Effects of acid mine drainage and sediment contamination on soil bacterial communities, interaction patterns, and functions in alkaline desert grassland.

Acid mine drainage and sediments (AMD-Sed) contamination pose serious ecological and environmental problems. This study investigated the geochemical parameters and bacterial communities in the sediment layer (A) and buried soil layer (B) of desert grassland contaminated with AMD-Sed and compared them to an uncontaminated control soil layer (CK). The results showed that soil pH was significantly lower and iron, sulfur, and electroconductivity levels were significantly higher in the B layer compared to CK. A and B were dominated by Proteobacteria and Actinobacteriota, while CK was dominated by Firmicutes and Bacteroidota. The pH, Fe, S, and potentially toxic elements (PTEs) gradients were key influences on bacterial community variability, with AMD contamination characterization factors (pH, Fe, and S) explaining 48.6 % of bacterial community variation. A bacterial co-occurrence network analysis showed that AMD-Sed contamination significantly affected topological properties, reduced network complexity and stability, and increased the vulnerability of desert grassland soil ecosystems. In addition, AMD-Sed contamination reduced C/N-cycle functioning in B, but increased S-cycle functioning. The results highlight the effects of AMD-Sed contamination on soil bacterial communities and ecological functions in desert grassland and provide a reference basis for the management and restoration of desert grassland ecosystems in their later stages.

Ythdf2-mediated STK11 mRNA decay supports myogenesis by inhibiting the AMPK/mTOR pathway.

An emerging research focus is the role of m6A modifications in mediating the post-transcriptional regulation of mRNA during mammalian development. Recent evidence suggests that m6A methyltransferases and demethylases play critical roles in skeletal muscle development. Ythdf2 is a m6A "reader" protein that mediates mRNA degradation in an m6A-dependent manner. However, the specific function of Ythdf2 in skeletal muscle development and the underlying mechanisms remain unclear. Here, we observed that Ythdf2 expression was significantly upregulated during myogenic differentiation, whereas Ythdf2 knockdown markedly inhibited myoblast proliferation and differentiation. Combined analysis of high-throughput sequencing, Co-IP, and RIP assay revealed that Ythdf2 could bind to m6A sites in STK11 mRNA and form an Ago2 silencing complex to promote its degradation, thereby regulating its expression and consequently, the AMPK/mTOR pathway. Furthermore, STK11 downregulation partially rescued Ythdf2 knockdown-induced impairment of proliferation and myogenic differentiation by inhibiting the AMPK/mTOR pathway. Collectively, our results indicate that Ythdf2 mediates the decay of STK11 mRNA, an AMPK activator, in an Ago2 system-dependent manner, thereby driving skeletal myogenesis by suppressing the AMPK/mTOR pathway. These findings further enhance our understanding of the molecular mechanisms underlying RNA methylation in the regulation of myogenesis and provide valuable insights for conducting in-depth studies on myogenesis.

Matrine improves the hepatic microenvironment and reverses epithelial-mesenchymal transition in hepatocellular carcinoma by inhibiting the Wnt-1/ß-catenin signaling pathway.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Despite rapid progress in targeted therapy and immunotherapy for HCC over the past 10 years, the overall efficacy remains unsatisfactory. This is mainly due to the presence of an intrahepatic microenvironment of cirrhosis in HCC patients, leading to cancer recurrence and drug resistance. METHODS: In this study, we investigated the correlations between the Wnt-1/ß-catenin signaling pathway and the prognosis as well as liver function of HCC patients. Additionally, we conducted in vitro experiments using different concentrations of matrine on HuH-7 cells. Furthermore, we verified the associations between the Wnt-1/ß-catenin signaling pathway, inflammation, and epithelial-mesenchymal transition (EMT) in a rat model of pre-hepatocellular carcinoma. Finally, matrine was employed to treat pre-hepatocellular carcinoma in rats and patients with advanced hepatocellular carcinoma. RESULTS: The results demonstrated the activation of the Wnt-1/ß-catenin signaling pathway, the occurrence of EMT, and exacerbated inflammation in human HCC tissues. In HuH-7 cell experiments, matrine effectively downregulated the Wnt-1/ß-catenin pathway, reversed EMT, and suppressed migration and invasion of HCC cells. In the rat model of pre-hepatocellular carcinoma, matrine dose-dependently inhibited the activation of the Wnt-1/ß-catenin signaling pathway, reversed the occurrence of EMT, and alleviated liver inflammation. Matrine analogues exhibited promising hepatoprotective effects in patients with advanced HCC. CONCLUSIONS: Matrine can reverse EMT, alleviate intrahepatic inflammation, and counteract immune depletion by inhibiting the Wnt-1/ß-catenin signaling pathway in HCC.

