Development and Characterization of an Antioxidant and Antimicrobial Film Composited by Hydroxyethyl Cellulose and Sulfated Rice Bran Polysaccharides for Food Packaging.

The nonantimicrobial properties and relatively poor mechanical properties of hydroxyethyl cellulose (HEC) limit its use in packaging. Sulfated rice bran polysaccharides (SRBP) possess significant antioxidant and antimicrobial activities. The purpose of this study was to investigate the effect of different concentrations of SRBP on the physical and mechanical properties and the functional characteristics of HEC/SRBP films. The physical properties of the HEC/20% SRBP films, such as water resistance, water vapor barrier, light barrier, and tensile strength, improved significantly (p < 0.05) compared with those of the HEC films. Scanning electron microscopy and Fourier transform infrared spectrometry showed that HEC formed hydrogen bonds with SRBP and exhibited better compatibility. Thermogravimetric analysis revealed that the addition of SRBP was beneficial to the thermal stability of the films. In addition, the antioxidant and bacteriostatic properties of the films were enhanced by the addition of SRBP to HEC, with the 20% SRBP films showing the most significant enhancement in activity. Therefore, the HEC/20% SRBP films show potential for development for use as active food packaging.

Identification, in silico selection, and mechanistic investigation of antioxidant peptides from corn gluten meal hydrolysate.

Seven novel antioxidant peptides (AWF, LWQ, WIY, YLW, LAYW, LPWG, and LYFY) exhibiting a superior activity compared to trolox were identified through in silico screening. Among these, the four peptides (WIY, YLW, LAYW, and LYFY) displayed notably enhanced performance, with ABTS activity 2.58-3.26 times and ORAC activity 5.19-8.63 times higher than trolox. Quantum chemical calculations revealed that the phenolic hydroxyl group in tyrosine and the nitrogen-hydrogen bond in the indole ring of tryptophan serve as the critical sites for antioxidant activity. These findings likely account for the potent chemical antioxidant activity. The corn peptides also exerted a protective effect against AAPH-induced cytomorphologic changes in human erythrocytes by modulating the antioxidant system. Notably, LAYW exhibited the most pronounced cytoprotective effects, potentially due to its high content of hydrophobic amino acids.

Physiological and transcriptomic analysis revealed the alleviating effect of 1,25(OH)2D3 on environmental iron overloading induced ferroptosis in zebrafish.

Iron overload in the aquatic environment can cause damage in fish bodies. Vitamin D3 (VD3) has been proven to have antioxidant and regulatory effects on iron transport. The current research investigated the effects of environmental iron overload on larval zebrafish and explored the effects of 1,25(OH)2D3 on ferroptosis in zebrafish larvae and zebrafish liver cells (ZFL) caused by iron overload in the environment and its possible regulatory mechanisms. The results showed that 1,25(OH)2D3 alleviated liver damage in zebrafish larvae and mitochondrial damage in ZFL after excessive ammonium ferric citrate (FAC) treatment, and improved the survival rate of ZFL. 1,25(OH)2D3 cleared and inhibited excessive FAC induced abnormal accumulation of ROS, lipid ROS, MDA, and Fe2+ in zebrafish larvae and ZFL, as well as enhanced the activity of antioxidant enzyme GPx4. Transcriptomic analysis showed that 1,25(OH)2D3 can regulate ferroptosis in ZFL by regulating signaling pathways related to oxidative stress, iron homeostasis, mitochondrial function, and ERS, mainly including ferroptosis, neoptosis, p53 signaling pathway, apoptosis, FoxO signaling pathway. Validation of transcriptome data showed that 1,25(OH)2D3 inhibits ferroptosis in zebrafish larvae and ZFL caused by excessive FAC via promoting the expression of slc40a1 and hmox1a genes and increasing SLC40A1 protein levels. In summary, 1,25(OH)2D3 can resist ferroptosis in zebrafish caused by iron overload in the environment mainly via regulating antioxidant capacity and iron ion transport.

Effect of M0 macrophage-derived exosome miR-181d-5p targeting BCL-2 to regulate NLRP3/caspase-1/GSDMD pathway on human renal mesangial cells pyroptosis.

