The oocyte， as the origin of life， provides half the chromosomes to the embryo and supplies the proteins， substrates， energy， and other support necessary for embryonic development. It is the decisive factor determining the embryo's developmental potential. Infertility caused by reproductive endocrine diseases targets the oocyte as the final target cell. Improving oocyte quality represents a key and difficult point in the field of modern reproductive medicine. The decline of oocyte quality is related to meiosis abnormalities， DNA damage， mitochondrial dysfunction， oxidative stress， and other mechanisms. For oocyte quality problems， there is no unified international guideline to recommend drugs. Because the drug intervention research on oocytes involves strict clinical ethical restrictions， the current relevant research only stays in the animal and in vitro experimental stage and has not yet been applied to the clinic. Traditional Chinese medicine compound formula has a multi-target and multi-pathway regulation mechanism and is widely used in clinics. More and more research began to pay attention to the potential mechanism of traditional Chinese medicine compound formulas in improving oocyte quality. Traditional Chinese medicine compound formula has the advantages of multi-target and multi-channel synergy as well as better safety， individualization， and conformity to clinical ethics in improving oocyte quality. This article systematically reviewed the research progress on traditional Chinese medicine compound formula interventions for oocyte quality， aiming to summarize existing findings and provide recommendations to improve oocyte quality and optimize the clinical diagnosis and treatment of female infertility within traditional Chinese medicine.

The oocyte， as the origin of life， provides half the chromosomes to the embryo and supplies the proteins， substrates， energy， and other support necessary for embryonic development. It is the decisive factor determining the embryo's developmental potential. Infertility caused by reproductive endocrine diseases targets the oocyte as the final target cell. Improving oocyte quality represents a key and difficult point in the field of modern reproductive medicine. The decline of oocyte quality is related to meiosis abnormalities， DNA damage， mitochondrial dysfunction， oxidative stress， and other mechanisms. For oocyte quality problems， there is no unified international guideline to recommend drugs. Because the drug intervention research on oocytes involves strict clinical ethical restrictions， the current relevant research only stays in the animal and in vitro experimental stage and has not yet been applied to the clinic. Traditional Chinese medicine compound formula has a multi-target and multi-pathway regulation mechanism and is widely used in clinics. More and more research began to pay attention to the potential mechanism of traditional Chinese medicine compound formulas in improving oocyte quality. Traditional Chinese medicine compound formula has the advantages of multi-target and multi-channel synergy as well as better safety， individualization， and conformity to clinical ethics in improving oocyte quality. This article systematically reviewed the research progress on traditional Chinese medicine compound formula interventions for oocyte quality， aiming to summarize existing findings and provide recommendations to improve oocyte quality and optimize the clinical diagnosis and treatment of female infertility within traditional Chinese medicine.

OBJECTIVE To conduct qualitative analysis of chemical constituents in the crude extract of Modified Ermiao Formu-la,along with its blood-absorbed components and metabolites in rats post-administration employing ultra-performance liquid chroma-tography coupled with quadrupole-exactive orbitrap tandem mass spectrometry(UPLC-Q-Exactive Orbitrap-MS/MS).METHODS Separation was performed on a Waters HSS T3 column(100 mm×2.1 mm,1.8 μm)using gradient elution with 0.1%formic acid in water(mobile phase A)and 0.1%formic acid in acetonitrile(mobile phase B),under controlled conditions:column temperature maintained at 40℃,flow rate set to 0.3 mL·min-1,and injection volume fixed at 2 μL.Mass spectrometric data acquisition utilized an electrospray ionization(ESI)source with scanning in both positive and negative ion modes.RESULTS By analyzing precise mo-lecular weights,retention times,and MS/MS fragmentation patterns,and cross-referencing these against established databases and published literature,173 chemical constituents were definitively identified in the Modified Ermiao Formula crude extract.These prima-rily comprised flavonoids,organic acids,and alkaloids.Additionally,32 prototype components and 13 metabolites were characterized in the serum of dosed rats.Organic acids constituted the predominant class of serum prototype components,undergoing in vivo metabo-lism principally through demethylation and carboxyl glucuronidation.CONCLUSION This study provides the initial delineation of blood-absorbed prototype components derived from Modified Ermiao Formula,with concomitant identification of their metabolites,thereby establishing a foundational framework for elucidating the pharmacologically active constituents of this formula.

