OBJECTIVE To optimize the extraction process of flavonoids from Potentilla discolor .METHODS Deep eutectic solvents （DESs） were used as the extraction solvent to prepare test sample solutions. The contents of rutin， quercitrin， and kaempferol were determined by ultra-performance liquid chromatography. The analytic hierarchy process combined with the criteria importance through intercriteria correlation weighting method was employed to assign comprehensive weights to the contents of the three flavonoids， and calculate the comprehensive score. The optimal DESs were screened based on the comprehensive score.Mean while， using the comprehensive score as the response variable and the liquid-to-solid ratio， ultrasonic time， and urltrasonic temperature as the influencing factors， the extraction technology of flavonoids from P.discolor was optimized by Box-Behnken response surface methodology and subsequently validated.RESULTS The comprehensive weight coefficients of rutin， quercitrin， and kaempferol were 0.646 7， 0.207 5， and 0.145 8， respectively. The optimal DESs were choline chloride-lactic acid （molar ratio 1∶4） with a water content of 40%. The optimal extraction conditions were determined as follows： liquid-to-solid ratio of 25∶1， ultrasonic time of 40 min， and ultrasonic temperature of 50 ℃. The validation results showed that the average comprehensive score of three batches of samples was 99.28， with an RSD of 0.54% （ n ＝3）.CONCLUSIONS The optimal extraction technology of flavonoids from P. discolor based on DESs obtained in this study was stable and feasible.

Objective:To investigate lymph node metastasis(LNM)in the prostatic anterior fat pad(PAFP)of PCa patients after robot-assisted radical prostatectomy(RARP),and analyze the clinicopathological features and prognosis of LNM in the PAFP.Methods:We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urolo-gy of PLA General Hospital from January 2017 to December 2022.All the patients underwent routine removal of the PAFP during RARP and pathological examination,with the results of all the specimens examined and reported by pathologists.Based on the pres-ence and locations of LNM,we grouped the patients for statistical analysis,compared the clinicopathological features between different groups using the Student's t,Mann-Whitney U and Chi-square tests,and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio.Results:Lymph nodes were detected in 77(7.7％)of the 1 003 PAFP samples,and LNM in 11(14.3％)of the 77 cases,with a positive rate of 1.1％(11/1 003).Of the 11 positive cases,9 were found in the upgraded pathological N stage,and the other 2 complicated by pelvic LNM.The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group(81.8％[9/11]vs 36.2％[359/992],P=0.005),and so did the cases with Gleason score ≥8(87.5％[7/8]vs 35.5％[279/786],P=0.009).No statisti-cally significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the pa-tients with PAFP LNM only and those with pelvic LNM only.Conclusion:The PAFP is a potential route to LNM,and patients with LNM in the PAFP are characterized by poor pathological features.There is no statistically significant difference in biochemical recur-rence-free survival between the patients with PAFP LNM only and those with pelvic LNM only.Routine removal of the PAFP and inde-pendent pathological examination of the specimen during RARP is of great clinical significance.

Objective To observe the clinical efficacy and safety of vericiguat tablets combined with sacubitril valsartan sodium(Sac/Val)tablets in the treatment of patients with heart failure with reduced ejection fraction(HFrEF).Methods The HFrEF patients were divided into control group and treatment group according to the cohort method.The control group was treated with Sac/Val tablets 200 mg per time,bid,orally.On the basis of control group,the treatment group was treated with vericiguat tablets 2.5 mg per time,qd,taken with meal.Two groups were treated for 3 months.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic dimension(LVEDD)and end-systolic diameter(LVESD),levels of high sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6),nitric oxide(NO),N-terminal pro-brain natriuretic peptide(NT-proBNP),blood urea nitrogen(BUN)and serum creatinine(SCr),and safety were compared between the two groups.During follow-up,the heart failure rehospitalization rates and major adverse cardiovascular events were compared between the two groups.Results Treatment group was enrolled 53 patients,control group was enrolled 53 patients.After treatment,the total effective rates of treatment and control groups were 94.34％(50 cases/53 cases)and 81.13％(43 cases/53 cases)with statistical significant difference(P＜0.05).After treatment,the LVEF of treatment and control groups were(48.02±5.20)％and(43.02±4.33)％,the LVEDDs were(52.85±6.30)and(55.63±6.88)mm,the LVESDs were(41.64±6.40)and(44.22±5.85)mm,the levels of hs-CRP were(10.22±2.63)and(14.60±2.98)mg L-1,the levels of IL-6 were(14.48±2.40)and(17.36±2.52)pg·mL-1,the levels of NO were(102.60±20.16)and(92.16±16.33)μmol·L-1,the levels of NT-proBNP were(898.74±102.20)and(1315.60±182.64)ng·L-1,the levels of BUN were(12.02±2.28)and(13.45±2.33)mmol·L-1,the levels of SCr were(82.22±5.89)and(85.64±6.03)μmol·L-1,the heart failure rehospitalization rates were 5.66％and 13.21％,respectively;the differences were statistical significant between two groups(all P＜0.05).The adverse drug reactions of treatment group were hyperkalemia,hypotension,renal dysfunction,dizziness and headache,while those in control group were renal dysfunction,hyperkalemia,and hypotension.The major adverse cardiovascular events of treatment group were angina pectoris and acute myocardial infarction,while those in control group were angina pectoris,acute myocardial infarction and atrial fibrillation.The incidences of total adverse drug reactions in treatment and control groups were 13.21％and 7.55％,the incidences of major adverse cardiovascular events were 5.66％and 13.21％,respectively,without statistically significant differences(all P＞0.05).Conclusion Vericiguat tablets combined with Sac/Val tablets have a definitive clinical efficacy in the treatment of HFrEF patients,which can improve cardiac and endothelial function,reduce inflammatory response and readmission times,without increasing the incidences of adverse drug reactions.

