Ecological environmental flow estimation for rivers with complicated hydraulic conditions.

Estimating ecological environmental flow in tidal rivers is one of the major challenges for sustainable water resource management in estuaries and river basins. This paper presents an ecological environmental flow framework that was developed to accommodate highly dynamic medium tidal estuaries found along the Yellow Sea coast of China. The framework not only proposes a method of water quality-based ecological flow for tidal gate-controlled rivers but also proposes a method of water demand for scouring and silting to protect ports in coastal viscous sediment environments. The framework integrates the instream water requirements of water quality, sediment and basic ecological flow, and considers the temporal and spatial variation differences for the environmental flow requirements of tidal rivers. This study emphasizes the significance and necessity of continuous monitoring of ecological data in determining the environmental flow of tidal rivers. The output of this study could provide vital references for decision-making and management of the water resource allocation and ecological protection in tidal rivers.

[Impact and Mechanism of Medium and Small Flood Regulation in the Three Gorges Reservoir on the Phytoplankton in Tributary Bays].

The regulation of small- and medium-sized floods （RSMF） has become the main mode of regulation in the flood season of the Three Gorges Reservoir （TGR）. To study the response of phytoplankton in the tributary bays of the TGR to the RSMF, a typical eutrophic tributary of the TGR, Xiangxi River, was investigated for the spatiotemporal distribution characteristics of phytoplankton and nutrients in the main and tributary streams from 2020 to 2021. The response characteristics of phytoplankton in the tributary bays to the RSMF were analyzed. The results indicated that during the RSMF, the chlorophyll a （Chl-a） in the water body of the Xiangxi River decreased with the increase in the water level in front of the dam, whereas during the reservoir impounding at the end of flood season, the concentration of Chl-a increased again. During the RSMF, the Chlorophyta and Diatoma were the main communities of planktonic algae in the Xiangxi River. The phytoplankton community changed with the RSMF. When the water level fluctuation increased, diatoms were the main species, whereas when the water level fluctuation was small, blue and green algae were the main species. The concentration of Chl-a was more sensitive to changes in TN concentration. When the flow velocity was >0.25 m·s-1 or the suspended sediment content was >10 mg·L-1, the concentration of Chl-a in the water was inhibited. After 2010, the typical outbreak time of algal blooms in the Xiangxi River Reservoir Bay shifted to the flood season, with only two non-flood season algal blooms. Further attention needs to be paid to the response of algal blooms in the reservoir to small- and medium-sized flood control during the flood season.

VEGFA contributes to tumor property of glioblastoma cells by promoting differentiation of myeloid-derived suppressor cells.

BACKGROUND: Glioblastoma (GBM) is a malignant astrocytic tumor and its progression involves the regulation of vascular endothelial growth factor-A (VEGFA). However, the mechanism of VEGFA in regulating GBM progression remains unclear. METHODS: VEGFA mRNA expression was analyzed by quantitative real-time polymerase chain reaction. Protein expression of VEGFA, cluster of differentiation 9 (CD9), CD81, and transforming growth factor-ß1 (TGF-ß1) was detected by western blotting assay. Flow cytometry assay was conducted to assess cell proliferation, cell apoptosis and myeloid-derived suppressor cell (MDSC) differentiation. TUNEL cell apoptosis detection kit was utilized to analyze cell apoptosis of tumors. Angiogenic capacity was investigated by tube formation assay. Transwell assay was used to assess cell migration and invasion. The effect of VEGFA on tumor formation was determined by a xenograft mouse model assay. Immunohistochemistry assay was used to analyze positive expression rate of VEGFA in tumor tissues. TGF-ß1 level was detected by enzyme-linked immunosorbent assay. RESULTS: VEGFA expression was upregulated in GBM tissues, GBM cells, and exosomes from GBM patients and GBM cells. VEGFA silencing led to decreased cell proliferation, tube formation, migration and invasion and increased cell apoptosis. Moreover, VEGFA knockdown also delayed tumor formation. VEGFA promoted MDSC differentiation and TGF-ß1 secretion by MDSCs by being packaged into exosomes. In addition, TGF-ß1 knockdown displayed similar effects with VEGFA silencing on GBM cell phenotypes, and MDSCs attenuated VEGFA knockdown-induced effects by secreting TGF-ß1 in A172 and U251 cells. CONCLUSION: VEGFA contributed to tumor property of GBM cells by promoting MDSC differentiation and TGF-ß1 secretion by MDSCs, providing potential targets for GBM treatment.

