Chat-ePRO: Development and pilot study of an electronic patient-reported outcomes system based on ChatGPT.

OBJECTIVE: Chatbots have the potential to improve user compliance in electronic Patient-Reported Outcome (ePRO) system. Compared to rule-based chatbots, Large Language Model (LLM) offers advantages such as simplifying the development process and increasing conversational flexibility. However, there is currently a lack of practical applications of LLMs in ePRO systems. Therefore, this study utilized ChatGPT to develop the Chat-ePRO system and designed a pilot study to explore the feasibility of building an ePRO system based on LLM. MATERIALS AND METHODS: This study employed prompt engineering and offline knowledge distillation to design a dialogue algorithm and built the Chat-ePRO system on the WeChat Mini Program platform. In order to compare Chat-ePRO with the form-based ePRO and rule-based chatbot ePRO used in previous studies, we conducted a pilot study applying the three ePRO systems sequentially at the Sir Run Run Shaw Hospital to collect patients' PRO data. RESULT: Chat-ePRO is capable of correctly generating conversation based on PRO forms (success rate: 95.7 %) and accurately extracting the PRO data instantaneously from conversation (Macro-F1: 0.95). The majority of subjective evaluations from doctors (>70 %) suggest that Chat-ePRO is able to comprehend questions and consistently generate responses. Pilot study shows that Chat-ePRO demonstrates higher response rate (9/10, 90 %) and longer interaction time (10.86 s/turn) compared to the other two methods. CONCLUSION: Our study demonstrated the feasibility of utilizing algorithms such as prompt engineering to drive LLM in completing ePRO data collection tasks, and validated that the Chat-ePRO system can effectively enhance patient compliance.

Cascade reaction triggered colorimetric array for identification of organophosphorus pesticides congeners.

A modern agriculture uses alternative pest control methods to boost productivity, leading to an accumulation of organophosphorus (OPPs) congeners. This necessitates an intuitive and quick way to identify OPPs congeners. A colorimetric sensor for detecting OPPs congeners using a double-enzyme cascade reaction has been successfully designed and constructed in this study. The OPPs regulate the color changes induced by manganese dioxide nanoflowers (MnO2 NFs) and specific alkaline phosphatases (ALP) during the etching of gold nanopyramids (Au NBPs). The ascorbic acid (AA) produced by ALP hydrolysis inhibits Au NBPs etching by MnO2 NFs oxidized 3, 3', 5, 5'-tetramethylbenzidine (TMB). By inhibiting ALP catalytic activity, OPPs prevent AA formation. In this process, Au NBPs will undergo further etching, resulting in various colors so they can be analyzed semi-quantitatively with the naked eye. It has been found that different types of OPPs inhibit enzymes differently and therefore result in varying degrees of etching of Au NBPs. Principal Component Analysis (PCA) is performed by smart devices that convert R, G, and B signals into digital signals. This colorimetric array tests various foods (tea, apple, and cabbage). Colorimetric visualization sensors combined with data analysis will be used in real-life product development.

Distinguishable Colorimetric Biosensor for Diagnosis of Prostate Cancer Bone Metastases.

Castration-resistant prostate cancer (PCa) causes severe bone metastasis (BM), which significantly increases mortality in men with PCa. Imaging tests and radiometric scanning require long analysis times, expensive equipment, specialized personnel, and a slow turnaround. New visualization technologies are expected to solve the above problems. Nonetheless, existing visualization techniques barely meet the urgency for precise diagnosis because the human eyes cannot recognize and capture even slight variations in visual information. By using dye differentiated superposition enhancement colorimetric biosensors, an effective method to diagnose prostate cancer bone metastases (PCa-BM) with excellent accuracy for naked-eye quantitative detection of alkaline phosphatase (ALP) is developed. The biomarker ALP specific hydrolytic product ascorbic acid can be detected by rhodamine derivatives (Rd) as gold nanobipyramids (Au NBPs) are deposited and grown. Color-recombining enhancement effects between Rd and Au NBPs significantly improved abundance. The 150 U L-1 threshold between normal and abnormal can be identified by color. And with color enhancement effect and double signal response, the ALP index is visually measured to diagnose PCa-BM and provide handy treatment recommendations. Additionally, the proposed colorimetric sensing strategy can be used to diagnose other diseases.

Logic gate-driven dual-index balanced visualization strategy for tumor metastasis diagnosis.

