Clinical practice guidelines for prevention and treatment of postoperative gastrointestinal disorder with Integrated Traditional Chinese and Western Medicine (2023).

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

In-depth discovery and taste presentation mechanism studies on umami peptides derived from fermented sea bass based on peptidomics and machine learning.

Umami peptides originating from fermented sea bass impart a distinctive flavor to food. Nevertheless, large-scale and rapid screening for umami peptides using conventional techniques is challenging because of problems such as prolonged duration and complicated operation. Therefore, we aimed to screen fermented sea bass using peptidomics and machine learning approaches. The taste presentation mechanism of umami peptides was assessed by molecular docking of T1R1/T1R3. Seventy umami peptides identified in fermented sea bass predominantly originated from 28 precursor proteins, including troponin, myosin, motor protein, and creatine kinase. Six umami peptides with the lowest energies formed stable complexes by binding to T1R3. SER170, SER147, GLN389, and HIS145 are critical binding sites for T1R1/T1R3. Four dominant interacting surface forces were identified: aromatic interactions, hydrogen bonding, hydrophilic bonds, and solvent-accessible surfaces. Our study unveils a method to screen umami peptides efficiently, providing a basis for further exploration of their flavor in fermented sea bass.

Application of LRG mechanism in normal pressure hydrocephalus.

Normal pressure hydrocephalus (NPH) is a prevalent type of hydrocephalus, including secondary normal pressure hydrocephalus (SNPH) and idiopathic normal pressure hydrocephalus (INPH). However, its clinical diagnosis and pathological mechanism are still unclear. Leucine-rich α-2 glycoprotein (LRG) is involved in various human diseases, including cancer, diabetes, cardiovascular disease, and nervous system diseases. Now the physiological mechanism of LRG is still being explored. According to the current research results on LRG, we found that the agency of LRG has much to do with the known pathological process of NPH. This review focuses on analyzing the LRG signaling pathways and the pathological mechanism of NPH. According to the collected literature evidence, we speculated that LRG probably be involved in the pathological process of NPH. Finally, based on the mechanism of LRG and NPH, we also summarized the evidence of molecular targeted therapies for future research and clinical application.

Research progress on the role of the Wnt signaling pathway in pituitary adenoma.

Pituitary adenoma (PA) is the third most common central nervous system tumor originating from the anterior pituitary, but its pathogenesis remains unclear. The Wnt signaling pathway is a conserved pathway involved in cell proliferation, Self-renewal of stem cells, and cell differentiation. It is related to the occurrence of various tumors, including PA. This article reviews the latest developments in Wnt pathway inhibitors and pathway-targeted drugs. It discusses the possibility of combining Wnt pathway inhibitors with immunotherapy to provide a theoretical basis for the combined treatment of PA.

Comparison of the taste mechanisms of umami and bitter peptides from fermented mandarin fish (Chouguiyu) based on molecular docking and electronic tongue technology.

Unclear taste mechanisms of peptides limit rapid screening of taste peptides with high intensity. In this study, the taste mechanisms of umami and bitter peptides from Chouguiyu were compared. After molecular docking of core umami (NWDDMEK, WFKDEEF, EEEKPKF, DFDDIQK, and DGEKVDF) and bitter (VQDVLKL, VELLKLE, LVVDGVK, VVDLTVR, and VVDGVKL) peptides with T1R1/T1R3 and TASR14, respectively, salt bridges and conventional hydrogen bonds were the main interactions in all taste peptides, in which acidic amino acid residues contributed to the interaction with their receptors. The taste intensity of peptides after solid-phase synthesis was further verified using electronic tongue technology. Spearman correlation analysis showed that docking energy was an important factor for the intensity of taste peptides, while interaction energy and the distance between the binding unit (BU) and the stimulating unit (SU) were also responsible for the bitter intensity. This study provides a theoretical basis to screen novel taste peptides with high taste intensity in fermented foods.

