A phase IV study to evaluate the safety of fruquintinib in Chinese patients in real-world clinical practice.

INTRODUCTION: Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. METHODS: Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). RESULTS: Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. CONCLUSIONS: The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.

Polyfluorinated Organic Diammonium Induced Lead Iodide ​ Arrangement for Efficient Two-Step-Processed Perovskite Solar Cells.

The inefficient conversion of lead iodide to perovskite has become one of the major challenges in further improving the performance of perovskite solar cells fabricated by the two-step method. Herein, the discontinuous lead iodide layer realized by introduction of a polyfluorinated organic diammonium salt, octafluoro-([1,1'-biphenyl]-4,4'-diyl)-dimethanaminium (OFPP) iodide which does not form low-dimensional perovskites, can enable the satisfactory conversion of lead iodide into perovskite, leading to meliorated crystallinity and enlarged grains in the OFPP modulated perovskite (OFPP-PVK) film. Combined with the effective defect passivation, the OFPP-PVK films show enhanced charge mobility and suppressed charge recombination. Accordingly, the OFPP-based perovskite solar cells exhibit a champion efficiency of 24.76% with better device stability. Moreover, a superior efficiency of 21.04% was achieved in a large-area perovskite module (100 cm2). Our work provides a unique insight into the function of organic diammonium additive in boosting photovoltaic performance.

Chirality-Induced Crystallization and Defect Passivation of Perovskites: Toward High-Performance Solar Cells.

As an additive for perovskites, in addition to functional groups, the steric configuration of molecules is worthy of consideration because it influences perovskite crystallization, thus determining whether defect passivation is effective without any side effects. In this work, the chiral molecules l- and d-pyroglutamic acid (l-PA and d-PA) were chosen as additives for perovskite passivators to reveal the reasons for the differences in passivation between amino acids with different steric configurations. Functional groups, such as the C═O groups and N-H groups of l-PA and d-PA, can passivate the perovskite defects. However, l-PA exhibited a more distorted steric configuration, while d-PA was more planar, leading to differences in the distances between the two C═O groups. Taking the Pb-Pb bond length as a reference, the shorter distance between the two C═O groups of l-PA distorts the perovskite lattice structure, which results in poor device stability. Conversely, the similar distance between the two C═O groups of d-PA promoted the preferred orientational growth of the perovskite. Finally, the d-PA-doped device accomplished an excellent efficiency of 24.11% with an improved open-circuit voltage of 1.17 V. Furthermore, the efficiency of the unencapsulated d-PA-doped device was maintained at 93% in N2 for more than 3000 h and 74% after 500 h of operation at maximum power point tracking under continuous illumination.

Identification and prognostic analysis of candidate biomarkers for lung metastasis in colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent types of malignant tumors. It's vital to explore new biomarkers and potential therapeutic targets in CRC lung metastasis through adopting integrated bioinformatics tools. Multiple cohort datasets and databases were integrated to clarify and verify potential key candidate biomarkers and signal transduction pathways in CRC lung metastasis. DAVID, STRING, UALCAN, GEPIA, TIMER, cBioPortal, THE HUMAN PROTEIN ATLAS, GSEA 4.3.2, FUNRICH 3.1.3, and R 4.2.3 were utilized in this study. The enriched biological processes and pathways modulated by the differentially expressed genes (DEGs) were determined with Gene Ontology, Kyoto Encyclopedia of Genes and Genomes. The search tool Retrieval of Interacting Genes and Cytoscape were used to construct a protein-protein interaction network among DEGs. Four hundred fifty-nine colorectal primary cancer and lung metastatic gene expression profiles were screened from 3 gene expression profiles (GSE41258, GSE68468, and GSE41568). Forty-one upregulated genes and 8 downregulated genes were identified from these 3 gene expression profiles and verified by the transcriptional levels of hub genes in other GEO datasets and The Cancer Genome Atlas database. Two pathways (immune responses and chemokine receptors bind chemokines), 13 key DEGs, 6 hub genes (MMP3, SFTPD, ABCA3, CLU, APOE, and SPP1), and 2 biomarkers (APOE, SPP1) with significantly prognostic values were screened. Forty-nine DEGs were identified as potential candidate diagnostic biomarkers for patients with CRC lung metastasis in present study. Enrichment analysis indicated that immune responses and chemokine receptors bind chemokines may play a leading role in lung metastasis of CRC, and further studies are needed to validate these findings.

