AIM: To assess the consistency of the new anterior segment analyzer, MS-39, the Sirius and Pentacam in measuring corneal white-to-white(WTW)and central anterior chamber depth(ACD), and to compare their differences in guiding implantable collamer lens(ICL)size selection.METHODS: Retrospective case study. A total of 210 consecutive patients(420 eyes)who treated at the Ophthalmology Refractive Surgery Center of the First Affiliated Hospital of Xi'an Jiaotong University between September 2019 and September 2020 were enrolled. Three anterior segment analysis systems, MS-39, Sirius, and Pentacam, were utilized to assess the WTW and ACD, with comparative analysis of the results. The sizing of the ICL V4c was simulated using the method recommended by the STAAR company. Data correlation and consistency were evaluated.RESULTS: The WTW measurement results obtained from MS-39, Sirius, and Pentacam were 11.39±0.35, 11.42±0.36, and 11.46±0.35 mm, respectively. Notably, the WTW measurement value from MS-39 was significantly lower than that from Pentacam(P=0.002), while no statistically significant differences were observed between MS-39 and Sirius, or between Sirius and Pentacam(all P>0.05). The WTW measurements from the three devices exhibited a strong positive correlation, with correlation coefficients(r)of 0.942 between MS-39 and Sirius, 0.925 between MS-39 and Pentacam, and 0.882 between Sirius and Pentacam(all P<0.0001). The ACD measurements values from the MS-39, Sirius and Pentacam were 3.28±0.22, 3.28±0.24, and 3.21±0.23 mm, respectively. While, no statistically significant difference was found between MS-39 and Sirius(P>0.05), both measurements were significantly higher than that of Pentacam(both P<0.0001). The ACD measurements also demonstrated a strong positive correlation, with r values of 0.959 between MS-39 and Sirius, 0.947 between MS-39 and Pentacam, and 0.932 between Sirius and Pentacam(all P<0.0001). In terms of ICL size selection based on the measurements from the three devices, the 12.6 mm size was the most frequently selected, while the 13.7 mm size was the least common, the distribution of size selections across the devices was similar.CONCLUSION: MS-39 demonstrated strong positive correlation with both Sirius and Pentacam for WTW and ACD measurements, indicating that the results can be considered clinically interchangeable. Furthermore, the outcomes derived from MS-39 for ICL size selection were closely aligned with those from Sirius and Pentacam, suggesting its clinical feasibility.

To investigate the effects and mechanisms of Yougui Pills(YGP) on oxidative damage induced by hydrogen peroxide(H_2O_2) in human ovarian granulosa cells(KGN). The components in serum with low-and high-doses of YGP were analyzed and compared through ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap mass spectrometry(UHPLC-QEMS), and selected the serum containing YGP high-dose group to follow-up experiments. To stimulated KGN with 200 μmol·L~(-1) H_2O_2to establish an oxidative damage model, which was divided into normal group, model group, low-, medium-, and high-dose of YGP groups, and the efficacy was further verified on the basis of silencing or overexpressing serine protease inhibitor(Serpina3k), further validating the efficacy based on the silencing or overexpression of Serpina3k. TUNEL staining was used to detect cell apoptosis,enzyme-linked immunosorbent assay(ELISA) was employed to measure the secretion levels of estradiol(E_2) and 17β-E_2 in KGN, and Western blot was utilized to assess the expression of Serpina3k and proteins related to the Keap1/Nrf2 signaling pathway. The results show that compared to the model group, each dose group of YGP not only significantly reduces granulocyte apoptosis and upregulates the secretion levels of E_2 and 17β-E_2, but also significantly upregulates Serpina3k and Nrf2 pathway. Further research has found that overexpression of Serpina3k not only enhances the therapeutic effect of YGP but also increases the expression of Nrf2 and inhibits the expression of Keap1. Conversely, interfering with Serpina3k partially reverses the therapeutic effect of YGP, while also partially. The results indicate that the mechanism by which YGP improves oxidative stress in KGN may be related to its upregulation of Serpina3k expression, which affects the conduction of the Keap1/Nrf2 signaling pathway. This study reveals the mechanism by which YGP protects granular cells, providing a certain theoretical basis for its clinical application.
NF-E2-Related Factor 2/genetics* ; Kelch-Like ECH-Associated Protein 1/genetics* ; Humans ; Female ; Signal Transduction/drug effects* ; Oxidative Stress/drug effects* ; Granulosa Cells/cytology* ; Drugs, Chinese Herbal/pharmacology* ; Apoptosis/drug effects* ; Serpins/genetics*

