The transcription factor RUNT-like regulates pupal cuticle development via promoting a pupal cuticle protein transcription.

Holometabolous insects undergo morphological remodeling from larvae to pupae and to adults with typical changes in the cuticle; however, the mechanism is unclear. Using the lepidopteran agricultural insect Helicoverpa armigera, cotton bollworm, as a model, we revealed that the transcription factor RUNT-like (encoded by Runt-like) regulates the development of the pupal cuticle via promoting a pupal cuticle protein gene (HaPcp) expression. The HaPcp was highly expressed in the epidermis and wing during metamorphosis and was found being involved in pupal cuticle development by RNA interference (RNAi) analysis in larvae. Runt-like was also strongly upregulated in the epidermis and wing during metamorphosis. Knockdown of Runt-like produced similar phenomena, a failure of abdomen yellow envelope and wing formation, to those following HaPcp knockdown. The insect molting hormone 20-hydroxyecdysonen (20E) upregulated HaPcp transcription via RUNT-like. 20E upregulated Runt-like transcription via nuclear receptor EcR and the transcription factor FOXO. Together, RUNT-like and HaPCP are involved in pupal cuticle development during metamorphosis under 20E regulation.

Fabrication of a Microfluidic-Based Device Coated with Polyelectrolyte-Capped Titanium Dioxide to Couple High-Performance Liquid Chromatography with Inductively Coupled Plasma Mass Spectrometry for Mercury Speciation.

Mercury (Hg) is a toxic element which impacts on biological systems and ecosystems. Because the toxicity of Hg species is highly dependent on their concentration levels and chemical forms, the sensitive identification of the chemical forms of Hg-i.e., Hg speciation-is of major significance in providing meaningful information about the sources of Hg exposure. In this study, a microfluidic-based device made of high-clarity poly(methyl methacrylate) (PMMA) was fabricated. Then, titanium dioxide nanoparticles (nano-TiO2s) were attached to the treated channel's interior with the aid of poly(diallyldimethylammonium chloride) (PDADMAC). After coupling the nano-TiO2-coated microfluidic-based photocatalyst-assisted reduction device (the nano-TiO2-coated microfluidic-based PCARD) with high-performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP-MS), a selective and sensitive, hyphenated system for Hg speciation was established. Validation procedures demonstrated that the method could be satisfactorily applied to the determination of mercury ions (Hg2+) and methylmercury ions (CH3Hg+) in both human urine and water samples. Remarkably, the zeta potential measured clearly indicated that the PDADMAC-capped nano-TiO2s with a predominance of positive charges indeed provided a steady force for firm attachment to the negatively charged device channel. The cause of the durability of the nano-TiO2-coated microfluidic-based PCARD was clarified thus.

Development of the insect adult fat body relies on glycolysis, lipid synthesis, cell proliferation, and cell adhesion.

The fat body of the holometabolous insect is remodeled by the degradation of the larval fat body and the development of the adult fat body during metamorphosis. However, the mechanism of adult fat body development is quite unclear. Using the agricultural pest Helicoverpa armigera, the cotton bollworm, as a model, we revealed that the development of adult fat body was regulated by glycolysis, triglyceride (triacylglycerol [TAG]) synthesis, cell proliferation, and cell adhesion. RNA sequencing detected a set of genes that were upregulated in the 8-d late pupal fat body at a late metamorphic stage compared with the 2-d pupal fat body at an earlier metamorphic stage. The pathways for glycolysis, TAG synthesis, cell proliferation, and cell adhesion were enriched by the differentially expressed genes, and the key genes linked with these pathways showed increased expression in the 8-d pupal fat body. Knockdown of phosphofructokinase (Pfk), acetyl-CoA carboxylase (Acc1), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit (P110) and collagen alpha-1(IV) chain (Col4a1) by RNA interference resulted in abnormal eclosion and death at pupal stages, and repressed lipid droplets accumulation and adult fat body development. The expression of Acc1, P110, and Col4a1 was repressed by the insect steroid hormone 20-hydroxyecdysone (20E). The critical genes in the 20E pathway appeared to decrease at the late pupal stage. These data suggested that the development of the insect adult fat body is regulated by glycolysis, lipids synthesis, cell proliferation, and cell adhesion at the late pupal stage when the 20E signal decreases.

