PGC-1α loss promotes mitochondrial protein lactylation in acetaminophen-induced liver injury via the LDHB-lactate axis.

Coronavirus disease 2019 (COVID-19) affected people worldwide, and fever is one of the major symptoms of this disease. Although Acetaminophen (APAP) is a common fever-reducing medication, it can also mediate liver injury. However, the role of PGC-1α in regulating mitochondrial quality control by lactate dehydrogenase B (LDHB), a vital enzyme catalyzing the conversion of lactate to pyruvate, in APAP-induced hepatotoxicity, is unclear. Here, gene expression omnibus data of patients with APAP-induced liver injury were used to explore gene expression profiles. AML12 cells and C57/BL6 mice were used to establish models of APAP-induced acute liver injury. SIRT1 and PGC-1α were overexpressed in vitro via lentiviral transfection to establish stable cell lines. The results showed that APAP treatment decreased SIRT1/PGC-1α/LDHB expression and increased protein lactylation, mitochondrial lactate levels, and pathological damage in liver mitochondria. PGC-1α upregulation or activation ameliorated APAP-induced damage in the cells and liver. Furthermore, PGC-1α overexpression increased LDHB synthesis, reduced lactylation, and induced a switch from lactate to pyruvate production. These results suggest that PGC-1α and LDHB play a role in APAP-induced liver injury by regulating mitochondrial quality control and lactate metabolic reprogramming. Therefore, the PGC-1α/LDHB axis is a potential therapeutic target for APAP-induced liver injury.

The important role of whole-process computed tomography guidance for percutaneous gastrostomy in esophageal cancer patients who are unsuitable for or have had unsuccessful attempts with endoscopic and fluoroscopic gastrostomy.

PURPOSE: To explore the value of clinical application with the whole process computed tomography (CT) guided percutaneous gastrostomy in esophageal tumor patients. MATERIALS AND METHODS: A consecutive series of 32 esophageal tumor patients in whom endoscopic gastrostomy or fluoroscopy guided gastrostomy were considered too dangerous or impossible due to the esophagus complete obstruction, complicate esophageal mediastinal fistula, esophageal trachea fistula or severe heart disease. All of the 32 patients were included in this study from 2 medical center and underwent the gastrostomy under whole process CT guided. RESULTS: All of the gastrostomy procedure was finished successfully under whole process CT guided and the technical success rate was 100%. The average time for each operation was 27 min. No serious complications occurred and the minor complications occurred in 3 patients, including local infection, severe hyperplasia of granulation tissue and tube dislodgment. There were no procedure related deaths. CONCLUSION: The technical success rate of whole process CT guided percutaneous gastrostomy is high and the complication is low. This technique can be used feasible and effectively in some special patients.

Venous-arterial extracorporeal membrane oxygenation for psittacosis pneumonia complicated with cardiogenic shock: case report and literature review.

INTRODUCTION: Dilated cardiomyopathy (DCM) is characterized by the enlargement of the left ventricle or biventricular, accompanied by myocardial systolic dysfunction. Chlamydia psittacosis (CP) is a zoonotic pathogen, which can cause severe pneumonia, respiratory failure, and acute organ dysfunction. The deterioration of DCM caused by CP infection is extremely rare, and few cases of successful management were reported. CASE PRESENTATION: We reported a 67-year-old male patient with DCM and chronic heart failure. Who was admitted to ICU with severe pneumonia, acute hypoxemic respiratory failure, acute decompensated heart failure, arrhythmia, and cardiogenic shock. Mechanical ventilation (MV) and venous-arterial extracorporeal membrane oxygenation (VA-ECMO) were established for respiratory and circulatory support. Broncho alveolar lavage fluid(BALF)was collected for culture and metagenomics next-generation sequencing (mNGS) test. Repeated mNGS tests indicated the high possibility of CP pneumonia, thereafter, moxifloxacin and doxycycline were prescribed. After targeted antibiotics and organ support treatment, pneumonia, respiratory and circulatory failure were gradually resolved, patient was successfully weaned from MV and VA-ECMO. Finally, the patient was recovered and discharged alive. CONCLUSIONS: Severe respiratory and circulatory failure caused by CP infection in DCM patients is a rare life-threatening clinical condition. Early accurate diagnosis, targeted antibiotic therapy, coupled with extracorporeal life support posed positive impact on the patient's disease course and outcome.

