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1.
J Intensive Med ; 4(2): 240-246, 2024 Apr.
Article En | MEDLINE | ID: mdl-38681793

Background: Prolonged length of stay (LOS) of sepsis can drain a hospital's material and human resources. This study investigated the correlations between T helper type 17 (Th17) and regulatory T (Treg) balance with LOS in sepsis. Methods: A prospective clinical observational study was designed in Changhai Hospital affiliated to Naval Medical University in Shanghai, China, from January to October 2020. The patients diagnosed with sepsis and who met the inclusion and exclusion criteria were recruited and whether the levels of cytokines, procalcitonin, subtypes, and biomarkers of T cells in the peripheral blood were detected. We analyzed the correlation between these and LOS. Results: Sixty septic patients were classified into two groups according to whether their intensive care unit (ICU) stay exceeded 14 days. The patients with LOS ≥14 days were older ([72.6±7.5] years vs. [63.3±10.4] years, P=0.015) and had higher Sequential Organ Failure Assessment (SOFA) (median [interquartile range]: 6.5 [5.0-11.0] vs. 4.0 [3.0-6.0], P=0.001) and higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (16.0 [13.0-21.0] vs. 8.5 [7.0-14.0], P=0.001). There was no difference in other demographic characteristics and cytokines, interleukin-6, tumor necrosis factor-α, and interleukin-10 between the two groups. The Th17/Treg ratio of sepsis with LOS <14 days was considerably lower (0.48 [0.38-0.56] vs. 0.69 [0.51-0.98], P=0.001). For patients with LOS ≥14 days, the area under the receiver operating characteristic curve for the Th17/Treg ratio was 0.766. It improved to 0.840 and 0.850 when combined with the SOFA and APACHE II scores, respectively. Conclusions: The Th17/Treg ratio was proportional to septic severity and can be used as a potential predictor of ICU stay in sepsis, presenting a new option for ICU practitioners to better care for patients with sepsis.

2.
Genomics ; 116(2): 110808, 2024 Mar.
Article En | MEDLINE | ID: mdl-38364976

Immunotherapy is currently approved for CRC whose tumors have high MSI-H. To find additional biomarkers for immunotherapy in CRC, targeted sequencing was performed on tumor tissues from a discovery cohort of 161 CRC patients. Validation cohorts from the cBioPortal were also used for survival and tumor cell infiltration analyses. The FAT1-mutated CRC group often co-occurred with MSI events and displayed a higher tumor mutational burden compared to the FAT1 wild-type CRC. Overall survival was higher in patients with FAT1 mutations than in patients with wild type FAT1. The altered PI3K-AKT pathway and immune pathways were enriched in the FAT1-mutated CRC. A higher infiltration rate of immune cells including CD4+ T cells, CD8+ T cells, macrophages M1 and regulatory T cells were also observed in the colorectal tumors with FAT1 mutation compared to tumors with wild type FAT1. The results showed that CRC patients with FAT1 mutations exhibited an immunotherapy-favorable profile.


Colorectal Neoplasms , Phosphatidylinositol 3-Kinases , Humans , Phosphatidylinositol 3-Kinases/genetics , Mutation , Colorectal Neoplasms/pathology , Microsatellite Instability , Immunity , Prognosis , Cadherins/genetics
3.
Ther Adv Med Oncol ; 16: 17588359231225035, 2024.
Article En | MEDLINE | ID: mdl-38293276

Background: Different RAS/BRAF allele mutations imply distinct biological properties in various solid tumors. Recently, several studies have focused on the predictive and prognostic roles of various RAS/BRAF allele mutations in colorectal cancer (CRC) but the results remain controversial. Methods: Between March 2017 and September 2022, the patients diagnosed as stages I-IV CRC with detailed medical records including next-generation sequencing (NGS) data and clinicopathological follow-up information available at our center were enrolled. Survival data were estimated using the Kaplan-Meier method, and the difference was tested in a log-rank test. Multivariate tests were carried out using Cox models. Results: A total of 1029 CRC patients were included, and the incidence of RAS/BRAF mutation was 58.4%. The hypermutated cohort was defined as patients with microsatellite instability-H or POLE/D mutation. In the non-hypermutational cohort, only KRAS G13D mutation was associated with a higher incidence and inferior disease-free survival in patients with stage I-III CRC. In the cohort of patients with non-hypermutated metastatic colorectal cancer (mCRC), we assessed the risk of various RAS/BRAF allele mutations and subsequently reclassified patients into four groups based on first-line median progression-free survival: wild type (group 1), low-risk RAS/BRAF mutation (group 2, RAS/BRAF mutations other than KRAS G13D/G12V/G12C or BRAF V600E), high-risk RAS mutation (group 3, KRAS G13D/G12V/G12C), and BRAF V600E mutation (group 4). mCRC patients with high-risk RAS mutation could significantly benefit from intensive triplet chemotherapy (hazard ratio, 2.54; 95% confidence interval, 1.36-5.12; p = 0.0091). Conclusion: In the non-hypermutated CRC cohort, the prognostic risk of various RAS/BRAF allele mutations varied between local and metastatic CRC. KRAS G13D mutation tended to be the only prognostic marker for stages I-III CRC; however, KRAS G13D/G12V/G12C mutations collectively defined a high-risk subgroup of mCRC patients with poor prognosis, who would benefit from intensive triplet chemotherapy.