The LRG-TGF-ß-Alk-1/TGFßRII-Smads as Predictive Biomarkers of Chronic Hydrocephalus after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Chronic hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage (aSAH); however, the risk factors and the mechanisms underlying its occurrence have yet to be fully elucidated. The purpose of this study was to identify biomarkers that could be used to predict chronic hydrocephalus after aSAH and to investigate the relationships. METHODS: We analyzed cerebrospinal fluid (CSF) samples from 19 patients with chronic hydrocephalus after aSAH and 44 controls without hydrocephalus after aSAH. Enzyme-linked immunosorbent assay was used to determine the levels of leucine-rich alpha-2-glycoprotein (LRG), transforming growth factor-ß (TGF-ß), Smad1, Smad4, Smad5, Smad8, activin receptor-like kinase 1 (Alk-1), activin receptor-like kinase 5 (Alk-5), P38, and TGF-ß type II receptor (TGFßRII) in CSF samples. RESULTS: In the CSF of patients with chronic hydrocephalus after aSAH, the levels of LRG, TGF-ß, Alk-1, Smad5, and TGFßRII were significantly increased (p < 0.05) and the levels of Smad1, Smad4, and Smad8 were significantly decreased (p < 0.05). There were no significant differences between the two groups concerning the levels of P38 and Alk-5 (p > 0.05). The analysis also identified significant correlations between specific biomarkers: LRG and Smad1, LRG and Smad5, TGF-ß and Alk-1, and Alk-1 and Smad4 (p < 0.05); the Pearson's correlation coefficients for these relationships were -0.341, 0.257, 0.256, and -0.424, respectively. CONCLUSION: The levels of LRG, TGF-ß, Alk-1, TGFßRII, Smad1/5/8, and Smad4 in the CSF are potentially helpful as predictive biomarkers of chronic hydrocephalus after aSAH. Moreover, the LRG-TGF-ß-Alk-1/TGFßRII-Smad1/5/8-Smad4 signaling pathway is highly likely to be involved in the pathogenic process of chronic hydrocephalus after aSAH.

Prediction of histopathologic grades of myxofibrosarcoma with radiomics based on magnetic resonance imaging.

PURPOSE: To develop a radiomics-based model from preoperative magnetic resonance imaging (MRI) for predicting the histopathological grades of myxofibrosarcoma. METHODS: This retrospective study included 54 patients. The tumors were classified into high-grade and low-grade myxofibrosarcoma. The tumor size, signal intensity heterogeneity, margin, and surrounding tissue were evaluated on MRI. Using the least absolute shrinkage and selection operator (LASSO) algorithms, 1037 radiomics features were obtained from fat-suppressed T2-weighted images (T2WI), and a radiomics signature was established. Using multivariable logistic regression analysis, three models were built to predict the histopathologic grade of myxofibrosarcoma. A radiomics nomogram represents the integrative model. The three models' performance was evaluated using the receiver operating characteristics (ROC) and calibration curves. RESULTS: The high-grade myxofibrosarcoma had greater depth (P = 0.027), more frequent heterogeneous signal intensity at T2WI (P = 0.015), and tail sign (P = 0.014) than the low-grade tumor. The area under curve (AUC) of these conventional MRI features models was 0.648, 0.656, and 0.668, respectively. Seven radiomic features were selected by LASSO to construct the radiomics signature model, with an AUC of 0.791. The AUC of the integrative model based on radiomics signature and conventional MRI features was 0.875. The integrative model's calibration curve and insignificant Hosmer-Lemeshow test statistic (P = 0.606) revealed good calibration. CONCLUSION: An integrative model using radiomics signature and three conventional MRI features can preoperatively predict low- or high-grade myxofibrosarcoma.

Exploring plant polyphenols as anti-allergic functional products to manage the growing incidence of food allergy.