Post-traumatic stress disorder and traumatic events in China: a nationally representative cross-sectional epidemiological study.

Post-traumatic stress disorder (PTSD) is one of the most severe sequelae of trauma. But a nationally representative epidemiological data for PTSD and trauma events (TEs) was unavailable in China. This article firstly demonstrated detailed epidemiological information on PTSD, TEs, and related comorbidities in the national-wide community-based mental health survey in China. A total of 9,378 participants completed the PTSD-related interview of the CIDI 3.0. Lifetime prevalence and 12-month prevalence of PTSD in total respondents were 0.3% and 0.2%. while the conditional lifetime and 12-month prevalence of PTSD after trauma exposure were 1.8% and 1.1%. The prevalence of exposure to any type of TE was 17.2%. Among individuals with the exposed to TEs, younger, without regular work (being a homemaker or retried), and intimate relationship breakdown (separated/Widowed/Divorced), living rurally were associated with either the lifetime PTSD or the 12-month PTSD, while the count of a specific TE, the unexpected death of loved one, was related to both. Alcohol dependence was the most common comorbidity among male participants with PTSD but major depressive disorder (MDD) for female counterparts. Our study can provide a reliable reference for future identification and intervention for people with PTSD.

Molecular typing and mutational characterization of rectal neuroendocrine neoplasms.

BACKGROUND: Rectal neuroendocrine neoplasms (NENs) are rare neoplasms with limited understanding of its genomic alterations and molecular typing. METHODS: The paraffin-embedded tissue specimens of 38 patients with rectal NENs after surgery were subjected to whole gene sequencing (WGS), and mutation profilings were drawn to identify high-frequency mutation genes, copy-number variations (CNVs), tumor mutation burden (TMB), signal pathways, mutation signatures, DNA damage repair (DDR) genes, and molecular types. The differences of mutated genes and signaling pathways in different pathological grades and metastatic/non-metastatic groups were compared. It helped to search for potential targets. RESULTS: C > T and T > C transitions are the most common base substitutions in rectal NENs. DNA mismatch repair deficiency, DNA base modifications, smoking and exposure to ultraviolet light might play a role in the occurrence of rectal NENs. DAXX, KMT2C, BCL2L1, LTK, MERTK, SPEN, PKN1, FAT3, and LRP2 mutations were found in only low-grade rectal NETs, whereas APC, TP53, NF1, SOX9, and BRCA1 mutations were common in high-grade rectal NECs/MiNENs. These genes helped in distinguishing poorly-differentiated or well-differentiated rectal NENs. Alterations in P53, Wnt and TGFß signaling pathways were more pronounced in rectal NECs and MiNENs. Alterations in Wnt, MAPK and PI3K/AKT signaling pathways promoted metastases. Rectal NENs were classified into two molecular subtypes by cluster analysis based on the mutant genes and signaling pathways combined with clinicopathological features. Patients with mutations in the LRP2, DAXX, and PKN1 gene showed a trend of well-differentiated and early-stage tumors with less metastasis (p = 0.000). CONCLUSIONS: This study evaluated risk factors for regional lymphatic and/or distant metastases, identified high-frequency mutated genes, mutation signatures, altered signaling pathways through NGS. Rectal NENs were divided into two molecular types. This helps to evaluate the likelihood of metastasis, formulate follow-up strategies for patients and provide a target for future research on precision treatment of rectal NENs. PARP inhibitors, MEK inhibitors, mTOR/AKT/PI3K and Wnt signaling pathway inhibitors may be effective drugs for the treatment of metastatic rectal NENs.