BACKGROUND: Lupus nephritis (LN) is a type of autoimmune disease that impacts the kidneys. Exosomes are valuable for in-depth studies of the pathogenesis of LN. This study aimed to explore miR-181d-5p expression levels in M0 macrophage-derived exosomes and their role in human renal mesangial cells (HRMC) pyroptosis through binding to BCL-2. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from patients with lupus nephritis (LN) and healthy subjects. Monocytes isolated from these samples were induced into M0 macrophages using recombinant human granulocyte colony-stimulating factor (rhG-CSF). In a parallel process, THP-1 cells were induced into M0 macrophages using Phorbol Myristate Acetate (PMA). LPS- and ATP-stimulated HRMC were used to construct a cell pyroptosis model. We then introduced different miR-181d-5p mimic fragments into the M0 macrophages derived from the THP-1 cells. Subsequently, exosomes from these macrophages were co-cultured with HRMC. To evaluate the impact on HRMC, we conducted proliferation and apoptosis assessments using CellCountingKit-8assay and flow cytometry. The effect of exosomal miR-181d-5p on HRMC pyroptosis was assessed using western blot. The miR-181d-5p and BCL-2 targeting relationship was detected using real-time fluorescence quantitative PCR. IL-6, IL-1ß, and TNF-α levels in cell supernatants were detected using ELISA kits. RESULTS: In this study, we observed an increase in miR-181d-5p levels within exosomes secreted from M0 macrophages obtained by induction of monocytes from LN patients. It was found that miR-181d-5p can target binding to BCL-2. Exosomes with elevated levels of miR-181d-5p contributed to a significant increase in miR-181d-5p within HRMC, facilitating its proliferation and inhibiting apoptosis. Furthermore, exosomes expressing high levels of miR-181d-5p were observed to promote an inflammatory response and pyroptosis in HRMC. Notably, these effects were reversed when the levels of miR-181d-5p in the exosomes were reduced. CONCLUSION: Inhibition of miR-181d-5p, derived from M0 macrophage exosomes, effectively suppresses inflammation and pyroptosis in HRMC. This discovery indicates that miR-181d-5p holds the potential as a valuable target in the development of treatments for Lupus Nephritis (LN).

Incorporation of Decidual Stromal Cells Derived Exosomes in Sodium Alginate Hydrogel as an Innovative Therapeutic Strategy for Advancing Endometrial Regeneration and Reinstating Fertility.

Intrauterine adhesion (IUA) stands as a prevalent medical condition characterized by endometrial fibrosis and scar tissue formation within the uterine cavity, resulting in infertility and, in severe cases, recurrent miscarriages. Cell therapy, especially with stem cells, offers an alternative to surgery, but concerns about uncontrolled differentiation and tumorigenicity limit its use. Exosomes, more stable and immunogenicity-reduced than parent cells, have emerged as a promising avenue for IUA treatment. In this study, a novel approach has been proposed wherein exosomes originating from decidual stromal cells (DSCs) are encapsulated within sodium alginate hydrogel (SAH) scaffolds to repair endometrial damage and restore fertility in a mouse IUA model. Current results demonstrate that in situ injection of DSC-derived exosomes (DSC-exos)/SAH into the uterine cavity has the capability to induce uterine angiogenesis, initiate mesenchymal-to-epithelial transformation (MET), facilitate collagen fiber remodeling and dissolution, promote endometrial regeneration, enhance endometrial receptivity, and contribute to the recovery of fertility. RNA sequencing and advanced bioinformatics analysis reveal miRNA enrichment in exosomes, potentially supporting endometrial repair. This finding elucidates how DSC-exos/SAH mechanistically fosters collagen ablation, endometrium regeneration, and fertility recovery, holding the potential to introduce a novel IUA treatment and offering invaluable insights into the realm of regenerative medicine.

[Meta-analysis of the role of fibular fixation in tibiofibular fractures].

OBJECTIVE: To compare the role and importance of fibular fixation in tibiofibular fractures by Meta-analysis. METHODS: The literature related to the comparison of the efficacy of fixation of the fibula with or without fixation on the treatment of tibiofibular fractures was searched through the databases of China Knowledge Network, Wipu, Wanfang, The Cochrane Library, Web of science and Pubmed, and statistical analysis was performed using RevMan 5.3 software. The rates of malrotation, rotational deformity, internal/external deformity, anterior/posterior deformity, non-union, infection, secondary surgery and operative time were compared between the fibula fixation and non-fixation groups. RESULTS: A total of 11 publications were included, six randomised controlled trials and five case-control trials, eight of which were of high quality. A total of 813 cases were included, of which 383 were treated with fibula fixation and 430 with unfixed fibulae.Meta-analysis results showed that fixation of the fibulae in the treatment of tibiofibular fractures reduced the rates of postoperative rotational deformity[RR=0.22, 95%CI(0.10, 0.45), P<0.000 1] and internal/external deformity[RR=0.34, 95%CI(0.14, 0.84), P=0.02] and promoted fracture healing [RR=0.76, 95%CI(0.58, 0.99), P=0.04]. In contrast, the rates of poor reduction [RR=0.48, 95% CI(0.10, 2.33), P=0.36], anterior/posterior deformity[RR=1.50, 95%CI(0.76, 2.96), P=0.24], infection[RR=1.43, 95%CI(0.76, 2.72), P=0.27], secondary surgery[RR=1.32, 95%CI(0.82, 2.11), P=0.25], and operative time[MD=10.21, 95%CI(-17.79, 38.21), P=0.47] were not statistically significant (P>0.05) for comparison. CONCLUSION: Simultaneous fixation of the tibia and fibula is clinically more effective in the treatment of tibiofibular fractures.

