At present, cancer is still one of the most serious threats to human health. Despite the wide application of multiple cancer therapies in clinical practice, the therapeutic effects of most cancers are still far from satisfactory. In recent years, the discovery of regulated cell death may be a good first step on the road to treat cancer. Ferroptosis is triggered by lipid peroxidation of unsaturated fatty acids in cell membrane catalyzed by iron ion. It has been widely concerned as an emerging target for cancer therapy. With the booming of biomedical nanotechnology, ferroptosis as an emerging therapeutic target has attracted extensive attention. Here, we review the advance on the intersection of ferroptosis and biomedical nanotechnology. First, the research background of ferroptosis and nano-preparation as well as the feasibility of ferroptosis-based nano-drug delivery systems (nano-DDS) for cancer treatment are presented and analyzed. Then, the strategies for inducing ferroptosis based on nano-DDS are summarized, mainly including: the promotion of Fenton reaction, the inhibition of glutathione peroxidase 4 (GPX-4) and the restriction of the cysteine-glutamate exchange transporter (system Xc^-). Furthermore, the combination therapy strategies based on biomedical nanotechnology induced ferroptosis are also discussed. Finally, we shine the spotlight on the prospects and challenges of ferroptosis-based nanotherapeutics in clinical application.

Objective: To explore the value of a two-stitch continuous suture in single- lumen ileostomy. Methods: This was a retrospective cohort study. Data for 98 patients who underwent single-lumen enterostomy were retrospectively collected between 1 January 2021 and 1 May 2022 at Zhujiang Hospital of Southern Medical University. All patients met the indications for prophylactic single-lumen ileostomy. Those older than 80 years of age, with complex underlying diseases, extremely poor systemic conditions who could not tolerate surgery, poor blood supply at the end of the bowel, and severe edema or severe infection at the end of the bowel were excluded. Among the included patients, patients who underwent surgery before 1 October 2021 underwent ileostomy with interrupted suture (control group, n=60), and patients operated on and after 1 October 2021 routinely underwent two-stitch continuous suture ileostomy (two-stitch stoma group, n=38). Two-stitch continuous suture ileostomy is performed as follows: the first continuous suture is used to suture the intestinal seromuscular layer, peritoneum, posterior sheath, and anterior sheath from deep to superficial layers. The bowel wall is then opened. The second continuous suture is used to suture the full thickness of the bowel and the skin. The differences in postoperative ostomy-related complications and operation time were compared between the groups. Results: There were no significant differences in baseline data between the groups (all, P>0.05). The operative time in the two-stitch stoma group was shorter than that of the control group (16.6±2.2 minutes vs. 25.1±2.4 minutes, respectively; t=-17.874;P<0.001). The incidences of mucocutaneous separation, dermatitis, and stoma rebound in the two-stitch stoma group were lower than those of the control group [5.3% (2/38) vs. 31.7% (19/60), χ²=9.633, P=0.002;5.3% (2/38) vs. 28.3% (17/60), χ²=7.923, P=0.005; and 2.6% (1/38) vs. 18.3% (11/60), P=0.026, respectively], while the incidences of parastomal hernia and stoma prolapse, and the postoperative visual analog scale scores in the two groups were similar (all P>0.05). Conclusion: Compared with traditional single-lumen ileostomy, two-stitch continuous suture ileostomy has the advantages of short operation time, simplicity, esthetic appearance of the stoma, and a significant reduction in the postoperative complications associated with ileostomy.
Humans ; Ileostomy/adverse effects* ; Retrospective Studies ; Suture Techniques/adverse effects* ; Surgical Stomas ; Sutures/adverse effects* ; Postoperative Complications/epidemiology*

