Traditional Chinese medicine (TCM) demonstrates distinctive advantages in disease prevention and treatment. However, analyzing its biological mechanisms through the modern medical research paradigm of "single drug, single target" presents significant challenges due to its holistic approach. Network pharmacology and its core theory of network targets connect drugs and diseases from a holistic and systematic perspective based on biological networks, overcoming the limitations of reductionist research models and showing considerable value in TCM research. Recent integration of network target computational and experimental methods with artificial intelligence (AI) and multi-modal multi-omics technologies has substantially enhanced network pharmacology methodology. The advancement in computational and experimental techniques provides complementary support for network target theory in decoding TCM principles. This review, centered on network targets, examines the progress of network target methods combined with AI in predicting disease molecular mechanisms and drug-target relationships, alongside the application of multi-modal multi-omics technologies in analyzing TCM formulae, syndromes, and toxicity. Looking forward, network target theory is expected to incorporate emerging technologies while developing novel approaches aligned with its unique characteristics, potentially leading to significant breakthroughs in TCM research and advancing scientific understanding and innovation in TCM.
Artificial Intelligence ; Medicine, Chinese Traditional ; Humans ; Network Pharmacology/methods* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Multiomics

ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg^-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe²⁺ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe²⁺ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.

Objective:To establish a nucleic acid detection and genotyping method for Mycoplasma pneumoniae ( Mp) based on nucleic acid in clinical samples. Methods:Through genomic comparison, the specific target sequences of Genotype 1 and Genotype 2 Mp strains were selected to design synthetic primers and probes, and a PCR detection and classification method for Mp dual fluorescent probe was established, and the specificity, accuracy, detection limit and repeatability of the method were evaluated. The established fluorescence PCR method was used to detect the nucleic acid of clinical specimens and compared with the reported fluorescent PCR methods. Results:The nucleic acid of 18 pathogens, including other species of Mycoplasma and common respiratory bacteria and viruses, which were closely related to the Mp species, were detected, and the results showed that there was no cross-reactivity. The accuracy of detection and typing of 90 Mp nucleic acid was 100%. The detection limits of Genotype 1 and Genotype 2 Mp samples were 1.0 copy/μl, and the experimental coefficient of variation of repeatability within groups and between groups was less than 2.5%. In the detection of 88 nucleic acid of clinical specimens, the Kappa value was 0.675 and the P value was 0.267 compared with the reported real-time PCR method, showing a high degree of agreement. Conclusions:The method for detecting and genotyping Mp in this study has high sensitivity, specificity, and accuracy, which can be applied to the monitoring and prevention and control of Mp in the disease control system of provinces and cities at all levels in China. This method promotes the improvement of the Mp prevention and control system in China, strengthens the surveillance ability, and is of great significance for the early warning and prediction of Mp.

Background::Liver cancer remains the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide, causing a heavy burden globally. An updated assessment of the global epidemiology of the liver cancer burden that addresses geographical disparities is necessary to better understand and promote healthcare delivery.Methods::Data were extracted from the GLOBOCAN 2022 database, including the number, crude, and age-standardized rates of incidence and mortality at the global, country, continent, and human development index (HDI) regional levels. Age-standardized rates (incidence and mortality) per 100,000 person-years were adjusted based on the Segi-Doll World standard population. The mortality-to-incidence ratios (MIR) for each region and country were calculated. The HDI and gross national income (GNI) for 2022 were obtained, and a Pearson correlation analysis was conducted with the incidence, mortality, and MIR.Results::In 2022, approximately 866,136 new liver cancer cases and 758,725 related deaths were recorded worldwide, with a global MIR of 0.86. Males had a disproportionately higher burden than females across all levels, and the highest burden was observed in the elderly population. Geographically, the regions with the highest incidence rates included Micronesia, Eastern Asia, and Northern Africa, and the regions with the highest mortality rates included Northern Africa, Southeastern Asia, Eastern Asia, and Micronesia. Notably, Mongolia had a strikingly high burden compared to other countries. The highest MIR was observed in North America and the lowest in Africa. Negative associations of HDI and GNI with liver cancer mortality and MIR were identified, irrespective of sex.Conclusions::The current liver cancer burden underscores the presence of remarkable geographic heterogeneity, which is particularly evident across countries with varying HDI levels, highlighting the urgent need to prioritize health accessibility and availability to achieve health inequities.

