Aloe-emodin alleviates inflammatory bowel disease in mice by modulating intestinal microbiome homeostasis via the IL-4/IL-13 axis.

Introduction: Inflammatory bowel disease (IBD) is a global health concern. Aloe-emodin (AE) has diverse pharmacological benefits, including anti-inflammatory effects. However, its role in IBD remains unclear, prompting our investigation of its regulatory effects and mechanisms in an IBD mouse model. Methods: We studied the therapeutic efficacy of AE in alleviating symptoms and modulating cytokine secretion in a murine model of dextran sulfate sodium (DSS)-induced colitis. BALB/c mice were administered DSS to induce colitis and were subsequently treated with varying doses of AE. Changes in body weight, fecal lipocalin-2 (LCN2) levels, colon tissue histology, and serum cytokine concentrations were evaluated to assess the effects of AE treatment. Additionally, 16 S rRNA sequencing was used to analyze alterations in the composition of the gut microbiota following AE intervention. Finally, the database was used to analyze the signaling pathways associated with IBD in AE and to detect the expression levels of interleukin (IL)-4 pathway using real-time quantitative reverse transcription PCR. Exogenous IL-4 was used in rescue experiments to observe its effects on the disease process of IBD under AE regulation. Results: AE treatment resulted in a dose-dependent mitigation of weight loss, reduction in fecal LCN2 levels, and amelioration of histological damage in DSS-induced colitis in mice. The levels of superoxide dismutase and catalase increased, whereas malondialdehyde decreased following AE treatment, indicating a dose-dependent alleviation of colitis symptoms. Furthermore, AE administration attenuated the secretion of pro-inflammatory cytokines, including IL-17, tumor necrosis factor-alpha (TNF-α), and chemokine ligand 1, while promoting the expression of anti-inflammatory cytokines IL-4 and IL-13. Analysis of the gut microbiota revealed that AE effectively suppressed the overgrowth of colitis-associated bacterial species and restored microbial homeostasis. Finally, we found that overexpression of IL-4 was able to reverse the therapeutic effect of AE for DSS-induced IBD. Conclusion: AE shows promise in alleviating colitis severity, influencing inflammatory cytokines, and modulating the gut microbiota in an IBD mouse model via the IL-4/IL-13 pathway, suggesting its potential as a natural IBD remedy.

Optimization of Ray-Tracing-Guided LASIK Outcomes: A Prospective Comparative Study of ZZ InnovEyes Strategy versus Automated Strategy.

Purpose: To evaluate the effectiveness of Zhang and Zheng's InnovEyes (ZZ InnovEyes) strategy for optimizing outcomes of ray-tracing-guided laser in situ keratomileusis (LASIK) compared to the standard automated strategy. Methods: A total of 38 patients (71 eyes) undergoing therapeutic refractive surgery at Hangzhou MSK Eye Hospital were randomly assigned to the ZZ InnovEyes and automated groups using double-masked randomization. The study assessed visual acuity, refractive outcomes, and higher-order aberrations preoperatively and at 1-day, 2-week, 1-month, and 3-month follow-ups. Statistical analysis was done with Microsoft Excel and SPSS 19.0. Results: The exposure and control groups comprised 36 and 35 eyes, respectively. The ZZ InnovEyes group demonstrated significant advantages in manifest refraction spherical equivalent (MRSE) correction compared to the automated approach group (0.13 ± 0.30 D vs 0.62 ± 0.40 D, p < 0.001), achieving 97.22% uncorrected distance visual acuity (UDVA) of 20/16 or better compared to 85.71% in the automated group at the 3-month follow-up (p = 0.08), and achieving 50.00% UDVA of 20/12.5 or better compared to 28.57% in the automated group at the 3-month follow-up (p = 0.06). Loss lines from preoperative corrected distance visual acuity to postoperative UDVA were lower in the ZZ InnovEyes group (0.00%) than the automated group (8.57%; p = 0.07). Both groups exhibited similar astigmatism corrections and higher-order aberrations. Conclusion: The ZZ InnovEyes strategy, which incorporates manifest and wavefront refraction for ray-tracing-guided LASIK, demonstrated superior MRSE correction and potential advantages in visual acuity outcomes compared to the standard automated strategy. This study highlights the need for ongoing optimization and research in refractive surgery. Clinical Trial Registration Number: ChiCTR2300078709.