Glioma-derived exosome Lncrna Agap2-As1 promotes glioma proliferation and metastasis by mediating Tgf-ß1 secretion of myeloid-derived suppressor cells.

Background: Glioma (GBM) is the most prevalent malignancy worldwide with high morbidity and mortality. Exosome-mediated transfer of long noncoding RNA (lncRNA) has been reported to be associated with human cancers, containing GBM. Meanwhile, myeloid-derived suppressor cells (MDSCs) play a vital role in mediating the immunosuppressive environments in GBM. Objectives: This study is designed to explore the role and mechanism of exosomal (Exo) lncRNA AGAP2-AS1 on the MDSC pathway in GBM. Methods: AGAP2-AS1, microRNA-486-3p (miR-486-3p), and Transforming growth factor beta-1 (TGF-ß1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, migration, and invasion were detected by 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and Transwell assays. E-cadherin, Vimentin, CD9, CD81, and TGF-ß1 protein levels were examined using Western blot. Exosomes were detected by a transmission electron microscope (TEM). Binding between miR-486-3p and AGAP2-AS1 or TGF-ß1 was predicted by LncBase or TargetScan and then verified using a dual-luciferase reporter assay. Results: AGAP2-AS1 was highly expressed in GBM tissues and cells. Functionally, AGAP2-AS1 absence or TGF-ß1 knockdown repressed tumor cell growth and metastasis. Furthermore, Exo-AGAP2-AS1 from GBM cells regulated TGF-ß1 expression via sponging miR-486-3p in MDSCs. Exo-AGAP2-AS1 upregulation facilitated GBM cell growth and metastasis via the MDSC pathway. Conclusion: Exo-AGAP2-AS1 boosted GBM cell development partly by regulating the MDSC pathway, hinting at a promising therapeutic target for GBM treatment.

Direct synthesis of branched amines enabled by dual-catalyzed allylic C─H amination of alkenes with amines.

Direct conversion of hydrocarbons into amines represents an important and atom-economic goal in chemistry for decades. However, intermolecular cross-coupling of terminal alkenes with amines to form branched amines remains extremely challenging. Here, a visible-light and Co-dual catalyzed direct allylic C─H amination of alkenes with free amines to afford branched amines has been developed. Notably, challenging aliphatic amines with strong coordinating effect can be directly used as C─N coupling partner to couple with allylic C─H bond to form advanced amines with molecular complexity. Moreover, the reaction proceeds with exclusive regio- and chemoselectivity at more steric hinder position to deliver primary, secondary, and tertiary aliphatic amines with diverse substitution patterns that are difficult to access otherwise.

Comparison of manual sutures and laparoscopic stapler for pancreatic stump closure techniques in robotic distal pancreatectomy: a single-center experience.

BACKGROUND: Postoperative pancreatic fistulas (POPFs) are prevalent and major postoperative complications of distal pancreatectomy (DP). There are numerous ways to manage the pancreatic stump. However, no single approach has been shown to be consistently superior. Moreover, the potential role of robotic systems in reducing POPFs has received little attention. METHODS: The clinical data of 119 patients who had consecutively received robotic distal pancreatectomy between January 2019 and December 2022 were retrospectively analyzed. Patients were divided into two groups according to the method of handling the pancreatic stump. The attributes of the patients and the variables during the perioperative period were compared. RESULTS: The analysis included 72 manual sutures and 47 stapler procedures. The manual suture group had a shorter operative time (removing installation time) than the stapler group (125.25 ± 63.04 min vs 153.30 ± 62.03 min, p = 0.019). Additionally, the manual suture group had lower estimated blood loss (50 mL vs 100 mL, p = 0.009) and a shorter postoperative hospital stay. There were no significant differences in the incidence of clinically relevant POPFs between the two groups (18.1% vs 23.4%, P > 0.05). No perioperative death occurred in either group. CONCLUSION: The manual suturing technique was shown to have an incidence of POPFs similar to the stapler technique in robotic distal pancreatectomy and to be safe and feasible.

