Robust differentiation of human pluripotent stem cells into mural progenitor cells via transient activation of NKX3.1.

Mural cells are central to vascular integrity and function. In this study, we demonstrate the innovative use of the transcription factor NKX3.1 to guide the differentiation of human induced pluripotent stem cells into mural progenitor cells (iMPCs). By transiently activating NKX3.1 in mesodermal intermediates, we developed a method that diverges from traditional growth factor-based differentiation techniques. This approach efficiently generates a robust iMPC population capable of maturing into diverse functional mural cell subtypes, including smooth muscle cells and pericytes. These iMPCs exhibit key mural cell functionalities such as contractility, deposition of extracellular matrix, and the ability to support endothelial cell-mediated vascular network formation in vivo. Our study not only underscores the fate-determining significance of NKX3.1 in mural cell differentiation but also highlights the therapeutic potential of these iMPCs. We envision these insights could pave the way for a broader use of iMPCs in vascular biology and regenerative medicine.

Methadone Conversion Using a 3-Day Switch Strategy in Patients with Cancer on High-Dose Opioids: A Retrospective Study.

INTRODUCTION: Methadone has shown effectiveness in pain control in patients with cancer who are intolerant to other opioids in China. However, the optimal strategy for methadone conversion from previous high doses of opioids in refractory cancer pain remains debatable. This study aimed to describe the efficacy and safety of a 3-day switch (3DS) strategy for methadone conversion in patients with refractory cancer pain on high doses of opioids. METHODS: We retrospectively reviewed 30-day medical records of 70 patients with refractory cancer pain who used a 3DS strategy for methadone conversion from previous high doses of opioids from July 2018 to December 2022. The 3DS strategy indicated that the methadone dose was increased by one third every day for 3 days. Data on the rate of successful conversion, the time to stable analgesia after conversion, the conversion efficiency, the corrected QT (QTc) interval, the actual conversion ratios, adverse events (AEs), and quality of life were analyzed. RESULTS: Seventy patients received 3DS methadone conversion and 64 patients were eligible for analysis. Fifty patients (78%) achieved stable analgesia, and the median time to stable analgesia was 8.14 ± 2.70 (range 6-14) days. The average dose of methadone was 77.94 ± 42.74 mg. The most common AEs (≥ 10%) included constipation, dry mouth, nausea, and cold sweats. The incidence of constipation was reduced post-methadone conversion, and a statistically significant but asymptomatic prolongation of the QTc interval was observed. Additionally, the actual conversion ratios were lower than Ayonrinde's recommended ratios. CONCLUSIONS: The 3DS strategy for methadone conversion is applicable in Chinese patients with refractory cancer pain on high doses of opioids.

Female urinary incontinence in China after 15 years' efforts: Results from large-scale nationwide surveys.

Urinary incontinence (UI) is a disease that quietly yet seriously impacts women's health and represents a global health burden that is often neglected. This study aims to systematically assess the prevalence and dynamics of female UI in China, and can inform further policies and have international implications. This study used three nationwide investigations: A national cross-sectional survey in 2021; another nationwide cross-sectional survey in 2006; and data regarding the institutions and physicians providing pelvic floor rehabilitation services from 2005 to 2019. The weighted prevalence of female UI and its subtypes, including stress UI (SUI), urgency UI (UUI), and mixed UI (MUI), were estimated as primary outcomes. Knowledge, attitude and care-seeking behaviors of UI were evaluated. It was found that the weighted prevalence of female UI was 16.0 % (95% CI, 13.3 %-19.1%) with SUI remaining the predominant subtype (7.0%) in 2021, followed by MUI (6.5%) and UUI (1.9%). The estimated absolute number of Chinese adult women with UI was 85.8 million in 2021. 52.7% (95% CI, 45.9%-59.4 %) of women were aware that UI was a medical condition, and only 10.1% of women with UI sought health care. After 15 years of development, there were 8400 pelvic floor rehabilitation institutions and nearly 10,000 relevant physicians in China-they were found to be associated with UI prevalence. The UI prevalence in China was significantly lower in 2021 compared to that in 2006. Despite the achievement, UI remains a public health problem, especially given China's fast aging and three-child policy. More innovations, especially those that can facilitate care seeking, are needed to address this prevalent yet treatable condition.

