OBJECTIVE: To explore the early changes in various liver function indicators in critically injured trauma patients assessed by intelligent calculation method, aiming to develop more advantageous diagnostic and treatment strategies for traumatic liver injury. METHODS: A retrospective study was conducted. Critically injured trauma patients [injury severity score (ISS) ≥ 16, age > 18 years old] admitted to the Emergency Medical Center of Tianjin Fifth Central Hospital from January 1, 2022, to December 1, 2023 were enrolled. ISS score and acute physiology and chronic health evaluation II (APACHE II) assessed by intelligent calculation method were collected upon patient admission to the emergency medical center. Trends in liver function indicators in fasting venous serum were analyzed at 6, 24 and 72 hours after admission, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), albumin (ALB), total bilirubin (TBil), prothrombin time (PT). Patients were grouped based on APACHE II scores into those with APACHE II < 15 and APACHE II ≤ 15, and liver function indicators within 6 hours of admission were compared between the two groups. RESULTS: A total of 112 critically injured trauma patients were included, with 83 males and 29 females, an average age of (47.78±14.84) years old. The median ISS score was 21.0 (18.0, 26.0). The most common cause of injury for critically injured trauma patients was road traffic accidents (68 cases, accounting for 60.71%), followed by falls from heights, compression injuries, heavy object injuries, knife stabs, and explosion injuries. The most common injured areas was the limbs and pelvis (97 cases, accounting for 86.61%), followed by chest injuries, surface skin and soft tissue injuries, abdominal and pelvic organ injuries, head injuries, and facial injuries. The proportion of elevated LDH, AST, and ALT within 6 hours of admission was 77.68%, 79.46%, and 52.68%, respectively, while the proportion of decreased ALB was 75.89%, the abnormal rates of ALP, GGT, TBil, and PT were all below 50%. The ALT and AST levels of patients at 24 hours and 72 hours after admission were significantly lower than those at 6 hours after admission [ALT (U/L): 37.0 (22.0, 66.0), 31.0 (21.2, 52.0) vs. 41.0 (25.0, 71.0), AST (U/L): 55.5 (30.0, 93.5), 40.0 (27.0, 63.2) vs. 69.5 (39.0, 130.8), all P < 0.05]. There was no statistically significant difference in ISS score between APACHE II > 15 group (45 cases) and APACHE II ≤ 15 group [67 cases; 21.0 (18.5, 26.5) vs. 20.0 (17.0, 22.0), P > 0.05]. Nevertheless, compared with patients with APACHE II ≤ 15, patients with APACHE II > 15 have a higher abnormality rate of ALT and AST within 6 hours of admission [ALT abnormal rate: 66.44% (29/45) vs. 44.78% (30/67), AST abnormal rate: 93.33% (42/45) vs. 70.15% (47/67), both P < 0.05], and the levels of ALT and AST were higher [ALT (U/L): 56.0 (30.0, 121.0) vs. 35.0 (21.0, 69.0), AST (U/L): 87.0 (48.0, 233.0) vs. 52.0 (31.0, 117.0), both P < 0.05]. CONCLUSIONS Severe trauma patients frequently exhibit a high incidence of reversible early liver function impairment. Based on intelligent calculation method, the utilization of both the ISS and APACHE II scores demonstrates a distinct advantage in the assessment of their early liver injury.
Humans ; Retrospective Studies ; Liver/physiopathology* ; Risk Assessment ; APACHE ; Wounds and Injuries ; Adult ; Injury Severity Score ; Male ; Middle Aged ; Female ; Liver Function Tests ; Alanine Transaminase/blood* ; Young Adult ; Aspartate Aminotransferases/blood*

Tumor immunotherapy occupies a pivotal position in the field of hematological malignancies.Chimeric antigen receptor(CAR)T-cell therapy has established a new therapeutic pattern for hematological immunotherapy and achieved satisfactory clinical results in the treatment of B-lineage hematological malignancies.However,CAR T-cell therapy has some limitations in the treatment of T-cell acute lymphoblastic leukemia because of the presence of CAR T-cell fratricide,tumor cell contamination,T-cell aplasia,and other clinically relevant problems.Therefore,the current major challenge is overcoming the existing bottlenecks to optimize CAR-T therapy and improve its efficacy against T-ALL while improving the prognosis of patients.