Green spaces exposure and the risk of common psychiatric disorders: A meta-analysis.

Objective: To explore the effects of green spaces exposure on common psychiatric disorders. Methods: PubMed, Embase, Web of Science and MEDLINE were screened and articles published prior to November 15, 2023 were included. Analyses were performed on common psychiatric disorders, categorized into depression, anxiety, dementia, schizophrenia, and attention deficit hyperactivity disorder (ADHD). And the subgroup analyses were conducted for depression, anxiety, dementia, and schizophrenia. Results: In total, 2,0064 studies were retrieved, 59 of which were included in our study; 37 for depression, 14 for anxiety, 8 for dementia, 7 for schizophrenia and 5 for ADHD. Green spaces were found to benefit the moderation of psychiatric disorders (OR = 0.91, 95% CI: 0.89 to 0.92). Green spaces positively influence depression (OR = 0.89, 95% CI: 0.86 to 0.93), regardless of the cross-sectional or cohort studies. Green spaces can also help mitigate the risk of anxiety (OR = 0.94, 95%CI:0.92 to 0.96). As an important index for measuring green spaces, a higher normalized difference vegetation index (NDVI) level related to a lower level of depression (OR = 0.95, 95%CI:0.91 to 0.98) and anxiety (OR = 0.95, 95%:0.92 to 0.98). The protection was also found in dementia (OR = 0.95, 95% CI: 0.93 to 0.96), schizophrenia (OR = 0.74, 95% CI: 0.67 to 0.82), and ADHD (OR = 0.89, 95% CI: 0.86 to 0.92) results. Conclusion: Green spaces decrease the risk of psychiatric disorders, including depression, anxiety, dementia, schizophrenia, and ADHD. Further studies on green spaces and psychiatric disorders are needed, and more green spaces should be considered in city planning.

Retrospective analysis of the impact of dose delay and reduction on outcomes of colorectal cancer patients treated with FOLFIRI­based treatment.

Objectives: To determine the relationship between chemotherapy dose delay/reduction with progression-free survival (PFS) and overall survival (OS) in colorectal cancer patients treated with FOLFIRI based first-line chemotherapy in real-world retrospectively study. Methods: We identified 144 eligible patients with advanced CRC who received FOLFIRI as first-line based treatment. The study protocol was submitted to the institutional review board and was exempted. Dose delay was defined as an average delay of more than 3 days (>3 days vs. ≤3 days) from the intended date. Dose reduction (actual dose/standard dose * 100%) ≤85% was considered as chemotherapy reduction in the chemotherapy dose relative to the standard (mg/m2) regimen for all cycles. Relative dose intensity (RDI) ≤80% was described as chemotherapy reduction. OS and PFS were measured using Kaplan-Meier and Cox proportional hazard models. Results: There were 114 patients with chemotherapy dose delay (dose delay >3 days). PFS of patients without dose delay had better survival than patients with dose delay (p = 0.002). There were 28.47% patients treated with dose reduction of 5-Fu. PFS and OS were better in patients without 5-Fu dose reduction than in patients with 5-Fu dose reduction with p values of 0.024 and <0.001, respectively. Patients with high 5-FU RDI had better PFS than patients with low 5-FU RDI (p < 0.001). While, there was no statistical difference in OS between the two groups. Then we stratified the analysis by age. In <65 years cohort, both PFS and OS were better in patients with high 5-Fu RDI than in those with low 5-Fu RDI (p < 0.001, p = 0.005, respectively). But, in ≥65 years cohort, OS were better in patients with low 5-Fu RDI than in those with high 5-Fu RDI (p = 0.025). Moreover, both dose reduction and RDI of irinotecan had no statistically significant difference in both PFS and OS. Conclusion: In the advanced colorectal cancer patients who received FOLFIRI based treatment as first-line regimen, chemotherapy dose delay and reduction dose of 5-Fu were associated with worse survival, especially among patients younger than 65 years.

Malnutrition accelerates the occurrence of infectious complications in patients with chronic kidney disease: A cross-sectional survey of 682 patients with chronic kidney disease.