A streamlined method to generate endothelial cells from human pluripotent stem cells via transient doxycycline-inducible ETV2 activation.

The development of reliable methods for producing functional endothelial cells (ECs) is crucial for progress in vascular biology and regenerative medicine. In this study, we present a streamlined and efficient methodology for the differentiation of human induced pluripotent stem cells (iPSCs) into induced ECs (iECs) that maintain the ability to undergo vasculogenesis in vitro and in vivo using a doxycycline-inducible system for the transient expression of the ETV2 transcription factor. This approach mitigates the limitations of direct transfection methods, such as mRNA-mediated differentiation, by simplifying the protocol and enhancing reproducibility across different stem cell lines. We detail the generation of iPSCs engineered for doxycycline-induced ETV2 expression and their subsequent differentiation into iECs, achieving over 90% efficiency within four days. Through both in vitro and in vivo assays, the functionality and phenotypic stability of the derived iECs were rigorously validated. Notably, these cells exhibit key endothelial markers and capabilities, including the formation of vascular networks in a microphysiological platform in vitro and in a subcutaneous mouse model. Furthermore, our results reveal a close transcriptional and proteomic alignment between the iECs generated via our method and primary ECs, confirming the biological relevance of the differentiated cells. The high efficiency and effectiveness of our induction methodology pave the way for broader application and accessibility of iPSC-derived ECs in scientific research, offering a valuable tool for investigating endothelial biology and for the development of EC-based therapies.

Pioneer factor ETV2 safeguards endothelial cell specification by recruiting the repressor REST to restrict alternative lineage commitment.

Mechanisms of cell fate specification remain a central question for developmental biology and regenerative medicine. The pioneer factor ETV2 is a master regulator for the endothelial cell (EC) lineage specification. Here, we studied mechanisms of ETV2-driven fate specification using a highly efficient system in which ETV2 directs human induced pluripotent stem cell-derived mesodermal progenitors to form ECs over two days. By applying CUT&RUN, single-cell RNA-sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) analyses, we characterized the transcriptomic profiles, chromatin landscapes, dynamic cis-regulatory elements (CREs), and molecular features of EC cell differentiation mediated by ETV2. This defined the scope of ETV2 pioneering activity and identified its direct downstream target genes. Induced ETV2 expression both directed specification of endothelial progenitors and suppressed acquisition of alternative fates. Functional screening and candidate validation revealed cofactors essential for efficient EC specification, including the transcriptional activator GABPA. Surprisingly, the transcriptional repressor REST was also necessary for efficient EC specification. ETV2 recruited REST to occupy and repress non-EC lineage genes. Collectively, our study provides an unparalleled molecular analysis of EC specification at single-cell resolution and identifies the important role of pioneer factors to recruit repressors that suppress commitment to alternative lineages.

Site-Specifically Modified Peptide Inhibitors of Protein Tyrosine Phosphatase 1B and T-Cell Protein Tyrosine Phosphatase with Enhanced Stability and Improved In Vivo Long-Acting Activity.

Protein tyrosine phosphatase 1B (PTP1B) and TC-PTP can function in a coordinated manner to regulate diverse biological processes including insulin and leptin signaling, T-cell activation, and tumor antigen presentation, which makes them potential targets for several therapeutic applications. We have previously demonstrated that the lipidated BimBH3 peptide analogues were a new class of promising PTP1B inhibitors with once-weekly antidiabetic potency. Herein, we chemically synthesized two series of BimBH3 analogues via site-specific modification and studied their structure-activity relationship. The screened analogues S2, S6, A2-14, A2-17, A2-20, and A2-21 exhibited an improved PTP1B/TC-PTP dual inhibitory activity and achieved good stability in the plasma of mice and dogs, which indicated long-acting potential. In mouse models of type 2 diabetes mellitus (T2DM), the selected analogues S6, S7, A2-20, and A2-21 with an excellent target activity and plasma stability generated once-weekly therapeutic potency for T2DM at lower dosage (0.5 µmol/kg). In addition, evidence was provided to confirm the cell permeability and targeted enrichment of the BimBH3 analogues. In summary, we report here that site-specific modification and long fatty acid conjugation afforded cell-permeable peptidomimetic analogues of BimBH3 with enhanced stability, in vivo activity, and long-acting pharmacokinetic profile. Our findings could guide the further optimization of BimBH3 analogues and provide a proof-of-concept for PTP1B/TC-PTP targeting as a new therapeutic approach for T2DM, which may facilitate the discovery and development of alternative once-weekly anti-T2DM drug candidates.