The seed kernel of Momordica cochinchinensis, i.e., Momordicae Semen, is used for medicinal purposes, but to date, no research has been reported on its chemical constituents. In this study, the chemical constituents of Momordicae Semen were investigated for the first time using silica gel column chromatography, semi-preparative HPLC, HR-MS, and NMR. As a result, eight compounds were isolated and identified as: p-hydroxybenzoic acid-7-O-trehaloside(mubeside A, 1), 2,6-dimethoxyphenol-O-β-D-apiosyl-(1→2)-β-D-glucoside(mubeside B, 2), 1-O-p-methoxybenzoyl-1,4-benzenediol-4-O-β-D-apiosyl-(1→2)-β-D-glucoside(mubeside C, 3), 1-O-p-hydroxybenzoyl-1,4-benzenediol-4-O-β-D-apiosyl-(1→2)-β-D-glucoside(mubeside D, 4), gypsogenin-3-O-β-D-galactosyl-(1→2)-β-D-glucuronoside(5), quillaic acid-3-O-β-D-galactosyl-(1→2)-β-D-glucuronoside(6), violanthin(7), and kaempferitrin(8). Compounds 1-4 are new compounds, while compounds 5-8 were isolated from Momordicae Semen for the first time.
Glycosides/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Molecular Structure ; Magnetic Resonance Spectroscopy ; Chromatography, High Pressure Liquid

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To evaluate the bioequivalence and safety of two cilostazol tablets 50 mg in healthy Chinese subjects.Methods This study was an open-lable,randomized,two-period crossover design.A total of 32 subjects respectively for fasting state were given a single oral dose of test or reference tedizolid phosphate tablets 50 mg.The plasma concentration of cilostazol was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS),and the concentration-time data was processed by SAS 9.4,the model method of the non-compartmental was used to calculate the pharmacokinetic parameters of tedizolid and to evaluate the bioequivalence.Results The Cmax of cilostazol test and reference were(358.10±125.80)and(346.90±115.30)ng·mL-1;tmax were 3.50 and 4.00 h;t1/2 were(9.63±7.12)and(8.57±5.15)h;AUC0_twere(5 235.00±2 268.00)and(5 190.00±1 747.00)h·ng·mL-1;AUC0-∞ were(5 377.00±2 367.00)and(5 308.00±1 848.00)h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of the main pharmacokinetic parameters of the test drug and reference drug were within the range of 80.00％to 125.00％.Conclusion Single oral test and reference cilostazol tablets were bioequivalent and safe in healthy Chinese subjects.

