Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective:To investigate the effects of prognostic nutritional index (PNI) on the readmission rate, complication rate, mortality rate and survival of patients with liver cirrhosis.Methods:From January 1, 2020 to December 31, 2022, 395 hospitalized patients with liver cirrhosis at Tianmen Hospital Affiliated to Wuhan University of Science and Technology were retrospectively enrolled. The clinical data were collected from the patients at their first hospitalization (baseline period) and re-hospitalization during follow-up period. The 18-month follow-up was divided into 4 periods, including the first period (from the 0th to the 3rd month), the second one was from the 4th to the 6th month, the third one was from the 7th to the 12th month, and the fourth one was from the 13th to the 18th month of follow-up. The prognostic value of PNI for patients with liver cirrhosis was evaluated through the receiver operating characteristic curve (ROC) of the baseline PNI. The 395 patients were divided into the low PNI group and the high PNI group based on the optimal cut-off value of PNI on the ROC. Patients readmitted during each follow-up period were divided into the PNI improvement group (PNI at follow-up -PNI at baseline>0) and the PNI non-improvement group (PNI at follow-up-PNI at baseline ≤0). Independent sample t-test, one-way analysis of variance (ANOVA), Mann-Whitney U test, chi-square test or Fisher′s exact test were used for statistical analysis. Survival curves depicting the relationship between PNI and overall survival rate of patients with liver cirrhosis were constructed using the Kaplan-Meier method. Results:The ROC analysis indicated that the optimal cut-off value of PNI at baseline was 32.65, with an area under the curve of 0.639 (95% confidence interval: 0.541 to 0.738, P=0.011), with a sensitivity of 0.567 and a specificity of 0.701. There were 269 cases in the high PNI group and 126 cases in the low PNI group. The readmission rate, complication rate and mortality rate in the low PNI group were all higher than those in the high PNI group at the first and fourth follow-up periods (32.5% (41/126) vs. 22.3% (60/269), 31.7% (40/126) vs. 20.4% (55/269), 6.3% (8/126) vs. 1.1% (3/269), 25.0% (29/116) vs. 16.2% (42/260), 25.0% (29/116) vs. 15.4% (40/260), 6.0% (7/116) vs. 1.5% (4/260)), and the differences were statistically significant ( χ2=4.72, 6.00, 6.86, 4.10, 4.95, and 4.24; P=0.030, 0.014, 0.009, 0.043, 0.026, and 0.040). The mortality rates of the PNI improvement group at the first and fourth follow-up periods were both lower than those of the PNI non-improvement group (4.3% (2/47) vs. 16.7% (9/54), 0 (0/24) vs. 23.4% (11/47)), and the differences were statistically significant ( χ2=3.99, Fisher′s exact test; P=0.046 and 0.012). There were no statistically significant difference in the incidence of complications between the PNI improvement group and the PNI non-improvement group at each follow-up period (all P>0.05). The Kaplan-Meier survival curve demonstrated that the average survival time of the high PNI group was longer than that of the low PNI group (17.54 months (95% confidence interval: 17.26 to 17.83 months) vs. 16.74 months (95% confidence interval: 16.96 to 17.52 months), and the difference was statistically significant ( χ2=9.18, P<0.001). The survival rate of the high PNI group at the 18th month of follow-up period was higher than that of the low PNI group (95.2% (256/269) vs. 86.5% (109/126), and the difference was statistically significant ( χ2=9.17, P=0.002). Conclusions:PNI has certain predictive efficacy for the survival period of patients with liver cirrhosis. Low-level PNI may increase the readmission rate, complication rate, and mortality of patients with liver cirrhosis, and shorten the survival period, indicating poor prognosis.

Objective : To predict and validate key targets for cisplatin(DDP) resistance in colorectal cancer(CRC) to provide more options for precision medicine in clinical treatment. Methods: Differentially expressed genes(DEGs) between normal colonic mucosa and CRC were screened from the gene expression omnibus(GEO) database. Key genes were identified using the STRING database and Cytoscape software. DEGs were subjected to enrichment analysis using the gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) databases. Key targets were validated through RNA-seq, qRT-PCR, and Western blot. The versican(VCAN) gene overexpression vector was transfected into human ileocecal colorectal adenocarcinoma cell line HCT8, and cell viability was assessed using the CCK-8 assay. Flow cytometry was used to assess apoptosis and cell cycle distribution. qRT-PCR and Western blot were performed to detect mRNA and protein levels of the target genes. Results : In this study, 118 upregulated DEGs and 146 downregulated DEGs were identified from the GEO database. DEGs were mainly enriched in extracellular matrix degradation, extracellular matrix organization, and the phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT) signaling pathway. Based on protein-protein interaction network analysis, 20 hub genes were identified. By comparing the transcriptome sequencing results of the HCT8 parental strain and DDP-resistant strain, the VCAN gene was further selected. In CRC tissues, the expression level of VCAN was higher than that in normal colonic mucosa, and patients with high VCAN expression had shorter overall survival(OS) and recurrence free survival(RFS) times. Overexpression of VCAN in CRC cells promoted cell proliferation(P<0.05), increased resistance to DDP, reduced DDP-induced apoptosis(P<0.05), and G0/G1phase arrest(P<0.05); upregulation of VCAN activated the protein kinase B(AKT)-mammalian target of rapamycin(mTOR) signaling pathway. Conclusion Bioinformatics and transcriptome sequencing identified VCAN as a key target gene for DDP resistance in CRC, potentially promoting CRC progression and DDP resistance by regulating the AKT-mTOR pathway.

