Gut-brain axis in the pathogenesis of sepsis-associated encephalopathy.

The gut-brain axis is a bidirectional communication network linking the gut and the brain, overseeing digestive functions, emotional responses, body immunity, brain development, and overall health. Substantial research highlights a connection between disruptions of the gut-brain axis and various psychiatric and neurological conditions, including depression and Alzheimer's disease. Given the impact of the gut-brain axis on behavior, cognition, and brain diseases, some studies have started to pay attention to the role of the axis in sepsis-associated encephalopathy (SAE), where cognitive impairment is the primary manifestation. SAE emerges as the primary and earliest form of organ dysfunction following sepsis, potentially leading to acute cognitive impairment and long-term cognitive decline in patients. Notably, the neuronal damage in SAE does not stem directly from the central nervous system (CNS) infection but rather from an infection occurring outside the brain. The gut-brain axis is posited as a pivotal factor in this process. This review will delve into the gut-brain axis, exploring four crucial pathways through which inflammatory signals are transmitted and elevate the incidence of SAE. These pathways encompass the vagus nerve pathway, the neuroendocrine pathway involving the hypothalamic-pituitary-adrenal (HPA) axis and serotonin (5-HT) regulation, the neuroimmune pathway, and the microbial regulation. These pathways can operate independently or collaboratively on the CNS to modulate brain activity. Understanding how the gut affects and regulates the CNS could offer the potential to identify novel targets for preventing and treating this condition, ultimately enhancing the prognosis for individuals with SAE.

Roles of Macrophages and Their Interactions with Schwann Cells After Peripheral Nerve Injury.

The adult peripheral nervous system has a significant ability for regeneration compared to the central nervous system. This is related to the unique neuroimmunomodulation after peripheral nerve injury (PNI). Unlike the repair of other tissues after injury, Schwann cells (SCs) respond immediately to the trauma and send out signals to precisely recruit macrophages to the injured site. Then, macrophages promote the degradation of the damaged myelin sheath by phagocytosis of local debris. At the same time, macrophages and SCs jointly secrete various cytokines to reconstruct a microenvironment suitable for nerve regeneration. This unique pathophysiological process associated with macrophages provides important targets for the repair and treatment of PNI, as well as an important reference for guiding the repair of other nerve injuries. To understand these processes more systematically, this paper describes the characteristics of macrophage activation and metabolism in PNI, discusses the underlying molecular mechanism of interaction between macrophages and SCs, and reviews the latest research progress of crosstalk regulation between macrophages and SCs. These concepts and therapeutic strategies are summarized to provide a reference for the more effective use of macrophages in the repair of PNI.

Effects of Cryopreservation and Replantation on Muscles: Application Scope of Limb Cryopreservation.

BACKGROUND: Wang successfully replanted the severed fingers of 2 patients after cryopreservation in 2002 and 2003, which has enabled us to share our own experience for the knowledge interests of our colleagues and to further develop this technology. METHODS: Fifteen healthy adult male Sprague-Dawley rats were selected and divided into 5 groups (group 1: normal control, group 2: cryopreservation with protectant, group 3: cryopreservation without protectant, group 4: 6-hour postoperative, and group 5: 72-hour postoperative). After harvesting the hind limbs, cryoprotectant was applied to 20 limbs, and the rest were cryopreserved without cryoprotectant for 15 days. After being thawed, the amputated limb was replanted in situ. Nerves, skins and gastrocnemius muscles were collected for hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and transmission electron microscopy observation. RESULTS: Muscle and skin tissues treated with cryoprotectant restored a better outline after being frozen than those not treated, whereas nerves were not significantly different between the 2 groups. After replantation, some of the myofibrils of the muscle were in disarray, but the sarcomere structure remained intact at approximately 6 hours postoperatively. At 72 hours, a transmission electron microscopy scan showed that the myofibrillar arrangement was disorderly, with segmental myofilament breakage, and the sarcomere structure was destroyed in some cases. In addition, the scan revealed increased apoptotic cells and collapse of basic structures in the skin and nerves. CONCLUSIONS: Relative to that of skin and neuronal tissue, the replantation of muscle tissues through the cryopreservation method is more difficult.

Mathematical definition and rules of the splitting/merging patterns in bundles of human peripheral nerve segment.

