Development and validation of [18 F]-PSMA-1007 PET-based radiomics model to predict biochemical recurrence-free survival following radical prostatectomy.

PURPOSE: Biochemical recurrence (BCR) following radical prostatectomy (RP) is a significant concern for patients with prostate cancer. Reliable prediction models are needed to identify patients at risk for BCR and facilitate appropriate management. This study aimed to develop and validate a clinical-radiomics model based on preoperative [18 F]PSMA-1007 PET for predicting BCR-free survival (BRFS) in patients who underwent RP for prostate cancer. MATERIALS AND METHODS: A total of 236 patients with histologically confirmed prostate cancer who underwent RP were retrospectively analyzed. All patients had a preoperative [18 F]PSMA-1007 PET/CT scan. Radiomics features were extracted from the primary tumor region on PET images. A radiomics signature was developed using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The performance of the radiomics signature in predicting BRFS was assessed using Harrell's concordance index (C-index). The clinical-radiomics nomogram was constructed using the radiomics signature and clinical features. The model was externally validated in an independent cohort of 98 patients. RESULTS: The radiomics signature comprised three features and demonstrated a C-index of 0.76 (95% CI: 0.60-0.91) in the training cohort and 0.71 (95% CI: 0.63-0.79) in the validation cohort. The radiomics signature remained an independent predictor of BRFS in multivariable analysis (HR: 2.48, 95% CI: 1.47-4.17, p < 0.001). The clinical-radiomics nomogram significantly improved the prediction performance (C-index: 0.81, 95% CI: 0.66-0.95, p = 0.007) in the training cohort and (C-index: 0.78 95% CI: 0.63-0.89, p < 0.001) in the validation cohort. CONCLUSION: We developed and validated a novel [18 F]PSMA-1007 PET-based clinical-radiomics model that can predict BRFS following RP in prostate cancer patients. This model may be useful in identifying patients with a higher risk of BCR, thus enabling personalized risk stratification and tailored management strategies.

Comparison of valganciclovir versus foscarnet for the treatment of cytomegalovirus viremia in adult acute leukemia patients after allogeneic hematopoietic cell transplantation.

Cytomegalovirus (CMV) reactivation increases treatment-related mortality (TRM) after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed 141 adult acute leukemia (AL) patients suffered allo-HCT between 2017 and 2021, who developed CMV viremia post-HCT and treated with valganciclovir or foscarnet, to evaluate effectiveness and safety of both drugs. Viremia clearance rates (14 and 21 d post treatment) and toxicities were similar in two groups. However, valganciclovir was associated with a lower cumulative incidence of CMV recurrence within 180 days (16.7% vs. 35.7%, p=0.029) post CMV clearance. Finally, 2-year TRM was lower in valganciclovir group (9.7% ± 0.2% vs. 26.2% ± 0.3%, p = 0.026), result a superior 2-year overall survival (OS; 88.1% ± 5.2% vs. 64.4% ± 5.5%, p = 0.005) and leukemia-free survival (LFS; 82.0% ± 5.9% vs. 58.9% ± 5.6%, p = 0.009). Valganciclovir might decrease CMV viremia recurrence and led to better long-term outcome than foscarnet in adult AL patients developed CMV viremia post-HCT. Considering the inherent biases of retrospective study, well-designed trials are warranted to validate our conclusion.

Silencing KPNA2 Promotes Ferroptosis in Laryngeal Cancer by Activating the FoxO Signaling Pathway.