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

This study analyzed the molecular mechanism of Huangjing Qianshi Decoction(HQD) in the treatment of prediabetes based on network pharmacology and molecular docking. The active components of HQD were identified and screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP, http://Lsp.nwu.edu.cn/tcmsp.php) and then the targets of the components and the genes related to prediabetes were retrieved, followed by identifying the common targets of the decoction and the disease. The medicinal component-target network was constructed by Cytoscape to screen key components. The protein-protein interaction(PPI) network was established by STRING and hub genes were identified by Cytoscape-CytoNCA, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) of the hub genes with R-clusterProfi-ler. Thereby, the possible signaling pathways were predicted and the molecular mechanism was deduced. A total of 79 active components of HQD and 785 diabetes-related targets of the components were screened out. The hub genes mainly involved the GO terms of tricarboxylic acid cycle, peptide binding, amide binding, hydrolase activity, and kinase activity regulation, and the KEGG pathways of AGE-RAGE signaling pathway, TNF signaling pathway, AMPK signaling pathway, IL-17 signaling pathway, and insulin signaling pathway. Western blot result showed that HQD-containing serum significantly reduced the expression of AKT1, AGE, and RAGE proteins in insulin resistance model cells. HQD's treatment of prediabetes is characterized by multiple pathways, multiple targets, and multiple levels. The main mechanism is that the components zhonghualiaoine, baicalein, kaempferol, and luteolin act on AKT1 and inhibit the AGE-RAGE axis.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Pharmacology ; Prediabetic State/genetics*

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

OBJECTIVE: To investigate the effect of long non-coding RNA-TUC338 on the proliferation and migration of lymphoma cells. METHODS: The expression of TUC338 in different lymphoma cells was detected by fluorescence quantitative PCR, cell proliferation by sulforhodamine B (SRB) assay, migration of lymphoma cells by transwell assay, and protein expression in PI3K/AKT signaling pathway by Western blot. RESULTS: The expression levels of TUC338 in lymphoma cells Daudi, U937, BC-3, and Raji significantly increased in comparison with human normal T lymphocytes H9 (t=13.277, 10.103, 16.200, and 26.687, P=0.002, 0.005, 0.001, and 0.000). Compared with NC-siRNA group, the number of cells crossing the chamber of TUC338-siRNA group was significantly reduced (t=30.508, P=0.000), the protein expression levels of p-PI3K and p-AKT significantly decreased (t=16.872 and 18.371, P=0.000 and 0.000), and OD CONCLUSION The expression of TUC338 significantly increases in lymphoma cells, and silence of TUC338 effectively inhibits the activation of PI3K/AKT signaling pathway, thereby inhibiting the proliferation and migration of lymphoma cells, which has a potential application value in diagnosis and treatment of lymphoma.
Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Humans ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; RNA, Long Noncoding/genetics* ; Signal Transduction

The aim of the present study was to determine the metabolic changes and possible toxic mechanisms of ketamine-associated bladder toxicity. Twenty-four male Sprague-Dawley (SD) rats were randomly allocated into a control group, a low-dose group and a high-dose group. The behavior of these rats was observed every day. In addition, the weight, 2 h urinary frequency and organ coefficient of the bladder were measured. Serum IL-6 and TNF-α levels were measured using an enzyme-linked immunosorbent assay (ELISA). Urinary metabolites were analyzed using gas chromatography-mass spectrometry (GC-MS). This research was approved by the Ethics Committee of the Animal Experiment Center of Southwest Medical University (No. 201901-98). After 12 weeks of administration, the frequency of 2 h urination and the bladder mass index were significantly different in the low-dose and high-dose groups compared with the control group. Serum IL-6 and TNF-α levels were higher than those of the control group (P<0.05). Bladder HE staining showed that long-term administration of ketamine could induce cystitis. The concentrations of the three common differential metabolites, including 3-aminoisobutyric acid, citric acid and uric acid in the low-dose and the high-dose groups were increased compared with those in the control group. This study indicates that 3-aminoisobutyric acid, citric acid and uric acid and their related metabolic pathways may be closely related to ketamine-associated bladder toxicity.

