Gene set enrichment analysis identifies immune subtypes of kidney renal clear cell carcinoma with significantly different molecular and clinical properties.

Background: Kidney renal clear cell carcinoma (KIRC) is the most prevalent renal malignancy, marked by a high abundance of tumor-infiltrating lymphocytes (TILs) and an unfavorable prognosis upon metastasis. Numerous studies have demonstrated that KIRC possesses a tumor microenvironment that is highly heterogeneous, and this is associated with significant variations in the effectiveness of most first-line drugs administered to KIRC patients. Therefore, it is crucial to classify KIRC based on the tumor microenvironment, although these subtyping techniques are still inadequate. Methods: By applying gene set enrichment scores of 28 immune signatures, we conducted a hierarchical clustering of KIRC and determined its immune subtypes. In addition, we conducted a comprehensive exploration of the molecular and clinical features of these subtypes, including survival prognosis, proliferation, stemness, angiogenesis, tumor microenvironment, genome instability, intratumor heterogeneity, and pathway enrichment. Results: Through cluster analysis, two immune subtypes of KIRC were identified and termed Immunity-High (Immunity-H) and Immunity-Low (Immunity-L). This clustering outcome was consistent in four independent KIRC cohorts. The subtype Immunity-H exhibited elevated levels of TILs, tumor aneuploidy, homologous recombination deficiency, stemness, and proliferation potential, along with a poorer prognosis for survival. Despite this, the Immunity-L subtype demonstrated elevated intratumor heterogeneity and a stronger angiogenesis signature in contrast to Immunity-H. According to the results of pathway enrichment analysis, the Immunity-H subtype was found to be highly enriched in immunological, oncogenic, and metabolic pathways, whereas the Immunity-L subtype was highly enriched in angiogenic, neuroactive ligand-receptor interaction, and PPAR pathways. Conclusions: Based on the enrichment of immune signatures in the tumor microenvironment, KIRC can be categorized into two immune subtypes. The two subtypes demonstrate considerably distinct molecular and clinical features. In KIRC, an increase in immune infiltration is linked to a poor prognosis. Patients with Immunity-H KIRC may exhibit active responses to PPAR and immune checkpoint inhibitors, whereas patients with Immunity-L may manifest favorable responses to anti-angiogenic agents and immune checkpoint inhibitors. The immunological classification provides molecular insights into KIRC immunity, as well as clinical implications for the management of this disease.

Enhanced M2 Polarization of Oriented Macrophages on the P(VDF-TrFE) Film by Coupling with Electrical Stimulation.

Electrical stimulation (ES) has been considered a promising strategy in regulating intracellular communication, membrane depolarization, ion transport, etc. Meanwhile, cell topography, such as the alignment and elongation in anisotropic orientation, also plays a critical role in triggering mechanotransduction as well as the cellular fate. However, coupling of ES and cell orientation to regulate the polarization of macrophages is yet to be explored. In this work, we intended to explore the polarization of macrophages on a poly(vinylidene fluoride-trifluoroethylene [P(VDF-TrFE)] film with intrinsic microstripe roughness, which was covered on indium tin oxide planar microelectrodes. We found that mouse bone marrow-derived macrophages (BMDMs) cultured on a P(VDF-TrFE) film exhibited an elongated morphology aligned with the microstripe crystal whisker, but their polarization behavior was not affected. However, the elongated cells were susceptible to ES and upregulated their M2 polarization, as verified by the related expression of phenotype markers, cytokines, and genes, while not affecting M1 polarization. This is due to the increased expression of the M2 polarization receptor interleukin-4Rα on the surface of elongated BMDMs, while the M1 polarization receptor toll-like receptor 4 was not affected. Thus, M2 polarization was singularly enhanced after activation of polarization by ES. The combination of surface morphology and ES to promote M2 single polarization in this work provides a new perspective for regulating macrophage polarization in the field of immunotherapy.

Self-Assembly of Selenium-Doped Carbon Quantum Dots as Antioxidants for Hepatic Ischemia-Reperfusion Injury Management.

