Objective:To explore the effects of Yishen Tonglong Granules (YSTLG) on cell proliferation and apoptosis in a nude mouse model of androgen independent prostate cancer subcutaneous transplantation based on non classical Wnt signaling pathway.Methods:The tumor-bearing nude mouse model was established using the human prostate cancer bone metastatic cell line PC-3. After successful modeling, the mice were equally divided into six groups using the random number table method: model group, Western medicine group, Chinese materia medica low-, medium-, and high-dosage groups, and Chinese materia medica-Western medicine combination group. Corresponding drug interventions were administered to each group. Following 28 consecutive days of drug administration, the nude mice were euthanized. Tumor tissues were harvested for pathological observation via HE staining. Cell proliferation was assessed by immunohistochemistry; apoptosis was detected using TUNEL assay; the expressions of non-canonical Wnt signaling pathway-related proteins (Wnt5a, Rac1, RhoA, NFATc1) were analyzed through Western blot and immunohistochemical methods.Results:THE staining results demonstrated that YSTLG could effectively ameliorate pathological alterations in tumor tissues. Compared with the model group, the Chinese materia medica low-, medium-, and high-dosage groups, as well as the Chinese materia medica-Western medicine combination group, exhibited reduced proliferation indices ( P<0.01), elevated apoptosis indices ( P<0.01), down-regulated protein expressions of Wnt5a, Rac1, RhoA, and NFATc1 ( P<0.01), and decreased optical density values of Wnt5a, Rac1, RhoA, and NFATc1 ( P<0.01). These effects displayed a dosage-dependent trend. The Chinese materia medica-Western medicine combination group achieved the most pronounced therapeutic outcomes. Conclusions:YSTLG may exert inhibitory effects on the proliferation of androgen-independent prostate cancer cells and promote apoptosis, possibly through suppression of the non-canonical Wnt signaling pathway. Furthermore, its combination with Wnt signaling inhibitors may exhibit synergistic therapeutic effects.

Protein arginine methyltransferase 5 (PRMT5) exhibits elevated expression levels in a variety of cancers and has emerged as a critical target for cancer therapy in recent years. However, first-generation PRMT5 inhibitors have exhibited inadequate selectivity, leading to significant hematological toxicity, thus limiting their clinical utility. The second-generation PRMT5 inhibitors have shown marked improvement in safety and efficacy by selectively targeting MTAP-null tumor cells without impacting normal cells. This review systematically summarizes the biological and functional roles of PRMT5 in MTAP-deficient tumor cells, and comprehensively analyzes the research and development process, molecular binding mechanisms, and the latest advancements in clinical trials of the five second-generation PRMT5 inhibitors currently under investigation, aiming to provide valuable insights for further in-depth studies in this field.

The finite element method(FEM)is a widely employed mathematical technique in mechanical research that divides an object into discrete and interacting finite elements. Medically, finite element analysis(FEA)enables the simulation of biomechanical experiments that are challenging to conduct. Orbital surgery poses significant challenges to ophthalmologists due to its inherent difficulty and steep learning curve. FEM enables the simulation and analysis of the mechanical properties of orbital tissue, offering a novel approach for diagnosing and treating orbital-related diseases. With technological advancements, FEM has significantly matured in the diagnosis and treatment of orbital diseases, becoming a popular area of research in orbital biomechanics. This paper reviewed the latest advancements in orbital FEM, encompassing the development of orbital FEA models, simulation of orbital structure, and its application in orbital-related diseases. Additionally, the limitations of FEM and future research directions are also discussed. As a digital tool for auxiliary diagnosis and treatment, orbital FEA will progressively unlock its potential for diagnosing and treating orbital diseases alongside technological advancements.

