Evaluation of the extended Japan NBI expert team classification of subtype 2B in laterally spreading colorectal tumors based on blue laser imaging.

OBJECTIVES: The Japan NBI Expert Team (JNET) classification has good diagnostic potential for colorectal diseases. We aimed to explore the diagnostic value of the JNET classification type 2B (JNET2B) criteria for colorectal laterally spreading tumors (LSTs) based on magnifying endoscopy with blue laser imaging (ME-BLI) examination. METHODS: Between January 2017 and June 2023, 218 patients who were diagnosed as having JNET2B-type LSTs using ME-BLI were included retrospectively. Endoscopic images were reinterpreted to categorize the LSTs as JNET2B-low (n = 178) and JNET2B-high (n = 53) LSTs. The JNET2B-low and JNET2B-high LSTs were compared based on their histopathological and morphological classifications. RESULTS: Among the 178 JNET2B-low LSTs, 86 (48.3%) were histopathologically classified as low-grade intraepithelial neoplasia, 54 (30.3%) as high-grade intraepithelial neoplasia (HGIN), 37 (20.8%) as intramucosal carcinoma (IMC), and one (0.6%) as superficial invasive submucosal carcinoma (SMC1). Among the 53 JNET2B-high LSTs, five (9.4%) were classified as HGIN, 28 (52.9%) as IMC, 15 (28.3%) as SMC1, and 5 (9.4%) as deep invasive submucosal carcinoma. There were significant differences in this histopathological classification between the two groups (P < 0.001). However, there was no significant difference between JNET2B-low and JNET2B-high LSTs based on their morphological classification (granular vs nongranular) or size (<20 mm vs ≥20 mm). Besides, the κ value for JNET2B subtyping was 0.698 (95% confidence interval 0.592-0.804) between the two endoscopists who reassessed the endoscopic images. CONCLUSION: The JNET2B subtyping of LSTs has a diagnostic potential in the preoperative setting, and may be valuable for treatment decision-making.

Combining genome-wide association study and linkage mapping in the genetic dissection of amylose content in maize (Zea mays L.).

KEY MESSAGE: Integrated linkage and association analysis revealed genetic basis across multiple environments. The genes Zm00001d003102 and Zm00001d015905 were further verified to influence amylose content using gene-based association study. Maize kernel amylose is an important source of human food and industrial raw material. However, the genetic basis underlying maize amylose content is still obscure. Herein, we used an intermated B73 × Mo17 (IBM) Syn10 doubled haploid population composed of 222 lines and a germplasm set including 305 inbred lines to uncover the genetic control for amylose content under four environments. Linkage mapping detected 16 unique QTL, among which four were individually repeatedly identified across multiple environments. Genome-wide association study revealed 17 significant (P = 2.24E-06) single-nucleotide polymorphisms, of which two (SYN19568 and PZE-105090500) were located in the intervals of the mapped QTL (qAC2 and qAC5-3), respectively. According to the two population co-localized loci, 20 genes were confirmed as the candidate genes for amylose content. Gene-based association analysis indicated that the variants in Zm00001d003102 (Beta-16-galactosyltransferase GALT29A) and Zm00001d015905 (Sugar transporter 4a) affected amylose content across multi-environment. Tissue expression analysis showed that the two genes were specifically highly expressed in the ear and stem, respectively, suggesting that they might participate in sugar transport from source to sink organs. Our study provides valuable genetic information for breeding maize varieties with high amylose.

The Neutrophil-to-Albumin Ratio (NAR): A Novel Index in Relation to Clinical Symptoms, Quality of Life, and Psychological Status in Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D).

Introduction: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and alterations in bowel habits. Despite the importance of biomarkers in disease management, the quest for precise and non-invasive biomarkers for IBS continues. Methods: This study focuses on investigating the clinical significance of the neutrophil-to-albumin ratio (NAR) as a potential biomarker in IBS. A cohort of 86 patients diagnosed with diarrhea-predominant IBS (IBS-D) and 106 healthy individuals were assessed for clinical symptoms, quality of life (QOL), psychological status, as well as serum and mucosal cytokine production. Results: Our findings revealed that NAR levels were notably elevated in patients with IBS-D compared to healthy controls. Positive correlations were observed between NAR levels and IBS clinical symptoms, while negative correlations were noted with QOL. Additionally, NAR showed positive associations with anxiety and depression scores, along with significant relationships with cytokine production (serum IL-6, TNF-α, IL-1ß, IL-17A, GM-CSF, IFN-γ, MCP-1; mucosal IL-6, TNF-α, IL-1ß, IL-17A) in IBS-D. Interestingly, patients with lower baseline NAR levels demonstrated potentially better clinical outcomes. Conclusion: The study underscores the potential utility of NAR as a novel biomarker in IBS, emphasizing its role in enhancing disease monitoring, understanding disease pathophysiology, and tailoring treatment strategies for patients with IBS-D.