Novel Withanolides from Tubocapsicum anomalum Suppress Triple-Negative Breast Cancer by Triggering Apoptosis and p53-ASCT2-SLC7A11-Mediated Ferroptosis.

Triple-negative breast cancer (TNBC) is a malignant breast cancer. There is an urgent need for effective drugs to be developed for TNBC. Tubocapsicum anomalum (T. anomalum) has been reported to have an anti-tumor effect, and six novel withanolides were isolated from it and designated as TAMEWs. However, its anti-TNBC effect is still unknown. The results of an MTT assay indicated a higher sensitivity of TNBC cells to TAMEWs compared to other cells. TAMEWs induced apoptosis via mitochondrial dysfunction. They caused increased levels of lipid ROS and Fe2+, with downregulation of GSH and cystine uptake, and it has been confirmed that TAMEWs induced ferroptosis. Additionally, the results of Western blotting indicate that TAMEWs significantly decrease the expressions of ferroptosis-related proteins. Through further investigation, it was found that the knockdown of the p53 gene resulted in a significant reversal of ferroptosis and the expressions of its associated proteins SLC7A11, ASCT2, and GPX4. In vivo, TAMEWs suppressed TNBC growth with no obvious damage. The IHC results also showed that TAMEWs induced apoptosis and ferroptosis in vivo. Our findings provide the first evidence that TAMEWs suppress TNBC growth through apoptosis and ferroptosis.

Eupalinolide J Inhibits Cancer Metastasis by Promoting STAT3 Ubiquitin-Dependent Degradation.

Eupalinolide J (EJ) is an active component from Eupatorium lindleyanum DC. (EL), which was reported to have good antitumor activity via STAT3 and Akt signaling pathways. In this study, we identified Eupalinolide J (EJ) as a potential anti-cancer metastatic agent by target prediction and molecular docking technique screening. Follow-up experiments demonstrated that EJ exhibited a good inhibitory effect on cancer cell metastasis both in vitro and in vivo, and could effectively reduce the expression of STAT3, MMP-2, and MMP-9 proteins in cells, while the knockdown of STAT3 could weaken the inhibitory effect of EJ on cancer cell metastasis. Further molecular biology experiments revealed that EJ promoted STAT3 ubiquitin-dependent degradation, and thus, downregulated the expression of the metastasis-related genes MMP-2 and MMP-9. In conclusion, our study revealed that EJ, a sesquiterpene lactone from EL, could act as a STAT3 degradation agent to inhibit cancer cell metastasis and is expected to be applied in cancer therapy.

Rosuvastatin Slows Progression of Carotid Intima-Media Thickness: The METEOR-China Randomized Controlled Study.

BACKGROUND: Atherosclerosis is the leading cause of cardiovascular disease worldwide, including in China. Primary prevention, through lipid-lowering, could avert development of atherosclerosis. Carotid intima-media thickness (CIMT) is a well-validated measure of atherosclerosis used in intervention studies as the primary outcome and alternative end point for cardiovascular disease events. METHODS: This randomized, double-blind, placebo-controlled, multicenter, parallel-group study assessed the effects of rosuvastatin 20 mg/d compared with placebo on progression of CIMT over 104 weeks in Chinese people with subclinical atherosclerosis. The primary end point was the annualized rate of change in mean of the maximum CIMT measurements taken 7× over the study period from each of 12 carotid artery sites (near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery). Secondary end points included CIMT changes at different artery sites and lipid-parameter changes. Safety was also assessed. RESULTS: Participants were randomized (1:1) to receive rosuvastatin (n=272) or placebo (n=271). Baseline characteristics were well balanced between groups. The change in mean of the maximum CIMT of the 12 carotid sites was 0.0038 mm/y (95% CI, -0.0023-0.0100) for the rosuvastatin group versus 0.0142 mm/y (95% CI, 0.0080-0.0204) for the placebo group, with a difference of -0.0103 mm/y (95% CI, -0.0191 to -0.0016; P=0.020). For the CIMT secondary end points, the results were generally consistent with the primary end point. There were clinically relevant improvements in lipid parameters with rosuvastatin. We observed an adverse-event profile consistent with the known safety profile of rosuvastatin. CONCLUSIONS: Rosuvastatin 20 mg/d significantly reduced the progression of CIMT over 2 years in Chinese adults with subclinical atherosclerosis and was well tolerated. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02546323.