Effects of Patient-Controlled Transcutaneous Electrical Acupoint Stimulation on Cancer Induced Bone Pain Relief in Patients with Non-Small Cell Lung Cancer: Study Protocol for a Randomized Controlled Trial.

Background: Transcutaneous Electrical Acupoint Stimulation (TEAS) therapy opens up the possibility for individuals with Cancer-induced bone pain (CIBP) to receive a home-based, patient-controlled approach to pain management. The aim of this study is designed to evaluate the efficacy of patient-controlled TEAS (PC-TEAS) for relieving CIBP in patients with non-small cell lung cancer (NSCLC). Methods/Design: This is a study protocol for a prospective, triple-blind, randomized controlled trial. We anticipate enrolling 188 participants with NSCLC bone metastases who are also using potent opioid analgesics from 4 Chinese medical centers. These participants will be randomly assigned in a 1:1 ratio to either the true PC-TEAS or the sham PC-TEAS group. All participants will receive standard adjuvant oncology therapy. The true group will undergo patient-controlled TEAS intervention as needed, while the sham group will follow the same treatment schedule but with non-conductive gel patches. Each treatment course will span 7 days, with a total of 4 courses administered. There will be 4 assessment time points: baseline, the conclusion of weeks 4, 8, and 12. The primary outcome of this investigation is the response rate of the average pain on the Brief Pain Inventory (BPI) scale at week 4 after treatment. Secondary outcomes include pain related indicators, quality of life scale, mood scales, and routine blood counts on the assessment days. Any adverse events will be promptly addressed and reported if they occur. We will manage trial data using the EDC platform, with a data monitoring committee providing regular quality oversight. Discussion: PC-TEAS interventions offer an attempt to achieve home-based acupuncture treatment and the feasibility of achieving triple blinding in acupuncture research. This study is designed to provide more rigorous trial evidence for the adjuvant treatment of cancer-related pain by acupuncture and to explore a safe and effective integrative medicine scheme for CIBP. Trial Registration: ClinicalTrials.gov NCT05730972, registered February 16, 2023.

Transcutaneous electrical acupoint stimulation for cancer-related pain management in patients receiving chronic opioid therapy: a randomized clinical trial.

PURPOSE: The opioid crisis resulting from its use disorder and overdose poses additional challenges for cancer pain management. The American Society of Clinical Oncology Practice Guideline recommends acupuncture therapy for the management of adult cancer-related pain (CRP), but the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) on CRP remains uncertain. METHODS: This 5-week prospective randomized clinical trial was conducted at 2 hospitals in China, and participants with CRP receiving chronic opioid therapy were randomized 1:1 into two groups between December 2014 and June 2018. The true TEAS group underwent 15 sessions of TEAS treatments over 3 consecutive weeks, while the control group received sham stimulation. The primary outcome was the numerical rating scale (NRS) score in the past 24h at week 3. The secondary outcomes included morphine equivalent daily dose, quality of life and adverse events. RESULTS: A total of 159 participants were included in the modified intention-to-treat population. The baseline characteristics were similar in both groups. The mean NRS scores were 0.98 points at week 3 in the true TEAS group and 1.41 points in the sham group, with the mean difference between groups of -0.43 points (P < 0.001; OR = 0.68, P < 0.05). The proportion of patients with NRS reduction more than thirty percentage at week 3 was 50.00% in the true TEAS group and 35.44% in the sham group (RD = 0.15, P > 0.05; RR = 1.41, P > 0.05). No significant difference in pain intensity between the two groups was observed during the follow-up period without TEAS intervention (week 4, OR = 0.83, P > 0.05; week 5, OR = 0.83, P > 0.05). The Karnofsky Performance Status value suggested that patients in the true TEAS group experienced an improved quality of life (Between-group differences: week 3, 3.5%, P < 0.05; week 4, 4.6%, P < 0.001; week 5, 5.6%, P < 0.001). CONCLUSIONS: The 3-week application of TEAS in patients with CRP receiving chronic opioid therapy resulted in a statistically significant reduction in pain scores, but the observed reduction was of uncertain clinical significance. The prolonged analgesic effect of TEAS was not confirmed in this trial. CLINICALTRIAL: GOV: ChiCTR-TRC-13003803.

