Role of drug-eluting bead bronchial arterial chemoembolisation in the treatment of non-small cell lung cancer: protocol for a meta-analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) has a poor prognosis. Transvascular intervention is an important approach for treating NSCLC. Drug-eluting bead bronchial artery chemoembolisation (DEB-BACE) is a technique of using DEBs loaded with chemotherapeutic drugs for BACE. This study aims to conduct a meta-analysis to comprehensively assess the effectiveness and safety of DEB-BACE in treating NSCLC and investigate a novel therapeutic strategy for NSCLC. METHODS AND ANALYSIS: Wanfang, China National Knowledge Infrastructure, Medline (via PubMed), Cochrane Library, Scopus and Embase databases will be searched in November 2024. A meta-analysis will be conducted to assess the effectiveness and safety of DEB-BACE in the treatment of NSCLC. The following keywords will be applied: "Carcinoma, Non-Small-Cell Lung", "Non-Small Cell Lung Cancer", "Drug-Eluting Bead Bronchial Arterial Chemoembolization" and "drug-eluting beads". Reports in Chinese or English comparing the efficacy of DEB-BACE with other NSCLC treatment options will be included. Case reports, single-arm studies, conference papers, abstracts without full text and reports published in languages other than English and Chinese will not be considered. The Cochrane Handbook for Systematic Reviews of Interventions will be used to independently assess the risk of bias for each included study. In case of significant heterogeneity between studies, possible sources of heterogeneity will be explored through subgroup and sensitivity analysis. For the statistical analysis of the data, RevMan V.5.3 will be used. ETHICS AND DISSEMINATION: This meta-analysis will seek publication in a peer-reviewed journal on completion. Ethical approval is not required for this study as it is a database-based study. PROSPERO REGISTRATION NUMBER: CRD42023411392.

The value of nanopore sequencing as a diagnostic tool in tuberculous meningitis: A protocol of systematic review and meta-analysis.

BACKGROUND: Rapid diagnosis of tuberculous meningitis (TBM) remains very difficult. Nanopore sequencing is gaining ground in the field of rapid tuberculosis (TB) diagnostics. The purpose of this study was to complete a protocol to guide the conduct of a systematic review and meta-analysis evaluating the accuracy of nanopore sequencing for the rapid diagnosis of TBM. METHODS: In accordance with the Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) guidelines, we completed this protocol, which was also registered on the PROSPERO platform. We will search the EMBASE, PubMed, the Cochrane Library, Wanfang database, and China National Knowledge Infrastructure databases for literature that evaluated the accuracy of nanopore sequencing for rapid diagnosis of TBM and screen them according to the inclusion and exclusion criteria, and qualified literature will be extracted with relevant data for further analysis. Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) will be used for evaluating the methodological quality of included studies. Stata (V 15.0; Stata Corp., College Station, TX, the USA) with midas module will be used to perform relevant meta-analysis. Heterogeneity between studies will be assessed by I2 statistics. When significant heterogeneity exists between studies, we will conduct meta-regression analyses, subgroup analyses and sensitivity analyses to further explore the sources of heterogeneity. CONCLUSION: We completed this study protocol, and this systematic review and meta-analysis will be the first systematic evaluation of the role of nanopore sequencing in the rapid diagnosis of TBM, which will allow clinicians to have a better understanding of the test. TRIAL REGISTRATION: Systematic review registration PROSPERO Registration number: CRD42024549837.

A Cascade-Amplified Pyroptosis Inducer: Optimizing Oxidative Stress Microenvironment by Self-Supplying Reactive Nitrogen Species Enables Potent Cancer Immunotherapy.

Selective generation of sufficient pyroptosis inducers at the tumor site without external stimulation holds immense significance for a longer duration of immunotherapy. Here, we report a cascade-amplified pyroptosis inducer CSCCPT/SNAP that utilizes reactive nitrogen species (RNS), self-supplied from the diffusion-controlled reaction between reactive oxygen species (ROS) and nitric oxide (NO) to potentiate pyroptosis and immunotherapy, while both endogenous mitochondrial ROS stimulated by released camptothecin and released NO initiate pyroptosis. Mechanistically, cascade amplification of the antitumor immune response is prompted by the cooperation of ROS and NO and enhanced by RNS with a long lifetime, which could be used as a pyroptosis trigger to effectively compensate for the inherent drawbacks of ROS, resulting in long-lasting pyroptosis for favoring immunotherapy. Tumor growth is efficiently inhibited in mouse melanoma tumors through the facilitation of reactive oxygen/nitrogen species (RONS)-NO synergy. In summary, our therapeutic approach utilizes supramolecular engineering and nanotechnology to integrate ROS producers and NO donors of tumor-specific stimulus responses into a system that guarantees synchronous generation of these two reactive species to elicit pyroptosis-evoked immune response, while using self-supplied RNS as a pyroptosis amplifier. RONS-NO synergy achieves enhanced and sustained pyroptosis and antitumor immune responses for robust cancer immunotherapy.

