high-dose groups （0.5， 1 g/kg）， with 8 mice in each group. Asthma models were induced by ovalbumin （OVA） sensitization and nebulization. Each group was given normal saline or drug intragastrically for 7 consecutive days. The contents of IgE and OVA-IgE in serum， the contents of interleukin 5 （IL-5）， IL-9， IL-13， IL-25， IL-33， thymic stromal lymphopoietin （TSLP） and mucin 5AC （MUC5AC） in bronchoalveolar lavage fluid （BALF） were determined by ELISA. HE staining was used to observe the pathological changes of lung tissues in mice. PAS staining was used to observe the changes of goblet cell proliferation in each group. The number of ILC2s in lung tissue was determined by flow cytometry （except for Wubao capsule low-dose group）. RESULTS Compared with model group， the contents of IgE and OVA-IgE in serum and the contents of IL-5， IL-9， IL-13， IL-25， IL-33， TSLP and MUC5AC in BALF were significantly reduced in Wubao capsule high-dose and low-dose groups （P＜0.01）. The infiltration of inflammatory cells and the thickening of basement membrane in lung tissue was alleviated to varying degrees， and the proliferation of goblet cells was inhibited； the number of ILC2s in lung tissues of mice in Wubao capsule high-dose group was significantly reduced （P＜0.01）. CONCLUSIONS Wubao capsule could effectively reduce the number of ILC2s in lung tissue， the contents of upstream and downstream cytokines of ILC2s in BALF of asthmatic model mice， so as to inhibit the airway inflammation and improve asthma.

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Objective:To study the active components and their potential mechanism of Yanghe Decoction for the treatment of chronic osteomyelitis (CO) via the methods of network pharmacology and molecular docking.Methods:Active components and action targets of Yanghe Decoction were screened from TCMSP, BATMAN-TCM and relevant literature. GeneCards, OMIM, DisGeNET, and PharmGKB databases were used to predict the targets for the CO. Cytoscape 3.8.0 software and STRING database were used to build the networks of "Chinese materia medica-active components-potential targets" and "protein-protein interaction", and according to topological parameters in the network, the core active components as well as Hub genes were screened. MCODE plug was used to accomplish clustering analysis of protein modules in PPI network. Then, intersection targets were enriched and analyzed by GO and KEGG in KOBAS database. Finally, molecular docking was carried out with the help of Autodock tool platform to predict the binding ability between the main active components and key targets.Results:A total of 120 active components of Yanghe Decoction and 402 targets were obtained; 1 464 CO-related targets were screened, and there were 103 intersection target genes of Yanghe Decoction-CO, 110 active components related to intersection targets, which mainly contained some flavonoids and Phytosterols, such as quercetin, Kaempferol, and Beta-Sitosterol. There were 9 Hub genes, including TNF, IL6, AKT1, etc., and 4 protein modules which involved the regulation of immune inflammatory response, vascular microcirculation, bone development, and formation, material synthesis and metabolism and other physiological processes. 193 signaling pathways and 1 552 GO results were acquired in KOBAS database. Molecular docking results showed that the active compounds had good binding activity with key targets based on the minimum binding energy of less than - 5 kcal/mol.Conclusion:The mechanism in the treatment of CO with Yanghe Decoction is a complex process of multiple components, multiple targets, and multiple pathways. It mainly regulates targets such as TNF, IL-6, CXCL8, VEGFA, and AKT1 through pathways such as TNF signaling pathway, IL-17 signaling pathway, and Toll-like receptors, participating in local inflammatory reactions, microcirculation, and bone cell metabolism in chronic osteomyelitis, and interfering with the immune escape mechanism of pathogenic bacteria.

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The study aimed to analyze the efficacy and safety of rituximab in the treatment of 23 cases of lupus nephritis and explore the prospect of half-dose rituximab in lupus nephritis treatment. Twenty-three patients with lupus nephritis hospitalized in the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital from May 2013 to December 2021 were selected. Eighteen patients received rituximab 375 mg/m 2 on the first and 14th days, 5 patients received 500 mg of rituximab on the first and 14th days, and rituximab was used as needed 6 months later. Methylprednisolone (80-120 mg) was given together with rituximab. Afterward, 1 mg/kg prednisone was used for 4 weeks, which was progressively tapered to maintenance doses or discontinued. B lymphocyte level, renal function, 24-h urine protein level, and systemic lupus erythematosus (SLE) disease activity index 2000 (SLEDAI2K) score before and after treatment were recorded. The efficacy and adverse reactions were analyzed. The results showed that 11 patients suffered from renal insufficiency [creatinine (162.7±58.6) μmol/L ] at baseline, while the creatinine level of 9 patients returned to normal 12 months after the treatment [ (66.3±10.1)μmol/L ]. Normal renal function of the other 12 patients was maintained during treatment. After 12 months, the 24-h urine protein level decreased from 4.00 (2.00,6.80) g in the baseline period to 0.10 (0.08,0.40) g. SLEDAI2K score decreased from 22 (18,26) in the baseline period to 3 (0,6) 12 months after the treatment. The B lymphocyte level reached 0.00 (0.00,0.01)% at 3 months. Of 23 patients, 13 patients achieved complete remission, and 7 patients achieved partial remission after 6 months of rituximab treatment. Five patients experienced adverse reactions related to rituximab, including 1 case of transfusion reaction, 1 case of perioral herpes with pulmonary infection, and 3 cases of decreased IgG levels. Therefore, rituximab regimen used in this study can be an effective treatment strategy for lupus nephritis.