Transarterial Chemoembolization Combined With PD-1 Inhibitors Plus Lenvatinib Showed Improved Efficacy for Treatment of Unresectable Hepatocellular Carcinoma Compared With PD-1 Inhibitors Plus Lenvatinib.

Background: Programmed cell death protein-1 inhibitors combined with lenvatinib have become a popular treatment option for patients with unresectable hepatocellular carcinoma. Transarterial chemoembolization combined with programmed cell death protein-1 inhibitors and lenvatinib has also shown preliminary efficacy in the unresectable hepatocellular carcinoma. We conducted this observational, retrospective, cohort study to compare the clinical outcomes and safety of transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib versus programmed cell death protein-1 inhibitors plus lenvatinib in patients with unresectable hepatocellular carcinoma. Methods: Between November 2019 and November 2021, patients who were diagnosed with unresectable hepatocellular carcinoma and received transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib or programmed cell death protein-1 inhibitors plus lenvatinib treatment were reviewed for eligibility. The primary endpoints included objective response rate, overall survival, and progression-free survival. The secondary endpoint was the frequency of key adverse events. Results: In total, 105 patients were eligible for the present study, and they were divided into the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group (n = 46) and the programmed cell death protein-1 inhibitors plus lenvatinib group (n = 59). The patient cohort after a one-to-one propensity score matching (n = 86) was also analyzed. The transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had a higher objective response rate both in the patient cohort before propensity score matching (54.3% vs 25.4%, P = .002) and after propensity score matching (55.8% vs 30.2%, P = .017). The patients in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had prolonged overall survival (median, 20.5 vs 12.6 months, P = .015) and progression-free survival (median, 10.2 vs 7.4 months, P = .035). For patient cohort- propensity score matching, the overall survival (20.5 vs 12.8 months, P = .013) and progression-free survival (12.1 vs 7.8 months, P = .030) were also significantly better in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group than in the programmed cell death protein-1 inhibitors plus lenvatinib group. There were no significant differences between the 2 groups concerning adverse reactions caused by immunotherapy and lenvatinib. The adverse reactions caused by transarterial chemoembolization were transient and were quickly reversed. Conclusions: Compared to programmed cell death protein-1 inhibitors plus lenvatinib, transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib may provide better treatment response and survival benefits for patients with unresectable hepatocellular carcinoma, and the adverse events were manageable.

The whole-cell proteome shows the characteristics of macrolides-resistant Bordetella pertussis in China linked to the biofilm formation.

The macrolides-resistant Bordetella pertussis (MR-Bp) isolates in China evolved from the ptxP1/fhaB3 allele and rapidly became predominant, suggestive of an adaptive transmission ability. This was different from the global prevalent ptxP3 strains, in which MR-Bp was rarely reported. The study aimed to determine the underlying mechanism responsible for fitness and resistance in these two strains. We identify proteomic differences between ptxP1/fhaB3 and ptxP3/fhaB1 strains using tandem mass tag (TMT)-based proteomics. We then performed in-depth bioinformatic analysis to determine differentially expressed genes (DEGs), followed by gene ontology (GO), and protein-protein interaction (PPI) network analysis. Further parallel reaction monitoring (PRM) analysis confirmed the expression of four target proteins. Finally, the crystal violet method was used to determine biofilm-forming ability. The results showed that the main significantly different proteins between the two represent isolates were related to biofilm formation. Furthermore, we have confirmed that ptxP1/fhaB3 showed hyperbiofilm formation in comparison with ptxP3/fhaB1. It is suggested that the resistance and adaptability of ptxP1/fhaB3 strains may be related to the formation of biofilm through proteomics. In a word, we determined the significantly different proteins between the ptxP1/fhaB3 and ptxP3/fhaB1 strains through whole-cell proteome, which were related to biofilm formation.