Treatment outcomes of endoscopic resection for nonampullary duodenal neuroendocrine tumors.

Background: The incidence rate of duodenal neuroendocrine tumors has been increasing in recent years. Endoscopic resection [ER; endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD)] is recommended for nonampullary duodenal neuroendocrine tumors (NAD-NETs) ≤10 mm in diameter that are confined to the submucosal layer and without lymph node or distant metastasis. However, the efficacy and safety of and indications for EMR/ESD remain unclear. Methods: Between November 2011 and April 2021, 12 NAD-NETs in 12 patients who underwent either EMR or ESD were analyzed retrospectively. The rates of en bloc resection, complete resection, pathologic complete resection, margin involvement, lymphovascular invasion, perineural invasion, complications and prognosis were determined during follow-up (median observation period 53.0 months). Results: EMR was performed for two tumors, and ESD was performed for ten tumors. En bloc resection was performed for both tumors (100%) in the EMR group, and complete resection was achieved in one case (50%). Pathological complete resection was achieved in one case (50%), while in the ESD group, these three rates were 90% (9/10), 80% (8/10), and 80% (8/10), respectively. Intraoperative perforation occurred in one patient (10%) during ESD treatment, with no intraoperative or delayed bleeding in either group. Recurrence and distant metastasis were not observed during the mean follow-up period of 53.0 months (range, 18-131 months). Conclusions: For NAD-NETs that measure ≤10 mm in size, are confined to the submucosal layer and have neither suspicious lymph nodes nor distant metastasis, ER (EMR and ESD) may be a safe, effective, and feasible endoscopic technique for removing them.

Emergent digital bio-computation through spatial diffusion and engineered bacteria.

Biological computing is a promising field with potential applications in biosafety, environmental monitoring, and personalized medicine. Here we present work on the design of bacterial computers using spatial patterning to process information in the form of diffusible morphogen-like signals. We demonstrate, mathematically and experimentally, that single, modular, colonies can perform simple digital logic, and that complex functions can be built by combining multiple colonies, removing the need for further genetic engineering. We extend our experimental system to incorporate sender colonies as morphogen sources, demonstrating how one might integrate different biochemical inputs. Our approach will open up ways to perform biological computation, with applications in bioengineering, biomaterials and biosensing. Ultimately, these computational bacterial communities will help us explore information processing in natural biological systems.

Heat stress upregulates arachidonic acid to trigger autophagy in sertoli cells via dysfunctional mitochondrial respiratory chain function.

As a key factor in determining testis size and sperm number, sertoli cells (SCs) play a crucial role in male infertility. Heat stress (HS) reduces SCs counts, negatively impacting nutrient transport and supply to germ cells, and leading to spermatogenesis failure in humans and animals. However, how HS affects the number of SCs remains unclear. We hypothesized that changes in SC metabolism contribute to the adverse effects of HS. In this study, we first observed an upregulation of arachidonic acid (AA), an unsaturated fatty acid after HS exposure by LC-MS/MS metabolome detection. By increasing ROS levels, expression of KEAP1 and NRF2 proteins as well as LC3 and LAMP2, 100 µM AA induced autophagy in SCs by activating oxidative stress (OS). We observed adverse effects of AA on mitochondria under HS with a decrease of mitochondrial number and an increase of mitochondrial membrane potential (MMP). We also found that AA alternated the oxygen transport and absorption function of mitochondria by increasing glycolysis flux and decreasing oxygen consumption rate as well as the expression of mitochondrial electron transport chain (ETC) proteins Complex I, II, V. However, pretreatment with 5 mM NAC (ROS inhibitor) and 2 µM Rotenone (mitochondrial ETC inhibitor) reversed the autophagy induced by AA. In summary, AA modulates autophagy in SCs during HS by disrupting mitochondrial ETC function, inferring that the release of AA is a switch-like response, and providing insight into the underlying mechanism of high temperatures causing male infertility.

Genomic structure analysis and construction of DNA fingerprint for four sheep populations.

