Clinicopathologic characteristics and prognostic factors of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix: A multicenter retrospective study.

OBJECTIVE: To evaluate the prognostic factors and survival outcomes of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix (NECC). METHODS: This multicenter, retrospective study involved 98 cervical cancer patients with stage IA2-IIA2 and IIIC1/2p high-grade NECC. We divided the patients into two groups based on histology: the pure and mixed groups. All clinicopathologic variables were retrospectively evaluated. Cox regression and Kaplan-Meier methods were used for analysis. RESULTS: In our study, 60 patients were in the pure group and 38 patients were in the mixed group. Cox multivariate analysis showed that mixed histology was a protective factor impacting overall survival (OS) (P = 0.026) and progression free survival (PFS) (P = 0.018) in surgically treated high-grade NECC. Conversely, survival outcomes were negatively impacted by ovarian preservation (OS: HR, 20.84; 95% CI: 5.02-86.57, P < 0.001), age >45 years (OS: HR, 4.50; 95% CI: 1.0-18.83, P = 0.039), tumor size >4 cm (OS: HR, 6.23; 95% CI: 2.34-16.61, P < 0.001), parity >3 (OS: HR, 4.50; 95% CI: 1.02-19.91, P = 0.048), and perineural invasion (OS: HR, 5.21; 95% CI: 1.20-22.53, P = 0.027). Kaplan-Meier survival curves revealed notable differences in histologic type (OS: P = 0.045; PFS: P = 0.024), chemotherapy (OS: P = 0.0056; PFS: P = 0.0041), ovarian preservation (OS: P = 0.00031; PFS: P = 0.0023), uterine invasion (OS: P < 0.0001; PFS: P < 0.0001), and depth of stromal invasion (OS: P = 0.043; PFS: P = 0.022). CONCLUSION: Patients with mixed histologic types who undergo surgery for high-grade NECC have a better prognosis. Meanwhile, ovarian preservation, tumor size >4 cm, parity >3, age >45 years and perineural invasion were poor prognostic predictors. Therefore, patients with high-risk factors should be considered in clinical practice.

A new prediction model for acute kidney injury following liver transplantation using grafts from donors after cardiac death.

Acute kidney injury (AKI) is a major complication following liver transplantation (LT), which utilizes grafts from donors after cardiac death (DCD). We developed a machine-learning-based model to predict AKI, using data from 894 LT recipients (January 2015-March 2021), split into training and testing sets. Five machine learning algorithms were employed to construct the prediction models using 17 clinical variables. The performance of the models was assessed by the area under the receiver operating characteristic curve (AUC), accuracy, F1-score, sensitivity and specificity. The best-performing model was further validated in an independent cohort of 195 LT recipients who received DCD grafts between April 2021 and December 2021. The Shapley additive explanations method was utilized to elucidate the predictions and identify the most crucial features. The gradient boosting machine (GBM) model demonstrated the highest AUC (0.76, 95% CI: 0.70-0.82), F1-score (0.73, 95% CI: 0.66-0.79) and sensitivity (0.74, 95% CI: 0.66-0.80) in the testing set and a comparable AUC (0.75, 95% CI: 0.67-0.81) in the validation set. The GBM model identified high preoperative indirect bilirubin, low intraoperative urine output, prolonged anesthesia duration, low preoperative platelet count and graft steatosis graded NASH Clinical Research Network 1 and above as the top five important features for predicting AKI following LT using DCD grafts. The GBM model is a reliable and interpretable tool for predicting AKI in recipients of LT using DCD grafts. This model can assist clinicians in identifying patients at high risk and providing timely interventions to prevent or mitigate AKI.

High-performance cost efficient simultaneous wireless information and power transfers deploying jointly modulated amplifying programmable metasurface.

Programmable metasurfaces present significant capabilities in manipulating electromagnetic waves, making them a promising candidate for simultaneous wireless information and power transfer (SWIPT), which has the potential to enable sustainable wireless communication in complex electromagnetic environments. However, challenges remain in terms of maximum power transmission distance and stable phase manipulation with high-power scattered waves. Additionally, waveform limitations restrict average scattered power and rectifier conversion efficiency, affecting data transmission rates and energy transmission distance. Here we show an amplifying programmable metasurface (APM) and a joint modulation method to address these challenges. The APM mitigates the peak-to-average power ratio and improves maximum power, phase response stability, average output power, and rectifier conversion efficiency. Through experimental validation, we demonstrate the feasibility of the SWIPT system, showcasing simultaneous LED array powering and movie video transmission. This innovative SWIPT system holds promise for diverse applications, including 6 G wireless communications, IoT, implanted devices, and cognitive radio networks.