Objective:To construct and validate a predictive model for pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy.Methods:This retrospective observational study included 595 patients with stage T2-4 and (or) N+M0 LARC diagnosed in the Cancer Hospital of Chinese Academy of Medical Sciences and the Fourth Hospital of Hebei Medical University who had no metastases, tolerated neoadjuvant therapy, completed neoadjuvant therapy, and had undergone radical surgery after neoadjuvant therapy. The training set comprised 299 patients admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from 2013 to 2018, the internal validation set 155 patients admitted from 2019 to 2023, and the external validation set 141 patients admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2021. They were divided into pCR group and non-pCR groups according to postoperative pathology. Among the 299 patients in the training set, 247 were in the non-PCR and 52 in the pCR group; among the 155 patients verified internally, 113 were in the non-PCR and 42 in the pCR group; and among the 141 patients validated externally, 132 were in the non-pCR and nine in the pCR group. Logistic regression was used for univariate and multifactorial analysis to explore the factors associated with pCR and construct a nomogram prediction model. Receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to validate the performance of the predictive model.Results:Univariate and multivariate logistic regression analysis showed that carbohydrate antigen 19-9 ( P=0.040, OR=0.97, 95%CI: 0.93-0.99), neutrophil count ( P<0.001, OR=0.66, 95%CI: 0.52-0.84), tumor T stage: Stage IV ( P=0.011, OR=0.22, 95%CI: 0.07-0.70), tumor N stage: Stage I ( P=0.003, OR=0.22,95%CI:0.08-0.60), Stage II ( P<0.001, OR=0.03, 95%CI: 0.01-0.09) and involvement of mesorectal fascia ( P=0.004, OR=0.09, 95%CI: 0.02-0.47) were independent predictors of pCR. In the training set, the area under the receiver operating characteristic curve of the model was 0.92 (95%CI: 0.87-0.96), whereas in the internal and external validation sets, the AUCs were 0.78 and 0.81, respectively. The calibration curve showed that the prediction model had good prediction efficiency in both the training and verification sets. Decision curve analysis showed that the net benefit of the model was largest when the threshold probability was in the range of 5.2% to 89.7% (in the internal and external validation sets, the threshold probabilities were in the range of 15.7% to 92.3% and 2.2% to 84.1%, respectively). Conclusion:The nomogram model constructed in this study showed efficacy in predicting whether patients with LARC will achieve pCR after receiving neoadjuvant chemoradiotherapy.

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective To determine the basic and clinical issues to be included in the Guidelines for the Prevention and Treatment of Adenomyosis based on the Delphi method.Methods Based on literature review,preliminary general research,and expert interviews,this study drafted a survey questionnaire for guideline questions.After selecting the expert group,two rounds of Delphi method were conducted to determine the basic and clinical issues included in the guidelines.The questionnaire results were statistically analyzed to evaluate the quality control of Delphi method.Results A total of 15 experts were selected to participate in two rounds of Delphi questionnaire surveys.Finally,39 basic and clinical questions were included,which were condensed into 8 guideline questions.The expert positivity coefficient was 100%,the average coefficient of variation of the two rounds of coordination was 0.23 and 0.30,respectively,and the expert authority coefficient was 0.903.The quality control of the two rounds of Delphi method was good.Conclusion Based on the Delphi method,the basic and clinical issues of the Guidelines for the Prevention and Treatment of Adenomyosis are determined,laying the foundation for the subsequent development of the guidelines.

Objective To identify the basic and clinical questions of the Guidelines for Preventive Treatment of Diseases in Endometriosis based on the Delphi method.Methods Based on the preliminary literature review,preliminary pan-research and expert interviews,the questions of the Guidelines for Preventive Treatment of Diseasesin in Endometriosis were drafted.Totally 15 experts were selected for two rounds of Delphi method expert correspondence and the results were statistically analyzed to finalize the questions for inclusion in the guidelines.Results A total of 65 entries were finally identified for inclusion in the guideline questions and condensed into 8 guideline questions.The quality control of the two rounds of Delphi method was good.The positive coefficient of experts in both rounds was 100%.The coefficient of authority of experts was>0.70.In the degree of Delphi coordination,the mean coefficients of variation were 0.23 and 0.26,and the coefficients of Kendall's concordance were 0.510 and 0.309,respectively(P<0.05).Conclusion This study uses two rounds of Delphi method to determine the issues included in the Guidelines for Preventive Treatment of Diseases in in Endometriosis,laying a solid foundation for the subsequent development of the guidelines.