We aim to clarify the specific role of Karyopherin α2 (KPNA2) in the progression of laryngeal cancer, a kind of malignant tumor with a poor curative effect. We performed the bioinformatic analysis to obtain the ferroptosis-related differentially expressed genes. KPNA2 was screened out. Then the CCK-8 assay, wound healing assay, and transwell assay were used to clarify the changes in the proliferation, migration, and invasion abilities of laryngeal cancer cells after silencing KPNA2. The concentrations of iron ions, glutathione, superoxide dismutase, and malondialdehyde were evaluated by the corresponding detection kits. The expression levels of cyclooxygenase 2, Acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, forkhead box O (FoxO)1a and FoxO3a were determined by Western Blot. A total of 45 ferroptosis-related differentially expressed genes in laryngeal cancer were obtained, and KPNA2 was selected after bioinformatic analysis. In ferroptosis-induced laryngeal cancer cells, the cell viability, migration rate, invasion ability, and the expression of glutathione peroxidase 4, glutathione, and superoxide dismutase were further decreased and the expression of cyclooxygenase 2, Acyl-CoA synthetase long-chain family member 4, iron ions, and malondialdehyde were further increased after silencing KPNA2. The expression levels of FoxO1a and FoxO3a in laryngeal cancer cells were increased by silencing KPNA2. KPNA2 may be a promising therapeutic target for laryngeal cancer. Down-regulation of KPNA2 can promote ferroptosis in laryngeal cancer by stimulating the FoxO signaling pathway.

Combined Use of Autologous Sustained-Release Scaffold of Adipokines and Acellular Adipose Matrix to Construct Vascularized Adipose Tissue.

BACKGROUND: Adipose tissue engineering plays a key role in the reconstruction of soft-tissue defects. The acellular adipose matrix (AAM) is a promising biomaterial for the construction of engineered adipose tissue. However, AAM lacks sufficient adipoinduction potency because of the abundant loss of matrix-bound adipokines during decellularization. METHODS: An adipose-derived extracellular matrix collagen scaffold, "adipose collagen fragment" (ACF), was prepared using a novel mechanical method that provides sustained release of adipokines. Here, the authors used label-free proteomics methods to detect the protein components in AAM and ACF. In vivo, ACF was incorporated into AAM or acellular dermal matrix and implanted into nude mice to evaluate adipogenesis. Neoadipocytes, neovessels, and corresponding gene expression were evaluated. The effects of ACF on adipogenic differentiation of human adipose-derived stem cells and tube formation by human umbilical vein endothelial cells were tested in vitro. RESULTS: Proteomics analysis showed that ACF contains diverse adipogenic and angiogenic proteins. ACF can release diverse adipokines and induce highly vascularized, mature adipose tissue in AAM, and even in nonadipogenic acellular dermal matrix. Higher expression of adipogenic markers peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha and greater numbers of tubule structures were observed in ACF-treated groups in vitro. CONCLUSION: The combination of ACF and AAM could serve as a novel and promising strategy to construct mature, vascularized adipose tissue for soft-tissue reconstruction. CLINICAL RELEVANCE STATEMENT: The combined use of AAM and ACF has been proven to induce a highly vascularized, mature, engineered adipose tissue in the nude mouse model, which may serve as a promising strategy for soft-tissue reconstruction.

Adipokines-enriched adipose extract restores skin barrier and ameliorates inflammatory dysregulation in an atopic dermatitis mouse model.