Objective:To explore the correlation of serum adiponectin (APN) , D-dimer (D-D) and neutrophil-to-lymphocyte ratio (NLR) levels with disease severity and prognosis in patients with diabetic foot ulcer infection.Methods:92 patients with diabetic foot ulcer infection in the Nantong Third Hospital Affiliated to Nantong University from Feb. 2020 to Feb. 2021 were selected, and they were divided into mild ( n=30) , moderate ( n=44) and severe ( n=18) patients according to the severity of the disease. The serum APN, D-D and NLR levels in patients with different severity were compared, the relationship between serum APN, D-D and NLR levels and disease severity in patients with diabetic foot ulcer infection were analyzed. Patients were followed up for 1 year, and the prognosis of the patients was counted. Factors affecting serum APN, D-D and NLR levels in patients with diabetic foot ulcer infection were analyzed, and the receiver operating curve (ROC) was used to analyze the value of serum APN, D-D and NLR levels in predicting poor prognosis of patients. Results:There were significant differences in serum APN, D-D and NLR levels in patients with different severity ( P<0.05) . APN level in severe patients was 5.35±0.98, in moderate patients was 7.64±1.25, both lower than that of the mild patients 9.19±1.73 ( P<0.05) . Serum APN level in severe patients was lower than that in moderate patients ( P<0.05) . Serum D-D and NLR levels were 3.49±0.72 and 2.86±0.58 in severe patients, respectively; and they were 3.02±0.63 and 2.24±0.46 in moderate patients, higher than that of mild patients 2.43±0.51; 1.71±0.33 ( P<0.05) . The levels of serum D-D and NLR in severe patients were higher than those in moderate patients ( P<0.05) . Spearman correlation analysis showed that the severity of the disease was negatively correlated with serum APN levels ( r=-0.414, P<0.001) , and positively correlated with serum D-D and NLR levels in patients with diabetic foot ulcer infection ( r=0.387, P<0.001; r=0.461, P<0.001) . Univariate analysis showed that the proportion of severe disease, serum fasting blood glucose, glycosylated hemoglobin, fibrinogen, D-D and NLR levels in patients with poor prognosis were higher than those in patients with good prognosis ( P<0.05) , and the APN level in patients with poor prognosis was lower than that in patients with good prognosis ( P<0.05) . Logistic multivariate regression analysis showed that severe disease, serum glycosylated hemoglobin, APN, D-D, and NLR levels were independent risk factors for poor prognosis in patients with diabetic foot ulcer infection ( P<0.05) . ROC analysis showed that the optimal cut-off points of serum APN, D-D and NLR levels for predicting poor prognosis of patients were 5.73 mg/L, 3.06 mg/L, 2.12, the sensitivity was 78.57%, 82.14%, 85.71%, the specificity was 76.56%, 67.19%, 73.44%, the area under the curve (AUC) was 0.793, 0.784, 0.818, the specificity and AUC of the three were 98.44 %, 0.918, respectively. Conclusions:Serum APN, D-D and NLR levels are related to the severity of the disease in patients with diabetic foot ulcer infection. Clinical detection of serum APN, D-D and NLR levels can be used as sensitive indicators to predict poor prognosis.

Objective:To systematically analyze the efficacy of nasal endoscopic transsphenoidal decompression and glucocorticoid pulse therapy for traumatic optic neuropathy (TON).Methods:PubMed, Web of Science, Cochrane Library, ClinicalTrial.gov, CNKI, Wanfang, China Biomedical and other databases were searched to retrieve clinical studies on endoscopic surgery and hormone therapy for TON since their establishment to November 1, 2020.Two researchers screened the literature and evaluated the quality of the included literatures.The improvement of visual acuity before and after treatment was taken as an effective indicator.RevMan 5.3 statistical software was used for meta-analysis.The sensitivity of the results was analyzed atfer literature exclusion.The publication bias of each study was double checked by funnel plot and Begg test.Results:Eight studies were included, including 7 cohort studies and 1 randomized controlled trial.There was no significant difference between the endoscopic decompression group and glucocorticoid group in the efficiency of visual acuity improvement in the treatment of TON [odds ratio ( OR)=1.65, 95% confidence interval ( CI)∶0.75-3.66, P=0.22], neither in TON patients with residual vision before surgery ( OR=2.17, 95% CI: 0.94-4.98, P=0.07). For nasal endoscopic decompression surgery, early surgery (disease course<7 days) was more effective than late surgery (disease course>7 days) ( OR=4.73, 95% CI: 2.55-8.78, P<0.01). Sensitivity analysis suggested that the results of this literature analysis were not robust.The Begg test showed that there was no literature publication bias. Conclusions:There is no significant difference between nasal endoscopic surgery and glucocorticoid therapy in the treatment of TON.Early endoscopic surgery may help improve visual acuity in patients with residual vision.

