ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

Objective:To explore the efficacy and safety of olverembatinib in treatment of chronic myeloid leukemia (CML) progressed to acute lymphoblastic leukemia with D241E mutation.Methods:The diagnosis and treatment of a patient with D241E mutant CML progressed to acute lymphoblastic leukemia admitted to the Fourth People's Hospital of Jinan in December 2018 were retrospectively analyzed, and relevant literature was reviewed.Results:The patient was a 47-year-old female, and her blood test result was abnormal during physical examination. She was diagnosed as CML and received treatment with imatinib and dasatinib for 2 years. The disease progressed to philadelphia chromosome (Ph)-positive acute B-lymphoblastic leukemia with BCR-ABL mutation (a D241E mutation). After 3 courses of chemotherapy combined with a targeted drug (ponatinib), the patient achieved complete remission, while the minimal residual disease continued to be positive. The patient received 1 course of chemotherapy combined with olverembatinib from the 4th course of treatment. After olverembatinib monotherapy maintenance therapy for 36 months, the patient achieved molecular complete remission with minimal residual disease. The patient developed complications such as skin pigmentation and elevated lipid levels, but all complications were tolerable.Conclusions:The application of olverembatinib in D241E mutant CML progressed to acute lymphoblastic leukemia can help patients obtain sustained molecular biological remission and good safety.

Objective:To investigate the management effectiveness of the integrated service mode of community cerebrovascular disease specialty and general practice team on stroke management.Methods:This was a randomized controlled trial. Patients with non-acute stroke who visited Fangzhuang Community Health Service Center in Fengtai District, Beijing between September 2022 and January 2023 were enrolled and randomly assigned to an integrated specialist-primary care group and a control group using a random number table method. Baseline clinical data were collected. Patients in the integrated specialist-primary care group received a collaborative care model combining stroke specialty services and primary care teams, while the control group received routine care. Neurological status, mental status, medical adherence, cognitive function, and psychological status were assessed using standardized scales at baseline, followed by evaluations every 3 months for 1 year, totaling 5 assessments.Results:A total of 142 non-acute stroke patients were included, with 71 in the specialist-primary care integrated service group, aged (69.5±7.6) years, including 43 males (60.56%), and 71 in the control group, aged (68.8±8.5) years, including 38 males (53.52%). There were no statistically significant differences in baseline clinical characteristics such as age, sex, and body mass index between the two groups (all P>0.05). Prior to the intervention, there were no statistically significant differences in the Mini-Mental State Examination scores between the two groups ( P>0.05). However, at 3, 6, 9, and 12 months post-intervention, the scores of the specialist-primary care integrated service group were significantly higher than those of the control group (all P<0.05). Before the intervention, there were no statistically significant differences between the two groups in the scores on Generalized Anxiety Disorder Scale and Patient Health Questionnaire Depression Scale (all P>0.05). At 6, 9, and 12 months post-intervention, the scores on these two scales for the specialist-primary care integrated service group were significantly lower than those of the control group (all P<0.05). There were no statistically significant differences in adherence behavior scores between the two groups before the intervention ( P>0.05), but at 6, 9, and 12 months post-intervention, the adherence behavior scores of the specialist-primary care integrated service group were significantly higher than those of the control group (all P<0.05). Conclusions:The integrated service mode of cerebrovascular disease specialists and general practice teams can effectively improve cognitive function, anxiety, depression, and compliance behavior, and is more conducive to the recovery of stroke patients in the community, which has popularization value.

Objective To investigate the consistency and diagnostic efficacy of 1.5T and 3.0T MRI in the kidney clear cell likeli-hood score(ccLS)v2.0.Methods A retrospective collection was conducted on the data of 176 pathologically confirmed small renal mass(SRM).Two radiologists independently scored the MRI images using the ccLS v2.0.The Kappa test was used to assess inter-observer consistency,and receiver operating characteristic(ROC)curves were plotted to analyze the diagnostic efficacy.The area under the curve(AUC),sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NP V)were calculated.Results The inter-observer consistency for ccLS v2.0 score was good for 1.5T MRI and excellent for 3.0T MRI(Kappa values were 0.754 and 0.836,respectively).On 1.5T MRI examination,a ccLS≥4 points was identified as the optimal threshold,with AUC of 0.935 and 0.923 for the two radiologists,sensitivities of 92.45％and 88.68％,and specificities of 88.00％and 92.00％,respec-tively.For 3.0T MRI examination,using the same threshold,the AUC were 0.933 and 0.901,with sensitivities of 91.43％and 90.00％,and specificities of 78.57％and 78.57％for both radiologists.Conclusion The ccLS v2.0 demonstrates good consistency across high and low field intensity MRI,and a threshold of ccLS≥4 pionts provides high diagnostic efficacy for clear cell renal cell carcinoma(ccRCC).

