Cytotoxicity, usually represented by cell viability, is a crucial parameter for evaluating drug safety in vitro. Accurate prediction of cell viability/cytotoxicity could accelerate drug development in the early stage. In this study, by integrating cellular transcriptome and cell viability data using four machine learning algorithms (support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM)) and two ensemble algorithms (voting and stacking), highly accurate prediction models of 50% and 80% cell viability were developed with area under the receiver operating characteristic curve (AUROC) of 0.90 and 0.84, respectively; these models also showed good performance when utilized for diverse cell lines. Concerning the characterization of the employed Feature Genes, the models were interpreted, and the mechanisms of bioactive compounds with a narrow therapeutic index (NTI) can also be analyzed. In summary, the models established in this research exhibit superior capacity to those of previous studies; these models enable accurate high-safety substance screening via cytotoxicity prediction across cell lines. Moreover, for the first time, Cytotoxicity Signature (CTS) genes were identified, which could provide additional clues for further study of mechanisms of action (MOA), especially for NTI compounds.

OBJECTIVE To retrospectively analyze the clinical efficacy of Qingchi San in the treatment of mild-to-moderate ul-cerative colitis.METHODS A retrospective analysis was conducted on 221 ulcerative colitis patients treated at the Gastroenterology Department of First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from December 2014 to February 2024.Participants were divided into an observation group(n=121)and a control group(n=100).The control group received oral me-salazine,while the observation group received Qingchi San enema in addition to the control group's treatment.Both groups received a 4-week course of treatment.The two groups were compared in terms of clinical efficacy,clinical remission rate,TCM syndrome score,time to intestinal bleeding remission,and changes in inflammatory markers(C-reactive protein,erythrocyte sedimentation rate,and white blood cells)and coagulation markers(platelets and D-dimer).RESULTS After treatment,the total effective rate and clinical remission rate in the observation group were significantly higher than those in the control group(P<0.05,P<0.01).The TCM syn-drome scores for each item(diarrhea,abdominal pain,bloody stools with mucus,and tenesmus)in the observation group were signifi-cantly improved compared with those in the control group(P<0.01).The time to intestinal bleeding remission in the observation group was significantly shorter than that in the control group(P<0.01).C-reactive protein,erythrocyte sedimentation rate,and white blood cell count in the observation group were significantly decreased compared with those in the control group(P<0.05,P<0.01).There was no statistically significant difference in coagulation markers(platelets and D-dimer)between the two groups(P>0.05).No signif-icant treatment-related adverse reactions,such as liver and kidney damage,were observed during treatment.CONCLUSION Qing-chi San enema can improve the clinical efficacy of patients with mild-to-moderate ulcerative colitis,improve clinical symptoms,short-en bleeding time,and reduce inflammatory markers.

OBJECTIVE To retrospectively analyze the clinical efficacy of Qingchi San in the treatment of mild-to-moderate ul-cerative colitis.METHODS A retrospective analysis was conducted on 221 ulcerative colitis patients treated at the Gastroenterology Department of First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from December 2014 to February 2024.Participants were divided into an observation group(n=121)and a control group(n=100).The control group received oral me-salazine,while the observation group received Qingchi San enema in addition to the control group's treatment.Both groups received a 4-week course of treatment.The two groups were compared in terms of clinical efficacy,clinical remission rate,TCM syndrome score,time to intestinal bleeding remission,and changes in inflammatory markers(C-reactive protein,erythrocyte sedimentation rate,and white blood cells)and coagulation markers(platelets and D-dimer).RESULTS After treatment,the total effective rate and clinical remission rate in the observation group were significantly higher than those in the control group(P<0.05,P<0.01).The TCM syn-drome scores for each item(diarrhea,abdominal pain,bloody stools with mucus,and tenesmus)in the observation group were signifi-cantly improved compared with those in the control group(P<0.01).The time to intestinal bleeding remission in the observation group was significantly shorter than that in the control group(P<0.01).C-reactive protein,erythrocyte sedimentation rate,and white blood cell count in the observation group were significantly decreased compared with those in the control group(P<0.05,P<0.01).There was no statistically significant difference in coagulation markers(platelets and D-dimer)between the two groups(P>0.05).No signif-icant treatment-related adverse reactions,such as liver and kidney damage,were observed during treatment.CONCLUSION Qing-chi San enema can improve the clinical efficacy of patients with mild-to-moderate ulcerative colitis,improve clinical symptoms,short-en bleeding time,and reduce inflammatory markers.

