With the continuous development of society, a large number of new chemicals are continuously emerging, which presents a challenge to current risk assessment and safety management of chemicals. Traditional toxicology research methods have certain limitations in quickly, efficiently, and accurately assessing the toxicity of many chemicals, and cannot meet the actual needs. In response to this challenge, computational toxicology that use mathematical and computer models to achieve the prediction of chemical toxicity has emerged. In the meantime, as researchers increasingly pay attention to understanding the interaction mechanisms between exogenous chemical substances and the body from the system level, and multiomics technologies develop rapidly such as genomics, transcriptomics, proteomics, and metabolomics, huge amounts of data have been generated, providing rich information resources for studying the interactions between chemical substances and biological molecules. System toxicology and network toxicology have also developed accordingly. Of these, network toxicology can integrate these multiomics data to construct biomolecular networks, and then quickly predict the key toxicological targets and pathways of chemicals at the molecular level. This paper outlined the concept and development of network toxicology, summarized the main methods and supporting tools of network toxicology research, expounded the application status of network toxicology in studying potential toxicity of exogenous chemicals such as agricultural chemicals, environmental pollutants, industrial chemicals, and foodborne chemicals, and analyzed the development prospects and limitations of network toxicology research. This paper aimed to provide a reference for the application of network toxicology in other fields.

Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL（OR=1.699）(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma（FFP）, cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.

ObjectiveTo investigate the effects of Tongluo Juanbi granules on chondrocyte apoptosis and Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway of rabbits with knee osteoarthritis （KOA） and study the mechanism of Tongluo Juanbi granules in the prevention and treatment of KOA. MethodThirty New Zealand rabbits were randomly assigned to the following five groups （n=6）： sham group， model group， low-dose and high-dose groups of Tongluo Juanbi granules （4.1 and 8.2 g·kg^-1·d^-1）， and celecoxib group （10.9 mg·kg^-1·d^-1）. The KOA model was established by destabilization of the medial meniscus （DMM） for six weeks. Six weeks after the modeling， the drug was given once a day for eight weeks. The pathological changes of cartilago articularis were observed by hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was performed to detect chondrocyte apoptosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in synovial fluid. The mRNA and protein expression levels of genes related to the TLR4/MyD88/NF-κB signaling pathway were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham group， the cartilago articularis of the model group significantly degenerated. Mankin's score was increased （P<0.01）， and the contents of IL-1β and TNF-α in synovial fluid were increased （P<0.01）. The number of apoptosis of chondrocytes was increased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were up-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were down-regulated （P<0.01）. Compared with the model group， chondrocyte degeneration in both low-dose and high-dose groups of Tongluo Juanbi granules was improved， and Mankin's score was decreased （P<0.01）. The contents of IL-1β and TNF-α were decreased （P<0.01）， and the number of apoptosis of chondrocytes was decreased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were down-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were up-regulated （P<0.01）. In addition， in the above observation indicators， the high-dose group of Tongluo Juanbi granules was significantly superior to the low-dose group of Tongluo Juanbi granules. ConclusionTongluo Juanbi granules could inhibit chondrocyte apoptosis in rabbits with KOA and improve cartilage degeneration， which may be related to inhibiting inflammatory responses mediated by TLR4/MyD88/NF-κB signaling pathway.

Objective This study aimed to explore the prognostic value of 18F-FDG PET/CT Metabolic and Heterogeneity Parameters Combined with Clinical Features Before Definitive Chemoradiotherapy(D-CRT)in predicting the prognosis of esophageal squamous cell carcinoma(ESCC)Patients.Methods A retrospective analysis was conducted on clinical data from 106 patients with ESCC who received D-CRT at the first affiliated Hospital of University of Science and Technology of China between January 2017 and December 2021.All patients underwent 18F-FDG PET/CT examination before the treatment.The primary tumor′s metabolic and heterogeneity parameters were obtained through data processing.All patients were followed up for overall survival.The Kaplan-Meier method and Cox proportional hazards models were used to analyze the association between clinical features,tumor metabo-lism and heterogeneity parameters and patient prognosis.Results The 1-and 1.5-year overall survival rates of all patients were 77.4%and 51.9%.The median survival time was 20 months.Univariate analysis showed that N stage,M stage,metabolic tumor volume,total lesion glycolysis,heterogeneity index-2(HI-2),and coefficient of variation with a threshold of 40%maximum standard uptake value(CV40%)were correlated with the prognosis of ESCC(all P<0.05).Multivariate analysis showed that N stage and CV40%were independent predictors of prognosis in patients with ESCC(P = 0.039 and P<0.001,respectively).Conclusion N stage and tumor metabolic heterogeneity parameter CV40%,which offering a degree of predictive value,are closely related to the prognosis of patients with ESCC treated with D-CRT.

