Objective To predict the current and future ecological suitability distribution areas of Scutellariae Radix in Shandong Province at present and in the future;To screen the main environmental factors affecting its suitable distribution;To provide a reference for the protection of wild resources and the site selection artificial planting of Scutellariae Radix.Methods Taking Scutellariae Radix as the research object,based on the MaxEnt model,the potential suitable habitats were predicted using 84 distribution points of and 48 environmental factors of Scutellariae Radix,and the main environmental factors affecting the distribution of Scutellariae Radix were explored.Its potential suitable habitat areas were predicted under four greenhouse gas emission concentration scenarios(SSP126,SSP245,SSP370,and SSP585)for the years 2021-2040,2041-2060,2061-2080 and 2081-2100.Results The MaxEnt model was optimized through feature combination and regularization constant parameters,and its predictive ability was good(AUC value of 0.871).The primary driving environmental factors affecting its distribution were the maximum temperature in the warmest month(bio_05),soil gravel content(cf05)and altitude(elev).Under the current climate conditions,Scutellariae Radix is mainly distributed in the hilly areas of central and southern Shandong and some areas of in the hilly areas of Jiaodong.Under the future climate conditions of SSP126,SSP245,SSP370 and SSP585,the areas of suitable habitat of Scutellariae Radix in Shandong will show a decreasing trend.Except for the SSP126,the medium and high adaptation areas of Scutellariae Radix will disappear in the other three modes.Conclusion The results of this study can provide an important reference for the protection,rational utilization and planting layout of Scutellariae Radix in Shandong Province.

Objective To investigate the impact of pomegranate peel polyphenols(PPP)on the malignant biological behavior of colon cancer cells through modulation of the miR-138-5p/hypoxia-inducible factor-1α(HIF-1α)pathway.Methods Quantitative real-time PCR(qRT-PCR)was employed to measure the expression levels of miR-138-5p and HIF-1α mRNA in the normal colon epithelial cell line FHC and three colorectal cancer cell lines:SW480,HCT116,and Caco-2.SW480 cells were divided into six groups:a blank control group,a negative control(mimics NC)group,a miR-138-5p mimics group,three different concentrations of PPP treatment groups(0.5 mg/mL,1 mg/mL,and 2 mg/mL),a PPP+inhibitor NC group at 2 mg/mL,and a PPP+miR-138-5p inhibitor group at 2 mg/mL.The effects on cell proliferation,invasion,and migration,as well as changes in apoptosis and related proteins including B-cell lymphoma 2(Bcl-2),migration invasion enhancer 1(MIEN1),and Cyclin D1,were evaluated separately.Additionally,the targeting relationship between miR-138-5p and HIF-1α was validated.The expression levels of miR-138-5p,HIF-1α mRNA,and protein were assessed in each experimental group.Results The expression levels of miR-138-5p were highest in FHC cells and lowest in SW 480 cells,while the expression levels of HIF-1α mRNA showed an opposite trend,being lowest in FHC cells and highest in SW 480 cells(P<0.05).Compared with the control group,different concentrations of PPP significantly promoted cell apoptosis,upregulated miR-138-5p expression,inhibited cell proliferation,invasion,and migration,and downregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein,with significant differences between groups(P<0.05).Compared with the mimics NC group,the miR-138-5p mimics group significantly enhanced cell apoptosis,upregulated miR-138-5p expression,inhibited cell proliferation,invasion,and migration,and downregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein(P<0.05).Compared with the 2 mg/mL PPP+inhibitor NC group,the 2 mg/mL PPP+miR-138-5p inhibitor group significantly suppressed cell apoptosis,downregulated miR-138-5p expression,promoted cell proliferation,invasion,and migration,and upregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein(P<0.05).These results indicate a targeted relationship between miR-138-5p and HIF-1α(P<0.05).Conclusion PPP inhibits the malignant biological behavior of colon cancer cells through upregulation of the miR-138-5p/HIF-1α pathway.

