AIM:To investigate the protective effects of soy isoflavones on retinal ganglion cells(RGCs)damage in diabetic rats and related mechanisms.METHODS: Totally 80 male SD rats(80 eyes), aged 4-6 weeks, were randomly divided into four groups(n=20 per group): a control group, a diabetic model group, a low-dose soy isoflavone treatment group, and a high-dose soy isoflavone treatment group. Among them, the control group was fed normal chow, while the diabetic group, soy isoflavone low-dose-treated group, and soy isoflavone high-dose-treated group were fed high-fat chow. After a feeding period of 4 wk, rats in the diabetic group, as well as those in the soy isoflavone low-dose and high-dose treatment groups, were injected intraperitoneally with streptozotocin(STZ)at a dose of 50 mg/kg to establish a diabetic model. Rats in the control group received an equivalent volume of sodium citrate buffer acid. The soy isoflavone low-dose-treated group was administered 360 mg/kg of soy isoflavones daily via gavage, while the soy isoflavone high-dose-treated group received 540 mg/kg of soy isoflavones daily via gavage. Both the control group and the diabetic group were given an equal amount of purified water daily via gavage. Body weight and blood glucose levels were measured at 4 and 8 wk post-gavage treatment. The eyes were extracted and the retinas were dissected at 8 wk following the gavage treatment. The number of RGCs in each group was determined using immunochemical tissue staining and protein blotting techniques, while the superoxide dismutase(SOD)activity and malondialdehyde(MDA)content of the rat retinal tissue were measured through histochemical methods.RESULTS: Compared with diabetic rats, treatment with high-dose soy isoflavones for 8 wk resulted in a reduction of blood glucose to 8.9±1.23 mmol/L, an increase in intraretinal SOD activity to 849.93±63.71 U/mgprot, a decrease in MDA content to 45.77±0.59 nmol/mgprot, and an increase in the number of RGCs to 76±1 cells/mm2, which is comparable to the control group's data(all P<0.05).CONCLUSION: Soy isoflavones can reduce retinal oxidative stress in diabetic rats and protect RGCs.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Tamoxifen(TAM)has been widely used for the treatment of ER+breast cancer.However,the inevitable emergence of resistance to tamoxifen obstructs the successful treatment of this cancer.The tumor suppressor gene N-myc downstream-regulated gene 2(NDRG2)plays a significant role in the de-velopment of ER+breast cancer.However,it is unclear whether NDRG2 participates in mediating TAM resistance in ER+breast cancer.Here,we investigate the expression of NDRG2 mRNA and protein in TAM-sensitive and TAM-resistant ER+breast cancer cells.The results of immunoblotting experiments re-vealed a negative correlation between NDRG2 expression and TAM resistance ability in ER+breast cancer cells(P＜0.001).CCK-8 cell viability assays and soft agar colony formation assays showed that NDRG2 overexpression in TAM resistant cells significantly reduced the TAM IC50 value and the soft agar colony formation rate(P＜0.001).For the mechanism,the ERAD reporter protein assays showed that NDRG2 overexpression upregulated the expression of the ERAD reporter protein CD3ε-YFP and increased the lev-els of spliced XBP1s mRNA,leading to severe endoplasmic reticulum stress in TAM resistant cells(P＜0.001).Immunoblot analysis confirmed that overexpression of NDRG2 significantly increased the level of phosphorylation of the endoplasmic reticulum stress sensor IRE 1α and the expression levels of its down-stream protein factors,including ERdj4,P58IPK,EDEM and PDIA5(P＜0.001).The in vivo xenograft tumor experiments in mice further verified that NDRG2 overexpression significantly inhibited the growth of resistant tumors,which enhanced the therapeutic effect of TAM(P＜0.001).These findings indicate that increasing NDRG2 expression and triggering severe endoplasmic reticulum stress upon TAM treatment can reverse the resistance of ER+breast cancer cells to TAM and inhibits the growth of ER+breast canc-er tumors.Our results provide valuable new insights and potential targets for improving the clinical man-agement of TAM-resistance and prognosis in ER+breast cancer.