Multicenter integration analysis of TRP channels revealed potential mechanisms of immunosuppressive microenvironment activation and identified a machine learning-derived signature for improving outcomes in gliomas.

AIM: This study aimed to explore the mechanisms of transient receptor potential (TRP) channels on the immune microenvironment and develop a TRP-related signature for predicting prognosis, immunotherapy response, and drug sensitivity in gliomas. METHODS: Based on the unsupervised clustering algorithm, we identified novel TRP channel clusters and investigated their biological function, immune microenvironment, and genomic heterogeneity. In vitro and in vivo experiments revealed the association between TRPV2 and macrophages. Subsequently, based on 96 machine learning algorithms and six independent glioma cohorts, we constructed a machine learning-based TRP channel signature (MLTS). The performance of the MLTS in predicting prognosis, immunotherapy response, and drug sensitivity was evaluated. RESULTS: Patients with high expression levels of TRP channel genes had worse prognoses, higher tumor mutation burden, and more activated immunosuppressive microenvironment. Meanwhile, TRPV2 was identified as the most essential regulator in TRP channels. TRPV2 activation could promote macrophages migration toward malignant cells and alleviate glioma prognosis. Furthermore, MLTS could work independently of common clinical features and present stable and superior prediction performance. CONCLUSION: This study investigated the comprehensive effect of TRP channel genes in gliomas and provided a promising tool for designing effective, precise treatment strategies.

System-wide identification of novel de-ubiquitination targets for USP10 in gastric cancer metastasis through multi-omics screening.

OBJECTIVE: Ubiquitin-specific peptidase 10 (USP10), a typical de-ubiquitinase, has been found to play a double-edged role in human cancers. Previously, we reported that the expression of USP10 was negatively correlated with the depth of gastric wall invasion, lymph node metastasis, and prognosis in gastric cancer (GC) patients. However, it remains unclear whether USP10 can regulate the metastasis of GC cells through its de-ubiquitination function. METHODS: In this study, proteome, ubiquitinome, and transcriptome analyses were conducted to comprehensively identify novel de-ubiquitination targets for USP10 in GC cells. Subsequently, a series of validation experiments, including in vitro cell culture studies, in vivo metastatic tumor models, and clinical sample analyses, were performed to elucidate the regulatory mechanism of USP10 and its de-ubiquitination targets in GC metastasis. RESULTS: After overexpression of USP10 in GC cells, 146 proteins, 489 ubiquitin sites, and 61 mRNAs exhibited differential expression. By integrating the results of multi-omics, we ultimately screened 9 potential substrates of USP10, including TNFRSF10B, SLC2A3, CD44, CSTF2, RPS27, TPD52, GPS1, RNF185, and MED16. Among them, TNFRSF10B was further verified as a direct de-ubiquitination target for USP10 by Co-IP and protein stabilization assays. The dysregulation of USP10 or TNFRSF10B affected the migration and invasion of GC cells in vitro and in vivo models. Molecular mechanism studies showed that USP10 inhibited the epithelial-mesenchymal transition (EMT) process by increasing the stability of TNFRSF10B protein, thereby regulating the migration and invasion of GC cells. Finally, the retrospective clinical sample studies demonstrated that the downregulation of TNFRSF10B expression was associated with poor survival among 4 of 7 GC cohorts, and the expression of TNFRSF10B protein was significantly negatively correlated with the incidence of distant metastasis, diffuse type, and poorly cohesive carcinoma. CONCLUSIONS: Our study established a high-throughput strategy for screening de-ubiquitination targets for USP10 and further confirmed that inhibiting the ubiquitination of TNFRSF10B might be a promising therapeutic strategy for GC metastasis.

Fitting-Shape-based Strategy for Topography-guided LASIK: A Prospective Study.

