ObjectiveThis paper aims to conduct a secondary analysis of a randomized controlled trial on the treatment of myelodysplastic syndrome （MDS） with deficiency of both the spleen and kidney and blockage of toxin and blood stasis with an arsenic-containing traditional Chinese medicine compound， by applying the mixed model for repeated measure （MMRM） and the method of stratified composite outcome with win ratio. The analysis includes the assessment of hematological efficacy and the composite outcome evaluation of adverse reactions， so as to more comprehensively assess the therapy of this regimen. MethodsThe MMRM and win ratio methods were used to evaluate the efficacy of a prospective，multi-center，double-blind，randomized controlled study. The blood routine （hemoglobin concentration，neutrophil count， and platelet count） and biochemical indexes （aspartate aminotransferase，alanine aminotransferase，serum creatinine，and serum ferritin） of the patients were detected at the time of enrollment and at the end of each course of treatment in the laboratory department of Xiyuan Hospital. The patients' syndromes at the time of enrollment and after treatment were recorded and scored according to the therapy standard of traditional Chinese medicine for diseases and syndromes. MMRM was used to analyze the blood routine indexes of the experimental group and the control group. This method has the advantages of high data reliability and dynamic efficacy under intervention and time. The win ratio method was used to evaluate the composite outcome of traditional Chinese medicine syndrome scores and biochemical indexes according to the priority and to verify the clinical safety of arsenic-containing traditional Chinese medicine compound. ResultsThe results of MMRM analysis showed that the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly compared with that before treatment in the group，while that in the placebo group decreased significantly （P<0.01）. When compared with that after treatment in the placebo group，the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly，and the mean difference of least squares （LS） was statistically significant （P<0.01）. When compared with those before treatment in the group，there were no statistically significant differences in the neutrophil count and platelet count in both groups. After treatment，there were no statistically significant differences in the neutrophil count， platelet count， and the mean difference of LS between the two groups. The analysis results of win ratio showed that the group with arsenic-containing traditional Chinese medicine compound had a significant advantage in the comparison of composite outcomes，with a win ratio （95% CI） of 2.01 （1.24-3.27） （P<0.01），and that the possibility of "winning" in terms of safety was 2.01 times that of the placebo group. The safety advantage of the group with arsenic-containing traditional Chinese medicine compound mainly came from the traditional Chinese medicine syndrome scores，renal function indexes， and iron reserve capacity indexes，and the number of winning times was less than that of losing times in the comparison of liver function outcomes. ConclusionThe MMRM analysis proves that the arsenic-containing traditional Chinese medicine compound can significantly improve the hemoglobin concentration of patients with myelodysplastic syndrome with refractory cytopenia and multilineage dysplasia （MDS-RCMD） of the type of deficiency of both the spleen and kidney and blockage of toxin and blood stasis. This conclusion is not interfered with by time trends and individual relationships and methodologically improves the credibility of the therapy of the arsenic-containing traditional Chinese medicine compound in treating MDS. Four outcomes are evaluated by the win ratio method，namely traditional Chinese medicine syndromes，liver function，renal function， and iron reserve capacity，proving that the arsenic-containing traditional Chinese medicine compound has the comprehensive advantages of improving the survival quality of the patients and reducing adverse reactions. The win ratio outcome provides clear comparative indexes for the evaluation of adverse reactions，making it easier for regulatory authorities，medical staff， and patients to understand the safety of the arsenic-containing traditional Chinese medicine compound in clinical application.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Objective To construct and verify a recurrence risk prediction model for patients with malig-nant pleural and peritoneal effusion after deep hyperthermia based on the proportion of peripheral blood CD3+T cell subsets and the expression profile of inflammatory cytokines.Methods A retrospective analysis was conducted on the clinical characteristics,diagnosis and treatment processes of 188 patients with malignant pleural and peritoneal effusion who visited this hospital from September 2023 to May 2024.All patients re-ceived chemotherapy combined with deep hyperthermia and were divided into the non-recurrence group(n=130)and the recurrence group(n=58)based on whether malignant pleural and peritoneal effusion recurred within 3 months after the end of treatment.The differences in general clinical data,conventional tumor mark-ers at the end of treatment,the proportion of CD3+T cell subsets,and the expression profile levels of inflam-matory cytokines between the two groups of patients were compared.The risk factors for recurrence in pa-tients with malignant pleural and peritoneal effusion were screened through univariate and multivariate Logis-tic regression analyses,and a risk prediction model was established.The receiver operating characteristic(ROC)curve was applied to evaluate the effectiveness of this prediction model for the recurrence risk of pa-tients with malignant pleural and peritoneal effusion after chemotherapy combined with deep hyperthermia.Results The age of patients in the recurrence group,the proportion of stage Ⅳ patients,the levels of serum CEA,CA125,TGF-β,and the proportion of CD8+T cells were significantly higher than those in the non-recur-rence group(P＜0.05),while the proportion of CD4+T cells,CD4+/CD8+,and the level of serum IL-10 were significantly lower than those in the non-recurrence group(P＜0.05).The results of univariate and multivari-ate Logistic regression analysis indicated that CD4+T,CD8+T,CD4+/CD8+,IL-10,and TGF-β were all im-portant influencing factors for recurrence after chemotherapy combined with deep hyperthermia in patients with malignant pleural and peritoneal effusion(P＜0.05).The AUC(95％CI)of the predictive model con-structed based on the above influencing factors by ROC curve analysis was 0.708(0.614-0.802),suggesting a high clinical predictive efficacy.Conclusion The predictive model constructed based on T-cell subset counts and serum inflammatory cytokines can effectively predict the recurrence risk of patients with malignant pleu-ral and peritoneal effusion after chemotherapy combined with deep hyperthermia.It has certain clinical value for the therapeutic effect evaluation of patients with malignant pleural and peritoneal effusion and for guiding the optimization of deep hyperthermia regimens.