Diagnostic efficacy of FibroScan for liver inflammation in patients with chronic hepatitis B: a single-center study with 1185 liver biopsies as controls.

BACKGROUND: Noninvasive diagnostic technologies that can dynamically monitor changes in liver inflammation are highly important for the management of chronic hepatitis B (CHB) patients and thus warrant further exploration. This study assessed the diagnostic efficacy of FibroScan for liver inflammation in CHB patients. METHODS: A total of 1185 patients were selected, and ultrasound-guided liver biopsy was performed within 1 month after the FibroScan test. The liver stiffness measurement (LSM), the reliability criteria (IQR/M) of LSM, the quality of liver biopsy (complete portal area, PA), and the liver inflammation grades were the main observation items of this study. With liver biopsy as the control, the diagnostic efficacy of FibroScan for liver inflammation in CHB patients was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The grade of liver inflammation was positively correlated with the stage of fibrosis (rho = 0.829, P < 0.001). Different grades of inflammation will have significant rise in LSM values within the same fibrosis stage, and LSM values were positively correlated with liver inflammation grade and fibrosis stage, and the rho is 0.579 and 0.593 respectively (P < 0.001). Significant differences in the LSM of FibroScan were observed among different grades of liver inflammation (P < 0.0001). Liver biopsy (PA > 10) served as the control, and the cutoff point and the area under ROC curves (AUCs) of the LSMs for different inflammation grades were as follows: G2, 8.6 kPa, 0.775; G3 9.8 kPa, 0.818; and G4, 11.0 kPa; 0.832. With LSM cutoff values of 8.6 kPa, 9.8 kPa and 11.0 kPa, FibroScan showed certain diagnostic value for CHB patients with G2, G3 and G4 liver inflammation, especially those with G4 inflammation. CONCLUSIONS: The grade of liver inflammation was positively correlated with the stage of fibrosis, different grades of inflammation will have significant rise in LSM values within the same fibrosis stage. In addition to liver fibrosis, FibroScan could evaluate liver inflammation in CHB patients in a noninvasive manner.

MIR31HG polymorphisms are related to steroid-induced osteonecrosis of femoral head among Chinese Han population.

BACKGROUNDS: MIR31 host gene (MIR31HG) polymorphisms play important roles in the occurrence of osteonecrosis. However, the association of MIR31HG polymorphisms with the risk of steroid-induced osteonecrosis of the femoral head (SONFH) remains unclear. In this study, we aimed to investigate the correlation between MIR31HG polymorphisms and SONFH susceptibility in the Chinese Han population. METHODS: A total of 708 volunteers were recruited to detect the effect of seven single nucleotide polymorphisms (SNPs) in the MIR31HG gene on SONFH risk in the Chinese Han population. Genotyping of MIR31HG polymorphisms was performed using the Agena MassARRAY platform. The odds ratio (OR) and 95% confidence interval (95% CI) were used to evaluate the correlation between MIR31HG polymorphisms and SONFH risk using logistic regression model. RESULTS: According to the results of genetic model, rs10965059 in MIR31HG was significantly correlated with the susceptibility to SONFH (OR = 0.56, p = 0.002). Interestingly, the stratified analysis showed that rs10965059 was associated with the reduced risk of SONFH in subjects aged > 40 years (OR = 0.30, p < 0.001) and male populations (OR = 0.35, p < 0 .001). Moreover, rs10965059 was associated with the reduced risk of bilateral SONFH (OR = 0.50, p = 0.002). Finally, multi-factor dimension reduction (MDR) results showed that the combination of rs1332184, rs72703442, rs2025327, rs55683539, rs2181559, rs10965059 and rs10965064 was the best model for predicting SONFH occurrence (p < 0.0001). CONCLUSION: The study indicated that rs10965059 could be involved in SONFH occurrence in the Chinese Han population, which might provide clues for investigating the role of MIR31HG in the pathogenesis of SONFH.