Objective:To compare the efficacy of dienogest (DNG) and levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of intrinsic and extrinsic subtypes of adenomyosis.Methods:Totally 232 patients were enrolled in the study who were diagnosed as adenomyosis by ultrasound or pelvic magnetic resonance imaging (MRI), and were classified into intrinsic and extrinsic subtypes according to different locations of lesions in MRI, treated with DNG (DNG group) or LNG-IUS (LNG-IUS group) in Peking University Third Hospital from July 2019 to December 2023. Clinical data of patients were retrospectively collected to analyze the clinical and imaging characteristics of different MRI subtypes of adenomyosis and whether there were differences in the therapeutic effects of DNG and LNG-IUS.Results:(1) Among the 232 patients enrolled, 129 were intrinsic subtype and 103 were extrinsic subtype. Among the 129 patients treated with DNG, the numbers of intrinsic and extrinsic subtype were 69 and 60, respectively. And among the 103 patients treated with LNG-IUS, the numbers of intrinsic and extrinsic subtype were 60 and 43, respectively. The mean age in DNG group [(37.5±5.6) years] was lower than that in LNG-IUS group [(40.3±4.3) years, P<0.001]. There were no significant differences in other clinical features (all P>0.05). (2) The visual analog scale (VAS) scores of dysmenorrhea and cancer antigen 125 (CA 125) levels in DNG group and LNG-IUS group were significantly decreased after treatment (all P<0.001), and hemoglobin levels were increased (both P<0.01). Compared between the two groups, the VAS score after treatment was lower in DNG group ( P<0.001), and the hemoglobin level was increased more significantly in DNG group ( P=0.016). The complete remission rates of dysmenorrhea in DNG group and LNG-IUS group were 73.0% (89/122) and 29.5% (28/95), respectively ( P=0.039). The incidence of irregular bleeding in DNG group was higher than LNG-IUS group, but there was no statistical significance [62.8% (81/129) vs 52.4% (54/103), P=0.112]. (3) Among patients with intrinsic adenomyosis, the incidence of menorrhagia was significantly higher than in those with extrinsic adenomyosis ( P<0.001), while the incidence and severity of dysmenorrhea were lower compared to extrinsic adenomyosis ( P=0.004, P=0.007, respectively). After treatment with DNG and LNG-IUS, there were no statistically significant differences in VAS scores between patients with intrinsic and extrinsic adenomyosis (all P>0.05). The incidence of irregular bleeding after DNG treatment was 78.3% (54/69) in intrinsic adenomyosis, which was higher than the 45.0% (27/60) observed in extrinsic adenomyosis ( P<0.01). Similarly, the incidence of irregular bleeding after LNG-IUS treatment was 63.3% (38/60) in intrinsic adenomyosis, higher than the 37.2% (16/43) in extrinsic adenomyosis ( P=0.009). (4) DNG treatment ( OR=19.163, 95% CI: 7.564-48.544; P<0.01) and duration of treatment ( OR=1.043, 95% CI: 1.012-1.075; P=0.007) were independent positive factors for complete remission of dysmenorrhea, while VAS score before treatment ( OR=0.654, 95% CI: 0.454-0.942; P=0.023) was negative factor. Intrinsic subtype was an independent risk factor for irregular bleeding ( OR=0.436, 95% CI: 0.235-0.811; P=0.009). Conclusions:DNG demonstrates greater advantages over LNG-IUS in terms of complete relief of dysmenorrhea and the degree of symptom alleviation. The incidence of irregular vaginal bleeding in patients with intrinsic adenomyosis is higher than in those with extrinsic adenomyosis. For patients with extrinsic adenomyosis, particularly those with prominent dysmenorrhea symptoms, DNG treatment offers greater benefits. However, for patients with intrinsic adenomyosis and those with significant menstrual disorders, a more cautious approach is required when selecting progestin therapy, along with enhanced monitoring and management.

Objective To explore the independent risk factors for long-term adverse prognosis after percutaneous renal artery angioplasty in patients with transplant renal artery stenosis(TRAS).Methods We retrospectively collected medical records and surgery details of TRAS patients who underwent renal artery angioplasty at the Department of Peripheral Vascular Diseases,The First Affiliated Hospital of Xi'an Jiaotong University,from January 2017 to June 2021.All patients were followed up for 3 years post-operation.Multivariate Cox regression analyses were performed to find the independent predictive factors for long-term adverse prognosis after renal artery angioplasty in the TRAS patients.Results A total of 45 TRAS patients who underwent percutaneous renal artery angioplasty were included in this study.During the five-year follow-up period,10 patients(22.2％)experienced long-term adverse events.These consisted of 3 patients(6.7％)who died from any cause,1 patient(2.2％)who developed transplant renal artery dissection,6 patients(13.3％)who had restenosis of the transplant renal artery,and 1 patient(2.2％)who lost the transplant kidney and received dialysis again.Multivariate Cox regression analysis showed that male gender(HR=4.915,95％CI:1.036-23.328,P=0.045)and balloon angioplasty alone(HR=8.594,95％CI:2.191-33.710,P=0.002)were independent risk factors for long-term adverse prognosis after renal artery angioplasty in TRAS patients.Conclusion Male gender and balloon angioplasty alone are independent risk factors for long-term adverse prognosis after renal artery angioplasty in TRAS patients.