Incorporation of PD-1 blockade into induction chemotherapy improved tumor response in patients with locoregionally advanced nasopharyngeal carcinoma in a retrospective patient cohort.

OBJECTIVE: To investigate the short-term efficacy and safety of induction chemotherapy (IC) combined with anti-PD-1 immunotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: A total of 217 patients diagnosed with LA-NPC at the First Affiliated Hospital of Nanchang University, including 67 who received IC combined with anti-PD-1 and 150 who received IC, were retrospectively enrolled. Efficacy was evaluated at the end of the IC cycles and one month after radiotherapy based on RECIST v1.1 criteria. Acute toxicities were graded based on the CTCAE v5.0 criteria. Quantitative variables were compared by unpaired t-tests, and categorical variables were evaluated by Fisher Freeman-Halton test or Pearson Chi-square test. RESULTS: At the end of all induction therapy cycles, the objective response rate (ORR) of the IC + anti-PD-1 group was 88.1 % (59/67) as opposed to 70.0 % (105/150) in the IC group. Subgroup analysis showed that patients in both stage Ⅲ and ⅣA achieved a significant improvement in ORR with the inclusion of anti-PD-1 therapy. Patients with T3-4 or N2-3 category appeared to benefit more from anti-PD-1 compared to patients with T1-2 or N0-1 category. However, neither ORR nor the complete response (CR) rate was significantly different between the two treatment groups one month after the end of radiotherapy. In addition, the frequency of Grade 3-4 adverse events were also similar in both groups. CONCLUSIONS: IC combined with anti-PD-1 immunotherapy significantly improved the ORR of LA-NPC patients after induction therapy compared to IC alone.

GPX4 inhibits apoptosis of thyroid cancer cells through regulating the FKBP8/Bcl-2 axis.

GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in cell apoptosis is rarely reported, and its role in apoptosis of thyroid cancer (TC) cell has not been reported. The analysis of TCGA database showed that both GPX4 and FKBP8 were highly expressed in TC tumor tissues; The expression of GPX4 and FKBP8 were positively correlated. The immunohistochemical analysis further confirmed that GPX4 and FKBP8 were highly expressed in TC tumor tissues. In addition, the high expression of GPX4 and FKBP8 were both significantly correlated with the poor prognosis of TC. Silencing GPX4 significantly inhibited the proliferation, induced apoptosis of TC cells, and reduced tumor growth in mice. The co-immunoprecipitation assay revealed a physical interaction between GPX4 and FKBP8 observed in the TC cells. Knockdown of FKBP8 significantly inhibited the proliferation and induced apoptosis of TC cells. Rescue experiments suggested that knockdown of FKBP8 could reverse the strengthens of cell proliferation and apoptosis and the higher expression of FKBP8 and Bcl-2 caused by overexpression of GPX4. Our results suggest that the GPX4/FKBP8/Bcl-2 axis promotes TC development by inhibiting TC cell apoptosis, which provides potential molecular targets for TC therapeutic strategies.

A newly proposed heatstroke-induced coagulopathy score in patients with heat illness: A multicenter retrospective study in China.