Perioperative stroke in patients undergoing spinal surgery: a retrospective cohort study.

BACKGROUND: The incidence of perioperative stroke following spinal surgery, including ischemic and hemorrhagic stroke, has not been fully investigated in the Chinese population. Whether specific spinal or emergency/elective procedures are associated with perioperative stroke remains controversial. This study aimed to investigate the incidence of perioperative stroke, health economic burden, clinical outcomes, and associated risk factors. METHOD: A retrospective cohort study using an electronic hospital information system database was conducted from Jan 1, 2015, to Jan 1, 2021, in a tertiary hospital in China. Patients aged ≥18 years who had undergone spinal surgery were included in the study. We recorded patient demographics, comorbidities, and health economics data. Clinical outcomes included perioperative stroke during hospitalization and associated risk factors. The patients' operative data, anesthetic data, and clinical manifestations were recorded. RESULT: A total of 17,408 patients who had undergone spinal surgery were included in this study. Twelve patients had perioperative stroke, including seven ischemic stroke (58.3%) and five hemorrhagic stroke (41.7%). The incidence of perioperative stroke was 0.07% (12/17,408). In total, 12 stroke patients underwent spinal fusion. Patients with perioperative stroke were associated with longer hospital stay (38.33 days vs. 9.78 days, p < 0.001) and higher hospital expenses (RMB 175,642 vs. RMB 81,114, p < 0.001). On discharge, 50% of perioperative patients had severe outcomes. The average onset time of perioperative stroke was 1.3 days after surgery. Stroke history (OR 146.046, 95% CI: 28.102-759.006, p < 0.001) and hyperlipidemia (OR 4.490, 95% CI: 1.182-17.060, p = 0.027) were associated with perioperative stroke. CONCLUSION: The incidence of perioperative stroke of spinal surgery in a tertiary hospital in China was 0.07%, with a high proportion of hemorrhagic stroke. Perioperative stroke patients experienced a heavy financial burden and severe outcomes. A previous stroke history and hyperlipidemia were associated with perioperative stroke.

First report of Alternaria alternata causing leaf yellow spot on Ginger (Zingiber officinale Roscoe) in Laifeng, China.