Objective:To understand the current status of pubertal sexual characteristics development of girls aged 6-18 years in Tongzhou District of Beijing and to compare the differences in sexual characteristics development among girls characterized as thin, normal, overweight, and obese.Methods:A cross-sectional survey was conducted among 2 844 girls aged 6-18 years in Tongzhou District of Beijing from September 2022 to July 2023. The developmental stages of breast and pubic hair were assessed on site, and menarche status was inquired. Weight and height were measured. The girls were subsequently characterized into thin, normal, overweight and obese groups. Basic information (including family and personal history) was obtained through questionnaires. Probit probability unit regression was applied to calculate the age of each Tanner stage of sexual characteristics development and the age of menarche. The χ 2 test was applied to compare the counting data between two or multiple groups. Results:A total of 2 844 girls were surveyed and 2 704 girls met the inclusion criteria, resulting in a valid response rate of 95.1%. Among these girls, 1 105 (40.9%) were aged 6-9 years, 1 053 (38.9%) were aged 10-13 years, and 546 (20.2%) were aged 14-18 years. The of height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and body mass index-for-age Z-score (BAZ) were 0.46(-0.23,1.16), 0.69(-0.16,1.67), and 0.67(-0.27,1.73) respectively. The prevalences of thin, overweight, and obesity were respectively 1.7% (45/2 704), 17.3% (467/2 704), and 19.9% (538/2 704), respectively. There were 45 girls in the thin group, 1 654 girls in the normal weight group, 1 005 girls in the overweight and obesity group. The age of Tanner stage breast 2 (B2), Tanner stage pubic hair 2 (P2), and menarche was 9.0 (95% CI 8.9-9.1), 10.5 (95% CI 10.4-10.6), and 11.4 (95% CI 11.3-1.5) years, respectively. The current status of breast and pubic hair maturity in girls with pubertal development shows that 64.6% (1 211/1 874) of these girls had breast development preceding pubic hair development, 32.4% (607/1 874) had concurrent breast and pubic hair development, and 3.0% (56/1 874) had pubic hairs development preceding breast development. The interval age between B2 and B5 was 4.7 (95% CI 4.6-4.8) years, between P2 and P5 was 4.5 (95% CI 4.4-4.6) years, and between B2 and menarche was 2.4 (95% CI 2.3-2.5) years. The ages of sexual characteristics development in overweight and obese groups were earlier than that in normal and thin groups. The ages of B2 in thin, normal, overweight, and obese groups were 10.0 (95% CI 9.5-10.6), 9.3 (95% CI 9.2-9.4), and 8.6 (95% CI 8.4-8.7) years, respectively. The age of menarche in thin, normal, overweight, and obese groups were 13.1 (95% CI 12.4-13.7), 11.6 (95% CI 11.4-11.7), and 11.1 (95% CI 11.0-11.2) years, respectively. The interval ages between B2 and B5 and between P2 and P5 was 4.5 and 4.1 years, respectively in the overweight and obese groups, and those in normal group and thin group was 4.7 and 4.5 years, 4.6 and 4.7 years, respectively. Conclusions:The ages of sexual characteristics development and menarche tend in Tongzhou District of Beijing to be earlier than that being reported of Beijing's survey 20 years ago. Girls characterized as overweight and obese not only start puberty at an earlier age than girls of normal weight, but also have a shorter developmental process.