Hepatic ischemia-reperfusion injury (HIRI) is a critical complication after liver surgery that negatively affects surgical outcomes of patients with the end-stage liver-related disease. Reactive oxygen species (ROS) are responsible for the development of ischemia-reperfusion injury and eventually lead to hepatic dysfunction. Selenium-doped carbon quantum dots (Se-CQDs) with an excellent redox-responsive property can effectively scavenge ROS and protect cells from oxidation. However, the accumulation of Se-CQDs in the liver is extremely low. To address this concern, the fabrication of Se-CQDs-lecithin nanoparticles (Se-LEC NPs) is developed through self-assembly mainly driven by the noncovalent interactions. Lecithin acting as the self-assembly building block also makes a pivotal contribution to the therapeutic performance of Se-LEC NPs due to its capability to react with ROS. The fabricated Se-LEC NPs largely accumulate in the liver, effectively scavenge ROS and inhibit the release of inflammatory cytokines, thus exerting beneficial therapeutic efficacy on HIRI. This work may open a new avenue for the design of self-assembled Se-CQDs NPs for the treatment of HIRI and other ROS-related diseases.

Photothermal extracellular matrix based nanocomposite films and their effect on the osteogenic differentiation of BMSCs.

Mild thermal stimulation in vivo could induce osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In this study, nano-functionalized photothermal extracellular matrix (ECM) nanocomposite films were obtained through adding graphene during cell culture, so that graphene could directly integrate with the ECM secreted by cells. Owing to the similarity of the ECM to the in vivo microenvironment and the apparent photothermal effect of graphene nanoflakes, heat could be generated and transferred at the material-cell interface in a biomimetic way. It was demonstrated that such nanocomposite films achieved an interface temperature rise with light illumination. This could be easily sensed by BMSCs through the ECM. According to alkaline phosphatase, osteogenic related gene expression, mineral deposition, and upregulated expression of heat shock protein (HSP70) and p-ERK, composite films with proper illumination significantly promoted the differentiation of BMSCs into osteoblasts. This work endeavors to study the thermal regulation of BMSC differentiation and provide a new perspective on biocompatible osteo-implant materials which can be remotely controlled.

Electrochemical deposition of Ppy/Dex/ECM coatings and their regulation on cellular responses through electrical controlled drug release.

Bone tissue engineering requires a material that can simultaneously promote osteogenic differentiation and anti-inflammatory effects at specific times in response to a series of problems after bone implantation. In this study, the porous network-like titanium matrix was constructed and polypyrrole/dexamethasone (Ppy/Dex) composite coatings with three-dimensional nano-network structure were prepared by electrochemical deposition. The biocompatibility of the composite coatings was further improved by the composite of the extracellular matrix (ECM). The Ppy/Dex/ECM composite coatings released Dex by changing the redox state of Ppy under the electrical stimulation of negative pulses, achieving a drug release controlled by electric field. In terms of osteogenic differentiation, the Ppy/Dex/ECM composite coatings exhibited the best osteogenic activity under electrical controlled release, indicating the synergistic effect of Dex and ECM on osteogenic differentiation. In terms of anti-inflammatory properties, ECM exhibited simultaneous inhibition of both pro- and anti-inflammatory process, while Dex demonstrated significant promotion of anti-inflammatory processes. In this work, the effect of electrical controlled drug release on osteogenic differentiation and inflammation in the ECM cell microenvironment was achieved by preparing Ppy/Dex/ECM composite coatings, which is of great significance for bone tissue engineering and regenerative medicine.

Comparison of the efficacy and safety of sacral root magnetic stimulation with transcutaneous posterior tibial nerve stimulation in the treatment of neurogenic detrusor overactivity: an exploratory randomized controlled trial.

