Phase I study of trifluridine/tipiracil (TAS-102) plus irinotecan in combination with bevacizumab as a second-line therapy for patients with metastatic colorectal cancer.

PURPOSE: This phase I trial is to determine the recommended dose of the TAS-102, irinotecan plus bevacizumab regimen and assess its safety and efficacy in patients with metastatic colorectal cancer refractory to fluoropyrimidine and oxaliplatin treatment. METHODS: A 3 + 3 designed dose escalation was performed. Patients were administered TAS-102 (30-35 mg/m2 twice daily on days 1-5) and irinotecan (150-165 mg/m2 on day 1) combined with a fixed dose of bevacizumab (5 mg/kg on day 1) every two weeks. The primary endpoint was the determination of the recommended phase II dose. RESULTS: Eighteen patients were enrolled: 6 at the Level 1 (TAS-102 30 mg/m2 twice daily, irinotecan 150 mg/m2 plus bevacizumab 5 mg/kg), six at the Level 2 (TAS-102 35 mg/m2 twice daily, irinotecan 150 mg/m2 plus bevacizumab 5 mg/kg), and six at the Level 3 (TAS-102 30 mg/m2 twice daily, irinotecan 165 mg/m2 plus bevacizumab 5 mg/kg). Five dose-limiting toxicities occurred: one observed at Level 1 (thrombocytopenia), two at Level 2 (neutropenia and diarrhea), and two at Level 3 (fatigue and neutropenia). The RP2D was established as TAS-102 30 mg/m2 twice daily and irinotecan 150 mg/m2 plus bevacizumab 5 mg/kg. The most frequent grade 3/4 treatment-related adverse events were neutropenia (33.3%), diarrhea (16.7%), and thrombocytopenia (11.1%). No treatment-related death occurred. Two patients (11.1%) experienced partial responses and 14 (77.8%) had stable disease. CONCLUSION: The regimen of TAS-102, irinotecan, and bevacizumab is tolerable with antitumor activity for metastatic colorectal cancer patients refractory to first-line fluoropyrimidines and oxaliplatin treatment.

Human epidermal growth factor receptor 2 expression level and combined positive score can evaluate efficacy of advanced gastric cancer.

BACKGROUND: Although treatment options for gastric cancer (GC) continue to advance, the overall prognosis for patients with GC remains poor. At present, the predictors of treatment efficacy remain controversial except for high microsatellite instability. AIM: To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1 (PD-1) inhibitor and chemotherapy. METHODS: We acquired data from 63 patients with human epidermal growth factor receptor 2 (HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital, Chinese Academy of Medical Sciences between November 2020 and October 2022. All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment. RESULTS: As of July 1, 2023, the objective response rate was 61.9%, and the disease control rate was 96.8%. The median progression-free survival (mPFS) for all patients was 6.3 months. The median overall survival was not achieved. Survival analysis showed that patients with a combined positive score (CPS) ≥ 1 exhibited an extended trend in progression-free survival (PFS) when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment. PFS exhibited a trend for prolongation as the expression level of HER2 increased. Based on PFS, we divided patients into two groups: A treatment group with excellent efficacy and a treatment group with poor efficacy. The mPFS of the excellent efficacy group was 8 months, with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery. The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery. Using good/poor efficacy as the endpoint of our study, univariate analysis revealed that both CPS score (P = 0.004) and HER2 expression level (P = 0.015) were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in patients with advanced GC (AGC). Finally, multivariate analysis confirmed that CPS score was a significant influencing factor. CONCLUSION: CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.

FOLFOXIRI plus cetuximab as conversion therapy for unresectable RAS/BRAF wild-type left-sided colorectal cancer with liver-limited metastases: a prospective dual-center pilot study.