PURPOSE: To assess and compare the visual acuity and refractive outcomes of topography-guided laser in situ keratomileusis (LASIK) based on the fitting-shape-based refractive compensated and Phorcides software strategies. METHODS: Consecutive patients who underwent topography-guided LASIK were included in this study. Through double-masked simple randomization, patients were assigned to the Zhang & Zheng Auto-compensate Refraction (ZZ AR) group (the fitting-shape-based refractive compensated strategy using the ZZ AR calculator was used) or the Phorcides group (the topography analysis algorithm in Phorcides software [Phorcides LLC] was used). Only one eye per patient with binocular correction was randomly enrolled. The preoperative and postoperative visual acuities and refraction were analyzed at the 6-month follow-up visit. RESULTS: The ZZ AR and Phorcides groups comprised 156 and 147 eyes, respectively. At the 6-month postoperative follow-up visit, the median (range) absolute residual cylindrical refraction was 0.35 (1.01) and 0.47 (1.63) diopters (D) for the ZZ AR and Phorcides groups, respectively (P < .001). The percentages of patients with residual cylindrical power within 0.25 D were 29.49% and 13.61% for the ZZ AR and Phorcides groups, respectively (P = .001). Based on the percentages of patients with residual cylindrical powers within 0.50 and 1.00 D, the ZZ AR group showed better outcomes (P = .02 and .01). The percentage of patients with visual acuity better than 20/16 was significantly higher for the ZZ AR group than for the Phorcides group (P = .03). CONCLUSIONS: The fitting-shape-based refractive compensated strategy for topography-guided LASIK procedures can better optimize the visual acuity and astigmatic refraction than the Phorcides software strategy. [J Refract Surg. 2024;40(5):e336-e343.].

Visual Outcomes and Patient Satisfaction of Trifocal or Trifocal Toric IOLs in Chinese Cataract Patients: Focus on Near Vision at 33 cm.

Purpose: To examine the visual outcomes, particularly at 33 cm, and assess patient satisfaction following the implantation of a diffractive trifocal intraocular lens (IOL) and its toric variant. Patients and Methods: This prospective single-arm observational study involved 45 Chinese patients (90 eyes) underwent bilateral cataract surgery and PanOptix or PanOptix toric intraocular lenses (IOLs) implantation. Postoperatively, visual acuity was evaluated at various distances, including 40 cm and 33 cm, for both monocular and binocular outcomes. Patient satisfaction was evaluated using the VF-14 questionnaire. Results: 72 eyes underwent PanOptix IOLs implantation, and 18 eyes received PanOptix toric IOLs. At 3-month postoperative mark, the mean monocular UDVA, UIVA, and UNVA at 40 cm and 33 cm were -0.02±0.09, 0.00±0.07, 0.02±0.07, and 0.07±0.14 logMAR, respectively, with proportions of visual acuity exceeding 0.1 logMAR were 96.7%, 96.7%, 94.4%, and 74.4%, respectively. The mean binocular UDVA, UIVA, and UNVA at 40 cm and 33 cm were -0.05±0.06, -0.03±0.05, 0.00±0.05, and 0.04±0.07 logMAR, respectively, with proportions of visual acuity exceeding 0.1 logMAR were 97.8%, 100.0%, 100.0%, and 91.1%, respectively. When the near point shifted from 40cm to 33cm, some patients showed a decline for UDVA, but the average reduction was less than one line. The overall VF-14 questionnaire score was 4.02±4.19. Conclusion: PanOptix can provide Chinese patients with a full range of satisfying visual acuity, near to 33cm. Though the visual acuity of some patients at 33 cm did not match the level at 40 cm, the gap of one line may not carry clinical significant.

Integration analysis of cell division cycle-associated family genes revealed potential mechanisms of gliomagenesis and constructed an artificial intelligence-driven prognostic signature.