Genetic and clinical characteristics of ZNF408-related familial exudative vitreoretinopathy.

OBJECTIVE: To analyze the clinical and genetic characteristics of zinc finger protein 408 (ZNF408)-related familial exudative vitreoretinopathy (FEVR) in a Chinese cohort. METHODS: Ninety families from Chongqing and 16 families from Xinjiang were selected according to fundus lesion characteristics. Peripheral venous blood was collected from patients and their families; genomic DNA was extracted for whole exome sequencing. Relationships between genotype and phenotype in patients with ZNF408-related FEVR were analyzed. RESULTS: ZNF408 variants were detected in three patients (2.83%, 3/106). ZNF408 variants in these three probands were all missense mutations at novel sites. One proband had a ZNF408 and LRP5 double-gene variant, and two probands had ZNF408 single-gene variants. Patients with double-gene variants did not display more severe clinical manifestations. CONCLUSIONS: This study expands the spectrum of known ZNF408 variants and confirms that ZNF408 variants can cause FEVR. Most variants detected in this study have not been reported in the literature and are suspected pathogenic variants of FEVR. In patients with FEVR, phenotype and genotype do not necessarily display a direct one-to-one relationship.

Reply to "A better interpretation of data regarding the opioid switching to methadone".

In our article ?Methadone switching for refractory cancer pain' (BMC palliative care, 2022) we explore the efficacy, safety and economics of methadone in treatment of patients with refractory cancer pain in China. Professor Mercadante provided a better interpretation of data regarding the opioid switching to methadone in the Matters Arising. In this article, we answered the questions in Mercadante et al.'s comments one by one.

In-Composition Graded Quantum Barriers for Polarization Manipulation in InGaN-Based Yellow Light-Emitting Diodes.

Highly efficient indium gallium nitride (InGaN)-based yellow light-emitting diodes (LEDs) with low efficiency droop have always been pursued for next-generation displays and lighting products. In this work, we report an InGaN quantum barrier (QB) with linear-increase In-composition along [0001] direction for InGaN-based yellow LEDs. With the In-composition in QBs systematically engineered, three QB structures including linear-increase QB (LIQB), linear-decrease QB (LDQB) and commonly used flat QB (FQB) were investigated by simulation. The results show that the LIQB not only yields enhanced electron confinement, but also contributes to suppressed polarization field. Consequently, the yellow LED incorporated with LIQBs demonstrates improved radiative recombination rates and the efficiency droop is alleviated. Under a current density of 100 A/cm2, the efficiency droop ratios of LEDs with FQBs, LDQBs and LIQBs are 58.7%, 62.2% and 51.5%, respectively. When current density varies from 1 A/cm2 to 60 A/cm2, the blueshift values of peak emission wavelength for LEDs with FQBs, LDQBs and LIQBs are 14.4 nm, 16.5 nm and 13.0 nm, respectively. This work is believed to provide a feasible solution for high-performance InGaN-based LEDs in long-wavelength spectral region.

Methadone switching for refractory cancer pain.

