Objective:To investigate the possible mechanism of treadmill exercise(TR)in improving cognitive function of rats with chronic unpredictable mild stress(CUMS)by detecting pathological changes and the expression of sigma-1 receptor(SIR),endoplasmic reticulum stress-related proteins in hippocampus.Methods:30 SD rats were ran-domly allocated into control group(n=10),CUMS group(n=10)and CUMS exercise group(CUMS+TR,n=10).Subsequently,depressive model was established in rats of CUMS group and CUMS+TR group,meanwhile,CUMS+TR group rats were subjected to 4 weeks of moderate intensity treadmill exercise(20 m/min).After the CUMS and tread-mill exercise,the eight-arm radial maze test(RAM)was carried out to evaluate the learning-memory functions.Subse-quently,the pathological changes of neurons in the hippocampus of rats were measured by HE staining,the protein expression of the GRP78,IRE1,XBP1,CHOP,caspase-3 and SIR in the hippocampus were measured by Western blot.Results:Compared with the control group,the time of finishing the eight-arm radial maze prolonged and the num-ber of total memory errors increased(P＜0.05)in the RAM of the CUMS group rats.The morphology and structure of neurons in the hippocampus of CUMS group rats showed obvious pathological changes,the protein expression levels of GRP78,IRE1,XBP1,CHOP and caspase-3 significantly increased and SIR protein expression decreased(P＜0.05)in hippocampus in the CUMS group compared with the control group rats.4-week treadmill exercise significantly im-prove the learning and memory ability and pathological changes of neurons in hippocampus of CUMS+TR group rats.Compared with CUMS group rats,the protein expression levels of GRP78,IRE1,XBP1,CHOP and caspase-3 signifi-cantly decreased,the SIR expression in hippocampus significantly increased in the CUMS+TR group rats(P＜0.05).Conclusion:Treadmill exercise can improve cognitive impairment in CUMS rats,and its mechanism may be related to the up-regulation of SIR expression and the inhibition of ERS-mediated apoptosis pathway in hippocampus.

Objective:To evaluate the prognostic value of droplet digital PCR(ddPCR)in conjunction with multiparametric flow cytometry(MFC)for measurable residual disease(MRD)detection in predicting relapse risk in patients with acute myeloid leukemia(AML).Methods:In this retrospective cohort study,we have analyzed 78 newly diagnosed patients with AML who underwent combined MRD monitoring using MFC and ddPCR at The Affiliated Hospital of Hebei University(January 2018-January 2025).Clinical outcomes-including MRD negativity rates,cumulative incidence of relapse(CIR),relapse-free survival(RFS),and overall survival(OS)-were systematically evaluated.Prognostic discrim-ination between the MRD-negative and MRD-positive subgroups was compared across standalone and combined detection approaches.Results:With a median follow-up of 17 months(range:2.4-86.7)and a median of one mutation tracked per patient(range:1-3),both MFC-MRD and ddPCR-MRD negative subgroups demonstrated superior 2-year RFS compared with MRD-positive counterparts.Notably,com-bined MFC/ddPCR monitoring enhanced prognostic discrimination,with MRD-negative patients achieving significantly prolonged 2-year RFS compared with MRD-positive patients.MFC-MRD negativity independently predicted improved 2-year OS.Conclusion:ddPCR-based multi-gene MRD profiling provides significant independent prognostic value in patients with AML.The synergistic application of MFC and ddPCR enables superior predictive accuracy for relapse risk and survival outcomes,supporting its integration into standardized MRD monitoring protocols.

