Patient-specific 3D-printed Brace for Adolescent Idiopathic Scoliosis: A Prospective Cohort Study.

OBJECTIVE: To evaluate the efficacy, safety of patient-tailored 3D printed brace in the treatment of adolescent idiopathic scoliosis (AIS), and to compare the health-related quality of life (HRQoL) of patients treated with two different types of brace. MATERIALS AND METHODS: From September 2017 to August 2020, 103 AIS patients requiring non-operative management were prospectively recruited in this study. All patients were followed up every 6 months, clinical and radiological examination were assessed at each follow-up time. Full-length anteroposterior X-ray of the spine in the standing position was performed obtained. At the last follow-up, each patient completed a standardized HRQoL questionnaire. Compliance is defined as that the patient insists on wearing the brace for ≥ 23h every day (full-time wearing) and follow-up every 6 months until bone maturity.The rate of major curve Cobb progression was defined that maximum Cobb Angle of major curve greater than 6° compared with that at the initial diagnosis, or aggravated to more than 45° so that orthopedic surgery was recommended during treatment, which was defined as the rate of conversion to surgery. The effects of these two types of braces on the rate of major curve Cobb progression and HRQoL were analyzed by independent sample t-test ad Chi-square test. RESULTS: The thickness was 4 mm for thoracolumbosacral orthosis (TLSO) and 3 mm for 3D-printed brace (3DPB). In addition, compared with the material used in TLSO, the weight (600-800 grams) of the 3DPB materials with the same area is reduced by about 25-30%. 55 patients (49.1%) and 48 patients (33.1%) were respectively included in the 3DPB cohort and the TLSO cohort.The maximum Cobb angle of major curve in the 3DPB cohort was significantly lower than those in the TLSO cohort at 6 months, 12 months and the last follow-up (p < 0.01). The thoracic kyphosis (TK) and lumbar lordosis (LL) of the two cohorts at the last follow-up were lower than those before brace treatment, in addition, there was a significant difference in TK (p = 0.001) and LL (p = 0.004) between the two cohorts at the follow-up. The scores of physical function, pain, self-image, mental health and treatment satisfaction in the Chinese version of SRS-22 in the 3DPB cohort were higher than those in the TLSO cohort (p < 0.01 and p < 0.05, respectively). The scores of the 3DPB cohort were significantly higher than those of the TLSO group in the four dimensions (p = 0.008, 0.013, 0.015, and 0.002, respectively) of the EuroQol-5D health description system except for mobility, and the overall health status of EuroQol-5D was higher for the 3DPB cohort (p < 0.001). At the last follow-up, One patient in the 3DPB cohort and ten patients in the TLSO cohort had major curve Cobb progression of greater than 6°, and the rate of major curve Cobb progression in 3DPB cohort was significantly lower than that in the TLSO cohort (OR 14.2, 95% CI 1.7∼115.8, p < 0.01). One patient in the 3DPB and seven patients in the TLSO cohorts received subsequent surgery or was recommended for surgery, and the rate of conversion to surgery was significantly lower than in the 3DPB cohort (OR 9.2, 95% CI 1.1∼77.9, p < 0.05). CONCLUSIONS: Patient-tailored 3D-printed brace is lighter, thinner, and more comfortable than conventional braces in the treatment of AIS. It can substantially improve the HRQoL of patients and can significantly reduce the progression of major curve Cobb progression and rate of conversion of surgery.

METTL3-modified lncRNA DSCAM-AS1 promotes breast cancer progression through inhibiting ferroptosis.

