Associations between vaginal microbiota and endometrial polypoid lesions in women of reproductive age: a cross-sectional study.

RESEARCH QUESTION: What are the different characteristics of vaginal microbial composition between patients with endometrial polypoid lesions and controls? DESIGN: This cohort study compared the pre-operative microbial compositions of vaginal samples in a cohort of 703 women with endometrial polypoid lesions [293 and 410 women diagnosed and not diagnosed with polyps pathologically (polyps group and not-polyps group, respectively] and 703 women in the control group. Bacterial abundance, diversity, differential taxa and microbial network structure were assessed using 16S rRNA gene sequencing. Predictive algorithms were used to determine the functional pathways of vaginal microbiota within the cohort. RESULTS: The control group exhibited higher relative abundance of Lactobacillus crispatus in comparison with the polypoid lesions group (P = 0.0427). Beta diversity of vaginal microbiota differed significantly between the groups (P < 0.05). Comparing the polyps group with the not-polyps group, Leptotrichia spp. and Cutibacterium spp. were more abundant in the polyps group, and Fannyhessea spp., Acinetobacter spp. and Achromobacter spp. were more abundant in the not-polyps group. The control group exhibited higher abundance of Bifidobacterium spp., Achromobacter spp. and Escherichia/Shigella spp. (false discovery rate < 0.05). Furthermore, the polyps group and not-polyps group displayed more complex co-occurrence networks compared with the control group. CONCLUSIONS: The results of this study provide compelling evidence supporting associations between vaginal microbiota and endometrial polypoid lesions, highlighting the potential relationship between a well-balanced vaginal microbial ecosystem and a healthy intrauterine environment.

The versatile thoracodorsal artery perforator flap for extremity reconstruction: from simple to five types of advanced applications and clinical outcomes.

BACKGROUND: Application of the thoracodorsal artery perforator (TDAP) flap is known to be a popular and reliable method for extremity reconstruction. This manuscript presents our clinical outcomes in reconstructing soft tissue defects using simple and advanced TDAP flaps. METHODS: From 2013 to 2022, 53 patients with a mean age of 23 years (ranging from 2 to 72 years) underwent reconstructive surgery with different patterns of free TDAP flaps, including chimeric TDAP flaps, double skin paddle TDAP flaps, flow-through TDAP flaps, conjoined TDAP flaps, and microdissected debulking TDAP flaps. RESULTS: All TDAP flaps survived. The size of the TDAP skin paddle ranged between 5 × 3 and 25 × 10 cm2. Primary closure of the donor site was achieved in all patients in the simple application group, and one patient in the advanced application group underwent partial skin grafting. Partial flap loss occurred in one case in the simple TDAP flap group and four cases in the advanced application group. There was one case of flap bulkiness and two cases of scar hyperplasia in the simple TDAP flap group. The mean follow-up duration was 11 months (4-46 months). CONCLUSIONS: The free TDAP flap, with five types of advanced applications, makes it versatile for reconstructing different kinds of soft tissue defects of the extremities that can be used to achieve individualized defect reconstruction, minimize donor site morbidities, and an aesthetic appearance.

Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway.

