Comparison of Cox regression and generalized Cox regression models to machine learning in predicting survival of children with diffuse large B-cell lymphoma.

Background: The incidence of diffuse large B-cell lymphoma (DLBCL) in children is increasing globally. Due to the immature immune system in children, the prognosis of DLBCL is quite different from that of adults. We aim to use the multicenter large retrospective analysis for prognosis study of the disease. Methods: For our retrospective analysis, we retrieved data from the Surveillance, Epidemiology and End Results (SEER) database that included 836 DLBCL patients under 18 years old who were treated at 22 central institutions between 2000 and 2019. The patients were randomly divided into a modeling group and a validation group based on the ratio of 7:3. Cox stepwise regression, generalized Cox regression and eXtreme Gradient Boosting (XGBoost) were used to screen all variables. The selected prognostic variables were used to construct a nomogram through Cox stepwise regression. The importance of variables was ranked using XGBoost. The predictive performance of the model was assessed by using C-index, area under the curve (AUC) of receiver operating characteristic (ROC) curve, sensitivity and specificity. The consistency of the model was evaluated by using a calibration curve. The clinical practicality of the model was verified through decision curve analysis (DCA). Results: ROC curve demonstrated that all models except the non-proportional hazards and non-log linearity (NPHNLL) model, achieved AUC values above 0.7, indicating high accuracy. The calibration curve and DCA further confirmed strong predictive performance and clinical practicability. Conclusions: In this study, we successfully constructed a machine learning model by combining XGBoost with Cox and generalized Cox regression models. This integrated approach accurately predicts the prognosis of children with DLBCL from multiple dimensions. These findings provide a scientific basis for accurate clinical prognosis prediction.

Transitioning weathered oil fields towards new energy: A review on utilizing hydrogenotrophic methanogens for petroleum hydrocarbons remediation.

The weathering process can cause the volatilization of light components in crude oil, leading to the accumulation of total petroleum hydrocarbons (TPH) in weathered oil field soils. These TPH compounds are relatively resistant to biodegradation, posing a significant environmental hazard by contributing to soil degradation. TPH represents a complex mixture of petroleum-based hydrocarbons classified as persistent organic pollutants in soil and groundwater. The release of TPH pollutants into the environment poses serious threats to ecosystems and human health. Currently, various methods are available for TPH-contaminated soil remediation, with bioremediation technology recognized as an environmentally friendly and cost-effective approach. While converting TPH to CO2 is a common remediation method, the complex structures and diverse types of petroleum hydrocarbons (PHs) involved can result in excessive CO2 generation, potentially exacerbating the greenhouse effect. Alternatively, transforming TPH into energy forms like methane through bioremediation, followed by collection and reuse, can reduce greenhouse gas emissions and energy consumption. This process relies on the synergistic interaction between Methanogens archaea and syntrophic bacteria, forming a consortium known as the oil-degrading bacterial consortium. Methanogens produce methane through anaerobic digestion (AD), with hydrogenotrophic methanogens (HTMs) utilizing H2 as an electron donor, playing a crucial role in biomethane production. Candidatus Methanoliparia (Ca. Methanoliparia) was found in the petroleum archaeal community of weathered Oil field in northeast China. Ca. Methanoliparia has demonstrated its independent ability to decompose and produce new energy (biomethane) without symbiosis, contribute to transitioning weathered oil fields towards new energy. Therefore, this review focuses on the principles, mechanisms, and developmental pathways of HTMs during new energy production in the degradation of PHs. It also discusses strategies to enhance TPH degradation and recovery methods.

Desmopressin nasal spray inhibiting parasympathetic function on isolated tracheal smooth muscle.