Is robotic-assisted vaginectomy a better choice in vaginal high-grade squamous intraepithelial lesions than conventional laparoscopic surgery?

BACKGROUND: Vaginectomy has been shown to be effective for select patients with vaginal high-grade squamous intraepithelial lesions (HSIL) and is favored by gynecologists, while there are few reports on the robotic-assisted laparoscopic vaginectomy (RALV). The aim of this study was to evaluate the safety and treatment outcomes between RALV and the conventional laparoscopic vaginectomy (CLV) for patients with vaginal HSIL. METHODS: This retrospective cohort study was conducted in 109 patients with vaginal HSIL who underwent either RALV (RALV group) or CLV (CLV group) from December 2013 to May 2022. The operative data, homogeneous HPV infection regression rate and vaginal HSIL regression rate were compared between the two groups. Student's t-test, the Mann-Whitney U test, Pearson χ2 test or the Fisher exact test, Kaplan-Meier survival analysis and Cox proportional-hazards models were used for data analysis. RESULTS: There were 32 patients in the RALV group and 77 patients in the CLV group. Compared with the CLV group, patients in the RALV group demonstrated less estimated blood loss (41.6 ± 40.3 mL vs. 68.1 ± 56.4 mL, P = 0.017), lower intraoperative complications rate (6.3% vs. 24.7%, P = 0.026), and shorter flatus passing time (2.0 (1.0-2.0) vs. 2.0 (2.0-2.0), P < 0.001), postoperative catheterization time (2.0 (2.0-3.0) vs. 4.0 (2.0-6.0), P = 0.001) and postoperative hospitalization time (4.0 (4.0-5.0) vs. 5.0 (4.0-6.0), P = 0.020). In addition, the treatment outcomes showed that both RALV group and CLV group had high homogeneous HPV infection regression rate (90.0% vs. 92.0%, P > 0.999) and vaginal HSIL regression rate (96.7% vs. 94.7%, P = 0.805) after vaginectomy. However, the RALV group had significantly higher hospital costs than that in the CLV group (53035.1 ± 9539.0 yuan vs. 32706.8 ± 6659.2 yuan, P < 0.001). CONCLUSIONS: Both RALV and CLV can achieve satisfactory treatment outcomes, while RALV has the advantages of less intraoperative blood loss, fewer intraoperative complications rate and faster postoperative recovery. Robotic-assisted surgery has the potential to become a better choice for vaginectomy in patients with vaginal HSIL without regard to the burden of hospital costs.

Exogenous 1,25(OH)2D3/VD3 counteracts RSL3-Induced ferroptosis by enhancing antioxidant capacity and regulating iron ion transport: Using zebrafish as a model.

RSL3 is a common inhibitor of glutathione peroxidase 4 (GPx4) that can induce ferroptosis. Ferroptosis is an iron ion-dependent, oxidative-type of programmed cell death. In this study, larval/adult zebrafish were stimulated with RSL3 to construct a ferroptosis model, and CYP2R1-/- zebrafish was used as a 1,25(OH)2D3 knock-down model to explore the regulatory effect and mechanism of 1,25(OH)2D3/VD3 on RSL3-induced ferroptosis. The results showed that 1,25(OH)2D3/VD3 alleviated RSL3 induced mitochondrial damage in liver of larval/adult zebrafish, reversed the decline of GPx4 activity, and reduced the accumulation of ROS, LPO and MDA. VD3 also inhibited hepcidin (HEPC) in adult fish liver, promoted the production of ferroportin (FPN), and reduced the aggregation of Fe2+. Exogenous 1,25(OH)2D3 increased the CYP2R1-/- survival and liver GPx4 activity after RSL3 treatment. At the gene level, 1,25(OH)2D3/VD3 activated Keap1-Nrf2-GPx4 and inhibited the NFκB-hepcidin axis. In the ferroptosis context, deletion of the cyp2r1 gene resulted in a more severe decline in gpx4 expression, but the exogenous 1,25(OH)2D3 increased the expression of the GPx4 gene and protein in CYP2R1-/- zebrafish liver after RSL3 treatment. The collective results indicated that 1,25(OH)2D3/VD3 can inhibit ferroptosis induced by RSL3 in liver of larval/adult zebrafish by improving the antioxidant capacity and regulating iron ion transport. Exogenous 1,25(OH)2D3 reverses the downregulation of GPx4 in the CYP2R1-/- zebrafish liver in the ferroptosis state. Compared with the ferroptosis inhibitor Fer-1, the mechanism of action of 1,25(OH)2D3/VD3 is diversified and nonspecific. This study demonstrated the resistance of VD3 to RSL3-induced ferroptosis at different developmental stages in zebrafish.

