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.

Objective: To develop a RHCE genotyping assay based on kompetitive allele-specific PCR (KASP) and assess its clinical accuracy for RhCE blood group determination. Methods: KASP primers were designed to interrogate three RHCE loci: the 109 bp insertion/deletion in intron 2, c. 307T>C, and c. 676C>G. A total of 1 194 RhD-positive inpatients from Chengdu were typed by both KASP genotyping and manual tube serology. Discordant samples (n=10) were retested by both methods and further resolved by Sanger sequencing. An additional 377 cases were tested for the c. 48C>G locus to evaluate the predictive accuracy of individual loci and combined locus testing for RhC antigen. Results: Genotyping concordance with serology was 100.0% for both the c. 676C>G locus (RhE/Rhe) and the c. 307T>C locus (Rhc). For RhC prediction using the 109 bp insertion, overall accuracy was 99.7% (1 191/1 194); the 3 discordant cases were confirmed by Sanger sequencing to be false negatives attributable to 109 bp deletion in intron 2. Testing the c. 48C>G allele for RhC prediction yielded 7 false positives, with an accuracy of 98.1% (370/377). RhC antigen status was determined by combining the 109 bp insertion and the c. 48C allele. After excluding 10 samples with inconsistent results between the two loci, the accuracy reached 100% in the remaining 367 samples. When both loci were applied in combination, accuracy reached 100% in the 367 cases with concordant results. Among the 1 194 patients, CCee (45.8%) and CcEe (31.7%) were the most common RhCE phenotypes. The e antigen had the highest positivity rate (92.2%), and the Ce haplotype was the most frequent (66.9%). Conclusion: The KASP-based RHCE genotyping method achieves high accuracy for clinical RhCE typing. Combining the 109 bp insertion/deletion with the c. 48C allele significantly improves RhC antigen prediction compared with either locus alone. This method was applied to RhCE genotyping of 1 194 RhD-positive inpatients in Chengdu, providing local RhCE phenotype and haplotype distribution data to support RhCE-matched transfusion practice.

ObjectiveThis study aimed to investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through regulating ferroptosis， and to screen key metabolites and analyze their association with ferroptosis. MethodsClinical samples of normal endometrium from patients without EMs and eutopic and ectopic endometrium from EMs patients （10 cases each） were collected and divided into control group， eutopic group， and EMs group. Hematoxylin-eosin （HE） staining was performed to observe ectopic lesions of EMs. Immunohistochemistry was used to detect the expression of solute carrier family 7 member 11 （SLC7A11） and glutathione peroxidase 4 （GPX4）. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of malondialdehyde （MDA）， ferrous ion （Fe²⁺）， GPX4 and glutathione （GSH） in endometrial tissues， as well as serum levels of Fe²⁺， GPX4 and GSH. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of SLC7A11， GPX4， transferrin receptor （TFR） and ferritin heavy chain 1 （FTH1）. In the in vitro experiment， primary stromal cells were isolated from ectopic lesions of EMs patients. Cell counting kit-8 （CCK-8） was used to determine the optimal concentration of drug-containing serum for intervention. The level of reactive oxygen species （ROS） was measured， and Real-time PCR was applied to detect ferroptosis-related indicators. In the animal experiments， an EM rat model was established， and the rats were randomly assigned to the sham operation group， EMs group， low-dose Luoshi Neiyi Formula group （7.87 g·kg^-1）， high-dose Luoshi Neiyi prescription group （15.74 g·kg^-1）， and danazol group （42 mg·kg^-1）. Untargeted metabolomics detection and pathway enrichment analysis were conducted on serum samples from patients and rats. Spearman correlation analysis was performed to assess the relationship between differential metabolites and ferroptosis indicators. The correlations between differential metabolites in patient endometrium and serum and key ferroptosis indicators （GPX4， Fe²⁺， MDA， GSH） as well as ferroptosis-related mRNAs （GPX4， SLC7A11， FTH1） were analyzed， and correlation heatmaps were generated accordingly. ResultsCompared with normal eutopic endometrium， ectopic lesions in EMs patients showed glandular disorganization and stromal fibrosis. In ectopic endometrium， the contents of MDA， ROS， and Fe²⁺ decreased， while GPX4 level increased， and the mRNA expression of SLC7A11 and GPX4 was upregulated （P<0.05， P<0.01）. In serum， the levels of GPX4 and Fe²⁺ were elevated， whereas the GSH level declined， suggesting abnormalities in ferroptosis-related pathways in ectopic lesions （P<0.05， P<0.01）. After intervention with Luoshi Neiyi prescription-containing serum， the intracellular ROS level in ectopic endometrial stromal cells was elevated， the mRNA expression of SLC7A11 and GPX4 was downregulated， and TFR mRNA expression was upregulated （P<0.05， P<0.01）. Metabolomics analysis revealed 1104 and 198 differential metabolites in EMs patients and EMs rats， respectively， compared with their corresponding control groups， and both low-dose and high-dose Luoshi Neiyi prescription were found to regulate this metabolic disturbance， with the core regulatory pathways mainly involving arginine and proline metabolism. Correlation analysis showed that the glycerophospholipids including PI（16∶0/17∶0） and PI［18∶2（9Z，12Z）］ were negatively correlated with GPX4 and positively correlated with MDA， while 17α-hydroxyprogesterone was positively correlated with GPX4， SLC7A11， and FTH1 q<0.05）. ConclusionLuoshi Neiyi prescription may systematically ameliorate disease-associated metabolic dysregulation via modulation of the serum arginine and proline metabolism pathway， and may regulate ferroptosis in ectopic lesions through a mechanism potentially linked to the serum glycerophospholipid and steroid metabolism pathways. Collectively， these findings provide experimental evidence for the clinical application of Luoshi Neiyi prescription.