BACKGROUND: Methadone is commonly considered an alternative opioid treatment for refractory cancer pain. This study aims to investigate the efficacy, safety, and cost of methadone in the treatment of refractory cancer pain. METHODS: A retrospective study was conducted in patients who used methadone for refractory cancer pain from April 2016 to December 2020 at a cancer specialized hospital. Pain control, evaluated via pain score and breakthrough pain frequency, and adverse events of methadone were compared with analgesic regimens prior to methadone administration. The factors potentially affecting the switching outcome were analyzed via multivariate analysis. Moreover, the cost of pain control was estimated. RESULTS: Ninety patients received methadone for poor pain control (74.4%), intolerable adverse events (10.0%), or both (15.6%) after prior opioid treatments. Sixty-four patients (71.1%) were successfully switched to methadone with median pain score significantly decreased from 4.0 to 2.0 (p < 0.001) and median daily frequency of breakthrough pain from 3.0 to 0.0 (p < 0.001) at a maintained median conversion ratio of 6.3 [interquartile range (IQR): 4.0-10.0] to prior opioid treatment. Similar adverse event profiles of constipation, nausea, vomiting, and dizziness were observed between methadone and prior opioid regimens. The median daily cost of analgesic regimens was significantly reduced from $19.5 (IQR: 12.3-46.2) to $10.8 (IQR: 7.1-18.7) (p < 0.01) after switching to methadone. The 3-day switch method significantly improved the rate of successful switching compared with the stop and go method (odds ratio = 3.37, 95% CI: 1.30-8.76, p = 0.013). CONCLUSION: Methadone is an effective, safe, and cost-saving treatment for patients with refractory cancer pain.

ß-Elemene Improves Morphine Tolerance in Bone Cancer Pain via N-Methyl-D-Aspartate Receptor 2B Subunit-Mediated µ-Opioid Receptor.

Background: Improving morphine tolerance (MT) is an urgent problem in the clinical treatment of bone cancer pain. Considering that ß-Elemene is widely used in the treatment of cancer pain, we explored the effects and mechanism of ß-Elemene in preventing MT of bone cancer pain. Method: Bone cancer pain and chronic MT rat model was established by injecting MADB106 cells and morphine (10 mg/kg). SH-SY5Y cells were treated with morphine (10 µg/mL) for 48 h to establish a cell model. The mechanical withdrawal threshold and thermal withdrawal latency of rats were detected by mechanical allodynia and thermal hyperalgesia tests, respectively. The protein expressions of µ-opioid receptor (MOPR), cyclic adenosine monophosphate (cAMP), N-methyl-D-aspartate receptor subunit 2B (NR2B), phosphorylated-calmodulin-dependent protein kinase II (p-CaMKII), and CaMKII were detected by western blot. The viability of SH-SY5Y cells was determined by the cell counting kit-8 assay. cAMP content in SH-SY5Y cells was measured by a LANCE cAMP kit. Result: Animal experiments showed that MT strengthened over time, while increased ß-Elemene dosage alleviated MT. The viability of SH-SY5Y cells was down-regulated by high-dose ß-Elemene. In the rat and cell models, long-term morphine treatment decreased the expression of MOPR and increased the cAMP and NR2B expressions and p-CaMKII/CaMKII, while ß-Elemene and siNR2B counteracted the effects of morphine treatment. In addition, siNR2B reversed the effects of ß-Elemene on related protein expressions and cAMP content in the cell model. Conclusion: ß-Elemene improved MT in bone cancer pain through the regulation of NR2B-mediated MOPR.

Pharmacist-Led Management Improves Treatment Adherence and Quality of Life in Opioid-Tolerant Patients With Cancer Pain: A Randomized Controlled Trial.

INTRODUCTION: Opioid-tolerant patients are more likely to deviate from recommended treatments and to experience inadequate analgesia than opioid-naive ones. The aim of this study was to examine whether pharmacist-led management could help improve treatment adherence and quality of life. METHODS: Eligible patients were randomized in a 1:1 ratio to control group and intervention group. The control group received routine education and support, while the intervention group received additional individualized pharmacist-led care. The primary endpoint was treatment adherence in the per-protocol analysis, as evaluated by blinded assessors. An interim analysis was planned when 30% patients completed the study. Alpha was divided into the interim analysis (0.015) and the final analysis (0.035). RESULTS: In the interim analysis (97 and 87 patients in the control and intervention groups, respectively), the primary endpoint was met. Pharmacist-led intervention significantly increased treatment adherence (93.3 vs. 79.8%; OR: 2.25; 95% CI 1.02, 4.94; P = 0.013), quality of life (0.81 ± 0.17 vs. 0.72 ± 0.25; P = 0.008), and reporting of adverse events (82.7 vs. 61.9%; OR: 1.88; 95% CI 1.16, 3.07; P = 0.004). The two groups did not differ in pain control rate (66.7 vs. 57.1%; OR: 1.25; 95% CI 0.87, 1.78; P = 0.218), breakthrough pain-free rate (66.7 vs. 61.9%; OR: 1.12; 95% CI 0.78, 1.59; P = 0.532) and pain score (1.97 ± 1.04 vs. 2.15 ± 1.24; P = 0.522). CONCLUSIONS: Pharmacist-led management improved treatment adherence, quality of life, and the reporting of adverse events in opioid-tolerant patients with cancer pain. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03455023.