Objective:This study investigated the independent risk factors for lymph node metastasis（LNM）in high-risk prostate cancer（HRPCa）patients undergoing robot-assisted radical prostatectomy（RARP），and constructed a nomogram model based on clinical data to improve the accuracy and clinical practicality of preoperative prediction of LNM.Methods:A retrospective analysis was conducted on the clinical data of 218 HRPCa patients who received RARP treatment at the First Medical Center of the PLA General Hospital from January 2020 to March 2025 as the modeling group. The age of the modeling group was（66.91±6.94）years old. 75 cases（34.40%）had a history of smoking，and 48 cases（22.02%）had a history of drinking. There were a body mass index（BMI）of 25.55（23.58，27.00）kg/m 2，a total prostate-specific antigen（tPSA）of 20.59（10.42，30.61）ng/ml，a free prostate-specific antigen（fPSA）of 1.87（1.04，3.26）ng/ml，a prostate volume（PV）of（41.19±21.00）ml，a prostate-specific antigen density（PSAD）of 0.52（0.30，0.84）ng/ml 2. Among the patients，60 cases（27.52%）had a preoperative biopsy Gleason score >8，and the percentage of positive biopsy cores（PPBC）was 50%（31%，80%）. Thirty-one patients（14.22%）were staged clinically as >T 2c. The diagnostic criteria for high-risk prostate cancer（HRPCa）were defined as meeting any one of the following：PSA >20 ng/ml，Gleason score on prostate biopsy ≥8，or clinical stage ≥T 3. Among the 218 patients in the modeling cohort，67 cases（30.73%）met two of the criteria，and 7 cases（3.21%）met all three criteria. All 218 patients underwent RARP，and based on postoperative pathology，they were divided into the LNM group and the non-LNM group. The relationship between the number of diagnostic criteria met and the occurrence of LNM was analyzed. An external validation cohort included 42 HRPCa patients who underwent RARP at the Third，Fifth Medical Centers of the PLA General Hospital between January 2023 and May 2025. Their mean age was（66.79±5.92）years. Eighteen patients（42.86%）had a smoking history，and nine（21.43%）had a history of alcohol consumption. The median BMI was 26.00（23.80，27.13）kg/m 2. The median tPSA level was 17.34（8.97，27.30）ng/ml. The median fPSA was 1.51（0.83，2.52）ng/ml，and the median PV was（35.57 ± 15.25）ml. The median PSAD was 0.57（0.23，0.87）ng/ml 2，and the median PPBC was 58%（36%，71%）. Three patients（7.14%）had a clinical stage >T 2c，and 12 patients（28.57%）had a Gleason score >8 on preoperative biopsy. Univariate and multivariate binary logistic regression analyses were used to identify independent risk factors for LNM，and a nomogram model was constructed based on these factors. The predictive performance of the model was evaluated using receiver operating characteristic（ROC）curves and calibration plots，and the model was validated in the external cohort. Result:According to postoperative pathology，45 patients were classified into the LNM group，and 173 into the non-LNM group. The probability of LNM increased proportionally with the number of diagnostic criteria met for HRPCa（meeting two criteria： OR = 4.762，95% CI 2.323-9.761， P < 0.01；meeting three criteria： OR = 10.667，95% CI 2.187-52.025， P=0.003）. Binary logistic regression analysis revealed that age（ OR=0.913，95% CI 0.859-0.971， P = 0.004），tPSA（ OR=1.039，95% CI 1.018-1.061， P<0.01），PPBC（ OR = 5.656，95% CI 1.101-29.056， P = 0.038），and clinical T stage（T 2c stage： OR=2.945，95% CI 0.888-9.769， P=0.077；>T 2c stage OR = 18.351，95% CI 4.790-70.306， P < 0.01）were independent risk factors for postoperative LNM in HRPCa patients after RARP. The ROC curve of the nomogram model based on these factors showed an area under the curve（AUC）of 0.853（95% CI 0.790-0.917）. In the external validation cohort，the nomogram achieved an AUC of 0.743（95% CI 0.556-0.929）. The calibration plots demonstrated good agreement between the predicted probabilities and actual observations. Conclusions:Age，tPSA，PPBC，and clinical T stage were independent predictors of postoperative LNM in HRPCa patients undergoing RARP. The greater the number of HRPCa diagnostic criteria met，the higher the likelihood of postoperative LNM. The nomogram developed in this study could effectively predict the risk of LNM in HRPCa patients after RARP.

