Objective To investigate programmed death including necroptosis,apoptosis,autophagy,ferroptosis,and pyroptosis in bone marrow megakaryocytes of mice during sepsis and its impact on platelet production capacity and coagulation function in mice.Methods C57BL/6J mice were randomly divided into a sham operation group(sham group)and a sepsis model group(CLP group).Peripheral blood platelets and coagulation function were measured by abdominal aortic blood sampling at 24 h postoperatively in both sham and CLP groups.After the mice were sacrificed,long bones of both lower limbs were taken,and bone marrow megakaryocytes were extracted using megakaryocyte separation solution and immunomagnetic bead separation.Laser confocal microscopy was used to observe the activation of programmed death-related marker molecules in mouse bone marrow megakaryocytes.Flow cytometry was used to detect programmed death rate,platelet production phenotype,and platelet surface markers(CD41,CD42b,CD61)of megakaryocytes.Western blotting was used to detect the expression of programmed death-related proteins in megakaryocytes.Results Compared with the sham group,the CLP group showed significant decreases in the number of platelets during acute sepsis(24 h)(P<0.000 1),significant increases in platelet distri-bution width(PDW)and mean platelet volume(MPV)(P<0.01),significant prolonging of thrombin time(TT),prothrombin time(PT),and activated partial thromboplastin time(APTT)(P<0.000 1,P<0.001,P<0.01),and significant reduction in fibrinogen(Fib)(P<0.000 1).Compared with the Con/sham group,the LPS/CLP group exhibited significant increases in the platelet production phenotype of megakaryocyte,the number of PLP in the supernatant,and the expression levels of platelet surface markers(CD41,CD42b,CD61).The rates of megakaryocyte necroptosis/apoptosis,pyroptosis,and ferroptosis were significantly elevated at 24 h post-CLP surgery.Laser confo-cal microscopy showed significant activation of LC3,P-MLKL,Caspase-1,and Fe2+in megakaryocytes of mice after CLP surgery.Western blotting results revealed that the CLP group exhibited a significant increase in the activa-tion rate of necroptosis-related protein P-MLKL(P<0.001),a significant increase in the cleavage of pyroptosis-related proteins GSDMD and GSDMD-N(P<0.01,P<0.001,respectively),a significant increase in the expres-sion of ferroptosis-related protein ACSL4(P<0.01),and a significant decrease in the expression of GPX4(P<0.01)compared to the sham group.Additionally,the CLP group demonstrated significant increases in the expression of apoptosis-related protein Bax,the cleavage of autophagy-related protein LC3B-Ⅱ,and the expression of P62(P<0.05,P<0.001,P<0.001,respectively).Inhibition of apoptosis with programmed cell death inhibitors decreased platelet production function of megakaryocyte,while inhibition of necroptosis and pyroptosis had limited effects on platelet production function of megakaryocyte.Inhibition of ferroptosis and autophagy enhanced platelet production function of megakaryocyte.Conclusion Significant programmed death of megakaryocytes was observed during the acute phase of sepsis(24 h).Among those megakaryocytes,apoptosis is an important mechanism for the differentia-tion of platelet production phenotype and increased platelet production capacity of megakaryocyte.Overactive autophagy and ferroptosis in megakaryocytes lead to megakaryocyte dysfunction,which is an important mechanism for coagulation abnormalities in sepsis.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective To investigate programmed death including necroptosis,apoptosis,autophagy,ferroptosis,and pyroptosis in bone marrow megakaryocytes of mice during sepsis and its impact on platelet production capacity and coagulation function in mice.Methods C57BL/6J mice were randomly divided into a sham operation group(sham group)and a sepsis model group(CLP group).Peripheral blood platelets and coagulation function were measured by abdominal aortic blood sampling at 24 h postoperatively in both sham and CLP groups.After the mice were sacrificed,long bones of both lower limbs were taken,and bone marrow megakaryocytes were extracted using megakaryocyte separation solution and immunomagnetic bead separation.Laser confocal microscopy was used to observe the activation of programmed death-related marker molecules in mouse bone marrow megakaryocytes.Flow cytometry was used to detect programmed death rate,platelet production phenotype,and platelet surface markers(CD41,CD42b,CD61)of megakaryocytes.Western blotting was used to detect the expression of