Sono-promoted piezocatalysis and low-dose drug penetration for personalized therapy via tumor organoids.

Chemotherapy is a widely used cancer treatment, however, it can have notable side effects owing to the high-doses of drugs administered. Sonodynamic therapy (SDT) induced by sonosensitizers has emerged as a promising approach to treat cancer, however, there is limited research evaluating its therapeutic effects on human tumors. In this study, we introduced a dual therapy that combines low-dose chemotherapeutic drugs with enhanced sonodynamic therapy, utilizing barium titanate (BaTiO3, BTO) nanoparticles (NPs) as sonosensitizers to treat tumor organoids. We demonstrated that ultrasound could improve the cellular uptake of chemotherapy drugs, while the chemotherapeutic effect of the drugs made it easier for BTO NPs to enter tumor cells, and the dual therapy synergistically inhibited tumor cell viability. Moreover, different patient-derived tumor organoids exhibited different sensitivities to this therapy, highlighting the potential to evaluate individual responses to combination therapies prior to clinical intervention. Furthermore, this dual therapy exhibited therapeutic effects equivalent to those of high-dose chemotherapy drugs on drug-resistant tumor organoids and showed the potential to enhance the efficacy of killing drug-resistant tumors. In addition, the biosafety of the BTO NPs was successfully verified in live mice via oral administration. This evidence confirms the reliable and safe nature of the dual therapy approach, making it a feasible option for precise and personalized therapy in clinical applications.

P(VDF-TrFE)/BaTiO3 Nanofibrous Membrane with Enhanced Piezoelectricity for High PM0.3 Filtration and Reusable Face Masks.

In the background of air pollution and regular COVID-19 prevention, personal protective masks are necessary for our daily life. However, protective masks with high PM0.3 filtration usually have poor air permeability and are mostly disposable, leading to a heavy burden on the environment. In this work, a reusable membrane based on piezoelectric poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] nanofibers embedded with BaTiO3 nanoparticles (BTO NPs) was developed. The P(VDF-TrFE)/BTO composite nanofibers not only have enhanced piezoelectricity and surface polarity but also have reduced diameters that could be beneficial for electrostatic adhesion, pole-polar interactions, and mechanical sieving to increase the PM0.3 capture capacity. Moreover, the BTO NPs also improved the charge storage capacity of the composite membrane, which could further enhance the PM0.3 filtration efficiency after corona treatment. The piezoelectric mask based on P(VDF-TrFE)/BTO composite nanofibers has high filtration efficiencies of 96% for PM0.3 and 98% for bacteria, while the pressure drop was only 182 Pa, which is lower than the commercial N95 standard of 343.2 Pa. Furthermore, the piezoelectric mask has a long and stable filtration performance after 5 cycles of 75% alcohol disinfection, demonstrating that the P(VDF-TrFE)/BTO composite membrane has a potential application in personal protective masks with comfortable and reusable properties.

Acoustic Bioprinting of Patient-Derived Organoids for Predicting Cancer Therapy Responses.

Cancer models, which are biologically representative of patient tumors, can predict the treatment responses and help determine the most appropriate cancer treatment for individual patients. Here, a point-of-care testing system called acoustically bioprinted patient-derived microtissues (PDMs) that can model cancer invasion and predict treatment response in individual patients with colorectal cancer (CRC), is reported. The PDMs are composed of patient-derived colorectal tumors and healthy organoids which can be precisely arranged by acoustic bioprinting approach for recapulating primary tissue's architecture. Particularly, these tumor organoids can be efficiently generated and can apprehend histological, genomic, and phenotypical characteristics of primary tumors. Consequently, these PDMs allow physiologically relevant in vitro drug (5-fluorouracil) screens, thus predicting the paired patient's responses to chemotherapy. A correlation between organoid invasion speed and normalized spreading speed of the paired patients is further established. It provides a quantitative indicator to help doctors make better decisions on ultimate anus-preserving operation for extremely low CRC patients. Thus, by combing acoustic bioprinting and organoid cultures, this method may open an avenue to establish complex 3D tissue models for precision and personalized medicine.