The active substances derived from plants have received increasing attention owing to their wide range of pharmacological applications, including anti-tumor, anti-allergic, anti-viral, and anti-oxidative activities. The allergy epidemic is a growing global public health problem that threatens human health and safety. Polyphenols from plants have significant anti-allergic effects and are an important source of anti-allergic drug research and development. Here, we describe recent advances in the anti-allergic efficacy of plant polyphenols, including their comprehensive effects on cellular or animal models. The current issues and directions for future development in this field are discussed to provide a theoretical basis for the development and utilization of these active substances as anti-allergic products.

Cooperative combination of non-targeted metabolomics and targeted taste analysis for elucidating the taste metabolite profile and pathways of traditional fermented golden pompano.

Fermentation plays a key role in taste formation in traditional fermented golden pompano and involves a series of complex metabolic reactions. Indeed, the taste profile of fermented golden pompano exhibits remarkable variation during early fermentation. Herein, nutritional fingerprinting (proteins, amino acids, lipids, etc.) was applied to discriminate the various biomolecular changes involved in golden pompano fermentation. Among the differential metabolites, amino acids, small peptides, lipids, and nucleotides were considered taste-related compounds. An increase in the amino acid content was observed during fermentation, while the peptide content decreased. Glutamic acid, alanine, and lysine had the highest taste activity values and were the main contributors to taste formation. Metabolic pathway enrichment analysis revealed that taste formation was primarily associated with alanine, aspartate, and glutamate metabolism. These findings provide a deeper understanding of taste mechanisms and establish a basis for the targeted regulation of taste formation in the fermented fish industry.

Immune Thrombocytopenia Could be an Independent Clinical Phenotype of Antiphospholipid Syndrome: A Prospective Cohort Study.

BACKGROUND: Patients with persistent positive antiphospholipid antibodies (aPLs) and immune thrombocytopenia (ITP) hardly develop thrombosis but share many similar characteristics with antiphospholipid syndrome (APS). METHODS: This is a prospective cohort study consecutively enrolling thrombocytopenic patients with continuous positive aPLs. Patients developing thrombotic events are classified as the APS group. Then we compare the clinical characteristics and prognosis between aPLs carriers and patients with APS. RESULTS: This cohort included 47 thrombocytopenic patients with continuous positive aPLs and 55 with diagnosed primary APS. The proportion of smoking and hypertension are higher in the APS group (p = 0.03, 0.04, 0.03, respectively). The platelet count of aPLs carriers at admission was lower than APS patients [26 × 109/l (9 × 109/l, 46 × 109/l) vs. 64 × 109/l (24 × 109/l, 89 × 109/l), p = 0.0002]. Triple aPLs positivity is more common in primary APS patients with thrombocytopenia [24 (51.1%) vs. 40 (72.7%), p = 0.04]. Regarding the treatment response, the complete response (CR) rate is similar between aPLs carriers and primary APS patients with thrombocytopenia (p = 0.2). Nonetheless, the proportion of response, no response, and relapse differed significantly between the two groups [13 (27.7%) vs. 4 (7.3%), p < 0.0001; 5 (10.6%) vs. 8 (14.5%), p < 0.0001; 5 (10.6%) vs. 8 (14.5%), p < 0.0001, respectively]. In Kaplan-Meier analysis, primary APS patients had significantly more thrombotic events than aPLs carriers (p = 0.0006). CONCLUSIONS: In the absence of other high-risk factors for thrombosis, thrombocytopenia could be an independent and long-lasting clinical phenotype of APS.

Folate receptor-positive circulating tumor cells in the preoperative diagnosis of indeterminate pulmonary nodules.