Dicer Suppresses Hepatocellular Carcinoma via Interleukin-8 Pathway.

Background: Elevated level of interleukin-8 (IL-8) promotes hepatocellular carcinoma (HCC) development and contributes to poor prognosis. Previously, we have proved that Dicer inhibits HCC progression. In this study, we evaluated the potential interaction between IL-8 and Dicer as well as their influence on HCC. Methods: Hepatocellular carcinoma cells of SMMC-7721 were divided into 2 groups for subsequent analysis: pCMV-Dicer group for Dicer-overexpressing lentivirus transfected cells (pCMV-Dicer cells) and pCMV-NC group for empty lentivirus transfected cells (pCMV-NC cells). Cell Counting kit-8 (CCK8), wound healing, and transwell were used to evaluate the inhibitory effect of Dicer overexpression on proliferation, migration, and invasion of HCC cells. The level of IL-8 was measured by flow cytometry bead-based immunoassays. Male nude BALB/c mice injected with pCMV-Dicer or pCMV-NC cell suspensions was used for transplant of HCC tumor. Results: We found that the secretion of IL-8 was reduced in the medium of pCMV-Dicer cells (P = .027). Recombinant human IL-8 (rhIL-8) reversed the inhibitory effect of Dicer on proliferation (P < .01), migration (P = .003), and invasion (P = .001), whereas IL-8 inhibitor of reparixin enhanced inhibitory effect of Dicer on proliferation (P < .05), migration (P = .008), and invasion (P = .000). Lenvatinib downregulated the IL-8 level of HCC cells (P = .000) as well as promote Dicer-induced inhibition for HCC cells referring to proliferation (P < .05), migration (P = .000), and invasion (P = .000). Animal experiments also demonstrated that Dicer cooperated with lenvatinib to inhibit the growth of HCC tumors (P < .05). Conclusions: Dicer cooperated with lenvatinib to inhibit HCC growth via downregulating IL-8, and Dicer displayed its potential capability to enhance the anti-tumor effect of lenvatinib.

Evaluation of soil heavy metals pollution and the phytoremediation potential of copper-nickel mine tailings ponds.

Heavy metal pollution in soils caused by mining has led to major environmental problems around the globe and seriously threatens the ecological environment. The assessment of heavy metal pollution and the local phytoremediation potential of contaminated sites is an important prerequisite for phytoremediation. Therefore, the purpose of this study was to understand the characteristics of heavy metal pollution around a copper-nickel mine tailings pond and screen local plant species that could be potentially suitable for phytoremediation. The results showed that Cd, Cu, Ni, and Cr in the soil around the tailings pond were at the heavy pollution level, Mn and Pb pollution was moderate, and Zn and As pollution was light; The positive matrix factorization (PMF) model results showed that the contributions made by industrial pollution to Cu and Ni were 62.5% and 66.5%, respectively, atmospheric sedimentation and agricultural pollution contributions to Cr and Cd were 44.6% and 42.8%, respectively, the traffic pollution contribution to Pb was 41.2%, and the contributions made by natural pollution sources to Mn, Zn, and As were 54.5%, 47.9%, and 40.0% respectively. The maximum accumulation values for Cu, Ni, Cr, Cd, and As in 10 plants were 53.77, 102.67, 91.10, 1.16 and 7.23 mg/kg, respectively, which exceeded the normal content of heavy metals in plants. Ammophila breviligulata Fernald had the highest comprehensive extraction coefficient (CEI) and comprehensive stability coefficient (CSI) at 0.81 and 0.83, respectively. These results indicate that the heavy metal pollution in the soil around the copper nickel mine tailings pond investigated in this study is serious and may affect the normal growth of plants. Ammophila breviligulata Fernald has a strong comprehensive remediation capacity and can be used as a remediation plant species for multiple metal compound pollution sites.