The Yongdeng Qishan sheep (QS) is a sheep population found locally in China. To gain in-depth knowledge of its population characteristics, three control groups were chosen, comprising the Lanzhou fat-tailed sheep (LFT), TAN sheep (TAN), and Minxian black fur sheep (MBF), inhabiting the nearby environments. This study genotyped a total of 120 individuals from four sheep populations: QS, LFT, TAN, and MBF. Using Specific-Locus Amplified Fragment Sequencing, we conducted genetic diversity, population structure, and selective sweep analysis, and constructed the fingerprint of each population. In total, there were 782 535 single nucleotide polymorphism (SNP) variations identified, with most being situated within regions that are intergenic or intronic. The genetic diversity analysis revealed that the QS population exhibited lower genetic diversity compared to the other three populations. Consistent results were obtained from the principal component, phylogenetic tree, and population structure analysis, indicating significant genetic differences between QS and the other three populations. However, a certain degree of differentiation was observed within the QS population. The linkage disequilibrium (LD) patterns among the four populations showed clear distinctions, with the QS group demonstrating the most rapid LD decline. Kinship analysis supported the findings of population structure, dividing the 90 QS individuals into two subgroups consisting of 23 and 67 individuals. Selective sweep analysis identified a range of genes associated with reproduction, immunity, and adaptation to high-altitude hypoxia. These genes hold potential as candidate genes for marker-assisted selection breeding. Additionally, a total of 86 523 runs of homozygosity (ROHs) were detected, showing non-uniform distribution across chromosomes, with chromosome 1 having the highest coverage percentage and chromosome 26 the lowest. In the high-frequency ROH islands, 79 candidate genes were associated with biological processes such as reproduction and fat digestion and absorption. Furthermore, a DNA fingerprint was constructed for the four populations using 349 highly polymorphic SNPs. In summary, our research delves into the genetic diversity and population structure of QS population. The construction of DNA fingerprint profiles for each population can provide valuable references for the identification of sheep breeds both domestically and internationally.

Bibliometric and visualized analysis of hydrogels in organoids research.

Over the past decades, there has been ongoing effort to develop complex biomimetic tissue engineering strategies for in vitro cultivation and maintenance of organoids. The defined hydrogels can create organoid models for various organs by changing their properties and various active molecules. An increasing number of researches has been done on the application of hydrogels in organoids, and a large number of articles have been published on the topic. Although there have been existing reviews describing the application of hydrogels in the field of organoids, there is still a lack of comprehensive studies summarizing and analyzing the overall research trends in this field. The citation can be used as an indicator of the scientific influence of an article in its field. This study aims to evaluate the application of hydrogels in organoids through bibliometric analysis, and to predict the hotspots and developing trends in this field.

Achyranthes bidentata polysaccharides improve cyclophosphamide-induced adverse reactions by regulating the balance of cytokines in helper T cells.

The manuscript aimed to study the immune function maintenance effect of Achyranthes bidentata polysaccharides (ABPs). The mice were divided into the control group, cyclophosphamide-induced (CTX) group, and ABPs-treated (ABP) group. The results showed that, compared with the CTX group, ABPs could significantly improve the spleen index and alleviate the pathological changes in immune organs. Ex vivo study of whole spleen cells, the levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were increased. The proliferation of lymphocytes and the proportion of CD3+CD4+ Th cells in peripheral blood mononuclear cells were increased. The transcription of GATA-3, Foxp3, and ROR γ t were decreased, while the transcription of T-bet was increased. The transcriptome sequencing analysis showed that the differentially expressed genes (DEGs) caused by ABPs-treated were mostly downregulated in CTX-induced mice. The Th2-related genes were significantly enriched in DEGs, with representative genes, including Il4, II13, Il9, etc., while increasing the expression of immune effector genes simultaneously, including Ccl3, Ccr5, and Il12rb2. It was suggested that ABPs possibly regulated the balance of cytokines in helper T cells to ameliorate the immune function of CTX-induced mice.

Linkages among stem xylem transport, biomechanics, and storage in lianas and trees across three contrasting environments.