Reconstruction of low-dose CT image faced problems such as low resolution,blurred artifacts and strong noise.Deep learning reconstruction met the needs of reducing radiation dose and improving imaging quality,promoted reconstruction of CT image towards high efficiency,intelligence and integration of clinical diagnosis and treatment.The research progresses in deep learning low-dose CT imaging reconstruction were reviewed in this article.

Objective:To explore the early predictive value of the triglyceride-glucose (TyG) index and the controlling nutritional status (CONUT) score for severe acute pancreatitis (SAP).Methods:Clinical data from 1 050 hospitalized patients with acute pancreatitis (AP) at the General Hospital of Central Theater Command between January 2019 and December 2023 were retrospectively analyzed. Patients were categorized into mild acute pancreatitis (MAP) group ( n=606), moderately severe acute pancreatitis (MSAP) group ( n=320), and SAP group ( n=124) based on AP severity. General clinical data, laboratory parameters, modified computed tomography severity index (MCTSI), bedside index for severity in acute pancreatitis (BISAP), TyG index, and CONUT score were compared among the three groups. Spearman correlation analysis was used to evaluate the relationship between TyG index, CONUT score and AP severity. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for AP severity. Receiver operating characteristic curves (ROC) were plotted to calculate the area under the curve (AUC), sensitivity, and specificity for evaluating the predictive efficacy of TyG index, CONUT score, and their combination for SAP. Results:Significant differences on TyG index and CONUT score were observed among AP patients with varying severity (all P value <0.001). Spearman correlation analysis further revealed positive correlations of TyG index ( r=0.174), CONUT score ( r=0.306) with AP severity (both P<0.001). Multivariate logistic regression identified neutrophil count ( OR=1.076, 95% CI 1.027-1.125), MCTSI ( OR=2.565, 95% CI 2.250-2.921), BISAP ( OR=3.522, 95% CI 2.726-4.549), TyG index ( OR=1.859, 95% CI 1.276-2.707), and CONUT score ( OR=1.155, 95% CI 1.035-1.288) as independent risk factors for AP severity. The combined predictive model equation was: -7.342+0.76×TyG+0.439×CONUT. ROC analysis showed that the AUC values of the TyG index, CONUT score, and the combined index (TyG index+CONUT score) were 0.583 (95% CI 0.529-0.637), 0.701 (95% CI 0.652-0.75), and 0.755 (95% CI 0.710-0.801), with sensitivities of 0.706, 0.677, and 0.742, and specificities of 0.884, 0.629, and 0.657, respectively (all P value <0.05). Conclusions:TyG index and CONUT score are positively correlated with AP severity and may serve as reliable predictors for SAP. Their combination could enhance the predictive accuracy for AP.

Objective:To explore the early predictive value of the triglyceride-glucose (TyG) index and the controlling nutritional status (CONUT) score for severe acute pancreatitis (SAP).Methods:Clinical data from 1 050 hospitalized patients with acute pancreatitis (AP) at the General Hospital of Central Theater Command between January 2019 and December 2023 were retrospectively analyzed. Patients were categorized into mild acute pancreatitis (MAP) group ( n=606), moderately severe acute pancreatitis (MSAP) group ( n=320), and SAP group ( n=124) based on AP severity. General clinical data, laboratory parameters, modified computed tomography severity index (MCTSI), bedside index for severity in acute pancreatitis (BISAP), TyG index, and CONUT score were compared among the three groups. Spearman correlation analysis was used to evaluate the relationship between TyG index, CONUT score and AP severity. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for AP severity. Receiver operating characteristic curves (ROC) were plotted to calculate the area under the curve (AUC), sensitivity, and specificity for evaluating the predictive efficacy of TyG index, CONUT score, and their combination for SAP. Results:Significant differences on TyG index and CONUT score were observed among AP patients with varying severity (all P value <0.001). Spearman correlation analysis further revealed positive correlations of TyG index ( r=0.174), CONUT score ( r=0.306) with AP severity (both P<0.001). Multivariate logistic regression identified neutrophil count ( OR=1.076, 95% CI 1.027-1.125), MCTSI ( OR=2.565, 95% CI 2.250-2.921), BISAP ( OR=3.522, 95% CI 2.726-4.549), TyG index ( OR=1.859, 95% CI 1.276-2.707), and CONUT score ( OR=1.155, 95% CI 1.035-1.288) as independent risk factors for AP severity. The combined predictive model equation was: -7.342+0.76×TyG+0.439×CONUT. ROC analysis showed that the AUC values of the TyG index, CONUT score, and the combined index (TyG index+CONUT score) were 0.583 (95% CI 0.529-0.637), 0.701 (95% CI 0.652-0.75), and 0.755 (95% CI 0.710-0.801), with sensitivities of 0.706, 0.677, and 0.742, and specificities of 0.884, 0.629, and 0.657, respectively (all P value <0.05). Conclusions:TyG index and CONUT score are positively correlated with AP severity and may serve as reliable predictors for SAP. Their combination could enhance the predictive accuracy for AP.