Objective:To investigate the effect of intensive lipid-lowering therapy on carotid artery intima-media thickness and plaque area in patients with acute cerebral infarction.Methods:Eighty-two patients with acute cerebral infarction who received treatment at the Changzhi Mental Health Center from July 2021 to July 2022 were included in this study. Using a randomized controlled trial design, the patients were randomly divided into an intensive treatment group ( n = 41) and a conventional treatment group ( n = 41) using the random number table method. All patients had surpassed the recommended time window for thrombolysis and were given conventional treatments, including antiplatelet aggregation and neuroprotection. The conventional treatment group received conventional lipid-lowering therapy, while the intensive treatment group underwent intensive lipid-lowering therapy. All treatments lasted 6 months. The levels of blood lipids (low-density lipoprotein cholesterol and total cholesterol), inflammatory factors (C-reactive protein and interleukin-6), and atherosclerosis indicators (carotid artery intima-media thickness and plaque area) were measured and compared between the two groups before and after treatment. Adverse reactions occurring during the treatment period, including myalgia, nausea, vomiting, and abnormal liver function were also recorded. Results:Before treatment, there were no significant differences in blood lipids, inflammatory factors or atherosclerosis indicators between the conventional treatment and intensive treatment groups (all P > 0.05). After treatment, the levels of low-density lipoprotein cholesterol and total cholesterol in the intensive treatment group were significantly lower than those in the conventional treatment group [(3.44 ± 0.42) mmol/L vs. (4.81 ± 0.53) mmol/L, (3.46 ± 0.35) mmol/L vs. (2.41 ± 0.27) mmol/L, t = 12.97, 15.21, both P < 0.05]. After treatment, serum levels of interleukin-6 and C-reactive protein in the intensive treatment group were significantly lower than those in the conventional treatment group [(4.79 ± 0.53) mg/L vs. (6.97 ± 0.81) mg/L, (38.45 ± 4.14) pg/L vs. (49.66 ± 5.07) pg/L, t = 14.42, 10.97, both P < 0.05]. Carotid artery intima-media thickness and plaque area in the intensive treatment group were significantly smaller than those in the conventional treatment group [(0.98 ± 0.10) mm vs. (1.17 ± 0.12) mm, (13.04 ± 1.37) mm 2vs. (17.96 ± 1.89 mm 2, t = 7.79, 13.50, both P < 0.001). There was no significant difference in the overall incidence of adverse reactions during treatment between the intensive treatment and conventional treatment groups ( P > 0.05). Conclusion:Intensive lipid-lowering therapy is highly effective in patients with acute cerebral infarction. It can reduce inflammatory reactions, delay the progression of atherosclerosis, and provide a safety profile similar to that of conventional lipid-lowering therapy.

Objective:To investigate the effectiveness of suicide prevention cognitive behavioral therapy for depression patients with suicide attempt.Methods:Eligible participants were recruited from the inpatient department of Beijing Huilongguan Hospital from September 2021 to August 2022. A total of 112 patients were randomly allocated into the intervention group (56 cases) and the control group (56 cases) by a random number table. Patients in the intervention group received 12 sessions of cognitive behavioral therapy for suicide prevention over 8 weeks,while participants in the control group received supportive psychotherapy. Patient Health Questionnaire Depression Scale (PHQ-9) and the Beck Scale for Suicide Ideation-Chinese Version (BSI-CV) were used to assess changes in depressive symptoms,suicidal ideation,and suicidal tendencies in both groups at baseline,4-week of treatment,the end of treatment,and at follow-up (weekends 4,8,12). General data and scale scores between the two groups were analyzed by t test,Mann-Whitney rank sum test,and χ 2 test; repeated measure ANOVA were used to assess the baseline and intervention effects. Results:The change of PHQ-9 at each time point of the 2 groups showed a downward trend,and the group x time interaction was significant ( F=2.75, P=0.047). Since the 8th week,the PHQ score in the intervention group was significantly lower than that in the control group ( t=7.03, P<0.05). Time and group effect were significant in the four time points of the total score of suicidal ideation in the last week in BSI-CV ( F=96.78,6.35,both P<0.05),but the interaction between group and time was not significant. At weeks 8 and 12,the scores of the intervention group were lower than those of the control group ( Z=-3.11,-3.30;both P<0.01). In BSI-CV,time effects in the total score of suicidal intention was significant at four time points ( F=11.83, P<0.05),but the interaction between group and time was not significant ( F=2.56, P=0.059). There was no significant difference in suicide tendency between the two groups at each time point ( F=0.001, P=0.975). The total scores of suicidality in 2 groups at 4,8 and 12 weeks were all lower than baseline ( P<0.05). Conclusions:Compared with the control group,the cognitive behavioral therapy for suicide prevention showed superior effects on suicidal ideation and depression,but the intervention effect on suicidal tendency was not significant. Further studies are needed to investigate the long-term effects of cognitive behavioral therapy for suicide prevention in patients with depression who have attempted suicide.