Permeability is one of the determinants of intestinal absorption and oral bioavailability. The non-cell-based permeation model is a kind of in vitro permeability measurement tool, which has the advantages of high efficiency, low cost, stable property, easy to use and customizable. According to the barrier type, non-cell-based permeation model can be divided into biomimetic barriers containing (phosphate) lipids and non-biomimetic barriers without lipids. Biomimetic permeation models include parallel artificial membrane permeability assay, vesicle-based permeation assay and PermeaPad®. Non biomimetic permeation models include Hollow fiber membrane models based on polyether sulfone materials. In foreign countries, the application of these four barriers for different purposes is gradually becoming a hot spot in drug absorption research. However, in China, there are only more applied studies on PMAPM and few published applied studies on the other three barriers. In order to meet the development needs of insoluble drug formulations, the author summarized the permeability devices and permeability calculation methods, searched the application of non-cell-based permeation model in the permeability of BSCⅡ drugs in recent years, and summarized the characteristic applications of three Biomimetic permeation models and hollow fiber membranes.

Objective:To explore the efficacy of precise and empirical bismuth-containing quadruple therapy guided by clarithromycin sensitivity testing in the first eradication of Helicobacter pylori ( H. pylori) in Ningxia. Methods:From August 12, 2022 to March 22, 2023, 600 patients diagnosed as H. pylori-positive by 14C-urea breath test ( 14C-UBT) for the first time in People′s Hospital of Ningxia Hui Autonomous Region, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region, Zhongwei People′s Hospital, Yanchi County People′s Hospital, and Pingluo People′s Hospital were selected, and divided into empirical treatment group (hereinafter referred to as the empirical group), genetic testing group (hereinafter referred to as the genetic group), and drug sensitivity testing group (hereinafter referred to as the drug sensitivity group) by using random number table with 200 patients in each group. The empirical group did not undergo drug sensitivity testing and genetic testing, while the genetic and drug sensitivity groups were confirmed to be sensitive to clarithromycin through genetic testing and drug sensitivity testing, and the patients with drug-resistant were excluded, respectively. All the patients of the 3 groups received the same clarithromycin bismuth-containing quadruple therapy. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed to compare the eradication rates of H. pylori among 3 groups. Cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER) were used for cost-effectiveness and sensitivity analysis based on the ITT. Chi-square test was used for statistical analysis. Results:There were 200, 126, and 168 patients included in the empirical group, genetic group, and drug sensitivity group in ITT analysis, and 190, 123, and 164 patients were enrolled in the 3 groups in PP analysis, respectively. The results of ITT analysis showed that the eradication rates of H. pylori in the empirical group, genetic group, and drug sensitivity group were 80.5% (161/200), 94.4% (119/126), and 95.2% (160/168), respectively. The results of PP analysis indicated that the eradication rates of H. pylori in the 3 groups were 84.7% (161/190), 96.7% (119/123), and 97.6% (160/164), respectively, and the differences were statistically significant ( χ2=25.39 and 24.93, both P<0.001). The H. pylori eradication rates of genetic group and drug sensitivity group were both higher than that of empirical group in ITT and PP analysis( χ2=12.40, 17.80, 11.42, and 17.13; all P<0.001). The cost-effectiveness analysis showed that the direct treatment cost of the empirical group, genetic group, and drug sensitivity group was 400.8, 729.2, and 779.2 yuan, respectively, and the CER was 4.98, 7.72, and 8.18 yuan/%, respectively. Compared to the empirical group, the ICER of the genetic group and drug sensitivity group was 23.6 and 25.7 yuan/%, respectively. The sensitivity analysis demonstrated that, when the cost of genetic testing reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 21.8 or 25.5 yuan/%, respectively. When the cost of drug sensitivity testing reduced or increased by 20%, the ICER of the drug sensitivity group compared to the empirical group was 23.3 or 28.2 yuan/%. When the cost of gastroscopy reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 20.8 or 26.5 yuan/%, and the ICER of the drug sensitivity group compared to the empirical group was 23.0 or 28.4 yuan/%, respectively. Conclusion:In Ningxia, if the clarithromycin bismuth-containing quadruple regimen is applied as the first H. pylori eradication regimen, in order to achieve the clinical eradication efficacy of H. pylori, and the patients can accept an additional payment of 23.6 or 25.7 yuan for each 1% increasing in the H. pylori eradication rate, then the precision treatment after clarithromycin resistance test is recommended.