Numerous studies have indicated that N6-methyladenosine (m6A) and lncRNAs play pivotal roles in human cancer. However, the underlying functions and mechanisms of m6A-lncRNA in the physiological processes of breast cancer remain unclear. Here, we found that DSCAM-AS1 is an m6A-modified lncRNA that was overexpressed in breast cancer tissues and cells, indicating poor clinical prognosis. Gain/loss functional assays suggested that DSCAM-AS1 inhibited erastin-induced ferroptosis in breast cancer cells. Mechanistically, there were remarkable m6A modification sites on both the 3'-UTR of DSCAM-AS1 and the endogenous antioxidant factor SLC7A11. M6A methyltransferase methyltransferase-like 3 (METTL3) methylated both SLC7A11 and DSCAM-AS1. Moreover, DSCAM-AS1 recognized m6A sites on the SLC7A11 mRNA, thereby enhancing its stability. Taken together, these findings indicated a potential therapeutic strategy for breast cancer ferroptosis in an m6A-dependent manner.

New evidence: Metformin unsuitable as routine adjuvant for breast cancer: a drug-target mendelian randomization analysis.

PURPOSE: The potential efficacy of metformin in breast cancer (BC) has been hotly discussed but never conclusive. This genetics-based study aimed to evaluate the relationships between metformin targets and BC risk. METHODS: Metformin targets from DrugBank and genome-wide association study (GWAS) data from IEU OpenGWAS and FinnGen were used to investigate the breast cancer (BC)-metformin causal link with various Mendelian Randomization (MR) methods (e.g., inverse-variance-weighting). The genetic association between type 2 diabetes (T2D) and the drug target of metformin was also analyzed as a positive control. Sensitivity and pleiotropic tests ensured reliability. RESULTS: The primary targets of metformin are PRKAB1, ETFDH and GPD1L. We found a causal association between PRKAB1 and T2D (odds ratio [OR] 0.959, P = 0.002), but no causal relationship was observed between metformin targets and overall BC risk (PRKAB1: OR 0.990, P = 0.530; ETFDH: OR 0.986, P = 0.592; GPD1L: OR 1.002, P = 0.806). A noteworthy causal relationship was observed between ETFDH and estrogen receptor (ER)-positive BC (OR 0.867, P = 0.018), and between GPD1L and human epidermal growth factor receptor 2 (HER2)-negative BC (OR 0.966, P = 0.040). Other group analyses did not yield positive results. CONCLUSION: The star target of metformin, PRKAB1, does not exhibit a substantial causal association with the risk of BC. Conversely, metformin, acting as an inhibitor of ETFDH and GPD1L, may potentially elevate the likelihood of developing ER-positive BC and HER2-negative BC. Consequently, it is not advisable to employ metformin as a standard supplementary therapy for BC patients without T2D.

USP15, activated by TFAP4 transcriptionally, stabilizes SHC1 via deubiquitination and deteriorates renal cell carcinoma.

Ubiquitin-specific peptidase 15 (USP15), a critical deubiquitinating enzyme, has been demonstrated to improve substrate stabilization by hydrolyzing the bond between the substrate and ubiquitin, and is implicated in multiple carcinogenic processes. Prompted by the information cited from The Cancer Genome Atlas (TCGA) database and the Cancer Proteogenomic Data Analysis Site (cProSite), USP15 is selectively overexpressed in clear cell renal cell carcinoma (ccRCC) samples. We aimed to investigate the function of USP15 on ccRCC malignant features, which was emphasized in its deubiquitination of SHC adaptor protein 1 (SHC1). The overexpression of USP15 promoted the capacity of proliferation, migration, and invasion in ccRCC CAKI1 and 769-P cells, and these malignant biological properties were diminished by USP15 deletion in 786-O cells. USP15 accelerated tumor growth and lung metastasis in vivo. In addition, deubiquitinase USP15 was further identified as a new protector for SHC1 from degradation by the ubiquitination pathway, the post-translational modification. In sequence, transcription factor activating enhancer binding protein 4 (TFAP4) was shown to be partly responsible for USP15 expression at the level of transcription, as manifested by the chromatin immunoprecipitation and pull-down assay. Based on the in vitro and in vivo data, we postulate that USP15 regulated by TFAP4 transcriptionally deteriorates ccRCC malignant biological properties via stabilizing SHC1 by deubiquitination.

Marine-derived EGFR inhibitors: novel compounds targeting breast cancer growth and drug resistance.