PREMISE: Stem xylem transports water and nutrients, mechanically supports aboveground tissues, and stores water and nonstructural carbohydrates. These three functions are associated with three types of cells-vessel, fiber, and parenchyma, respectively. METHODS: We measured stem theoretical hydraulic conductivity (Kt), modulus of elasticity (MOE), tissue water content, starch, soluble sugars, cellulose, and xylem anatomical traits in 15 liana and 16 tree species across three contrasting sites in Southwest China. RESULTS: Lianas had higher hydraulic efficiency and tissue water content, but lower MOE and cellulose than trees. Storage traits (starch and soluble sugars) did not significantly differ between lianas and trees, and trait variation was explained mainly by site, highlighting how environment shapes plant storage strategies. Kt was significantly positively correlated with vessel diameter and vessel area fraction in lianas and all species combined. The MOE was significantly positively correlated with fiber area fraction, wood density, and cellulose in lianas and across all species. The tissue water content was significantly associated with parenchyma area fraction in lianas. Support function was strongly linked with transport and storage functions in lianas. In trees, transport and support functions were not correlated, while storage function was tightly linked with transport and support functions. CONCLUSIONS: These findings enhance our understanding of the relationship between stem xylem structure and function in lianas and trees, providing valuable insights into how plants adapt to environmental changes and the distinct ecological strategies employed by lianas and by trees to balance the demands of hydraulic transport, mechanical support, and storage.

KAT8 is upregulated and recruited to the promoter of Atg8 by FOXO to induce H4 acetylation for autophagy under 20-hydroxyecdysone regulation.

Selective gene expression in cells in physiological or pathological conditions is important for the growth and development of organisms. Acetylation of histone H4 at K16 (H4K16ac) catalyzed by histone acetyltransferase 8 (KAT8) is known to promote gene transcription; however, the regulation of KAT8 transcription and the mechanism by which KAT8 acetylates H4K16ac to promote specific gene expression are unclear. Using the lepidopteran insect Helicoverpa armigera as a model, we reveal that the transcription factor FOXO promotes KAT8 expression and recruits KAT8 to the promoter region of autophagy-related gene 8 (Atg8) to increase H4 acetylation at that location, enabling Atg8 transcription under the steroid hormone 20-hydroxyecdysone (20E) regulation. H4K16ac levels are increased in the midgut during metamorphosis, which is consistent with the expression profiles of KAT8 and ATG8. Knockdown of Kat8 using RNA interference results in delayed pupation and repression of midgut autophagy and decreases H4K16ac levels. Overexpression of KAT8-GFP promotes autophagy and increases H4K16ac levels. FOXO, KAT8, and H4K16ac colocalized at the FOXO-binding region to promote Atg8 transcription under 20E regulation. Acetylated FOXO at K180 and K183 catalyzed by KAT8 promotes gene transcription for autophagy. 20E via FOXO promotes Kat8 transcription. Knockdown or overexpression of FOXO appeared to give similar results as knockdown or overexpression of KAT8. Therefore, FOXO upregulates KAT8 expression and recruits KAT8 to the promoter region of Atg8, where the KAT8 induces H4 acetylation to promote Atg8 transcription for autophagy under 20E regulation. This study reveals the mechanism that KAT8 promotes transcription of a specific gene.

Radiomics using CT images for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma: a multi-centric study.

OBJECTIVES: To develop a CT-based radiomics model for preoperative prediction of lymph node (LN) metastasis in perihilar cholangiocarcinoma (pCCA). METHODS: The study enrolled consecutive pCCA patients from three independent Chinese medical centers. The Boruta algorithm was applied to build the radiomics signature for the primary tumor and LN. The k-means algorithm was employed to cluster the selected LNs based on the radiomics signature LN. Support vector machines were used to construct the prediction models. The diagnostic efficiency was measured by the area under the receiver operating characteristic curve (AUC). The optimal model was evaluated in terms of calibration, clinical usefulness, and prognostic value. RESULTS: A total of 214 patients were included in the study (mean age: 61.6 years ± 9.4; 130 male). The selected LNs were classified into two clusters, which were significantly correlated with LN metastasis in all cohorts (p < 0.001). The model incorporated the clinical risk factors, radiomics signature primary tumor, and the LN cluster obtained the best discrimination, with AUC values of 0.981 (95% CI: 0.962-1), 0.896 (95% CI: 0.810-0.982), and 0.865 (95% CI: 0.768-0.961) in the training, internal validation, and external validation cohorts, respectively. High-risk patients predicted by the optimal model had shorter overall survival than low-risk patients (median, 13.7 vs. 27.3 months, p < 0.001). CONCLUSIONS: The study proposed a radiomics model with good performance to predict LN metastasis in pCCA. As a noninvasive preoperative prediction tool, this model may help in patient risk stratification and personalized treatment. CLINICAL RELEVANCE STATEMENT: A CT-based radiomics model accurately predicts lymph node metastasis in perihilar cholangiocarcinoma patients. This noninvasive preoperative tool can aid in patient risk stratification and personalized treatment, potentially improving patient outcomes. KEY POINTS: • The radiomics model based on contrast-enhanced CT is a useful tool for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma. • Radiomics features extracted from lymph nodes show great potential for predicting lymph node metastasis. • The study is the first to identify a lymph node phenotype with a high probability of metastasis based on radiomics.

