Combined Effects of Cadmium and Lead on Growth Performance and Kidney Function in Broiler Chicken.

Cadmium (Cd) and lead (Pb) are heavy metals prevalent in the environment and feed, and they reduce production performance of domestic animals, as well as they result in residue in animal tissues. The kidney is the target tissue for Cd and Pb. And the kidney is crucial for the reabsorption of calcium (Ca), which consequently influences bone strength. However, there are relatively few studies related to the effects of Cd and Pb exposure on performance, bone strength and kidney damage in livestock. The purpose of this experiment was to explore the combined effect of Cd and Pb on growth performance and renal impairment and the possible underlying mechanism. For this, 168 1-day-old Ross 308 broilers were randomly divided into four groups of six birds each, with seven replicates in each group: control group, 50 mg Cd/kg body weight group, 200 mg Pb/kg body weight group and 50 mg Cd/kg body weight + 200 mg Pb/kg body weight group. Feed intake was recorded daily and body weight was recorded weekly. The results show that at the end of the 3rd and 6th week, one broiler from each replicate was randomly selected for sampling. Boilers co-exposed to Cd and Pb for 3 weeks and 6 weeks had significantly decreased average daily feed intake (ADFI) and average daily body weight gain (ADG) than the control group, and the ratio of feed-to-weight gain (F/G) significantly increased after 6 weeks of co-exposure to Cd and Pb. Microscopic picture and ultrastructure analyses of the kidneys showed that Cd and Pb caused kidney damage to broiler chickens, and the damage was more serious in the Cd + Pb group, which was manifested by increased renal tubular epithelial degeneration and increased interstitial stasis points. Dietary exposure to Cd and Pb impaired production performance and induced renal oxidative damage in broilers. The combined effects of Cd and Pb on the kidneys are greater than their effects alone. The PERK-ATF4 pathway mediated endoplasmic reticulum stress participates the renal oxidative damage during chronic Cd and Pb exposure.

Taurine Inhibits Lung Metastasis in Triple-Negative Breast Cancer by Modulating Macrophage Polarization Through PTEN-PI3K/Akt/mTOR Pathway.

SUMMARY: Taurine (Tau) has been found to inhibit triple-negative breast cancer (TNBC) invasion and metastasis. However, its effect on tumor-promoting macrophages and tumor suppressor macrophages in breast cancer progression remains unknown. In this study, we investigated the effects of Tau on macrophage polarization and its role in TNBC cell growth, invasion, and metastasis. We induced human THP-1 monocytes to differentiate into M2 macrophages through exogenous addition of interleukin-4. We used the TNBC cell lines MDA-MB-231 and BT-549 cultured in a conditioned medium from M2 macrophages to investigate the effect of Tau on tumor growth and invasion. We analyzed macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression by quantitative polymerase chain reaction. We also detected the PTEN-PI3K/Akt/mTOR signaling pathway that mediates M1 macrophage to suppress tumor invasion using western blotting. Our results showed that Tau inhibits breast cancer metastasis to the lungs in vivo and cell invasion by altering the polarization of tumor-associated macrophage in vitro. In addition, Tau can up-regulate PTEN expression, suppress the PI3K-Akt signaling pathway, and promote the M1 polarization of macrophages, which ultimately inhibits the metastasis of TNBC cells. Our findings suggest that Tau inhibits the activation of the PI3K-Akt-mTOR signaling pathway by up-regulating PTEN, promotes the proportion of M1 macrophages in tumor-associated macrophage, and suppresses the invasion and metastasis of TNBC. This provides a potential therapeutic approach to influence cancer progression and metastasis.

[A prospective comparative study on effectiveness of single versus continuous adductor canal block combined with local infiltration anesthesia in unicompartmental knee arthroplasty].