Antibody-drug conjugates(ADCs)represent a major breakthrough in the treatment of human epidermal growth factor receptor-2(HER-2)-positive breast cancer as they are responsible for significantly improving clinical outcomes.However,their widespread use is accom-panied by severe adverse effects that not only impact the quality of life of patients and treatment adherence but also life-threatening,ulti-mately leading to treatment discontinuation.This article systematically reviews the underlying mechanisms and management strategies for ADC-related toxicities in HER-2-positive breast cancer.Additionally,it focuses on key adverse events,including thrombocytopenia,interstitial lung disease,and cardiotoxicity,that are induced by ADCs such as trastuzumab emtansine(T-DM1)and trastuzumab deruxtecan(T-DXd).Based on the clinical evidence,we proposed early monitoring and standardized intervention measures,emphasizing the importance of timely recognition and systematic management to mitigate risks.Furthermore,we explored future directions for optimizing ADC design to reduce their toxicity and provide valuable insights into their safe clinical application.

OBJECTIVE To conduct qualitative analysis of chemical constituents in the crude extract of Modified Ermiao Formu-la,along with its blood-absorbed components and metabolites in rats post-administration employing ultra-performance liquid chroma-tography coupled with quadrupole-exactive orbitrap tandem mass spectrometry(UPLC-Q-Exactive Orbitrap-MS/MS).METHODS Separation was performed on a Waters HSS T3 column(100 mm×2.1 mm,1.8 μm)using gradient elution with 0.1%formic acid in water(mobile phase A)and 0.1%formic acid in acetonitrile(mobile phase B),under controlled conditions:column temperature maintained at 40℃,flow rate set to 0.3 mL·min-1,and injection volume fixed at 2 μL.Mass spectrometric data acquisition utilized an electrospray ionization(ESI)source with scanning in both positive and negative ion modes.RESULTS By analyzing precise mo-lecular weights,retention times,and MS/MS fragmentation patterns,and cross-referencing these against established databases and published literature,173 chemical constituents were definitively identified in the Modified Ermiao Formula crude extract.These prima-rily comprised flavonoids,organic acids,and alkaloids.Additionally,32 prototype components and 13 metabolites were characterized in the serum of dosed rats.Organic acids constituted the predominant class of serum prototype components,undergoing in vivo metabo-lism principally through demethylation and carboxyl glucuronidation.CONCLUSION This study provides the initial delineation of blood-absorbed prototype components derived from Modified Ermiao Formula,with concomitant identification of their metabolites,thereby establishing a foundational framework for elucidating the pharmacologically active constituents of this formula.

Objective:To construct and validate a predictive model for pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy.Methods:This retrospective observational study included 595 patients with stage T2-4 and (or) N+M0 LARC diagnosed in the Cancer Hospital of Chinese Academy of Medical Sciences and the Fourth Hospital of Hebei Medical University who had no metastases, tolerated neoadjuvant therapy, completed neoadjuvant therapy, and had undergone radical surgery after neoadjuvant therapy. The training set comprised 299 patients admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from 2013 to 2018, the internal validation set 155 patients admitted from 2019 to 2023, and the external validation set 141 patients admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2021. They were divided into pCR group and non-pCR groups according to postoperative pathology. Among the 299 patients in the training set, 247 were in the non-PCR and 52 in the pCR group; among the 155 patients verified internally, 113 were in the non-PCR and 42 in the pCR group; and among the 141 patients validated externally, 132 were in the non-pCR and nine in the pCR group. Logistic regression was used for univariate and multifactorial analysis to explore the factors associated with pCR and construct a nomogram prediction model. Receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to validate the performance of the predictive model.Results:Univariate and multivariate logistic regression analysis showed that carbohydrate antigen 19-9 ( P=0.040, OR=0.97, 95%CI: 0.93-0.99), neutrophil count ( P<0.001, OR=0.66, 95%CI: 0.52-0.84), tumor T stage: Stage IV ( P=0.011, OR=0.22, 95%CI: 0.07-0.70), tumor N stage: Stage I ( P=0.003, OR=0.22,95%CI:0.08-0.60), Stage II ( P<0.001, OR=0.03, 95%CI: 0.01-0.09) and involvement of mesorectal fascia ( P=0.004, OR=0.09, 95%CI: 0.02-0.47) were independent predictors of pCR. In the training set, the area under the receiver operating characteristic curve of the model was 0.92 (95%CI: 0.87-0.96), whereas in the internal and external validation sets, the AUCs were 0.78 and 0.81, respectively. The calibration curve showed that the prediction model had good prediction efficiency in both the training and verification sets. Decision curve analysis showed that the net benefit of the model was largest when the threshold probability was in the range of 5.2% to 89.7% (in the internal and external validation sets, the threshold probabilities were in the range of 15.7% to 92.3% and 2.2% to 84.1%, respectively). Conclusion:The nomogram model constructed in this study showed efficacy in predicting whether patients with LARC will achieve pCR after receiving neoadjuvant chemoradiotherapy.