Objective To identify core targets of hepatocellular carcinoma (HCC) by using bioinformatics and specific algorithms, explore their relationships with immune cells, and investigate the causal relationships between immune cells and HCC through Mendelian randomization. Methods Relevant genes associated with the development of HCC were screened using the GEO and TCGA databases. Immune infiltration analysis was conducted using GSVA and CIBERSORT algorithms. A bidirectional Mendelian randomization analysis was then performed to explore the causal relationships between immune cells and HCC. Results A total of 284 HCC-related genes were identified, with 120 genes recognized within the protein interaction network. Immune infiltration analysis revealed significant correlations between key genes and immune cells. Mendelian randomization results indicated that HLA DR on CD33⁺ HLA DR⁺ CD14dim (OR=1.097, 95%CI: 1.002–1.201, P=0.045, P_Bonferroni=0.091) and CD8 on CD28⁺ CD45RA⁺ CD8⁺ T cell (OR=1.123, 95%CI: 1.027–1.228, P=0.011, P_Bonferroni=0.022) were the risk factors for HCC. Conversely, HLA DR⁺⁺ monocyte absolute count was identified as a protective factor for HCC (OR=0.812, 95%CI: 0.702–0.938, P=0.005, P_Bonferroni=0.139). Conclusion The occurrence and development of liver cancer may be related to CDK1, CCNB1, and CDC20, showing a high degree of correlation with Th2 cells, T helper cells, Th17 cells, and DCs. Mendelian randomization shows that HLA DR on CD33⁺HLA DR⁺ CD14dim and CD8 on CD28⁺CD45RA⁺CD8⁺T cells are associated with an increased risk of HCC. The risk of hepatocellular carcinoma is associated with a decrease in the level of HLA DR⁺⁺monocyte absolute count.

Lumbosacral radiculopathy refers to the pain syndrome caused by inflammation or mechanical compression of the lumbar nerve root, mainly manifested as low back pain, and radiating to the lower limbs in cutaneous mode, which can be accompanied by numbness, paresthesia, tingling, muscle weakness and loss of specific reflexes and other symptoms, which not only bring physical pain and life inconvenience to the patients, but also bring huge economic burden to the social medical care. Selective nerve root block(SNRB), as a safe, effective, low-cost, precise and minimally invasive clinical technique, can accurately intervene in specific nerve roots and quickly relieve pain symptoms by reducing inflammation and improving the surrounding environment of nerves. However, there are still many challenges and controversies in practice, such as precise targeting requirements, drug selection, potential risks and complications, and differences in efficacy among different patient populations. The purpose of this review is to systematically review and analyze the existing research results on SNRB, so as to provide useful reference and guidance for the further development of this field.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

ObjectiveUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to identify the metabolites of harmine in rats， in order to explore the differences in distribution of metabolites in rats after single dose（40 mg·kg^-1） intragastric administration of harmine， as well to speculate the metabolic pathways. MethodSD rats were given a single dose of harmine by intragastric administration. Plasma， bile， urine and feces samples were collected after administration， and the samples were processed for determination by UPLC-Q-TOF-MS. The separation was performed on an ACQUITY UPLC™ HSS T3 columu（2.1 mm×100 mm， 1.8 μm） with acetonitrile（A）-0.1% formic acid aqueous solution（B） as mobile phase for gradient elution（0-2 min， 5%A； 2-9 min， 5%-35%A； 9-9.5 min， 35%-100%A； 9.5-12 min， 100%A； 12-12.5 min， 100%-5%A； 12.5-14 min， 5%A）， the mass spectra were obtained in positive ion mode with electrospray ionization（ESI）， the scanning range was m/z 50-1 200. The metabolites of harmine were identified based on the information of the obtained compounds and the literature data， and the metabolic pathways were hypothesized. ResultA total of 42 compounds（harmine and its metabolites） were identified in rats， including 27 in plasma， 17 in bile， 26 in urine and 13 in feces. The metabolic pathways involved in these 42 metabolites included monohydroxylation， dihydroxylation， demethylation， glucuronidation and sulfation. ConclusionHarmine can undergo phase Ⅰ and phase Ⅱ metabolic reactions in rats， and the prototype drug is metabolized rapidly in vivo， and the metabolites are mainly excreted by the kidneys， which can provide a reference basis for the pharmacodynamics and material basis of harmine.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.