Research progress on psychological problems and interventions among healthcare workers during the COVID-19 pandemic / 预防医学

@#The coronavirus disease 2019 (COVID-19) pandemic poses negative impacts on psychological health among healthcare workers. If timely diagnosis and interventions are not given, the pandemic not only threatens physical and psychological health among healthcare workers, and greatly reduces the quality and efficiency of medical treatment. Based on review of national and international publications pertaining to psychological problems and interventions among healthcare workers during the COVID-19 pandemic, this article describes the prevalence of psychological problems among healthcare workers, influencing factors and psychological interventions, so as to provide insights into the protection of psychological health among healthcare workers.

Accumulation of DNA damage alters microRNA gene transcription in Arabidopsis thaliana.

BACKGROUND: MicroRNAs (miRNAs) and other epigenetic modifications play fundamental roles in all eukaryotic biological processes. DNA damage repair is a key process for maintaining the genomic integrity of different organisms exposed to diverse stresses. However, the reaction of miRNAs in the DNA damage repair process is unclear. RESULTS: In this study, we found that the simultaneous mutation of zinc finger DNA 3'-phosphoesterase (ZDP) and AP endonuclease 2 (APE2), two genes that play overlapping roles in active DNA demethylation and base excision repair (BER), led to genome-wide alteration of miRNAs. The transcripts of newly transcribed miRNA-encoding genes (MIRs) decreased significantly in zdp/ape2, indicating that the mutation of ZDP and APE2 affected the accumulation of miRNAs at the transcriptional level. In addition, the introduction of base damage with the DNA-alkylating reagent methyl methanesulfonate (MMS) accelerated the reduction of miRNAs in zdp/ape2. Further mutation of FORMAMIDOPYRIMIDINE DNA GLYCOSYLASE (FPG), a bifunctional DNA glycosylase/lyase, rescued the accumulation of miRNAs in zdp/ape2, suggesting that the accumulation of DNA damage repair intermediates induced the transcriptional repression of miRNAs. CONCLUSIONS: Our investigation indicates that the accumulation of DNA damage repair intermediates inhibit miRNAs accumulation by inhibiting MIR transcriptions.

Psychological outcomes and associated factors amongst healthcare workers during a single wave, deeper into the COVID-19 pandemic in China.

Background: To date, the repeated breakout of the novel coronavirus disease 2019 (COVID-19) pandemic across many regions in China has caused continuous physical and mental harm to health care workers. This study investigates the psychological burden of the pandemic and its associated risk factors among Chinese healthcare workers (HCWs) during a single wave of COVID-19. Methods: For this cross-sectional web-based survey conducted from January 16, 2022 to February 5, 2022, a total of 412 HCWs from Northwestern China were recruited. Their socio-demographic data and COVID-19 related survey variables were then collected using online self-rating questionnaires. In addition, the Chinese versions of well-validated instruments, including the 12-item General Health Questionnaire for psychiatric morbidity, the Generalized Anxiety Disorder Scale-7 for anxiety, the Patient Health Questionnaire-9 for depression and the Insomnia Severity Index-7 for insomnia, were used to assess the participants' mental health status. Multivariate logistic regression analysis was eventually performed to identify the risk factors associated with the psychological outcomes. Results: Of the 388 participants who were included in the final study (94.17% response rate), the prevalence of anxiety, depression, and insomnia symptoms were 25.3% (95% CI: 20.9-29.6%), 40.7% (95% CI: 35.8-45.6%), and 30.9% (95% CI: 26.3-35.5%), respectively. Multivariate logistic regression analysis revealed that being a woman and having a perceived need for psychological support were risk factors for all psychological outcomes, while poor disease cognition and perceived susceptibility were risk factors for anxiety. Poor disease cognition and being unvaccinated against COVID-19 were risk factors for depression, with the latter also being an independent risk factor for insomnia. Conclusion: This study has identified a relatively lower prevalence rate of psychological disorders among Chinese HCWs during a single wave, deeper into the COVID-19 pandemic. Female HCWs, and those who had a perceived need for psychological support, had poor disease cognition, were perceived as susceptible to COVID-19 and had not been vaccinated against COVID-19 deserve more attention.