Objectives: Nocturia with or without asthma is one of the aging diseases. Desmopressin has been used as a nasal spray for patients who are suffering from nocturia. This study determined the effects of desmopressin on isolated tracheal smooth muscle in vitro. Methods: We evaluated desmopressin's efficiency on isolated rat tracheal smooth muscle. Desmopressin was evaluated for the following effects on tracheal smooth muscle: (1) effect on resting tension; (2) effect on contraction brought on by parasympathetic mimetic 10-6 M methacholine; and (3) effect on electrically produced tracheal smooth muscle contractions. Results: As the concentration grew, desmopressin by itself had no impact on the trachea's baseline tension. Addition of desmopressin at doses of 10-5 M or above elicited a significant relaxation response to 10-6 M methacholine-induced contraction. Desmopressin could also inhibit spike contraction of the trachea induced by electrical field. Conclusion: According to this study, desmopressin at high quantities may prevent the trachea's parasympathetic activity. Due to its ability to block parasympathetic activity and lessen the contraction of the tracheal smooth muscle brought on by methacholine, Desmopressin nasal spray might help nocturia sufferers experience fewer asthma attacks.

[Effects of Straw and Fertilizer Managements on Nitrogen Loss in Rice Cultivation in Taihu Lake Basin].

Nitrogen loss from rice systems is an important source of agricultural non-point source pollution. Many studies revolve around reducing the rate of nitrogen fertilizer application. However, studies examining the characteristics of nitrogen loss in multiple loss paths （runoff, leaching, and lateral seepage） under different straw and fertilizer managements are lacking. Therefore, a study was carried out based on a rice field planted for more than 20 years with straw continuously returned to the field for more than 5 years in Taihu lake basin. The effects of straw and fertilizer managements on nitrogen loss in different paths during the whole growth period of rice were studied. Moreover, straw and fertilizer managements were evaluated by their production suitability and environmental friendliness based on crop yield, nitrogen use efficiency, and nitrogen loss. The results showed that straw removal from the field increased the response sensitivity of nitrogen accumulation in plant tissue to nitrogen application. The nitrogen loss in the rice season was 9-17 kg·hm-2, accounting for 5%-7% of the nitrogen application rate. Straw removal increased the risk of nitrogen loss when soaking water discharged. Straw returning could decrease the nitrogen loss by more than 15%, though the effect of straw on nitrogen loss via lateral seepage was not clear. Furthermore, the suitable substitution of organic fertilizer （30% in this study） could respectively reduce the amount of nitrogen loss via runoff, leaching, and lateral seepage by 16%, 26%, and 37% compared with the fertilizer application under the same nitrogen gradient. In conclusion, the implementation of straw returning and fertilizer type optimization measures effectively reduced the nitrogen loss for unit weight of rice production and realized the balance between agricultural production and environmental protection.

Co-formulation of the rF1V plague vaccine with depot-formulated cytokines enhances immunogenicity and efficacy to elicit protective responses against aerosol challenge in mice.

This study evaluated a depot-formulated cytokine-based adjuvant to improve the efficacy of the recombinant F1V (rF1V) plague vaccine and examined the protective response following aerosol challenge in a murine model. The results of this study showed that co-formulation of the Alhydrogel-adsorbed rF1V plague fusion vaccine with the depot-formulated cytokines recombinant human interleukin 2 (rhuIL-2) and/or recombinant murine granulocyte macrophage colony-stimulating factor (rmGM-CSF) significantly enhances immunogenicity and significant protection at lower antigen doses against a lethal aerosol challenge. These results provide additional support for the co-application of the depot-formulated IL-2 and/or GM-CSF cytokines to enhance vaccine efficacy.

Atrophy of the cholinergic regions advances from early to late mild cognitive impairment.