【Objective】 To compare the effects of 3 rehydration methods before blood donation on the prevention of on-site and delayed blood donation-related vasovagal response (VVR) . 【Methods】 From January to June 2021, 6 250 whole blood donors in 6 fixed blood donation sites signed informed consent and were divided into 198 clusters according to donor sites and dates, then they were randomly assigned to receive either oral rehydration salts (ORS), sugar water, or water group, and each drank 500 mL of ORS, sugar water or water within 20 minutes before blood donation. The researchers recorded the actual intervention accepted on site, and recorded the immediate VVR and related information. At rest after blood donation, donors submitted an electronic questionnaire containing socio-demographic information. At 48 hours after blood donation, the researchers called back every donor to record delayed VVR and related information. Logistic regression based on intention to treat (ITT) was used to analyze the difference of the incidence of VVR among the three groups, and the average treatment effect on treated (ATT) was calculated. PASS 2021was used to estimate the sample size and R (4.2.0) for statistical analysis. 【Results】 The cumulative incidence of blood donation-related VVR was 2.67% (2.29%-3.11%) among street whole blood donors under the 3 rehydration methods, in which, the incidence of immediate and delayed VVR was 1.02% (0.79%-1.31%) and 1.65% (1.36%-2.01%) respectively. ITT analysis found that ORS were more effective than water in reducing the incidence of delayed VVR【OR=0.59,95% CI[0.37,0.94]】.There was no significant difference in the incidence of immediate VVR between any two groups (P > 0.05), and there was no significant difference in the incidence of delayed VVR in the sugar water group compared with the water group (P > 0.05). There was a difference of -0.013 (【95% CI[-0.022, -0.004]】or -0.008【95% CI[-0.017, -0.000]】in the incidence of delayed VVR in the ORS group compared with water group or sugar water group, the difference was significant (P<0.05). The cumulative VVR of the three groups showed similar results to the delayed VVR. 【Conclusion】 Drinking ORS before blood donation is the most effective rehydration method to prevent delayed VVR. The next step is to establish the predictive model of delayed VVR to screen the susceptible population and provide them with ORS before blood donation, while other population can choose any liquid they like, thus achieving personalized blood donation-related VVR prevention and control.

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism* ; HMGB1 Protein/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Bone Substitutes/metabolism* ; Dendritic Cells/metabolism*

Objective:To systematically review and evaluate the effect of intraoperative regional cerebral oxygen saturation (rSO 2) monitoring on perioperative neurocognitive disorders (PNDs) in elderly patients undergoing non-cardiac surgery. Methods:China National Knowledge Infrastructure, Wanfang Database, China Biomedical Literature Database, China Science and Technology Journal Database, PubMed, Cochrane Library, Embase and Web of Science databases were searched from inception to October 2022 for randomized controlled trials involving the effects of intraoperative rSO 2 monitoring on PND in elderly patients underwent non-cardiac surgery. The primary outcome measure was the incidence of PND (1-7 days after surgery), and secondary outcome measures were intraoperative minimum rSO 2 (rSO 2min), intraoperative mean rSO 2 (rSO 2mean), maximum percentage of decrease (rSO 2% max) in rSO 2 from baseline (rSO 2baseline), and the Montreal Cognitive Assessment Scale was used to evaluate the quality of references that met the inclusion criteria, and data were extracted for meta-analysis using RevMan5.4 software. Results:Thirteen randomized controlled trials were enrolled, involving 1 134 patients with 557 patients in experimental group (anesthesia under rSO 2 monitoring) and 577 patients in control group. The results of meta-analysis showed that the incidence of PND was significantly lower in experimental group than in control group ( RR=0.32, 95% confidence interval [ CI] 0.25-0.41, P<0.001), the intraoperative rSO 2min was significantly higher in experimental group than in control group ( MD=7.46, 95% CI 5.05-9.86, P<0.001), and the intraoperative rSO 2mean was significantly higher in experimental group than in control group ( MD=5.49, 95% CI 3.97-7.02, P<0.001), the intraoperative rSO 2% max was significantly lower in experimental group than in control group ( MD=-6.55, 95% CI-9.03--4.07, P<0.001), and the postoperative Montreal Cognitive Assessment Scale score was significantly higher in experimental group than in control group ( MD=1.37, 95% CI 0.74-1.99, P<0.001). Conclusions:Intraoperative application of rSO 2 monitoring can reduce the occurrence of PND in elderly patients undergoing non-cardiac surgery.

