Fluorescent small molecule donors.

Small molecule donors (SMDs) play subtle roles in the signaling mechanism and disease treatments. While many excellent SMDs have been developed, dosage control, targeted delivery, spatiotemporal feedback, as well as the efficiency evaluation of small molecules are still key challenges. Accordingly, fluorescent small molecule donors (FSMDs) have emerged to meet these challenges. FSMDs enable controllable release and non-invasive real-time monitoring, providing significant advantages for drug development and clinical diagnosis. Integration of FSMDs with chemotherapeutic, photodynamic or photothermal properties can take full advantage of each mode to enhance therapeutic efficacy. Given the remarkable properties and the thriving development of FSMDs, we believe a review is needed to summarize the design, triggering strategies and tracking mechanisms of FSMDs. With this review, we compiled FSMDs for most small molecules (nitric oxide, carbon monoxide, hydrogen sulfide, sulfur dioxide, reactive oxygen species and formaldehyde), and discuss recent progress concerning their molecular design, structural classification, mechanisms of generation, triggered release, structure-activity relationships, and the fluorescence response mechanism. Firstly, from the large number of fluorescent small molecular donors available, we have organized the common structures for producing different types of small molecules, providing a general strategy for the development of FSMDs. Secondly, we have classified FSMDs in terms of the respective donor types and fluorophore structures. Thirdly, we discuss the mechanisms and factors associated with the controlled release of small molecules and the regulation of the fluorescence responses, from which universal guidelines for optical properties and structure rearrangement were established, mainly involving light-controlled, enzyme-activated, reactive oxygen species-triggered, biothiol-triggered, single-electron reduction, click chemistry, and other triggering mechanisms. Fourthly, representative applications of FSMDs for trackable release, and evaluation monitoring, as well as for visible in vivo treatment are outlined, to illustrate the potential of FSMDs in drug screening and precision medicine. Finally, we discuss the opportunities and remaining challenges for the development of FSMDs for practical and clinical applications, which we anticipate will stimulate the attention of researchers in the diverse fields of chemistry, pharmacology, chemical biology and clinical chemistry. With this review, we hope to impart new understanding thereby enabling the rapid development of the next generation of FSMDs.

Developing NIR xanthene-chalcone fluorophores with large Stokes shifts for fluorescence imaging.

A series of novel near-infrared (NIR) xanthene-chalcone fluorophores were constructed through a modular synthesis with the electron-donating xanthene moiety and the electron-withdrawing chalcone moiety. These fluorophores are convenient for fluorescence imaging in living cells, benefiting from their NIR emissions (650-710 nm), large Stokes shifts (>100 nm), moderate quantum yields and low cytotoxicity. The substituted hydroxyl group of the xanthene-chalcone fluorophore HCA-E facilitates the development of multifunctional fluorescent probes. As an example, a highly sensitive and selective probe N-HCA-E for glutathione (GSH) detection was developed based on the fluorophore HCA-E. A 4-nitrobenzenesulfonyl (4-Ns) group was introduced to cage the hydroxyl group of HCA-E, which was used as a selective recognition site for the thiol of GSH and an effective fluorescence quencher. Probe N-HCA-E revealed NIR "turn-on" fluorescence (709 nm) for endogenous and exogenous GSH detection in lysosomes with a large Stokes shift (129 nm) and high anti-interference ability.

Discovery of novel 20S proteasome subunit ß5 PROTAC degraders as potential therapeutics for pharyngeal carcinoma and Bortezomib-resistant multiple myeloma.

Resistance to proteasome inhibitors like Bortezomib is a major challenge in the treatment of multiple myeloma (MM). Proteolysis targeting chimeras (PROTACs), an emerging therapeutic approach that induces selective degradation of target proteins, offer a promising solution to overcome drug resistance. In this study, we designed and synthesized novel small-molecule PROTACs that induce 20S proteasome subunit ß5 degradation as a strategy to overcome Bortezomib resistance. These 20S proteasome subunit ß5 PROTACs demonstrated considerable binding affinity to 20S proteasome subunit ß5 and cereblon (CRBN), effectively induced 20S proteasome subunit ß5 degradation, and exhibited potent antiproliferative activity against a panel of cancer cell lines. Notably, PROTACs 12f and 14 displayed robust antitumor effects against both the pharyngeal carcinoma cell line FaDu and the Bortezomib-resistant MM cell line KM3/BTZ in vitro and in vivo with excellent safety profiles. Taken together, our findings highlight the potential of PROTACs 12f and 14 as novel 20S proteasome subunit ß5-degrading agents for the treatment of pharyngeal carcinoma and overcoming Bortezomib resistance in MM.