Background: Both repetitive sacral root magnetic stimulation (rSMS) and transcutaneous posterior tibial nerve stimulation (TTNS) have demonstrated clinical benefits for lower urinary tract dysfunction. However it still remains unclear that which method is more effective and safer to treat neurogenic detrusor overactivity (NDO). Methods: From December 2020 to December 2021, 50 patients (31 men and 19 women, aged 47.9±12.4 years) with NDO secondary to suprasacral spinal cord injury (SCI) were enrolled and randomly allocated to the rSMS or TTNS group based on a computer-generated random numbers table. The stimulation was applied continuously 5 times per week for 20 sessions. Urodynamic test was conducted at baseline and the day after the final 20th treatment session. The primary outcome was the individual change (Δ) in maximum cystometric capacity (MCC) from baseline to post-treatment. Secondary outcomes included changes (Δ) for the following parameters: volume at 1st involuntary detrusor contraction (1st IDCV), maximal detrusor pressure (Pdetmax), bladder compliance (BC), postvoid residual (PVR) volume, and bladder voiding efficiency (BVE). Additionally, adverse reactions including pain and skin irritation during stimulation were observed and recorded as safety outcomes. Results: Finally 47 patients completed the study (23 in rSMS and 24 in TTNS group). A per-protocol (PP) analysis was performed, and Mann-Whitney U test and unpaired t-test were used for statistical analysis. Compared with the efficacy of TTNS, rSMS showed statistically greater ΔMCC [median +43 mL (IQR, 22-62 mL) vs. +20 mL (IQR, 15-25 mL), P=0.001, with a between-group difference of +22 mL (95% CI: +7 to +35 mL)] and ΔBVE [median +10.0% (IQR, 3.8-15.7%) vs. +3.5% (IQR, 0.0-7.8%), P=0.003, with a between-group difference of +5.9% (95% CI: +1.2% to +9.7%)]. No significant differences were found in Δ1st IDCV (P=0.40), ΔPdetmax (P=0.67), ΔBC (P=0.79) and ΔPVR (P=0.92) between the two groups. Meanwhile, patients exhibited high tolerance to both protocols, and no adverse reactions were observed. Conclusions: RSMS may be more effective to improve urodynamics in the treatment for NDO than TTNS, cause it led to a statistical improvement in bladder capacity and voiding efficiency, without any side effects. RSMS is thus worthy of further clinical promotion. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100050663.

Pan-Cancer Analysis Reveals That E1A Binding Protein p300 Mutations Increase Genome Instability and Antitumor Immunity.

E1A binding protein p300 (EP300) is mutated in diverse cancers. Nevertheless, a systematic investigation into the associations of EP300 mutations with genome instability and antitumor immunity in pan-cancer remains lacking. Using the datasets from The Cancer Genome Atlas, we analyzed the correlations between EP300 mutations and genome instability and antitumor immune response in 11 cancer types. Compared to EP300-wild-type cancers, EP300-mutated cancers had significantly higher tumor mutation burden (TMB) in 10 cancer types. EP300-mutated cancers harbored a much higher fraction of microsatellite instable cancers in the colon and gastric cancers. EP300 was co-mutated with genes involved in DNA damage repair pathways in multiple cancers. Furthermore, compared to EP300-wild-type cancers, EP300-mutated cancers had significantly higher immune cytolytic activity scores and ratios of immune-stimulatory over immune-inhibitory signatures in diverse cancers. Also, EP300-mutated cancers showed significantly higher programmed death-ligand 1 (PD-L1) expression levels than EP300-wild-type cancers. The increased TMB, antitumor immune activity, and PD-L1 expression indicated a favorable response to immune checkpoint inhibitors (ICIs) in EP300-mutated cancers, as evident in three cancer cohorts treated with ICIs. Thus, the EP300 mutation could be a predictive biomarker for the response to immunotherapy.

Evaluation of the stability of cucurbit[8]uril-based ternary host-guest complexation in physiological environment and the fabrication of a supramolecular theranostic nanomedicine.