BACKGROUND: To investigate the influencing factors of infectious complications in patients with chronic kidney disease (CKD) and provide a basis for clinical diagnosis and prognosis evaluation of CKD. METHODS: A total of 682 patients with CKD were selected and divided into CKD stage 1-5 subgroups according to their glomerular filtration rate. Infectious complications, length of hospital stay, and total cost of hospitalization were recorded. The Global Leadership Initiative on Malnutrition (GLIM) diagnostic tool was used to assess the detection rate of malnutrition among patients. Univariate and multivariate analyses were performed in patients with and without infectious complications. RESULTS: The incidence rates of infectious complications in CKD stages 1-5 were 45.6%, 22.7%, 28.3%, 30.8%, and 40.4%, respectively. The overall detection rate of malnutrition among patients based on the GLIM criteria was 16.7%. The total detection rate of severe malnutrition was 14.2%, with all patients with severe malnutrition in CKD stages 3-5. The incidences of infectious complications in patients with and without malnutrition were 62.3% and 29%, respectively. Binary multivariate logistic regression analysis shows that malnutrition is a risk factor for infectious complications in patients with CKD, who are at 2.41 times higher risk than patients without malnutrition. There were significant differences in length of hospital stay and hospitalization costs between the patients with CKD with and without infectious complications (P < 0.01). CONCLUSION: Infectious complications are relatively common in patients with CKD. As CKD advances, the incidence of infectious complications increases. Moreover, malnutrition accelerates the occurrence of infectious complications in patients with CKD.

Case report: Circulating tumor DNA technology displays temporal and spatial heterogeneity in Waldenström macroglobulinemia during treatment with BTK inhibitors.

Background: Waldenström macroglobulinemia (WM) is a rare subtype of B-cell lymphoma. Rituximab-based combination therapy and Bruton's tyrosine kinase (BTK) inhibitors have greatly improved the prognosis of WM. Despite the high response rate and good tolerance of BTK inhibitors in treatment of WM, a proportion of patients still experience disease progression. Case presentation: We report a 55-year-old man with relapsed WM. The patient achieved partial remission after six courses of CHOP chemotherapy and multiple plasma exchanges in initial treatment. He was admitted to the hospital with abdominal distension, and was diagnosed with relapsed WM and subsequently started on zanubrutinib. Disease progression and histological transformation occurred during treatment. We performed liquid biopsies on transformed plasma, tumor tissue and ascites at the same time and found high consistency between ascites and tissues. Moreover, we detected resistance mutations of BTK inhibitors (BTK, PLCG2) in ascites that were not detected in plasma or tissue. Eventually, the patient died during the 15-month follow-up after relapse. Conclusion: We describe a rare case of WM transformation to DLCBCL treated with chemoimmunotherapy and BTK inhibition. We analyzed tumor DNA obtained at different anatomic sites and circulating tumor DNA (ctDNA) derived from plasma and ascites specimens, with apparent significant temporal and spatial heterogeneity. The case specifically highlights the clinical value of ctDNA of ascites supernatant from WM patients, which is a more convenient and relatively noninvasive method compared with traditional invasive tissue biopsy.

Higher Levels of Tumour-Infiltrating Lymphocytes (TILs) are Associated with a Better Prognosis, While CDK5 Plays a Different Role Between Nonmetastatic and Metastatic Colonic Carcinoma.

OBJECTIVE: We investigated the prognostic value of cyclin-dependent kinase 5 (CDK5) in a true population-based cohort of patients with colon cancer. METHODS: 1. Immunohistochemical (IHC) staining was used to retrospectively analyse the expression of CDK5 in colon cancer tissue samples of 296 patients. The χ2 test, Kaplan-Meier method and Cox proportional regression model were used to analyse the difference between the patients with differential expression of CDK5 and with different stages (metastatic and nonmetastatic); 2. The number of tumour-infiltrating lymphocytes (TILs) in tumour sections was determined, and its relationship with prognosis was explored. RESULTS: 1. Among 296 patients stained for CDK5, 18 cases (6.09%) showed negative expression, 77 cases (26.01%) showed weak expression (+1), 124 cases (41.89%) showed medium positive expression (2+), and 77 cases (26.01%) showed strong positive expression (3+). The expression of CDK5 was neither related to mismatch repair nor TILs (p > .05). In non-metastatic patients, longer progression-free survival (PFS) and cancer-specific survival (CSS) were observed in patients with high CDK5 expression (2+ or 3+) than low CDK5 expression (- or 1+), while in metastatic disease, the opposite was true (p < .001). 2. TILs in 226 patients were detected in the study. Among them, 115 cases (50.88%) showed a low number of TILs (TILs-L), and 111 cases (49.12%) showed a high number of TILs (TILs-H). Patients with a TIL ratio greater than .2 had a significantly better CSS (p < .001) or PFS (p = .008) than patients with a lower TIL ratio. By multivariate analysis, TILs-H was a protective factor for CSS, however failed to reach a significant difference (hazard ratio: .59, 95% CI: .33∼1.06, p = .079), and so was the PFS (HR: .65, 95% CI: .29∼1.43, p = .279). CONCLUSION: High expression of CDK5 indicates a good prognosis in nonmetastatic colon cancer, while it is the opposite in metastatic colon cancer, and the expression of CDK5 is unrelated to TILs. Patients with TIL-H have a better prognosis, with a proper cut-off value of 20% for colon cancer.