Breast cancer (BC) continues to be a major health challenge globally, ranking as the fifth leading cause of cancer mortality among women, despite advancements in cancer detection and treatment. In this study, we identified four novel compounds from marine organisms that effectively target and inhibit the Epidermal Growth Factor Receptor (EGFR), crucial for BC cell growth and proliferation. These compounds not only induced early apoptosis through Caspase-3 activation but also showed significant inhibitory effects on EGFR mutations associated with drug resistance (T790M, L858R, and L858R/T790M), demonstrating high EGFR kinase selectivity. Cell Thermal Shift Assay (CETSA) experiments indicated that Tandyukisin stabilizes EGFR in a concentration-dependent manner. Furthermore, binding competition assays using surface plasmon resonance technology revealed that Tandyukisin and Trichoharzin bound to distinct sites on EGFR and that their combined use enhanced apoptosis in BC cells. This discovery may pave the way for developing new marine-derived EGFR inhibitors, offering a promising avenue for innovative cancer treatment strategies and addressing EGFR-mediated drug resistance.

Efficacy of Raw Corn Starch in Insulinoma-Related Hypoglycemia: A Promising Supportive Therapy.

Objective To investigate the efficacy of raw corn starch (RCS) in clinical management of insulinoma-induced hypoglycemia.Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively, and analyzed the therapeutic effects of the RCS intervention on blood glucose control, weight change, and its adverse events.Results The study population consisted of 24 case of insulinoma patients, 7 males and 17 females, aged 46.08 ± 14.15 years. Before RCS-supplemented diet, all patients had frequent hypoglycemic episodes (2.51 ± 3.88 times/week), concurrent with neuroglycopenia (in 83.3% of patients) and autonomic manifestations (in 75.0% of patients), with the median fasting blood glucose (FBG) of 2.70 [interquartile range (IQR): 2.50-2.90] mmol/L. The patients' weight increased by 0.38 (IQR: 0.05-0.65) kg per month, with 8 (33.3%) cases developing overweight and 7 (29.2%) cases developing obesity. All patients maintained the RCS-supplemented diet until they underwent tumor resection (23 cases) and transarterial chemoembolization for liver metastases (1 case). For 19 patients receiving RCS throughout the day, the median FBG within one week of nutritional management was 4.30 (IQR: 3.30-5.70) mmol/L, which was a significant increase compared to pre-nutritional level [2.25 (IQR: 1.60-2.90) mmol/L; P = 0.000]. Of them, 10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment [3.20 (IQR: 2.60-3.95) mmol/L vs. 2.15 (IQR: 1.83-2.33) mmol/L; P = 0.000). Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management [3.50 (IQR: 2.50-3.65) mmol/L vs. 2.20 (IQR:1.80-2.60) mmol/L; P = 0.000], but only one patient who continued to receive RCS for over 4 weeks did not have a significant improvement in FBG. No improvement in weight gain was observed upon RCS supplementation. Mild diarrhea (2 cases) and flatulence (1 case) occurred, and were relieved by reduction of RCS dose.Conclusion The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.

Long-term relapse-free survival enabled by integrating targeted antibacteria in antitumor treatment.

The role of tumor-resident intracellular microbiota (TRIM) in carcinogenesis has sparked enormous interest. Nevertheless, the impact of TRIM-targeted antibacteria on tumor inhibition and immune regulation in the tumor microenvironment (TME) remains unexplored. Herein, we report long-term relapse-free survival by coordinating antibacteria with antitumor treatment, addressing the aggravated immunosuppression and tumor overgrowth induced by TRIM using breast and prostate cancer models. Combining Ag+ release with a Fenton-like reaction and photothermal conversion, simultaneous bacteria killing and multimodal antitumor therapy are enabled by a single agent. Free of immune-stimulating drugs, the agent restores antitumor immune surveillance and activates immunological responses. Secondary inoculation and distal tumor analysis confirm lasting immunological memory and systemic immune responses. A relapse-free survival of >700 days is achieved. This work unravels the crucial role of TRIM-targeted antibacteria in tumor inhibition and unlocks an unconventional route for immune regulation in TME and a complete cure for cancer.

Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis.

Given the extremely high inter-patient heterogeneity among acute myeloid leukemia (AML), identifying biomarkers for prognostic assessment and therapeutic guidance is crucial. Cell surface markers (CSMs) have been shown to play an important role in AML leukemogenesis and progression. In this study, we evaluate the prognostic potential of all human CSMs in AML patients based on differential gene expression analysis and univariate Cox regression analysis. Utilizing multi-model analysis, including Adaptive LASSO regression, LASSO regression, and Elastic Net, we construct a 9-CSMs prognostic model for risk stratification of AML patients. The predictive value of the 9-CSMs risk score is further confirmed in three independent datasets. Multivariate Cox regression analysis shows that the risk score is an independent prognostic factor for AML patients. AML patients with high 9-CSMs risk scores have shorter overall and event-free survival time than those with lower scores. Notably, our single-cell RNA-seq analysis indicates that patients with high 9-CSMs risk scores exhibit chemotherapy resistance. Further, PI3K inhibitors are identified as potential treatments for these high-risk patients. In conclusion, we construct a 9-CSMs prognostic model which is an independent prognostic factor for the survival of AML patients and has the potential to guide drug therapy.

GPS2 promotes erythroid differentiation in K562 erythroleukemia cells primarily via NCOR1.

G protein pathway suppressor 2 (GPS2) has been shown to play a pivotal role in human and mouse definitive erythropoiesis in an EKLF-dependent manner. However, whether GPS2 affects human primitive erythropoiesis is still unknown. This study demonstrated that GPS2 positively regulates erythroid differentiation in K562 cells, which have a primitive erythroid phenotype. Overexpression of GPS2 promoted hemin-induced hemoglobin synthesis in K562 cells as assessed by the increased percentage of benzidine-positive cells and the deeper red coloration of the cell pellets. In contrast, knockdown of GPS2 inhibited hemin-induced erythroid differentiation of K562 cells. GPS2 overexpression also enhanced erythroid differentiation of K562 cells induced by cytosine arabinoside (Ara-C). GPS2 induced hemoglobin synthesis by increasing the expression of globin and ALAS2 genes, either under steady state or upon hemin treatment. Promotion of erythroid differentiation of K562 cells by GPS2 mainly relies on NCOR1, as knockdown of NCOR1 or lack of the NCOR1-binding domain of GPS2 potently diminished the promotive effect. Thus, our study revealed a previously unknown role of GPS2 in regulating human primitive erythropoiesis in K562 cells.

SpCTP3 from the hyperaccumulator Sedum plumbizincicola positively regulates cadmium tolerance by interacting with SpMDH1.

Cadmium (Cd) is a heavy metal pollutant mainly originating from the discharge of industrial sewage, irrigation with contaminated water, and the use of fertilizers. The phytoremediation of Cd polluted soil depends on the identification of the associated genes in hyperaccumulators. Here, a novel Cd tolerance gene (SpCTP3) was identified in hyperaccumulator Sedum plumbizincicola. The results of Cd2+ binding and thermodynamic analyses, revealed the CXXC motif in SpCTP3 functions is a Cd2+ binding site. A mutated CXXC motif decreased binding to Cd by 59.93%. The subcellular localization analysis suggested that SpCTP3 is primarily a cytoplasmic protein. Additionally, the SpCTP3-overexpressing (OE) plants were more tolerant to Cd and accumulated more Cd than wild-type Sedum alfredii (NHE-WT). The Cd concentrations in the cytoplasm of root and leaf cells were significantly higher (53.75% and 71.87%, respectively) in SpCTP3-OE plants than in NHE-WT. Furthermore, malic acid levels increased and decreased in SpCTP3-OE and SpCTP3-RNAi plants, respectively. Moreover, SpCTP3 interacted with malate dehydrogenase 1 (MDH1). Thus, SpCTP3 helps regulate the subcellular distribution of Cd and increases Cd accumulation when it is overexpressed in plants, ultimately Cd tolerance through its interaction with SpMDH1. This study provides new insights relevant to improving the Cd uptake by Sedum plumbizincicola.

