The role of inflammasome in chronic viral hepatitis.

Infections of hepatotropic viruses cause a wide array of liver diseases including acute hepatitis, chronic hepatitis and the consequently developed cirrhosis and hepatocellular carcinoma (HCC). Among the five classical hepatotropic viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) usually infect human persistently and cause chronic hepatitis, leading to major troubles to humanity. Previous studies have revealed that several types of inflammasomes are involved in the infections of HBV and HCV. Here, we summarize the current knowledge about their roles in hepatitis B and C. NLRP3 inflammasome can be activated and regulated by HBV and HCV. It is found to exert antiviral function or mediates inflammatory response in viral infections depending on different experimental models. Besides NLRP3 inflammasome, IFI16 and AIM2 inflammasomes participate in the pathological process of hepatitis B, and NALP3 inflammasome may sense HCV infection in hepatocytes. The inflammasomes affect the pathological process of viral hepatitis through its downstream secretion of inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 or induction of pyroptosis resulting from cleaved gasdermin D (GSDMD). However, the roles of inflammasomes in different stages of viral infection remains mainly unclear. More proper experimental models of viral hepatitis should be developed for specific studies in future, so that we can understand more about the complexity of inflammasome regulation and multifunction of inflammasomes and their downstream effectors during HBV and HCV infections.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

B-Cell Lymphoma With Prominent Presentation of Lactic Acidosis: A Case Report and Brief Review of the Literature.

Lactic acidosis is a rare but severe complication of B-cell lymphoma, often associated with rapid disease progression and poor prognosis. We present a case of a 60-year-old male admitted with fever, splenomegaly, hemophagocytic tendencies, and lactic acidosis. The patient underwent several dialysis sessions before bone marrow flow cytometry finally confirmed B-cell lymphoma. However, hyperlactatemia persisted and recurred. The case underscores the challenges in diagnosing lymphomas with atypical presentations and emphasizes the critical role of timely bone marrow analysis. Additionally, the paper discusses the association between B-cell lymphoma and lactic acidosis, highlighting the importance of early recognition and intervention.

Adjuvant Transarterial Chemoembolization Plus Immunotherapy for Huge Hepatocellular Carcinoma: A Propensity Score Matching Cohort Study.

Purpose: The prognosis of patients with huge hepatocellular carcinoma (huge HCC, diameter ≥10 cm) is poor owing to the high early recurrence rate. This study aimed to explore the clinical value of postoperative adjuvant transarterial chemoembolization (PA-TACE) plus programmed cell death-1 (PD-1) inhibitors for huge HCC. Patients and Methods: Data from consecutive huge HCC patients treated with hepatectomy during June 2017 and July 2022 were retrospectively collected. Baseline differences were balanced between huge HCC patients who underwent PA-TACE with (AIT group) or without PD-1 inhibitors (AT group) by propensity-score matching (PSM). We compared recurrence-free survival (RFS), overall survival (OS) and recurrence patterns between the two groups. Independent risk factors for RFS and OS were confirmed by Cox regression analysis, and subgroup analysis was also conducted. Results: A total of 294 patients were enrolled, and 77 pairs of patients in the AIT and AT groups were matched by PSM. The 1-year and 2-year RFS were 49.9% and 35.7% in the AIT group compared to 24.7% and 15.5% in the AT group respectively (p<0.001). The 1-year and 2-year OS were 83.6% and 66.9% in the AIT group compared to 50.6% and 36.8% in the AT group respectively (p<0.001). There were no significant differences in recurrence patterns between the two groups. Multivariable analysis demonstrated that combined therapy of PA-TACE plus PD-1 inhibitors was a protective factor related to both RFS and OS. Conclusion: PA-TACE plus PD-1 inhibitors could improve survival outcomes for huge HCC patients.

Effect of GnRH Active Immunisation on Reproductive Performance of Male Sprague Dawley Rats.