BACKGROUND: The use of FR + CTC to distinguish lung cancer from benign lung disease has been well studied. However, the effective method to differentiate precursor glandular lesions from benign/malignant pulmonary diseases is rare. METHODS: 380 patients with indeterminate pulmonary nodules were prospectively recruited. Peripheral blood samples were collected from all participants before surgery for analyzing FR + CTC levels. The performance of FR + CTC to identify lung precursor lesions were analyzed by receiver operating characteristic (ROC) curve. RESULTS: FR + CTC can effectively differentiate precursor from benign pulmonary diseases in all included patients (cutoff: 9.22 FU/3 ml, AUC = 0.807, (p < 0.0001, sensitivity: 69.17%, specificity: 82.46%) and patients with single pulmonary lesion (cutoff: 9.03 FU/3 ml, AUC = 0.842, p = 0.0001, sensitivity: 75.20%, specificity: 83.00%). However, FR + CTC cannot differentiate precursor from benign pulmonary diseases in multiple lesions patients (p = 0.110). FR + CTC neither differentiate precursor from malignant pulmonary lesions in all included patients (p = 0.715), single nor multiple lesions patients (p = 0.867, p = 0.692, respectively). Total number of pulmonary nodules, MTD, location (lower vs upper) were independent risk factors for malignancy (AOR, 95% CI: 3.104 (1.525, 6.316), 3.148 (1.722, 5.754), 2.098 (1.132, 3.888), respectively. CONCLUSION: Preoperative FR + CTC can be identified in precursor glandular lesions and utilized to differentiate from benign pulmonary diseases. Total number of pulmonary nodules, MTD, location (lower vs upper) were independent risk factors for malignancy.

Novel insight into the formation mechanism of umami peptides based on microbial metabolism in Chouguiyu, a traditional Chinese fermented fish.

Umami peptides formed by microbial metabolism play an important role in the umami taste of Chouguiyu. In this study, 138 umami peptides and 6 kinds of proteases in two categories from 35 microbial genera were identified from Chouguiyu during the fermentation process by peptidomics and metagenomics analysis, respectively. The interaction network maps between the umami peptides and protease-producing microbial genera in each protease classification were constructed based on Pearson's correlation coefficient after a two-way orthogonal partial least squares (O2PLS) evaluation. The proteases classified in 34 clusters of orthologous groups (COG) from Vagococcus, Peptostreptococcus, Acinetobacter, Psychrobacter, and Enterococcus played a major role in the formation of umami peptides. The core umami peptides with the highest abundance and correlation were mainly derived from troponin and myosin in mandarin fish. The lactic acid bacteria contributed most to the hydrolysis preparation of these umami peptides. This study is beneficial to screen the proteases and related microbial strains to improve the umami taste of Chouguiyu.

Humanized CD19 CAR-T cells in relapsed/refractory B-ALL patients who relapsed after or failed murine CD19 CAR-T therapy.

BACKGROUND: For CD19-positive relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) after treatment with murine CD19 (mCD19) CAR-T, the reinfusion of mCD19 CAR-T cells may be ineffective due to anti-mouse single-chain variable fragment (scFv) antibody caused by mCD19 CAR. To overcome this immunogenicity, we applied humanized CD19 (hCD19) CAR-T cells to treat r/r B-ALL patients with prior mCD19 CAR-T therapy. METHODS: Nineteen pediatric and adult patients were included, 16 relapsed after and 3 were primarily resistant to mCD19 CAR-T. All patients presented with more than 5% blasts in bone marrow and/or extramedullary disease, and still showed CD19 antigen expression. Humanized CD19-CARs were lentiviral vectors carrying a second generation CAR with 4-1-BB co-stimulatory and CD3ζ signaling domains. Patient-derived cells were collected for producing CAR-T cells, the median dose of infused hCD19 CAR-T cells was 2.4 × 105/kg (range, 1.0-18.0 × 105/kg). RESULTS: hCD19 CAR-T resulted in a complete remission (CR) rate of 68% (13/19). Among 13 remission patients, 11 underwent allogeneic hematopoietic cell transplantation (allo-HCT) (3 were second HCT) and 10 remained in CR; the event-free survival rates at 12-18 months were 91% in 11 patients received following allo-HCT and 69% in all CR patients. Six cases had no response to hCD19 CAR-T, 3 died of disease progression; another 3 received salvage second transplantation, of them, 2 relapsed again (one died). Cytokine release syndrome (CRS) occurred in 95% (18/19) of patients, most CRS events were grade 1 and grade 2 (n = 17), there was only one grade 4 CRS. Two cases experienced grade 1 neurotoxicity. CONCLUSIONS: Humanized CD19 CAR-T cell therapy could be a treatment option for CD19-positive B-ALL patients who relapsed after or resisted prior murine CD19 CAR-T, hCD19 CAR-T followed by allo-HCT provided a longer remission in CR patients. Nevertheless, the prognosis of non-responders to hCD19 CAR-T remained dismal. TRIAL REGISTRATION: Chinese Clinical Trial Registry/WHO International Clinical Trial Registry ( ChiCTR1900024456 , URL: www.chictr.org.cn ); registered on July 12, 2019.