TNF-α, IL-6 and hsCRP in patients with melancholic, atypical and anxious depression: an antibody array analysis related to somatic symptoms.

Background: The association between inflammation and major depressive disorder (MDD) remains poorly understood, given the heterogeneity of patients with MDD. Aims: We investigated inflammatory markers, such as interleukin (IL)-6, high-sensitivity C reactive protein (hsCRP) and tumour necrosis factor-α (TNF-α) in melancholic, atypical and anxious depression and explored whether baseline inflammatory protein levels could indicate prognosis. Methods: The sample consisted of participants (aged 18-55 years) from a previously reported multicentre randomised controlled trial with a parallel-group design registered with ClinicalTrials.gov, including melancholic (n=44), atypical (n=37) and anxious (n=44) patients with depression and healthy controls (HCs) (n=33). Subtypes of MDD were classified according to the 30-item Inventory of Depressive Symptomatology, Self-Rated Version and the 17-item Hamilton Depression Rating Scale. Blood levels of TNF-α, IL-6 and hsCRP were assessed using antibody array analysis. Results: Patients with MDD, classified according to melancholic, atypical and anxious depression subtypes, and HCs did not differ significantly in baseline TNF-α, IL-6 and hsCRP levels after adjustment. In patients with anxious depression, hsCRP levels increased significantly if they experienced no pain (adjusted (adj.) p=0.010) or mild to moderate pain (adj. p=0.038) compared with those with severe pain. However, the patients with anxious depression and severe pain showed a lower trend in hsCRP levels than patients with atypical depression who experienced severe pain (p=0.022; adj. p=0.155). Baseline TNF-α (adj. p=0.038) and IL-6 (adj. p=0.006) levels in patients in remission were significantly lower than those in patients with no remission among the participants with the atypical depression subtype at the eighth-week follow-up. Conclusions: This study provides evidence of differences in inflammatory proteins in patients with varied symptoms among melancholic, atypical and anxious depression subtypes. Further studies on the immunoinflammatory mechanism underlying different subtypes of depression are expected for improved individualised therapy. Trial registration number: NCT03219008.

Passivation of heavy metals in copper-nickel tailings by in-situ bio-mineralization: A pilot trial and mechanistic analysis.

Metal tailings contain a variety of toxic heavy metals and have potential environmental risks owing to long-term open piling. In the present study, a strain of ureolytic bacteria with bio-mineralization ability, Lysinibacillus fusiformis strain Lf, was isolated from copper-nickel mine tailings in Xinjiang and applied to a pilot trial of tailings solidification under field conditions. The results of the pilot trial (0.5 m3 in scale) showed that strain Lf effectively solidified the tailings. The compressive strength of the solidified tailings increased by 121 ± 9 % and the permeability coefficient decreased by 68 ± 3 %. Compared to the control, the leaching reduction of the solidified tailings of Cu and Ni was >98 %, and that of As was 92.5 ± 1.7 %. Two mechanisms of tailings solidification and heavy metal passivation were proposed based on the findings of Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM), and energy-dispersive X-ray spectroscopy (EDS) mapping. Biogenic calcite filled the interstices of the tailings particles and cemented the adjacent particles. This improved the mechanical properties and reduced permeability. Moreover, heavy metal colloids were incorporated into large-sized calcite crystals, and heavy metal ions were sequestered within the calcite lattice. This method of using indigenous ureolytic bacteria to solidify tailings was successful in this work and may be replicated to remediate other tailings.

Sarcopenia and Systemic Inflammation Response Index Predict Response to Systemic Therapy for Hepatocellular Carcinoma and Are Associated With Immune Cells.