PURPOSE: We investigated the volumetric changes in the components of the cholinergic pathway for patients with early mild cognitive impairment (EMCI) and those with late mild cognitive impairment (LMCI). The effect of patients' apolipoprotein 4 (APOE-ε4) allele status on the structural changes were analyzed. METHODS: Structural magnetic resonance imaging data were collected. Patients' demographic information, plasma data, and validated global cognitive composite scores were included. Relevant features were extracted for constructing machine learning models to differentiate between EMCI (n = 312) and LMCI (n = 541) and predict patients' neurocognitive function. The data were analyzed primarily through one-way analysis of variance and two-way analysis of covariance. RESULTS: Considerable differences were observed in cholinergic structural changes between patients with EMCI and LMCI. Cholinergic atrophy was more prominent in the LMCI cohort than in the EMCI cohort (P < 0.05 family-wise error corrected). APOE-ε4 differentially affected cholinergic atrophy in the LMCI and EMCI cohorts. For LMCI cohort, APOE-ε4 carriers exhibited increased brain atrophy (left amygdala: P = 0.001; right amygdala: P = 0.006, and right Ch123, P = 0.032). EMCI and LCMI patients showed distinctive associations of gray matter volumes in cholinergic regions with executive (R2 = 0.063 and 0.030 for EMCI and LMCI, respectively) and language (R2 = 0.095 and 0.042 for EMCI and LMCI, respectively) function. CONCLUSIONS: Our data confirmed significant cholinergic atrophy differences between early and late stages of mild cognitive impairment. The impact of the APOE-ε4 allele on cholinergic atrophy varied between the LMCI and EMCI groups.

Efficacy of levocetirizine in isolated rat tracheal smooth muscle.

Histamine receptor-1 (H1) antagonists like levocetirizine are frequently used nowadays to treat rhinitis patients who experience rhinorrhea and sneezing. The trachea may be affected by the H1 antagonist when it is used to treat nasal symptoms, either orally or through inhalation. The purpose of this study was to ascertain in vitro effects of levocetirizine on isolated tracheal smooth muscle. As a parasympathetic mimetic, methacholine (10-6 M) causes contractions in tracheal smooth muscle, which is how we tested effectiveness of levocetirizine on isolated rat tracheal smooth muscle. We also tested the drug's impact on electrically induced tracheal smooth muscle contractions. The impact of menthol (either before or after) on the contraction brought on by 10-6 M methacholine was also investigated. According to the results, the addition of levocetirizine at concentrations of 10-5 M or more caused a slight relaxation in response to methacholine's 10-6 M contraction. Levocetirizine could prevent spike contraction brought on by electrical field stimulation (EFS). As the concentration rose, it alone had a neglect effect on the trachea's basal tension. Before menthol was applied, levocetirizine might have also inhibited the function of the cold receptor. According to this study, levocetirizine might potentially impede the parasympathetic function of the trachea. If levocetirizine was used prior to menthol addition, it also reduced the function of cold receptors.

[Effects of Fertilizer Application Strategy Adjustments on Nitrogen and Phosphorus Loss from Typical Crop Systems in Taihu Lake Region].

The intensity of crop farming fertilizer input is generally high in the Taihu Lake Region, with chemical fertilizer as the main form. Due to inappropriate fertilizer application, nitrogen and phosphorus loss have occurred, causing serious agricultural non-point source pollution. The Ministry of Agriculture and Rural Affairs of China has launched the "zero-growth action for chemical fertilizer use" and "replacement action with organic fertilizer" ("two actions" for short) campaigns since 2015. Local agricultural sectors adjusted fertilizer application strategies of crop farming to respond to the call of two actions. However, the current research is still focusing on reducing the total amount of fertilizer application and increasing the area of organic fertilizer application, which is mainly based on grain crops. The study of agricultural environment problems is still lacking, especially in vegetable, orchard, and tea systems. Therefore, a study was carried out in the typical agricultural area of Suzhou City Wuzhong District from 2019 to 2021. Based on the data of the amount of nitrogen and phosphorus removal by harvest crops and soil nitrogen and phosphorus residual in paddy, vegetable, orchard, and tea systems, the loss was estimated. The responses of nitrogen and phosphorus loss from typical crop systems to fertilizer application strategy adjustments were studied through analysis of different factors. The results showed that fertilizer application rate was the key to control nitrogen and phosphorus loss. Additionally, the suitable replacement ratio of organic fertilizer could further reduce the loss risk. It should be noted that the urgent demand for nutrients in crop growth should be considered to determine the timing of organic fertilizer application, and agricultural machinery should be used to assist organic fertilizer application to reduce labor output if possible. Fertilizer efficiency was the core of environmental friendliness and economic benefits of crop farming. Hence, improving fertilizer efficiency should be the guidance of fertilizer application strategy adjustment. Our suggestions on the adjustment of fertilizer application strategy in different crop systems in the study area are as follows:attention should be paid to the nitrogen, phosphorus, and potassium input ratio in paddy systems to further reduce nitrogen and phosphorus loss. Planting structure adjustment should be emphasized in vegetable systems to promote fertilizer efficiency. The strategy to satisfy both tea and orchard growth from a composite system perspective would help to build crop systems that meet the needs of green agricultural development.