ObjectiveThis study aimed to investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through regulating ferroptosis， and to screen key metabolites and analyze their association with ferroptosis. MethodsClinical samples of normal endometrium from patients without EMs and eutopic and ectopic endometrium from EMs patients （10 cases each） were collected and divided into control group， eutopic group， and EMs group. Hematoxylin-eosin （HE） staining was performed to observe ectopic lesions of EMs. Immunohistochemistry was used to detect the expression of solute carrier family 7 member 11 （SLC7A11） and glutathione peroxidase 4 （GPX4）. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of malondialdehyde （MDA）， ferrous ion （Fe²⁺）， GPX4 and glutathione （GSH） in endometrial tissues， as well as serum levels of Fe²⁺， GPX4 and GSH. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of SLC7A11， GPX4， transferrin receptor （TFR） and ferritin heavy chain 1 （FTH1）. In the in vitro experiment， primary stromal cells were isolated from ectopic lesions of EMs patients. Cell counting kit-8 （CCK-8） was used to determine the optimal concentration of drug-containing serum for intervention. The level of reactive oxygen species （ROS） was measured， and Real-time PCR was applied to detect ferroptosis-related indicators. In the animal experiments， an EM rat model was established， and the rats were randomly assigned to the sham operation group， EMs group， low-dose Luoshi Neiyi Formula group （7.87 g·kg^-1）， high-dose Luoshi Neiyi prescription group （15.74 g·kg^-1）， and danazol group （42 mg·kg^-1）. Untargeted metabolomics detection and pathway enrichment analysis were conducted on serum samples from patients and rats. Spearman correlation analysis was performed to assess the relationship between differential metabolites and ferroptosis indicators. The correlations between differential metabolites in patient endometrium and serum and key ferroptosis indicators （GPX4， Fe²⁺， MDA， GSH） as well as ferroptosis-related mRNAs （GPX4， SLC7A11， FTH1） were analyzed， and correlation heatmaps were generated accordingly. ResultsCompared with normal eutopic endometrium， ectopic lesions in EMs patients showed glandular disorganization and stromal fibrosis. In ectopic endometrium， the contents of MDA， ROS， and Fe²⁺ decreased， while GPX4 level increased， and the mRNA expression of SLC7A11 and GPX4 was upregulated （P<0.05， P<0.01）. In serum， the levels of GPX4 and Fe²⁺ were elevated， whereas the GSH level declined， suggesting abnormalities in ferroptosis-related pathways in ectopic lesions （P<0.05， P<0.01）. After intervention with Luoshi Neiyi prescription-containing serum， the intracellular ROS level in ectopic endometrial stromal cells was elevated， the mRNA expression of SLC7A11 and GPX4 was downregulated， and TFR mRNA expression was upregulated （P<0.05， P<0.01）. Metabolomics analysis revealed 1104 and 198 differential metabolites in EMs patients and EMs rats， respectively， compared with their corresponding control groups， and both low-dose and high-dose Luoshi Neiyi prescription were found to regulate this metabolic disturbance， with the core regulatory pathways mainly involving arginine and proline metabolism. Correlation analysis showed that the glycerophospholipids including PI（16∶0/17∶0） and PI［18∶2（9Z，12Z）］ were negatively correlated with GPX4 and positively correlated with MDA， while 17α-hydroxyprogesterone was positively correlated with GPX4， SLC7A11， and FTH1 q<0.05）. ConclusionLuoshi Neiyi prescription may systematically ameliorate disease-associated metabolic dysregulation via modulation of the serum arginine and proline metabolism pathway， and may regulate ferroptosis in ectopic lesions through a mechanism potentially linked to the serum glycerophospholipid and steroid metabolism pathways. Collectively， these findings provide experimental evidence for the clinical application of Luoshi Neiyi prescription.