Modeling cancer metastasis using acoustically bio-printed patient-derived 3D tumor microtissues.

Cancer metastasis causes most cancer-related deaths, and modeling cancer invasion holds potential in drug discovery and companion diagnostics. Although 2D cocultures have been developed to study cancer invasion, it is challenging to recreate the 3D cancer invasion of an individual cancer patient. Here, we report an acoustic bioprinting technology that can precisely construct tumor microtissues for modeling cancer invasion in 3D. By using acoustic droplet technology, we can precisely encapsulate cancer associated fibroblasts (CAFs) derived from a colorectal cancer patient into gel droplets and print them into a 3D CAF microtissue. After depositing a tumor organoid derived from the same patient, our 3D bio-printed microtissue can be used to model cancer cell migration and invasion from the tumor organoid to the 3D CAF microtissue. We further used 3D bio-printed microtissues to investigate cancer invasion dynamics as well as their treatment response using time-lapse imaging. Thus, our acoustic 3D bioprinting technology can be widely used for establishing various microtissues for modeling cancer invasion and other diseases, highlighting its potential in personalized treatment.

Acoustic Droplet Printing Tumor Organoids for Modeling Bladder Tumor Immune Microenvironment within a Week.

Current organoid models are limited by the incapability of rapidly fabricating organoids that can mimic the immune microenvironment for a short term. Here, an acoustic droplet-based platform is presented to facilitate the rapid formation of tumor organoids, which retains the original tumor immune microenvironment and establishes a personalized bladder cancer tumor immunotherapy model. In combination with a hydrophobic substrate, the acoustic droplet printer can yield a large number of homogeneous and highly viable bladder tumor organoids in vitro within a week. The generated organoids consist of all components of bladder tumor, including diverse immune elements and tumor cells. By coculturing tumor organoids with autologous immune cells for 2 days, tumor reactive T cells are induced in vitro. Furthermore, it is also demonstrated that these tumor-reactive T cells can also enhance the killing efficiency of matched organoids. Because of the easy operation, repeatability, and stability, the proposed acoustic droplet platform will provide a reliable approach for personalized tumor immunotherapy.

Scaffold-free generation of heterotypic cell spheroids using acoustofluidics.

3D cell cultures such as cell spheroids are widely used for tissue engineering, regenerative medicine, and translational medicine, but challenges remain in recapitulating the architectural complexity and spatiotemporal heterogeneity of tissues. Thus, we developed a scaffold-free and versatile acoustofluidic device to fabricate heterotypic cell spheroids with complexity over cell architectures and components. By varying the concentrations of cell suspension, we can precisely control the size of spheroids aggregated by a contact-free acoustic radiation force. By tuning the cell components including tumor cells, fibroblasts, and endothelial cells, heterotypic spheroids were controllably fabricated. These heterotypic spheroids can be used as a proof-of concept to model the spatial organization of tumor tissues. We demonstrated that the assembled components can self-assemble into layered structures as instructed by their cadherin expression. Finally, we demonstrated the acoustic assembly of mouse mammary gland components into spheroids and observed their maturation in culture. To conclude, we developed an acoustofluidic platform to fabricate complex spheroids with multiple components. We envision that this platform will pave the way for the high accuracy of spheroid fabrication and offer broad applications in numerous areas, such as tumor research, tissue engineering, developmental biology, and drug discovery.

Comparison of Postoperative Pain Management Outcomes in the United States and China.

To compare pain management outcomes in postoperative patients from an American hospital and a Chinese hospital. A convenience sample of 244 patients in the United States and 268 patients in China with similar surgical sites completed the American Pain Society Patient Outcome Questionnaire-Revised (APS-POQ-R) and the Pain Management Index (PMI) was calculated on their first postoperative day. Patients in the United States reported a higher score on the "perception of pain management" subscale of the APS-POQ-R and a higher proportion of adequate treatment as measured by the PMI (85.2% vs. 39.0%, p < .001). Patient education and degrees of pain relief predicted patient satisfaction with pain management (item in APS-POQ-R) in patients from both countries. A higher level of compliance with pain management guidelines has contributed to a higher level of perception in patients in the United States. Establishing procedure-specific protocols and clinical pathways may improve pain management outcomes for Chinese patients.