Cell division cycle-associated (CDCA) gene family members are essential cell proliferation regulators and play critical roles in various cancers. However, the function of the CDCA family genes in gliomas remains unclear. This study aims to elucidate the role of CDCA family members in gliomas using in vitro and in vivo experiments and bioinformatic analyses. We included eight glioma cohorts in this study. An unsupervised clustering algorithm was used to identify novel CDCA gene family clusters. Then, we utilized multi-omics data to elucidate the prognostic disparities, biological functionalities, genomic alterations, and immune microenvironment among glioma patients. Subsequently, the scRNA-seq analysis and spatial transcriptomic sequencing analysis were carried out to explore the expression distribution of CDCA2 in glioma samples. In vivo and in vitro experiments were used to investigate the effects of CDCA2 on the viability, migration, and invasion of glioma cells. Finally, based on ten machine-learning algorithms, we constructed an artificial intelligence-driven CDCA gene family signature called the machine learning-based CDCA gene family score (MLCS). Our results suggested that patients with the higher expression levels of CDCA family genes had a worse prognosis, more activated RAS signaling pathways, and more activated immunosuppressive microenvironments. CDCA2 knockdown inhibited the proliferation, migration, and invasion of glioma cells. In addition, the MLCS had robust and favorable prognostic predictive ability and could predict the response to immunotherapy and chemotherapy drug sensitivity.

Long Term Evaluation of Surgically Induced Astigmatism and Corneal Higher-Order Aberrations After 2.2 Mm Clear Corneal Incisions in Femtosecond Laser-Assisted Cataract Surgery: Temporal versus Superior Approach.

Purpose: To assess long term changes of the surgically induced astigmatism (SIA) and corneal higher-order aberrations (HOAs) after 2.2 mm clear corneal incisions (CCIs) in femtosecond laser-assisted cataract surgery and compare them between 2 types of CCIs: temporal and superior approach. Patients and Methods: Patients received the temporal CCIs (Group A) or the superior CCIs (Group B). Outcome measures included visual acuity, manifest refraction, corneal astigmatism, SIA, flattening effect, and corneal HOAs. Correlation between postoperative corneal HOA and SIA at each follow-up were analysed. Results: This study assessed data from 106 eyes, of which 64 in Group A and 42 in Group B. The two groups had similar postoperative visual acuity of distance, intermediate and near (all P > 0.05). SIA and corneal HOAs were significantly lower in Group A than Group B in the early postoperative period, while there was no significant difference in the late postoperative period. At 6 months after surgery, the arithmetic mean of SIA over corneal 4mm zone was 0.33 ± 0.19D for temporal incision, and 0.37 ± 0.25D for superior incision. For Group A, the correlations of HOAs and SIA persisted from 1 week to 6 months after surgery. For Group B, the changes in corneal HOAs were significantly related to the SIA at 1 week and 1 month postoperatively. Conclusion: This study suggested the consistency of increasing and recovering process of corneal HOAs and SIA after surgery. Compared to the superior incisions, temporal incisions might induce quicker corneal recovery and less change in SIA and corneal HOAs.

Traditional Chinese medicine for gastric cancer: An evidence mapping.

As a complementary and alternative therapy, traditional Chinese medicine (TCM) has been playing a significant role in gastric cancer treatment. Data from individual systematic reviews have not been comprehensively summarized, and the relationship between certain interventions and outcomes are ill-defined. This study aimed to analyze the advantages of TCM interventions for gastric cancer by the method of evidence mapping. We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Chinese Scientific Journals Database, and Wanfang Database for systematic reviews of TCM treating gastric cancer up to December 31, 2023. We used Excel, Endnote 20, and Python software for the analysis of incorporated studies. We assessed the quality of included SRs by AMSTAR-2 and performed evidence mapping including 89 SRs, 1648 RCTs and 122,902 patients, identifying 47 types of interventions and 39 types of outcomes. From a visual overview, we displayed that most SRs reported beneficial effects in improving short- and long-term survival, myelosuppression, and immune function, even though the quality of evidence was generally low. The benefits of Brucea javanica Oil Emulsion Injection, ShenQiFuZheng Injection, XiaoAiPing, Astragalus-Containing TCM and Guben Xiaoji Therapy were found the most solid in corresponding aspects. Our findings suggest that although more rigorous clinical trials and SRs are needed to identify the precise effectiveness, integrating such evidence into clinical care of gastric cancer is expected to be beneficial.

Immune modulatory roles of radioimmunotherapy: biological principles and clinical prospects.

