Patient-Reported Outcomes and Complication Profiles of Implant-Based Breast Reconstruction in Patients With Postmastectomy Radiation Therapy.

OBJECTIVE: This study aims to investigate the patient-reported outcomes (PROs) and complications of distinct implant-based breast reconstruction modality for patients with postmastectomy radiation therapy (PMRT). METHODS: A retrospective review was conducted on breast cancer patients with stage II-III disease who performed implant-based breast reconstruction following with PMRT between September 2016 and April 2022. The patients were categorized into two matched groups: (1) patients receiving prepectoral breast reconstruction (PBR) or (2) subpectoral breast reconstruction (SBR) followed by PMRT. Following reconstruction, the patients were further compared for PMRT with the tissue expander (PMRT-TE) versus PMRT with permanent implant (PMRT-PI). PROs were measured with BREAST-Q questionnaire. Early and late complications were recorded and analyzed. RESULTS: A total of 55 eligible patients were recruited. Patients who underwent PBR reported significantly higher satisfaction with breasts scores (P = 0.003) compared with the SBR group. The PMRT-TE group had higher satisfaction with breasts (P = 0.001) but lower physical well-being (P = 0.029) scores compared with PMRT-PI group. Moreover, patients in SBR cohort had a higher risk of capsular contracture (Baker grade III or IV) (20.5% vs 6.3%) and implant dislocation (48.7% vs 12.5%) than patients in PBR cohort. Patients in PMRT-PI group had a slightly higher rate of capsular contracture (Baker grade III or IV) than PMRT-TE group (20.8% vs 12.9%). CONCLUSIONS: PBR was associated with lower rates of late complications, especially for implant dislocation, and higher satisfaction with breasts scores compared to SBR. In addition, compared to PMRT-TE with PMRT-PI, patients in PMRT-TE cohort reported superior PROs of satisfaction with breasts.

Crosstalk between cancer-associated fibroblasts and regulated cell death in tumors: insights into apoptosis, autophagy, ferroptosis, and pyroptosis.

Cancer-associated fibroblasts (CAFs), the main stromal component of the tumor microenvironment (TME), play multifaceted roles in cancer progression through paracrine signaling, exosome transfer, and cell interactions. Attractively, recent evidence indicates that CAFs can modulate various forms of regulated cell death (RCD) in adjacent tumor cells, thus involving cancer proliferation, therapy resistance, and immune exclusion. Here, we present a brief introduction to CAFs and basic knowledge of RCD, including apoptosis, autophagy, ferroptosis, and pyroptosis. In addition, we further summarize the different types of RCD in tumors that are mediated by CAFs, as well as the effects of these modes of RCD on CAFs. This review will deepen our understanding of the interactions between CAFs and RCD and might offer novel therapeutic avenues for future cancer treatments.

Targeting pyroptosis in breast cancer: biological functions and therapeutic potentials on It.

Pyroptosis is a lytic and inflammatory type of programmed cell death that is mediated by Gasdermin proteins (GSDMs). Attractively, recent evidence indicates that pyroptosis involves in the development of tumors and can serve as a new strategy for cancer treatment. Here, we present a basic knowledge of pyroptosis, and an overview of the expression patterns and roles of GSDMs in breast cancer. In addition, we further summarize the available evidence of pyroptosis in breast cancer progression and give insight into the clinical potential of applying pyroptosis in anticancer strategies for breast cancer. This review will deepen our understanding of the relationship between pyroptosis and breast cancer, and provide a novel potential therapeutic avenue for breast cancer.

Neobavaisoflavone inhibits antitumor immunosuppression via myeloid-derived suppressor cells.

Neobavaisoflavone (Neo), as a traditional Chinese medicine, is the active ingredient in the herb Psoralea corylifolial and has antitumor activity. Myeloid-derived suppressor cells (MDSCs), which are a heterogeneous population of haematopoietic cells of the myeloid lineage, have been reported to be closely related to the pathogenesis of tumour progression, but whether Neo can regulate MDSC expansion and function remains unclear. Here, we found that Neo could inhibit the expansion and suppressive function of MDSCs by targeting STAT3. Importantly, Neo inhibited the growth of 4T1 and LLC tumours in vivo, as well as lung metastasis of 4T1 tumours in vivo. Furthermore, we identified MDSCs as the direct targets by which Neo attenuated tumour progression. In addition, Neo notably enhanced anti-PD-1 efficacy in anti-PD-1-insensitive 4T1 tumours. Therefore, our study sheds light on the development of Neobased therapeutic strategies against cancer.

Exosomes Derived from Mouse Adipose-Derived Mesenchymal Stem Cells Alleviate Benzalkonium Chloride-Induced Mouse Dry Eye Model via Inhibiting NLRP3 Inflammasome.