In vitro oogenesis from murine premeiotic germ cells using a new three-dimensional culture system.

A faithful reconstitution of the complete process of oogenesis in vitro is helpful for understanding the molecular mechanisms, genetics, and epigenetic changes related to gametogenesis; it can also be useful for clinical drug screening, disease research, and regenerative medicine. To this end, given the consensus that murine female germ cells initiate meiosis at E13.5, substantial works have reported the successful generation of fertile oocytes using E12.5 female gonads as starting materials. Nevertheless, our data demonstrated that murine germ cells at E12.5 have heterogeneously initiated a meiotic transcriptional program based on a measurement of pre-mRNAs (unspliced) and mature mRNAs (spliced) at a single-cell level. Therefore, to establish a platform that faithfully recapitulates the entire process in vitro (from premeiotic murine germ cells to fully developed oocytes), we here report a novel three-dimensional organoid culture (3-DOC) system, which successfully induced fully developed oocytes from E11.5 premeiotic female germ cells (oogonia). Compared with 2D culture and other 3D culture methods, this new culture system is more cost-effective and can create high-quality oocytes similar to in vivo oocytes. In summary, our new culture platform provides an experimental model for future research in regenerative medicine and reproductive biology.

Single-cell transcriptomics allows novel insights into the endocrine-disrupting chemicals induced mammalian reproductive disorder.

Increasing environmental pollution has led to the spread of many endocrine-disrupting chemicals (EDCs) around the world, which are toxic substances in the form of compounds that pose a great threat to the reproductive health of mammals and become a potential cause of many reproductive function-related diseases. In the past decade, the rapid development of single-cell RNA sequencing (scRNA-seq) technology has greatly promoted the study of the toxic mechanisms of EDCs in the mammalian reproductive system, including DEHP, ZEN, BPA, and BDE47. These studies aim to resolve the interference of EDCs in critical stages of reproductive development, including prepubertal and pubertal in males, meiosis I and early follicle formation in females. This paper introduces the sequencing process and analysis methods of current mainstream scRNA-seq technology, systematically reviews the outstanding contributions and specific research ideas of this technology in the study of reproductive system toxicity, lists representative cases of using this technology to explore reproductive damage caused by EDCs, and summarizes in detail the connection between environmental pollution and reproductive development disorders. It provides an important theoretical basis and direction for further exploring the mechanism of damage to the physiological functions of toxic substances on the reproductive system and the prevention and treatment of reproductive diseases.

Effects of Exergaming on Musculoskeletal Pain in Older Adults: Systematic Review and Meta-analysis.

BACKGROUND: Exercise is effective for musculoskeletal pain. However, physical, social, and environmental factors make it difficult for older adults to persist in exercising. Exergaming is a new pathway that combines exercise with gameplay and may be helpful for older adults to overcome these difficulties and engage in regular exercise. OBJECTIVE: This systematic review aimed to determine the efficacy of exergaming to improve musculoskeletal pain in older adults. METHODS: The search was performed in 5 databases (PubMed, Embase, CINAHL, Web of Science, and Cochrane Library). The risk of bias for randomized controlled studies was assessed using the revised Cochrane Risk of Bias tool in randomized trials (RoB 2), and the methodological quality was assessed using the Physiotherapy Evidence-Based Database scale. Standardized mean difference and 95% CI were calculated using fixed-effects model meta-analyses in the Review Manager version 5.3 (RevMan 5.3). RESULTS: Seven randomized controlled studies were included, which contained 264 older adults. Three of the 7 studies reported significant improvements in pain after the exergaming intervention, but only 1 reported a significant difference between groups after adjustment for baseline (P<.05), and another reported a significant improvement in thermal pain between the 2 groups (P<.001). The results of the meta-analysis of the 7 studies showed no statistically significant improvement in pain compared to the control group (standardized mean difference -0.22; 95% CI -0.47 to 0.02; P=.07). CONCLUSIONS: Although the effects of exergames on musculoskeletal pain in older adults are unknown, exergame training is generally safe, fun, and appealing to older adults. Unsupervised exercise at home is feasible and cost-effective. However, most of the current studies have used commercial exergames, and it is recommended that there should be more cooperation between industries in the future to develop professional rehabilitation exergames that are more suitable for older adults. The sample sizes of the studies included are small, the risk of bias is high, and the results should be interpreted with caution. Further randomized controlled studies with large sample sizes, high quality, and rigor are needed in the future. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42022342325; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=342325.