Three-dimensional printed personalised digital guide plate for greater palatine block in trigeminal neuralgia.

The nerve block is a safe and effective method to therapy trigeminal neuralgia (TN). In terms of the V2 trigeminal neuralgia, the most difficult procedure in nerve block is accurate and fast greater palatine foramen (GPF) insertion. In this study, we developed a new technique using a personalized digital tooth-supported guide plate to increase insertion accuracy and success rates and reduce the pain of patients during injection. A total of 18 patients with TN (11 female and 7 male) were enrolled and treated between September 2020 and June 2022. Before injection, the guide plate was designed via Mimics three-dimensional (3D) reconstruction technology and printed via 3D printer. Then, all patients underwent maxillary nerve block with a guide plate for each injection. In this study, placement of all guide plates was completed within one minute and all punctures were successful at first time. The depth of the injection needle was over 2.5 cm in all cases and the guide plate was stability-supported by the maxillary teeth. The various pain scores had an obvious improvement. No patients presented symptoms of local anaesthetic toxicity or onset of new neurological sequelae. Using this new technology, we can significantly reduce the difficulty of GPF insertion and decrease patient pain during injection. The enhanced success rate of nerve block can achieve better therapeutic effect. For surgeons, personalized digital tooth-supported guide plates make the operation easier, especially for novice surgeons.

Combining systemic inflammatory response index and albumin fibrinogen ratio to predict early serious complications and prognosis after resectable gastric cancer.

BACKGROUND: Gastric cancer has a high incidence and fatality rate, and surgery is the preferred course of treatment. Nonetheless, patient survival rates are still low, and the incidence of major postoperative complications cannot be disregarded. The systemic inflammatory response, nutritional level, and coagulation status are key factors affecting the postoperative recovery and prognosis of gastric cancer patients. The systemic inflammatory response index (SIRI) and the albumin fibrinogen ratio (AFR) are two valuable comprehensive indicators of the severity and prognosis of systemic inflammation in various medical conditions. AIM: To assess the clinical importance and prognostic significance of the SIRI scores and the AFR on early postoperative outcomes in patients undergoing radical gastric cancer surgery. METHODS: We conducted a retrospective analysis of the clinicopathological characteristics and relevant laboratory indices of 568 gastric cancer patients from January 2018 to December 2019. We calculated and compared two indicators of inflammation and then examined the diagnostic ability of combined SIRI and AFR values for serious early postoperative complications. We scored the patients and categorized them into three groups based on their SIRI and AFR levels. COX analysis was used to compare the three groups of patients the prognostic value of various preoperative SIRI-AFR scores for 5-year overall survival (OS) and disease-free survival (DFS). RESULTS: SIRI-AFR scores were an independent risk factor for prognosis [OS: P = 0.004; hazards ratio (HR) = 3.134; DFS: P < 0.001; HR = 3.543] and had the highest diagnostic power (area under the curve: 0.779; 95% confidence interval: 0.737-0.820) for early serious complications in patients with gastric cancer. The tumor-node-metastasis stage (P = 0.001), perioperative transfusion (P = 0.044), positive carcinoembryonic antigen (P = 0.014) findings, and major postoperative complications (P = 0.011) were factors associated with prognosis. CONCLUSION: Preoperative SIRI and AFR values were significantly associated with early postoperative survival and the occurrence of severe complications in gastric cancer patients.

Prediction of Th17/Treg cell balance on length of stay in intensive care units of patients with sepsis.

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.

Retrobisabolane A, a Novel Bisabolane-Derived Sesquiterpenoid Isolated from Deep-Sea-Derived Fungus Retroconis fusiformis MCCC 3A00792.

