bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scavenger receptor a is a major homeostatic regulator that restrains drug-induced liver injury
Authors: Guo Chunqing , Liu Wenjie , Liu Zheng , Cai Jinyang , Yu Xiaofei , Wang Hongxia , Li Xia , Zuo Daming , Jiang Xixian , Zhang Bei , Liu Jinze , Sanyal Arun J. , Puri Puneet , Zhou Huiping , Wang Xiang-Yang 
Published: January 2023

Background and Aim:
Drug-induced liver injury occurs frequently and can be life threatening. Although drug-induced liver injury is mainly caused by the direct drug cytotoxicity, increasing evidence suggests that the interplay between hepatocytes and immune cells can define this pathogenic process. Here, we interrogate the role of the pattern recognition scavenger receptor A (SRA) for regulating hepatic inflammation and drug-induced liver injury.

Approach and Results:
Using acetaminophen (APAP) or halothane-induced liver injury models, we showed that SRA loss renders mice highly susceptible to drug hepatotoxicity, indicated by the increased mortality and liver pathology. Mechanistic studies revealed that APAP-induced liver injury exaggerated in the absence of SRA was associated with the decreased anti-inflammatory and prosurvival cytokine IL-10 concomitant with excessive hepatic inflammation. The similar correlation between SRA and IL-10 expression was also seen in human following APAP uptake. Bone marrow reconstitution and liposomal clodronate depletion studies established that the hepatoprotective activity of SRA mostly resized in the immune sentinel KCs. Furthermore, SRA-facilitated IL-10 production by KCs in response to injured hepatocytes mitigated activation of the Jun N-terminal kinase-mediated signaling pathway in hepatocytes. In addition, supplemental use of IL-10 with N-acetylcysteine, only approved treatment of APAP overdose, conferred mice improved protection from APAP-induced liver injury.

Conclusion:
We identify a novel hepatocyte-extrinsic pathway governed by the immune receptor SRA that maintains liver homeostasis upon drug insult. Giving that drug (ie, APAP) overdose is the leading cause of acute liver failure, targeting this hepatoprotective SRA-IL-10 axis may provide new opportunities to optimize the current management of drug-induced liver injury.
Increasing gallstone disease prevalence and associations with gallbladder and biliary tract mortality in the US
Authors: Unalp-Arida Aynur , Ruhl Constance E. 
Published: January 2023

Background and Aims:
We examined gallbladder and biliary tract mortality predictors in the US National Health and Nutrition Examination Survey (NHANES), 1988-1994, with 31 years of linked mortality data, and gallstone disease prevalence trends and associations in NHANES 2017-March 2020 prepandemic data.

Approach and Results:
In NHANES 1988-1994, 18,794 participants were passively followed for mortality, identified by death certificate underlying or contributing causes, by linkage to the National Death Index through 2019. In NHANES 2017-March 2020, gallstone disease history was ascertained from 9232 adults. During NHANES 1988-2019 follow-up (median, 23.3 y), 8580 deaths occurred from all causes and 72 deaths with gallbladder or biliary tract disease. In multivariable-adjusted analysis, older age, male sex, prediabetes or diabetes, and physical inactivity were associated with gallbladder and biliary tract mortality, and non-Hispanic Black and Mexican American race-ethnicity were inversely associated. Between 1988-1994 and 2017-March 2020, gallstone disease prevalence increased from 7.4% to 13.9% and gallbladder surgery from 6.0% to 11.6%. In 2017-March 2020 in multivariable-adjusted analysis, female sex, diabetes, liver disease, proton pump inhibitors, abdominal pain, increased age, BMI, and liver stiffness were associated with gallstone disease, and non-Hispanic Black and non-Hispanic Asian race and alcohol were inversely associated.

Conclusions:
In the US population, gallstone disease prevalence doubled over 3 decades, possibly because of the worsening of metabolic risk factors and growth of laparoscopic cholecystectomy. Gallbladder and biliary tract mortality and gallstone disease associations included factors such as prediabetes or diabetes, liver stiffness and proton pump inhibitors.
Mapping the hepatic immune landscape identifies monocytic macrophages as key drivers of steatohepatitis and cholangiopathy progression
Authors: Guillot Adrien , Winkler Marc , Silva Afonso Milessa , Aggarwal Abhishek , Lopez David , Berger Hilmar , Kohlhepp Marlene S. , Liu Hanyang , Özdirik Burcin , Eschrich Johannes , Ma Jing , Peiseler Moritz , Heymann Felix , Pendem Swetha , Mahadevan Sangeetha , Gao Bin , Diehl Lauri , Gupta Ruchi , Tacke Frank 
Published: January 2023

Background and Aims:
The progression of chronic liver diseases towards liver cirrhosis is accompanied by drastic tissue changes. This study combines elaborate transcriptomic and histological methods aiming at spatially resolving the hepatic immune microenvironment in NAFLD (including NASH, primary sclerosing cholangitis, primary biliary cholangitis, and severe alcoholic hepatitis).