BACKGROUND: Atopic dermatitis (AD) is a chronic dermatosis with high incidence worldwide characterized by skin barrier abnormalities and immune dysregulation. Conventional therapies are usually limited by side effects and high cost. Given the anti-inflammatory and repairing properties, adipokines are increasingly considered as promising therapeutic agents for dermatoses. Adipose collagen fragments (ACF), a novel adipokine-enriched product, may alleviate AD through modulating immune microenvironment and restoring skin barrier. METHODS: ACF was extracted from adipose tissue via high-speed homogenization (10000 rpm/min, 1min) and centrifugation (3000 g, 3min). Ovalbumin-induced AD female BALB/c mice (6-week-old) were intradermally injected with 0.2ml of ACF or PBS (negative control), with normal mice being set as normal control (n=6). Dermatitis severity, inflammatory metrics (epidermal thickness, infiltrated mast cells, Th-type cytokines expression), and skin barrier-related metrics (transepidermal water loss [TEWL], skin barrier-related proteins expression) were evaluated after the AD induction period (day 50). ACF-derived bioactive components were also evaluated using proteomic analysis. RESULTS: ACF-derived adipokines contained anti-inflammatory, skin barrier- and lipid biosynthesis-related components. ACF treatment decreased dermatitis severity (6.2±1.8, p<0.0001), epidermal thickness (25.7±12.8 µm, p=0.0045), infiltrated mast cells (31.3±12.4 cells/field, p=0.0475), and Th-type cytokines expression (INF-γ, TNF-α, IL-4, IL-4R, IL-13, and IL-17A; p<0.05) in AD skins. TEWL (29.8±13.8 g/m 2.h, p=0.0306) and skin barrier-related proteins expression (filaggrin: 14258±4375, p=0.0162; loricrin: 6037±1728, p=0.0010; claudin-1: 20043±6406, p=0.0420; ZO-1: 4494±1114, p=0.0134) were also improved. CONCLUSIONS: ACF improved AD in murine model by ameliorating inflammatory dysregulation and skin barrier defects (Graphical abstract, Supplementary Digital Content 1). Further validation is needed in more advanced animal models.

Underwater versus conventional endoscopic mucosal resection for colorectal lesions: An updated meta-analysis of randomized controlled trials.

Background and study aims Colorectal malignancy is a leading cause of death. Conventional endoscopic mucosal resection (CEMR) is a strategy used to resect precancerous lesions that involves injecting fluid beneath a polyp to create a gap for resection. Underwater endoscopic mucosal resection (UEMR) is a newer method that forgoes injection, instead filling the intestinal cavity with water to facilitate polyp resection. Our aim was to compare the safety and efficacy of these approaches by synthesizing the most contemporary evidence. Methods PubMed, Embase, and Cochrane libraries were searched from inception through November 11, 2022 for randomized controlled trials (RCTs) comparing UEMR and CEMR for resection of colorectal lesions. The primary outcome was the rate of en bloc resection and secondary outcomes included recurrence, procedure time, and adverse events (AEs). Results A total of 2539 studies were identified through our systematic literature search. After screening, seven RCTs with a total of 1581 polyps were included. UEMR was associated with significantly increased rates of en bloc resection (RR 1.18 [1.03, 1.35]; I 2 = 76.6%) versus conventional approaches. No significant differences were found in procedure time, recurrence, or AEs. Conclusions UEMR is a promising effective technique for removal of colorectal lesions. The most contemporary literature indicates that it improves en bloc resection rate without increasing procedure time, recurrence, or AEs (PROSPERO ID CRD42022374935).

Pathological characteristics of breast nodules after large-volume fat grafting for breast augmentation.

BACKGROUND: The complications of large-volume fat grafting (LVFG) for breast augmentation remain unpredictable and include palpable breast nodules, oil cysts, and calcifications. AIMS: This study was aimed to provide an optimal treatment option for breast nodules after LVFG and evaluate their pathological characteristics. PATIENTS/METHODS: We effectively performed complete resection of breast nodules in 29 patients after LVFG using a minimal skin incision with the vacuum-assisted breast biopsy (VABB) system under ultrasound guidance. And we further carried on histologic examination of excised nodules and evaluated their pathological characteristics. RESULTS: The breast nodules were excised thoroughly with cosmetic effect satisfactorily. Interestingly, subsequent histologic examination showed that type I and VI collagens were strongly expressed in the fibrotic area and type IV collagen were positively expressed around the blood vessel. Furthermore, we found that the type VI collagen+ area appeared around mac2+ macrophages and α-SMA+ myofibroblasts. CONCLUSIONS: The VABB system may be the optimal treatment option for breast nodules after LVFG. And type VI collagens may serve as a biomarker of grafted adipose tissue fibrosis. The relationship between macrophages, fibroblasts, and collagen formation may be therapeutic targets for regulating fibrosis.