Objective:This study aims to summarize the theoretical basis and practical effect of interdisciplinary team building in the National Clinical Medical Research Center for Aging and Medicine, Huashan Hospital.Methods:Interactive memory was employed as the theoretical basis for building cross-disciplinary teams, and the work was carried out in three dimensions of specialization, credibility, and coordination.Results:The center had shaped a coordinative team atmosphere and strengthened its integrity in five dimensions, including discipline construction, open platform, innovation curation, science popularization, and technology transfer. The center also promoted the implementation of research tasks in the three core areas.Conclusions:As the aging healthcare issues are highly diversified, complex, and systematic, the center needs to continuously improve its ability to build interdisciplinary teams and provide a platform for integrating various types of resources into the solution of healthcare problems of the elderly.

Objective:To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants.Methods:This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1 st, 2015 to December 31 st, 2021 of the Seventh Medical Center of the People′s Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children′s Hospital from January 1 st, 2020 to December 31 st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks′ corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model′s discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results:A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95% CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions:A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.

BACKGROUND:Nanocomposite hydrogel has great research prospects and application potential in the treatment of osteoarthritis. OBJECTIVE:To review the research progress of nanocomposite hydrogel in osteoarthritis and cartilage repair. METHODS:Databases such as CNKI and PubMed were searched.The English key words were"nanocomposite hydrogel,nanogel,osteoarthritis,cartage,physical encapsulation,electrostatic interaction,covalent crosslinking",and the Chinese key words were"nanocomposite hydrogel,nanogel,osteoarthritis,cartage,physical encapsulation,physical encapsulation,electrostatic effect,covalent cross-linking".After an initial screening of all articles based on inclusion and exclusion criteria,71 articles with high correlation were retained for review. RESULTS AND CONCLUSION:In cell or animal experiments,nanocomposite hydrogel has the effect of improving osteoarthritis.Nanocomposite hydrogel can promote cartilage repair,improve the internal environment of osteoarthritis,and achieve the therapeutic purpose of osteoarthritis by improving the mechanical environment between joints,carrying targeted drugs,and promoting the chondrogenesis of seed cells.At present,the research of nanocomposite hydrogel in osteoarthritis disease still has a huge space to play.It is expected to open up a new way for the clinical treatment of osteoarthritis by continuing to deepen the research of material preparation and actively carrying out cell and animal experiments.

Objective To analyze the medication rule of Traditional Chinese Medicine(TCM)in treating diabetes nephropathy(DN)and to explore the interaction between core components and key targets.Methods Based on the ancient and modern medical case cloud platform,the medication rules of TCMs and the drug pairs with the highest frequency in treating DN were summarized.Then the network pharmacology approach was utilized to analyze the pharmacodynamic material basis and mechanisms of the highest frequency-drug pairs.The potential targets were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)databases.TTD,DISGENET,and GENECARD databases were used to obtain the related targets of DN and screen out the potential targets for DN.In order to clarify the relationships between the active ingredients,the core targets,and pathways,STRING and Cytoscape 3.7.1 software were used to construct the protein-protein interaction(PPI)network and core drugs-ingredients-targets-disease interaction network,DAVID database was screened for Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis of core targets.Sybyl 2.1 software and biofilm interference verify the combined capacity between the core ingredients and key targets.Results Among 183 prescriptions,Astragali Radix had the highest use frequency and average dose,43 times and 37 g,respectively,followed by Salviae miltiorrhizae Radix and Poria cocos.To find the core combined with the highest confidence in association analysis was astragalus,salvia miltiorrhiza,and tuckahoe.Correlation analysis indicates that the core combination with the highest confidence was Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos.Network pharmacologic showed 89 potential targets and 15 key signaling pathways for the treatment of DN by the drug pair.TNF signaling pathway,Nod-like receptor signaling pathway,and MAPK signaling pathway were disease-related pathways,and IL-6,TNF,and vascular endothelial growth factor A(VEGFA)were core targets.Isorhamnetin and quercetin of the drug pair had high binding ability with IL6,the scores were 8.2 and 7.4,respectively,and the dissociation constants(KD)were 5.6×10-5 mol·L-1 and 6.8×10-5 mol·L-1,respectively.Conclusion This study preliminarily finds the prescription rule of treating DN with Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos as the core drug pair,isorhamnetin,and quercetin are probably the main active compounds of this drug pair in DN treatment,which provides a basis for clinical treatment and drug discovery of DN.