Radiation therapy (RT) not only can directly kill tumor cells by causing DNA double-strand break, but also exerts anti-tumor effects through modulating local and systemic immune responses. The immunomodulatory effects of RT are generally considered as a double-edged sword. On the one hand, RT effectively enhances the immunogenicity of tumor cells, triggers type I interferon response, induces immunogenic cell death to activate immune cell function, increases the release of proinflammatory factors, and reshapes the tumor immune microenvironment, thereby positively promoting anti-tumor immune responses. On the other hand, RT stimulates tumor cells to express immunosuppressive cytokines, upregulates the function of inhibitory immune cells, leads to lymphocytopenia and depletion of immune effector cells, and thus negatively suppresses immune responses. Nonetheless, it is notable that RT has promising abscopal effects and may achieve potent synergistic effects, especially when combined with immunotherapy in the daily clinical practice. This systematic review will provide a comprehensive profile of the latest research progress with respect to the immunomodulatory effects of RT, as well as the abscopal effect of radioimmunotherapy combinations, from the perspective of biological basis and clinical practice.

Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. METHODS: Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. RESULTS: The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation. CONCLUSIONS: A novel method for harvesting MSCs with neural crest origin from 3D human brain organoids under serum-free culture conditions was reported. We demonstrate that the pMSCs support human UCB-HSPC expansion in vitro in a long-term culture and the maintenance of their transplantable ability. RNA and proteomic sequencing indicated that pMSCs provided an improved microenvironment for HSC maintenance via mechanisms involving cell-cell contact and secreted factors and suppression of Wnt signaling. This represents a novel method for large-scale production of MSCs of neural crest origin and provides a potential approach for development of human hematopoietic stromal cell therapy for treatment of dyshematopoiesis.

Efficacy and Safety of Ketamine to Treat Cancer Pain in Adult Patients: A Systematic Review.

CONTEXT: Ketamine is a well-characterized anesthetic agent, and subanesthetic ketamine possesses analgesic effects in both acute and chronic pain. OBJECTIVES: A systematic review was performed to ascertain the efficacy and safety of ketamine in treating pain for cancer patients. METHODS: Eight databases were searched from the inception to March 20th, 2023 to obtain randomized controlled trials (RCTs) on ketamine for treating pain in cancer patients. Two reviewers independently screened studies, extracted the data and assessed the risk of bias of included studies; then, meta-analysis was performed by using Revman 5.3 software and Stata 14.0 software. RESULTS: Thirty-five studies were included, involving 2279 patients with cancer pain. The results of meta-analysis showed that ketamine could significantly reduce pain intensity. Subgroup analysis revealed that, when compared with control group, ketamine decreased markedly visual analogue scale (VAS) scores in two days after the end of treatment with ketamine, and ketamine administrated by patient controlled epidural analgesia (PCEA) was effective. Meanwhile, ketamine could significantly reduce the number of patient-controlled analgesia (PCA) compressions within 24 hours and morphine dosage. Ketamine could not decrease Ramsay sedation score. Additionally, the adverse events significantly decreased in the ketamine group, including nausea and vomiting, constipation, pruritus, lethargy, uroschesis, hallucination, and respiratory depression. In addition, compared with the control group, ketamine could reduce Hamilton depression scale (HAMD) score and relieve depressive symptoms. CONCLUSION: Ketamine may be used as an effective therapy to relieve cancer pain. However, more rigorously designed RCTs with larger sample sizes are required to verify the above conclusions.

Cuproptosis facilitates immune activation but promotes immune escape, and a machine learning-based cuproptosis-related signature is identified for predicting prognosis and immunotherapy response of gliomas.

AIMS: Cell death, except for cuproptosis, in gliomas has been extensively studied, providing novel targets for immunotherapy by reshaping the tumor immune microenvironment through multiple mechanisms. This study aimed to explore the effect of cuproptosis on the immune microenvironment and its predictive power in prognosis and immunotherapy response. METHODS: Eight glioma cohorts were included in this study. We employed the unsupervised clustering algorithm to identify novel cuproptosis clusters and described their immune microenvironmental characteristics, mutation landscape, and altered signaling pathways. We verified the correlation among FDX1, SLC31A1, and macrophage infiltration in 56 glioma tissues. Next, based on multicenter cohorts and 10 machine learning algorithms, we constructed an artificial intelligence-driven cuproptosis-related signature named CuproScore. RESULTS: Our findings suggested that glioma patients with high levels of cuproptosis had a worse prognosis owing to immunosuppression caused by unique immune escape mechanisms. Meanwhile, we experimentally validated the positive association between cuproptosis and macrophages and its tumor-promoting mechanism in vitro. Furthermore, our CuproScore exhibited powerful and robust prognostic predictive ability. It was also capable of predicting response to immunotherapy and chemotherapy drug sensitivity. CONCLUSIONS: Cuproptosis facilitates immune activation but promotes immune escape. The CuproScore could predict prognosis and immunotherapy response in gliomas.