TRAF6 promotes osteogenesis in ADSCs through Raf-Erk-Merk-Hif1-a pathway.

Critical-size defects (CSDs) are challenging oral clinical issues that need to be solved. Adipose-derived mesenchymal stem cells (ADSCs) and gene therapy offer a new target to solve these issues. Consequently, ADSCs attract more and more attention because of advantages such as easy obtainability and no ethical concerns. TNF receptor-associated factor 6 (TRAF6) is a significant binding protein both of tumour necrosis factor superfamily and of the toll/interleukin-1 receptor superfamily. Evidence is accumulating that TRAF6 inhibited osteoclast formation and promoted the proliferation of multiple myeloma cell lines and bone resorption. Here, we reported that overexpression of TRAF6 enhanced the proliferation, migration and osteogenesis of ADSCs through Raf-Erk-Merk-Hif1a pathway. Cell sheet of ADSCs combined with TRAF6 accelerated the healing of CSDs. In a word, TRAF6 enhanced osteogenesis, migration and proliferation through Raf-Erk-Merk-Hif1a pathway.

Efficacy of Intravenously Administered Gepotidacin in Cynomolgus Macaques following a Francisella tularensis Inhalational Challenge.

Francisella tularensis (F. tularensis) is a Centers for Disease Control (CDC) category "A" Gram-negative biothreat pathogen. Inhalation of F. tularensis can cause pneumonia and respiratory failure and is associated with high mortality rates without early treatment. Gepotidacin is a novel, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action. Gepotidacin selectively inhibits bacterial DNA replication via a unique binding mode, has activity against multidrug-resistant target pathogens, and has demonstrated in vitro activity against diverse collections of F. tularensis isolates (MIC90 of 0.5 to 1 µg/mL). Gepotidacin was evaluated in the cynomolgus macaque model of inhalational tularemia, using the SCHU S4 strain, with treatment initiated after exposure and sustained fever. Macaques were dosed via intravenous (i.v.) infusion with saline or gepotidacin at 72 mg/kg/day to support a human i.v. infusion dosing regimen of 1,000 mg three times daily. The primary study endpoint was survival, with survival duration and bacterial clearance as secondary endpoints. Gepotidacin treatment resulted in 100% survival compared to 12.5% in the saline-treated control group (P < 0.0001) at Day 43 postinhalational challenge. All gepotidacin-treated animals were blood and organ culture negative for F. tularensis at the end of the study. In contrast, none of the saline control animals were blood and organ culture negative. Gepotoidacin's novel mechanism of action and the efficacy data reported here (aligned with the Food and Drug Administration Animal Rule) support gepotidacin as a potential treatment for pneumonic tularemia in an emergency biothreat situation.

Cleanup of Cr(VI)-polluted groundwater using immobilized bacterial consortia via bioreduction mechanisms.