4.
Cardiology ; 149(2): 176-182, 2024.
Article En | MEDLINE | ID: mdl-37939678

INTRODUCTION: Adiponectin is a cellular protein secreted by adipocytes, which is closely related to a variety of diseases, including atrial fibrillation (AF). Idiopathic atrial fibrillation (IAF) is defined as AF without hypertension, diabetes, and other underlying diseases. Genetic polymorphism of adiponectin affects serum adiponectin concentration. However, the association of serum adiponectin concentration and its genetic polymorphism with IAF has not been studied. This study investigated the relationship between serum levels of adiponectin, adiponectin gene polymorphisms, and the risk of developing IAF in a Chinese Han population. METHODS: Patients with IAF (n = 172, IAF group) and healthy individuals (n = 150, control group) were consecutively and randomly recruited and fasting peripheral blood samples were collected. All participants were examined for serum adiponectin concentrations and the polymorphisms SNP45T>G (SmaI locus, rs2241766) and SNP276G>T (BsmI locus, rs1501299) of the adiponectin gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Related clinical data from the two groups were also collected. RESULTS: Plasma adiponectin levels in the IAF group were significantly lower than those in the control group (9.9 ± 2.6 mg/L vs. 16.1 ± 7.0 mg/L, p = 0.006). There were no significant differences among the three genotypes (wild type, mutant heterozygote, and homozygote) of SNP45T>G or SNP276G>T in the prediction value of IAF. The frequency of the T allele of SNP45 T>G was 70.3% in the IAF group and significantly different from that of the control group (71.3%; p = 0.02). In the case of SNP276G>T, the frequency of the G allele was 68.61% in patients with IAF compared to 73.34% in the control group (p = 0.35). Furthermore, a comparison of the clinical data of individuals in the two groups revealed that the left atrial diameter (LAD) in patients in the IAF group was obviously higher than that in the control group (43.3 ± 6.7 mm vs. 37.9 ± 5.1 mm, respectively; p < 0.001). The left ventricular ejection fraction (LVEF) in the IAF group was obviously reduced than that in the control group (54.7 ± 11.9% vs. 60.2 ± 5.6%, respectively; p < 0.001). CONCLUSIONS: Low plasma adiponectin levels were significantly associated with IAF. Hypoadiponectinemia can thus serve as an important factor for the incidence of IAF. The genotypes of SNP45T>G and SNP276G>T in the adiponectin gene may not correlate with the occurrence of IAF. However, our results demonstrate that the T allele of SNP45T>G may be responsible for IAF development in the Chinese Han population.


Atrial Fibrillation , Humans , Atrial Fibrillation/genetics , Adiponectin/genetics , Stroke Volume , Polymorphism, Single Nucleotide , Ventricular Function, Left , Genotype , Gene Frequency , Genetic Predisposition to Disease , Case-Control Studies
5.
Ann Surg ; 2023 Dec 13.
Article En | MEDLINE | ID: mdl-38088199

OBJECTIVE: To examine the outcomes of intestinal autotransplantation (IATx) in patients with locally advanced or recurrent colon cancer (LACC or LRCC) invading the superior mesenteric artery (SMA). BACKGROUND: SMA Involvement in LACC or LRCC is deemed unresectable and is associated with a poor prognosis. Combined extended resections of multiple organs together with SMA, followed by IATx may offer favorable clinical outcomes. However, data on its safety and efficacy are scarce. DESIGN: This retrospective cohort study included patients undergoing IATx between May 2018 and December 2022 in intestinal transplant programs at two university-affiliated hospitals in China. Patients with LACC or LRCC concomitantly with SMA contact of more than 180° were included. Patients with a locoregional peritoneal, pelvic, or distal metastasis were excluded. RESULTS: Ten patients underwent either IATx combined with pancreaticoduodenectomy (n=8) or IATx alone (n=2). Eight patients (80%) were male, and the median age was 55 years (range, 32 - 71 y). The Kaplan-Meier estimates for recurrence-free survival and overall survival at 3 years after IATx were 68% and 80%, respectively. No perioperative deaths occurred. All ten patients experienced postoperative complications including Clavien-Dindo grade I (n=1), grade II (n=4), grade IIIa (n=1), grade IIIb (n=3) and grade IVa (n=1), which comprised acute venous thromboses, upper gastrointestinal hemorrhage, anastomotic leak, gastropareses and significant pleural effusions. With an average follow-up of 23.9 months, eight patients (80%) were currently alive without evidence of disease. CONCLUSION: Extended resection for LACC or LRCC invading SMA can be performed safely and is associated with prolonged survival.

