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Purpose: This study aimed to analyse the correlation between blood glucose control and the severity of COVID-19 infection in patients with diabetes. Methods: Clinical and imaging data of a total of 146 patients with diabetes combined with COVID-19 who visited our hospital between December 2022 and January 2023 were retrospectively collected. The patients were divided into the 'good blood glucose control' group and the 'poor blood glucose control' group based on an assessment of their blood glucose control. The clinical data, computed tomography (CT) appearance and score and the severity of COVID-19 infection of the two groups were compared, with the severity of COVID-19 infection being the dependent variable to analyse other influencing factors. Results: The group with poor blood glucose control showed a higher lobar involvement degree and total CT severity score (CTSS) than the group with good blood glucose control (13.30 ± 5.25 vs. 10.38 ± 4.84, p < 0.05). The two groups exhibited no statistically significant differences in blood lymphocyte, leukocyte, C-reaction protein, pleural effusion, consolidation, ground glass opacity or crazy-paving signs. Logistic regression analysis showed that the total CTSS significantly influences the clinical severity of patients (odds ratio 1.585, p < 0.05), whereas fasting plasma glucose and blood glucose control are not independent factors influencing clinical severity (both p > 0.05). The area under the curve (AUC) of CTSS prediction of critical COVID-19 was 0.895 with sensitivity of 79.3% and specificity of 88.1% when the threshold value is 12. Conclusion: Blood glucose control is significantly correlated with the CTSS; the higher the blood glucose is, the more severe the lung manifestation. The CTSS can also be used to evaluate and predict the clinical severity of COVID-19. [ABSTRACT FROM AUTHOR]

Background: With the continuous discovery of new borderline thyroid lesions and benign and malignant "gray areas", coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear. Methods: In our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied. Results: Among 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P < 0.05). The expression levels of Cyclin D1 and P21 were positively correlated with tumor size and lymph node metastasis (P < 0.05) but not with sex, age, number of tumor lesions, histological subtype, chronic lymphocytic thyroiditis or TNM stage (P < 0.05). The expression levels of Cyclin D1 and P21 were significantly correlated (P < 0.05). The positivity rates of Cyclin D1 and P21 in intralymph node PTC metastases were 97.96% (48/49) and 89.80% (44/49), respectively, which were significantly higher than those in intralymph node ectopic thyroid tissue (P < 0.05). The sensitivity (Se) and negative predictive value (NPV) of Cyclin D1 and P21 detection alone or in combination were higher than those of the combined detection of the classical antibody markers CK19, HBME-1 and Galectin-3. Besides, the Se, Sp, PPV and NPV of Cyclin D1 and P21 in differentiating intralymph node PTC metastases and intralymph node ectopic thyroid tissue were higher. Conclusions: The results of our study show that Cyclin D1 and P21 are highly sensitive and specific markers for the diagnosis of PTC that are superior to traditional classical antibodies. And, these two markers are of great value in the differential diagnosis of intralymph node PTC metastases and intralymph node ectopic thyroid tissue. [ABSTRACT FROM AUTHOR]

Background: Infratentorial craniotomy patients have a high incidence of postoperative nausea and vomiting (PONV). Enhanced Recovery After Surgery (ERAS) protocols have been shown in multiple surgical disciplines to improve outcomes, including reduced PONV. However, very few studies have described the application of ERAS to infratentorial craniotomy. The aim of this study was to examine whether our ERAS protocol for infratentorial craniotomy could improve PONV. Methods: We implemented an evidence-based, multimodal ERAS protocol for patients undergoing infratentorial craniotomy. A total of 105 patients who underwent infratentorial craniotomy were randomized into either the ERAS group (n = 50) or the control group (n = 55). Primary outcomes were the incidence of vomiting, nausea score, and use of rescue antiemetic during the first 72 h after surgery. Secondary outcomes included postoperative anxiety level, sleep quality, and complications. Results: Over the entire 72 h post-craniotomy observation period, the cumulative incidence of vomiting was significantly lower in the ERAS group than in the control group. Meanwhile, the incidence of vomiting was significantly lower in the ERAS group on postoperative days (PODs) 2 and 3. Notably, the proportion of patients with mild nausea (VAS 0–4) was higher in the ERAS group as compared to the control group on PODs 2 or 3. Additionally, the postoperative anxiety level and quality of sleep were significantly better in the ERAS group. Conclusion: Successful implementation of our ERAS protocol in infratentorial craniotomy patients could attenuate postoperative anxiety, improve sleep quality, and reduce the incidence of PONV, without increasing the rate of postoperative complications. Trial registration: ChiCTR-INR-16009662, 27 Oct 2016, Clinical study on the development and efficacy evaluation of Enhanced Recovery After Surgery (ERAS) in Neurosurgery. [ABSTRACT FROM AUTHOR]