Reconstruction of low-dose CT image faced problems such as low resolution,blurred artifacts and strong noise.Deep learning reconstruction met the needs of reducing radiation dose and improving imaging quality,promoted reconstruction of CT image towards high efficiency,intelligence and integration of clinical diagnosis and treatment.The research progresses in deep learning low-dose CT imaging reconstruction were reviewed in this article.

Objective:To investigate the effects of prognostic nutritional index (PNI) on the readmission rate, complication rate, mortality rate and survival of patients with liver cirrhosis.Methods:From January 1, 2020 to December 31, 2022, 395 hospitalized patients with liver cirrhosis at Tianmen Hospital Affiliated to Wuhan University of Science and Technology were retrospectively enrolled. The clinical data were collected from the patients at their first hospitalization (baseline period) and re-hospitalization during follow-up period. The 18-month follow-up was divided into 4 periods, including the first period (from the 0th to the 3rd month), the second one was from the 4th to the 6th month, the third one was from the 7th to the 12th month, and the fourth one was from the 13th to the 18th month of follow-up. The prognostic value of PNI for patients with liver cirrhosis was evaluated through the receiver operating characteristic curve (ROC) of the baseline PNI. The 395 patients were divided into the low PNI group and the high PNI group based on the optimal cut-off value of PNI on the ROC. Patients readmitted during each follow-up period were divided into the PNI improvement group (PNI at follow-up -PNI at baseline>0) and the PNI non-improvement group (PNI at follow-up-PNI at baseline ≤0). Independent sample t-test, one-way analysis of variance (ANOVA), Mann-Whitney U test, chi-square test or Fisher′s exact test were used for statistical analysis. Survival curves depicting the relationship between PNI and overall survival rate of patients with liver cirrhosis were constructed using the Kaplan-Meier method. Results:The ROC analysis indicated that the optimal cut-off value of PNI at baseline was 32.65, with an area under the curve of 0.639 (95% confidence interval: 0.541 to 0.738, P=0.011), with a sensitivity of 0.567 and a specificity of 0.701. There were 269 cases in the high PNI group and 126 cases in the low PNI group. The readmission rate, complication rate and mortality rate in the low PNI group were all higher than those in the high PNI group at the first and fourth follow-up periods (32.5% (41/126) vs. 22.3% (60/269), 31.7% (40/126) vs. 20.4% (55/269), 6.3% (8/126) vs. 1.1% (3/269), 25.0% (29/116) vs. 16.2% (42/260), 25.0% (29/116) vs. 15.4% (40/260), 6.0% (7/116) vs. 1.5% (4/260)), and the differences were statistically significant ( χ2=4.72, 6.00, 6.86, 4.10, 4.95, and 4.24; P=0.030, 0.014, 0.009, 0.043, 0.026, and 0.040). The mortality rates of the PNI improvement group at the first and fourth follow-up periods were both lower than those of the PNI non-improvement group (4.3% (2/47) vs. 16.7% (9/54), 0 (0/24) vs. 23.4% (11/47)), and the differences were statistically significant ( χ2=3.99, Fisher′s exact test; P=0.046 and 0.012). There were no statistically significant difference in the incidence of complications between the PNI improvement group and the PNI non-improvement group at each follow-up period (all P>0.05). The Kaplan-Meier survival curve demonstrated that the average survival time of the high PNI group was longer than that of the low PNI group (17.54 months (95% confidence interval: 17.26 to 17.83 months) vs. 16.74 months (95% confidence interval: 16.96 to 17.52 months), and the difference was statistically significant ( χ2=9.18, P<0.001). The survival rate of the high PNI group at the 18th month of follow-up period was higher than that of the low PNI group (95.2% (256/269) vs. 86.5% (109/126), and the difference was statistically significant ( χ2=9.17, P=0.002). Conclusions:PNI has certain predictive efficacy for the survival period of patients with liver cirrhosis. Low-level PNI may increase the readmission rate, complication rate, and mortality of patients with liver cirrhosis, and shorten the survival period, indicating poor prognosis.

Primary sclerosing cholangitis(PSC)is a cholestatic disease characterized by chronic progressive bile duct inflammation and has a low incidence rate and poor prognosis in China.There is still no drug therapy that can change the course of PSC,and liver transplantation is the only effective treatment for PSC,with a 5-year survival rate of 85%after transplantation.Drug therapy for PSC is facing great challenges based on the current status of PSC.At present,drugs for the treatment of PSC are in the stage of clinical trials and have shown certain application prospect,among which ursodeoxycholic acid is the most widely studied and commonly used drug.In addition,there are many emerging drugs in the pipeline.This article summarizes the latest advances in drug therapy for PSC.