Phosphatidylinositol-3-kinase (PI3K) inhibitors can increase the sensitivity of tumor cells to Poly ADP-ribose polymerase-1 (PARP-1) inhibitors. Therefore, the simultaneous inhibition of the PARP-1 and PI3K activities are expected to overcome the drug resistance of PARP-1 inhibitors.In our previous work, two compounds XW-1 and WZ-1 with excellent activities against PARP-1 and PI3K were obtained with the limitation to further study due to their poor water solubility.Therefore, XW-1 and WZ-1 were chosen as lead compounds to optimize their solubility by introducing a salt-forming site via a urea group, and 11 novel compounds were designed and synthesized. The structure of all target compounds was confirmed by 1H NMR, 13C NMR, and HRMS.The enzyme activities of the compounds against PARP-1 and PI3K were measured, and the results showed that most of the compounds demonstrated good inhibitory activities against PARP-1 and PI3K.Based on the above result, the inhibitory activities of compounds 8b, 8e, and 8f against MDA-MB-231, MDA-MB-468, HCC1937, HCT116, and olaparib-resistant HCT116R were determined by MTT, respectively.Additionally, the structure-activity relationship was discussed. The results showed that these compounds displayed excellent antiproliferation activity.Among them, compound 8f demonstrated antiproliferation remarkably against all five tumor cells, which was more potent than that of olaparib, and was comparable to that of BKM120.Furthermore, the solubility of hydrochloride salts of compound 8b and 8f was significantly improved compared to the lead compounds.The results of this study will provide a theoretical basis for the further development of PARP-1 and PI3K dual-target inhibitors with good pharmaceutical properties and strong inhibitory activities.

Birth defects and rare diseases have become major public health problems, and early prevention and control are the most effective interventions. In recent years, with the rapid development of genomic techniques such as high-throughput sequencing, the level of screening and diagnosis of genetic birth defects and rare diseases has been greatly improved. This article reviews the application of genomic technologies in the pre-pregnancy, preimplantation, prenatal and neonatal stages, as well as the trend of clinical transformation, highlighting the broad prospects of constructing an early and precise prevention and control system in the era of genomic medicine.

Birth defects and rare diseases have become major public health problems, and early prevention and control are the most effective interventions. In recent years, with the rapid development of genomic techniques such as high-throughput sequencing, the level of screening and diagnosis of genetic birth defects and rare diseases has been greatly improved. This article reviews the application of genomic technologies in the pre-pregnancy, preimplantation, prenatal and neonatal stages, as well as the trend of clinical transformation, highlighting the broad prospects of constructing an early and precise prevention and control system in the era of genomic medicine.