Murine skin-derived multipotent papillary dermal fibroblast progenitors show germline potential in vitro.

BACKGROUND: Many laboratories have described the in vitro isolation of multipotent cells with stem cell properties from the skin of various species termed skin-derived stem cells (SDSCs). However, the cellular origin of these cells and their capability to give rise, among various cell types, to male germ cells, remain largely unexplored. METHODS: SDSCs were isolated from newborn mice skin, and then differentiated into primordial germ cell-like cells (PGCLCs) in vitro. Single-cell RNA sequencing (scRNA-seq) was then applied to dissect the cellular origin of SDSCs using cells isolated from newborn mouse skin and SDSC colonies. Based on an optimized culture strategy, we successfully generated spermatogonial stem cell-like cells (SSCLCs) in vitro. RESULTS: Here, using scRNA-seq and analyzing the profile of 7543 single-cell transcriptomes from newborn mouse skin and SDSCs, we discovered that they mainly consist of multipotent papillary dermal fibroblast progenitors (pDFPs) residing in the dermal layer. Moreover, we found that epidermal growth factor (EGF) signaling is pivotal for the capability of these progenitors to proliferate and form large colonies in vitro. Finally, we optimized the protocol to efficiently generate PGCLCs from SDSCs. Furthermore, PGCLCs were induced into SSCLCs and these SSCLCs showed meiotic potential when cultured with testicular organoids. CONCLUSIONS: Our findings here identify pDFPs as SDSCs derived from newborn skin and show for the first time that such precursors can be induced to generate cells of the male germline.

The complete mitochondrial genome of Rhinogobius szechuanensis (Gobiiformes: Ggobiidae: Gobionellinae).

Here, we sequenced the complete mitogenome of Rhinogobius szechuanensis using the Illumina HiSeq platform and submitted the genome to Genbank with accession number OM617727. Assembly circular mitogenome (16,492 bp) consisted of 54.4% AT content, 13 protein-coding genes, 22 tRNA genes, two rRNA genes, an origin of light-strand replication, and a control region. Phylogenetic analysis supported that R. szechuanensis was grouped with R. rubromaculatus and clustered with other Rhinogobius species. The basal molecular data will be essential for further genetics studies such as evolution, taxonomy, DNA barcoding, and population genetics of Rhinogobius.

Assembly and phylogenetic analysis of the complete mitogenome of Devario interruptus (Teleostei, Cypriniformes, Danionidae).

The complete mitochondrial DNA genome of Devario interruptus was sequenced on the Illumina HiSeq platform and found to be 16,735 bp and included 37 genes encoding 13 proteins, 22 tRNAs, two rRNAs, and two non-coding regions. The proportion of nucleotides in mitochondrial genome was T (27.9%), C (23.7%), A (33%), G (15.4%), and the deviation of AT was 60.9%. A Maximum-Likelihood phylogenetic tree was reconstructed using the concatenated mitochondrial protein-coding genes of D. interruptus and other 18 species of fishes. Phylogenetic analysis results supported that D. interruptus was closely related to Devario shanensis. Fundamental genetic data of D. interruptus will be essential for further genetic studies.

Correlative increasing expressions of KIF5b and Nav1.7 in DRG neurons of rats under neuropathic pain conditions.

Nav1.7, one of tetrodotoxin-sensitive voltage-gated sodium channels, mainly expressed in the small diameter dorsal root ganglion (DRG) neurons. The expression and accumulation on neuronal membrane of Nav1.7 increased following peripheral tissue inflammation or nerve injury. However, the mechanisms for membrane accumulation of Nav1.7 remained unclear. We report that KIF5b, a highly expressed member of the kinesin-1 family in DRGs, promoted the translocation of Nav1.7 to the plasma membrane in DRG neurons of the rat. Following nociceptive behaviors in rats induced by peripheral spared nerve injury (SNI), synchronously increased KIF5b and Nav1.7 expressions were observed in DRGs. Immunohistochemistry staining demonstrated the co-expressions of KIF5b and Nav1.7 in the same DRG neurons. Immunoprecipitation experiments further confirmed the interactions between KIF5b and Nav1.7. Moreover, intrathecal injections of KIF5b shRNA moderated the SNI-induced both mechanical and thermal hyperalgesia. The rescued analgesic effects also alleviated SNI-induced anxiety-like behaviors. In sum, KIF5b was required for the membrane localizations of Nav1.7, which suggests a novel mechanism for the trafficking of Nav1.7 involved in neuropathic pain.