One novel bisabolane-derived sesquiterpenoid retrobisabolane A (1), featuring a methyl group location at the C-4 position instead of C-3 in the bisabolanes, and a known ester-substituted eremophilane-type sesquiterpenoid cryptosphaerolide (2), along with three known indole alkaloids (3-5) were discovered from the fermented cultures of a deep-sea-derived fungus Retroconis fusiformis MCCC 3A00792. The planar structure of new compound 1 was determined by extensive analysis of the NMR and HRESIMS spectra. The relative and absolute configurations of 1 were resolved by the coupling constant (J), calculation of ECD and NMR spectra, and the DP4+ probability analysis of the 1H and 13C NMR data. Interestingly, retrobisabolane A was the new subclass of bisabolanes bearing a methyl group linkage at C-4 instead of C-3 position. Three human cancer cell lines (Hela, AGS, and BIU-87) were subjected to evaluate the cytotoxic activities of compounds 1-5. As a result, compound 2 exhibited significant inhibitory activities against three cell lines with IC50 values ranging from 9.95 to 18.77 µM.

Splenectomy versus splenic preservation in total gastrectomy for gastric cancer: a systematic review and meta-analysis comparing survival benefits and short-term complications.

BACKGROUND: There is an ongoing debate regarding the comparative merits of splenectomy (SP) and splenic preservation in the surgical management of gastric cancer. This systematic review and meta-analysis aims to shed light on potential differences in survival outcomes and postoperative complications associated with these two procedures. METHOD: An exhaustive literature search was conducted across multiple databases, namely PubMed, Embase, Cochrane Library, and Web of Science. We utilized a random-effects model via RevMan 5.4 software to conduct a meta-analysis of the hazard ratios (HRs) and risk ratios (RRs) associated with SP and spleen preservation. Subgroup analyses were based on various attributes of the included studies. We employed funnel plots to assess publication bias, and sensitivity analysis was conducted to gauge the stability of the combined results. Both funnel plots and sensitivity analysis were performed using Stata 12. RESULT: Our research incorporated 23 observational studies and three randomized controlled trials, involving a total of 6,255 patients. SP did not yield superior survival outcomes in comparison to splenic preservation, a conclusion that aligns with the combined results of the randomized controlled trials. No statistically significant difference in survival prognosis was observed between SP and splenic preservation, irrespective of whether the patients had proximal gastric cancer or proximal gastric cancer invading the stomach's greater curvature. SP exhibited a higher incidence of all postoperative complications, notably pancreatic fistula and intraabdominal abscesses. However, it did not significantly differ from splenic preservation in terms of anastomotic leakage, incision infection, intestinal obstruction, intra-abdominal bleeding, and pulmonary infection. No significant difference in postoperative mortality between SP and splenic preservation was found. Funnel plots suggested no notable publication bias, and sensitivity analysis affirmed the stability of the combined outcomes. CONCLUSION: Despite the lack of significant differences in certain individual complications and postoperative mortality, the broader pattern of our data suggests that SP is associated with a greater overall frequency of postoperative complications, without providing additional survival benefits compared to splenic preservation. Thus, the routine implementation of SP is not advocated.

When doctors perform surgery for gastric (stomach) cancer, they sometimes remove the spleen, a procedure known as splenectomy (SP). However, there's a debate on whether removing the spleen is better than preserving it. Our study aimed to compare these two methods in terms of patient survival and the risk of complications after surgery. To do this, we looked at data from 26 studies involving 6,255 patients. Our analysis was thorough, using advanced statistical methods to ensure accuracy. Here's what we found: patients who had their spleen removed did not live longer than those who kept their spleen. Whether the cancer was just in the upper part of the stomach or had spread to the nearby large curve of the stomach, the survival rates were similar for both groups. Patients who underwent SP faced more postoperative complications, especially issues like pancreatic fistula and intra-abdominal abscesses. However, for some complications like leakage from the surgical joint, infection of the wound, bowel obstruction, internal bleeding, and lung infections, there was no significant difference between the two groups. The chances of dying post-surgery were similar whether patients had their spleen removed or not. Our findings suggest that routinely removing the spleen during gastric cancer surgery does not improve survival rates and is linked to more postoperative complications. Therefore, it may be better to avoid removing the spleen unless absolutely necessary.