Downregulation of AC092894.1 promotes oxaliplatin resistance in colorectal cancer via the USP3/AR/RASGRP3 axis.

BACKGROUND: Oxaliplatin resistance is a complex process and has been one of the most disadvantageous factors and indeed a confrontation in the procedure of colorectal cancer. Recently, long non-coding RNAs (lncRNAs) have emerged as novel molecules for the treatment of chemoresistance, but the specific molecular mechanisms mediated by them are poorly understood. METHODS: The lncRNAs associated with oxaliplatin resistance were screened by microarray. lncRNA effects on oxaliplatin chemoresistance were then verified by gain- and loss-of-function experiments. Finally, the potential mechanism of AC092894.1 was explored by RNA pull-down, RIP, and Co-IP experiments. RESULTS: AC092894.1 representation has been demonstrated to be drastically downregulated throughout oxaliplatin-induced drug-resistant CRC cells. In vivo and in vitro experiments revealed that AC092894.1 functions to reverse chemoresistance. Studies on the mechanism suggested that AC092894.1 served as a scaffold molecule that mediated the de-ubiquitination of AR through USP3, thereby increasing the transcription of RASGRP3. Finally, sustained activation of the MAPK signaling pathway induced apoptosis in CRC cells. CONCLUSIONS: In conclusion, this study identified AC092894.1 as a suppressor of CRC chemoresistance and revealed the idea that targeting the AC092894.1/USP3/AR/RASGRP3 signaling axis is a novel option for the treatment of oxaliplatin resistance.

The value of PET/CT for the diagnosis and evaluation of immunotherapy in occult primary renal cell carcinoma: a case report.

Skin and soft tissue diffusion metastasis (also known as occult cancer) is rare in renal cell carcinoma (RCC). Here, we report an extremely rare case of a 67-year-old male patient with occult primary RCC who developed metastases to the gums, skin, and diffuse soft tissue. The primary renal lesion was missed by computed tomography (CT), ultrasound, and 18F-fluorodeoxyglucose positron emission tomography (PET)/CT, and the diagnosis was confirmed by biopsy of gums and subcutaneous nodules. Subsequent enhanced CT revealed a lesion in the left kidney. The patient had progression-free survival of 16 months after treatment with axitinib and pembrolizumab. Pseudoprogression and tumor heterogeneity pose major challenges in the evaluation of immunotherapy. PET/CT is indispensable especially for cases with multiple metastases, widespread distribution of lesions, and major heterogeneity. In this case, the total lesion glycolysis was calculated by PET/CT and was used to evaluate systemic tumor load before and after immunotherapy, which was calculated as the product of the metabolic tumor volume and the mean standardized uptake value of the target lesion, which increased the accuracy of assessing diffuse lesions. Total lesion glycolysis can be used as a new method to quantitatively evaluate the efficacy of immunotherapy.

The predictive model for risk of chemotherapy-induced thrombocytopenia based on antineoplastic drugs for solid tumors in eastern China.