To investigate the effect of active immunisation with gonadotropin-releasing hormone (GnRH) on the reproductive function in male Sprague Dawley (SD) rats, 24 42-day-old rats were randomly assigned to treatment with GnRH6-MAP, GnRH-OVA, a surgical castration group, and a blank control group. Each rat in the treatment groups was intramuscularly injected at 6, 8, and 10 weeks of age. The serum concentrations of testosterone (T), follicle-stimulating hormone (FSH), luteinising hormone (LH), and anti-GnRH antibodies were determined using enzyme-linked immunosorbent assays. The results showed that active immunisation with recombinant GnRH6-MBP and GnRH-OVA significantly increased the serum levels of anti-GnRH antibodies and reduced the serum concentrations of testosterone compared to the black control. Eight weeks after immunisation, the rats' testes were surgically removed for morphological evaluation, showing atrophy of the convoluted vasculature, relative emptying of the lumen, and insignificant differentiation of spermatogonial cells, which were increased in weight and volume compared with the blank control group. These findings indicated that active immunisation with GnRH can lead to testicular atrophy and reduce gonadal hormone concentrations, suggesting that GnRH is a highly effective immunogen.

Effective Treatment of Anlotinib Combined With Chemotherapy in Children With Desmoplastic Small Round Cell Tumor: A Case Series in a Single-center and Literature Review.

INTRODUCTION: Desmoplastic small round cell tumor (DSRCT) is a highly aggressive primitive sarcoma with a 5-year survival rate estimated at only 15% to 30%. Although few curative treatment options exist, patients are most often treated with a combination of aggressive chemotherapy, radiation, and surgery. Targeted therapy inhibitors of platelet-derived growth factor A, insulin-like growth factor receptor 1, and vascular endothelial growth factor receptor-2, which are almost uniformly overexpressed in DSRCT, have largely failed in clinical trials. Anlotinib is a multitarget receptor tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor α/ß, c-Kit, and Met. In this study, we presented 3 cases of DSRCT treated effectively with anlotinib combined with chemotherapy. CASE PRESENTATION: Three children DSRCT patients were enrolled from September 2020 to December 2021 and monitored until August 30, 2022. The clinical data were prospectively studied. The peritoneal cancer index classified all 3 patients as stage IV. After surgery, all 3 patients received anlotinib in combination with chemotherapy and reacted to the medication. For all 3 patients, clinical symptoms were substantially eased, and the size of the masses was reduced. Patient 1 and patient 3's progression-free survival had been extended, and anlotinib was continued as a maintenance medication in the 2 patients who were in good health at the end of the follow-up. Patient 2 died of postoperative complications 1 month after second-stage surgery. The main side effects of anlotinib were fatigue and hypertension. However, its toxicity was controllable and tolerable in children patients. CONCLUSIONS: This is the first report that anlotinib is effective in children with DSRCT. This report may provide an additional option for the treatment of metastatic DSRCT.

[Clinical characteristics and prognosis of children with perianal fistulizing Crohn's disease]. / å„¿ç«¥è‚›å‘¨ç˜˜ç®¡åž‹å ‹ç½—æ©ç— çš„ä¸´åºŠç‰¹å¾åŠé¢„åŽ.

OBJECTIVES: To investigate the clinical characteristics, treatment, and prognosis of children with perianal fistulizing Crohn's disease (pfCD). METHODS: A retrospective analysis was conducted on the children, aged 6-17 years, who were diagnosed with Crohn's disease (CD) from April 2015 to April 2023. According to the presence or absence of perianal fistulizing lesions, they were divided into two groups: pfCD (n=60) and non-pfCD (n=82). The two groups were compared in terms of clinical characteristics, treatment, and prognosis. RESULTS: The incidence of pfCD was 42.3% (60/142). The proportion of males in the pfCD group was higher than that in the non-pfCD group. Compared with the non-pfCD group, the pfCD group had a significantly higher proportion of children with involvement of the colon and small intestine or those with upper gastrointestinal lesions (P<0.05). Compared with the non-pfCD group, the pfCD group had a significantly higher rate of use of infliximab during both induction and maintenance treatment (P<0.05). In the pfCD group, the children with complex anal fistula accounted for 62% (37/60), among whom the children receiving non-cutting suspended line drainage accounted for 62% (23/37), which was significantly higher than the proportion among the children with simple anal fistula patients (4%, 1/23) (P<0.05). There were no significant differences between the two groups in mucosal healing rate and clinical remission rate at week 54 of treatment (P>0.05). The pfCD group achieved a fistula healing rate of 57% (34/60) at week 54, and the children with simple anal fistula had a significantly higher rate than those with complex anal fistula (P<0.05). CONCLUSIONS: There is a high incidence rate of pfCD in children with CD, and among the children with pfCD, there is a high proportion of children with the use of biological agents. There is a high proportion of children receiving non-cutting suspended line drainage among the children with complex anal fistula. The occurrence of pfCD should be closely monitored during the follow-up in children with CD.