Objective:To investigate the effectiveness of suicide prevention cognitive behavioral therapy for depression patients with suicide attempt.Methods:Eligible participants were recruited from the inpatient department of Beijing Huilongguan Hospital from September 2021 to August 2022. A total of 112 patients were randomly allocated into the intervention group (56 cases) and the control group (56 cases) by a random number table. Patients in the intervention group received 12 sessions of cognitive behavioral therapy for suicide prevention over 8 weeks,while participants in the control group received supportive psychotherapy. Patient Health Questionnaire Depression Scale (PHQ-9) and the Beck Scale for Suicide Ideation-Chinese Version (BSI-CV) were used to assess changes in depressive symptoms,suicidal ideation,and suicidal tendencies in both groups at baseline,4-week of treatment,the end of treatment,and at follow-up (weekends 4,8,12). General data and scale scores between the two groups were analyzed by t test,Mann-Whitney rank sum test,and χ 2 test; repeated measure ANOVA were used to assess the baseline and intervention effects. Results:The change of PHQ-9 at each time point of the 2 groups showed a downward trend,and the group x time interaction was significant ( F=2.75, P=0.047). Since the 8th week,the PHQ score in the intervention group was significantly lower than that in the control group ( t=7.03, P<0.05). Time and group effect were significant in the four time points of the total score of suicidal ideation in the last week in BSI-CV ( F=96.78,6.35,both P<0.05),but the interaction between group and time was not significant. At weeks 8 and 12,the scores of the intervention group were lower than those of the control group ( Z=-3.11,-3.30;both P<0.01). In BSI-CV,time effects in the total score of suicidal intention was significant at four time points ( F=11.83, P<0.05),but the interaction between group and time was not significant ( F=2.56, P=0.059). There was no significant difference in suicide tendency between the two groups at each time point ( F=0.001, P=0.975). The total scores of suicidality in 2 groups at 4,8 and 12 weeks were all lower than baseline ( P<0.05). Conclusions:Compared with the control group,the cognitive behavioral therapy for suicide prevention showed superior effects on suicidal ideation and depression,but the intervention effect on suicidal tendency was not significant. Further studies are needed to investigate the long-term effects of cognitive behavioral therapy for suicide prevention in patients with depression who have attempted suicide.

Accurate and efficient methods for identifying and tracking each animal in a group are needed to study complex behaviors and social interactions. Traditional tracking methods (e.g., marking each animal with dye or surgically implanting microchips) can be invasive and may have an impact on the social behavior being measured. To overcome these shortcomings, video-based methods for tracking unmarked animals, such as fruit flies and zebrafish, have been developed. However, tracking individual mice in a group remains a challenging problem because of their flexible body and complicated interaction patterns. In this study, we report the development of a multi-object tracker for mice that uses the Faster region-based convolutional neural network (R-CNN) deep learning algorithm with geometric transformations in combination with multi-camera/multi-image fusion technology. The system successfully tracked every individual in groups of unmarked mice and was applied to investigate chasing behavior. The proposed system constitutes a step forward in the noninvasive tracking of individual mice engaged in social behavior.
Animals ; Mice ; Deep Learning ; Zebrafish ; Algorithms ; Neural Networks, Computer ; Social Behavior

Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.