Exfoliated tumor cells are integral to malignant tumors diagnosis. The process of clinical cytology of exfoliation involves several complex steps that require at least two days of preparation. Here, we develop a balanced-etching visual kit based on concentration differences of Glutathione/Glucose (GSH/Glu) to distinguish normal from exfoliated tumor cells rapidly and accurately. The balanced-etching visualization kit can be used to obtain color cards and screen exfoliated tumor cells initially (within 10 min). Furthermore, by utilizing logic gates and machine learning algorithms for RGB extraction of the color card obtained from the kit, accurate screening of exfoliated tumor cells is achieved. Finally, a series of clinical tumor samples, such as urine, pleural fluids, ascites, and gastric fluids, have been validated. With effective experimental methods, accurate disease information, and appropriate therapeutic programs, the novel diagnostic strategy is expected to promote precision medicine.

Propofol combined with alfentanil for general anesthesia in vocal cord polypectomy under suspension laryngoscopy.

OBJECTIVE: To investigate the clinical effect of propofol combined with alfentanil in vocal cord polypectomy under suspension laryngoscopy. METHODS: A total of 308 patients undergoing vocal cord polypectomy under suspension laryngoscopy in the First Affiliated Hospital of Nanchang University were included in this prospective study, and the patients were randomly divided into an observation group and a control group. Patients in the observation group received alfentanil combined with propofol, while those in the control group were anesthetized with sufentanil combined with propofol. The heart rate (HR), mean arterial pressure (MAP), real portfolio project (RPP), and Steward postanesthetic recovery scores were compared between the two groups before anesthesia induction (T0), at intubation (T1), 5 min after intubation (T2), at the time of placing suspension laryngoscopy (T3), 1 min after placing the suspension laryngoscopy (T4), 1 min after extraction of support laryngoscope (T5), and 1 min after extubation (T6). In addition, the propofol dosage and peripheral plasma levels of epinephrine (E) and norepinephrine (NE) were also compared between the groups. RESULTS: The MAP, HR, and RPP of the patients in the observation group were higher than those in the control group at T1-T5 (all P<0.05), while there was no statistical difference at T0 and T6 (all P>0.05). The Steward postanesthetic recovery scores and the propofol dosage in the observation group were lower than those in the control group. In addition, there was a statistically significant difference in the E and NE levels between the two groups after surgery (P<0.001). There was also an interaction effect between the groups and among the time points (both P<0.001). CONCLUSION: Alfentanil can reduce the fluctuation of hemodynamics during vocal cord polypectomy under suspension laryngoscopy, and therefore improve anesthesia effect. Simultaneously, the usage of propofol was reduced, as well as the stress levels. CLINICAL TRIAL NUMBER: ChiCTR2100054186.

In Vivo Bioimaging and Photodynamic Therapy Based on Two-Photon Fluorescent Conjugated Polymers Containing Dibenzothiophene-S,S-dioxide Derivatives.

As a critical component for photodynamic therapy toward cancer treatment, photosensitizers require high photoinduced reactive oxygen species generation efficiency, good biocompatibility, and high phototoxicity. Herein, a series of donor-acceptor conjugated polymers containing dibenzothiophene-S,S-dioxide derivatives are designed and synthesized, which can be used as effective photosensitizers. The resulting copolymer PTA5 shows strong green light emission with high photoluminescence quantum yields owing to the intercrossed excited state of local existed and charge transfer states. The PTA5 nanoparticles can be fabricated by encapsulation with a biocompatible polymer matrix. Upon excitation at 800 nm, these nanoparticles present a relatively large two-photon absorption cross section of 3.29 × 106 GM. These nanoparticles also exhibit good photostability in water and thus can be utilized for bioimaging. The tissue-penetrating depths of up to 170 µm for hepatic vessels and 380 µm for blood vessels of mouse ear were achieved using PTA5 nanoparticles. Furthermore, PTA5 nanoparticles show impressive reactive oxygen species generation capability under the irradiation of a white light source. This can be attributed to the effective intersystem crossing between high-level excited state. Upon irradiation with white light (400-700 nm) at 50 mW cm-2 for 5 min every other day, the tumor growth can be effectively suppressed in the presence of PTA5 nanoparticles. These findings demonstrate that PTA5 nanoparticles can be used as a photosensitizer for photodynamic therapy.

Efficient near-infrared anionic conjugated polyelectrolyte for photothermal therapy.

