ObjectiveTo investigate the chromosomal characteristics of blastocysts and pregnancy outcomes in patients with polycystic ovary syndrome （PCOS）， and to analyze the impact of PCOS on embryonic aneuploidy rate and the risk of miscarriage. MethodsThe retrospective cohort study was conducted on the preimplantation genetic testing（PGT） in the First Affiliated Hospital of Sun Yat-sen University， including cycles of PGT for aneuploidy（PGT-A） and PGT for monogenic disorders（PGT-M）. The 191 PCOS cycles（PCOS group） were matched with 564 control cycles（control group） using propensity score matching. The oocyte and embryo viability， chromosomal testing results of blastocysts， and cumulative clinical outcomes were compared between two groups. Subgroup analysis was performed by stratifying PCOS patients based on oocyte retrieval （＞20 vs. ≤20）. And the pregnancy outcomes after euploid embryo transfer were compared under different levels of ovarian response. ResultsPCOS group showed a significantly higher rate of aneuploidy per blastocyst compared to control group （21.8% vs. 19.0%， P=0.044）. Clinically， the overall miscarriage rate in the PCOS group was significantly higher than control group （17.2% vs. 10.3%， P=0.024）， even after euploid embryo transfer （17.2% vs. 10.0%， P=0.019）. In the PCOS subgroup with ＞ 20 oocytes ， the miscarriage rate following euploid embryo transfer was dramatically increased compared to control group （21.4% vs. 6.7%， P=0.001）， accompanied by higher risks of early miscarriage （15.7% vs. 5.7%， P=0.011）. Conversely， the PCOS subgroup with ≤ 20 oocytes showed outcomes comparable to control group. ConclusionsPatients with PCOS exhibit a significantly higher rate of blastocyst aneuploidy compared to the control group. Furthermore， PCOS is associated with a marked increase in miscarriage rates following blastocyst transfer， even with euploid embryos， particularly among patients with high ovarian response.

To evaluate patient satisfaction levels in a gynecological teaching clinic and to explore its associated influencing factors, so as to provide evidence for optimizing the operational model of teaching clinics.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Diabetic kidney disease (DKD) with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression. Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials. In this study, we integrated large-scale plasma proteomics, genetic-driven causal inference, and experimental validation to identify prioritized targets for DKD using the UK Biobank (UKB) and FinnGen cohorts. Among 2844 diabetic patients (528 with DKD), we identified 37 targets significantly associated with incident DKD, supported by both observational and causal evidence. Of these, 22% (8/37) of the potential targets are currently under investigation for DKD or other diseases. Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4 (IGFBP4), family with sequence similarity 3 member C (FAM3C), and prostaglandin D2 synthase (PTGDS)-were associated with a 4.35, 3.51, and 3.57-fold increased likelihood of developing DKD, respectively. In addition, population-level protein-altering variants (PAVs) analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD, through the classic NLR family pyrin domain containing 3 (NLRP3)-caspase-1-gasdermin D (GSDMD) apoptotic axis. Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

This report presents the management of a critically ill 36-year-old woman diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph +ALL) at 28 weeks of gestation. The patient rapidly deteriorated, developing disseminated intravascular coagulation (DIC) , diffuse alveolar hemorrhage (DAH) , septic shock, and multi-organ dysfunction, necessitating admission to the hematological intensive care unit. Given her critical condition and advanced pregnancy, a chemotherapy-free induction regimen comprising imatinib and dexamethasone was initiated, alongside comprehensive supportive measures, including mechanical ventilation, continuous renal replacement therapy (CRRT) , broad-spectrum antibiotics, and high-dose corticosteroids. During treatment, intrauterine fetal demise occurred, and a stillborn was delivered following obstetric intervention. With aggressive treatment, the patient's respiratory failure, DIC, and DAH gradually resolved, and she achieved complete remission. She subsequently received consolidation chemotherapy, CAR-T cell therapy, and allogeneic hematopoietic stem cell transplantation, achieving sustained complete molecular remission on long-term follow-up. This case demonstrates that for critically ill pregnant patients with Ph + ALL, a chemotherapy-free regimen of targeted therapy and corticosteroids, when combined with intensive supportive care, is a safe and effective approach that may offer a therapeutic option for similar cases.