Cr(VI) bioreduction has become a remedial alternative for Cr(VI)-polluted site cleanup. However, lack of appropriate Cr(VI)-bioreducing bacteria limit the field application of the in situ bioremediation process. In this study, two different immobilized Cr(VI)-bioreducing bacterial consortia using novel immobilization agents have been developed for Cr(VI)-polluted groundwater remediation: (1) granular activated carbon (GAC) + silica gel + Cr(VI)-bioreducing bacterial consortia (GSIB), and (2) GAC + sodium alginate (SA) + polyvinyl alcohol (PVA) + Cr(VI)-bioreducing bacterial consortia (GSPB). Moreover, two unique substrates [carbon-based agent (CBA) and emulsified polycolloid substrate (EPS)] were developed and used as the carbon sources for Cr(VI) bioreduction enhancement. The microbial diversity, dominant Cr-bioreducing bacteria, and changes of Cr(VI)-reducing genes (nsfA, yieF, and chrR) were analyzed to assess the effectiveness of Cr(VI) bioreduction. Approximately 99% of Cr(VI) could be bioreduced in microcosms with GSIB and CBA addition after 70 days of operation, which caused increased populations of total bacteria, nsfA, yieF, and chrR from 2.9 × 108 to 2.1 × 1012, 4.2 × 104 to 6.3 × 1011, 4.8 × 104 to 2 × 1011, and 6.9 × 104 to 3.7 × 107 gene copies/L. In microcosms with CBA and suspended bacteria addition (without bacterial immobilization), the Cr(VI) reduction efficiency dropped to 60.3%, indicating that immobilized Cr-bioreducing bacteria supplement could enhance Cr(VI) bioreduction. Supplement of GSPB led to a declined bacterial growth due to the cracking of the materials. The addition of GSIB and CBA could establish a reduced condition, which favored the growth of Cr(VI)-reducing bacteria. The Cr(VI) bioreduction efficiency could be significantly improved through adsorption and bioreduction mechanisms, and production of Cr(OH)3 precipitates confirmed the occurrence of Cr(VI) reduction. The main Cr-bioreducing bacteria included Trichococcus, Escherichia-Shigella, and Lactobacillus. Results suggest that the developed GSIB bioremedial system could be applied to cleanup Cr(VI)-polluted groundwater effectively.

Two putative novel serotypes of Tibet orbivirus isolated from Culicoides spp. in Yunnan, China.

Tibet orbivirus (TIBOV) was identified as a novel orbivirus in 2014. Antibodies against TIBOV were detected in cattle, Asian buffalo, and goats, while all the sequenced TIBOV strains were isolated from mosquitos and Culicoides. The known TIBOV strains have been classified into four putative serotypes. In this study, two TIBOV strains isolated from Culicoides spp. in Shizong County of Yunnan Province, China, were fully sequenced. The phylogenetic analysis of outer capsid protein 2 (VP2) indicated that these two viral strains belong to two novel putative serotypes of TIBOV. The updated putative serotypes may help in an investigation of the distribution and virulence of TIBOV.

Two putative novel serotypes of Tibet orbivirus isolated from Culicoides spp.in Yunnan, China

Tibet orbivirus (TIBOV) was identified as a novel orbivirus in 2014. Antibodies against TIBOV were detected in cattle, Asian buffalo, and goats, while all the sequenced TIBOV strains were isolated from mosquitos and Culicoides. The known TIBOV strains have been classified into four putative serotypes. In this study, two TIBOV strains isolated from Culicoides spp. in Shizong County of Yunnan Province, China, were fully sequenced. The phylogenetic analysis of outer capsid protein 2 (VP2) indicated that these two viral strains belong to two novel putative serotypes of TIBOV. The updated putative serotypes may help in an investigation of the distribution and virulence of TIBOV.

A case of malignant peritoneal mesothelioma / 中华劳动卫生职业病杂志

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleural cavity, followed by the peritoneum and pericardium. Malignant peritoneal mesothelioma (MPM) accounts for 10%-15% of all mesothelioma. The most important risk factor for MPM is exposure to asbestos. MPM has no specific clinical symptoms, imaging and histopathology are critical for the diagnosis. There are currently no generally accepted guidelines for curative treatment of MPM. The patient mainly presented with abdominal pain, abdominal distension and discomfort. Due to extensive omentum metastasis, no further surgical treatment was performed. Pemetrexed combined with cisplatin chemotherapy was given for 2 cycles, and the patient is still alive.

Development of a Well-Characterized Cynomolgus Macaque Model of Sudan Virus Disease for Support of Product Development.