PURPOSE: In patients with heatstroke, disseminated intravascular coagulation (DIC) is associated with greater risk of in-hospital mortality. However, time-consuming assays or a complex diagnostic system may delay immediate treatment. Therefore, the present study proposes a new heatstroke-induced coagulopathy (HIC) score in patients with heat illness as an early warning indicator for DIC. METHODS: This retrospective study enrolled patients with heat illness in 24 Chinese hospitals from March 2021 to May 2022. Patients under 18 years old, with a congenital clotting disorder or liver disease, or using anticoagulants were excluded. Data were collected on demographic characteristics, routine blood tests, conventional coagulation assays and biochemical indexes. The risk factors related to coagulation function in heatstroke were identified by regression analysis, and used to construct a scoring system for HIC. The data of patients who met the diagnostic criteria for HIC and International Society on Thrombosis and Haemostasis defined-DIC were analyzed. All statistical analyses were performed using SPSS 26.0. RESULTS: The final analysis included 302 patients with heat illness, of whom 131 (43.4%) suffered from heatstroke, including 7 death (5.3%). Core temperature (OR = 1.681, 95% CI 1.291 - 2.189, p < 0.001), prothrombin time (OR = 1.427, 95% CI 1.175 - 1.733, p < 0.001) and D-dimer (OR = 1.242, 95% CI 1.049 - 1.471, p = 0.012) were independent risk factors for heatstroke, and therefore used to construct an HIC scoring system because of their close relation with abnormal coagulation. A total score ≥ 3 indicated HIC, and HIC scores correlated with the score for International Society of Thrombosis and Hemostasis -DIC (r = 0.8848, p < 0.001). The incidence of HIC (27.5%) was higher than that of DIC (11.2%) in all of 131 heatstroke patients. Meanwhile, the mortality rate of HIC (19.4%) was lower than that of DIC (46.7%). When HIC developed into DIC, parameters of coagulation dysfunction changed significantly: platelet count decreased, D-dimer level rose, and prothrombin time and activated partial thromboplastin time prolonged (p < 0.05). CONCLUSIONS: The newly proposed HIC score may provide a valuable tool for early detection of HIC and prompt initiation of treatment.

CsA promotes trophoblast invasion accompanied by changes in leukaemic inhibitory factor and fibroblast growth factor in peri-implantation blastocysts.

During the early stages of human pregnancy, successful implantation of embryonic trophoblast cells into the endometrium depends on good communication between trophoblast cells and the endometrium. Abnormal trophoblast cell function can cause embryo implantation failure. In this study, we added cyclosporine A (CsA) to the culture medium to observe the effect of CsA on embryonic trophoblast cells and the related mechanism. We observed that CsA promoted the migration and invasion of embryonic trophoblast cells. CsA promoted the expression of leukaemic inhibitory factor (LIF) and fibroblast growth factor (FGF). In addition, CsA promoted the secretion and volume increase in vesicles in the CsA-treated group compared with the control group. Therefore, CsA may promote the adhesion and invasion of trophoblast cells through LIF and FGF and promote the vesicle dynamic process, which is conducive to embryo implantation.

Homotypic antibodies target novel E glycoprotein domains after natural DENV 3 infection/vaccination.

The envelope (E) glycoprotein is the primary target of type-specific (TS) neutralizing antibodies (nAbs) after infection with any of the four distinct dengue virus serotypes (DENV1-4). nAbs can be elicited to distinct structural E domains (EDs) I, II, or III. However, the relative contribution of these domain-specific antibodies is unclear. To identify the primary DENV3 nAb targets in sera after natural infection or vaccination, chimeric DENV1 recombinant encoding DENV3 EDI, EDII, or EDIII were generated. DENV3 EDII is the principal target of TS polyclonal nAb responses and encodes two or more neutralizing epitopes. In contrast, some were individuals vaccinated with a DENV3 monovalent vaccine-elicited serum TS nAbs targeting each ED in a subject-dependent fashion, with an emphasis on EDI and EDIII. Vaccine responses were also sensitive to DENV3 genotypic variation. This DENV1/3 panel allows the measurement of serum ED TS nAbs, revealing differences in TS nAb immunity after natural infection or vaccination.

Connexin43 reduces LPS-induced inflammation in hDPCs through TLR4-NF-κB pathway via hemichannels.

OBJECTIVES: Connexin43 (Cx43) is involved in the inflammation of many tissue types. Dental caries is infectious disease resulting from mineralized tissue dissolution by a specific bacterial population, causing pulp inflammation. However, Cx43's role in dental pulp remains unclear. Here, we investigated the function of Cx43 during pulp inflammation. MATERIALS AND METHODS: We constructed a dentin injury model in Sprague-Dawley rats to investigate changes in Cx43 expression during pulp inflammation. Cx43 was inhibited in human dental pulp cells (hDPCs) that had been stimulated with lipopolysaccharide (LPS) to investigate the effect of Cx43 on inflammatory response. Promotion of TLR4-NF-κB pathway activity and special Cx43 channel inhibitors were used to clarify the function of Cx43 in hDPCs. RESULTS: Dentin injury led to low-level inflammation in dental pulp. Following dentin injury, Cx43 expression initially decreased before gradually recovering to normal levels. Cx43 inhibition reduced LPS-induced expression of inflammatory cytokines and NF-κB pathway activity. Promotion of NF-κB pathway activity counteracted the effect of Cx43 in hDPCs. Furthermore, inhibition of Cx43 hemichannels reduced LPS-induced inflammatory cytokine expression. CONCLUSIONS: Cx43 is involved in inflammation of dental pulp, while its inhibition reduced LPS-induced inflammation in hDPCs through NF-κB pathway via blockage of hemichannels.