programmed death-related proteins in megakaryocytes.Results Compared with the sham group,the CLP group showed significant decreases in the number of platelets during acute sepsis(24 h)(P<0.000 1),significant increases in platelet distri-bution width(PDW)and mean platelet volume(MPV)(P<0.01),significant prolonging of thrombin time(TT),prothrombin time(PT),and activated partial thromboplastin time(APTT)(P<0.000 1,P<0.001,P<0.01),and significant reduction in fibrinogen(Fib)(P<0.000 1).Compared with the Con/sham group,the LPS/CLP group exhibited significant increases in the platelet production phenotype of megakaryocyte,the number of PLP in the supernatant,and the expression levels of platelet surface markers(CD41,CD42b,CD61).The rates of megakaryocyte necroptosis/apoptosis,pyroptosis,and ferroptosis were significantly elevated at 24 h post-CLP surgery.Laser confo-cal microscopy showed significant activation of LC3,P-MLKL,Caspase-1,and Fe2+in megakaryocytes of mice after CLP surgery.Western blotting results revealed that the CLP group exhibited a significant increase in the activa-tion rate of necroptosis-related protein P-MLKL(P<0.001),a significant increase in the cleavage of pyroptosis-related proteins GSDMD and GSDMD-N(P<0.01,P<0.001,respectively),a significant increase in the expres-sion of ferroptosis-related protein ACSL4(P<0.01),and a significant decrease in the expression of GPX4(P<0.01)compared to the sham group.Additionally,the CLP group demonstrated significant increases in the expression of apoptosis-related protein Bax,the cleavage of autophagy-related protein LC3B-Ⅱ,and the expression of P62(P<0.05,P<0.001,P<0.001,respectively).Inhibition of apoptosis with programmed cell death inhibitors decreased platelet production function of megakaryocyte,while inhibition of necroptosis and pyroptosis had limited effects on platelet production function of megakaryocyte.Inhibition of ferroptosis and autophagy enhanced platelet production function of megakaryocyte.Conclusion Significant programmed death of megakaryocytes was observed during the acute phase of sepsis(24 h).Among those megakaryocytes,apoptosis is an important mechanism for the differentia-tion of platelet production phenotype and increased platelet production capacity of megakaryocyte.Overactive autophagy and ferroptosis in megakaryocytes lead to megakaryocyte dysfunction,which is an important mechanism for coagulation abnormalities in sepsis.

OBJECTIVE To investigate the types of bacteria isolated from skin lesions in adolescent patients with ac-ne vulgaris and analyze their drug resistance to commonly used antibacterial drugs.METHODS A total of 80 ado-lescent patients with acne vulgaris admitted to the Seventh Medical Center of Chinese PLA General Hospital from Mar.2022 to Mar.2024 were enrolled.The contents of facial acne skin lesions were collected for bacterial identifi-cation and the E-test method was employed to evaluate the drug resistance rates of isolated bacteria to commonly used antibacterial drugs.RESULTS Among the collected skin lesion samples in this study,74 strains(92.50％)of Propionibacterium acnes,76 strains(95.00％)of Staphylococcus epidermidis and 12 strains(15.00％)of S.aureus were detected.No statistically significant differences were observed in the detection rates of P.acnes,S.epidermidis and S.aureus among patients of different genders,ages,disease courses or severity levels.P.ac-nes exhibited high sensitivity to tetracycline,doxycycline and minocycline(all＞95％)but was almost completely resistant to metronidazole.Its sensitivity rate to macrolides such as erythromycin,clarithromycin,clindamycin,roxithromycin and azithromycin were low(＜50％).S.epidermidis showed sensitivity rates of 67.11％,81.58％and 82.89％to tetracycline,doxycycline and minocycline,respectively,with high drug resistance to metronidazole(96.05％)and low sensitivity rate to erythromycin,clarithromycin,clindamycin,roxithromycin and azithromycin(＜60％).S.aureus demonstrated sensitivity rates of 58.33％,75.00％and 75.00％to tetracycline,doxycycline and minocycline,respectively,while its sensitivity rates to erythromycin,clarithromycin,clindamycin,roxithro-mycin and azithromycin were 33.33％,41.67％,50.00％,41.67％and 33.33％,respectively.CONCLUSIONS The predominant bacteria isolated from skin lesions in adolescent patients with acne vulgaris are S.epidermidis and P.acnes,with a lower detection rate of S.aureus.All three isolated bacteria exhibit high sensitivity to tetra-cycline antibacterial drugs but significant drug resistance to macrolides and near-complete drug resistance to met-ronidazole.