Objective To investigate the value of predicting microsatellite instability(MSI)status in endometrial cancer based on whole-tumor apparent diffusion coefficient(ADC)histogram.Methods The data of 131 endometrial cancer patients who underwent preoperative MRI examination and were confirmed by pathology were retrospectively analyzed.According to the pathological immu-nohistochemical results,they were divided into microsatellite stability(MSS)group(103 cases)and MSI group(28 cases).The whole-tumor volume of interest(VOI)was outlined using ITK-SNAP software,and ADC histogram analysis was performed using uAI Research Portal software.The t-test or Mann-Whitney U-test were used to compare the differences between the two groups,and multifactorial logistic regression analysis was used to screen independent predictors for the above parameters with differences.The area under the curve(AUC),sensitivity and specificity were calculated using the receiver operating characteristic(ROC)curve.Results The ADC histogram parameters that were statistically significant between groups were ADC10th,ADC90th,ADCmaximum,ADCmedian,ADCmean,ADCrange,ADCinterquartile range,ADCuniformity,ADCvariance,ADCenergy,ADCentropy,ADCtotal energy,ADCroot mean square,ADCmean absolute deviation,ADCrobust mean absolute deviation,all the above parameters were significantly smaller in the MSI group than in the MSS group.Further multifactorial logistic regression analysis results showed that ADCmedian[odds ratio(OR)=1.019,P=0.020]and ADCroot mean square(OR=0.977,P=0.005)were independent predictors of the MSI status in endometrial cancer.The results of ROC curve showed that the AUC of ADCmedian and ADCroot mean square for predicting MSI status were 0.699 and 0.731,respectively,and the AUC of combining the two parameters to predict MSI status was 0.760,with a sensitivity of 57.14%and a specificity of 86.41%.Conclusion The parameters of ADCmedian and ADCroot mean square based on whole-tumor ADC histogram can be used to predict the MSI status of endometrial cancer,and the combined use of these two parameters helps to improve the efficacy of predicting MSI.

Objective To explore the influencing factors of readmission within 90 days in frail patients with chronic obstructive pulmonary disease(COPD),construct an early warning model and evaluate its discrimination and effectiveness.Methods A total of 831 COPD patients with frailty were included and divided into the readmission group(290 cases)and the control group(541 cases)based on whether they were readmitted within 90 days after discharge.The electronic medical record data were collected and compared between the two groups of patients.Multivariate Logistic regression analysis was used to screen independent influencing factors for readmission within 90 days in COPD weak patients.A predictive model was established.The column chart was drawn.The discriminability of the predictive model was evaluated through receiver operating characteristic(ROC)curves.The clinical practicality and the predictive model calibration were evaluated through decision curves and calibration curves.Results The body mass index(BMI)of the readmission group was lower than that of the non readmission group,and the proportion of acute exacerbation of COPD hospitalizations≥2 times in the past year,the Edmonton frailty scale(REFS)score and the Chalson comorbidity index(CCI)were higher in the readmission group than those of the non readmission group(P＜0.05).Multivariate Logistic regression analysis showed that BMI(OR=0.721,95%CI:0.636-0.818),the number of acute exacerbations of COPD hospitalizations in the past year(OR=3.040,95%CI:1.944-4.753),REFS score(OR=1.726,95%CI:1.486-2.005)and CCI score(OR=3.917,95%CI:3.079-4.983)were all independent influencing factors for readmission within 90 days in COPD frail patients(P＜0.05).Based on the results of multiple factor Logistic regression analysis,the column chart warning model was constructed.The AUC value of the ROC curve was 0.847(95%CI:0.820-0.874),the specificity was 87.20%and the sensitivity was 64.50%.The calibration curve of the predictive model was close to the diagonal,and the calibrationa degree was good.The decision curve suggested that the prediction model had clinical practicality.Conclusion The early warning model constructed based on the influencing factors of readmission hospitalization within 90 days in weak patients with COPD has good predictive effect and clinical practicability.

