Population Genomics Provide Insights into the Evolution and Adaptation of the Asia Corn Borer.

Understanding the genetic basis of pest adaptive evolution and the risk of adaptation in response to climate change is essential for the development of sustainable agricultural practices. However, the genetic basis of climatic adaptation for the Asian corn borer (ACB), Ostrinia furnacalis, the main pest of corn in Asia and Oceania, is poorly understood. Here, we revealed the genomic loci underlying the climatic adaptation and evolution in ACB by integrating population genomic and environmental factors. We assembled a 471-Mb chromosome-scale reference genome of ACB and resequenced 423 individuals covering 27 representative geographic areas. We inferred that the ACB effective population size changes tracked with the global temperature and followed by a recent decline. Based on an integrated analysis of whole-genome selection scans and genome-wide genotype-environment association studies, we revealed the genetic basis of ACB adaption to diverse climates. For diapause traits, we identified a major effect association locus containing a circadian clock gene (period) by analyzing a diapause-segregating population. Moreover, our predictions indicated that the northern populations were more ecologically resilient to climate change than the southern populations. Together, our results revealed the genomic basis for ACB environmental adaptation and provided potential candidate genes for future evolutionary studies and genetic adaptation to climate change, intending to maintain the efficacy and sustainability of novel control techniques.

Incidence and Risk Factors for Dysphagia Following Cerebellar Stroke: a Retrospective Cohort Study.

The cerebellum is known to play a supportive role in swallowing-related functions; however, wide discrepancies about the incidence rate of swallowing disorders following cerebellar strokes exist within the literature. This study aimed to investigate the incidence rate of dysphagia and the factors which may affect the presence of dysphagia and clinical recovery in individuals diagnosed with cerebellar stroke. A retrospective chart audit of 1651 post-stroke patients (1049 males and 602 females) admitted with a cerebellar stroke to a comprehensive tertiary hospital in China was conducted. Data on demographics, medical, along with swallowing function assessment were collected. Differences between dysphagic and non-dysphagic groups were evaluated using t-tests and Pearson's chi-square test. Univariate logistic regression analysis was performed to establish factors associated with the presence of dysphagia. A total of 11.45% of participants were identified with dysphagia during inpatient admission. Individuals with mixed types of stroke, multiple lesions in the cerebellum, and ages older than 85 years old were more likely to develop dysphagia. Moreover, the prognosis of dysphagia following a cerebellar stroke was associated with lesions in different parts of the cerebellum. The cumulative recovery rates from the best to worse were the right hemisphere group, the cerebellum vermis or peduncle group, and both the hemisphere group and the left hemisphere group, respectively.

Identification of MRI features associated with injury type, severity, and prognosis in drug-induced liver injury.

OBJECTIVES: To identify magnetic resonance imaging (MRI) features associated with injury type, severity, and liver transplantation (LT)/liver-related death (LRD) in drug-induced liver injury (DILI). METHODS: The eligible DILI patients (2016 to 2020) who underwent contrast abdominal MRI within 3 months of onset were retrospectively analysed at Beijing Friendship Hospital, Capital Medical University. The MRI features independently associated with severity and prognosis were identified by backwards logistic regression. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) are given. RESULTS: The median age of 180 patients was 55.5 years, with 126 (70.0%) women. The injury types included hepatocellular (135 cases, 75.0%), mixed (23, 12.8%), and cholestatic (22, 12.2%). The proportion of periportal oedema in patients with hepatocellular and mixed injury was significantly higher than that in cholestatic injury (62.2%, 47.8% vs. 18.2%, p < 0.001). For severity, 157 (87.2%) patients had mild to moderate injury, and 23 (12.8%) had severe to fatal/LT. Irregularity of the liver surface (6.56 (95% CI, 1.27-22.84)), transient hepatic attenuation difference (THAD) (3.27 (95% CI, 1.14-9.36)), and splenomegaly (5.86 (95% CI, 1.96-17.53)) were independently associated with severity. Eight (4.4%) patients died/underwent LT. THAD (8.89 (95% CI, 1.35-58.43)), and ascites (64.63 (95% CI, 6.93-602.40)) were independently associated with LT/LRD. The prediction of the new model employing THAD and ascites for LT/LRD within 1 year was 0.959 (95% CI, 0.917-1.000). CONCLUSIONS: Periportal oedema was associated with the type of injury. Irregularity of the liver surface, THAD, and splenomegaly were associated with severity. THAD and ascites may have potential clinical utility in predicting LT/LRD outcomes within 1 year. KEY POINTS: • Contrast abdominal magnetic resonance imaging features can help clinicians evaluate the type of injury, severity, and poor prognosis of drug-induced liver injury. • Transient hepatic attenuation difference and ascites have potential clinical utility in the prediction of the poor prognosis of liver transplantation/liver-related death. • The new model predicting poor prognosis has a relatively high sensitivity of 0.875 and a high specificity of 0.919.