Approach and Results:
Human liver samples were subjected to RNA-sequencing (n=225) and imaging cytometry (n=99) across 3 independent patient cohorts. Liver samples from alcoholic hepatitis and primary biliary cholangitis patients were used for comparison. Myeloid populations were further characterized in corresponding mouse models. Imaging, clinical, and phenotypical data were combined for multidimensional analysis. NAFLD/NASH and primary sclerosing cholangitis disease stages were associated with loss of parenchymal areas, increased ductular cell accumulation, and infiltration of immune cells. NASH patients predominantly exhibited myeloid cell accumulation, whereas primary sclerosing cholangitis patients additionally had pronounced lymphoid cell responses. Correlating to disease stage, both etiologies displayed intense IBA1+CD16lowCD163low macrophage aggregation in nonparenchymal areas, with a distinct spatial proximity to ductular cells. Mouse models revealed that disease-associated IBA1+ hepatic macrophages originated from bone marrow–derived monocytes. Using an unbiased, machine learning–based algorithm, IBA1 in combination with hepatocyte and ductular cell immunostaining–predicted advanced cirrhosis in human NASH, primary sclerosing cholangitis, and alcoholic hepatitis.

Conclusions:
Loss of hepatocytes and increased ductular reaction are tightly associated with monocyte-derived macrophage accumulation and represent the most prominent common immunological feature revealing the progression of NAFLD, primary sclerosing cholangitis, primary biliary cholangitis, and alcoholic hepatitis, suggesting IBA1+CD163low macrophages are key pathogenic drivers of human liver disease progression across diverse etiologies.
Portal hypertension and variceal bleeding in patients with liver cancer: Evidence gaps for prevention and management
Authors: Allaire Manon , Thabut Dominique 
Published: January 2023

Background and Aims:
Portal hypertension (PHT) and HCC are 2 major complications of cirrhosis that often coexist in the same patient and impact the prognosis, especially in patients with acute variceal bleeding. In this review, we aim to discuss the best strategy for PHT screening and primary prophylaxis, as well as the management of acute variceal bleeding, to improve the management of PHT in HCC patients.

Results:
Recent therapeutic advances observed in the management of HCC, notably through the advent of immunotherapy, have led to a clear improvement in the survival of patients. The prevention of complications related to underlying cirrhosis, such as PHT and acute variceal bleeding, is now part of the management of HCC patients. The Baveno VII conference recently redefined screening and prophylaxis in patients with cirrhosis. However, data regarding the applicability of these criteria in patients with HCC have been sparse. From our point of view, the Baveno criteria are not appropriate to exclude high-risk esophageal varices (EV) in HCC patients, and endoscopy should be performed except in HCC patients with a liver stiffness measurement (LSM) ≥25 kPa, who should benefit from nonselective beta-blockers (NSSBs) without performing endoscopy. We are also in favor of using NSBBs as primary prophylaxis in patients with EV regardless of the size and with gastric varices since these patients display clinically significant PHT.

Conclusions:
Appropriate evaluation and treatment of PHT remain major issues in improving the outcomes of HCC patients. Many questions remain unanswered, opening the field to many areas of research.
Benefit of treatment based on indapamide mostly combined with perindopril on mortality and cardiovascular outcomes: a pooled analysis of four trials
Authors: Chalmers John , Mourad Jean-Jacques , Brzozowska-Villatte Romualda , De Champvallins Martine , Mancia Giuseppe 
Published: January 2023

Objective:
The aim of this study was to assess the reduction in all-cause death and cardiovascular outcomes associated with the administration of the thiazide-like diuretic indapamide monotherapy or in combination with perindopril as a blood pressure lowering drug in randomized controlled trials (RCTs).