AIM:To investigate the protective effects of Klotho protein against hypoxia/reoxygenation(H/R)-in-duced damage in rat cardiomyocytes,and to elucidate its underlying mechanisms.METHODS:Rat cardiomyocyte H9c2 cells were divided into 4 groups:control,H/R,low-concentration(1 μmol/L)Klotho+H/R,and high-concentration(10 μmol/L)Klotho+H/R groups.Cells were pretreated with Klotho at specified concentrations before induction of H/R injury.Flow cytometry was used to determine cardiomyocyte apoptosis rates,while reactive oxygen species(ROS)levels were measured using the DCFH-DA probe.Additionally,superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were assessed using biochemical assay kits.Mitochondrial membrane potential was evaluated using the JC-1 as-say,and activity of caspase-3 and caspase-9 was quantified.Western blot analysis was conducted to measure the protein expression of cytochrome C(Cyt-C),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in cardio-myocytes from each group.RESULTS:Compared with the control group,the H/R group exhibited significantly increased apoptosis rates(P<0.05),elevated ROS levels and MDA content,decreased SOD activity(P<0.05),reduced mitochon-drial membrane potential(P<0.05),increased caspase-3 and caspase-9 activity(P<0.05),decreased mitochondrial Cyt-C and Bcl-2 protein expression(P<0.05),and increased cytoplasmic Cyt-C and Bax protein expression(P<0.05).In comparison with the H/R group,both low-and high-concentration Klotho treatments significantly reduced cardiomyocyte apoptosis(P<0.05),lowered ROS levels and MDA content(P<0.05),increased SOD activity(P<0.05),restored mito-chondrial membrane potential(P<0.05),decreased caspase-3 and caspase-9 activity(P<0.05),increased mitochondrial Cyt-C and Bcl-2 expression(P<0.05),and decreased cytoplasmic Cyt-C and Bax expression(P<0.05).Notably,the high-concentration Klotho group demonstrated more pronounced protective effects(P<0.05).CONCLUSION:Klotho protein exerts protective effects against H/R-induced cardiomyocyte injury,possibly by inhibiting mitochondria-mediated apoptosis.

Objective To compare the therapeutic efficacy of sequential therapy with gonadotropin releasing hormone agonist(GnRH-a)combined with dienogest(DNG)versus DNG alone in patients with adenomyosis.Methods A retrospective analysis was conducted on clinical data from 129 patients diagnosed with adenomyosis by ultrasound and MRI between August 2020 and December 2023.Among them,60 patients received sequential therapy with GnRH-a followed by DNG(combination group)and 69 patients received DNG monotherapy(monotherapy group).There were no significant differences in baseline characteristics,including age,incidence of dysmenorrhea,incidence of menorrhagia,uterine volume,and type of adenomyosis between the two groups(P>0.05).The combination group received subcutaneous injections of leuprorelin3.75 mg every28 d for3 to 6 cycles,followed by oral DNG 2 mg/d for more than 3 months.The monotherapy group received oral DNG 2 mg/d alone for more than 3 months.Treatment outcomes and adverse reactions were compared between the two groups.Results The median duration of DNG treatment was 16.0(10.2,26.0)months in the combination group and13.0(6.0,23.0)months in the monotherapy group.The difference between the two groups was not statistically significant(Z=-1.587,P=0.113).Both groups showed a significant reduction in dysmenorrhea as measured by the Visual Analogue Scale(VAS)score,a significant decrease in serum CA125 levels,and a significant increase in hemoglobin levels after treatment compared to before treatment(all P<0.001).There were no significant differences between the two groups(P>0.05).Regarding uterine volume,the combination group showed a trend toward reduction after treatment[146.3(77.6,250.4)cm3 vs.118.4(82.4,233.4)cm3,Z=0.272,P=0.785],while the monotherapy group showed a significant increase in uterine volume compared to before treatment[162.9(110.8,256.0)cm3 vs.187.6(123.7,276.2)cm3,Z=2.945,P=0.003].The incidence of irregular vaginal bleeding in the combination group[50.0%(30/60)]was lower than that in the monotherapy group[75.4%(52/69),χ2=8.914,P=0.003].Conclusions Both sequential therapy with GnRH-a combined with DNG and DNG monotherapy are effective in relieving dysmenorrhoea,reducing CA125 levels,and increasing hemoglobin levels in patients with adenomyosis.However,sequential therapy is associated with a lower incidence of irregular vaginal bleeding compared to monotherapy and demonstrates a potential advantage in controlling uterine volume growth.