Accurately measuring the spatial extension distance of nerve bundles in completing a split/merge is impossible because no clear mathematical definition exists for the starting and ending positions in nerve-bundle splitting/merging. We manually count the number of nerve-bundle splits/merges in long nerve segments, which is labor-intensive, inefficient, and prone to counting errors. Currently, the mathematics are unclear for the nerve-bundle diameter before and after splitting/merging. This paper explores these problems and proposes nerve-bundle splitting/merging rules. Based on the method of defining the beginning and ending positions of nerve-bundle splitting/merging, we explored the mathematical law of equivalent diameter of nerve bundles before and after splitting/merging. The experimental results revealed that the moving average of circularity of nerve bundle accurately defines the beginning and ending positions of nerve-bundle splitting/merging. The diameter of the nerve bundles before and after split/merge approximately conforms to the principles of the Da Vinci formula. The proposed automatic counting algorithm based on centroid offset matching obtains the number of split/merged nerve bundles in the sequence scan images with 100 % accuracy. The mathematical definition of the starting and ending positions of nerve-bundle splitting/merging proposed in this paper is accurate and strict and is the foundation of subsequent research. The proposed automatic counting algorithm based on centroid offset matching (ACA-COM) can accurately and efficiently count the number of times the nerve bundles split and merge in sequential images. The mathematical law satisfied by the diameter of the nerve bundles before and after splitting/merging reflects that the nerve bundles tend to have better capability to resist breaking.

Severe cytokine release syndrome induced by immune checkpoint inhibitors in cancer patients - A case report and review of the literature.

Cytokine release syndrome (CRS) can be induced by immune checkpoint inhibitors (ICIs). Although the incidence of CRS is low, it is often underreported. Here, we report two severe CRS cases and summarize and review 51 patients with ICI-induced CRS to explore the possible contributing factors to the disease prognosis and provide assistance for therapy. Our analysis found that the population with ICI-induced CRS consists mainly of male patients with an average age of 61.74 years. The primary malignant tumor type was lung cancer, and the clinical stage of most patients was stage IV. Notably, patients who experience a longer time to CRS onset, higher IL-6 levels, and lower platelet counts may be more likely to develop severe CRS. Cardiovascular, respiratory, neurological, and coagulation toxicities are more common in higher-grade CRS and may serve as markers for patient experiencing ICU admission, oxygen supplementation, hypotension, high-dose vasopressors usage, and intubation.

The early predictive roles of NLR and NE% in in-hospital mortality of septic patients.

Background: This study aimed to retrospectively investigate the early predictive value of inflammation-related parameters in-hospital mortality of septic patients. Methods: We retrospectively recruited 606 patients from Wuhan Union Hospital from January 2009 to October 2022. The inflammation-related parameters including neutrophil-to-lymphocyte ratio (NLR), neutrophil percentage (NE%), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in survivals and non-survivals on day 1, 2, 3 and 7 after hospitalization were collected and analyzed. Results: NLR and NE% in non-survivals (n = 185) were significantly higher than those in survivals (n = 421). The area under the receiver operating characteristic curve (AUC) of NLR or NE% was 0.880 or 0.852 on day 1, 0.770 or 0.790 on day 2, 0.784 or 0.777 on day 3, and 0.732 or 0.741 on day 7. The optimal cut-off values of NLR or NE% for predicting in-hospital mortality were 10.769 or 87.70% on day 1, 17.544 or 90.69% on day 2, 14.395 or 85.00% on day 3, and 9.105 or 83.93% on day 7. The day 1, 2 and 3 NLR and NE% were significant predictors of in-hospital mortality in the Cox proportional hazards models. Conclusions: NLR ≥10.769 and NE% ≥ 87.70% could be used early biomarkers for predicting in-hospital mortality of septic patients.

Systematic review of humeral shaft fracture (OTA/AO 12) complicated with iatrogenic radial nerve injury.

OBJECTIVES: To compare the iatrogenic radial nerve injury (iRNI) rate of different implant (plate vs. intramedullary nail) and surgical approaches during humeral shaft fracture surgery. METHODS: The online PubMed database was used to search for articles describing iRNI after humeral fracture with a publication date from Jan 2000 to October 2023. The following types of articles were selected: (1) case series associating with adult humeral shaft fracture, preoperative radial nerve continuity, non-pathological fracture and non-periprosthetic fracture; (2) involving humeral shaft (OTA/AO 12) fractures. Articles where we were unable to judge surgical approach or fracture pattern (OTA/AO 12) were excluded. The data were analyzed by SPSS 27.0 and Chi-square test was performed to identify incidence of iRNI associated with different implant and surgical approaches. RESULTS: Fifty-four articles with 5063 cases were included, with 3510 cases of the plate, 830 cases of intramedullary nail and 723 cases of uncertain internal fixation. The incidences of iRNI with plate and intramedullary nail were 5.95% (209/3510) and 2.77% (23/830) (p < 0.05). And iRNI incidences of different surgical approaches were 3.7% (3/82) for deltopectoral approach, 5.74% (76/1323) for anterolateral approach, 13.54% (26/192) for lateral approach and 6.68% (50/749) for posterior approach. The iRNI rates were 0.00% (0/33) for anteromedial MIPO, 2.67% (10/374) for anterolateral MIPO and 5.40% (2/37) for posterior MIPO (p > 0.05). The iRNI rates were 2.87% (21/732) for anterograde intramedullary nail and 2.04% (2/98) for retrograde intramedullary nail (p > 0.05). In humeral bone nonunion surgery, the rate of iRNI was 15.00% (9/60) for anterolateral approach, 16.7% (2/12) for lateral approach and 18.2% (6/33) for posterior approach (p > 0.05). CONCLUSION: Intramedullary nailing is the preferred method of internal fixation for humeral shaft fractures that has the lowest rate of iRNI. Compared with anterolateral and posterior approaches, the lateral surgical approach had a higher incidence of iRNI. The rate of iRNI in MIPO was lower than that in open reduction and internal fixation. LEVEL OF EVIDENCE: Level IV.