Method:
Aggregate data from four published RCTs conducted versus matching placebo were pooled: PATS, a 2-year study (indapamide), and PROGRESS, a 4-year study (indapamide and perindopril), both in patients with a history of stroke or transient ischemic attack; ADVANCE, a 4-year study in patients with type 2 diabetes and cardiovascular risk factor (single-pill combination perindopril/indapamide) and HYVET, a 2-year study in very elderly hypertensive individuals (indapamide and an option of perindopril). The pooled effect (fixed and random) estimate (hazard ratio) was reported with corresponding 95% confidence intervals and P values. Treatment discontinuations were also analysed to assess the net benefit of the treatment.

Results:
The population involved 24 194 patients (active: 12 113, placebo: 12 081). The fixed-effects meta-analysis of the three mortality endpoints found low statistical heterogeneity (I
2 = 0). Statistically significant risk reductions in the indapamide with or without perindopril-treated patients as compared to placebo were observed for all-cause death (−15%), cardiovascular death (−21%), fatal stroke (−36%) and all strokes (−27%). Other cardiovascular outcomes were improved (risk reduction, 22 to 36%). As expected, discontinuation rates for safety (two studies) were higher in the active group (6.4 vs. 3.9%), while they were similar when discontinuation for any reason is concerned (18.4 vs. 18.0%).

Conclusion:
Across medium to high cardiovascular risk population, long-term indapamide, mostly combined with perindopril-based treatment, provided evidence of benefit on mortality and morbidity.
Safety and Efficacy of Resident-Performed Gonioscopy-Assisted Transluminal Trabeculotomy
Authors: Patterson Ian , Avdagic Ema , Qiu Mary 
Published: January 2023

Précis:
GATT can be performed efficaciously and safely by PGY-3 and PGY-4 residents, with clinical outcomes and complication rates that mirror those of attending-performed GATT cohorts from the literature.

Purpose:
Report outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) performed by PGY-3 and PGY-4 residents.

Methods:
A retrospective chart review was performed for patients undergoing resident-performed GATT. Eyes with previous traditional glaucoma surgery (trabeculectomy or aqueous shunt) or neovascular glaucoma were excluded from this analysis. The primary aim was to assess whether resident-performed GATTs demonstrated success rates comparable with the GATT literature. Surgical success was defined as intraocular pressure (IOP)<21 mmHg, and an IOP reduction of 20% from baseline, and no subsequent IOP-lowering surgery. The secondary and tertiary aims were to describe complication rates and operating times for resident-performed GATTs, respectively.

Results:
A total of 50 eyes from 40 patients with various types of glaucoma were included. Eyes either underwent resident-performed GATT-alone (N=9) or GATT+cataract extraction with intraocular lens implantation (CEIOL) (N=41). The surgical success rate at 6 months was 71% for GATT-alone and 42% for GATT+CEIOL. Three eyes required subsequent IOP-lowering surgery. The hyphema rate was 16% at postoperative week 1 and 6% at postoperative month 1. The IOP spike (>30 mmHg) rate was 18%. Mean surgical time for both GATT-alone and GATT+CEIOL was longer for PGY-4s than for PGY-3s, attributable to less attending assistance during PGY-4 cases and more resident-performed cataracts in PGY-4 GATT+CEIOL cases (85%) compared with PGY-3 cases (35%).

Conclusions:
GATT can be performed efficaciously and safely by PGY-3 and PGY-4 residents, with clinical outcomes and complication rates that mirror those of attending-performed GATT cohorts from the literature.
miR-1306-3p directly activates P2X3 receptors in primary sensory neurons to induce visceral pain in rats
Authors: Wu Yan-Yan , Wang Qian , Zhang Ping-An , Zhu Cheng , Xu Guang-Yin 
Published: January 2023

Abstract
Mounting evidence indicates that microRNAs (miRNAs) play critical roles in various pathophysiological conditions and diseases, but the physiological roles of extracellular miRNAs on the disease-related ion channels remain largely unknown. Here, we showed that miR-1306-3p evoked action potentials and induced inward currents of the acutely isolated rat dorsal root ganglion (DRG) neurons. The miR-1306-3p–induced effects were significantly inhibited by A317491, a potent inhibitor of the P2X3 receptor (P2X3R), or disappeared after the knockdown of P2X3Rs in DRG neurons. We further identified R180, K315, and R52 as the miR-1306-3p interaction sites on the extracellular domain of P2X3Rs, which were distinct from the orthosteric ATP-binding sites. Intrathecal injection of miR-1306-3p produced visceral pain but not somatic pain in normal control rats. Conversely, intrathecal application of a miR-1306-3p antagomir and A317491 significantly alleviated visceral pain in a rat model of chronic visceral pain. Together, our findings suggest that miR-1306-3p might function as an endogenous ligand to activate P2X3Rs, eventually leading to chronic visceral pain.
Impact of Transfusing Packed Red Blood Cells Through a Rapid Infuser on Potassium Levels
Authors: Metcalf Ashley , Kitchens Debra , Reddic John , Liao Wesley , Whitcomb John , Wallenborn Grace , Cull John 
Published: January 2023