Highly Reversible Zn Anodes Achieved by Enhancing Ion-Transport Kinetics and Modulating Zn (002) Deposition.

Uncontrolled dendrite growth and water-related side reactions in mild electrolytes are the main causes of poor cycling stability of zinc anodes, resulting in the deterioration of aqueous zinc-based batteries. Herein, a multifunctional fluorapatite (Ca5(PO4)3F) aerogel (FAG) interface layer is proposed to realize highly stable zinc anodes via the integrated regulation of Zn2+ migration kinetics and Zn (002) orientation deposition. Owing to the well-defined aerogel nanochannels and the rich Zn2+ adsorption sites resulting from the ion exchange between Ca2+ and Zn2+, the FAG interface layer could significantly accelerate the Zn2+ migration and effectively homogenize the Zn2+ flux and nucleation sites, thus promoting rapid and uniform Zn2+ migration at the electrode/electrolyte interface. Additionally, during the cycling process, the F atoms from FAG promote the in situ generation of ZnF2, which facilitates the manipulation of the preferred Zn (002) orientation deposition, thus efficiently suppressing dendrite growth and side reactions by combining with the above synergistic effects. Consequently, the FAG-modified Zn anode displays a stable cycle life of over 4000 h at 1 mA cm-2 and exhibits highly reversible Zn plating/stripping behavior. Meanwhile, the Zn||MnO2 full cells exhibit improved cycle stability over 2000 cycles compared with that of the bare Zn, highlighting the virtues of the FAG protective layer for highly reversible Zn anodes. Our work brings the insight in to stabilize Zn anodes and power the commercial applications of aqueous zinc-based batteries.

Achieving Ultra-Stable All-Solid-State Sodium Metal Batteries with Anion-Trapping 3D Fiber Network Enhanced Polymer Electrolyte.

All-solid-state sodium metal batteries paired with solid polymer electrolytes (SPEs) are considered a promising candidate for high energy-density, low-cost, and high-safety energy storage systems. However, the low ionic conductivity and inferior interfacial stability with Na metal anode of SPEs severely hinder their practical applications. Herein, an anion-trapping 3D fiber network enhanced polymer electrolyte (ATFPE) is developed by infusing poly(ethylene oxide) matrix into an electrostatic spun fiber framework loading with an orderly arranged metal-organic framework (MOF). The 3D continuous channel provides a fast Na+ transport path leading to high ionic conductivity, and simultaneously the rich coordinated unsaturated cation sites exposed on MOF can effectively trap anions, thus regulating Na+ concentration distribution for constructing stable electrolyte/Na anode interface. Based on such advantages, the ATFPE exhibits high ionic conductivity and considerable Na+ transference number, as well as enhanced interfacial stability. Consequently, Na/Na symmetric cells using this ATFPE possess cyclability over 600 h at 0.1 mA cm-2 without discernable Na dendrites. Cooperated with Na3 V2 (PO4 )3 cathode, the all-solid-state sodium metal batteries (ASSMBs) demonstrate significantly improved rate and cycle performances, delivering a high discharge capacity of 117.5 mAh g-1 under 0.1 C and rendering high capacity retention of 78.2% after 1000 cycles even at 1 C.

SLC11A2: a promising biomarker and therapeutic target in ovarian cancer.

Ovarian cancer has the highest mortality rate among gynecologic tumors, with a 5-year survival rate of less than 25%. There is an urgent need for early diagnosis and new drugs to reduce the disease burden of ovarian cancer. The aim of this study was to investigate the effectiveness of SLC11A2 as a therapeutic target and marker for ovarian cancer. Expression data of SLC11A2 were obtained from public databases. Then, the biological functions of SLC11A2 were validated in four ovarian cancer cell lines. Finally, we collected ovarian cancer clinical tissues, serum, and plasma exosomes and used immunohistochemistry, Elisa, and liquid chromatography-mass spectrometry (LC-MS) to validate the test efficacy of SLC11A2. The results showed that ovarian cancers with high SLC11A2 mRNA expression had shorter 5-year PFS and MST. Knockdown of SLC11A2 reduced ovarian cancer migration and increased cisplatin-induced apoptosis. Serum SLC11A2 may help improve the detection rate of ovarian cancer.