The "Self-Sacrifice" of ImmuneCells in Sepsis.

Sepsis is a life-threatening organ dysfunction caused by the host's malfunctioning response to infection. Due to its high mortality rate and medical cost, sepsis remains one of the world's most intractable diseases. In the early stage of sepsis, the over-activated immune system and a cascade of inflammation are usually accompanied by immunosuppression. The core pathogenesis of sepsis is the maladjustment of the host's innate and adaptive immune response. Many immune cells are involved in this process, including neutrophils, mononuclear/macrophages and lymphocytes. The immune cells recognize pathogens, devour pathogens and release cytokines to recruit or activate other cells in direct or indirect manner. Pyroptosis, immune cell-extracellular traps formation and autophagy are several novel forms of cell death that are different from apoptosis, which play essential roles in the progress of sepsis. Immune cells can initiate "self-sacrifice" through the above three forms of cell death to protect or kill pathogens. However, the exact roles and mechanisms of the self-sacrifice in the immune cells in sepsis are not fully elucidated. This paper mainly analyzes the self-sacrifice of several representative immune cells in the forms of pyroptosis, immune cell-extracellular traps formation and autophagy to reveal the specific roles they play in the occurrence and progression of sepsis, also to provide inspiration and references for further investigation of the roles and mechanisms of self-sacrifice of immune cells in the sepsis in the future, meanwhile, through this work, we hope to bring inspiration to clinical work.

Transverse myelitis in systemic lupus erythematosus: A case report and systematic literature review.

OBJECTIVE: Acute transverse myelitis (TM) is a rare complication secondary to systemic lupus erythematosus (SLE) that can cause patients' extensive and severe neuropsychiatric disorders. Due to the rarity of the onset of acute TM, there is still no standard treatment protocol. This study was to summarize the clinical features of SLE-TM through a case report and systematic review. METHODS: We report a case of acute TM with the initial symptoms of headache and fever on admission to hospital, with lesions in medulla oblongata, cervical medulla, and thoracic medulla. Furthermore, all cases of SLE combined with acute TM from January 1975 to February 2022 were concluded and reviewed to compare the disease's current treatment strategies and prognosis. RESULTS: Patients with SLE-TM are mainly female (97.65%), with an average age of 36.89, a TM incidence of 24.51% and a longitudinal myelitis (LM) incidence of 67.76%. In addition, 68.63% of patients present an increased albumin, and only 16.50% of patients could recover. 32.35% of patients showed positive anti-cardiolipin antibody. Moreover, the patients who could recover are generally younger than those in the improved and paraparesis groups. After classifying the statistical results twice according to magnetic resonance imaging results and prognosis respectively, the erythrocyte sedimentation rate (ESR) in LM group was significantly higher than that in the other two groups. The positive rate of anti-DNA and anti-cardiolipin antibody (ANCL) in TM group was significantly higher than that of the other groups. According to the prognostic grouping, ESR in the recovery group was significantly higher than those in the other two groups. The positive ANCL in the poor prognosis group was slightly higher than that in the other two groups. CONCLUSION: We offer a novel insight for this rare disease and hope to bring some inspiration the basic research for SLE-TM.

Current scenario of indole derivatives with potential anti-drug-resistant cancer activity.

Cancer chemotherapy is frequently hampered by drug resistance, so the resistance to anticancer agents represents one of the major obstacles for the effective cancer treatment. Indole derivatives have the potential to act on diverse targets in cancer cells and exhibit promising activity against drug-resistant cancers. Moreover, some indole-containing compounds such as Semaxanib, Sunitinib, Vinorelbine, and Vinblastine have already been applied in clinics for various kinds of cancer even drug-resistant cancer therapy. Thus, indole derivatives are one of significant resources for the development of novel anti-drug-resistant cancer agents. This review focuses on the recent development of indole derivatives with potential therapeutic application for drug-resistant cancers, and the mechanisms of action, the critical aspects of design as well as structure-activity relationships, covering articles published from 2010 to 2020.