OBJECTIVE To explore the clinical efficacy of Chaihu Jia Longgu Muli Decoction Derivative in the treatment of non-valvu-lar paroxysmal atrial fibrillation based on the pathogenesis theory of"mutual fanning of liver wind and heart fire".METHODS A total of 80 patients with non-valvular paroxysmal atrial fibrillation admitted to Hainan Provincial Traditional Chinese Medicine Hospital from January 2021 to July 2022 were prospectively selected as the research subjects and randomly divided into an observation group and a control group with 40 cases in each group.The control group was given conventional treatment such as western medicine anticoagulation and ventricular rate con-trol.The observation group was given Chaihu Jia Longgu Muli Decoction Derivative on the basis of the control group.The treatment course of both groups was 30 d.The two groups were compared in terms of TCM syndrome scores,atrial fibrillation episodes(number of episodes,du-ration),clinical efficacy,changes in electrocardiogram parameters(P wave duration,P wave dispersion),heart rate variability indexes[standard deviation of RR interval(SDNN),root mean square difference of adjacent RR intervals(RMSSD),standard deviation of the mean value of RR interval(SDANN)],left ventricular function indexes[left atrial diameter(LAD),left ventricular ejection fraction(LVEF),ear-ly diastolic mitral annular motion velocity(EM)and left ventricular early diastolic blood flow propagation velocity(VP)]and the occurrence of adverse reactions.RESULTS After treatment,the TCM syndrome scores of the two groups of patients were significantly reduced(P<0.05,P<0.01),and the observation group was better than the control group(P<0.05,P<0.01);the number and duration of atrial fibrilla-tion in the two groups were significantly decreased(P<0.05,P<0.01),and the observation group was superior to the control group(P<0.05,P<0.01);the clinical efficacy of the observation group was better than that of the control group(P<0.05);the heart rate variability indexes,electrocardiogram parameters and left ventricular function indexes were significantly improved(P<0.05),and the observation group was supe-rior to the control group(P<0.05);there was no significant difference in the occurrence of adverse reactions between the two groups(P>0.05).CONCLUSION Based on the pathogenesis theory of"mutual fanning of liver wind and heart fire",the application of Chaihu Jia Longgu Muli Decoction Derivative for the treatment of non-valvular paroxysmal atrial fibrillation can improve clinical symptoms,reduce atrial fibrillation,enhance cardiac function,and has good clinical efficacy.

Objective To predict the current and future ecological suitability distribution areas of Scutellariae Radix in Shandong Province at present and in the future;To screen the main environmental factors affecting its suitable distribution;To provide a reference for the protection of wild resources and the site selection artificial planting of Scutellariae Radix.Methods Taking Scutellariae Radix as the research object,based on the MaxEnt model,the potential suitable habitats were predicted using 84 distribution points of and 48 environmental factors of Scutellariae Radix,and the main environmental factors affecting the distribution of Scutellariae Radix were explored.Its potential suitable habitat areas were predicted under four greenhouse gas emission concentration scenarios(SSP126,SSP245,SSP370,and SSP585)for the years 2021-2040,2041-2060,2061-2080 and 2081-2100.Results The MaxEnt model was optimized through feature combination and regularization constant parameters,and its predictive ability was good(AUC value of 0.871).The primary driving environmental factors affecting its distribution were the maximum temperature in the warmest month(bio_05),soil gravel content(cf05)and altitude(elev).Under the current climate conditions,Scutellariae Radix is mainly distributed in the hilly areas of central and southern Shandong and some areas of in the hilly areas of Jiaodong.Under the future climate conditions of SSP126,SSP245,SSP370 and SSP585,the areas of suitable habitat of Scutellariae Radix in Shandong will show a decreasing trend.Except for the SSP126,the medium and high adaptation areas of Scutellariae Radix will disappear in the other three modes.Conclusion The results of this study can provide an important reference for the protection,rational utilization and planting layout of Scutellariae Radix in Shandong Province.

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 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.