Objective: To compare the early analgesic effects and the impact on knee joint function recovery after unicompartmental knee arthroplasty (UKA) between single adductor canal block (SACB) and continuous adductor canal block (CACB) combined with local infiltration anesthesia (LIA) using a prospective study. Methods: The patients with knee osteoarthritis admitted between April 2022 and December 2023 were enrolled as a subject. Among them, 60 patients met the selection criteria and were enrolled in the study. They were randomly assigned to the SACB group or CACB group in a ratio of 1:1 using a random number table method. There was no significant difference between the two groups ( P>0.05) in terms of age, gender, height, body mass, body mass index, affected side, and preoperative resting visual analogue scale (VAS) score and active VAS score, Oxford knee score (OKS), and American Hospital of Special Surgery (HSS) score. All patients received multimodal analgesia management using LIA combined with SACB or CACB. The operation time, pain related indicators (resting and activity VAS scores, number and timing of breakthrough pain, opioid consumption), joint function related indicators (quadriceps muscle strength, knee range of motion, OKS score, and HSS score), as well as postoperative block complications and adverse events were recorded and compared between the two groups. Results: There was no significant difference in the operation time between the two groups ( P<0.05). All patients in the two groups were followed up with a follow-up time of (9.70±4.93) months in the SACB group and (12.23±5.05) months in the CACB group, and the difference was not significant ( P>0.05). The CACB group had a significant lower resting VAS score at 24 hours after operation compared to the SACB group ( P<0.05). There was no significant difference in resting and active VAS scores between the two groups at other time points ( P>0.05). The CACB group had a significantly lower incidence of breakthrough pain compared to the SACB group [9 cases (30.00%) vs. 17 cases (56.67%); P<0.05). However, there was no significant difference in the timing of breakthrough pain occurrence and opioid consumption between the two groups ( P>0.05). Four cases in the SACB group and 7 cases in the CACB group experienced adverse events, with no significant difference in the incidence of adverse events between the two groups ( P>0.05). The CACB group had significantly better knee joint mobility than the SACB group at 1 and 2 days after operation ( P<0.05). There was no significant difference between the two groups in knee joint mobility on 0 day after operation and quadriceps muscle strength and OKS and HSS scores at different time points ( P>0.05). Conclusion: In UKA, the analgesic effects and knee joint function recovery are similar when compared between LIA combined with SACB and LIA combined with CACB. However, SACB is simpler to perform and can avoid adverse events such as catheter displacement and dislocation. Therefore, SACB may be a better choice.

Construction of a prognosis model of head and neck squamous cell carcinoma pyroptosis and an analysis of immuno-phenotyping based on bioinformatics.

Background: Head and neck squamous cell carcinoma (HNSCC) is currently the sixth most common cancer worldwide, and its prevalence and recurrence rates are gradually increasing. To study the relationship between HNSCC and cell pyroptosis and provide new treatment options for HNSCC, a prognostic model of pyroptosis-related genes (PRGs) was established to predict the prognosis of patients with HNSCC, and an immune correlation analysis was performed. Methods: A total of 53 PRGs were selected. We comprehensively analyzed the role of these PRGs in HNSCC through multiple omics data-set integration. We then identified two different molecular subtypes and found that changes in multi-layer PRGs were associated with clinicopathological characteristics, prognosis, and tumor microenvironment cell-infiltration characteristics in patients. Next, prognostic models were generated for nine PRGs; that is, cytotoxic T lymphocyte antigen 4 (CTLA4), V-set and immunoglobulin domain containing 4 (VSIG4), heparin-binding-epidermal growth factor (HBEGF), aquaporin-1 (AQP1), sodium channel epithelial 1 subunit delta (SCNN1D), argininosuccinate synthase 1 (ASS1), family with sequence similarity 83 member (FAM83), cyclin dependent kinase inhibitor 2A (CDKN2A), and serine protease inhibitor Kazal 6 (SPINK6). Finally, a risk-score model was constructed, and the Kaplan-Meier method was used to evaluate overall survival. In addition, the immune environment and drug sensitivity were analyzed. Results: This study showed that pyroptosis is closely related to HNSCC. The scores generated by the risk markers based on the new nine PRGs were identified as independent risk factors for predicting HNSCC. The differentially expressed genes between the low- and high-risk groups were further found to be related to the tumor immune cells and pathways. In addition, the risk score was found to be significantly correlated with chemosensitivity. Conclusions: Our comprehensive analysis of PRGs revealed their potential role in the tumor immune microenvironment, clinicopathological characteristics, and prognosis. These findings may improve our understanding of pyroptosis in HNSCC and may provide new ideas for evaluating prognosis and developing more effective immunotherapy strategies.

Remission effect of Canagliflozin in patients with newly diagnosed type 2 diabetes mellitus: a protocol for a multicenter, parallel-group, randomized, controlled, open-label trial.