Comparison of [18F]-OC PET/CT and contrast-enhanced CT/MRI in the detection and evaluation of neuroendocrine neoplasms.

OBJECTIVES: Gallium-68 (68Ga)-labeled somatostatin analog (SSA) PET imaging has been widely used in clinical practice of neuroendocrine neoplasms (NENs). Compared with 68Ga, 18F has a great practical and economic advantage. Although a few studies have shown the characteristics of [18F] AlF-NOTA-octreotide ([18F]-OC) in healthy volunteers and small NEN patient groups, its clinical value needs further investigation. Herein, this retrospective study aimed to evaluate the diagnostic accuracy of [18F]-OC PET/CT in detecting NENs, as well as to compare it with contrast-enhanced CT/MRI. METHODS: We retrospectively reviewed the data of 93 patients who had undergone [18F]-OC PET/CT and CT or MRI scans. Of these patients, there were 45 patients with suspected NENs for diagnostic evaluation, and 48 patients with pathologically confirmed NENs for detecting metastasis or recurrence. [18F]-OC PET/CT images were evaluated visually and semi-quantitatively by measuring maximum standardized uptake value of tumor (SUVmax), tumor-to-background SUVmax ratio (TBR), and SUVmax of hypophysis (SUVhypophysis). A total of 276 suspected NEN lesions were found in these 93 patients. The results of histopathology or radiographic follow-up served as the reference standard for the final diagnosis. RESULTS: Forty-five patients with suspected NENs were confirmed by histopathological examination via resection or biopsy. [18F]-OC PET/CT showed high radiotracer uptake in the lesions of G1-G3 NENs. [18F]-OC PET/CT showed superior performance with 96.3% of sensitivity, 77.8% of specificity, and 88.9% of accuracy in diagnosing NENs compared to CT/MRI. When cutoffs of SUVmax, TBR, and SUVhypophysis were 8.3, 3.1, and 15.4, [18F]-OC PET/CT had the best equilibrium between sensitivity and specificity for differentiating NEN from non-NEN lesions. For a total of 276 suspected NEN lesions, the sensitivity, specificity, and accuracy of [18F]-OC PET/CT for diagnosis of NENs were 90.5%, 82.1%, and 88.8%, respectively, and were higher than those of CT and MRI. G1 and G2 NENs had higher TBR and lower CT enhancement intensity than G3. The SUVmax and TBR had a positive correlation with CT enhancement intensity in G2 rather than in G1 or G3. CONCLUSIONS: [18F]-OC PET/CT is a promising imaging modality for initial diagnosis and detecting metastasis or postoperative recurrence in NENs.

[Clinical application of modified fistulectomy in the treatment of congenital pyriform sinus fistula based on segmental anatomy of fistula].

Objective:To discuss the clinical application and significance of the modified piriform fossa fistulectomy based on segmental anatomy of fistula. Methods:The clinical data of 84 patients with CPSF treated by modified pyriform sinus fistulectomy were analyzed retrospectively. The modified piriform fossa fistula resection adopts the fistula anterograde anatomy method to fine dissect the fistula. The operation procedure can be summarized into four parts: retrograde anatomy of recurrent laryngeal nerve, anatomy of external branch of superior laryngeal nerve, anterograde anatomy of fistula and partial thyroidectomy. Results:All 84 patients successfully completed the operation and discharged from the hospital. The operation time was（64.6±20.0） min, the intraoperative bleeding was（19.6±13.0） mL, and the average hospital stay was（6.8±1.1） d. Postoperative infection occurred in 1 case（1.19%）, temporary vocal cord paralysis in 1 case（1.19%）, no bleeding, pharyngeal fistula, dysphagia, permanent vocal cord paralysis and choking cough. The incidence of complications was 2.3%（2/84）. No complications such as permanent vocal cord paralysis and hypothyroidism occurred. Follow up for 57-106（Median 74） months showed no recurrence. Conclusion:A modified procedure based on segmental dissection of the fistula not only simplifies the traditional procedure, but also procedures the specific steps to provide a targeted and precise resection, which provides a proven surgical solution for complete eradication of the lesion and significantly reduces complications and recurrence.