The interaction of MC3R and MC4R with MRAP2a in rainbow trout (Oncorhynchus mykiss).

Melanocortin 3 and 4 receptors are two important neural G protein-coupled receptors that regulate energy homeostasis in vertebrates. Melanocortin receptor accessory protein 2 (MRAP2) is also involved in the regulation of food intake and body weight as a variable regulator of melanocortin receptors. Rainbow trout (Oncorhynchus mykiss) is a valuable cold-water fish cultured worldwide. In the rainbow trout model, we cloned and identified mrap2a, a paralog of mrap2. Rainbow trout mrap2a consisted of a 690 bp ORF and was expected to encode a putative protein of 229 amino acids. The qPCR results showed that rainbow trout mrap2a was expressed at high levels in brain tissue similar to mc3r and mc4r. In addition, co-immunoprecipitation verified that MRAP2a interacts with MC3R and MC4R in vitro and that MRAP2a is involved in and regulates the constitutive activity and signaling of MC3R and MC4R. MRAP2a reduced constitutive and agonist-stimulated cAMP levels of MC3R; furthermore, MRAP2a increased constitutive ERK1/2 activation but reduced ligand-induced stimulation at high levels of expression. For MC4R, MRAP2a showed decreased cAMP basal activity but increased agonist-stimulated cAMP signaling and increased ACTH ligand sensitivity. However, MRAP2a failed to affect MC4R constitutive activity and agonist-induced ERK1/2 signaling. Undoubtedly, our study will have great significance for revealing the conserved role of MC4R and MC3R signaling in teleost fish, especially in cold-water fish growth and energy homeostasis.

Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation.

BACKGROUND: Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients. However, they can also damage normal cells and cause serious intestinal toxicity, leading to gastrointestinal mucositis[1]. Traditional Chinese medicine is effective in improving the side effects of chemotherapy. Wumei pills (WMP) was originally documented in the Treatise on Exogenous Febrile Diseases. It has a significant effect on chronic diarrhea and other gastrointestinal diseases, but it is not clear whether it affects chemotherapy-induced intestinal mucositis (CIM). AIM: To explore the potential mechanism of WMP in the treatment of CIM through experimental research. METHODS: We used an intraperitoneal injection of 5-fluorouracil (5-Fu) to establish a CIM mouse model and an oral gavage of WMP decoction (11325 and 22650 mg/kg) to evaluate the efficacy of WMP in CIM. We evaluated the effect of WMP on CIM by observing the general conditions of the mice (body weight, food intake, spleen weight, diarrhea score, and hematoxylin and eosin stained tissues). The expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, and myeloperoxidase (MPO), as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway proteins and tight junction proteins (zonula occludens-1, claudin-1, E-cadherin, and mucin-2) was determined. Furthermore, intestinal permeability, intestinal flora, and the levels of short-chain fatty acids (SCFA) were also assessed. RESULTS: WMP effectively improved the body weight, spleen weight, food intake, diarrhea score, and inflammatory status of the mice with intestinal mucositis, which preliminarily confirmed the efficacy of WMP in CIM. Further experiments showed that in addition to reducing the levels of TNF-α, IL-1ß, IL-6, and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins, WMP also repaired the integrity of the mucosal barrier of mice, regulated the intestinal flora, and increased the levels of SCFA (such as butyric acid). CONCLUSION: WMP can play a therapeutic role in CIM by alleviating inflammation, restoring the mucosal barrier, and regulating gut microbiota.

Various BDNF administrations attenuate SPS-induced anxiety-like behaviors.