Vitamin D3 promotes fish oocyte development by directly regulating gonadal steroid hormone synthesis†.

Vitamin D receptors and vitamin D3-metabolizing enzymes have been found to be highly expressed in the ovaries and spermatophores of fish. However, the role of vitamin D3 on fish gonadal development has rarely been reported. In this study, 2-month-old female zebrafish were fed with different concentrations of vitamin D3 diets (0, 700, 1400, and 11 200 IU/kg) to investigate the effects of vitamin D3 on ovarian development. The diet with 0 IU/kg vitamin D3 resulted in elevated interstitial spaces, follicular atresia, and reproductive toxicity in zebrafish ovaries. Supplementation with 700 and 1400 IU/kg of vitamin D3 significantly increased the oocyte maturation rate; upregulated ovarian gonadal steroid hormone synthesis capacity; and elevated plasma estradiol, testosterone, and ovarian vitellogenin levels. Furthermore, the current study identified a vitamin D response element in the cyp19a1a promoter and demonstrated that 1.25(OH)2D3-vitamin D response directly activated cyp19a1a production through activating the vitamin D response element. In conclusion, this study shows that an appropriate concentration of vitamin D3 can promote zebrafish ovarian development and affect vitellogenin synthesis through the vdr/cyp19a1a/er/vtg gene axis.

TMT quantitative proteomics reveals key proteins relevant to microRNA-1-mediated regulation in osteoarthritis.

Osteoarthritis (OA) is the second-commonest arthritis, but pathogenic and regulatory mechanisms underlying OA remain incompletely understood. Here, we aimed to identify the mechanisms associated with microRNA-1 (miR-1) treatment of OA in rodent OA models using a proteomic approach. First, N = 18 Sprague Dawley (SD) rats underwent sham surgery (n = 6) or ACL transection (n = 12), followed at an interval of one week by randomization of the ACL transection group to intra-articular administration of either 50 µL placebo (control group) or miR-1 agomir, a mimic of endogenous miR-1 (experimental group). After allowing for eight weeks of remodeling, articular cartilage tissue was harvested and immunohistochemically stained for the presence of MMP-13. Second, N = 30 Col2a1-cre-ERT2 /GFPf1/fl -RFP-miR-1 transgenic mice were randomized to intra-articular administration of either placebo (control group, N = 15) or tamoxifen, an inducer of miR-1 expression (experimental group, N = 15), before undergoing surgical disruption of the medial meniscus (DMM) after an interval of five days. After allowing for eight weeks of remodeling, articular cartilage tissue was harvested and underwent differential proteomic analysis. Specifically, tandem mass tagging (TMT) quantitative proteomic analysis was employed to identify inter-group differentially-expressed proteins (DEP), and selected DEPs were validated using real-time quantitative polymerase chain reaction (RT-qPCR) technology. Immunohistochemically-detected MMP-13 expression was significantly lower in the experimental rat group, and proteomic analyses of mouse tissue homogenate demonstrated that of 3526 identified proteins, 345 were differentially expressed (relative up- and down-regulation) in the experimental group. Proteins Fn1, P4ha1, P4ha2, Acan, F2, Col3a1, Fga, Rps29, Rpl34, and Fgg were the *top ten most-connected proteins, implying that miR-1 may regulate an expression network involving these proteins. Of these ten proteins, three were selected for further validation by RT-qPCR: the transcript of Fn1, known to be associated with OA, exhibited relative upregulation in the experimental group, whereas the transcripts of P4ha1 and Acan exhibited relative downregulation. These proteins may thus represent key miR-1 targets during OA-regulatory mechanisms, and may provide additional insights regarding therapeutic mechanisms of miR-1 in context of OA.