Objective:To investigate the pregnancy outcomes and cumulative live birth rate (CLBR) after in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in patients with high basal follicle-stimulating hormone (bFSH) levels. Methods:This retrospective cohort study included clinical data from patients who underwent IVF/ICSI-ET treatment at the Reproductive Medical Center of Peking University Third Hospital from January 2018 to December 2022. Patients were divided into three groups based on the highest bFSH level during all cycles of treatment: group A (15 U/L≤bFSH<25 U/L), group B (25 U/L≤bFSH<40 U/L), and group C (bFSH≥40 U/L). After propensity score matching (PSM) based on the female body mass index, the baseline data, embryology laboratory outcomes, and assisted reproductive outcomes such as clinical pregnancy rate among the three groups of patients were compared. Binary logistic regression analysis was used to explore the impact of various factors on live birth, and the trend of CLBR across multiple cycles was also studied.Results:After PSM, 340 cycles were included in group A, 340 cycles were included in group B, 127 cycles were included in group C. There were statistically significant differences among the three groups in antral follicle count, bFSH, basal progesterone, basal luteinizing hormone, and anti-Müllerian hormone levels ( P=0.004, P<0.001, P<0.001, P<0.001, P<0.001). In the analysis of controlled ovarian stimulation (COS) protocols, groups A and B mainly used conventional COS protocol, while group C primarily used mild stimulation protocol. The duration and dosage of gonadotropin used were the highest in group A [10 (7, 12) d, 2 728 (1 650, 3 725) U], with statistically significant differences among the three groups (all P<0.001). On the day of human chorionic gonadotropin injection, there were statistically significant differences in estradiol and progesterone levels among the three groups ( P=0.022 and P=0.048, respectively). The cancellation rate of cycles did not differ significantly among the three groups ( P>0.05), while the number of oocytes retrieved ( P<0.001) and the rate of cycles with no transferable embryos ( P=0.034) showed statistically significant differences. The type of embryos transferred in all three groups was mainly cleavage-stage embryos, and there were statistically significant differences in the rate of two pronuclei and high-quality embryos among the groups ( P=0.003 and P=0.006, respectively). The rate of high-quality embryos decreased with increasing bFSH levels, and comparisons between group A and group B, as well as group A and group C, showed statistically significant differences (all P<0.016 7). The biochemical pregnancy rate and the clinical pregnancy rate in fresh cycles differed significantly among the three groups ( P=0.025 and P=0.010, respectively), while the live birth rate per initiated cycle showed marginal significance ( P=0.058). However, the miscarriage rate and the live birth rate per transfer cycle did not differ significantly among the groups (all P>0.05). Binary logistic regression analysis revealed that bFSH ( OR=0.955, 95% CI: 0.912-1.000, P=0.050) and the number of oocytes retrieved ( OR=1.104, 95% CI: 1.009-1.207, P=0.031) were independent predictors of live birth. Analysis of CLBR curves across multiple oocyte retrieval cycles showed that CLBR gradually increased with the number of oocyte retrievals and stabilized at 14.32% after the fifth retrieval. Conclusion:High bFSH levels reduce the live birth rate per initiated cycle but do not affect the live birth rate per transfer cycle. Increasing age and a low number of oocytes retrieved can both decrease the live birth rate. Multiple oocyte retrieval and transfer cycles can improve CLBR in patients with high bFSH level to some extent, but it tends to stabilize after the fifth cycle.