[The managements of cervical chondrocutaneous branchial remnants].

Objective:To investigate the embryologic origin and diagnosis and management of cutaneous cartilage remains of gill origin in the neck. Methods:A total of 15 patients with cervical chondrocutaneous branchial remnants treated in Guangdong Provincial People's Hospital from January 2005 to December 2021 were retrospectively analyzed. They had a common feature showing a tumor in the lower third of the front of sternocleidomastoid muscle. The tumor looked like accessory auricle, never appeared pain or other symptoms of infection, and had no skin orifice. All patients underwent ultrasound examination, which showed an anechoic area under subcutaneous tissue of the neck or face. MRI examination in 6 cases showed subcutaneous irregular nodules the location of the lesion. Surgical resection of cervical chondrocutaneous branchial remnants was performed in all cases. Results:Postoperative pathological examination showed elastic cartilage. No complications were noticed. Recurrence was not observed in the cases by following-up of 8 months to 52 months（median: 41 months）. Conclusion:Cervical chondrocutaneous branchial remnants are relatively rare, which may originate from the second branchial arch and may be associated with other congenital malformations. The curative treatment is a complete excision preschool.

Adipose Collagen Fragment: A Novel Adipose-Derived Extracellular Matrix Concentrate for Skin Filling.

BACKGROUND: Skin filler is an option for treating skin aging and wrinkles; however, currently used fillers are limited by poor biocompatibility, rapid degradation, and possible hypersensitivity reactions. Autologous adipose tissue-derived products have been recognized as promising options for skin rejuvenation. OBJECTIVES: This study aimed to develop a novel adipose-derived product for skin filling. METHODS: Adipose collagen fragment (ACF) was prepared through pulverization, filtration, and centrifugation. The macrography, structure, types of collagen, and cell viability of ACF were evaluated by immunostaining, western blotting, and cell culture assays. ACF, nanofat, and phosphate-buffered saline (9 spots/side, 0.01 mL/spot) were intradermally injected in the dorsal skin of 36 female BALB/c nude mice; the skin filling capacity and the collagen remodeling process were then investigated. Twenty-one female patients with fine rhytides in the infraorbital areas were enrolled and received clinical applications of ACF treatment. Therapeutic effects and patients' satisfaction scores were recorded. RESULTS: The mean [standard deviation] yield of ACF from 50 mL of Coleman fat was 4.91 [0.25] mL. ACF contained nonviable cells and high levels of collagen I, collagen IV, and laminin. Fibroblasts and procollagen significantly increased in ACF and ACF-treated dermis (P < 0.05). Overall, 85.7% of patients were satisfied with the therapy results, and no infections, injection site nodules, or other unwanted side effects were observed. CONCLUSIONS: ACF significantly improved dermal thickness and collagen synthesis and may serve as a potential autologous skin filler.

Macrophage-mediated extracellular matrix remodeling after fat grafting in nude mice.

Clinical unpredictability and variability following fat grafting remain non-negligible problems due to the unknown mechanism of grafted fat retention. The role of the extracellular matrix (ECM), which renders cells with structural and biochemical support, has been ignored. This study aimed to clarify the ECM remodeling process, related cellular events, and the spatiotemporal relationship between ECM remodeling and adipocyte survival and adipogenesis after fat grafting. Labeled Coleman fat by the matrix-tracing technique was grafted in nude mice. The ECM remodeling process and cellular events were assessed in vivo. The related cytokines were evaluated by qRT-PCR. An in vitro cell migration assay was performed to verify the chemotactic effect of M2-like macrophages on fibroblasts. The results demonstrated that in the periphery, most of the adipocytes of the graft survived or regenerated, and the graft-derived ECM was gradually replaced by the newly-formed ECM. In the central parts, most adipocytes in the grafts died shortly after, and a small part of the graft-derived and newly-formed ECM was expressed with irregular morphology. Adipose ECM remodeling is associated with increased infiltration of macrophages and fibroblasts, as well as up-regulated expression of cytokines in the adipose tissue. To sum up, our results describe the various preservation mode of fat grafts after transplantation and underscore the importance of macrophage-mediated ECM remodeling in graft preservation after fat grafting. The appreciation and manipulation of underlying mechanisms that are operant in this setting stand to explore new therapeutic approaches and improve clinical outcomes of fat grafting.