The acoustic droplet printing of functional tumor microenvironments.

The fabrication of functional tissue is important for tissue engineering, regenerative medicine, and biological research. However, current 3D bioprinting technologies mean it is hard to precisely arrange bioinks (composed of cells and materials) in a high-fidelity 3D structure and print cells of multiple types with sufficient concentrations and superior viabilities; this can severely constrain cell growth, interactions, and functions. Here, an acoustic droplet printing method is introduced to solve these problems in 3D bioprinting. Being nozzle-free, the acoustic printer stably enables high-concentration cells, or even cell spheroids, to be printed without clogging. Cell viability (>94%) using post acoustic printing is higher than those obtained with currently used inkjet-based (>85%) and extrusion-based (40-80%) bioprinting methods. Also, this method involves a small printer that can be flexibly integrated, allowing different kinds of bioinks to be printed. Moreover, the limited printability of low-concentration gelatin methacryloyl (5% (w/v) GelMA) materials is overcome by determining the positioning, fluidity (e.g., spreading), and 3D morphology of the GelMA droplets; therefore, high-fidelity 3D constructs can be fabricated. As a proof of concept, a tumor microenvironment consisting of one tumor spheroid surrounded by a high concentration of cancer-associated fibroblasts (CAFs) was constructed; this was able to establish a dynamic tumor invasion function modulated by reciprocal tumor cell-CAF interactions. The nozzle-free, contact-free, and low cell-damage merits of this method will advance bioprinting, allowing the creation of more functional native tissues, organoids, or disease models.

One-Stop Microfluidic Assembly of Human Brain Organoids To Model Prenatal Cannabis Exposure.

Prenatal cannabis exposure (PCE) influences human brain development, but it is challenging to model PCE using animals and current cell culture techniques. Here, we developed a one-stop microfluidic platform to assemble and culture human cerebral organoids from human embryonic stem cells (hESC) to investigate the effect of PCE on early human brain development. By incorporating perfusable culture chambers, air-liquid interface, and one-stop protocol, this microfluidic platform can simplify the fabrication procedure and produce a large number of organoids (169 organoids per 3.5 cm × 3.5 cm device area) without fusion, as compared with conventional fabrication methods. These one-stop microfluidic assembled cerebral organoids not only recapitulate early human brain structure, biology, and electrophysiology but also have minimal size variation and hypoxia. Under on-chip exposure to the psychoactive cannabinoid, Δ-9-tetrahydrocannabinol (THC), cerebral organoids exhibited reduced neuronal maturation, downregulation of cannabinoid receptor type 1 (CB1) receptors, and impaired neurite outgrowth. Moreover, transient on-chip THC treatment also decreased spontaneous firing in these organoids. This one-stop microfluidic technique enables a simple, scalable, and repeatable organoid culture method that can be used not only for human brain organoids but also for many other human organoids including liver, kidney, retina, and tumor organoids. This technology could be widely used in modeling brain and other organ development, developmental disorders, developmental pharmacology and toxicology, and drug screening.

Rapid Microfluidic Formation of Uniform Patient-Derived Breast Tumor Spheroids.