[Application of nasal nitric oxide in primary diffuse chronic rhinosinusitis].

Objective:This study aimed to investigate whether nasal nitric oxide（nNO） could be used to identify the main clinical phenotypes of primary diffuse chronic sinusitis（CRS） and reflect the severity of sinus mucosal lesions. Methods:A total of 57 patients with primary diffuse CRS were included as the case group in this study. And the patients were divided into eosinophilic CRS（EosCRS） group and non-EosCRS group according to the percentage of eosinophils in peripheral blood. At the same time, 32 healthy volunteers were selected as the control group. According to whether there is nasal polyps under nasal endoscopy, the EosCRS group was classified into EosCRS with nasal polyps（EosCRSwNP） and EosCRS without nasal polyps（EosCRSsNP）. In the same way, the non-EosCRS group was assigned to non-EosCRS with nasal polyps（non-EosCRSwNP） and non-EosCRS without nasal polyps（non-EosCRSsNP）. The levels of nNO were detected by single nostril air extraction with 10 mL/s flow rate and soft palate closure. The severity of sinus lesions were evaluated by Lund-Mackay score. The difference of nNO levels were compared by the Rank sum test. The correlation between nNO levels and Lund-Mackay score was analyzed by Pearson correlation analysis. Results:①The levels of nNO in EosCRS group [315.00（88.00, 446.50） ×10⁻9] and non-EosCRS group [419.00（181.00, 469.00） ×10⁻9] were significantly lower than those in the control group [457.00（431.00, 493.75） ×10⁻9]（P<0.01）. ②The levels of nNO in EosCRSwNP group [260.00（71.75, 391.50） ×10⁻9] were significantly lower than that in EosCRSsNP group [557.00（442.50, 619.75） ×10⁻9], and that in non-EosCRSwNP group [210.00（159.75, 434.25） ×10⁻9] were significantly lower than non-EosCRSsNP group [455.00（425.00, 481.00） ×10⁻9]（P<0.05）. ③There was a medially negative correlation between the levels of nNO and the total score of Lund-Mackay score in the EosCRS group（r=-0.567, P<0.01）. Conclusion:The levels of nNO can be used to determine whether primary diffuse CRS is accompanied by nasal polyps and reflect the severity of nasal sinus mucosal lesions, instead of identifying the main clinical phenotypes of primary diffuse CRS.

Conversion of the Sagittal Functional Safe Zone to the Coronal Plane Using a Mathematical Algorithm: The Reason for Failure of the Lewinnek Safe Zone.