The primary objective of this study was to characterize the disease course in cynomolgus macaques exposed to Sudan virus (SUDV), to determine if infection in this species is an appropriate model for the evaluation of filovirus countermeasures under the FDA Animal Rule. Sudan virus causes Sudan virus disease (SVD), with an average case fatality rate of approximately 50%, and while research is ongoing, presently there are no approved SUDV vaccines or therapies. Well characterized animal models are crucial for further developing and evaluating countermeasures for SUDV. Twenty (20) cynomolgus macaques were exposed intramuscularly to either SUDV or sterile phosphate-buffered saline; 10 SUDV-exposed animals were euthanized on schedule to characterize pathology at defined durations post-exposure and 8 SUDV-exposed animals were not part of the scheduled euthanasia cohort. Survival was assessed, along with clinical observations, body weights, body temperatures, hematology, clinical chemistry, coagulation, viral load (serum and tissues), macroscopic observations, and histopathology. There were statistically significant differences between SUDV-exposed animals and mock-exposed animals for 26 parameters, including telemetry body temperature, clinical chemistry parameters, hematology parameters, activated partial thromboplastin time, serum viremia, and biomarkers that characterize the disease course of SUDV in cynomolgus macaques.

Natural History of Marburg Virus Infection to Support Medical Countermeasure Development.

The Biomedical Advanced Research and Development Authority, part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, recognizes that the evaluation of medical countermeasures under the Animal Rule requires well-characterized and reproducible animal models that are likely to be predictive of clinical benefit. Marburg virus (MARV), one of two members of the genus Marburgvirus, is characterized by a hemorrhagic fever and a high case fatality rate for which there are no licensed vaccines or therapeutics available. This natural history study consisted of twelve cynomolgus macaques challenged with 1000 PFU of MARV Angola and observed for body weight, temperature, viremia, hematology, clinical chemistry, and coagulation at multiple time points. All animals succumbed to disease within 8 days and exhibited signs consistent with those observed in human cases, including viremia, fever, systemic inflammation, coagulopathy, and lymphocytolysis, among others. Additionally, this study determined the time from exposure to onset of disease manifestations and the time course, frequency, and magnitude of the manifestations. This study will be instrumental in the design and development of medical countermeasures to Marburg virus disease.

Development of a Well-Characterized Cynomolgus Macaque Model of Marburg Virus Disease for Support of Vaccine and Therapy Development.

Marburg virus (MARV) is a filovirus that can infect humans and nonhuman primates (NHPs), causing severe disease and death. Of the filoviruses, Ebola virus (EBOV) has been the primary target for vaccine and therapeutic development. However, MARV has an average case fatality rate of approximately 50%, the infectious dose is low, and there are currently no approved vaccines or therapies targeted at infection with MARV. The purpose of this study was to characterize disease course in cynomolgus macaques intramuscularly exposed to MARV Angola variant. There were several biomarkers that reliably correlated with MARV-induced disease, including: viral load; elevated total clinical scores; temperature changes; elevated ALT, ALP, BA, TBIL, CRP and decreased ALB values; decreased lymphocytes and platelets; and prolonged PTT. A scheduled euthanasia component also provided the opportunity to study the earliest stages of the disease. This study provides evidence for the application of this model to evaluate potential vaccines and therapies against MARV and will be valuable in improving existing models.

Effect of underdilated transjugular intrahepatic portosystemic shunt on prognosis in patients with prior splenectomy: a propensity score-matched case-control study.