Background: Infratentorial craniotomy patients have a high incidence of postoperative nausea and vomiting (PONV). Enhanced Recovery After Surgery (ERAS) protocols have been shown in multiple surgical disciplines to improve outcomes, including reduced PONV. However, very few studies have described the application of ERAS to infratentorial craniotomy. The aim of this study was to examine whether our ERAS protocol for infratentorial craniotomy could improve PONV.Methods: We implemented an evidence-based, multimodal ERAS protocol for patients undergoing infratentorial craniotomy. A total of 105 patients who underwent infratentorial craniotomy were randomized into either the ERAS group (n = 50) or the control group (n = 55). Primary outcomes were the incidence of vomiting, nausea score, and use of rescue antiemetic during the first 72 h after surgery. Secondary outcomes included postoperative anxiety level, sleep quality, and complications.Results: Over the entire 72 h post-craniotomy observation period, the cumulative incidence of vomiting was significantly lower in the ERAS group than in the control group. Meanwhile, the incidence of vomiting was significantly lower in the ERAS group on postoperative days (PODs) 2 and 3. Notably, the proportion of patients with mild nausea (VAS 0-4) was higher in the ERAS group as compared to the control group on PODs 2 or 3. Additionally, the postoperative anxiety level and quality of sleep were significantly better in the ERAS group.Conclusion: Successful implementation of our ERAS protocol in infratentorial craniotomy patients could attenuate postoperative anxiety, improve sleep quality, and reduce the incidence of PONV, without increasing the rate of postoperative complications.Trial Registration: ChiCTR-INR-16009662, 27 Oct 2016, Clinical study on the development and efficacy evaluation of Enhanced Recovery After Surgery (ERAS) in Neurosurgery. [ABSTRACT FROM AUTHOR]

Background: During cell-cycle progression, substrates of a single master regulatory enzyme can be modified in a specific order. Here, we used experimental and computational approaches to dissect the quantitative mechanisms underlying the ordered degradation of the substrates of the ubiquitin ligase APC/CCdc20, a key regulator of chromosome segregation in mitosis. Results: We show experimentally that the rate of catalysis varies with different substrates of APC/CCdc20. Using a computational model based on multi-step ubiquitination, we then show how changes in the interaction between a single substrate and APC/CCdc20 can alter the timing of degradation onset relative to APC/CCdc20 activation, while ensuring a fast degradation rate. Degradation timing and dynamics depend on substrate affinity for the enzyme as well as the catalytic rate at which the substrate is modified. When two substrates share the same pool of APC/CCdc20, their relative enzyme affinities and rates of catalysis influence the partitioning of APC/CCdc20 among substrates, resulting in substrate competition. Depending on how APC/CCdc20 is partitioned among its substrates, competition can have minor or major effects on the degradation of certain substrates. We show experimentally that increased expression of the early APC/CCdc20 substrate Clb5 does not delay the degradation of the later substrate securin, arguing against a role for competition with Clb5 in establishing securin degradation timing. Conclusions: The degradation timing of APC/CCdc20 substrates depends on the multi-step nature of ubiquitination, differences in substrate-APC/CCdc20 interactions, and competition among substrates. Our studies provide a conceptual framework for understanding how ordered modification can be established among substrates of the same regulatory enzyme, and facilitate our understanding of how precise temporal control is achieved by a small number of master regulators to ensure a successful cell division cycle. [ABSTRACT FROM AUTHOR]