Ginger (Zingiber officinale Roscoe) is a highly important commercial crop in China, which is widely cultivated for its medicinal and nutritional qualities. Fengtou ginger is a variety mainly grown in Central China. From June to September of 2021, leaf yellow spot symptoms were observed on ginger plants var. Fengtou in commercial fields, localized in Laifeng county (29.37゜N, 109.31゜E), Hubei Province, China. Early symptoms were small yellow spots (approximately 0.2 cm) on leaves, but these spots gradually expanded, and the middle turn brown. The incidence of yellow spot on plants was 15% to 35%. To identify the causal agent of the disease, 15 symptomatic leaves were collected on from plants in the field. From each ginger leaf, small fragments (2 to 4 mm) were cut from the margin of the lesions and surface disinfected with 75% ethanol and 2% sodium hypochlorite for 30 s and 60 s, respectively, and rinsed three times with sterile water (Zhong et al. 2022). The disinfected small fragments were placed on Rose Bengal Agar medium at 25 ℃. After 3 to 5 days of incubation, a total of 11 isolates from leaf samples were obtained, of which 8 showed a radial mycelial growth that was grayish and then darkened. Conidiophores were brown and branched. Conidia were multicellular, obclavate to obpyriform within 9.1-22.6 µm (average 14.3 µm) in length and 6.0-13.5 µm (average 7.9 µm) in width (n=30). The isolates were identified as Alternaria sp. according to their morphological characteristics (Simmons 2007). For further molecular identification, genomic DNAs of two representative isolates (isolate 1 and isolate 4) were extracted and amplificated using a set of primers ITS1/ITS4 (White et al. 1990), RPB2-5F/RPB2-7R (Liu et al. 1999) and gpd1/gpd2 (Berbee et al. 1999), for the internal transcribed spacer (ITS)-rDNA region, partial RNA polymerase II largest subunit (RPB2), and Glyceraldehyde 3-phosphate (GADPH), respectively. The sequences were submitted to GenBank with submission Nos. OM701795 and OM701794 for ITS-rDNA; OM864662 and OM864663 for RPB2; OM864664 and OM864665 for the GADPH gene. A BLAST analysis in GenBank showed 100% identity with A. alternata for ITS (GenBank No. MN907440), RPB2 (GenBank No. KP057228) and GADPH (GenBank No. MK637444), respectively. A pathogenicity test was performed on potted healthy plants of ginger var. Fengtou of 2.5-month-old in a greenhouse. A total of five plants were sprayed with a conidial suspension (105 spores/mL) of each isolate on leaves until runoff (3 to 5 ml per plant) occurred. Five plants were sprayed with sterile water. The plants were grown in a greenhouse at 25 ℃. Eight days after inoculation, the symptoms similar to diseased leaves in the field appeared on the inoculated leaves, while the controls remained healthy. The fugus re-isolated from infected tissues was morphologically and molecularly identical to the original isolates of A. alternata, which fulfill the Koch's postulates. To our knowledge, this is the first report of A. alternata causing yellow spot on ginger in China. The work will be beneficial to develop effective management methods for preventing and treating this disease and avoid yield and economic loss of ginger in China.

Design, Synthesis, and Cytotoxic Activity of Novel Natural Arylsulfonamide-Inspired Molecules.

Primary arylsulfonamide functional groups feature prominently in diverse pharmaceuticals. However, natural arylsulfonamides are relatively infrequent. In this work, two novel arylsulfonamide natural products were first synthesized, and then a series of novel molecules derived from natural arylsulfonamides were designed and synthesized, and their in vitro cytotoxic activities against A875, HepG2, and MARC145 cell lines were systematically evaluated. The results indicate that some of these arylsulfonamide derivatives exhibit significantly good cytotoxic activity against the tested cell lines compared with the control 5-fluorouracil (5-FU), such as compounds 10l, 10p, 10q, and 10r. In particular, the potential molecule 10q, containing a carbazole moiety, exhibited the highest inhibitory activity against all tested cell lines, with IC50 values of 4.19 ± 0.78, 3.55 ± 0.63, and 2.95 ± 0.78 µg/mL, respectively. This will offer the potential to discover novel drug-like compounds from the sparsely populated area of natural products that can lead to effective anticancer agents.

Percutaneous Gastrostomy Compared with Esophageal Stent Placement for the Treatment of Esophageal Cancer with Dysphagia.

PURPOSE: To compare the outcomes of self-expandable metal stent placement and percutaneous gastrostomy (PG) for the treatment of patients with esophageal cancer (EC) and dysphagia. MATERIALS AND METHODS: This retrospective observational study consisted of 113 patients with EC and dysphagia who underwent either stent placement (n = 47) or PG (n = 66) at a single center between June 2014 and June 2018. RESULTS: There were 63 men and 50 women, with a mean age of 76.5 years (standard deviation 4.9 years). The 2 groups had similar baseline characteristics, except that the PG group had a higher percentage of patients with cervical EC (22.7% vs 2.1%, P < .001). The PG group had better maintenance of nutritional status in terms of reduction in serum albumin level (P = .039) and weight loss (P = .041). Compared with the stent group, the PG group demonstrated a lower incidence of local severe pain (0% vs 21.3%, P < .001) and lower incidence of dislodgment of device (1.5% vs 19.1%, P = .002). The PG group demonstrated longer overall survival compared with the stent group for Stages II and III (201 vs 185 days, P = .034) and Stage IV (122 vs 86 days, P = .001). CONCLUSIONS: Compared with stent insertion, PG is associated with better maintenance of nutritional status, fewer complications, and better survival. Thus, PG may be the preferred choice for treating malnutrition in patients with EC and dysphagia.