Organoids,recognized as invaluable models in tumor and stem cell research,assume a pivotal role in the meticulous analysis of diverse datasets pertaining to their growth dynamics,drug screening processes and related phenomena.However,the manual scrutiny and conventional statistical methodologies employed in handling organoid data often grapple with challenges such as diminished precision and efficiency,heightened complexity,escalated human resource requirements,and a degree of subjectivity.Acknowledging the remarkable efficacy of artificial intelligence(AI)in the realms of biology and medicine,the incorporation of AI into organoid research stands poised to enhance the objectivity,precision and expediency of analyses.This integration empowers organoids to more effectively fulfill objectives such as disease modeling,drug screening and precision medicine.Notably,significant strides have been made in AI-driven analyses of organoid image data.The amalgamation of deep learning into image analysis facilitates a more meticulous delineation of the microstructural intricacies and nuanced changes within organoids,achieving a level of accuracy akin to that of experts.This not only elevates the precision of organoid morphology and growth recognition,but also contributes to substantial time and cost savings in research endeavors.Furthermore,the infusion of AI technology has yielded breakthroughs in the processing of organoid omics data,resulting in heightened efficiency in data processing and the identification of latent gene expression patterns.This furnishes novel tools for comprehending cellular development and unraveling the intricate mechanisms underlying various diseases.In addition to image data,AI techniques applied to diverse organoid datasets,encompassing electrical signals and spectra,have realized an unbiased classification of organoid types and states,embarking on a comprehensive journey towards characterizing organoids holistically.In the pivotal domain of drug screening for organoids,AI emerges as a stalwart companion,providing robust support for real-time process monitoring and result prediction.Leveraging high-content microscopy images and sophisticated deep learning models,researchers can dynamically monitor organoid responses to drugs,effecting non-invasive detection of drug impacts and amplifying the precision and efficiency of drug screening processes.Despite the significant strides made by AI in organoid research,challenges persist,encompassing hurdles in data acquisition,constraints in sample quality and quantity,and quandaries associated with model interpretability.Overcoming these challenges necessitates dedicated future research efforts aimed at enhancing data consistency,fortifying model interpretability,and exploring methodologies for the seamless fusion of multimodal data.Such endeavors are poised to usher in a more comprehensive and dependable application of AI in organoid research.In summation,the integration of AI technology introduces unparalleled opportunities to organoid research,resulting in noteworthy advancements.Nevertheless,interdisciplinary research and collaborative efforts remain imperative to navigate challenges and propel the more profound integration of AI into organoid research.The future holds promise for AI to assume an even more prominent role in advancing organoid research toward clinical translation and precision medicine.