Purpose: To explore the efficacy and safety of FOLFOXIRI plus cetuximab regimen as conversion therapy for patients with unresectable RAS/BRAF wild-type colorectal liver-limited metastases (CLM). Patients and methods: This was a dual-center, phase II trial with the rate of no evidence of disease (NED) achieved as the primary endpoint. All enrolled patients with initially unresectable left-sided RAS/BRAF wild-type colorectal liver-limited metastases received a modified FOLFOXIRI plus cetuximab regimen as conversion therapy. Results: Between October 2019 and October 2021, fifteen patients were enrolled. Nine patients (60%) achieved NED. The overall response rate (ORR) was 92.9%, and the disease control rate (DCR) was 100%. The median relapse-free survival (RFS) was 9 (95% CI: 0-20.7) months. The median progression-free survival (PFS) was 13.0 months (95% CI: 5.7-20.5), and the median overall survival (OS) was not reached. The most frequently occurring grade 3-4 adverse events were neutropenia (20%), peripheral neurotoxicity (13.3%), diarrhea (6.7%), and rash acneiform (6.7%). Conclusion: The FOLFOXIRI plus cetuximab regimen displayed tolerable toxicity and promising anti-tumor activity in terms of the rate of NED achieved and response rate in patients with initially unresectable left-sided RAS/BRAF wild-type CLM. This regimen merits further investigation.

Case report: Immunotherapy in rare high TMB pancreatic acinar carcinoma.

This case report details a patient with Pancreatic Acinar Cell Carcinoma (PACC), a rare malignancy with distinctive biological and imaging features. In the absence of standardized treatment protocols for PACC, we embarked on a diagnostic journey that led to the adoption of an innovative therapeutic regimen in our institution. A 45-year-old female patient presented with a pancreatic mass, which was histologically confirmed as PACC following a biopsy. Subsequent genomic profiling revealed a high tumor mutational burden (21.4/Mb), prompting the initiation of combined immunotherapy and targeted therapy. Notably, the patient experienced a unique adverse reaction to the immunotherapy-recurrent subcutaneous soft tissue nodules, particularly in the gluteal and lower limb regions, accompanied by pain, yet resolving spontaneously. Following six cycles of the dual therapy, radiological evaluations indicated a decrease in tumor size, leading to a successful surgical excision. Over a 20-month post-surgical follow-up, the patient showed no signs of disease recurrence. This narrative adds to the existing knowledge on PACC and highlights the potential efficacy of immunotherapy in managing this challenging condition, emphasizing the importance of close monitoring for any adverse reactions.

The Remarkable Role of Indium in Synergistically Optimizing Carrier Concentration and Phase Distribution of AgCuTe-Based Materials.

Carrier regulation has proven to be an effective approach for optimizing the thermoelectric performance of materials. One common method to adjust the carrier concentration is through element doping. In the case of AgCuTe-based materials, it tends to form with cation vacancies, resulting in a high hole concentration and complex phase composition at low temperatures, which also hinders material stability. However, this also offers additional opportunities to manipulate the carrier concentration. In this study, the improved performance of AgCuTe through indium doping is reported, which leads to a reduction in hole concentration. In combination with a significant increase in the effective mass of the carriers, the enhanced Seebeck coefficient is also realized. Particularly, a notable improvement in power factor is observed in the hexagonal phase near room temperature. Furthermore, a lower electron thermal conductivity is achieved, contributing to an average figure of merit value of ≈1.21 (between 523 and 723 K). Additionally, the presence of indium inhibits the formation of the second phase and ensures a homogeneous phase distribution, which reduces the instability arising from phase transition. This work significantly enhances the potential of AgCuTe-based materials for low to medium-temperature applications.

Thermo-growing ion clusters enabled healing strengthening and tough adhesion for highly reliable skin electronics.

Self-healing and self-adhesion capacities are essential for many modern applications such as skin-interfaced electronics for improving longevity and reliability. However, the self-healing efficiency and adhesive toughness of most synthetic polymers are limited to their original network, making reliability under dynamic deformation still challenging. Herein, inspired by the growth of living organisms, a highly stretchable supramolecular elastomer based on thermo-responsive ion clusters and a dynamic polysulfide backbone was developed. Attributed to the synergic growth of ion clusters and dynamic exchange of disulfide bonds, the elastomer exhibited unique healing strengthening (healing efficiency >200%) and thermo-enhanced tough adhesion (interfacial toughness >500 J m-2) performances. To prove its practical application in highly reliable skin electronics, we further composited the elastomer with a zwitterion to prepare a highly conductive ionic elastomer and applied it in wearable strain sensing and long-term electrophysiological detection. This work provides a new avenue to realize high reliability in skin interfaced electronics.