Characterization of intratumoral and circulating IL-10-producing B cells in gastric cancer.

The tumor microenvironment harbors multiple immunosuppressive mechanisms, many of which involve suppressive immune cells. B regulatory (Breg) cells, as critical regulators of immune responses, were investigated in patients with gastric carcinoma. In the present study, the B cells that expressed IL-10 were highly enriched in tumor-infiltrating B cells, and could also be found at reduced frequencies in circulating B cells. These cells expressed high CD19 and CD20, and were almost exclusively CD27+CD10-. The IL-10 expression was significantly higher in CD27+CD10--sorted B cells than in CD27-CD10--sorted B cells. In an in vitro coculture of B cells and autologous T cells, CD27+CD10- B cells were capable of reducing the levels of CD4 T cell-mediated IFNγ, TNF, and IL-17 expression and the levels of CD8 T cell-mediated IFNγ and TNF expression. These regulatory effects were dependent on IL-10 as well as CD80/CD86. Interestingly, CD27+CD10- B cells also significantly elevated IL-10 production from CD4 and CD8 T cells in an IL-10-dependent manner. Overall, we here report enrichment of IL-10-expressing CD27+CD10- B cells in the intratumoral environment, which could significantly alter the cytokine production profile by CD4 and CD8 T cells.

Circulating levels of Elabela and Apelin in the second and third trimesters of pregnancies with gestational diabetes mellitus.

We design this study to detect levels of Elabela (ELA) and Apelin (APLN) in women with and without gestational diabetes mellitus (GDM) in the second and third trimesters, and to identify whether there is any association between ELA, APLN, and metabolic parameters. Seventy-nine GDM and 80 control subjects in the second trimester and 87 GDM and 88 healthy subjects in the third trimester were included. In the second trimester, lower ELA levels [(14.1 versus 16.9) ng/ml, p = .025] and higher APLN levels [(1021.8 versus 923.5) pg/ml, p = .046] were observed in GDM patients compared to controls. ELA levels were positively correlated with fasting plasma glucose (FPG) (r = 0.423, p < .001) in the control group, and APLN levels were negatively correlated with triglycerides (TG) (r = -0.251, p = .025) in the control group and total cholesterol (TC) (r = -0.227, p = .044) in the GDM group. ELA appeared to be related to glucose metabolism and APLN is involved in lipid metabolism during pregnancy. The expression of ELA is significantly downregulated from the second trimester to the third trimester.

LIGHT-INDUCED RICE1 Regulates Light-Dependent Attachment of LEAF-TYPE FERREDOXIN-NADP+ OXIDOREDUCTASE to the Thylakoid Membrane in Rice and Arabidopsis.

LIR1 (LIGHT-INDUCED RICE1) encodes a 13-kD, chloroplast-targeted protein containing two nearly identical motifs of unknown function. LIR1 is present in the genomes of vascular plants, mosses, liverworts, and algae, but not in cyanobacteria. Using coimmunoprecipitation assays, pull-down assays, and yeast two-hybrid analyses, we showed that LIR1 interacts with LEAF-TYPE FERREDOXIN-NADP(+) OXIDOREDUCTASE (LFNR), an essential chloroplast enzyme functioning in the last step of photosynthetic linear electron transfer. LIR1 and LFNR formed high molecular weight thylakoid protein complexes with the TIC62 and TROL proteins, previously shown to anchor LFNR to the membrane. We further showed that LIR1 increases the affinity of LFNRs for TIC62 and that the rapid light-triggered degradation of the LIR1 coincides with the release of the LFNR from the thylakoid membrane. Loss of LIR1 resulted in a marked decrease in the accumulation of LFNR-containing thylakoid protein complexes without a concomitant decrease in total LFNR content. In rice (Oryza sativa), photosynthetic capacity of lir1 plants was slightly impaired, whereas no such effect was observed in Arabidopsis thaliana knockout mutants. The consequences of LIR1 deficiency in different species are discussed.