6.
J Intensive Med ; 3(3): 275-282, 2023 Jul 31.
Article En | MEDLINE | ID: mdl-37533812

Background: The predictive value of red blood cell distribution width (RDW) for mortality in patients with sepsis-induced acute kidney injury (SI-AKI) remains unclear. The present study aimed to investigate the potential association between RDW at admission and outcomes in patients with SI-AKI. Methods: The Medical Information Mart for Intensive Care (MIMIC)-IV (version 2.0) database, released in June of 2022, provides medical data of SI-AKI patients to conduct our related research. Based on propensity score matching (PSM) method, the main risk factors associated with mortality in SI-AKI were evaluated using Cox proportional hazards regression analysis to construct a predictive nomogram. The concordance index (C-index) and decision curve analysis were used to validate the predictive ability and clinical utility of this model. Patients with SI-AKI were classified into the high- and low-RDW groups according to the best cut-off value obtained by calculating the maximum value of the Youden index. Results: A total of 7574 patients with SI-AKI were identified according to the filter criteria. Compared with the low-RDW group, the high-RDW group had higher 28-day (9.49% vs. 31.40%, respectively, P <0.001) and 7-day (3.96% vs. 13.93%, respectively, P <0.001) mortality rates. Patients in the high-RDW group were more prone to AKI progression than those in the low-RDW group (20.80% vs. 13.60%, respectively, P <0.001). Based on matched patients, we developed a nomogram model that included age, white blood cells, RDW, combined hypertension and presence of a malignant tumor, treatment with vasopressor, dialysis, and invasive ventilation, sequential organ failure assessment, and AKI stages. The C-index for predicting the probability of 28-day survival was 0.799. Decision curve analysis revealed that the model with RDW offered greater net benefit than that without RDW. Conclusion: The present findings demonstrated the importance of RDW, which improved the predictive ability of the nomogram model for the probability of survival in patients with SI-AKI.

7.
Mil Med Res ; 10(1): 27, 2023 06 19.
Article En | MEDLINE | ID: mdl-37337301

BACKGROUND: Sustained yet intractable immunosuppression is commonly observed in septic patients, resulting in aggravated clinical outcomes. However, due to the substantial heterogeneity within septic patients, precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking. METHODS: We adopted cross-species, single-cell RNA sequencing (scRNA-seq) analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis. Flow cytometry, laser scanning confocal microscopy (LSCM) imaging and Western blotting were applied to identify the presence of S100A9+ monocytes at protein level. To interrogate the immunosuppressive function of this subset, splenic monocytes isolated from septic wild-type or S100a9-/- mice were co-cultured with naïve CD4+ T cells, followed by proliferative assay. Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage. RESULTS: ScRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis, for which distinct monocyte subsets were enriched in disparate subclusters of septic patients. We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR (HLA-DR), which were prominently enriched in septic patients and might exert immunosuppressive function. By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments, we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice, corresponding to HLA-DRlowS100Ahigh monocytes in human sepsis. Moreover, we found that S100A9+ monocytes exhibited profound immunosuppressive function on CD4+ T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression. CONCLUSIONS: This study identifies HLA-DRlowS100Ahigh monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis.


Monocytes , Sepsis , Humans , Animals , Mice , Monocytes/chemistry , Monocytes/metabolism , Disease Models, Animal , HLA-DR Antigens/analysis , HLA-DR Antigens/metabolism , Sepsis/genetics
8.
Cell Prolif ; 56(11): e13493, 2023 Nov.
Article En | MEDLINE | ID: mdl-37128180