Long-acting microneedle patch loaded with adipose collagen fragment for preventing the skin photoaging in mice.

Skin photoaging is one of the most serious public health problems in the 21st century that may lead to thin, saggy, and structurally weakened skin. Adipokine therapy toward skin photoaging is always associated with poor permeability, biologic stability and the short in vivo release duration. Our laboratory previously extracted an extracellular matrix component of adipose tissue by purely physical methods, namely "adipose collagen fragment (ACF)", which holds promise for preventing skin photoaging. However, the injection treatment of ACF requires repeated preparation processes and injection procedures, which may be time-consuming and painful. Therefore, we describe the fabrication and assessment of a detachable ACF-microneedle (ACF-MN) patch that creates minimally invasive dermal microtrauma upon application. And we evaluated the morphology characterization, mechanical properties and puncture performance in vitro. The delivery efficiency of ACF from the patches was estimated in vitro and vivo. Then, the therapeutic efficacy was identified through applying ACF-MN patches into the dermis of UVA-induced photoaging mice and the related detection of skin photoaging was estimated. Our results demonstrated that ACF-MN exhibited well skin puncture performance and could release ACF component slowly. Meanwhile, this microneedle device loaded with ACF exhibited the treatment efficiency on skin photoaging in a mouse model. Therefore, implantation of the microtrauma-mediated, long-acting ACF-MN system can be utilized as a potential candidate for preventing skin photoaging in the clinic.

Adverse impact of a high allelic burden FLT3-ITD mutation on allogeneic hematopoietic stem cell transplantation in patients with cytogenetically normal AML.

Risks associated with the FLT3-ITD mutation in patients receiving chemotherapy alone for cytogenetic normal acute myeloid leukemia (CN-AML) depend on the allelic ratio (AR) and concomitant NPM1 mutation. Nevertheless, their prognostic ability after allogeneic hematopoietic cell transplantation (allo-HCT) remains undetermined. Moreover, previous studies have revealed that haploidentical transplantation improves outcomes of FLT3-ITD patients. To elucidate whether this alteration also impacts prognosis of myeloablative allo-HCT upon first remission, we retrospectively reviewed the prognostic ability of FLT3-ITD mutations in 205 CN-AML patients. Our analysis demonstrated that FLT3-ITD AR was closely related to pretransplant MRD and induction response. Multivariate analysis showed that high-AR FLT3-ITD, pretransplant MRD and induction response were independent risk factors for CN-AML. In addition, we presented evidence that the high-AR FLT3-ITD patient prognosis was not overcome by haploidentical transplantation, but was markedly improved by cGVHD. More importantly, among patients with negative pretransplant MRD, high-AR FLT3-ITD patients did not have increased relapse risk, compared to low-AR FLT3-ITD and wild-type FLT3 patients. Our findings will aid in accurate prognostic stratification of FLT3-ITD patients. We also recommend further targeted and coordinated approaches to sustain durable remission following induction chemotherapy and allo-HCT in this high-risk patient population.

IL-39 promotes chronic graft-versus-host disease by increasing T and B Cell pathogenicity.