BACKGROUND: Supramolecular theranostics have exhibited promising potentials in disease diagnosis and therapy by taking advantages of the dynamic and reversible nature of non-covalent interactions. It is extremely important to figure out the stability of the driving forces in physiological environment for the preparation of theranostic systems. METHODS: The host-guest complexation between cucurbit[8]uril (CB[8]), 4,4'-bipyridinium, and napththyl guest was fully studied using various characterizations, including nuclear magnetic resonance spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, isothermal titration calorimetry (ITC). The association constants of this ternary complex were determined using isothermal titration calorimetry. The stability of the non-covalent interactions and self-assemblies form from this molecular recognition was confirmed by UV-vis spectroscopy and dynamic light scattering (DLS). A supramolecular nanomedicine was constructed on the basis of this 1:1:1 ternary recognition, and its in vitro and in vivo anticancer efficacy were thoroughly evaluated. Positron emission tomography (PET) imaging was used to monitor the delivery and biodistribution of the supramolecular nanomedicine. RESULTS: Various experiments confirmed that the ternary complexation between 4,4'-bipyridinium, and napththyl derivative and CB[8] was stable in physiological environment, including phosphate buffered solution and cell culture medium. Supramolecular nanomedicine (SNM@DOX) encapsulating a neutral anticancer drug (doxrubincin, DOX) was prepared based on this molecular recognition that linked the hydrophobic poly(ε-caprolactone) chain and hydrophilic polyethylene glycol segment. The non-covalent interactions guaranteed the stability of SNM@DOX during blood circulation and promoted its tumor accumulation by taking advantage of the enhanced permeability and retention effect, thus greatly improving the anti-tumor efficacy as compared with the free drug. CONCLUSION: Arising from the host-enhanced charge-transfer interactions, the CB[8]-based ternary recognition was stable enough in physiological environment, which was suitable for the fabrication of supramolecular nanotheranostics showing promising potentials in precise cancer diagnosis and therapy.

The spliceosome pathway activity correlates with reduced anti-tumor immunity and immunotherapy response, and unfavorable clinical outcomes in pan-cancer.

Alterations in the spliceosome pathway (SP) have been associated with diverse human cancers. In this study, we explored associations of the SP activity with various clinical features, anti-tumor immune signatures, tumor immunity-related genomic and molecular features, and the response to immunotherapies and targeted therapies in 29 cancer types from The Cancer Genome Atlas (TCGA) database. We showed that the SP activity was an oncogenic signature, as evidenced by its hyperactivation in cancer and invasive cancer subtypes and correlations with unfavorable clinical outcomes and anti-tumor immunosuppression in various cancers. The SP activity showed positive correlations with tumor mutation burden (TMB) and aneuploidy in diverse cancers, suggesting its association with genomic instability. However, the negative association between the SP activity and anti-tumor immune response was independent of its associations with aneuploidy and TMB. Furthermore, we supported that the SP activity had a negative correlation with immunotherapy response in four cancer cohorts treated by immune checkpoint inhibitors. Moreover, elevated SP activity is correlated with increased drug sensitivity for a broad spectrum of anti-tumor targeted therapies. In conclusion, the SP activity is a negative biomarker for anti-tumor immune response, prognosis, and the response to immunotherapeutic and targeted drugs in pan-cancer.

Hyperoside suppresses BMP-7-dependent PI3K/AKT pathway in human hepatocellular carcinoma cells.

BACKGROUND: New therapeutics for hepatocellular carcinoma (HCC) are urgently needed and searching for new anti-cancer compounds in plant medicines may represent a promising approach. The present study was conducted to clarify the role of hyperoside (HP) and its underlying molecular mechanism in a cancer cell. METHODS: Bone morphogenetic protein 7 (BMP-7) protein expression was measure in Human HCC tissue. In in vitro experiments, HP effects on cell proliferation and the mechanism were investigated deeply. RESULTS: The result showed a higher expression of BMP-7 in human HCC compared to adjacent noncancerous counterparts, and that silencing of BMP-7 suppressed HepG2 cell proliferation, suggesting BMP-7 plays an anti-cancer role in HCC. Furthermore, we found that HP could induce cell cycle arrest in proliferating HepG2 cells at the G1 phase by decreasing BMP-7 expression and that the phosphorylation of AKT and expression of PI3K were significantly down-regulated upon treatment of HP or BMP-7 knockdown. In addition, silencing of BMP-7 abrogated the difference of AKT phosphorylation between cells with and without HP treatment. CONCLUSIONS: Our results indicated that HP suppressed cell proliferation by inhibiting the BMP-7-dependent PI3K/AKT signaling pathway in HepG2 HCC cells, and either HP supplement or targeting BMP-7 might be a promising treatment against HCC.

Hypoxia Inducible Factor-1α Attenuates Ischemic Brain Damage by Modulating Inflammatory Response and Glial Activity.

