To observe the clinical efficacy of dulaglutide injection combined with letrozole tablets in the treatment of obese polycystic ovary syndrome (PCOS) infertility patients.

Obese infertility patients with PCOS were divided into control group and treatment group according to medication regimen. The control group was given letrozole tablets 5 mg orally, once a day for 3 months on the basis of conventional treatment; the treatment group was given dulaglutide injection 1.5 mg, subcutaneous injection once a week, and letrozole tablets were treated with the same method as the control group for 3 months. The clinical efficacy, glucose metabolism characteristics, visceral fat, body composition and the occurrence of adverse drug reactions were compared between the two groups.

42 patients were included in the treatment group and 38 in the control group. After treatment, the total effective rate of treatment group and control group was 90.48% (38 cases /42 cases) and 73.68% (28 cases /38 cases), the difference was statistically significant (P<0.05). After treatment, the fasting plasma glucose (FPG) of the treatment group and the control group were (4.37±0.85) and (4.84±0.81) mmol·L^-1, respectively; glycosylated hemoglobin (HbA1c) were (4.84±0.82)% and (5.25±0.88)%, respectively; homeostasis model assessment for insulin resistance (HOMA-IR) were 2.45±0.41 and 2.73±0.48, respectively; visceral fat mass were (687.19±97.29) and (739.37±105.24) g, respectively; visceral fat volume were (751.21±106.34) and (821.82±112.64) cm³, respectively; visceral fat area were (143.29±27.88) and (156.39±25.26) cm², respectively; body mass index (BMI) were (32.04±3.65) and (34.33±3.56) kg·m^-2, respectively; waist-hip ratio (WHR) were 0.96±0.22 and 1.10±0.25, respectively; body fat percentage were (31.43±4.87)% and (34.37±4.54)%, respectively. The differences of the above indexes between the two groups were statistically significant (P<0.05, P<0.01). The main adverse drug reactions in the treatment group were nausea, vomiting, and loss of appetite, while no obvious adverse reactions occurred in the control group. There was no statistically significant difference in the total incidence of adverse reactions between the two groups (P>0.05).

Dulaglutide injection combined with letrozole tablets has significant clinical efficacy in the treatment of obese PCOS infertility patients, which can regulate the level of glucose and lipid metabolism, visceral fat content and body composition, reduce insulin resistance, and has certain safety.

To analyze the effect of conbercept ophthalmic injection on aqueous humor glucose (AHG) and vascular endothelial growth factor (VEGF) in elderly patients with diabetes retinopathy (DR) and vitreous hemorrhage, and the correlation with blood glucose.

A total of 80 elderly patients with DR and vitreous hemorrhage were selected as the study subjects. All of them received intravitreal injection of 0.05 mL of conbercept ophthalmic injection for 7 consecutive days, and then underwent vitrectomy. They were divided into the standard reaching group and the non-standard reaching group according to whether blood glucose control met the standard. The changes in ocular signs and visual recovery indicators [central macular thickness (CMT), hemorrhagic spot area and best corrected visual acuity (BCVA)], aqueous humor AHG, VEGF, inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] and blood glucose before and after conbercept ophthalmic injection treatment were compared between groups. Pearson method was used to analyze the correlation between AHG, VEGF and blood glucose level. Logistic regression method was used to identify the independent influencing factors of inadequate blood glucose control.

49 patients were included in the standard reaching group, and 31 patients were included in the non-standard reaching group. After treatment, the CMT values of standard reaching and the non-standard reaching groups were (215.63±22.45) and (254.68±26.73) μm, respectively; the bleeding spot areas were (1.18±0.14) and (1.46±0.17) mm², respectively; the BCVA values were 0.85±0.07 and 0.71±0.08, respectively; the AHG values for aqueous humor were (4.68±0.54) and (6.27±0.65) mmol·L^-1, respectively; VEGF levels were (121.46±13.65) and (158.72±16.39) pg·mL^-1, respectively; IL-6 levels were (18.13±1.89) and (19.44±2.31) pg·mL^-1, respectively; TNF-α levels were (6.73±0.75) and (7.16±0.73) pg·mL^-1, respectively; the blood glucose levels were (5.16±0.57) and (7.22±0.78) mmol·L^-1, respectively; the above indicators of standard reaching group were compared with those of the non-standard reaching group, and the differences were statistically significant (all P<0.05). Correlation analysis found that the levels of aqueous humor AHG, VEGF, IL-6 and TNF-α were positively correlated with blood glucose levels in elderly patients with DR and vitreous hemorrhage (P<0.05). Logistic regression analysis showed that aqueous humor AHG, VEGF, and IL-6 were independent risk factors for inadequate blood glucose control in elderly patients with DR and vitreous hemorrhage (P<0.05).