BACKGROUND: Studies reporting the effects of metabolic surgery, lifestyle intervention, and intensive insulin therapy for the remission of type 2 diabetes (T2DM) has been increasing, with fruitful results better conducted and yielded. However, there are only a few studies on the remission of T2DM using oral hypoglycemic drugs. Therefore, this study aims to investigate the remission effect of canagliflozin and metformin on participants with newly diagnosed T2DM and its possible underlying mechanism(s) through which these two medications elicit diabetes remission. METHOD: To this end, we performed a multicenter, parallel-group, randomized, controlled, and open-label trial. A total of 184 participants with a ≤ 3-year course of T2DM will be enrolled and randomly assigned to the canagliflozin or metformin treatment group in a ratio of 1:1. Participants in each group will maintain their medication for 3 months after achieving the target blood glucose level and then stop it. These participants will be followed up for one year to determine remission rates in both groups. DISCUSSION: In this study, we will establish that whether canagliflozin is superior to metformin in terms of remission rate in participants with newly diagnosed T2DM. The results of this trial may provide robust evidence regarding the efficacy and mechanisms of the action of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in T2DM remission. TRIAL REGISTRATION: ChiCTR2100043770(February 28, 2021).

Pan cancer characterization of genes whose expression has been associated with LINE-1 antisense promoter activity.

BACKGROUND: Long interspersed nuclear element-1 (LINE-1 or L1) comprises 17% of the human genome. As the only autonomous and active retrotransposons, L1 may take part in cancer initiation and progression in some ways. The studies of L1 in cancer mainly focus on the impact of L1 insertion into the new genome locus. The L1 5´ untranslated region (UTR) also contains antisense promoter (ASP) activity, generating L1-gene chimeric transcripts to a neighbor exon. Some of these ASP-associated genes have been reported to be overexpressed in cancer and promote cancer cell growth. However, little is known about overall expression patterns and the roles of L1 ASP-associated genes in human cancers. RESULTS: L1 ASP-associated genes were frequently dysregulated in cancer and associated with the cell cycle, the PI3K/AKT pathway, and the GTPase signaling pathway. The expression of L1 ASP-associated genes was correlated with tumor patient prognosis. Hub L1 ASP-associated genes CENPU and MCM2 showed a correlation with immune infiltration, clinical T stage, and cancer stemness in pan-cancer. Knockdown of L1 ASP-associated gene LINC00491 resulted in a significant decrease in tumor growth and migration ability. CONCLUSIONS: The expression of L1 ASP-associated genes is significantly dysregulated at the pan-cancer level, which is closely related to the tumor microenvironment, progression, and patient prognosis. Hub genes CENPU and MCM2 are expected to be new tumor diagnostic markers and therapeutic targets.

Extensive spinal epidural abscess due to Streptococcus intermedius: a case report treated conservatively and literature review.

Purpose: To describe the clinical significance of prompt, adequate, and targeted intravenous antibiotic (IV antibiotic) therapy in the successful management of spinal epidural abscess (SEA) associated with Streptococcus intermedius (S. intermedius) infection. Case description: SEA is a rare, but catastrophic infection that may result in a high risk of permanent neurological disability. A 52-year-old Chinese female patient was presented to the emergency department due to 2 years of low back pain and 3 days of decreased muscle strength in the extremities. The blood culture confirmed the presence of S. intermedius infection, and gadolinium-enhanced magnetic resonance imaging (MRI) demonstrated widespread epidural abscesses in the cervical, thoracic, and lumbar spine canal. Empirical IV antibiotic therapy with vancomycin was promptly initiated, with meropenem and moxifloxacin added subsequently based on blood culture results. After 5 days of IV antibiotic treatment, the patient's blood culture became negative. 6 weeks later, a follow-up MRI showed a decrease in the size of the abscess. The patient's muscle strength was mostly restored after 2 months of IV antibiotic treatment. Conclusion: Repeat examinations or gadolinium-enhanced MRI should be considered when initial MRI findings are not diagnostic of SEA. For extensive SEA caused by Streptococcus intermedius infection, surgery may be non-essential, and the judicious antibiotic selection and adequate treatment duration are pivotal for successful conservative management. Furthermore, for patients who are not amenable to surgery, a comprehensive evaluation of their condition and meticulous implementation of a precise pharmacological regimen holds noteworthy clinical significance.