Targeted activation of ferroptosis in colorectal cancer via LGR4 targeting overcomes acquired drug resistance.

Acquired drug resistance is a major challenge for cancer therapy and is the leading cause of cancer mortality; however, the mechanisms of drug resistance are diverse and the strategy to specifically target drug-resistant cancer cells remains an unmet clinical issue. Here, we established a colorectal cancer-derived organoid biobank and induced acquired drug resistance by repeated low-level exposures of chemo-agents. Chemosensitivity profiling and transcriptomic analysis studies revealed that chemoresistant cancer-derived organoids exhibited elevated expression of LGR4 and activation of the Wnt signaling pathway. Further, we generated a monoclonal antibody (LGR4-mAb) that potently inhibited LGR4-Wnt signaling and found that treatment with LGR4-mAb notably sensitized drug-induced ferroptosis. Mechanistically, LGR4-dependent Wnt signaling transcriptionally upregulated SLC7A11, a key inhibitor of ferroptosis, to confer acquired drug resistance. Our findings reveal that targeting of Wnt signaling by LGR4-mAb augments ferroptosis when co-administrated with chemotherapeutic agents, demonstrating a potential opportunity to fight refractory and recurrent cancers.

The effect of preoperative different dexamethasone regimens on postoperative glycemic control in patients with type 2 diabetes mellitus undergoing total joint arthroplasty: a retrospective cohort study.

BACKGROUND: Concerns have been raised regarding the impact of preoperative intravenous dexamethasone on postoperative glycemic control in diabetic patients undergoing total joint arthroplasty (TJA). This study aimed to determine relationships between preoperative different dexamethasone regimens and postoperative fasting blood glucose (FBG), as well as to identify risk factors for postoperative FBG ≥ 200 mg/dl in diabetic patients undergoing TJA. METHODS: This retrospective study included 1216 diabetic patients undergoing TJA and categorized into group A (dexamethasone = 0 mg), group B (dexamethasone = 5 mg), and group C (dexamethasone = 10 mg). All dexamethasone was administered before skin incision. FBG levels were monitored until postoperative day (POD) 3. Analyses were conducted for periprosthetic joint infection (PJI) and wound complications during 90 days postoperatively. And the risk factors for postoperative FBG ≥ 200 mg/dl were identified. RESULTS: Preoperative dexamethasone administration resulted in a transiently higher FBG on POD 0 and POD 1 (all P < 0.001). However, no differences were observed on POD 2 (P = 0.583) and POD 3 (P = 0.131) among three groups. While preoperative dexamethasone led to an increase in postoperative mean FBG and postoperative maximum FBG (all P < 0.001), no differences were found in wound complications (P = 0.548) and PJI (P = 1.000). Increased HbA1c and preoperative high FBG, but not preoperative dexamethasone, were identified as risk factors for postoperative FBG ≥ 200 mg/dl. Preoperative HbA1c level of ≥ 7.15% was associated with an elevated risk of postoperative FBG ≥ 200 mg/dl. CONCLUSIONS: Although preoperative intravenous administration of 5 mg or 10 mg dexamethasone in diabetic patients showed transient effects on postoperative FBG after TJA, no differences were found in the rates of PJI and wound complications during 90 days postoperatively. Notably, patients with a preoperative HbA1c level of ≥ 7.15% and elevated preoperative FBG may encountered postoperative FBG ≥ 200 mg/dl.

Application of machine learning-based multi-sequence MRI radiomics in diagnosing anterior cruciate ligament tears.