PURPOSE: The objective of the study was to investigate efficacy and mechanisms of mouse adipose-derived mesenchymal stem cell-derived exosomes (mADSC-Exos) in the benzalkonium chloride (BAC)-induced mouse dry eye model. METHODS: Exosomes in the mADSC culture supernatant were isolated by ultracentrifugation. Western blotting, nanoparticle tracking analysis, and transmission electron microscopy were used to characterize mADSC-Exos. An experimental mouse model of dry eye was established by instillation of 0.2% BAC. mADSC-Exos were administered following BAC treatment. The positive control group was treated with commercial eye drops (0.1% pranoprofen). Corneal fluorescein staining, tear secretion, and tear film break-up time (BUT) were evaluated, and histologic analysis of the cornea and conjunctiva was performed by hematoxylin and eosin and periodic acid-Schiff staining. Apoptosis in the corneal epithelium was detected with the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and by Western blotting. Levels of pro-inflammatory cytokines in the cornea and conjunctiva were evaluated by flow cytometry, and mRNA and protein levels of NLR family pyrin domain-containing 3 (NLRP3) pathway components were assessed by quantitative real-time PCR and Western blotting, respectively. RESULTS: mADSC-Exos were characterized as vesicles with a bilayer membrane. The particle size distribution peak was at 134 nm. mADSC-Exos specifically expressed cluster of differentiation (CD)9, CD63, and CD81. mADSC-Exos treatment repaired ocular surface damage. Additionally, mADSC-Exos inhibited cell apoptosis, decreased the levels of interleukin (IL)-1ß, IL-6, IL-1α, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, and increased levels of the anti-inflammatory cytokine IL-10. Meanwhile, NLRP3 inflammasome activation and upregulation of caspase-1, IL-1ß, and IL-18 were reversed by mADSC-Exos. CONCLUSIONS: mADSC-Exos alleviate ocular surface inflammation, suggesting that it is a promising treatment for dry eye.

Neobavaisoflavone-mediated TH9 cell differentiation ameliorates bowel inflammation.

Neobavaisoflavone (Neo), is the active constituent of the herb Psoralea corylifolial, used in the traditional Chinese medicine, and has anti-inflammatory activity, but whether Neo could regulate colitis remains unclear. T helper 9 (TH9) cells, a subset of CD4+ T helper cells characterized by secretion of IL-9, have been reported to be involved in the pathogenesis of many autoimmune and inflammatory diseases, but whether Neo could control TH9 cell differentiation also remains unclear. Here, we found that Neo could decrease IL-9 production of CD4+ T cells by targeting PU.1 in vitro. Importantly, Neo had therapeutic effects on DSS-induced colitis. Furthermore, we identified TH9 cells as the direct target of Neo for attenuating bowel inflammation. Therefore, Neo could serve as a lead for developing new therapeutics against inflammatory bowel disease.

Exenatide Twice Daily Plus Glargine Versus Aspart 70/30 Twice Daily in Patients With Type 2 Diabetes With Inadequate Glycemic Control on Premixed Human Insulin and Metformin.

OBJECTIVE: Many patients with type 2 diabetes treated with premixed insulin gradually have inadequate glycemic control and switch to a basal-bolus regimen, which raises some concerns for weight gain and increased hypoglycemic risk. Switching to combination use of glp-1 agonist and basal insulin may be an alternative option. METHODS: After a 12-week premixed human insulin 70/30 dosage optimization period, 200 patients with HbA1c of 7.0% to 10.0% were randomized into 24-week treatment groups with exenatide twice a day plus glargine or with aspart 70/30 twice a day. RESULTS: After 24 weeks, the patients receiving exenatide plus glargine (n = 90) had improved HbA1c control compared with those receiving aspart 70/30 (n = 90) (least squares mean change: ‒0.59 vs ‒0.13%; difference [95% CI]: ‒0.45 [‒0.74 to ‒0.17]) in the full analysis set population. Weight decreased 3.5 kg with exenatide and decreased 0.4 kg with aspart 70/30 (P < .001). The insulin dose was reduced 10.7 units/day (95% CI, ‒12.2 to ‒9.2 units; P < .001) with exenatide, and increased 9.7 units/day (95% CI, 8.2 to 11.2 units; P < .001) with aspart 70/30. The most common adverse events were gastrointestinal adverse effects in the exenatide group (nausea [21%], vomiting [16%], diarrhea [13%]). The incidence of hypoglycemia was similar in 2 groups (27% for exenatide and 38% for aspart 70/30; P = .1). CONCLUSION: In premixed human insulin‒treated patients with type 2 diabetes with inadequate glycemic control, switching to exenatide twice a day plus glargine was superior to aspart 70/30 twice a day for glycemic and weight control.