In this work, an anionic conjugated polyelectrolyte (PCP-SO3K), in which the backbone contains alternating 4,4-bis-alkyl-4H-cyclopenta-[2,1-b;3,4-b']-dithiophene and benzene structural units and the charges are provided by pendant sulfonate groups, was synthesized. The ionic nature of PCP-SO3K renders it soluble in water, and PCP-SO3K aqueous solution exhibits good photostability, with two main absorbance bands centered at 490 nm and 837 nm before and after laser irradiation. Its NIR absorption in water, negligible photoluminescence and insignificant intersystem crossing endow PCP-SO3K with efficient photothermal therapy performance, and an effective photothermal conversion efficiency of 56.7% was realized. Thus, PCP-SO3K aqueous solution can be used as an effective photothermal agent for in vivo applications as its photoactivity can be triggered by NIR light and can convert laser energy into thermal energy in a water environment. Of particular importance is the fact that complete tumor remission without recurrence in 4T1 tumor-bearing mice was realized after intravenous injection of PCP-SO3K aqueous solution and laser irradiation (2.0 W cm-2, 808 nm). The results indicate that the application of anionic conjugated polyelectrolytes as photothermal agents in photothermal therapy provides a new platform for the design of photothermal agents for clinical cancer treatment.

A thermosensitive nanoplatform for photoacoustic imaging and NIR light triggered chemo-photothermal therapy.

Temperature-sensitive liposomes (TSLs) have received constant attention due to the release of contents around the physiological temperature, which holds great potential in the treatment of tumors. However, the development of TSLs is limited by the long-term biotoxicity and low photothermal conversion efficiency of heat-generation materials. In this study, we develop a new D-A (donor-acceptor) structure NIR absorbing dye (C720) which exhibits a high photothermal conversion efficiency (62%), good photostability, and photothermal reproducibility. Then C720 is doped in the lipid bilayer and DOX (doxorubicin) is wrapped in the core of temperature sensitive liposomes to construct a C720 and DOX-loaded thermosensitive nanoplatform (CDTSL). The as-prepared CDTSL achieves NIR light controlled drug release and can be applied for photoacoustic imaging. In vitro and in vivo studies confirm that CDTSL exhibits high tumor suppressive efficiency by synergistic photothermal therapy and chemotherapy. Our research provides fundamental insights for the rational design and preparation of a promising nanoplatform for photoacoustic imaging and chemo-photothermal therapy.

Anti-tumor activity and linear-diarylheptanoids of herbal couple Curcumae Rhizoma-Sparganii Rhizoma and the single herbs.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumae Rhizoma and Sparganii Rhizoma (CR-SR) are the classical herbal couple for activating blood circulation and treating tumor in clinics. AIM OF THE STUDY: To investigate the anti-tumor activity and to clarify the bioactive ingredients of herbal couple CR-SR and the single herbs Curcumae Rhizoma (CR) and Sparganii Rhizoma (SR). MATERIALS AND METHODS: The active fractions of CR-SR decoction were fractioned by column chromatography. And isolated compounds were characterized by IR, ESI-MS, 1D and 2D-NMR techniques. Detecting linear-diarylheptanoids in CR-SR, CR and SR was realized through UPLC-LTQ-Orbitrap MSn, based on the fragmentation pathways established in this study, comparison with MS data of isolated compounds and references. The anti-tumor activities of different solvent fractions from CR-SR, CR and SR, as well as isolated ingredients were tested by CCK-8 method. RESULTS: Ultimately, a new compound (1), having a sulfonic acid group at C-3, named demethoxyshogasulfonic acid, along with another structurally similar 17 known linear-diarylheptanoids were isolated. These linear-diarylheptanoids (1-18) were divided into 12 categories based on the differences of substituents at C-3 and C-5 on the straight chain of seven carbons. Six fragmentation pathways were established by summarizing MS data of the 18 isolated compounds collected from UPLC-MS. Based on that, and retention times and MS fragmentation ions, 47 linear-diarylheptanoids were identified in CR-SR and CR, in which 12 linear-diarylheptanoids were also detected in SR. Most importantly, 5 sulfonated linear-diarylheptanoids were new compounds detected in CR and CR-SR. And the biological assay indicated that compounds 1-4 and 12-15 significantly reduced the proliferation and inhibited colony formation of MCF-7 and HepG2 cells. CONCLUSION: The new compound (1) exhibited good anti-cancer activity, which suggests that a great effort has to be paid to investigate the bioactivity of sulfonated compounds. The fractions of CR-SR decoction exhibited stronger anti-tumor activities than that of CR and SR against 5 different cancer cells. As for chemical composition, it is the first time to report that diarylheptanoids are in Sparganiaceae and the sulfonated compounds in Zingiberaceae. Moreover, the linear-diarylheptanoids found in SR which being tested to possess good anti-tumor activity, plus those compounds in CR enhance the capacity of CR-SR. It shows importance of TCM compatibility.