BACKGROUND: Ante-inclination (AI) of the cup is a key component of the combined sagittal index (CSI) for predicting joint stability after total hip arthroplasty (THA). We aimed to (1) validate a mathematical algorithm relating AI to radiographic anteversion (RA), radiographic inclination (RI), and pelvic tilt (PT); (2) convert the AI criterion of the CSI into the coronal functional safe zone (CFSZ) and explore the influences of standing-to-sitting pelvic motion (PM) and pelvic incidence (PI) on the CFSZ; and (3) attempt to locate a universal cup orientation that always fulfills the AI criterion of the CSI for all patients. METHODS: In the first phase, a phantom pelvis was designed to simulate a range of PT values, and an acetabular cup was implanted with different RA, RI, and PT settings using a robot-assisted technique and scanned using the EOS imaging system. The second phase involved patient radiographs. We enrolled 100 patients who underwent robot-assisted THA from April 2019 to December 2019, and EOS images before THA and at the 12-month follow-up were recorded. The AI was measured on a lateral radiograph; this angle was used as the reference and compared with the calculated AI to assess the accuracy of the algorithm. Linear regression was conducted to explore the relationship between the size of the CFSZ and the values of PM and PI. We calculated the intersection of the CFSZs of the patients to find a universal cup orientation (RA and RI) for the CSI. RESULTS: The algorithm was accurate according to both the phantom study and patient radiographs using PT at the time of follow-up, with mean absolute errors (MAEs) of 1.5° (width of 95% confidence interval [CI], 2.2°) and 2.8° (width of 95% CI, 3.0°), respectively. However, the preoperatively predicted AI had an MAE of 9.0° (width of 95% CI, 10.5°). In patient subgroups with lower PM or PI, the sizes of the CFSZ and of its intersection with the Lewinnek safe zone were significantly smaller (p < 0.017). No universal cup orientation existed to fulfill the CSI criteria for all patients or for any of the PM or PI subgroups. CONCLUSIONS: The target orientation for the cup in THA should be individualized. Our validated algorithm may serve as a quantitative tool for the patient-specific optimization of cup AI on the basis of the functional safe zone. CLINICAL RELEVANCE: The Lewinnek safe zone fails because it cannot predict the functional orientation of the cup. The concept of a universal safe zone of cup orientation should be abandoned and replaced by a patient-specific surgical target.

Effects of ferric ammonium citrate on iron accumulation, bone turnover and bone density in ovariectomized rat models with osteoporosis.

To analyze the effect of ferric ammonium citrate on iron accumulation, bone turnover and bone density in ovariectomized rat models with osteoporosis, 40 female SD rats were randomized into four groups, that were, sham-operated, model, low and high-dose ferric ammonium citrate groups (i.e. low and high-dose groups) respectively, each of them had ten rats. Except for the sham-operated group, bilateral ovariectomy was performed in the other groups to establish models with osteoporosis; one week after the operation, those in the low and high-dose groups were given 90 mg/kg and 180 mg/kg ferric ammonium citrate, respectively. Those in the other two groups received isodose saline for nine weeks, with the frequency of twice per week. The changes in bone tissue morphology, serum ferritin concentration, tibial iron content, serum osteocalcin, carboxyl terminal peptide (ß - CTX), bone density, bone volume fraction and trabecular thickness were compared. Results showed that the rats in the low and high-dose groups contained a higher concentration of serum ferritin and tibial iron content compared to the other groups (P < 0.05). In contrast to the model group, the bone trabeculae in the low and high-dose groups were sparse in morphology and increased in spacing. It was obvious that the rats contained more osteocalcin and ß - CTX in the model group, the low and high-dose groups versus the sham-operated group (P < 0.05), and those had more ß - CTX in the high-dose group versus the model group and the low-dose group (P < 0.05). The bone density, bone volume fraction and trabecular thickness of the rats in the model group, the low and high-dose groups showed lower versus the sham-operated group (P < 0.05); those in the low and high-dose groups significantly presented lower bone density and bone volume fraction versus the model group (P < 0.05). Iron accumulation can aggravate osteoporosis in ovariectomized rats, and its mechanism may be associated with accelerating bone turnover, promoting bone absorption, reducing bone density and sparsely trabecular structure. Therefore, it is particularly important to understand iron accumulation in postmenopausal osteoporosis patients.