BACKGROUND: Chronic graft-versus-host disease (cGVHD) remains a major complication during the late phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). IL-39, a newly described pro-inflammatory cytokine belonging to the IL-12 family, plays a role in lupus development. Recently, IL-39 has been identified as a pathogenic factor in acute GVHD (aGVHD). However, the role of IL-39 in the pathogenesis of cGVHD remains unclear. METHODS: We constructed a recombinant IL-39 plasmid and established scleroderma and lupus-like cGVHD models. Quantitative PCR and enzyme-linked immunosorbent assay (ELISA) were used to detect IL-39 expression in mice and patients post transplantation, respectively. Hydrodynamic gene transfer (HGT) was performed to achieve IL-39 overexpression in vivo. Multiparameter flow cytometry, western blotting, and assays in vitro were performed to investigate the effect of IL-39 on cGVHD. RESULTS: The relative expression of IL-23p19 and EBi3 was significantly increased in the intestine of cGVHD mice on day 40 post allo-HSCT, and IL-39 levels were significantly elevated in the serum of patients following allo-HSCT. Overexpression of IL-39 significantly aggravated the severity of cGVHD. Increased IL-39 levels promoted T-cell activation and germinal center responses, and may exacerbate thymic damage. Consistently, blocking IL-39 markedly ameliorated immune dysregulation in the cGVHD mice. Furthermore, we found that IL-39 was produced by B cells, CD11b+ cells, and CD8+T cells after activation. Stimulation of IL-39 led to upregulation of the IL-39 receptor on CD4+T cells and further caused activation of the STAT1/STAT3 pathway, through which IL-39 may exert its pro-inflammatory effects. CONCLUSION: Our study reveals a critical role for IL-39 in cGVHD pathogenesis and indicates that IL-39 may serve as a potential therapeutic target for cGVHD prevention.

[The Role and Mechanism of Tfh and B Cell in Human Chronic Graft-Versus-Host-Disease].

AbstractObjective: To investigate the role and mechanism of circulating follicular helper T cells (cTfh), extrafollicular helper T cells, B cells and their subsets in chronic graft-versus-host disease (cGVHD) after transplantation. METHODS: Peripheral blood of cGVHD 64 patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Soochow University from 2016 to 2019 were collected. The percentage of cTfh cells, extrafollicular helper T cells, B cells and subsets were detected by flow cytometry. The healthy donors were detected as control. Percentage of each cell subpopulation between the two groups were compared by the two-tailed Students' T test. RESULTS: The percentage of circulating follicular helper T cells (cTfh, CD4+CXCR5+) was markedly decreased in patients with cGVHD as compared with that in the healthy donors (0.53%±0.10% vs 3.91%±0.60%, P<0.001). The percentage of extrafollicular helper T cells (CD44hiCD62LloPSGL-1loCD4+T) of the patients in cGVHD and the healthy donors were 8.86%±0.45% and 5.38%±0.79% (P=0.003). A significant change in B cell subsets was found in the patients with cGVHD. The two types of antigen-stimulate CD27+ B cell: the percentages of pre-GC B cells (CD19+IgD+CD38hiCD27+) and plasmablast/plasma cells (PB/PC, CD19+IgD-CD38hiCD27+) of patients with cGVHD were 20.91%±2.70% and 41.05%±5.00%, respectively, which were significantly higher than those in healthy donors (P=0.005, P=0.014). Meanwhile, the percentage of unstimulated CD27- B cells in patients with cGVHD was significantly reduced, especially the naive B cells (CD19+IgD+CD38loCD27-, 12.59%±2.63%, P=0.025). There was a positive correlation between the percentage of extrafollicular helper T cells and plasmablast/ plasma cells (PB/PC) in cGVHD patients (r=0.43). CONCLUSION: Compared with healthy donor, cTfh cells, extrafollicular helper T cells and B cell subsets in the peripheral blood of patients with cGVHD after transplantation changed in varying degress.

Adipose Collagen Fragment: A Novel Adipose-Derived Extracellular Matrix Concentrate for Skin Filling.