Identification of co-expressed genes and immune infiltration features related to the progression of atherosclerosis.

Atherosclerosis is a chronic inflammatory disease that affects arterial walls and is a leading cause of cardiovascular disease. Gene co-expression modules can provide insight into the molecular mechanisms underlying atherosclerosis progression. In this study, gene co-expression network analysis (WGCNA) was done to identify gene co-expression modules associated with atherosclerosis progression. Before conducting WGCNA, preprocessing and soft power selection were performed on the GSE28829, GSE100927, GSE43292, GSE10334, and GSE16134 datasets ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi ). Co-expression modules were identified using dynamic tree cuts, and their correlations and trait associations were visualized. Enrichment analysis was performed on the blue and magenta modules to identify biological processes (BP) and pathways related to atherosclerosis. The CIBERSORT algorithm was used to predict immune cell infiltration in early and advanced atherosclerotic plaques. We identified 12 co-expression modules, in which blue and magenta were most highly correlated with atherosclerosis progression. The blue module was enriched for inflammation- and immune-related BP and pathways, including phagosome, lysosome, osteoclast differentiation, chemokine signaling pathway, platelet activation, NF-kappa B signaling pathway, Fc gamma R-mediated phagocytosis, lipid and atherosclerosis, autophagy, and apoptosis. The magenta module was significantly enriched for vascular permeability regulation, positive and negative regulation of epithelial to mesenchymal transition, and lamellipodium. Additionally, the CIBERSORT algorithm predicted less abundance of T regulatory cells and monocytes in advanced compared to early atherosclerotic plaques. The enrichment analysis of BP, cellular components, molecular functions, and atherosclerosis-related pathways in the blue and magenta modules showed that inflammation and immune response played a key role in the progression of atherosclerosis. Our study provides insights into the molecular mechanisms underlying atherosclerosis progression and identifies potential therapeutic targets for the treatment of atherosclerosis. The identification of immune cell subtypes associated with atherosclerosis could lead to the development of immunomodulatory therapies to prevent or treat atherosclerosis.

Enhancing Thermoelectric Performance in P-Type Sb2Te3-Based Compounds Through Nb─Ag Co-Doping with Donor-Like Effect.

P-type Sb2Te3 has been recognized as a potential thermoelectric material for applications in low-medium temperature ranges. However, its inherent high carrier concentration and lattice thermal conductivity led to a relatively low ZT value, particularly around room temperature. This study addresses these limitations by leveraging high-energy ball milling and rapid hot-pressing techniques to substantially enhance the Seebeck coefficient and power factor of Sb2Te3, yielding a remarkable ZT value of 0.55 at 323 K due to the donor-like effect. Furthermore, the incorporation of Nb─Ag co-doping increases hole concentration, effectively suppressing intrinsic excitations ≈548 K while maintaining the favorable power factor. Simultaneously, the lattice thermal conductivity can be significantly reduced upon doping. As a result, the ZT values of Sb2Te3-based materials attain an impressive range of 0.5-0.6 at 323 K, representing an almost 100% improvement compared to previous research endeavors. Finally, the ZT value of Sb1.97Nb0.03Ag0.005Te3 escalates to 0.92 at 548 K with a record average ZT value (ZTavg) of 0.75 within the temperature range of 323-573 K. These achievements hold promising implications for advancing the viability of V-VI commercialized materials for low-medium temperature application.

Comparison of clinicopathological characteristics and survival outcomes between gallbladder mucinous adenocarcinoma and gallbladder adenocarcinoma: A propensity score-matched study.