The predictive value of the modified AFP model for liver transplantation outcomes in multinodular hepatocellular carcinoma patients.

BACKGROUND: There is a lack of studies focusing on the benefit of liver transplantation (LT) in hepatocellular carcinoma (HCC) patients with > 3 tumors. This study aims to establish a model to effectively predict overall survival in Chinese HCC patients with multiple tumors (> 3 tumors) who undergo LT. METHODS: This retrospective study included 434 HCC liver transplant recipients from the China Liver Transplant Registry. All HCC patients had more than 3 tumor nodules. Three selection criteria systems (i.e., AFP, Metroticket 2.0, and Up-to-7) were compared regarding the prediction of HCC recurrence. The modified AFP model was established by univariate and multivariate competing risk analyses. RESULTS: The AFP score 2 and the AFP score ≥ 3 groups had 5-year recurrence rates of 19.6% and 40.5% in our cohort. The prediction of HCC recurrence based on the AFP model was associated with a c-statistic of 0.606, which was superior to the Up-to-7 and Metroticket 2.0 models. AFP level > 1000 ng/mL, largest tumor size ≥ 8 cm, vascular invasion, and MELD score ≥ 15 were associated with overall survival. The 5-year survival rate in the modified AFP score 0 group was 71.7%. CONCLUSIONS: The AFP model is superior in predicting tumor recurrence in HCC patients with > 3 tumors prior to LT. With the modified AFP model, patients likely to derive sufficient benefit from LT can be identified.

Integrative analyses of transcriptome and carotenoids profiling revealed molecular insight into variations in fruits color of Citrus Reticulata Blanco induced by transplantation.

Citrus fruits exhibit vivid color and are favored extensively. However, the biochemical and molecular mechanism of Citrus Reticulata Blanco fruits coloring, especially the effect of transplantation on fruits coloring, is unclear. Herein, RNA-Seq and carotenoids profiling were applied to investigate the effect of transplantation on Orah mandarin fruits coloring. Transplantation induces fruit color shallowing, Ca2+ and ACC level declining and IAA level increasing. Transplantation induced variation in fruit skin and pulp carotenoids, mainly ß-citraurin as one of the important pigments of citrus peel. 2253 up-regulated genes, 1103 down-regulated genes in skin and 815 up-regulated genes, 534 down-regulated genes in pulp of transplanted tree fruits were identified by RNA-Seq. The DEGs involved hormone signal, carotenoids biosynthesis and TFs such as MYB and bHLH family TFs. The carotenoid cleavage dioxygenase gene (Ciclev10028113m.g) is positively correlated with ß-citraurin and regulated directly and/or indirectly by MYB1R1, PIF4, ACC and IAA. Integrative analyses revealed potential molecular insights into Orah mandarin peel color variation during transplantation.

E2F7 promotes mammalian target of rapamycin inhibitor resistance in hepatocellular carcinoma after liver transplantation.

The mammalian target of rapamycin (mTOR) pathway is frequently deregulated and has critical roles in cancer progression. mTOR inhibitor has been widely used in several kinds of cancers and is strongly recommended in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). However, the poor response to mTOR inhibitors due to resistance remains a challenge. Hypoxia-associated resistance limits the therapeutic efficacy of targeted drugs. The present study established models of HCC clinical samples and cell lines resistance to mTOR inhibitor sirolimus and screened out E2F7 as a candidate gene induced by hypoxia and promoting sirolimus resistance. E2F7 suppressed mTOR complex 1 via directly binding to the promoter of the TSC1 gene and stabilizes hypoxia-inducible factor-1α activating its downstream genes, which are responsible for E2F7-dependent mTOR inhibitor resistance. Clinically, low E2F7 expression could be an effective biomarker for recommending patients with HCC for anti-mTOR-based therapies after LT. Targeting E2F7 synergistically inhibited HCC growth with sirolimus in vivo. E2F7 is a promising target to reverse mTOR inhibition resistance. Collectively, our study points to a role for E2F7 in promoting mTOR inhibitor resistance in HCC and emphasizes its potential clinical significance in patients with HCC after LT.