Objective:To investigate the outcomes of natural cycle (NC) and modified natural cycle (MNC) assisted reproductive technology (ART) in patients with diminished ovarian reserve (DOR), and to provide a scientific basis for individualized treatment strategies for DOR patients.Methods:A retrospective cohort analysis was performed on the clinical data of DOR patients who underwent ART at the Center for Reproductive Medicine of the Department of Obstetrics and Gynecology, Peking University Third Hospital from January 1, 2015 to December 31, 2023. Patients were divided into the NC group ( n=801) and the MNC group ( n=385) based on their treatment protocol. The primary outcomes were cycle cancellation rate and oocyte retrieval rate. Secondary outcomes included clinical pregnancy rate and live birth rate per fresh embryo transfer cycle and frozen-thawed embryo transfer cycle, cumulative pregnancy rate and cumulative live birth rate per started cycle and per transfer cycle, as well as laboratory parameters such as the number of retrieved oocytes, the number of two pronuclei (2PN) fertilized oocytes, the number of transferable embryos, and transferable embryo formation rate. Further, multivariate logistic regression was used to analyze the impact of the treatment protocol on pregnancy and live birth outcomes. Results:There were no statistically significant differences between the NC and MNC groups in terms of general characteristics such as age, body mass index, and baseline hormone levels (all P>0.05). The cycle cancellation rate was significantly higher in the NC group [19.10% (153/801)] than in the MNC group [10.65% (41/385), P<0.001], and the oocyte retrieval rate was significantly lower in the NC group [66.31% (431/650)] than in the MNC group [74.86% (259/346), P=0.005]. The number of retrieved oocytes [1 (0,1)], the number of 2PN fertilized oocytes [1 (0,1)], and the number of transferable embryos [0 (0, 1)] were also significantly lower in the NC group than in the MNC group [1 (1, 2), P<0.001; 1 (1, 1), P<0.001; 0 (0, 1), P<0.001]. However, there were no statistically significant differences in 2PN fertilization rate and transferable embryo formation rate between the NC and MNC groups (all P>0.05). In both fresh embryo transfer cycles and frozen-thawed embryo transfer cycles, there were no statistically significant differences in clinical pregnancy rate and live birth rate between the NC and MNC groups (all P>0.05). The cumulative pregnancy rate per started cycle and transfer cycle, the cumulative live birth rate per started cycle and per transfer cycle were also not significantly different between the NC and MNC groups (all P>0.05). Multivariate logistic analysis showed no significant association between NC and clinical pregnancy or live birth compared with MNC. Conclusion:While MNC to some extent reduced the cycle cancellation rate and improved oocyte retrieval rates compared with NC, it did not ultimately improve pregnancy outcomes in DOR patients.

Objective To analyze the trends in disease burden and risk factors of depression among the elderly population in China from 1990 to 2021,and to provide a theoretical basis for the prevention,treatment,and policy-making of geriatric depression in China.Methods Data on the disease burden of geriatric depres-sion in China from 1990 to 2021,including the number of incident cases,disability-adjusted life years(DALYs),incidence rate,and DALY rate,were extracted from the 2021 Global Burden of Disease(GBD)database.The Joinpoint regression model was used to analyze the trends by calculating the annual percentage change(APC)and average annual percentage change(AAPC).The autoregressive integrated moving average(ARIMA)model was employed to predict the disease burden of geriatric depression over the next five years.Population attributable fractions(PAFs)were used to describe the risk factors for geriatric depression in China in 1990 and 2021.Results From 1990 to 2021,the number of incident cases and the incidence rate of geri-atric depression in China showed an overall upward trend.The most significant increase in incidence was ob-served in the 60-64 age group,while the prevalence rate increased notably in the ≥ 95 age group.The DALY rate showed the most pronounced upward trend in the 65-69 age group.The incidence,prevalence,and DALY rates of geriatric depression were higher in women than in men.Major risk factors included child-hood sexual abuse and intimate partner violence,with the impact of intimate partner violence being particular-ly significant among women.The ARIMA model predicted that the incidence,prevalence,and DALY rates of geriatric depression in China would decline over the next five years,with a greater decline observed in women than in men.Conclusions From 1990 to 2021,the incidence,prevalence,and DALY rates of geriatric de-pression in China showed an overall upward trend,with higher rates observed in women than in men.Greater attention should be paid to the elderly female population,with a focus on early prevention to reduce the dis-ease burden of geriatric depression.