OBJECTIVES: This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival. METHODS: The exosomes were isolated from the supernatant of MSCs pretreated with LPS. LPS pre-Exo and rapamycin were injected via the tail vein into C57BL/6 mice allografted with BALB/c skin; graft survival was observed and evaluated. The accumulation and polarization of macrophages were examined by immunohistochemistry. The differentiation of macrophages in the spleen was analyzed by flow cytometry. For in vitro, an inflammatory model was established. Specifically, bone marrow-derived macrophages (BMDMs) were isolated and cultured with LPS (100 ng/ml) for 3 h, and were further treated with LPS pre-Exo for 24 h or 48 h. The molecular signaling pathway responsible for modulating inflammation was examined by Western blotting. The expressions of downstream inflammatory cytokines were determined by Elisa, and the polarization of macrophages was analyzed by flow cytometry. RESULTS: LPS pre-Exo could better ablate inflammation compared to untreated MSC-derived exosomes (BM-Exo). These loaded factors inhibited the expressions of inflammatory factors via a negative feedback mechanism. In vivo, LPS pre-Exo significantly attenuated inflammatory infiltration, thus improving the survival of allogeneic skin graft. Flow cytometric analysis of BMDMs showed that LPS pre-Exo were involved in the regulation of macrophage polarization and immune homeostasis during inflammation. Further investigation revealed that the NF-κB/NLRP3/procaspase-1/IL-1ß signaling pathway played a key role in LPS pre-Exo-mediated regulation of macrophage polarization. Inhibiting NF-κB in BMDMs could abolish the LPS-induced activation of inflammatory pathways and the polarization of M1 macrophages while increasing the proportion of M2 cells. CONCLUSION: LPS pre-Exo are able to switch the polarization of macrophages and enhance the resolution of inflammation. This type of exosomes provides an improved immunotherapeutic potential in prolonging graft survival.

Substance P promote macrophage M2 polarization to attenuate secondary lymphedema by regulating NF-kB/NLRP3 signaling pathway.

Secondary lymphedema often occurs after filariasis, trauma, lymph node dissection and radiation therapy, which is manifested by infiltration of inflammatory cells and fibrosis formation in pathologically. Substance P is a widely used neuropeptide in the field of tissue repair, while the regenerative potential of the substance P has not been proven in the secondary lymphedema. In this study, animal model of secondary lymphedema was constructed by excising the skin and subcutaneous lymphatic network in the tail of mice, and the degree of swelling in the tail of mice was evaluated after 6 weeks under the treatment with substance P. Immunofluorescence staining was also performed to assess immune cell infiltration, subcutaneous fibrosis and lymphangiogenesis. The results revealed that substance P significantly alleviated post-surgical lymphedema in mice. Furthermore, we found that substance P promoted macrophages M2 polarization, a process associated with downregulation of the NF-kB/NLRP3 pathway. After application of disodium clodronate (macrophage scavenger, CLO), the positive effect of substance P in lymphedema is significantly inhibited. In vitro experiments, we further demonstrated the polarizing effect of substance P on bone marrow-derived macrophages (BMDMs), while substance P inhibited the activation of the NF-kB/NLRP3 pathway in BMDMs after the treatment of lipopolysaccharide (LPS). In addition, polarized macrophages were demonstrated to promote the proliferation, tube-forming and migratory functions of human lymphatic endothelial cells (hLEC). In conclusion, our study provides preliminary evidence that substance P alleviates secondary lymphedema by promoting macrophage M2 polarization, and this therapeutic effect may be associated with downregulation of the NF-kB/NLRP3 pathway.

Efficacy comparison of vascularized iliac crest bone flap and Ilizarov bone transport in the treatment of traumatic bone defects of the tibia combined with large soft tissue defects.