Background:
Hyperkalemia is associated with the rapid transfusion of packed red blood cells in trauma patients. Rapid infusers can infuse blood up to 500 ml/min.

Objective:
This study aimed to determine whether infusing packed red blood cells through a rapid infuser impacts the potassium levels of the infused blood.

Methods:
Two baseline samples were obtained to measure potassium and hemolysis scores in 12 units of expired blood prior to infusion. The blood was then infused via the Belmont Rapid Infuser into collection bags at varying infusion rates (50, 100, 250, and 500 ml/min) utilizing different gauge catheter sizes (18-gauge, 16-gauge, and Cordis catheter). Two postinfusion blood samples were collected and tested for potassium and hemolysis scores and compared with preinfusion values. This process was then repeated with fresh blood.

Results:
The potassium levels of the samples taken from each unit prior to infusion (average difference 0.245) and after infusion (average difference 0.08) correlated well. There was no difference in potassium levels pre- and postinfusion at any infusion rate after accounting for catheter size and age of blood. The median potassium level of the fresh blood was 5.025 prior to infusion and 4.875 after infusion. The median potassium level of the expired blood was 16.05 prior to infusion and 16.4 postinfusion. There was no significant difference in the hemolysis scores between the preinfusion and postinfusion samples.

Conclusions:
Hyperkalemia in trauma patients undergoing massive transfusions is not a result of mechanical hemolysis from the high rates of blood infusion.
Peritoneal carcinomatosis secondary to metastatic lung cancer complicated with acute suppurative appendicitis: A case report and literature review
Authors: Fu Ji-Xin , Wang Xu-Jie , Xia Min , Wang Xin-Jian 
Published: January 2023

Rationale:
Lung cancer (LC) is a malignant tumor with the highest morbidity and mortality in the world. The most common metastatic sites of LC are the brain (47%), bone (36%), liver (22%), adrenal glands (15%), thoracic cavity (11%) and distant lymph nodes (10%). Peritoneal carcinomatosis (PC) is a rare clinical event in LC patients. Considering the rarity and nonspecific clinical symptoms of peritoneal metastasis among LC patients, a case of peritoneal metastasis secondary to LC incidentally observed by laparoscopic appendectomy is unusual.

Patient concerns:
Here, we present a 53-year-old never-smoker woman who presented to the emergency department with a 2-day history of pain in the right abdominal quadrant. Later, laparoscopy revealed acute suppurative appendicitis accompanied by a peritoneal metastatic mass.

Diagnosis:
The patient was diagnosed with PC secondary to metastatic LC complicated with acute suppurative appendicitis by immunohistochemistry. Positron emission tomography computed tomography (PET CT) findings further strengthen the evidence of PC from LC.

Outcomes:
Based on the results of genomic analysis, the patient received targeted therapy with osimertinib 80 mg/d.

Lessons:
Due to the discovery of new targets, the use of molecular therapies improved progression-free survival (PFS) and overall survival (OS), which increases the chance of identifying peritoneal metastasis of LC. For LC patients with abdominal symptoms, clinicians should be aware of the possibility of peritoneal metastasis from LC, especially for patients diagnosed with lung adenocarcinoma or with pleural effusion.
Robot-assisted anterior transpedicular screw fixation with 3D printed implant for multiple cervical fractures: A case report
Authors: Pei Lei , Yuan Wei , Liu Xinchun , Cong Lin , Zhu Yue 
Published: January 2023

Rationale:
The anterior transpedicular screw (ATPS) fixation in the cervical spine provides the advantages of both anterior and posterior cervical surgery; however, it poses a high risk of screw insertion. In addition, a 3D printed implant can match ATPS fixation and reconstruction of the vertebral body. Robot-assisted surgery can make this process easier and potentially improve the safety and accuracy of the procedure.