BACKGROUND:Ovarian tissue vitrification cryopreservation is one of the important methods for preserving fertility.Tanshinone ⅡA has various pharmacological activities,including anti-oxidation,inhibition of inflammatory response,and reduction of apoptosis,but its role as an additive for vitrification cryoprotection of ovarian tissue is still unclear.OBJECTIVE:To explore the protective effect of tanshinone ⅡA on vitrification cryopreservation of mouse ovarian tissue.METHODS:Twenty-five 6-week-old female KM mice were randomly selected and their ovarian tissues were randomly divided into five groups,with 10 ovaries per group.The fresh group was not cryopreserved.The frozen control group used vitrification cryoprotectant.The 0.5,2.5,and 5 μmol/L tanshinone ⅡA groups used vitrification cryoprotectant containing 0.5,2.5,and 5 μmol/L tanshinone ⅡA,respectively,and were cryopreserved in liquid nitrogen.After 3 days of storage,the cryopreserved tubes were taken out and thawed.The ovarian tissue and follicle morphology of each group were observed by hematoxylin-eosin staining,and the normal follicle morphology and survival rate were analyzed.The levels of superoxide dismutase,catalase,malondialdehyde,tumor necrosis factor-α,interleukin-1β,and interleukin-17 in the ovary were detected by enzyme-linked immunosorbent assay.RT-qPCR and western blot assay were used to detect the mRNA and protein expressions of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)in the mouse ovary.RESULTS AND CONCLUSION:(1)Compared with the fresh group,the frozen control group had abnormal morphology of follicles at all levels in the ovary,decreased follicle survival rate(P＜0.05),decreased superoxide dismutase and catalase activities(P＜0.05);the levels of malondialdehyde,and tumor necrosis factor α,interleukin 1β,and interleukin 17 were all increased(P＜0.05),and the mRNA and protein expressions of Nrf2 and HO-1 were decreased(P＜0.05).(2)Compared with the frozen control group,different concentrations of tanshinone ⅡA could improve the morphology of follicles at all levels in the ovary,increase the survival rate of follicles,enhance the activities of superoxide dismutase and catalase,and reduce the levels of malondialdehyde,tumor necrosis factor α,interleukin 1β,and interleukin 17,increased the mRNA and protein expression of Nrf2 and HO-1 in a concentration-dependent manner,with 5 μmol/L tanshinone ⅡA having the most significant effect.(3)The results show that tanshinone ⅡA may reduce the oxidative stress level and inflammatory response of mouse ovarian tissue by mediating the Nrf2/HO-1 signaling pathway,thereby alleviating the reproductive damage caused by vitrification cryopreservation of mouse ovaries.

Diabetic kidney disease(DKD)with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression.Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials.In this study,we integrated large-scale plasma proteomics,genetic-driven causal inference,and experimental validation to identify prioritized targets for DKD using the UK Biobank(UKB)and FinnGen cohorts.Among 2844 diabetic patients(528 with DKD),we identified 37 targets significantly associated with incident DKD,supported by both observational and causal evi-dence.Of these,22％(8/37)of the potential targets are currently under investigation for DKD or other diseases.Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4(IGFBP4),family with sequence similarity 3 member C(FAM3C),and prostaglandin D2 synthase(PTGDS)—were associated with a 4.35,3.51,and 3.57-fold increased likeli-hood of developing DKD,respectively.In addition,population-level protein-altering variants(PAVs)analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD,through the classic NLR family pyrin domain containing 3(NLRP3)-caspase-1-gasdermin D(GSDMD)apoptotic axis.Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