The umbrella trial has received increasing attention in the design of clinical trials for oncology drugs in recent years. This trial design categorizes a single disease into multiple sub-types based on predictive biomarkers or other predictive factors, and simultaneously evaluates the efficacy of multiple targeted therapies. When compared with the traditional drug development model of phase Ⅰ, phaseⅡ, and phase Ⅲ randomized controlled trials, umbrella trials are a more scientifically rigorous trial design that can speed up drug evaluation to address the conflict between numerous untested drugs and diseases with a lack of effective treatment options. This article will focus on the concept, main characteristics, eligibility criteria, design and statistical considerations, ethical considerations, and future directions of umbrella trials, with the aim of providing methodological guidance for the design of clinical trials for oncology drugs.

Gaining a better understanding of autoprotection against drug-induced liver injury(DILI)may provide new strategies for its prevention and therapy.However,little is known about the underlying mechanisms of this phenomenon.We used single-cell RNA sequencing to characterize the dynamics and functions of hepatic non-parenchymal cells(NPCs)in autoprotection against DILI,using acetaminophen(APAP)as a model drug.Autoprotection was modeled through pretreatment with a mildly hepatotoxic dose of APAP in mice,followed by a higher dose in a secondary challenge.NPC subsets and dynamic changes were identified in the APAP(hepatotoxicity-sensitive)and APAP-resistant(hepatotoxicity-resistant)groups.A chemokine(C-C motif)ligand 2+endothelial cell subset almost disappeared in the APAP-resistant group,and an R-spondin 3+endothelial cell subset promoted hepatocyte proliferation and played an important role in APAP autoprotection.Moreover,the dendritic cell subset DC-3 may protect the liver from APAP hepatotoxicity by inducing low reactivity and suppressing the autoimmune response and occurrence of inflammation.DC-3 cells also promoted angiogenesis through crosstalk with endothelial cells via vascular endothelial growth factor-associated ligand-receptor pairs and facilitated liver tissue repair in the APAP-resistant group.In addition,the natural killer cell subsets NK-3 and NK-4 and the Sca-1-CD62L+natural killer T cell subset may promote autoprotection through interferon-y-dependent pathways.Furthermore,macrophage and neutrophil subpopulations with anti-inflammatory phenotypes promoted tolerance to APAP hepatotoxicity.Overall,this study reveals the dynamics of NPCs in the resistance to APAP hepatotoxicity and provides novel insights into the mechanism of autoprotection against DILI at a high resolution.

Two patients (patient 1, a 61-year-old male; patient 2, a 58-year-old female) received red yeast rice 6 g once daily orally because of abnormal blood lipids. Patient 1 had schistosomal cirrhosis and cholestatic hepatitis, with triacylglycerol 5.32 mmol/L. After 26 days of oral administration of red yeast rice, the patient developed limb weakness, with creatine kinase (CK) 604 U/L. Red yeast rice was stopped immediately and 3 days later, the patient developed lower limb muscle soreness, with CK 117 748 U/L. After 12 days of treatments with dexamethasone and rehydration, his symptoms gradually disappeared, with CK 79 U/L. Patient 2 had acute hepatitis, with triacylglycerol 2.34 mmol/L. After 24 days of oral administration of red yeast rice, the patient developed weakness and muscle soreness in both lower limbs, with CK 52 222 U/L. Red yeast rice was stopped immediately, and after 12 days of treatments with methylprednisolone and hydration, her symptoms were improved, with CK 210 U/L.

Two patients (patient 1, a 61-year-old male; patient 2, a 58-year-old female) received red yeast rice 6 g once daily orally because of abnormal blood lipids. Patient 1 had schistosomal cirrhosis and cholestatic hepatitis, with triacylglycerol 5.32 mmol/L. After 26 days of oral administration of red yeast rice, the patient developed limb weakness, with creatine kinase (CK) 604 U/L. Red yeast rice was stopped immediately and 3 days later, the patient developed lower limb muscle soreness, with CK 117 748 U/L. After 12 days of treatments with dexamethasone and rehydration, his symptoms gradually disappeared, with CK 79 U/L. Patient 2 had acute hepatitis, with triacylglycerol 2.34 mmol/L. After 24 days of oral administration of red yeast rice, the patient developed weakness and muscle soreness in both lower limbs, with CK 52 222 U/L. Red yeast rice was stopped immediately, and after 12 days of treatments with methylprednisolone and hydration, her symptoms were improved, with CK 210 U/L.