Neoadjuvant therapy for locally advanced colorectal cancer has made great progress in the past 20 years, but there are still limitations such as side effects, organ dysfunction and unsatisfactory control of metastasis. In recent years, with the improvement of surgical techniques and further development of molecular research, how to further improve local control, reduce distant metastasis, and even avoid surgery according to clinical remission to achieve organ preservation, is the current demand and research goal. With the advancement of molecular research, colorectal cancer has different treatment strategies based on microsatellite status. For patients with microsatellite instability locally advanced colorectal cancer, immune checkpoint inhibitor therapy significantly increased the pathologic complete response rate, reduced the incidence of adverse events and improved organ function compared with conventional chemoradiotherapy. For patients with microsatellite stable locally advanced colon cancer, neoadjuvant therapy is still in the exploratory stage. The standard of care is surgery combined with perioperative chemotherapy. For microsatellite stable locally advanced rectal cancer, the complete response rate is improved by enhancing neoadjuvant therapy, which helps to preserve organs. On the other hand, selective radiotherapy preserves organ function and improves quality of life. This article reviews the neoadjuvant treatment strategies for locally advanced colorectal cancer based on organ-sparing strategies.

Neoadjuvant therapy for locally advanced colorectal cancer has made great progress in the past 20 years, but there are still limitations such as side effects, organ dysfunction and unsatisfactory control of metastasis. In recent years, with the improvement of surgical techniques and further development of molecular research, how to further improve local control, reduce distant metastasis, and even avoid surgery according to clinical remission to achieve organ preservation, is the current demand and research goal. With the advancement of molecular research, colorectal cancer has different treatment strategies based on microsatellite status. For patients with microsatellite instability locally advanced colorectal cancer, immune checkpoint inhibitor therapy significantly increased the pathologic complete response rate, reduced the incidence of adverse events and improved organ function compared with conventional chemoradiotherapy. For patients with microsatellite stable locally advanced colon cancer, neoadjuvant therapy is still in the exploratory stage. The standard of care is surgery combined with perioperative chemotherapy. For microsatellite stable locally advanced rectal cancer, the complete response rate is improved by enhancing neoadjuvant therapy, which helps to preserve organs. On the other hand, selective radiotherapy preserves organ function and improves quality of life. This article reviews the neoadjuvant treatment strategies for locally advanced colorectal cancer based on organ-sparing strategies.