Objective To observe the clinical efficacy and safety of olanzapine tablets combined with magnesium valproate sustained-release tablets in the treatment of adolescent depressed patients.Methods Adolescents with depression were divided into control group and treatment group by simple random method.The control group was treated with oral olanzapine tablets with 5 mg·d-1 as the starting dose.After 1 week of treatment,the drug dose was adjusted according to the symptoms and kept within 20 mg·d-1.The treatment group was given oral magnesium valproate sustained-release tablet combined treatment on the basis of the control group,with 0.5 g as the initial dose,and the maximum dose was adjusted according to clinical symptoms after 1 week of treatment,and the maximum dose was no more than 1 g·d-1.Both groups were treated for 12 weeks.The clinical efficacy,excitatory amino acid(EAA),connectin level,intestinal fatty acid binding protein(Ⅰ-FABP),Hamilton depression scale(HAMD),Bech-Rafaelsen Mania Rating Scale(BRMS)and safety of the two groups were compared.Results Sixty-three cases were included in the treatment group and control group,respectively.After treatment,the total effective rates of the treatment group and the control group were 92.06％(58 cases/63 cases)and 79.37％(50 cases/63 cases),respectively,and the difference was statistically significant(P＜0.05).After treatment,the levels of EAA in the treatment group and the control group were(29.98±3.44)and(27.97±3.88)μg·mL-1;the levels of zonulin were(189.45±19.56)and(182.33±19.89)ng·mL-1;the levels of Ⅰ-FABP were(99.27±9.13)and(103.84±9.36)pg·mL-1,respectively;the HAMD scores of the treatment group and the control group were 9.88±1.03 and 10.74±1.95;the BRMS scores were 5.08±0.32 and 5.32±0.51,respectively.Compared with the control group,the differences of above indexes in the treatment group were statistically significant(all P＜0.05).The main adverse drug reactions in the two groups were weight gain,dry mouth,and drowsiness.The total incidences of adverse drug reactions in the treatment group and the control group were 12.70％and 15.87％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion Olanzapine tablets combined with magnesium valproate sustained-release tablets can effectively increase plasma Ⅰ-FABP,EAA,and zonulin levels in adolescent depressed patients,and improve HAMD and BRMS scores,with good safety.

Objective:To investigate the clinical significance of tumor budding as an indicator of postoperative distant organ metastasis after radical gastrectomy in elderly patients diagnosed with gastric cancer.Methods:The clinical and pathological data of 124 elderly patients who experienced metastasis after undergoing radical gastrectomy were retrospectively analyzed.The analysis was conducted from March 2015 to June 2022, focusing on the clinicopathological factors that influenced the occurrence of postoperative distant metastasis in these patients.Tumor budding in gastric cancer tissues was assessed using hematoxylin-eosin staining, and its clinical significance was analyzed.Results:The tumor budding grade of gastric cancer tissues showed a significant correlation with vascular invasion( χ2=6.731, P=0.009), the number of lymph node metastases( rs=0.481, P<0.001), and the time of distant metastasis( rs=-0.450, P<0.001).In the univariate analysis, factors such as tumor budding grade, tumor size, vascular invasion, postoperative chemotherapy, cancerous nodule, preoperative serum carbohydrate antigen 125, and the number of lymph node metastases were found to influence distant metastasis-free survival after radical gastrectomy in elderly patients(all P<0.05).The multifactorial analysis also indicated that tumour outgrowth grade was an important independent prognostic factor for postoperative distant metastasis in elderly gastric cancer patients( HR=3.731, P<0.001). Conclusions:The findings of this study indicate that tumor budding may serve as a potential marker for predicting distant organ metastasis in elderly patients who have undergone radical gastrectomy.This discovery holds significant clinical implications.

Aim To investigate the regulatory effect of Cortaetin on pathological myocardial hypertrophy induced by isoprenaline (ISO) and the underlying mechanism. Methods ISO was used to stimulate neonatal rat cardiomyocytes for 24 h, and myocardial hypertrophy model was established at the cellular level. C57BL/6 mice were injected subcutaneously with ISO for one week to establish myocardial hypertrophy model at animal level. RT-qPCR was used to detect the changes of mRNA and Western blot was used to detect the changes of relative protein content. Immunofluorescence was used to measure the subcellular location of Cortaetin and the change of its expression. The overex-pression of Cortaetin by adenovirus infection and the knockdown of Cortaetin by transfection of small interfering RNA were studied. Results On the cellular and animal levels, ISO-induced myocardial hypertrophy models were successfully established, and it was observed that ISO caused the decrease of Cortaetin and N-cadherin protein levels. Overexpression of Cortaetin could reverse the decrease of N-cadherin protein level and myocardial hypertrophy caused by ISO. Knockdown of Cortaetin showed the opposite effect. Conclusion Cortaetin, in combination with N-cadherin, may play a role in combating myocardial hypertrophy by enhancing the connections between cardiomyocytes.