Treatment outcomes and cognitive function following electroconvulsive therapy in patients with severe depression.

BACKGROUND: Traditional treatments for major depressive disorder (MDD), including medication and therapy, often fail and have undesirable side effects. Electroconvulsive therapy (ECT) uses electrical currents to induce brief seizures in the brain, resulting in rapid and potent antidepressant effects. However, owing to misconceptions and controversies, ECT is not as widely used as it could and often faces stigmatization. AIM: To evaluate the efficacy and safety of ECT compared to those of medication and/or therapy in patients with severe MDD. METHODS: This prospective cohort study included 220 individuals with severe MDD who were divided into the ECT and non-ECT groups. The patients in the ECT group underwent bilateral ECT three times a wk until they either achieved remission or reached a maximum of 12 sessions. The non-ECT group received medication and/or therapy according to clinical guidelines for MDD. The primary outcome was the variation in the hamilton depression rating scale (HDRS) score from treatment/ECT initiation to week 12. In addition, patients' quality of life, cognitive abilities, and biomarkers were measured throughout the study. RESULTS: Although both groups showed significant improvements in their HDRS scores over time, the improvement was more pronounced in the ECT group than in the non-ECT group. Additionally, the ECT group exhibited a more substantial improvement in the quality of life and cognitive function than those of the non-ECT group. Compared with the non-ECT group, the ECT group exhibited evi-dently lower variations in the brain-derived neurotrophic factor (BDNF) and cytokine interleukin-6 (IL-6) levels. The side effects were generally mild and comparable between the two groups. ECT is safer and more potent than medication and/or therapy in mitigating depressive symptoms, enhancing well-being, and bolstering cognitive capabilities in individuals with severe MDD. ECT may also affect the levels of BDNF and IL-6, which are indicators of neuroplasticity and inflammation, respectively. CONCLUSION: ECT has emerged as a potentially advantageous therapeutic approach for patients with MDD who are unresponsive to alternative treatments.

Symmetrical femtosecond laser arc incision in correcting corneal astigmatism in cataract patients.

AIM: To evaluate the effect of symmetrical arc incision correcting corneal astigmatism in femtosecond laser-assisted phacoemulsification (FLACS). METHODS: This study enrolled patients with cataract combined with regular corneal astigmatism of >0.75 D, who underwent FLACS. Symmetrical arc incision was set at 8 mm diameter and 85% depth. The follow-up time was 3-24mo (4.92±3.49mo). Pentacam recorded the corneal astigmatism and higher-order aberration at pre-operation and post-operation. The changes in corneal astigmatism were analyzed by Alpins method. The correlation of astigmatism type, age, corneal horizontal diameter, corneal thickness, arc incision length, and correction index (CI) was analyzed, and the residual corneal astigmatism was compared with the residual whole eye astigmatism. RESULTS: Totally 79 patients (102 eyes) were enrolled, 10 patients had corneal epithelial injury, 1 patient occurred corneal epithelial hyperplasia. The corneal astigmatism was 1.23±0.38 D pre-operation, and decreased to 0.76±0.39 D post-operation (t=10.146, P=0.000). Corneal high-order aberration was 0.17±0.08 µm pre-operation and 0.24±0.11 µm post-operation (t=-5.186, P=0.000). The residual corneal astigmatism and residual whole eye astigmatism were no significant difference (t=-0.347, P=0.729). Using Alpin's method, the following were determined: target-induced astigmatism (TIA) =1.23±0.38 D, surgery-induced astigmatism (SIA) =0.77±0.45 D, difference vector (DV)=0.77±0.39 D, and CI=0.54±0.28. Age, astigmatism size, corneal horizontal diameter, corneal thickness, and arc incision length were not correlated with CI. The CI for against the rule astigmatism (ATR) was better than that for with the rule astigmatism (WTR; P=0.001). CONCLUSION: Femtosecond laser-assisted astigmatic keratotomy has better CI of ATR, but increase higher-order corneal aberration. CI is not ideal, it's not a perfect choice if we pursue ideal correction effect.