Background: The precise mechanisms underlying preeclampsia (PE) pathogenesis remain unclear. Mesenchymal stem cells (MSCs) are involved in the pathology of PE. The aim of our study was to identify the effects of protein phosphatase 2 regulatory subunit B α (PPP2R2A) on MSCs and ascertain its latent role in the progression of PE. Methods: Reverse-transcription quantitative polymerase chain reaction and western blot analyses were performed to determine the expression of PPP2R2A in decidual tissue and decidual (d)MSCs from healthy pregnant women and patients with PE as well as the expression levels of Bax and Bcl-2 in dMSCs. The levels of p-PI3K, PI3K, p-AKT, and AKT were determined using western blotting. Cell growth, apoptosis, and migration were analyzed using MTT, flow cytometry, and Transwell assays, respectively. Human umbilical vein endothelial cell (HUVEC) tube formation ability was assayed using a HUVEC capillary-like tube formation assay. Results: PPP2R2A was downregulated in decidual tissues and dMSCs of patients with PE when compared with that in healthy pregnant women. Moreover, upregulation of PPP2R2A enhanced cell proliferation, reduced apoptotic dMSC, inhibited Bax expression, and increased Bcl-2 levels. Conditioned medium from PPP2R2A-overexpressing dMSCs promoted HTR-8/SVneo cell migration and angiogenesis of HUVEC. Furthermore, the PPP2R2A plasmid suppressed PI3K/AKT pathway activation in dMSCs. However, these effects were partially reversed by LY2940002 treatment. Conclusion: PPP2R2A inhibition contributes to PE by regulating the proliferation, apoptosis, and angiogenesis of MSCs, providing a new therapeutic target for PE diagnosis and treatment. [ABSTRACT FROM AUTHOR]

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12883-020-02027-1. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is a common cancer among women globally, and the assessment of lymph node metastasis plays a crucial role in the treatment of this malignancy. The primary objective of our study was to identify the risk factors associated with lymph node metastasis in patients with ovarian cancer and develop a predictive model to aid in the selection of the appropriate surgical procedure and treatment strategy. Methods: We conducted a retrospective analysis of data from patients with ovarian cancer across three different medical centers between April 2014 and August 2022. Logistic regression analysis was employed to establish a prediction model for lymph node metastasis in patients with ovarian cancer. We evaluated the performance of the model using receiver operating characteristic (ROC) curves, calibration plots, and decision analysis curves. Results: Our analysis revealed that among the 368 patients in the training set, 101 patients (27.4%) had undergone lymph node metastasis. Maximum tumor diameter, multifocal tumor, and Ki67 level were identified as independent risk factors for lymph node metastasis. The area under the curve (AUC) of the ROC curve in the training set was 0.837 (95% confidence interval [CI]: 0.792–0.881); in the validation set this value was 0.814 (95% CI: 0.744–0.884). Calibration plots and decision analysis curves revealed good calibration and clinical application value. Conclusions: We successfully developed a model for predicting lymph node metastasis in patients with ovarian cancer, based on ultrasound examination results and clinical data. Our model accurately identified patients at high risk of lymph node metastasis and may guide the selection of appropriate treatment strategies. This model has the potential to significantly enhance the precision and efficacy of clinical management in patients with ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Endometriosis, a common gynaecological disease in women, affects 10% of women of childbearing age. Among infertile women, this proportion is as high as 30–50%. Despite the high prevalence of endometriosis, the pathogenesis of endometriosis is still unclear. Methods: In the present study, bioinformatics analysis and molecular and animal experiments were employed to explore the functions of PCGEM1 in the pathogenesis of endometriosis. We established an endometriosis rat model and isolated endometrial stromal cells (ESCs) and primary normal ESCs (NESCs). Bioinformatics analysis was adopted to study the roles of PCGEM1 in promoting the pathogenesis of endometriosis. Luciferase reporter assays and RNA pull-down assays were carried out to study the mechanism by which PCGEM1 regulates ANTXR2. Results: Our results indicated that PCGEM1 promoted the motility and proliferation of ectopic endometrial cells, and the underlying mechanism was due to the direct binding of PCGEM1 to miR-124-3p to modulate ANTXR2 expression. Conclusion: PCGEM1 can influence endometrial stromal cell proliferation and motility and may be a novel therapeutic target for endometriosis. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic within the United States, much of the responsibility for diagnostic testing and epidemiologic response has relied on the action of county-level departments of public health. Here we describe the integration of genomic surveillance into epidemiologic response within Humboldt County, a rural county in northwest California. Methods: Through a collaborative effort, 853 whole SARS-CoV-2 genomes were generated, representing ~58% of the 1,449 SARS-CoV-2-positive cases detected in Humboldt County as of March 12, 2021. Phylogenetic analysis of these data was used to develop a comprehensive understanding of SARS-CoV-2 introductions to the county and to support contact tracing and epidemiologic investigations of all large outbreaks in the county. Results: In the case of an outbreak on a commercial farm, viral genomic data were used to validate reported epidemiologic links and link additional cases within the community who did not report a farm exposure to the outbreak. During a separate outbreak within a skilled nursing facility, genomic surveillance data were used to rule out the putative index case, detect the emergence of an independent Spike:N501Y substitution, and verify that the outbreak had been brought under control. Conclusions: These use cases demonstrate how developing genomic surveillance capacity within local public health departments can support timely and responsive deployment of genomic epidemiology for surveillance and outbreak response based on local needs and priorities. [ABSTRACT FROM AUTHOR]