Hypoxia-inducible factor 1 can sufficiently control the progress of neurological symptoms after ischemic stroke owing to their actions associated with its downstream genes. In this study, we evaluated the role of HIF-1α in attenuating brain damage after endothelin-1 injection. Focal cerebral ischemia in mice were induced by endothelin-1 microinjection. Hypoxia-inducible factor 1 activator, dimethyloxalylglycine (DMOG), and HIF-1α inhibitor, acriflavine (ACF), were used to evaluate the hypoxia-inducible factor 1 activity during cerebral ischemia. The expression levels of HIF-1α, glial fibrillary acidic protein (GFAP), interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), phosphorylated I-kappa-B-alpha/total I-kappa-B-alpha (p-IκBα/IκBα) and nuclear factor kappa B (NF-kB) were assessed. Besides, mRNA levels of IL-10, tumor necrosis factor- alpha (TNF-α), and NF-kB were also analyzed. Results showed a noticeable increase in hypoxia-inducible factor 1 and IL-10 levels in the DMOG group with a decline in iNOS, TNF-α, and NF-kB levels, implying the anti-inflammatory role of hypoxia-inducible factor 1 activator following stroke. These findings were further corroborated by GFAP immunostaining that showed astrocytic activation to be inhibited 12 days post-ischemia, as well as histological and TEM analyses that demonstrated hypoxia-inducible factor 1 induction to alleviate neuronal soma damage and cell death. Based on our study, HIF-1α could be a potential therapeutic target for ischemic stroke.

Therapeutic Opportunities of Interleukin-33 in the Central Nervous System.

Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is involved in various diseases. IL-33 exerts its effects via its heterodimeric receptor complex, which comprises suppression of tumorigenicity 2 (ST2) and the IL-1 receptor accessory protein (IL-1RAP). Increasing evidence has demonstrated that IL-33/ST2 signaling plays diverse but crucial roles in the homeostasis of the central nervous system (CNS) and the pathogenesis of CNS diseases, including neurodegenerative diseases, cerebrovascular diseases, infection, trauma, and ischemic stroke. In the current review, we focus on the functional roles and cellular signaling mechanisms of IL-33 in the CNS and evaluate the potential for diagnostic and therapeutic applications.

Rationally Designed, Self-Assembling, Multifunctional Hydrogel Depot Repairs Severe Spinal Cord Injury.

Following severe spinal cord injury (SCI), dysregulated neuroinflammation causes neuronal and glial apoptosis, resulting in scar and cystic cavity formation during wound healing and ultimately the formation of an atrophic microenvironment that inhibits nerve regrowth. Because of this complex and dynamic pathophysiology, a systemic solution for scar- and cavity-free wound healing with microenvironment remodeling to promote nerve regrowth has rarely been explored. A one-step solution is proposed through a self-assembling, multifunctional hydrogel depot that punctually releases the anti-inflammatory drug methylprednisolone sodium succinate (MPSS) and growth factors (GFs) locally according to pathophysiology to repair severe SCI. Synergistically releasing the anti-inflammatory drug MPSS and GFs in the hydrogel depot throughout SCI pathophysiology protects spared tissues/axons from secondary injury, promotes scar boundary- and cavity-free wound healing, and results in permissive bridges for remarkable axonal regrowth. Behavioral and electrophysiological studies indicate that remnants of spared axons, not regenerating axons, mediate functional recovery, strongly suggesting that additional interventions are still required to render the rebuilt neuronal circuits functional. These findings pave the way for the development of a systemic solution to treat acute SCI.

The emergency surgical infection management checklist of hospitalized patients with coronavirus disease 2019 (COVID-19) in Zhejiang, China.

The novel coronavirus disease 2019 (COVID-19) epidemic broke out in 2019, it is highly contagious, and the infection rate among medical staff is high. The management of infection prevention and control during emergency surgery of COVID-19 patients has been outlined and the perioperative infection management checklist for emergency surgery of COVID-19 patients has been summarized and validated. There have been 13 emergency surgeries performed on COVID-19 patients at our hospital during this time. Two cases were cured and discharged, and the others were discharged after improvement and transferred to further rehabilitation, 30-day mortality of the emergency surgical is 0%. Once the emergency surgery protocol in the hospital is successfully established, emergency surgery can be performed as soon as the surgical planning decision is made, and the operating room can be prepared for use at any time. The incidence of surgical site infection (SSI) was largely higher than that of ordinary patients in the same time; however, the successful implementation of emergency surgery for COVID-19 had positive significance in reducing the incidence of death, risk of bleeding, and hypoxia. The current cumulative cure rate of COVID-19 in our hospital is 98%, patient mortality rate is 0%, and the incidence of COVID-19 infection in medical staff is 0%. The emergency surgical infection management checklist is feasible and effective in guiding the preoperative and intraoperative surgical procedures.