Convergent relationships between flower economics and hydraulic traits across aquatic and terrestrial herbaceous plants.

Maintaining open flowers is critical for successful pollination and depends on long-term water and carbon balance. Yet the relationship between how flower hydraulic traits are coordinated in different habitats is poorly understood. Here, we hypothesize that the coordination and trade-offs between floral hydraulics and economics traits are independent of environmental conditions. To test this hypothesis, we investigated a total of 27 flower economics and hydraulic traits in six aquatic and six terrestrial herbaceous species grown in a tropical botanical garden. We found that although there were a few significant differences, most flower hydraulics and economics traits did not differ significantly between aquatic and terrestrial herbaceous plants. Both flower mass per area and floral longevity were significantly positively correlated with the time required for drying full-hydrated flowers to 70% relative water content. Flower dry matter content was strongly and positively related to drought tolerance of the flowers as indicated by flower water potential at the turgor loss point. In addition, there was a trade-off between hydraulic efficiency and the construction cost of a flower across species. Our results show that flowers of aquatic and terrestrial plants follow the same economics spectrum pattern. These results suggest a convergent flower economics design across terrestrial and aquatic plants, providing new insights into the mechanisms by which floral organs adapt to aquatic and terrestrial habitats.

Construction and validation of a predictive model for postoperative urinary retention after lumbar interbody fusion surgery.

BACKGROUND: Postoperative urine retention (POUR) after lumbar interbody fusion surgery may lead to recatheterization and prolonged hospitalization. In this study, a predictive model was constructed and validated. The objective was to provide a nomogram for estimating the risk of POUR and then reducing the incidence. METHODS: A total of 423 cases of lumbar fusion surgery were included; 65 of these cases developed POUR, an incidence of 15.4%. The dataset is divided into a training set and a validation set according to time. 18 candidate variables were selected. The candidate variables were screened through LASSO regression. The stepwise regression and random forest analysis were then conducted to construct the predictive model and draw a nomogram. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and the calibration curve were used to evaluate the predictive effect of the model. RESULTS: The best lambda value in LASSO was 0.025082; according to this, five significant variables were screened, including age, smoking history, surgical method, operative time, and visual analog scale (VAS) score of postoperative low back pain. A predictive model containing four variables was constructed by stepwise regression. The variables included age (ß = 0.047, OR = 1.048), smoking history (ß = 1.950, OR = 7.031), operative time (ß = 0.022, OR = 1.022), and postoperative VAS score of low back pain (ß = 2.554, OR = 12.858). A nomogram was drawn based on the results. The AUC of the ROC curve of the training set was 0.891, the validation set was 0.854 in the stepwise regression model. The calibration curves of the training set and validation set are in good agreement with the actual curves, showing that the stepwise regression model has good prediction ability. The AUC of the training set was 0.996, and that of the verification set was 0.856 in the random forest model. CONCLUSION: This study developed and internally validated a new nomogram and a random forest model for predicting the risk of POUR after lumbar interbody fusion surgery. Both of the nomogram and the random forest model have high accuracy in this study.

Exploring the role of macrophages in the progression from atypical hyperplasia to endometrial carcinoma through single-cell transcriptomics and bulk transcriptomics analysis.

Introduction: In this study, we aimed to identify key genes in endometrial cancer by conducting single-cell analysis of macrophages. Methods: We sourced clinical data from the TCGA database as well as supplementary datasets GSE201926 and GSE173682. Using bulk-seq data of atypical endometrial hyperplasia and endometrial cancer, we pinpointed key differentially expressed genes. Single-cell RNA sequencing was utilized for further gene expression analysis. Cluster analysis was conducted on TCGA tumor data, identifying two distinct subtypes. Statistical methods employed included LASSO regression for diagnostic modeling and various clustering algorithms for subtype identification. Results: We found that subtype B was closely related to cellular metabolism. A diagnostic model was established using LASSO regression and was based on the genes CDH18, H19, PAGE2B, PXDN, and THRB. This model effectively differentiated the prognosis of cervical cancer. We also constructed a prognosis model and a column chart based on these key genes. Discussion: Through CIBERSORT analysis, CDH18 and PAGE2B were found to be strongly associated with macrophage M0. We propose that these genes influence the transformation from atypical endometrial hyperplasia to endometrial cancer by affecting macrophage M0. In conclusion, these key genes may serve as therapeutic targets for endometrial cancer. A new endometrial cancer risk prognosis model and column chart have been constructed based on these genes, offering a reliable direction for future cervical cancer treatment.