BACKGROUND: Gallbladder mucinous adenocarcinoma (GBMAC) is a rare subtype of gallbladder adenocarcinoma (GBAC), with limited knowledge of its survival outcomes from small case series and single-center retrospective analysis. AIM: To compare the clinicopathological characteristics of GBMAC with typical GBAC and its prognostic factors to gain insights into this field. METHODS: This study was conducted using data from the Surveillance, Epidemiology, and End Results database, including cases of GBMAC and typical GBAC diagnosed from 2010 to 2017. The Pearson chi-square test or Fisher exact test was used to examine the differences in clinicopathological features between these two cohorts. In addition, propensity score matching (PSM) analysis was performed to balance the selection biases. Univariate and multivariate Cox hazards regression analyses were performed to determine independent prognostic factors for cancer-specific survival (CSS) and overall survival (OS). The Kaplan-Meier curves and log-rank tests were used to assess the OS and CSS of GBMAC and typical GBAC patients. RESULTS: The clinicopathological and demographic characteristics of GBMAC were different from typical GBAC. They included a larger proportion of patients with unmarried status, advanced American Joint Committee on Cancer (AJCC) stage, higher T stage, higher N1 stage rate and lower N0 and N2 stage rates (P < 0.05). Multivariate analyses demonstrated that surgery [OS: Hazard ratio (HR) = 2.27, P = 0.0037; CSS: HR = 2.05, P = 0.0151], chemotherapy (OS: HR = 6.41, P < 0.001; CSS: HR = 5.24, P < 0.001) and advanced AJCC stage (OS: Stage IV: HR = 28.99, P = 0.0046; CSS: Stage III: HR = 12.31, P = 0.015; stage IV: HR = 32.69, P = 0.0015) were independent prognostic indicators for OS and CSS of GBMAC patients. Furthermore, after PSM analysis, there was no significant difference between GBMAC and matched typical GBAC patients regarding OS (P = 0.82) and CSS (P = 0.69). CONCLUSION: The biological behaviors of GBMAC are aggressive and significantly different from that of typical GBAC. However, they show similar survival prognoses. Surgery, chemotherapy, and lower AJCC stage were associated with better survival outcomes. Further research is needed in the future to verify these results.

Current neoadjuvant therapy for operable locally advanced esophageal cancer.

Locally advanced esophageal cancer has a poor prognosis, while an increasing number of patients are diagnosed with that. Neoadjuvant therapy has become a hot topic in treating locally advanced esophageal cancer to improve its survival benefit. The efficacy of neoadjuvant therapy followed by surgery has been confirmed by many studies, and neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy are included in the guidelines. In recent years, targeted therapy and immunotherapy have emerged, and more studies are evaluating the efficacy of combining them with neoadjuvant therapy for operable esophageal cancer patients. Even though the preliminary data is disappointing, many trials are still under investigation without improving survival benefits. New indexes used as surrogate endpoints (e.g., major pathologic response and pathological complete response) are emerging to accelerate the development and approval of neoadjuvant drugs. This review summarized the research progress in neoadjuvant therapy for locally advanced esophageal cancer and discussed which primary endpoint should be used in neoadjuvant therapy trials.

Recent advances in targeted therapy for pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PDAC) is a fatal disease with a 5-year survival rate of 8% and a median survival of 6 mo. In PDAC, several mutations in the genes are involved, with Kirsten rat sarcoma oncogene (90%), cyclin-dependent kinase inhibitor 2A (90%), and tumor suppressor 53 (75%-90%) being the most common. Mothers against decapentaplegic homolog 4 represents 50%. In addition, the self-preserving cancer stem cells, dense tumor microenvironment (fibrous accounting for 90% of the tumor volume), and suppressive and relatively depleted immune niche of PDAC are also constitutive and relevant elements of PDAC. Molecular targeted therapy is widely utilized and effective in several solid tumors. In PDAC, targeted therapy has been extensively evaluated; however, survival improvement of this aggressive disease using a targeted strategy has been minimal. There is currently only one United States Food and Drug Administration-approved targeted therapy for PDAC - erlotinib, but the absolute benefit of erlotinib in combination with gemcitabine is also minimal (2 wk). In this review, we summarize current targeted therapies and clinical trials targeting dysregulated signaling pathways and components of the PDAC oncogenic process, analyze possible reasons for the lack of positive results in clinical trials, and suggest ways to improve them. We also discuss emerging trends in targeted therapies for PDAC: combining targeted inhibitors of multiple pathways. The PubMed database and National Center for Biotechnology Information clinical trial website (www.clinicaltrials.gov) were queried to identify completed and published (PubMed) and ongoing (clinicaltrials.gov) clinical trials (from 2003-2022) using the keywords pancreatic cancer and targeted therapy. The PubMed database was also queried to search for information about the pathogenesis and molecular pathways of pancreatic cancer using the keywords pancreatic cancer and molecular pathways.