OBJECTIVE: This study aimed to characterize the diagnostic and vaccine potential of a novel Mycobacterium tuberculosis antigen Rv0674. METHODS: To evaluate the diagnostic potential and antigenicity of Rv0674, IgG was evaluated using ELISA and interferon (IFN)-γ was done by using ELISpot assay among TB patients and healthy donors. For immunogenicity evaluation, BALB/c mice were immunized with Rv0674. Cytokine production was determined by cytokine release assay using an ELISA kit, and the antibodies were tested using ELISA. RESULTS: The results of serum Elisa tests showed that Rv0674 specific immunoglobulin G (IgG) response was higher in TB patients than negative controls. And Rv0674 had good performance in serological test with sensitivity and specificity of 77.1% and 81.1%, respectively. While it shows poor sensitivity and specificity of 26.23% and 79.69% for IFN-γ tests. In BALB/c mice, Rv0674 adjuvant by DDA/Poly I:C could also induce a high level of IFN-γ, interleukin-2 and interleukin-6 as well as a high IgG titer in both high- and low-dose groups indicating that Rv0674 is essential in humoral and cellular immunity. Moreover, the cytokine profile and IgG isotype characterized Rv0674 as a Th1/Th2-mixed-type protective immunity with the predominance of Th1 cytokines. CONCLUSION Rv0674 may be a good potential candidate for the development of TB serological diagnosis and a new TB vaccine.
Adult ; Aged ; Animals ; Antigens, Bacterial ; immunology ; Female ; Humans ; Immunity, Cellular ; Immunity, Humoral ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Tuberculosis ; diagnosis ; immunology ; Young Adult

Objective To evaluate the cost-effectiveness of comprehensive schistosomiasis control measures with focus on total removal of cattle and sheep in Juanshan District,Yueyang City.Methods The schistosome infection status of human,cat-tle,sheep and Oncomelania hupensis snails and costs of control measures were gathered during the period of 2006 to 2016.The costs for different periods and cost-effectiveness ratios were calculated.Results The prevalence of schistosome infection in resi-dents in the pilot villages decreased from 3.44% in 2006 to 0 in 2016.The annual costs of schistosomiasis prevention and control were 4 708 500 yuan from 2006 to 2008,5 094 700 yuan from 2009 to 2012 and 9 522 700 yuan from 2013 to 2016.The cost-ef-fectiveness analysis showed that the average annual cost of reduction in the residents'infection rate by 1% were 79 500 yuan from 2006 to 2008,101 200 yuan from 2009 to 2012,and 95 200 yuan from 2013 to 2016,respectively. Conclusion The comprehensive schistosomiasis control strategy with focus on cattle and sheep removal in Junshan District is cost effective, which could be extended to other lake and marshland schistosomiasis endemic areas.

Objective To investigate the therapeutic effect of probiotics and traditional Chinese medicine syndrome-differentiation treatment for children rotavirus enteritis. Methods One hundred and twenty cases of children with rotavirus enteritis were randomly divided into Chinese medicine group, probiotics group and control group,40 cases in each group. The 3 groups were given conventional treatment such as proper feeding, prevention of dehydration and correction of dehydration. Additionally, Chinese Medicine group was separately given modified Gegen Qinlian Decoction for patients with damp-heat syndrome, modified Huoxiang Zhengqi Decoction for patients with wind-cold syndrome, modified Baohe Pills for patients impaired by overeating, modified Shenling Baizhu Powder for patients with spleen deficiency syndrome;probiotics group received Probiotic Bifidobacterium Triple Viable Enteric Capsules;the control group was given oral use of Smecta. Daily defecation frequency and stool characteristics were recorded,and the clinical efficacy was analyzed on treatment day 3 and 5. Results(1)After treatment for 3 days,the total effective rate of the 3 groups arrived to 100%,the difference being insignificant between the 3 groups (P > 0.05);after treatment for 3 days, Chinese medicine group had higher markedly effective rate than probiotics group and control group,the difference being significant (P < 0.05). (2) After treatment for 3 and 5 days,the defecation frequency of the 3 groups was much reduced as compared with that before treatment (P < 0.05), and the improvement of defecation frequency in Chinese medicine group was superior to that in probiotic group and control group, the difference being significant (P <0.05). (3)The mean course of disease in Chinese medicine group was shorter than that in probiotic group and control group,the difference being significant (P < 0.05). Conclusion Traditional Chinese medicine syndrome-differentiation treatment exerts certain effect for the treatment of rotavirus enteritis, and can quickly reduce defection frequency and shorten the course of disease.