Cell migration and proliferation are conducive to wound healing; however, regulating cell proliferation remains challenging, and excessive proliferation is an important cause of scar hyperplasia. Here, we aimed to explore how a subvacuum environment promotes wound epithelisation without affecting scar hyperplasia. Human immortalized keratinocyte cells and human skin fibroblasts were cultured under subvacuum conditions (1/10 atmospheric pressure), and changes in cell proliferation and migration, target protein content, calcium influx, and cytoskeleton and membrane fluidity were observed. Mechanical calcium (Ca2+ ) channel blockers were used to prevent Ca2+ influx for reverse validation. A rat wound model was used to elucidate the mechanism of the subvacuum dressing in promoting healing. The subvacuum environment was observed to promote cell migration without affecting cell proliferation; intracellular Ca2+ concentrations and PI3K, p-PI3K, AKT1, p-AKT 1 levels increased significantly. The cytoskeleton was depolymerized, pseudopodia were reduced or absent, and membrane fluidity increased. The use of Ca2+ channel blockers weakened or eliminated these changes. Animal experiments confirmed these phenomena and demonstrated that subvacuum dressings can effectively promote wound epithelisation. Our study demonstrates that the use of subvacuum dressings can enhance cell migration without affecting cell proliferation, promote wound healing, and decrease the probability of scar hyperplasia.


Cicatrix, Hypertrophic , Humans , Rats , Animals , Cicatrix, Hypertrophic/metabolism , Hyperplasia/metabolism , Calcium/metabolism , Wound Healing , Cell Movement , Fibroblasts/metabolism , Cell Proliferation , Phosphatidylinositol 3-Kinases/metabolism
9.
Cancer Med ; 12(11): 12482-12494, 2023 06.
Article En | MEDLINE | ID: mdl-37081776

BACKGROUND: Limited data have been used to evaluate the efficacy of immunotherapy in metastatic colorectal cancer (mCRC). Furthermore, potential markers that can be used to identify responding patients and to further improve efficacy have not been fully explored. METHODS AND RESULTS: In our study, we included a total of 97 patients with mCRC, who each received programmed death-1 (PD-1) inhibitor-based combination therapy at our center. All 12 hypermutated patients benefited from immunotherapy, with median progression-free survival (mPFS) reaching 28.3 months, regardless of liver metastasis. The objective response rate (ORR) of non-hypermutated patients was 16.5% (14/85), with an mPFS of 4.0 months. For non-hypermutated patients, multivariate analysis revealed that the combination of liver metastasis and baseline lesion number significantly stratified response and survival. The lesion-based analysis indicated that the lymph node was the most responsive, followed by the peritoneum and lung, with liver metastasis being the least responsive. None of the patients (0/7) with negative programmed ligand-1 (PD-L1) expression responded, and positive PD-L1 expression may serve as a biomarker (mPFS 5.7 vs. 2.2 months, p = 0.002) that can be used to further guide treatment in non-hypermutated mCRC with liver metastasis (CRLMs). CONCLUSION: Patients with hypermutated mCRC benefited significantly from immunotherapy, whereas the non-hypermutated cohort with liver metastasis and numerous lesions showed less benefit. The lesion sites reflected varying levels of efficacy, among which PD-L1 potentially cooperated to guide the immunotherapy of CRLMs.


Colonic Neoplasms , Liver Neoplasms , Lung Neoplasms , Rectal Neoplasms , Humans , B7-H1 Antigen/metabolism , Immune Checkpoint Inhibitors/therapeutic use , Liver Neoplasms/drug therapy , Lung Neoplasms/pathology
10.
Nanoscale ; 15(14): 6745-6758, 2023 Apr 06.
Article En | MEDLINE | ID: mdl-36942933

Effective drugs that can be quickly delivered to and retained for a long time in the renal tubule are necessary for acute kidney injury (AKI) treatment. In this study, a gold nanoparticle-modified mesoporous silica (Au@MSN-NH2)-camouflaged (methoxyphenyl)(morpholino)phosphinodithioic acid (GYY4137) asymmetrical nanosystem decorated with L-serine (S; an AKI-targeting agent) and D-Arg-dimethylTyr-Lys-Phe-NH2 (TK-SS31; a reactive oxygen species (ROS)-sensitive thioketal linker/mitochondria-targeted antioxidant) was constructed for the treatment of renal tubule and mitochondrial injury as well as the synergistic and active treatment of AKI. Due to the enhanced permeability and retention (EPR) of nanomotors, they could progressively accumulate in renal sites. The asymmetrical nanosystem achieved effective drug distribution in the kidney as well as pH-responsive hydrogen sulfide (H2S) release and ROS-responsive SS31 release, resulting in an active therapeutic effect mediated by nanomotor motion resulting from asymmetrical H2S release.