Schisandrin B-mediated TH17 cell differentiation attenuates bowel inflammation.

Schisandrin B (Sch B) is the major active constituent of the traditional Chinese medicine Schisandra chinensis and has anti-inflammatory activity, but the target of Sch B remains unclear. T helper 17 (TH17) cells have been involved in the pathogenesis of many autoimmune and inflammatory diseases. Here, we showed that Sch B could decrease IL-17A production of CD4+ T cells by targeting STAT3 in vitro. Importantly, Sch B has therapeutic effects on DSS-induced acute and chronic colitis, CD4+CD45RBhigh T cell-induced colitis. Furthermore, we identified TH17 cells as the direct target of Sch B for mediating its anti-inflammatory activity. Sch B could serve as a lead for developing new therapeutics against TH17 cells or IL-17A cytokine-driven diseases.

Astragaloside IV inhibits cell proliferation and metastasis of breast cancer via promoting the long noncoding RNA TRHDE-AS1.

Astragaloside IV (ASV), which has several pharmacological abilities, shows potential therapeutic effects on certain cancers by regulating the expression of long noncoding RNA (lncRNA). However, the anticancer role that ASV plays by regulating lncRNAs in breast cancer remains unknown. In this study, we first demonstrated that the lncRNA of TRHDE antisense RNA 1 (TRHDE-AS1) was downregulated in breast cancer tissues and cells. Low TRHDE-AS1 expression is associated with poor outcomes in patients with breast cancer and potentially contributes to the aggressive tumor biology of breast cancer. Furthermore, ASV significantly increased TRHDE-AS1 expression in a dose- and time-dependent manner in breast cancer cells. By upregulating TRHDE-AS1, ASV repressed breast cancer cell growth and metastasis both in vitro and in vivo. Taken together, our data indicated that TRHDE-AS1 participates in the anticancer role of ASV in breast cancer, which provides evidence for the application of ASV for breast cancer therapy.

Paclitaxel Promotes Tumor-Infiltrating Macrophages in Breast Cancer.

OBJECTIVE: Breast cancer remains the most threatening triggers of cancer death in women. Drug resistance inevitably leads to the weakness of treatment for breast cancer. Macrophages, as one of the most abundant immune cells in tumor immune-infiltrating microenvironment, involves in cell survival, migration, and invasion of breast cancer. METHODS: In this study, we compared the proportions of macrophages in patients with breast cancer with and without paclitaxel treatment, and investigated the targeted genes associated with macrophages for paclitaxel response. To explore the relationship between drug-related genes and breast cancer prognosis, survival analysis based on the drug-related genes were performed by website of Kaplan-Meier plotter with the threshold of significant P value < .05. RESULTS: Compared to the normal samples, we revealed that paclitaxel significantly enhanced the ratio of macrophages in the tumor microenvironment. Furthermore, the expression of 3 drug-related genes (IFT46, PEX11A, and TMEM223) were significantly negatively associated with the proportions of macrophages. And it is worth to notice that PEX11A and TMEM223 were associated with better progression-free survival outcomes of patients with breast cancer. Moreover, PEX11A was associated with longer overall survival time of breast cancer. CONCLUSION: Taken all together, all the findings support to gain a better understanding to the development of more effective therapies targeted with paclitaxel.

A Unique Four-Point Approach for Removal of Giant Breast Fibroadenoma With Marked Asymmetry: A Modified Round Block Technique.

Purpose: The removal of the giant breast fibroadenoma (GFA) with esthetic repair of the severe deformed breast is a surgical challenge. Materials and Methods: This was a retrospective study of data of 10 patients with GFAs who treated with a modified round block technique at the Department of Breast Surgery, Hangzhou First People's Hospital (Hangzhou, Zhejiang province, China) from March 2014 to June 2017. Preoperatively, according to the degree of excess skin and asymmetry, a four-point approach was designed. The area between the inner and outer circles was de-epidermized. The tumors were entirely stripped off along the capsule through an incision on a part of the outer circle. To avoid the nipple-areola complex widening, purse-string suture technique was used. Results: Patients' age ranged from 12 to 32 years (mean age, 23 years), and the largest tumor weighed 2 kg, with a diameter of 16.5 cm. After a mean follow-up of 25 months (range, 9-32 months), no local recurrences were found. Cosmetic results were satisfactory with breast symmetry and minimal scarring. Complications were minimal and widening of the periareolar scar was slight as well. Conclusion: The modified round block technique is recommended to resect GFA in order to improve the cosmetic results with minimal scar.

Iris reconstruction combined with iris-claw intraocular lens implantation for the management of iris-lens injured patients.