High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function.

Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses. Deletion of Zfp318 did not alter the magnitude of primary responses but markedly reduced MBC participation in recall. CD40 ligation promoted Zfp318 expression, whereas B cell receptor (BCR) signaling was inhibitory. Enforced ZFP318 expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficient MBCs expressed less mitochondrial genes, had structurally compromised mitochondria, and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressing MBCs, instead of the number of antigen-specific MBCs, correlated with the potency of prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and represents a quality checkpoint of humoral immune memory.

Diagnostic accuracy of nanopore sequencing for the rapid diagnosis of pulmonary tuberculosis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Pulmonary tuberculosis (PTB) is the most common type of tuberculosis (TB). Rapid diagnosis of PTB can help in TB control. Although the use of molecular tests (such as the GeneXpert MTB/RIF) has improved the ability to rapidly diagnose PTB, there is still room for improvement. Nanopore sequencing is a novel means of rapid TB detection. The purpose of this study was to establish a systematic review and meta-analysis protocol for evaluating the accuracy of nanopore sequencing for the rapid diagnosis of PTB. METHODS: We completed this protocol according to the Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement and registered on the PROSPERO platform. We will screen studies related to nanopore sequencing for diagnosis of PTB by searching through PubMed, EMBASE, the Cochrane Library using English, and Wanfang database, CNKI (China National Knowledge Infrastructure) using Chinese. Eligible studies will be screened according to the inclusion and exclusion criteria established in the study protocol. We will evaluate the methodological quality of the individual included studies using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We will use Stata (version 15.0) with the midas command and RevMan (version 5.3) for meta-analysis and forest plots and SROC curves generation. A p < 0.05 was treated as a statistically significant difference. When significant heterogeneity exists between studies, we will explore sources of heterogeneity through meta-regression analysis and subgroup analysis. CONCLUSION: To the best of our knowledge, this will be the first systematic review and meta-analysis of nanopore sequencing for the diagnosis of PTB. We hope that this study will find a new and effective tool for the early diagnosis of PTB. PROSPERO REGISTRATION NUMBER: CRD42023495593.

The Important Role of Preoperative D-Dimer in Constrictive Pericarditis.

Background: The impact of coagulation indicators on postoperative outcomes of patients with constrictive pericarditis undergoing pericardiectomy has been poorly investigated. This study aimed to assess the prognostic role of preoperative coagulation indicators in these patients. Methods: We retrospectively included 158 patients with constrictive pericarditis undergoing pericardiectomy. The diagnostic values of coagulation indicators for postoperative complications were evaluated by ROC curves. Patients were divided into two groups according to the cutoff value calculated by ROC curve. Postoperative outcomes were compared between the two groups. Logistic regression analysis was performed to identify risk factors of postoperative complications. Results: ROC curve showed that among different coagulation indicators, preoperative D-dimer (DD) level could effectively identify patients with postoperative complications (AUC 0.771, 95% CI 0.696-0.847, P < 0.001). Patients were divided into the low DD group and the high DD group. The comparison of postoperative outcomes suggested that high preoperative DD level was significantly associated with longer durations of vasoactive agents using (P = 0.018), intubation (P = 0.020), ICU stay (P = 0.008), chest drainage (P=0.004) and hospital stay (P = 0.002). Multivariable analysis showed that high preoperative DD level was the independent risk factor of postoperative complications (OR 6.892, 95% CI 2.604-18.235, P < 0.001). Conclusion: High preoperative DD level was significantly linked to poor postoperative outcomes and could provide an effective prediction ability for postoperative complications in patients with constrictive pericarditis.

Supramolecular Lipid Nanoparticles Based on Host-Guest Recognition: A New Generation Delivery System of mRNA Vaccines For Cancer Immunotherapy.