Post-traumatic stress disorder (PTSD) has become epidemic following severely stressful incidents. Previous studies have shown that brain-derived neurotrophic factor (BDNF) has anxiolytic effects on various anxiety or depression disorders including PTSD. However, the detailed mechanisms of BDNF for treating PTSD were rarely investigated. In the current study, single-prolonged stress (SPS) was used as an animal model recapitulating specific aspects for a PTSD-like phenotype. The effects of BDNF on SPS-induced anxiety-like behaviors were investigated. We showed that the levels of BDNF in the cerebro-spinal fluid (CSF) were significantly reduced after the rats experienced SPS. The SPS-induced reductions of percentages of time spent in the central area to total time in the open field test, were dose-dependently mitigated after BDNF intracerebroventricular (i.c.v.) injections. BDNF i.c.v. administration also dose-dependently increased the preference of the light box in the light-dark box test. Both expressions of tyrosine kinase receptor B (TrkB) protein and mRNA in the prefrontal cortex (PFC) and amygdala were significantly increased after SPS challenges. BDNF i.c.v. administration attenuated these compensatory increases of TrkB. At last, the anxiolytic effects of BDNF on SPS model were also observed by using other two injection methods. These results inspired us to study that different administrations of BDNF were used in patients with PTSD in the future, in-depthly.

Anatomical Evidence for the Neural Connection from the Emotional Brain to Autonomic Innervation in the Anterior Chamber Structures of the Eye.

OBJECTIVE: Previous studies have shown that the autonomic nervous system (ANS), which can be affected by emotions, is important in the occurrence or progression of glaucoma. The autonomic innervation distributed in the anterior chamber (AC) structures might play an efferent role in the neural regulation of intraocular pressure (IOP). This study aimed to investigate the anatomic neural connection from the emotional brain to autonomic innervation in the AC. METHODS: A retrograde trans-multisynaptic pseudorabies virus encoded with an enhanced green fluorescent protein (PRV531) and non-trans-synaptic tracer FAST Dil were injected into the right eye of mice, respectively. Fluorescent localization in the emotional brain and preganglionic nuclei was studied. Five and a half days after PRV531 injection into the right AC, fluorescent signals were observed in several emotional brain regions, including the amygdala, agranular insular cortex, lateral septal nuclei, periaqueductal gray, and hypothalamus. Autonomic preganglionic nuclei, including Edinger-Westphal nucleus, superior salivatory nucleus, and intermediolateral nucleus, were labeled using PRV531. RESULTS: The sensory trigeminal nuclei were not labeled using PRV531. The fluorescence signals in the nuclei mentioned above showed bilateral distribution, primarily on the ipsilateral side. Seven days after injecting FAST Dil into the AC, we observed no FAST Dil-labeled neurons in the central nervous system. CONCLUSION: Our results indicate a neural connection from the emotional brain to autonomic innervation in the AC, which provides anatomical support for the emotional influence of IOP via the ANS.

Biogeography of the Respiratory Tract Microbiome in Patients With Malignant Tracheal Tumors.

BACKGROUND: This study aimed to characterize the bacterial microbiota in the oral cavity (OC), throat, trachea, and distal alveoli of patients with primary malignant tracheal tumors (PMTT), including squamous cell carcinoma (SCC) and salivary gland carcinoma patients (SGC), for comparison with a matched non-malignant tracheal tumor (NMTT) group. METHODS: Patients with pathological diagnosis of PMTT and NMTT were included in this study. Saliva, throat swab (TS), trachea protected specimen brush (PSB), and bronchoalveolar lavage fluid (BALF) samples were collected for 16S rRNA gene sequencing. The composition, diversity, and distribution of the microbiota were compared among biogeographic sampling sites and patient groups. The relationship between the genera-level taxon abundance and tracheal tumor types was also investigated to screen for candidate biomarkers. FINDINGS: The most represented phyla in the four sites were Bacteroidetes, Firmicutes, Proteobacteria, and Fusobacteria. In SCC patients, the relative abundance of Bacteroidetes and Firmicutes gradually decreased with increasing depth into the respiratory tract, while the relative abundance of Proteobacteria gradually increased. Bacterial communities at the four biogeographic sites formed two distinct clusters, with OC and TS samples comprising one cluster and PSB and BALF samples comprising the other group. Principal coordinate analysis showed that trachea microbiota in SCC patients were distinct from that of SGC or NMTT patients. In the trachea, AUCs generated by Prevotella and Alloprevotella showed that the abundance of these genera could distinguish SCC patients from both NMTT and SGC patients. INTERPRETATION: The structure of respiratory tract microbiota in PMTT patients is related to tumor type. Certain bacteria could potentially serve as markers of SCC, although verification with large-sample studies is necessary.

A C-type lectin with a single CRD from Onychostoma macrolepis mediates immune recognition against bacterial challenge.