[Clinical analysis of 11 cases of otogenic intracranial complications treated by multidisciplinary collaboration].

Objective:To analyze the clinical diagnosis, treatment ，and surgical timing of otogenic intracranial complications. Methods:The clinical data of 11 patients with intracranial complications with ear symptoms as the first manifestation in Department of Otorhinolaryngology Head and Neck Surgery, Qilu Hospital of Shandong University（Qingdao） from December 2014 to June 2022 were collected, including 8 males and 3 females, aged from 4 to 69 years. All patients had complete otoendoscopy, audiology, imaging and etiology examination, and the diagnosis and treatment plan was jointly developed through multidisciplinary consultation according to the critical degree of clinical symptoms and imaging changes. Among the 11 patients, 5 cases were treated with intracranial lesions first in neurosurgery department and middle ear lesions later in otolaryngology, 3 cases of meningitis, were treated with middle ear surgery after intracranial infection control, 1 case was treated with middle ear lesions and intracranial infection simultaneously, and 2 cases were treated with sigmoid sinus and transverse sinus thrombosis conservatively. They were followed up for 1-6 years. Descriptive statistical methods were used for analysis. Results:All the 11 patients had ear varying symptoms, including ear pain, pus discharge and hearing loss, etc, and then fever appeared, headache, disturbance of consciousness, facial paralysis and other intracranial complication. Otoendoscopy showed perforation of the relaxation of the tympanic membrane in 5 cases, major perforation of the tension in 3 cases, neoplasia in the ear canal in 1 case, bulging of the tympanic membrane in 1 case, and turbidity of the tympanic membrane in 1 case. There were 4 cases of conductive hearing loss, 4 cases of mixed hearing loss and 3 cases of total deafness. Imaging examination showed cholesteatoma of the middle ear complicated with temporal lobe brain abscess in 4 cases, cerebellar abscess in 2 cases, cholesteatoma of the middle ear complicated with intracranial infection in 3 cases, and sigmoid sinus thrombophlebitis in 2 cases. In the etiological examination, 2 cases of Streptococcus pneumoniae were cultured in the pus of brain abscess and cerebrospinal fluid, and 1 case was cultured in streptococcus vestibularis, Bacteroides uniformis and Proteus mirabilis respectively. During the follow-up, 1 patient died of cardiovascular disease 3 years after discharge, and the remaining 10 patients survived. There was no recurrence of intracranial and middle ear lesions. Sigmoid sinus and transverse sinus thrombosis were significantly improved. Conclusion:Brain abscess, intracranial infection and thrombophlebitis are the most common otogenic intracranial complications, and cholesteatoma of middle ear is the most common primary disease. Timely diagnosis, multidisciplinary collaboration, accurate grasp of the timing in the treatment of primary focal and complications have improved the cure rate of the disease.

Reactive Oxygen Species-Mediated Mitophagy and Cell Apoptosis are Involved in the Toxicity of Aluminum Chloride Exposure in GC-2spd.

Aluminum chloride is an inorganic polymeric coagulant commonly found in daily life and various materials. Although male reproductive toxicity has been associated with AlCl3 exposure, the underlying mechanism remains unclear. This study aimed to examine the impact of AlCl3 exposure on mitophagy and mitochondrial apoptosis in testicular tissue and mouse spermatocytes. Reactive oxygen species (ROS) and ATP levels were measured in GC-2spd after AlCl3 exposure using a multifunctional enzyme labeler. The changes in mitochondrial membrane potential (MMP) and TUNEL were observed through confocal laser microscopy, and the expression of proteins associated with mitophagy and apoptosis was analyzed using Western blot. Our results demonstrated that AlCl3 exposure disrupted mitophagy and increased apoptosis-related protein expression in testicular tissues. In the in vitro experiments, AlCl3 exposure induced ROS production, suppressed cell viability and ATP production, and caused a decrease in MMP, leading to mitophagy and cell apoptosis in GC-2spd cells. Intervention with N-acetylcysteine (NAC) reduced ROS production and partially restored mitochondrial function, thereby reversing the resulting mitophagy and cell apoptosis. Our findings provide evidence that ROS-mediated mitophagy and cell apoptosis play a crucial role in the toxicity of AlCl3 exposure in GC-2spd. These results contribute to the understanding of male reproductive toxicity caused by AlCl3 exposure and offer a foundation for future research in this area.

Adipose transplantation improves olfactory function and neurogenesis via PKCα-involved lipid metabolism in Seipin Knockout mice.