Paroxysmal nocturnal hemoglobinuria is a clonal disease caused by PIG-A mutation of hematopoietic stem cells. At present, there is no suitable PNH animal model for basic research, therefore, it is urgent to establish a stable animal model. We constructed a Pig-a conditional knock-out mice model by ES targeting technique and Vav-iCre. The expressions of GPI and GPI-AP were almost completely absent in CKO homozygote mice, and the proportion of the deficiency remained stable from birth. In CKO heterozygote mice, the proportion of the deficiency of GPI and GPI-AP was partially absent and decreased gradually from birth until it reached a stable level at 3 months after birth and remained there for life. Compared with normal C57BL/6N mice and Flox mice, pancytopenia was found in CKO homozygous mice, and leukopenia and anemia were found in CKO heterozygotes mice. Meanwhile, in CKO mice, the serum LDH, TBIL, IBIL, complement C5b-9 levels were increased, and the concentration of plasma FHb was increased. Hemosiderin granulosa cells can be seen more easily in the spleens of CKO mice. What's more, CKO mice had stable transcription characteristics. In conclusion, our mouse model has stable GPI-deficient and mild hemolysis, which may be an ideal in vivo experimental model for PNH. [ABSTRACT FROM AUTHOR]

Background: Acute care for critical illness requires very strict treatment timeliness. However, healthcare providers usually cannot accurately figure out the causes of low efficiency in acute care process due to the lack of effective tools. Besides, it is difficult to compare or conformance processes from different patient groups. Methods: To solve these problems, we proposed a novel process mining framework with time perspective, which integrates four steps: standard activity construction, data extraction and filtering, iterative model discovery, and performance analysis. Results: It can visualize the execution of actual clinical activities hierarchically, evaluate the timeliness and identify bottlenecks in the treatment process. We take the acute ischemic stroke as a case study, and retrospectively reviewed 420 patients' data from a large hospital. Then we discovered process models with timelines, and identified the main reasons for in-hospital delay. Conclusions: Experiment results demonstrate that the framework proposed could be a new way of drawing insights about hospitals' clinical process, to help clinical institutions increase work efficiency and improve medical service. [ABSTRACT FROM AUTHOR]

Background: Acute care for critical illness requires very strict treatment timeliness. However, healthcare providers usually cannot accurately figure out the causes of low efficiency in acute care process due to the lack of effective tools. Besides, it is difficult to compare or conformance processes from different patient groups.Methods: To solve these problems, we proposed a novel process mining framework with time perspective, which integrates four steps: standard activity construction, data extraction and filtering, iterative model discovery, and performance analysis.Results: It can visualize the execution of actual clinical activities hierarchically, evaluate the timeliness and identify bottlenecks in the treatment process. We take the acute ischemic stroke as a case study, and retrospectively reviewed 420 patients' data from a large hospital. Then we discovered process models with timelines, and identified the main reasons for in-hospital delay.Conclusions: Experiment results demonstrate that the framework proposed could be a new way of drawing insights about hospitals' clinical process, to help clinical institutions increase work efficiency and improve medical service. [ABSTRACT FROM AUTHOR]