Enhanced Optoelectronic Performance of Yellow Light-Emitting Diodes Grown on InGaN/GaN Pre-Well Structure.

InGaN-based long-wavelength light-emitting diodes (LEDs) are indispensable components for the next-generation solid-state lighting industry. In this work, we introduce additional InGaN/GaN pre-wells in LED structure and investigate the influence on optoelectronic properties of yellow (~575 nm) LEDs. It is found that yellow LED with pre-wells exhibits a smaller blue shift, and a 2.2-fold increase in light output power and stronger photoluminescence (PL) intensity compared to yellow LED without pre-wells. The underlying mechanism is revealed by using Raman spectra, temperature-dependent PL, and X-ray diffraction. Benefiting from the pre-well structure, in-plane compressive stress is reduced, which effectively suppresses the quantum confined stark effect. Furthermore, the increased quantum efficiency is also related to deeper localized states with reduced non-radiative centers forming in multiple quantum wells grown on pre-wells. Our work demonstrates a comprehensive understanding of a pre-well structure for obtaining efficient LEDs towards long wavelengths.

Toward efficient long-wavelength III-nitride emitters using a hybrid nucleation layer.

The realization of efficient III-nitride emitters in the green-to-amber region is fundamental to the monolithic integration of multicolor emitters and the development of III-nitride-based full-color high-resolution displays. A hybrid nucleation layer, which includes sputtered AlN and mid-temperature GaN components, was proposed for the development of efficient III-nitride emitters in the green-to-amber region. The mid-temperature GaN component in the hybrid nucleation layer induced the formation of a stacking fault band structure, which effectively relaxed the misfit stress at the GaN/sapphire interface. A reduced dislocation density and in-plane compressive stress in InGaN/GaN multiple quantum wells were obtained on the hybrid nucleation layer in comparison with the conventional sputtered AlN nucleation layer. Consequently, a significantly enhanced internal quantum efficiency and improved light output power were achieved for the LEDs grown on the hybrid nucleation layer. This gain is attributed to the increased localization depth and spatial overlapping of the electron and hole wave functions. In the present study, the hybrid nucleation layer provides a promising approach for the pursuit of efficient III-nitride emitters in the green-to-amber region.

CUL5-ASB6 Complex Promotes p62/SQSTM1 Ubiquitination and Degradation to Regulate Cell Proliferation and Autophagy.

p62/SQSTM1 (sequestosome-1) is a key protein involved in multiple cellular bioprocesses including autophagy, nutrient sensing, cell growth, cell death, and survival. Therefore, it is implicated in human diseases such as obesity and cancer. Here, we show that the CUL5-ASB6 complex is a ubiquitin E3 ligase complex mediating p62 ubiquitination and degradation. Depletion of CUL5 or ASB6 induced p62 accumulation, and overexpression of ASB6 promoted ubiquitination and degradation of p62. Functionally, ASB6 overexpression can inhibit the proliferation of MEF and hepatocellular carcinoma cells by reducing p62 protein level, and impair the occurrence of autophagy. Overall, our study identified a new molecular mechanism regulating p62 stability, which may provide additional insights for understanding the delicate control of p62 and cell proliferation-autophagy control in physiological and pathological settings.

Asymptomatic and Symptomatic Patients With Non-severe Coronavirus Disease (COVID-19) Have Similar Clinical Features and Virological Courses: A Retrospective Single Center Study.