Aim To investigate the effects of multi-gly-cosides of Tripterygium wilfordii(GTW)on mitochon-drial dynamics-related proteins and the mechanism of nephroprotective effects in IgA nephrophathy(IgAN)rats.Methods SPF grade male SD rats were random-ly divided into the Control group,modelling group,prednisone group(6.25 mg·kg·d-1)and GTW group(6.25 mg·kg·d-1).The IgAN rat model was established by the method of"bovine serum albumin(BSA)+carbon tetrachloride(CCl4)+lipopolysac-charide(LPS)".The total amount of urinary protein(24 h-UTP)and erythrocyte count in urine were meas-ured in 24 h urine.Blood biochemistry of serum albu-min(ALB),alanine aminotransferase(ALT),urea ni-trogen(BUN),and creatinine(Scr)were measured in abdominal aorta of the rats;immunofluorescence and HE staining were used to observe the histopathology of the kidneys;RT-PCR and Western blotting were used to detect the mRNA and protein expression levels of key proteins regulating mitochondrial division and fu-sion:dynamin-related protein 1(Drp1),mitochondrial fusion protein 1(Mfn1),and mitochondrial fusion pro-tein 2(Mfn2),and PTEN-induced putative kinase 1(Pink1),in the kidney tissue of rats.Results GTW significantly reduced urinary erythrocyte count and 24 h-UTP,decreased serum ALT,BUN and Scr levels,in-creased serum ALB levels,improved renal histopatho-logical status in IgAN rats,increased the protein and mRNA expression levels of Mfn1,Mfn2,and Pink1,and decreased the protein and mRNA expression levels of Drp1 in renal tissues.Conclusions GTW may regu-late mitochondrial structure and maintain the dynamic balance of mitochondrial dynamics by promoting the ex-pression of Mfn1,Mfn2,Pink1 and decreasing Drp1.This may result in a reduction in urinary erythrocyte counts and proteinuria,and an improvement in renal function.

To investigate the relationship between male semen parameters and sperm DNA fragment index with age. Adopt cross-sectional sampling survey design, 3 203 male patients who visited the Department of Reproductive Andrology in the Third Affiliated Hospital of Zhengzhou University from January 2019 to June 2021 were selected as subjects. Age range is 18-57 years, with the median age of 30 years. Through quartile regression analysis, the correlation between age and different male semen parameters and DNA fragment index (DFI) was presented. The study population was divided into ≤30 years old group and >30 years old group, and the correlation between age and semen volume, sperm concentration, total sperm count, progressive motility, total motility, percentage of normal sperm and DFI level were compared and analyzed. The results showed that there were significant differences in progressive motility, total motility and DFI level among different age groups (χ²=-4.608, -4.604, -7.719,P all <0.05), but there was no significant difference in semen volume, sperm concentration, total sperm count and percentage of normal sperm (χ²=-1.712, -1.203, -0.149, -0.175,P all >0.05). In the>30 years old age group, there was a very weak negative correlation between male age and semen volume, progressive motility and total motility (r=-0.137, -0.101 and -0.056, P all <0.05). There was a very weak positive correlation between male age and sperm concentration and sperm DFI level (r=0.061, 0.190, P all <0.05), while there was no correlation between male age and total sperm count and percentage of normal sperm (r=-0.018, -0.016,P all >0.05). In conclusion, with the increase of age, especially after the age of 30, semen volume, progressive motility and total motility decreased, while sperm concentration and DFI level increased, and semen quality decreased.