The effect of in-hospital physiotherapy on handgrip strength and physical activity levels after cardiac valve surgery: a randomized controlled trial.

BACKGROUND: Patients who undergo cardiac valve surgery undertake routine physical therapy program. Despite its routine use, its influence on physical activity level post- surgery has not been illustrated. This study was to investigate whether 5 days of in-hospital physiotherapy could improve physical activity levels after cardiac valve surgery. METHODS: The study is a single-blind randomized controlled trial which performed in Cardiothoracic Surgery Department. Patients who underwent cardiac valve surgery (n=34) for confirmed cardiac valve disorders were assessed during hospitalization. The intervention group received a daily post-operative physiotherapy intervention, consisting of individualized mobilization, breathing exercises, ambulation with or without a walking aid. There was no physiotherapy treatment in the control group. Measurements: physical activity was assessed with the handgrip strength test and the timed up and go test. RESULTS: The treatment group showed significantly greater handgrip strength [20.58 (7.17) vs. 12.96 (4.65) kg] and less time on the timed up and go test [5.92 (2.91) vs. 6.53 (1.60) s] compared to the control group on the 5th post-operative day. Whilst there was no significant difference on the timed up and go test between the 2 groups, handgrip strength on the 5th post-operative day was significantly different between the 2 groups. CONCLUSIONS: Patients who received physiotherapy during hospitalization showed increased levels of handgrip strength and physical activity on the 5th day after cardiac valve surgery compared to the control group. The clinical value of increased levels of physical activity after in-hospital physiotherapy following cardiac valve surgery requires further investigation.

Hyperbaric Oxygen Therapy in Liver Diseases.

Hyperbaric oxygen therapy (HBOT) is an efficient therapeutic option to improve progress of lots of diseases especially hypoxia-related injuries, and has been clinically established as a wide-used therapy for patients with carbon monoxide poisoning, decompression sickness, arterial gas embolism, problematic wound, and so on. In the liver, most studies positively evaluated HBOT as a potential therapeutic option for liver transplantation, acute liver injury, nonalcoholic steatohepatitis, fibrosis and cancer, especially for hepatic artery thrombosis. This might mainly attribute to the anti-oxidation and anti-inflammation of HBOT. However, some controversies are existed, possibly due to hyperbaric oxygen toxicity. This review summarizes the current understandings of the role of HBOT in liver diseases and hepatic regeneration. Future understanding of HBOT in clinical trials and its in-depth mechanisms may contribute to the development of this novel adjuvant strategy for clinical therapy of liver diseases.

[Application of rehabilitation medicine in enhanced recovery after surgery].

Enhanced recovery after surgery (ERAS) has been widely used in perioperative optimization. As an important component of ERAS, rehabilitation medicine mainly focuses on perioperative physical fitness management, respiratory training, exercise training to reduce the incidence of postoperative pulmonary infection, improve gastrointestinal and cardiopulmonary function. This paper explains rehabilitation medicine for respiratory, musculoskeletal, cardiovascular and digestive systems during the perioperative period.

Albumin resuscitation protects against traumatic/hemorrhagic shock-induced lung apoptosis in rats.