BACKGROUND: Lipodystrophy-associated metabolic disorders caused by Seipin deficiency lead to not only severe lipodystrophy but also neurological disorders. However, the underlying mechanism of Seipin deficiency-induced neuropathy is not well elucidated, and the possible restorative strategy needs to be explored. METHODS: In the present study, we used Seipin knockout (KO) mice, combined with transcriptome analysis, mass spectrometry imaging, neurobehavior test, and cellular and molecular assay to investigate the systemic lipid metabolic abnormalities in lipodystrophic mice model and their effects on adult neurogenesis in the subventricular zone (SVZ) and olfactory function. After subcutaneous adipose tissue (AT) transplantation, metabolic and neurological function was measured in Seipin KO mice to clarify whether restoring lipid metabolic homeostasis would improve neurobehavior. RESULTS: It was found that Seipin KO mice presented the ectopic accumulation of lipids in the lateral ventricle, accompanied by decreased neurogenesis in adult SVZ, diminished new neuron formation in the olfactory bulb, and impaired olfactory-related memory. Transcriptome analysis showed that the differentially expressed genes (DEGs) in SVZ of adult Seipin KO mice were significantly enriched in lipid metabolism. Mass spectrometry imaging showed that the levels of glycerophospholipid and diglyceride (DG) were significantly increased. Furthermore, we found that AT transplantation rescued the abnormality of peripheral metabolism in Seipin KO mice and ameliorated the ectopic lipid accumulation, concomitant with restoration of the SVZ neurogenesis and olfactory function. Mechanistically, PKCα expression was up-regulated in SVZ tissues of Seipin KO mice, which may be a potential mediator between lipid dysregulation and neurological disorder. DG analogue (Dic8) can up-regulate PKCα and inhibit the proliferation and differentiation of neural stem cells (NSCs) in vitro, while PKCα inhibitor can block this effect. CONCLUSION: This study demonstrates that Seipin deficiency can lead to systemic lipid disorder with concomitant SVZ neurogenesis and impaired olfactory memory. However, AT restores lipid homeostasis and neurogenesis. PKCα is a key mediator mediating Seipin KO-induced abnormal lipid metabolism and impaired neurogenesis in the SVZ, and inhibition of PKCα can restore the impaired neurogenesis. This work reveals the underlying mechanism of Seipin deficiency-induced neurological dysfunction and provides new ideas for the treatment of neurological dysfunction caused by metabolic disorders.

Pancreatic cancer incidence and mortality trends in urban Shanghai, China from 1973 to 2017: a joinpoint regression and age-period-cohort analysis.

Background and purpose: To provide a comprehensive overview of epidemiological features and temporal trends of pancreatic cancer in urban Shanghai from 1973 to 2017. Methods: Data on pancreatic cancer in urban Shanghai were obtained through the Shanghai Cancer Registry and the Vital Statistics System. Joinpoint analysis was used to describe the temporal trends and annual percent changes (APCs) and age-period-cohort analysis were used to estimate the effects of age, period, and birth cohort on pancreatic cancer. Results: There were a total of 29,253 cases and 27,105 deaths of pancreatic cancer in urban Shanghai over the 45-year study period. The overall average annual age-standardized incidence and mortality rates were 5.45/100,000 and 5.02/100,000, respectively. Both the incidence and mortality rates demonstrated fluctuating upward trends, with an average annual increase rate of 1.51% (APC = 1.51, P < 0.001) and 1.04% (APC = 1.04, P < 0.001), respectively. The upward trend in incidence was greater for females than for males, while the trend in mortality was seen in both sexes equally and continuously. In recent years (2013-2017), the age-specific incidence rates increased further than before, with statistically significant changes in the 35-year, 45- to 55-year and 70- to 85-year age groups (P < 0.05). The age-specific mortality rates also showed obvious upward trends, which in the 50- to 55-year, and 75- to 85-year age groups increased significantly. The results of the age-period-cohort analysis suggested significant effects of age, period, and cohort on the prevalence of pancreatic cancer. Conclusion: The prevalence of pancreatic cancer, dramatically influenced by socioeconomic development and lifestyles, demonstrated a significant upward trend from 1973 to 2017 in urban Shanghai and underscored the necessity and urgency for additional efforts in primary and secondary prevention measures.

Natto: A medicinal and edible food with health function.

Natto is a soybean product fermented by natto bacteria. It is rich in a variety of amino acids, vitamins, proteins and active enzymes. It has a number of biological activities, such as thrombolysis, prevention of osteoporosis, antibacterial, anticancer, antioxidant and so on. It is widely used in medicine, health-care food, biocatalysis and other fields. Natto is rich in many pharmacological active substances and has significant medicinal research value. This paper summarizes the pharmacological activities and applications of natto in and outside China, so as to provide references for further research and development of natto.

miR-31 ameliorates type 2 diabetic vascular damage through up-regulation of hypoxia-inducible factor-1α/vascular endothelial growth factor-A.