Objective:To investigate the possible mechanism of treadmill exercise(TR)in improving cognitive function of rats with chronic unpredictable mild stress(CUMS)by detecting pathological changes and the expression of sigma-1 receptor(SIR),endoplasmic reticulum stress-related proteins in hippocampus.Methods:30 SD rats were ran-domly allocated into control group(n=10),CUMS group(n=10)and CUMS exercise group(CUMS+TR,n=10).Subsequently,depressive model was established in rats of CUMS group and CUMS+TR group,meanwhile,CUMS+TR group rats were subjected to 4 weeks of moderate intensity treadmill exercise(20 m/min).After the CUMS and tread-mill exercise,the eight-arm radial maze test(RAM)was carried out to evaluate the learning-memory functions.Subse-quently,the pathological changes of neurons in the hippocampus of rats were measured by HE staining,the protein expression of the GRP78,IRE1,XBP1,CHOP,caspase-3 and SIR in the hippocampus were measured by Western blot.Results:Compared with the control group,the time of finishing the eight-arm radial maze prolonged and the num-ber of total memory errors increased(P＜0.05)in the RAM of the CUMS group rats.The morphology and structure of neurons in the hippocampus of CUMS group rats showed obvious pathological changes,the protein expression levels of GRP78,IRE1,XBP1,CHOP and caspase-3 significantly increased and SIR protein expression decreased(P＜0.05)in hippocampus in the CUMS group compared with the control group rats.4-week treadmill exercise significantly im-prove the learning and memory ability and pathological changes of neurons in hippocampus of CUMS+TR group rats.Compared with CUMS group rats,the protein expression levels of GRP78,IRE1,XBP1,CHOP and caspase-3 signifi-cantly decreased,the SIR expression in hippocampus significantly increased in the CUMS+TR group rats(P＜0.05).Conclusion:Treadmill exercise can improve cognitive impairment in CUMS rats,and its mechanism may be related to the up-regulation of SIR expression and the inhibition of ERS-mediated apoptosis pathway in hippocampus.

Objective:To evaluate the prognostic value of droplet digital PCR(ddPCR)in conjunction with multiparametric flow cytometry(MFC)for measurable residual disease(MRD)detection in predicting relapse risk in patients with acute myeloid leukemia(AML).Methods:In this retrospective cohort study,we have analyzed 78 newly diagnosed patients with AML who underwent combined MRD monitoring using MFC and ddPCR at The Affiliated Hospital of Hebei University(January 2018-January 2025).Clinical outcomes-including MRD negativity rates,cumulative incidence of relapse(CIR),relapse-free survival(RFS),and overall survival(OS)-were systematically evaluated.Prognostic discrim-ination between the MRD-negative and MRD-positive subgroups was compared across standalone and combined detection approaches.Results:With a median follow-up of 17 months(range:2.4-86.7)and a median of one mutation tracked per patient(range:1-3),both MFC-MRD and ddPCR-MRD negative subgroups demonstrated superior 2-year RFS compared with MRD-positive counterparts.Notably,com-bined MFC/ddPCR monitoring enhanced prognostic discrimination,with MRD-negative patients achieving significantly prolonged 2-year RFS compared with MRD-positive patients.MFC-MRD negativity independently predicted improved 2-year OS.Conclusion:ddPCR-based multi-gene MRD profiling provides significant independent prognostic value in patients with AML.The synergistic application of MFC and ddPCR enables superior predictive accuracy for relapse risk and survival outcomes,supporting its integration into standardized MRD monitoring protocols.

Objective:To evaluate the impact of self-crosslinked hyaluronic acid (SCH) gel on endometrium recovery after artificial abortion.Methods:A multicenter, prospective randomized controlled trial was conducted across 18 hospitals from December 2021 to February 2023, involving 382 women who underwent artificial abortion. Participants were randomly allocated to receive either treatment with SCH gel (SCH group) or no treatment (control group) in a 1∶1 ratio. The primary outcome was endometrium thickness in 14 to 18 days after the first postoperative menstruation. Secondary outcomes included changes in menstrual volume during the first postoperative menstruation, menstruation resumption within 6 postoperative weeks, time to menstruation resumption, duration of the first postoperative menstruation, and incidence of dysmenorrhea.Results:Baseline characteristics of participants were comparable between the two groups (all P>0.05), with 95.3% (182/191) in SCH group and 92.7% (177/191) in the control group completed the study. The postoperative endometrial thickness in SCH group was significantly greater than that in the control group [(9.78±3.15) vs (8.95±2.32) mm; P=0.005]. SCH group also had significantly fewer participants with reduced menstrual volume [23 cases (12.6%, 23/182) vs 31 cases (17.5%, 31/177); P=0.038]. Although SCH group experienced less dysmenorrhea during the first postoperative menstrual period, this difference was not statistically significant [28.5% (51/179) vs 37.1% (65/175); P=0.083]. Outcomes were similar between SCH group and the control group regarding the proportion of participants who resumed menstruation within 6 weeks postoperatively, time to menstruation resumption, and duration of the first postoperative menstruation ( P=0.792, 0.485, and 0.254, respectively). No serious adverse events were observed during the study period, and no adverse events were attributed to SCH gel treatment. Conclusion:The application of SCH gel after artificial abortion is safe and might aid in the recovery of the endometrium.