Defocus Curve and Satisfaction of Patients with Presbyopia After LASIK Using the Differential Modulation of Binocular Longitudinal Spherical Aberration.

Purpose: To investigate the visual acuity and satisfaction of patients after Zhang & Zheng's corneal laser-enhanced accommodation refraction Q (ZZ-CLEAR-Q) surgery utilizing differential modulation of binocular longitudinal spherical aberration and determine its clinical significance. Patients and Methods: This prospective observational study enrolled a consecutive cohort of patients with presbyopia who underwent ZZ-CLEAR-Q surgery between December 2020 and January 2023. The study assessed visual acuity, distance-corrected defocus curve, satisfaction, Q factor, manifest spherical equivalent, and primary spherical aberration, among others, at 3 months postoperatively. Additionally, the study conducted a binocular comparison to analyze the clinical significance of setting the different longitudinal spherical aberrations. Results: A total of 232 eyes of 116 patients were included. The binocular uncorrected distance visual acuity was 20/20 for all patients. At 3 months postoperatively, the binocular uncorrected near visual acuity was Jaeger 1 for 96% of the patients and Jaeger 2 for 100% of the patients. Furthermore, 93.1% of the patients expressed satisfaction. The monocular distance-corrected defocus curve revealed that the dominant eyes had significantly better visual acuity at 0 D (P<0.001), while the non-dominant eyes had significantly better visual acuity across various defocus levels except 0 and -0.50 D (All P<0.05). At 3 months, there were no significant differences between the expected and achieved manifest spherical equivalents, corneal Q factor values, and ocular primary spherical aberration values of both groups. Conclusion: Patients with presbyopia who underwent ZZ-CLEAR-Q surgery were likely to achieve normal uncorrected visual acuity and be satisfied. The increased depth of field has clinical significance for assisting near vision.

Anti-PD-1/PD-L1 for nasopharyngeal carcinoma: a comprehensive analysis of registered trials on ClinicalTrials.gov.

Objective: Clinical trials play an important role in the development of healthcare. However, the current status of clinical trials on anti-PD-1/PD-L1 for nasopharyngeal carcinoma remains unclear. Therefore, this study aims to provide a comprehensive analysis of the registered trials related to anti-PD-1/PD-L1 for nasopharyngeal carcinoma on ClinicalTrials.gov. Methods: A search was conducted on the ClinicalTrials.gov database to identify all registered trials related to anti-PD-1/PD-L1 for nasopharyngeal carcinoma up to 26 February 2023. The characteristics of the trials were examined, and the studied drugs, disease conditions, as well as details of trials with available results were analyzed. Publication status was assessed by a PubMed search using the ClinicalTrials.gov NCT number. Results: A total of 112 interventional clinical trials registered between 2015 and 2023 were included. Of the trials, 90 were carried out in Asia, 72 were in phase 2, and 31 trials had either companies or universities as sponsors/collaborators. The sample sizes across the trials varied greatly, with a median of 71.5 participants per trial. The majority of trials were recruiting participants, with only 6 had posted results. PD-1 inhibitors were preferred over PD-L1, and Toripalimab emerged as the most extensively studied drug. About one-third (33.9%) of the studies looked into recurrent/metastatic nasopharyngeal cancer. Conclusion: This study provides an overview of all registered trials of anti-PD-1/PD-L1 for NPC. It is needed to improve the completeness, outcome selection, randomization and masking of trials and to be transparent and timely in reporting of results.

HDAC1 participates in polycystic ovary syndrome through histone modification by regulating H19/miR-29a-3p/NLRP3-mediated granulosa cell pyroptosis.