Humans ; Male ; Adult ; Adolescent ; Young Adult ; Middle Aged ; Semen ; Semen Analysis ; Cross-Sectional Studies ; Infertility, Male/genetics* ; Sperm Motility ; DNA Fragmentation ; Spermatozoa ; Sperm Count ; DNA

Objective: To evaluate and compare the short-term efficacy of domestic mechanical-locked (Clip2Edge) and elastic self-locked (ValveClip) transcranial mitral valve edge-to-edge interventional repair (TEER) devices in the treatment of functional mitral regurgitant valves. Methods: In this retrospective non-randomized comparative study, patients underwent TEER procedure in Fuwai Yunnan Cardiovascular Disease Hospital from May 2022 to April 2023 for heart failure combined with moderate to severe or severe functional mitral valve were divided into Clip2Edge and ValveClip groups based on the TEER system used. Baseline, perioperative, and postoperative 30 d follow-up data were collected and compared between the two groups. The primary outcome was the success rate on the 30 d post operation, while secondary outcomes included immediate postoperative technical success rate and the incidence of all-cause mortality on the 30 d post operation, readmission rate of acute heart failure, cerebral infarction, severe bleeding, and other serious adverse events rates. Results: A total of 60 patients were enrolled, 34 patients were in the Clip2Edge group and 26 in the ValveClip group, mean age was (63.8±9.3) years, and 24 patients (40%) were female. There were no significant differences in baseline data of age, cardiac function, comorbidities, mitral regurgitation 4+(19(73%) vs. 29(85%)), the end-diastolic volume of left ventricle ((220.8±91.2) ml vs. (210.8±71.7) ml) between the two groups (all P>0.05). The technical success rate immediately after the procedure was 100%. There were no readmission of acute heart failure, death, cerebral infarction, severe bleeding, and other serious adverse events up to the 30 d follow-up. Device success rate was similar between the ValveClip group (24 cases (100%)) and the Clip2Edge group (27 cases (96%)) (P>0.05). Conclusion: Both types of novel domestic TEER devices are safe and feasible in treating patients with functional mitral regurgitation.
Humans ; Female ; Middle Aged ; Aged ; Male ; Mitral Valve Insufficiency/etiology* ; Retrospective Studies ; East Asian People ; Heart Valve Prosthesis Implantation ; Treatment Outcome ; China ; Heart Failure/etiology* ; Cardiac Catheterization

To investigate the relationship between male semen parameters and sperm DNA fragment index with age. Adopt cross-sectional sampling survey design, 3 203 male patients who visited the Department of Reproductive Andrology in the Third Affiliated Hospital of Zhengzhou University from January 2019 to June 2021 were selected as subjects. Age range is 18-57 years, with the median age of 30 years. Through quartile regression analysis, the correlation between age and different male semen parameters and DNA fragment index (DFI) was presented. The study population was divided into ≤30 years old group and >30 years old group, and the correlation between age and semen volume, sperm concentration, total sperm count, progressive motility, total motility, percentage of normal sperm and DFI level were compared and analyzed. The results showed that there were significant differences in progressive motility, total motility and DFI level among different age groups (χ²=-4.608, -4.604, -7.719,P all <0.05), but there was no significant difference in semen volume, sperm concentration, total sperm count and percentage of normal sperm (χ²=-1.712, -1.203, -0.149, -0.175,P all >0.05). In the>30 years old age group, there was a very weak negative correlation between male age and semen volume, progressive motility and total motility (r=-0.137, -0.101 and -0.056, P all <0.05). There was a very weak positive correlation between male age and sperm concentration and sperm DFI level (r=0.061, 0.190, P all <0.05), while there was no correlation between male age and total sperm count and percentage of normal sperm (r=-0.018, -0.016,P all >0.05). In conclusion, with the increase of age, especially after the age of 30, semen volume, progressive motility and total motility decreased, while sperm concentration and DFI level increased, and semen quality decreased.
Humans ; Male ; Adult ; Adolescent ; Young Adult ; Middle Aged ; Semen ; Semen Analysis ; Cross-Sectional Studies ; Infertility, Male/genetics* ; Sperm Motility ; DNA Fragmentation ; Spermatozoa ; Sperm Count ; DNA