The value of serum uric acid levels to differentiate causes of transient loss of consciousness.

BACKGROUND: Generalized tonic-clonic seizures (GTCS), syncope, and psychogenic nonepileptic seizures (PNES) are common emergent neurological conditions that cause transient disturbances of consciousness; however, it is sometimes difficult to distinguish them. OBJECTIVE: This study aimed to explore the value of serum uric acid levels in differentiating among GTCS, syncope, and PNES by analyzing serum uric acid levels in patients with GTCS, syncope, and PNES. METHODS: A total of 391 patients were retrospectively analyzed. Venous blood was drawn from the patients within 20 min of their arrival to the emergency department; serum uric acid levels were measured using the uricase method. RESULTS: Serum uric acid levels and the percentage of patients with elevated uric acid (elevation percentage) were significantly higher in the group with GTCS (n = 179) than in the groups with syncope (n = 156) (p < 0.001) and PNES (n = 56) (p < 0.001). The result remained the same when the serum uric acid level of male or female patients in the group with GTCS were compared separately with that in the other two groups (all p < 0.001). In the group with GTCS, both the serum uric acid level (p < 0.001) and elevation percentage (p < 0.05) were significantly higher in males than in females. The receiver operating characteristics (ROC) analysis in male patients yielded a serum uric acid value of 428.50 µmol/L with a sensitivity of 0.78 and a specificity of 0.99 as the optimal cutoff value to distinguish GTCS from other events. In female patients, a cutoff value of 338.00 µmol/L had a sensitivity of 0.69 and a specificity of 0.91 to distinguish GTCS from other events. For the group with GTCS, the period of time between the onset of seizure and serum uric acid levels dropping to normal were analyzed in 40 patients. The duration was 44.56 ±â€¯11.46 h for males (n = 23) and 40.37 ±â€¯9.78 h for females (n = 17) with no significant difference (p = 0.325). CONCLUSION: Serum uric acid levels provided certain clinical value for the differentiation of GTCS, syncope, and PNES; however, this requires verification in prospective studies with larger sample sizes.

Hypoxic Macrophage-Derived VEGF Promotes Proliferation and Invasion of Gastric Cancer Cells.

BACKGROUND: Gastric cancer (GC) is one of the most common causes of cancer death. Hypoxia is an important property of the tumor microenvironment of GC. Increasing evidence demonstrates that tumor-associated macrophages are related to the metastasis of GC, while the precise mechanism of how hypoxic macrophages affect tumor progression is still not fully understood. AIMS: To examine whether the mediators released from hypoxic macrophages contribute to the invasion and proliferation of GC cells. METHODS: Cell Counting Kit-8 was utilized to determine the proliferation of SGC7901 and MKN45 cells. The invasion of SGC7901 and MKN45 cells was measured by transwell invasion assay. Expression of VEGF mRNA in THP-1-derived macrophages was determined by RT-PCR, and protein level of VEGF in the culture medium was detected by ELISA. RESULTS: The proliferation and invasion of SGC7901 and MKN45 cells were dramatically increased after treatment with conditioned medium (CM) collected from THP-1-derived macrophages under hypoxia (H-CM), and the phosphorylation of Akt and p38 in SGC7901 and MKN45 cells was also up-regulated by H-CM stimulation. Notably, blockage of PI3K-Akt or p38 MAP kinase abolished the effects of H-CM on the proliferation and invasion of SGC7901 and MKN45 cells. Furthermore, VEGF was increased in macrophages after hypoxia and administration with nintedanib, an inhibitor of VEGFR, significantly decreases the phosphorylation of Akt and p38, as well as the proliferation and invasion of SGC7901 and MKN45 cells in response to H-CM. CONCLUSIONS: Our findings suggest that hypoxia-injured macrophages contribute to the proliferation and invasion of GC cells through the release of mediators such as VEGF.