Chemotherapy-related thrombocytopenia (CIT) is a significant adverse event during chemotherapy, which can lead to reduced relative dose intensity, increased risk of serious bleeding and additional medical expenditure. Herein, we aimed to develop and validate a predictive nomogram model for prediction of CIT in patients with solid tumor. From Jun 1, 2018 to Sep 9, 2021, a total of 1541 patients who received 5750 cycles of chemotherapy were retrospectively enrolled. Cox regression analysis was performed to identify predictive factors to establish the nomogram model for CIT. The incidence of chemotherapy-induced thrombocytopenia was 21.03% for patient-based and 10.26% for cycles of chemotherapy. The top five solid tumors with CIT are cervix, gastric, bladder, biliary systemic, and ovarian. The incidence of chemotherapy dose delays in any cycle because of CIT was 5.39%. Multivariate analysis showed that tumor site, treatment line, AST, oxaliplatin, and capecitabine were significantly associated with CIT. Moreover, we established a nomogram model for CIT probability prediction, and the model was well calibrated (Hosme-Lemeshow P = 0.230) and the area under the receiver operating characteristic curve was 0.844 (Sensitivity was 0.625, Specificity was 0.901). We developed a predictive model for chemotherapy-induced thrombocytopenia based on readily available and easily assessable clinical characteristics. The predictive model based on clinical and laboratory indices represents a promising tool in the prediction of CIT, which might complement the clinical management of thrombocytopenia.

The impact of age on outcomes of breast cancer in different hormone receptor and HER2 groups.

OBJECTIVE: The aim of the current study was to explore the association between age and outcomes in breast cancer. METHODS: Patients during 2010-2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and breast cancer-specific death (BCSD) were taken as endpoints. The restrict cubic spline graph (RCS) was used to explore the relationship between age and outcomes in patients, and the cumulative incidence of BCSD and non-BCSD was calculated using the Gray method. Age-specific gene expression profiles were studied using RNA sequence data from the Cancer Genome Atlas (TCGA) database to explore whether there were young age-related gene or gene sets. RESULTS: A total of 142,755 patients with breast cancer were included. The hazard ratio (HR) of OS for Patients with stage I-III breast cancer was roughly stable before 53 years old and increased significantly after that, and the HR of BCSD for these patients showed a U-shaped distribution when plotted against age, with patients younger than 50 years and patients older than 70 years experiencing the worst survival. Further stratified analysis according to molecular subtype revealed that the U-shaped distribution of the HR of BCSD with was only found in the Hormone receptor-positive/HER2-negative (HoR+/HER2-) subgroup. The cumulative incidence plots showed that young age was associated with worse BCSD in the breast cancer patients with stage I-III and HoR+/HER2- subgroup. In stage IV breast cancer, there was a linearity of the relationship between poor OS and increasing age. We failed to find any differentially expressed age-specific genes between 20-40 years and 41-60 years groups in 258 patients with stage I-III and HoR+/HER2- subtype. CONCLUSION: Young age could predict worse BCSD of patient with stage I-III and HoR+/HER2- breast cancer. The escalating therapy was recommended to young age breast cancer with stage I-III and HoR+/HER2- subtype.

Adequate Number of Lymph Nodes Sampled May Determine Appropriate Surgical Modality for Early-Stage NSCLC: A Population-Based Real-World Study.

BACKGROUND: The standard surgical procedure for ≤ 2 cm non-small cell lung cancer (NSCLC), including the number of lymph nodes sampled (nLN) and surgical modality, remains controversial. This study was designed to determine the optimal cohort in which sublobectomy could be an alternative to lobectomy. MATERIALS (OR PATIENTS) AND METHODS: Patients from 1998 to 2017 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The optimal cutoff value of nLN was identified using a restrictive cubic spline graph (RCS). Kaplan-Meier analysis was used to determine cancer-specific survival (CSS). The COX proportional hazard regression model was used to identify the influence of clinical and demographic variables on survival, and propensity score matching (PSM) was used to balance differences in baseline characteristics. Finally, we used an external cohort from a single-center medical institution to verify the conclusions drawn from the SEER database. RESULTS: A total of 6150 patients were included. The sublobectomy subgroup included segmentectomy (308, 5.0%) and wedge resection (1611, 26.2%). The cutoff value for nLN was 7. In the nLN ≥7 subgroup of the PSM cohort, the CSS of segmentectomy and wedge resection was close to that of the lobectomy subgroup (P = .12), whereas in the nLN <7 subgroup, the CSS of the lobectomy subgroup was significantly higher than that of the sublobectomy with P < .001). Surgical methods, nLN, age, sex, and differentiated grade were independent predictors of CSS. External cohort validation: A total of 1106 patients from the Affiliated Jinhua Hospital of Zhejiang University School of Medicine between 2013 and 2020 were included. The grouping criteria were consistent with the SEER database. In the nLN≥7 subgroup, sublobectomy had a survival outcome similar to that of lobectomy (P = .81). CONCLUSION: Sublobectomy and nLN < 7 were strongly associated with poorer CSS for early-stage NSCLC. On the premise of nLN ≥ 7, sublobectomy could provide similar survival outcomes to lobectomy for these patients.