Dendritic cell (DC) maturation is a crucial process for antigen presentation and the initiation of T cell-mediated immune responses. Toll-like receptors play pivotal roles in stimulating DC maturation and promoting antigen presentation. Here, a novel message RNA (mRNA) cancer vaccine is reported that boosts antitumor efficacy by codelivering an mRNA encoding tumor antigen and a TLR7/8 agonist (R848) to DC using supramolecular lipid nanoparticles (SMLNP) as a delivery platform, in which a new ionizable lipid (N2-3L) remarkably enhances the translation efficiency of mRNA and a ß-cyclodextrin (ß-CD)-modified ionizable lipid (Lip-CD) encapsulates R848. The incorporation of R848 adjuvant into the mRNA vaccine through noncovalent host-guest complexation significantly promotes DC maturation and antigen presentation after vaccination, thus resulting in superior antitumor efficacy in vivo. Moreover, the antitumor efficacy is further boosted synergized with immune checkpoint blockade by potentiating the anticancer capability of cytotoxic T lymphocytes infiltrated in tumor sites. This work indicates that SMLNP shows brilliant potential as next-generation delivery system in the development of mRNA vaccines with high efficacy.

Biodegradable Lipid-Modified Poly(Guanidine Thioctic Acid)s: A Fortifier of Lipid Nanoparticles to Promote the Efficacy and Safety of mRNA Cancer Vaccines.

Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.

Dual-Responsive Supramolecular Polymeric Nanomedicine for Self-Cascade Amplified Cancer Immunotherapy.

Insufficient tumor immunogenicity and immune escape from tumors remain common problems in all tumor immunotherapies. Recent studies have shown that pyroptosis, a form of programmed cell death that is accompanied by immune checkpoint inhibitors, can induce effective immunogenic cell death and long-term immune activation. Therapeutic strategies to jointly induce pyroptosis and reverse immunosuppressive tumor microenvironments are promising for cancer immunotherapy. In this regard, a dual-responsive supramolecular polymeric nanomedicine (NCSNPs) to self-cascade amplify the benefits of cancer immunotherapy is designed. The NCSNPs are formulated by ß-cyclodextrin coupling nitric oxide (NO) donor, a pyroptosis activator, and NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor, and self-assembled through host-guest molecular recognition and hydrophobic interaction to obtain nanoparticles. NCSNPs possess excellent tumor accumulation and bioavailability attributed to ingenious supramolecular engineering. The study not only confirms the occurrence of NO-triggered pyroptosis in tumors for the first time but also reverses the immunosuppressive microenvironment in tumor sites via an IDO inhibitor by enhancing the infiltration of cytotoxic T lymphocytes, to achieve remarkable inhibition of tumor proliferation. Thus, this study provides a novel strategy for cancer immunotherapy.

Evaluation of Nanopore Sequencing for Diagnosing Pulmonary Tuberculosis Using Negative Smear Clinical Specimens.

Purpose: This study aimed to evaluate the efficacy of nanopore sequencing for diagnosing pulmonary tuberculosis (PTB) using smear-negative clinical specimens. Methods: We conducted a retrospective study based on a review of patient medical records to assess the accuracy of nanopore sequencing as a diagnostic tool for smear-negative PTB. Compared with clinical diagnosis, we determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of nanopore sequencing. Results: A total of 647 patients were evaluated. Nanopore sequencing demonstrated an overall sensitivity of 91.7%, specificity of 85.3%, PPV of 95.1%, NPV of 76.4%, and AUC of 0.88. Notably, the overall diagnostic accuracy of nanopore sequencing was significantly higher than that of Mycobacterium tuberculosis (MTB) culture technique. Conclusion: Nanopore sequencing exhibited satisfactory overall diagnostic accuracy for smear-negative PTB, regardless of MTB culture status. Therefore, if conditions permit, nanopore sequencing is recommended as a diagnostic method for smear-negative PTB.

Drug-initiated poly(thiocitc acid) polymer incorporating host-guest interaction for cancer combination chemotherapy.