OBJECTIVE: To compare the diagnostic power among various machine learning algorithms utilizing multi-sequence magnetic resonance imaging (MRI) radiomics in detecting anterior cruciate ligament (ACL) tears. Additionally, this research aimed to create and validate the optimal diagnostic model. METHODS: In this retrospective analysis, 526 patients were included, comprising 178 individuals with ACL tears and 348 with a normal ACL. Radiomics features were derived from multi-sequence MRI scans, encompassing T1-weighted imaging and proton density (PD)-weighted imaging. The process of selecting the most reliable radiomics features involved using interclass correlation coefficient (ICC) testing, t tests, and the least absolute shrinkage and selection operator (LASSO) technique. After the feature selection process, five machine learning classifiers were created. These classifiers comprised logistic regression (LR), support vector machine (SVM), K-nearest neighbors (KNN), light gradient boosting machine (LightGBM), and multilayer perceptron (MLP). A thorough performance evaluation was carried out, utilizing diverse metrics like the area under the receiver operating characteristic curve (ROC), specificity, accuracy, sensitivity positive predictive value, and negative predictive value. The classifier exhibiting the best performance was chosen. Subsequently, three models were developed: the PD model, the T1 model, and the combined model, all based on the optimal classifier. The diagnostic performance of these models was assessed by employing AUC values, calibration curves, and decision curve analysis. RESULTS: Out of 2032 features, 48 features were selected. The SVM-based multi-sequence radiomics outperformed all others, achieving AUC values of 0.973 and 0.927, sensitivities of 0.933 and 0.857, and specificities of 0.930 and 0.829, in the training and validation cohorts, respectively. CONCLUSION: The multi-sequence MRI radiomics model, which is based on machine learning, exhibits exceptional performance in diagnosing ACL tears. It provides valuable insights crucial for the diagnosis and treatment of knee joint injuries, serving as an accurate and objective supplementary diagnostic tool for clinical practitioners.

Effect of basal metabolic rate on rheumatoid arthritis: a Mendelian randomization study.

PURPOSE: Basal metabolic rate (BMR) as one of the most basic and significant indicators of metabolism has been associated with human health. Previous studies showed that the development of rheumatoid arthritis (RA) is linked to BMR; however, the causal relationship between BMR and RA is unknown. Thus, we aimed to explore the causal relationship between BMR and RA as well as RA-related factors. METHODS: Mendelian randomization (MR) analysis was performed on collected genome-wide association studies information. The effect of horizontal pleiotropy was detected by MR-PRESSO and MR-Radial. Five MR analysis methods were applied, including inverse variance weighted, MR-Egger, weighted median, weighted mode, and simple mode. Four sensitivity analysis methods were used for the validation of the significant MR analysis results. A two-component mixture of regressions method was additionally used to validate single nucleotide polymorphisms and to verify results. RESULTS: Genetically, there is a causal effect of BMR on overall RA (odds ratio = 1.25, 95% confidence interval: 1.07-1.47, PIVW = .006), seropositive RA (odds ratio = 1.20, 95% confidence interval: 1.01-1.44, PIVW = .035), and seronegative RA (odds ratio = 1.36, 95% confidence interval: 1.04-1.78, PIVW = .023). Sensitivity analyses validated the robustness of the above associations. No evidence supported the effect of RA on BMR. Moreover, BMR showed no causal relationship with rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate, interleukin-1ß, tumor necrosis factor-α, and matrix metallopeptidase 3. CONCLUSION: MR results implied the causal effect of BMR on RA and raised our attention to the importance of BMR in RA's pathology.

Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis.

Coronary artery disease (CAD) is characterized by atherosclerotic plaque formation in the arterial wall. CAD progression involves complex interactions and phenotypic plasticity among vascular and immune cell lineages. Single-cell RNA-seq (scRNA-seq) studies have highlighted lineage-specific transcriptomic signatures, but human cell phenotypes remain controversial. Here, we perform an integrated meta-analysis of 22 scRNA-seq libraries to generate a comprehensive map of human atherosclerosis with 118,578 cells. Besides characterizing granular cell-type diversity and communication, we leverage this atlas to provide insights into smooth muscle cell (SMC) modulation. We integrate genome-wide association study data and uncover a critical role for modulated SMC phenotypes in CAD, myocardial infarction, and coronary calcification. Finally, we identify fibromyocyte/fibrochondrogenic SMC markers (LTBP1 and CRTAC1) as proxies of atherosclerosis progression and validate these through omics and spatial imaging analyses. Altogether, we create a unified atlas of human atherosclerosis informing cell state-specific mechanistic and translational studies of cardiovascular diseases.