FOXP1-GINS1 axis promotes DLBCL proliferation and directs doxorubicin resistance.

GINS1 is overexpressed in several types of cancers including leukemia and linked to poor outcomes. However, GINS1 remains poorly investigated in DLBCL (diffuse large B-cell lymphoma). This project aimed to explore the expression, functions and regulation of GINS1 in DLBCL. In this study, through analysis of clinical specimens from DLBCL patients, we uncovered that GINS1 was upregulated in DLBCL. By EMSA, ChIP and luciferase reporter assays, it was found that FOXP1 transcriptionally activated GINS1 expression by directly binding to the promoter region of the GINS1 gene. Western blotting and RT-PCR also revealed that GINS1 expression positively correlated with FOXP1 in human DLBCL specimens and cell lines. In an in vivo xenograft lymphoma mouse model, the FOXP1/GINS1 regulatory axis was also validated. Moreover, with CCK8 cell proliferation assays and colony formation assay, elevated GINS1 expression was found to be associated with doxorubicin resistance in lymphoma cells. Our findings showed that the FOXP1-GINS1 axis played a critical role in DLBCL development and doxorubicin resistance, and targeting the FOXP1-GINS1 axis could be a potential therapeutic approach for DLBCL treatment.

Activity Relationship of Poly(ethylenimine)-Based Liposomes as Group A Streptococcus Vaccine Delivery Systems.

Untreated group A Streptococcus (GAS) can lead to a range of life-threatening diseases, including rheumatic heart disease. To date, no therapeutic or prophylactic vaccines are commercially available to treat or prevent GAS infection. Development of a peptide-based subunit vaccine offers a promising solution, negating the safety issues of live-attenuated or inactive vaccines. Subunit vaccines administer small peptide fragments (antigens), which are typically poorly immunogenic. Therefore, these peptide antigens require formulation with an immune stimulant and/or vaccine delivery platform to improve their immunogenicity. We investigated polyelectrolyte complexes (PECs) and polymer-coated liposomes as self-adjuvanting delivery vehicles for a GAS B cell peptide epitope conjugated to a universal T-helper epitope and a synthetic toll-like receptor 2-targeting moiety lipid core peptide-1 (LCP-1). A structure-activity relationship of cationic PEC vaccines containing different external PEI-coatings (poly(ethylenimine); 10 kDa PEI, 25 kDa PEI, and a synthetic mannose-functionalized 25 kDa PEI) formed vaccines PEC-1, PEC-2, and PEC-3, respectively. All three PEC vaccines induced J8-specific systemic immunoglobulin G (IgG) antibodies when administered intranasally to female BALB/c mice without the use of additional adjuvants. Interestingly, PEC-3 induced the highest antibody titers among all tested vaccines, with the ability to effectively opsonize two clinically isolated GAS strains. A comparative study of PEC-2 and PEC-3 with liposome-based delivery systems was performed subcutaneously. LCP-1 was incorporated into a liposome formulation (DPPC, DPPG and cholesterol), and the liposomes were externally coated with PEI (25 kDa; Lip-2) or mannosylated PEI (25 kDa; Lip-3). All liposome vaccines induced stronger humoral immune responses compared to their PEC counterparts. Notably, sera of mice immunized with Lip-2 and Lip-3 produced significantly higher opsonic activity against clinically isolated GAS strains compared to the positive control, P25-J8 emulsified with the commercial adjuvant, complete Freund's adjuvant (CFA). This study highlights the capability of a PEI-liposome system to act as a self-adjuvanting vehicle for the delivery of GAS peptide antigens and protection against GAS infection.

Immune-related biomarkers predict the prognosis and immune response of breast cancer based on bioinformatic analysis and machine learning.

Breast cancer (BC) is the malignancy with the highest mortality rate among women, identification of immune-related biomarkers facilitates precise diagnosis and improvement of the survival rate in early-stage BC patients. 38 hub genes significantly positively correlated with tumor grade were identified based on weighted gene coexpression network analysis (WGCNA) by integrating the clinical traits and transcriptome analysis. Six candidate genes were screened from 38 hub genes basing on least absolute shrinkage and selection operator (LASSO)-Cox and random forest. Four upregulated genes (CDC20, CDCA5, TTK and UBE2C) were identified as biomarkers with the log-rank p < 0.05, in which high expression levels of them showed a poor overall survival (OS) and recurrence-free survival (RFS). A risk model was finally constructed using LASSO-Cox regression coefficients and it possessed superior capability to identify high risk patients and predict OS (p < 0.0001, AUC at 1-, 3- and 5-years are 0.81, 0.73 and 0.79, respectively). Decision curve analysis demonstrated risk score was the best prognostic predictor, and low risk represented a longer survival time and lower tumor grade. Importantly, multiple immune cell types and immunotherapy targets were observed increase in expression levels in high-risk group, most of which were significantly correlated with four genes. In summary, the immune-related biomarkers could accurately predict the prognosis and character the immune responses in BC patients. In addition, the risk model is conducive to the tiered diagnosis and treatment of BC patients.