After conbercept ophthalmic injection treatment, there are significant differences in the levels of AHG and VEGF in elderly patients with DR and vitreous hemorrhage, and visual acuity is restored. Moreover, AHG and VEGF are positively correlated with blood glucose. Monitoring them can assist in efficacy evaluation.

To observe the clinical efficacy and safety of retroauricular injection of dexamethasone sodium phosphate injection in the treatment of sudden deafness.

Patients with sudden deafness were divided into control group and treatment group according to actual treatment method. Both groups were given conventional treatment (neurotrophy and microcirculation improvement) according to guidelines. The control group received additional intravenous drip of methylprednisolone sodium succinate (80 mg once daily for 4 d, reduced to 40 mg for 4 d, then further reduced to 20 mg for 2 d). The treatment group was given retroauricular injection of dexamethasone (5 mg every other day) in addition to the control group’s regimen. Both groups were treated for 10 d. The efficacy, metabolomic differences, hearing recovery status, hemorheological indexes, and immune function indexes were compared between the two groups. Meanwhile, the safety was evaluated.

38 cases and 42 cases were included in the control group and the treatment group, respectively. After treatment, the effective rates in the treatment group and the control group were 80.95% (34 cases/42 cases) and 57.89% (22 cases/38 cases), with statistically significant difference (P<0.05). There were significant increases in 11 metabolites and significant decreases in 18 metabolites before treatment for sudden deafness. The four metabolites showing the most significant increases were ascorbic acid, tauroursodeoxycholic acid, D-pantothenic acid, and glucaric acid. The most significantly decreased metabolites were lysophosphatidylethanolamine and vanillic acid. After treatment, patients with sudden deafness in the effective group showed significant increases in 37 metabolites and significant decreases in 8 metabolites compared to the ineffective group. The three metabolites showing the most significant increases were L-leucine, undecanoylcarnitine, and lauroylcarnitine, while the three with the most notable decreases were L-histidine, 2-pyridylacetic acid, and D-pantothenic acid. After treatment, hearing thresholds under 0.5, kHz in the control group and the treatment group were (49.82±7.03) and (43.69±5.38) dB, respectively; hearing thresholds under 1.0 kHz were (58.14±7.39) and (46.33±6.25) dB, respectively; hearing thresholds under 2.0 kHz were (60.05±8.23) and (49.51±5.30) dB, respectively; hearing thresholds under 4.0 kHz were (62.29±8.14) and (51.36±5.87) dB, respectively, with statistically significant differences between two groups (P<0.05). After treatment, superoxide dismutase (SOD) levels in the control group and the treatment group were (94.65±14.06) and (99.72±13.56) μg·L^-1; malondialdehyde (MDA) levels were (4.36±0.51) and (3.94±0.40) μmol·L^-1, with statistically significant differences between groups (P<0.05). After treatment, plasma viscosity in the control group and the treatment group was (2.12±0.30) and (1.55±0.26) mPa·s; erythrocyte aggregation index was 3.38±0.30 and 2.97±0.19; low-shear viscosity was (10.13±1.60) and (9.06±1.19) mPa·s; high-shear viscosity was (5.96±0.39) and (5.33±0.31) mPa·s, with statistically significant differences between groups (P<0.05). After treatment, CD3⁺ in the control group and the treatment group was 57.76±4.70 and 63.52±5.46; CD4⁺ was 33.29±3.38 and 37.42±3.68; CD4⁺/CD8⁺ was 1.43±0.22 and 1.70±0.30; immunoglobulin (Ig) G levels were (12.16±1.12) and (10.23±0.93) g·L^-1; IgA levels were (2.36±0.23) and (2.11±0.15) g·L^-1, with statistically significant differences between groups (all P<0.05). No significant adverse reactions occurred in either group during the treatment.