Patient concerns:
A 64-year-old female was hit by a heavy object 4 days before presentation to our hospital. The patient exhibited a muscle strength of 0/5 in both the lower limbs and 3/5 in both the upper limbs. The visual analogue scale (VAS) for the neck was 5 points. Computed tomography (CT) of the cervical spine identified a burst fracture of the C5 vertebral body, and longitudinal splitting fracture of the C6 and C7 vertebral bodies accompanied with a split in the lamina. Magnetic resonance imaging (MRI) revealed a spinal cord edema from the C3 to the C7 level.

Diagnosis:
Multiple cervical fractures with spinal cord injury.

Interventions:
Anterior C4-5 and C5-6 disc resection, C5 corpectomy, robot-assisted ATPS fixation with the 3-D printed implant was performed.

Outcomes:
The CT scans revealed a satisfactory location of the internal implantation without any signs of complications associated with implantations. Six months later, the muscle strength of both the upper limbs increased from level 3 to level 5, VAS of neck decreased from 5 to 0.

Lessons:
Robot-assisted ATPS internal fixation combined with custom implantation surgery using a 3D printed vertebral body provides an important solution to solve special cases.
Effectiveness and safety of different academic schools of traditional Chinese medicine in the treatment of obesity: A protocol for systematic review and meta-analysis
Authors: Gang Xiaochao , Gao Tianjiao , Han Yiran , Tai Yuxing , Zhong Chongwen , Chen Shaotao , Gao Ying , Li Lijie , Xiao Zhenxiang , Barat Dilnur , Liu Mingjun 
Published: January 2023

Background:
Obesity is a global epidemic. Since 1975, the global obesity rate has almost tripled. Although many systematic reviews and clinical trials have shown that traditional Chinese medicine (TCM) can effectively treat obesity, the effectiveness and safety of different academic schools of TCM in treating obesity have not been systematically evaluated.

Methods:
The retrieval language of this study was Chinese and English. From the date of creation of the following data to June 2023, the data of Medline, PubMed, Embase, Cochrane Science Network, China Biomedical Literature Database, Central Controlled Trial Registration Center, and China Science Journal Database were retrieved, respectively. This study included clinical randomized controlled trials related to the treatment of obesity by different academic schools of TCM. The main outcome measures were body mass index, waist circumference, hip circumference, waist hip ratio, body fat content, fasting blood glucose, glycosylated hemoglobin, and blood lipid level. In addition, we manually searched other resources, including reference lists of identified publications, conference articles, and gray literature.

Results:
This study will provide a more diverse choice of treatment options.

Conclusion:
The purpose of this study is to summarize and evaluate the effectiveness and safety of different academic schools of TCM in improving and treating obese patients from clinical trials, so as to provide more options for obesity treatment.
Expression of LINE-1 retrotransposon in early human spontaneous abortion tissues
Authors: Lou Chao , Qiang Rong , Wu Hanzhi , Zhang Liping , Li Wei , Jia Ting , Liu Xing 
Published: January 2023

Background:
The aim of this study is to investigate a new mechanism that may affect spontaneous abortions (SA): Can long interspersed nuclear element-1 (LINE-1) insertions in embryo cells lead to early SA?

Methods:
The method involves prospective study on new mechanism of human early SA. Twenty SA tissues and 10 induced abortion (IA) tissues were utilized for this experiment. Western Blot, Immunohistochemistry (IHC), and reverse transcription-polymerase chain reaction were used to analyze different LINE-1 proteins and mRNA expression between early SA tissues and early IA tissues. SPSS software version 21.0 was used for statistical analysis.

Results:
Western Blot demonstrated that the LINE-1 protein expression in SA tissues (Mean: 60.2%) is higher than in IA tissues (Mean: 30.3%) in 91% of the compared samples. reverse transcription-polymerase chain reaction showed that LINE-1 mRNA expression in SA tissues (Mean: 64.2%) is higher than in IA tissues (Mean: 29.2%) in 6 primer pairs in 89% of the compared samples. IHC showed that the LINE-1 protein expression in SA tissues (Mean: 59.2%) is higher than in IA tissues (Mean: 28.8%) in 83% of the compared samples.

Conclusions:
Expression of LINE-1 in early SA tissues is higher than in IA tissues, LINE-1 may lead to early SA and LINE-1 plays a role in early SA, this shows that a new mechanism may be involved in SA.