BACKGROUND:Ovarian tissue vitrification cryopreservation is one of the important methods for preserving fertility.Tanshinone ⅡA has various pharmacological activities,including anti-oxidation,inhibition of inflammatory response,and reduction of apoptosis,but its role as an additive for vitrification cryoprotection of ovarian tissue is still unclear.OBJECTIVE:To explore the protective effect of tanshinone ⅡA on vitrification cryopreservation of mouse ovarian tissue.METHODS:Twenty-five 6-week-old female KM mice were randomly selected and their ovarian tissues were randomly divided into five groups,with 10 ovaries per group.The fresh group was not cryopreserved.The frozen control group used vitrification cryoprotectant.The 0.5,2.5,and 5 μmol/L tanshinone ⅡA groups used vitrification cryoprotectant containing 0.5,2.5,and 5 μmol/L tanshinone ⅡA,respectively,and were cryopreserved in liquid nitrogen.After 3 days of storage,the cryopreserved tubes were taken out and thawed.The ovarian tissue and follicle morphology of each group were observed by hematoxylin-eosin staining,and the normal follicle morphology and survival rate were analyzed.The levels of superoxide dismutase,catalase,malondialdehyde,tumor necrosis factor-α,interleukin-1β,and interleukin-17 in the ovary were detected by enzyme-linked immunosorbent assay.RT-qPCR and western blot assay were used to detect the mRNA and protein expressions of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)in the mouse ovary.RESULTS AND CONCLUSION:(1)Compared with the fresh group,the frozen control group had abnormal morphology of follicles at all levels in the ovary,decreased follicle survival rate(P＜0.05),decreased superoxide dismutase and catalase activities(P＜0.05);the levels of malondialdehyde,and tumor necrosis factor α,interleukin 1β,and interleukin 17 were all increased(P＜0.05),and the mRNA and protein expressions of Nrf2 and HO-1 were decreased(P＜0.05).(2)Compared with the frozen control group,different concentrations of tanshinone ⅡA could improve the morphology of follicles at all levels in the ovary,increase the survival rate of follicles,enhance the activities of superoxide dismutase and catalase,and reduce the levels of malondialdehyde,tumor necrosis factor α,interleukin 1β,and interleukin 17,increased the mRNA and protein expression of Nrf2 and HO-1 in a concentration-dependent manner,with 5 μmol/L tanshinone ⅡA having the most significant effect.(3)The results show that tanshinone ⅡA may reduce the oxidative stress level and inflammatory response of mouse ovarian tissue by mediating the Nrf2/HO-1 signaling pathway,thereby alleviating the reproductive damage caused by vitrification cryopreservation of mouse ovaries.

This report presents the management of a critically ill 36-year-old woman diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph +ALL) at 28 weeks of gestation. The patient rapidly deteriorated, developing disseminated intravascular coagulation (DIC) , diffuse alveolar hemorrhage (DAH) , septic shock, and multi-organ dysfunction, necessitating admission to the hematological intensive care unit. Given her critical condition and advanced pregnancy, a chemotherapy-free induction regimen comprising imatinib and dexamethasone was initiated, alongside comprehensive supportive measures, including mechanical ventilation, continuous renal replacement therapy (CRRT) , broad-spectrum antibiotics, and high-dose corticosteroids. During treatment, intrauterine fetal demise occurred, and a stillborn was delivered following obstetric intervention. With aggressive treatment, the patient's respiratory failure, DIC, and DAH gradually resolved, and she achieved complete remission. She subsequently received consolidation chemotherapy, CAR-T cell therapy, and allogeneic hematopoietic stem cell transplantation, achieving sustained complete molecular remission on long-term follow-up. This case demonstrates that for critically ill pregnant patients with Ph + ALL, a chemotherapy-free regimen of targeted therapy and corticosteroids, when combined with intensive supportive care, is a safe and effective approach that may offer a therapeutic option for similar cases.

Postoperative pain seriously affects the recovery process of patients, resulting in prolonged hospital stay and increased care costs. Appropriate application of patient-controlled analgesia devices can effectively relieve perioperative acute pain. In 1994 patient-controlled analgesia began to be used in Peking Union Medical College Hospital, and the Acute Pain Service Working Group was established in 2004. With the cooperation of anesthesiologists and specialist nurses, the group jointly has implemented the whole process and standardized management based on patient-controlled analgesia, and constantly improved and innovated working methods, laying a solid foundation for the development of postoperative pain management. This paper systematically reviews and summarizes the work from the aspects of clinical focus, nursing management experience, promotion and dissemination of pain treatment concepts, and development of acute pain service model under the new situation, with the hope of providing valuable reference for comprehensively strengthening pain management in the process of diagnosis and treatment, and enhancing patients' satisfaction with perioperative analgesia services.