Impact of the Kasai Procedure and the Length of Native Liver Survival Time on Outcomes of Liver Transplantation for Biliary Atresia.

The aim is to explore the impact of the Kasai procedure (KP) and the length of native liver survival time (NLST) on outcomes of liver transplantation (LT). Patients with biliary atresia (BA), who underwent LT in Beijing Friendship Hospital from January 2017 to December 2019, were enrolled and divided into non-KP (N-KP) and post-KP (P-KP) groups. The patients in the P-KP group were further divided into early failure (KP-EF) defined by NLST <1 year, medium failure (KP-MF, NLST 1-5 years), and late failure (KP-LF, NLST >5 years) subgroups. Clinical data at baseline and during follow-up were collected. The inverse probability of treatment weighting method was used to evaluate the independent effect of KP and the length of NLST on clinical outcomes. Among 197 patients with BA, the N-KP group accounted for 43 (21.8%), KP-EF 71 (46.1%), KP-MF 59 (38.3%), and KP-LF 24 (15.6%) cases, respectively. The N-KP and KP-EF groups had significantly longer hospitalization and intensive care unit stays after LT. Graft and overall survival rates were 93.0% in the N-KP group and 97.4% in P-KP group, respectively. The mortality rate in the P-KP group were significantly lower compared with that of the N-KP group with a hazard ratio (HR) of 0.2 (P = 0.02). The risks of biliary and vascular complications and cytomegalovirus (CMV) infection after LT were significantly higher in KP-EF group than those in the KP-MF and KP-LF groups (HRs = 0.09, 0.2, and 0.3, respectively; all P < 0.001). The KP significantly improved after LT overall survival. Patients with early native liver failure after KP have significantly higher risks for biliary and vascular complications and CMV infection.

Cloxacillin-induced acute vanishing bile duct syndrome: A case study and literature review.

Ductopenia is often regarded as a chronic process where ≥50% of portal tracts lack bile ducts, which is also known as vanishing bile duct syndrome (VBDS). One aetiology is drug-induced liver injury. Cloxacillin, an antistaphylococcal penicillin, typically causes "bland" cholestasis. We present the first case of cloxacillin-induced acute ductopenia or VBDS and a review of published cloxacillin-induced liver injuries. A 66-year-old woman with no prior liver disease, but known penicillin allergy, was treated for postcarotid angioplasty staphylococcal infection with 6 weeks of cloxacillin. She presented with a 2-week history of weakness and jaundice. Laboratory work-up showed elevated liver enzymes with a cholestatic pattern, hyperbilirubinemia and eosinophilia. She required ICU transfer for hypotension and was started empirically on prednisone. Liver biopsy revealed severe centrilobular cholestasis, mild necroinflammation and ductopenia with epithelial injury, but no ductular reaction. Two months later she was discharged on hydrocortisone and ursodiol with persistently elevated alkaline phosphatase and bilirubin. She was considered for liver transplantation but died of liver failure 4 months later. Four additional articles were found with histopathologic descriptions of cloxacillin-related liver injury. These included portal inflammation, cholestasis and mild necroinflammation. Clinical features were reported in two cases; both had mild symptoms with cholestatic liver enzymes and hyperbilirubinemia. Both patients recovered completely within 10-60 days. Cloxacillin-induced cholestasis can be secondary to acute ductopenia, which can result in worse clinical outcomes than previously described "bland" cholestasis. Liver biopsy is recommended to identify cases with acute VBDS.

Value of liver biopsy in anorexia nervosa-related transaminitis: A case study and literature review.