Objective:To evaluate the efficacy of avatinib plus allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of recurrent/refractory RUNX1-RUNX1T1 positive acute myeloid leukemia (AML) with KIT mutations.Method:A retrospective study was conducted on the clinical data of seven relapsed/refractory AML patients containing the RUNX1-RUNX1T1 fusion gene and KIT mutation who received afatinib plus allo-HSCT treatment at the First Affiliated Hospital of Soochow University from June 2019 to June 2023.Results:The seven AML patients included one male and six females with a median age of 37 (18-56) years. All seven patients had KIT mutations (five positive for D816V and two positive for D816Y) . There were two refractory patients and five relapsed patients (all of whom had bone marrow recurrence) . All patients had to complete at least one course of treatment with afatinib before transplantation. Four patients achieved complete remission (CR) after treatment with afatinib, six patients had negative KIT gene mutations, and one had a decreased KIT gene mutational burden. There were three cases of unrelated identical transplantation and four cases of haploidentical transplantation. All patients received the modified Bu/Cy pretreatment regimen. After transplantation, all patients were successfully implanted and a bone marrow examination showed CR and minimal residual disease turned negative. Five patients exhibited negative fusion genes. Two patients died from infection following transplantation.Conclusion:Afatinib plus allo-HSCT may be an effective and safe new treatment strategy for RUNX1-RUNX1T1 positive AML patients with KIT-D816 mutation.

OBJECTIVE To explore the potential mechanism of the effect of Xuebijing injection （XBJ） on neurological function and survival of rats after cardiac arrest （CA）/cardiopulmonary resuscitation （CPR） based on the S-nitrosoglutathione reductase （GSNOR）/S-nitrosoglutathione （GSNO） pathway. METHODS The CA/CPR rat model was established by ventricular fibrillation. Using a sham operation group as control， high-throughput sequencing was employed to analyze and mine the differentially expressed genes （DEGs）. Enzyme-linked immunosorbent assay was used to determine the contents of GSNOR and GSNO in the hippocampus； the active components of XBJ were screened and subjected to molecular docking analysis with GSNOR. The rats successfully modeled using the same method were divided into model group （n＝30）， inhibitor （GSNOR inhibitor） group （n＝30）， XBJ group （n＝30） and XBJ+inhibitor group （n＝30）， and a sham operation group （n＝30） was set up. Neurological function was evaluated and survival status was recorded at 3 hours， 24 hours and 3 days after the first 89） drug intervention. The contents of GSNOR and GSNO in the hippocampus of rats were determined in each group at the 0191） above time points， and the relationship of the contents of GSNOR and GSNO with modified neurologic severity scale （mNSS） score was analyzed. RESULTS GSNOR coding gene was differentially expressed between the model group and the sham operation group. Compared with the sham operation group， GSNOR content increased significantly in the hippocampus of rats in model group， while GSNO content decreased significantly （P＜0.05）. The active components of XBJ， such as 4- methylenemiltirone and salviolone， could be bound to GSNOR protein， with the binding energy lower than －6 kcal/mol， mainly connected by hydrogen bonds. Animal experiments revealed that mNSS score and GSNOR levels in the hippocampus of rats in the model group were significantly higher than those in the sham operation group （P＜0.05）， while GSNO levels and survival rate were significantly lower than those in the sham operation group （P＜0.05）. The above indexes of rats were improved significantly in administration groups， the mNSS score in the XBJ group was significantly lower than that in the inhibitor group， the content changes of GSNOR and GSNO in the inhibitor group were more obvious than those in the XBJ group， and the various indicators in the XBJ+inhibitor group were significantly better than the XBJ group and the inhibitor group （P＜0.05）. GSNOR content was positively correlated with the mNSS score， and GSNO content was negatively correlated with the mNSS score （P＜0.05）. CONCLUSIONS XBJ can improve the neurological function of rats and enhance their survival rates after CA/CPR， the mechanism of which may be associated with the down-regulation of GSNOR and the up-regulation of GSNO.

OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.