Retroauricular injection of dexamethasone sodium phosphate injection is markedly effective in the treatment of sudden deafness, and it has advantages in improving metabolomic differences, hemorheology and immune function.

To comparatively analyze the molecular characteristics of linear plasmids in Enterococcus avium, clarify the global transmission trajectory of linear plasmids in Enterococcus, and explore the genetic stability of linear plasmids in different host strains through subculture of transconjugants, thereby providing a theoretical basis for the prevention and control of clinically drug-resistant bacteria.

The minimum inhibitory concentrations (MICs) of vancomycin against Enterococcus avium ZB195, three recipient strains (Enterococcus avium 07H170, Enterococcus faecalis FA2-2, and Enterococcus faecium BM4105RF), and their corresponding transconjugants were determined using the broth microdilution method. Whole-genome sequencing of strain ZB195 was performed to characterize its plasmid features. Linear plasmid sequences from 18 global Enterococcus faecium strains isolated between 2000 and 2019 were collected, and phylogenetic trees and Bayesian evolutionary trees were constructed using MAFFT, IQtree, and BEAST software. The global transmission trajectory was simulated with SpreaD3 software. The genetic stability of linear plasmids in different host strains was evaluated through a 15-day subculture experiment without antibiotic selection pressure.

For the first time, this study identified a linear plasmid in the genome of Enterococcus avium ZB195, which harbors the vancomycin resistance vanA gene and was capable of horizontal transfer to three recipient strains. Sequence alignment showed that the linear plasmid of ZB195 had the highest sequence identity with that of Enterococcus faecium AA708 from Japan, and phylogenetic analysis confirmed that they were most closely related. Simulation of global transmission trajectories revealed that the linear plasmid in Enterococcus was first detected in Japan in 2000, and then gradually spreaded to China, the United States, Norway, Denmark, India and other countries. Passage experiments indicated that the linear plasmid exhibited the highest stability in Enterococcus avium hosts.

The linear plasmids detected in Enterococcus strains in China may have originated from the horizontal transmission of Enterococcus faecium from Japan. Moreover, after transferring to Enterococcus avium, these plasmids can form better host adaptability. This suggests that it is necessary to strengthen cross-regional monitoring of linear plasmids in Enterococcus to curb the global spread of drug-resistant genes.

To investigate the effects of lycorine (LYC) on the proliferation and apoptosis of acute promyelocytic leukemia (APL) cells by regulating the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway.

Human APL cells (NB4) were treated with 1.0-32.0 μmol·L^-1 LYC, the cell viability was detected, and the LYC experimental concentration was screened. NB4 cells were divided into group A (control group), group B, group C, group D (lycorine low concentration group, medium concentration group, high concentration group), group E (high concentration lycorine+PI3K activator 740 Y-P group). Except for the control group, groups B, C, and D were treated with 4.0, 8.0 and 16.0 μmol·L^-1 lycorine, respectively, for 24 hours. Group E was treated with 16.0 μmol·L^-1 lycorine combined with 25.0 μmol·L^-1 740 Y-P for 24 hours. Cell proliferation, apoptosis, invasion, migration, and cell cycle status were detected, and the expression of related proteins was detected.