BACKGROUND: Skin filler is an option for treating skin aging and wrinkles; however, currently used fillers are limited by poor biocompatibility, rapid degradation, and possible hypersensitivity reactions. Autologous adipose tissue-derived products have been recognized as promising options for skin rejuvenation. OBJECTIVES: This study aimed to develop a novel adipose-derived product for skin filling. METHODS: Adipose collagen fragment (ACF) was prepared through pulverization, filtration, and centrifugation. The macrography, structure, types of collagen, and cell viability of ACF were evaluated by immunostaining, western blotting, and cell culture assays. ACF, nanofat, and phosphate-buffered saline (9 spots/side, 0.01 mL/spot) were intradermally injected in the dorsal skin of 36 female BALB/c nude mice; the skin filling capacity and the collagen remodeling process were then investigated. Twenty-one female patients with fine rhytides in the infraorbital areas were enrolled and received clinical applications of ACF treatment. Therapeutic effects and patients' satisfaction scores were recorded. RESULTS: The mean [standard deviation] yield of ACF from 50 mL of Coleman fat was 4.91 [0.25] mL. ACF contained nonviable cells and high levels of collagen I, collagen IV, and laminin. Fibroblasts and procollagen significantly increased in ACF and ACF-treated dermis (P < 0.05). Overall, 85.7% of patients were satisfied with the therapy results, and no infections, injection site nodules, or other unwanted side effects were observed. CONCLUSIONS: ACF significantly improved dermal thickness and collagen synthesis and may serve as a potential autologous skin filler.

Clinical Outcomes of B Cell Acute Lymphoblastic Leukemia Patients Treated with Haploidentical Stem Cells Combined with Umbilical Cord Blood Transplantation.

Clinical outcomes of hematopoietic stem cell transplantation (HSCT) using a haploidentical stem cell graft and an unrelated umbilical cord blood unit (haplo-cord HSCT) for the treatment of B cell acute lymphoblastic leukemia (B-ALL) remain unclear. This study was conducted to explore the clinical outcomes of haplo-cord HSCT in patients with B-ALL. A total of 112 B-ALL patients who underwent haplo-cord HSCT and 64 B-ALL patients who underwent haploidentical HSCT (haplo-HSCT) at our center between 2010 and 2020 were retrospectively included in this study, and clinical outcomes and prognostic factors were further analyzed. Of the 112 haplo-cord HSCT recipients, 106 (94.6%) achieved complete haploidentical chimerism and 6 (5.4%) had mixed cord blood chimerism. No differences in neutrophil and platelet recovery or in the incidences of graft-versus-host disease, cytomegalovirus/Epstein-Barr virus viremia, bloodstream infection, or hemorrhagic cystitis were observed between the haplo-cord HSCT and haplo-HSCT groups. Compared with the haplo-HSCT group, the haplo-cord HSCT group had a higher absolute number of CD3+ cells (P = .029) and a lower ratio of CD3+CD4+ /CD3+CD8+ cells (P = .049) at 1 month post-transplantation. Moreover, the haplo-cord HSCT group had lower minimal residual disease (MRD) levels at 1 month (P = .020) and 100 days (P = .038) post-transplantation and a better 3-year prognosis (overall survival, P = .016; disease-free survival, P = .041; cumulative incidence of relapse [CIR], P = .016). The CIRs in patients with adverse genomic features (P = .040) or flow cytometry-based MRD (FCM-MRD) ≥1 × 10-4 (P = .033) were improved by haplo-cord HSCT. Multivariate analysis revealed that haplo-cord HSCT could independently improve the 3-year OS, DFS, and CIR of B-ALL patients (OS, P = .029; DFS, P = .024; CIR, P = .024). In addition, allo-HSCT at first complete remission was an independent parameter associated with 3-year OS for B-ALL patients (P = .014). An FCM-MRD ≥1 × 10-4 pre-HSCT could independently predict unfavorable 3-year DFS and CIR (DFS, P = .020; CIR, P = .036) in B-ALL patients. Our data suggest that the use of haplo-cord HSCT can independently improve survival in patients with B-ALL.