Breast cancer is a highly complex, heterogeneous, and multifactorial disease that poses challenges for rapid and efficient treatment and development of personalized therapy. Here, we describe a rapid and reliable method to generate three-dimensional (3D) tumor spheroids in vitro that recapitulate an individual patient's tumor for testing treatments. By employing droplet microfluidics and scaffold materials, tumor cells were encapsulated into a large number of Matrigel-in-oil droplets with precise control over cell numbers and components per droplet. After removal of the oil, large numbers of uniform tumor spheroids were formed within a few hours via Matrigel-supported cell self-assembly. Our microfluidic technique produces uniform-sized tumor spheroids in less than 1 day. This method was used to reproducibly and rapidly generate uniform-sized tumor spheroids derived from patients' breast tumor tissues. As a proof-of-concept application, this method was used to quickly evaluate cancer treatments. We demonstrated that our microfluidic patient-derived tumor cultures not only preserve the genetic characteristics of the original tumor tissue but also provide heterogeneous responses to targeted therapies within 2 days. We believe this method will enable a timely and reliable 3D in vitro culture model, which may be applicable to personalized treatment prediction, drug discovery, and toxicity testing.

Efficient Detection and Single-Cell Extraction of Circulating Tumor Cells in Peripheral Blood.

Circulating tumor cells (CTCs) play an important role in cancer biology studies. To further elucidate the role of single CTCs in tumor metastasis and prognosis, effective methods must be developed to isolate and encapsulate single CTCs. In this work, a single CTC capture and encapsulation platform based on ZnO nanofibers and surface acoustic waves was constructed. We also demonstrated that this platform can capture and encapsulate single CTCs efficiently. We first validated that the dense ZnO nanofibers provide additional binding sites, resulting in an increased capture efficiency of up to 93.3%. We then demonstrated that the release efficiency was increased to 100% by dissolving the substrate with ultralow concentration (25 mM) phosphoric acid, and the activity of the released cells was not affected. Furthermore, the released cells were suspended in alginate solution and encapsulated single CTCs via droplet-based surface acoustic wave devices. The encapsulating rate of a single cell is up to 13% under a pulse width duration of 520 µs. Few technology based on nanofibers and acoustic tweezers for single-cell encapsulation via acoustic droplet vaporization has been reported. It has a wide range of potential applications to acquire single target cells, which may facilitate further early clinical diagnosis and treatment of cancer patients.

Anaesthetic management of cardiac phaeochromocytoma: A case series.

INTRODUCTION: Primary cardiac phaeochromocytoma is uncommon, with few anaesthetists encountering this rare pathology in clinical practice. Further, there is little information available on the detailed intraoperative and postoperative haemodynamics and principles of the anaesthetic management of this condition. PRESENTATION OF CASE: We present a retrospective, single-centre case series of four patients with cardiac phaeochromocytoma who presented for surgical excision. We describe the perioperative evaluation and management of these patients, consideration of the requirements for cardiopulmonary bypass, and the analgesic and pharmacologic interventions needed to maintain stable perioperative and intraoperative haemodynamics. DISCUSSION: Octreotide scintigraphy, in addition to echocardiography, cardiac MRI and coronary angiography proved vital in the preoperative evaluation of these patients. Preoperative anaesthetic management of cardiac phaeochromocytoma involved alpha-adrenergic blockade, judicious beta-adrenergic blockade and hydration. Intraoperatively, the administration of vasodilatory agents prior to, and vasoconstricting agents with volume therapy after tumour excision, were the key elements of anaesthetic management. Furthermore, we believe that cardiopulmonary bypass plays a pertinent role in cardiac phaeochromocytoma excision and that the risks and benefits of pulmonary artery catheters should be considered before use in these patients. CONCLUSION: Management of cardiac phaeochromocytoma is complex and demands careful perioperative planning and management. Perioperative morbidity is common and anaethetists play an important role in achieving a successful outcome for patients who present for excision of cardiac phaeochromocytoma.

Reliability and Validity of the Chinese Version of the Revised American Pain Society Patient Outcome Questionnaire in Postoperative Patients.