Alignment strategy for different types of varus knee with generic instruments: Mechanical alignment or kinematic alignment?

OBJECTIVE: A thorough examination of the available approaches is crucial to comprehensively understand the variance among the alignment strategies employed in total knee arthroplasty (TKA). In this study, we assessed the functional outcomes during the perioperative and postoperative periods of TKA in patients using generic instruments with varus knee to compare the mechanical alignment (MA) and kinematic alignment (KA) procedures. METHODS: A total of 127 patients from the First Affiliated Hospital of Wannan Medical College who had undergone unilateral TKA between November 2019 and April 2021 were included. The patients with varus knee deformity were categorized into two groups [type I (n = 64) and type IV (n = 63)] based on the modified coronal plane alignment of the knee (mCPAK) classification. The type I and IV groups were further subdivided into MA (n = 30 and n = 32) and KA subgroups (n = 34 and n = 21), respectively. The clinical information collected included sex, surgical side, age, body mass index, and perioperative data [including operation time, intraoperative blood loss, length of hospital stay, and the American Society of Anesthesiologists (ASA) classification]. All patients were monitored for 12 months post-surgery to evaluate the recovery of knee joint function. During this period, the Knee Disability and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) and the active range of motion (AROM) and visual analog scale (VAS) pain scores were compared at different time points, i.e., before the operation and 6 weeks, 6 months, and 12 months post-operation. Additionally, the patients' subjective experiences were assessed at 6 and 12 months post-surgery using Forgotten Joint Score Knee (FJS-12 Knee), while complications were recorded throughout the monitoring period. RESULTS: No significant variances were observed in ASA classification, operation duration, blood loss volume during surgery, and hospital stay length between the patients who underwent KA TKA and those who received MA TKA (P > 0.05). During the initial 6 weeks post-operation, the KA group exhibited a significantly reduced average VAS pain score (P < 0.05), with no such differences at 6 months and 1 year after the surgery (P > 0.05). Furthermore, the KA group had significantly higher scores on the KOOS JR at 6 weeks, 6 months, and 1 year following the surgery (P < 0.05). Moreover, the AROM score of the KA group significantly improved only at 6 weeks after the surgery (P < 0.05); however, no prominent differences were found at 6 months and 1 year after the operation (P > 0.05). The KA cohort also exhibited a significant increase in FJS-12 Knee at 1 year following the operation (P < 0.05), whereas no such difference was detected at 6 months following the surgery (P > 0.05). Thus, compared to the MA method, the KA procedure provided pain relief and improved active motion range within 6 weeks after the surgery in patients undergoing TKA. Further, the KOOS JR exhibited significant increases at 6 weeks, 6 months, and 1 year while the FJS-12 Knee demonstrated a significant increase at 1 year after the KA TKA procedure. CONCLUSION: Therefore, our study results suggest that the KA approach can be considered in patients using generic instruments with varus alignment of the knee, particularly those with mCPAK type I and IV varus knees, to help improve patient satisfaction.

Ferroptosis of CD163+ tissue-infiltrating macrophages and CD10+ PC+ epithelial cells in lupus nephritis.