Highly sensitive and selective detection of amoxicillin using molecularly imprinted ratiometric fluorescent nanosensor based on quantum dots.

A dual-emission ratiometric fluorescence sensor (CDs@CdTe@MIP) with a self-calibration function was successfully constructed for AMO detection. In the CDs@CdTe@MIP system, non-imprinted polymer-coated CDs and molecule-imprinted polymer-coated CdTe quantum dots were used as the reference signal and response elements, respectively. The added AMO quenched the fluorescence of the CdTe quantum dots, whereas the fluorescence intensity of the CDs remained almost unchanged. The AMO concentration was monitored using the fluorescence intensity ratio (log(I647/I465)0/(I647/I465)) to reduce interference from the testing environment. The sensor with a low detection limit of 0.15 µg/L enabled detection of the AMO concentration within 6 min. The ratiometric fluorescence sensor was used to detect AMO in spiked pork samples; it exhibited a high recovery efficiency and relative standard deviation (RSD) of 97.94-103.70% and 3.77-4.37%, respectively. The proposed highly sensitive and selective platform opens avenues for sensitive, reliable, and rapid determination of pharmaceuticals in the environment and food safety monitoring using ratiometric sensors.

The use of Treatment and Education of Autistic and Related Communication Handicapped Children in schools to improve the ability of children with autism to complete tasks independently: A single-case meta-analysis.

OBJECTIVE: To investigate the effectiveness of a Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) intervention in schools for improving independent task performance in children with autism spectrum disorders (ASD). METHODS: We screened relevant studies published up to December 2022 from Web of science, ERIC, PsycINFO and other databases using predefined inclusion/exclusion criteria to identify suitable intervention studies for meta-analysis. Tau-U effect sizes were calculated for each A-B comparison extracted from the included experiments. Moderated analyses were conducted to examine the type of intervention (independent variable), intervention target behaviours (dependent variable), participant characteristics, setting characteristics and intervener characteristics. RESULTS: A total of 14 studies (38 participants) met the criteria and were included in the meta-analysis. The analysis results showed that TEACCH had a significant intervention effect, and the overall intervention effect size was Tau-U = 0.85[0.77, 0.91]. There were significant differences in the intervention target behaviour variables (p < 0.01), limited variation in the intervention type variables, but no differences in participant characteristics, setting characteristics and intervenor characteristics. CONCLUSION: The use of TEACCH is effective in improving independent task completion in children with ASD and provides evidence-based recommendations for its extended use in schools.

Design, Synthesis, Antifungal Evaluation, Structure-Activity Relationship (SAR) Study, and Molecular Docking of Novel Spirotryprostatin A Derivatives.

Phytopathogenic fungi cause plant diseases and economic losses in agriculture. To efficiently control plant pathogen infections, a total of 19 spirotryprostatin A derivatives and 26 spirooxindole derivatives were designed, synthesized, and tested for their antifungal activity against ten plant pathogens. Additionally, the intermediates of spirooxindole derivatives were investigated, including proposing a mechanism for diastereoselectivity and performing amplification experiments. The bioassay results demonstrated that spirotryprostatin A derivatives possess good and broad-spectrum antifungal activities. Compound 4d exhibited excellent antifungal activity in vitro, equal to or higher than the positive control ketoconazole, against Helminthosporium maydis, Trichothecium roseum, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium graminearum, Alternaria brassicae, Alternaria alternate, and Fusarium solan (MICs: 8-32 µg/mL). Compound 4k also displayed remarkable antifungal activity against eight other phytopathogenic fungi, including Fusarium oxysporium f. sp. niveum and Mycosphaerella melonis (MICs: 8-32 µg/mL). The preliminary structure-activity relationships (SARs) were further discussed. Moreover, molecular docking studies revealed that spirotryprostatin A derivatives anchored in the binding site of succinate dehydrogenase (SDH). Therefore, these compounds showed potential as natural compound-based chiral fungicides and hold promise as candidates for further enhancements in terms of structure and properties.

Design, Synthesis and Bioactivity Evaluation of Novel 2-(pyrazol-4-yl)-1,3,4-oxadiazoles Containing an Imidazole Fragment as Antibacterial Agents.