Recent Development of 1,2,4-triazole-containing Compounds as Anticancer Agents.

1,2,4-Triazole derivatives possess promising in vitro and in vivo anticancer activity, and many anticancer agents such as fluconazole, tebuconazole, triadimefon, and ribavirin bear a 1,2,4-triazole moiety, revealing their potential in the development of novel anticancer agents. This review emphasizes the recent advances in 1,2,4-triazole-containing compounds with anticancer potential, and the structureactivity relationships as well as mechanisms of action are also discussed.

[Analysis of therapeutic effects of cannulated compression screws for the treatment of femoral neck fractures].

OBJECTIVE: To evaluate the therapeutic effects of cannulated compression screws for the treatment of femoral neck fractures, and to investigate the related factors influencing the avascular necrosis of femoral head after surgery. METHODS: A retrospective review was done for 96 patients with femoral neck fractures treated with cannulated compression screws from January 2003 to June 2009. Among them, there were 44 males and 52 females with 21 to 88 years old (averaged 56.3 years old). According to Garden classification, 4 patients were type I, 34 patients were type II, 37 patients were type III and 21 patients were type IV. Factors such as patients' age, gender, fracture type, duration from injury to surgery and fracture reduction quality were statistically analysed to find correlations with nonunion and avascular necrosis of femoral head. RESULTS: Eighty-four patients were followed up ranging from 9 to 60 months and the mean time was 25.4 months. Postoperative complications included deep venous thrombosis of lower extremity in 2 cases, bone nonunion in 8 cases and avascular necrosis of femoral head in 11 cases. According to Harris criterion, the total postoperative Harris score was 86.20 +/- 11.00, and 40 patients got an excellent result, 32 good, 7 fair and 5 poor. The incidence of avascular necrosis of femoral head in nondisplaced fracture group and displaced fractures group were 3.22% and 18.87% respectively;and there were significant difference between the two groups (P = 0.037). The incidence of avascular necrosis of femoral head in anatomical reduction group and non-anatomical reduction group were 5.00% and 20.45% respectively; also,significant difference was existed between the two groups (P = 0.036). However, there was no statistically significant difference of the incidence of avascular necrosis of femoral head according to different age, sex, operative time. CONCLUSION: The therapeutic effect of cannulated compression screws for non-displaced femoral neck fractures is good. The fracture type and reduction quality are found to be main factors correlated with avascular necrosis of femoral head statistically. For young patients with a displaced femoral neck fracture,in order to avoid incidence of avascular necrosis of femoral head, anatomical reduction should be ensured. For elder patients with a severe displaced femoral neck fracture, the total hip replacement should be recommended.

[Treatment of tibial avulsion fracture of the posterior cruciate ligament with open reduction and steel-wire internal fixation].

OBJECTIVE: To study the curative effects of the treatment of tibial avulsion fracture of the posterior cruciate ligament with open reduction and steel-wire internal fixation. METHODS: From January 2003 to June 2009, 28 patients of tibial avulsion fracture of the posterior cruciate ligament were treated with open reduction and steel-wire internal fixation through posteromedial inverted "L" approach. There were 19 males and 9 females with an average age of 35.3 years old ranging from 16 to 55 years. The X-ray examination showed that there were II degree displaced in 10 cases and III degree in 18 patients. The affected lower extremity was put in a controlled hinge knee brace after operation. The patients were asked to do passive extension and flexion of the knee joint with the assistance of a CPM 2 weeks after operation,and allowed to be partial weight-bearing as tolerated with the hinged brace locked in extension if concomitant injuries allowed 4 weeks postoperatively. The brace were removed 6 weeks later. RESULTS: Among them, 25 patients were followed up for 6 to 24 months with an average of 15 months. The X-ray examination showed satisfactory reduction, and bony union was obtained in all the patients. The Lachman test was negative in all patients. No complications such as malunion or joint stiffness were found. The extension of affected knee was normal and its flexion were (136 +/- 12) degrees. According to Lysholm knee score system,it was preoperatively (41.80 +/- 6.16) and (94.10 +/- 8.26) six months after surgery respectively. Twenty-two cases were excellent, 2 cases good and 1 fair. CONCLUSION: Treatment of tibial avulsion fracture of the posterior cruciate ligament with open reduction and internal fixation with wires through posteromedial inverted "L" approach is a safe, effective method, due to its stable fixation and relatively low expense. It is believed as an ideal choice for tibial avulsion fracture of the posterior cruciate ligament.