Expansion of Betatorquevirus and/or Gammatorquevirus in Patients with Severe Clinical Outcomes of the Liver Diseases.

Anellovirus (AV) is a ubiquitous virus in the human population. Individuals can be infected with multiple AV genera and species to form a heterogeneous repertoire, termed the anellome. Using advanced methods, we examined the anellomes from 12 paired serum and liver samples, as well as 2701 subjects with different clinical diagnoses. Overall, anellomes are remarkably individualized, with significant among-group differences (Kruskal-Wallis test p = 6.6 × 10-162 for richness and p = 7.48 × 10-162 for Shannon entropy). High dissimilarity scores (beta diversity) were observed between patient groups, except for paired serum and liver samples. At the population level, the relative abundance of combinational AV genus Betatorquevirus (torque teno mini viruses, TTMV), and Gammatorquevirus (torque teno midi viruses, TTMDV) exhibited an exponential distribution with a low bound point at 32%. Defined by this value, the AV TTMV/TTMDV-expanded anellome was significantly enriched among patients with acute liver failure (31.7%) and liver transplantation (40.7%), compared with other patient groups (χ2 test: p = 4.1 × 10-8-3.2 × 10-3). Therefore, anellome heterogeneity may be predictive of clinical outcomes in certain diseases, such as liver disease. The consistency of anellome between paired serum and liver samples indicates that a liquid biopsy approach would be suitable for longitudinal studies to clarify the causality of the AV TTMV/TTMDV-expanded anellome in the outcomes of liver disease.

AIE-enabled transfection-free identification and isolation of viable cell subpopulations differing in the level of autophagy.

ABBREVIATIONS: 3-MA, 3-methyladenine; AIE, aggregation-induced emission; AIEgens, aggregation-induced emission luminogens; ATG5, autophagy related 5; BMDM, bone marrow-derived macrophage; CQ, chloroquine; DiD, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate; DiO, 3,3'-dioctadecyloxacarbocyanine perchlorate; DMSO, dimethyl sulfoxide; d-THP-1, differentiated THP-1; FACS, fluorescence activated cell sorting; FBS, fetal bovine serum; FCCP, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone; GABARAP, GABA type A receptor-associated protein; GFP, green fluorescent protein; HBSS, Hanks' balanced salt solution; HPLC, high-performance liquid chromatography; HRP, horseradish peroxidase; IL1B, interleukin 1 beta; KT, an AIE probe composed of a cell-penetrating peptide and an AIEgen tetraphenyl ethylene; LC3-II, lipidated LC3; LDH, lactate dehydrogenase; LIR, LC3-interacting region; LKR, engineered molecular probe composed of an LC3-interacting peptide, a cell-penetrating peptide and a non-AIE fluorescent molecule rhodamine; LKT, engineered molecular probe composed of an LC3-interacting peptide, a cell-penetrating peptide and an AIEgen tetraphenyl ethylene; LPS, lipopolysaccharide; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MEF, mouse embryonic fibroblast; mRFP, monomeric red fluorescent protein; NHS, N-hydroxysuccinimide; NLRP3, NLR family pyrin domain containing 3; PBS, phosphate-buffered saline; PCC, pearson's correlation coefficient; PL, photoluminescence; PMA, phorbol 12-myristate 13-acetate; RAP, rapamycin; RIM, restriction of intramolecular motions; s.e.m., standard error of the mean; SPR, surface plasmon resonance; SQSTM1/p62, sequestosome 1; TAX1BP1, Tax1 binding protein 1; TPE, tetraphenylethylene; TPE-yne, 1-(4-ethynylphenyl)-1,2,2-triphenylethene; Tre, trehalose; u-THP-1: undifferentiated THP-1; UV-Vis, ultraviolet visible.

Nickle-cobalt alloy nanocrystals inhibit activation of inflammasomes.