Proline-Rich Protein 11 Regulates Self-Renewal and Tumorigenicity of Gastric Cancer Stem Cells.

BACKGROUND/AIMS: Gastric cancer is a highly aggressive tumor containing cancer stem cells (CSCs), which participate in tumor initiation, therapeutic resistance, and tumor relapse. Proline-rich protein 11 (PRR11) has been shown to be up-regulated in human cancers; however, its role in gastric CSCs is unknown. We hypothesize that PRR11 may affect tumorigenicity of gastric CSCs. In this study, we explored the biological function and regulation of PRR11 in gastric CSCs. METHODS: Expression of PRR11 was evaluated in gastric CSC cell line by real-time quantitative PCR and western blot. The effect of PRR11 on tumorigenicity was examined by interference with gene expression using lentiviral vector-loaded shRNA. A xenograft tumor model using NOD/SCID mice was established to examine the role of PRR11 in tumor development. RESULTS: Data showed that PRR11 was highly expressed in gastric CSCs. PRR11 was responsible for the maintenance of self-renewal and tumorigenicity of gastric CSCs, and overexpression of exogenous PRR11 could restore the self-renewal of gastric non-CSCs. Furthermore, interference with PRR11 altered the expression of stemness transcription factors. Interestingly, MAPK signaling controlled PRR11 expression by increasing PRR11 protein stability, and maintained gastric CSCs self-renewal in a PRR11 dependent manner. CONCLUSIONS: PRR11 regulated self-renewal and tumorigenicity of gastric CSCs through MAPK signaling, and could be used as a therapeutic target for gastric cancer.

Association between first caesarean delivery and adverse outcomes in subsequent pregnancy: a retrospective cohort study.

BACKGROUND: Few studies have explored the association between a previous caesarean section (CS) and adverse perinatal outcomes in a subsequent pregnancy, especially in women who underwent a non-indicated CS in their first delivery. We designed this study to compare the perinatal outcomes of a subsequent pregnancy in women who underwent spontaneous vaginal delivery (SVD) or CS in their first delivery. METHODS: This retrospective cohort study included women who underwent singleton deliveries at the International Peace Maternity and Child Health Hospital from January 2013 to December 2016. Data on the perinatal outcomes of all the women were extracted from the medical records. Multivariate logistic regression was conducted to assessed the association between CS in the first delivery and adverse perinatal outcomes in the subsequent pregnancy. RESULTS: CS delivery in the subsequent pregnancy was more likely for women who underwent CS in their first birth than for women with previous SVD (97.3% versus 13.2%). CS in the first birth was also associated with a significantly increased risk of adverse outcomes in the subsequent pregnancy, especially in women who underwent a non-indicated CS. Adverse perinatal outcomes included pregnancy-induced hypertension [adjusted odds ratio (OR), 95% confidence interval (CI): 2.20, 1.59-3.05], gestational diabetes mellitus (1.82, 1.57-2.11), gestational anaemia (1.27, 1.05-1.55), placenta previa (3.18, 2.15-4.71), placenta accreta (2.75, 1.75-4.31), and polyhydramnios (2.60, 1.57-4.31) in the mother and preterm delivery (1.37, 1.06-1.78), low birth weight (3.78, 2.07-6.90), macrosomia (5.04, 3.95-6.44), and neonatal jaundice (1.72, 1.39-2.14) in the baby. CONCLUSIONS: CS in the first delivery markedly increases the risk of repeated CS and maternal-fetal complications in the subsequent pregnancy, especially in women with a non-indicated CS.