Acute Kidney Injury , Metal Nanoparticles , Nanoparticles , Humans , Reactive Oxygen Species , Gold , Kidney , Hydrogen-Ion Concentration
11.
Am J Orthod Dentofacial Orthop ; 164(1): 57-66, 2023 Jul.
Article En | MEDLINE | ID: mdl-36842949

INTRODUCTION: This retrospective study aimed to evaluate the further development of the lateral incisor and its associated periodontium adjacent to the treated labial inversely impacted maxillary central incisor. METHODS: We enrolled 23 participants (average age, 8.24 ± 1.43 years) undergoing a mean follow-up period of 31.10 ± 13.05 months. Each participant had an unimpacted lateral incisor and a successfully treated unilateral labial inversely impacted maxillary central incisor. The contralateral lateral incisors served as controls. Cone-beam computed tomography data were available for treatment completion and follow-up stages. The variables (including root length, dental age, root canal width, root-crown angulation, and alveolar bone loss and thickness) were evaluated with Dolphin Imaging software (version 11.95; Dolphin Imaging and Management Solutions, Chatsworth, Calif). RESULTS: At the follow-up stage, the lateral incisors in the impacted side had significantly longer root lengths, smaller root canal widths, and thinner labial bone widths at the apex than at the posttreatment stage (P <0.001, P = 0.036, and P = 0.001, respectively). A significant lateral incisor root length reduction was noted when comparing the impacted and contralateral sides, although no variation was observed in root canal width. Similarly, crown-root angulation of the lateral incisor on the impacted side was significantly larger than that of the contralateral lateral incisor. The lateral incisor on the impacted side also had thicker labial and thinner lingual bone widths at the apex than the contralateral lateral incisor. CONCLUSIONS: The lateral incisor adjacent to the successfully treated labial inversely impacted maxillary central incisor showed continuous growth during follow-up stages, exhibiting a similar morphology and alveolar bone quality but shorter root length, larger root angulation, and thinner lingual bone width at the apex than those of the contralateral lateral incisors.


Incisor , Tooth, Impacted , Humans , Incisor/diagnostic imaging , Follow-Up Studies , Retrospective Studies , Tooth Root/diagnostic imaging , Tooth, Impacted/diagnostic imaging , Tooth, Impacted/therapy , Cone-Beam Computed Tomography/methods , Maxilla/diagnostic imaging
12.
Molecules ; 28(3)2023 Jan 22.
Article En | MEDLINE | ID: mdl-36770781

Breast cancer is one of the most prevalent malignancies and the leading cause of cancer-associated mortality in China. Icaritin (ICT), a prenyl flavonoid derived from the Epimedium Genus, has been proven to inhibit the proliferation and stemness of breast cancer cells. Our previous study demonstrated that IC2, a derivative of ICT, could induce breast cancer cell apoptosis by Stearoyl-CoA desaturase 1 (SCD1) inhibition. The present study further investigated the mechanism of the inhibitory effects of IC2 on breast cancer cells in vitro and in vivo. Our results proved that IC2 could stimulate autophagy in breast cancer cells with the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling and mitogen-activated protein kinase (MAPK) signaling. Combination treatment of the AMPK inhibitor decreased IC2-induced autophagy while it markedly enhanced IC2-induced apoptosis. In common with IC2-induced apoptosis, SCD1 overexpression or the addition of exogenous oleic acid (OA) could also alleviate IC2-induced autophagy. In vivo assays additionally demonstrated that IC2 treatment markedly inhibited tumor growth in a mouse breast cancer xenograft model. Overall, our study was the first to demonstrate that IC2 induced cytoprotective autophagy by SCD1 inhibition in breast cancer cells and that the autophagy inhibitor markedly enhanced the anticancer activity of IC2. Therefore, IC2 was a potential candidate compound in combination therapy for breast cancer.


AMP-Activated Protein Kinases , Breast Neoplasms , Humans , Animals , Mice , Female , AMP-Activated Protein Kinases/metabolism , Apoptosis , Flavonoids/pharmacology , Breast Neoplasms/metabolism , Autophagy , Cell Line, Tumor , Stearoyl-CoA Desaturase/genetics
13.
Ann Surg ; 278(5): e1055-e1062, 2023 11 01.
Article En | MEDLINE | ID: mdl-36727746