BACKGROUND:Mesenchymal stem cells are susceptible to senescence during in vitro expansion,which greatly hinders their application in vivo and in vitro.How to improve the replicative senescence of mesenchymal stem cells is an urgent problem to be solved in tissue engineering. OBJECTIVE:To determine whether vascular endothelial growth factor combined with basic fibroblast growth factor can improve the aging of bone marrow mesenchymal stem cells caused by replicative passage. METHODS:Rat bone marrow mesenchymal stem cells were extracted by whole bone marrow adhesion method.Passage 2 cells were selected as normal control group.Passage 7 and later algebraic cells were selected as aging model group.Vascular endothelial growth factor(50 μg/L),basic fibroblast growth factor(10 μg/L),and their combination were administered.Cell proliferation was detected by CCK-8 assay.Cell senescence was observed by β-galactosidase activity staining.Cytoskeleton size and colony formation ability were observed by phalloidine staining and Giemsa staining,respectively,and the levels of senescence-related genes P16,P21,and P53 were detected by qRT-PCR.Gene expression levels of P16,P21,and P53 were tested by qRT-PCR. RESULTS AND CONCLUSION:(1)Vascular endothelial growth factor combined with basic fibroblast growth factor could promote the proliferation of aged bone marrow mesenchymal stem cells,which began to enter the plateau stage on day 9,and the absorbance value of the combined intervention group was significantly higher than that of the model group on day 9(P<0.05).(2)The phenotypic markers of the cells in the combined intervention group did not change,and the cell morphology changed from broad to slender.(3)Compared with the model group,the positive rate of β-galactosidase was significantly decreased(P<0.01);the number of nuclei increased(P<0.001);the total area of cytoskeleton increased(P<0.01);colony formation ability was enhanced(P<0.05);expression level of P16 was decreased(P<0.01)in the combined intervention group.These results indicate that vascular endothelial growth factor combined with basic fibroblast growth factor can improve the senescence of bone marrow mesenchymal stem cells caused by replicative passage without changing the cell phenotype.

Colorectal cancer （CRC） is a malignant tumor of the intestinal tract with changes in bowel habits， blood in the stool， and pain as the main clinical manifestations. With the change in lifestyle and diet structure in recent years， the incidence of CRC has been increasing year by year. The pathogenesis of CRC is closely related to abnormal immune response and chronic inflammation， intestinal microbial dysbiosis， and the production of oncogenic metabolites. There is a two-way communication between the intestinal microbiota and the body's immunity， which not only plays a key role in maintaining the body's health but also has a close relationship with the development of diseases. An increasing number of studies have shown that abnormal immune responses accelerate the disease process by producing inflammatory factors， causing chronic inflammation in the body， disrupting the intestinal mucosal barrier， and increasing mucosal permeability， thus resulting in dysbiosis of the intestinal microbial ecology and a large number of pathogenic microorganisms and their metabolites. In addition， dysbiosis of intestinal microbes， by suppressing the normal immune response， leads to the disruption of multiple metabolic pathways in the body， affecting the internal and external stress response of the intestine， inducing inflammation， and thus producing disease. Therefore， the complex crosstalk mechanism between the immune response and intestinal microbial axis is closely related to the development of CRC. Based on traditional Chinese medicine theory and clinical research， it was found that dietary factors are an important causative factor in the development of CRC. The deficiency of positive energy is the root cause of the disease， and damp-heat accumulation is the key pathogenesis. Through modern medical and biological research， it is believed that abnormal immune response is the microscopic manifestation of damp-heat entrapment， while intestinal microbial dysbiosis is the biological basis of toxic injection into the large intestine， and in the pathogenesis of CRC， the imbalance of immune response-intestinal microbial axis is compatible with damp-heat accumulation in traditional Chinese medicine. This study aims to explore the biological connotation of CRC due to damp-heat accumulation from the immune response-intestinal microbial axis， so as to interpret the pathogenesis of CRC due to damp-heat accumulation with objective data and provide new ideas and theoretical basis for the pathogenesis and treatment strategies of CRC due to damp-heat accumulation.

Most of the current research on depression focuses on neuronal regulation,while the astrocytic mechanism of depression is far from explored.Astrocytes are the most numerous and widely distributed glial cells in the central nervous system.With a complex structural morphology,astrocytes play an important role in a variety of neuropsychiatric disorders by interacting with neuronal synapses,vasculature and other glial cells.Recent studies have shown that astrocytes may be involved in depression by regulating monoamine transmitters,glutamate cycle,synaptic plasticity,energy metabo-lism,and neuroinflammation.This review is intended to inspire new ideas for the treatment of depres-sion and the development of novel drugs based on astrocyte regulation.