Case report: The intrauterine suture surgery-an original method in the treatment of old uterine false passage.

Objective: To introduce an effective approach using the hysteroscopy system for patients with old uterine false passage after a failed conservative treatment. Materials and methods: This study presents the case of a 34-year-old woman who was treated in the Department of Gynecology of Shenzhen Integrated Traditional Chinese and Western Medicine Hospital in 2018 with the complaint of "menstrual volumereduction for 2 years after abortion." A hysteroscopy was performed to make a clear diagnosis: (1) uterine cavity adhesion and (2) old uterine false passage. After the separation of adhesions, the patient was treated with estradiol and progesterone in sequence (estradiol valerate 3 mg, b.i.d., oral for 21 days; and dydrogesterone tablets 10 mg, b.i.d., oral for the second half of the cycle) for 3 months. After the review of the hysteroscopy results, it was found that there was no improvement in the old false passage; therefore, a suture and knotting surgery under hysteroscopy was performed to treat the old false passage in the uterus within 10 min, and the intraoperative blood loss was 2 ml. The patient was discharged 24 h postoperatively without any adverse perioperative complications. Results: Two months after the operation, the review of the hysteroscopy results showed that the old false passage in the uterus disappeared. After the 6-month follow-up, the menstrual volume increased compared with the previous one, close to the normal menstrual volume, and the patient experienced no pain and menstrual discomfort. The patient was lost to follow-up and was contacted again in 2022. It was found out that in 2019, she was pregnant with a baby boy who is now 3 years old and healthy. Conclusion: The intrauterine suture surgery presents a clear visual field to old uterine false passage after a failed conservative treatment. In patients with old uterine false passage suffering from reduced fertility, the intrauterine suture surgery can be a minimally invasive and effective alternative if the conservative treatment for old uterine false passage failed.

Tendency of dynamic vasoactive and inotropic medications data as a robust predictor of mortality in patients with septic shock: An analysis of the MIMIC-IV database.

Background: Septic shock patients fundamentally require delicate vasoactive and inotropic agent administration, which could be quantitatively and objectively evaluated by the vasoactive-inotropic score (VIS); however, whether the dynamic trends of high-time-resolution VIS alter the clinical outcomes remains unclear. Thus, this study proposes the term VIS Reduction Rate (VRR) to generalise the tendency of dynamic VIS, to explore the association of VRR and mortality for patients with septic shock. Methods: We applied dynamic and static VIS data to predict ICU mortality by two models: the long short-term memory (LSTM) deep learning model, and the extreme gradient boosting (XGBoost), respectively. The specific target cohort was extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database by the sophisticated structured query language (SQL). Enrolled patients were divided into four groups by VRR value: ≥50%, 0 ~ 50%, -50% ~ 0, and < -50%. Statistical approaches included pairwise propensity score matching (PSM), Cox proportional hazards regression, and two doubly robust estimation models to ensure the robustness of the results. The primary and secondary outcomes were ICU mortality and in-hospital mortality, respectively. Results: VRR simplifies the dosing trends of vasoactive and inotropic agents represented by dynamic VIS data while requiring fewer data. In total, 8,887 septic shock patients were included. Compared with the VRR ≥50% group, the 0 ~ 50%, -50% ~ 0, and < -50% groups had significantly higher ICU mortality [hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.17-1.50, p < 0.001; HR 1.79, 95% CI 1.44-2.22, p < 0.001; HR 2.07, 95% CI 1.61-2.66, p < 0.001, respectively] and in-hospital mortality [HR 1.43, 95% CI 1.28-1.60, p < 0.001; HR 1.75, 95% CI 1.45-2.11, p < 0.001; HR 2.00, 95% CI 1.61-2.49, p < 0.001, respectively]. Similar findings were observed in two doubly robust estimation models. Conclusion: The trends of dynamic VIS in ICU might help intensivists to stratify the prognosis of adult patients with septic shock. A lower decline of VIS was remarkably associated with higher ICU and in-hospital mortality among septic shock patients receiving vasoactive-inotropic therapy for more than 24 h.