Imidazole alkaloids, a common class of five-membered aromatic heterocyclic compounds, exist widely in plants, animals and marine organisms. Because of imidazole's extensive and excellent biological and pharmacological activities, it has always been a topic of major interest for researchers and has been widely used as an active moiety in search of bioactive molecules. To find more efficient antibacterial compounds, a series of novel imidazole-fragment-decorated 2-(pyrazol-4-yl)-1,3,4-oxadiazoles were designed and synthesized based on our previous works via the active substructure splicing principle, and their bioactivities were systematically evaluated both in vitro and in vivo. The bioassays showed that some of the target compounds displayed excellent in vitro antibacterial activity toward three virulent phytopathogenic bacteria, including Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa), affording the lowest EC50 values of 7.40 (7c), 5.44 (9a) and 12.85 (9a) µg/mL, respectively. Meanwhile, compound 7c possessed good in vivo protective and curative activities to manage rice bacterial leaf blight at 200 µg/mL, with control efficacies of 47.34% and 41.18%, respectively. Furthermore, compound 9a showed commendable in vivo protective and curative activities to manage kiwifruit bacterial canker at 200 µg/mL, with control efficacies of 46.05% and 32.89%, respectively, which were much better than those of the commercial bactericide TC (31.58% and 17.11%, respectively). In addition, the antibacterial mechanism suggested that these new types of title compounds could negatively impact the cell membranes of phytopathogenic bacteria cells and cause the leakage of the intracellular component, thereby leading to the killing of bacteria. All these findings confirm that novel 2-(pyrazol-4-yl)-1,3,4-oxadiazoles containing an imidazole fragment are promising lead compounds for discovering new bactericidal agents.

Bright chemiluminescent dioxetane probes for the detection of gaseous transmitter H2S.

Hydrogen sulfide (H2S), the third gaseous transmitter after CO and NO, is a double-edged sword in the human body. A specific concentration of H2S can attenuate myocardial ischemia-reperfusion injury by preserving mitochondrial function, in contrast, cause illness, including inflammation and stroke. There are already some probes for the real-time monitoring of the level of H2S in the biological environment. However, they have some disadvantages, such as phototoxicity, low sensitivity, and low quantum yield. In this research, by linking 4-dinitrophenyl-ether (DNP), a specific recognition group for H2S, with a chemiluminophore 1,2-dioxetane, we designed and synthesized the probe SCL-1. To tackle the barrier that the traditional chemiluminescent group has a short emission wavelength and is not easy to penetrate deep tissues, an acrylonitrile electron-withdrawing substituent was installed to the ortho-position of the 1,2-dioxanol hydroxy group. According to the same design strategy as SCL-1, the probe SCL-2 was designed with the modified chemiluminescent group. Studies have shown that SCL-2 with electron-withdrawing acrylonitrile has higher luminescence quantum yield and high sensitivity than SCL-1, realizing real-time detection of H2S in vitro and in vivo. The LOD of SCL-2 was 0.185 µM, which was the best among the currently available luminescent probes for detecting H2S. We envisage that SCL-2 may be a practical toolbox for studying the biological functions of H2S and H2S-related diseases.

Disclosure experience among COVID-19-confirmed patients in China: A qualitative study.

AIM: To understand COVID patients' experiences of and perspectives on disclosure of their illness and to explore and describe the factors affecting disclosure decisions among COVID patients in China. BACKGROUND: Disease disclosure is a critical component of prevention and control of a virus outbreak, and this is especially true during the COVID-19 pandemic. Understanding COVID patients' experiences and perspectives on disclosure could play a vital role in COVID management. DESIGN: A qualitative study. METHODS: A semi-structured interview guide was used to conduct qualitative in-depth interviews from April to June 2020. All the interviews were audio-recorded and transcribed, and then, a thematic analysis was conducted. The Standards for Reporting Qualitative Research (SRQR) were applied to this study. RESULTS: A total of 26 COVID-confirmed patients were recruited for the in-depth interviews. Four themes emerged from the thematic analysis on disclosure: persons disclosed to, reasons for disclosure, reasons for nondisclosure and impact of disclosure. The participants disclosed their COVID diagnosis to different groups, including family, close friends, community members and workplace contacts. The main reasons for disclosure included the following: government policy, social responsibility, gaining support and fear of being blamed for nondisclosure. However, some participants decided not to disclose to some groups for fear of facing stigma and discrimination or to protect family members from discrimination. Despite the potential benefits of obtaining support after disclosure, many participants did experience stigma and discrimination, privacy exposure, psychological distress and social isolation. CONCLUSIONS: An individual's decision as to whether to disclose their COVID-positive status is affected by many factors. To prevent the spread of COVID-19 and reduce the potential risks of disclosure, such as discrimination and privacy exposure, a balanced intervention should be designed to protect COVID patients and to secure any contact tracing. Therefore, the chances of discrimination could be decreased and patients' confidentiality could be protected. RELEVANCE TO CLINICAL PRACTICE: As the number of COVID patients increases, disclosure of an individual's infectious status is encouraged by health departments. Despite the potential benefits of disclosure, discrimination and privacy exposure should not be ignored. A disclosure protocol is necessary to ensure patients' privacy regarding their COVID status.