BACKGROUND: Traumatic tibial defect complicated with soft tissue defect is a difficult problem in clinic. Vascularized iliac crest bone flap (VIBF) and Ilizarov bone transport are effective methods to treat tibial defects with limited defect length, which most need to be explored accordingly. METHODS: In this study, a total of 68 patients with traumatic tibial defect (ranging from 4 to 10 cm) and large soft tissue defect were collected retrospectively. The soft tissue defects were repaired by latissimus dorsal musculocutaneous flap (LD), anterolateral thigh flap (ALTF) or both. Thirty-three cases were treated with vascularized iliac crest bone flap transplantation and 35 cases were treated with Ilizarov bone transport. Intraoperative and postoperative follow-up data (including operation time, blood loss, bone union time, external fixation time, external fixation index, complication rate, reoperation rate, and functional evaluation) were recorded, and comparative analysis was performed. RESULTS: The median follow-up time was 32 months. Compared with Ilizarov group, the VIBF group exhibited statistically faster bone union time (6.3 ± 1.0 vs. 18.2 ± 3.0 months). Moreover, the VIBF group showed shorter EFT (7.3 ± 1.0 vs. 19.2 ± 3.0 months) and a better EFI (34.8 ± 9.2 vs. 84.2 ± 23.7 days/cm). The excellent and good rate of lower limb appearance evaluation in VIBP group was significantly better than that in Ilizarov group. The complication rate and reoperation rate were significantly higher in Ilizarov group. CONCLUSION: In summary, compared with Ilizarov bone transport, VIBP has the advantages of faster healing, shorter external fixation time, lower complication and reoperation rate, and better appearance within the limited defect length. Ilizarov bone transport is still preferred when the defect length exceeds the maximum repair length of the iliac flap. The daily handling required by bone transport process is painful. LEVEL OF EVIDENCE: III, Case-control study.

The free chimeric medial sural artery perforator flap for individualised and three-dimensional reconstruction of complex soft-tissue defects in extremities.

Trauma or lesion resection often causes complex wounds with deep soft tissue defects in extremities. Simply covering with a skin flap will leave a deep dead space resulting in infection, non-healing wounds, and poor long-term outcomes. Thus, effectively reconstructing complex wounds with dead space leaves a clinical challenge. This manuscript presents our experience using chimeric medial sural artery perforator (cMSAP) flap, to reconstruct complex soft tissue defects of the extremities, thereby exploring broader analysis and indications for future reference. Between March 2016 and May 11, 2022, patients (8 males and 3 females) with a mean age of 41 years (range from 26 to 55 years) underwent reconstructive surgery with the cMSAP flap. The cMSAP flap consists of an MSAP skin paddle and a medial sural muscle paddle. The size of the MSAP skin paddle ranged between 9 × 5 cm and 20 × 6 cm, and the size of the medial sural muscle paddle ranged between 2 × 2 cm and 14 × 4 cm. Primary closure of the donor site was achieved in all cases. Of the 11 patients, the cMSAP flap survived in 10 cases. The vascular compromise occurred in one special case and was treated with surgical procedures. The mean follow-up duration was 16.5 months (range of 5-25 months). Most patients present satisfactory cosmetic and functional results. The free cMSAP flap is a good option for reconstructing complex soft tissue defects with deep dead space in extremities. The skin flap can cover the skin defect, and the muscle flap can fill the dead space against infection. In addition, three types of cMSAP flaps can be used in a broader range of complex wounds. This procedure can achieve an individualised and three-dimensional reconstruction of the defects and minimise the donor site morbidities.

Calcium ionophore improves embryonic development and pregnancy outcomes in patients with previous developmental problems in ICSI cycles.

BACKGROUND: Calcium (Ca2+) ionophores are now mainly considered as efficient treatments for fertilization failure. Recently, its application for rescuing poor embryo development was proposed but still non-routine. This study aimed to explore whether Ca2+ ionophore improves embryo development and pregnancy outcomes in patients with poor embryo development in previous intracytoplasmic sperm injection (ICSI) cycles. METHODS: This study included 97 patients undergoing assisted oocyte activation (AOA) with Ca2+ ionophore (calcimycin, A23187) treatment. Preimplantation embryonic development and clinical outcomes were compared between ICSI-AOA cycles (AOA group) and previous ICSI cycles of the same patients in which poor embryo developmental potential was present (non-AOA group). Subgroups stratified by maternal age (< 35, 35-40, ≥ 40 years, respectively) were analyzed separately. RESULTS: A total of 642 MII oocytes were collected in AOA group, and 689 in non-AOA group. Significantly higher day 3 good quality embryo rate (P = 0.034), good quality blastocyst formation rate (P <  0.001), and utilization rate (P <  0.001) were seen in AOA group. Similar results were seen in each subgroup. For pregnancy outcomes, there were significant differences in clinical pregnancy rate (P = 0.039) and live birth rate (P = 0.045) in total group. In subgroup aged < 35 years, biochemical (P = 0.038), clinical (P = 0.041), and ongoing pregnancy rate (P = 0.037) in AOA group were significantly higher than that in non-AOA group. No significant improvement for clinical outcomes for subgroups aged 35-40 and aged ≥40. CONCLUSION: The study suggests that calcimycin could improve preimplantation development and pregnancy outcomes in patients aged < 35 years with embryo developmental problems in previous ICSI cycles.