AIMS: microRNA may be a new therapeutic direction for diabetes. As a typical tumor marker, miR-31 is involved in a variety of metabolic diseases, but the specific role is still unclear. This study aimed to investigate the effect of miR-31 on type 2 diabetes mellitus and its accompanying vascular injury, as well as on the effects of hypoxia-inducible factor-1α inhibitor (HIF1AN), hypoxia-inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF)-A expression in vitro and in vivo. MATERIALS AND METHODS: In vitro, a model of high-fat and high-glucose-induced human aortic endothelial cell (HAEC) injury was established to simulate diabetes mellitus (DM). Cell functions were compared between the control group, the DM damage group, and the group transfected with miR-31 after DM damage. In vivo, overexpressing miR-31 FVB mice and FVB mice were divided into the control and induced type 2 diabetes mellitus groups. Type 2 diabetes mellitus models were induced by a high-fat diet combined with streptozotocin. The lipid metabolism levels, viscera, and vascular damage were compared between the control and type 2 diabetes mellitus groups. RESULTS: In vitro, miR-31 improved the proliferation ability of damaged cells by targeting HIF1AN and up-regulating the expression of HIF-1α and VEGF-A. In vivo, miR-31 ameliorated the development of type 2 diabetes mellitus, disturbance of glucose and lipid metabolism, and damage to some organs. Meanwhile, miR-31 had a protective effect on vascular damage complicated by type 2 diabetes mellitus by increasing the levels of HIF-1α and VEGF-A. CONCLUSION: Our experiments show that miR-31 can delay the progression of type 2 diabetes mellitus and ameliorate diabetic vascular injury.

Correlation analysis of circulating tumor cells and Claudin-4 in breast cancer.

Objective: We aimed to explore the relationship between peripheral blood circulating tumor cells (CTCs) and the expression of Claudin-4 in patients with breast cancer, and further explore the potential impact on clinical prognosis and risk assessment. Methods: We classified and enumerated circulating tumor cells in the blood of breast cancer patients by CTC-enriched in situ hybridization and the detection of Claudin-4 expression by immunohistochemistry. We carried out an analysis of the correlation between the two and the comparison of their impact on clinical parameters and prognosis. Results: There were 38 patients with a low expression of Claudin-4 and 27 patients with a high expression of Claudin-4. Compared with Claudin-4 low-expression patients, the number of CTCs was higher in patients with high Claudin-4 expression (11.7 vs. 7.4, p < 0.001). High Claudin-4 expression was associated with a lower count of epithelial CTCs (E-CTCs) (3.4 vs. 5.0, p = 0.033), higher counts of mesenchymal CTCs (M-CTC) (4.4 vs. 1.1, p < 0.001), and epithelial/mesenchymal CTCs (E/M-CTCs) (4.0 vs. 3.5, p = 0.021). The intensity of Claudin-4 was positively correlated with CTC (rs = 0.43, p = 0.001). Multivariate COX regression analysis showed that CTC counts (HR = 1.3, p < 0.001), Claudin-4 (HR = 4.6, p = 0.008), and Lymphatic metastasis (HR = 12.9, p = 0.001) were independent factors for poor prognosis. COX regression of CTC classification showed that epithelial/mesenchymal CTCs (E/M-CTC) (HR = 1.9, p = 0.001) and mesenchymal CTCs (M-CTC) (HR = 1.5, p = 0.001) were independent influencing factors of adverse reactions in breast cancer patients. Conclusion: The number of CTC in breast cancer is positively correlated with the expression of Claudin-4. High CTC counts and a high proportion of M-CTCs correlated with Claudin-4 expression. CTC counts and Claudin-4 expression were independent predictors of poor prognosis in breast cancer patients.

Adverse birth outcomes among offspring born to women diagnosed with cancer: a population-based cohort study.