Background: PEST-containing nuclear protein (PCNP), a novel nuclear protein, is involved in cell proliferation and tumorigenesis. However, the precise mechanism of action of PCNP in the process of tumor growth has not yet been fully elucidated.Methods: ShRNA knockdown and overexpression of PCNP were performed in human neuroblastoma cells. Tumorigenic and metastatic effects of PCNP were examined by tumor growth, migration, and invasion assays in vitro, as well as xenograft tumor assay in vivo.Results: PCNP over-expression decreased the proliferation, migration, and invasion of human neuroblastoma cells and down-regulation of PCNP showed reverse effects. PCNP over-expression increased protein expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase, as well as ratios of B-cell lymphoma-2 (Bcl-2)-associated X protein/Bcl-2 and Bcl-2-associated death promoter/B-cell lymphoma-extra large in human neuroblastoma cells, however PCNP knockdown exhibited reverse trends. PCNP over-expression increased phosphorylations of extracellular signal-regulated protein kinase 1/2, p38, c-Jun N-terminal kinase, as well as decreased phosphorylations of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), nevertheless PCNP knockdown exhibited opposite effects. Furthermore, PCNP over-expression significantly reduced the growth of human neuroblastoma xenograft tumors by down-regulating angiogenesis, whereas PCNP knockdown markedly promoted the growth of human neuroblastoma xenograft tumors through up-regulation of angiogenesis.Conclusions: PCNP mediates the proliferation, migration, and invasion of human neuroblastoma cells through mitogen-activated protein kinase and PI3K/AKT/mTOR signaling pathways, implying that PCNP is a therapeutic target for patients with neuroblastoma. [ABSTRACT FROM AUTHOR]

Background: We prepared an oral W/O microemulsion for the removal of colonic ammonia (ME-RCA). The effect of this microemulsion was influenced by the digestion process in the gastrointestinal tract. In this paper, we aim to show that stability was improved by using a microemulsion-based gel for the removal of colonic ammonia (MBG-RCA).Methods: MBG-RCA was prepared by adding sodium alginate to the ME-RCA. MBG-RCA and ME-RCA were passed through a simulated gastrointestinal environment, and the amount of colonic ammonia present was then determined by titration with a standard solution of hydrochloric acid. The pH of the gastrointestinal fluid was measured using a pH test paper and the size and form of the microemulsions were examined under the microscope. 18 healthy rats were randomly divided into three groups, fasted for 24 hours and allowed to drink normally. Three-way pipes were placed at the gastroduodenal junction in Group I, and at the terminal ileum in Group II. After the intragastric administration of ME-RCA, the stomach contents in Group I, the effluent from the terminal ileum in Group II and discharge from the anus in Group III were collected. The pH values of the gastrointestinal juice were measured by the pH test paper and those of the colon were determined by a universal indicator. These animal experiments were also used to test the effect of MBG-RCA.Results: MBG-RCA showed a better removal rate of artificial colonic ammonia than ME-RCA (P < 0.05). The decrease in pH value of the artificial small intestinal fluid due to ME-RCA did not occur when MBG-RCA was used. In the simulated gastrointestinal process, MBG-RCA maintained greater stability and released the emulsion (ME-RCA) in the colonic fluid. In the gastrointestinal tract of normal SD rats, ME-RCA decreased in size and lost its stable form after entering the small intestine, while MBG-RCA remained stable and intact emulsion-drops were observed from the anus. Neither substance had any effect on the pH of the stomach or colon of normal rats (partly because normal rats were fasted for 24 hours and allowed to drink normally, which resulted in a low level of ammonia production in the colon). Unlike ME-RCA, MBG-RCA did not reduce the pH of the small intestine.Conclusions: MBG-RCA was more stable in the gastrointestinal tract and more effective at removing colonic ammonia when a higher concentration of ammonia was present. This made it possible to achieve the targeted removal of colonic ammonia and is a promising method to prevent hepatic encephalopathy (HE) in future studies. [ABSTRACT FROM AUTHOR]