A NIR fluorescent probe for detection of viscosity and lysosome imaging in live cells.

Lysosomes, as the cellular recycling center, are filled with numerous hydrolases that can degrade most cellular macromolecules. Studies have shown that the abnormality of viscosity in lysosomes will disrupt the normal function of lysosomes. Herein, a D-π-A structure near-infrared fluorescent probe containing N,N-dimethylamino benzene as an electron donor, benzothiozole as an electron acceptor, and a vinyl group as a π unit, Lyso-BTC, is explored for fluorescence imaging of lysosomes and detection of lysosomal viscosity changes. Lyso-BTC exhibits a large Stokes shift (∼180 nm), NIR emission (685 nm), good biocompatibility, excellent photostability, and fluorescence response to viscosity. Moreover, the results of in vitro studies reveal that Lyso-BTC is lysosome-targeted and could be applied for the detection of viscosity changes in lysosomes caused by chloroquine treatment. These results confirm that Lys-BTC could be employed to monitor lysosomal viscosity changes in living cells.

Near-Infrared Organic Fluorescent Nanoparticles for Long-term Monitoring and Photodynamic Therapy of Cancer.

Photodynamic therapy (PDT), which utilizes reactive oxygen species to ablate tumor, has attracted much attention in recent years. Photosensitizers with near-infrared (NIR) fluorescence as well as efficient ROS generation ability have been used for precise diagnosis and simultaneous treatment of cancer. However, photosensitizers frequently suffer from low ROS generation ability and NIR fluorescence quenching in aqueous media due to the aggregation. Methods: We prepare an effective AIE active NIR emissive photosensitizer containing rhodanine as electron acceptor and triphenylvinylthiophene as electron donor is prepared, and encapsulate the corresponding photosensitizer into Pluronic F127 to fabricate NIR organic fluorescent nanoparticles. We then evaluate the NIR fluorescence bioimaging and photodynamic therapy ability of TPVTR dots in vitro and in vivo. Results: The yielded organic fluorescent nanoparticles exhibit effective ROS generation ability, bright NIR emission, high photostability, and good biocompatibility. Both in vitro and in vivo experiments confirm that NIR organic fluorescent nanoparticles demonstrate good performances in long-term tracing and photodynamic ablation of tumor. Conclusion: In summary, the synthesized organic fluorescent nanoparticles, TPVTR dots, showed great potentials in long-term cell tracing and photodynamic therapy of tumor. Our study highlights the efficient strategy for developing promising near-infrared organic fluorescent nanoparticles in advancing the field of bioimaging and further image-guide clinical applications.

Aggregation-Induced Emission-Active Near-Infrared Fluorescent Organic Nanoparticles for Noninvasive Long-Term Monitoring of Tumor Growth.

Effective long-term monitoring of tumor growth is significant for the evaluation of cancer therapy. Aggregation-induced emission-active near-infrared (NIR) fluorescent organic nanoparticles (TPFE-Rho dots) are designed and synthesized for long-term in vitro cell tracking and in vivo monitoring of tumor growth. TPFE-Rho dots display the advantages of NIR fluorescent emission, large Stokes shift (∼180 nm), good biocompatibility, and high photostability. In vitro cell tracing studies demonstrate that TPFE-Rho dots can track SK-Hep-1 cells over 11 generations. In vivo optical imaging results confirm that TPFE-Rho dots can monitor tumor growth for more than 19 days in a real-time manner. This work indicates that TPFE-Rho dots could act as NIR fluorescent nanoprobes for real-time long-term in situ in vivo monitoring of tumor growth.

Synthesis and antioxidant activity of curcumin analogs.

Numerous biological activities including antioxidant, antitumor, anti-inflammation, and antivirus of the natural product curcumin were reported. However, the clinical application of it was significantly limited by its instability, poor solubility, less body absorbing, and low bioavailability. This review focuses on the structure modification and antioxidant activity evaluation of curcumin. To study the structure-activity relationship (SAR), five series of curcumin analogs were synthesized and their antioxidant activity were evaluated in vitro. The results showed that electron-donating groups, especially the phenolic hydroxyl group are an essential component to improve the antioxidant activity.