PAX5 and circ1857 affected DLBCL progression and B-cell proliferation through regulating GINS1.

PAX5, a member of the paired box gene family of transcription factors, is a B-cell-specific activator protein that plays important roles during B lymphopoiesis. Two putative PAX5 binding sites in the human GINS1 promoter region were identified. EMSA, ChIP and luciferase assay showed that PAX5 functions as a positive transcription factor for GINS1 expression. Furthermore, coordinated expression of PAX5 and GINS1 was observed in mice B cells under physiological conditions and LPS stimulation situations. A similar pattern was also observed in human DLBCL cell lines under differentiation-inducing conditions. In addition, both PAX5 and GINS1 were highly expressed and significantly correlated in DLBCL specimens and cell lines. These findings suggested that dysregulation of PAX5 played an extremely important role in controlling the universal phenomenon of tumor progression through increased expression of GINS1 in DLBCL. In addition, circ1857 that was generated using back splicing of PAX5 pre-mRNA could further stabilize GINS1 mRNA, modulate GINS1 expression and promote lymphoma progression. To the best of our knowledge, this report is the first to demonstrate the role of GINS1 in DLBCL progression, and the mechanism of GINS1 upregulation using both circ1857 and PAX5 in DLBCL was revealed. Our results suggested that GINS1 may be a possible therapeutic target for DLBCL.

Liposomal Formulations of a Polyleucine-Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer.

Human papilloma virus (HPV) is responsible for all cases of cervical cancer. While prophylactic vaccines are available, the development of peptide-based vaccines as a therapeutic strategy is still under investigation. In comparison with the traditional and currently used treatment strategies of chemotherapy and surgery, vaccination against HPV is a promising therapeutic option with fewer side effects. A peptide derived from the HPV-16 E7 protein, called 8Qm, in combination with adjuvants showed promise as a therapeutic vaccine. Here, the ability of polymerized natural amino acids to act as a self-adjuvating delivery system as a therapeutic vaccine was investigated for the first time. Thus, 8Qm was conjugated to polyleucine by standard solid-phase peptide synthesis and self-assembled into nanoparticles or incorporated in liposomes. The liposome bearing the 8Qm conjugate significantly increased mice survival and decreased tumor growth after a single immunization. Further, these liposomes eradicated seven-day-old well-established tumors in mice. Dendritic cell (DC)-targeting moieties were introduced to further enhance vaccine efficacy, and the newly designed liposomal vaccine was tested in mice bearing 11-day-old tumors. Interestingly, these DCs-targeting moieties did not significantly improve vaccine efficacy, whereas the simple liposomal formulation of 8Qm-polyleucine conjugate was still effective in tumor eradication. In summary, a peptide-based anticancer vaccine was developed that stimulated strong cellular immune responses without the help of a classical adjuvant.

Increased Expression of TMPRSS11E Is Involved in LPS- or Poly(I:C)-mediated Inflammation.

Transmembrane serine proteases are a group of enzymes that are implicated in diverse biological processes. Transmembrane serine protease 11E (TMPRSS11E) is expressed in epithelial cells. Previous studies on TMPRSS11E mainly focused on its function in tumor progression. In this study, we investigated the association of TMPRSS11E with the inflammatory response. We found that TMPRSS11E levels were upregulated in the BAL fluid of patients with acute respiratory distress syndrome and LPS-stimulated cultured epithelial cells. In an LPS-induced acute lung injury mouse model and a cercal ligation and puncture-induced sepsis model, increased expression levels of TMPRSS11E were also observed in the lung tissues. Knockdown of TMPRSS11E suppressed the proinflammatory cytokine release and alleviated lung injury. In addition, increased TMPRSS11E expression was detected in lung tissues of poly(I:C)-challenged mice, and overexpression of TMPRSS11E aggregated the lung injury. Unexpectedly, ectopic TMPRSS11E expression in macrophages was observed. Protease-activated receptor-1 was proteolytically activated by TMPRSS11E and enhanced the levels of proinflammatory cytokines. Taken together, our results indicate that TMPRSS11E can be induced during inflammatory response triggered by infection. Therefore, interventions with TMPRSS11E can aid in the treatment of pulmonary inflammation.