C-type lectins (CTL) are a large group of pattern-recognition proteins and to play important roles in glycoprotein metabolism, multicellular integration, and immunity. Based on their overall domain structure, they can be classified as different groups that possess different physiological functions. A typical C-type lectin (named as OmLec1) was identified from the fish, Onychostoma macrolepis, an important cultured fish in China. Open reading frame of OmLec1 contains a 570 bp, encoding a protein of 189 amino acids that includes a signal peptide and a single carbohydrate-recognition domain. The phylogenetic analysis showed that OmLec1 could be grouped with C-type lectin from other fish. OmLec1 was expressed in all the tissues in our study, and the expression level was highest in liver. And its relative expression levels were significantly upregulated following infection with Aeromonas hydrophila. The recombinant OmLec1 protein (rOmLec1) could agglutinate some Gram-negative bacteria and Gram-positive bacteria in vitro in the presence of Ca2+, showing a typical Ca2+-dependent carbohydrate-binding protein. Furthermore, rOmLec1 purified from E. coli BL21 (DE3), strongly bound to LPS and PGN, as well as all tested bacteria in a Ca2+-dependent manner. These results indicate that OmLec1 plays a central role in the innate immune response and as a pattern recognition receptor that recognizes diverse pathogens among O. macrolepis.

A C-type lectin (OmCTL) in Onychostoma macrolepis: Binding ability to LPS, PGN and agglutinating activity against bacteria.

C-type lectins (CTLs) are calcium-dependent carbohydrate-binding proteins that mainly bind to carbohydrate-based or other ligands to mediate cell adhesion, recognize pathogens, and play important roles in the immune system. In the present study, a novel C-type lectin (OmCTL) isolated from Onychostoma macrolepis was investigated. The open reading frame of OmCTL comprises 468 bp, encoding a 155 amino acid polypeptide with an 18 amino acid putative signaling peptide. The predicted primary OmCTL structure contains a signal peptide, a single carbohydrate recognition domain (CRD) and an EPN/WND motif required for carbohydrate-binding specificity. Using tissue expression pattern analysis, OmCTL has been shownto be highly expressed in the liver, and is also detected in other tissues. OmCTL was significantly upregulated in the liver and spleen following infection with Aeromonas hydrophila, suggesting its involvement in immune response. The recombinant OmCTL protein (rOmCTL) agglutinated two gram-negative bacteria, Escherichia coli and A. hydrophila, in vitro in the presence of Ca2+, showing that it is a typical Ca2+-dependent carbohydrate-binding protein.Furthermore, rOmCTL purified from E. coli BL21 (DE3) strongly bound to LPS and PGN, as well as all tested bacteria in a Ca2+-independent manner. These results indicate that OmCTL plays a central role in the innate immune response and as a pattern recognition receptor that recognizes diverse pathogens among O. macrolepis.

The efficacy and safety of methylprednisolone in hepatitis B virus-related acute-on-chronic liver failure: a prospective multi-center clinical trial.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe condition with high mortality due to lack of efficient therapy. Until now, the use of methylprednisolone (MP) in HBV-ACLF is still controversial. We aimed to evaluate the efficacy and safety of MP in HBV-ACLF. METHODS: Totally 171 HBV-ACLF patients from three medical centers were randomly allocated into MP group (83 patients treated with MP intravenously guttae for 7 days plus standard treatment: 1.5 mg/kg/day [day 1-3], 1 mg/kg/day [day 4-5], and 0.5 mg/kg/day [day 6-7]) and control group (88 patients treated with standard treatment). The primary endpoints were 6-month mortality and prognostic factors for 6-month survival. The survival time, cause of death, adverse events, liver function, and HBV DNA replication were analyzed. RESULTS: The 6-month mortality was significantly lower in MP group than control group [32.4% vs. 42.5%, P = 0.0037]. MP treatment was an independent prognostic factor for 6-month survival [HR (95% CI) 0.547(0.308-0.973); P = 0.040]. Factors associated with reduced 6-month mortality in MP group included HBV DNA and lymphocyte/monocyte ratio (LMR) (P < 0.05). Based on ROC curve, LMR+MELD had a better predictive value for prognosis of HBV-ACLF under MP treatment. No significant difference in HBV DNA replication was observed between groups (P > 0.05). CONCLUSIONS: MP therapy is an effective and safe clinical strategy in HBV-ACLF, increasing the 6-month survival rate. Clinical trials registered at http://www.chictr.org.cn as ChiCTR-TRC-13003113 registered on 16 March 2013.