Unveiling novel anti-viral mechanisms of ε-poly-l-lysine on tobacco mosaic virus-infected Nicotiana tabacum through microRNA and transcriptome sequencing.

MicroRNAs (miRNAs) play important roles in plant defense against various pathogens. ε-poly-l-lysine (ε-PL), a natural anti-microbial peptide produced by microorganisms, effectively suppresses tobacco mosaic virus (TMV) infection. To investigate the anti-viral mechanism of ε-PL, the expression profiles of miRNAs in TMV-infected Nicotiana tabacum after ε-PL treatment were analyzed. The results showed that the expression levels of 328 miRNAs were significantly altered by ε-PL. Degradome sequencing was used to identify their target genes. Integrative analysis of miRNAs target genes and gene-enriched GO/KEGG pathways indicated that ε-PL regulates the expression of miRNAs involved in critical pathways of plant hormone signal transduction, host defense response, and plant pathogen interaction. Subsequently, virus induced gene silencing combined with the short tandem targets mimic technology was used to analyze the function of these miRNAs and their target genes. The results indicated that silencing miR319 and miR164 reduced TMV accumulation in N. benthamiana, indicating the essential roles of these miRNAs and their target genes during ε-PL-mediated anti-viral responses. Collectively, this study reveals that microbial source metabolites can inhibit plant viruses by regulating crucial host miRNAs and further elucidate anti-viral mechanisms of ε-PL.

Dual contrastive learning for synthesizing unpaired fundus fluorescein angiography from retinal fundus images.

Background: Fundus fluorescein angiography (FFA) is an imaging method used to assess retinal vascular structures by injecting exogenous dye. FFA images provide complementary information to that provided by the widely used color fundus (CF) images. However, the injected dye can cause some adverse side effects, and the method is not suitable for all patients. Methods: To meet the demand for high-quality FFA images in the diagnosis of retinopathy without side effects to patients, this study proposed an unsupervised image synthesis framework based on dual contrastive learning that can synthesize FFA images from unpaired CF images by inferring the effective mappings and avoid the shortcoming of generating blurred pathological features caused by cycle-consistency in conventional approaches. By adding class activation mapping (CAM) to the adaptive layer-instance normalization (AdaLIN) function, the generated images are made more realistic. Additionally, the use of CAM improves the discriminative ability of the model. Further, the Coordinate Attention Block was used for better feature extraction, and it was compared with other attention mechanisms to demonstrate its effectiveness. The synthesized images were quantified by the Fréchet inception distance (FID), kernel inception distance (KID), and learned perceptual image patch similarity (LPIPS). Results: The extensive experimental results showed the proposed approach achieved the best results with the lowest overall average FID of 50.490, the lowest overall average KID of 0.01529, and the lowest overall average LPIPS of 0.245 among all the approaches. Conclusions: When compared with several popular image synthesis approaches, our approach not only produced higher-quality FFA images with clearer vascular structures and pathological features, but also achieved the best FID, KID, and LPIPS scores in the quantitative evaluation.

Antidepressant effects of esketamine via the BDNF/AKT/mTOR pathway in mice with postpartum depression and their offspring.

Postpartum depression (PPD) is a serious mental health problem that can negatively affect future generations. BDNF/AKT/mTOR signaling in the frontal lobe and hippocampus in mice is associated with depression, but its role in mice with PPD and their offspring is unknown. This study was aimed at investigating the effects of esketamine (ESK), a drug approved for treatment of refractory depression, on the BDNF/AKT/mTOR pathway in mice with PPD and their offspring. A model of chronic unpredictable mild stress with pregnancy was used. ESK was injected into postpartum mice, and behavioral tests were conducted to predict the severity of symptoms at the end of lactation and in the offspring after adulthood. Both mice with PPD and their offspring showed significant anxiety- and depression-like behaviors that were ameliorated with the ESK intervention. ESK enhanced exploratory behavior in unfamiliar environments, increased the preference for sucrose, and ameliorated the impaired BDNF/AKT/mTOR signaling in the frontal and hippocampal regions in mice. Thus, ESK may have great potential in treating PPD and decreasing the incidence of depression in offspring.