Discovery of Small-Molecule Sulfonamide Fluorescent Probes for GPR120.

GPR120 is a novel target for the treatment of metabolic disease and type 2 diabetes. The small-molecule fluorescent probe could help us locate GPR120 visually and guide in-depth study of GPR120. In this study, we synthesized six nonacidic sulfonamide fluorescent probes and tested their optical and biological properties. Compared to previous probes for GPR120, these probes, with sulfonamide structure, have high selectivity on GPR120. We used these probes to establish a BRET binding assay system to screen agonists and antagonists of GPR120. It is expected that these novel fluorescent probes may become useful tools in studying pharmacology and physiology of GPR120.

A functional Variant (Rs35592567) in TP63 at 3q28 is Associated with Gastric Cancer Risk via Modifying its Regulation by MicroRNA-140.

BACKGROUND/AIMS: TP63 was believed to play an important role in the development of many malignancies, while the polymorphisms located at the miRNA binding sites within the 3'UTR of TP63 mRNA may interfere with its expression. In this study, we aimed to study the role of TP63 regulation in the tumorigenesis of gastric cancer (GC). METHODS: Computational and luciferase analysis were used to search and confirm the target of miR-140. Real-time PCR, western-blot, MTT assay, and flow cytometry cell cycle analysis were utilized to explore the molecular pathway of miR-140 involved in the progression of GC. RESULTS: TP63 was identified as a direct target gene of miR-140. In HT-29 cells over-expressing miR-140, the luciferase activity was decreased when the cells were transfected with wild-type TP63 3'UTR, but remained unchanged when the cells were transfected with mutant 1 and mutant 2 TP63 3'UTR. In addition, the level of TP63 in HT-29 cells transfected with miR-140 mimic was evidently down-regulated, whereas the level of TP63 in HT-29 cells transfected with miR-140 inhibitor was significantly up-regulated. Furthermore, based on the results from MTT assay and flow cytometry cell cycle analysis, HT-29 cells transfected with miR-140 mimics were associated with significantly higher viability compared to the cells transfected with the control plasmid, suggesting that an increased expression of miR-140 protected HT-29 cells against apoptosis. Finally, when miR-140 expression was high, the number of cells at the G1 phase was notably increased, accompanied by a remarkably diminished number of cells at the S phase. CONCLUSIONS: The rs35592567 polymorphism in TP63 affected the expression of TP63 by interfering with its interaction with miR-140, and could serve as an explanation for the increased risk of GC.

Synthesis of Low Pt-Based Quaternary PtPdRuTe Nanotubes with Optimized Incorporation of Pd for Enhanced Electrocatalytic Activity.

Improving heteroatomic interactions via alloying or forming heterogeneous catalysts is of importance to the enhancement in terms of electrocatalytic activity and stability. In this work, a simple galvanic replacement reaction was utilized to synthesize low Pt-based quaternary nanotubes (NTs). It is easy to obtain PtPdRuTe NTs with different composition and controlled shape using ultrathin Te nanowires (NWs) as sacrificial templates for its high activity. The NT wall thickness and formed NPs on the surface are closely related with the composition, especially Pd content. The optimized incorporation of Pd atoms into ternary PtRuTe NTs formed a uniform protecting PtPd surface and modified the Pt electronic structure to improve the methanol oxidation reaction (MOR) performance. X-ray photoelectron spectroscopy (XPS) reveals a larger extent of electron transfer from neighboring atoms to Pt on PtPdRuTe, consequently leading to a weaker bonding of the intermediate on Pt. As a result, the quaternary PtPdRuTe NTs exhibit enhanced activity and stability toward efficient MOR.