Objective:To analyze the changes of fasting plasma glucose(FPG)level before and after menopause.Methods:Kailuan health checkup cohort was used to extract data of women aged≥18 years who participated in the first physical examination of Kailuan physical examination cohort and had menopausal age at the end of the seventh physical examination. A total of 3 749 women with 22 057 physical examination records were included in the analysis. Natural logarithmic transformation was applied to FPG, and a segmented linear mixed-effects model was used to analyze the changes in ln-transformed FPG before and after menopause. Additionally, an interaction analysis was performed to assess the multiplicative effect of baseline age and baseline body mass index(BMI)on ln-transformed FPG concerning pre- and post-menopausal periods.Results:The average age of the first physical examination for women in this study was (45.63±4.52)years, the median menopausal age was 51(50~53)years, and the median number of physical examinations was 6(5~7)times. The results of the piecewise linear mixed effect model showed that lnFPG increased from 1 year before menopause, with an average annual increase of 0.021 mmol/L, and continued to increase from menopause to 5 years after menopause, with an average annual increase of 0.007 mmol/L. LnFPG tended to be stable after 5 years of menopause. Baseline age could affect the changes of lnFPG before and after menopause, and there was a negative multiplicative interaction between baseline age ≥45 years and the time period from 6 years to 1 year before menopause( P=0.032). Women with baseline age ≥45 years had a higher average annual increase in lnFPG from 1 year before menopause to 5 years after menopause than women with baseline age <45 years( P<0.05). On lnFPG, there was a positive multiplicative interaction between baseline BMI and time segments around menopause. Compared to women with BMI <24.0 kg/m 2, obese women displayed more annual increase in lnFPG from 6 years to 1 year before menopause as well as from menopause to 5 years after menopause( P<0.05). Conclusions:Menopause has an adverse impact on FPG, with the most significant changes occurring within the period of one year before menopause and up to five years after menopause. Age and BMI significantly influence the changes in FPG before and after menopause.

Jiawei Xiaoyao San (JWXYS) has shown excellent clinical efficacy in anxiety disorder, but has not yet attracted widespread attention. The animal experiments, clinical trials and mechanism studies of JWXYS were reviewed in this article, which may provide a reference for developing new anxiolytic drugs based on this prescription. The literature was searched in PubMed and CNKI and the documents written in English or with English abstracts were selected. JWXYS could reduce the anxiety symptoms of patients alone and reduce the adverse reactions when it is used in combination with other drugs in the clinic. In preclinical studies, JWXYS also showed therapeutic effects in reducing anxiety-like behavior. The mechanisms may include improving the hypothalamic-pituitaryadrenal (HPA) axis and hormone disorders, increasing neurotransmitter content, neurogenesis, and regulating the synthesis of related enzymes. This article shows that JWXYS could effectively treat anxiety disorders by regulating the central nervous system. In the future, with the participation of more researchers, it is expected to develop innovative drugs for the treatment of anxiety disorders based on JWXYS.