Background: Dysregulation of cell death and defective clearance of dying cells are closely related to the pathogenesis of lupus nephritis (LN). However, the contribution of a recently discovered form of programmed cell death (PCD) called ferroptosis to LN has not been explored in detail. The purpose of this study was to investigate the role of ferroptosis and its associated metabolic pathways in the pathogenesis of LN. Methods: The composite gene expression scores were calculated by averaging the z-scored transformed log2 expressed genes within each form of PCD and pathway. Immunohistochemistry and immunofluorescence assays were used to verify the bioinformatics results. Results: We determined that ferroptosis is prominently and specifically elevated in the glomerular compartment of LN patients compared to other forms of PCD and kidney disease. This finding was then verified by immunohistochemical staining of 4-HNE (a key indicator for ferroptosis) expression in our own cohort (P < 0.0001). Intercorrelation networks were observed between 4-HNE and blood urea nitrogen, SLE disease activity index, serum creatinine, and complement 4, and negatively correlated with glomerular filtration rate in our own LN cohort (P < 0.05). Furthermore, enhanced iron metabolism and reduced fatty acid synthesis may be the most important factors for ferroptosis within the glomerulus. Through analysis of a single cell sequencing dataset and verification of immunohistochemical and immunofluorescence staining, aberrantly activated lipid peroxidation in CD163+ macrophages and CD10+ PC+ (pyruvate carboxylase) epithelial cells indicated that they may be undergoing ferroptosis in the glomerular compartment. Conclusions: Two dysregulated genes, CD163 and PC, were identified and verified that were significantly associated with lipid peroxidation. Targeting ferroptosis in CD163+ macrophages and CD10+ PC+ epithelial cells may provide novel therapeutic approaches in LN.

"Sandwich" protocol based on modified SMILE regimen for children with newly extranodal NK/T cell lymphoma, nasal type: a single-arm, single-center clinical study.

Extranodal NK/T-cell lymphoma, nasal type (ENKTL), which is a rare form of mature T/NK cell lymphoma in children, currently lacks a standardized first-line treatment approach. However, a treatment protocol known as the "sandwich" regimen has been used in children newly diagnosed with ENKTL. This protocol combines the administration of methotrexate, ifosfamide, etoposide, pegaspargase, and dexamethasone (referred to as SMILE) with the addition of radiotherapy (RT). From September 2017 to December 2020, a total of five patients were included in the study, consisting of three males and two females. The median age of onset was 10.6 years (range, 9.8 to 14.0 years). Among the patients, four had nasal/nasopharyngeal disease at stage II, while one patient had extra nasal disease involving the skin at stage IV. The median EBV-DNA level in plasma was 1.68 × 103 copies/ml (range, 0.44 to 21.1 × 103copies/ml). All the patients had good overall response after 2 cycles of chemotherapy and radiotherapy, including 4 of the patients who had a complete response and 1 of the patients with partial remission. The patient with stage IV received allogeneic hematopoietic stem cell transplantation after the EBV-DNA level was elevated again during treatment. One patient in the low-risk group experienced grade 4 oral mucositis, while no other severe complications or treatment-related deaths were observed. The median follow-up period was 22 months (range, 5 to 57 months). All five patients successfully completed their treatment, with four patients achieving event-free survival, and one patient was lost to follow-up. The median OS time and EFS time was 33 months (range: 18-57 months) and 20 months (range: 5-47 months), respectively. The sandwich protocol has demonstrated a high response rate, good tolerance to chemotherapy, and no treatment-related fatalities. However, further confirmation is necessary through additional clinical studies involving larger sample sizes. Clinical trial registration number: Due to modified SMILE regimens with sandwiched radiotherapy yielded promising outcomes in children ENKTL, we have carried out a phase II multicenter clinical trial (ChiCTR220005954) for children ENKTL in China to further verify the efficacy and safety.

Mussel- and nacre-inspired dual-bionic alginate-based hydrogel coating with multi-matrix applicability, high separation stability and antifouling performance for oil/water separation.

Natural hydrogel-modified porous matrices with superwetting interfaces are ideal for oil/water separation. In this study, inspired by two marine organisms, a novel hydrogel coating with multi-matrix suitability, high oil/water separation capability and antifouling properties was developed. Specifically, inspired by mussel byssus, hydrogel coating was successfully deposited on porous matrix surface based on the introduction of tannic acid (TA). Moreover, inspired by the "brick and mortar" microstructure of Pinctada nacre, silica particles were in-situ synthesized in the sodium alginate (SA)/Ca2+ hydrogel to provide the filling effect and to increase strength. Furthermore, Sodium alginate-tannic acid-tetraethyl orthosilicate (SA-TA-TEOS) hydrogel coating-modified membrane exhibited super-hydrophilic and underwater super-oleophobic performance (underwater oil contact angle >150°), and achieved efficient oil/water separation for four oil/water emulsions (flux = 493-584 L·m-2·h-1 and rejection = 97.3-99.5 %). The modified membrane also demonstrated good anti-fouling performance and flux recovery. Notably, hydrogel coating-modified non-woven fabric also had high oil/water separation capacity (rejection >98 %) and cyclic stability, which proved the universal applicability of this hydrogel coating. In short, this work provides new insights into the fabrication of hydrogel coating-modified porous materials based upon a marine organism biomimetic strategy, which has potential applications in separating oil/water emulsions in industrial scenarios.