Research Progress of Interfacial Design between Thermoelectric Materials and Electrode Materials.

Intensive efforts have been conducted to realize the reliable interfacial joining of thermoelectric materials and electrode materials with low interfacial contact resistance, which is an essential step to make thermoelectric materials into thermoelectric devices for industrial application. In this review, the roles of structural integrity, interdiffusion, and contact resistance in long-term reliabilities of thermoelectric modules are outlined first. Then interfacial reactions of near-room-temperature Bi2Te3-based thermoelectric materials and various electrode materials are reviewed comprehensively. We also summarized the joining behavior of the mid-temperature PbTe-based thermoelectric materials and commonly used electrode materials. Subsequently, for other thermoelectric materials systems, i.e., SiGe, CoSb3, and Mg3Sb2, previous attempts to join with some electrode materials are also recapitulated. Finally, some future prospects to further improve the joint reliability in thermoelectric device manufacturing are proposed. We believe that this review will provide guidance for preparing thermoelectric devices and optimizing thermoelectric device design.

Intracellular and extracellular factors of colorectal cancer liver metastasis: a pivotal perplex to be fully elucidated.

Metastasis is the leading cause of death in colorectal cancer (CRC) patients, and the liver is the most common site of metastasis. Tumor cell metastasis can be thought of as an invasion-metastasis cascade and metastatic organotropism is thought to be a process that relies on the intrinsic properties of tumor cells and their interactions with molecules and cells in the microenvironment. Many studies have provided new insights into the molecular mechanism and contributing factors involved in CRC liver metastasis for a better understanding of the organ-specific metastasis process. The purpose of this review is to summarize the theories that explain CRC liver metastasis at multiple molecular dimensions (including genetic and non-genetic factors), as well as the main factors that cause CRC liver metastasis. Many findings suggest that metastasis may occur earlier than expected and with specific organ-anchoring property. The emergence of potential metastatic clones, the timing of dissemination, and the distinct routes of metastasis have been explained by genomic studies. The main force of CRC liver metastasis is also thought to be epigenetic alterations and dynamic phenotypic traits. Furthermore, we review key extrinsic factors that influence CRC cell metastasis and liver tropisms, such as pre-niches, tumor stromal cells, adhesion molecules, and immune/inflammatory responses in the tumor microenvironment. In addition, biomarkers associated with early diagnosis, prognosis, and recurrence of liver metastasis from CRC are summarized to enlighten potential clinical practice, including some markers that can be used as therapeutic targets to provide new perspectives for the treatment strategies of CRC liver metastasis.

A predictive model for early death in elderly patients with gastric cancer: A population-based study.

