Objective To study the photodynamic performance and the killing effect of photodynamic therapy on lung cancer of novel chlorin compounds 2-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） acetic acid（D1）and 4-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） butanoic acid （D2）. Methods The ultraviolet visible absorption spectrum and fluorescence spectrum of D1 and D2 were determined. The singlet oxygen generation capacity of D1 and D2 was measured by using DPBF as singlet oxygen capture agent. Fluorescence assay was used to detect the cellular phagocytosis rate of the compounds in A549 cells, and MTT assay was used to detect their dark toxicity and phototoxicity. A nude mouse model of lung cancer was established to investigate the antitumor activity of the compounds mediated photodynamic action in vivo, and the blood concentration of D2 in nude mice, its distribution in tumor tissue and skin tissue were further detected. Results D1 and D2 had strong absorption at 652 nm with the best excitation wavelength at 429 nm and 427 nm, and the optimal emission wavelength was at about 659 nm. They also had a higher singlet oxygen generation rate than the control drug m-THPC. D1 and D2 had no dark toxicity at concentrations below 10 μmol/L, and could be ingested by A549 cells, basically reaching saturation in 18~24 hours. After laser irradiation at 650 nm wavelength, D1 and D2 showed significant antitumor activity in vivo and in vitro （P<0.01）. However, D2 could selectively accumulate in tumor tissues after administration, and the optimal treatment time was less than 30 min after administration. Conclusion D2 had excellent photodynamic antitumor activity and could selectively aggregate in tumor tissues, which had the potential to be a candidate drug for photosensitizer and treatment of lung cancer with independent intellectual property rights, and was worth further research.

ObjectiveTo investigate the value of predictive models established based on machine learning methods in predicting the risk of metabolic associated fatty liver disease （MAFLD）， and to analyze its key risk factors. MethodsA retrospective analysis was performed for the 50 variables of 2 168 healthy individuals who underwent physical examination in Department of Health Assessment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， from January 2021 to December 2024， including body composition， past history， and laboratory tests， and according to whether they were diagnosed with MAFLD or not， they were divided into MAFLD group with 265 individuals and non-MAFLD group with 1 903 individuals. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. Randomly split the research data into a training set and a validation set in a 70% to 30% ratio. Predictive factors were screened from the training set data using univariate analysis， LASSO regression， and multivariate Logistic regression analysis. Predictive models were then constructed using seven machine learning methods： Logistic regression， decision tree， random forest （RF）， eXtreme gradient boosting， light gradient boosting machine， support vector machine， and artificial neural network. Model performance was evaluated by plotting receiver operating characteristic curve for the validation set and calculating the area under the curve （AUC）， sensitivity， specificity， and Youden index for each model. Furthermore， the SHapley Additive exPlanation （SHAP） method was used to analyze the contribution of variables in the optimal model. ResultsThe prevalence rate of MAFLD among the 2 168 subjects was 12.22% （265/2 168）. Smoking， diastolic blood pressure， phase angle， visceral fat area， muscle fat ratio， waist-to-hip ratio， aspartate aminotransferase， non-HDL-C/HDL-C ratio， triglyceride-glucose index， and gallstones were independent risk factors for MAFLD （all P<0.05）. The seven predictive models of support vector machine， eXtreme gradient boosting， decision tree， light gradient boosting machine， artificial neural network， RF， and Logistic regression had an AUC of 0.738， 0.754， 0.757， 0.786， 0.795， 0.796， and 0.815， respectively， in the validation set， among which the RF model had the best discriminatory ability （AUC=0.796， 95% confidence interval： 0.754 — 0.839）， with a sensitivity of 81.01%， a specificity of 63.16%， and a Youden index of 44.17%. The SHAP analysis showed that visceral fat area， waist-to-hip ratio， and diastolic blood pressure were the top three predictive factors in terms of importance. ConclusionThe RF model， constructed based on body composition and clinical indicators， has a good performance in predicting the risk of MAFLD， and its interpretability can help to identify high-risk individuals in the early stage in clinical practice.