The American Pain Society Patient Outcome Questionnaire and the subsequent revised version are the most frequently reported measures of the quality of pain management. However, the reliability and validity of the revised questionnaire have not been reported in Chinese patients. This study sought to evaluate the psychometric properties of the Chinese version of the revised questionnaire in postoperative patients in China. The study was a descriptive, cross-sectional psychometric study. The revised questionnaire was translated into Chinese according to international guidelines and then administered to participants. The patients' present, average, and worst pain intensity were evaluated in face-to-face interviews. The Pain Management Index was calculated according to the worst pain intensity and the classification of analgesic drugs used by the patients. The continuous items in the revised questionnaire demonstrated excellent construct validity and acceptable internal consistency reliability (0.732). Cronbach's alpha coefficients for the following subscales were acceptable: pain severity and sleep interference (0.773), activity interference (0.812), affective (0.824), and adverse effects (0.636); the exception was for the perception of pain care subscale (0.492). Patients with different anticipated pain management outcomes were differentiated as expected. Satisfaction could be predicted (31.3% of the variance) using subscales and items in the questionnaire. Although our evidence supports the psychometric properties of the Chinese version of the revised questionnaire when tested with postoperative patients, further study is needed, especially on the subscale perception of pain care.

[Non-inferiority study of lornoxicam to patient-controlled analgesia in patients after hysterectomy].

OBJECTIVE: To evaluate the non-inferiority of lornoxicam to fentanyl in patient-controlled intravenous analgesia after hysterectomy. METHODS: In this prospective randomized controlled study, 117 patients who suffered from moderate to severe pain i.e. pain visual analogue scale (VAS) ≥4 after hysterectomy were allocated to receive lornoxicam (Group L) or fentanyl (Group F) for patient-controlled analgesia. The patients were given a loading dose of lornoxicam 4 mg or fentanyl 50 µg after the enrollment according to the patients' grouping and connected to the patient-controlled analgesia device containing lornoxicam 0.4 g/L or fentanyl 5 mg/L with bolus dose set at 2.5 mL and lockout interval set at 10 min. Pain scores were rated using VAS at 6, 12, and 24 h postoperatively. Pain intensity difference (PID) was the difference between pain scores rated immediately after surgery and 6, 12 and 24 h postoperatively. The sum of pain intensity difference over 24 h (SPID-24) was the sum of PID at 6, 12 and 24 h. non-inferiority could be claimed if the lower limit of the 95% confidence interval (CI) for SPID-24 difference between the two groups was greater than pre-specified non-inferiority margin -3. RESULTS: No difference was detected for pain scores at any time point between the two groups. SPID-24 were 12.0±6.1 and 10.2±5.4 (P>0.05). SPID-24 difference between the two groups was 0.66, 95%CI -1.24 to 2.56, and the lower limit greater than non-inferiority margin -3. Adverse effects, such as nausea, vomiting, and drowsiness were significantly less in lornoxicam group than in fentanyl group (P<0.05). CONCLUSION: Lornoxicam is not inferior to the equivalent dose of fentanyl with regard to the margin pre-specified at -3 in reducing moderate to severe postoperative pain after hysterectomy.

[Pharmacokinetic and pharmacodynamic characteristics of the domestic sevoflurane for transabdominal hysterectomy].

OBJECTIVE: To evaluate the clinical efficacy of domestic sevoflurane by comparing the pharmacokinetic and pharmacodynamic characteristics of domestic sevoflurane and an imported product. METHODS: Eighty patients undergoing general anesthesia for transabdominal hysterectomy were equally randomized into domestic sevoflurane group and imported sevoflurane group. The following data were recorded and compared: vital signs; change of sevoflurane concentrations in the induction period and recovery period; the time when inhaled sevoflurane concentration reached half of the pre-set concentration of the vaporizer; the time when the end-tidal sevoflurane concentration reached half of the pre-set concentration of the vaporizer; the time when the end-tidal sevoflurane concentration reached half of inhaled sevoflurane concentration; the time of the end-tidal sevoflurane concentration reached 0. 8 MAC in the induction period; the recovery time; the extubation time; and time to recovery of consciousness. RESULTS: The general conditions of the two groups were not significantly different. The pharmacokinetic and pharmacodynamic parameters at the intra-operative time points as well as the minimal alveolar concentration, the inspired and end-tidal sevoflurane concentrations, and the time to recovery of consciousness also showed no significant differences between the two groups. CONCLUSION: The domestic sevoflurane has similar pharmacokinetic and pharmacodynamic characteristics as the imported products. It can serve as a cost-effective product for transabdominal hysterectomy.