Objective:To investigate the risk factors for positive surgical margins（PSM）after robot-assisted radical prostatectomy（RARP），and to develop and validate a predictive nomogram.Methods:We retrospectively analyzed the clinicopathological data of 874 prostate cancer patients who underwent RARP performed by a single surgeon at the First Medical Center of Chinese PLA General Hospital between January 2012 and December 2018. Patients were divided into positive surgical margin（n=327）and negative surgical margin（n=547）groups based on postoperative margin status.The PSM group had significantly higher preoperative median tPSA［31.200（19.050，54.400）ng/ml vs. 15.050（9.840，27.590）ng/ml， P<0.01］，higher proportion of patients with PSAD>1 ng/ml 2［49.5%（162/327）vs. 21.2%（116/547）， P<0.01］，biopsy Gleason score ≥8［33.3%（109/327）vs. 21.2%（116/547）， P<0.01］，ISUP grade 4-5［33.3%（109/327）vs. 21.2%（116/547）， P<0.01］，clinical T stage ≥cT 3［11.3%（37/327）vs. 4.2%（23/547）， P<0.01］，and high-risk classification［82.3%（269/327）vs. 55.9%（306/547）， P<0.01］compared to the negative surgical margin group. Conversely，the PSM group had a lower prevalence of hypertension［29.7%（97/327）vs. 40.2%（220/547）， P=0.002］.Patients were randomly split into a training cohort（n=656，75%）and an internal validation cohort（n=218，25%）. An external validation cohort included 71 patients who underwent RARP by different surgeons between January 2014 and December 2016. No significant differences in baseline characteristics were observed between cohorts（ P>0.05）.Univariate and multivariate logistic regression analyses identified independent predictors of PSM，which were incorporated into a nomogram. Predictive performance was assessed using receiver operating characteristic（ROC）curves，decision curve analysis（DCA），and calibration curve. Internal and external validations were performed. Results:The PSM group had longer postoperative hospitalization［6（5，8）vs. 6（5，7）days， P=0.028］，higher rates of pathologic Gleason score ≥8［41.5%（115/277）vs. 24.9%（111/446）， P<0.01］，ISUP grade 4-5［41.5%（115/277）vs. 24.9%（111/446）， P<0.01］，pT 3 stage［52.3%（171/327）vs. 17.4%（95/547）， P<0.01］，pN 1 stage［12.8%（42/327）vs. 3.8%（21/547）， P<0.01］，extracapsular extension［52.3%（171/327）vs. 17.4%（95/547）， P<0.01］，and seminal vesicle invasion［34.6%（113/327）vs. 9.1%（50/547）， P<0.01］.Multivariate analysis identified elevated tPSA（ OR=1.014，95% CI 1.004—1.024，P=0.006）and PSAD ≥0.15 ng/（ml/g）（ OR=11.638，95% CI 1.450—93.396，P=0.021）as independent risk factors for PSM. The area under the ROC curve（AUC）of the nomogram constructed based on the above variables was 0.770（95% CI 0.735—0.805）. The AUC values for the internal and external validation sets were 0.698（95% CI 0.630—0.767）and 0.643（95% CI 0.513—0.774），respectively. The calibration curve demonstrated good agreement between the predicted and observed outcomes，and the DCA indicated that the predictive model has potential clinical utility in decision-making. Conclusion:tPSA and PSAD were identified as independent risk factors for PSM. The nomogram constructed based on these two independent predictive variables effectively predicted PSM after RARP.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To compare the cost-effectiveness between sodium valproate and levetiracetam in the treatment of childhood epilepsy and provide an economic basis for clinical medication choices. Methods A cost-effectiveness analysis was conducted using a decision tree model to compare the effectiveness and drug costs of sodium valproate and levetiracetam in treating childhood epilepsy. Single-factor sensitivity analysis and probabilistic sensitivity analysis were used to assess the impact of parameter variations on the study results. Results The treatment cost of levetiracetam was significantly higher than that of sodium valproate. The incremental cost-effectiveness ratio （ICER） of levetiracetam compared to sodium valproate was ¥8 628.43. Sensitivity analysis results were consistent with the base-case analysis. The probabilistic sensitivity analysis showed that, over a 6-month treatment period, levetiracetam became a more cost-effective option when the willingness-to-pay （WTP） threshold was ¥9,000 or higher. One-way sensitivity analysis revealed that the price of levetiracetam was the most influential factor affecting the ICER. Conclusion When the WTP per effective pediatric epilepsy case is ¥9,000 or higher, levetiracetam demonstrates a cost-effectiveness advantage.

Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.