Objective:To investigate the correlation between serum complement C1q/tumor necrosis factor associated protein 3 (CTRP3) and carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).Methods:From January 2018 to December 2019, 111 T2DM patients hospitalized in the Endocrinology Department of Nantong Third People ′s Hospital Affiliated to Nantong University, and 30 healthy physical examiners in the physical examination center of Nantong Third People 's Hospital Affiliated to Nantong University in the same period were selected. Thirty cases of healthy physical examination were the control group, 111 cases of T2DM were divided into 52 cases of T2DM group and 59 cases of T2DM+NAFLD group according to whether they were combined with NAFLD. The cross-sectional study method was used to collect the relevant clinical data of three groups. The comparison data between multiple groups conformed to the normal distribution and the variance was uniform. One way ANOVA was used. SNK- q test was used for pairwise comparison, χ2 test for qualitative data comparison. The correlation between carotid intima-media thickness (IMT) and influencing factors was analyzed by partial correlation analysis, and the influencing factors of carotid IMT were analyzed by multi factor linear regression. Results:In the control group, T2DM group and T2DM+NAFLD group, body mass index (BMI) (23.65±2.81), (25.52±3.12), (24.90±2.94) kg/m 2,systolic blood pressure (119.43±15.81), (130.63±10.20), (139.37±14.11) mmHg, diastolic blood pressure (72.93±9.74), (73.40±9.44), (77.97±10.00) mmHg, and fasting blood glucose (5.12±0.77), (9.78±1.37), (9.24±1.46) mmol/L,glycosylated hemoglobin (HbA1c) (4.87±1.43)%, (7.99±1.10)%, (8.56±1.29)%,homeostasis model assessment of insulin resistance (HOMA-IR)(1.56±0.37),(2.80±1.00), (3.47±0.94), high density lipoprotein cholesterol (HDL-C) (1.52±0.34),(1.23±0.31), (1.22±0.31) mmol/L,low density lipoprotein cholesterol (LDL-C) (2.41±0.53), (2.73±0.61), (2.93±0.59) mmol/L, CTRP3 (292.93±68.54), (241.69±61.01), (150.80±56.67) μg/L, the difference between groups were statistically significant ( F=3.712,23.023,4.074,134.285,90.818,47.105,10.139,7.941,60.035,all P<0.05). Pairwise comparison shows that the systolic blood pressure, diastolic blood pressure, HbA1c and HOMA-IR in T2DM+NAFLD group were higher than those in control group and T2DM group,and CTRP3 was lower than those in control group and T2DM group, the difference was statistically significant (all P<0.05). BMI, fasting blood glucose, HbA1c, HOMA-IR, HDL-C and LDL-C in T2DM group were higher than those in the control group, CTRP3 was lower than that in the control group (all P<0.05). In the control group, T2DM group and T2DM+NAFLD group, IMT were (0.75±0.13), (1.11±0.17) and (1.25±0.15) cm; Crouse scores were (1.28±0.97), (3.22±1.42) and (4.54±1.22); the plaque detection rates 16.7%(5/30), 65.4%(34/52) and 78.0%(46/59), and there were significant differences between the two groups ( F=105.941,67.063, χ2=32.108, all P<0.001). There were significant differences between the two groups (all P<0.05). T2DM+NAFLD group was the highest, followed by T2DM group, and the control group was the lowest. Partial correlation analysis showed that carotid IMT was positively correlated with systolic blood pressure, fasting blood glucose, HbA1c, HOMA-IR, triglyceride and LDL-C ( r=0.356, 0.572, 0.575, 0.620, 0.172, 0.291, all P<0.05), and negatively correlated with HDL-C and CTRP3 ( r=-0.335, -0.675, all P<0.001). Multivariate linear regression analysis showed that HbA1c, HDL-C and ctrp3 were the influencing factors of carotid atherosclerosis ( t=2.621, -3.764, -7.280, all P<0.05) Conclusion:Serum CTRP3 is associated with carotid atherosclerosis in T2DM patients with NAFLD,and may have a protective effect on vascular lesions in T2DM patients with NAFLD.

At present, immunotherapy is in full swing in the treatment of non-small cell lung cancer, melanoma, bladder cancer and other tumor species, and its treatment methods are also diverse, including tumor vaccine treatment, adoptive T cell therapy, immune checkpoint inhibitor treatment, etc, but current immunotherapy for colorectal cancer mainly focuses on immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 inhibitors). Since PD-1/PD-L1 inhibitors have shown amazing efficacy in patients with dMMR/MSI-H advanced colorectal cancer, immune checkpoint inhibitors have gained more and more attention in the field of colorectal cancer, and the treatment options have gradually shifted from late line treatment to first-line treatment or neoadjuvant therapy, and have achieved success. This paper summarizes the research progress of immune checkpoint therapy on colorectal cancer.