Synergistic Effects of Interfacial Energy Level Regulation and Stress Relaxation via a Buried Interface for Highly Efficient Perovskite Solar Cells.

An electron-transport layer with appropriate energy alignment and enhanced charge transfer is critical for perovskite solar cells (PSCs). In addition, interface stress and lattice distortion are inevitable during the crystallization process of perovskite. Herein, IT-4F is introduced into PSCs at the buried SnO2 and perovskite interface, which assists in releasing the residual stress in the perovskite layer. Meanwhile, the work function of SnO2/IT-4F is lower than that of SnO2, which facilitates charge transfer from perovskite to ETL and consequently leads to a significant improvement in the power conversion efficiency (PCE) to 23.73%. The VOC obtained is as high as 1.17 V, corresponding to a low voltage deficit of 0.38 V for a 1.55 eV bandgap. Consequently, the device based on IT-4F maintains 94% of the initial PCE over 2700 h when stored in N2 and retains 87% of the initial PCE after operation for 1000 h.

Dopant-Free Polymer Hole Transport Materials for Highly Stable and Efficient CsPbI3 Perovskite Solar Cells.

All-inorganic perovskite CsPbI3 contains no volatile organic components and is a thermally stable photoactive material for wide-bandgap perovskite solar cells (PSCs); however, CsPbI3 readily undergoes undesirable phase transitions due to the hygroscopic nature of the ionic dopants used in commonly used hole transport materials. In the current study, the popular donor material PM6 in organic solar cells is used as a hole transport layer (HTL). The benzodithiophene-based backbone-conjugated polymer requires no dopant and leads to a higher power conversion efficiency (PCE) than 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9'-spirobifluorene (Spiro-OMeTAD). Moreover, PM6 also shows priorities in hole mobility, hydrophobicity, cascade energy level alignment, and even defect passivation of perovskite films. With PM6 as the dopant-free HTL, the PSCs achieve a champion PCE of 18.27% with a competitive fill factor of 82.8%. Notably, the present PCE is based on the dopant-free HTL in CsPbI3 PSCs reported thus far. The PSCs with PM6 as the HTL retain over 90% of the initial PCE stored in a glovebox filled with N2 for 3000 h. In contrast, the PSCs with Spiro-OMeTAD as the HTL maintain ≈80% of the initial PCE under the same conditions.

Cost-effectiveness analysis of multiple first-line PD-1 inhibitors immunotherapy strategies for advanced esophageal squamous cell carcinoma / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：评估多种PD-1抑制剂联合化疗用于晚期、复发或转移性食管鳞状细胞癌（ESCC）患者一线治疗的成本效用。方法：基于4项晚期ESCC一线Ⅲ期临床试验（JUPITER-06、ESCORT-1st、ORIENT-15和KEYNOTE-590研究），应用TreeagePro 2011软件建立传统的马尔科夫（Markov）模型，包括无进展生存期（PFS）、疾病进展（PD）和死亡3种状态，以质量调整生命年（QALY）为主要效用指标衡量健康结果，以增量成本-效用比（ICER）为治疗策略经济学效益的评价指标，进一步通过敏感性分析验证结果可靠性。结果：特瑞普利单抗联合化疗组、卡瑞利珠单抗联合化疗组、信迪利单抗联合化疗组、帕博利珠单抗联合化疗组和安慰剂联合化疗组的总成本分别为66 327.58、63 473.64、62 268.18、295 515.26和32 753.79元，效用值分别为0.648、0.605、0.673、0.585和0.536 QALY；其中，信迪利单抗联合化疗组的ICER值为217 018.13元/QALY，低于中国患者意愿支付阈值的242 928元/QALY，是一种相对可接受的治疗策略。敏感性分析显示，贴现率及信迪利单抗的成本对模型影响最大。结论：在中国目前的经济形势下，信迪利单抗联合化疗是ESCC患者可接受的一种一线PD-1抑制剂免疫治疗的策略。

Resection of primary lesion with chemotherapy improves the survival of patients with metastatic colorectal neuroendocrine carcinoma.