Dynamic volume variation of uterine leiomyomas during pregnancy.

OBJECTIVE: To investigate the volume variation of uterine leiomyomas and explore factors predicting their growth trends during pregnancy. METHOD: A retrospective observational study was performed on pregnant women with uterine leiomyomas between January 2016 and April 2020. The uterine leiomyoma volume was acquired from obstetrical ultrasound at the first, second, and third trimesters of gestation. A binary logistic regression analysis was conducted to explore the factors influencing the volume variation of uterine leiomyomas during pregnancy. RESULTS: A total of 278 pregnant women diagnosed with uterine leiomyomas were enrolled. The volumetric increase in uterine leiomyomas during pregnancy exhibited a higher growth rate from the first to second trimester (34.09%) than that from the second to third trimester (30.08%). Smaller uterine leiomyomas were more likely to increase in size from the first to second trimester and from the first to third trimester. Retroplacental uterine leiomyomas were more likely to increase in volume than that for uterine leiomyomas located away from the placenta in pregnant women from the second to third trimester. CONCLUSION: The uterine leiomyoma volume was potentially enlarged in a nonlinear growth pattern during pregnancy, which was associated with the former volume of uterine leiomyomas and the spatial relationship between leiomyoma-placental site.

[Validation the clinical value of good outcome following attempted resuscitation scores in Chinese populations in predicting the prognosis of in-hospital cardiac arrest].

OBJECTIVE: To verify the clinical value of the good outcome following attempted resuscitation (GO-FAR) score in predicting the neurological status of patients with in-hospital cardiac arrest (IHCA) in the Chinese population. METHODS: The clinical data of patients with IHCA who were admitted to the Zigong Fourth People's Hospital from January 1 to December 31, 2020 were retrospectively analyzed. Used Glasgow-Pittsburgh cerebral performance category (CPC) score 1 point as the end point, the subjects were divided into 4 groups according to the score: ≤ 0 group, 1-8 group, 9-20 group and ≥ 21 group. Taken the group which GO-FAR score ≤ 0 as the reference group, the odds ratio (OR) of the other three groups compared with this group was calculated. The receiver operator characteristic curve (ROC curve) was performed to evaluate the predictive value of the GO-FAR score in favorable neurological outcome. A calibration curve was drawn for the Hosmer-Lemeshow test to analyze the degree of calibration of the GO-FAR score for predicting good neurological outcome. RESULTS: A total of 230 IHCA patients were enrolled in the study, including 130 males, aged 74 (65, 81) years old, and 23 case (10.0%) had good neurological prognosis. There were statistically significant differences in GO-FAR-related variables, including age, a normal neurological function on admitted, acute stroke, metastatic cancer, septicemia, medical noncardiac admission, hepatic insufficiency, hypotension, renal insufficiency or dialysis, respiratory insufficiency, pneumonia, etc (all P < 0.05). Taken the GO-FAR score ≤ 0 group as the reference group, the OR values of good neurological prognosis in the GO-FAR score 1-8 group were 0.54 [95% confidence interval (95%CI) was 0.17-1.53, P = 0.250], 9-20 group were 0.17 (95%CI was 0.02-0.67, P = 0.009) and ≥ 21 group were 0.25 (95%CI was 0.05-0.85, P = 0.025). The area under the ROC curve (AUC) of the GO-FAR score for predicting favorable neurological outcome in IHCA patients was 0.653 (95%CI was 0.529-0.777, P = 0.015) and there was no significant difference in Hosmer-Lemeshow test (P = 0.311). All these suggested that there was no significant difference between the predicted value and the actual value. CONCLUSIONS: GO-FAR score can be applied to predict neurological prognosis of IHCA patients in Chinese population. It can help clinicians to predict the prognosis of cardio-pulmonary resuscitation (CPR) and propose critical recommendations in treatment for these patients or their families.