Background: The mean age of gastric cancer (GC) patients has increased due to the aging society. Elderly GC patients with poor physical status tend to develop complications during the treatment courses, which cause early death. This study aimed to identify risk factors and establish nomograms for predicting total early death and cancer-specific early death in elderly GC patients. Methods: Data for elderly GC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were randomly assigned to a training cohort and a validation cohort. The univariate logistic regression model and backward stepwise logistic regression model were used to identify independent risk factors for early death. Nomograms were constructed to predict the overall risk of early death and their performance was validated by receiver operating characteristic (ROC) curve, calibration curve, decision curve analyses (DCA), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) in both training and validation cohorts. Results: Among the 3102 enrolled patients, 1114 patients died within three months from the first diagnosis and 956 of them died due to cancer-specific causes. Non-Asian or Pacific Islander (API) race, non-cardia/fundus or lesser/greater curvature, higher AJCC stage, no surgery and no chemotherapy were all related to a high risk of both all-cause early death and cancer-specific early death. Higher T stage and N0 stage were only positively related to total early mortality, while liver metastasis was only positively related to cancer-specific early mortality. Based on these identified factors, two nomograms were developed for predicting the risk of all-cause and cancer-specific early death, which showed good performance with the AUC of the nomograms were 0.775 and 0.766, respectively. The calibration curves, DCAs, NRI, and IDI also confirmed the value of these nomograms. Conclusions: These nomogram models were considered a practical tool to identify the early death of elderly GC patients and help provide a more individualized treatment strategy.

Rare Recurrent EWSR1-PLAGL1 Rearranged Intracranial Tumor With Biphasic Epithelioid Differentiation: One Case Report With Literature Review.

EWSR1-rearranged tumors encompass a rare and heterogeneous group of entities with features of the central nervous system (CNS) mesenchymal and primary glial/neuronal tumors. EWSR1-PLAGL1 gene fusion is a particularly rare form of rearrangement. We presented a recurrent intracranial EWSR1-PLAGL1 rearranged tumor and reviewed the relevant literature. In this case, histopathology and immunohistochemistry (IHC) were evaluated for both the primary and relapsed tumors. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) were performed for the relapsed tumor. We compared the morphology, IHC results and molecular features with the previously reported EWSR1-PLAGL1 rearranged CNS tumors. Our case exhibited a unique feature with a variable biphasic pattern of epithelioid differentiation, which differed from the two reported groups. The primary and relapsed tumors both expressed cytokeratin of the focal area with epithelioid differentiation. The recurrent tumor showed an increased proliferation index (average Ki-67 index of 15%) compared with the primary tumor (average Ki-67 index of 5%). NGS showed that TERT promoter mutation was the only molecular change besides EWSR1-PLAGL1 fusion. Our study provides further insight into intracranial tumors with EWSR1-PLAGL1 fusion, representing a distinct CNS tumor with no-reported histological and immunohistochemical features. Future studies, particularly for the biphasic differentiation and the role of TERT promoter mutation were needed to clarify this unusual chromosomal rearrangement in the CNS tumor.

Efficacy and safety of AnluoHuaxian pills on chronic hepatitis B with normal or minimally elevated alanine transaminase and early liver fibrosis: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). AIM OF THE STUDY: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. RESULTS: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. CONCLUSIONS: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.

Source contribution analysis of PM2.5 using Response Surface Model and Particulate Source Apportionment Technology over the PRD region, China.

Identifying the emission source contributions to PM2.5 is essential for a sound PM2.5 pollution control policy. In this study, we conduct a comparative analysis of PM2.5 source contributions over the Pearl River Delta (PRD) region of China using two advanced source contribution modeling techniques: Response Surface Model (RSM) and Particulate Source Apportionment Technology (PSAT). Our comparative analyses show that RSM and PSAT can both reasonably predict the contribution of primary PM2.5 emission sources to PM2.5 formation due to its linear nature. For the secondary PM2.5 formed by the nonlinear reactions among PM2.5 precursors, however, our study shows that PSAT appears to have limitations in quantifying the nonlinear contribution of PM2.5 precursors to emission reductions, while RSM seems to better address the nonlinear relationship among PM2.5 precursors (e.g., PM2.5 disbenefits due to local NOx emission reductions in major cities with high NOx emissions). The pilot study case results show that for the ambient PM2.5 in the central cities (Guangzhou, Shenzhen, Foshan, Dongguan, and Zhongshan) of the PRD, the regional source emissions contribute the most by 42-66%; the dust emissions are the top contribution sources (29-34% by RSM and 27-31% by PSAT), and the mobile sources are listed as the secondary contributors accounting for 16-25% by RSM and 19-30% by PSAT among the anthropogenic emission sources. The city-scale cooperation on emission reductions and the enhancement of dust and mobile emission control are recommended to effectively reduce the ambient PM2.5 concentration in the PRD.