OBJECTIVE: To achieve radical resection of locally advanced pancreatic ductal adenocarcinoma (PDAC), and tested the safety and benefits of intestinal autotransplantation in pancreatic surgery. BACKGROUND: PDAC has an extremely dismal prognosis. Radical resection was proved to improve the prognosis of patients with PDAC; however, the locally advanced disease had a very low resection rate currently. We explored and evaluated whether the combination of modern advances in systemic treatment and this macroinvasive surgery was feasible in clinical practice. METHODS: Patients diagnosed as PDAC with superior mesenteric artery involvement and with or without celiac trunk involvement were included. Patients were treated with modified-FOLFIRINOX chemotherapy with or without anti-PD-1 antibodies and were applied to tumor resection combined with intestinal autotransplantation. Data on operative parameters, pathologic results, mortality, morbidity, and survival were analyzed. RESULTS: A total of 36 consecutive cases were applied to this strategy and underwent radical resection combined with intestinal autotransplantation. Among these patients, 24 of them received the Whipple procedure, 11 patients received total pancreatectomy, and the other 1 patient received distal pancreatectomy. The median operation time was 539 minutes. Postoperative pathology showed an R0 resection rate of 94.4%, and tumor invasion of a superior mesenteric artery or superior mesenteric vein was confirmed in 32 patients. The median number of dissected lymph nodes was 43, and 25 patients were positive for lymph node metastasis. The median time of intensive care unit stay was 4 days. Two patients died within 30 days after surgery due to multiorgan failure. The severe postoperative adverse events (equal to or higher than grade 3) were observed in 12 out of 36 patients, and diarrhea, gastroparesis, and abdominal infection were the most frequent adverse events. Postoperative hospital stay was averagely of 34 days. The recurrence-free survival is 13.6 months. The median overall survival of patients after diagnosis and after surgery was 21.4 months and 14.5 months, respectively. CONCLUSIONS: Our attempt suggests the safety of this modality and may be clinically beneficial for highly selected patients with PDAC. However, the experience in multidisciplinary pancreatic cancer care and intestinal transplantation is warranted.


Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/pathology , Neoadjuvant Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Transplantation, Autologous , Carcinoma, Pancreatic Ductal/pathology , Pancreatectomy/methods , Retrospective Studies , Pancreatic Neoplasms
14.
J Transl Med ; 21(1): 25, 2023 01 13.
Article En | MEDLINE | ID: mdl-36639643

BACKGROUND: Circulating soluble programmed death ligand 1 (sPD-L1) can negatively regulate T-cell function and serve as a prognostic or predictive marker in a variety of cancers. However, rare studies have evaluated the potential roles of sPD-L1, and no study has estimated its predictive value for the efficacy of immune treatment in colorectal cancer (CRC). METHODS: Plasma samples from 192 CRC patients were used to estimate correlations between clinicopathological features and sPD-L1, secreted PD-L1 (secPD-L1) and exosomal PD-L1 (exoPD-L1). Baseline and posttreatment sPD-L1 levels were also investigated in 55 patients with metastatic CRC (mCRC) treated with chemotherapy ± targeted therapy and 40 patients with proficient mismatch repair (pMMR) mCRC treated with combination immunotherapy. Both sPD-L1 and secPD-L1 were quantified by enzyme-linked immunosorbent assay, while exoPD-L1 was analyzed using flow cytometry. RESULTS: secPD-L1 was the major component and positively correlated with sPD-L1 in CRC, while exoPD-L1 was almost undetectable. Higher levels of sPD-L1 were detected in patients with distant metastasis, especially those with distant lymph node metastasis and tissue combined positive score (CPS) instead of tumor proportion score (TPS). Chemotherapy or targeted therapy did not significantly impact sPD-L1 concentration. Progressive disease on combination immunotherapy was associated with an increase in sPD-L1 level, whereas no significant change was observed in patients with durable clinical benefit. CONCLUSION: sPD-L1 mainly consisted of secPD-L1, and its level was higher in patients with distant metastasis, especially distant lymph node metastasis and positive CPS. sPD-L1 is a potential dynamic marker to identify rapid progression on combination immunotherapy and avoid ineffective treatment for pMMR CRC.


B7-H1 Antigen , Colonic Neoplasms , Humans , Lymphatic Metastasis , DNA Mismatch Repair , Biomarkers, Tumor , Immunotherapy
15.
Int Wound J ; 20(6): 1882-1892, 2023 Aug.
Article En | MEDLINE | ID: mdl-36480439

Platelet-rich plasma (PRP) has attracted attention because of its potential to accelerate the wound healing process. However, resources for evaluating research trends in the treatment of wounds with PRP were limited. In this study, we aimed to make a bibliometric analysis of the literature related to PRP in the treatment of wounds and explore the research status, hotspots and frontiers in this field in recent 20 years. Studies about PRP treatment for wounds from 2002 to 2021 were retrieved from the Science Citation Index Expanded (SCI-E) of Web of Science (WOS) database. Visualisation softwares such as VOSviewer and SCImago Graphica, and CiteSpace were used to analyse the research trends and features. A total of 1748 studies were identified in the SCI-Expanded from 2002 to 2021. The number of publications on PRP in the treatment of wounds has shown an increasing trend, from 6 (in 2002) to 228 (in 2021). The papers published in the United States have led in times cited (14637) and H-index (63). Though Italy was slightly lower than China in the number of publications, the H-index and average cited (47, 28.45) were higher than that of China (38, 27.01). The strongest keyword was "fibrin" (strength = 13.07), and the longest burst duration keyword was "thrombin" (began in 2002 and ended in 2014). The largest 10 co-citation clusters are as follows: endothelial cell proliferation (#0), regenerative medicine-associated treatment (#1), diabetic wound healing (#2), autologous derived (#3), platelet-rich fibrin (#4), tissue engineering (#5), regenerative potential (#6), clinical randomised trial (#7), histologic observation (#8), and wound bacteria (#9). The United States has made the most outstanding contribution in this field. Chinese researchers need to enhance the quality of publications further. Wound Repair Regen. is the most noteworthy journal. The mechanism of growth factors of PRP, combination therapy, preparation of PRP, and related clinical trials may be topics that need attention.