Objective To compare the differences of baseline characteristics of patients with myelodysplastic syndrome(MDS)who achieved platelet(PLT)response after arsenic-containing TCM compounds combined with Western medicine treatment.Methods Totally 72 MDS patients were selected from 12 outpatient departments and wards,such as Xiyuan Hospital,China Academy of Chinese Medical Sciences,Dongfang Hospital,Beijing University of Chinese Medicine from October 2021 to October 2024.Among them,45 patients received arsenic-containing TCM compounds combined with Western medicine treatment,27 patients received Western medicine treatment.The blood routine[white blood cell(WBC)count,hemoglobin,PLT,neutrophil count],TCM syndrome scores,safety indicators,and adverse events were observed before and after three courses of treatment.The efficacy of all patients was evaluated,and the baseline characteristics of patients who achieved PLT response in the arsenic-containing TCM compounds group and the Western medicine treatment group were compared.Results Comparing the differences of baseline characteristics of the two groups,it was found that the patients who achieved PLT response in the arsenic-containing TCM compounds group were compared with those in the Western medicine treatment group:Age<60 years old(P=0.038),longer disease duration(P=0.012),lower WBC(P=0.017),lower reticulocyte percentage(P=0.037),lower blood urea nitrogen(P=0.046),lower high-density lipoprotein cholesterol(P=0.014),and lower N-terminal pro-B-type natriuretic peptide(P=0.034),abnormal electrocardiogram(P=0.013),high blasts(P=0.009),grade 0 reticular fiber staining(P<0.01),normal chromosome karyotype(P<0.01),gene mutation(P<0.01)and high TCM syndrome scores(P=0.013)were found.Conclusion Arsenic-containing TCM compounds consisting of Qinghuang Powder and Bushen Jianpi Decoction combined with Western medicine is used to treat MDS.Patients with age<60 years old,long disease duration,low WBC count,low reticulocyte percentage,low blood urea nitrogen,low high-density lipoprotein cholesterol,low N-terminal pro-B-type natriuretic peptide,abnormal electrocardiogram,high blasts,grade 0 reticular fiber staining,normal chromosome karyotype,gene mutation and high TCM syndrome score are more likely to obtain PLT response.