Anorexia nervosa (AN) is a complex eating disorder that affects multiple organs. 60% of patients have liver injury with transaminitis. The mechanism of liver injury in AN remains unclear. We present a case of a 19-year-old female with AN was admitted to our hospital with marked transaminitis but near normal liver histology on biopsy. Her transaminitis eventually improved as she regained weight. We also conducted a literature review of similar cases to delineate the clinicopathologic spectrum of liver injury in AN patients. English published cases of adult AN patients with elevated transaminases who underwent a liver biopsy or autopsy were selected. 32 cases (including ours). All except four patients were female, with median age of 26.5 years and median body mass index 11.9 kg/m2 . Presentations mainly included hypoglycemic coma and weight loss. 63% of patients had severe transaminitis (AST >15x ULN). Other lab findings included elevated international normalized ratio (72%) and hypoalbuminemia (47%). Microscopically, all cases showed intact hepatic architecture. Fibrosis was reported in 12 cases and necroinflamfmation in 8, but only half of each had severe transaminitis. AN patients display a wide spectrum of liver histopathology which often does not correlate with the degree of transaminitis. In severe persistent AN-related transaminitis, liver biopsy is useful to assess the degree of liver injury and to exclude other potential etiologies.

A High Serum Level of Taurocholic Acid Is Correlated With the Severity and Resolution of Drug-induced Liver Injury.

BACKGROUND & AIMS: Alterations in the serum levels of bile acids are associated with drug-induced liver injury (DILI). We investigated the association between serum levels of bile acids and the severity and outcome of DILI, along with the potential role of variants in the ATP binding cassette subfamily B member 11 (ABCB11) gene and expression of its product, ABCB11 (also called BSEP). METHODS: We performed this prospective study of 95 patients (median age, 53 years; 73.7% female) with DILI from August 2018 through August 2019. Patients were matched for age, gender, and body mass index with healthy individuals (n = 100; healthy controls) and patients with chronic hepatitis B (n = 105; CHB controls). We collected demographic and biochemical data at baseline and 1 week, 1 month, 3 months, and 6 months after DILI onset and at the time of biochemical recovery, liver failure or liver transplantation. Serum levels of bile acids were measured using high-performance liquid-chromatography tandem mass-spectrometry. All 27 exons of ABCB11 were sequenced and expression of BSEP was analyzed by immunohistochemistry in liver biopsy specimens. RESULTS: Levels of 30 of the 37 bile acids analyzed differed significantly between patients with DILI and healthy controls. Changes in levels of taurocholic acid (TCA), glycocholic acid, taurochenodeoxycholate, and glycochenodeoxycholate associated with the increased levels of bilirubin and greater severity of DILI, and were also associated with CHB. Cox regression analysis showed that only change in the levels of TCA independently associated with biochemical resolution of DILI. Combination of TCA level (≥ 1955.41 nmol/L), patient age, and DILI severity was associated with abnormal blood biochemistry at 6 months after DILI onset (area under the curve, 0.81; 95% confidence interval, 0.71-0.88; sensitivity, 0.69; specificity, 0.81). ABCB11 missense variants were not associated with differences in the serum bile acid profiles, DILI severity, or clinical resolution. However, lower levels of BSEP in bile canaliculi in liver biopsies were associated with altered serum levels of bile acids. CONCLUSIONS: In this prospective study performed in Chinese patients, we found that the serum levels of TCA were associated with the severity and clinical resolution of DILI. Reduced protein expression of BSEP in liver tissue, rather than variants of the ABCB11 gene were associated with altered serum levels of bile acids.

Comparison and development of advanced machine learning tools to predict nonalcoholic fatty liver disease: An extended study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a public health challenge and significant cause of morbidity and mortality worldwide. Early identification is crucial for disease intervention. We recently proposed a nomogram-based NAFLD prediction model from a large population cohort. We aimed to explore machine learning tools in predicting NAFLD. METHODS: A retrospective cross-sectional study was performed on 15 315 Chinese subjects (10 373 training and 4942 testing sets). Selected clinical and biochemical factors were evaluated by different types of machine learning algorithms to develop and validate seven predictive models. Nine evaluation indicators including area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), accuracy, positive predictive value, sensitivity, F1 score, Matthews correlation coefficient (MCC), specificity and negative prognostic value were applied to compare the performance among the models. The selected clinical and biochemical factors were ranked according to the importance in prediction ability. RESULTS: Totally 4018/10 373 (38.74%) and 1860/4942 (37.64%) subjects had ultrasound-proven NAFLD in the training and testing sets, respectively. Seven machine learning based models were developed and demonstrated good performance in predicting NAFLD. Among these models, the XGBoost model revealed the highest AUROC (0.873), AUPRC (0.810), accuracy (0.795), positive predictive value (0.806), F1 score (0.695), MCC (0.557), specificity (0.909), demonstrating the best prediction ability among the built models. Body mass index was the most valuable indicator to predict NAFLD according to the feature ranking scores. CONCLUSIONS: The XGBoost model has the best overall prediction ability for diagnosing NAFLD. The novel machine learning tools provide considerable beneficial potential in NAFLD screening.