Platelet-Rich Plasma , Wound Healing , Humans , Combined Modality Therapy , Regenerative Medicine , Bibliometrics , Biomedical Research/trends
16.
Appl Biochem Biotechnol ; 195(5): 3217-3228, 2023 May.
Article En | MEDLINE | ID: mdl-36576652

The predictive value of red blood cell distribution width (RDW) in severely burned patients remains unclear. This study aimed to investigate the potential association between admission RDW and outcomes in patients with severe burns. Data of severely burned patients in the burn center of Changhai Hospital were retrospectively evaluated. The relationship between admission RDW and mortality was analyzed and displayed using the receiver operating characteristic curve, Kaplan-Meier curve, Cox proportional hazards regression, and the nomogram method. A total of 342 patients were identified according to the filter criteria. The 30-day mortality was 12.9%, and the mortality rates in 7 days and 90 days were 2.9% and 16.7%, respectively. Patients with high admission RDW value were more likely to die than those with low RDW value. Multivariate analysis revealed that higher admission RDW, age, full-thickness burned area, and inhalation injury were independent risk factors with 30-day mortality. The nomogram based on these risk factors was established to predict survival probability in severe burn patients. The C-index of different follow-up times was computed between 0.867 and 0.904, and the nomogram model list fits the data well. Admission RDW played a valuable role in predicting short-term mortality in patients with severe burns. The nomogram containing admission RDW was established to predict mortality, which helps burn care providers identify the patients at higher risk of short-term mortality after severe burns. More attention should be paid to the application of these easy and inexpensive biochemical indicators in the early prediction of disease progression.


Erythrocyte Indices , Humans , Retrospective Studies , Prognosis , ROC Curve , Risk Factors
17.
Clin Transplant ; 37(3): e14865, 2023 03.
Article En | MEDLINE | ID: mdl-36416299

INTRODUCTION: Sensitization to human leukocyte antigen (HLA) creates an immunological barrier to intestinal transplantation (ITx). Current desensitization therapies are limited and ineffective in the most highly sensitized patients. A co-transplanted whole liver transplant can protect a kidney, heart, or intestinal allograft from antibody-mediated injury. Whether an auxiliary partial liver allograft provides effective protection for highly sensitized intestinal transplant recipients is unknown. METHODS: Two patients with strong HLA donor-specific antibody at high titer against their deceased donors underwent combined auxiliary partial liver and ITx across a positive cross-match. The left lateral lobes from the combined-graft recipients and the right liver lobes from the deceased donors were transplanted as a domino procedure to other four patients. RESULTS: Two combined-graft recipients have had an uneventful postoperative course without major complications at a 12- and 24-month follow-up, respectively. Intestinal graft function has been excellent with no evidence of humoral or cellular rejection. While a positive cross-match turned negative, titers of donor-specific HLA antibodies gradually declined over time after transplant. The left liver lobes procured from the combined-graft recipients were successfully transplanted into two pediatric patients (age 1.9, 2.4 years) and the right lobes from two deceased donors were successfully transplanted into two adult patients. All transplant procedures went well, without post-operative complications related to the splitting technique. CONCLUSION: Our results indicate that an auxiliary liver transplant can effectively protect a co-transplanted intestinal allograft against rejection and suggest that this combined procedure may serve as a useful therapeutic adjunct for a highly sensitized intestinal transplant candidate.


Kidney Transplantation , Adult , Humans , Child , Kidney Transplantation/methods , Kidney , Antibodies , Liver , Transplantation, Homologous
18.
Am J Transplant ; 22(12): 3053-3060, 2022 12.
Article En | MEDLINE | ID: mdl-36066568

Intestinal transplantation from deceased donors is the established procedure for patients with irreversible intestinal failure. However, a living-donor intestinal transplant has not been routinely performed yet because of undefined surgical risks to the donor. In this report, we reviewed our experience with living-donor ileal resection from May 1999 to December 2021. A total of 40 living-donor ileal resections were performed for 40 intestinal transplant recipients. Clinical data were prospectively collected and analyzed for postoperative complications after ileal procurement. None of the donors experienced life-threatening complications or mortality. Six (15%) of 40 donors experienced minor operative complications. Transit intestinal graft inadequacy including weight loss, diarrhea, and vitamin B12 deficiency was common early following surgery, but was manageable and disappeared in most cases within a year. All donors had significant reductions in total plasma cholesterol and low-density lipoprotein cholesterol concentrations after donation as compared with the baseline levels. With an average follow-up of 67.8 months, bilateral kidney stones occurred in one donor and gallstones in the other. All the donors have regained their normal capacity for work. Living-donor ileal resection is associated with minimal short- and long-term morbidity and remains an attractive alternative for potential recipients when suitable deceased donors are unavailable.