The current outbreak of coronavirus disease 2019 (COVID-19) has been defined as a pandemic by the World Health Organization. We aimed to evaluate the clinical features and virological course of non-severe COVID-19 patients with or without symptoms who were admitted to a Chinese cabin hospital. In this retrospective single center study, we reviewed 252 laboratory-confirmed COVID-19 patients treated at one temporary cabin hospital in Wuhan, China. Demographic, clinical, serial chest computed tomography (CT), and serial viral test data were compared between asymptomatic and symptomatic patients. The association between clinical features and symptomatic status or patient referral status was analyzed. Among all 252 patients, 74 (29.4%) were asymptomatic and 138 (54.76%) had more than two family members who developed COVID-19. The probability for family clustering was similar between asymptomatic and symptomatic patients (59.70 vs. 61.64%, P = 0.79). Asymptomatic patients and symptomatic patients were equally likely to reach a virus-free state during their stay at the cabin hospital (93.15 vs. 86.44%, P = 0.13). The initial chest CT screening showed that 81 (32.1%) patients had no visible pneumonia, 52 (20.6%) had unilateral pneumonia, and 119 (47.2%) had bilateral pneumonia. Symptomatic patients had a higher chance to have bilateral pneumonia (P < 0.0001) and were less likely to show improvement on the follow-up CT scan (P = 0.0002). In total, 69 (27.4%) patients were referred to the designated hospital and only 23 (9.1%) patients were referred due to the progression of pneumonia. Non-severe COVID-19 patients can transmit the disease regardless of their symptomatic status. It is highly recommended that asymptomatic patients be identified and quarantined to eliminate the transmission of COVID-19.

Durvalumab monotherapy as a third-line treatment for extensive-stage small-cell lung cancer: a case report.

The global incidence and mortality rates of lung cancer are the highest of any cancer. Smallcell lung cancer (SCLC) is an undifferentiated carcinoma which accounts for 15-20% of all lung cancers. Compared with the other major lung cancer type, non-small cell lung cancer, SCLC exhibits worse biological behavior, has a higher degree of malignancy, and develops more rapidly. The majority of SCLC present with extensive-stage disease, and the prognosis for these patients remains poor. Recently, immunotherapy has been demonstrated clinical activity in extensive-stage SCLC (ES-SCLC); however, the efficacy and safety of immunotherapy in ES-SCLC needs further confirmation. Durvalumab, a selective, high-affinity human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, showed durable clinical activity and a manageable safety profile in patients with pretreated ES-SCLC as a first-line treatment. Here, we report the case of an ES-SCLC patient who achieved complete remission (CR) of local lesions after receiving durvalumab monotherapy as a third-line treatment, experiencing no obvious immune-related side effects, such as rash, diarrhea, fatigue, myelosuppression, or thyroid dysfunction. No immune-related pulmonary or hepatorenal toxicities occurred. The case suggests that immunotherapy can be selected for third-line or multi-line treatment of ES-SCLC, and anti-PD-L1 antibody may be the better choice for patients who have poor performance status (PS) scores.

Multidisciplinary intervention incorporating pharmacists in management of opioid-naïve patients with moderate to severe cancer pain.

OBJECTIVE: This study aims to investigate the impact of intervention of multidisciplinary team incorporating pharmacists for management of opioid-naïve patients with moderate to severe cancer pain. METHODS: A retrospective cohort study was conducted to compare pre- and post-multidisciplinary intervention groups in opioid-naïve patients with moderate to severe cancer pain. Primary outcome was the proportions of appropriate pain assessment and opioid titration. Secondary outcomes were pain intensity (PI), length of hospital stay, opioid escalation index percentage (OEI%) and incidences of opioid-related adverse events. RESULTS: A total of 400 patients were included in the study (pre-intervention, n = 200; post-intervention, n = 200). Continuous improvement in pain assessment and titration was recorded after intervention. Though no substantial differences existed between groups in PI on the day of discharge, post-intervention group was associated with reduced length of hospital stay as well as decreased proportion of subjects with OEI% >5%. As for safety, significant decreases in constipation and vomiting were seen. CONCLUSION: Findings suggest that interventions of multidisciplinary team incorporating pharmacists could improve cancer pain management for opioid-naïve patients. Pharmacists should be considered as an important member of a multidisciplinary team in good pain management.