Background: Systemic therapies, including immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), have challenged the use of conventional therapies for hepatocellular carcinoma (HCC). It is crucial to determine which patients could benefit most from combination therapy. This study aims to examine the associations of sarcopenia and systemic inflammation response index (SIRI) with the treatment responses and efficacies in patients with HCC treated with ICIs and tyrosine kinase inhibitors TKIs, as well as investigate the correlation between sarcopenia and inflammatory or immune states. Methods: We reviewed 160 patients with HCC treated with TKIs and ICIs. The patients' psoas muscle size was measured on axial computed tomography scans and normalized for the patients' height squared. This value was referred to as the psoas muscle index (PMI). Sarcopenia was determined from PMI and their relationships with patients' clinicopathological characteristics, inflammation indexes, peripheral blood T-cell subsets and survival were evaluated. Results: Sarcopenia and systemic inflammation response index (SIRI) were independent predictors for overall survival and progression-free survival. Patients with high PMI and low SIRI demonstrated significantly better median overall survival and progression-free survival (36.0 months and 9.6 months, respectively) than those with either low PMI or high SIRI (20.8 months and 6.0 months, respectively) and those with both high SIRI and low PMI (18.6 months and 3.0 months, respectively). Portal vein tumor thrombus (P=0.003), eastern cooperative oncology group performance status score of 1 (P=0.048), high alkaline phosphatase (P=0.037), high neutrophil-to-lymphocyte ratio (NLR) (P=0.012), low lymphocyte-to-monocyte ratio (LMR) (P=0.031), high platelet-to-lymphocyte ratio (PLR) (P=0.022) and high SIRI (P=0.012) were closely associated with an increased incidence of sarcopenia. PMI was negatively correlated with SIRI (r = -0.175, P=0.003), NLR (r = -0.169, P=0.036), and PLR (r = -0.328, P=0.000) and was significantly positively correlated with LMR (r = 0.232, P=0.004). The CD3+ and CD4+ T-cell counts of the high PMI group were significantly higher than those of the low PMI group. Conclusion: Sarcopenia and high SIRI were associated with reduced survival in patients with HCC treated with ICIs and TKIs. Sarcopenia could affect inflammatory states and the immune microenvironment.

Prognosis of hepatocellular carcinoma and its association with immune cells using systemic inflammatory response index.

Aim: To explore the prognostic value of the systemic inflammatory response index (SIRI) and peripheral blood T-cell subsets in patients with hepatocellular carcinoma (HCC) and the relationship between them. Materials & methods: We treated 352 patients with HCC with sorafenib and/or immune checkpoint inhibitors (ICIs) and analyzed SIRI and peripheral blood T cells. Results: SIRI was an independent prognostic factor for patients with HCC receiving systemic therapy. Patients with high SIRI and low baseline peripheral blood T-cell counts showed a poor response to ICIs. SIRI was significantly and negatively correlated with CD3+, CD4+ and CD8+ T-cell counts. Conclusion: SIRI markers can be employed to noninvasively assess the presence of cancer-promoting inflammation in the tumor microenvironment and predict the efficacy of targeted therapy and immunotherapy.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The change of immune microenvironment plays an important role in the occurrence and development of HCC. Recently, targeted therapy and immunotherapy have brought new hope to patients with advanced HCC. However, owing to the complexity of the immune microenvironment, not all patients can benefit from it. This study explores a simple, non-invasive method based on blood cell count to assess the immune microenvironment of HCC and predict the efficacy of treatment.

[Establishment of a Mouse Model of Acquired Aplastic Anemia Mediated by Cyclophosphamide Combined with Cyclosporine].

OBJECTIVE: To establish a stable mouse model of acquired aplastic anemia. METHODS: Female BALB/C mice aged 6 months were intraperitoneally injected with cyclophosphamide and cyclosporine for 14 days. The number of peripheral blood cells, the concentration of hemoglobin, the number of bone marrow nucleated cells, bone marrow smear, bone marrow pathological sections and other indexes were observed. RESULTS: In BALB/C mice injected intraperitoneally with cyclophosphamide and cyclosporine, the number of peripheral blood cells and the concentration of hemoglobin were significantly decreased, especially the white blood cells and platelets. Bone marrow smear showed a significant decrease in the number of nucleated cells and bone marrow hyperplasia. Bone marrow pathology showed decreased hematopoietic cells and increased non-hematopoietic cells such as adipocytes. CONCLUSION: The mouse model with intraperitoneal injection of cyclophosphamide and cyclosporine can meet the diagnostic criteria of acquired aplastic anemia, which can be used as a mouse model for the study of the pathogenesis and treatment of acquired aplastic anemia.