Combination chemotherapy has shown considerable promise for cancer therapy. However, the hydrophobicity of chemotherapeutic agents and the difficulties of precise drug co-administration severely hinder the development of combination chemotherapy. Herein, we develop a polymeric drug delivery system (D-PTA-CD) to provide robust loading capacity, glutathione-responsive drug release, and precise combination therapy. The vehicle is prepared based on poly(thioctic acid) (PTA) polymers using DM1, a chemotherapeutic agent, as the initiator to endow the vehicle with cancer-inhibiting activity. ß-cyclodextrins are incorporated into the side chains to enhance drug loading capacity via host-guest interactions. Attributing to the sufficient disulfide bond on the backbone, D-PTA-CD exhibits accelerated drug release triggered by elevated glutathione levels. Doxorubicin (DOX) and camptothecin (CPT) are encapsulated by D-PTA-CD to afford the combination chemotherapy nanoparticles (NP), DOX-NP, and CPT-NP, respectively, which exhibit significant synergetic anti-cancer effects, highlighting the enormous potential of D-PTA-CD as a versatile drug delivery platform for cancer combination chemotherapy.

Separation of benzene and toluene associated with vapochromic behaviors by hybrid[4]arene-based co-crystals.

The combination of macrocyclic chemistry with co-crystal engineering has promoted the development of materials with vapochromic behaviors in supramolecular science. Herein, we develop a macrocycle co-crystal based on hybrid[4]arene and 1,2,4,5-tetracyanobenzene that is able to construct vapochromic materials. After the capture of benzene and toluene vapors, activated hybrid[4]arene-based co-crystal forms new structures, accompanied by color changes from brown to yellow. However, when hybrid[4]arene-based co-crystal captures cyclohexane and pyridine, neither structures nor colors change. Interestingly, hybrid[4]arene-based co-crystal can separate benzene from a benzene/cyclohexane equal-volume mixture and allow toluene to be removed from a toluene/ pyridine equal-volume mixture with purities reaching 100%. In addition, the process of adsorptive separation can be visually monitored. The selectivity of benzene from a benzene/cyclohexane equal-volume mixture and toluene from a toluene/ pyridine equal-volume mixture is attributed to the different changes in the charge-transfer interaction between hybrid[4]arene and 1,2,4,5-tetracyanobenzene when hybrid[4]arene-based co-crystal captures different vapors. Moreover, hybrid[4]arene-based co-crystal can be reused without losing selectivity and performance. This work constructs a vapochromic material for hydrocarbon separation.

Development of Mannosylated Lipid Nanoparticles for mRNA Cancer Vaccine with High Antigen Presentation Efficiency and Immunomodulatory Capability.

Insufficient accumulation of lipid nanoparticles (LNPs)-based mRNA vaccines in antigen presenting cells remains a key barrier to eliciting potent antitumor immune responses. Herein, we develop dendritic cells (DCs) targeting LNPs by taking advantage of mannose receptor-mediated endocytosis. Efficient delivery of mRNA to DCs is achieved in vitro and in vivo utilizing the sweet LNPs (STLNPs-Man). Intramuscular injection of mRNA vaccine (STLNPs-Man@mRNAOVA ) results in a four-fold higher uptake by DCs in comparison with commercially used LNPs. Benefiting from its DCs targeting ability, STLNPs-Man@mRNAOVA significantly promotes the antitumor performances, showing a comparable therapeutic efficacy by using one-fifth of the injection dosage as the vaccine prepared from normal LNPs, thus remarkably avoiding the side effects brought by conventional mRNA vaccines. More intriguingly, STLNPs-Man@mRNAOVA exhibits the ability to downregulate the expression of cytotoxic T-lymphocyte-associated protein 4 on T cells due to the blockade of CD206/CD45 axis, showing brilliant potentials in promoting antitumor efficacy combined with immune checkpoint blockade therapy.

Clinical Significance of Preoperative Pyrazinamide-Containing Therapy in Tuberculous Constrictive Pericarditis.

Background: Tuberculous constrictive pericarditis (TCP) is recommended to be treated with anti-tuberculosis (TB) therapy before pericardiectomy. Whether different preoperative anti-TB regimens may lead to different outcomes is unclear. Methods: We retrospectively collected patients diagnosed as TCP and received pericardiectomy from April 2016 to June 2023. The study patients were assigned into the active TCP (A-TCP) group and the inactive TCP (IA-TCP) group according to the results of Mycobacterium tuberculosis (MTB) culture and MTB RNA assay. Baseline characteristics including anti-TB regimens and surgical outcomes were compared between the two groups. Logistic regression analysis and subgroup analysis were conducted to identify the protective factors of A-TCP. Results: Of the 102 study patients, 24 was in the A-TCP group and 78 was in the IA-TCP group. The rate of preoperative anti-TB regimen containing pyrazinamide was 37.5% in the A-TCP group, as compared with 74.4% in the IA-TCP group (P = 0.001). Multivariate analysis showed that preoperative use of pyrazinamide was the protective factor of A-TCP (OR 0.194, 95% CI 0.053-0.703, P = 0.013). Subgroup analysis based on age also showed consistent findings. In the analyses of surgical outcomes, A-TCP was the independent risk factor of postoperative cardiac complications (OR 4.231, 95% CI 1.317-13.593, P = 0.015) and associated with longer hospital stay (P = 0.004) and higher hospitalization cost (P = 0.001). Conclusion: A strategy involving anti-TB regimen containing pyrazinamide before pericardiectomy was superior to that without pyrazinamide in the patients with TCP. The strategy was associated with lower risk of A-TCP and might lead to better postoperative recovery and cost-effectiveness.