Dualistic classification of high grade serous ovarian carcinoma has its root in spatial heterogeneity.

INTRODUCTION: Widespread intra-peritoneal metastases is a main feature of high grade serous ovarian carcinoma (HGSOC). Recently, the extent of tumour heterogeneity was used to evaluate the cancer genomes among multi-regions in HGSOC. However, there is no consensus on the effect of tumour heterogeneity on the evolution of the tumour metastasis process in HGSOC. OBJECTIVES: We performed whole-exome sequencing in multiple regions of matched primary and metastatic HGSOC specimens to reveal the genetic mechanisms of ovarian tumourigenesis and malignant progression. METHODS: 63 samples (including ovarian carcinoma, omentum metastasis, and normal tissues) were used. We analyzed the genomic heterogeneity, traced the subclone dissemination and establishment history and compared the different genetic characters of cancer evolutionary models in HGSOC. RESULTS: We found that HGSOC had substantial intra-tumour heterogeneity (median 54.2, range 0 âˆ¼ 106.7), high inter-patient heterogeneity (P < 0.001), but relatively limited intra-patient heterogeneity (P = 0.949). Two COSMIC mutational signatures were identified in HGSOCs: signature 3 was related to homologous recombination, and signature 1 was associated with aging. Two scenarios were identified by phylogenetic reconstruction in our study: 3 cases (33.3 %) showed star topology, and the other 6 cases (66.7 %) displayed tree topology. Compared with star topology group, more driver events were identified in tree topology group (P < 0.001), and occurred more frequently in early stage than in late stage of clonal evolution (P < 0.001). Moreover, compared with the star topology group, the tree topology group showed higher rate of intra-tumour heterogeneity (P = 0.045). CONCLUSION: A dualistic classification model was proposed for the classification of HGSOC based on spatial heterogeneity, which may contribute to better managing patients and providing individual treatment for HGSOC patients.

Ultrasonic Imaging of Cardiovascular Disease Based on Image Processor Analysis of Hard Plaque Characteristics.

Cardiovascular disease detection and analysis using ultrasonic imaging expels errors in manual clinical trials with precise outcomes. It requires a combination of smart computing systems and intelligent image processors. The disease characteristics are analyzed based on the configuration and precise tuning of the processing device. In this article, a characteristic extraction technique (CET) using knowledge learning (KL) is introduced to improve the analysis precision. The proposed method requires optimal selection of disease features and trained similar datasets for improving the characteristic extraction. The disease attributes and accuracy are identified using the standard knowledge update. The image and data features are segmented using the variable processor configuration to prevent false rates. The false rates due to unidentifiable plaque characteristics result in weak knowledge updates. Therefore, the segmentation and data extraction are unanimously performed to prevent feature misleads. The knowledge base is updated using the extracted and identified plaque characteristics for consecutive image analysis. The processor configurations are manageable using the updated knowledge and characteristics to improve precision. The proposed method is verified using precision, characteristic update, training rate, extraction ratio, and time factor.

Spontaneous healing after conservative treatment of isolated grade IV pancreatic duct disruption caused by trauma: A case report.

BACKGROUND: Trauma is a common cause of pancreatic duct disruption. Surgical treatment is recommended in current clinical guidelines for adult pancreatic injury because non-surgical treatments have higher risks of serious complications or even death compared with surgical treatment. CASE SUMMARY: A 22-year-old woman was admitted to Tiantai People's Hospital of Zhejiang Province after 1-h duration of abdominal pain and distension following trauma. The diagnosis was "traumatic pancreatic rupture". The patient's symptoms were not severe, her vital signs were stable, and signs of peritonitis were not obvious. Therefore, conservative treatment could be considered, with the possibility of emergency surgery if necessary. After 2 mo of conservative treatment with duct drainage, the pancreatic duct healed spontaneously with no significant complications. CONCLUSION: We report a case of pancreatic duct disruption in the head and neck caused by trauma that was treated conservatively and healed spontaneously, providing a new choice for clinical practice. For isolated pancreatic injury with rupture of the pancreatic duct in the head and neck, conservative treatment under close observation is feasible.