A Preliminary Study of Different Treatment Strategies for Anxious Depression.

BACKGROUND: Despite the best treatments, about 20% of patients with major depressive disorder (MDD) receiving drugs and psychological intervention show little or no improvement. There is no trial comparing different treatment methods in patients with anxiety/somatic subtype MDD. AIM: To compare the efficacy and safety of various treatments in patients with anxiety/somatic subtype MDD. METHODS: This was a preliminary multicenter randomized controlled trial at eight participating hospitals in China (09/2016-06/2019) (ClinicalTrials.gov #NCT03219008). The patients were randomized to mirtazapine/SNRIs, mirtazapine/SNRIs+cognitive behavioral therapy (CBT), mirtazapine+SNRIs, or mirtazapine+SNRIs+physical therapies (modified electroconvulsive treatment or repetitive transcranial magnetic stimulation). The primary endpoint was the 17-item Hamilton Depression Scale (HAMD-17). The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) and Quality of Life (QOL)-6 were the secondary endpoints. The adverse events (AEs) were monitored. The patients were assessed at baseline (0 weeks), and at the end of the 2nd, 4th, 6th, 8th, and 12th week during treatment. RESULTS: Finally, 107 patients were included: mirtazapine/SNRIs (n=36), mirtazapine/SNRIs+CBT (n=28), mirtazapine+SNRIs (n=29), and mirtazapine+SNRIs+physical therapies (n=14). The 17-HDRS and QIDS-SR scores decreased in all four groups, and the QOL-6 scores increased. There were no differences in the 17-HDRS (P=0.099), QIDS-SR (P=0.407), and QOL-6 (P=0.485) scores among the four groups. There were no differences in the occurrence of AEs among the four groups (P=0.942). CONCLUSION: This preliminary trial suggests that all four interventions (mirtazapine/SNRIs, mirtazapine/SNRIs+CBT, mirtazapine+SNRIs, or mirtazapine+SNRIs+physical therapies) achieved similar response and remission rates in patients with anxiety/somatic subtype MDD. The safety profile was manageable.

The association of depressive symptoms with disability among adults in China.

BACKGROUND: The symptoms that patients with major depressive disorder (MDD) experience are the dominant contributing factors to its heavy disease burden. This study sought to identify key symptoms leading to disability in patients with MDD. METHODS: Subjects consisted of patients who had a 12-month MDD diagnosis based on the China Mental Health Survey (CMHS). World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to assess the degree of disability. The associations between depressive symptoms and disability were analyzed using a linear regression and logistic regression with a complex sampling design. RESULTS: Of the 32,552 community residents, 655 patients were diagnosed with 12-month MDD. The disability rate due to MDD was 1.06% (95% CI: 0.85%-1.28%) among adults in Chinese community and 50.7% (95% CI: 44.3%-57.1%) among MDD patients. Depression was associated with all functional losses measured by the WHODAS. Feelings of worthlessness in life or inappropriate guilt, and psychomotor agitation or retardation were the key symptoms related to disability. Economic status, co-morbidity of physical diseases or anxiety disorders were correlates of disability scores. LIMITATIONS: The disability rate might be underestimated due to the exclusion of MDD patients living in hospitals. The effect of treatments on disability was excluded. CONCLUSIONS: Psychological symptoms, not somatic symptoms, contribute to disability in MDD patients. Disability worsens when physical diseases or anxiety disorders are present. More attention could be paid to psychological symptoms, physical diseases, and anxiety disorders in MDD patients with disabilities.