After treatment with concentrations of 4.0, 8.0 and 16.0 μmol·L^-1 of lycorine, the survival rate of NB4 cells prominently decreased, therefore, they were used for subsequent experiments. The colony formation numbers of NB4 cells in group A, group B, group C, group D and group E were 151.38±16.42, 117.15±12.78, 81.04±8.36, 56.17±6.05 and 105.02±10.64, respectively. The scratch healing rates were (89.62±9.15) %, (72.57±7.45)%, (55.34±5.83)%, (36.78±3.72)% and (65.59±6.58)%, respectively. The number of cell invasion was (168.27±17.82), (132.69±14.39), (90.58±9.25), (61.64±6.37) and (110.59±12.27), respectively. The proportion of cells in S phase was (46.17±4.71)%, (35.18±3.56)%, (28.20±3.13)%, (20.52±2.16)% and (32.01±3.32)%, respectively. The percentages of cells in G₂/M phase were (24.68±2.56)%, (19.34±1.97)%, (15.62±1.55)%, (11.15±1.23)% and (17.03±1.89)%, respectively. The levels of cyclin dependent kinase 1 (CDK1) were 0.95±0.09, 0.74±0.07, 0.50±0.05, 0.32±0.03 and 0.63±0.06, respectively. The levels of matrix metalloproteinase 2 (MMP-2) were 1.14±0.11, 0.83±0.08, 0.56±0.05, 0.37±0.03 and 0.69±0.06, respectively. The levels of matrix metalloproteinase 9 (MMP-9) were 0.94±0.09, 0.70±0.07, 0.47±0.04, 0.26±0.02 and 0.55±0.05, respectively. The phosphorylated phosphatidylinositol 3-kinase (p-PI3K)/PI3K were 0.86±0.08, 0.71±0.07, 0.45±0.04, 0.26±0.02 and 0.55±0.05, respectively. The expression levels of phosphorylated protein kinase B (p-AKT)/AKT were 0.91±0.09, 0.78±0.07, 0.53±0.05, 0.31±0.03 and 0.69±0.06, respectively. The apoptosis rates were (2.23±0.26)%, (17.41±1.82)%, (26.34±2.75)%, (39.62±4.05)% and (21.58±2.27)%, respectively. The proportion of cells in G₀/G₁ phase was (29.15±3.06)%, (45.48±4.67)%, (56.18±5.73)%, (68.33±6.88)% and (50.96±5.01)%, respectively. The levels of Bcl-2 associated X protein (Bax) were 0.26±0.02, 0.41±0.04, 0.72±0.07, 0.98±0.09 and 0.66±0.06, respectively. The levels of PTEN were 0.32±0.03, 0.45±0.04, 0.74±0.07, 0.96±0.09 and 0.61±0.06, respectively. Group B, group C, group D compared with group A, group E compared with group D, the above indicators were statistically significant (P<0.05). After NK cells were co-cultured with NB4 cells, compared with the A group, the cell killing rate of B, C and D groups increased (P<0.001). Compared with the D group, the cell killing rate of E group decreased (P<0.001).

Lycorine inhibited APL cells with up-regulation of PTEN expression and inhibition of PI3K/AKT pathway, and its effect is dependent on PI3K/AKT pathway.

To explore the mechanism by which hedysarum polybotrys polysaccharide (HPS) improves iron death of steatotic hepatocytes through the protein kinase RNA-like endoplasmic reticulum kinase- nuclear factor-erythroid 2-related factor 2 (PERK-Nrf2) signaling pathway.

The cells were cultured with 0.6 mmol·L^-1 fatty acids to replicate the non-alcoholic fatty liver disease cell model. The LO-2 cell were divided into normal group (complete medium), model group (0.6 mmol·L^-1 fatty acid solution), positive control group (0.6 mmol·L^-1 fatty acid solution+24 μmol·L^-1 liproxstain-1) and experimental group (0.6 mmol·L^-1 fatty acid solution + 50 mg·L^-1 HPS), culture for 24 h. Stain with Oil Red O was used to analyze the positive area (%Area) of cell lipid deposition; the content of lipid peroxide(LPO), 4-hydroxynonenal(4-HNE), glutathione(GSH) and superoxide dismutase(SOD) was detected by enzyme-linked immunosorbent assay(Elisa) method; the relative expressions levels of PERK-Nrf2 signaling pathway protein in hepatocytes were detected by Western blot; immunofluorescence assay was used to detect the relative expression levels of GPX4 and SLC7A11 proteins.