Protein Panel of Serum-Derived Small Extracellular Vesicles for the Screening and Diagnosis of Epithelial Ovarian Cancer.

Although ovarian cancer, a gynecological malignancy, has the highest fatality rate, it still lacks highly specific biomarkers, and the differential diagnosis of ovarian masses remains difficult to determine for gynecologists. Our study aimed to obtain ovarian cancer-specific protein candidates from the circulating small extracellular vesicles (sEVs) and develop a protein panel for ovarian cancer screening and differential diagnosis of ovarian masses. In our study, sEVs derived from the serum of healthy controls and patients with cystadenoma and ovarian cancer were investigated to obtain a cancer-specific proteomic profile. In a discovery cohort, 1119 proteins were identified, and significant differences in the protein profiles of EVs were observed among groups. Then, 23 differentially expressed proteins were assessed using the parallel reaction monitoring in a validation cohort. Through univariate and multivariate logistic regression analyses, a novel model comprising three proteins (fibrinogen gamma gene (FGG), mucin 16 (MUC16), and apolipoprotein (APOA4)) was established to screen patients with ovarian cancer. This model exhibited an area under the receiver operating characteristic curve (AUC) of 0.936 (95% CI, 0.888-0.984) with 92.0% sensitivity and 82.9% specificity. Another panel comprising serum CA125, sEV-APOA4, and sEV-CD5L showed excellent performance (AUC 0.945 (95% CI, 0.890-1.000), sensitivity of 88.0%, specificity of 93.3%, and accuracy of 89.2%) to distinguish malignancy from benign ovarian masses. Altogether, our study provided a proteomic signature of circulating sEVs in ovarian cancer. The diagnostic proteomic panel may complement current clinical diagnostic measures for screening ovarian cancer in the general population and the differential diagnosis of ovarian masses.

Clinical effect of trans-areolar resection and minimally invasive mammotome biopsy in the treatment of breast fibroadenoma and its impact on the quality of life of patients.

OBJECTIVE: To explore the effects of trans-areolar resection and minimally invasive mammotome biopsy on therapeutic effect. METHODS: A total of 131 patients with breast fibroadenoma were selected as the research subjects. Among them, 58 patients were treated by trans-areolar resection and included in group A (GA), and 73 patients were treated by minimally invasive mammotome biopsy and included in group B (GB). The changes of blood pressure, intraoperative blood loss and incision length in patients were detected before anesthesia, during resection and after operation. The pain score and operation time of patients were analyzed. The incidence of postoperative complications and the therapeutic effect were compared in the two groups. The Vancouver Scar Scale (VSS) was used to assess scar condition of patients in the two groups, and the lower the score, the more normal the skin. After operation, the satisfaction with breast appearance was assessed, and the quality of life was compared between the two groups. RESULTS: During resection, DBP and SBP indexes of blood pressure in GA were lower than GB . The intraoperative blood loss in GA was greater than GB, and the incision length was also greater than GB. The VAS pain score in GA was higher than GB (P<0.05), and operation time was also longer than GB. The incidence of complications in GB was significantly lower than GA. The total effective rate in GB was significantly higher than GA. The scar score in GA was significantly higher than GB. The satisfaction in GB was significantly higher than GA, and the quality of life in GB was higher than GA. All P<0.05. CONCLUSION: Compared with trans-areolar resection, minimally invasive mammotome biopsy has a better therapeutic effect on patients with breast fibroadenoma, and it can improve their quality of life more significantly.

Repeated intracerebral hemorrhage after craniotomy for a distal middle cerebral artery aneurysm: A case report.