Kidney Transplantation , Living Donors , Humans , Cholesterol , Graft Survival , Kidney Transplantation/adverse effects , Postoperative Complications/etiology , Transplant Recipients
19.
Am J Orthod Dentofacial Orthop ; 162(6): 907-916, 2022 Dec.
Article En | MEDLINE | ID: mdl-36123228

INTRODUCTION: This study investigated the position and morphologic characteristics of multiple impacted anterior teeth in the unilateral maxillary area. METHODS: Cone-beam computed tomography images of 21 patients (11 males and 10 females; median age 9.42 years [9.08-11.29]) with multiple teeth impacted were collected and imported into Dolphin Imaging software (Dolphin Imaging and Management Solutions, Chatsworth, Calif). The vertical height, crown orientation, twist direction, and root curvature of each impacted tooth were described. The crown length, root length, and root canal width of impacted and homonym teeth were measured. RESULTS: The positions of the impacted lateral incisors are lower than that of the other 2 anterior teeth. Most crowns of impacted central incisors are positioned distally, labial surfaces in mesial torsion, with most roots, bent toward the distal and labial. Crowns of impacted lateral incisors are positioned mesiolabially, with labial surfaces mostly in distal torsion, and most roots bent toward the mesial and labial. Crowns of impacted canines are mostly positioned mesiolabially, with labial surfaces in mesial torsion. The crowns and roots of the impacted central and lateral incisors were shorter than those of the homonym (P <0.05); however, the difference in crown length is clinically negligible, and there was no difference in root canal widths. There was no difference in the comparison of parameters for the canine group. CONCLUSIONS: There are certain rules in the vertical height, crown orientation, twist direction, and root curvature of multiple impacted anterior teeth in the unilateral maxillary area. Root development of impacted central and lateral incisors was restricted.


Tooth, Impacted , Male , Female , Humans , Tooth, Impacted/diagnostic imaging , Retrospective Studies , Tooth Root/diagnostic imaging , Maxilla/diagnostic imaging , Cone-Beam Computed Tomography/methods , Cuspid/diagnostic imaging
20.
Ann Surg ; 276(5): e444-e449, 2022 11 01.
Article En | MEDLINE | ID: mdl-35968890

OBJECTIVE: To examine outcomes of living-donor intestinal transplant (LDITx) recipients. BACKGROUND: LDITx is not routinely performed because of surgical risks to the donor and the potential inferior physiologic performance of the segmental graft. However, data on the effectiveness of LDITx are scarce. DESIGN: This retrospective cohort study included patients undergoing LDITx between May 1999 and December 2021 in intestinal transplant programs in 2 university-affiliated hospitals in China. RESULTS: Actuarial survival rates were 80%, 72.7%, 66.7% for patient and 72.4%, 63.6%, 60% for graft at 1, 3, and 5 years, respectively. Recipients with >3/6 HLA-matched grafts had superior patient and graft survival rates than those with ≤3/6 HLA-matched grafts ( P <0.05). There were 12 deaths among the recipients, with infection being the leading cause (41.7%), followed by rejection (33.3%), surgical complications (16.7%), and others (8.3%). There were 16 graft losses among the recipients, with acute cellular rejection being the predominant cause (37.5%), followed by infection (25%), technical failure (12.5%), chronic rejection (12.5%), and others (12.5%). With an average follow-up of 3.7 (range, 0.6-23) years, the rates of acute and chronic rejection were 35% and 5%, and the rate of cytomegalovirus disease and post-transplant lymphoproliferative disease were 5% and 2.5%, respectively. Of the 40 patients, 28 (70%) are currently alive and have achieved enteral autonomy. CONCLUSIONS: LDITx is a valuable treatment option for patients with end-stage intestinal failure. Improved immunosuppression, better HLA matching, and shorter cold ischemia times were associated with reduced rates of rejection, viral-mediated infection and improved graft survival.


Kidney Transplantation , Living Donors , Graft Rejection/epidemiology , Graft Survival , Humans , Retrospective Studies
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