PURPOSE: This study aimed to investigate whether underdilated transjugular intrahepatic portosystemic shunt (TIPS) could reduce the risk of hepatic encephalopathy (HE) and ameliorate impaired hepatic function in patients with a history of splenectomy. METHODS: A retrospective case-control study was conducted with 96 patients who had prior splenectomy and TIPS placement from August 2016 to May 2022. All patients were divided into two groups based on the diameter of expansion balloon catheters, the underdilated group (6-mm balloon catheter, n = 60) and a control group (8-mm balloon catheter, n = 36). Following the 1:1 propensity score matching (PSM), 33 patients in the underdilated group and 33 patients in the control group were included. RESULTS: During a median follow-up of 36 months, a quicker recovery in liver function after TIPS placement was showed in the underdilated group. The mean TBIL content (16.562 ± 6.549 µmol/L vs 23.871 ± 11.609 µmol/L, P = 0.019) and the mean CLIF-C AD score (41.108 ± 5.223 vs 45.100 ± 4.429, P = 0.033) in the underdilated group were significantly lower than those in the control group during 6 to 12 months after the procedure. In line with the control group, the ability to reduce portal pressure gradient (PPG) and achieve a significantly clinical remission of PVT and ascites severity was showed in the underdilated group 3 months after TIPS creation (P < 0.001). The Kaplan-Meier analysis demonstrated that no statistically significant differences were found in the cumulative incidence of no overt HE (OHE) (log-rank P = 0.383), cumulative incidence without shunt dysfunction (log-rank P = 0.283), cumulative incidence of no variceal rebleeding (log-rank P = 0.696), and survival (log-rank P = 0.341) (log-rank P = 0.341) between the two groups during the follow-up period. CONCLUSION: For patients with prior splenectomy, it is safe to employ underdilated TIPS, as the stents will eventually self-expand to 8 mm. The present study has shown some degree of liver function preservation in the underdilated group, which may be related to slower progressive changes in the portal hemodynamics.

Inclusion of sarcopenia improves the prognostic value of MELD score in patients after transjugular intrahepatic portosystemic shunt.

OBJECTIVE: To explore the predictive value of model for end-stage liver disease (MELD)-Sarcopenia score for survival of cirrhotic patients after transjugular intrahepatic portosystemic shunt (TIPS) placement. METHODS: 289 patients who underwent TIPS between February 2016 and December 2020 were included, they were divided into the sarcopenia group ( n = 138) and non-sarcopenia group ( n = 151) according to whether they were complicated with sarcopenia. Kaplan-Meier curve was used to analyze and compare the prognosis of the above two groups and multivariate Cox regression analysis was used to identify the independent prognostic factors. The performance of different predictive models was compared using C-index. RESULTS: During the follow-up, Kaplan-Meier analyses indicated that cumulative survival was significantly lower in sarcopenia group than that in non-sarcopenia group [74.6% vs. 92.7%, HR, 0.24 (95% confidence interval (CI), 0.12-0.46), Log-rank P < 0.001]. After multivariate Cox analysis, age [HR, 1.040 (95% CI, 1.015-1.065), P = 0.002], sarcopenia [HR, 3.948 (95% CI, 1.989-7.838), P < 0.001], albumin [HR, 0.945 (95% CI, 0.897-0.997), P = 0.037], and MELD score [HR, 1.156 (95% CI, 1.097-1.217), P < 0.001] were identified as the independent risk factors for mortality after TIPS. The C-indexes of MELD-Sarcopenia, Child-Pugh, MELD, MELD-Na, and the Freiburg index of post-TIPS survival (FIPS) scores were 0.782, 0.688, 0.719, 0.734, and 0.770, respectively. CONCLUSION: Sarcopenia is independently correlated with post-TIPS mortality, and MELD-Sarcopenia score showed the best performance in predicting post-TIPS mortality than the traditional predictive models.

CTCF functions as an insulator for somatic genes and a chromatin remodeler for pluripotency genes during reprogramming.

CTCF mediates chromatin insulation and long-distance enhancer-promoter (EP) interactions; however, little is known about how these regulatory functions are partitioned among target genes in key biological processes. Here, we show that Ctcf expression is progressively increased during induced pluripotency. In this process, CTCF first functions as a chromatin insulator responsible for direct silencing of the somatic gene expression program and, interestingly, elevated Ctcf expression next ensures chromatin accessibility and contributes to increased EP interactions for a fraction of pluripotency-associated genes. Therefore, CTCF functions in a context-specific manner to modulate the 3D genome to enable cellular reprogramming. We further discover that these context-specific CTCF functions also enlist SMARCA5, an imitation switch (ISWI) chromatin remodeler, together rewiring the epigenome to facilitate cell-fate switch. These findings reveal the dual functions of CTCF in conjunction with a key chromatin remodeler to drive reprogramming toward pluripotency.