Objective To analyze the combined effect of body mass index(BMI)and age with cancer occurrence among a hypertensive population in Minhang District,Shanghai.Methods Participants of this study were 212 394 hypertensive patients without cancer in Minhang District,Shanghai,registered in the electronic health information system from 2007 to 2015.Age and BMI were included as smoothing functions in the generalized additive Cox proportional risk model.The bivariate response model was constructed to visualize results using surface plots and to comprehensively analyze the association of BMI and age with the risk of cancer occurrence.Results A total of 22 141 participants developed cancer by Dec 31,2018.The association between age and the risk of cancer incidence showed an overall linear trend while the association between BMI and the risk of cancer incidence showed an overall"U"shape.BMI at about 26 kg/m2 showed the lowest risk of cancer incidence.The risk of cancer occurrence increased with increasing age in people with different BMIs.The associations between BMI and the risk of cancer incidence were different at different age groups:there was no significant association between BMI and the risk of cancer incidence in the young people(20-44 years).While in the middle-aged and older people aged over 45 years,BMI was associated with the risk of cancer incidence in a"U"shape.The lowest risk of cancer incidence was around the BMI of 26 kg/m2.Conclusion BMI among the population with hypertension should be controlled in a reasonable range,especially in the middle-aged and older population,to prevent cancer occurrence.

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Objective:To analyze the effects of SARS-CoV-2 infection and vaccination on virus mutation.Methods:The whole genome sequencing sequences of 2 659 local SARS-CoV-2 specimens from Jiangsu Province in 2023 were selected for analysis, and relevant information such as demographic and clinical characteristics were collected, and the effects of infection and vaccination on the genome-wide mutation rate and S gene′s selective pressure of the virus were analyzed by univariate and multivariate linear regression models.Results:The average age of these infected patients was 55.0 (31.0, 74.0) years, 1 150 cases (43.2%) in the age group of ≥60 years, 1 367 cases (51.4%) were males, 2 044 cases (76.9%) had a history of COVID-19 vaccination, and 1 629 cases (61.3%) had the first-time infection. The clinical symptoms of the infected patients were mainly mild, with a total of 2434 cases (91.5%), and 29 cases (1.1%) with severe symptoms or more. The average substitution rate of SARS-CoV-2 was 9.69 (9.38, 9.98)×10 -4 subs/site/year, and the dN/dS value of the S gene was 6.08 (5.56, 8.66), which was significantly greater than that of 1 ( P<0.001), indicating positive selection. The result of univariate and multivariate linear regression model analysis showed that the SARS-CoV-2 substitution rate was higher in those with vaccination history and reinfection, aged 20-30 years, ≥60 years, and the SARS-CoV-2 substitution rate was lower in males with moderate clinical symptoms and severe disease and above. Those with a history of vaccination and reinfection, aged 50-60 years old, ≥60 years old have smaller S gene dN/dS. Conclusions:Under the immune pressure exerted by vaccination and infection, the genome-wide mutation of SARS-COV-2 accelerated, but the non-synonymous mutation rate of the S gene decreased. The mechanism causing these phenomena needs further study.