CAR-T therapy followed by allogeneic hematopoietic stem cell transplantation for refractory/relapsed acute B lymphocytic leukemia: Long-term follow-up results.

Background: Patients with refractory/relapsed (r/r) acute B lymphocytic leukemia (B-ALL) can achieve complete response (CR) after chimeric antigen receptor T-cell (CAR-T) therapy, but recurrence occurs in the short term. To reduce recurrence and improve survival, CAR-T therapy followed by transplantation is a feasible option. We analyzed the long-term follow-up outcomes and the risk factors for allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR by CAR-T therapy in this study. Methods: A total of 144 patients who underwent allo-HSCT after CAR-T therapy in our hospital were enrolled in this study. Target gene analysis was performed in 137 r/r B-ALL patients receiving allo-HSCT after CR by CAR-T therapy. Among the 137 patients, 87 were evaluated for germline predisposition gene mutations, and 92 were evaluated for tumor somatic gene mutations using NGS. The clinical factors, germline predisposition gene and somatic gene mutations associated with the prognosis of patients receiving transplantation after CAR-T therapy were analyzed using univariate Cox regression. Factors related to disease-free survival (DFS) and overall survival (OS) were analyzed using multivariate Cox regression analysis. Results: In 137 r/r B-ALL patients, the 2-year cumulative incidence of recurrence (CIR), OS and DFS in patients receiving allo-HSCT after CAR-T therapy was 31.5%, 71.4%, and 60.5%, respectively. The 2-year OS and DFS in MRD-negative patients were 80.9% and 69.3%, respectively. Univariate Cox analysis showed that pretransplant MRD positivity, fungal infection, germline EP300 mutation and somatic TP53 mutation were associated with a poor prognosis after transplantation; a TBI-based regimen was a protective factor for survival and recurrence after transplantation. Multivariate Cox regression analysis showed that the TBI-based regimen was an independent protective factor for DFS, fungal infection and MRD positivity were independent risk factors for DFS, and tumor somatic TP53 mutation and germline EP300 mutation were independent risk factors for DFS and OS. Conclusion: Germline EP300 mutation and tumor somatic TP53 mutation are poor prognostic factors for posttransplant recurrence and survival in r/r B-ALL patients achieving CR after CAR-T therapy. The prognostic risk factors should be considered in adjusting treatment strategies to improve the efficacy of clinical diagnosis and treatment.

Exosomal microRNA­302a promotes trophoblast migration and proliferation, and represses angiogenesis by regulating the expression levels of VEGFA in preeclampsia.

The global morbidity rate of preeclampsia (PE) is 3­7, and 10­20% of maternal deaths are associated with PE. However, the mechanism of its pathogenesis remains unknown. The aim of the present study was to examine the relationship between microRNA­302a (miR­302a) and PE. Firstly, the relative expression levels of miR­302a in placental tissues from patients with PE and normal controls were analyzed using reverse transcription­quantitative PCR. miR­302a expression was upregulated in PE tissues, particularly in severe PE. Subsequently, HTR­8/SVneo cells were transfected with miR­302a vectors to overexpress miR­302a. The overexpression of miR­302a markedly promoted cell proliferation, colony formation, migration and invasion in vitro. Subsequently, the present study examined the function of exosomes secreted by HTR­8/SVneo cells transfected with miR­302a vectors. Compared with the negative control vector group, miR­302a expression was markedly increased in exosomes in the miR­302a overexpression group. Additionally, exosomes with miR­302a overexpression had repressed HUVEC invasion and ring formation. The luciferase reporter assay indicated that VEGFA was a direct target of miR­302a, and miR­302a expression was negatively correlated with VEGFA expression. In conclusion, the present results demonstrated that upregulation of miR­302a may promote HTR­8/SVneo cell proliferation, migration and invasion, and repress angiogenesis by targeting VEGFA, indicating that miR­302a may be a potential target for the development of PE therapies.