RATIONALE: Distal middle cerebral artery aneurysms are very rare in the clinic, and craniotomy clipping is the better treatment after diagnosis. However, patients can also have repeated acute intracerebral hemorrhage after craniotomy for aneurysm, which has not been previously reported. PATIENT CONCERNS: A 24-year-old male patient was admitted to our hospital with headache, nausea, and vomiting. He was well before, had no family history of cerebrovascular disease or hypertension, and had no history of trauma. DIAGNOSES: Computer tomography and digital subtraction angiography of the brain revealed intracranial hematoma and an aneurysm located at the M4 segment of the left middle cerebral artery. INTERVENTIONS: The patient underwent 2 surgeries to treat the aneurysm, followed by 2 operations for acute cerebral hemorrhage. OUTCOMES: Despite repeated surgical treatments, the patient had a poor prognosis and eventually died of respiratory and circulatory failure after repeated brain bleeding. LESSONS: Briefly, it is of great importance to consider the risk factors of cerebral hemorrhage, and provide individualized treatment and psychological counseling for patients with intracerebral hemorrhage.

A comprehensive comparison of data fusion approaches to multi-source precipitation observations: a case study in Sichuan province, China.

With the complex landform and climate in the Sichuan region, the need for practical and scientific research production by only utilising the rainfall data derived from ground stations or satellites has not been satisfied. To overcome this difficulty, rainfall data from 161 meteorological stations in 2016 are used in this study. According to the distribution of stations, 146 rainfall data from 161 meteorological stations in 2016 are used for inverse distance weighted interpolation, and then, linear regression, weighted regression, and Kalman filter fusion and optimal interpolation method data fusion are performed with TRMM 3B42 satellite rainfall data, respectively. Then, 15 meteorological stations evenly distributed in the study area are selected for the accuracy test. The results show that compared with the measurement at ground stations, linear regression shows the best merging effect on rainfall data derived from ground stations and satellite rainfall estimates across the daily scale: the correlation coefficient is the most significantly improved (0.2-0.7) and the reduction in root-mean-square error (RMSE) is the largest. The method is applicable for use in Sichuan Province when merging rainfall data. At the monthly scale, the rainfall data processed by using the Kalman filter present the highest accuracy (0.72-0.84). At this scale, the Kalman filter is more suitable.

Realizing the full reservoir operation potential during the 2020 Yangtze river floods.

Five severe floods occurred in the Yangtze River Basin, China, between July and August 2020, and the Three Gorges Reservoir (TGR) located in the middle Yangtze River experienced the highest inflow since construction. The world's largest cascade-reservoir group, which counts for 22 cascade reservoirs in the upper Yangtze River, cooperated in real time to control floods. The cooperation prevented evacuation of 600,000 people and extensive inundations of farmlands and aquacultural areas. In addition, no water spillage occurred during the flood control period, resulting in a world-record annual output of the TGR hydropower station. This work describes decision making challenges in the cooperation of super large reservoir groups based on a case-study, controlling the 4th and 5th floods (from Aug-14 to Aug-22), the efforts of technicians, multi-departments, and the state, and reflects on these. To realize the full potential of reservoir operation for the Yangtze River Basin and other basins with large reservoir groups globally, we suggest: (i) improve flood forecast accuracy with a long leading time; (ii) strengthen and further develop ongoing research on reservoir group cooperation; and (iii) improve and implement institutional mechanisms for coordinated operation of large reservoir groups.

Clinicopathological Significance and Molecular Mechanism of AKT/GSK3ß Pathway-based Fibrillin-1 Expression in Gastric Cancer Progression.