Histone deacetylase 1 (HDAC1) is known to participate in the molecular etiology of polycystic ovary syndrome (PCOS). However, its role in granulosa cell (GC) pyroptosis remains unclear. This study sought to investigate the mechanism of HDAC1 in PCOS-induced GC pyroptosis through histone modification. Clinical serum samples and the general data of study subjects were collected. PCOS mouse models were established using dehydroepiandrosterone and cell models were established in HGL5 cells using dihydrotestosterone. Expressions of HDAC1, H19, miR-29a-3p, and NLR family pyrin domain containing 3 (NLRP3) and pyroptosis-related proteins and levels of hormones and inflammatory cytokines were determined. Ovarian damage was observed by hematoxylin-eosin staining. Functional rescue experiments were conducted to verify the role of H19/miR-29a-3p/NLRP3 in GC pyroptosis in PCOS. HDAC1 and miR-29a-3p were downregulated whereas H19 and NLRP3 were upregulated in PCOS. HDAC1 upregulation attenuated ovarian damage and hormone disorders in PCOS mice and suppressed pyroptosis in ovarian tissues and HGL5 cells. HDAC1 inhibited H3K9ac on the H19 promoter and H19 competitively bound to miR-29a-3p to improve NLRP3 expression. Overexpressed H19 or NLRP3 or inhibited miR-29a-3p reversed the inhibition of GC pyroptosis by HDAC1 upregulation. Overall, HDAC1 suppressed GC pyroptosis in PCOS through deacetylation to regulate the H19/miR-29a-3p/NLRP3 axis.

Zero valent iron-electro-Fenton-peroxymonosulfate (ZVI-E-Fenton-PMS) process for industrial wastewater treatment.

Advanced oxidation processes are frequently applied to a variety of refractory organic wastewater, but rarely is electro-Fenton combined with activated persulfate technology applied to the removal of refractory pollutants. In this work, the electro-Fenton process was combined with zero-valent iron (ZVI) activated peroxymonosulfate (PMS), two advanced oxidation processes based on different radicals, to form the ZVI-E-Fenton-PMS process to treat wastewater, whose main advantages are the generation of more reactive oxygen species and the reduction of oxidant cost to achieve rapid removal of pollutants. This process can not only produce H2O2 and activate PMS at the cathode, but also reduce Fe(iii) to realize the sustainable Fe(iii)/Fe(ii) redox cycle. The main reactive oxygen species in the ZVI-E-Fenton-PMS process were found to be ˙OH, SO4˙- and 1O2 by radical scavenging experiments and electron paramagnetic resonance (EPR), and the relative contributions of the three reactive oxygen species for the degradation of MB were estimated to 30.77%, 39.62% and 15.38%, respectively. Then, by calculating the ratio of the relative contributions of each component to the removal of pollutants at different PMS doses, it was found that the synergistic effect of the process was better when the proportion of ˙OH in the oxidation of reactive oxygen species (ROS) was higher and the proportion of non-ROS oxidation increased year-on-year. This study provides a new perspective on the combination of different advanced oxidation processes and reveals the advantages and potential of this process for application.

Gene Targets of CAR-T Cell Therapy for Glioblastoma.

Glioblastoma (GBM) is an aggressive primary brain tumor with a poor prognosis following conventional therapeutic interventions. Moreover, the blood-brain barrier (BBB) severely impedes the permeation of chemotherapy drugs, thereby reducing their efficacy. Consequently, it is essential to develop novel GBM treatment methods. A novel kind of pericyte immunotherapy known as chimeric antigen receptor T (CAR-T) cell treatment uses CAR-T cells to target and destroy tumor cells without the aid of the antigen with great specificity and in a manner that is not major histocompatibility complex (MHC)-restricted. It has emerged as one of the most promising therapy techniques with positive clinical outcomes in hematological cancers, particularly leukemia. Due to its efficacy in hematologic cancers, CAR-T cell therapy could potentially treat solid tumors, including GBM. On the other hand, CAR-T cell treatment has not been as therapeutically effective in treating GBM as it has in treating other hematologic malignancies. CAR-T cell treatments for GBM have several challenges. This paper reviewed the use of CAR-T cell therapy in hematologic tumors and the selection of targets, difficulties, and challenges in GBM.