Obesity is a chronic low-grade inflammation and a risk factor for diseases such as diabetes， hypertension， dyslipidemia， and malignant tumors， demonstrating an increasingly grim development situation. The nuclear factor-kappa B （NF-κB） signaling pathway is a key signaling pathway involved in the immune response and inflammatory response. In obese individuals， the expression of NF-κB is overactivated， which leads to abnormal inflammatory responses in the body. Therefore， it is expected to alleviate inflammation and treat obesity by regulating the NF-κB signaling pathway， which has been proven effective by a large number of studies. The available studies on the NF-κB signaling pathway mostly focus on tumors， and there is no systematic review of the mechanism of this pathway in mediating obesity and the traditional Chinese medicine （TCM） treatment. We reviewed the research progress in the pathological and physiological processes of obesity mediated by NF-κB signaling pathway and TCM treatment， aiming to give insights into the clinical treatment of obesity with TCM and provide reference targets and research directions for exploring the biological foundations and the development of new TCM preparations.

Objective: To compare the value of a body shape index (ABSI) and body roundness index (BRI) in predicting non-alcoholic fatty liver disease (NAFLD) among non-obese population, so as to provide a reference for the early identification of populations at high risk of NAFLD. Methods: Adults with a body mass index (BMI) of less than 28 kg/m2 who underwent health check-ups in Xiyuan Hospital of China Academy of Chinese Medical Sciences from 2022 to 2024 were selected as the study subjects. Demographic information, disease history, height, weight, waist circumference, blood pressure, and blood lipid indicators were collected, and ABSI and BRI were calculated. NAFLD was diagnosed using abdominal ultrasound. A multivariable logistic regression model was employed to analyze the relationships between ABSI, BRI and NAFLD among non-obese population. A generalized additive model combined with the penalized spline method was used to fit smooth curves to identify nonlinear relationships, and threshold effects were utilized to determine inflection points. The values of ABSI and BRI in predicting NAFLD among non-obese population were used the receiver operating characteristic (ROC) curve. Results: A total of 1 195 individuals were surveyed, including 345 males (28.87%) and 850 females (71.13%). A total of 348 cases of NAFLD were detected among the non-obese population, with a detection rate of 29.12%. The adjusted ABSI (sABSI) in the NAFLD group and non-NAFLD group were 7.95±0.33 and 8.08±0.34, while the BRI were 3.35±0.79 and 4.15±0.64, respectively, with statistically significant differences between the two groups (both P<0.05). Multivariable logistic regression analysis showed that, after adjusting for demographic information, disease history, blood pressure, and blood lipid indicators, both sABSI (OR=1.932, 95%CI: 1.184-3.158) and BRI (OR=1.594, 95%CI: 1.071-2.360) were significantly associated with NAFLD among non-obese population. Nonlinear positive correlations were observed between sABSI, BRI, and NAFLD among non-obese population. When sABSI≤8.46 and BRI≥2.72, both indices were positively associated with NAFLD. The area under the ROC curve for ABSI and BRI in predicting NAFLD risk among non-obese population were 0.619 and 0.782, respectively, with optimal cut-off values of 0.082 and 3.656, respectively. Conclusions ABSI and BRI show a non-linear relationship with NAFLD among non-obese population. BRI demonstrates relatively better performance in predicting NAFLD risk among this population and can serve as an auxiliary indicator for the early identification of NAFLD among non-obese population.

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

Patient 1, a 3-year-6-month-old male, presented with feeding difficulties and delayed motor development. He exhibited poor responsiveness at birth, weak crying, intellectual and motor delays, low immunity, recurrent respiratory infections, hypotonia of the limbs, and distinctive facial features (low-set ears, double chin, and high arched palate), as well as a single transverse palmar crease on the right hand. Genetic testing revealed a c.1096C>T heterozygous variant in the SMARCB1 gene. Patient 2, a 3-year-old male, presented with developmental delay and distinctive facial features. Genetic testing identified the same pathogenic mutation as in Patient 1. The two patients are unrelated, and clinical phenotyping and genetic testing confirmed both cases as Coffin-Siris syndrome type 3. Coffin-Siris syndrome is a rare genetic disorder, and early genetic testing can aid in diagnosis.
Child, Preschool ; Humans ; Male ; Abnormalities, Multiple/genetics* ; Chromosomal Proteins, Non-Histone/genetics* ; Ear/abnormalities* ; Face/abnormalities* ; Hand Deformities, Congenital/genetics* ; Intellectual Disability/genetics* ; Micrognathism/genetics* ; Mutation ; Neck/abnormalities*