Long-term survival of a patient with pancreatic cancer and lung metastasis: A case report and review of literature.

BACKGROUND: Pancreatic cancer (PC) is a leading cause of cancer-related death, given its poor prognosis and the limited benefits of traditional therapies. As tumors become more genetically disorganized as they progress, genetic mutations might become new markers for us to predict their behavior. Nowadays, many inhibitors can selectively target gene products as a form of targeted therapy, with some showing promise as treatment for various types of cancer. CASE SUMMARY: We describe a rare case of a PC patient with long-term survival of more than 8 yr. The patient was diagnosed with pancreatic ductal adenocarcinoma (PDAC) with BAP1 and PIK3CA gene mutations and Raf1 fusion and achieved partial response twice after treatment with apatinib in combination with chemotherapy. CONCLUSION: BAP1, PIK3CA mutations, and Raf1 fusion are rare in PDAC. Patients with these three gene alterations of PDAC may achieve long-term survival with apatinib. Further research in other contexts is needed to determine whether apatinib has ideal efficacy for PC treatment.

Source impact and contribution analysis of ambient ozone using multi-modeling approaches over the Pearl River Delta region, China.

Quantification of source impacts and contributions is a key element for the design of effective air pollution control policies. In this study, O3 source impacts and contributions were comprehensively assessed over the Pearl River Delta (PRD) region of China using brute-force method (BFM), response surface modeling with BFM (RSM-BFM) and differential method (RSM-DM) respectively, high-order decoupled direct method (HDDM), and ozone source apportionment technology (OSAT). The multi-modeling comparison results indicated that under typical nonlinear atmospheric conditions during the O3 formation, BFM, RSM-BFM, and HDDM seemed to be appropriate for assessing the impact of single source emissions; however, the results of HDDM could deviate from those of BFM when the emission reduction ratio was higher than 50 %. Under multi-source control scenarios, the results of source contribution analyses obtained from RSM-DM and OSAT were reasonably well, but the performance of OSAT was limited by its capability in representing the nonlinearity of O3 response to emission reductions of its precursors, particularly NOx. The results of this pilot study in the PRD showed that the RSM-DM appeared to replicate the nonlinearity of O3 chemistry reasonably well (e.g., O3 disbenefits due to local NOx emission reductions in Guangzhou city). Based on the source contribution results, on-road mobile (including both NOx and VOC emissions) and industrial process (mainly VOC emissions) sources were identified as two major contribution sectors by both RSM-DM and OSAT, contributing an average of 31.5 % and 11.4 % (estimated by RSM-DM) and 29.2 % and 13.0 % (estimated by OSAT) respectively to O3 formation in 9 cities of the PRD. Therefore, the reinforced emission reductions on NOx and VOC from on-road mobile and industrial process sources in the central cities (i.e., Guangzhou, Foshan, Dongguan, Shenzhen, and Zhongshan) were suggested to effectively mitigate the ambient O3 levels in the PRD.

Promising Molecular Targets for the Targeted Therapy of Biliary Tract Cancers: An Overview.

Biliary tract cancer (BTC) is a leading cause of cancer-related death, due to the limited benefits of current systematic therapies and the heterogeneity of the tumor itself. High heterogeneity means that the clinical and molecular features vary between different subtypes of BTC, while the underlying molecular mechanisms remain unclear. Targeted therapy, where inhibitors are developed to selectively combine with targeted molecules in order to block abnormal signaling pathways in BTC, has shown promise as an emerging form of treatment for various types of cancer. In this article, a comprehensive review is conducted to examine potential molecular targets for BTC targeted therapy and their mechanisms. Furthermore, preliminary data published from clinical trials is utilized to analyze the main drugs used to combat BTC. The collective information presented in this article has provided useful insights into the current understanding of BTC.