Scalable Bromide-Triggered Synthesis of Pd@Pt Core-Shell Ultrathin Nanowires with Enhanced Electrocatalytic Performance toward Oxygen Reduction Reaction.

This article reports a novel scalable method to prepare ultrathin and uniform Pd@Pt nanowires (NWs) with controllable composition and shell thickness, high aspect ratio, and smooth surface, triggered by bromide ions via a galvanic replacement reaction between PtCl6(2-) and Pd NWs. It was found that bromide ions played a vital role in initiating and promoting the galvanic reaction. The bromide ions served as capping and oxidized etching agents, counterbalancing the Pt deposition and Pd etching on the surface to give final Pd@Pt core-shell nanostructures. Such a counterbalance and the formation PtBr6(2-) with lower redox potential could lower the reaction rate and be responsible for full coverage of a smooth Pt shell. The full coverage of Pt deposited on Pd NWs is important for the enhancement of the activity and stability, which depend strongly on the Pt content and Pt shell thickness. Significantly, the Pd@Pt NWs with Pt content of 21.2% (atomic ratio) exhibited the highest mass activity (810 mA mg(-1)(Pt)) and specific activity (0.4 mA cm(-2)). Interestingly, the mass activity (1560 mA mg(-1)(Pt)) and specific activity (0.98 mA cm(-2)) of Pd@Pt (21.2%) NWs increased to 2.45 and 1.95 times the initial values after 60k cycles tests, 8.5 and 9.0 times greater than those of Pt/C catalysts. In addition, these ultrathin NW electrocatalysts with large aspect ratio are easy to form into a freestanding film, which improves the mass transport, electrical conductivity, and structure stability.

Copper-Catalyzed Enantioselective Synthesis of Spirohydroindoles by Ethoxyformylmethylene Oxindole and Iminoester 1,3-Dipole Cycloaddition: An Examination of Associated Biological Activities.

A highly enantioselective 1,3-dipolar cycloaddition of ethoxyformylmethylene oxindole with iminoesters has been achieved using the Cu(I)-(S,Sp)-Ph Phosferrox catalytic system, generating a series of chiral spiro[pyrrolidin-3,3'-oxindole] compounds with four consecutive stereocenters, including a spirocycle quaternary center (71%-99% yield, up to >20:1 dr and 95:5 er). The compounds exhibited good inhibitory activity against Valsa mali (V.m.), Fusarium oxysporium (F.o.), and Alternaria brassicae (A.b.).

Visual monitoring of biocatalytic processes using small molecular fluorescent probes: strategies-mechanisms-applications.

Real-time monitoring of biocatalytic-based processes is significantly improved and simplified when they can be visualized. Visual monitoring can be achieved by integrating a fluorescent unit with the biocatalyst. Herein, we outline the design strategies of fluorescent probes for monitoring biocatalysis: (1) probes for monitoring biocatalytic transfer: γ-glutamine is linked to the fluorophore as both a recognition group and for intramolecular charge transfer (ICT) inhibition; the probe is initially in an off state and is activated via the transfer of the γ-glutamine group and the release of the free amino group, which results in restoration of the "Donor-π-Acceptor" (D-π-A) system and fluorescence recovery. (2) Probes for monitoring biocatalytic oxidation: a propylamine is connected to the fluorophore as a recognition group, which cages the hydroxyl group, leading to the inhibition of ICT; propylamine is oxidized and subsequently ß-elimination occurs, resulting in exposure of the hydroxyl group and fluorescence recovery. (3) Probes for monitoring biocatalytic reduction: a nitro group attached to a fluorophore as a fluorescence quenching group, this is converted to an amino group by catalytic reduction, resulting in fluorescence recovery. (4) Probes for monitoring biocatalytic hydrolysis: ß-D-galactopyranoside or phosphate acts as a recognition group attached to hydroxyl groups of the fluorophore; the subsequent biocatalytic hydrolysis reaction releases the hydroxyl group resulting in fluorescence recovery. Following these 4 mechanisms, fluorophores including cyanine, coumarin, rhodamine, and Nile-red, have been used to develop systems for monitoring biocatalytic reactions. We anticipate that these strategies will result in systems able to rapidly diagnose and facilitate the treatment of serious diseases.

Degradation of extracellular and membrane proteins in targeted therapy: Status quo and quo vadis.