In China, the level of ambient fine particulate matter (PM 2.5 ) pollution far exceeds the air quality standards recommended by the World Health Organization. Moreover, the health effects of PM 2.5 exposure have become a major public health issue. More than half of PM 2.5 -related excess deaths are caused by cardiopulmonary disease, which has become a major health risk associated with PM 2.5 pollution. In this review, we discussed the latest epidemiological advances relating to the health effects of PM 2.5 on cardiopulmonary diseases in China, including studies relating to the effects of PM 2.5 on mortality, morbidity, and risk factors for cardiovascular and respiratory diseases. These data provided important evidence to highlight the cardiopulmonary risk associated with PM 2.5 across the world. In the future, further studies need to be carried out to investigate the specific relationship between the constituents and sources of PM 2.5 and cardiopulmonary disease. These studies provided scientific evidence for precise reduction measurement of pollution sources and public health risks. It is also necessary to identify effective biomarkers and elucidate the biological mechanisms and pathways involved; this may help us to take steps to reduce PM 2.5 pollution and reduce the incidence of cardiopulmonary disease.
Humans ; Particulate Matter/analysis* ; Air Pollution/adverse effects* ; Risk Factors ; Respiratory Tract Diseases ; China/epidemiology* ; Environmental Exposure/adverse effects*

Objective To identify M1 macrophage-related genes in rejection after kidney transplantation and construct a risk prediction model for renal allograft survival. Methods GSE36059 and GSE21374 datasets after kidney transplantation were downloaded from Gene Expression Omnibus (GEO) database. GSE36059 dataset included the samples from the recipients with rejection and stable allografts. Using this dataset, weighted gene co-expression network analysis (WGCNA) and differential analysis were conducted to screen the M1 macrophage-related differentially expressed gene (M1-DEG). Then, GSE21374 dataset (including the follow-up data of graft loss) was divided into the training set and validation set according to a ratio of 7∶3. In the training set, a multivariate Cox's model was constructed using the variables screened by least absolute shrinkage and selection operator (LASSO), and the ability of this model to predict allograft survival was evaluated. CIBERSORT was employed to analyze the differences of infiltrated immune cells between the high-risk group and low-risk group, and the distribution of human leukocyte antigen (HLA)-related genes was analyzed between two groups. Gene set enrichment analysis (GSEA) was used to further clarify the biological process and pathway enrichment in the high-risk group. Finally, the database was employed to predict the microRNA (miRNA) interacting with the prognostic genes. Results In the GSE36059 dataset, 14 M1-DEG were screened. In the GSE21374 dataset, Toll-like receptor 8 (TLR8), Fc gamma receptor 1B (FCGR1B), BCL2 related protein A1 (BCL2A1), cathepsin S (CTSS), guanylate binding protein 2(GBP2) and caspase recruitment domain family member 16 (CARD16) were screened by LASSO-Cox regression analysis, and a multivariate Cox's model was constructed based on these 6 M1-DEG. The area under curve (AUC) of receiver operating characteristic of this model for predicting the 1- and 3-year graft survival was 0.918 and 0.877 in the training set, and 0.765 and 0.736 in the validation set, respectively. Immune cell infiltration analysis showed that the infiltration of rest and activated CD4⁺ memory T cells, γδT cells and M1 macrophages were increased in the high-risk group (all P < 0.05). The expression level of HLA I gene was up-regulated in the high-risk group. GSEA analysis suggested that immune response and graft rejection were enriched in the high-risk group. CTSS interacted with 8 miRNA, BCL2A1 and GBP2 interacted with 3 miRNA, and FCGR1B interacted with 1 miRNA. Conclusions The prognostic risk model based on 6 M1-DEG has high performance in predicting graft survival, which may provide evidence for early interventions for high-risk recipients.