The % Area of cell lipid deposition in hepatocytes of normal group, model group, control group and experimental group were 0.02±0.01, 0.26±0.08, 0.09±0.02 and 0.15±0.04; the contents of LPO were (2.62±0.17), (13.47±1.55), (6.31±1.12) and (5.71±1.50) nmol·mL^-1; the contents of 4-HNE were (8.06±0.40), (14.60±2.02), (9.40±0.81) and (12.94±0.56) ng·L^-1; the contents of GSH were (120.73±7.75), (34.60±2.98), (67.86±2.08) and (59.33±7.46) mg·L^-1; the contents of SOD were (7.25±0.61), (3.77±0.44), (5.22±0.76) and (8.12±0.78) U·mL^-1; the levels of Grp78 mRNA were 1.01±0.15, 1.47±0.11, 1.41±0.08 and 1.02±0.05; the levels of PERK mRNA were 1.00±0.09, 1.85±0.16, 1.02±0.27 and 1.16±0.01; the levels of Nrf2 mRNA were 1.01±0.12, 0.26±0.07, 0.68±0.09 and 0.66±0.05; the levels of GPX4 mRNA were 1.00±0.05, 0.79±0.02, 0.87±0.17 and 0.83±0.10; the levels of SLC7A11 mRNA were 1.01±0.17, 0.50±0.14, 0.91±0.09 and 0.98±0.05; the relative expression levels of Grp78 protein were 1.00±0.11, 2.72±0.07, 1.83±0.04 and 2.24±0.06; the relative expression levels of PERK protein were 1.00±0.06, 1.21±0.08, 1.03±0.07 and 0.95±0.06; the relative expression levels of p-PERK protein were 1.00±0.04, 2.70±0.08, 1.40±0.07 and 1.76±0.06; the relative levels of PERK protein phosphorylation were 1.00±0.09, 2.24±0.21, 1.36±0.03 and 1.85±0.09; the relative expression levels of Nrf2 protein were 1.00±0.03, 0.52±0.01, 0.73±0.02 and 0.84±0.02; the protein fluorescence intensity of GPX4 were 24.34±0.86, 13.86±1.65, 18.01±2.03 and 16.20±1.55; the protein fluorescence intensity of SLC7A11 were 69.58±4.13, 34.24±6.73, 60.75±9.35 and 45.18±6.46. Compared with the normal group, there were significant differences in the above indexes of model group (all P<0.05) ; compared with the model group, there were significant differences in the above indexes of experimental group (all P<0.05).

HPS may protect liver cells by regulating the PERK-Nrf2 signaling pathway, reducing lipid peroxidation and iron death in liver cells.

To study the mechanism of mangiferin alleviating liver injury induced by high-fat and high-sugar diet in obese rats based on oxidative stress signaling pathway.

Forty SD rats were divided into blank control group (NC) (raised normally and given the same amount of normal saline), model group (fed with high-fat and high-sugar diet and given the same amount of normal saline), the mangiferin administration group (MGF) (fed with high-fat and high-sugar diet), and mangiferin administration+miR-195-3p mimics group (MGF+miR-195-3p mimics) (fed with high-fat and high-sugar diet and administered 40 mg·kg^-1 mangiferin suspension, in addition, recombinant lentiviruses containing miR-195-3p mimics were injected into the tail vein), with 10 rats in each group. After treatment, body mass, visceral fat mass and liver coefficient were measured, blood glucose, blood lipid, aminotransferase, liver glycogen and oxidative stress related factors were detected by kit, and histopathological status of liver was detected by hematoxylin-eosin (HE) staining. Real-time quantitative fluorescence polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect the levels of miR-195-3p, and protein Western blot (WB) was used to detect the expression levels of nuclear factor erythroidderived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1).

After different treatment, the liver coefficients of NC group, Model group and MGF group were (2.20±0.29)%, (3.11±0.40)% and (2.75±0.32)%, respectively. Insulin was (310.63±38.06), (426.59±55.35) and (378.57±42.81) ng·L^-1; glutamic pyruvic transaminase was (55.17±6.11), (137.57±17.45) and (106.85±12.66) U·L^-1, respectively. The liver glycogen was (21.64±2.98), (7.96±1.03) and (15.52±2.16) mg·g^-1, respectively. The malondialdehyde levels in Model group, MGF group and MGF+miR-195-3p mimics group were (9.63±1.22), (7.79±0.91) and (9.11±1.16) mmol·g^-1, respectively, super oxide dismutase was (110.42±14.57), (251.36±36.26) and (181.45±20.95) U·g^-1, and Nrf2 mRNA was 1.00±0.12, 1.97±0.20, 1.29±0.15, respectively. The mRNA of HO-1 was 1.00±0.14, 2.84±0.35 and 1.81±0.29, respectively. Comparison of Model group with NC group, MGF group with Model group and MGF+miR-195-3p mimics group with MGF group showed statistically significant differences in the above indexes (all P<0.05).