OBJECTIVE: To determine the effects of albumin administration on lung injury and apoptosis in traumatic/hemorrhagic shock (T/HS) rats. METHODS: Studies were performed on an in vivo model of spontaneously breathing rats with induced T/HS; the rats were subjected to femur fracture, ischemia for 30 min, and reperfusion for 20 min with Ringer's lactate solution (RS) or 5% (w/v) albumin (ALB), and the left lower lobes of the lungs were resected. RESULTS: Albumin administered during reperfusion markedly attenuated injury of the lung and decreased the concentration of lactic acid and the number of in situ TdT-mediated dUTP nick-end labelling (TUNEL)-positive cells. Moreover, immunohistochemistry performed 24 h after reperfusion revealed increases in the level of nuclear factor kappaB (NF-kappaB), and phosphorylated p38 mitogen-activated protein kinase (MAPK) in the albumin-untreated group was down-regulated by albumin treatment when compared with the sham rats. CONCLUSION: Resuscitation with albumin attenuates tissue injury and inhibits T/HS-induced apoptosis in the lung via the p38 MAPK signal transduction pathway that functions to stimulate the activation of NF-kappaB.

Can albumin administration relieve lung injury in trauma/hemorrhagic shock?

AIM: To study the effect of albumin administration on lung injury in trauma/hemorrhagic shock (T/HS). METHODS: Sixty experimental animals were randomly divided into three groups: rats undergoing laparotomy without shock (T/SS); rats with T/HS and resuscitation with blood plus twice the volume of shed blood as Ringer's lactate (RL), and rats with T/HS and resuscitation with blood plus additional 3 mL of 50 g/L human albumin. Expression of polymorphonuclear neutrophil (PMN) CD11b/CD18, intercellular adhesion molecule-1 (ICAM-1) of jugular vein blood and the severity of lung injuries [determined mainly by measuring activity of lung tissue myeloperoxidase (MPO) and lung injury score (LIS)] were measured after a 3-h recovery period. RESULTS: All three groups showed a significant difference in the expressions of CD11b/CD18, ICAM-1, and severity of lung injury. The expressions of CD11b/CD18 in T/SS group, T/HS + RL group, T/HS + albumin group were 17.76% +/- 2.11%, 31.25% +/- 3.48%, 20.36% +/- 3.21%, respectively (F = 6.25, P < 0.05). The expressions of ICAM-1 (U/mL) in T/SS group, T/HS + RL group, T/HS + albumin group were 258.76 +/- 98.23, 356.23 +/- 65.6, 301.01 +/- 63.21, respectively (F = 5.86, P < 0.05). The expressions of MPO (U/g) in T/SS group, T/HS + RL group, T/HS + albumin group were 2.53 +/- 0.11, 4.63 +/- 1.31, 4.26 +/- 1.12, respectively (F = 6.26, P < 0.05). Moreover, LIS in T/HS + RL group, T/HS + albumin group was 2.62 +/- 0.23, 1.25 +/- 0.24, respectively. The expressions of CD11b/CD18, ICAM-1 and MPO in T/HS + RL group were significantly increased compared to T/SS group (P = 0.025, P = 0.036, P = 0.028, respectively). However, administration of 3 mL of 50 g/L albumin significantly down-regulated the expressions of CD11b/CD18, ICAM-1 and lung injury index (MPO and LIS) when compared with the T/HS + RL rats (P = 0.035, P = 0.046, P = 0.038, P = 0.012, respectively). CONCLUSION: The infusion of albumin during resuscitation period can protect lung from injury and decrease the expressions of CD11b/CD18, ICAM-1 in T/HS rats.

Liver fibrosis caused by choledocholith to regress after biliary drainage.

AIM: To study the correlation between liver fibrosis severity and biliary drainage in patients with choledocholith. METHODS: A follow-up study on seven patients with liver fibrosis due to choledocholith was made. The data, including biochemical tests (aspartate aminotransferase, alanine aminotransferase) and liver histological features before and after biliary drainage, were collected and studied. The fibrosis severity was scored on a scale from 0 to 3, with 0 denoting none, 1 portal and periportal fibrosis, 2 the presence of numerous fiber septa, and 3 cirrhosis. The average liver fibrosis severity scores of the first and second biopsy were compared with statistical method. RESULTS: The first, second liver fibrosis severity scores of these seven patients were 2,1; 2,1; 1,0; 1,1; 2,1; 2,1; 1,0 respectively. The results showed that the average liver fibrosis severity score of the second liver biopsy decreased significantly compared with the first liver biopsy (n = 7, t = 4.25, P<0.05). CONCLUSION: Liver fibrosis due to choledocholith may regress after biliary drainage.