BACKGROUND: With increasing cancer incidence and survival rates, the prevalence of maternal cancer and its effect on adverse birth outcomes are important for prenatal care and oncology management. However, the effects of different types of cancer at different gestational stages have not been widely reported. OBJECTIVE: This study aimed to describe the epidemiologic characteristics of pregnancy-associated cancers (during and 1 year after pregnancy) and evaluate the association between adverse birth outcomes and maternal cancers. METHODS: Of 983,162 cases, a history of maternal cancer, including pregestational cancer, pregnancy-associated cancer, and subsequent cancer, was identified in 16,475 cases using a health information network. The incidence and 95% confidence interval of pregnancy-associated cancer were calculated with the Poisson distribution. The adjusted risk ratio with 95% confidence interval of the association between adverse birth outcomes and maternal cancer were estimated using the multilevel log-binomial model. RESULTS: A total of 38,295 offspring were born to mothers with a cancer history. Of these, 2583 (6.75%) were exposed to pregnancy-associated cancer, 30,706 (80.18%) had a subsequent cancer diagnosis, and 5006 (13.07%) were exposed to pregestational cancer. The incidence of pregnancy-associated cancer was 2.63 per 1000 pregnancies (95% confidence interval, 2.53‰-2.73‰), with cancer of the thyroid (1.15‰), breast (0.25‰), and female reproductive organs (0.23‰) being the most common cancer types. The increased risks of preterm birth and low birthweight were significantly associated with cancer diagnosed during the second and third trimester of pregnancy, whereas increased risks of birth defects (adjusted risk ratio, 1.48; 95% confidence interval, 1.08-2.04) were associated with cancer diagnosed in the first trimester. Increased risks of preterm birth (adjusted risk ratio, 1.16; 95% confidence interval, 1.02-1.32), low birthweight (adjusted risk ratio, 1.24; 95% confidence interval, 1.07-1.44), and birth defects (adjusted risk ratio, 1.22; 95% confidence interval, 1.10-1.35) were observed in thyroid cancer survivors. CONCLUSION: Careful monitoring of fetal growth should be implemented for women diagnosed with cancer in the second and third trimester to ensure timely delivery and balance the benefits of neonatal health and cancer treatment. The higher incidence of thyroid cancer and increased risk of adverse birth outcomes among thyroid cancer survivors suggested that the regular thyroid function monitoring and regulation of thyroid hormone levels are important in maintaining pregnancy and promoting fetal development among thyroid cancer survivors before and during pregnancy.

Sensitive photoelectrochemical immunosensor for carcinoembryonic antigen detection based on copolymer of thiophene and thiophene-3-acetic acid modified phosphate-doped Bi2WO6.

In this study, PO43- doped Bi2WO6 (BWO-PO) was prepared by hydrothermal method, and then copolymer of thiophene and thiophene-3-acetic acid (P(Th-T3A)) was chemically deposited on the BWO-PO surface. The introduction of PO43- created point defects, greatly improving the photoelectric catalytic performance of Bi2WO6; the copolymer semiconductor could form heterojunction with Bi2WO6 to promote the separation of photo-generated carriers, due to its proper band gap. Furthermore, the copolymer could enhance the light absorption ability and photo-electronic conversion efficiency. Hence, the composite had good photoelectrochemical properties. When it was combined with carcinoembryonic antibody through the interaction of -COOH groups of the copolymer and the end groups of antibody for constructing ITO-based PEC immunosensor, the resulting sensor exhibited superb response to carcinoembryonic antigen (CEA), with a wide linear range of 1 pg/mL-20 ng/mL, and a relatively low detection limit of 0.41 pg/mL. It also showed high anti-interference ability, stability, and simplicity. The sensor has been successfully applied to monitor the concentration of CEA in serum. The sensing strategy can also be applied to the detection of other markers by changing the recognition elements, hence it has good application potential.

Association between excessive fetal growth and maternal cancer in Shanghai, China: a large, population-based cohort study.

The prevalence of high birth weight or large for gestational age (LGA) infants is increasing, with increasing evidence of pregnancy-related factors that may have long-term impacts on the health of the mother and baby. We aimed to determine the association between excessive fetal growth, specifically LGA and macrosomia, and subsequent maternal cancer by performing a prospective population-based cohort study. The data set was based on the Shanghai Birth Registry and Shanghai Cancer Registry, with medical records from the Shanghai Health Information Network as a supplement. Macrosomia and LGA prevalence was higher in women who developed cancer than in women who did not. Having an LGA child in the first delivery was associated with a subsequently increased risk of maternal cancer (hazard ratio [HR] = 1.08, 95% confidence interval [CI] 1.04-1.11). Additionally, in the last and heaviest deliveries, there were similar associations between LGA births and maternal cancer rates (HR = 1.08, 95% CI 1.04-1.12; HR = 1.08, 95% CI 1.05-1.12, respectively). Furthermore, a substantially increased trend in the risk of maternal cancer was associated with birth weights exceeding 2500 g. Our study supports the association between LGA births and increased risks of maternal cancer, but this risk requires further investigation.