A network pharmacology-based exploration of the active compounds and potential drug targets of Si-Jun-Zi decoction in the treatment of cutaneous squamous cell carcinoma.

Background: Cutaneous squamous cell carcinoma (cSCC), a kind of skin cancer with high rates of morbidity and mortality, occurs frequently in the clinic. Although early surgical treatment can achieve good results, there is no effective prevention and treatment for the recurrence and metastasis of cSCC. As a useful resource to protect humans from disease, traditional Chinese medicine (TCM) has been adopted by clinicians for thousands of years. Methods: In this study, we collected a Chinese medicine formula and then employed a data mining method to analyze drug combinations of Si-Jun-Zi (SJZ) decoction. Multiple databases were used in this study to predict various ingredients, compounds, and their targets in the decoction. The potential targets of cSCC were also obtained from the database in the same way. In addition, as bioinformatics analysis methods, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used in our research as supplementary means to network pharmacology. Finally, we used ultra-performance liquid chromatography (UPLC) fingerprinting to analyze the effective components of the TCM decoction. Results: We detected 559 active compounds from Ginseng, Largehead Atractylodes, India Bread, and Glycyrrhiza Inflata, and selected 136 molecules under specific conditions. The mechanisms of the TCM formula were illustrated by the network pharmacology, such as compounds-herb network, compounds-target network, disease-target network, and target-target interaction network, as well as characteristics of the TCM. Then, GO analysis and KEGG analysis were performed on the compounds in the network using multiple methods of data mining and bioinformatics, and 10 candidate targets were identified. In addition, the UPLC fingerprinting method was used to analyze the components of SJZ decoction. Conclusions: Network pharmacology was performed to investigate the characteristics and mechanism of SJZ decoction, and a bioinformatics method was used to analyze the relationship between the effective compounds of the SJZ TCM decoction and cSCC-related specific targets and pathways, to find a variety of candidate compounds with multi-target activity.

Combined assessment of tumour cell nest size and desmoplastic reaction as an excellent prognostic predictor in oesophageal squamous cell carcinoma.

AIMS: Tumour budding (TB) activity, cell nest size (CNS), and desmoplastic reaction (DR) have been confirmed to be significantly correlated with prognosis in oesophageal squamous cell cancer (ESCC) recently. However, there are limited data on the prognostic significance of combined assessment of cellular dissociation and tumour stroma in ESCC. METHODS: In all, 265 cases with resected ESCCs diagnosed between January 2018 and August 2019 were retrospectively reviewed. All slides were reviewed for assessing TB, CNS, and DR. The Cellular Dissociation Grading and our Combined CNS and DR (CNS/DR) Grading systems were adopted to re-grade ESCCs. RESULTS: High TB activity, small CNS, and immature DR had a strong association with shorter overall survival (OS) and progression-free survival (PFS) (P < 0.001, respectively) in ESCC. Combined assessment of CNS and DR in a 4-tiered grading system displayed a prognostic excellence for survival (P < 0.001), and outperformed the Cellular Dissociation Grading for both OS (area under the curve [AUC], 0.728 versus 0.644, P = 0.043) and PFS (AUC, 0.763 versus 0.667, P = 0.018) by receiver operator characteristic curves. Also, Combined CNS/DR Grading showed superiority in recognizing a G4 subgroup with the worst outcome in our cohort, to whom the most urgent attention needs to be called. CONCLUSIONS: This is the first study to propose a novel Combined Grading system based on CNS and DR in ESCC, which has been demonstrated to be relatively superior to Cellular Dissociation Grading in predicting prognosis. The findings shed new light on the histopathological grading of ESCC and facilitates identifying biologically aggressive ESCCs.

Sulfonylurea receptor 1-expressing cancer cells induce cancer-associated fibroblasts to promote non-small cell lung cancer progression.

Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression; however, how CAFs are induced remains elusive. Sulfonylurea receptor 1 (SUR1) is a tumor-enhancer in non-small cell lung carcinoma (NSCLC). Here, we probed the influence of SUR1-expressing cancer cells on CAFs. Results showed that high SUR1 expression positively correlated with α-SMA positive staining of CAFs in tumor tissues and poor prognosis of NSCLC patients. SUR1 contributed to normal fibroblast (NF) transformation into CAFs and facilitated the growth and metastasis of NSCLC in vivo. Conditioned medium (CM) and exosomes from SUR1-expressing cancer cells induced CAFs and promoted fibroblast migration. In cancer cells, SUR1 promoted p70S6K-induced KH-type splicing regulatory protein (KHSRP) phosphorylation at S395 to inhibit the binding of KHSRP with let-7a precursor (pre-let-7a) and decreasing mature let-7a-5p expression in cancer cells and exosomes. Let-7a-5p delivered by exosomes blocked NF transformation into CAFs by targeting TGFBR1 to inactivate the TGF-ß signaling pathway. Glibenclamide, which targets SUR1, restrained CAFs and suppressed tumor growth in patient-derived xenograft models. Furthermore, we found that let-7a-5p was decreased in the tissues and plasma exosomes of NSCLC patients. In summary, SUR1-expressing cancer cells induce NF transformation into CAFs in the tumor microenvironment and promote NSCLC progression by transferring less exosomal let-7a-5p. Glibenclamide is a promising anti-cancer drug, and plasma exosomal let-7a-5p level is a potential diagnostic biomarker for NSCLC patients. These findings provide new therapeutic strategies by targeting SUR1 in NSCLC.

Epigenetic imprinting alterations as effective diagnostic biomarkers for early-stage lung cancer and small pulmonary nodules.

BACKGROUND: Early lung cancer detection remains a clinical challenge for standard diagnostic biopsies due to insufficient tumor morphological evidence. As epigenetic alterations precede morphological changes, expression alterations of certain imprinted genes could serve as actionable diagnostic biomarkers for malignant lung lesions. RESULTS: Using the previously established quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) method, elevated aberrant allelic expression of imprinted genes GNAS, GRB10, SNRPN and HM13 was observed in lung cancers over benign lesions and normal controls, which were pathologically confirmed among histologically stained normal, paracancerous and malignant tissue sections. Based on the differential imprinting signatures, a diagnostic grading model was built on 246 formalin-fixed and paraffin-embedded (FFPE) surgically resected lung tissue specimens, tested against 30 lung cytology and small biopsy specimens, and blindly validated in an independent cohort of 155 patients. The QCIGISH diagnostic model demonstrated 99.1% sensitivity (95% CI 97.5-100.0%) and 92.1% specificity (95% CI 83.5-100.0%) in the blinded validation set. Of particular importance, QCIGISH achieved 97.1% sensitivity (95% CI 91.6-100.0%) for carcinoma in situ to stage IB cancers with 100% sensitivity and 91.7% specificity (95% CI 76.0-100.0%) noted for pulmonary nodules with diameters ≤ 2 cm. CONCLUSIONS: Our findings demonstrated the diagnostic value of epigenetic imprinting alterations as highly accurate translational biomarkers for a more definitive diagnosis of suspicious lung lesions.

Synthesis of Nickel In Situ Modified SAPO-11 Molecular Sieves and Hydroisomerization Performance of Their NiWS Supported Catalysts.

SAPO-11 molecular sieves were modified with different Ni contents by the in situ modification method. The Ni-modified SAPO-11 molecular sieves were used as the supports to prepare the corresponding NiW-supported catalysts for the hydroisomerization of n-hexadecane. The Ni-modified SAPO-11 and the corresponding NiW-supported catalysts were characterized by X-ray diffraction, scanning electron microscopy, N2 adsorption-desorption, NH3-temperature-programmed desorption, pyridine adsorbed infrared, high-resolution transmission electron microscopy, and X-ray photoelectron spectroscopy. The results showed that Ni in situ modification preserved the crystal structure of SAPO-11; increased the BET specific surface area, mesopore volume, and medium and strong Brønsted acid amount of SAPO-11; and increased the stacking number of the active phase of the catalysts. 3Ni-SAPO-11 possessed the largest BET specific surface area, mesopore volume, and medium and strong Brønsted acid amount. NiW/3Ni-SAPO-11 possessed the highest dispersion of the active phase and the highest sulfidation degree of the active metals. The results of the hydroisomerization of n-hexadecane showed that Ni in situ modification improved the catalytic activity and selectivity of the catalysts for the hydroisomerization of n-hexadecane to varying degrees. Especially, NiW/3Ni-SAPO-11 had the highest catalytic activity and isomer selectivity, and the maximum yield of isomeric hexadecane could reach 71.18%.