AIM: To study the efficiency and safety of iris reconstruction combined with iris-claw intraocular lens (IOL) implantation in the patients with iris-lens injuries. SETTINGS AND DESIGN: Retrospective, noncomparable consecutive case series study. MATERIALS AND METHODS: Eleven patients (11 eyes) following iris-lens injuries underwent iris reconstructions combined with iris-claw IOL implantations. Clinical data, such as cause and time of injury, visual acuity (VA), iris and lens injuries, surgical intervention, follow-up period, corneal endothelial cell count, and optical coherence tomography, were collected. RESULTS: Uncorrected VA (UCVA) in all injured eyes before combined surgery was equal to or <20/1000. Within a 1.1-4.2-year follow-up period, a significant increase, equal to or better than 20/66, in UCVA was observed in six (55%) cases, and in best-corrected VA (BCVA) was observed in nine (82%) cases. Postoperative BCVA was 20/40 or better in seven cases (64%). After combined surgery, the iris returned to its natural round shape or smaller pupil, and the iris-claw IOLs in the 11 eyes were well-positioned on the anterior surface of reconstructed iris. No complications occurred in those patients. CONCLUSIONS: Iris reconstruction combined with iris-claw IOL implantation is a safe and efficient procedure for an eye with iris-lens injury in the absence of capsular support.

A novel method for the localization and management of traumatic cyclodialysis cleft.

Purpose. To propose a novel surgical method for the localization and management of traumatic cyclodialysis clefts. Methods. Five patients with traumatic cyclodialysis clefts who underwent the innovative surgery were retrospectively reviewed. The new method was introduced to repair a cyclodialysis cleft with two running sutures from the middle to each end of the cleft under the guidance of a probe. Preoperative and postoperative visual acuity (VA), intraocular pressure (IOP), slit lamp and gonioscopic results, ultrasound biomicroscopy (UBM), and optical coherence tomography (OCT) findings were recorded. Results. Cyclodialysis clefts were completely closed postoperatively in four patients (four eyes); this was confirmed by progressively improved VA, restoration into the normal range of the IOP, disappearance of suprachoroidal fluid, and reduced macular edema. Only one patient with multiple clefts had an incomplete reattachment. Conclusions. This clinical study offers a novel and efficient method to localize and repair the cyclodialysis clefts.

Anterior and pan-endophthalmitis caused by Candida albicans and Aspergillus fumigatus: report of two cases.

We report two posttraumatic fungal endophthalmitis cases with anterior and entire segment involvement caused, respectively, by Candida albicans and Aspergillus fumigatus. The anterior endophthalmitis induced by C. albicans presented multifocal lesions with hyphael structures in anterior chamber, but without involvement of posterior vitreous. The pan-endophthalmitis caused by A. fumigatus displayed significant hypopyon and vitritis. Treatment strategies are anterior chamber cleaning for anterior endophthalmitis and vitrectomy for pan-endophthalmitis, excepting systemic and topical antifungal drug applications including intravitreal injection for both types of endophthalmitis. There is a much better outcome in the case with anterior segment involvement than that with entire segment involvement. This case report provides evidence that the different types of posttraumatic fungal endophthalmitis related to different fungal infections indeed existed and should be managed with different strategies.

Combination surgery for management of perforating eye injury with retained magnetic intraorbital foreign body.

PURPOSE: The objective of this study was to evaluate the feasibility and safety of vitrectomy combined with magnetic intraorbital foreign body (IOrFB) removal in the patients with perforating eye injury and retained magnetic IOrFBs. METHODS: A consecutive series of 7 patients with perforating eye injury and retained magnetic IOrFBs were included to perform secondary combination surgery (vitrectomy combined with IOrFB removal) after primary repair. Clinical data such as age, sex, hours and cause of injury, site and size of penetrating wound and IOrFB, involved intraocular tissues, surgical intervention, interval between surgeries, length of follow-up, anatomic recovery, visual outcome, and so on were recorded. RESULTS: Except for an unsuccessful IOrFB removal in case 6 in which IOrFB was finally extracted after 3 months, the remaining 6 cases had been operated on successfully both in vitrectomy and IOrFB removal. All the cases resulted in not only anatomic recovery but also good visual outcomes. No complications occurred. Seven cases revealed flat retina after silicone oil removal at a 3- to 12-month follow-up. Final best correct visual acuity equal to or better than 0.05 and 0.2 were 6 (85.7%) and 4 (57%) cases, respectively, and only 1 case was without improvement because of macular involvement. CONCLUSIONS: A combination surgery of vitrectomy with IOrFB removal is a highly efficient and safe procedure for the management of perforating eye injury with magnetic IOrFB. Prompt and proper management, such as preoperative exact localization of IOrFB, thoroughly cleaning of vitreous hemorrhage, complete sealing of retinal hole, and so on, is crucial for the successful achievement.