Engineering Clinically Relevant Probiotics with Switchable "Nano-Promoter" and "Nano-Effector" for Precision Tumor Therapy.

Probiotics have the potential as biotherapeutic agents for cancer management in preclinical models and human trials by secreting antineoplastic or immunoregulatory agents in the tumor microenvironment (TME). However, current probiotics lack the ability to dynamically respond to unique TME characteristics, leading to limited therapeutic accuracy and efficacy. Although progress has been made in customizing controllable probiotics through synthetic biology, the engineering process is complex and the predictability of production is relatively low. To address this, here, for the first time, this work adopts pH-dependent peroxidase-like (POD-like) artificial enzymes as both an inducible "nano-promoter" and "nano-effector" to engineer clinically relevant probiotics to achieve switchable control of probiotic therapy. The nanozyme initially serves as an inducible "nano-promoter," generating trace amounts of nonlethal reactive oxygen species (ROS) stress to upregulate acidic metabolites in probiotics. Once metabolites acidify the TME to a threshold, the nanozyme switches to a "nano-effector," producing a great deal of lethal ROS to fight cancer. This approach shows promise in subcutaneous, orthotopic, and colitis-associated colorectal cancer tumors, offering a new methodology for modulating probiotic metabolism in a pathological environment.

A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection.

The respiratory system, especially the lung, is the key site of pathological injury induced by SARS-CoV-2 infection. Given the low feasibility of targeted delivery of antibodies into the lungs by intravenous administration and the short half-life period of antibodies in the lungs by intranasal or aerosolized immunization, mRNA encoding broadly neutralizing antibodies with lung-targeting capability can perfectly provide high-titer antibodies in lungs to prevent the SARS-CoV-2 infection. Here, we firstly identify a human monoclonal antibody, 8-9D, with broad neutralizing potency against SARS-CoV-2 variants. The neutralization mechanism of this antibody is explained by the structural characteristics of 8-9D Fabs in complex with the Omicron BA.5 spike. In addition, we evaluate the efficacy of 8-9D using a safe and robust mRNA delivery platform and compare the performance of 8-9D when its mRNA is and is not selectively delivered to the lungs. The lung-selective delivery of the 8-9D mRNA enables the expression of neutralizing antibodies in the lungs which blocks the invasion of the virus, thus effectively protecting female K18-hACE2 transgenic mice from challenge with the Beta or Omicron BA.1 variant. Our work underscores the potential application of lung-selective mRNA antibodies in the prevention and treatment of infections caused by circulating SARS-CoV-2 variants.

Poly(ethyl ethylene phosphate): Overcoming the "Polyethylene Glycol Dilemma" for Cancer Immunotherapy and mRNA Vaccination.

Polyethylene glycol conjugation (PEGylation) is the most successful strategy to promote the stability, pharmacokinetics, and efficacy of therapeutics; however, anti-PEG antibodies induced by repeated treatments raise serious concerns about the future of PEGylated therapeutics. In order to solve the "PEG dilemma", polymers with excellent water solubility and biocompatibility are urgently desired to attenuate the generation of anti-PEG antibodies. Here, poly(ethyl ethylene phosphate) (PEEP) with excellent degradability and stealth effects is used as an alternative to PEG to overcome the "PEG dilemma". PEEPylated liposomes exhibit lower immunogenicity and generate negligible anti-PEEP antibodies (IgM and IgG) after repeated treatments. In vivo studies confirm that PEEPylated liposomes loaded with oxaliplatin (PEEPlipo@OxPt) show better pharmacokinetics compared to PEGlipo@OxPt, and they exhibit potent antitumor performances, which can be further promoted with checkpoint blockade immunotherapy. In addition, PEEPylated lipid nanoparticle is also used to develop an mRNA vaccine with the ability to evoke a potent antigen-specific T cell response and achieve excellent antitumor efficacy. PEEP shows promising potentials in the development of next-generation nanomedicines and vaccines with higher safety and efficacy.