OBJECTIVE To investigate the types of bacteria isolated from skin lesions in adolescent patients with ac-ne vulgaris and analyze their drug resistance to commonly used antibacterial drugs.METHODS A total of 80 ado-lescent patients with acne vulgaris admitted to the Seventh Medical Center of Chinese PLA General Hospital from Mar.2022 to Mar.2024 were enrolled.The contents of facial acne skin lesions were collected for bacterial identifi-cation and the E-test method was employed to evaluate the drug resistance rates of isolated bacteria to commonly used antibacterial drugs.RESULTS Among the collected skin lesion samples in this study,74 strains(92.50％)of Propionibacterium acnes,76 strains(95.00％)of Staphylococcus epidermidis and 12 strains(15.00％)of S.aureus were detected.No statistically significant differences were observed in the detection rates of P.acnes,S.epidermidis and S.aureus among patients of different genders,ages,disease courses or severity levels.P.ac-nes exhibited high sensitivity to tetracycline,doxycycline and minocycline(all＞95％)but was almost completely resistant to metronidazole.Its sensitivity rate to macrolides such as erythromycin,clarithromycin,clindamycin,roxithromycin and azithromycin were low(＜50％).S.epidermidis showed sensitivity rates of 67.11％,81.58％and 82.89％to tetracycline,doxycycline and minocycline,respectively,with high drug resistance to metronidazole(96.05％)and low sensitivity rate to erythromycin,clarithromycin,clindamycin,roxithromycin and azithromycin(＜60％).S.aureus demonstrated sensitivity rates of 58.33％,75.00％and 75.00％to tetracycline,doxycycline and minocycline,respectively,while its sensitivity rates to erythromycin,clarithromycin,clindamycin,roxithro-mycin and azithromycin were 33.33％,41.67％,50.00％,41.67％and 33.33％,respectively.CONCLUSIONS The predominant bacteria isolated from skin lesions in adolescent patients with acne vulgaris are S.epidermidis and P.acnes,with a lower detection rate of S.aureus.All three isolated bacteria exhibit high sensitivity to tetra-cycline antibacterial drugs but significant drug resistance to macrolides and near-complete drug resistance to met-ronidazole.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective:To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative fatigue syndrome in patients with Parkinson′s diseases undergoing bilateral deep brain electrical stimulation.Methods:Sixty patients with Parkinson′s disease, aged 60-80 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with body mass index of 18.5-29.9 kg/m 2, undergoing elective bilateral deep brain electrical stimulation, were divided into transcutaneous electrical acupoint stimulation group (TEAS group) and sham stimulation group (Sham group), with 30 patients in each group, using the random number table method. The TEAS of bilateral Zusanli and Sanyin points was performed on admission to the operating room with alternative stimulation at a frequency of 2/10 Hz and an intensity of 6-15 mA. The stimulation was stopped when the neurosurgeon performed the microelectrode recording, and TEAS was continued until the end of operation after the microelectrode recording was finished. In Sham group, electrode pads were only placed at the acupoint with no stimulation. The Christensen score was assessed at 1 day preoperatively (T 0) and 1, 3 and 7 days postoperatively (T 1-3) to evaluate the occurrence of postoperative fatigue syndrome. The 15-item Quality of Recovery scale score, emergence agitation and rescue analgesia within 48 h after surgery were recorded. Results:Compared with Sham group, Christensen scores were significantly decreased at T 1-3, 15-item Quality of Recovery scale scores were increased, and the incidence of postoperative fatigue syndrome and emergence agitation and rate of rescue analgesia were decreased in TEAS group than in Sham group ( P<0.05). Conclusions:TEAS can reduce the development of postoperative fatigue syndrome in the patients with Parkinson′s diseases undergoing bilateral deep brain electrical stimulation.

Objective To explore the clinical efficacy of Xuanfei Liyan decoction in treating post-infectious cough(PIC)with wind-heat invading lung syndrome.Methods A total of 60 patients with PIC were selected from January 2023 to January 2024 in Lishui Hospital of Traditional Chinese Medicine and were classified into 30 cases each in groups of control and observation by using method of randomized numerical table.The control group was given western medicine compound methenamine,and observ groups was given Xuanfei Liyan decoction,one dose per day,and the course of treatment for both groups was a week.After continuous treatment for one week,the efficacy of two groups were evaluated,and the Chinese medicine symptom scores and visual analogue scores before and after treatment were assessed.Results The therapeutic efficacy of observation group was higher than that of control group(P＜0.05).The Chinese medicine symptom scores and visual analogue scale of two groups were lower than those before treatment,and the decline levels of observation group were more favourable than those of control group(P＜0.05).Conclusion Xuanfei Liyan decoction was clinically effective in treatment of PIC and the wind-heat invading lung syndrome.