The Safety of Chemotherapy for Ovarian Malignancy during Pregnancy.

BACKGROUND: Data on epidemiologic features, treatments and outcomes in women diagnosed with ovarian malignancy during pregnancy are very sparse due to its low incidence. The goal of our study was to summarize the epidemiologic characteristics of pregnant women complicated with ovarian malignancy and investigate the safety and efficacy of chemotherapy during pregnancy. METHODS: We retrospectively analyzed the clinicopathological data of eight patients suffering from ovarian malignancy during pregnancy in our institution from June 2011 to July 2021. Furthermore, a systematic literature search was conducted in PubMed up to 1 September 2021, which identified 92 cases with ovarian malignancy during pregnancy eligible for the analysis. Therefore, we collected the data of 100 pregnant patients complicated with ovarian malignancy, including clinical demographics, tumor characteristics, treatment interventions and outcomes. RESULTS: In total, 100 pregnant patients complicated with ovarian malignancy were investigated and classified into three groups: 34 cases in the epithelial ovarian cancer (EOC) group, 38 cases in the germ cell tumors (GCTs) group and 28 cases in the sex cord-stromal tumors (SCSTs) group. The onset age of pregnant patients with epithelial ovarian cancer was significantly higher than that of other patients. Pelvic mass and abdominal pain were the common clinical presentations of pregnant patients with ovarian malignancy. For distinguishing epithelial ovarian cancer during pregnancy, the area under the curve (AUC) of CA-125 was 0.718 with an optimal cutoff value of 58.2 U/mL. Moreover, 53 patients underwent surgery during pregnancy, the majority of whom underwent unilateral adnexectomy in the second trimester. Furthermore, 43 patients received chemotherapy during pregnancy, and 28 delivered completely healthy newborns at birth; 13 neonates showed transient abnormalities without further complications; and 2 died during the neonatal period. CONCLUSIONS: Our study reveals the safety of chemotherapy for ovarian malignancy during pregnancy. However, large-sample prospective studies are still needed to further explore the safety of chemotherapy in pregnant patients with malignancy to choose the appropriate chemotherapy regimen and achieve the maximum benefit for patients.

FK506-loaded PLGA nanoparticles improve long-term survival of a vascularized composite allograft in a murine model.

BACKGROUND: The side effects of life-long administration of FK506 limit the clinical practice of vascularized composite allografts (VCAs). This study aimed to evaluate the feasibility of FK506-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (FK506 NPs) for prolonging the long-term survival of VCAs and reducing the side effects of FK506. METHODS: PLGA nanoparticles loaded with FK506 were prepared by the solvent evaporation method. The characterization of FK506 NPs was evaluated by electron microscopy. To confirm the function and safety of FK506 NPs, these particles were administrated into rats by intraperitoneal injection. The survival time of the allograft, systemic concentration of FK506, anti-rejection activity, and side-effect of FK506 NPs were evaluated in a Brown Norway (BN)-to-Sprague Dawley (SD) epigastric VCA transplantation model. RESULTS: Compared with the nontreatment, PLGA control and FK506 groups, the median survival times (MST) of the FK506 NP groups were significantly prolonged. The FK506 NPs could maintain therapeutic drug concentration for 60 days. Moreover, cytokine concentrations, flow cytometry of regulatory T cells (Tregs) and histopathology of allografts revealed significantly prolonged immunosuppression by FK506 NPs. FK506 NPs also ameliorated FK506 nephrotoxicity. CONCLUSIONS: FK506 NPs prolong the survival time of VCAs in a murine model with minimal nephrotoxicity, and provide a potential clinical strategy for ameliorating long-term side effects of immunosuppressive therapy.