USP22 promotes hypoxia-induced hepatocellular carcinoma stemness by a HIF1α/USP22 positive feedback loop upon TP53 inactivation.

OBJECTIVE: We aimed to elucidate the mutual regulation mechanism of ubiquitin-specific protease 22 (USP22) and hypoxia inducible factor-1α (HIF1α), and the mechanism they promote the stemness of hepatocellular carcinoma (HCC) cells under hypoxic conditions. DESIGN: Cell counting, migration, self-renewal ability, chemoresistance and expression of stemness genes were established to detect the stemness of HCC cells. Immunoprecipitation, ubiquitination assay and chromatin immunoprecipitation assay were used to elucidate the mutual regulation mechanism of USP22 and HIF1α. HCC patient samples and The Cancer Genome Atlas data were used to demonstrate the clinical significance. In vivo USP22-targeting experiment was performed in mice bearing HCC. RESULTS: USP22 promotes hypoxia-induced HCC stemness and glycolysis by deubiquitinating and stabilising HIF1α. As direct target genes of HIF1α, USP22 and TP53 can be transcriptionally upregulated by HIF1α under hypoxic conditions. In TP53 wild-type HCC cells, HIF1α induced TP53-mediated inhibition of HIF1α-induced USP22 upregulation. In TP53-mutant HCC cells, USP22 and HIF1α formed a positive feedback loop and promote the stemness of HCC. HCC patients with a loss-of-function mutation at TP53 and high USP22 and/or HIF1α expression tend to have a worse prognosis. The USP22-targeting lipopolyplexes caused high tumour inhibition and high sorafenib sensitivity in mice bearing HCC. CONCLUSION: USP22 promotes hypoxia-induced HCC stemness by a HIF1α/USP22 positive feedback loop on TP53 inactivation. USP22 is a promising target for the HCC therapy.

Hangzhou criteria as downstaging criteria in hepatocellular carcinoma before liver transplantation: A multicenter study from China.

BACKGROUND: The downstaging of hepatocellular carcinoma (HCC) has been confirmed to benefit liver transplantation (LT) patients whose tumors are beyond the transplantation criteria. Milan criteria (MC), a tumor size and number-based assessment, is currently used as the endpoint in these patients. However, many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy. Hence, this study aimed to explore the feasibility of Hangzhou criteria (HC), which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number, as an endpoint of downstaging. METHODS: We performed a multicenter and retrospective study of 206 patients accepted locoregional therapy (LRT) as downstaging/bridge treatment prior to LT in three centers of China. RESULTS: Recipients were divided into four groups: failed downstaging to the HC (group A, n = 46), successful downstaging to the HC (group B, n = 30), remained within the HC all the time (group C, n = 113), and tumor progressed (group D, n = 17). The 3-year HCC recurrence probabilities of groups B and C were not significantly different (10.3% vs. 11.6%, P = 0.87). The HCC recurrent rate was significantly higher in group A (52.3%) compared with that in group B/C (P < 0.05). Seven patients (7/76, 9.2%) whose tumor exceeded the the HC were successfully downstaged to the MC, and 39.5% (30/76) to the the HC. In group B, 23 patients remained beyond the MC and their survivals were as well as those of patients within the MC. CONCLUSIONS: Compared to the MC, HC downstaging criteria can give more HCC patients access to LT and furthermore, the outcome of these patients is the same as those matching MC downstaging criteria. Hangzhou downstaging criteria therefore is applicable in clinical practice.

Clinical effect of simvastatin combined with exercise training in the treatment of stationary chronic obstructive pulmonary disease complicated with metabolic syndrome.