Targeted Delivery of Mesenchymal Stem Cell-Derived Bioinspired Exosome-Mimetic Nanovesicles with Platelet Membrane Fusion for Atherosclerotic Treatment.

Purpose: Accumulating evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes hold significant potential for the treatment of atherosclerosis. However, large-scale production and organ-specific targeting of exosomes are still challenges for further clinical applications. This study aims to explore the targeted efficiency and therapeutic potential of biomimetic platelet membrane-coated exosome-mimetic nanovesicles (P-ENVs) in atherosclerosis. Methods: To produce exosome-mimetic nanovesicles (ENVs), MSCs were successively extruded through polycarbonate porous membranes. P-ENVs were engineered by fusing MSC-derived ENVs with platelet membranes and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. The stability and safety of P-ENVs were also assessed. The targeted efficacy of P-ENVs was evaluated using an in vivo imaging system (IVIS) spectrum imaging system and immunofluorescence. Histological analyses, Oil Red O (ORO) staining, and Western blot were used to investigate the anti-atherosclerotic effectiveness of P-ENVs. Results: Both ENVs and P-ENVs exhibited similar characteristics to exosomes. Subsequent miRNA sequencing of P-ENVs revealed their potential to mitigate atherosclerosis by influencing biological processes related to cholesterol metabolism. In an ApoE-/- mice model, the intravenous administration of P-ENVs exhibited enhanced targeting of atherosclerotic plaques, resulting in a significant reduction in lipid deposition and necrotic core area. Our in vitro experiments showed that P-ENVs promoted cholesterol efflux and reduced total cholesterol content in foam cells. Further analysis revealed that P-ENVs attenuated intracellular cholesterol accumulation by upregulating the expression of the critical cholesterol transporters ABCA1 and ABCG1. Conclusion: This study highlighted the potential of P-ENVs as a novel nano-drug delivery platform for enhancing drug delivery efficiency while concurrently mitigating adverse reactions in atherosclerotic therapy.

Spermidine attenuates monocrotaline-induced pulmonary arterial hypertension in rats by inhibiting purine metabolism and polyamine synthesis-associated vascular remodeling.

Ensuring the homeostatic integrity of pulmonary artery endothelial cells (PAECs) is essential for combatting pulmonary arterial hypertension (PAH), as it equips the cells to withstand microenvironmental challenges. Spermidine (SPD), a potent facilitator of autophagy, has been identified as a significant contributor to PAECs function and survival. Despite SPD's observed benefits, a comprehensive understanding of its protective mechanisms has remained elusive. Through an integrated approach combining metabolomics and molecular biology, this study uncovers the molecular pathways employed by SPD in mitigating PAH induced by monocrotaline (MCT) in a Sprague-Dawley rat model. The study demonstrates that SPD administration (5 mg/kg/day) significantly corrects right ventricular impairment and pathological changes in pulmonary tissues following MCT exposure (60 mg/kg). Metabolomic profiling identified a purine metabolism disorder in MCT-treated rats, which SPD effectively normalized, conferring a protective effect against PAH progression. Subsequent in vitro analysis showed that SPD (0.8 mM) reduces oxidative stress and apoptosis in PAECs challenged with Dehydromonocrotaline (MCTP, 50 µM), likely by downregulating purine nucleoside phosphorylase (PNP) and modulating polyamine biosynthesis through alterations in S-adenosylmethionine decarboxylase (AMD1) expression and the subsequent production of decarboxylated S-adenosylmethionine (dcSAM). These findings advocate SPD's dual inhibitory effect on PNP and AMD1 as a novel strategy to conserve cellular ATP and alleviate oxidative injuries, thus providing a foundation for SPD's potential therapeutic application in PAH treatment.