Evaluating the accuracy of hand models obtained from two 3D scanning techniques.

The aim of this study was to identify an efficient approach for 3D imaging of hand. The 3D photographs of hand were taken with Gemini structured-light scanning system (SL scanning) and CT scanning. The 3D photographs, average time of scanning and reconstruction were compared between these two indirect techniques. The reliability, reproducibility and accuracy were evaluated in these two indirect techniques and the direct measurement (DM). Statistical differences in the measurements were assessed by 99% probability, with clinical significance at > 0.5 mm. The Gemini structured-light scanning system established a complete and smooth 3D hand photograph with shorter scanning and reconstruction time. Reproducibility of CT scanning and SL scanning methods was better (P < 0.01, both) than the DM, but did not differ significantly from each other (P = 0.462). Of the 19 (31.58%) measurements obtained, 6 showed significant differences (P < 0.01). Significant differences were observed more often for circumference dimensions (5/9, 55.56%) than for length dimensions (1/10, 10%). Mean absolute error (AE) of the 10 subjects was very low for 3D CT (0.29 ± 0.10 mm) and SL scanning (0.30 ± 0.11 mm). Absolute percentage error (APE) was 4.69 ± 2.33% and 4.88 ± 2.22% for 3D CT and SL scanning, respectively. AE for the PIP circumference between the 3rd finger (0.58 mm) and 4th finger (0.53 mm) scan was > 0.5 mm, indicating significant difference between DM and CT scanning at the level of 99% probability. In this study, the Gemini structured-light scanning system not only successfully established a complete and smooth 3D hand photograph, but also shortened the scanning and reconstruction time. Compared to the DM, measurements obtained using the two indirect techniques did not show any statistically or clinically insignificant difference in the values of the remaining 17 of 19 measurements (89.47%). Therefore, either of the two alternative techniques could be used instead of the direct measurement method.

Reconstruction of moderate-sized soft tissue defects in foot and ankle in children: Free deep inferior epigastric artery perforator flap versus circumflex scapular artery perforator flap.

BACKGROUND: This retrospective study was conducted to compare the outcomes between the free deep inferior epigastric artery perforator (DIEP) flap and the circumflex scapular artery perforator (CSAP) flap in reconstruction of moderate-sized soft tissue defects in the foot and ankle of pediatric patients. PATIENTS AND METHODS: From January 2004 to December 2016, 42 patients, ranging from 2 to 13 years old, underwent foot and ankle reconstruction, with a free DIEP flap in 21 cases and a free CSAP flap in the other 21cases. RESULTS: All the flaps survived. No marked differences were observed in the demographics, flap size, recipient vessels, and overall early or late complication rate (p > 0.05). The CSAP group had a shorter operation time (134.3 ±â€¯25 min vs. 202.4 ±â€¯24.3 min, p < 0.05) and flap harvest time (29.7 ±â€¯8.1 min vs. 52.2 ±â€¯9.8 min, p < 0.05) than the DIEP group had. In long-term follow-up, the CSAP group showed a lower fat hyperplasia rate (14% vs. 52%, p < 0.05) and better cosmetic outcomes than the DIEP group did (p < 0.05). The functional outcomes had no marked differences (p > 0.05). CONCLUSIONS: The DIEP flap and the CSAP flap are both good options for foot and ankle reconstruction of moderate-sized defects in pediatric patients. The CSAP flap has a shorter operation time and flap harvest time, a lower fat hyperplasia rate, and better long-term cosmetic outcomes than the DIEP flap does.