Objective:To investigate the efficacy of venetoclax combined with hypomethylating agents (Ven-HMA), in patients with core binding factor acute myeloid leukemia (CBF-AML) intolerant to intensive induction therapy.Methods:This study retrospectively analyzed patients newly diagnosed with CBF-AML who were aged <60 years and who received Ven-HMA as induction therapy at the Department of Hematology, the First Affiliated Hospital of Soochow University, between January 2020 and June 2023. Baseline characteristics and treatment responses of the patients were collected.Results:A total of 70 treatment-na?ve patients receiving Ven-HMA induction therapy were enrolled, of which 38 were men and 32 women [median age: 43 (34 - 55) years]. Of the 70 patients, 44 (62.9%) achieved complete remission (CR) /CR with incomplete hematologic recovery (CRi), 16 (22.9%) achieved partial remission, and 10 (14.2%) exhibited no response after one induction cycle. Among the 32 t (8;21) -positive patients with AML, only 8 (25.0%) achieved CR/CRi, of whom 3 (37.5%) remained measurable residual disease (MRD) -positive; among the 38 inv (16) -positive patients, 36 (94.7%) achieved CR/Cri, of whom 12 (33.3%) remained MRD-positive. Patients harboring the CBFβ::MYH11 fusion gene showed significantly higher response rates to Ven-HMA induction than those with the RUNX1:: RUNX1T1 fusion gene ( P<0.01) . Conclusion:Ven-HMA represents a novel therapeutic strategy that exhibits significant efficacy in inv (16) -positive patients; however, it demonstrates relatively lower remission rates in t (8; 21) -positive patients.

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.

Purpose To analyze and compare the impact of incorporating molecular classification into the new FI-GO(2023)staging system for endometrial cancer(EC).Methods A retrospective analysis was conducted on 332 ca-ses of EC diagnosed and molecular subtyped by Department of Pathology Tianjin Central Hospital of Gynecology Obstet-rics in 2023.All cases were staged according to the FIGO(2023)staging criteria for EC.Results The median age of the 332 EC patients was 56 years(range:27-76 years).Molecular subtypes included 30 POLE mutation(POLE-mut),80 mismatch repair deficiency(MMRd),194 no specific molecular profile(NSMP),and 28 p53 abnormal(p53abn).Significant differences were observed among the four molecular subtypes regarding age,FIGO stage,patho-logical type,and lymph node metastasis rate(P＜0.05).However,no significant differences were found in the depth of myometrial invasion or lymphovascular space invasion.In the POLEmut group,19 cases(63.33％)were of non-ag-gressive histological types and 11(36.67％)were aggressive.After incorporating molecular subtyping,all 11 stage Ⅱ patients were downgraded to stage Ⅰ AmPOLEmut,increasing the proportion of stage Ⅰ patients from 62.07％to 100％.In the p53abn group,9 cases(32.14％)were non-aggressive and 19(67.86％)were aggressive.Molecular integra-tion led to the upstaging of 4 stage Ⅰ patients with myometrial invasion to stage Ⅱ Cmp53abn,increasing the proportion of stage Ⅱ patients from 34.61％to 50％.Conclusion Molecular subtypes p53abn and POLEmut are associated with distinct alterations in EC staging,specifically leading to tumor upstaging or downstaging.Our findings underscore the critical importance of comprehensive molecular subtyping in EC staging,as it refines prognostic risk stratification and provides valuable guidance for adjuvant treatment decisions.

Objective To construct an evaluation index system for rational drug use management of key monitoring drugs,and to provide references for medical institutions.Methods The preliminary index framework was formed by researching the policies and regulations,management norms,and guiding principles related to key monitoring drugs.Two rounds of Delphi questionnaire survey were conducted with 26 experts to improve and optimize the index system.The weights of the indicators were obtained by constructing the judgment matrix by analytic hierarchy process(AHP).Results The recovery rates of the two rounds of questionnaire were both 100％,and the authority coefficient was 0.87.The key monitoring drug rational use management evaluation index system was finally constructed to include three primary indicators[ex-ante management(0.253 6),in-process management(0.503 1),and ex-post management(0.243 2)],15 secondary indicators[including prescription review(0.302 6),formulate rational drug use norms(0.133 1),supernormal early warning management(0.103 2)],and 62 tertiary indicators[inclu-ding formulate strict prescription review rules(0.152 5),pharmacists prescription intervention strength(0.085 7)and effective-ness management(0.052 5)].and the index judgment matrix passed the consistency test.Conclusion The evaluation index system for the rational drug use management of key monitoring drugs constructed can satisfy the closed loop of the supervision and management process,achieve the prior reminder,monitoring,and post-supervision,and provide references for medical institutions to ensure the refinement and standardization of the management process.