Activation of inflammasomes-immune system receptor sensor complexes that selectively activate inflammatory responses-has been associated with diverse human diseases, and many nanomedicine studies have reported that structurally and chemically diverse inorganic nanomaterials cause excessive inflammasome activation. Here, in stark contrast to reports of other inorganic nanomaterials, we find that nickel-cobalt alloy magnetic nanocrystals (NiCo NCs) actually inhibit activation of NLRP3, NLRC4 and AIM2 inflammasomes. We show that NiCo NCs disrupt the canonical inflammasome ASC speck formation process by downregulating the lncRNA Neat1, and experimentally confirm that the entry of NiCo NCs into cells is required for the observed inhibition of inflammasome activation. Furthermore, we find that NiCo NCs inhibit neutrophil recruitment in an acute peritonitis mouse model and relieve symptoms in a colitis mouse model, again by inhibiting inflammasome activation. Beyond demonstrating a highly surprising and apparently therapeutic impact for an inorganic nanomaterial on inflammatory responses, our work suggests that nickel- and cobalt-containing nanomaterials may offer an opportunity to design anti-inflammatory nanomedicines for the therapeutics of macrophage-mediated diseases.

Prediction of overall survival after radical gastrectomy using nomograms created by tumor markers.

Prediction of prognosis after radical resection of gastric cancer has not been well established. Therefore, we aimed to establish a prognostic model based on a new score system of patients with gastric cancer. A total of 1235 patients who underwent curative gastrectomy at our hospital from October 2015 to April 2017 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. Construction of the nomogram was based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve. Multivariate analysis showed that tumor size, T, N, carcinoembryonic antigen, CA125, and CA19-9 were independent prognostic factors. The new score model had a greater AUC (The area under the ROC curve) than other systems, and the C-index of the nomogram was highly reliable for evaluating the survival of patients with gastric cancer. Based on the tumor markers and other clinical indicators, we developed a precise model to predict the prognosis of patients with gastric cancer after radical surgery. This score system can be helpful to both surgeons and patients.

A genome-wide co-expression network analysis revealed ZmNRAMP6-mediated regulatory pathway involved in maize tolerance to lead stress.

KEY MESSAGE: A metal transporter ZmNRAMP6 was identified by using a trait-associated co-expression network analysis at a genome-wide level. ZmNRAMP6 confers maize sensitivity to Pb by accumulating it to maize shoots. ZmNRAMP6 knockout detains Pb in roots, activates antioxidant enzymes, and improves Pb tolerance. Lead (Pb) is one of the most toxic heavy metal pollutants, which can penetrate plant cells via root absorption and thus cause irreversible damages to the human body through the food chain. To identify the key gene responsible for Pb tolerance in maize, we performed a trait-associated co-expression network analysis at a genome-wide level, using two maize lines with contrasting Pb tolerances. Finally, ZmNRAMP6 that encodes a metal transporter was identified as the key gene among the Pb tolerance-associated co-expression module. Heterologous expression of ZmNRAMP6 in yeast verified its role in Pb transport. Combined Arabidopsis overexpression and maize mutant analysis suggested that ZmNRAMP6 conferred plant sensitivity to Pb stress by mediating Pb distribution across the roots and shoots. Knockout of ZmNRAMP6 caused Pb retention in the roots and activation of the antioxidant enzyme system, resulting in an increased Pb tolerance in maize. ZmNRAMP6 was likely to transport Pb from the roots to shoots and environment. An integration of yeast one-hybrid and dual-luciferase reporter assay uncovered that ZmNRAMP6 was negatively regulated by a known Pb tolerance-related transcript factor ZmbZIP54. Collectively, knockout of ZmNRAMP6 will aid in the bioremediation of contaminated soil and food safety guarantee of forage and grain corn.

Nasal Acinic Cell Carcinoma Misdiagnosed as Hemangioma of the Nasal Septum.

Acinic cell carcinoma (AciCC) is a low-grade, slow-growing malignant tumor that commonly originates from the parotid gland and occasionally from the minor gland of the oral cavity, but rarely from the nasal cavity. Here, we present a 57-year-old woman who presented with an 8-month history of obstruction and epistaxis of the right nasal cavity. Rhinoscopy revealed a reddish-gray fleshy mass with tiny blood vessels on the surface blocking the right postnaris. Computed tomography showed a 3 × 2 cm2 well-demarcated tumor filling the right nasal common meatus with a clear boundary. There were no signs of local bone erosion in the bony window. Magnetic resonance imaging revealed abnormal signals in the nasal meatus with iso-intensity in the T1W1 sequence with homogeneous enhancement. We diagnosed it as a right nasal hemangioma, and the patient underwent endoscopic resection. However, histopathological evaluation of the surgical specimen confirmed a primary AciCC. The patient refused further radical surgery and instead underwent adjuvant radiotherapy. There was no clinical evidence of recurrence for 2 years, and the patient has returned for follow-up yearly. We discuss the clinical nature of sinonasal AciCC and the treatment of this rare condition.