Anti-inflammatory Activity of Gegen Decoction and Its Modulatory Mechanism on the NF-κB and MAPK Signaling Pathways.

Gegen Decoction as anti-inflammatory medicine is used in clinic widespread, however the specific anti-inflammatory molecular mechanism of Gegen Decoction is still unclear. The purpose was to study the anti-inflammatory activity of Gegen Decoction in vivo and to research its anti-inflammatory molecular mechanism. The content of main essential components in Gegen Decoction were determined by HPLC method. The anti-inflammatory activity of Gegen Decoction was confirmed through in vivo animal experiments. Furthermore, RAW 264.7 cells were stimulated by lipopolysaccharides to induce inflammatory reaction, the modulatory effect of Gegen Decoction on the activation process of mitogen-activated protein kinases and nuclear factor-κB signaling pathways was investigated. The content of puerarin was the highest among all the index components. Gegen Decoction inhibited carrageenan-induced paw edema in rats and xylene-induced ear swelling in mice. Gegen Decoction had no obvious toxicity against RAW 264.7 cells at the concentrations of 10-40 mg/mL; significantly inhibited the release of nitric oxide, prostaglandin E2, tumor necrosis factor-α and interleukin-6; down-regulated the high expression of inflammatory proteins inducible nitric oxide synthase and cyclooxygenase-2. It inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs)/extracellular regulated protein kinases (ERK)/c-Jun N-terminal kinase (JNK), the degradation of nuclear factor-κB (NF-κB)/inhibitor of NF-κB-α (IκB-α) and the nuclear translocation of NF-κB/p65 into nucleus. Gegen Decoction exerts significant anti-inflammatory activity, mainly by blocking the activation of both MAPKs and NF-κB pathway.

Contrast-enhanced ultrasound and contrast-enhanced computed tomography for differentiating mass-forming pancreatitis from pancreatic ductal adenocarcinoma: a meta-analysis.

BACKGROUND: Patients with mass-forming pancreatitis (MFP) or pancreatic ductal adenocarcinoma (PDAC) presented similar clinical symptoms, but required different treatment approaches and had different survival outcomes. This meta-analysis aimed to compare the diagnostic performance of contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) in differentiating MFP from PDAC. METHODS: A literature search was performed in the PubMed, EMBASE (Ovid), Cochrane Library (CENTRAL), China National Knowledge Infrastructure (CNKI), Weipu (VIP), and WanFang databases to identify original studies published from inception to August 20, 2021. Studies reporting the diagnostic performances of CEUS and CECT for differentiating MFP from PDAC were included. The meta-analysis was performed with Stata 15.0 software. The outcomes included the pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves of CEUS and CECT. Meta-regression was conducted to investigate heterogeneity. Bayesian network meta-analysis was conducted to indirectly compare the overall diagnostic performance. RESULTS: Twenty-six studies with 2115 pancreatic masses were included. The pooled sensitivity and specificity of CEUS for MFP were 82% (95% confidence interval [CI], 73%-88%; I2  = 0.00%) and 95% (95% CI, 90%-97%; I2  = 63.44%), respectively; the overall +LR, -LR, and DOR values were 15.12 (95% CI, 7.61-30.01), 0.19 (95% CI, 0.13-0.29), and 78.91 (95% CI, 30.94-201.27), respectively; and the area under the SROC curve (AUC) was 0.90 (95% CI, 0.87-92). However, the overall sensitivity and specificity of CECT were 81% (95% CI, 75-85%; I2  = 66.37%) and 94% (95% CI, 90-96%; I2  = 74.87%); the overall +LR, -LR, and DOR values were 12.91 (95% CI, 7.86-21.20), 0.21 (95% CI, 0.16-0.27), and 62.53 (95% CI, 34.45-113.51), respectively; and, the SROC AUC was 0.92 (95% CI, 0.90-0.94). The overall diagnostic accuracy of CEUS was comparable to that of CECT for the differential diagnosis of MFP and PDAC (relative DOR 1.26, 95% CI [0.42-3.83], P  > 0.05). CONCLUSIONS: CEUS and CECT have comparable diagnostic performance for differentiating MFP from PDAC, and should be considered as mutually complementary diagnostic tools for suspected focal pancreatic lesions.