AIM:To investigate the effects and underlying mechanism of Toona sinensis bark extract(TAE)on the colon mucosal barrier and gut microbiota in mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS).METHODS:Sixty C57BL/6J mice were randomly assigned to control,model,and mesalazine(0.2 g/kg)groups,as well as TAE groups(low,medium,and high-doses equal to crude drug concentrations of 2.3,4.6 and 9.2 g/kg,respectively).The UC model was induced by drinking of 2.5％DSS,and mean while the drugs were administered for 10 days.The mice were then evaluated in terms of weight,disease activity index(DAI),colon length,spleen index,and pathological changes in the colon tissues.In addition,the level of apoptosis in colon tissues was assessed by terminal de-oxynucleotidyl transferase dUTP nick-end labeling(TUNEL)fluorescence staining,and the expression of related proteins was evaluated by Western blot,levels of inflammatory factors were determined by enzyme-linked immunosorbent assays(ELISA),and the activities of total superoxide dismutase(T-SOD)and catalase(CAT)and malondialdehyde(MDA)content were assessed by biochemical assays.Furthermore,the constitution and diversity of the gut microbiota were inves-tigated by 16S rRNA gene sequencing.RESULTS:Compared with the control group,mice in the model group showed significantly reduced body weights(P<0.01),and the colon length was shortened significantly(P<0.05).Marked in-creases in the DAI and spleen index were observed(P<0.01),along with severe damage to the colon mucosa(P<0.01).Mechanistically,the level of intestinal epithelial cell apoptosis was significantly raised(P<0.01).The model group showed markedly reduced expression of occludin and claudin-1(P<0.01),the level of IL-10,and activities of T-SOD and CAT in the colon tissues(P<0.01).While the levels of IL-6,IL-1β,TNF-α,and the MDA content were increased signif-icantly(P<0.05).The abundance and diversity of the gut microbiota were decreased in the model group(P<0.05).Com-pared with the model group,all these indicators were ameliorated by the administration of TAE(P<0.05).The abundance of pathogenic bacteria,including Proteobacteria and Escherichia-Shigella,was decreased remarkably(P<0.05),while that of probiotics,including Bacteroidota and Muribaculaceae,were increased significantly(P<0.05).The abundance and diversity of the gut microbiota were increased.CONCLUSION:Taken together,Toona sinensis bark alcohol extract can alleviate damage to the intestinal mucosa by suppressing the apoptosis of intestinal epithelial cell,reducing the inflam-matory response,and mitigating oxidative stress.Treatment with TAE could also maintain the homeostasis of the gut micro-biota by regulating the abundance,ultimately meliorate the function of intestinal mucosal barrier.

Objective To investigate the impacts of sevoflurane combined with lung protective ventilation strategy on pulmonary ventilation function and lung compliance in obese patients undergoing laparoscopic weight loss surgery.Methods 60 obese patients underwent laparoscopic weight loss surgery were randomly divided into two groups.The control group was given lung protective ventilation intervention alone during anesthesia,and the study group was given sevoflurane inhalation anesthesia combined with lung protective ventilation intervention.Arterial blood was collected before tracheal intubation(T0),5 min after tracheal intubation(T1),40 min after tracheal intubation(T2)and 5 min after tracheal extubation(T3)for blood gas analysis.The pulmonary ventilation function and lung compliance of patients in the two groups were compared.Results Peak airway pressure(Ppeak)and plateau airway pressure(Pplat)at T2 were lower in the study group than those in the control group,and the differences were statistically significant(P<0.05);At T2 and T3 time points,the dynamic lung compliance(Cldyn)of the study group was higher than that of the control group,and the differences were statistically significant(P<0.05);7 days after surgery,the forced vital capacity(FVC)and forced expiratory volume in one second(FEV1)in the study group were higher than those in the control group,and the differences were statistically significant(P<0.05);At time points T1,T2 and T3,the levels of serum transforming growth factor-β1(TGF-β1),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in the study group were lower than those in the control group(P<0.05);After surgery,the awakening time,spontaneous breathing recovery time,and extubation time in the study group were shorter than those in the control group,the number of adverse events during the recovery period was less than that in the control group,after awakening,the Ramsay score was lower than that in the control group(P<0.05).Conclusion The combination of sevoflurane and lung protective ventilation strategy can reduce inflammatory response,improve pulmonary ventilation function,and improve lung compliance in obese patients undergoing laparoscopic weight loss surgery,with good safety and fast postoperative recovery.