Objective:To investigate the therapeutic efficacy and prognosis of multiple myeloma (MM) patients with early relapse and the influencing factors of early relapse.Methods:The clinical data of 164 patients with newly diagnosed MM admitted to Affiliated Hospital of Hebei University from January 2018 to January 2021 were retrospectively analyzed, and 53 cases (32.3%) relapsed at the end of the follow-up. According to the recurrence within 12 months or not, the patients were divided into early relapse group and advanced relapse group; the clinical characteristics, overall response rate (ORR) and overall survival (OS) of both groups were compared. Logistic regression was used to analyze if the following indexes including age, gender, albumin, lactate dehydrogenase (LDH), β 2-microglobulin (β 2-MG), hemoglobin, creatinine, serum calcium, bone marrow plasma cell ratio, extramedullary disease, high-risk fluorescent in situ hybridization (FISH) were the influencing factors of the early relapse. Based on 7 published clinical trials, simplified early relapse MM (S-ERMM) scoring system was constructed to subgroup all relapsed patients. The difference in risk stratification between early relapsed patients and advanced relapsed patients was compared. Results:The median follow-up time of 164 newly diagnosed MM patients was 26 months (12-48 months). Among 53 relapsed MM patients, 24 cases had early relapse and 29 cases had advanced relapse. The ORR of patients with early relapse was decreased compared with that of those with advanced relapse [70.8% (17/24) vs. 89.7% (26/29), χ2 = 3.04, P = 0.001]. The median OS of the early relapse group was shorter than that of the advanced relapse group (24 months vs. not reached, P < 0.001). The OS of patient in the early relapse group with the best response ≥ complete remission (CR), ≥ very good partial remission (VGPR) and ≥ partial remission (PR) during initial induction therapy was worse than that of those in the advanced relapse group, and the differences were statistically significant ( P values were 0.008, 0.011, 0.012, respectively). Multivariate Logistic regression analysis showed low albumin (<35 g/L vs. ≥35 g/L: OR = 1.644, 95% CI 1.076-2.511, P = 0.022) and high LDH (< the upper limit of normal value vs. ≥ the upper limit of normal value: OR = 0.998, 95% CI 0.985-1.011, P = 0.030) were independent influencing factors of early relapse. Among 24 early relapse patients, there were 5 cases (20.8%), 13 cases (54.2%), 6 cases (25.0%), respectively in the S-ERMM scoring system low-risk, middle-risk, high-risk groups; among 29 advanced relapse patients, there were 18 cases (62.1%),9 cases (31.0%), 2 cases (6.9%), respectively in the S-ERMM scoring system low-risk, middle-risk, high-risk groups; the difference in risk stratification of the S-ERMM scoring system between the early relapse group and the advanced relapse group was statistically significant ( χ2 = 9.09, P = 0.003). Conclusions:MM patients with early relapse have poor therapeutic efficacy and prognosis. The prognosis is not affected by the depth of remission to first-line therapy. Low albumin and high LDH may be independent risk factors of MM patients with early relapse.

Objective:To explore the efficacy of venetoclax plus azacitidine (VA) in the treatment of patients with newly diagnosed chronic myelomonocytic leukemia (CMML).Methods:The clinical data of 4 newly diagnosed CMML-2 patients treated with VA regimen in the Affiliated Hospital of Hebei University from February 2022 to March 2023 were retrospectively analyzed, and the related literature was reviewed.Results:All 4 CMML-2 patients achieved the effect of ≥ partial bone marrow remission (PMR) after 1 course of treatment, and with the deepened extension of treatment course, the overall response rate and complete remission (CR) rate was 100% and 50%, respectively. In terms of dose adjustment, the dose and usage day of venetoclax were determined by using dynamic frailty assessment and adverse events. Among the 2 patients who achieved CR, 1 patient initially received venetoclax 200 mg for 14 days, and 1 patient received venetoclax 400 mg for 28 days and then the usage reduced to venetoclax 200 mg for 14 days due to hematological adverse events. All 4 patients maintained CR status. The most common grade 3 and 4 adverse events were neutropenia and thrombocytopenia.Conclusions:The first-line application of VA regimen in the treatment of newly diagnosed CMML-2 patients may achieve faster remission and better safety compared with traditional HMA monotherapy.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.