DTDHM: detection of tandem duplications based on hybrid methods using next-generation sequencing data.

Background: Tandem duplication (TD) is a common and important type of structural variation in the human genome. TDs have been shown to play an essential role in many diseases, including cancer. However, it is difficult to accurately detect TDs due to the uneven distribution of reads and the inherent complexity of next-generation sequencing (NGS) data. Methods: This article proposes a method called DTDHM (detection of tandem duplications based on hybrid methods), which utilizes NGS data to detect TDs in a single sample. DTDHM builds a pipeline that integrates read depth (RD), split read (SR), and paired-end mapping (PEM) signals. To solve the problem of uneven distribution of normal and abnormal samples, DTDHM uses the K-nearest neighbor (KNN) algorithm for multi-feature classification prediction. Then, the qualified split reads and discordant reads are extracted and analyzed to achieve accurate localization of variation sites. This article compares DTDHM with three other methods on 450 simulated datasets and five real datasets. Results: In 450 simulated data samples, DTDHM consistently maintained the highest F1-score. The average F1-score of DTDHM, SVIM, TARDIS, and TIDDIT were 80.0%, 56.2%, 43.4%, and 67.1%, respectively. The F1-score of DTDHM had a small variation range and its detection effect was the most stable and 1.2 times that of the suboptimal method. Most of the boundary biases of DTDHM fluctuated around 20 bp, and its boundary deviation detection ability was better than TARDIS and TIDDIT. In real data experiments, five real sequencing samples (NA19238, NA19239, NA19240, HG00266, and NA12891) were used to test DTDHM. The results showed that DTDHM had the highest overlap density score (ODS) and F1-score of the four methods. Conclusions: Compared with the other three methods, DTDHM achieved excellent results in terms of sensitivity, precision, F1-score, and boundary bias. These results indicate that DTDHM can be used as a reliable tool for detecting TDs from NGS data, especially in the case of low coverage depth and tumor purity samples.

Therapeutic Prospects of Mesenchymal Stem Cell and Their Derived Exosomes in the Regulation of the Gut Microbiota in Inflammatory Bowel Disease.

Mesenchymal stem cells (MSCs) have shown great potential in the treatment of several inflammatory diseases due to their immunomodulatory ability, which is mediated by exosomes secreted by MSCs (MSC-Exs). The incidence of inflammatory bowel disease (IBD) is increasing globally, but there is currently no long-term effective treatment. As an emerging therapy, MSC-Exs have proven to be effective in alleviating IBD experimentally, and the specific mechanism continues to be explored. The gut microbiota plays an important role in the occurrence and development of IBD, and MSCs and MSC-Exs can effectively regulate gut microbiota in animal models of IBD, but the mechanism involved and whether the outcome can relieve the characteristic dysbiosis necessary to alleviate IBD still needs to be studied. This review provides current evidence on the effective modulation of the gut microbiota by MSC-Exs, offering a basis for further research on the pathogenic mechanism of IBD and MSC-Ex treatments through the improvement of gut microbiota.

Comparative study of topical 5-aminolevulinic acid photodynamic therapy and surgery in treating vaginal high-grade squamous intraepithelial lesions following hysterectomy.

OBJECTIVE: To compare the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and surgery in treating vaginal high-grade squamous intraepithelial lesions (HSIL) after hysterectomy due to cervical cancer (CC) or precancerous lesions. METHODS: A retrospective study was performed comprising 41 women with histologically confirmed vaginal HSIL after hysterectomy for CC or cervical HSIL. Patients were treated with surgery or ALA-PDT and were followed up at 3, 6 and 12 months and then every six months afterwards. Clinical data were collected and the efficacy and safety of the two groups were analyzed. RESULTS: Of the 41 patients with vaginal HSIL after hysterectomy, 18 were treated with ALA-PDT and 23 underwent surgery. There was no significant difference in the lesions' complete remission (CR) rate or the human papillomavirus (HPV) clearance rate between the ALA-PDT group and the surgery group (P > 0.05). In the surgery group, the clearance rate of HPV16/18 was higher than that of other high-risk HPV (HR-HPV) and HPV16/18 combined with other HR-HPV (87.50 % vs. 45.45 % vs. 0.00 %, P = 0.014). No significant difference in the recurrence rate between the two groups was noted (P > 0.05). And none of the patients progressed. In the surgery group, one patient developed significant thickening of the vaginal stump, and one patient had increased vaginal discharge. In women treated with ALA-PDT, there was no vaginal bleeding or harmful effects on the organizational structure or functions compared to the surgery group. CONCLUSIONS: The efficacy of ALA-PDT was comparable to that of surgery in treating vaginal HSIL following hysterectomy due to CC or cervical HSIL, with fewer side effects.