The aim of this study is to observe and analyze the clinical efficacy of simvastatin combined with exercise training in the treatment of stationary chronic obstructive pulmonary disease complicated with metabolic syndrome. In this study, 180 patients who had been treated for stable chronic obstructive pulmonary disease (COPD) complicated with metabolic syndrome in our hospital were enrolled as research objects. The selected patients were randomly divided into research group receiving simvastatin combined with exercise training and control group accepting routine therapy, each containing 90 cases. The therapeutic effects of the two groups were compared. The CAT score, insulin resistance index and 6 min walking distance of the two groups were compared. The results showed that compared with the control group, the improvement effect of the research group was more obvious, and the effect was better than that of the control group, p<0.05. The levels of IL-6 (interleukin-6), IL-8 (interleukin-8) and other inflammatory factors were significantly lower in the research group than those in the control group, p<0.05. Simvastatin combined with exercise training in the treatment of stationary chronic obstructive pulmonary disease with metabolic syndrome is an effective treatment, which can significantly improve the treatment effect and help patients to achieve a higher quality of life.

New-onset hyperglycemia immediately after liver transplantation: A national survey from China Liver Transplant Registry.

BACKGROUND: New-onset hyperglycemia (NOH) is a common phenomenon after liver transplantation (LT), but its impact on clinical outcomes has not yet been fully assessed. We aimed to evaluate the etiology and prognosis of NOH within 1 month after LT. METHODS: The data of 3339 adult patients who underwent primary LT from donation after citizen death between January 2010 and June 2016 were extracted from China Liver Transplant Registry database and analyzed. NOH was defined as fasting blood glucose ≥7.0 mmol/L confirmed on at least two occasions within the first post-transplant month with or without hypoglycemic agent. RESULTS: Of 3339 liver recipients, 1416 (42.4%) developed NOH. Recipients with NOH had higher incidence of post-transplant complications such as graft and kidney failure, infection, biliary stricture, cholangitis, and tumor recurrence in a glucose concentration-dependent manner as compared to non-NOH recipients (P < 0.05). The independent risk factors of NOH were donor warm ischemic time >10 min, cold ischemic time >10 h, anhepatic time >60 min, recipient model for end-stage liver disease score >30, moderate ascites and corticosteroid usage (P < 0.05). Liver enzymes (alanine aminotransferase and gamma-glutamyltranspeptidase) on post-transplant day 7 significantly correlated with NOH (P < 0.001). CONCLUSIONS: NOH leads to increased morbidity and mortality in liver recipients. Close surveillance and tight control of blood glucose are desiderated immediately following LT particularly in those with delayed graft function and receiving corticosteroid. Strategic targeting graft ischemic injury may help maintain glucose homeostasis.

Percutaneous liver biopsy: retrospective study of primary and secondary hepatic lymphoma in twenty-one patients.

BACKGROUND: Hepatic lymphoma (HL) is categorized as primary and secondary hepatic lymphoma (PHL and SHL). This disorder can present as hepatic mass or mass-like lesion. Chemotherapy often is the first line treatment for patients with HL. Thus, an accurate pre-management histological diagnosis is essential to potentially improve clinical outcomes. The present study was to explore the prevalence of HL in ultrasound guided liver biopsies for hepatic mass or mass-like lesions, to investigate HL associated clinicopathological features, to raise the awareness of early recognition and proper diagnosis of this entity, and to assess specimen adequacy in needle core biopsy. METHODS: Twenty-one cases of HL were enrolled. Clinical and pathological characteristics were evaluated, quality of biopsies was assessed and pertinent literature was reviewed. RESULTS: HL was diagnosed in 0.94% of 2242 liver biopsy cases with ambiguous clinical presentation, laboratory tests and image studies. There were two cases of PHL (0.09%), and nineteen cases of SHL (0.85%). Histopathologically, diffuse large B-cell lymphoma was the most common type, followed by B-cell lymphoma not otherwise specified, T-cell lymphoma, Hodgkin's lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Additionally, three lymphocytic infiltration patterns were documented microscopically. The nodular infiltration was the most common type. CONCLUSIONS: HL is a rare entity and histopathology along with ancillary tests remains the only way to make the diagnosis. Clinicians' awareness of this entity and early liver biopsy are essential in patient management.

Association between ADIPOQ gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation.