Targeted protein degradation (TPD) strategies, such as proteolysis-targeting chimeras (PROTACs) only work for intracellular protein degradation because they involve the intracellular protein degradation machinery. Several new technologies have emerged in recent years for TPD of extracellular and membrane proteins. Even though some progress has been demonstrated in the extracellular and membrane protein degradation field, the application of these technologies is still in its infancy. In this review, we survey the therapeutic potential of existing technologies by summarizing and reviewing discoveries and hurdles in extracellular and membrane protein-of-interest (POI) degradation.

Targeted Protein Degradation Induced by HEMTACs Based on HSP90.

Targeted protein degradation (TPD) strategies open up new avenues for therapeutics and provide powerful tools for biological inquiry. Herein, we present a brand-new approach, termed heat shock protein 90 (HSP90)-mediated targeting chimeras (HEMTACs), to induce intracellular protein degradation by bridging a target protein to HSP90 to drive the downregulation of proteins. We successfully showcase HEMTACs for cyclin-dependent kinase 4 and 6 (CDK4/6) by using a flexible linker to connect the targeting warhead of CDK4/6 with the HSP90 ligand. Overall, our study delivers a series of evidence that HEMTACs can serve as a valuable addition to TPD strategies, most prominently proteolysis-targeting chimera technology.

Accurate photoactivation monitoring via the construction of an intramolecular synergistic counteracting mechanism of FRET and IFE.

The synergistic modulation of fluorescence resonance energy transfer (FRET) and the inner filter effect (IFE) was constructed within a molecule to control the stable fluorescence intensity as the internal standard, providing a new strategy for the accurate monitoring of photoactivation.

Cancer Cell-Specific Fluorescent Prodrug Delivery Platforms.

Targeting cancer cells with high specificity is one of the most essential yet challenging goals of tumor therapy. Because different surface receptors, transporters, and integrins are overexpressed specifically on tumor cells, using these tumor cell-specific properties to improve drug targeting efficacy holds particular promise. Targeted fluorescent prodrugs not only improve intracellular accumulation and bioavailability but also report their own localization and activation through real-time changes in fluorescence. In this review, efforts are highlighted to develop innovative targeted fluorescent prodrugs that efficiently accumulate in tumor cells in different organs, including lung cancer, liver cancer, cervical cancer, breast cancer, glioma, and colorectal cancer. The latest progress and advances in chemical design and synthetic considerations in fluorescence prodrug conjugates and how their therapeutic efficacy and fluorescence can be activated by tumor-specific stimuli are reviewed. Additionally, novel perspectives are provided on strategies behind engineered nanoparticle platforms self-assembled from targeted fluorescence prodrugs, and how fluorescence readouts can be used to monitor the position and action of the nanoparticle-mediated delivery of therapeutic agents in preclinical models. Finally, future opportunities for fluorescent prodrug-based strategies and solutions to the challenges of accelerating clinical translation for the treatment of organ-specific tumors are proposed.

Thalidomide for Recurrence of Symptoms following HIV-Associated Cryptococcal Meningitis.

INTRODUCTION: Cryptococcal meningitis (CM) is a serious and fatal fungal infection that affects individuals infected with human immunodeficiency virus (HIV). Despite treatment, recurrence of symptoms is common and could lead to poor outcomes. Corticosteroids are not always useful in treating symptom recurrence following HIV/CM; thus, alternative therapy is needed. Thalidomide has been reported to be effective in treating symptom recurrence in several patients with HIV/CM. This retrospective study aimed to investigate the efficacy and safety of thalidomide in the treatment of symptom recurrence following HIV/CM. METHODS: Patients who were treated with thalidomide for symptom recurrence following HIV/CM were retrospectively included. Clinical outcomes and adverse events were recorded and analyzed. RESULTS: Sixteen patients admitted between July 2018 and September 2020 were included in the analysis. During a median follow-up period of 295 (166, 419) days, all patients achieved clinical improvement in a median of 7 (4, 20) days. Among them, nine (56%) achieved complete resolution of symptoms at a median of 187 (131, 253) days, including 40% (2/5) of immune reconstitution inflammatory syndrome (IRIS), 50% (3/6) of patients with elevated ICP only, and 80% (4/5) of patients with symptoms only. Seven (43%) patients experienced nine episodes of adverse events, but no severe adverse event attributable to thalidomide was observed. None of the patients withdrew from thalidomide due to adverse events. CONCLUSION: Thalidomide appears to be effective and safe in treating different types of symptom recurrence in HIV/CM. This study provides preliminary evidence supporting future randomized clinical trials to further investigate the efficacy and safety of thalidomide in treating symptom recurrence in this population.