Comparative study of topical 5-aminolevulinic acid photodynamic therapy and surgery for recurrent cervical high-grade squamous intraepithelial lesions following surgery.

OBJECTIVE: The study aimed to compare the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and surgery in treating recurrent cervical high-grade squamous intraepithelial lesions (HSIL) after surgery due to precancerous lesions. METHODS: A total of 41 patients with recurrent cervical HSIL after surgery for precancerous lesions were studied retrospectively. Patients underwent ALA-PDT or surgery and were followed up at 3, 6, 9 and 12 months and then every six months after that. Clinical data were collected and the efficacy and safety of the two treatment methods were compared. RESULTS: Of the 41 patients with recurrent cervical HSIL after conization, 15 cases received ALA-PDT and 26 received surgery. At the six-month follow-up, the lesions' complete remission (CR) rate was 93.33 % in ALA-PDT group and 88.46 % in the surgery group. The human papillomavirus (HPV) clearance rates were 66.67 % and 73.08 %, respectively. No significant differences concerning the lesions' CR rate and the HPV clearance rate were observed between the two groups (P>0.05). At the twelve-month follow-up, the HPV clearance rates were 80.00 % and 91.67 %. No significant differences concerning the HPV clearance rate were observed between the two groups (P>0.05). In the surgery group, the HPV clearance rate and the lesions' CR rate were lower in patients over 45 years of age (25.00% vs. 81.82 %, P = 0.031; 50.00% vs. 95.45 %, P = 0.052). During the follow-up, there was no significant difference in the recurrence rate between the two groups (P>0.05). In addition, none of the patients progressed. In women treated with ALA-PDT, there was no vaginal bleeding, and no harmful effects on the cervical organizational structure or functions compared to the surgery group, and two women delivered successfully after ALA-PDT treatment. CONCLUSIONS: The efficacy of ALA-PDT was similar to that of surgery in treating recurrent cervical HSIL following surgery, with fewer side effects.

Surgery combined with photodynamic therapy for early-stage endometrial carcinoma, a report of two cases.

BACKGROUND: Endometrial carcinoma (EC) is one of the most prevalent gynecological malignancies and the onset age of EC tends to be younger. This case report explored the feasibility of surgery combined with photodynamic therapy (PDT) in two young patients with early-stage EC. METHODS: A 31 years old patient and a 24 years old patient were treated with surgery and PDT, respectively. The intraoperative PDT was performed 3 h after oral administration of 5-aminolevulinic acid (ALA) with intrauterine light irradiation of 630 nm laser light. RESULTS: The patients were followed up for 3 years and 4 months, respectively. There were no signs of recurrence. CONCLUSION: Intraoperative and intrauterine PDT was feasible and might be used for EC patients who attempt to preserve fertility.

Nutrient vitamins enabled metabolic regulation of ferroptosis via reactive oxygen species biology.

Vitamins are dietary components necessary for cellular metabolic balance, especially redox homeostasis; deficient or excessive supply may give rise to symptoms of psychiatric disorders. Exploring the nutritional and metabolic pathways of vitamins could contribute to uncovering the underlying pathogenesis of ferroptosis-associated diseases. This mini-review aims to provide insights into vitamins closely linked to the regulation of ferroptosis from the perspective of cellular reactive oxygen species biology. The mainstream reprogramming mechanisms of ferroptosis are overviewed, focusing on unique biological processes of iron metabolism, lipid metabolism, and amino acid metabolism. Moreover, recent breakthroughs in therapeutic interventions targeting ferroptosis via fully utilizing vitamin-based pharmacological tools were overviewed, covering vitamins (B, C, E, and K). Finally, mechanism insight related to vitamin-associated nutrient signaling was provided, highlighting the pharmacological benefits of metabolically reprogramming ferroptosis-associated diseases.