[Caesarean sections performed under general anesthesia].

OBJECTIVE: To analyse the preoperative conditions and intraoperative anesthetic managements of parturients who underwent Caesarean section and explore possible relationship between perianesthetic managements and prognosis of parturients and fetuses. METHODS: A group of 30 parturients who underwent Caesarean sections under general anesthesia were analysed retrospectively. RESULTS: All the 30 Caesarean sections were smooth in terms of both procedure and anesthesia. CONCLUSIONS: General anesthesia is still indicated in Caesarean section, although multiple risks may still exist. Considerate perinatal planning, careful preoperative preparations, and delicate intraoperative managements positively contribute to the good prognosis of parturient and fetus.

Application of lornoxicam to patient-controlled analgesia in patients undergoing abdominal surgeries.

OBJECTIVE: To assess the efficacy and safety of lornoxicam, one non-steroidal anti-inflammatory drug (NSAID) in patient-controlled analgesia (PCA) in patients undergoing abdominal surgeries. METHODS: Thirty-nine patients scheduled for abdominal surgeries were randomly assigned to different PCA treatment groups using either lornoxicam or fentanyl postoperatively. Pain intensity difference (PID) and sum of pain intensity difference (SPID) were used to assess the analgesic efficacy of both drugs during a 24-hour period. RESULTS: The analgesic efficacy of lornoxicam is 1/66 of fentanyl, which was shown by SPID value of 3.250 and 3.058, respectively (P > 0.05). Lornoxicam caused fewer adverse events than fentanyl (33% vs. 68%, P < 0.05). CONCLUSION: In clinic, we can use lornoxicam to treat postoperative pain effectively and with less adverse reactions compared with fentanyl.

[Evaluation of tracheal intubation in critical SARS patients].

OBJECTIVE: To analyze tracheal intubation and respiratory treatment in the critical severe acute respiratory syndrome (SARS) patients. METHODS: Review and analyze tracheal intubation and respiratory treatment in critical SARS patients in intensive care unit (ICU). RESULTS: Three of thirteen patients had been intubated or received tracheotomy before they entered into ICU, the other patients received treatment of nasal cannula or oxygen mask. With the development of the disease, two patients had been intubated because of respiratory failure or tracheotomy. Tracheal intubation was twice made in two patients in order to replace tracheal tubes. CONCLUSIONS: The patient should be intubated or received tracheotomy if non-invasive respiratory support has no effect. Standard protection could protect medical staff from infection under tracheal intubation.

[Influence of obesity on pharmacokinetics and pharmacodynamics of isoflurane].

OBJECTIVE: To observe the effect of obesity on pharmacokinetics and pharmacodynamics of isoflurane. METHODS: Twenty-six patients undergoing cholecystectomy were divided into obese group (Group A, BMI > or = 27, n = 13) and normal body weight group (Group N, BMI < or = 24, n = 13) according to body mass index (BMI). All patients were given to the same isoflurane anesthesia. Inspired and end-expired concentrations of isoflurane were monitored and uptake fraction of isoflurane were calculated. RESULTS: Isoflurane concentrations of vaporizer in Group A [(1.8 +/- 0.3)%] were evidently higher than those in Group N [(1.5 +/- 0.1)%] at all observed points (P < 0.05 or P < 0.01). Uptake fraction of isoflurane in Group A were higher than those in Group N at observed points (P < 0.05, P < 0.01 or P < 0.001), but there were no differences in the time when isoflurane concentration was lowered to 50% and awake time between the two groups after discontinuing inhaling isoflurane. CONCLUSIONS: Obese patients demand higher inspired concentration and uptake of isoflurane than those in normal weight patients but discharge of isoflurane was influenced by obesity within the observed period of (66 +/- 33) min.