Objective:To investigate the clinical effect of jujube core-shaped tissue resection technique in the treatment of alar reduction.Methods:A retrospective analysis was performed for the clinical data of patients who underwent alar reduction from February 2019 to June 2022. A spindle-shaped incision line was designed along the outer edge of the base of the nasal lobule, with a width of 4-5 mm and a length of 8-12 mm. The incision line was 1-2 mm away from the alar groove, and the inner side of the design line was extended to the inside of the nasal vestibule. After the incision was made, the subcutaneous tissue was undermining dissected with curved sharp scissors, and the shape of the extended excision tissue was similar to that of jujube core. After reduction, the incision was closed with vertical mattress suture. The surgical effect and complications were followed up after surgery, and an independent attending plastic surgeon evaluated the outcome and scarring based on photos before and at the last postoperative follow-up using the global aesthetic improvement scale (GAIS) and the Vancouver scar scale (VSS). GAIS is graded as 1, 2, 3, 4, and 5 points, and the lower the score, the better the improvement(≤3 points as effective improvement). VSS includes four parameters: color (0-3 points), thickness (0-4 points), vascular distribution (0-3 points), and softness (0-5 points). The higher the score, the more significant the scar is.Results:A total of 20 patients were enrolled, including 6 males and 14 females, aged 20 to 33 years, with an average age of 24.9 years. Before the operation, there were different degrees of alar flare and alar hypertrophy. After surgery, 13 patients had mild swelling, ecchymosis, which resolved after 3 days. There were no major complications as infection, incision dehiscence, and delayed healing. After 3 to 16 months of postoperative follow-up, 2 patients gradually developed cartilage deformation and affected the appearance of the nostrils 6 to 9 months after surgery due to the combination of rib-based rhinoplasty, and the satisfactory results were obtained after revision surgery. The symmetry of the nostrils was significantly improved. The GAIS score of 20 patients was (1.20±0.41) points, of which, 16 patients were rated as 1 point and 4 patients were rated as 2 points, all of which met the improvement criteria, and the VSS score was (1.45±0.60) points, in which the average score for color, thickness, vasculature and compliance are 0.60, 0.05, 0.55 and 0.30 points respectively.Conclusion:The application of jujube core-shaped tissue resection technique for alar reduction can increase the amount of tissue removal with the same incision width, which can not only fully narrow the alar effectively but also correct the hypertrophy of the alar tissue.

Objective:To investigate the clinical effect of jujube core-shaped tissue resection technique in the treatment of alar reduction.Methods:A retrospective analysis was performed for the clinical data of patients who underwent alar reduction from February 2019 to June 2022. A spindle-shaped incision line was designed along the outer edge of the base of the nasal lobule, with a width of 4-5 mm and a length of 8-12 mm. The incision line was 1-2 mm away from the alar groove, and the inner side of the design line was extended to the inside of the nasal vestibule. After the incision was made, the subcutaneous tissue was undermining dissected with curved sharp scissors, and the shape of the extended excision tissue was similar to that of jujube core. After reduction, the incision was closed with vertical mattress suture. The surgical effect and complications were followed up after surgery, and an independent attending plastic surgeon evaluated the outcome and scarring based on photos before and at the last postoperative follow-up using the global aesthetic improvement scale (GAIS) and the Vancouver scar scale (VSS). GAIS is graded as 1, 2, 3, 4, and 5 points, and the lower the score, the better the improvement(≤3 points as effective improvement). VSS includes four parameters: color (0-3 points), thickness (0-4 points), vascular distribution (0-3 points), and softness (0-5 points). The higher the score, the more significant the scar is.Results:A total of 20 patients were enrolled, including 6 males and 14 females, aged 20 to 33 years, with an average age of 24.9 years. Before the operation, there were different degrees of alar flare and alar hypertrophy. After surgery, 13 patients had mild swelling, ecchymosis, which resolved after 3 days. There were no major complications as infection, incision dehiscence, and delayed healing. After 3 to 16 months of postoperative follow-up, 2 patients gradually developed cartilage deformation and affected the appearance of the nostrils 6 to 9 months after surgery due to the combination of rib-based rhinoplasty, and the satisfactory results were obtained after revision surgery. The symmetry of the nostrils was significantly improved. The GAIS score of 20 patients was (1.20±0.41) points, of which, 16 patients were rated as 1 point and 4 patients were rated as 2 points, all of which met the improvement criteria, and the VSS score was (1.45±0.60) points, in which the average score for color, thickness, vasculature and compliance are 0.60, 0.05, 0.55 and 0.30 points respectively.Conclusion:The application of jujube core-shaped tissue resection technique for alar reduction can increase the amount of tissue removal with the same incision width, which can not only fully narrow the alar effectively but also correct the hypertrophy of the alar tissue.