BACKGROUND: The results of studies comparing Billroth-I (B-I) with Roux-en-Y (R-Y) reconstruction on the quality of life (QoL) are still inconsistent. The aim of this trial was to compare the long-term QoL of B-I with R-Y anastomosis after curative distal gastrectomy for gastric cancer. METHODS: A total of 140 patients undergoing curative distal gastrectomy with D2 lymphadenectomy in West China Hospital, Sichuan University from May 2011 to May 2014 were randomly assigned to the B-I group ( N  = 70) and R-Y group ( N  = 70). The follow-up time points were 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after the operation. The final follow-up time was May 2019. The clinicopathological features, operative safety, postoperative recovery, long-term survival as well as QoL were compared, among which QoL score was the primary outcome. An intention-to-treat analysis was applied. RESULTS: The baseline characteristics were comparable between the two groups. There were no statistically significant differences in terms of postoperative morbidity and mortality rates, and postoperative recovery between the two groups. Less estimated blood loss and shorter surgical duration were found in the B-I group. There were no statistically significant differences in 5-year overall survival (79% [55/70] of the B-I group vs. 80% [56/70] of the R-Y group, P  = 0.966) and recurrence-free survival rates (79% [55/70] of the B-I group vs. 78% [55/70] of the R-Y group, P  = 0.979) between the two groups. The scores of the global health status of the R-Y group were higher than those of the B-I group with statistically significant differences (postoperative 1 year: 85.4 ± 13.1 vs . 88.8 ± 16.1, P  = 0.033; postoperative 3 year: 87.3 ± 15.2 vs . 92.8 ± 11.3, P  = 0.028; postoperative 5 year: 90.9 ± 13.7 vs . 96.4 ± 5.6, P  = 0.010), and the reflux (postoperative 3 year: 8.8 ± 12.9 vs . 2.8 ± 5.3, P  = 0.001; postoperative 5 year: 5.1 ± 9.8 vs . 1.8 ± 4.7, P  = 0.033) and epigastric pain (postoperative 1 year: 11.8 ± 12.7 vs. 6.1 ± 8.8, P  = 0.008; postoperative 3 year: 9.4 ± 10.6 vs. 4.6 ± 7.9, P  = 0.006; postoperative 5 year: 6.0 ± 8.9 vs . 2.7 ± 4.6, P  = 0.022) were milder in the R-Y group than those of the B-I group at the postoperative 1, 3, and 5-year time points. CONCLUSIONS: Compared with B-I group, R-Y reconstruction was associated with better long-term QoL by reducing reflux and epigastric pain, without changing survival outcomes. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR-TRC-10001434.
Humans ; Stomach Neoplasms/pathology* ; Anastomosis, Roux-en-Y/methods* ; Quality of Life ; Treatment Outcome ; Gastrectomy/methods* ; Postoperative Complications ; Gastroenterostomy/methods* ; Pain

Objective:To construct an artificial intelligence-assisted diagnosis system to recognize the characteristics of Helicobacter pylori ( HP) infection under endoscopy, and evaluate its performance in real clinical cases. Methods:A total of 1 033 cases who underwent 13C-urea breath test and gastroscopy in the Digestive Endoscopy Center of Renmin Hospital of Wuhan University from January 2020 to March 2021 were collected retrospectively. Patients with positive results of 13C-urea breath test (which were defined as HP infertion) were assigned to the case group ( n=485), and those with negative results to the control group ( n=548). Gastroscopic images of various mucosal features indicating HP positive and negative, as well as the gastroscopic images of HP positive and negative cases were randomly assigned to the training set, validation set and test set with at 8∶1∶1. An artificial intelligence-assisted diagnosis system for identifying HP infection was developed based on convolutional neural network (CNN) and long short-term memory network (LSTM). In the system, CNN can identify and extract mucosal features of endoscopic images of each patient, generate feature vectors, and then LSTM receives feature vectors to comprehensively judge HP infection status. The diagnostic performance of the system was evaluated by sensitivity, specificity, accuracy and area under receiver operating characteristic curve (AUC). Results:The diagnostic accuracy of this system for nodularity, atrophy, intestinal metaplasia, xanthoma, diffuse redness + spotty redness, mucosal swelling + enlarged fold + sticky mucus and HP negative features was 87.5% (14/16), 74.1% (83/112), 90.0% (45/50), 88.0% (22/25), 63.3% (38/60), 80.1% (238/297) and 85.7% (36 /42), respectively. The sensitivity, specificity, accuracy and AUC of the system for predicting HP infection was 89.6% (43/48), 61.8% (34/55), 74.8% (77/103), and 0.757, respectively. The diagnostic accuracy of the system was equivalent to that of endoscopist in diagnosing HP infection under white light (74.8% VS 72.1%, χ2=0.246, P=0.620). Conclusion:The system developed in this study shows noteworthy ability in evaluating HP status, and can be used to assist endoscopists to diagnose HP infection.