BACKGROUND: New-onset diabetes after transplantation (NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation (LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver recipients. METHODS: A total of 256 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom MassARRAY. Modified clinical models in predicting NODAT were established and evaluated. RESULTS: The GG genotype of ADIPOQ rs1501299 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients (56% vs 39%, P=0.014). Dominant model (GG vs GT+TT, P=0.030) and recessive model (GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age (OR=1.048, P=0.004), BMI (OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT (OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs1501299 could improve the ability of clinical model in predicting NODAT (AUROC=0.743, P<0.001). CONCLUSION: ADIPOQ rs1501299 gene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.

Complementary and alternative medicine: A narrative review of nutritional approaches for cancer-related fatigue.

Cancer-related fatigue (CRF) is a common symptom among patients with cancer, with a prevalence of >49%. CRF significantly affects the quality of life of patients and may also affect their overall survival. Pharmacological interventions serve as a last resort after carefully weighing the risks and benefits, with limited benefits for patients, many side effects, and adverse reactions. Compared to traditional medicine, nutritional approaches have fewer side effects, are highly accepted by patients, and do not affect the antitumor treatment of patients. Many studies have shown that nutritional approaches, as a form of complementary and alternative medicine, help improve the symptoms of CRF and the quality of life of patients. This study was designed to examine nutritional approaches to CRF and assess their effectiveness of nutritional approaches in improving CRF. We present an overview of clinical trials investigating nutritional approaches for CRF that have been published over the last 2 decades. A total of 33 records were obtained from 3 databases: Web of Science, MEDLINE, and PubMed. Some nutritional approaches, such as melatonin, PG2, and S-adenosyl-l-methionine, are potential options for CRF treatment. However, the trials included in the review varied widely in quality, most were weak in methodology, and there is currently insufficient evidence to conclude with certainty the effectiveness of nutritional approaches in reducing CRF. Therefore, the design and methods used in future complementary and alternative medicine trials should be more rigorous.

Histopathological characteristics of liver biopsy performed at different time points in drug-induced liver injury.

BACKGROUND AND AIMS: Liver biopsy can provide critical information in patients with drug-induced liver injury (DILI). Our study aimed to compare the histopathological features of DILI at different time points from the onset to liver biopsy. METHODS: We conducted a single-centre retrospective observational study. The clinical and follow-up data were extracted, and the pathological slides were reviewed. RESULTS: 129 patients were included. The median age was 52 and 75% were women. They were divided into <1 month, 1-3 months, and >3 months groups according to the durations from onset of the disorder to liver biopsy. The aminotransferase, alkaline phosphatase, and bilirubin levels showed no significant differences at onset but significantly decreased with time among the three groups (all p<0.05) at the time of liver biopsy. Histological injury patterns were significantly different among the three groups (p<0.01). Hepatocellular, canalicular, and cholestasis of Kupffer cells were significantly less frequent in the >3 months group (p<0.01). For patients taking herbs, bridging necrosis and cholestatic injury were significantly more frequent in the <1 month group (p<0.01). Furthermore, ductopenia, cholate stasis, and foam-like cells were equally distributed in the three groups but were significantly associated with poor prognosis. CONCLUSIONS: Biopsy time significantly affects liver pathology: the earlier, the more acute cholestatic-hepatitic pattern, the later, the more chronic injury patterns. The prognostic features (ductopenia, cholate stasis, and foam-like cells) occurred equally in all three groups. Our study provides valuable information for liver pathologists aiding in their better interpretation of the liver biopsy from patients with DILI.

Astragalus membranaceus: A Review of Its Antitumor Effects on Non-Small Cell Lung Cancer.

The rising global morbidity and mortality rates of non-small cell lung cancer (NSCLC) underscore the urgent need for more effective treatments. Current therapeutic modalities-including surgery, radiotherapy, chemotherapy, and targeted therapy-face several limitations. Recently, Astragalus membranaceus, a traditional Chinese medicine (TCM), has captured significant attention due to its broad pharmacological properties, such as immune regulation, anti-inflammatory effects, and the modulation of reactive oxygen species (ROS) and enzyme activities. This review delivers a comprehensive summary of the most recent advancements and ongoing applications of Astragalus membranaceus in NSCLC treatment, underlining its potential for integration into existing treatment protocols. It also highlights essential areas for future research, including the elucidation of its molecular mechanisms, optimization of dosage and administration, and evaluation of its efficacy and safety alongside standard therapies, all of which could potentially improve therapeutic outcomes for NSCLC patients.