Objective To investigate the predictive value of nutritional status assessment for postoperative delirium (POD) risk in elderly patients with hip fracture. Methods A total of 114 elderly patients with hip fracture were selected as study subjects. According to the occurrence of POD, they were divided into delirium group (43 cases) and non-delirium group (71 cases). General information, laboratory indicators, geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) scores were collected for the two groups. Multivariate Logistic regression analysis was used to explore the independent influencing factors of POD occurrence. Receiver operating characteristic (ROC) curves were plotted, and the area under the curves (AUC) were calculated to analyze the predictive value of each independent influencing factor for POD risk. Results The proportion of diabetic patients, fasting blood glucose and CONUT scores in the delirium group were higher, but GNRI and PNI were lower than that in the non-delirium group (P < 0.05). Multivariate Logistic regression analysis showed that blood glucose, GNRI, PNI, and CONUT scores were independent influencing factors for POD occurrence (P < 0.05). ROC curve analysis revealed that the AUCs of blood glucose, GNRI, PNI, and CONUT scores alone in predicting POD risk were 0.610, 0.780, 0.821, and 0.749, respectively, which were lower than the AUC (0.897) when the four factors were combined. Conclusion Blood glucose, GNRI, PNI, and CONUT scores are independent influencing factors for POD occurrence in elderly patients with hip fracture. The combined use of these four factors has good predictive value for POD risk.

This paper aimed to investigate the role and potential mechanism of p53 on primordial follicle activation. Firstly, the p53 mRNA expression in the ovary of neonatal mice at 3, 5, 7 and 9 days post-partum (dpp) and the subcellular localization of p53 were detected to confirm the expression pattern of p53. Secondly, 2 dpp and 3 dpp ovaries were cultured with p53 inhibitor Pifithrin-μ (PFT-μ, 5 μmol/L) or equal volume of dimethyl sulfoxide for 3 days. The function of p53 in primordial follicle activation was determined by hematoxylin staining and whole ovary follicle counting. The proliferation of cell was detected by immunohistochemistry. The relative mRNA levels and protein levels of the key molecules involved in the classical pathways associated with the growing follicles were examined by immunofluorescence staining, Western blot and real-time PCR, respectively. Finally, rapamycin (RAP) was used to intervene the mTOR signaling pathway, and ovaries were divided into four groups: Control, RAP (1 μmol/L), PFT-μ (5 μmol/L), PFT-μ (5 μmol/L) + RAP (1 μmol/L) groups. The number of follicles in each group was determined by hematoxylin staining and whole ovary follicle counting. The results showed that the expression of p53 mRNA was decreased with the activation of primordial follicles in physiological condition. p53 was expressed in granulosa cells and oocyte cytoplasm of the primordial follicles and growing follicles, and the expression of p53 in the primordial follicles was higher than that in the growing follicles. Inhibition of p53 promoted follicle activation and reduced the primordial follicle reserve. Inhibition of p53 promoted the proliferation of the granulosa cells and oocytes. The mRNA and protein expression levels of key molecules in the PI3K/AKT signaling pathway including AKT, PTEN, and FOXO3a were not significantly changed after PFT-μ treatment, while the expression of RPS6/p-RPS6, the downstream effectors of the mTOR signaling pathway, was upregulated. Inhibition of both p53 and mTOR blocked p53 inhibition-induced primordial follicle activation. Collectively, these findings suggest that p53 may inhibit primordial follicle activation through the mTOR signaling pathway to maintain the primordial follicle reserve.
Female ; Animals ; Mice ; Tumor Suppressor Protein p53/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Hematoxylin ; Signal Transduction/physiology* ; TOR Serine-Threonine Kinases ; Sirolimus ; RNA, Messenger

Delayed wound healing in diabetes is a global challenge, and the development of related drugs is a clinical problem to be solved. In this study, purpurolide C (PC), a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum, was found to promote diabetic wound healing. To investigate the key regulation targets of PC, in vitro RNA-seq, molecular docking calculations, TLR4-MD2 dimerization SDS-PAGE detection, and surface plasmon resonance (SPR) were performed, indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation. Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing. Furthermore, a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC (PC@MLIP MN) was developed, which overcame the poor water solubility and weak skin permeability of PC, so that successfully punctured the skin and delivered PC to local tissues, and accurately regulated macrophage polarization in diabetic wound management. Overall, PC is an anti-inflammatory small molecule compound with a well-defined structure and dual-target regulation, and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*