(±)-Sarcanan A, a pair of new enantiomeric dihydrobenzofuran neolignans from the aerial parts of Sarcandra glabra.

(+)-Sarcanan A (1a) and (-)-Sarcanan A (1b), a pair of new dihydrobenzofuran neolignan enantiomers, together with six known compounds (2-7), were isolated from the aerial parts of Sarcandra glabra. Their structures were elucidated by spectroscopic analysis, and the absolute configurations of 1a and 1b were determined by analyses of the electronic circular dichroism (ECD) data. All compounds were evaluated for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells, and compounds 2-4 exhibited moderate inhibition against NO production.

Cyclosporin A Promotes Invasion and Migration of Extravillous Trophoblast Cells Derived from Human-Induced Pluripotent Stem Cells and Human Embryonic Stem Cells.

Extravillous trophoblast (EVT) cells play an essential role in the maternal-fetal interaction. Although abnormal development and function of EVT cells, including impaired migration and invasion capability, are believed to be etiologically linked to severe pregnancy disorders including pre-eclampsia, the associated molecular mechanisms are not clear due to the lack of an appropriate cell model in vitro. Cyclosporin A (CsA) is a macrolide immunosuppressant and also used in clinic to improve pregnancy outcomes. However, whether CsA has any effects on the function of EVT cells has not been well investigated. In this study, we induced differentiation of human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) into EVT cells (hiPSC-EVT and hESC-EVT cells, respectively) by Y27632, neuregulin-1 (NRG1), A83-01, and matrigel, and collected these derived EVT cells by flow cytometry for sorting cells positive for double human leukocyte antigen-G (HLA-G) and Cytokeratin7 (KRT7), both of which are EVT markers. We then investigated the effects of CsA on the invasion and migration of these derived EVT cells. We found that the hiPSC-EVT and hESC-EVT cells expressed high levels of the EVT markers such as KRT7, integrin alpha 5 (ITGA5), and HLA-G but low levels of OCT4, a stem cell marker, and that CsA significantly promoted the invasion and migration of hiPSC-EVT and hESC-EVT cells compared with HTR-8/SVneo cells. These results represent a possible cell model for studying the function of EVT cells and mechanism of pregnancy-related disorders associated with EVT. In addition, CsA may be used to treat pregnancy complications in clinic associated with deficient EVT function.

Intelligent selection of healthcare supply chain mode - an applied research based on artificial intelligence.

Introduction: Due to the inefficiency and high cost of the current healthcare supply chain mode, in order to adapt to the great changes in the global economy and public health, it is urgent to choose an effective mode for sustainable development of healthcare supply chain. The aim of this paper is to use artificial intelligence systems to make intelligent decisions for healthcare supply chain mode selection. Methods: Firstly, according to the economic benefits, social benefits and environmental benefits of healthcare supply chain, this paper identifies different healthcare supply chain modes in combination with artificial intelligence technology. Secondly, this paper presents the intelligent choice optimization method of healthcare supply chain mode based on deep reinforcement learning algorithm. Finally, the effect of artificial intelligence in healthcare supply chain mode selection is verified by simulation experiment. Results and Discussion: The experimental results show that healthcare supply chain mode selected by artificial intelligence is basically consistent with the target mode, while healthcare supply chain mode selected by the basic selection method, BP neural network method and big data method is different from the target mode, which indicates that AI has more advantages in the selection of medical supply chain mode. Therefore, we recommend the application of artificial intelligence to healthcare supply chain management. This study not only makes up for the ineffective problems of existing methods, but also makes up for the gaps in the application of AI technology in the field of healthcare supply chain. The scientific value of this paper is that the proposed framework and the artificial intelligence algorithm enrich the relevant theories of healthcare supply chain research and provide methodological guidance for intelligent decision-making of healthcare supply chain. At the same time, for medical enterprises, this research provides a new practical guideline for the application of artificial intelligence in the sustainable development and modern management of healthcare supply chain.

Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial.

BACKGROUND: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. METHODS: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. RESULTS: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). CONCLUSIONS: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.