OBJECTIVE: To evaluate the effect of resection of primary lesion and chemotherapy on survival of patients with metastatic colorectal neuroendocrine carcinoma (CRNEC). METHODS: Clinical data of 393 patients with metastatic CRNECs between January 2010 and December 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, including 171 patients who received resection of primary lesion and 221 patients who did not undergo surgery. With the propensity score matching method 172 non-operated patients were selected as controls. Kaplan-Meier method and Log-rank test were used to evaluate the survival differences, while the prognostic factors were analyzed by Cox proportional-hazards model. Metastatic CRNEC patients from January 2001 to December 2021 in Affiliated Jinhua Hospital, Zhejiang University School of Medicine were selected for validation. RESULTS: Compared with non-operated patients, patients who received resection had longer cause-specific survival ( P<0.05). Patients with resected positive lymph nodes>8 had a poorer prognosis compared to those with resected positive lymph nodes≤8 ( P<0.05). Multivariate analysis showed that gender, location of primary lesion and treatments were independent risk factors for cause-specific survival in patients with metastatic CRNEC (all P<0.05). For metastatic CRNEC patients with resection of primary lesion, rectal neuroendocrine carcinoma, positive resected lymph nodes≤8 and resection of primary lesion combined with chemotherapy were associated with better cause-specific survival (all P<0.05). CONCLUSIONS: Patients with metastatic CRNEC may benefit from resection of primary lesion, and resection of primary lesion combined with chemotherapy might be the better strategy for metastatic CRNECs. The number of positive lymph nodes resected is correlated with the prognosis of patients.

A Prediction Model for Chemotherapy-Induced Thrombocytopenia Based on Real-World Data and a Close Relationship Between AST/ALT Ratio and Platelet Count in Patients with Solid Tumors.

Objective: Chemotherapy-induced thrombocytopenia (CIT) can lead to chemotherapy dose delay or reduction, and even serious bleeding. This study aimed to develop a CIT-predicting model based on the laboratory indices of cancer patients undergoing chemotherapy. Material and Methods: From Jun 1, 2017 to Dec 30, 2021, a total of 2043 patients who had received 7676 cycles of chemotherapy were retrospectively enrolled. A logistic regression analysis was performed to identify predictive factors, on the basis of which a nomogram model for predicting CIT was established. A bootstrapping technique was applied for internal validation. A generalized additive mixed model (GAMM) was constructed to analyze the trends in the changes of aspartate aminotransferase (AST), ratio of AST to alanine transaminase (ALT) (AST/ALT ratio), and platelet (PLT) count in patients with solid tumors. P values ≤0.05 were considered statistically significant. Results: The patient-based incidence of CIT was 20.51% and the cycle-based incidence was 10.01%. The multivariate analysis showed that AST level, AST/ALT ratio, and total bilirubin (Tbil), white blood cell (WBC), platelet (PLT), hemoglobin (Hb) levels were significantly associated with the risk of CIT. The GAMM analysis showed that PLT level was inversely associated with AST/ALT ratio and AST level, more significantly with AST/ALT ratio. And both exhibited statistically predictive abilities for CIT. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.793, a sensitivity of 0.543 and a specificity of 0.930. Conclusion: The AST/ALT ratio was inversely associated with the CIT risk in cancer patients. The GAMM model based on laboratory indices presented a high accuracy in predicting the risk of CIT, and a potential to be translated into clinical management.

An R-Based Landscape Validation of a Competing Risk Model.

The Cox proportional hazard model is widely applied for survival analyses in clinical settings, but it is not able to cope with multiple survival outcomes. Different from the traditional Cox proportional hazard model, competing risk models consider the presence of competing events and their combination with a nomogram, a graphical calculating device, which is a useful tool for clinicians to conduct a precise prognostic prediction. In this study, we report a method for establishing the competing risk nomogram, that is, the evaluation of its discrimination (i.e., concordance index and area under the curve) and calibration (i.e., calibration curves) abilities, as well as the net benefit (i.e., decision curve analysis). In addition, internal validation using bootstrap resamples of the original dataset and external validation using an external dataset of the established competing risk nomogram were also performed to demonstrate its extrapolation ability. The competing risk nomogram should serve as a useful tool for clinicians to predict prognosis with the consideration of competing risks.