Meta-analysis of diagnostic accuracy of nucleic acid amplification tests for abdominal tuberculosis.

BACKGROUND: Abdominal tuberculosis (TB) is a severe extrapulmonary TB, which can lead to serious complications. Early diagnosis and treatment are very important for the prognosis and the diagnosis of abdominal TB is still difficult. METHODS: We searched PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure, and the Wanfang database for studies evaluating the diagnostic accuracy of NAATs for abdominal TB until August 2020. Any types of study design with full text were sought and included. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Subgroup analysis, meta-regression analysis and sensitivity analysis were used to explore the sources of heterogeneity. Stata version 15.0 with the midas command packages was used to carry out meta-analyses. RESULTS: We included a total of 78 independent studies from 53 articles; 64 with CRS as the reference standard, and 14 with culture as the reference standard. The pooled sensitivity, specificity, and the areas under summary receiver operating characteristic (SROC) curves (AUC) were 58% (51%-64%; I2 = 87%), 99% (97%-99%; I2 = 81%), and 0.92 (0.89-0.94) compared with CRS, respectively. The pooled sensitivity, specificity, and the AUC values of the SROC were 80% (66%-90%; I2 = 56%), 96% (92%-98%; I2 = 84%), and 0.97 (0.95-0.98) compared with culture, respectively. The heterogeneity of sensitivity and specificity was significant. CONCLUSIONS: NAATs had excellent efficacy in the diagnosis of abdominal TB regardless of the reference standard and regardless of the subtype of abdominal TB. Multiplex PCR with multiple target genes may improve diagnostic sensitivity, and stool specimens may also be used for the diagnosis of abdominal TB in addition to tissue and ascites.

Fabrication of An Immunostimulatory Supramolecular Nanomedicine for Potent Cancer Chemoimmunotherapy.

Chemoimmunotherapy can boost strong antitumor immune responses by triggering immunogenic cell death (ICD), which highlights a promising prospect in clinical applications. However, current chemoimmunotherapy shows limited efficacy due to the low delivery efficiency and insufficient immunogenicity of available chemotherapeutic drugs. A supramolecular polymeric nanomedicine (Pt-Tu@NP) is herein reported using cucurbit[7]uril-based host-guest recognition and noncovalent self-assembly. Pt-Tu@NPs have excellent biodistribution and strongly evoke the endoplasmic reticulum stress-mediated ICD of tumor cells, triggering potent antitumor immune responses by promoting dendritic cell (DC) maturation and cytotoxic T cell infiltration. The coordinated butyrate promotes a positive feedback regulation between DCs and CD8+ T cells. Pt-Tu@NPs stimulate immune cold tumors into hot ones, working in synergy with an immune checkpoint blockade to effectively suppress tumor growth and metastasis, which suggests a promising approach for cancer chemoimmunotherapy.

Supramolecular Biomaterials for Cancer Immunotherapy.

Cancer immunotherapy has achieved tremendous successful clinical results and obtained historic victories in tumor treatments. However, great limitations associated with feeble immune responses and serious adverse effects still cannot be neglected due to the complicated multifactorial etiology and pathologic microenvironment in tumors. The rapid development of nanomedical science and material science has facilitated the advanced progress of engineering biomaterials to tackle critical issues. The supramolecular biomaterials with flexible and modular structures have exhibited unparalleled advantages of high cargo-loading efficiency, excellent biocompatibility, and diversiform immunomodulatory activity, thereby providing a powerful weapon for cancer immunotherapy. In past decades, supramolecular biomaterials were extensively explored as versatile delivery platforms for immunotherapeutic agents or designed to interact with the key moleculars in immune system in a precise and controllable manner. In this review, we focused on the crucial role of supramolecular biomaterials in the modulation of pivotal steps during tumor immunotherapy, including antigen delivery and presentation, T lymphocyte activation, tumor-associated macrophage elimination and repolarization, and myeloid-derived suppressor cell depletion. Based on extensive research, we explored the current limitations and development prospects of supramolecular biomaterials in cancer immunotherapy.