OBJECTIVE: To study the genetic polymorphism of red blood cell blood group among in Shenzhen Han, Indian and Xinjiang Uyghur populations, to provide scientific basis for the demand prediction and collection strategy of rare blood group, and to explore the genetic differences of blood group between Han and Caucasians. METHODS: The haplotypes of antigen coding genes of 10 target blood group systems from 87 Han Chinese and 50 Indian blood donors in Shenzhen, and 49 healthy Uyghur people in Xinjiang were obtained by three-generation sequencing technology, and the polymorphism and frequency characteristics were analyzed. RESULTS: Only a single genotype was detected the Langereis and Vel blood group systems in samples from three different populations. Only one genotype of Dombrock blood group was detected in Shenzhen Han, and Junior blood group in Xinjiang Uygur populations. In the MNS, Duffy, Kidd, Dombrock and Junior blood group systems, the haplotype frequency of Indian and Uyghur people was significantly different from that of Han people. Compared with the Han ethnic group, the rare blood group s-, Fy(a-), Jk(a-b-), and Do(a+b-) have a higher frequency among the Uyghur and Indian populations. CONCLUSION Haplotype frequencies of antigen genes for MNS, Duffy, Kidd, Dombrock and Junior blood group system in Shenzhen Han, Indian and Uyghur populations displayed a polymorphic difference with unique distribution characteristics different from the ethnic groups in other regions.
Humans ; Blood Group Antigens/genetics* ; China/ethnology* ; Erythrocytes ; Ethnicity/genetics* ; Gene Frequency ; Genotype ; Haplotypes ; India/ethnology* ; Polymorphism, Genetic ; White People/genetics* ; Central Asian People/genetics* ; East Asian People/genetics*

OBJECTIVE: To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis. METHODS: A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table, including the control group, the model group, miR-30a agomir group, SMI low-dose (SMI-L) group, and SMI high-dose (SMI-H) group, with 8 rats in each group. Except for the control group, the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury, and were given different regimens of continuous intervention for 2 weeks. Cardiac function was detected by echocardiography and myocardial pathological changes were observed by Van Gieson (VG) staining. Myocardial injury serum markers, including creatine kinase (CK), lactate dehydrogenase (LDH), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble ST2 (sST2), and growth differentiation factor-15 (GDF-15) were detected by enzyme linked immunosorbent assay (ELISA). Cardiomyocyte apoptosis was observed by terminal deoxynucleotidyl transferase-mediated biotinylated dUTP triphosphate nick end labeling (TUNEL) and transmission electron microscopy, and the expressions of target proteins and mRNA were detected by Western blot and quantitative real time polymerase chain reaction (qRT-RCR), respectively. RESULTS: The treatment with different doses of SMI reduced rat heart mass index and left ventricular mass index (P<0.05), significantly improved the left ventricular ejection fraction (P<0.05), decreased the levels of serum CK, LDH, cTnT, and NT-proBNP (P<0.05 or P<0.01), reduced the levels of serum sST2 and GDF-15 (P<0.05 or P<0.01), decreased the collagen volume fraction, reduced the expressions of rat myocardial type I and type III collagen (P<0.05 or P<0.01), and effectively alleviated myocardial fibrosis. And the study found that SMI promoted the expression levels of miR-30a and Bcl-2 in myocardium, and down-regulated the expression of Bax, which inhibited the activation of Caspase-3 and Caspase-9 (P<0.05 or P<0.01), and improved myocardial cell apoptosis. CONCLUSIONS SMI can alleviate myocardial injury and apoptosis caused by DOX, and its mechanism possibly by promoting the targeted expression of myocardial Bcl-2 protein through miR-30a.
Animals ; Myocytes, Cardiac/metabolism* ; Apoptosis/drug effects* ; MicroRNAs/genetics* ; Rats, Sprague-Dawley ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Doxorubicin/pharmacology* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Drug Combinations ; Injections ; Rats

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*