This research was developed to explore the significance of fibrillin-1 (FBN1) in the progression of gastric cancer and its relationship with the activation of the AKT/glycogen synthase kinase-3beta (GSK3ß) pathway. For this aim, immunohistochemical assays were adopted to detect FBN1 expression in chronic superficial gastritis, chronic atrophic gastritis, gastric cancer, and normal mucosa. The expression of FBN1 in gastric cancer and adjacent tissue samples was detected by reverse transcription-quantitative (RT-q) PCR and Western blot, and the relationship between FBN1 and the clinicopathological features of gastric cancer patients was analyzed. Lentivirus was utilized to construct SGC-7901 gastric cancer cell lines stably overexpressing and silencing FBN1, and the effects on cell proliferation, colony formation, and apoptosis were analyzed. AKT, GSK3ß, and their phosphorylated proteins were detected by Western blot. Results showed that the positive expression rate of FBN1 increased successively in chronic superficial gastritis, chronic atrophic gastritis, and gastric cancer. FBN1 was up-regulated in gastric cancer tissues and correlated with the depth of tumor invasion. Overexpression of FBN1 promoted the proliferation and colony formation of gastric cancer cells, inhibited apoptosis, and promoted the phosphorylation of AKT and GSK3ß. Silencing FBN1 expression inhibited the proliferation and clonal formation of gastric cancer cells, promoted apoptosis, and inhibited the phosphorylation of AKT and GSK3ß. In conclusion, FBN1 was up-regulated in gastric cancer tissues and correlated with the depth of gastric tumor invasion. FBN1 silencing inhibited the progression of gastric cancer through the AKT/GSK3ß pathway.

A Genotype Signature for Predicting Pathologic Complete Response in Locally Advanced Rectal Cancer.

PURPOSE: To construct and validate a predicting genotype signature for pathologic complete response (pCR) in locally advanced rectal cancer (PGS-LARC) after neoadjuvant chemoradiation. METHODS AND MATERIALS: Whole exome sequencing was performed in 15 LARC tissues. Mutation sites were selected according to the whole exome sequencing data and literature. Target sequencing was performed in a training cohort (n = 202) to build the PGS-LARC model using regression analysis, and internal (n = 76) and external validation cohorts (n = 69) were used for validating the results. Predictive performance of the PGS-LARC model was compared with clinical factors and between subgroups. The PGS-LARC model comprised 15 genes. RESULTS: The area under the curve (AUC) of the PGS model in the training, internal, and external validation cohorts was 0.776 (0.697-0.849), 0.760 (0.644-0.867), and 0.812 (0.690-0.915), respectively, and demonstrated higher AUC, accuracy, sensitivity, and specificity than cT stage, cN stage, carcinoembryonic antigen level, and CA19-9 level for pCR prediction. The predictive performance of the model was superior to clinical factors in all subgroups. For patients with clinical complete response (cCR), the positive prediction value was 94.7%. CONCLUSIONS: The PGS-LARC is a reliable predictive tool for pCR in patients with LARC and might be helpful to enable nonoperative management strategy in those patients who refuse surgery. It has the potential to guide treatment decisions for patients with different probability of tumor regression after neoadjuvant therapy, especially when combining cCR criteria and PGS-LARC.

Concurrent Chemoradiotherapy With Nedaplatin Versus Cisplatin in Patients With Stage IIB-IVA Cervical Cancer: A Randomized Phase III Trial.

BACKGROUND: In this trial, we aimed to assess the efficacy and safety of radiotherapy with nedaplatin or cisplatin in patients with locally advanced cervical cancer. METHODS: We conducted an open-label, non-inferiority, phase III, randomized, controlled trial. Eligible patients with stage IIB-IVA cervical carcinoma were randomly assigned to receive either nedaplatin or cisplatin for two cycles concurrently with radiotherapy. We reported the therapy-associated harms and survival. The study was registered with chictr.org.cn, number ChiCTR1800020527. RESULTS: We randomly assigned 68 patients to nedaplatin-based or cisplatin-based concurrent chemoradiotherapy. Study treatment was stopped early after a data analysis found a higher number of patients suffered severe hematologic harms in the nedaplatin group than in the cisplatin group. Patients in the nedaplatin group had a significantly higher frequency of grade 3-4 neutropenia (19·4% vs. 13%; P < 0·001), severe thrombocytopenia (16·1% vs. 4·3%), and grade 1-2 anemia (51·6% vs. 43·5%) than patients in the cisplatin group. The 1-year PFS and OS in the nedaplatin and cisplatin groups were similar. CONCLUSION: Our findings showed that nedaplatin-based concurrent chemoradiotherapy expressed remarkably higher severe hematologic harms which were mortal. Though the results were negative, the experiences and lessons we learned from it were important.