Mangiferin can reduce liver injury and regulate glucose and lipid metabolism in obese rats, and its mechanism may be related to the down-regulation of miR-195-3p expression and activation of Nrf2/HO-1 signaling pathway.

To establish an ultra-high performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) for the determination of the contents of cholic acid, imperatorin, quercetin, isoquercetin, ferulic acid, chlorogenic acid, rutin, and cryptochlorogenic acid in the Huoxuexiaozhong capsule.

The analysis was performed by UPLC-MS/MS. Chromatographic conditions: separation was achieved on an Agilent Poroshell 120 EC-C₁₈ column (2.1×150 mm, 1.9 μm). The mobile phase consisted of acetonitrile (A) and 0.1% formic acid in water (B) with gradient elution, at a flow rate of 0.3 mL·min^-1 and a column temperature of 35 ℃. Mass spectrometry conditions: multiple reaction monitoring (MRM) with positive/negative ion switching mode was used electrospray ionization source. The ion source voltage was set at +5.5 kV and -4.5 kV, with the ion source temperature maintained at 550 ℃. The gas settings were as follows: GS1 344.74 kPa, GS2 344.74 kPa, and CUR 241.32 kPa. The specificity, standard curves and limits of detection and quantification, precision and recovery, and stability were investigated.

The analytical method demonstrated good linearities for cholic acid, quercetin, isoquercitrin, ferulic acid, chlorogenic acid, cryptochlorogenic acid, rutin and imperatorin over the concentration ranges of (0.26-25.70), (0.03-1.68), (0.03-1.51), (0.03-1.47), (0.40-10.34), (0.56-27.05), (0.03-1.37), and (2.50-759.65) μg·mL^-1, respectively (R² ≥ 0.9911). The relative standard deviations (RSD) of peak areas for reference standards and test samples were ≤ 2.44% and ≤ 2.87%, respectively. Recoveries for all components ranged from 96.54% to 107.86%, with RSD values between 0.47% and 5.41%, indicating good precision and accuracy. The stability of the method showed an RSD of ≤ 2.77%.

The UPLC-MS/MS method was established to determine the concentration of eight components in Huoxuexiaozhong capsule simultaneously. This method has high sensitivity, specificity and stability, which can be used as a reliable reference for the quality control of the capsule.

To investigate the prevalence and associated influencing factors of potentially inappropriate medications (PIM) in elderly hospitalized patients with ischemic stroke, and to construct a risk prediction model for this population. This study aimed to provide decision support for identifying high-risk patients and ensuring rational clinical medication use.

Retrospective analysis was performed on the medical records of elderly hospitalized patients with ischemic stroke admitted to our hospital from January 2021 to December 2023. The 2023 version of the Beers Criteria was adopted to assess PIM. Univariate and multivariate Logistic regression analyses were applied to identify risk factors associated with PIM, and the optimal model was ascertained via the Akaike information criterion (AIC) followed by nomogram development. The discriminative ability, calibration, and clinical utility of the model were evaluated systematically.

A total of 1 797 patients were included, among whom 866 (48.19%) had PIM, involving 1 756 PIM episodes. Multivariate Logistic regression analysis revealed that female gender, number of medications≥10 types, National Institutes of Health Stroke Scale (NIHSS) score of >5 points, personal history of cerebral infarction, type 2 diabetes mellitus, coronary heart disease, and atrial fibrillation were independent risk factors for PIM (P<0.05, P<0.001). Validation of the nomogram model showed an area under curve (AUC) of the receiver operating characteristic of 0.73. The Hosmer-Lemeshow goodness-of-fit test showed a P-value >0.05, meaning the model fit well, and there was good agreement between the calibration curve and the ideal curve. Clinical decision curve analysis (DCA) demonstrated that when the threshold probability ranged from 15% to 87%, the model achieved a high net benefit, confirming its clinical practical value.

The constructed nomogram model exhibits good discriminative ability, calibration, and clinical applicability. It can accurately predict the risk of PIM in elderly patients with ischemic stroke, facilitating early clinical risk identification and targeted intervention implementation.