Effect of Dan-Lou tablets on coronary heart disease revealed by microarray analysis integrated with molecular mechanism studies.

Dan-Lou tablets (DLT) effectively treat coronary heart disease (CHD). However, its pharmacological mechanism in CHD treatment requires further investigation. This study aimed to elucidate the underlying pharmacological mechanisms of DLT in the treatment of CHD through clinical trials, microarray research, bioinformatics analysis, and molecular mechanism research. In this study, DLT improved coagulation function, endothelial injury, and levels of lipids, metalloproteases, adhesion molecules, inflammatory mediators, and homocysteine. The results of molecular biology research demonstrated that DLT can increase the gene and protein expressions of meningioma expressed antigen 5 (MGEA5) and mouse doubleminute 2 (MDM2) and inhibited the gene and protein expressions of signal transcription and transcription activator 5 B (STAT5B), tropomyosin-1 (TPM1), and aromatic hydrocarbon receptor nuclear transpose (ARNT). The results indicate that DLT reduced the extent of vascular endothelial damage in CHD rats by reducing the expressions of STAT5B, TPM1, and MDM2; inhibiting the inflammatory reaction; and increasing the expressions of ARNT and MGEA5.

Cytoprotective Role of Heme Oxygenase-1 in Cancer Chemoresistance: Focus on Antioxidant, Antiapoptotic, and Pro-Autophagy Properties.

Chemoresistance remains the foremost challenge in cancer therapy. Targeting reactive oxygen species (ROS) manipulation is a promising strategy in cancer treatment since tumor cells present high levels of intracellular ROS, which makes them more vulnerable to further ROS elevation than normal cells. Nevertheless, dynamic redox evolution and adaptation of tumor cells are capable of counteracting therapy-induced oxidative stress, which leads to chemoresistance. Hence, exploring the cytoprotective mechanisms of tumor cells is urgently needed to overcome chemoresistance. Heme oxygenase-1 (HO-1), a rate-limiting enzyme of heme degradation, acts as a crucial antioxidant defense and cytoprotective molecule in response to cellular stress. Recently, emerging evidence indicated that ROS detoxification and oxidative stress tolerance owing to the antioxidant function of HO-1 contribute to chemoresistance in various cancers. Enhanced HO-1 expression or enzymatic activity was revealed to promote apoptosis resistance and activate protective autophagy, which also involved in the development of chemoresistance. Moreover, inhibition of HO-1 in multiple cancers was identified to reversing chemoresistance or improving chemosensitivity. Here, we summarize the most recent advances regarding the antioxidant, antiapoptotic, and pro-autophagy properties of HO-1 in mediating chemoresistance, highlighting HO-1 as a novel target for overcoming chemoresistance and improving the prognosis of cancer patients.

Cell transplantation therapies for spinal cord injury focusing on bone marrow mesenchymal stem cells: Advances and challenges.

Spinal cord injury (SCI) is a devastating condition with complex pathological mechanisms that lead to sensory, motor, and autonomic dysfunction below the site of injury. To date, no effective therapy is available for the treatment of SCI. Recently, bone marrow-derived mesenchymal stem cells (BMMSCs) have been considered to be the most promising source for cellular therapies following SCI. The objective of the present review is to summarize the most recent insights into the cellular and molecular mechanism using BMMSC therapy to treat SCI. In this work, we review the specific mechanism of BMMSCs in SCI repair mainly from the following aspects: Neuroprotection, axon sprouting and/or regeneration, myelin regeneration, inhibitory microenvironments, glial scar formation, immunomodulation, and angiogenesis. Additionally, we summarize the latest evidence on the application of BMMSCs in clinical trials and further discuss the challenges and future directions for stem cell therapy in SCI models.